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Names: Baysinger, Curtis L., editor. | Bucklin, Brenda A., editor. |

Gambling, David R., editor.
Title: A practical approach to obstetric anesthesia / editors, Curtis L.
Baysinger, Brenda A. Bucklin, David R. Gambling.
Description: 2nd edition. | Philadelphia : Wolters Kluwer Health, [2016] |
Preceded by A practical approach to obstetric anesthesia / editors, Brenda
A. Bucklin, David R. Gambling, David Wlody. c2009. | Includes
bibliographical references and index.
Identifiers: LCCN 2015046281 | ISBN 9781469882864
Subjects: | MESH: Anesthesia, Obstetrical | Pregnancy Complications | Labor,
Obstetric
Classification: LCC RG732 | NLM WO 450 | DDC 617.9/682—dc23 LC record available at
http://lccn.loc.gov/2015046281

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 Dedication
To the memory of Dr. Geraldine O’Sullivan
Preface
A PRACTICAL APPROACH TO OBSTETRIC ANESTHESIA, 2ND EDITION

There is certainly no shortage of obstetric anesthesia texts currently available,

from introductory handbooks to encyclopedic treatises. What has been lacking is
a book that straddles the middle ground between those extremes, a book that
would serve to supply both experienced and novice clinicians with guidance for
managing routine and complicated parturients, as well as providing an
explanation of the physiologic and pharmacologic principles underlying clinical
care. We think that A Practical Approach to Obstetric Anesthesia has achieved
this goal by assembling and reviewing the most up-to-date information relevant
to the practice of obstetric anesthesiology.

The book is a portable user-friendly reference that gives easy-to-follow guidance

in an outline format. The table of contents is divided into six sections:
Pharmacology and Physiology, Antepartum Considerations, Labor and Delivery,
Postpartum Issues, Disease States, and Guidelines from National Organizations.
The book contains 33 chapters that have been organized within a particular
section. Key points are noted at the beginning of each chapter. Clinical Pearls are
embedded within the text. Each chapter also contains a list of current and
relevant references. The use of color in this edition highlights important sections
to improve readability.

This book would not have been possible without the commitment and hard work
of more than 40 contributors as well as the production staff at Wolters Kluwer.
Acknowledgments
I would like to dedicate this book to the memory of Sol Shnider, who started me
on my career in obstetric anesthesia; to my parents, Roy and Mary Lee, whose
resources and encouragement helped make my career in medicine a reality; to
my children, Charles and Katherine, who have honored me by pursuing careers
as physicians; and to my wife Mary, whose love and support I receive daily.

Curtis L. Baysinger

I would like to dedicate this book to my husband, Uli, my parents, and all of the
learners who study obstetric anesthesiology.

Brenda A. Bucklin

I would like to acknowledge two important mentors, Professor Graham

McMorland and Professor Joanne Douglas, who facilitated my understanding of
obstetric anesthesia. I dedicate this book to the memory of my father Gordon and
to acknowledge the love and support of my wife Kimberley; my children
Carwyn, Jake, and Samantha; and my mother Sadie.

David R. Gambling
Contributors
Bryan S. Ahlgren, DO
Assistant Professor
University of Colorado School of Medicine
Aurora, Colorado

Mrinalini Balki, MB, BS; MD

Associate Professor
University of Toronto
Department of Anesthesia and Pain Management
Department of Obstetrics and Gynaecology
Mount Sinai Hospital
Toronto, Ontario, Canada

Curtis L. Baysinger, MD
Professor of Anesthesiology
Division of Obstetric Anesthesia
Department of Anesthesiology
Vanderbilt University School of Medicine
Nashville, Tennessee

Yaakov Beilin, MD
Professor of Anesthesiology and Obstetrics
Gynecology and Reproductive Science
Vice Chair for Quality
Department of Anesthesiology
Director, Obstetric Anesthesiology
Icahn School of Medicine at Mount Sinai
New York, New York

Jessica Booth, MD
Assistant Professor
Department of Anesthesiology
Wake Forest School of Medicine
Winston-Salem, North Carolina

James P.R. Brown, MBChB(Hons), MRCP, FRCA

Consultant Anesthesiologist, Clinical Instructor
Anesthesia Fellow
BC Women’s Hospital & Health Centre
Vancouver, British Columbia, Canada

Brenda A. Bucklin, MD
Professor of Anesthesiology
Assistant Dean, Clinical Core Curriculum
University of Colorado School of Medicine
Aurora, Colorado

William Camann, MD
Director, Obstetric Anesthesia Service
Brigham and Women’s Hospital
Associate Professor
Harvard Medical School
Boston, Massachusetts

Christopher R. Cambic, MD
Assistant Professor
Department of Anesthesiology
Northwestern University Feinberg School of Medicine
Chicago, Illinois

Laurie A. Chalifoux, MD
Assistant Professor of Anesthesiology
Northwestern University Feinberg School of Medicine
Chicago, Illinois

Debnath Chatterjee, MD
Associate Professor of Anesthesiology
Children’s Hospital Colorado/University of Colorado School of Medicine
Aurora, Colorado

Mary DiMiceli-Zsigmond, MD
Assistant Professor of Anesthesiology
Vanderbilt University School of Medicine
Nashville, Tennessee

M. Joanne Douglas, MD, FRCPC, CM

Clinical Emeritus Professor
Department of Anesthesiology
Pharmacology and Therapeutics
University of British Columbia
Consultant Anesthesiologist
BC Women’s Hospital & Health Centre
Vancouver, British Columbia, Canada

Lior Drukker, MD
Lecturer
Department of Obstetrics and Gynecology
Shaare Zedek Medical Center
Hebrew University Medical School
Jerusalem, Israel

Sharon Einav, MSc, MD

Director of Surgical Intensive Care
Shaare Zedek Medical Centre
Professor of Intensive Care Medicine
Hebrew University School of Medicine
Jerusalem, Israel

Tammy Y. Euliano, MD
Professor of Anesthesiology and Obstetrics & Gynecology
University of Florida College of Medicine
Gainesville, Florida
Roshan Fernando, MB, BCh, FRCA
Consultant Anesthetist
University College London Hospitals NHS Foundation Trust
London, United Kingdom

Michael Frölich, MD, MS

Professor of Anesthesiology
University of Alabama at Birmingham
Birmingham, Alabama

Robert R. Gaiser, MD, MSEd

Professor of Anesthesiology and Critical Care
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania

David R. Gambling, MB, BS; FRCPC

Staff Anesthesiologist
Sharp Mary Birch Hospital for Women and Newborns
Clinical Professor (Voluntary)
Department of Anesthesiology
University of California San Diego (UCSD)
San Diego, California

Andrew Geller, MD
Assistant Professor and Assistant Fellowship Director
Department of Anesthesiology
Cedars-Sinai Medical Center
Los Angeles, California

Stephanie R. Goodman, MD
Professor of Anesthesiology
Department of Anesthesiology
Columbia University Medical Center
New York, New York

Joy L. Hawkins, MD
Professor of Anesthesiology
Director of Obstetric Anesthesia
University of Colorado School of Medicine
Aurora, Colorado

Mary A. Herman, MD, PhD

Assistant Professor
Department of Anesthesiology
University of Florida College of Medicine
Gainesville, Florida

Jennifer Hofer, MD
Assistant Professor
Department of Anesthesia & Critical Care
University of Chicago
Chicago, Illinois

Rachel M. Kacmar, MD
Assistant Professor
Department of Anesthesiology
University of Colorado School of Medicine
Aurora, Colorado

Erin J. Keely, MD, FRCPC

Professor
Departments of Medicine and Obstetrics and Gynecology
University of Ottawa
Chief, Division of Endocrinology
The Ottawa Hospital
Ottawa, Ontario, Canada

Ellen M. Lockhart, MD
Associate Professor and Vice Chairman
Department of Anesthesiology
Washington University School of Medicine
St. Louis, Missouri

Janine Malcolm, MD
Assistant Professor
Department of Endocrinology and Metabolism
University of Ottawa Hospital
Endocrinologist
Department of Endocrinology and Metabolism
The Ottawa Hospital
Ottawa, Ontario, Canada

M. Susan Mandell, MD, PhD

Director
Anesthesia for Abdominal Transplantation
University of Colorado Hospital
Aurora, Colorado

Suzanne K.W. Mankowitz, MD

Assistant Professor of Anesthesiology
Columbia University College of Physicians and Surgeons
Columbia University Medical Center
New York, New York

Jill M. Mhyre, MD
Associate Professor of Anesthesiology
University of Arkansas for Medical Sciences
Little Rock, Arkansas

Rebecca D. Minehart, MD
Director, CA-1 Tutorial Simulation
Department of Anesthesia, Critical Care & Pain Medicine
Massachusetts General Hospital
Boston, Massachusetts

Dominique Moffitt, MD
Instructor in Anaesthesia
Harvard Medical School
Brigham and Women’s Hospital
Boston, Massachusetts

Wint Mon, FRCA

Research Fellow
University College London Hospitals NHS Foundation Trust
London, United Kingdom

Richard A. Month, MD
Assistant Professor of Clinical Anesthesiology and Interim Chief of Obstetric
Anesthesia
Department of Anesthesiology and Critical Care
University of Pennsylvania Health System
Philadelphia, Pennsylvania

Uma Munnur, MD
Associate Professor
Baylor College of Medicine
Anesthesiologist
Ben Taub Hospital
Houston, Texas

Geraldine O’Sullivan, MD, FRCA†

Lead Clinician in Obstetric Anaesthesia
Consultant Anaesthetist
Department of Anaesthetics
Guy’s and St. Thomas’ NHS Foundation Trust
London, United Kingdom

Quisqueya T. Palacios, MD
Associate Professor
Department of Anesthesiology
Associate Professor
Department of Obstetrics and Gynecology
Baylor College of Medicine
Houston, Texas

Arvind Palanisamy, MD, FRCA

Assistant Professor of Anesthesia
Department of Anesthesiology
Perioperative and Pain Medicine
Harvard Medical School
Brigham and Women’s Hospital
Boston, Massachusetts

Peter H. Pan, MD
Professor
Obstetrical and Gynecological Anesthesiology
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina

Ruchira Patel, MBBS, BSc, FRCA

Fellow
Mount Sinai Hospital
Toronto, Ontario, Canada

Michael G. Richardson, MD
Associate Professor of Anesthesiology
Director, Obstetric Anesthesiology Fellowship Program
Vanderbilt University School of Medicine
Nashville, Tennessee

Barbara M. Scavone, MD
Professor
Department of Anesthesia & Critical Care
Professor
Department of Obstetrics & Gynecology
University of Chicago
Chicago, Illinois
Scott Segal, MD
Professor and Chair
Department of Anesthesiology
Wake Forest University School of Medicine
Winston-Salem, North Carolina

Hen Y. Sela, MD
Attending Physician
Department of Obstetrics and Gynecology
Shaare Zedek Medical Center
Hebrew University School of Medicine
Jerusalem, Israel
Adjunct Professor
Division of Maternal Fetal Medicine
Department of Obstetrics and Gynecology
Columbia University Medical Center
New York, New York

Yelena Spitzer
Instructor of Anesthesiology
Albert Einstein School of Medicine
Yeshiva University
New York, New York

Barton Staat, MD, LtCol, USAF

MCAF/SG Consultant for Obstetrics/Maternal-Fetal Medicine Assistant
Professor
Uniformed Services University of Health Sciences
Bethesda, Maryland

John T. Sullivan, MD
Professor
Department of Anesthesiology
Northwestern University Feinberg School of Medicine
Chicago, Illinois
William J. Sullivan, QC, LLB, MCL
Adjunct Professor
Faculty of Medicine
University of British Columbia
Partner
Guild Yule LLP Barristers and Solicitors
Vancouver, British Columbia, Canada

Maya S. Suresh, MD
Professor & Chairman
Department of Anesthesiology
Baylor College of Medicine
Chief of Anesthesiology
Ben Taub Hospital
Houston, Texas

Andrea J. Traynor, MD
Clinical Associate Professor
Department of Anesthesiology
Stanford University School of Medicine
Stanford, California

Carolyn F. Weiniger, MB, ChB

Senior Lecturer
Department of Anesthesiology and Critical Care Medicine
Hadassah Hebrew University Medical Center
Jerusalem, Israel
Department of Anesthesia
Stanford University School of Medicine
Stanford, California

Nathaen S. Weitzel, MD
Associate Professor
Department of Anesthesiology
University of Colorado Hospital
Aurora, Colorado

Richard N. Wissler, MD, PhD

Director of Obstetric Anesthesia
Medical Director of Perioperative Services
University of Rochester Medical Center
Rochester, New York

David Wlody, MD
Professor of Clinical Anesthesiology
SUNY, Downstate Medical Center
Brooklyn, New York

Cynthia A. Wong, MD
Professor and Vice Chair
Department of Anesthesiology
Northwestern University Feinberg School of Medicine
Chicago, Illinois

Jessica L. Young, MD, MPH, FACOG

Assistant Professor
Department of Obstetrics and Gynecology
Vanderbilt University Medical Center
Nashville, Tennessee

Mark I. Zakowski, MD
Associate Professor of Anesthesiology
Adjunct
Charles R. Drew University of Medicine and Science
Chief, Obstetric Anesthesiology
Cedars-Sinai Medical Center
Los Angeles, California

Kathryn J. Zuspan, MD
Obstetric Anesthesiologist
Edina, Minnesota
Contents
Preface
Acknowledgments
Contributors

SECTION I: PHARMACOLOGY AND PHYSIOLOGY

1. Physiologic Changes of Pregnancy

Rachel M. Kacmar and Andrea J. Traynor

2. Uteroplacental Anatomy, Blood Flow, Respiratory Gas Exchange, Drug

Transfer, and Teratogenicity
Curtis L. Baysinger and Barton Staat

3. Local Anesthetics and Toxicity

Jennifer Hofer and Barbara M. Scavone

4. Obstetric Medications
Ruchira Patel and Mrinalini Balki

SECTION II: ANTEPARTUM CONSIDERATIONS

5. Ethical and Legal Considerations in Obstetric Anesthesia

M. Joanne Douglas and William J. Sullivan

6. Nonobstetric Surgery during Pregnancy

Joy L. Hawkins and Debnath Chatterjee

SECTION III: LABOR AND DELIVERY

7. Fetal Assessment and Monitoring

Michael G. Richardson, Mary DiMiceli-Zsigmond, and David R. Gambling
 8. Maternal Infection and Fever
Rebecca D. Minehart, William Camann, and Scott Segal

9. Non-neuraxial Analgesic Techniques

Wint Mon, Roshan Fernando, and Geraldine O’Sullivan

10. Choice of Neuraxial Analgesia and Local Anesthetics

Dominique Moffitt and Arvind Palanisamy

11. Ultrasound and Echocardiographic Techniques in Obstetric Anesthesia

Laurie A. Chalifoux and John T. Sullivan

12. Impact of Neuraxial Analgesia on Obstetric Outcomes

Christopher R. Cambic and Cynthia A. Wong

13. Anesthetic Considerations for Women Receiving Cesarean Delivery

Robert R. Gaiser

14. Difficult Airway Management in the Pregnant Patient

Uma Munnur and Maya S. Suresh

15. Anesthesia for Multiple Gestation and Breech Presentation

Carolyn F. Weiniger

16. Obstetric Emergencies

Michael Frölich and Brenda A. Bucklin

17. Newborn Resuscitation

Richard A. Month

SECTION IV: POSTPARTUM ISSUES

18. Postcesarean Analgesia

Richard N. Wissler

19. Management of Postdural Puncture Headache

David Wlody
20. Neurologic Deficits Following Labor and Delivery
Mark I. Zakowski and Andrew Geller

21. Postpartum Tubal Ligation

Brenda A. Bucklin

SECTION V: DISEASE STATES

22. Hypertensive Disorders of Pregnancy

Yelena Spitzer and Yaakov Beilin

23. Endocrine Disorders

Jessica Booth, Peter H. Pan, Janine Malcolm, and Erin J. Keely

24. Thrombophilias/Coagulopathies
James P.R. Brown and M. Joanne Douglas

25. Cardiac Disease in the Obstetric Patient

Nathaen S. Weitzel and Bryan S. Ahlgren

26. Neurologic and Neuromuscular Disease

Tammy Y. Euliano and Mary A. Herman

27. Renal and Hepatic Disease in the Pregnant Patient

Quisqueya T. Palacios and M. Susan Mandell

28. Obstetric Anesthesia for Parturients with Respiratory Diseases

Suzanne K.W. Mankowitz and Stephanie R. Goodman

29. Obesity and Pregnancy

Brenda A. Bucklin and David R. Gambling

30. Trauma in the Obstetric Patient

Hen Y. Sela, Lior Drukker, and Sharon Einav

31. Management of the Opioid Dependent Parturient

Jessica L. Young, Ellen M. Lockhart, and Curtis L. Baysinger
32. Maternal Morbidity and Mortality
Jill M. Mhyre

SECTION VI: GUIDELINES FROM NATIONAL ORGANIZATIONS

33. Guidelines from National Organizations

Kathryn J. Zuspan

Index
Pharmacology
and Physiology
 Physiologic Changes of Pregnancy
Rachel M. Kacmar and Andrea J. Traynor

I. Cardiovascular system
A. Central hemodynamic changes
B. Electrocardiogram changes and rhythm disturbances
C. Aortocaval compression
II. Respiratory system
A. Arterial blood gases
B. Lung volumes and capacities and respiratory mechanics
C. Mechanisms of hypoxemia in pregnancy
D. Upper airway changes
E. Respiratory consequences of uncontrolled maternal pain
F. Oxygen delivery
III. Hematologic system
A. Dilutional anemia
B. Platelet count and function
C. Coagulation factors
D. Leukocytes and immune function
IV. Gastrointestinal system
A. Gastric position and pressure
B. Lower esophageal sphincter tone
C. Gastric secretion
D. Gastric emptying
V. Hepatic function
 A. Increase in serum estrogen and progesterone
B. Hepatic blood flow
C. Increase in splanchnic, portal, and esophageal venous
pressure
D. Serum albumin concentration
VI. Renal system
A. Anatomic changes/alterations in renal blood flow
B. Changes in glomerular filtration rate/measures of renal
function
VII. Endocrine system
A. Thyroid function
B. Pancreatic function and glucose metabolism
C. Pituitary function
VIII. Musculoskeletal
A. Lumbar lordosis
B. Joint mobility
IX. Central nervous system
A. Inhalation anesthetics and minimum alveolar concentration
B. Neuraxial anesthesia/local anesthetics
X. Anesthetic implications of maternal physiologic changes during
pregnancy
A. Increased minute ventilation and reduced functional residual
capacity
B. Hypoxemia
C. Aortocaval compression
D. Upper airway changes
E. Endotracheal intubation
F. Use of muscle relaxants
G. Replacement of blood loss
H. Subarachnoid and epidural doses
I. Morbidity and mortality


KEYPOINTS
1. Aortocaval compression occurs as the uterus enlarges beyond the pelvis
at 16 to 20 weeks’ gestation and is responsible for decreased venous
return and cardiac output in the supine position.
2. Decreased functional residual capacity due to atelectasis from the
enlarging uterus and increased oxygen consumption render the parturient
particularly susceptible to periods of apnea.
3. Increases in progesterone result in decreased lower esophageal sphincter
tone and render the parturient at high risk for aspiration of gastric
contents.
4. Renal blood flow increases during pregnancy, resulting in increased
glomerular filtration rate. This leads to increased creatinine clearance and
decreased blood urea nitrogen (BUN) and creatinine (normal ~0.5 to 0.6
mg per dL at term).
5. Pain tolerance increases throughout pregnancy. Hormonal changes lead to
decreases in anesthetic requirements and an approximately 30% decrease
in minimum alveolar concentration (MAC).

NORMAL PREGNANCY IS MARKED BY significant physiologic changes in every

organ system in order to meet the metabolic demands of the growing uterus,
fetus, and placenta. Knowledge of these changes is critical for the obstetric
anesthesiologist because they have significant implications for anesthetic
management of the parturient. In addition, these physiologic changes can have a
significant impact on preexisting pathophysiology.

In this chapter we describe the system-based physiologic changes of pregnancy

as well as the anesthetic considerations that result from these changes. Each
section in this chapter discusses potential impact of normal physiologic changes
on relevant preexisting patient comorbidities.
I. Cardiovascular system
A. Central hemodynamic changes
Pregnancy is associated with profound adaptive changes in
maternal hemodynamics.
1. Blood volume
a. Blood volume increases during pregnancy1,2 (Table 1.1).
This increase begins in early pregnancy, rises rapidly in
the second trimester, and peaks and stabilizes around 34
weeks’ gestation. Plasma volume increases more than red
blood cell volume, resulting in a “physiologic anemia of
pregnancy” with a normal hemoglobin concentration of
11.6 g per dL at term pregnancy.3 This level may be less if
there is superimposed iron deficiency anemia.

b. Blood volume does not return to the prepregnancy level

for greater than 6 weeks’ postpartum.
2. Cardiac output4 (Table 1.2)

a. Cardiac output (CO) begins to increase at 10 weeks’

gestation, peaking at 40% to 50% of baseline at 32 weeks’
gestation.
 b. The increase in CO is a result of combined increases in
stroke volume (SV) and heart rate (HR) during pregnancy.
HR peaks at 10 to 20 beats per minute (bpm) above the
prepregnancy rate at term. During labor, SV increases
dramatically, whereas HR increases slightly, leading to up
to an additional 40% increase in CO by the second stage
of labor.
c. Immediately postpartum, it is possible for maternal CO to
rise 75% above predelivery values.
d. CO returns to a prepregnancy level around 2 weeks
postpartum.
3. Systemic vascular resistance. Systemic vascular resistance
(SVR) is decreased through a number of mechanisms5:
a. The low-resistance placental circulation is essentially in
parallel with the systemic circulation. Because the sum of
two resistances in parallel is less than either alone, the
placental bed serves to decrease afterload.
b. Progesterone contributes to vasodilation through its
effect on vascular smooth muscle.
c. Plasma levels of prostacyclin, a potent vasodilator, are
increased in pregnancy.
d. Blood viscosity is a significant determinant of afterload.
The dilutional anemia of pregnancy improves the
rheology of blood,1 decreasing afterload.
4. Myocardial contractility
a. Left ventricular (LV) end diastolic volume increases
during pregnancy but LV end systolic volume remains the
same, which results in an increase in ejection fraction.6
b. Left ventricular hypertrophy (LVH) occurs progressively
throughout pregnancy, with a 23% increase in mass from
the first to third trimesters.7
c. Although an increase in myocardial contractility is
suggested by an increase in the velocity of LV
circumferential fiber shortening, this can be explained on
 the basis of an increase in HR and decrease in SVR.
Intrinsic contractility as measured by left ventricular
stroke work index (LVSWI) is unchanged.
d. HR increases steadily throughout pregnancy, peaking at
10 to 20 bpm above baseline at term. Further increases are
seen as a result of the pain and stress of labor.
B. Electrocardiogram changes and rhythm disturbances
1. The electrocardiogram (ECG) at term pregnancy may show
changes that result from a leftward shift of the heart because
of elevation of the diaphragm by the gravid uterus. The
following are all potentially normal ECG findings in
pregnancy8:
a. Shift in QRS axis in any direction
b. Small rightward deviation of average mean QRS axis in
the first trimester
c. Small leftward deviation of mean QRS axis due to
progressive elevation of left hemidiaphragm in the third
trimester
d. Lead III often shows small Q-T wave inversions.
e. Transient ST-T wave changes are common.
2. Functional flow murmurs are common during the
hyperdynamic state of pregnancy,9 and there may be a
predisposition to tachydysrhythmias (especially
supraventricular). The most common dysrhythmias in
pregnancy are premature ectopic atrial and ventricular
depolarizations and sinus tachycardia.10 Pregnant women
become more aware of their heartbeat, changes in HR, and
skipped beats. Mechanisms for pregnancy-induced
dysrhythmias include:
a. Changes in cardiac ion channel conduction
b. Increase in cardiac size (atrial stretch, increased end
diastolic volume, LVH)
c. Changes in autonomic tone
d. Hormonal fluxes
 C. Aortocaval compression
1. Compression of the inferior vena cava against the vertebral
column by the enlarged uterus (significant once the uterus
moves out of the pelvis between 16 and 20 weeks’ gestation)
when in a supine position will lead to a reduction in venous
return. Although this is partially compensated by collateral
blood flow, for example, through the azygos system, the net
result is a decrease in venous return to the heart and
subsequently CO is decreased.
2. Compression of the aorta by the enlarged uterus may increase
measured blood pressure in the arm, by a mechanism
analogous to an aortic cross clamp. Because the hypogastric
artery, of which the uterine artery is a branch, arises distal to
the point of compression, uteroplacental perfusion may be
decreased in spite of an apparently increased systemic blood
pressure as described earlier. Significant aortoiliac artery
compression by the gravid uterus is seen in 15% to 20% of
pregnant women. In many nonlaboring patients, this is
asymptomatic.
3. A recent study evaluated the degree of tilt necessary to
minimize aortocaval compression in term, nonlaboring
patients prior to cesarean delivery (CD). CO and pulse
pressure were highest at 15 degrees of left tilt, equal to full
90-degree left lateral position. This was significantly higher
than at 0 and 7.5 degrees of left tilt, suggesting that 15
degrees is sufficient to restore CO.11
4. As a result, the supine position should be avoided in all
pregnant patients at 20 weeks’ gestation or greater, and
especially in all term parturients. This applies even more
following placement of a neuraxial anesthetic.

CLINICAL PEARL The enlarged uterus causes aortocaval

compression in the supine position and may lead to decreased
venous return, decreased CO, and severe hypotension. When the
 supine position is required, the patient must be placed with at least a
15-degree left lateral tilt. One of the most effective ways to assess
for effective left uterine displacement is to visualize the
displacement of the uterus from the perspective of the head of the
patient’s bed.

II. Respiratory system

A. Arterial blood gases
1. Progesterone sensitizes central respiratory centers, increasing
the ventilatory response to CO2.12 Both tidal volume (major
contributor) and respiratory rate (negligible to 1 to 2 bpm) are
increased and contribute to pregnancy-induced increased
minute ventilation. A recent study has shown that the
hyperventilation of human pregnancy is the result of
pregnancy-induced changes in wakefulness and central
chemoreflex drives for breathing, acid–base balance,
metabolic rate, and cerebral blood flow.13 This explains why
normal PaCO2 in a pregnant patient is 30 to 32 mm Hg (Table
1.3). Although there is increased urinary excretion of
bicarbonate (normal pregnant level 20 mm Hg), pH is
partially corrected; normal pH is 7.41 to 7.44.14

2. Hyperventilation causes decreased alveolar CO2, which, by

the alveolar gas equation, leads to an increase in PaO2 (normal
103 to 107 mm Hg).
B. Lung volumes and capacities and respiratory mechanics8
(Table 1.4)
 1. Anatomic changes listed below contribute to altered
ventilatory mechanics over the course of a normal
pregnancy.15
a. Elevation of the diaphragm occurs due to increased
intraabdominal volume with the growing uterus.
Diaphragmatic excursion increases relative to the
nonpregnant state.
b. An increase in the anterior–posterior diameter of the
thoracic cage causes decreased chest wall excursion.
C. Mechanisms of hypoxemia in pregnancy16
1. Oxygen consumption (Table 1.5)
a. The high metabolic demands of the enlarged uterus,
placenta, and the fetus cause oxygen consumption to
increase throughout pregnancy, increasing 40% to 60%
above prepregnancy levels at term.17
b. Oxygen desaturation occurs much more rapidly during a
period of apnea, for example, during anesthetic induction
or eclamptic seizures. This effect is accentuated by
changes in pulmonary volumes (q.v.). In one study,
reduced apnea tolerance in pregnancy was
demonstrated by simulating the physiologic changes of
rapid sequence induction.18 The authors found that after
99% denitrogenation, the time taken to decrease to a
SaO2 <90% was 4 minutes in pregnant subjects and 7
minutes 25 seconds in nonpregnant subjects. In
addition, the time taken for SaO2 to fall to 40% from 90%
was 35 seconds in pregnant subjects and 45 seconds in
nonpregnant subjects. During pregnancy, the hypoxic
ventilatory response is increased due to elevations in
estrogen and progesterone.
c. Fetal hemoglobin has a P50 of approximately 18 mm Hg,
providing very effective loading of oxygen (and
unloading of maternal hemoglobin) in the uteroplacental
bed. In addition, fetal hemoglobin does not interact with
2,3-diphosphoglycerate, which also favors loading of
oxygen molecules from maternal hemoglobin. Thus, the
fetus effectively extracts the maximum amount of oxygen
possible from maternal blood.
 2. Decreased functional residual capacity. Elevation of the
diaphragm during pregnancy leads to increased basilar
alveolar atelectasis. Functional residual capacity (FRC)
essentially represents the stores of oxygen available during a
period of apnea; therefore, a decrease in FRC shortens the
time to development of hypoxemia.

CLINICAL PEARL Parturients are susceptible to rapid

decreases in oxygen saturation with periods of apnea due to
decreases in FRC and increased oxygen consumption.
Preoxygenation of the parturient prior to general anesthesia and
endotracheal intubation is essential and will help alleviate severe
arterial oxygen desaturation.

3. Compared to sitting or standing, FRC is significantly lower in

the supine position due to further cephalad movement of the
diaphragm and increased posterior basilar atelectasis. In the
supine position, FRC exceeds closing capacity. This leads to
small airway closure, an increase in ventilation/perfusion (
) mismatch, and decreased O2 saturation.
4. Decreased CO in the supine position will cause decreased
mixed venous saturation and therefore decreased arterial O2
saturation. Appropriate left uterine displacement will help
maintain adequate venous return and subsequent CO.
D. Upper airway changes (see Section IX: Anesthetic
considerations)
E. Respiratory consequences of uncontrolled maternal pain
1. Uncontrolled maternal pain causes exaggerated
hyperventilation during contractions. Minute ventilation can
increase by as much as 140% above prepregnant values in the
first stage of an unmedicated labor and 200% in the second
stage.19,20 As a result, maternal PaCO2 can fall to 10 to 15 mm
Hg. This extreme degree of hypocarbia may cause subsequent
 maternal hypoventilation.
2. At the same time, oxygen consumption is increased (i.e., a
doubling of ventilation by the parturient can increase oxygen
consumption by as much as 50%).19 As a result, significant
hypoxemia can occur between contractions. Maternal blood
lactate increases, indicating that aerobic oxygen requirements
exceed oxygen consumption during labor. Although hypoxic
ventilatory drive is increased during pregnancy, it may not be
possible to match oxygen consumption without supplemental
oxygen.
F. Oxygen delivery
1. The mild increase in dissolved oxygen in maternal blood
during pregnancy does not improve oxygen delivery to the
fetus.
2. However, oxygen delivery to the fetus is improved by a
shift of the maternal oxygen dissociation curve to the
right.21 The maternal P50 increases from 26 to 30 mm Hg at
term.
3. As mentioned earlier, fetal ability to extract oxygen from
maternal hemoglobin is augmented by the higher oxygen
affinity of fetal hemoglobin, which has a P50 of 18 mm Hg.
III. Hematologic system
Normal pregnancy is associated with multiple changes in the
hematologic system (Table 1.6) and it is important that the
anesthesiologist be aware of these changes in order to determine what
is normal and what is abnormal when reviewing laboratory results in
the pregnant woman.
A. Dilutional anemia
1. Red cell mass is increased during pregnancy. Plasma volume
increases to a greater extent, however, producing the so-called
dilutional anemia of pregnancy.
2. In the absence of dietary iron supplementation, hemoglobin
levels of 9 to 10 g per dL are typical.3
3. Hemoglobin levels of >13 g per dL suggest
hemoconcentration and may be a sign of preeclampsia.
B. Platelet count and function
1. In most parturients, there is either a moderate decrease in
platelet count or no change. Some studies have indicated that
there is evidence of increased platelet consumption during
pregnancy. However, other studies have shown increases in
platelet production and turnover.
2. Gestational thrombocytopenia (platelet count 90 to 100 × 109
per L) is a physiologic condition that occurs in a small
percentage of parturients.22 It resolves spontaneously
postpartum and is not associated with abnormal platelet
function or clinical bleeding.
C. Coagulation factors
1. Normal pregnancy is associated with profound alterations in
 the coagulation and fibrinolytic systems (Table 1.6).
2. Although physiologic procoagulant changes serve to
minimize intrapartum blood loss, they also increase the risk of
thromboembolism during pregnancy and the postpartum
period sixfold.23
3. The net effect of these changes is to increase the efficiency of
clotting and to impair fibrinolysis.24
4. Fibrinogen levels increase throughout pregnancy and at term
are often >400 mg per dL. If fibrinogen is less than 200 to 250
mg per dL, a pathologic process should be suspected.
5. This hypercoagulable state cannot be detected by
conventional tests such as the prothrombin time and activated
partial thromboplastin time because results of these tests
remain only slightly below or in the normal range. However,
calibrated automated thrombography (CAT) is able to
demonstrate an increase in endogenous thrombin potential
throughout pregnancy.25 The CAT test measures protein S
levels and activity, which are reduced significantly during
pregnancy, and is able also to indicate increases in
plasminogen activator inhibitor-1, thrombin–antithrombin
complex, and tissue factor pathway inhibitor during
pregnancy. Antithrombin levels and protein C levels remain
stable throughout pregnancy. It is unknown whether these
observed changes correlate with thromboembolic disease.

CLINICAL PEARL Pregnancy is associated with

hyperfibrinogenemia. Decreases in serum fibrinogen, especially
below 200 mg per dL, are associated with severe postpartum
hemorrhage. In this situation, one should consider early
replacement of clotting factors by administration of fresh frozen
plasma (FFP) or cryoprecipitate.

D. Leukocytes and immune function

 1. The blood leukocyte count rises progressively throughout
pregnancy, increasing from 6,000 per mm3 to 9,000 to 11,000
per mm3. The increase is mostly due to polymorphonuclear
cells, whereas lymphocyte, eosinophil, and basophil counts
fall. The monocyte count is unchanged. Further increases in
the leukocyte count are seen during labor and may reach
15,000 per mm3 on the first day postpartum.
2. Polymorphonuclear leukocyte function is impaired during
pregnancy, which may account for the increased incidence
and severity of infection during pregnancy as well as the
reduction of symptoms in some pregnant women with
autoimmune disease.26 Impaired immune response is likely an
evolutionary development to prevent maternal cells from
attacking fetal tissue in a host-versus-graft reaction.
3. However, autoantibody production is unchanged during
pregnancy. Serum levels of immunoglobulin A, G, and M are
unaltered during pregnancy, whereas humoral antibody titers
to certain viruses, such as measles, influenza A, and herpes
simplex, are decreased.
IV. Gastrointestinal system
A. Gastric position and pressure
1. As the uterus enlarges, it displaces abdominal contents,
including the stomach, in a cephalad direction. This not only
impacts the interaction of the lower esophageal sphincter
(LES) and diaphragm (see subsequent text) but also causes
intragastric pressure to increase.
B. Lower esophageal sphincter tone
1. Progesterone (and to some degree estrogen) relaxes the
smooth muscle of the LES,27 decreasing the barrier pressure
that normally prevents gastroesophageal reflux. Elevation and
rotation of the stomach by the enlarging uterus eliminates the
“pinch valve” at the entry point of the esophagus through the
diaphragm, further decreasing the barrier to reflux. All of
these changes increase both the risk of regurgitation and
 aspiration of gastric contents as well as the severity of the
pulmonary injury that can be expected after aspiration.
LES tone reaches a nadir at 36 weeks’ gestation and returns to
prepregnancy tone by 4 weeks postpartum.
C. Gastric secretion
1. Ectopic gastrin is elaborated by the placenta. This has the
potential to increase both the volume and acidity of gastric
secretions. However, several studies have demonstrated that
plasma gastrin levels are reduced or unchanged during
pregnancy. This results in reduced gastric acid secretion,
reaching its lowest levels at 20 to 30 weeks’ gestation.28
2. Studies29,30 of gastric volume and pH in nonpregnant women
undergoing elective surgery and pregnant women at CD
showed no difference between the two groups in terms of
percentage of women with pH <2.5 (80%) and gastric volume
>25 mL (50%). The number of women with both a low pH
and high gastric volume was the same in both groups (40% to
50%). The same investigation of women at 15 weeks’
gestation showed similar results.30
D. Gastric emptying
1. Ultrasonographic studies and investigations of paracetamol
absorption demonstrate that gastric emptying remains normal
throughout gestation.31,32
2. However, with the onset of painful contractions during labor,
gastric emptying is slowed.33 Parenteral opioids have a
similar effect.
3. Neuraxial analgesia during labor has no impact on gastric
emptying unless fentanyl (or other opioid) boluses are used to
supplement the local anesthetic.34 Epidural fentanyl in doses
>100 µg has a significant effect on gastric emptying. A 25-µg
dose of intrathecal fentanyl will also impair gastric
emptying.35 Epidural infusions with low dose fentanyl (i.e., 2
µg per mL) do not cause significant changes in gastric
emptying in parturients.34,36
 4. The consumption of clear liquids appears to promote gastric
emptying, and current American Society of Anesthesiologists
(ASA) recommendations suggest that consumption of clear
liquids by laboring patients without additional risk factors
(e.g., morbid obesity, diabetes, difficult airway) is
acceptable.37 Gastric emptying returns to nonpregnant levels
18 hours postpartum.32
V. Hepatic function
A. Increase in serum estrogen and progesterone. Pregnancy
induces reversible anatomic, physiologic, and functional changes
in the liver as a result of an increase in serum estrogen and
progesterone. These changes can be problematic if liver disease is
present because, for example, spider nevi and palmar erythema
are signs of liver disease but may be seen in some pregnant
women as a result of increased estrogen levels. Indeed,
telangiectasia may appear in up to 60% of normal pregnancies.38
B. Hepatic blood flow. In normal pregnancy, liver size remains
unchanged and there is no change in hepatic blood flow despite
the physiologic increases in blood volume and CO. In fact, the
percentage of CO that goes to the liver falls by 35% during
pregnancy.39 Clearance of drugs dependent on hepatic blood flow
is reduced as a result of the larger volume of distribution.
C. Increase in splanchnic, portal, and esophageal venous
pressure. There is an increase in splanchnic, portal, and
esophageal venous pressure in term pregnancy, and 60% of
healthy women will develop esophageal varices that resolve
postpartum.39
D. Serum albumin concentration. Serum albumin concentration
falls by up to 60% due to the increase in plasma volume, which
leads to a 20% reduction in total serum protein by mid
pregnancy.40 Other changes in liver function tests are listed in
Table 1.7.39,41
 VI. Renal system
A. Anatomic changes/alterations in renal blood flow
1. The ovarian hormone relaxin mediates renal vasodilatation
during pregnancy. The renal pelvis and ureters dilate by the
end of the first trimester as a result of hormonal changes,
primarily a progesterone effect. Further dilation can occur in
late pregnancy as a result of obstruction of the ureter(s) by the
enlarging uterus.42
2. The kidneys enlarge during pregnancy, primarily as a result of
the 75% increase in renal blood flow. They return to normal
size by 6 months postpartum. The increase in renal blood flow
is due to profound reductions in the renal afferent and efferent
arteriolar resistances.43
B. Changes in glomerular filtration rate/measures of renal
function
1. The glomerular filtration rate (GFR) increases from 100 to
150 mL per minute by the second trimester, which in turn
causes increased creatinine clearance and a fall in blood urea
nitrogen (BUN) and creatinine (normal ~0.5 to 0.6 mg per dL
at term). Thus, in a parturient, a “normal” or slightly
 increased BUN and creatinine (0.8 to 1.0 mg per dL) indicates
poor renal function.
2. Proteinuria increases slightly and is due to the increased GFR,
reduced proximal tubular reabsorption, and perhaps alteration
in the electrostatic charge of the glomerular filter.43
3. A reduction in the tubular reabsorption and an increase in
renal excretion of glucose occurs and in some pregnant
women it may contribute to the development of gestational
diabetes mellitus.44
4. Tubular reabsorption of bicarbonate also decreases, producing
a compensatory metabolic acidosis in response to the
respiratory alkalosis seen in pregnant women.45
5. The kidney produces more vitamin D, erythropoietin, and
renin during pregnancy, but their effects are masked by other
changes.39

CLINICAL PEARL During pregnancy, renal blood flow

increases and is associated with increased GFR and creatinine
clearance. Serum creatinine concentration decreases during
pregnancy. A creatinine of 0.8 to 1 mg per dL, which would be
normal in a nonpregnant individual, is pathologic in pregnancy.

VII. Endocrine system

A. Thyroid function
1. The thyroid gland enlarges during pregnancy both from
follicular hyperplasia and increased vascularity.8
2. Total T3 and T4 levels are raised by 50% as a result of
estrogen-induced increases in thyroid-binding globulin. This
occurs during the first trimester and persists until term. Free
T3 and T4 levels remain unchanged during pregnancy.
3. Thyroid-stimulating hormone (TSH) levels fall during the
first trimester but return to nonpregnant levels shortly after
and remain so throughout the remainder of pregnancy.
 4. Some studies have indicated that there are trimester-specific
changes in some measures of thyroid function, and if thyroid
disease is suspected, an endocrinologist should be
consulted.46,47
5. Subclinical hyperthyroidism occurs in 1.7% of all screened
pregnant women. These women have suppressed TSH but
normal T4 levels. There are no adverse pregnancy
outcomes.48
B. Pancreatic function and glucose metabolism
1. Pregnancy is associated with a reduced tissue sensitivity to
insulin. This diabetogenic effect is caused primarily by human
placental lactogen. This means that a pregnant woman will
have higher blood glucose levels after a carbohydrate load
than a nonpregnant woman, despite a hyperinsulinemic
response in pregnancy.
2. The fasting blood sugar during the third trimester is lower
than in nonpregnant controls. The altered response to fasting
during pregnancy is a result of the high glucose consumption
by the fetoplacental unit. The relative hypoglycemic state
causes fasting hypoinsulinemia and pregnant women exhibit
an exaggerated starvation ketosis.
C. Pituitary function
1. Prolactin. Normal pregnancy stimulates hyperplasia of the
lactotrophic cells in the pituitary gland.49 Neuroendocrine
control of prolactin secretion is markedly altered by
pregnancy to allow a state of hyperprolactinemia. Placental
lactogen and dopamine both play a role in this regard.50
2. Oxytocin. Posterior pituitary stores of oxytocin increase
around 30% by term. This is mainly due to decreased
oxytocin secretion and allows for significant release of
oxytocin during labor and immediately after delivery. In
addition, normal oxytocin response to stress is reduced in late
pregnancy, likely as a protective measure against initiating
preterm labor.51
 VIII. Musculoskeletal
The maternal axial skeleton is subjected to significant change and
stress during pregnancy.
A. Lumbar lordosis
Uterine growth during pregnancy results in lumbar lordosis,
which acts to maintain the woman’s center of gravity over the
legs. An exaggerated lumbar lordosis can stretch the lateral
femoral cutaneous nerve of the thigh, causing meralgia
paresthetica (a mild sensory loss over the anterolateral thigh). The
lordosis can also be associated with anterior flexion of the neck
and slumping shoulders, which if severe can cause a brachial
plexus neuropathy.8 Lordosis also narrows the distance between
interspinous processes, which, in addition to difficulty in lumbar
flexion caused by a gravid uterus, can make neuraxial anesthesia
difficult.
B. Joint mobility
There is an increase in joint mobility during pregnancy, especially
in the sacroiliac (SI), sacrococcygeal, and pubic joints, to prepare
for passage of the fetus. The symphysis pubis is widened by 30
weeks’ gestation. SI joint pain is common among pregnant
women and is often attributed to sciatica, an important distinction
to make during the preanesthetic interview. All of these changes
are secondary to the effects of the hormones relaxin,
progesterone, and the mechanical stresses of pregnancy.8
IX. Central nervous system
A. Inhalation anesthetics and minimum alveolar concentration
1. Anesthetic requirements for the commonly used volatile
anesthetic agents, as measured by minimum alveolar
concentration (MAC), are decreased by as much as 30% from
the nonpregnant state.52 Proposed mechanisms for this
decrease include:
a. Increased levels of plasma endorphins53
b. Increased levels of progesterone (10- to 20-fold during
late pregnancy), which have central nervous system
 depressant effects54
2. This is significant because inhaled concentrations of
anesthetics that would be appropriate in a nonpregnant patient
might have exaggerated effects in the pregnant patient. For
example, an inspired concentration of 50% N2O used for
supplementation of neuraxial anesthesia during CD might
cause loss of consciousness.
3. A similar increased sensitivity to intravenous induction and
sedative agents is also observed.55
B. Neuraxial anesthesia/local anesthetics
Neuraxial anesthetic requirements are decreased by
approximately 25% to 40% at term. A dual mechanism is likely
responsible for changes in requirements.
1. Mechanical changes
Compression of the inferior vena cava by the enlarged uterus
causes distension of the epidural venous plexus.56,57 This
decreases the free volume of the epidural space and also the
volume of cerebrospinal fluid (CSF) per spinal segment.
Therefore, a given dose of epidural or intrathecal local
anesthetic will produce a greater degree of dermatomal
spread compared to nonpregnant patients.
2. Biochemical changes
The decreased dose requirement for neuraxial anesthesia
occurs as early as the end of the first trimester, long before
significant epidural venous distension occurs. This suggests
that a biochemical or hormonal mechanism may be at work.
a. Progesterone. The concentration of local anesthetic
required to block nerve conduction of in vitro vagus nerve
obtained from male rabbits chronically exposed to
progesterone is decreased.58
(1) This effect is not seen in vagus nerve preparations
acutely exposed to progesterone.59
(2) This suggests that chronic exposure to progesterone
causes changes in protein channels within neuronal
 membranes leading to increased sensitivity to local
anesthetics.
b. β-Endorphins. Increased circulating β-endorphins and
activated spinal cord κ-opioid receptors leads to increased
pain tolerance during pregnancy, and even more so during
labor.60

CLINICAL PEARL Parturients have decreased anesthetic

requirements resulting in an approximate 30% reduction in MAC as
well as decreased need for analgesic and anesthetic medications.

X. Anesthetic implications of maternal physiologic changes during

pregnancy
A. Increased minute ventilation and reduced functional residual
capacity. These significantly affect anesthetic management.
Ventilation during general anesthesia should be adjusted to
maintain PaCO2 at 30 mm Hg. The rate of inhaled anesthetic
induction is increased because the increase in minute ventilation
and reduced FRC will increase the rate of rise of alveolar
anesthetic concentration compared with that of inspired gases.
The concentration of volatile anesthetic administered should be
adjusted to account for the 15% to 40% reduction in MAC value
during pregnancy.
B. Hypoxemia. Pregnant women become hypoxemic more
rapidly than nonpregnant women during periods of apnea,
which is a result of reduced FRC and an increase in maternal
oxygen consumption.
C. Aortocaval compression. Avoid aortocaval compression by the
gravid uterus by using left uterine displacement (≥15 degrees)
or full left lateral position. This is especially true for term
women who have had a neuraxial block for labor analgesia or
operative delivery.
D. Upper airway changes
 1. Increased mucosal friability and vascularity of the upper
airway has implications for airway management.
a. Mucosal injury during laryngoscopy is more likely, and
should such injury occur, there is an increased risk of
excessive bleeding.
b. Pregnant women will typically require a smaller
endotracheal tube, usually 6.0 to 6.5 mm.
c. Increased vascularity and consequent mucosal
engorgement can be expected to be even greater in
preeclampsia.
2. Nasotracheal intubation and placement of nasogastric tubes
should be avoided unless absolutely necessary because of the
potential for significant epistaxis.
3. Mallampati classification worsens during pregnancy and can
change further during labor and in cases of severe
preeclampsia.61 Endotracheal intubation may be more
difficult in laboring women as a result of these airway
changes.
E. Endotracheal intubation
1. Because endotracheal intubation may be more difficult
during pregnancy, it should be preceded by a period of
denitrogenation, using 100% oxygen and a rapid sequence
induction with cricoid pressure, to avoid regurgitation and
aspiration of gastric contents.
2. Positioning is crucial for successful intubation. Many
pregnant women have enlarged breasts which can move
cephalad when in the supine position and can interfere with
placement of a laryngoscope. Use of a ramp, removal of
garments such as bras, and a short laryngoscope handle is
often useful.
F. Use of muscle relaxants
1. Despite 25% reduction in plasma cholinesterase during
pregnancy, normal doses of succinylcholine should be used
to facilitate endotracheal intubation (1.5 mg per kg).
 2. Use standard or slightly reduced doses of rocuronium because
pregnant women show increased sensitivity to the
aminosteroid muscle relaxants such as rocuronium and
vecuronium.
3. The action of atracurium is unchanged by pregnancy.
4. If short-acting nondepolarizing neuromuscular blockers are
used to maintain paralysis during a lengthy CD or
cesarean/hysterectomy, then use a peripheral nerve stimulator
to guide therapy.
G. Replacement of blood loss
1. Blood volume is increased and a dilutional anemia is
normal during pregnancy. Thus, adjustments must be made
to calculations relating to replacement of lost blood. If blood
replacement is considered in a hemodynamically unstable
parturient at CD with ongoing blood loss, then one may
calculate a percentage of blood loss as a guide to therapy
(e.g., 15% to 20% of an estimated total blood volume of 95
mL per kg—not 75 mL per kg). If it is a twin gestation, then
the estimated total blood volume is higher, at 105 mL per kg.
2. A lower threshold to transfuse cryoprecipitate or plasma (i.e.,
fibrinogen levels <200 mg per dL with ongoing blood loss) is
suggested because parturients have a baseline
hyperfibrinogenemia.62
H. Subarachnoid and epidural doses
1. Subarachnoid dose requirements are reduced by 25%
during pregnancy and the epidural dose will be less than in a
nonpregnant woman if a small dose is used.63
2. Pregnant women will also experience a more rapid onset and
increased duration of spinal anesthesia compared to
nonpregnant women. Studies have shown that this is not the
case for large epidural doses.
I. Morbidity and mortality
Most anesthetic-related morbidity and mortality occurs
during airway management, especially emergence from
 general anesthesia and in the immediate postanesthetic
period.64 Morbidity and mortality can also occur following
induction of epidural or spinal anesthesia, either from
respiratory compromise following a rapid high sensory level
or from profound cardiovascular collapse.65,66

REFERENCES
1. Scott DE. Anemia in pregnancy. Obstet Gynecol Annu. 1972;1:219–244.
2. Ueland K. Maternal cardiovascular dynamics. VII. Intrapartum blood volume changes. Am J Obstet
Gynecol. 1976;126: 671–677.
3. Recommendations to prevent and control iron deficiency in the United States. Centers for Disease
Control and Prevention. MMWR Recomm Rep. 1998;47:1–29.
4. Clark SL, Cotton DB, Lee W, et al. Central hemodynamic assessment of normal term pregnancy. Am J
Obstet Gynecol. 1989;161:1439–1442.
5. Clapp JF III, Capeless E. Cardiovascular function before, during, and after the first and subsequent
pregnancies. Am J Cardiol. 1997;80:1469–1473.
6. Kametas NA, McAuliffe F, Hancock J, et al. Maternal left ventricular mass and diastolic function
during pregnancy. Ultrasound Obstet Gynecol. 2001;18:460–466.
7. Schannwell CM, Zimmermann T, Schneppenheim M, et al. Left ventricular hypertrophy and diastolic
dysfunction in healthy pregnant women. Cardiology. 2002;97:73–78.
8. Gaiser R. Physiologic changes of pregnancy. In: Chestnut DH, Wong CA, Tsen LC, et al, eds.
Chestnut’s Obstetric Anesthesia: Principles and Practice. 5th ed. Philadelphia, PA: Elsevier Science,
Mosby; 2014:15–36.
9. Cutforth R, MacDonald CB. Heart sounds and murmurs in pregnancy. Am Heart J. 1966;71:741–747.
10. Shotan A, Ostrzega E, Mehra A, et al. Incidence of arrhythmias in normal pregnancy and relation to
palpitations, dizziness, and syncope. Am J Cardiol. 1997;79:1061–1064.
11. Lee SW, Khaw KS, Ngan Kee WD, et al. Haemodynamic effects from aortocaval compression at
different angles of lateral tilt in non-labouring term pregnant women. Br J Anaesth. 2012;109:950–
956.
12. Lyons HA, Antonio R. The sensitivity of the respiratory center in pregnancy and after the
administration of progesterone. Trans Assoc Am Physicians. 1959;72:173–180.
13. Jensen D, Duffin J, Lam YM, et al. Physiological mechanisms of hyperventilation during human
pregnancy. Respir Physiol Neurobiol. 2008;161:76–86.
14. Lim VS, Katz AI, Lindheimer MD. Acid-base regulation in pregnancy. Am J Physiol. 1976;231:1764–
1769.
15. Conklin KA. Maternal physiological adaptations during gestation, labor and the puerperium. Semin
Anesth. 1991;10: 221–234.
16. Crapo RO. Normal cardiopulmonary physiology during pregnancy. Clin Obstet Gynecol. 1996;39:3–
16.
17. Prowse CM, Gaensler EA. Respiratory and acid-base changes during pregnancy. Anesthesiology.
1965;26:381–392.
18. McClelland SH, Bogod DG, Hardman JG. Apnoea in pregnancy: an investigation using physiological
modelling. Anaesthesia. 2008;63:264–269.
19. Hagerdal M, Morgan CW, Sumner AE, et al. Minute ventilation and oxygen consumption during labor
with epidural analgesia. Anesthesiology. 1983;59:425–427.
20. Spätling L, Fallenstein F, Huch A, et al. The variability of cardiopulmonary adaptation to pregnancy at
rest and during exercise. Br J Obstet Gynaecol. 1992;99(suppl 8):1–40.
21. Kambam JR, Handte RE, Brown WU, et al. Effect of normal and preeclamptic pregnancies on the
oxyhemoglobin dissociation curve. Anesthesiology. 1986;65:426–427.
22. Burrows RF, Kelton JG. Incidentally detected thrombocytopenia in healthy mothers and their infants.
N Engl J Med. 1988;319:142–145.
23. Franchini M. Haemostasis and pregnancy. Thromb Haemost. 2006;95:401–413.
24. Lockwood CJ. Pregnancy-associated changes in the hemostatic system. Clin Obstet Gynecol.
2006;49:836–843.
25. Rosenkranz A, Hiden M, Leschnik B, et al. Calibrated automated thrombin generation in normal
uncomplicated pregnancy. Thromb Haemost. 2008;99:331–337.
26. Stirrat GM. Pregnancy and immunity. BMJ. 1994;308:1385–1386.
27. Shah S, Nathan L, Singh R, et al. E2 and not P4 increases NO release from NANC nerves of the
gastrointestinal tract: implications in pregnancy. Am J Physiol Regul Integr Comp Physiol.
2001;280:R1546–R1554.
28. Murray FA, Erskine JP, Fielding J. Gastric secretion in pregnancy. J Obstet Gynaecol Br Emp.
1957;64:373–381.
29. Cohen SE, Jasson J, Talafre ML, et al. Does metoclopramide decrease the volume of gastric contents
in patients undergoing cesarean section? Anesthesiology. 1984;61:604–607.
30. Wyner J, Cohen SE. Gastric volume in early pregnancy: effect of metoclopramide. Anesthesiology.
1982;57:209–212.
31. Wong CA, McCarthy RJ, Fitzgerald PC, et al. Gastric emptying of water in obese pregnant women at
term. Anesth Analg. 2007;105:751–755.
32. Whitehead EM, Smith M, Dean Y, et al. An evaluation of gastric emptying times in pregnancy and the
puerperium. Anaesthesia. 1993;48:53–57.
33. Carp H, Jayaram A, Stoll M. Ultrasound examination of the stomach contents of parturients. Anesth
Analg. 1992;74: 683–687.
34. Porter JS, Bonello E, Reynolds F. The influence of epidural administration of fentanyl infusion on
gastric emptying in labour. Anaesthesia. 1997;52:1151–1156.
35. Kelly MC, Carabine UA, Hill DA, et al. A comparison of the effect of intrathecal and extradural
fentanyl on gastric emptying in laboring women. Anesth Analg. 1997;85:834–838.
36. Zimmermann DL, Breen TW, Fick G. Adding fentanyl 0.0002% to epidural bupivacaine 0.125% does
not delay gastric emptying in laboring parturients. Anesth Analg. 1996;82:612–616.
37. American Society of Anesthesiologists. Practice guidelines for obstetric anesthesia: an updated report
by the American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Anesthesiology.
2007;106:843–863.
38. Angel Garcia AL. Effect of pregnancy on pre-existing liver disease physiological changes during
pregnancy. Ann Hepatol. 2006;5:184–186.
39. Paech MJ, Scott K. Liver and renal disease. In: Gambling DR, Douglas MJ, McKay RSF, eds.
Obstetric Anesthesia and Uncommon Disorders. 2nd ed. Cambridge, United Kingdom: Cambridge
University Press; 2008:249–257.
40. Carter J. Liver function in normal pregnancy. Aust N Z J Obstet Gynaecol. 1990;30:296–302.
41. Bacq Y, Zarka O, Bréchot JF, et al. Liver function tests in normal pregnancy: a prospective study of
103 pregnant women and 103 matched controls. Hepatology. 1996;23:1030–1034.
42. Jeyabalan A, Lain KY. Anatomic and functional changes of the upper urinary tract during pregnancy.
 Urol Clin North Am. 2007;34:1–6.
43. Jeyabalan A, Conrad KP. Renal function during normal pregnancy and preeclampsia. Front Biosci.
2007;12:2425–2437.
44. Klein P, Polidori D, Twito O, et al. Impaired decline in renal threshold for glucose during pregnancy—
a possible novel mechanism for gestational diabetes mellitus. Diabetes Metab Res Rev. 2014;30:140–
145.
45. Dafnis E, Sabatini S. The effect of pregnancy on renal function: physiology and pathophysiology. Am
J Med Sci. 1992;303: 184–205.
46. Marwaha RK, Chopra S, Gopalakrishnan S, et al. Establishment of reference range for thyroid
hormones in normal pregnant Indian women. BJOG. 2008;115:602–606.
47. Soldin OP, Tractenberg RE, Hollowell JG, et al. Trimester-specific changes in maternal thyroid
hormone, thyrotropin, and thyroglobulin concentrations during gestation: trends and associations
across trimesters in iodine sufficiency. Thyroid. 2004;14:1084–1090.
48. Casey BM, Dashe JS, Wells CE, et al. Subclinical hyperthyroidism and pregnancy outcomes. Obstet
Gynecol. 2006;107: 337–341.
49. Scheithauer BW, Sano T, Kovacs KT, et al. The pituitary gland in pregnancy: a clinicopathologic and
immunohistochemical study of 69 cases. Mayo Clin Proc. 1990;65:461–474.
50. Grattan DR, Steyn FJ, Kokay IC, et al. Pregnancy-induced adaptation in the neuroendocrine control of
prolactin secretion. J Neuroendocrinol. 2008;20:497–507.
51. Russell JA, Brunton PJ. Neuroactive steroids attenuate oxytocin stress responses in late pregnancy.
Neuroscience. 2006;138:879–889.
52. Chan MT, Mainland P, Gin T. Minimum alveolar concentration of halothane and enflurane are
decreased in early pregnancy. Anesthesiology. 1996;85:782–786.
53. Abboud TK, Sarkis F, Hung TT, et al. Effects of epidural anesthesia during labor on maternal plasma
beta-endorphin levels. Anesthesiology. 1983;59:1–5.
54. Datta S, Hurley RJ, Naulty JS, et al. Plasma and cerebrospinal fluid progesterone concentrations in
pregnant and nonpregnant women. Anesth Analg. 1986;65:950–954.
55. Christensen JH, Andreasen F, Jansen JA. Pharmacokinetics of thiopental in caesarian section. Acta
Anaesthesiol Scand. 1981;25:174–179.
56. Igarashi T, Hirabayashi Y, Shimizu R, et al. The fiberscopic findings of the epidural space in pregnant
women. Anesthesiology. 2000;92:1631–1636.
57. Kerr MG. The mechanical effects of the gravid uterus in late pregnancy. J Obstet Gynaecol Br
Commonw. 1965;72:513–529.
58. Flanagan HL, Datta S, Lambert DH, et al. Effect of pregnancy on bupivacaine-induced conduction
blockade in the isolated rabbit vagus nerve. Anesth Analg. 1987;66:123–126.
59. Bader AM, Datta S, Moller RA, et al. Acute progesterone treatment has no effect on bupivacaine-
induced conduction blockade in the isolated rabbit vagus nerve. Anesth Analg. 1990;71:545–548.
60. Ohel I, Walfisch A, Shitenberg D, et al. A rise in pain threshold during labor: a prospective clinical
trial. Pain. 2007;132(suppl 1):S104–S108.
61. Kodali BS, Chandrasekhar S, Bulich LN, et al. Airway changes during labor and delivery.
Anesthesiology. 2008;108:357–362.
62. Cortet M, Deneux-Tharaux C, Dupont C, et al. Association between fibrinogen level and severity of
postpartum haemorrhage: secondary analysis of a prospective trial. Br J Anaesth. 2012;108:984–989.
63. Abouleish EI. Postpartum tubal ligation requires more bupivacaine for spinal anesthesia than does
cesarean section. Anesth Analg. 1986;65:897–900.
64. Mhyre JM, Riesner MN, Polley LS, et al. A series of anesthesia-related maternal deaths in Michigan,
1985-2003. Anesthesiology. 2007;106:1096–1104.
65. Hawkins JL, Chang J, Palmer SK, et al. Anesthesia-related maternal mortality in the United States
1979-2002. Obstetr Gynecol. 2011;117:69–74.
66. D’Angelo R, Smiley RM, Riley ET, et al. Serious complications related to obstetric anesthesia: the
serious complication repository project of the Society for Obstetric Anesthesia and Perinatology.
Anesthesiology. 2014;120:1505–1512.
 Uteroplacental Anatomy, Blood Flow, Respiratory Gas
Exchange, Drug Transfer, and Teratogenicity
Curtis L. Baysinger and Barton Staat

I. Anatomy
A. Anatomic and physiologic changes
B. Human placenta
C. Fetal circulation
II. Uteroplacental circulation
A. Placental circulatory development
B. Uterine blood flow
C. Umbilical blood flow
III. Respiratory gas exchange
A. Oxygen transfer
B. Carbon dioxide transfer
IV. Nutrient/drug transfer
A. Mechanisms of exchange
B. Drug transfer
C. Nutrient transfer
V. Teratogenicity
A. Classification of birth defects
B. Etiology of congenital malformations
C. Principles of teratology
D. Drug teratogenicity


KEYPOINTS
1. Placental growth depends on changes in the maternal circulation in
response to the metabolic demands associated with fetal growth.
2. The uterine artery primarily, and the ovarian artery secondarily, provide
maternal blood to the uterus and branch into the spiral arteries. These
provide blood to the intervillous space where maternal and fetal gas,
nutrient, and waste exchange occurs.
3. Successful placental and fetal development depends on maternal spiral
artery remodeling early in gestation, which converts the maternal
placental circulation into a low-resistance, high-flow circulatory system
that is maximally vasodilated.
4. Few mechanisms increase uterine blood flow; therefore, clinicians should
avoid interventions that decrease uterine blood flow.
5. Oxygen and carbon dioxide exchange are uterine blood flow dependent,
thus emphasizing the need to maintain adequate uterine perfusion for
adequate gas transfer.
6. Fetal compensatory mechanisms allow the fetus to tolerate reductions in
uterine blood flow for long periods of time without significant long-term
injury.
7. Most drugs cross the placenta by diffusion down a concentration gradient
from mother to fetus or vice versa. Increases in maternal–fetal gradient,
decreased maternal/increased fetal protein binding, lower molecular
weight, less ionization, and greater lipid solubility promote maternal to
fetal transfer.
8. Anesthetic agents are not teratogens. Identification of drugs that are weak
teratogens may require an extensive clinical experience in their use
before they can be identified.

THE PLACENTA ALLOWS THE MATERNAL AND FETAL CIRCULATIONS to exchange

nutrients, gases, and waste essential to fetal growth. It also affects the transport
of maternally administered drugs to the fetus. Placental growth during pregnancy
accompanies the increase in uterine blood flow required for fetal growth and
development. Uterine blood flow is one of the most important determinants of
successful maternal–fetal gas exchange. The transport of medications from
mother to fetus depends on uterine perfusion, maternal drug concentration,
placental anatomy, protein binding, membrane barrier to diffusion, and fetal
blood concentration. Understanding the safety of drugs administered during
pregnancy is important because up to 60% of women take a prescription
medication during pregnancy.1 The American College of Obstetricians and
Gynecologists (ACOG) considers anesthetic agents to be safe when administered
to pregnant women.
I. Anatomy. Understanding the anatomy of the maternal vascular
supply to the gravid uterus, the gross and microscopic anatomy of the
placenta (see Fig. 2.1), and blood flow from the placenta to the fetus
are necessary to comprehend the physiology of the uteroplacental
circulation, placental gas exchange, and drug transfer across the
placenta.
 A. Anatomic and physiologic changes. Maternal anatomic and
physiologic changes occur during pregnancy to ensure enough
blood flow is delivered to the uterus. Uterine blood flow occurs
through two routes.
1. The uterine arteries are the primary source of blood flow to
the gravid uterus. The uterine arteries are branches of the
internal iliac artery, also known as the hypogastric artery.
Blood flow through the uterine vessels is characterized as
high flow through a low-resistance circuit. Uterine blood flow
increases throughout gestation. The uterus receives up to 20%
of the maternal cardiac output during the third trimester.2
Flow through each uterine artery can reach 225 to 375 mL per
minute at term.3

CLINICAL PEARL Up to 20% of the maternal cardiac output

goes to the uterus at term, which increases the urgency of treating
the hemorrhaging parturient.

2. Ovarian arteries provide up to 15% of uterine blood flow in

addition to that provided by the uterine arteries. The ovarian
artery originates from the aorta, and after passing through the
infundibulopelvic ligament, it enters the uterus through the
uteroovarian ligament.
3. Anastomosis occurs between the uterine and ovarian vessels
near the uterine fundus. The anastomosis between the uterine
and ovarian vessels provides the placenta with a low-
resistance, high-flow circulation.
4. The uterine and ovarian arteries end as spiral arteries that
supply the intervillous space. These arteries bathe the terminal
villi of the fetal side of the placenta.
B. Human placenta. The human placenta serves many functions in
addition to forming a link between the fetus and mother. The
growing fetus is dependent on the placenta for respiratory,
endocrine, and renal functions, as well as transport of
nutrients and wastes. What is especially remarkable is that the
placenta is able to perform these functions without significant
mixing of maternal and fetal blood. The placenta undergoes
changes from early gestation, when the uterine environment is
relatively hypoxic, to a term placenta that is highly vascularized.
The placenta grows during pregnancy in direct correlation with
fetal growth, reaching a diameter of 16 to 19 cm and a weight of
500 g at term.4
1. Macroscopically, the full-term placenta consists of the
chorionic plate, which is considered the fetal side of the
placenta, and, on the maternal side, the basal plate, which is
attached to the maternal endometrium. There are three types
of placentas found in mammals: hemochorial,
endotheliochorial, and epitheliochorial based on the layers
between maternal and fetal blood.4
 a. The human placenta is considered to be hemochorial
(i.e., maternal blood is in direct contact with the chorionic
trophoblast).
b. There is a separation of the maternal basal plate and fetal
chorionic plate. It is at the separation of these two
plates that causes the maternal spiral arteries to
surround the fetal villous trees with blood as the trees
enter through the chorionic plate.5
2. Microscopically, placentation begins with implantation of the
blastocyst (precursor to the embryo) into the lining of the
uterus (i.e., maternal endometrium).
a. Villi, which are the functional units on the fetal side of the
placenta, develop during the first trimester. The
trophoblast cells invade the maternal endometrium and
proliferate with finger-like outgrowths. These outgrowths
are termed primary villi.
b. The primary villi continue to branch through angiogenesis
and form subsequent generations of villi. The branching
of villi creates a dense network of capillaries that reduce
the vascular impedance and provide greater surface area
for the exchange of nutrients and wastes.6
c. Spiral arteries receive the maternal blood flow from the
uterine and ovarian arteries and supply blood to the
intervillous space, which contain the terminal villi.6
d. The villous membrane that separates maternal and fetal
blood consists of the syncytiotrophoblast, matrix of the
villous core, and the endothelium of the fetal capillary. It
is through this membrane that gas, nutrient, and drug
exchange occur between the fetus and the mother.6
C. Fetal circulation. The fetal circulation begins with the paired
umbilical arteries that are branches of the fetal internal iliac
arteries. These arteries carry deoxygenated blood from the fetus
to the placenta.
1. Umbilical arteries branch into smaller umbilical capillaries
 that feed the placental villi.
2. After the fetal blood passes through the terminal villus, it
leaves the placenta through a single umbilical vein.
3. The umbilical vein enters the fetus and travels through the
fetal liver and joins the hepatic vein.
4. The umbilical and hepatic veins empty into the ductus
venosus, which enters the right atrium.
5. Oxygenated blood can cross the right atrium through the
foramen ovale into the left atrium where it will enter the main
fetal circulation.
II. Uteroplacental circulation
A. Placental circulatory development. Successful development of
the fetal and maternal circulation requires successful invasion
of the fetal trophoblast into the decidua; remodeling of maternal
spiral arteries with loss of arterial musculature; and conversion to
a high-volume, low-resistance system for maternal blood flow.7
1. Low oxygen tension stimulates placental angiogenesis
through activation of hypoxia inducible factor-1α, which
activates vascular endothelial growth factor (VEGF) and
endothelial nitric oxide synthetase (eNOS). This allows
successful trophoblast invasion. Relative hypoxia is required
for successful angiogenesis because the presence of reactive
oxygen species within the trophoblast results from a higher
oxygen environment and is thought to interfere with vascular
development.8
2. Remodeling of the spiral arteries occurs during early
implantation.
a. Failure of the spiral arteries to remodel is the anatomic
defect nearly always seen in women with preeclampsia.
b. Early, higher than normal oxygenation in the intervillous
space is thought to be a primary pathogenic factor, leading
to reduced blood flow and failure of vascular
development.8
CLINICAL PEARL Remodeling of the maternal arteries that
supply blood to the intervillous space is essential for normal fetal
development. Its failure is the main pathogenic feature of
preeclampsia.

B. Uterine blood flow (see Fig. 2.2). At term, uterine blood flow
(UBF) is approximately 700 mL per minute of which
approximately 70% to 90% passes through the intervillous space.
The rest supplies the metabolic demands of the myometrium.9

1. The uterine arterial bed is thought to be maximally

 vasodilated at term, with little ability to dilate further because
it is not autoregulated.10 During labor, uterine blood flow is
intermittently interrupted by uterine contractions and cord
compression; this is the most probable mechanism by which
fetal compromise occurs during most normal labors. Blood
flow is determined by the gradient/resistance relationship:

UBF = uterine artery pressure − uterine venous pressure ÷ uterine

vascular resistance

2. A variety of factors can lead to decreases in uterine blood

flow.11
a. Regular uterine contractions and abnormal uterine
hypertonus due to placental abruption, tachysystole, and
excess α-adrenergic agent activity (most often due to
excess endogenous maternal catecholamines) are causes
for decreased blood flow during labor.
b. Maternal hypotension due to sympathetic block,
aortocaval compression, low cardiac output, and relative
maternal hypovolemia (as might occur during neuraxial
analgesia/anesthesia) as well as hemorrhage and poor
patient positioning, can contribute.
c. Acute maternal hypertension (chronic, medication
induced [e.g., cocaine]) can lead to placental abruption;
chronic hypertension can cause uterine vessel
abnormalities over time, chronically reducing blood flow.
d. The administration of exogenous vasoconstrictors (most
often α-adrenergic agents) can reduce blood flow;
however, their use is indicated when treating hypotension
associated with neuraxial analgesia/anesthesia.
e. Local anesthetics can reduce uterine blood flow if injected
intravascularly.
f. Uterine tone can increase due to maternal pain relief after
neuraxial blockade. This may be related to decreased
endogenous sympathetic activity. Maternal epinephrine
 levels decrease, whereas norepinephrine levels tend to be
maintained during neuraxial analgesia, perhaps leading to
a relative increase in α-adrenergic activity.

CLINICAL PEARL Increases in uterine tone leading to

alteration of fetal heart rate can accompany the onset of neuraxial
analgesia. This is probably due to changes in maternal
catecholamines.

3. There are few useful mechanisms to increase uterine blood

flow.11 Treatment of chronic hypertension with
antihypertensives (such as hydralazine) can improve blood
flow. Neuraxial analgesia administered during labor is
associated with an increase in uterine blood flow, especially in
women with preeclampsia. However, these and other
measures are not of clinical usefulness.11
4. Measurements of uteroplacental blood flow based on
uterine artery flow may not accurately reflect total flow due to
ovarian artery contributions.12
a. Intervillous blood flow closely approximates clinically
relevant placental flow. In laboratory animals, flow can be
measured following the injection of traceable compounds
by use of Fick equation calculations. This requires
collecting total venous outflow from the uterus, which is
impossible in human studies. Injections of trace amounts
of xenon 133 and calculation of radioactive decay over
the uterus or administering radiolabeled albumin have
been used in clinical studies of human intervillous flow.12
b. Doppler ultrasonography of the uterine artery near its
take off from the iliac artery at the pelvic brim is the most
clinically relevant means of assessing uterine blood flow.
The relationship below is used to calculate blood flow:
 Q = VRBC × A where VRBC = (Δf/ / fo) × (c / 2 × cos θ)

where Q is total flow, VRBC is the red blood cell velocity,

Δf/ is Doppler shift in sound wave frequency, fo is the
initial sound wave frequency, c is speed of sound in
tissue, and θ is angle of the probe to the axis of the artery.
Because the results rely on accurate measurement of θ,
indices that can be derived from the Doppler waveform
that do not depend on θ can be followed to assess vascular
impedance over time (systolic/diastolic ratio, pulsatility
index, resistance index).12
C. Umbilical blood flow. Umbilical blood flow is approximately
100 to 120 mL/kg/min at term when measured by Doppler
ultrasound (see Fig. 2.2).
1. The fetoplacental circulation has no systemic sympathetic
nervous innervation except the most proximal portions of the
umbilical vessels. Thus, fetal regulation of blood flow is
determined by circulating hormonal effects (primarily
catecholamines) and local autoregulatory effects mediated by
nitric oxide and acetylcholine metabolism.13
2. Hypoxia induces vasoconstriction in the fetal circulation
probably by reducing endothelial released nitric oxide and
thus may redistribute blood flow in the fetal circulation
much like hypoxic pulmonary vasoconstriction in the
lung.14
3. Doppler ultrasound can be used to assess umbilical artery
blood flow by measuring red blood cell velocity and using the
relationship described above. The pulsatility index, resistive
index, and systolic/diastolic ratio can be followed over time as
an assessment of fetal artery resistance in obstetric disease
states (intrauterine growth restriction, preeclampsia). These
measurements can help determine the time for optimal
delivery.15
 III. Respiratory gas exchange (see Fig. 2.2). Oxygen demand by the
fetus is higher than in adults (8 mL 2/min/kg body weight vs. 4
mL/min/kg body weight). The placenta is much less efficient than the
lung for gas exchange with only 30% of its surface area available for
gas transfer and a thicker membrane across which diffusion occurs.
About 20% of uterine arterial blood and 40% of the oxygen
provided by the uterine artery are shunted away from gas
exchange to serve the metabolic demands of the placenta and
uterine tissue; this shunt is stable over a wide range of maternal
blood pressures and oxygen saturations.16 The fetal and maternal
circulation most likely contact each other in a concurrent fashion,
thus near the equilibration of maternal vein and umbilical vein PaO2
and PCO2.17 The respiratory gas values noted in Figure 2.2 may differ
from those noted in other texts17 probably because the values noted in
Figure 2.2 are from women undergoing elective cesarean delivery
versus values published elsewhere from women undergoing labor and
vaginal delivery, which will reflect the stress of labor.

CLINICAL PEARL Prolonged labor can be associated with a

progressive degradation of the fetal intrauterine environment over
time.

A. Oxygen transfer
1. The main determinant of oxygen delivery is maternal
blood flow, despite the barrier to oxygen diffusion.18 As a
result, increasing maternal PaO2 has little effect on increasing
fetal PaO2 (see Fig. 2.3).18 The normal placenta can
compensate for decreases in flow up to 50% without
decreasing fetal oxygen transfer.17
2. Oxygen content in fetal blood is enhanced by the high fetal
hemoglobin (Hgb) concentration (17 g per 100 mL fetus vs.
12 g per 100 mL mother) and higher affinity of fetal Hgb for
oxygen (P50 fetal Hgb is 18 mm Hg vs. P50 of 27 mm Hg
adult Hgb).19
3. The oxygen binding of Hgb is reduced by acidosis (Bohr
effect). As carbon dioxide diffuses from the fetus to the
mother, creating a relative maternal acidosis, maternal Hgb
releases oxygen more readily. Because the opposite is
occurring to fetal Hgb, this is often termed the “double Bohr
effect.”11 However, this effect accounts for only up to 8% of
oxygen transfer.20
4. Fetal compensatory measures to hypoxemia
a. The fetus has an oxygen reserve of only 42 mL; however,
irreversible fetal brain damage does not begin when
oxygen reserves are exhausted in 2 minutes but only after
approximately 10 minutes due to fetal compensatory
 mechanisms that redistribute fetal cardiac output to vital
organs. A total cessation of placental blood flow occurs
rarely, except in cases of umbilical cord prolapse or acute
total placental abruption.21
b. Blood flow is redistributed to core organs (e.g., brain,
heart, placenta) by the release of vasopressin by the
fetus.22 Acute small decreases in uterine blood flow
(10%) cause increases in fetal catecholamines that aid in
fetal blood flow redistribution.22 (see Fig. 2.4).

c. Larger decreases in uterine blood flow from 30% to 35%

will cause fetal blood pressure to rise and decrease fetal
heart rate.22
d. Fetal oxygen consumption decreases only after the
oxygen supply decreases by 40%.21 Fetal oxygen
consumption can decrease by 50% with a shift to
anaerobic metabolism by some organs.22
 e. When uterine blood flow decreases, the efficiency of fetal
oxygen extraction increases.19
B. Carbon dioxide transfer. Carbon dioxide transfer is primarily
dependent on maternal blood flow. Thus, the factors affecting
its transfer are similar to that affecting oxygen transfer. Carbon
dioxide has a 20-fold higher diffusion coefficient compared to
oxygen. The concentration gradient between fetal and maternal
blood is the major determinant of carbon dioxide transfer (fetal
carbon dioxide tension in mixed fetal blood is 40 mm Hg vs. 28
mm Hg in maternal arterial blood).2
1. Although CO2 transfer can occur by transfer of carbonic acid,
bicarbonate ion, and carbonate ion, it is primarily
transferred by diffusion of dissolved CO2, in balance with
bicarbonate ion (which does not readily cross due to its
charge) and carbonic anhydrase activity.23
2. Transfer of CO2 is enhanced by increasing levels of maternal
deoxygenated Hgb, which has less affinity for CO2, and
increased levels of fetal oxygenated Hgb as gas exchange
proceeds (Haldane effect). This can account for
approximately 45% of CO2 transfer.16
3. During uterine contractions, an accumulation of CO2 may
lead to a decrease in pH and respiratory acidosis. The healthy
placenta recovers during uterine relaxation. Acute decreases
in uterine blood flow for short periods due to umbilical cord
compromise cause a similar rise in dissolved CO2. However,
if oxygen flow is compromised over time, fetal oxygen
consumption will decrease and anaerobic metabolism will
begin, leading to a metabolic acidosis and elevation of fetal
lactate accompanied by decreases in bicarbonate.19

CLINICAL PEARL The placental exchange of oxygen and

carbon dioxide are flow dependent; when uterine blood flow is
reduced, increasing maternal PaO2 or maternal hyperventilation will
 not significantly alter fetal oxygenation or reduce acidosis.

IV. Nutrient/drug transfer

A. Mechanisms of exchange. Exchange of nutrients, wastes, and
drugs between the mother and fetus occurs through one of four
mechanisms.24
1. Bulk flow is the movement of water and some dissolved
solutes across differences in hydrostatic and osmotic pressure
gradients. Water movement is dependent on solute
concentrations, which are dependent on Na+/K+ ATPase pump
activity. This process may be compromised during periods of
ischemia.
2. Diffusion occurs when there is a concentration gradient
across the barrier and exchange follows the concentration
gradient. Most maternally administered drugs cross the
placenta by this mechanism. Facilitated diffusion involves use
of the concentration gradient created by the transport
mechanism of another substance (see glucose transport
mentioned in the following text).
3. Transporter-mediated transport relies on membrane bound
proteins that are responsible for transporting solutes across the
plasma membrane, which may occur at a faster rate than by
diffusion alone. This transport mechanism may occur against
a concentration gradient.
4. Pinocytosis is a mechanism within the membrane that entraps
molecules to be transported, forms a vesicle, and then releases
the contents into the fetal circulation. This mechanism is
unlikely to significantly participate in either drug or nutrient
transfer across the placenta.
B. Drug transfer. Drugs can be classified into whether they are
diffusion/transport limited or flow limited in transport
depending on their permeability. Highly permeable drugs are
placental blood flow limited versus poorly permeable drugs,
which are less dependent on placental blood flow for transfer.
 One-time measurements of the ratio of fetal to maternal plasma
concentration (F/M ratio) from blood samples obtained at
delivery allow for an estimation of anesthetic drug transfer from
mother to fetus. In contrast, the dual-perfused human placental
model allows for independent perfusion of maternal and fetal
placental circulations. Determination of steady state clearance of
drug in either direction (maternal to fetus) can be obtained and
has been used to assess placental transfer of some anesthetic
agents.23

CLINICAL PEARL A drug’s F/M ratio gives an incomplete

picture of fetal accumulation when a drug is administered over long
periods of time.

1. Factors affecting diffusion. Because most drugs cross by

diffusion, factors that affect the drug concentration gradient
across the placenta, the permeability of the placental
membrane, and the diffusion distance determine the extent to
which drugs cross from the mother to the fetus.5
a. Drug concentration gradient
(1) This is primarily determined by concentration of free
drug in maternal arterial blood, concentration of the
free drug in the fetal circulation, and maternal and
fetal placental blood flow.5
(2) Maternal and fetal protein binding of drugs affect
the amount of free unbound drug on both sides of the
placental barrier, with high maternal protein binding
retarding drug transfer and high fetal drug binding
promoting transfer. This may affect free drug
concentrations at differing gestational ages as
maternal albumin concentrations fall, whereas fetal
plasma protein concentrations rise during the course
of gestation.5
 b. Factors affecting placental permeability. Placental
permeability depends on characteristics of the placental
membrane as well as the substance being transferred.
(1) Molecular weight. Molecules with a higher
molecular weight (>1,000 Da) are unlikely to cross
the villous membrane by diffusion into the fetal
circulation. However, molecules with low molecular
weight (<500 Da) can easily cross the placenta by
diffusion, whereas drugs of intermediate weight cross
incompletely.25
(2) Lipid solubility. Highly lipid-soluble drugs freely
cross the placenta, whereas poorly lipid-soluble
drugs are unlikely to cross.25
(3) Ionization/electric charge
(a) Ionization of drugs is determined by the
Henderson-Hasselbalch equation:

pH = pKa + log [base] / [acid]

(b) Highly ionized medications, such as the muscle

relaxants, their reversal agents, and heparin, do
not cross the placenta.26
(c) Fetal plasma pH influences the rate of transfer
because the mixed fetal plasma is approximately
0.1 pH units lower than maternal plasma pH.
The transfer of weak bases such as local
anesthetics and opioids is facilitated by fetal
acidemia and a distressed fetus is therefore more
likely to accumulate basic drugs.5
(4) Spatial configuration of the drug (i.e., steric
hindrance) can also affect molecular transfer.
Linearly shaped molecules are less likely to cross the
placenta than more spherical substances.5
2. For clinical purposes, it is perhaps best to separate drugs
 into those that readily cross the placenta versus those that
do not (see Table 2.1).

C. Nutrient transfer
1. Glucose is transported by diffusion down the concentration
gradient from mother to fetus and by glucose transporters.
Regulation of transport is by a complicated signaling pathway
relying on mechanistic target of rapamycin complex
(mTORC) activation within the trophoblast.27
2. Amino acid transport relies on diffusion and an active
transport system linked to a Na+/K+ ATPase pump.27
3. Fatty acids transfer to the fetus by diffusion; however,
proteins to which free fatty acids bind are involved in an
active transport mechanism.27
V. Teratogenicity. The ACOG notes that severe congenital anomalies
are found in 3% of live births in the general population and 4.5% of
children manifest birth defects by age 5.28 The etiology of most
congenital malformations is unknown. Understanding how a drug
may cause a structural or functional defect relies on knowledge of the
six basic principles of teratology (see below). Knowledge of drug
teratogenicity is important because nearly 60% of women will take
medications other than vitamins during pregnancy.28 Birth defects
consist of malformations, deformations, and disruptions.
A. Classification of birth defects
1. Malformations are alterations of normal development that
occur as a result of an intrinsic abnormality in the
developmental process.
2. Deformations result from an abnormal mechanical force on
an otherwise normal fetus.
3. Disruptions are due to the disruption of an otherwise normal
developmental process.
B. Etiology of congenital malformations
1. Unknown: 65% to 75%
2. Genetic: 15% to 25%
3. Environmental: 10%
a. Environmental factors include drugs, chemicals, and
physical factors such as ionizing radiation and others.
Prescription medications are responsible for only a small
fraction of congenital malformations.29
C. Principles of teratology. The six principles of teratology form a
foundation of knowledge about the biologic plausibility of a
teratogen28:
1. Genetic susceptibility is the inherent resistance or
susceptibility of an organism to specific teratogens and
depends on the genotype of the fetus as well as the manner in
which it interacts with adverse environmental factors. Fetal
and maternal factors are likely to play a role. Inherited traits
can lead to increased sensitivity. Some of the factors that
affect susceptibility include:
a. Dose of exposure
b. Threshold dose
c. Pharmacokinetics and metabolism of drug/chemical
d. Pregnancy-related physiologic changes
 e. Placental transport of substances.30
2. Timing of exposure can be critical when determining if an
effect on the fetus is possible.
a. Gestational age of 2 to 5 weeks is thought to be “all or
none.” Exposure at this time is likely to cause either
spontaneous abortion or no harm. Early in gestation, any
cell can be totipotential. If a single cell is damaged, it can
be replaced by one that is not damaged, but if a critical
number are damaged then the pregnancy is lost.
b. Gestational age of 5 to 10 weeks is critical for
organogenesis. This is the time when most organs are
developing and represents a fairly limited window for
teratogenicity.
c. After 10 weeks, most fetal organs grow and differentiate,
and exposure may decrease growth or decrease
differentiation.31
3. Mechanisms of teratogenesis
Teratogenic agents act in specific ways on developing cells
and tissues to initiate sequences of abnormal developmental
events. When a substance is suspected of being a teratogen, it
is necessary to ask whether there is biologic plausibility for
the production of the specific malformation by that substance.
4. Manifestations. A teratogenic agent is associated with
certain, specific malformations that have been previously
described. The manifestations of deviant development are
death, malformation, growth retardation, and functional
deficit.
5. Agent effects are often dependent on timing, dose, and
interactions.
a. Drugs. Many illicit drugs and alcohol are known
teratogens.29
b. Chemicals
c. Infections
Many infections are known to cause congenital
 anomalies. The most common and well known are the
TORCH infections. TORCH refers to toxoplasmosis,
rubella, cytomegalovirus, herpes simplex, and others
including varicella.
d. Maternal diseases can also cause congenital anomalies
with the most common being diabetes mellitus. Poorly
controlled diabetes increases the risk of many fetal
anomalies, including congenital heart defects and sacral
agenesis.
6. Dose effect. The manifestations of abnormal development
increase in frequency and degree as dosage increases. There is
a dosage level below which malformations are not observed.
This is often extrapolated from animal models. A high risk of
teratogenicity is suspected if the dose-producing birth defects
in animals is less than tenfold higher than the maximum
human therapeutic dose. There is low risk if the teratogenic
dose in animals is >100-fold higher than the maximum human
therapeutic dose.32
D. Drug teratogenicity. Since 1975, the U.S. Food and Drug
Administration (FDA) has required that all drugs be
categorized on the basis of their ability to produce birth
defects. In December 2014, the FDA revised the standards for
reporting information about medication use during pregnancy.
This change occurred over several years in response to
widespread criticism of the previous letter classification system.
33 The old letter system (A, B, C, D, X) had serious

shortcomings: lack of agreement with that of other countries who

have published similar standards; 34 recognition by most
providers as being over simplistic; misinterpretation by many as a
grading system, which overestimated the risk of drug
teratogenicity and underestimated drug benefit in the pregnant
patient.36 The clinician decision-making process was further
complicated by a lack of knowledge of the teratogenic effects of
most drugs approved for use over the past 20 years, in many
cases, the disclosure had not been previously required.35 Indeed,
the use of a drug over many years may be required to determine
the teratogenic risk if the incidence of anomaly is very low.
1. Table 2.2 summarizes the newly released FDA requirements
for drug labeling.

2. Table 2.3 lists medications that might likely be taken by

women either before or during pregnancy and their accepted
teratogenic potential.36–41 Because the teratogenic profile of
a given drug may change with recent information, using
the noted web-based references will offer the most current
information concerning a particular drug.
 3. Virtually, all anesthetic drugs are not associated with a
significant risk of increased fetal defects when administered
during nonobstetric surgery. The ACOG does not consider
anesthetic agents to be teratogenic.37

CLINICAL PEARL Most drugs administered during pregnancy,

including anesthetic drugs, are not teratogenic. An extensive history
of use must be obtained before the risk of an individual drug can be
determined. Anesthetic drug administration has recently been
associated with the development of central nervous system
apoptosis. The significance in humans has yet to be determined (see
Chapter 6, Nonobstetric Surgery during Pregnancy).

REFERENCES
1. Brent RL. Environmental causes of human congenital malformations: the pediatrician’s role in dealing
with these complex clinical problems caused by a multiplicity of environmental and genetic factors.
Pediatrics. 2004;113:957–968.
2. Asśali NS, Nuwayhid B, Zugaib M. Control of the uteroplacental circulation in health and disease. Eur
J Obstet Gynecol Reprod Biol. 1978;8:43–55.
3. Clapp JF III, Capeless E. Cardiovascular function before, during, and after the first and subsequent
pregnancies. Am J Cardiol. 1997;80:1469–1473.
4. Cross JC. Placental function in development and disease. Reprod Fertil Dev. 2006;18:71–76.
5. Syme M, Paxton JW, Keelan JA. Drug transfer and metabolism by the human placenta. Clin
Pharmacokinet. 2004;43:487–514.
6. Kingdom J, Huppertz B, Seaward G, et al. Development of the placental villous tree and its
consequences for fetal growth. Eur J Obstet Gynecol Reprod Biol. 2000;92:35–43.
7. Kaufmann P, Hans-George F. Placental development. In: Polin RA, Fox WW, Abman SH, eds. Fetal
and Neonatal Physiology. 3rd ed. Philadelphia, PA: W.B. Saunders; 2004:85–96.
8. Krause BJ, Hanson MA, Casanello P. Role of nitric oxide in placental vascular development and
function. Placenta. 2011;32:797–805.
9. Konje JC, Kaufmann P, Bell SC, et al. A longitudinal study of quantitative uterine blood flow with use
of color power angiography in appropriate for gestational age pregnancies. Am J Obstet Gynecol.
2001;185:608–613.
10. Laird MR, Faber JJ, Binder ND. Maternal placental blood flow is reduced in proportion to reduction in
uterine driving pressure. Pediatr Res. 1994;36:102–110.
11. Zakowski MI, Ramanathan S. Uteroplacental circulation and respiratory gas exchange. In: Suresh MS,
Segal S, Preston RL, et al, eds. Shnider and Levinson’s Anesthesia for Obstetrics. 5th ed. Philadelphia,
PA: Wolters Kluwer; 2013:19–45.
12. Urban G, Vergani P, Ghidini A, et al. State of the art: non-invasive ultrasound assessment of the
uteroplacental circulation. Semin Perinatol. 2007;31:232–239.
13. Sastry BV. Human placental cholinergic system. Biochem Pharmacol. 1997;53:1577–1586.
14. Ramasubramanian R, Johnson RF, Downing JW, et al. Hypoxemic fetoplacental vasoconstriction: a
graduated response to reduced oxygen conditions in the human placenta. Anesth Analg.
2006;103:439–442.
15. Tuuli M, Odibo AO. The role of serum markers and uterine artery Doppler in identifying at-risk
pregnancies. Clin Perinatol. 2011;38:1–19.
16. Wilkening RB, Meschia G. Fetal oxygen uptake, oxygenation, and acid-base balance as a function of
uterine blood flow. Am J Physiol. 1983;244:H749–H755.
17. Crawford JS. Placental physiology. In: Crawford JS, ed. Principles and Practice of Obstetric
Anesthesia. 5th ed. Boston, MA: Blackwell Science; 1984:101–131.
18. Ramanathan S, Gandhi S, Arismendy J, et al. Oxygen transfer from mother to fetus during cesarean
section under epidural anesthesia. Anesth Analg. 1982;61:576–581.
19. Parer JT. Uteroplacental physiology and exchange. In: Parer JT, ed. Handbook of Fetal Heart Rate
 Monitoring. 2nd ed. Philadelphia, PA: W.B. Saunders; 1997:22–43.
20. Hill EP, Power GG, Longo LD. A mathematical model of carbon dioxide transfer in the placenta and
its interaction with oxygen. Am J Physiol. 1973;224:283–299.
21. Myers RE. Two patterns of perinatal brain damage and their conditions of occurrence. Am J Obstet
Gynecol. 1972;112:246–276.
22. Gu W, Jones CT, Parer JT. Metabolic and cardiovascular effects on fetal sheep of sustained reduction
of uterine blood flow. J Physiol. 1985;368:109–129.
23. Zakowski MI, Geller A. The placenta: anatomy, physiology, and transfer of drugs. In: Chestnut DH,
Wong CA, Tsen LC, et al, eds. Chestnut’s Obstetric Anesthesia: Principles and Practice. 5th ed.
Philadelphia, PA: Elsevier Mosby; 2014:55–74.
24. Myllynen P, Pasanen M, Pelkonen O. Human placenta: a human organ for developmental toxicology
research and biomonitoring. Placenta. 2005;26:361–371.
25. Pacifici GM, Nottoli R. Placental transfer of drugs administered to the mother. Clin Pharmacokinet.
1995;28:235–269.
26. Ní Mhuireachtaigh R, O’Gorman DA. Anesthesia in pregnant patients for nonobstetric surgery. J Clin
Anesth. 2006;18:60–66.
27. Larqué E, Ruiz-Palacios M, Koletzko B. Placental regulation of fetal nutrient supply. Curr Opin Clin
Nutr Metab Care. 2013;16:292–297.
28. Niebyl JR, Simpson JL. Drugs and environmental agents in pregnancy and lactation: embryology,
teratology, epidemiology. In: Gabbe SG, ed. Obstetrics: Normal and Problem Pregnancies. 5th ed.
Philadelphia, PA: Elsevier Science; 2007:184–214.
29. Adam MP, Polifka JE, Friedman JM. Evolving knowledge of the teratogenicity of medications in
human pregnancy. Am J Med Genet C Semin Med Genet. 2011;157C:175–182.
30. Gedeon C, Koren G. Designing pregnancy centered medications: drugs which do not cross the human
placenta. Placenta. 2006;27:861–868.
31. Cragan JD, Friedman JM, Holmes LB, et al. Ensuring the safe and effective use of medications during
pregnancy: planning and prevention through preconception care. Matern Child Health J.
2006;10:S129–S135.
32. Brent RL, Fawcett LB. Developmental toxicology, drugs, and fetal teratogenesis. In: Hobbins JC, ed.
Clinical Obstetrics: The Mother and Fetus. 3rd ed. Oxford, United Kingdom: Blackwell Science;
2007:217–291.
33. U.S. Food and Drug Administration. Content and format of labeling for human prescription drug and
biological products; requirements for pregnancy and lactation labeling.
https://www.federalregister.gov/articles/2014/12/04/2014-28241/content-and-format-of-labeling-for-
human-prescription-drug-and-biological-products-requirements-for. Accessed July 30, 2015.
34. Merlob P, Stahl B. Classification of drugs for teratogenic risk: an anachronistic way of counseling.
Teratology. 2002;66:61–62.
35. Bianca S. Drug use during pregnancy: are risk classifications more dangerous than the drugs? Lancet.
2003;362:329.
36. Cheek TG, Baird E. Anesthesia for nonobstetric surgery: maternal and fetal considerations. Clin
Obstet Gynecol. 2009;52:535–545.
37. American College of Obstetricians and Gynecologists. ACOG educational bulletin. Teratology.
Number 236. Int J Gynaecol Obstet. 1997;57:319–326.
38. Reproductive Toxicology Center. Reprotox. http://www.reprotox.org/. Accessed July 30, 2015.
39. TERIS (Teratogen Information System), University of Washington. Clinical tetralogy web: a resource
guide for clinicians. http://depts.washington.edu/terisweb/teris/. Accessed July 30, 2015.
40. Organization for Teratology Information Specialists. Welcome to MotherToBaby.
 http://www.mothertobaby.org/. Accessed July 30, 2015.
41. American College of Obstetricians and Gynecologists. WEBTREATS: teratology/toxicology.
http://www.acog.org/About-ACOG/ACOG-Departments/Resource-Center/WEBTREATS-Teratology-
Toxicology. Accessed July 30, 2015.
 Local Anesthetics and Toxicity
Jennifer Hofer and Barbara M. Scavone

I. Chemical structure
A. Local anesthetics in common clinical use
B. Amino-ester/amino-amide local anesthetics
C. Stereochemistry
II. Mechanism of action
A. Local anesthetic entry into the cell
B. Local anesthetic binding to the sodium channel
C. Local anesthetic dissociation from binding site
D. Local anesthetic effects on other membrane-bound proteins
III. Differential blockade
A. Physiologic basis
B. Anesthetic implications
IV. Additives
A. Bicarbonate
B. Epinephrine
C. Phenylephrine
D. Opioids
V. Effect of pregnancy on local anesthetic action
VI. Pharmacokinetics
A. Systemic absorption
B. Distribution
C. Clearance
 D. Elimination
E. Amide protein binding
F. Local anesthetic continuous infusions
G. Effect of pregnancy on pharmacokinetics
H. Chronobiology
VII. Local anesthetics rapidly cross the placenta
VIII. Systemic toxicity
A. Incidence
B. Signs and symptoms
C. Effect of comorbidities on toxicity
D. Effect of pregnancy on toxicity
E. Prevention
F. Treatment
IX. Other types of reactions may occur
A. Neurotoxicity
B. TNS syndrome
C. Back pain
D. Myotoxic
E. Allergic reactions

KEYPOINTS
1. Lipid solubility, pKa, and protein binding all determine the clinical
profile of local anesthetics.
2. The pKa of any specific local anesthetic partially determines its speed of
onset, in that a molecule with a pKa closer to physiologic pH will be less
ionized and thus have a faster speed of onset than a similar molecule with
a higher pKa.
3. Increased lipid solubility facilitates entry of the local anesthetic molecule
into the cell membrane and increases local anesthetic potency.
4. Moderate lipid solubility aids departure of local anesthetics from the
 binding site, but extreme lipid solubility (e.g., bupivacaine) favors
continued binding and increases duration of action.
5. Pregnancy alters local anesthetic neural blockade, susceptibility to
toxicity, and pharmacokinetics.
6. Prevention of local anesthetic systemic toxicity (LAST) includes (1)
frequent aspiration prior to injection, (2) slow incremental injection, (3)
limiting the total dose, and (4) use of a test dose.
7. Rapid treatment of convulsions and cardiovascular toxicity results in
decreased morbidity and mortality from local anesthetic overdose.
8. Treatment of severe local anesthetic toxicity includes lipid emulsion
(20%) therapy.

LOCAL ANESTHETICS ARE A CLASS of drugs that reversibly block nerve

conduction following regional administration.
I. Chemical structure
A. Local anesthetics in common clinical use share a similar chemical
structure: a lipophilic aromatic ring, linked to an intermediate
hydrocarbon chain, which terminates in a hydrophilic tertiary or
quaternary amine (see Fig. 3.1).1

B. Local anesthetics with an ester bond linking the aromatic ring to

the hydrocarbon chain are classified as amino-ester local
anesthetics. These include procaine, 2-chloroprocaine, tetracaine,
 and cocaine (see Table 3.1). The amino-amide local anesthetics
contain an amide bond between the aromatic ring and the
hydrocarbon chain. Common amino-amides include lidocaine,
bupivacaine, ropivacaine, and mepivacaine.

C. Amides, except lidocaine, have chiral centers with the levorotary

isomer of bupivacaine (levobupivacaine, currently not marketed
in the United States) conveying greater vasoconstrictor properties
and less toxicity than either its racemic mixture (used commonly
in clinical practice) or its dextrorotatory form.2 Ropivacaine is
available in its levorotary form only.
II. Mechanism of action. Lipid solubility, pKa, and protein binding all
determine the clinical profile of local anesthetics. Local anesthetics
act on the sodium channel by reversibly binding to the intracellular
portion of voltage-gated sodium channel that, in turn, disrupts action
potentials along the nerve fibers.
A. Local anesthetic entry into the cell. Only the uncharged form of
the local anesthetic molecule readily enters and/or crosses the cell
membrane.3
1. Commonly used local anesthetics are weak bases that have a
pKa greater than physiologic pH. (A base is defined as a
molecule capable of accepting a proton, and pKa is defined as
the pH at which 50% of the molecules will be in the
protonated form.)
2. When local anesthetics are administered at physiologic pH,
more than 50% of the molecules become protonated at the
 terminal amine. These molecules exist in the ionized form and
are unable to enter or cross the cell membrane due to their
charge.
3. Local anesthetics are marketed as water-soluble salts, usually
hydrochlorides, in order to increase their solubility; therefore,
most preparations are acidic, which further increases the
protonated ionic form of the molecule.
4. The pKa of any specific local anesthetic partially
determines its speed of onset, in that a molecule with a pKa
closer to physiologic pH will be less ionized and thus have a
faster speed of onset than a similar molecule with a higher
pKa.
5. An increased ratio of lipid soluble form to the protonated
form of the local anesthetic facilitates drug entry into the cell
membrane. Thus, increasing lipophilicity is associated with
increasing local anesthetic potency.3
6. Increased protein binding retards absorption from sites of
injection, thus lowering blood levels of those local
anesthetics.4

CLINICAL PEARL The clinical profile of a local anesthetic is

determined by its lipid solubility, pKa, and protein binding
characteristics.

B. Local anesthetic binding to the sodium channel

1. Once the molecule has entered the cell membrane, the
protonated form enters the voltage-gated sodium channel
and reversibly binds at a specific binding site on its inner
pore.5
2. Binding occurs more readily when the sodium channel is in
the activated or the deactivated state (i.e., the states associated
with depolarization) rather than the resting state. This results
in a phasic block (sometimes called use-dependent or
 frequency-dependent block): a block that increases with
repetitive depolarizations and represents increased local
anesthetic binding with repetitive depolarizations.
3. Binding interferes with the conformational changes of the
sodium channel that are necessary for activation and thus
prevents the passage of sodium ions that is necessary for
generating an action potential.3
C. Local anesthetic dissociation from binding site
1. Dissociation from the binding site involves a complex
interaction of molecular size, charge, and lipid solubility.
2. Smaller local anesthetics dissociate from the sodium
channel binding site more rapidly than larger molecules.
Moderate lipophilicity aids departure of local anesthetics from
the binding site, but extreme lipophilicity (e.g., bupivacaine)
favors continued binding and increases duration of
action.6
D. Local anesthetic effects on other membrane-bound proteins.
Local anesthetics probably affect many other membrane-bound
proteins in addition to sodium channels, especially during
epidural and spinal anesthesia, and this may contribute to their
effects. These proteins include adenylate cyclase, guanylate
cyclase, sodium/potassium ATPase, calcium/magnesium ATPase,
and potassium channels.3
III. Differential blockade
A. Physiologic basis. Not all sensory and motor nerves are blocked
equally by local anesthetics. Differential blockade refers to the
observed tendency of different types of nerves to demonstrate
different susceptibilities (i.e., successive disappearance of
temperature sensation, proprioception, motor function, sharp pain,
and light touch) to local anesthetic–mediated conduction
blockade.
1. See Table 3.2 for a list of the different types of nerve fibers
present in humans, along with data regarding axon diameter,
presence or absence of myelination, and function of each type
 of nerve. Presence of a myelin sheath and larger nerve size
result in faster conduction velocities. Large-diameter,
myelinated fibers (e.g., A fibers) are mostly involved in
sensory and motor functions. Speed of nerve transmission is
critical for these functions. Unmyelinated small-diameter C
fibers have slower conduction velocities and relay sensory
functions (e.g., pain, temperature, and autonomic functions).

2. Presence or absence of a myelin sheath differentiates nerves

in the central and peripheral nervous systems. Myelinated
axons are more sensitive to local anesthetic blockade than
unmyelinated axons because the myelin sheath has
interruptions (i.e., nodes of Ranvier) that facilitate conduction
so that an action potential is generated. Unmyelinated fibers
require more local anesthetic exposure for similar degrees of
nerve conduction blockade to result.6
3. In general, axons of smaller diameter are more sensitive to
local anesthetic action than larger diameter axons. For
example, local anesthetics produce an orderly progression of
loss of temperature sensation, followed by proprioception,
motor function, sensation, and light touch. This may not be a
function of size per se but may reflect the fact that large-
diameter nerves may have longer distances between nodes of
Ranvier than small-diameter nerves. When there is a longer
spacing between nodes, a longer critical length of nerve
exposure to local anesthetic may be required before blockade
 occurs.6
4. Axonal size corresponds with different nerve cell function.
Blockade that appears to vary according to diameter may
actually reflect variation according to anatomic and
physiologic differences among nerves with different
functions, such as differences in density and gating of ion
channels, differences in myelination, differences in the
density of sodium/potassium ATPase or other ion pumps, and
so on.7
5. Conduction blockade characteristics may also be a function of
the location of a nerve fiber within a large nerve trunk.
6. Phasic block dictates that nerves with higher baseline firing
rates will demonstrate greater blockade sensitivity than nerves
with lower firing rates. Preganglionic sympathetic vasomotor
nerves may be more susceptible to phasic block because they
have a tonic vasoconstrictor function and a high basal rate of
firing. Similarly, because sensory nerves tend to fire at
increased rates compared to motor nerves, phasic block may
be stronger in sensory than motor nerves.

CLINICAL PEARL Differential blockade refers to the observed

tendency of different types of nerves to demonstrate different
susceptibilities (i.e., successive disappearance of temperature
sensation, proprioception, motor function, sharp pain, and light
touch) to local anesthetic–mediated conduction blockade.

B. Anesthetic implications
1. Sympathetic blockade exceeds sensory blockade by several
dermatomes during spinal and epidural anesthesia, although
sympathetic block is not always complete.8–10
2. Sensory blockade exceeds motor blockade during spinal
and epidural anesthesia. Epidural labor analgesia with low
concentrations of local anesthetics can be used to provide pain
 relief with minimal effects on maternal expulsive efforts.11
3. The Aδ fibers, associated with sharp or fast pain,
demonstrate more susceptibility to local anesthetic effects
than C fibers, associated with burning or slow pain.7
4. Cold temperature–sensing fibers demonstrate more
conduction blockade than pain-sensing fibers.12,13 The degree
of differential blockade is dependent on the concentration of
local anesthetic and volume. The use of less concentrated
solutions and greater volume often produces less motor block
but a more uniform sensory block.
5. A sensory level to pain, as opposed to temperature sensation,
should be used to gauge the adequacy of sensory blockade
during regional analgesia/anesthesia.
IV. Additives. Additives are combined with local anesthetics to achieve
various clinical effects.
A. Bicarbonate. As noted earlier, commonly used local anesthetics
are ionized because they are weak bases with pKa higher than
physiologic pH. Addition of bicarbonate to the local anesthetic
solution (1 mEq/mL) (8.4%) adjusts local anesthetic pH closer
to pKa and increases the ratio of the lipid-soluble form to the
protonated form. This results in less ionization, facilitates drug
entry, and hastens speed of onset.
B. Epinephrine. Epinephrine is an important additive to increase
local anesthetic activity. Besides intensifying local anesthetic–
induced anesthesia and analgesia, epinephrine prolongs the
duration of the block and reduces the systemic absorption of the
local anesthetic. Greater reliability and intensity of the block
are observed when epinephrine is added to epidurally
administered local anesthetics. Epinephrine has intrinsic analgesic
effects that are similar to drugs (e.g., clonidine) which produce
analgesia by stimulation of α2-adrenergic receptors in the spinal
cord. Although epinephrine has a bupivacaine dose-sparing effect
when used as an additive for epidural labor analgesia,14 it is
 associated with increased motor block. Epinephrine causes
vasoconstriction and thus reduces clearance of drugs from the
intrathecal and epidural spaces into the central circulation.15
Epinephrine reduces mean peak plasma concentrations of
epidurally administered lidocaine and bupivacaine, which is
significant when considering the potential for local anesthetic
toxicity.16 Intrathecal epinephrine is administered in doses
between 50 and 200 μg and epidurally in doses of 1 to 5 μg per
mL of local anesthetic.

CLINICAL PEARL When epinephrine is added to lidocaine, it

improves the density as well as prolongs the duration of the block
and reduces the systemic absorption of the local anesthetic.

C. Phenylephrine. Phenylephrine as a vasoconstricting additive has

fallen out of favor due to an increased incidence of transient
neurologic symptoms (see following text) associated with its
use.17
D. Opioids. Opioids are often added to local anesthetics
administered in the spinal or epidural spaces and have synergistic
effects without evidence of toxicity.
V. Effect of pregnancy on local anesthetic action. Pregnancy
enhances local anesthetic effects. Pregnancy alters local anesthetic
neural blockade, susceptibility to toxicity, and pharmacokinetics.
Pregnant women typically require smaller doses of local anesthetic
compared to nonpregnant women. Long-acting amide local
anesthetics, such as bupivacaine, are beneficial for labor neuraxial
analgesia because they produce a relative motor-sparing block as
compared to other local anesthetics. The motor-sparing effect appears
to be enhanced during pregnancy. For instance, the ED50 for motor
block after intrathecally administered bupivacaine was lower in
pregnant women as compared to nonpregnant ones, 3.96 and 4.14,
respectively.18 These effects may be evident as early as the second
trimester.19,20 Although the difference has been attributed to enhanced
spread of local anesthetic due to epidural venous engorgement,
mechanical effects alone do not account for the observation that the
spread of spinal and epidural analgesia in early pregnancy is similar
to that in pregnant women at term.
A. High spinal or epidural block accounted for 16% of
anesthesia-related pregnancy deaths from 1992 to 2002.21
B. Increased cephalad spread during pregnancy is due to both
mechanical and nonmechanical factors.
1. Mechanical compression of the vena cava by the gravid uterus
leads to distension of the epidural veins, which in turn
decreases intrathecal volume.20 Therefore, equal doses of
local anesthetics may result in higher anesthetic levels in
pregnant compared to nonpregnant patients.18
2. Nonmechanical factors: Pregnancy increases median nerve
sensitivity to lidocaine block.22 In vitro preparations from
pregnant versus nonpregnant animals demonstrate increased
susceptibility to bupivacaine and lidocaine conduction
blockade.23–25 Anatomic differences alone do not account for
these observed peripheral and in vitro differences. These
differences are due to progesterone and/or other hormonal
mediators that affect membrane excitability, increase
permeability of the neural sheath, and/or potentiate the
analgesic effect of endogenous opioids.18,19,26
C. Cerebrospinal fluid has a greater pH and lower PCO2 during
pregnancy. These physiologic changes can favor diffusion of
the non-ionized form of the local anesthetic across the nerve
cell membrane. However, it is not completely understood what
effect this may have on cephalad spread of analgesia.
D. It is not known when local anesthetic requirements return to
normal, but patients for postpartum tubal ligation require a higher
dose of intrathecal bupivacaine per blocked segment 36 to 48
hours after delivery compared to patients undergoing cesarean
delivery.27
 CLINICAL PEARL Equal doses of local anesthetics result in
higher neural blockade in pregnant compared to nonpregnant
patients due to mechanical and hormonally mediated factors.

VI. Pharmacokinetics. An understanding of the pharmacokinetics of

local anesthetics requires knowledge of the principles of absorption
from injection site, distribution, and clearance.
A. Systemic absorption
1. Kinetic variables relevant to a discussion of absorption
include the maximal blood concentration (Cmax) that occurs
after perineural injection and the time at which Cmax occurs.
2. Systemic absorption from the site of injection is dependent on
local blood flow and local tissue binding such that drugs are
absorbed more rapidly from highly vascular sites such as
the epidural space than from peripheral nerve or
subcutaneous sites. However, the level at which the epidural
space is entered does not affect absorption.4,28
Vasoconstrictors reduce Cmax and increase mean
absorption time. These effects are greatest in highly vascular
tissues such as the epidural space.16 Rate of absorption
slows for drugs that are highly bound to local adipose
tissues (which depends on drug lipid solubility) or local
tissue proteins (which depends on drug protein binding
strength).4,29
3. A biphasic pattern of absorption exists due to relatively
rapid absorption from the aqueous phase but a delayed
slower absorption from adipose tissue.4
B. Distribution. Volume of distribution depends on the degree of
plasma and blood cell versus tissue binding of drug. The volume
of distribution is smaller for highly protein-bound drugs (e.g.,
bupivacaine). Enantiomeric differences in volume of distribution
exist due to differences in plasma protein binding;
levobupivacaine is more highly protein bound and has a smaller
 volume of distribution than racemic bupivacaine.30
C. Clearance
1. Ester-type anesthetics are hydrolyzed by plasma esterases,
including pseudocholinesterase, red cell, and liver esterases.
Hydrolysis occurs within a few minutes in both the mother
and the fetus.4,29 One exception is cocaine because it is slowly
metabolized by the liver. It is generally not used in obstetrics
due to its vasoconstrictive effects.
2. Clearance of amide-type local anesthetics occurs almost
exclusively in the liver.
a. Lidocaine has a high hepatic extraction ratio (70% to 75%
first pass), and thus, its clearance is largely dependent on
hepatic blood flow, which can be reduced during epidural
anesthesia and with alterations in protein binding. Other
factors that limit hepatic blood flow (e.g., volatile
anesthetics, congestive cardiac failure, intravascular
volume depletion) reduce clearance.
b. Conversely, bupivacaine and ropivacaine have more
intermediate hepatic extraction ratios (<50% first pass), so
clearance is more dependent on free drug concentration
and intrinsic enzymatic activity.4
c. Patients with renal dysfunction or severe cardiac disease
also have reduced clearance of local anesthetics and
require dose reduction of medication during repeated
dosing or continuous infusion. Uremia causes a
hyperdynamic circulation that rapidly increases the
plasma concentration of bupivacaine and ropivacaine;
however, a concomitant increase in α1-acid glycoprotein
is protective, binding toxic levels of unbound local
anesthetic.29,31
D. Elimination. Drug elimination is offset by continued systemic
absorption, so measured serum half-lives are longer after epidural
than intravenous administration.32 Because elimination occurs
at a faster rate than absorption after epidural administration,
 mean residence time (the mean time drug molecules remain in
the body) may be a more meaningful measure than
elimination half-time.
E. Amide protein binding. The amides bupivacaine, ropivacaine,
and levobupivacaine are highly protein bound to α1-acid
glycoprotein.33
F. Local anesthetic continuous infusions. During continuous
bupivacaine or ropivacaine infusion, a slow rise in serum
concentration of drug occurs over time.34,35 This is offset by
increases in α1-acid glycoprotein concentrations that occur in the
postoperative population, leading to increased protein binding,
such that concentrations of free drug remain unchanged over
time.36,37
G. Effect of pregnancy on pharmacokinetics. During pregnancy,
volumes of distribution of bupivacaine and ropivacaine are
lower; however, clearance is also decreased so that serum
half-life of elimination and mean residence time are
unchanged.33,38 Therefore, following inadvertent intravascular
injection in a pregnant patient, one might expect a higher peak
serum concentration but normal elimination.
H. Chronobiology. Diurnal neuroendocrine or other external factors
may affect pain sensitivity. For example, in one study, the
duration of action of epidural ropivacaine was approximately 20–
28% longer in the diurnal period (morning and afternoon) when
compared with the nocturnal period (evening and night).39 In a
more recent study, the peak effect of labor analgesia occurred
between 2:00 AM and 5:59 AM. Some have suggested that these
differences may be explained by the fact the chronobiology may
also be affected by such influences as shift change for nurses and
anesthesiologists.40
VII. Local anesthetics rapidly cross the placenta.38
A. Although the total drug concentration is lower in the fetal than in
the maternal circulation, the fetus possesses lower concentrations
 of α1-acid glycoprotein, so that fetal and maternal free drug
concentrations are approximately equivalent.4,41
B. When a fetus is acidotic, ion trapping may occur because local
anesthetics may be relatively more ionized than maternal
blood. This can lead to fetal drug accumulation.
VIII. Systemic toxicity from high circulating plasma levels of local
anesthetics can occur after unintentional intravenous injection or
from absorption of local anesthetic after neural blockade. In most
cases, larger doses of local anesthetics are required to produce
cardiovascular toxicity compared to doses producing central nervous
system toxicity. Unintentional venous cannulation and injection are
more likely to occur during epidural anesthesia in the pregnant
patient, secondary to engorgement of epidural veins. Because blood
levels rise rapidly, direct intravascular injection is associated with
rapid onset of seizure activity. In contrast, toxicity that occurs due to
absorption of local anesthetic resulting from epidural blockade is
associated with a 20- to 30-minute delay in onset of symptoms. Blood
concentrations of local anesthetics may remain elevated for longer
periods of time than after unintentional intravenous injection.42 See
Table 3.3 for symptoms of local anesthetic systemic toxicity (LAST).

A. Incidence. The incidence of LAST and death due to LAST

among parturients has decreased in recent years.42,43 However,
LAST has been recognized for decades as an important potential
cause of maternal mortality.44 The decrease in maternal deaths
may be due to changes in U.S. Food and Drug Administration
(FDA) recommendations that include avoiding higher than 0.5%
 concentration of bupivacaine in pregnant patients, increased
clinician awareness of local anesthetic toxicity, and subsequent
use of safety measures (e.g., catheter aspiration, incremental
dosing, dosing limits) during epidural anesthesia. Authors
estimate the incidence of epidural anesthesia–associated LAST to
be 1 to 1.3 per 10,000 epidural anesthetics.45,46
B. Signs and symptoms. Signs and symptoms of LAST follow a
typical progression as serum concentrations increase in the
central nervous system (CNS) and cardiovascular system.
1. CNS effects occur because inhibitory neurons are more
susceptible to local anesthetic blockade resulting in a
period of excitation. Initially, patients may complain of
numbness of the tongue, tinnitus, or light-headedness. At
higher plasma concentrations, convulsions occur because of a
selective blockade of central inhibitory neurons subsequently
leading to increased CNS excitation, manifested by muscle
twitching, and, eventually, generalized tonic-clonic seizures.
At still higher concentrations, generalized CNS depression or
coma may result from reversible blockade of both inhibitory
and excitatory neuronal pathways. Finally, depression of the
brainstem and cardiorespiratory centers may occur.47 Potency
regarding seizure generation is roughly proportionate to
potency regarding neural blockade such that different local
anesthetics given at equipotent doses are equally likely to
result in seizures. One exception is that the S enantiomer of
bupivacaine has less propensity to cause seizures.48
a. Factors that increase the risk of CNS toxicity include
acidosis, vasoconstriction, and decreased protein binding.
b. Factors that decrease the risk of CNS toxicity include
medications (e.g., benzodiazepines, barbiturates) and
decreased systemic absorption due to the addition of
epinephrine in the local anesthetic.
c. Estimates suggest that the incidence of CNS toxicity with
epidural injection is approximately 3 per 10,000.
 2. The cardiovascular system is affected both indirectly through
the CNS and directly due to local anesthetic effects on the
myocardium itself. Overall, much larger doses of local
anesthetics are required to produce cardiovascular toxicity
than CNS toxicity. All local anesthetics produce blockade of
the cardiac conduction system by a dose-dependent block of
sodium channels.
a. Subconvulsant doses of local anesthetics result in small
degrees of myocardial depression as evidenced by
decreased cardiac contractility and increased heart rate;
mild depression of cardiac conductivity is observed.48,49
b. Onset of seizures heralds increases in heart rate,
myocardial contractility, cardiac output, and mean
arterial pressure mediated through the central
sympathetic nervous system.48,50 As the CNS becomes
more depressed, sympathetic nervous system output
decreases and indirect cardiac effects become depressive.
c. At increasing doses, local anesthetics directly cause
dose-dependent myocardial depression with potency
approximately proportionate to potency for neural
blockade. However, because ropivacaine is less lipophilic
than bupivacaine, it may produce fewer negative inotropic
effects.48,51–53
d. Local anesthetics disturb cardiac conduction by
causing QRS prolongation and dysrhythmias,
including ventricular fibrillation. Propensity to cause
dysrhythmias is not proportionate to potency and differs
regarding chirality.48,54

CLINICAL PEARL Overall, much larger doses of local

anesthetics are required to produce cardiovascular toxicity than
CNS toxicity.
(1) Lidocaine is less often associated with ventricular
dysrhythmias than either racemic bupivacaine or
ropivacaine.55–57 Lidocaine binds to cardiac sodium
channels quickly but dissociates rapidly (i.e., “fast-in-
fast-out” binding), so it does not accumulate inside
cardiac cells. Bupivacaine binds in a “fast-in-slow-
out” manner and has a stronger binding affinity to
resting and inactivated sodium channels.58
(2) Ropivacaine is also less often associated with
ventricular dysrhythmias than racemic
bupivacaine.49,52,57,59 Questions have been raised
regarding these findings because ropivacaine
appears to be less potent than bupivacaine. Studies
that measure the median effective concentration of a
local anesthetic in a 20-mL volume that provides
epidural labor analgesia (median local anesthetic
concentration, or MLAC, a measure of ED50)
determined the ropivacaine to bupivacaine potency
ratio to be 0.6.60,61 Similar studies examining the
median local anesthetic dose (MLAD) required for
intrathecal labor analgesia determined the potency
ratio between the two drugs to be 0.65.62 Other
authors have questioned the validity of using MLAC
studies to compare potencies of local anesthetics,
pointing out that isolated ED50 measurements may
lack importance because drugs with different ED50
values may have dose–response curves that overlap
in their ED95 range, the more clinically significant
range.63 Van de Velde et al.64 recently determined the
full dose–response relation of intrathecal bupivacaine
and ropivacaine combined with sufentanil for labor
analgesia and found the ED95 of ropivacaine equal to
4.8 mg and that of racemic bupivacaine equal to 3.3
 mg (p < 0.05), for a ratio of 0.69.
(3) Despite these concerns, some authors conclude that
ropivacaine is more likely to be less cardiotoxic than
racemic bupivacaine even accounting for differences
in potency.42,65 Studies comparing equipotent doses
of the two drugs demonstrate fewer QRS effects and
dysrhythmias after ropivacaine.52,66 Unsuccessful
resuscitation from ropivacaine toxicity occurred in
only 10% of dogs, but from bupivacaine toxicity
occurred in 50% of dogs. This result was not
statistically significant due to the small number of
animals studied.67
(4) Case reports of cardiac arrest after ropivacaine
administration exist in the obstetric and regional
anesthesia literature.68–70 Toxic effects of ropivacaine
typically present early, within 3 to 5 minutes post–
epidural injection with a sustained toxic response of 3
to 15 minutes (t1/2 5 to 7 minutes).68,70 However,
delayed onset of ropivacaine toxicity 60 minutes
post–peripheral nerve block has been described.69
(5) Levobupivacaine possesses less CNS and
cardiotoxicity than racemic bupivacaine but is no
longer available in the United States.54
(6) The ratio of doses of local anesthetic that cause
cardiovascular collapse versus seizures (CV/CNS
ratio) is lower for bupivacaine than for other agents.71
This suggests a decreased safety margin for
bupivacaine when detecting imminent cardiac arrest
based on CNS changes.72
C. Effect of comorbidities on toxicity. Presence of comorbidities
increases the likelihood of LAST. Older age, heart failure,
ischemic heart disease, conduction abnormalities, liver disease,
metabolic (mitochondrial) disease, low plasma protein
concentrations, and acidosis (metabolic or respiratory) all
 increase propensity for LAST. In the setting of severe cardiac
dysfunction and greatly decreased left ventricular ejection
fraction, the circulation time for intravascular local anesthetics is
prolonged, causing patients with these conditions to be more
susceptible to “stacked” injections and toxicity.73
D. Effect of pregnancy on toxicity. Pregnancy may raise
susceptibility to toxicity. An early study demonstrated increased
toxicity from bupivacaine in pregnant compared to nonpregnant
sheep, but the study was not blinded and consisted of a small
sample size.74 A more recent study found no difference in the
systemic toxicity of either bupivacaine or ropivacaine in pregnant
versus nonpregnant sheep.75 The same group of investigators did
show the dose of bupivacaine, ropivacaine, or levobupivacaine
required to produce convulsions was lower in pregnant as
opposed to nonpregnant sheep; however, the dose of local
anesthetic which resulted in hypotension, apnea, or circulatory
collapse was not affected by pregnancy.76
E. Prevention. Numerous safety steps in current practice may be
responsible for the decreased incidence of LAST observed during
the past several decades, including frequent aspiration prior to
injection, slow incremental injection of small doses, dose
limitation, and the use of epidural test doses.42
1. Incremental dosing reduces peak blood levels, thus reducing
potential toxicity. Also, it allows for early recognition by the
anesthesiologist.77
2. Current recommendations regarding maximum doses of local
anesthetics are presented in Table 3.4. The reader is
cautioned, however, that these recommendations may not be
evidence-based and that safe dosing is influenced by factors
such as site of injection, age, concomitant illness,
comorbidities, and pregnancy.29
 3. Test doses are used to detect intravascular injection. The most
commonly used test dose contains 15 μg epinephrine, which
will increase the heart rate by at least 10 bpm within 40 to
60 seconds of injection.78 Its sensitivity and specificity have
been questioned in obstetric patients, but it is still
recommended by experts.79,80 Alternatively, small doses of
local anesthetics themselves (bupivacaine 25 mg, lidocaine
100 mg, chloroprocaine 100 mg) can produce mild
neurologic symptoms such as dizziness, perioral numbness,
and tinnitus.42 Some have described the injection of 1 mL air
that produces a mill wheel murmur and is heard via a
fetal heart Doppler monitor placed on the maternal
precordium.81

CLINICAL PEARL Frequent aspiration of an epidural catheter

prior to injection, slow incremental injection of small doses, dose
limitation, and the use of an epidural test dose can be used to reduce
the risk of LAST.

F. Treatment
1. Rapid treatment of convulsions and cardiovascular toxicity
results in decreased morbidity and mortality from local
anesthetic overdose.82 McCutchen and Gerancher83
administered lipid in a suspected case of bupivacaine
intoxication manifested by convulsions and early signs of
 cardiovascular toxicity, consequently preventing progression
to full cardiovascular collapse. Therefore, the
anesthesiologist must be prepared for a rapid response to
LAST.
2. Because hypoxemia and/or acidosis enhance both the CNS
and cardiac toxicities of bupivacaine, initial resuscitative
measures must include attention to airway management,
oxygenation, and ventilation.84,85 The aim of ventilation is
to produce normocapnia not hypocapnia.78
3. Treatment of convulsions with small amounts of
benzodiazepines and/or barbiturates with or without
muscle relaxants will aid in airway management efforts and
decrease convulsion-mediated acidosis.
4. Current data support using amiodarone to treat
bupivacaine-induced severe ventricular dysrhythmias.78
Nine of 10 pigs with bupivacaine-induced severe
dysrhythmias survived after resuscitation including
amiodarone versus only 4 of 10 that received bretylium and 6
of 10 controls. The results were not significantly different
between groups, possibly due to small sample size.86 The
mechanism of amiodarone’s benefit in treating local
anesthetic toxicity is twofold: inhibition of outward potassium
channels that prolong repolarization and an antiadrenergic
effect.31,87
5. Lipid emulsions have been used successfully for prevention
and treatment of bupivacaine-induced cardiovascular collapse,
possibly because the lipophilic bupivacaine partitions into
the emulsion (the so-called “lipid sink” hypothesis).88–90 In
addition, lipid emulsion restores myocardial adenosine
triphosphate (ATP) via reversal of local anesthetic inhibition
of myocardial fatty acid oxidation. 31,71,91–93
a. Several case reports describe the successful use of lipid
emulsion during LAST in human patients, including one
description of a parturient.94–96 However, recurrence of
 bupivacaine-induced cardiac arrest following lipid therapy
has also been described. This highlights the importance of
prolonged monitoring of patients after LAST.97
b. Optimal timing of lipid therapy remains unanswered.
Current recommendations include immediately
discontinuing administration of the local anesthetic,
treating hypoxia and acidosis with oxygen and ventilation,
and administering benzodiazepines to suppress
seizures.72,98 However, case reports support early lipid
emulsion administration at the first sign of CNS toxicity
to prevent progression to CV collapse,96,98,99 suggesting
improvement in mental status, agitation, or seizures when
lipid emulsion was administered early in the course of
LAST. (Weinberg100 explains that because lipid is not an
energy source for the brain, the reversal of neurologic
symptoms by lipid infusions supports the lipid sink
hypothesis rather than a direct metabolic effect on the
brain.)
c. See Figure 3.2 for recommendations regarding the use
of lipid emulsion for treatment of LAST. Practitioners
should ensure that lipid preparations are available
wherever regional anesthetics are administered.
6. The role of sympathomimetics, epinephrine, and vasopressin
in restoring hemodynamic stability is
controversial.73,78,100–103 The American Heart Association
Advanced Cardiovascular Life Support (ACLS)
Guidelines call for vasopressin administration along with
epinephrine
 (http://circ.ahajournals.org/cgi/content/full/112/24_suppl/IV-
58). Although these are first-line drugs in the ACLS
algorithm, the etiology of cardiac arrest is heterogenous, and
when treating cardiac arrest from LAST, the role for
epinephrine and/or vasopressin may be more limited.100
a. In a rabbit model, epinephrine at moderate to high doses
was necessary for the return of spontaneous circulation;
however, the animals subsequently suffered hemodynamic
deterioration.103
b. In a rodent model comparing lipid emulsion alone versus
low-dose epinephrine plus lipid to treat cardiac toxicity, a
delayed but sustained response to spontaneous circulation
was witnessed in the lipid-only group. The return to
spontaneous circulation was faster with the addition of
low-dose epinephrine (10 μg/kg), but with higher
epinephrine doses (>10 μg/kg), resuscitation was
impaired, possibly due to delayed cardiovascular collapse
from hyperlactatemia.
c. The conclusion is that high-dose epinephrine may impair
recovery from local anesthetic-induced cardiac arrest;
however, smaller doses of epinephrine with lipids may
speed early resuscitation by increasing coronary perfusion
pressure and increasing systemic vascular resistance
without having adverse effects on long-term recovery.102
This conclusion is reflected in the 2012 checklist for
treatment of LAST published by the American Society of
Regional Anesthesia and Pain Medicine.15,100
7. In extreme cases, treatment of bupivacaine toxicity may
require cardiopulmonary bypass.104

CLINICAL PEARL Treatment of severe local anesthetic toxicity

includes lipid emulsion (20%) therapy.
 IX. Other types of reactions may occur.
A. All local anesthetics demonstrate neurotoxicity if applied at
high enough concentrations for a long enough period of
time.105–107
1. In the 1990s, there were several case reports of cauda equina
syndrome following intrathecal 5% hyperbaric lidocaine
administration via a continuous microcatheter
technique.108,109 It has been hypothesized that pooling of the
local anesthetic through the small-gauge catheter resulted in
high local anesthetic concentrations around the cauda equina
and subsequent nerve damage.
2. Serious neurologic injury after regional anesthesia is rare
and is most often not related to local anesthetic
neurotoxicity but to trauma or other causes. In two large
surveys by Auroy,46,110 neurologic damage occurred rarely
but was more frequent after spinal than epidural anesthesia
and more frequent after lidocaine than other local anesthetics.
It should be noted that these surveys were not randomized
studies.
B. The syndrome of transient neurologic symptoms (TNS)
describes pain in the buttocks that radiates to both lower
extremities after the resolution of spinal anesthesia that
resolves within a few days. Reports of occurrence vary widely
from 0% to 37%.47 A recent meta-analysis showed lidocaine is
over four times more likely to produce TNS than bupivacaine,
prilocaine, or procaine; the incidence of TNS does not
decrease according to the dose, concentration, or osmolarity
of lidocaine, nor after dilution of lidocaine with cerebrospinal
fluid, nor is it affected by the presence of glucose.111–115 The
addition of phenylephrine to tetracaine caused an increased
incidence of TNS.17 TNS is also more common after cases done
in lithotomy position. Despite the name of the syndrome, it does
not seem to be associated with any neurologic abnormalities and
probably does not represent local anesthetic-induced
 neurotoxicity.111,116 It appears to occur less often in pregnant
patients.117

CLINICAL PEARL Lidocaine is over four times more likely to

produce TNS than bupivacaine, prilocaine, or procaine; the
incidence of TNS does not decrease according to the dose,
concentration, or osmolarity of lidocaine, nor after dilution of
lidocaine with cerebrospinal fluid, nor is it affected by presence of
glucose. TNS appears to occur less often in pregnant patients.

C. Back pain, not related to needle placement, which is poorly

localized, aching or burning, occurs after epidural chloroprocaine,
especially if ethylenediamine tetraacetic acid (EDTA) is used as a
preservative and/or if large volumes are used.118
D. Local anesthetics are myotoxic, including the newer drugs such
as ropivacaine.119 Dysregulation of intracellular calcium
concentrations produces skeletal muscle injury when local
anesthetics are inadvertently injected intramuscularly.
E. Allergic reactions to local anesthetics do occur, but they are
rare events.
1. Allergists estimate that less than 1% of reported allergic
reactions to local anesthetics are immune system–mediated
and that the majority of these cases actually involve
epinephrine reactions, vasovagal reactions, systemic
toxicity, etc.120 When 177 patients reporting adverse
reactions to local anesthetics were subjected to allergy tests
(skin prick, intracutaneous and subcutaneous challenge tests,
and radioimmunoassay to detect immunoglobulin E [IgE]),
only three patients had positive challenge results, none of
them IgE mediated. 121
2. Amino-ester hydrolysis yields para-aminobenzoic acid, or
PABA, which is a known allergen, so allergy to amino-esters
is more common than allergy to amino-amides. Amino-esters
 demonstrate cross-sensitivity regarding allergic reactions,
so all amino-esters should be avoided in patients
demonstrating allergy to one type. Amino-amides do not
exhibit cross-sensitivity either with each other or with
amino-esters. Allergy to paraben and sulfite preservatives
may occur.120
3. Obstetric patients presenting with a local anesthetic
“allergy” history should be sent as early as possible for
allergy consultation for provocative testing with
appropriate local anesthetic.

CLINICAL PEARL The majority of reports of allergic reactions

to local anesthetics actually involve epinephrine reactions,
vasovagal reactions, or systemic toxicity.

ACKNOWLEDGMENT
The authors wish to thank Ms. Yvonne Kennedy for her assistance in the
preparation of this manuscript.

REFERENCES
1. Catterall WA, Mackie K. Local anesthetics. In: Brunton LL, Chabner BA, Knollmann BC, eds.
Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. New York, NY: The
McGraw-Hill; 2011:565–582.
2. Groban L. Central nervous system and cardiac effects from long-acting amide local anesthetic toxicity
in the intact animal model. Reg Anesth Pain Med. 2003;28:3–11.
3. Butterworth JF IV, Strichartz GR. Molecular mechanisms of local anesthesia: a review.
Anesthesiology. 1990;72:711–734.
4. Tucker GT. Pharmacokinetics of local anaesthetics. Br J Anaesth. 1986;58:717–731.
5. Catterall WA. From ionic currents to molecular mechanisms: the structure and function of voltage-
gated sodium channels. Neuron. 2000;26:13–25.
6. Lin Y, Liu S. Local anesthetics. In: Barash PG, Cullen BF, Stoelting RK, et al, eds. Handbook of
Clinical Anesthesia. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013:310–324.
7. Huang JH, Thalhammer JG, Raymond SA, et al. Susceptibility to lidocaine of impulses in different
somatosensory afferent fibers of rat sciatic nerve. J Pharmacol Exp Ther. 1997;282:802–811.
8. Cook PR, Malmqvist LA, Bengtsson M, et al. Vagal and sympathetic activity during spinal analgesia.
Acta Anaesthesiol Scand. 1990;34:271–275.
9. Malmqvist LA, Bengtsson M, Björnsson G, et al. Sympathetic activity and haemodynamic variables
 during spinal analgesia in man. Acta Anaesthesiol Scand. 1987;31:467–473.
10. Chamberlain DP, Chamberlain BD. Changes in the skin temperature of the trunk and their relationship
to sympathetic blockade during spinal anesthesia. Anesthesiology. 1986;65:139–143.
11. Chestnut DH, Laszewski LJ, Pollack KL, et al. Continuous epidural infusion of 0.0625% bupivacaine-
0.0002% fentanyl during the second stage of labor. Anesthesiology. 1990;72:613–618.
12. Brull SJ, Greene NM. Time-courses of zones of differential sensory blockade during spinal anesthesia
with hyperbaric tetracaine or bupivacaine. Anesth Analg. 1989;69:342–347.
13. Brull SJ, Greene NM. Zones of differential sensory block during extradural anaesthesia. Br J Anaesth.
1991;66:651–655.
14. Polley LS, Columb MO, Naughton NN, et al. Effect of epidural epinephrine on the minimum local
analgesic concentration of epidural bupivacaine in labor. Anesthesiology. 2002;96:1123–1128.
15. Neal JM. Effects of epinephrine in local anesthetics on the central and peripheral nervous systems:
neurotoxicity and neural blood flow. Reg Anesth Pain Med. 2003;28:124–134.
16. Burm AG, van Kleef JW, Gladines MP, et al. Epidural anesthesia with lidocaine and bupivacaine:
effects of epinephrine on the plasma concentration profiles. Anesth Analg. 1986;65:1281–1284.
17. Sakura S, Sumi M, Sakaguchi Y, et al. The addition of phenylephrine contributes to the development
of transient neurologic symptoms after spinal anesthesia with 0.5% tetracaine. Anesthesiology.
1997;87:771–778.
18. Zhan Q, Huang S, Geng G, et al. Comparison of relative potency of intrathecal bupivacaine for motor
block in pregnant versus non-pregnant women. Int J Obstet Anesth. 2011;20:219–223.
19. Hirabayashi Y, Shimizu R, Saitoh K, et al. Cerebrospinal fluid progesterone in pregnant women. Br J
Anaesth. 1995;75:683–687.
20. Lee GY, Kim CH, Chung RK, et al. Spread of subarachnoid sensory block with hyperbaric
bupivacaine in second trimester of pregnancy. J Clin Anesth. 2009;21:482–485.
21. Hawkins JL, Chang J, Palmer SK, et al. Anesthesia-related maternal mortality in the United States:
1979-2002. Obstet Gynecol. 2011;117:69–74.
22. Butterworth JF IV, Walker FO, Lysak SZ. Pregnancy increases median nerve susceptibility to
lidocaine. Anesthesiology. 1990;72:962–965.
23. Flanagan HL, Datta S, Lambert DH, et al. Effect of pregnancy on bupivacaine-induced conduction
blockade in the isolated rabbit vagus nerve. Anesth Analg. 1987;66:123–126.
24. Popitz-Bergez FA, Leeson S, Thalhammer JG, et al. Intraneural lidocaine uptake compared with
analgesic differences between pregnant and nonpregnant rats. Reg Anesth. 1997;22:363–371.
25. Datta S, Lambert DH, Gregus J, et al. Differential sensitivities of mammalian nerve fibers during
pregnancy. Anesth Analg. 1983;62:1070–1072.
26. Hocking G, Wildsmith JA. Intrathecal drug spread. Br J Anaesth. 2004;93:568–578.
27. Abouleish EI. Postpartum tubal ligation requires more bupivacaine for spinal anesthesia than does
cesarean section. Anesth Analg. 1986;65:897–900.
28. Mayumi T, Dohi S, Takahashi T. Plasma concentrations of lidocaine associated with cervical, thoracic,
and lumbar epidural anesthesia. Anesth Analg. 1983;62:578–580.
29. Rosenberg PH, Veering BT, Urmey WF. Maximum recommended doses of local anesthetics: a
multifactorial concept. Reg Anesth Pain Med. 2004;29:564–575.
30. Burm AG, van der Meer AD, van Kleef JW, et al. Pharmacokinetics of the enantiomers of bupivacaine
following intravenous administration of the racemate. Br J Clin Pharmacol. 1994;38:125–129.
31. Dillane D, Finucane BT. Local anesthetic systemic toxicity. Can J Anaesth. 2010;57:368–380.
32. Burm AG, Vermeulen NP, van Kleef JW, et al. Pharmacokinetics of lignocaine and bupivacaine in
surgical patients following epidural administration. Simultaneous investigation of absorption and
disposition kinetics using stable isotopes. Clin Pharmacokinet. 1987;13:191–203.
33. Thomas JM, Schug SA. Recent advances in the pharmacokinetics of local anaesthetics. Long-acting
amide enantiomers and continuous infusions. Clin Pharmacokinet. 1999;36:67–83.
34. Richter O, Klein K, Abel J, et al. The kinetics of bupivacaine (Carbostesin) plasma concentrations
during epidural anesthesia following intraoperative bolus injection and subsequent continuous
infusion. Int J Clin Pharmacol Ther Toxicol. 1984;22:611–617.
35. Emanuelsson BM, Zaric D, Nydahl PA, et al. Pharmacokinetics of ropivacaine and bupivacaine during
21 hours of continuous epidural infusion in healthy male volunteers. Anesth Analg. 1995;81:1163–
1168.
36. Erichsen CJ, Sjövall J, Kehlet H, et al. Pharmacokinetics and analgesic effect of ropivacaine during
continuous epidural infusion for postoperative pain relief. Anesthesiology. 1996;84:834–842.
37. Burm AG, Stienstra R, Brouwer RP, et al. Epidural infusion of ropivacaine for postoperative analgesia
after major orthopedic surgery: pharmacokinetic evaluation. Anesthesiology. 2000;93:395–403.
38. Santos AC, Arthur GR, Lehning EJ, et al. Comparative pharmacokinetics of ropivacaine and
bupivacaine in nonpregnant and pregnant ewes. Anesth Analg, 1997;85:87–93.
39. Debon R, Chassard D, Duflo F, et al. Chronobiology of epidural ropivacaine: variations in the duration
of action related to the hour of administration. Anesthesiology. 2002;96:542–545.
40. Shafer SL, Lemmer B, Boselli E, et al. Pitfalls in chronobiology: a suggested analysis using intrathecal
bupivacaine analgesia as an example. Anesth Analg. 2010;111:980–998.
41. Simpson D, Curran MP, Oldfield V, et al. Ropivacaine: a review of its use in regional anaesthesia and
acute pain management. Drugs. 2005;65:2675–2717.
42. Mulroy MF. Systemic toxicity and cardiotoxicity from local anesthetics: incidence and preventive
measures. Reg Anesth Pain Med. 2002;27:556–561.
43. Hawkins JL, Koonin LM, Palmer SK, et al. Anesthesia-related deaths during obstetric delivery in the
United States, 1979-1990. Anesthesiology. 1997;86:277–284.
44. Bern S, Weinberg G. Local anesthetic toxicity and lipid resuscitation in pregnancy. Curr Opin
Anaesthesiol. 2011;24:262–267.
45. Brown DL, Ransom DM, Hall JA, et al. Regional anesthesia and local anesthetic-induced systemic
toxicity: seizure frequency and accompanying cardiovascular changes. Anesth Analg. 1995;81:321–
328.
46. Auroy Y, Narchi P, Messiah A, et al. Serious complications related to regional anesthesia: results of a
prospective survey in France. Anesthesiology. 1997;87:479–486.
47. Faccenda KA, Finucane BT. Complications of regional anaesthesia incidence and prevention. Drug
Saf. 2001;24:413–442.
48. Mather LE, Copeland SE, Ladd LA. Acute toxicity of local anesthetics: underlying pharmacokinetic
and pharmacodynamic concepts. Reg Anesth Pain Med. 2005;30:553–566.
49. Knudsen K, Beckman Suurküla M, Blomberg S, et al. Central nervous and cardiovascular effects of
i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers. Br J Anaesth. 1997;78:507–514.
50. Rutten AJ, Nancarrow C, Mather LE, et al. Hemodynamic and central nervous system effects of
intravenous bolus doses of lidocaine, bupivacaine, and ropivacaine in sheep. Anesth Analg.
1989;69:291–299.
51. Chang DH, Ladd LA, Copeland S, et al. Direct cardiac effects of intracoronary bupivacaine,
levobupivacaine and ropivacaine in the sheep. Br J Pharmacol. 2001;132:649–658.
52. Reiz S, Häggmark S, Johansson G, et al. Cardiotoxicity of ropivacaine—a new amide local anaesthetic
agent. Acta Anaesthesiol Scand. 1989;33:93–98.
53. Graf BM. The cardiotoxicity of local anesthetics: the place of ropivacaine. Curr Top Med Chem.
2001;1:207–214.
54. Nau C, Strichartz GR. Drug chirality in anesthesia. Anesthesiology. 2002;97:497–502.
55. Moller R, Covino BG. Cardiac electrophysiologic properties of bupivacaine and lidocaine compared
with those of ropivacaine, a new amide local anesthetic. Anesthesiology. 1990;72:322–329.
56. Nancarrow C, Rutten AJ, Runciman WB, et al. Myocardial and cerebral drug concentrations and the
mechanisms of death after fatal intravenous doses of lidocaine, bupivacaine, and ropivacaine in the
sheep. Anesth Analg. 1989;69:276–283.
57. Feldman HS, Arthur GR, Covino BG. Comparative systemic toxicity of convulsant and
supraconvulsant doses of intravenous ropivacaine, bupivacaine, and lidocaine in the conscious dog.
Anesth Analg. 1989;69:794–801.
58. Clarkson CW, Hondeghem LM. Mechanism for bupivacaine depression of cardiac conduction: fast
block of sodium channels during the action potential with slow recovery from block during diastole.
Anesthesiology. 1985;62:396–405.
59. Morrison SG, Dominguez JJ, Frascarolo P, et al. A comparison of the electrocardiographic cardiotoxic
effects of racemic bupivacaine, levobupivacaine, and ropivacaine in anesthetized swine. Anesth Analg.
2000;90:1308–1314.
60. Polley LS, Columb MO, Naughton NN, et al. Relative analgesic potencies of ropivacaine and
bupivacaine for epidural analgesia in labor: implications for therapeutic indexes. Anesthesiology.
1999;90:944–950.
61. Capogna G, Celleno D, Fusco P, et al. Relative potencies of bupivacaine and ropivacaine for analgesia
in labour. Br J Anaesth. 1999;82:371–373.
62. Camorcia M, Capogna G, Columb MO. Minimum local analgesic doses of ropivacaine,
levobupivacaine, and bupivacaine for intrathecal labor analgesia. Anesthesiology. 2005;102:646–650.
63. D’Angelo R, James RL. Is ropivacaine less potent than bupivacaine? Anesthesiology. 1999;90:941–
943.
64. Van de Velde M, Dreelinck R, Dubois J, et al. Determination of the full dose-response relation of
intrathecal bupivacaine, levobupivacaine, and ropivacaine, combined with sufentanil, for labor
analgesia. Anesthesiology. 2007;106:149–156.
65. Stienstra R. The place of ropivacaine in anesthesia. Acta Anaesthesiol Belg. 2003;54:141–148.
66. Dony P, Dewinde V, Vanderick B, et al. The comparative toxicity of ropivacaine and bupivacaine at
equipotent doses in rats. Anesth Analg. 2000;91:1489–1492.
67. Groban L, Deal DD, Vernon JC, et al. Cardiac resuscitation after incremental overdosage with
lidocaine, bupivacaine, levobupivacaine, and ropivacaine in anesthetized dogs. Anesth Analg.
2001;92:37–43.
68. Yoshida M, Matsuda H, Fukuda I, et al. Sudden cardiac arrest during cesarean section due to epidural
anaesthesia using ropivacaine: a case report. Arch Gynecol Obstet. 2008;277:91–94.
69. Chazalon P, Tourtier JP, Villevielle T, et al. Ropivacaine-induced cardiac arrest after peripheral nerve
block: successful resuscitation. Anesthesiology. 2003;99:1449–1451.
70. Klein SM, Pierce T, Rubin Y, et al. Successful resuscitation after ropivacaine-induced ventricular
fibrillation. Anesth Analg. 2003;97:901–903.
71. Butterworth JF IV. Models and mechanisms of local anesthetic cardiac toxicity: a review. Reg Anesth
Pain Med. 2010;35:167–176.
72. Neal JM, Bernards CM, Butterworth JF, et al. ASRA practice advisory on local anesthetic systemic
toxicity. Reg Anesth Pain Med. 2010;35:152–161.
73. Neal JM, Mulroy MF, Weinberg GL, et al. American Society of Regional Anesthesia and Pain
Medicine checklist for managing local anesthetic systemic toxicity: 2012 version. Reg Anesth Pain
Med. 2012;37:16–18.
74. Morishima HO, Pedersen H, Finster M, et al. Bupivacaine toxicity in pregnant and nonpregnant ewes.
Anesthesiology. 1985;63:134–139.
75. Santos AC, Arthur GR, Wlody D, et al. Comparative systemic toxicity of ropivacaine and bupivacaine
in nonpregnant and pregnant ewes. Anesthesiology. 1995;82:734–740.
76. Santos AC, DeArmas PI. Systemic toxicity of levobupivacaine, bupivacaine, and ropivacaine during
continuous intravenous infusion to nonpregnant and pregnant ewes. Anesthesiology. 2001;95:1256–
1264.
77. Mulroy MF. Local anesthetics: helpful science, but don’t forget the basic clinical safety steps. Reg
Anesth Pain Med. 2005;30:513–515.
78. Weinberg GL. Current concepts in resuscitation of patients with local anesthetic cardiac toxicity. Reg
Anesth Pain Med. 2002;27:568–575.
79. Birnbach DJ, Chestnut DH. The epidural test dose in obstetric patients: has it outlived its usefulness?
Anesth Analg. 1999;88:971–972.
80. Guay J. The epidural test dose: a review. Anesth Analg. 2006;102:921–929.
81. Leighton BL, Norris MC, DeSimone CA, et al. The air test as a clinically useful indicator of
intravenously placed epidural catheters. Anesthesiology. 1990;73:610–613.
82. Feldman HS, Arthur GR, Pitkanen M, et al. Treatment of acute systemic toxicity after the rapid
intravenous injection of ropivacaine and bupivacaine in the conscious dog. Anesth Analg.
1991;73:373–384.
83. McCutchen T, Gerancher JC. Early intralipid therapy may have prevented bupivacaine-associated
cardiac arrest. Reg Anesth Pain Med. 2008;33:178–180.
84. Sage DJ, Feldman HS, Arthur GR, et al. Influence of lidocaine and bupivacaine on isolated guinea pig
atria in the presence of acidosis and hypoxia. Anesth Analg. 1984;63:1–7.
85. Heavner JE, Dryden CF Jr, Sanghani V, et al. Severe hypoxia enhances central nervous system and
cardiovascular toxicity of bupivacaine in lightly anesthetized pigs. Anesthesiology. 1992;77:142–147.
86. Haasio J, Pitkänen MT, Kyttä J, et al. Treatment of bupivacaine-induced cardiac arrhythmias in
hypoxic and hypercarbic pigs with amiodarone or bretylium. Reg Anesth. 1990;15:174–179.
87. Corcoran W, Butterworth J, Weller RS, et al. Local anesthetic-induced cardiac toxicity: a survey of
contemporary practice strategies among academic anesthesiology departments. Anesth Analg.
2006;103:1322–1326.
88. Weinberg GL, VadeBoncouer T, Ramaraju GA, et al. Pretreatment or resuscitation with a lipid infusion
shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology. 1998;88:1071–1075.
89. Weinberg GL, Ripper R, Murphy P, et al. Lipid infusion accelerates removal of bupivacaine and
recovery from bupivacaine toxicity in the isolated rat heart. Reg Anesth Pain Med. 2006;31:296–303.
90. Weinberg G, Ripper R, Feinstein DL, et al. Lipid emulsion infusion rescues dogs from bupivacaine-
induced cardiac toxicity. Reg Anesth Pain Med. 2003;28:198–202.
91. Picard J, Meek T. Lipid emulsion to treat overdose of local anaesthetic: the gift of the glob.
Anaesthesia. 2006;61:107–109.
92. Shi K, Xia Y, Wang Q, et al. The effect of lipid emulsion on pharmacokinetics and tissue distribution
of bupivacaine in rats. Anesth Analg. 2013;116:804–809.
93. Kuo I, Akpa BS. Validity of the lipid sink as a mechanism for the reversal of local anesthetic systemic
toxicity: a physiologically based pharmacokinetic model study. Anesthesiology. 2013;118:1350–1361.
94. Rosenblatt MA, Abel M, Fischer GW, et al. Successful use of a 20% lipid emulsion to resuscitate a
patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology. 2006;105:217–218.
95. Litz RJ, Popp M, Stehr SN, et al. Successful resuscitation of a patient with ropivacaine-induced
asystole after axillary plexus block using lipid infusion. Anaesthesia. 2006;61:800–801.
96. Spence AG. Lipid reversal of central nervous system symptoms of bupivacaine toxicity.
Anesthesiology. 2007;107:516–517.
97. Marwick PC, Levin AI, Coetzee AR. Recurrence of cardiotoxicity after lipid rescue from bupivacaine-
 induced cardiac arrest. Anesth Analg. 2009;108:1344–1346.
98. Wolfe JW, Butterworth JF. Local anesthetic systemic toxicity: update on mechanisms and treatment.
Curr Opin Anaesthesiol. 2011;24:561–566.
99. Litz RJ, Roessel T, Heller AR, et al. Reversal of central nervous system and cardiac toxicity after local
anesthetic intoxication by lipid emulsion injection. Anesth Analg. 2008;106:1575–1577.
100. Weinberg GL. Treatment of local anesthetic systemic toxicity (LAST). Reg Anesth Pain Med.
2010;35:188–193.
101. Di Gregorio G, Schwartz D, Ripper R, et al. Lipid emulsion is superior to vasopressin in a rodent
model of resuscitation from toxin-induced cardiac arrest. Crit Care Med. 2009;37:993–999.
102. Hiller DB, Gregorio GD, Ripper R, et al. Epinephrine impairs lipid resuscitation from bupivacaine
overdose: a threshold effect. Anesthesiology. 2009;111:498–505.
103. Harvey M, Cave G, Prince G, et al. Epinephrine injection in lipid-based resuscitation from
bupivacaine-induced cardiac arrest: transient circulatory return in rabbits. Anesth Analg.
2010;111:791–796.
104. Long WB, Rosenblum S, Grady IP. Successful resuscitation of bupivacaine-induced cardiac arrest
using cardiopulmonary bypass. Anesth Analg. 1989;69:403–406.
105. Li DF, Bahar M, Cole G, et al. Neurological toxicity of the subarachnoid infusion of bupivacaine,
lignocaine or 2-chloroprocaine in the rat. Br J Anaesth. 1985;57:424–429.
106. Lambert LA, Lambert DH, Strichartz GR. Irreversible conduction block in isolated nerve by high
concentrations of local anesthetics. Anesthesiology. 1994;80:1082–1093.
107. Kanai Y, Katsuki H, Takasaki M. Lidocaine disrupts axonal membrane of rat sciatic nerve in vitro.
Anesth Analg. 2000;91:944–948.
108. Rigler ML, Drasner K, Krejcie TC, et al. Cauda equina syndrome after continuous spinal anesthesia.
Anesth Analg. 1991;72:275–281.
109. Schell RM, Brauer FS, Cole DJ, et al. Persistent sacral nerve root deficits after continuous spinal
anaesthesia. Can J Anaesth. 1991;38:908–911.
110. Auroy Y, Benhamou D, Bargues L, et al. Major complications of regional anesthesia in France: The
SOS Regional Anesthesia Hotline Service. Anesthesiology. 2002;97:1274–1280.
111. Zaric D, Christiansen C, Pace NL, et al. Transient neurologic symptoms (TNS) following spinal
anaesthesia with lidocaine versus other local anaesthetics. Cochrane Database Syst Rev. 2005;
(4):CD003006.
112. Hampl KF, Schneider MC, Pargger H, et al. A similar incidence of transient neurologic symptoms
after spinal anesthesia with 2% and 5% lidocaine. Anesth Analg. 1996;83:1051–1054.
113. Pollock JE, Liu SS, Neal JM, et al. Dilution of spinal lidocaine does not alter the incidence of transient
neurologic symptoms. Anesthesiology. 1999;90:445–450.
114. Tong D, Wong J, Chung F, et al. Prospective study on incidence and functional impact of transient
neurologic symptoms associated with 1% versus 5% hyperbaric lidocaine in short urologic
procedures. Anesthesiology. 2003;98:485–494.
115. Hampl KF, Schneider MC, Thorin D, et al. Hyperosmolarity does not contribute to transient radicular
irritation after spinal anesthesia with hyperbaric 5% lidocaine. Reg Anesth. 1995;20:363–368.
116. Pollock JE, Burkhead D, Neal JM, et al. Spinal nerve function in five volunteers experiencing transient
neurologic symptoms after lidocaine subarachnoid anesthesia. Anesth Analg. 2000;90:658–665.
117. Wong CA, Slavenas P. The incidence of transient radicular irritation after spinal anesthesia in obstetric
patients. Reg Anesth Pain Med. 1999;24:55–58.
118. Stevens RA, Urmey WF, Urquhart BL, et al. Back pain after epidural anesthesia with chloroprocaine.
Anesthesiology. 1993;78:492–497.
119. Zink W, Seif C, Bohl JR, et al. The acute myotoxic effects of bupivacaine and ropivacaine after
 continuous peripheral nerve blockades. Anesth Analg. 2003;97:1173–1179.
120. Finucane BT. Allergies to local anesthetics—the real truth. Can J Anaesth. 2003;50:869–874.
121. Gall H, Kaufmann R, Kalveram CM. Adverse reactions to local anesthetics: analysis of 197 cases. J
Allergy Clin Immunol. 1996;97:933–937.
 Obstetric Medications
Ruchira Patel and Mrinalini Balki

I. Tocolytic medications
A. β-Mimetic therapy
B. Calcium channel blockers
C. Magnesium sulfate
D. Cyclooxygenase (prostaglandin synthase) inhibitors
E. Nitroglycerin
F. Oxytocin antagonists (atosiban)
II. Uterotonic medications
A. Oxytocin
B. Carbetocin
C. Ergot alkaloids (ergonovine or methylergonovine)
D. Prostaglandins (F2α, E1, and E2 analog)

KEYPOINTS
1. β-Mimetic agents, calcium channel blockers, or nonsteroidal anti-
inflammatory drugs (NSAIDs) are the most commonly used tocolytics for
the short-term prolongation of pregnancy (up to 48 hours) to allow for the
administration of antenatal steroids or for women to be transferred to
tertiary care.
2. Magnesium sulfate is mainly indicated for the prevention and treatment
 of seizures in severe preeclampsia and for fetal neuroprotection in
threatened preterm (<32 weeks) labor; however, it has a limited role in
tocolysis.
3. Oxytocin is considered the first-line agent for the treatment of postpartum
hemorrhage secondary to uterine atony, followed by ergonovine and
prostaglandins; however, a multimodal pharmacotherapy approach is
recommended.
4. The commonly encountered side effects of uterotonic drugs include
hypotension with oxytocin, hypertension with ergonovine, and
bronchospasm with carboprost.

THE UTERUS IS MADE UP of three layers (serosa, myometrium, and

endometrium). In pregnancy, the uterus increases in average weight from 30–60
g to 750–1,000 g due to hyperplasia and hypertrophy of the smooth muscle
within the myometrium, largely due to the influence of estrogen. The myometrial
smooth muscle cells communicate with one another through connections called
gap junctions. In the final weeks of pregnancy, when irregular contractions
increase, the myometrial gap junctions increase in number until the
commencement of labor. These junctions are believed to synchronize
myometrial contractility by the conduction of electrical activity during labor.
Depolarization results in an increase in intracellular calcium and uterine smooth
muscle contraction.
Hormonal changes play an important role in myometrial contractility, leading
up to the time of labor. Because the ratio of estrogen to progesterone rises in the
last trimester, there is an increase in the number and sensitivity of oxytocin
receptors. Thus, the ability of oxytocin to contract the uterus is increased
significantly.
Uterine contractility can be influenced by drugs that relax the uterus
(tocolytic medications), to prevent threatened preterm labor, and drugs that
stimulate the uterus (uterotonic medications), for the induction/augmentation of
labor, to aid with delivery of the placenta, and prevent postpartum hemorrhage
(PPH).
I. Tocolytic medications
Preterm birth, defined as birth occurring before 37 completed weeks
of pregnancy, is the leading cause of neonatal mortality and morbidity
worldwide. Tocolytic medications are mainly indicated for the
prolongation of pregnancy for short intervals in women with preterm
labor. The rationale for using tocolytics is to improve perinatal
outcomes by (a) enhancing fetal lung maturation by giving
corticosteroid treatment to the mother, (b) administering
antibiotic therapy to the mother to prevent neonatal group B
streptococcal infection, (c) allowing time to treat any underlying
cause of preterm labor, and (d) allowing time for maternal
transfer to a tertiary care center with better facilities for care of
the premature newborn including neonatal intensive care
facilities.
Although tocolytic medications are most often used in the setting of
preterm labor, they have several other obstetric uses.
A. β-Mimetic therapy
1. Drugs
a. Terbutaline
b. Ritodrine
c. Salbutamol
2. Uses
a. Tocolysis for preterm labor
β-Mimetic agents are used for the prolongation of
pregnancy in women with threatened preterm labor
who would benefit from a 48-hour delay in delivery.1 A
Cochrane review found that the use of β-mimetic therapy
decreased the number of women giving birth within 48
hours (relative risk [RR] 0.68; 95% confidence interval
[CI], 5.3 to 0.88) and within 7 days (RR 0.80; 95% CI,
0.65 to 0.98) but not before 37 weeks of gestation (RR
0.95; 95% CI, 0.88 to 1.03) as compared to placebo.2 β-
Mimetic agents are associated with a reduction in
neonatal respiratory distress syndrome but have no
effect on the neonatal death rate.1 Data are too limited
 to support the use of any particular β-mimetic drug over
another. However, in the United States, terbutaline is the
most commonly used drug, whereas ritodrine is no longer
available in Canada or the United States. The U.S. Food
and Drug Administration (FDA) has warned that
injectable terbutaline should not be used to prevent
preterm labor for longer than 48 to 72 hours because of
the potential for serious maternal risk associated with
these agents.3 A systematic review assessing ritodrine in
preterm labor concluded that the effectiveness of
intravenous ritodrine was limited and the use of oral
ritodrine was not supported.4
b. Uterine hypertonus
In the setting of uterine hypertonus and nonreassuring
fetal heart rate, which often results from aggressive
oxytocin administration, the use of β-agonists to acutely
relax the uterus can be useful. For many clinicians, this is
the primary indication for their use. After combined
spinal-epidural (CSE) placement, unopposed oxytocin-
induced tetany can result from rapidly decreasing
catecholamine levels, primarily epinephrine. The
unopposed norepinephrine action may result in
myometrial contractility. β-Agonists should be considered
in these situations.
3. Mechanism of action
β-Receptor agonists cause uterine smooth muscle relaxation
by binding to uterine β2 receptors and increasing intracellular
adenyl cyclase. This leads to an increase in intracellular cyclic
AMP, activation of protein kinase, and phosphorylation of
intracellular proteins. The subsequent reduction in
intracellular calcium interferes with the activity of myosin
light-chain kinase and decreases myometrial contractility (see
Fig. 4.1).
4. Route of administration/dose
a. Terbutaline can be administered intravenously (IV) or
subcutaneously (SC). However, it is most commonly
administered by intermittent injection in doses of 0.25 mg
every 20 to 30 minutes up to 4 doses until uterine
quiescence is achieved. Terbutaline (0.25 mg) can then be
administered subcutaneously every 3 to 4 hours. For acute
tocolysis, terbutaline can be administered IV at a rate of
2.5–5 mcg/min. The dose is increased by 2.5–5 mcg/min
up to a maximum of 25 mcg/min. The infusion rate
should be titrated based on uterine quiescence or maternal
side effects. One or two doses of 0.25 μg IV or SC are
often effective in relieving uterine hypertonus.
b. Salbutamol 100 μg IV or terbutaline 250 μg IV over 1 to 2
minutes can be useful for uterine hyperstimulation.
c. Ritodrine 50 μg per minute IV is increased by 50 μg per
minute every 10 minutes until response is achieved,
usually at 150 μg per minute, with a maximum dose 350
μg per minute. Alternatively, 10 mg IM can be given
 every 3 to 8 hours for 12 to 48 hours. Once contractions
have stopped after IV or IM treatment, 10 mg can be
given orally every 2 hours for 24 hours, followed by 10 to
20 mg every 4 to 6 hours to a maximum of 120 mg daily.
5. Toxicity/side effects (see Table 4.1)

a. Maternal cardiopulmonary side effects are mainly related

to the stimulation of β1 receptors leading to tachycardia,
dysrhythmias, and myocardial ischemia due to increased
oxygen demand. Careful consideration should be given to
their use in parturients with significant cardiac disease.
b. β2 receptor stimulation can cause hyperglycemia and
hypokalemia. Their use is contraindicated in women with
uncontrolled diabetes.
c. Pulmonary edema is a rare but serious complication of β-
agonist use in pregnancy. The etiology is multifactorial
and includes physiologic plasma volume expansion in
pregnancy, exacerbated by β2-mediated increased
pulmonary capillary permeability and β1-mediated left
ventricular failure, particularly in women with preexisting
cardiac disease.5
d. The central nervous system symptoms associated with the
use of β-mimetic therapy include tremors, headache, and
 nervousness.
e. Fetal tachycardia and hypoglycemia can occur as these
drugs readily cross the placenta.
6. Anesthetic considerations
a. Cardiovascular side effects, typically tachycardia and
hypotension, can occur even after discontinuation of the
drug due to prolonged half-lives of these medications in
pregnant women (up to 90 minutes). Therefore, anesthetic
drugs that cause tachycardia should be avoided and
profound tachycardia should be treated with β-blockers.
Treatment of hypotension with either ephedrine or
phenylephrine, depending on the heart rate, is acceptable.
b. One should avoid aggressive hydration prior to neuraxial
block because these patients are at risk for the
development of pulmonary edema. The amount of fluids
should be carefully titrated, and vasopressors should be
used to maintain normal blood pressure.
c. Hyperventilation should be avoided because it can lead to
respiratory alkalosis and worsen hypokalemia due to
intracellular movement of potassium.
d. These drugs should be used with caution in women at risk
for massive hemorrhage due to the increased risk of
hypotension and tachycardia. The presence of these signs
may interfere with the ability of the mother to compensate
for the hemorrhagic response and also confuse the clinical
presentation.
e. These drugs are relatively contraindicated in patients with
tachycardia-sensitive heart disease, poorly controlled
hyperthyroidism, or diabetes mellitus due to the potential
for worsening metabolic effects.
f. Prolonged use of these drugs can result in desensitization
of the β receptors and tachyphylaxis.

CLINICAL PEARL The cardiovascular effects of β-agonist

therapy can persist for more than 1 hour after discontinuation of
their use; means to treat severe maternal tachycardia should be
available if emergency anesthesia and fetal delivery is required.

B. Calcium channel blockers

1. Nifedipine is the most commonly administered calcium
channel blocker.
Calcium channel blockers are divided into two major
categories based on their predominant physiologic effects:
dihydropyridines, which are predominantly vasodilators, and
the nondihydropyridines, which reduce vascular permeability.
Nifedipine is a short-acting dihydropyridine and is the main
calcium channel blocker used in pregnant women.
2. Uses
a. Tocolysis to prolong pregnancy in threatened preterm
labor. In a systematic review and meta-analysis of
Cochrane Collaboration, the use of a calcium channel
blocker reduced the risk of delivery within 48 hours of
trial entry compared with placebo/no treatment (RR
0.30; 95% CI, 0.21 to 0.43), but there was no statistically
significant reduction in this outcome compared with other
classes of tocolytics such as β-agonists, glyceryl trinitrate
patch, nonsteroidal anti-inflammatory drugs (NSAIDs),
magnesium sulphate, and oxytocin receptor antagonists.
However, calcium channel blockers showed significant
benefits over β-agonists with respect to prolongation of
pregnancy, serious neonatal morbidity, and maternal
adverse effects.6 The relative safety, maternal
tolerance, ease of administration, and reduction in
adverse neonatal outcomes support the use of
nifedipine over other tocolytic drugs for inhibition of
acute preterm labor.6
b. Antihypertensive therapy in acute hypertensive
situations. Nifedipine is most commonly used over other
 calcium channel blockers because of its minimal effects
on the cardiac conducting system.7 Nifedipine causes
vasodilation of the systemic and pulmonary vasculature,
which is reversed on stopping the drug and it exhibits a
lack of tachyphylaxis.7
3. Mechanism of action. Calcium channel blockers directly
block the influx of calcium ions across L-type channels of cell
membranes. They also inhibit the release of intracellular
calcium from the sarcoplasmic reticulum and increase
calcium efflux from the cell. The resulting decrease in
intracellular free calcium leads to inhibition of calcium-
dependent myosin light-chain kinase phosphorylation and in
smooth muscle relaxation of the blood vessels and uterus (see
Fig. 4.1).
4. Route of administration/dose
a. Nifedipine 20 to 30 mg oral loading dose is followed by
10 to 20 mg every 4 to 6 hours to a maximum of 180 mg
per day. This can be given for up to 72 hours to inhibit
preterm labor.
b. Long-acting nifedipine 30 to 90 mg once daily as a
sustained release tablet can be administered for
hypertension in pregnancy.
5. Toxicity/side effects
a. Peripheral vasodilatation from nifedipine results in
decreased systemic vascular resistance and may cause
symptoms such as nausea, flushing, headache, dizziness,
and palpitations.
b. A compensatory increase in heart rate and stroke volume
results in an increase in cardiac output, which maintains
blood pressure in women with no underlying cardiac
dysfunction.8
c. There have been case reports of severe hypotension with
adverse fetal effects following nifedipine
administration.9,10
 6. Anesthetic considerations
a. A variable degree of hypotension may occur
intraoperatively.
b. Conduction abnormalities can also be seen when
combined with an inhalational agent.
c. The coadministration of a calcium channel blocker and
magnesium sulfate can synergistically suppress muscular
contractility and result in maternal respiratory depression
due to respiratory muscle weakness.11
d. Refractory PPH can occur in the setting of uterine atony.
Because oxytocin and prostaglandin agonists act through
calcium channel mechanisms, their effect in treating
uterine atony may also be limited.12

CLINICAL PEARL Calcium channel blockers interfere with the

action of oxytocin and prostaglandins and may act synergistically
with concomitant magnesium therapy to inhibit calcium activity and
increase the risk of obstetric hemorrhage.

C. Magnesium sulfate
1. Uses
a. Prevention and treatment of seizures in
preeclampsia/eclampsia. Magnesium sulfate is
recommended in patients with preeclampsia for whom
there is concern about the risk of eclampsia.13 The
Magpie trial demonstrated that women with
preeclampsia who were given magnesium had a 58%
lower risk of eclampsia than those allocated to receive
placebo.14 The number needed to treat to prevent one
seizure for women with severe preeclampsia was 63 (95%
CI, 38 to 181) and for those without severe preeclampsia
was 109 (95% CI, 72 to 225). The American College of
Obstetricians and Gynecologists (ACOG)15
 recommends administration of magnesium sulfate to
women with eclampsia and preeclampsia with severe
features but not to those with mild preeclampsia
without any symptoms or gestational hypertension.
Magnesium sulfate is usually continued for 24 hours
postpartum.
b. Fetal neurodevelopment. Antenatal magnesium sulfate
therapy for women at risk for preterm birth is
established as being neuroprotective against motor
disorders for the preterm fetus.16,17 Magnesium therapy
given to women at risk for preterm birth substantially
reduced the risk of cerebral palsy in their children (RR
0.68; 95% CI, 0.54 to 0.87). The number of women
needed to treat to prevent one baby from developing
cerebral palsy was 63 (95% CI, 43 to 155). Two large
randomized controlled trials further support the use of
prenatal magnesium for preventing neurodisabilities in
preterm infants.18,19
c. Tocolysis to prolong pregnancy. Magnesium sulfate
inhibits uterine activity and has been used as a tocolytic
agent in women with preterm labor to prevent delivery.
However, its efficacy in preventing preterm delivery has
been shown on numerous occasions to be equivalent to
placebo. A recent Cochrane review found that magnesium
sulfate is ineffective at delaying birth or preventing
preterm birth, has no apparent advantages for a range of
neonatal and maternal outcomes as a tocolytic agent, and
its use for this indication may be associated with an
increased risk of total fetal, neonatal, or infant mortality.20
The ACOG, however, continues to support the short-term
use of magnesium for up to 48 hours to allow for the
administration of corticosteroids in women between 24
and 34 weeks’ gestation with preterm labor.21
CLINICAL PEARL Magnesium significantly improves
pulmonary and neurologic outcomes in neonates delivered preterm
and thus is used commonly in women with both preeclampsia who
often deliver preterm and in the treatment of preterm labor.

2. Mechanism of action
a. The anticonvulsant effect of magnesium sulfate is
attributed to its antagonistic action on the N-methyl-D-
aspartate (NMDA) receptor and direct cerebral
vasodilatation.
b. It competes with calcium for binding sites on the
sarcoplasmic reticulum and decreases intracellular
calcium levels. It hyperpolarizes the plasma membrane
and inhibits myosin light-chain kinase activity reducing
myometrial contractility (see Fig. 4.1).
c. It increases PGI2 production by vascular endothelium
resulting in smooth muscle relaxation and dilation.
3. Route of administration/dose
a. Magnesium sulfate is given as a bolus 4 to 6 g IV over 20
minutes and then as an infusion of 1 to 2 g per hour for
short-term (usually less than 48 hours) use in preterm
labor or fetal neuroprotection.
b. In the prevention and treatment of seizures, it is
administered in similar doses and continued for up to 24
hours postpartum.
4. Toxicity/side effects
a. Increasing plasma levels of magnesium are associated
with adverse effects (see Table 4.2). Because severe
adverse effects are seen above the plasma magnesium
level at which deep tendon reflexes are lost, patients
should be monitored by regularly checking reflexes.
 b. Fetal cardiac or respiratory effects are not of concern
unless maternal toxicity is present.
c. It may prolong labor and increase the risk of PPH due to
its tocolytic effect.
d. Magnesium is renally excreted and hence toxicity is more
common in patients with renal impairment.
e. If magnesium toxicity occurs, the infusion should be
discontinued, and either 10 mL of calcium chloride 10%
or 30 mL of calcium gluconate 10% administered by slow
intravenous infusion.
5. Anesthetic considerations
a. Magnesium causes generalized muscle weakness; hence,
it is contraindicated in women with myasthenia gravis.
b. Magnesium increases the sensitivity to muscle relaxants.
A defasciculating dose of a nondepolarizing muscle
relaxant before succinylcholine administration should be
avoided. The intubating dose of succinylcholine does not
need to be altered; however, the maintenance dose of
nondepolarizing agents should be reduced.
c. Magnesium use may exacerbate hypotension caused by
hemorrhage or neuroaxial block due to a decrease in
systemic vascular resistance.
d. Magnesium has been shown to inhibit platelet function, to
decrease the amount of inhaled volatile agents required,
and to amplify the analgesic effect of opioids.
e. Magnesium toxicity can lead to respiratory depression and
cardiac arrest (see Table 4.2).
D. Cyclooxygenase (prostaglandin synthase) inhibitors
1. Drugs
a. Indomethacin
b. Sulindac
c. Ketorolac
2. Uses. Tocolysis to prolong pregnancy in threatened preterm
labor
a. The enzyme cyclooxygenase (COX), officially known as
prostaglandin-endoperoxide synthase, exists in two
isoforms: COX-1 synthesizes protective prostaglandins,
which are responsible for preserving the integrity of the
stomach lining, renal function, and platelet aggregation;
COX-2 is induced during the inflammatory process and
prostaglandins made by COX-2 are also important for
inducing uterine contractions during labor.22 NSAIDs
such as indomethacin can therefore delay premature labor
by inhibiting production of these prostaglandins.
b. Indomethacin is the most commonly used NSAID in
cases of threatened preterm labor. A Cochrane review
found that compared to placebo, indomethacin resulted in
a reduction in birth before 37 weeks’ gestation (RR 0.21;
95% CI, 0.07 to 0.62), an increase in gestational age
(weighted mean difference [WMD] 3.53 weeks; 95% CI,
1.13 to 5.92), and birth weight (WMD 716 g; 95% CI,
426 to 1,007). In addition, compared to other tocolytics,
COX inhibition resulted in a reduction in maternal drug
reactions requiring cessation of treatment. Surprisingly,
no differences were detected in neonatal outcomes.23
c. There is some data on the use of selective COX-2
inhibitors (nimesulide,24 celecoxib,25 rofecoxib26,27) for
the treatment of preterm labor; however, most of these
agents have been withdrawn or issued with black box
warnings because of the adverse cardiovascular risk and
severe fetal side effects associated with their use.28
3. Mechanism of action
 a. NSAIDs inhibit COX (prostaglandin synthase) enzyme,
which reduces the synthesis of prostaglandins from the
precursor arachidonic acid (see Fig. 4.1). The extent of
enzyme inhibition varies among different NSAIDs, by
either general inhibition or specific inhibition of COX-2.
The synthesis of prostaglandins E2 and F2α, which are
potent uterine smooth muscle stimulants, is decreased.
b. Indomethacin is a nonspecific COX inhibitor.
4. Route of administration/dose
a. Indomethacin 50 to 100 mg oral or rectal loading dose is
followed by 25 to 50 mg every 4 to 6 hours.
b. It is recommended for use only before 32 weeks’
gestation and should only continue for 48 to 72 hours due
to the risk of severe fetal side effects.
5. Toxicity/side effects
a. The maternal gastrointestinal side effects associated with
the use of these medications include nausea, esophageal
reflux, gastritis, and emesis.
b. Platelet dysfunction is seen due to inhibition of
thromboxane A2.
c. Renal function may worsen in patients with renal
insufficiency from decreased renal blood flow. This is due
to inhibition of prostaglandin E2 and I2 activity.
d. There is an increased risk of cardiovascular side effects
such as myocardial infarction and stroke.

CLINICAL PEARL Despite minimal maternal side effects, the

risk of severe fetal side effects of premature ductus closure,
necrotizing enterocolitis, and oligohydramnios limits use of
NSAIDs in this setting.

6. Anesthetic considerations
a. Anesthetic management is not significantly impacted.
 b. Platelet inhibition is reversible and transient; therefore,
neuraxial anesthesia is not contraindicated.
E. Nitroglycerin
1. Uses. Nitroglycerin is used for multiple indications. It
induces rapid, profound, and short-duration uterine
relaxation for:
a. Fetal head entrapment
b. Extraction of second twin
c. Manual removal of placenta
d. Uterine inversion
e. External cephalic version
f. Preeclampsia
g. Tetanic contractions of uterus
2. Mechanism of action
a. Nitroglycerin is converted to nitric oxide, which activates
guanylate cyclase and increases cGMP. This in turn
inhibits calcium influx and relaxes smooth muscle (see
Fig. 4.1).
b. At low doses, nitroglycerin will dilate veins more than
arteries, thereby reducing preload, but at higher doses it
also dilates arteries, thereby reducing afterload.
3. Route of administration/dose
a. Nitroglycerin 50 μg IV followed by up to four additional
doses of 50 μg is used to treat most obstetric indications.
Aerosol form can be administered as a metered spray
sublingually in a dose of 400 μg each.
b. Sublingual tablet (0.3 to 0.6 mg) and continuous IV
infusion (5 to 15 μg per minute) are used for nonobstetric
indications, mainly cardiac disease.
c. Doses in excess of 1,500 μg have been administered
without significant adverse effects noted.
4. Toxicity/side effects
a. Nitroglycerin acts more on uterine than vascular smooth
muscle; however, vascular effects include transient
 hypotension and reflex tachycardia.
b. Maternal headache and light-headedness can occur.
c. No significant fetal effects have been reported.

CLINICAL PEARL Nitroglycerin is particularly useful in

treating myometrial overactivity due to its rapid effect, short
duration, and minimal transient effects on maternal hemodynamics.

5. Anesthetic considerations
a. Nitroglycerin has a very short half-life and is useful when
short-term effect is required. For sustained effect, as for
the treatment of hypertension, multiple doses or an
infusion may be required.
b. Vascular effects can result in transient hypotension
and tachycardia; therefore, hemodynamic monitoring
is required.
c. Hypoxia, possibly due to pulmonary vasodilation and
blunting of protective hypoxic pulmonary
vasoconstriction, is common with continuous infusion of
nitroglycerin and has also been reported with bolus doses
in an obstetric patient.29
F. Oxytocin antagonist (atosiban)
1. Uses. Tocolysis to prolong pregnancy in threatened
preterm labor
a. Atosiban, an oxytocin antagonist, was originally
considered to be a promising tocolytic agent with a
favorable side effect profile. A Cochrane review found
atosiban to be as effective as β-receptor agonists for
preventing preterm birth within 48 hours of initiating
treatment (RR 0.89; 95% CI, 0.66 to 1.22). However, it
was not found superior, as a tocolytic agent, to placebo, β-
mimetics, or calcium channel blockers in terms of
pregnancy prolongation or neonatal outcomes.30
 b. The use of atosiban was associated with a lower risk of
maternal side effects requiring cessation of treatment than
β-receptor agonists.30 However, in one study, atosiban
resulted in an increase in extremely preterm birth (before
28 weeks’ gestation) and infant deaths (up to 12 months),
which warrants caution with its use in women with
gestational age less than 28 weeks. This finding may be
confounded due to randomization of more women with
less than 26 weeks’ gestation to atosiban in the study and
small sample size.30
c. Although commonly used in Europe, the FDA declined to
approve the use of atosiban for tocolysis because of
concerns about the drug’s safety when used in fetuses less
than 28 weeks of gestation.31
2. Mechanism of action. It is a competitive inhibitor of
oxytocin at myometrial and decidual receptors (see Fig. 4.1).
3. Route of administration/dose. Atosiban 6.75 mg IV bolus is
followed by a 300 μg per minute infusion for 3 hours, then
100 μg per minute for up to 45 hours.
4. Toxicity/side effects
a. There are no major maternal side effects, and the overall
frequency of side effects is significantly less than that
reported for any other drug used for inhibition of preterm
labor.32 The sensitivity of myometrium to oxytocin
remains unaffected. For these reasons, it is considered a
second-line tocolytic after calcium channel blockers in
practices where it is available.
b. There is minimal placental transfer and no adverse fetal
side effects.
5. Anesthetic considerations. No known significant anesthetic
interactions have been reported.
II. Uterotonic medications
PPH is one of the major causes of mortality in pregnant women
worldwide and occurs in up to 5% of all deliveries. The etiology of
PPH can be classified into four main groups: uterine atony (tone);
retained products (tissue); vaginal, cervical, or uterine injury (trauma);
and coagulopathy (thrombin). The most common cause of PPH is
uterine atony, and the correct and prompt use of uterotonics can
prevent significant morbidity and mortality from hemorrhage. In
addition, these agents have other obstetric indications including
induction and augmentation of labor and termination of pregnancy.
A. Oxytocin
Oxytocin is a hormone produced in the hypothalamus and
secreted from the posterior lobe of the pituitary gland in a
pulsatile fashion. Its synthetic analog, Pitocin, is among the most
potent uterotonic agents known. Pitocin possesses fewer
antidiuretic hormone (ADH)-related side effects (water
intoxication) than oxytocin.
1. Uses
a. Induction and augmentation of labor. Synthetic oxytocin
is used to induce labor and produce periodic uterine
contractions first demonstrable at approximately 20 weeks
of gestation. There is an increase in responsiveness to
oxytocin as the gestational age advances, primarily due to
an increase in myometrial oxytocin binding sites.33
Higher concentrations of estrogen during pregnancy
increase the density and binding kinetics of the oxytocin
receptor and enhance uterine sensitivity to oxytocin.34
There is little change in myometrial sensitivity to
oxytocin from 34 weeks to term; however, once
spontaneous labor begins, uterine sensitivity to oxytocin
increases rapidly.35
b. Uterine atony and active management of third stage.
Oxytocin is the first-line agent in the prevention and
treatment of PPH. In a Cochrane review, prophylactic
oxytocin reduced the risk of blood loss exceeding 500
mL (RR 0.53; 95% CI, 0.38 to 0.74) and the need for
therapeutic uterotonic agents (RR 0.56; 95% CI, 0.36
 to 0.87) compared with placebo.36 Active management
of the third stage of labor, involving prophylactic
administration of oxytocin before delivery of the placenta,
has been shown to reduce the incidence of PPH by
>60%.36
c. Contraction stress testing
A contraction stress test (CST) can be performed near the
end of pregnancy to determine how well the fetus will
cope with the contraction of childbirth. Oxytocin is given
intravenously to stimulate uterine contractions. The fetus
is monitored for any signs of distress once the parturient
experiences three contractions in 10 minutes. A positive
CST indicates high risk of fetal death due to hypoxia and
is a contraindication to labor. The CST is seldom
performed nowadays given the wide availability of other
tests of the fetal environment, such as the nonstress test
and biophysical profile measurements.
2. Mechanism of action. Oxytocin activates uterine G-protein-
coupled oxytocin receptors, which increases intracellular
calcium (via inositol triphosphate) and prostaglandin
production (via diacylglycerol). The increase in calcium and
prostaglandins induces uterine smooth muscle contraction
(see Fig. 4.2).
3. Route of administration/dose
a. Oxytocin 1 to 2 IU per minute IV infusion, titrated up to
32 IU per minute can be administered for
induction/augmentation of labor and CST.
b. For active management of the third stage of labor,
prophylactic oxytocin is routinely administered to reduce
uterine atony and PPH. A small loading dose of oxytocin
(ED 90 ± 0.35 IU; 95% CI, 0.18 to 0.52) has been
determined to be sufficient in producing adequate uterine
contractions during elective cesarean deliveries in
nonlaboring women and a similarly low loading dose (ED
90 ± 2.99 IU; 95% CI, 2.32 to 3.67) is required in
laboring women.37,38 This is followed by an infusion,
such as 20 to 40 units diluted in a liter of isotonic fluid IV
over 2 to 6 hours depending on the institutional policy.
For the treatment of PPH, slow boluses of oxytocin 5 IU
can be administered IV. It is preferable to administer this
drug as an infusion rather than boluses to minimize
hemodynamic side effects.
CLINICAL PEARL Small doses of oxytocin, often much less
than that used by many practitioners, are required to provide
adequate uterine contraction following elective, repeat cesarean
delivery; this is not true in women who have undergone a period of
labor where much larger doses are often required.

4. Toxicity/side effects
a. Maternal adverse effects include significant
hypotension, tachycardia, decreased free water
clearance, hyponatremia (although only seen when
administered in very high doses or with concurrent
hypotonic fluid administration), peripheral flushing,
nausea, emesis, and signs of myocardial ischemia.
b. Hemodynamic side effects are more pronounced when
oxytocin is administered as a rapid bolus (hypotension
is nearly always seen when administered as an IV
bolus of 5 to 10 units); hence, it should be used with
caution in those with cardiac disease or hemodynamic
instability. There are three reported cases of maternal
death resulting from cardiovascular collapse
secondary to an IV bolus of 10 IU oxytocin.39
c. Fetal effects, such as desaturation,40 hyperbilirubinemia,41
and retinal hemorrhage,42 have been reported following
oxytocin use.
5. Anesthetic considerations
a. Induction/augmentation of labor with oxytocin can induce
a state of uterine tetany resulting in nonreassuring fetal
heart rate patterns.43
b. Hypertonic uterine contractions and fetal bradycardia can
occur following CSE placement in women receiving an
infusion of oxytocin.43 If this occurs, discontinue
oxytocin infusion and consider IV terbutaline or
nitroglycerin to provide uterine relaxation.
 c. The vasodilatory effects of oxytocin can produce
significant hypotension, especially when administered as
a bolus in patients with hypovolemia.
B. Carbetocin
1. Uses. Treatment of uterine atony for active management of
third stage of labor to reduce PPH
a. Carbetocin is a synthetic analog of the hormone oxytocin
with the advantage of having a longer half-life of 40
minutes compared to 4 to 10 minutes for oxytocin. The
Society of Obstetricians and Gynecologists of Canada
guidelines recommend carbetocin 100 µg over oxytocin
to prevent PPH in elective cesarean delivery and
vaginal delivery with one risk factor for PPH.44
b. A 2009 systematic review concluded that carbetocin is
not superior over currently available uterotonic agents
for the prevention of PPH, both in vaginal and
cesarean deliveries.45 According to a recent Cochrane
review, carbetocin significantly reduced the need for
additional uterotonics (RR 0.62; 95% CI, 0.44 to 0.88)
and the risk of PPH following cesarean deliveries
compared to oxytocin (RR 0.55; 95% CI, 0.31 to 0.95).
However, these results were limited by a small number of
studies and risk of bias, warranting further studies to
validate these findings.46 A dose finding study found that
the ED 90 of carbetocin at elective cesarean delivery was
14.8 µg (95% CI, 13.7 to 15.8); this is less than one-fifth
the recommended dose.47 A recent study found an ED 90
of carbetocin to be 120.5 µg (95% CI, 110.9 to 130.2;
99% CI, 107.8 to 133.2) in women with labor arrest;
however, there was a high incidence of dysrhythmias at
higher doses.48 They suggested uncertainty regarding the
efficacy of carbetocin in this patient population.
Therefore, further research is needed to establish the
appropriate dose, efficacy, and also the side effect profile
 of carbetocin.

CLINICAL PEARL At present, there is insufficient evidence to

recommend the routine use of carbetocin over oxytocin. Carbetocin
is not available in the United States.

2. Mechanism of action. Carbetocin is an oxytocin receptor

agonist in the smooth muscle of the uterus; it increases
intracellular calcium and stimulates uterine contraction (see
Fig. 4.2).
3. Route of administration/dose. Carbetocin can be
administered as an intravenous bolus of 100 µg over 1 minute
or 100 µg intramuscularly.
4. Toxicity/side effects
a. The hemodynamic effects of carbetocin are similar to
those of oxytocin, with an acceptable safety profile.49
b. Headache; tremor; dizziness; flushing; shortness of
breath; tachycardia; abdominal pain; nausea and
vomiting; metallic taste; pruritus; back pain; feeling of
warmth, chills, or sweating may occur.50
5. Anesthetic considerations. These are similar to those of
oxytocin noted earlier.
C. Ergot alkaloids (ergonovine or methylergonovine)
Methylergonovine is the ergot alkaloid most commonly used
because it causes less peripheral vasoconstriction than
ergonovine. It increases uterine muscle tone and is used as a
second-line agent in the treatment of uterine atony and PPH.
A Cochrane review found that the use of injected ergot alkaloids
compared to no uterotonics in the third stage of labor significantly
decreased PPH of at least 500 mL (RR 0.38; 95% CI, 0.21 to
0.69) and the use of therapeutic uterotonics (RR 0.25; 95% CI,
0.10 to 0.66). However, ergot alkaloids increased the risk of
hypertension and pain after birth particularly when administered
 intravenously.51
1. Uses. Treatment of uterine atony for the active management
of third stage of labor to reduce PPH
2. Mechanism of action
a. A partial agonist on α-adrenergic, tryptaminergic, and
dopaminergic receptors.
b. The α-adrenergic receptors likely play the greatest role in
uterine contraction (see Fig. 4.2).
3. Route of administration/dose
a. Methylergonovine 0.2 mg or 0.25 mg can be given
intramuscularly or IV (slowly) and may be repeated once
at 15 minutes but only as an intramuscular dose.
b. If further doses are required, additional 0.2 mg or 0.25 mg
may be repeated every 2 to 4 hours.
c. IV administration should be used with extreme caution
because it increases the risk of severe adverse effects.

CLINICAL PEARL The use of methylergonovine should be

considered early in the setting of PPH in women who have
undergone prolonged labor with oxytocin augmentation.

4. Toxicity/side effects
a. Methylergonovine can cause peripheral
vasoconstriction resulting in hypertension, increased
pulmonary artery pressures, pulmonary edema,
cerebral hemorrhage, and retinal damage.
b. Nausea and vomiting can occur in up to 20% of patients.
c. IV administration may lead to angina from coronary
artery vasospasm and cardiac arrest from myocardial
infarction.
5. Anesthetic considerations
a. Ergonovine should be avoided in patients with chronic
hypertension, preeclampsia, peripheral vascular disease,
 and ischaemic heart disease.
b. Vasodilators should be available to treat hypertension and
antiemetics available to treat nausea and vomiting.
D. Prostaglandins (F2α, E1, and E2 analog)
1. Drugs
a. Carboprost (15-Methyl PGF2α)
b. Misoprostol (PGE1)
c. Dinoprostol (PGE2)
2. Uses
a. Induction of labor
(1) Induction of labor is one of the most commonly
performed obstetrical procedures in North America.
The first step in labor induction of women with an
unfavorable cervix is administration of dinoprostol or
misoprostol. This alone can initiate labor in many
women and obviate the need for oxytocin.
(2) A Cochrane review found that the use of dinoprostol
resulted in a reduction in unfavorable cervix after 12
to 24 hours (RR 0.41; 95% CI, 0.27 to 0.65), a
probable modest reduction in the rate of cesarean
deliveries (RR 0.91; 95% CI, 0.81 to 1.02), and a
possible lower rate of failing to achieve vaginal
delivery within 24 hours (RR 0.32; 95% CI, 0.02 to
4.83).52
(3) Misoprostol is an effective alternative to dinoprostol
preparations for cervical ripening and labor
induction.53 The ACOG has indicated that the use
of misoprostol appears safe and efficacious when
used as a cervical ripening and/or labor induction
agent.54 However, misoprostol is not advised for
cervical ripening or labor induction in women in the
third trimester with prior uterine incisions due to the
risk of uterine rupture.55
b. Treatment of uterine atony
 (1) Misoprostol is less effective than oxytocin or
ergometrine for active management of the third stage
of labor and is associated with a higher risk of severe
PPH compared to conventional injectable uterotonics
(RR 1.33; 95% CI, 1.16 to 1.52).56
(2) Carboprost is the most common prostaglandin
used for uterine atony and is typically
administered after oxytocin and ergometrine. It is
the only prostaglandin currently available that
can be administered parenterally.
3. Mechanism of action
a. Prostaglandins cause dissolution of collagen bundles and
an increase in the submucosal water content of the cervix,
which leads to a cervical state that is associated with a
greater success of labor induction with oxytocin.57
b. Prostaglandins increase myometrial calcium
concentration, which causes the uterus to contract (see
Fig. 4.2). This may initiate labor or in the postpartum
period prevent uterine atony and PPH.
4. Route of administration/dose
a. Misoprostol (Cytotec) can be administered via vaginal,
rectal, or oral route for labor induction in doses of 50 to
400 μg (depending on the gestational age), every 4 hours
to a maximum of 6 doses.
b. For prevention or treatment of PPH, misoprostol 600 to
1,000 μg can be administered either orally, sublingually,
vaginally, or rectally.
c. Dinoprostone (Cervidil) 10 mg is inserted in the posterior
fornix for labor induction. It can be replaced after 12
hours and removed at the onset of active labor.
d. Carboprost (Hemabate) 250 μg can be administered IM or
intramyometrial for uterine atony, repeated every 15
minutes up to a total dose of 2 mg.
5. Toxicity/side effects
 a. All prostaglandins can cause nausea, vomiting, diarrhea,
shivering, and fever.
b. Carboprost (15-Methyl PGF2α) causes increased
systemic and pulmonary vascular resistance and can
cause bronchoconstriction and hypoxemia due to
intrapulmonary shunting and ventilation–perfusion
mismatch.58
c. PGE2 administration on the other hand causes decreased
systemic vascular resistance and blood pressure, increased
cardiac output, and relaxes the gastroesophageal
sphincter, potentially increasing the risk of passive
regurgitation.
d. Misoprostol (PGE1) can cause uterine hyperstimulation
when administered for labor induction but appears to have
minimal effect on maternal hemodynamics.

CLINICAL PEARL Carboprost should be used with caution in

patients susceptible to bronchospasm.

6. Anesthetic considerations
a. The use of prostaglandins to induce labor in patients
attempting vaginal birth after previous cesarean delivery
can increase the risk of uterine rupture.
b. Carboprost should be used with caution in patients with
reactive airway disease, and avoided if cardiac disease
and pulmonary hypertension are present.
c. An antiemetic and antidiarrheal may be needed after
carboprost administration.

REFERENCES
1. American College of Obstetricians and Gynecologists, Committee on Practice Bulletins–Obstetrics.
ACOG Practice Bulletin no. 127: management of preterm labor. Obstet Gynecol. 2012;119:1308–
1317.
 2. Neilson JP, West HM, Dowswell T. Betamimetics for inhibiting preterm labour. Cochrane Database
Syst Rev. 2014;(2):CD004352.
3. U.S. Food and Drug Administration. FDA Drug Safety Communication: New warnings against use of
terbutaline to treat preterm labor. http://www.fda.gov/Drugs/DrugSafety/ucm243539.htm. Accessed
January 26, 2015.
4. Yaju Y, Nakayama T. Effectiveness and safety of ritodrine hydrochloride for the treatment of preterm
labour: a systematic review. Pharmacoepidemiol Drug Saf. 2006;15:813–822.
5. Lamont RF. The pathophysiology of pulmonary oedema with the use of beta-agonists. BJOG.
2000;107:439–444.
6. Flenady V, Wojcieszek AM, Papatsonis DN, et al. Calcium channel blockers for inhibiting preterm
labour and birth. Cochrane Database Syst Rev. 2014;(6):CD002255.
7. Smith P, Anthony J, Johanson R. Nifedipine in pregnancy. BJOG. 2000;107:299–307.
8. Cornette J, Duvekot J, Roos-Hesselink J, et al. Maternal and fetal haemodynamic effects of nifedipine
in normotensive pregnant women. BJOG. 2011;118:510–540.
9. van Veen AJ, Pelinck MJ, van Pampus MG, et al. Severe hypotension and fetal death due to tocolysis
with nifedipine. BJOG. 2005;112:509–510.
10. Impey L. Severe hypotension and fetal distress following sublingual administration of nifedipine to a
patient with severe pregnancy induced hypertension at 33 weeks. Br J Obstet Gynaecol.
1993;100:959–961.
11. Feldman S, Karalliedde L. Drug interactions with neuromuscular blockers. Drug Saf. 1996;15:261–
273.
12. Csapo AI, Puri CP, Tarro S, et al. Deactivation of the uterus during normal and premature labor by the
calcium antagonist nicardipine. Am J Obstet Gynecol. 1982;142:483–491.
13. Duley L, Gülmezoglu AM, Henderson-Smart DJ. Magnesium sulphate and other anticonvulsants for
women with pre-eclampsia. Cochrane Database Syst Rev. 2003;(2):CD000025.
14. Altman D, Carroli G, Duley L, et al. Do women with pre-eclampsia, and their babies, benefit from
magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet.
2002;359:1877–1890.
15. American College of Obstetricians and Gynecologists. Hypertension in pregnancy. Report of the
American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy.
Obstet Gynecol. 2013;122:1122–1131.
16. Doyle LW, Crowther CA, Middleton P, et al. Magnesium sulphate for women at risk of preterm birth
for neuroprotection of the fetus. Cochrane Database Syst Rev. 2009;(1):CD004661.
17. Doyle LW, Crowther CA, Middleton P, et al. Antenatal magnesium sulfate and neurologic outcome in
preterm infants: a systematic review. Obstet Gynecol. 2009;113:1327–1333.
18. Rouse DJ, Hirtz DG, Thom E, et al. A randomized, controlled trial of magnesium sulfate for the
prevention of cerebral palsy. N Engl J Med. 2008;359:895–905.
19. Marret S, Marpeau L, Follet-Bouhamed C, et al. Effect of magnesium sulphate on mortality and
neurologic morbidity of the very-preterm newborn (of less than 33 weeks) with two-year neurological
outcome: results of the prospective PREMAG trial. Gynecol Obstet Fertil. 2008;36:278–288.
20. Crowther CA, Hiller JE, Doyle LW. Magnesium sulphate for preventing preterm birth in threatened
preterm labour. Cochrane Database Syst Rev. 2002;(4):CD001060.
21. American College of Obstetricians and Gynecologists Committee on Obstetric Practice Society for
Maternal-Fetal Medicine. Committee Opinion No. 573: magnesium sulfate use in obstetrics. Obstet
Gynecol. 2013;122:727–728.
22. Vane JR, Bakhle YS, Botting RM. Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol.
1998;38:97–120.
23. King J, Flenady V, Cole S, et al. Cyclo-oxygenase (COX) inhibitors for treating preterm labour.
Cochrane Database Syst Rev. 2005;(2):CD001992.
24. Locatelli A, Vergani P, Bellini P, et al. Can a cyclo-oxygenase type-2 selective tocolytic agent avoid
the fetal side effects of indomethacin? BJOG. 2001;108:325–326.
25. Stika CS, Gross GA, Leguizamon G, et al. A prospective randomized safety trial of celecoxib for
treatment of preterm labor. Am J Obstet Gynecol. 2002;187:653–660.
26. McWhorter J, Carlan SJ, OLeary TD, et al. Rofecoxib versus magnesium sulfate to arrest preterm
labor: a randomized trial. Obstet Gynecol. 2004;103:923–930.
27. Groom KM, Shennan AH, Jones BA, et al. TOCOX—a randomised, double-blind, placebo-controlled
trial of rofecoxib (a COX-2-specific prostaglandin inhibitor) for the prevention of preterm delivery in
women at high risk. BJOG. 2005;112:725–730.
28. Loudon JA, Groom KM, Bennett PR. Prostaglandin inhibitors in preterm labour. Best Pract Res Clin
Obstet Gynaecol. 2003;17:731–744.
29. Saroa R, Sachan S, Palta S, et al. Obstetric use of nitroglycerin: anesthetic implications. Saudi J
Anaesth. 2013;7:350–352.
30. Flenady V, Reinebrant HE, Liley HG, et al. Oxytocin receptor antagonists for inhibiting preterm
labour. Cochrane Database Syst Rev. 2014;(6):CD004452.
31. Romero R, Sibai BM, Sanchez-Ramos L, et al. An oxytocin receptor antagonist (atosiban) in the
treatment of preterm labor: a randomized, double-blind, placebo-controlled trial with tocolytic rescue.
Am J Obstet Gynecol. 2000;182:1173–1183.
32. Gyetvai K, Hannah ME, Hodnett ED, et al. Tocolytics for preterm labor: a systematic review. Obstet
Gynecol. 1999;94:869–877.
33. Fuchs AR, Fuchs F, Husslein P, et al. Oxytocin receptors in the human uterus during pregnancy and
parturition. Am J Obstet Gynecol. 1984;150:734–741.
34. Zeeman GG, Khan-Dawood FS, Dawood MY. Oxytocin and its receptor in pregnancy and parturition:
current concepts and clinical implications. Obstet Gynecol. 1997;89:873–883.
35. Calderyro-Barcia R, Sereno JA. The response of human uterus to oxytocin throughout pregnancy. In:
Caldeyro-Barcia R, Heller H, eds. Oxytocin. London, United Kingdom: Pergamon Press; 1959:177–
202.
36. Westhoff G, Cotter AM, Tolosa JE. Prophylactic oxytocin for the third stage of labour to prevent
postpartum haemorrhage. Cochrane Database Syst Rev. 2013;(10):CD001808.
37. Carvalho JC, Balki M, Kingdom J, et al. Oxytocin requirements at elective cesarean delivery: a dose-
finding study. Obstet Gynecol. 2004;104:1005–1010.
38. Balki M, Ronayne M, Davies S, et al. Minimum oxytocin dose requirement after cesarean delivery for
labor arrest. Obstet Gynecol. 2006;107:45–50.
39. Balki M, Tsen L. Oxytocin protocols for cesarean delivery. Int Anesthesiology Clin. 2014;52:48–66.
40. Simpson KR, James DC. Effects of oxytocin-induced uterine hyperstimulation during labor on fetal
oxygen status and fetal heart rate patterns. Am J Obstet Gynecol. 2008;199:34.e1–e5.
41. Beazley JM, Alderman B. Neonatal hyperbilirubinaemia following the use of oxytocin in labour. Br J
Obstet Gynaecol. 1975;82:265–271.
42. Schoenfeld A, Buckman G, Nissenkorn I, et al. Retinal hemorrhages in the newborn following labor
induced by oxytocin or dinoprostone. Arch Ophthalmol. 1985;103:932–934.
43. Tsen LC, Balki M. Oxytocin protocols during caesarean delivery: time to acknowledge the risk/benefit
ratio. Int J Obstet Anesth. 2010;19:243–245.
44. Leduc D, Senikas V, Lalonde AB, et al. Active management of the third stage of labour: prevention
and treatment of postpartum hemorrhage. J Obstet Gynaecol Can. 2009;235:980–993.
45. Peters NC, Duvekot J. Carbetocin for the prevention of postpartum hemorrhage: a systematic review.
 Obstet Gynecol Surv. 2009;64:129–135.
46. Su LL, Chong YS, Samuel M. Carbetocin for preventing postpartum haemorrhage. Cochrane
Database Syst Rev. 2012;(2):CD005457.
47. Khan M, Balki M, Ahmed I, et al. Carbetocin at elective cesarean delivery: a sequential allocation trial
to determine the minimum effective dose. Can J Anaesth. 2014;61:242–248.
48. Nguyen-Lu N, Carvalho JC, Farine D, et al. Carbetocin at cesarean delivery for labour arrest: a
sequential allocation trial to determine the effective dose. Can J Anaesth. 2015;62:866–874.
49. Moertl MG, Friedrich S, Kraschl J, et al. Haemodynamic effects of carbetocin and oxytocin given as
intravenous bolus on women undergoing caesarean delivery: a randomized trial. BJOG.
2011;118:1349–1356.
50. Su LL, Chong YS, Samuel M. Oxytocin agonists for preventing postpartum haemorrhage. Cochrane
Database Syst Rev. 2007;(3):CD005457.
51. Liabsuetrakul T, Choobun T, Peeyananjarassri K, et al. Prophylactic use of ergot alkaloids in the third
stage of labor. Cochrane Database Syst Rev. 2007;(2):CD005456.
52. Thomas J, Fairclough A, Kavanagh J, et al. Vaginal prostaglandin (PGE2 and PGF2a) for induction of
labour at term. Cochrane Database Syst Rev. 2014;(6):CD003101.
53. Hofmeyr GJ, Gülmezoglu AM, Pileggi C. Vaginal misoprostol for cervical ripening and induction of
labour. Cochrane Database Syst Rev. 2010;(10):CD000941.
54. American College of Obstetricians and Gynecologists Committee on Practice Bulletins—Obstetrics.
ACOG Practice Bulletin No. 107: induction of labor. Obstet Gynecol. 2009;114:386–397.
55. American College of Obstetricians and Gynecologists Committee on Practice Bulletins—Obstetrics.
ACOG Practice Bulletin No. 115: vaginal birth after previous cesarean delivery. Obstet Gynecol.
2010;116:450–463.
56. Tunçalp Ö, Hofmeyr GJ, Gülmezoglu AM. Prostaglandins for preventing postpartum haemorrhage.
Cochrane Database Syst Rev. 2012;(8):CD000494.
57. Keirse MJ. Natural prostaglandins for induction of labor and preinduction cervical ripening. Clin
Obstet Gynecol. 2006;49:609–626.
58. Hankins G, Berryman G, Scott R, et al. Maternal arterial desaturation with 15-methyl prostaglandin F2
alpha for uterine atony. Obstet Gynecol. 1988;3:367–370.
Antepartum
Considerations
 Ethical and Legal Considerations in Obstetric
Anesthesia
M. Joanne Douglas and William J. Sullivan

I. Introduction to ethics
II. Informed consent
A. Background
B. Can laboring women give informed consent?
C. Implied consent
D. Presentation of information and risk
E. Purpose of the informed consent discussion
F. Withholding information
G. Refusal to be informed
III. Other consent issues
A. Delegation of informed consent
B. Refusal/withdrawal of consent
C. Obtaining consent from minors
D. Written consent
E. Birth plans—the Ulysses directive
F. Exceptions to informed consent
IV. Professional negligence: The law
V. Informed consent: The law
VI. Litigation specific to obstetric anesthesia
VII. Disclosure and apology
VIII. Maternal autonomy and fetal beneficence
 Summary

KEYPOINTS
1. Ethics: Ethics are a vital component of all health care. Anesthesiologists
and patients may differ in their perception as to optimal treatment,
creating an ethical dilemma. Before making a medical or ethical decision,
all of the facts must be ascertained.
2. Informed consent: Informed consent requires consent be given and the
consent be informed. Informed consent honors, and in law, enforces the
woman’s autonomy. Consenting is a process, and written consent by itself
is not enough. Women have the right to give consent, withdraw consent,
refuse consent, and to delegate that right to another. Women lose that
right if incapable, but informed consent is still required.
3. Communication: Good communication is an essential part of ethics and
informed consent.
4. The law: Informed consent, in law, enforces patient autonomy. The
patient must consent to the proposed treatment and that consent must be
informed. Failure to obtain consent will normally constitute a battery or
an assault. Failure to properly inform will normally constitute negligence.
The patient must be capable to give informed consent. Even if the patient
is incapable, informed consent is still required unless it is an emergency
and there is no one present legally to consent.
5. Maternal autonomy and fetal beneficence: Occasionally, the interests
of the woman and her fetus may differ, presenting the physician with a
dilemma. In most circumstances, legally and ethically, the woman’s
autonomy should be respected.

I. Introduction to ethics
A. Ethical decision making in health care in the Western world is
based mainly on the application of the four prima facie ethical
principles:
 1. Autonomy (choice)
2. Nonmaleficence (do no harm)
3. Beneficence (prevent harm, remove harm)
4. Justice (be fair, treat like cases alike) to the facts of the
particular health care case.1 This method replaced the older
way of “doctor knows best” decision-making (strong
paternalism).
B. Remember that not all choices are ethical in nature. Whether
to use a 16 or 19 gauge needle for an epidural may require a
decision, but the decision is solely a medical one.
C. Ethical decision-making is not done in a vacuum. The facts are
essential. Knowing which facts are relevant can only be
determined after ascertaining all of the facts available. This
includes not only the patient’s pertinent medical facts but also
social, economic, and cultural facts that may influence the
decision. An ethical dilemma may seem to appear when one does
not know all of the facts but may disappear once sufficient facts
are available.
D. Questions to ask when assessing the facts
1. What will the proposed treatment accomplish?
2. What happens if there is no treatment?
3. Are there alternatives to the proposed treatment?
4. What are the risks and benefits of the proposed treatment, the
alternate treatments, and no treatment?
5. What does the patient want? (This is where nonmedical facts
enter into the decision-making.)
6. What other considerations are there in the case?
E. Jonsen et al.2 suggest setting out the facts under the headings of
“medical indications,” “patient preferences” (autonomy), “quality
of life” (including with and without treatment), and “contextual
features” (other factors such as religion and allocation of
resources).
F. The facts will identify the possible choices of action. It may be
that when applying the ethical principles to the choices, the
 principles will align with one choice and there is no ethical
dilemma. The patient chooses an epidural for labor pain
(autonomy), the recommended treatment (beneficence and
nonmaleficence), and therefore no dilemma exists (provided the
ethical principle of justice is not wronged).
G. However, the ethical principles may conflict. If more than one
principle applies and, in choosing one, the other(s) cannot be
followed, there is an ethical dilemma. An example is the laboring
parturient who is in pain. The physician wants to relieve the pain
(beneficence) and the parturient refuses (autonomy). The result is,
whichever one is chosen, the other is excluded. When facing an
ethical dilemma, the challenge for the practitioner is determining
which ethical principle to follow.
H. Each of the prima facie principles is applied to the relevant
facts. The principle that discloses the stronger obligation, or as
stated by Beauchamp and Childress,1 the “strongest right” on
those facts is the principle to be followed. Notwithstanding this,
the law is very clear on the importance of autonomy. “Every
human being of adult years and of sound mind has a right to
determine what shall be done with his own body and a surgeon
who performs an operation without his patient’s consent commits
an assault, for which he is liable in damages.”3
II. Informed consent
A. Background
1. Informed consent underlines and legally enforces the
principle of patient autonomy—the woman chooses
(hopefully in consultation with the anesthesiologist) what she
wants after she has been fully informed. This legal
requirement consists of two separate parts. The first is the
requirement of consent.
2. Consent must be:
a. Voluntary
b. For the proposed procedure and who will do it
c. Given by a capable patient
 3. Care must be taken not to confuse lack of knowledge of the
world, intellectual disability, or mental illness or instability
with a lack of capability to consent to health care. If the
woman understands:
a. The nature and purpose of the proposed treatment
b. The condition for which the procedure is proposed
c. The risks and benefits of the procedure
d. The consequences of consenting or not consenting
e. That the procedure applies to her situation, then, unless
there is law in a particular jurisdiction to the contrary, she
has capability to give or withhold consent

CLINICAL PEARL The fact that someone is incapable of that

understanding in regard to a complex procedure does not preclude
her of being capable of that understanding for a simple procedure.
Indeed, she may be incapable of consenting during a contraction but
capable of doing so between contractions.

4. Consent must be informed. The physician is responsible for:

a. Providing full information about the proposed
intervention
b. Taking reasonable steps to ensure the woman understands
the proposed intervention
c. Informing the woman
(1) How the procedure is done
(2) Why it is done
(3) The benefits and the risks associated with doing it
(4) Any alternative treatments and their benefits and
risks

CLINICAL PEARL The woman should be given the opportunity

to consider her choices and to ask questions. If there are any
concerns about her understanding, she should be asked to repeat the
information in her own words.

d. Finally, the anesthesiologist should document the

discussion, including any concerns expressed by the
woman and information given in response to those
concerns.
B. Can laboring women give informed consent?
1. Some question whether women having severe labor pain can
assimilate the information in order to provide informed
consent.4 Not only might pain interfere with the woman’s
understanding, but opioids, such as morphine, given to
alleviate pain, also might interfere. Pattee et al.5 examined
this question and found that women felt that the ability to give
consent was not affected by opioid premedication, anxiety, or
the amount of pain. This ability to consent was confirmed in
two other studies.6,7 In the latter study, more than 90% agreed
that they had received sufficient information to make a
decision and were satisfied with the process.7
2. Other studies have examined what a patient recalled about the
risks provided during the consent discussion to see if they
were informed. The patients were asked to recall certain risks
within 24 hours,8 on postpartum day 1,9 36 to 48 hours later,10
and 5 to 7 months later.11 They used the number of risks
recalled as a measure of whether informed consent was
obtained. The results did not differ from studies of recall in
nonobstetric patients.8,11

CLINICAL PEARL It is important to remember that although

information may not be recalled, it does not mean that the patient
did not understand it at the time.12

C. Implied consent
This can occur from either the action or the words of a patient
 indicating consent. A note as to how that determination was made
should be added to the patient’s chart.

CLINICAL PEARL Implied consent is only consent. The

requirement that the consent be informed has not been met.

D. Presentation of information and risk

1. Ideally, prior to the woman’s admission in labor, information
on obstetric analgesia/anesthesia would be presented10 and
informed consent obtained, but this rarely happens. Many
pregnant women do not seek information on anesthetic
intervention for labor analgesia or operative procedures. This
may be due to the belief that they will not require
anesthesia.13
2. The options for presenting information to the patient are:
a. Verbal alone (provided by the individual who will do the
procedure/intervention; if done by someone else, the one
doing the procedure is still responsible if informed
consent is inadequate)
b. Written alone
c. Verbal plus written
3. Similar to nonobstetric patients,14 women who received a
combination of verbal plus written information about
anesthetic options, risks, and procedures were more
knowledgeable than those who only received verbal
information.9,11 Smedstad and Beilby15 point out that
although written information assists the discussion between
the physician and the patient, it does not eliminate the need
for that discussion.
4. Generally speaking, the individual has to be informed about:
a. Risks that are common even though not serious (e.g.,
headache)
b. Risks that are serious even though not common (e.g.,
 death, permanent paralysis)16
5. The challenge is to what extent the risks between those two
extremes need to be disclosed.
The law is clear.
a. In a few jurisdictions, it still is what a reasonable
physician would tell a patient.
b. In most, however, it is what a reasonable patient would
want to know.
c. In some, it is what a reasonable patient, in that patient’s
circumstances, would want to know.17,18
d. The latter best recognizes autonomy and will offer the
greatest legal protection.
6. Studies have shown that:
a. Parturients want to be informed about most, if not all, of
the risks associated with neuraxial6,19–21 and general
anesthesia.22
b. Many anesthesiologists fail to discuss important risks.23,24
c. One way to provide risk information is to relate it to
familiar events so that the risk is in context.16,20
E. Purpose of the informed consent discussion
1. The informed consent discussion
a. Provides full information about a proposed intervention
b. Shows respect for the patient and acknowledges the
patient’s autonomy
c. Satisfies the ethical and legal requirement for informed
consent
d. Establishes a relationship between the anesthesiologist
and the patient because it encourages dialogue25
2. In a study looking at the importance of 40 items relating to
obstetric care, the women rated “The doctors talking to you in
a way you can understand” as the second most important.
(Having a healthy baby ranked number one.)26
F. Withholding information
1. Some physicians feel that too much information might
 engender anxiety, preventing the woman from accepting
appropriate treatment.27
2. Others suggest that information should only be provided if the
patient asks.28,29 Under those circumstances, informed
consent likely has not been obtained and the physician could
be accountable in a court of law.
G. Refusal to be informed
1. Refusal to be informed is acceptable because it is an exercise
of the woman’s autonomy.
2. The physician must ensure that the refusal is voluntary.
3. A woman in the throes of labor may indicate that she does not
want to receive information about neuraxial analgesia. She
may say, “Just do it!”
4. Refusal to be informed does not relieve the anesthesiologist
from attempting to provide the information.
5. If she refuses to be informed, document what happened,
including the woman’s reasons, in case later there is a
difference of opinion on whether she really meant that refusal.
6. Refusal to receive information is not a reason for the
anesthesiologist to refuse care. If the anesthesiologist is the
only one available and refuses to provide care, then that
anesthesiologist is open to censure and possible legal liability.
III. Other consent issues
A. Delegation of informed consent
1. Women may defer to their husbands/partners with respect to
giving consent.
2. It is acceptable because she is exercising her autonomy.
3. The delegation must be genuine and done voluntarily.12 To
confirm that it is voluntary, verify it when family members are
not present.
B. Refusal/withdrawal of consent
1. One should not assume that the woman lacks capability
because she disagrees with her physician.
2. Having consented to a procedure, a woman may change her
 mind and withdraw consent.
3. The woman may refuse to consent to a procedure that her
physician feels is important. Examples of this include refusal
of an epidural when the woman appears to be suffering from
pain, refusal of a cesarean delivery when her fetus is showing
signs of distress,30 and refusal of neuraxial anesthesia for a
cesarean delivery.
a. Doing a procedure without her consent (or if incapable,
without the consent of her legal substitute decision maker)
is, depending on the jurisdiction, an assault or a battery
and will result in an award of damages against the
physician.
b. The mere act of doing it without consent (unless it is an
emergency and there is not one to consent) creates the tort
for which damages are awarded.
c. Negligence is not a factor.
d. Acting in her best interest is not a factor.

CLINICAL PEARL Based on the principle of autonomy and in

the absence of a court order to the contrary, the physician must
honor the woman’s choice.

4. The physician may emphasize potential benefits for her and

possibly her fetus. If the woman still refuses and even if the
physician feels that the alternative places the woman (and/or
her fetus) at greater risk, the physician must accept the
woman’s wishes.

CLINICAL PEARL The discussion must be fully documented.

If the physician is unable to honor the woman’s choice, due to their
own moral code, they are responsible to find a physician who will.

5. Simon et al.31 describe two cases where women refused to

 have any needles inserted or emergency cesarean delivery due
to needle phobia. Both had a normal airway and the women
ultimately agreed to the procedure providing a needle would
not be inserted until anesthesia was induced. A sevoflurane
mask induction was performed; once the women were
unconscious, an intravenous line was inserted. Anesthesia and
surgery proceeded uneventfully. Although an intravenous
induction was considered safer, the women’s choice of not
having a needle inserted until they were unconscious, was
honored.
C. Obtaining consent from minors
1. The ability to consent can become an issue when the pregnant
patient is a minor.
2. In most jurisdictions, the minor’s ability to consent is based
on their understanding and not on age. The question is
whether the minor is mature enough to appreciate the
proposed procedure and the consequences of consenting or
refusing consent.
3. Statute law setting an age requirement before consent can be
given may be a factor in some jurisdictions.
D. Written consent
1. There is a potential risk in relying on a general written
consent obtained by the hospital on a patient’s admission. It
may (or may not) be sufficient to cover consent and it is
unlikely it will cover the required informed part of informed
consent for anesthesia. In the past, anesthetic consent was
considered part of surgical consent (the rationale being you
could not have surgery without an anesthetic), but now, the
expectation is that there should be a separate consent for
anesthesia.32

CLINICAL PEARL Many hospitals now insist on a separate,

written consent for analgesia/anesthesia.33 However, signing a
consent form does not equal giving informed consent.
 2. As pointed out by Meisel and Kuczewski,34 “Perhaps the
most fundamental and pervasive myth about informed consent
is that . . . [it] has been obtained when a patient signs a
consent form. Nothing could be further from the truth, as
many courts have pointed out to physicians who were only
too willing to believe this myth.”
E. Birth plans—the Ulysses directive
1. When admitted to hospital, some women will bring written
instructions as to what treatment they will or will not accept.
That should not change one’s general practice of obtaining
informed consent. The challenge for the anesthesiologist is
when the birth plan refuses pain relief and goes on to say, that
even if she later wants it, it is not to be given to her (known as
a Ulysses directive or contract).35 During labor, the woman
asks for pain relief. The dilemma for the anesthesiologist is
that at one level, the woman has changed her mind from
refusing pain relief to now consenting; at another level, she
has said in advance, “Even if I change my mind, I am still
refusing.”
2. This is the ethical dilemma.
a. Autonomy (honor her directive)
b. Beneficence and nonmaleficence (give pain relief)
3. Some physicians opt for beneficence.36,37 Scott37 argues
“against withholding analgesia because of a birth plan as the
birth plan was made at a time when the woman did not have
pain.” She feels that “the only time when consent to a pain-
relieving procedure is valid is when the person concerned
knows what the pain is like.” However, Thornton and
Moore38 feel that “acceding to her apparent immediate
request (ignoring the birth plan) does not respect her long-
term preferences.”
4. The legal consequences of either of the ethical choices are
unclear, but there is a risk that providing pain relief may
 constitute a civil wrong, given the Ulysses directive.

CLINICAL PEARL Ideally, an anesthesiologist would have the

opportunity to review the birth plan in the antepartum period and
discuss the various options with the woman.36 This could result in
an alteration to the birth plan.

F. Exceptions to informed consent39

1. An emergency—usually life-threatening
a. If the woman is incapable of giving or withholding
consent and no one is available with the legal authority to
speak for her, the treatment can proceed. It must be to
save life or health and the need must be immediate.
b. If the procedure can be postponed in order to get consent
from her or a substitute decision-maker, then it must be
postponed. Convenience for the doctor or even for the
patient by itself is not an acceptable reason to proceed.
2. Waiver of consent: The challenge is whether the waiver truly
constitutes a refusal of the right to be informed. Ethically and
legally, a patient can waive the right to informed consent.
Respect for autonomy requires that right. The important
consideration is to ensure that the patient is in fact refusing to
be informed and is doing so voluntarily. Notes should be
made of any discussion.

CLINICAL PEARL The physician must understand that the

concept of autonomy is so powerful that, unless one of the
exceptions applies, informed consent is always needed.

3. Informed consent may not come from the woman, but it must
come from someone with the authority to give it. The law as
to who has that authority will vary from jurisdiction to
jurisdiction. As well, in some jurisdictions (where they are
 legally binding), the authority may come from an advance
directive, whereas in others, it may come from a court order.
IV. Professional negligence: The law
A. Professional negligence occurs when the physician does a
procedure and in doing so does it to a lesser standard than the
recognized standard of care for that procedure causing injury to
the patient.
B. To succeed, the patient must establish negligence, which is all of
the following:
1. Duty (usually a given)
2. Breach of the standard of care. In most jurisdictions, the
standard of care is that of a reasonable practitioner in that
specialty. One should be acquainted with the definition of
standard of care in the jurisdiction in which they practice.
3. Damages (the patient suffered an injury)
4. Causation (the injury was caused by the breach of standard of
care)
V. Informed consent: The law
A. Failure to obtain informed consent occurs
1. First, consent to do the procedure is not obtained. To succeed,
the patient must only establish that no consent was given.
Damages will be awarded even if there is no injury. The fact
that the physician met the standard of care in doing the
procedure is immaterial.
2. Second, the patient is insufficiently informed. To succeed, the
patient must establish negligence, which is all of the
following :
a. Duty—usually a given
b. Breach of the standard of care which in most jurisdictions
is what would a reasonable patient want to know. In some
others, it is what would a reasonable physician tell a
patient, and in others, what a reasonable patient in that
patient’s circumstances would want to know.1,39
 c. Damages (the patient suffered an injury)
d. Causation (If the patient would nevertheless have had the
procedure even if fully informed, there is no causation.)
VI. Litigation specific to obstetric anesthesia
A. The American Society of Anesthesiologists (ASA) Closed
Claims Project related to obstetric anesthesia40 found that:
1. The proportion of claims due to substandard care decreased
after 1990.
2. Claims related to newborn death or brain damage resulted
from delays in providing anesthetic care for emergency
deliveries and poor communication between obstetrician and
anesthesiologist.
3. Maternal morbidity/mortality resulted from a delayed
response to an unexpected event such as a high neuraxial
block and/or substandard care.
B. Metzner et al.41 recommended the following to improve
practice and decrease the risk of litigation:
1. Better communication between patient and anesthesiologist
including informed consent and appropriate follow-up
2. Following practice guidelines concerning decision-to-incision
interval; better communication between obstetrics and
anesthesia
3. Earlier diagnosis and treatment of anesthetic complications
(e.g., high block, difficult intubation)
4. Improved treatment of maternal disease, such as hemorrhage
C. Although this Closed Claims report did not discuss whether
informed consent was an issue in the claims, a study from the
United Kingdom found that 10% of all claims related to regional
anesthesia (obstetric and nonobstetric) asserted that there was a
lack of consent.42
VII. Disclosure and apology

CLINICAL PEARL If a patient has the right to be told what may

go wrong (informed consent), then the patient has the moral right to
be told what actually went wrong.

A. Although many physicians are reluctant to disclose adverse

events because of concerns regarding possible litigation, there are
advantages to full disclosure.18,43 According to Beauchamp and
Childress,1 “Nondisclosure is morally indefensible.”
Some hospitals have policies regarding disclosure of adverse
events and some states now mandate disclosure of serious adverse
events.44

CLINICAL PEARL The physician must be aware of the law in

their jurisdiction. The ASA summarizes well the key components
for disclosure of a medical error.18

B. An apology is a recognized ethical response when harm is

caused to another. Although studies show that an apology can
reduce claims45 and when claims are made, reduce awards,43
there is a reluctance to apologize for fear a court would consider
it an admission of wrongdoing. To remove that concern, some
jurisdictions have enacted apology legislation making the apology
inadmissible as evidence in a lawsuit.44

CLINICAL PEARL A physician needs to know whether such

legislation exists in the jurisdiction in which they practice and how
far that legislation goes in protecting the use of an apology. Some
protect only against an expression of sympathy, others against an
admission of fault. One must be satisfied as to whether protection is
partial or absolute.

CLINICAL PEARL Proper communication is vital.44 An

 apology expressing regret for the event, as opposed to admitting
responsibility for the event, is appropriate until the facts are known.

C. An apology should be seen to be sincere. Bad outcomes can

occur without negligence, and it is an adverse event until medical
error is established. Words such as “negligent” or “negligence” or
“my fault” are often inappropriate and, in most cases, only apply
when a court makes that finding.
VIII. Maternal autonomy and fetal beneficence
A. Sometimes the pregnant woman’s autonomous choice of
treatment (particularly the refusal to accept the physician’s
recommendation) will, in the physician’s opinion, put the fetus at
unnecessary risk. Assuming capability, it is generally acceptable,
ethically and legally, that the woman’s autonomous decision
cannot be overruled.46
B. The legal rationale underpinning this ethical right to make
choices that might adversely affect the fetus is that to force her to
do otherwise (forced obstetric intervention) “would result in very
extensive and unacceptable intrusions into the bodily integrity,
privacy, and autonomy rights of women.”47 The law in England48
and Canada49 is clear. Whatever the risk to the fetus, the capable
pregnant woman’s decision is binding. Generally in the United
States, the woman’s autonomy has been recognized in law.
Occasionally, it has not.50 The District of Columbia Court of
Appeal’s decision expressed it this way. “We emphasize,
nevertheless, that it would be an extraordinary case indeed in
which a court might ever be justified in overriding the patient’s
wishes and authorizing a major surgical procedure such as a
cesarean section.”51 This was further qualified by the court:
“Some may doubt that there could ever be a situation
extraordinary or compelling enough to justify a massive intrusion
into a person’s body, such as a cesarean section against that
person’s will.”51
 C. In those rare cases where a decision is made to attempt to
overrule the woman’s choice, consent is still needed. This is
usually done by attempting to obtain a court order that allows the
unwanted procedure.

CLINICAL PEARL If the anesthesiologist is to be a party to this

procedure, it is important that the court order be wide enough to
cover the anesthetic care. Otherwise, there is no consent and it is a
battery for which the anesthesiologist is liable in damages.

SUMMARY
It is important to understand the ethical duty to respect autonomy. That ethical
duty is enforced by the legal requirement for informed consent. Failure to
properly obtain informed consent may well result in a damage award against a
physician. Decisions, whether medical or ethical, cannot be made in a vacuum.
Know the facts of the case.

REFERENCES
1. Beauchamp TL, Childress JF. Principles of Biomedical Ethics. 7th ed. Oxford, United Kingdom:
Oxford University Press; 2013.
2. Jonsen AR, Siegler M, Winslade WJ. Clinical Ethics. 6th ed. New York, NY: McGraw-Hill
Companies, Inc.; 2006.
3. Schloendorff v Society of New York Hospital, 105, NE 92 (NY 1914).
4. Black JD, Cyna AM. Issues of consent for regional analgesia in labour: a survey of obstetric
anaesthetists. Anaesth Intensive Care. 2006;34:254–260.
5. Pattee C, Ballantyne M, Milne B. Epidural analgesia for labour and delivery: informed consent issues.
Can J Anaesth. 1997;44:918–923.
6. Jackson A, Henry R, Avery N, et al. Informed consent for labour epidurals: what labouring women
want to know. Can J Anesth. 2000;47:1068–1073.
7. Jackson GNB, Sensky T, Reide P, et al. The capacity to consent to epidural analgesia in labour. Int J
Obstet Anesth. 2011;20:269–270.
8. Affleck PJ, Waisel DB, Cusick MJ, et al. Recall of risks following labor epidural analgesia. J Clin
Anesth. 1998;10:141–144.
9. White LA, Gorton P, Wee MYK, et al. Written information about epidural analgesia for women in
labour: did it improve knowledge? Int J Obstet Anesth. 2003;12:93–97.
10. Swan HD, Borshoff DC. Informed consent—recall of risk information following epidural analgesia in
labour. Anaesth Intens Care. 1994;22:139–141.
11. Gerancher JC, Grice SC, Dewan DM, et al. An evaluation of informed consent prior to epidural
analgesia for labor and delivery. Int J Obstet Anesth. 2000;9:168–173.
12. Hoehner PJ. Ethical aspects of informed consent in obstetric anesthesia—new challenges and
solutions. J Clin Anesth. 2003;15:587–600.
13. Fortescue C, Wee MYK, Malhotra S, et al. Is preparation for emergency obstetric anaesthesia
adequate? A maternal questionnaire survey. Int J Obstet Anesth. 2007;16:336–340.
14. Straessle R, Gilliard N, Frascarolo P, et al. Is a pre-anaesthetic information form really useful? Acta
Anaesthesiol Scand. 2011;55:517–523.
15. Smedstad KG, Beilby W. Informed consent for epidural analgesia in labour. Can J Anesth.
2000;47:1055–1059.
16. Jenkins K, Baker AB. Consent and anaesthetic risk. Anaesthesia. 2003;58:962–984.
17. DiGiovanni LM. Ethical issues in obstetrics. Obstet Gynecol Clin N Am. 2010;37:345–357.
18. American Society of Anesthesiologists. ASA Committee on Professional Liability. Manual on
Professional Liability. Park Ridge, IL: American Society of Anesthesiologists; 2010.
19. Kelly GD, Blunt C, Moore PAS, et al. Consent for regional anaesthesia in the United Kingdom: what
is material risk? Int J Obstet Anesth. 2004;13:71–74.
20. Bethune L, Harper N, Lucas DN, et al. Complications of obstetric regional analgesia: how much
information is enough? Int J Obstet Anesth. 2004;13:30–34.
21. Plaat F, McGlennan A. Women in the 21st century deserve more information: disclosure of material
risk in obstetric anaesthesia. Int J Obstet Anesth. 2004;13:69–70.
22. Jackson GNB, Robinson PN, Lucas DN, et al. What mothers know, and want to know, about the
complications of general anaesthesia. Acta Anaesthesiol Scand. 2012;56:585–588.
23. Zollo RA, Lurie SJ, Epstein R, et al. Patterns of communication during the preanesthesia visit.
Anesthesiology. 2009;111:971–978.
24. Broaddus BM, Chandrasekhar S. Informed consent in obstetric anesthesia. Anesth Analg.
2011;112:912–915.
25. Waisel DB. Let the patient drive the informed consent process: ignore legal requirements. Anesth
Analg. 2011;113:13–15.
26. Drew NC, Salmon P, Webb L. Mothers’, midwives’ and obstetricians’ views on the features of
obstetric care which influence satisfaction with childbirth. Br J Obstet Gynaecol. 1989;96:1084–1088.
27. Slusarenko P, Noble WH. Epidural anaesthesia: concerns regarding informed consent. Can Anaesth
Soc J. 1985;32:681–682.
28. Lanigan C, Reynolds F. Risk information supplied by obstetric anaesthetists in Britain and Ireland to
mothers awaiting elective caesarean section. Int J Obstet Anesth. 1995;4:7–13.
29. Epstein RM, Korones DN, Quill TE. Withholding information from patients—when less is more. N
Engl J Med. 2010;362:380–381.
30. Weiniger CF, Elchalal U, Sprung CL, et al. Holy consent—a dilemma for medical staff when maternal
consent is withheld for emergency caesarean section. Int J Obstet Anesth. 2006;15:145–148.
31. Simon GR, Wilkins CJ, Smith I. Sevoflurane induction for emergency caesarean section: two case
reports in women with needle phobia. Int J Obstet Anesth. 2002;11:296–300.
32. Marco AP. Informed consent for surgical anesthesia care: has the time come for separate consent?
Anesth Analg. 2010;110:280–282.
33. Marcucci C, Seagull FJ, Loreck D, et al. Capacity to give surgical consent does not imply capacity to
give anesthesia consent: implications for anesthesiologists. Anesth Analg. 2010;110:596–600.
34. Meisel A, Kuczewski M. Legal and ethical myths about informed consent. Arch Intern Med.
1996;156:2521–2526.
35. Brooks H, Sullivan WJ. The importance of patient autonomy at birth. Int J Obstet Anesth.
 2002;11:196–203.
36. Burcher P. The Ulysses contract in obstetrics: a woman’s choices before and during labour. J Med
Ethics. 2013;39:27–30.
37. Scott WE. Ethics in obstetric anaesthesia. Anaesthesia. 1996;51:717–718.
38. Thornton J, Moore M. Women who request epidural analgesia in labour should always be given it:
opposer. Int J Obstet Anesth. 1995;4:41–43.
39. American College of Obstetricians and Gynecologists Committee on Ethics. ACOG Committee
Opinion No. 439: informed consent. Obstet Gynecol. 2009;114:401–408.
40. Davies JM, Posner KL, Lee LA, et al. Liability associated with obstetric anesthesia: a closed claims
analysis. Anesthesiology. 2009;110:131–139.
41. Metzner J, Posner KL, Lam MS, et al. Closed claims’ analysis. Best Pract Res Clin Anaesthesiol.
2011;25:263–276.
42. Szypula K, Ashpole KJ, Bogod D, et al. Litigation related to regional anaesthesia: an analysis of
claims against the NHS in England 1995-2007. Anaesthesia. 2010;65:443–452.
43. Hall MA, Bobinski MA, Orentlicher D. Health Care Law and Ethics. 7th ed. New York, NY: Wolters
Kluwer; 2007:284–285.
44. Frenkel DN, Liebman CB. Words that heal. Ann Intern Med. 2004;140:482–483.
45. Van Dusen V, Spies A. Professional apology: dilemma or opportunity? Am J Pharm Educ.
2003;67(4):3.
46. American College of Obstetricians and Gynecologists Committee on Ethics. ACOG Committee
Opinion No. 321: maternal decision making, ethics, and the law. Obstet Gynecol. 2005;106:1127–
1137.
47. Dobson v Dobson, 2 SCR 753 (1999).
48. Re MB. 2 FCR 541 (1997).
49. Winnipeg Child and Family Service v DFG, 3 SCR 925 (1997).
50. Pemberton v Tallahassee, 66 F Supp. 2d, 1247 (ND Fla 1999).
51. Re AC, 573 A 2d, 1235 (DC App 1990).
 Nonobstetric Surgery during Pregnancy
Joy L. Hawkins and Debnath Chatterjee

I. Incidence and anesthetic concerns specific to pregnancy
A. Alterations in maternal physiology
B. Maintenance of fetal oxygenation
C. Prevention and treatment of preterm labor
II. Teratogenicity of anesthetic agents
III. Preoperative plan and counseling
IV. Intraoperative anesthetic management
V. Postoperative care
VI. Special situations
A. Trauma
B. Neurosurgical procedures
C. Cardiac surgery requiring cardiopulmonary bypass
D. Laparoscopic surgeries
E. Fetal interventions
Summary

KEYPOINTS
1. A wide variety of nonobstetric surgeries have been performed
successfully during pregnancy with good maternal and fetal outcomes. A
perioperative team approach that includes obstetric consultation,
 surgeons, anesthesiology, neonatology, and nursing is key.
2. Physiologic changes of pregnancy will alter preoperative and
intraoperative anesthetic techniques, but no anesthetic agents need be
avoided during pregnancy. No anesthetic medications have been shown to
have any teratogenic effects in humans at any gestational age.
3. Fetal heart rate monitoring should be done preand postoperatively, but
intraoperative monitoring may also provide useful information for
positioning and cardiorespiratory management and may influence the
decision to deliver a viable fetus.
4. Intraoperative and postoperative pneumatic compression devices and
early postoperative ambulation are recommended to prevent deep venous
thrombosis. Optimizing postoperative pain control is critical to
mobilization.

I. Incidence and anesthetic concerns specific to pregnancy

Discovering that an otherwise “routine” surgical patient is pregnant
heightens anxiety for most anesthesiologists. Yet approximately 2% of
parturients will have surgery during their pregnancy, involving more
than 80,000 anesthetics in the United States alone each year. This
number is increasing, with laparoscopic procedures accounting for
much of this increase. Most surgeries are performed to treat
conditions common to the childbearing age-group: traumatic injuries,
ovarian cysts, appendicitis, cholelithiasis, breast masses, and cervical
incompetence. However, major procedures such as craniotomy,
cardiopulmonary bypass (CPB), and liver transplantation may also be
necessary in the pregnant patient and usually result in good outcomes
for mother and fetus.1 Despite favorable results overall, both
medically trained and nonmedical individuals have concerns about
medications being used and procedures being performed during
pregnancy. For example, during published and broadcast
congressional testimony on late-term abortions in 1995, an erroneous
statement was made by a physician that “the fetus usually dies from
the anesthesia administered to the mother before the procedure
begins.” With the dissemination of such misinformation, a pregnant
 patient who requires surgery is likely to present with extreme anxiety.
In one study, after women were exposed to nonteratogenic drugs
before they discovered they were pregnant, they estimated that they
had a 25% risk of major congenital malformations due to that
exposure, rather than the 3% actual overall risk.2 How should
anesthesiologists counsel a pregnant patient having surgery and
anesthesia? What evidence-based information can she be given about
the risks to her pregnancy associated with anesthesia?

CLINICAL PEARL Surgery performed during pregnancy is not

uncommon. Maternal and fetal outcomes are generally very good.

Anesthetic management of the case will involve two patients and

alterations in her physiology specific to pregnancy. Therefore, several
unique concerns should be addressed when creating an anesthetic
plan.
A. Alterations in maternal physiology (see Chapter 1). Physiologic
changes involve almost every organ system, but those most
important to anesthetic management include the following:
1. Respiratory. The pregnant woman will have increased
oxygen consumption due to metabolic demands, decreased
functional residual capacity (FRC), lower arterial PCO2 due to
increased minute ventilation, increased mucosal vascularity
with increased potential for bleeding, and greater likelihood
of difficult intubation.
2. Cardiovascular. Physiologic changes include increased blood
volume and cardiac output (maximal at approximately 28
weeks), dilutional anemia caused by plasma volume
expansion, aortocaval compression in the supine position, and
decreased vascular responsiveness despite increased
baroreceptor sensitivity.
3. Gastrointestinal. Gastric volume, pH, and emptying are
probably not altered during pregnancy, but gastroesophageal
 sphincter tone is usually reduced, and women often describe
gastroesophageal reflux symptoms.
4. Central nervous system. Local anesthetic requirements and
minimum alveolar concentration (MAC) for inhalational
agents are both decreased by 25% to 40% during pregnancy.

CLINICAL PEARL The physiologic changes of pregnancy most

relevant to the anesthesiologist are decreased FRC, aortocaval
compression if supine, decreased lower esophageal sphincter tone,
and reduced anesthetic requirement. Difficult intubation is more
common.

B. Maintenance of fetal oxygenation. Maintenance of

uteroplacental perfusion and adequate maternal oxygenation
preserves fetal oxygenation. These functions are of utmost
importance to any anesthetic administered during pregnancy. The
physician must be aware of the effects of interventions on
maternal cardiac output, oxygen delivery, and uterine blood flow.
Above all, avoid maternal hypoxia and hypotension.
C. Prevention and treatment of preterm labor. Preterm labor is
the most difficult problem to overcome perioperatively, and
preterm delivery is the most common cause of fetal loss. Preterm
labor is probably not influenced by anesthetic management but by
the underlying disease and the surgery itself. Unfortunately, there
are no reliable therapies to prevent or treat preterm labor. Most
outcome studies have shown that women who have undergone
surgery while pregnant will deliver earlier in gestation than those
who have not, even if delivery is remote from surgery and that
their babies will be smaller.3
II. Teratogenicity of anesthetic agents
Teratogenic effects due to anesthetic agents have not been
conclusively demonstrated in humans (see Table 6.1). A problem for
physicians and patients is that drugs of any type are rarely tested for
safety in pregnancy, either before or after they are marketed.4
Inadequate information is available for women and their physicians to
determine the risks of most drugs. The anesthetic drugs that usually
generate the most concern are nitrous oxide and the benzodiazepines.
In animal studies, nitrous oxide increases adrenergic tone and may
vasoconstrict uterine vessels and reduce uterine blood flow if not
combined with a halogenated (sympatholytic) agent.5 This leads to
abortions and congenital anomalies in small animal studies. It is
important to emphasize that no adverse effects of nitrous oxide have
been demonstrated in human pregnancy despite extensive use.6

An association between benzodiazepine use and oral cleft

anomalies was reported in the 1970s, but later case-control and
prospective studies failed to demonstrate a relationship between oral
cleft anomalies and benzodiazepine use during pregnancy.7–9
Benzodiazepines are now even recommended as a treatment to be
considered with refractory hyperemesis gravidarum.10 Opioids,
intravenous induction agents, and local anesthetics have a long history
of safety when used during pregnancy. A meta-analysis of studies on
anesthetic exposure in the workplace concluded that a slight increased
risk of miscarriage is the only potential obstetric problem for
operating room (OR) personnel.11 The risk of smoking during
pregnancy or ionizing radiation risks for pregnant personnel working
in radiology departments are much higher than any potential risk for
OR staff exposed to trace anesthetics.
 Of concern, however, is recent animal work on N-methyl-D-
aspartate (NMDA) receptor blockers (e.g., ketamine, nitrous oxide)
and gamma aminobutyric acid (GABAA) receptor enhancers (e.g.,
benzodiazepines, intravenous induction agents, volatile
anesthetics).12,13 Currently used anesthetics are thought to act by one
of these mechanisms. In animal studies, fetal or newborn exposure to
these agents results in widespread apoptotic neurodegeneration and
persistent memory/learning impairment. For example, 7-day-old rats
(the equivalent of 0 to 6 months of age in humans), which received 6
hours of general anesthesia using midazolam, nitrous oxide, and
isoflurane had memory and learning impairments, apoptotic
neurodegeneration, and hippocampal synaptic function deficits.14 The
relevance to human exposure is unclear, but the equivalent period in
humans is from the third trimester to approximately age 3. Are these
results in animals attributable to the direct effects of anesthetics, or
are they the result of factors we would not see clinically, for example,
high anesthetic doses over long periods of time, hypoxia, respiratory
acidosis, or starvation? At present, there is not enough information to
change our clinical practice, and alleviation of pain and stress during
surgery is obviously an essential clinical goal.15,16

CLINICAL PEARL No anesthetic agents are documented

teratogens, including nitrous oxide and the benzodiazepines, but
anesthetic neurotoxicity to the developing brain is of concern and
the focus of ongoing research.

III. Preoperative plan and counseling

Preoperative assessment should include pregnancy testing if her
pregnancy status is uncertain or if the patient requests it, counseling
the patient on anesthetic risks (or lack thereof) to the fetus and
pregnancy, and educating her about symptoms of preterm labor and
the need for uterine displacement at all times after 24 weeks of
gestation (see Tables 6.2 and 6.3).
 Mandatory pregnancy testing is controversial, raising both medical
and ethical issues.17 Any female patient between 12 and 50 years of
age should have the date of her last menstrual period documented on
the anesthetic record. Pregnancy testing should be offered if more
than 3 weeks has elapsed. If surgery can be delayed until the second
trimester, the risks of teratogenicity and spontaneous miscarriage are
less. In addition, preterm labor is not as common during the second
trimester as it is during the third trimester.

CLINICAL PEARL Mandatory pregnancy testing is

controversial, but testing should be offered and available.

Administration of preoperative medications to allay anxiety or pain is

appropriate because elevated maternal catecholamines may decrease
uterine blood flow. The decision to use benzodiazepines such as
midazolam is up to the judgment of the anesthesiologist and the
wishes of the patient. Consider aspiration prophylaxis with some
combination of an antacid, metoclopramide, and/or H2-receptor
antagonist. Discuss perioperative tocolysis with the patient’s
 obstetrician. Indomethacin (oral or suppository), oral nifedipine, and
intravenous infusion of magnesium sulfate are the most commonly
used perioperative tocolytics. Indomethacin has few anesthetic
implications, but nifedipine can contribute to hypotension.
Magnesium sulphate potentiates nondepolarizing muscle relaxants
and attenuates vascular responsiveness, making hypotension more
difficult to treat during acute blood loss or volume shifts.
IV. Intraoperative anesthetic management
There is no evidence that any intraoperative anesthetic technique is
preferred over another as long as maternal oxygenation and
uteroplacental perfusion are maintained. A small study found a higher
risk of preterm labor in patients undergoing surgery for an adnexal
mass when regional anesthesia was used compared to general
anesthesia.18 However, there is no outcome data from larger studies
showing that type of surgery, type of anesthetic, trimester in which
surgery occurs, length of surgery, estimated surgical blood loss, or
length of anesthesia influences pregnancy outcome. Monitoring
should include blood pressure, pulse oximetry, end-tidal CO2, and
temperature. PCO2 is decreased by approximately 10 mm Hg during
pregnancy due to increased minute ventilation, and end-tidal CO2
should be corrected accordingly. Maternal metabolic requirements are
increased while FRC is decreased; therefore, arterial desaturation
occurs more quickly during apnea or hypoventilation. Blood glucose
should be checked during long procedures to ensure normoglycemia.

CLINICAL PEARL No specific anesthetic technique has been

proven to affect outcome. Maternal oxygenation, perfusion, optimal
pain control, and early mobilization are key goals.

If it will not interfere with the surgical field, intermittent or

continuous fetal monitoring may be performed to ensure that the
intrauterine environment is optimized. This may be as simple as
checking fetal heart tones (fetal heart rate [FHR]) before and after
 surgery or as complex as continuously monitoring the FHR
throughout surgery. Monitoring should be approached as a medical
issue, not a medicolegal one. Justify whether this modality will
change your management. The American College of Obstetricians and
Gynecologists (ACOG) and the American Society of
Anesthesiologists (ASA) have issued a joint statement on
“Nonobstetric Surgery in Pregnancy” which states in part that “the
decision to use fetal monitoring should be individualized, and, if used,
should be based on gestational age, type of surgery, and facilities
available. Ultimately, each case warrants a team approach (anesthesia,
obstetric care providers, surgery, pediatrics, and nursing) for optimal
safety of the woman and the fetus.”19 At a minimum, an obstetric
consultation should be obtained before surgery to document the
preoperative well-being of the fetus and to introduce the woman to
their service in case obstetric intervention is needed perioperatively.

CLINICAL PEARL Fetal monitoring should be discussed with

the obstetric team as part of their preoperative consult.

When continuous monitoring is performed, loss of beat-to-beat

variability will occur during general anesthesia or sedation, but fetal
bradycardia should not. Decelerations may indicate the need to
increase maternal oxygenation, elevate maternal blood pressure,
increase uterine displacement, change the site of surgical retraction, or
begin tocolysis. Fetal monitoring can help the anesthesiologist assess
adequacy of perfusion during induced hypotension, CPB, or
procedures involving large fluid shifts. If the mother is awake during
regional anesthesia, it can be very reassuring for her to hear fetal heart
tones during the procedure. However, intraoperative fetal monitoring
may be impractical in urgent situations or during abdominal surgery.
Monitoring has not been shown to improve fetal outcome. Personnel
with labor and delivery (L&D) expertise may not be readily available,
and misinterpretation of the fetal monitor tracing could lead to
unnecessary preterm delivery.20 ACOG supports preoperative
 consultation with an obstetrician before any nonobstetric surgery
during pregnancy but states that the need for fetal monitoring should
be decided on a case-by-case basis.19
General anesthesia should include full preoxygenation and
denitrogenation, rapid sequence induction with cricoid pressure, and
avoidance of hypoxia. Keep in mind the pregnant airway is more
edematous and vascular, and visualization may be more difficult
during laryngoscopy. During the first trimester, high-dose ketamine
(>2 mg per kg) may cause uterine hypertonus although usual doses
are safe. MAC is decreased 25% to 40% during pregnancy, and
inhalational agents should be kept below 2.0 MAC to prevent
decreased maternal cardiac output. Nitrous oxide may be used at the
anesthesiologist’s discretion. Administering muscle relaxant reversal
agents slowly has been recommended to prevent acute increases in
acetylcholine that might induce uterine contractions.
Regional anesthetic techniques have the advantage of minimizing
drug exposure in early pregnancy. If sedation is avoided, there should
be no changes in FHR variability during continuous fetal monitoring.
Prevent hypotension after neuraxial techniques with adequate volume
replacement and uterine tilt and treat hypotension aggressively with
pressors (phenylephrine or ephedrine) if needed. Decrease the
neuraxial dose of local anesthetic by approximately one-third from
that used in nonpregnant patients. Regional anesthetics provide
excellent postoperative pain control, reducing maternal sedation so
that (a) the patient can report symptoms of preterm labor, (b) FHR
variability is maintained, and (c) early mobilization can occur,
reducing the risk of thromboembolic complications.
V. Postoperative care
Postoperative monitoring of FHR and uterine activity should
continue. Preterm labor must be treated early and aggressively.
Monitoring may require recovery in the L&D unit or provision of
L&D nursing expertise in the surgical recovery area or intensive care
unit (ICU). Remember that parenteral pain medications will decrease
FHR variability; therefore, neuraxial techniques or peripheral nerve
 blocks should be used when possible. Pregnant patients are at high
risk for thromboembolism and should be mobilized as quickly as
possible—another reason for aggressive postoperative pain
management. If mobilization is not possible, prophylactic
anticoagulation should be considered. Maintain maternal oxygenation
and left uterine displacement. Neonatology should be notified if the
fetus is more than 23 weeks’ gestational age so that the mother can be
counseled should preterm labor occur.

CLINICAL PEARL Key postoperative management includes

continued monitoring of FHR and uterine activity if the fetus is
viable and use of thromboprophylactic measures.

VI. Special situations

A. Trauma. Trauma is a leading cause of maternal death. Fetal loss
in these situations is due to hemodynamic instability, placental
abruption, or maternal death.21 Early ultrasonography should be
performed in the emergency room to determine fetal viability.
Fetal monitoring should be performed continuously if ≥23 weeks’
gestation. The mother should receive all needed diagnostic tests
to optimize her management, with shielding for the fetus when
possible. Radiation exposure of <5 rad (e.g., head computed
tomography [CT] is <1 rad) does not pose increased risk to the
fetus.22 Ultrasonography and magnetic resonance imaging (MRI)
are alternatives that do not utilize ionizing radiation. There are
few indications for an emergent cesarean delivery (CD) in the
setting of acute trauma, but these would include (a) a stable
mother with a viable fetus in distress, (b) traumatic uterine
rupture, (c) a gravid uterus interfering with intraabdominal
surgical repairs in the mother, and (d) a mother who cannot be
saved with a fetus that is viable. If the fetus is previable or dead,
focus on optimizing maternal condition. She will tolerate vaginal
delivery at a later time better than an emergent laparotomy for
 CD.
B. Neurosurgical procedures. Neurosurgical procedures such as
aneurysm clipping or arteriovenous malformation (AVM) repair
may be required in this age-group.23 A variety of anesthetic
approaches have been successful for neurosurgical procedures
during pregnancy. Fetal monitoring may be helpful when
hypotension is expected or if large volume shifts or blood loss are
anticipated. Aggressive diuresis may reduce uterine perfusion if
the maternal cardiac output is impaired. In animal studies, very
high doses of mannitol cause fetal dehydration, but this is
probably not clinically relevant. Hyperventilation may be
necessary but reduces maternal cardiac output and decreases
oxygen release to the fetus by shifting the maternal
oxyhemoglobin dissociation curve to the left. Endovascular
treatment of acutely ruptured intracranial aneurysms has been
performed successfully during pregnancy, thereby avoiding
craniotomy.24 Fetal shielding should be used during
interventional radiology procedures.
C. Cardiac surgery requiring cardiopulmonary bypass. Cardiac
surgery has been performed successfully during pregnancy. The
physiologic increase in blood volume and cardiac output is
maximal at 28 to 30 weeks, and this is when cardiac
decompensation may occur in parturients with stenotic valvular
lesions or pulmonary hypertension. Another high-risk period
occurs immediately postpartum. After delivery, the release of
aortocaval compression and autotransfusion of uteroplacental
blood increases cardiac output to its maximum. Women who have
severe cardiac symptoms during pregnancy, unresponsive to
medical management, may benefit from surgery. If possible,
surgery should be delayed until the second trimester when the
major risk of teratogenicity (e.g., from cardiac medications, x-
rays, and low-flow or hypoxic states) is less and preterm labor is
also less likely. In patients close to term, combined CD and valve
replacement has been performed successfully. Do not withhold
 surgery if it is indicated for maternal reasons; maternal mortality
during pregnancy is comparable to nonpregnant rates, although
fetal morbidity may be high.25
Beyond 24 weeks’ gestation, monitor the fetus and maintain
left uterine displacement to optimize perfusion. Optimal pressures
and flows on bypass are unknown, but animal studies indicate
higher flows and pressures may be beneficial during pregnancy to
maintain uterine blood flow and fetal oxygenation. FHR
monitoring is a very sensitive measure of perfusion and can be
used to optimize pressure and flow. Fetal bradycardia commonly
occurs at the onset of CPB and slowly returns to a low normal
rate with little or no beat-to-beat variability. Hypothermia has
been used successfully, although some authors advocate for
normothermia on bypass. Optimizing intraoperative and
postoperative maternal condition is the best way to ensure good
fetal outcome.26

CLINICAL PEARL Complex surgical procedures can be

performed during pregnancy with attention to optimizing
uteroplacental perfusion.

D. Laparoscopic surgeries. Laparoscopy may be used to avoid

laparotomy when abdominal pain presents a diagnostic challenge
during pregnancy. Surgical procedures including cholecystectomy
and appendectomy can be performed laparoscopically.
Interestingly, fetal outcomes are similar with either laparotomy or
laparoscopy, although the maternal benefits of minimally invasive
surgery are similar to those in nonpregnant patients.3 Animal
investigations in near-term sheep have shown that CO2
pneumoperitoneum does not cause hypoxia or significant fetal
hemodynamic changes but does induce fetal respiratory acidosis.
Normalizing maternal end-tidal CO2 produces late and
incomplete correction in the fetus,27 but it is unknown if this is
 biologically significant to the developing brain. Recent work in
preterm animals indicates that insufflation-induced hypercapnia
and acidosis are accompanied by prolonged fetal hypoxia and
cardiovascular depression, even after insufflation is
discontinued.28 Intraabdominal pressure should be kept as low as
possible and operative time (i.e., insufflation time) kept to a
minimum. Other technical considerations should include fetal
shielding during cholangiograms, use of pneumatic compression
stockings, left lateral table rotation, and open trocar placement.29
E. Fetal interventions. Fetal surgery is a rapidly evolving speciality.
Advances in the field of prenatal imaging and continued
refinements in minimally invasive surgical techniques have
changed the approach to fetal interventions. A wide range of fetal
interventions are being performed at different stages of pregnancy
to save the life of the fetus or prevent irreversible fetal organ
damage (Table 6.4). Maternal safety is paramount, and risks to the
mother and fetus must be balanced against benefits to the fetus.

Minimally invasive interventions are the most commonly

performed fetal interventions and include both ultrasound-guided
and fetoscopic interventions. Fetoscopic interventions involve
ultrasound-guided percutaneous placement of trocar(s) through
the uterus into the amniotic cavity. A fetoscope is then inserted
through the trocar to visualize and perform the intended
procedure. The location of the placenta determines the surgical
approach, and fetal monitoring is usually limited to intermittent
measurement of FHR using Doppler ultrasonography. Advances
in surgical techniques and instrumentation have altered the
anesthetic management, with more procedures now being
performed with local anesthetic infiltration or neuraxial
techniques with sedation.30
Ex utero intrapartum treatment (EXIT) procedures are
commonly performed to secure the airway in fetuses with large
oropharyngeal or neck masses. Indications for the EXIT
procedure continue to evolve and now include resection of large
fetal mediastinal or lung masses and extracorporeal membrane
oxygenation (ECMO) cannulation while still preserving
uteroplacental circulation.31 Unlike a CD, the central principle of
an EXIT procedure is achieving controlled uterine hypotonia to
preserve the uteroplacental circulation. Maternal blood pressure is
maintained within 10% of baseline to ensure adequate
uteroplacental blood flow and fetal oxygenation. To prevent
uterine contractions and placental abruption, uterine volume is
preserved by using an amnioinfusion and only partially delivering
the fetus, if possible. Typically, EXIT procedures are performed
under general endotracheal anesthesia using high doses (2 to 3
MAC) of inhalational agents for adequate uterine relaxation.
Preoperatively, a lumbar epidural catheter is placed for
postoperative analgesia. Continuous fetal monitoring is critical
during the EXIT procedure and includes fetal echocardiography
and fetal pulse oximetry.32 Fetal bradycardia is a sign of fetal
distress that warrants prompt attention and treatment. Common
causes of fetal distress include mechanical compression or
kinking of the umbilical cord, placental separation, uterine
contractions, fetal hypovolemia, and maternal hypotension. Upon
partially delivering the fetus, intramuscular administration of a
 cocktail comprising fentanyl, vecuronium, and atropine ensures
fetal analgesia and immobilization. Regardless of the indication
for the EXIT procedure, securing the fetal airway should be the
first step and is performed via direct laryngoscopy. Flexible
and/or rigid bronchoscopy or a tracheostomy may be necessary in
fetuses with distorted airway anatomy. EXIT-to-ECMO allows
insertion of arterial and venous cannulas for ECMO while still on
placental support. An EXIT-to-resection strategy has been used in
fetuses with large chest masses presenting late in gestation with
persistent mediastinal compression.33 Just before clamping the
cord and completing the EXIT procedure, the inhalational agent is
decreased to allow uterine tone to return to normal; the umbilical
cord is clamped and cut, followed by delivery of the fetus.
Following placental delivery, uterine tone is augmented by
administration of oxytocin and manual uterine massage by the
surgeon. Blood products and additional uterotonic drugs should
be readily available. A separate team consisting of an
anesthesiologist, surgeon, neonatologist, and nurses must be
readily available for resuscitation and completion of surgery on
the newborn if necessary.

CLINICAL PEARL Unlike a CD, the central principle of an

EXIT procedure is achieving controlled uterine hypotonia to
preserve the uteroplacental circulation.

Open mid-gestation fetal surgery is performed for selected

indications including closure of myelomeningocele and resection
of intrathoracic lesions presenting with hydrops early in
gestation.34 The perioperative considerations are similar to an
EXIT procedure with a few exceptions. Following repair of the
specific defect, the fetal parts are returned to the uterine cavity
before closure of the uterus. Aggressive tocolysis is maintained
with magnesium sulfate infusion, rectal indomethacin, and oral
 nifedipine. To reduce the risk of maternal pulmonary edema,
intraoperative administration of intravenous fluids is
minimized.35 Preterm labor, preterm premature rupture of
membranes, and preterm delivery are common after open fetal
surgery.36 Although the hysterotomy for open fetal surgery and
EXIT procedures is typically not in the lower uterine segment, it
increases the risk of uterine rupture and a CD must be performed
prior to onset of labor in the current pregnancy as well as in all
future pregnancies.

CLINICAL PEARL Despite aggressive tocolysis, managing

preterm labor continues to be a vexing problem after open fetal
surgery.

SUMMARY
In conclusion, surgery may be necessary during pregnancy. Anesthesiologists
should reassure the mother that anesthetic drugs and techniques themselves will
not put the fetus or the pregnancy at risk. Prevention of preterm labor is the
greatest concern and may require perioperative monitoring and tocolysis.
Effective postoperative pain management without sedation will aid in early
diagnosis and treatment of preterm labor and assist with early mobilization to
prevent thromboembolic complications.

REFERENCES
1. Reitman E, Flood P. Anaesthetic considerations for non-obstetric surgery during pregnancy. Br J
Anaesth. 2011;107(suppl 1): i72–i78.
2. Koren G, Bologa M, Long D, et al. Perception of teratogenic risk by pregnant women exposed to
drugs and chemicals during the first trimester. Am J Obstet Gynecol. 1989;160:1190–1194.
3. Chohan L, Kilpatrick C. Laparoscopy in pregnancy: a literature review. J Clin Obstet Gynecol.
2009;52:557–569.
4. Lo WY, Friedman JM. Teratogenicity of recently introduced medications in human pregnancy. Obstet
Gynecol. 2002;100:465–473.
5. Mazze RI, Fujinaga M, Baden JM. Halothane prevents nitrous oxide teratogenicity in Sprague-Dawley
rats; folinic acid does not. Teratology. 1988;38:121–127.
6. Mazze RI, Källén B. Reproductive outcome after anesthesia and operation during pregnancy: a
 registry study of 5405 cases. Am J Obstet Gynecol. 1989;161:1178–1185.
7. Rosenberg L, Mitchell AA, Parsells JL, et al. Lack of relation of oral clefts to diazepam use during
pregnancy. N Engl J Med. 1983;309:1282–1285.
8. Shiono PH, Mills JL. Oral clefts and diazepam use during pregnancy. N Engl J Med. 1984;311:919–
920.
9. Dolovich LR, Addis A, Vaillancourt JM, et al. Benzodiazepine use in pregnancy and major
malformations or oral cleft: meta-analysis of cohort and case-control studies. BMJ. 1997;317:839–
843.
10. Buhimschi CS, Weiner CP. Medications in pregnancy and lactation (Parts 1 and 2). Obstet Gynecol.
2009;113:166–188 and 417–432.
11. Boivin JF. Risk of spontaneous abortion in women occupationally exposed to anaesthetic gases: a
meta-analysis. Occup Environ Med. 1997;54:541–548.
12. Ikonomidou C, Bosch F, Miksa M, et al. Blockade of NMDA receptors and apoptotic
neurodegeneration in the developing brain. Science. 1999;283:70–74.
13. Ikonomidou C, Bittigau P, Ishimaru MJ, et al. Ethanol-induced apoptotic neurodegeneration and fetal
alcohol syndrome. Science. 2000;287:1056–1060.
14. Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al. Early exposure to common anesthetic agents
causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J
Neurosci. 2003;23:876–882.
15. Olney JW, Young C, Wozniak DF, et al. Anesthesia-induced developmental neuroapoptosis: does it
happen in humans? Anesthesiology. 2004;101:273–275.
16. Jevtovic-Todorovic V, Absalom AR, Blomgren K, et al. Anaesthetic neurotoxicity and neuroplasticity:
an expert group report and statement based on the BJA Salzburg Seminar. Br J Anaesth.
2013;111:143–151.
17. Palmer SK, Van Norman GA, Jackson SL. Routine pregnancy testing before elective anesthesia is not
an American Society of Anesthesiologists standard. Anesth Analg. 2009;108:1715–1716.
18. Hong JY. Adnexal mass surgery and anesthesia during pregnancy: a 10-year retrospective review. Int J
Obstet Anesth. 2006;15:212–216.
19. American College of Obstetricians and Gynecologists Committee on Obstetric Practice. ACOG
Committee Opinion No. 474: nonobstetric surgery during pregnancy. Obstet Gynecol. 2011;117:420–
421. http://www.asahq.org. Accessed 9/22/15.
20. Immer-Bansi A, Immer FF, Henle S, et al. Unnecessary emergency caesarean section due to silent
CTG during anaesthesia? Br J Anaesth. 2001;87:791–793.
21. Brown HL. Trauma in pregnancy. Obstet Gynecol. 2009;114:147–160.
22. Baysinger CL. Imaging during pregnancy. Anesth Analg. 2010;110:863–867.
23. Wang LP, Paech MJ. Neuroanesthesia for the pregnant woman. Anesth Analg. 2008;107:193–200.
24. Piotin M, de Souza Filho CB, Kothimbakam R, et al. Endovascular treatment of acutely ruptured
intracranial aneurysms in pregnancy. Am J Obstet Gynecol. 2001;185:1261–1262.
25. Khandelwal M, Rasanen J, Ludormirski A, et al. Evaluation of fetal and uterine hemodynamics during
maternal cardiopulmonary bypass. Obstet Gynecol. 1996;88:667–671.
26. John AS, Gurley F, Schaff HV, et al. Cardiopulmonary bypass during pregnancy. Ann Thoracic Surg.
2011;91:1191–1197.
27. Reynolds JD, Booth JV, de la Fuente S, et al. A review of laparoscopy for non-obstetric-related
surgery during pregnancy. Curr Surg. 2003;60:164–173.
28. Uemura K, McClaine RJ, de la Fuente SG, et al. Maternal insufflation during the second trimester
equivalent produces hypercapnia, acidosis, and prolonged hypoxia in fetal sheep. Anesthesiology.
2004;101:1332–1338.
29. Pearl J, Price R, Richardson W, et al. The Society of American Gastrointestinal Endoscopic Surgeons
(SAGES) guidelines for diagnosis, treatment, and use of laparoscopy for surgical problems during
pregnancy. Surg Endosc. 2011;25:3479–3492. doi:10.1007/s00464-011-1927-3.
30. Lin EE, Tran KM. Anesthesia for fetal surgery. Semin Pediatr Surg. 2013;22:50–55.
31. Marwan A, Crombleholme TM. The EXIT procedure: principles, pitfalls, and progress. Semin Pediatr
Surg. 2006;15:107–115.
32. Rychik J, Tian Z, Cohen MS, et al. Acute cardiovascular effects of fetal surgery in the human.
Circulation. 2004;110:1549–1556.
33. Cass DL, Olutoye OO, Cassady CI, et al. EXIT-to-resection for fetuses with large lung masses and
persistent mediastinal compression near birth. J Ped Surg. 2013;48:138–144.
34. Adzick NS, Thom EA, Spong CY, et al. A randomized trial of prenatal versus postnatal repair of
myelomeningocele. N Engl J Med. 2011;364:993–1004.
35. Ferschl M, Ball R, Lee H, et al. Anesthesia for in utero repair of myelomeningocele. Anesthesiology.
2013;118:1211–1223.
36. Golombeck K, Ball RH, Lee H, et al. Maternal morbidity after maternal-fetal surgery. Am J Obstet
Gynecol. 2006;194:834–839.
Labor and Delivery
 Fetal Assessment and Monitoring
Michael G. Richardson, Mary DiMiceli-Zsigmond, and David R.
Gambling

I.Physiologic basis of fetal monitoring
II.Electronic fetal monitoring
III.Interpretation of electronic fetal monitoring
IV. Antepartum fetal monitoring
V. Intrapartum fetal surveillance
A. Physiology
B. Intrapartum electronic fetal monitoring–nomenclature and
interpretation
C. Classification of electronic fetal monitoring tracings
D. Management of abnormal electronic fetal monitoring patterns
and in utero resuscitation
E. Intermittent auscultation
VI. Medication and anesthetic effects on fetal surveillance
A. Maternally administered medications
B. Regional anesthesia
C. General anesthesia

KEYPOINTS
1. The goal of antepartum and intrapartum fetal monitoring is to improve
 neonatal outcomes, namely to reduce neonatal mortality and neurologic
morbidity.
2. A working knowledge of EFM allows the obstetric anesthesiologist to
anticipate problems and communicate effectively with the obstetrician or
perinatologist.
3. The physiologic basis underlying antepartum fetal monitoring is fetal
dependence on continuous delivery of adequate amounts of oxygen via a
pathway of transfer steps from maternal to fetal circulations. Any process
that interferes with this transfer of oxygen can lead to fetal hypoxia and
acidosis.
4. Electronic fetal monitoring (EFM) has a low positive predictive value,
and there has been considerable interindividual variation as to how a fetal
heart rate (FHR) pattern is interpreted.
5. Other forms of antepartum surveillance include nonstress test, contraction
stress test, biophysical profile, and umbilical artery Doppler velocimetry.
They help to diagnose fetal abnormalities, monitor fetal well-being, and
determine optimal time for delivery.
6. In recent years, renewed attention has been aimed at standardizing
definitions, interpretation of EFM, interventions, and underlying
physiology, with the hope of enhancing the effectiveness and safety of
fetal monitoring and its contribution to better neonatal outcomes.
7. Continuous EFM during labor is associated with a reduction in neonatal
seizures but no difference in rates of cerebral palsy or infant mortality.
However, continuous EFM is associated with an increase in cesarean and
instrumental vaginal deliveries.
8. It is important to understand how certain medications and anesthetic
techniques can affect fetal physiology, either directly or indirectly. This
will, in turn, impact on the ability to interpret EFM appropriately and act
accordingly.

THE GOAL OF ANTEPARTUM AND intrapartum fetal monitoring is to improve

neonatal outcomes, namely to reduce neonatal mortality and neurologic
morbidity.1–5 The premise is that fetal monitoring can detect signs of
unfavorable fetal oxygenation and acid–base status, allowing timely intervention
to either improve fetal oxygen delivery or deliver the fetus if improved oxygen
delivery is ineffective.3 Although fetal monitoring technology has improved
during the 50 years since its inception, the application of a uniform classification
and interpretation of electronic fetal monitoring (EFM) has lagged. As a result,
the positive predictive value (PPV) of abnormal fetal surveillance remains low,
and evidence of improved neonatal mortality and neurologic morbidity is
lacking, even though cesarean delivery rates have climbed significantly.6–8
When such monitoring is applied universally, instead of when indicated (in the
context of low risk for or low prevalence of fetal hypoxia), the false-positive rate
for abnormal results is high.9,10 This is a concern because abnormal results often
prompt urgent surgical delivery. In turn, this may lead to unnecessary surgery
and has the potential to contribute to fetal and maternal morbidity. In recent
years, there have been renewed efforts to standardize definitions, EFM
interpretation, and clinical interventions in order to enhance the effectiveness
and safety of fetal surveillance and its contribution to better neonatal outcomes.
Despite its limitations, antenatal surveillance is widely recommended1–4 and
is used to monitor fetal growth and well-being. It also allows the means to
consider the risks of continuing pregnancy versus delivery, especially in the
presence of complicating conditions. Similarly, intrapartum fetal surveillance is
used routinely in the United States during spontaneous and induced labor and
during the conduct of anesthesia before cesarean delivery, in order to monitor the
adequacy of fetal oxygenation and acid–base status.2–5,11 Because the use of
EFM and other surveillance techniques during pregnancy are so pervasive, it
behooves the obstetric anesthesiologist to be familiar with fetal monitoring in
order to contribute to patient care in a way that helps promote maternal and fetal
health.

I. Physiologic basis of fetal monitoring

The physiologic basis underlying antenatal fetal testing is fetal
dependence upon an adequate delivery of oxygen via a pathway that
involves a number of steps of oxygen transfer.12 These are the main
steps:
Atmosphere/environment → maternal lungs → maternal blood
 → maternal systemic circulation → uterine artery blood flow
→ spiral arteries/intervillous space → maternal–fetal gas
transfer → fetal umbilical perfusion → fetal vital organs.
A significant barrier to this stepwise transport of oxygen toward the
fetus can rapidly lead to fetal hypoxia and acidosis, causing
neurologic and cardiovascular changes, ultimately culminating in fetal
death if uncorrected. The fetal responses to hypoxemia and acidosis
include decreased amniotic fluid volume and decline in fetal
biophysical variables (movement, tone, breathing, disappearance of
normal fetal heart rate [FHR] variability, which requires an intact
autonomic nervous system, and changes in baseline FHR).3,13 Fetal
surveillance aims to detect these signs, which are adaptive fetal
“cardiovascular defensive” responses to hypoxia14: a decreased heart
rate and attenuation of nonvital functions (movement) reduce
myocardial and overall oxygen consumption, help preserve oxygen
stores, and redirect perfusion to vital organs (brain, heart, and adrenal
glands). In contrast to the acute fetal cardiovascular response to
insufficient fetal oxygen delivery, lesser degrees of chronic
uteroplacental insufficiency may contribute to fetal growth restriction
(FGR) and reduced renal perfusion, with oligohydramnios from
reduced fetal urine output.13,15 Accordingly, antenatal fetal
surveillance indirectly indicates the presence of acute or chronic fetal
hypoxia or acidosis. Of note, measures of antenatal fetal well-being
are affected by maternal medications (e.g., β-blockers, corticosteroids,
opioids), drug and tobacco use, fetal sleep–wake cycles, gestational
age, and fetal comorbidities and anomalies.
II. Electronic fetal monitoring
A. Electronic FHR monitoring is the fundamental technology used
for fetal assessment. It is a key component of antepartum
surveillance (nonstress test; oxytocin challenge test) and serves to
monitor babies during labor. Although the first fetal
electrocardiogram was reported in 1906,16 EFM was not used
clinically until the 1960s, after which EFM gained increasingly
widespread acceptance as a screening tool in clinical obstetrics.10
 B. Modern monitors receive several inputs, including one or two
channels for FHR input, one that records uterine contractions, and
one that may receive fetal or maternal electrocardiogram (ECG)
input. Most commonly, FHR input is delivered by a noninvasive,
external Doppler transducer applied to the parturient’s abdomen
and directed at the fetal heart. Alternatively, input may be
delivered by a fetal scalp electrode (FSE)—a spiral ECG
electrode inserted into scalp surface skin, which provides direct
ECG input. Interpretation of EFM requires examination of
patterns in temporal relationship with uterine contractions; hence,
an external tocodynamometer is built into most monitors. This
noninvasive pressure transducer simply reveals the timing and
frequency of contractions, not contraction strength. Alternatively,
insertion of an intrauterine pressure catheter (IUPC) allows
quantitative assessment of uterine contraction strength, which the
obstetrician may use to assess adequacy of labor contractions and
precisely titrate oxytocin infusions. Use of internal monitors (FSE
and IUPC) is limited to women with ruptured membranes.
Application of FSE requires a singleton, vertex presentation.
Internal monitors carry the remote risks of uterine perforation,
intrauterine infection, and placental abruption.
III. Interpretation of electronic fetal monitoring
A. EFM interpretation is subjective and context-dependent, likely
contributing to persistent poor inter- and intraobserver
interpretation reliability.8
B. The first consensus on EFM standards, in 1997, defined FHR
characteristics, with the goals of promoting evidence-based
management of fetal compromise and for facilitating research on
fetal assessment and intervention.17
C. In 2008, EFM interpretation schemes and interventions were
proposed, which clarified and revised nomenclature.18 The
authors of these guidelines recommended a three-tiered
classification system for EFM and suggested intervention
responses for each EFM category.
 D. This approach to improving EFM reliability (i.e., reducing false-
positive rates) may not be ideal for the following reasons:
1. EFM continues to be used as a “screening test” in populations
with low prevalence of “disease.”
2. The variables involved are context-dependent.
3. There is continued reliance on human interpretation.8,10
E. More recent attempts to improve diagnostic performance focus on
evidence-based intervention responses to category 2 EFM19–24
and greater integration of pathophysiologic principles underlying
such interventions.12,25,26
IV. Antepartum fetal monitoring
A. Purpose and principles
1. Antepartum monitoring is performed before labor begins
and has two primary objectives: to diagnose fetal
abnormalities and to monitor the condition of the fetus to
determine the optimal timing of delivery.3 The latter concerns
preventing fetal death by identifying the fetus that may be
exposed to some degree of uteroplacental compromise,
thereby allowing for intervention before progressive
hypoxemia and acidosis lead to fetal demise.1
2. Subtle abnormalities in fetal surveillance tests begin to occur
after villous obliteration has affected approximately a third of
the villous vasculature.
3. Doppler-assessed umbilical artery (UA) end diastolic velocity
(EDV) may be absent or reversed once 60% to 70% of the
villous vasculature is affected, with resulting increased risk of
fetal hypoxemia and/or acidemia.13
4. Antepartum assessment methods include:
a. Maternal perception of movement
b. Nonstress test (NST)
c. Contraction stress test (CST)
d. Biophysical profile (BPP) and modified BPP
e. UA Doppler velocimetry
 5. American College of Obstetricians and Gynecologists
(ACOG) currently recommends antepartum fetal surveillance
for pregnancies at increased risk for intrauterine fetal demise,
whether due to preexisting maternal conditions or
complications of pregnancy (Table 7.1).1

6. Individualized risk assessment determines choice of modality.

The risk of iatrogenic premature delivery, prompted by false-
positive testing results, must be considered.
B. Screening ultrasound survey
1. A screening ultrasound exam is commonly performed at 16 to
 20 weeks and sometimes during the first trimester27 in order
to:
a. Determine the number of fetuses
b. Estimate fetal age
c. Identify placental location
d. Assess fetal anatomy to detect any anomalies or problems
2. Benefits include improvement in:
a. Estimation of gestational age, to decrease the risk of
postterm pregnancy
b. Detection of aneuploidy (e.g., Down syndrome)
c. Identification of multiple gestations
d. Detection of congenital anomalies27
C. Maternal monitoring of fetal movement is available to all
women, without need for technology, and is recommended
beginning at 26 to 32 weeks for all pregnancies with risk factors
for adverse perinatal outcomes.3
1. Healthy women without risk factors may benefit from being
aware of the significance of fetal movements during the third
trimester and should perform a fetal movement count if they
perceive less movement.3
2. The best movement-counting protocol (number of
movements; duration of counting) has not been established.
Hence, there are a number of protocols in use at present.1
D. NST uses EFM to assess for temporary FHR accelerations, which
accompany spontaneous movement in a fetus that is either
acidotic or neurologically depressed.
1. NST is categorized as reactive (i.e., reassuring) if the fetus
has two or more accelerations (≥15 beats per minute [bpm]
increase, lasting ≥15 seconds) within 20 minutes.
2. NST is characterized as nonreactive if there are less than two
accelerations in 40 minutes.
3. If there are no fetal movements, vibroacoustic stimulation
may be applied for 1 to 2 seconds to arouse a sleeping fetus to
elicit FHR accelerations, which are predictive of fetal well-
 being.
4. NST relies on an intact fetal autonomic nervous system—fetal
movement is accompanied by increased sympathetic output,
accounting for FHR acceleration. These neural pathways do
not mature until 28 weeks’ gestation. Prior to 28 weeks, 50%
of NSTs may be nonreactive and 15% prior to 32 weeks. This
is due to autonomic nervous system immaturity.
5. Lower thresholds (≥10 bpm rise, ≥10 seconds) for deeming
the NST reactive appear to preserve the predictive value of a
normal test. In addition to reactive/nonreactive categorization
of NST results, the other basic parameters of EFM are
assessed (baseline rate, variable, decelerations).
6. If uterine contractions are present, then a NST is technically a
spontaneous CST, although contractions may not be frequent
enough to qualify as a formal CST.
7. Although a reactive NST is reliable in confirming fetal well-
being (i.e., a high negative predictive value [NPV]), a
nonreactive NST falsely predicts fetal hypoxemia/acidosis
55% to 90% of the time.28–31
8. An abnormal result prompts a stepwise approach to further
fetal assessment, typically a CST or BPP. Depending on the
clinical situation, in utero resuscitation, or even expedited
fetal delivery, may be indicated.
E. CST, also known as oxytocin challenge test (OCT) was first
described in 1972.
1. It is a means of providing a physiologic stress to the fetus, the
response to which may reflect the degree of fetoplacental
respiratory reserve.32
2. Uterine contractions normally reduce uterine perfusion and
fetal oxygen delivery, such that a fetus with diminished
uteroplacental reserve may develop hypoxia and/or asphyxia
sufficient enough to cause alterations in fetal compensatory
physiologic parameters.3
3. A NST is performed before a CST. During the latter, the
 patient is placed in the lateral recumbent position, continuous
EFM is performed, and intravenous (IV) oxytocin is titrated to
effect an adequate contraction pattern (at least three
contractions of at least 40 seconds duration each, within 10
minutes).
4. Nipple stimulation (woman rubs one nipple with her fingers,
through her clothes, rapidly, but gently, for 2 minutes, then
stops for 5 minutes) is equally or more successful in inducing
adequate contractions for a CST, compared to exogenous
oxytocin administration.
5. CST results are classified as follows:
a. Negative: normal FHR baseline rate with no late or
significant variable decelerations
b. Positive: late FHR decelerations occurring with >50% of
induced contractions (even if contraction frequency is <3
per 10 minutes)
c. Equivocal-suspicious: intermittent late FHR
decelerations, or significant variable FHR decelerations
d. Equivocal: FHR decelerations occurring with
contractions more frequent than two per 10 minutes, or
lasting >90 seconds.
e. Unsatisfactory: less than the requisite contraction rate of
three per 10 minutes, or uninterpretable cardiotocography.
6. Like the NST, a CST has excellent NPV but poor PPV for
perinatal morbidity (8.7% to 14.9%).
7. CST has been supplanted by newer methods (i.e., assessment
of biophysical variables and vascular flow measurements) but
is still used for many at-risk fetuses—preterm, postdates,
uteroplacental pathology, growth restriction.
8. The only contraindications include those that would preclude
labor or vaginal delivery and a gestational age (<24 weeks)
that would preclude intervention if the result were abnormal.
F. Biophysical profile. BPP combines the NST with sonography to
assess current fetal well-being.
1. Sonography is performed over 30 minutes, assesses fetal
behaviors (fetal movement, tone, breathing movements), and
measures amniotic fluid volume.
2. BPP serves as a sensitive method of detecting acute or chronic
fetal hypoxia.
3. Each of five assessed components is assigned 2 points if
criteria (outlined in Table 7.2) are met, or 0 if they are not. A
composite score is calculated: 8 to 10 is normal, 6 is
equivocal, and 4 or less is abnormal.

4. Fetal adaptive responses to hypoxia include redirection of

blood flow to the fetal brain and heart, but away from fetal
kidneys. As a result, renal blood flow and urine output
decrease, resulting in oligohydramnios as assessed by
amniotic fluid volume.3
5. Ultrasonography is used to measure amniotic fluid volume in
four intrauterine quadrants and calculate the amniotic fluid
index (AFI). Alternatively, the maximal vertical pocket
(MVP) is measured.
6. Oligohydramnios is defined as either AFI <5 cm or MVP <2
cm. Both methods appear to be equivalent in predicting
adverse outcomes, but use of AFI is associated with higher
rates of cesarean delivery and induction of labor without
improved perinatal outcome.
7. A “modified BPP” (mBPP), which consists of only NST
(short-term indicator of fetal hypoxia/acidemia) and AFI
(indicator of long-term placental insufficiency), is simpler and
quicker to perform. Its effectiveness in identifying a
 compromised fetus is similar to BPP.
8. BPP and mBPP both have an NPV of >99% (0.8 stillbirths per
1,000 reassuring BPP or mBPP results).15 Progressively lower
BPP test scores correlate directly with fetal acidemia,
measured by umbilical vein (UV) pH. BPP scores of 8 to 10
are not associated with fetal acidemia, a score of 6 is
equivocal, and 0 to 4 is highly associated with fetal
acidemia.33–35
9. BPP scores are inversely related to perinatal morbidity, as
measured by five outcome variables.
a. Fetal decelerations prompting operative obstetric
intervention
b. Five-minute Apgar score <7
c. UV pH <7.20
d. Fetal growth restriction (FGR) (<10% percentile for
gestational age)
e. Admission to the neonatal intensive care unit (NICU)
10. Perinatal mortality (total, and corrected for major fetal
anomaly) exhibits a significant inverse exponential
relationship to BPP scores without intervention.33
11. BPP results must be interpreted in context.
a. First, the test should be performed when indicated (see
Table 7.1) and at an appropriate gestational age (not
before 32 0/7 weeks for most at-risk patients).
b. In the case of a nonpersistent indication (e.g., one episode
of decreased fetal movement) and reassuring testing, then
repeated surveillance testing is not necessary.
c. If the risk factor that prompts testing persists, but testing
is reassuring, then surveillance testing is typically
repeated weekly, although it may be performed more
frequently for some high-risk conditions.
d. An abnormal result is considered in clinical context.
Abnormal results associated with acute maternal
conditions often normalize once the maternal condition is
 corrected.
e. Abnormal BPP results typically prompt further evaluation,
to minimize risk of unnecessary premature delivery based
on one false-positive result.
f. Contributing to high false-positive results are various
benign factors, such as fetal sleep, hypoglycemia, supine
hypotension syndrome, and maternally administered
opioids and sedatives.
G. Doppler velocimetry is a noninvasive assessment technique used
in conjunction with other fetal surveillance modalities,
specifically when FGR is suspected.
1. In normal pregnancy, trophoblasts invade the media of
maternal spiral arteries and transform them into high-flow,
low-resistance shunts.3 In parallel, villous development
(sprouting and differentiation) reduces resistance in the fetal
circulation through the placenta.13 Consequently, both
maternal uterine arterial and fetal umbilical arterial flows
increase early in pregnancy and continue to increase
throughout normal pregnancy. They are characterized by high
diastolic flow, and Doppler velocimetry flow indices are
commonly used to assess them, including:
a. Systolic-to-diastolic ratio (S/D): ratio of frequency shift
during systole to that during diastole; commonly used to
evaluate fetal UA flow
b. Pulsatility index (PI): difference between frequency
shifts during systole and diastole, divided by mean
frequency shift; commonly used to evaluate maternal
uterine arterial flow and fetal middle cerebral artery
(MCA) flow
c. Resistance index (RI): difference between frequency
shifts during systole and diastole, divided by frequency
shift during systole; most often used to assess MCA flow
2. Many conditions (e.g., hypertensive disorders, diabetes
mellitus, collagen vascular disease, chronic placental
 abruption, placental infarction, thin or circumvallate
placentas) may interfere with normal placental vascular
development, thereby jeopardizing gas exchange and nutrient
delivery.
3. Placental dysfunction is associated with higher vascular
resistance and uteroplacental insufficiency, that is, reduced
blood flow to the fetus, risking growth restriction. Increased
resistance reduces diastolic flow to a greater degree than
systolic flow, increasing all three Doppler index values.
4. There is ongoing research into the usefulness of Doppler
velocimetry measurements of fetal MCA, UV, ductus venosus
(DV), inferior vena cava, descending aorta, and renal arteries
for fetal assessment. Although evidence for improved
outcome is still lacking, some centers are using several of
these surveillance modalities in conjunction with ultrasound
anatomic surveys and BPP to guide management of preterm
growth restricted fetuses.
5. UA Doppler ultrasound velocimetry is the most commonly
used Doppler surveillance for high-risk pregnancies,
particularly those at risk for uteroplacental insufficiency.15 It
is also used to distinguish between the growth restricted and
constitutionally small fetus.
6. In the progression of placental dysfunction and FGR, once a
third of the placental vasculature is affected by disease, UA
S/D ratio is consistently increased, while after half of the fetal
villi are obliterated, UA blood flow becomes pulsatile
(exhibits absent or reversed end diastolic flow).13,36 Reversed
end diastolic flow predicts increased rates of NICU admission
and perinatal mortality,37–39 as well as long-term neurologic
complications.40
7. There is a predictable progression of fetal responses to
placental vascular dysfunction.
a. Before UA Doppler becomes abnormal, UV and DV
flows are decreased—increased DV shunting away from
 the liver and associated alterations in glucose–insulin
metabolism lead to decreased fetal abdominal
circumference, observable before estimated fetal weight
falls below the 10th percentile.
b. Decreased UA Doppler index ensues, and chronic
deprivation of nutrients and oxygen result in subclinical
delays in FHR milestones (higher baseline, lower
variability, delays in achieving reactivity).
c. Increased MCA S/D reflects compensatory fetal central
nervous system (CNS) autoregulation-induced increases
in cerebral perfusion. Once reduced or absent EDV is
observed, the BPP becomes abnormal within 2 to 3 days.
d. Biophysical parameters are affected sequentially in order
of relative sensitivity to progressive acidosis.
(1) Decreased FHR variability
(2) Decreased fetal breathing
(3) Reduced amniotic fluid volume
(4) Finally, reduced fetal movement and tone

CLINICAL PEARL Absent and reversed diastolic flow velocity

is associated with fetal hypoxemia and acidosis and has been
correlated with increased perinatal mortality.41–43

8. In a meta-analysis of 18 randomized and nonrandomized trials

involving more than 10,000 high-risk pregnancies, use of
Doppler ultrasound yielded a 29% reduction in perinatal
mortality.44
9. In contrast, a systematic review of trials of UA Doppler as a
screening test in low-risk pregnancies, including five studies
with more than 14,000 women, failed to demonstrate any
benefit.45
10. The decision to deliver hinges balancing fetal well-being
versus delivery at an early gestational age.
 a. Management of early-onset FGR (<34 weeks) emphasizes
safe prolongation of pregnancy (preventing morbidity and
mortality owing to preterm delivery).
b. Management of late-onset FGR emphasizes accurate
diagnosis to prevent stillbirth.
V. Intrapartum fetal surveillance
A. Physiology
1. Uteroplacental perfusion is intermittently reduced by uterine
contractions, resulting in repetitive hypoxia during labor.14
2. Normal maternal, uteroplacental, and fetal physiology confer
a wide margin of safety for fetal oxygenation such that
reduced oxygen delivery to the fetal circulation during labor
contractions is usually well tolerated.
3. Neonates born after experiencing labor commonly exhibit
mild cord blood acid–base abnormalities (mild respiratory
acidosis with normal base deficit) compared to those born
without experiencing labor, with no ill effect.
4. Contractions in the presence of greater degrees of
uteroplacental insufficiency cause increasingly severe gas
exchange impairment, causing fetal asphyxia and metabolic
acidosis. If this is severe, it may contribute to neonatal
hypoxemic ischemic encephalopathy.
5. The goal of intrapartum monitoring is to detect potential fetal
hypoxemic/acid–base decompensation to allow for early
intervention, first to improve gas exchange, then to deliver the
baby, if necessary.
B. Intrapartum electronic fetal monitoring—nomenclature and
interpretation
1. As noted earlier, despite demonstrating no evidence of long-
term beneficial outcomes, intrapartum EFM is routinely
performed, with the premise that EFM changes during labor
will appear before potential neurologic injury to the fetus,
allowing for timely intervention and hence mitigating
neurologic injury.
2. The recommendations of the 2008 consensus workshop,
sponsored by National Institute of Child Health and Human
Development (NICHD), ACOG, and the Society for
Maternal-Fetal Medicine, regarding EFM nomenclature and
classification scheme and standard intrapartum management,
have been adopted widely (ACOG; Association of Women’s
Health, Obstetric and Neonatal Nurses; and American College
of Nurse Midwives) and are as follows.2,18,46
a. Uterine activity. Interpretation of EFM occurs in relation
to uterine activity, which is characterized as:
(1) Normal: five or fewer contractions per 10 minutes,
averaged over a 30-minute window
(2) Tachysystole (formerly “uterine hyperstimulation”):
more than five contractions in 10 minutes,
averaged over 30 minutes.
b. Characterization of FHR includes five individual
elements: baseline heart rate, variability, accelerations,
decelerations, and changes in patterns or trends during
labor, as follows:
(1) Baseline FHR is determined as the mean FHR
rounded to 5 bpm during a 10-minute period, that is
devoid of accelerations, decelerations, or marked
variability.
(a) Normal: 110 to 160 bpm
(b) Tachycardia: greater than 160 bpm.
Tachycardia may be caused by maternal fever,
maternal medication administration, fetal cardiac
dysrhythmias, or fetal asphyxia.
(c) Bradycardia: less than 110 bpm. Fetal
bradycardia can occur as a consequence of fetal
cardiac conduction defect, maternal medications,
uteroplacental insufficiency, maternal
hypothermia, or as a normal variant.
(2) Baseline variability is defined as the fluctuation in
FHR and is visually represented by the amplitude of
each wave, from trough to peak, in the FHR tracing.
Accurate determination of baseline variability is
made during a 10-minute window that is devoid of
accelerations or decelerations.
(a) Normal or moderate variability: amplitude
range of 6 to 25 bpm (Fig. 7.1)

(b) Absent: no detectable change in amplitude (Fig.

7.2)
 (c) Minimal: amplitude range of 5 bpm or less (Fig.
7.3)

(d) Marked: amplitude range of >25 bpm

(3) The presence of normal or moderate variability is an
excellent predictor of the absence of fetal metabolic
academia. Minimal or absent variability alone is not
specific for presence of fetal compromise in the form
 of hypoxemia or metabolic academia because
decreased variability can be seen during fetal sleep
cycle, maternal narcotic use, or magnesium therapy
for preeclampsia.

CLINICAL PEARL Minimal or absent variability in the

presence of decelerations or other signs of potential fetal
compromise (e.g., chorioamnionitis, meconium) may signify
concurrent or impending fetal hypoxemia and metabolic acidemia.

(4) Accelerations are increases in FHR ≥15 bpm (≥32

weeks’ gestation) or 10 bpm (<32 weeks’ gestation),
which occur abruptly, that is, the peak of the
acceleration is ≤30 seconds from its onset and lasts
≥15 seconds. FHR increases exceeding 10 minutes
constitute a change in the baseline (Fig. 7.4).
Accelerations may occur during periods of fetal
movement, uterine contractions, or fetal
manipulation/stimulation during pelvic examination.

CLINICAL PEARL The presence of fetal accelerations ensures

the absence of fetal acidemia or hypoxia, providing reliable
reassurance of fetal well-being.

(5) Decelerations are decreases in FHR and are

classified as early, late, or variable (Table 7.3),
including the relationship of the nadir of the FHR
decrease to the peak of a uterine contraction.

(a) Early decelerations are characterized by a

gradual decline in the FHR, with the nadir
mirroring the peak of a uterine contraction,
followed by a gradual, symmetric return to
baseline (Fig. 7.5). Early decelerations are
thought to be due to fetal head compression and
are not associated with fetal hypoxia, acidemia,
or low Apgar scores.
(b) Late decelerations are also characterized by a
gradual decline in FHR, but the nadir occurs
after the peak of a contraction returning to
baseline after the contraction has ceased (Fig.
7.6). They usually indicate uteroplacental
insufficiency.

(c) Variable decelerations appear as an abrupt

decrease in FHR of 15 bpm or more, typically
reaching the nadir within 30 seconds, lasting 15
seconds or more, but less than 2 minutes. They
are often immediately preceded and followed by
a slight FHR acceleration, or shoulder (Fig. 7.7).
Their occurrence has been ascribed to different
rates of occlusion of the UV compared with
arteries.26 Others contest this mechanism and
ascribe at least some of these changes to a
developing fetal acidosis and hypotension.47
(d) Prolonged decelerations last longer than 2
minutes, but less than 10 minutes (Fig. 7.8),
whereas a deceleration lasting ≥10 minutes is
considered a change in baseline. Decelerations
may be prolonged in cases of uncorrected
maternal hypotension, maternal supine position,
uterine hyperstimulation (Fig. 7.9), prolapsed
cord, cord entanglement, uterine rupture, or
placental abruption. Decelerations are also
considered recurrent if they occur with ≥50% of
contractions during a 20-minute period and
intermittent if they occur with <50% of
contractions.
 (6) A sinusoidal pattern is unique and is defined as a
smooth, sine wave-like, undulating pattern, with a
cycle frequency of 3 to 5 per minute and amplitude of
5 to 15 bpm, which persists for 20 minutes or more.
Alone, this is considered to be abnormal and strongly
predictive of fetal asphyxia.19
C. Classification of electronic fetal monitoring tracings
The 2008 NICHD consensus promoted development of an
evidence-based, standardized approach to management of
abnormal results. The resulting three-tier EFM categorization
system, endorsed by ACOG, groups EFM patterns into categories
based on presence or absence of specific characteristics detailed
in Table 7.4. Category I tracings are normal and highly
predictive of normal fetal acid–base status, whereas category III
tracings are highly predictive of abnormal fetal acid–base
status. Unfortunately, the majority of abnormal EFM tracings are
classified as category II, which are indeterminate in terms of
reliably predicting fetal acid–base status.23 Despite attempts to
standardize a management protocol for category II tracings,20
there remains much variation in practice owing to lack of
consensus.47 Parer and Ikeda21 developed an alternative five-tier
classification system in which all possible FHR patterns were
classified into five categories according to their potential risk for
fetal acidemia. Each category was color-coded (green, blue,
yellow, orange, red) as an indicator of the escalating risk, that is,
from “no acidemia” to “evidence of actual or impending
damaging fetal asphyxia.” Although complex, the five-tier system
was shown to have strong agreement between expert clinicians
and a computerized analysis algorithm.22 There are critics of
these classifications and management algorithms, and they have
proposed alternatives.47,48
 In addition, there are even differences among national
guidelines.4,49 Some argue that the current widely adopted
terminology (especially used for decelerations) is unrelated to the
known physiology of fetal compensation for brief hypoxia during
uterine contractions and is, therefore, confusing and unhelpful.26
They propose shifting attention from descriptive labels to better
physiologic understanding and recognition of EFM pattern
changes that indicate progressive loss of fetal compensation.
D. Management of abnormal electronic fetal monitoring patterns
and in utero resuscitation
Clinical evidence suggesting loss of fetal compensation is
ultimately interpreted by the obstetrician and should prompt
measures to augment fetal oxygen delivery and to ameliorate fetal
hypoxia/acidosis. These corrective measures should address the
pathophysiologic basis for the derangement when known (e.g.,
maternal hypotension or hypoxemia, tachysystole, cord prolapse).
Standard interventions for in utero resuscitation promote
enhanced fetal oxygen delivery and address each step of the
maternal-to-fetal oxygen transfer cascade (see Table 7.5).12
1. Increase maternal alveolar oxygen tension
a. Administer supplemental oxygen by high-flow face
mask to increase inspired fraction of oxygen.
b. Ensure adequate ventilation: Tell the conscious patient
to breathe; administer naloxone if opioid-induced
hypoventilation is suspected; assist/control ventilation, if
necessary (e.g., high spinal block; magnesium toxicity).
2. Ensure oxygen uptake into maternal systemic circulation
a. Assess adequacy of the cardiac output, using common
surrogates (maternal blood pressure, heart rate, mental
status).
b. Augment cardiac output: IV fluid bolus; vasoactive
drugs (ephedrine, phenylephrine); uterine displacement
(alleviate inferior vena cava occlusion, augmenting left
ventricular preload)
3. Increase uterine perfusion: Uterine perfusion is directly
proportional to perfusion pressure (uterine artery pressure
minus uterine venous pressure) and inversely proportional to
resistance.
a. Increase uterine artery pressure
(1) Uterine displacement to alleviate aortic compression,
45 degrees or more50,51
(2) Administration of α-agonist vasopressor (e.g.,
phenylephrine)
(3) IV fluid bolus
b. Decrease uterine venous pressure
 (1) Uterine displacement to alleviate vena caval
occlusion
c. Decrease resistance to uterine perfusion
(1) Discontinue administration of oxytocin.
(2) Administer a tocolytic (e.g., terbutaline).

CLINICAL PEARL Acute EFM changes may be precipitated by

anesthetic and labor analgesic interventions when the latter cause
maternal hypotension or hypoxemia. The obstetric anesthesiologist
should therefore be prepared to rapidly institute or assist with
instituting these in utero resuscitation measures.

4. The obstetrician may choose to perform a manual vaginal

examination to assess for cord prolapse or rapid fetal descent
as a cause of acute EFM changes and to attempt fetal scalp
stimulation. An acceleratory response (≥15 bpm lasting ≥15
minutes) has a predictive value for absence of fetal acidosis.
In the case of cord prolapse, manual support may be
administered to prevent further prolapse and facilitate safe
transport to the operating room (OR) for cesarean delivery.
Amnioinfusion may also be performed for presumed cord
compression resulting in repetitive and significant variable
decelerations. While participating in resuscitation, the
anesthesiologist must also quickly begin preparing to provide
anesthesia for emergent operative delivery (forceps-assisted
vaginal or emergent cesarean delivery). Ideally, there should
be an institutional policy of informing the anesthesiologist as
soon as category III EFM develops in order to allow sufficient
time for safe conduct of emergent anesthesia if needed.
E. Intermittent auscultation
After its introduction in the 1960s, EFM ultimately replaced
intermittent auscultation (IA) of FHR as the predominant method
of intrapartum fetal assessment. By the early 21st century, survey
 studies suggested that most parturients giving birth in the United
States and Canada experience continuous EFM during labor,3,11 a
practice now “entrenched without robust evidence to support it.”5
Studies during ensuing decades have failed to demonstrate a clear
outcome benefit of EFM compared to IA of FHR.2,3,5 Intrapartum
continuous EFM contributes to more obstetric interventions
(operative vaginal and cesarean delivery) and appears to reduce
the incidence of neonatal seizures, but does not alter long-term
outcomes (i.e., mortality, cerebral palsy).52 There is no
demonstrated benefit for women with low-risk pregnancies of
performing EFM upon admission for labor,53 and several
professional colleges recommend against this practice,3,5
although ACOG is silent on the issue.2
VI. Medication and anesthetic effects on fetal surveillance
A. Maternally administered medications
Maternal administration of certain drugs, including anesthetic
drugs, as well as maternal cardiovascular effects of anesthetic
interventions, may cause changes in baseline FHR and variability,
altering EFM results in ways that might prompt obstetric
interventions (see Table 7.6). Medications commonly
administered to the mother during pregnancy and labor include
the following:

1. CNS depressants: Opioids, benzodiazepines, barbiturates,

 and phenothiazines can cause decreased FHR variability.
Diminished FHR variability, with or without an increased
incidence of decelerations, has also been demonstrated after
IV meperidine and butorphanol administration.54–56 In a
double-blind randomized controlled trial, meperidine patient-
controlled analgesia (PCA) was associated with more
decelerations and decreased variability when compared to
remifentanil PCA, although abnormal FHR tracings still
occurred using the latter.57 Remifentanil PCA has been shown
to produce more maternal sedation and oxygen desaturation
compared to meperidine or fentanyl PCA but without
increasing fetal adverse events.58
2. Corticosteroids: Betamethasone, but not dexamethasone,
administered to hasten preterm fetal lung maturation, has been
shown in numerous studies to have biphasic effects on FHR
and variability. Mean FHR decreases on the first day of
administration, then increases on days 2 and 3. FHR
variability increases on the first day and decreases
thereafter.59 Decreased baseline FHR is thought to reflect
corticosteroid-induced fetal hypertension with increased
baroreceptor-mediated vagal output and reflex inhibition of
sympathetic output. The known inverse relationship between
baseline FHR and its variation may explain the observed
increase in the latter. Gonadotropin receptor activation causes
decreased fetal movement, which may also contribute.59
3. Magnesium sulfate administered to women with
preeclampsia for prevention of seizures is associated with
lower baseline FHR and decreased variability, without
adverse effects on neonatal outcome.60 Similar findings were
demonstrated in a randomized trial performed in 34 normal,
nonlaboring patients, with peak effects seen 3 hours after
administration of a loading dose and initiation of an
infusion.61
4. Cardiovascular drugs: β-Blockers cross the placenta into
 the fetal circulation and, with long-term administration, have
been associated with significant fetal adverse effects,
including fetal bradycardia, hypoglycemia, and FGR.62–64 On
the other hand, calcium channel blockers and adenosine
have been administered to parturients without adverse effects
in the fetus.65 Adverse fetal side effects have been
documented with amiodarone use during pregnancy,
resulting in fetal hypothyroidism, delayed growth, and
prematurity.64
5. Terbutaline is often given as a tocolytic when category III
EFM is accompanied by suspected tachysystole. In a single
study examining the effects of two subcutaneous doses (250
and 500 μg) on EFM, the larger dose caused a significant
increase in baseline FHR at 20 and 40 minutes (+6 and +10
bpm change from baseline).66 The smaller dose had little
effect on EFM.
B. Regional anesthesia
1. Neuraxial analgesia can affect EFM in three ways.
a. Maternal hypotension is a common complication of
neuraxial labor analgesia and can lead to decreased
uteroplacental perfusion, fetal hypoxemia, and fetal
decelerations.
b. FHR decelerations may occur, even in the absence of
maternal hypotension, shortly after the onset of neuraxial
analgesia, especially with spinal analgesic
techniques.67–70 A large systematic review of 24 trials
including more than 3,500 parturients revealed increased
risk of fetal bradycardia (odds ratio 1.8; 95% confidence
interval [CI], 1.0 to 3.1).71 This is thought to be due to the
abrupt imbalance in circulating maternal catecholamines
accompanying rapid onset of analgesia, inducing uterine
hypertonus.72,73
c. Finally, opioids added to epidural local anesthetics are
readily taken up into the maternal circulation, but appear
 to have no effect on EFM.74 Likewise, epidural clonidine
redistributes rapidly into maternal, and then, fetal
circulations. Clonidine has been shown to lower baseline
FHR when combined with dilute bupivacaine.75

CLINICAL PEARL Neuraxial analgesia should be administered

slowly and carefully to all patients, particularly in parturients with
risk factors for uteroplacental insufficiency, to avoid causing FHR
abnormalities and potential for emergency cesarean delivery.
Prompt treatment of hypotension and uterine overactivity will
correct most cases of fetal bradycardia before an expedited
operative delivery is necessary (see Table 7.5).70

2. Paracervical block is a relatively simple technique for

providing effective, but short-lived, analgesia during first
stage of labor.76,77 However, it has fallen out of favor owing
to its short duration, ineffectiveness in providing second-stage
analgesia, ready availability of continuous neuraxial analgesic
techniques, and concerns regarding fetal bradycardia.
Hypotheses explaining the latter include uptake by nearby
uterine arteries and rapid fetal transfer of local anesthetic
resulting in impaired uterine artery blood flow from local
vasospasm, or mechanical effects.76 The incidence of the fetal
bradycardia in healthy multiparous women appears to be
lower than initially reported.77–79 The incidence of fetal
bradycardia after paracervical block was found to be equal to
that from single-shot spinal analgesia and is minimized by
administration of superficial injections of dilute local
anesthetic by an experienced obstetrician.77
C. General anesthesia
1. As with neuraxial anesthesia, general anesthesia decreases
maternal sympathetic output, which may cause maternal
hypotension, diminished fetal oxygen delivery, and EFM
 changes. CNS depressant general anesthetics and opioids
cross the placenta and depress the fetal CNS, decreasing fetal
movement and altering EFM patterns, particularly decreasing
variability.
2. Neostigmine, the acetylcholinesterase inhibitor routinely
administered to antagonize neuromuscular blockade, is a
positively charged quaternary amine, but may cross the
placenta. When administered, as it customarily is, with
glycopyrrolate to prevent intense muscarinic agonist effects
(bradycardia or asystole), it has been reported to cause
significant fetal bradycardia. Coadministering atropine, a
lipid-soluble tertiary amine that crosses the placenta, instead
of glycopyrrolate, may prevent this iatrogenic complication.80

CLINICAL PEARL If EFM is used during nonobstetric surgery,

loss of beat-to-beat variability is often seen. Intraoperative
bradycardia may be due to a temporary decrease in cardiac output
and hence uterine blood flow. Often, this can be overcome by
improving cardiac function and optimizing fluid management.

REFERENCES
1. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 145: antepartum
fetal surveillance. Obstet Gynecol. 2014;124:182–192.
2. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 106: intrapartum
fetal heart rate monitoring: nomenclature, interpretation, and general management principles. Obstet
Gynecol. 2009;114:192–202.
3. Liston R, Sawchuck D, Young D. Fetal health surveillance: antepartum and intrapartum consensus
guideline. J Obstet Gynaecol Can. 2007;29:S3–S56.
4. National Collaborating Centre for Women’s and Children’s Health. Intrapartum Care: Care of Healthy
Women and Their Babies During Childbirth, Clinical Guideline 190. London, United Kingdom:
National Institute for Health and Care Excellence; 2014.
5. Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Intrapartum Fetal
Surveillance, Clinical Guideline. 3rd ed. Victoria, Australia: The Royal Australian and New Zealand
College of Obstetricians and Gynaecologists; 2014.
6. Clark SL, Hankins GD. Temporal and demographic trends in cerebral palsy—fact and fiction. Am J
Obstet Gynecol. 2003;188:628–633.
 7. Graham EM, Ruis KA, Hartman AL, et al. A systematic review of the role of intrapartum hypoxia-
ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol. 2008;199:587–595.
8. Costantine MM, Saade GR. The first cesarean: role of “fetal distress” diagnosis. Semin Perinatol.
2012;36:379–383.
9. Grimes DA, Schulz KF. Uses and abuses of screening tests. Lancet. 2002;359:881–884.
10. Grimes DA, Peipert JF. Electronic fetal monitoring as a public health screening program: the
arithmetic of failure. Obstet Gynecol. 2010;116:1397–1400.
11. Declercq ER, Sakala C, Corry MP, Applebaum S. Listening to Mothers II: report of the Second
National U.S. Survey of Women’s Childbearing Experiences: conducted January–February 2006 for
Childbirth Connection by Harris Interactive in partnership with Lamaze International. J Perinat Educ.
2007;16:15–17. doi:10.1624/105812407X244778.
12. Miller DA, Miller LA. Electronic fetal heart rate monitoring: applying principles of patient safety. Am
J Obstet Gynecol. 2012;206:278–283.
13. Baschat AA. Fetal growth restriction—from observation to intervention. J Perinat Med. 2010;38:239–
246.
14. Fletcher AJ, Gardner DS, Edwards CM, et al. Development of the ovine fetal cardiovascular defense
to hypoxemia towards full term. Am J Physiol Heart Circ Physiol. 2006;291:H3023–H3034.
15. Thompson JL, Kuller JA, Rhee EH. Antenatal surveillance of fetal growth restriction. Obstet Gynecol
Surv. 2012;67:554–565.
16. Sureau C. Historical perspectives: forgotten past, unpredictable future. Baillieres Clin Obstet
Gynaecol. 1996;10:167–184.
17. National Institute of Child Health and Human Development Research Planning Workshop. Electronic
fetal heart rate monitoring: research guidelines for interpretation. National Institute of Child Health
and Human Development Research Planning Workshop. Am J Obstet Gynecol. 1997;177:1385–1390.
18. Macones GA, Hankins GD, Spong CY, et al. The 2008 National Institute of Child Health and Human
Development Workshop report on electronic fetal monitoring: update on definitions, interpretation,
and research guidelines. Obstet Gynecol. 2008;112:661–666.
19. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 116: management
of intrapartum fetal heart rate tracings. Obstet Gynecol. 2010;116:1232–1240.
20. Clark SL, Nageotte MP, Garite TJ, et al. Intrapartum management of category II fetal heart rate
tracings: towards standardization of care. Am J Obstet Gynecol. 2013;209:89–97.
21. Parer JT, Ikeda T. A framework for standardized management of intrapartum fetal heart rate patterns.
Am J Obstet Gynecol. 2007;197:26.e1–26.e6.
22. Parer JT, Hamilton EF. Comparison of 5 experts and computer analysis in rule-based fetal heart rate
interpretation. Am J Obstet Gynecol. 2010;203:451.e1–451.e7.
23. Coletta J, Murphy E, Rubeo Z, et al. The 5-tier system of assessing fetal heart rate tracings is superior
to the 3-tier system in identifying fetal acidemia. Am J Obstet Gynecol. 2012;206:226.e1–226.e5.
24. Sadaka A, Furuhashi M, Minami H, et al. Observation on validity of the five-tier system for fetal heart
rate pattern interpretation proposed by Japan Society of Obstetricians and Gynecologists. J Matern
Fetal Neonatal Med. 2011;24:1465–1469.
25. Garite TJ, Simpson KR. Intrauterine resuscitation during labor. Clin Obstet Gynecol. 2011;54:28–39.
26. Westgate JA, Wibbens B, Bennet L, et al. The intrapartum deceleration in center stage: a physiologic
approach to the interpretation of fetal heart rate changes in labor. Am J Obstet Gynecol.
2007;197:236.e1–236.e11.
27. Reddy UM, Filly RA, Copel JA. Prenatal imaging: ultrasonography and magnetic resonance imaging.
Obstet Gynecol. 2008;112:145–157.
28. Clark SL, Sabey P, Jolley K. Nonstress testing with acoustic stimulation and amniotic fluid volume
 assessment: 5973 tests without unexpected fetal death. Am J Obstet Gynecol. 1989;160:694–697.
29. Miller DA, Rabello YA, Paul RH. The modified biophysical profile: antepartum testing in the 1990s.
Am J Obstet Gynecol. 1996;174:812–817.
30. Freeman RK, Anderson G, Dorchester W. A prospective multi-institutional study of antepartum fetal
heart rate monitoring. I. Risk of perinatal mortality and morbidity according to antepartum fetal heart
rate test results. Am J Obstet Gynecol. 1982;143:771–777.
31. Devoe LD. Antenatal fetal assessment: contraction stress test, nonstress test, vibroacoustic stimulation,
amniotic fluid volume, biophysical profile, and modified biophysical profile—an overview. Semin
Perinatol. 2008;32:247–252.
32. Ray M, Freeman R, Pine S, et al. Clinical experience with the oxytocin challenge test. Am J Obstet
Gynecol. 1972;114:1–9.
33. Manning FA, Harman CR, Morrison I, et al. Fetal assessment based on fetal biophysical profile
scoring. IV. An analysis of perinatal morbidity and mortality. Am J Obstet Gynecol. 1990;162:703–
709.
34. Manning FA, Snijders R, Harman CR, et al. Fetal biophysical profile score. VI. Correlation with
antepartum umbilical venous fetal pH. Am J Obstet Gynecol. 1993;169:755–763.
35. Vintzileos AM, Nochimson DJ, Guzman ER, et al. Intrapartum electronic fetal heart rate monitoring
versus intermittent auscultation: a meta-analysis. Obstet Gynecol. 1995;85:149–155.
36. Morrow RJ, Adamson SL, Bull SB, et al. Effect of placental embolization on the umbilical arterial
velocity waveform in fetal sheep. Am J Obstet Gynecol. 1989;161:1055–1060.
37. Mandruzzato GP, Bogatti P, Fischer L, et al. The clinical significance of absent or reverse end-diastolic
flow in the fetal aorta and umbilical artery. Ultrasound Obstet Gynecol. 1991;1:192–196.
38. Karsdorp VH, van Vugt JM, van Geijn HP, et al. Clinical significance of absent or reversed end
diastolic velocity waveforms in umbilical artery. Lancet. 1994;344:1664–1668.
39. Vasconcelos RP, Brazil Frota Aragão JR, Costa Carvalho FH, et al. Differences in neonatal outcome in
fetuses with absent versus reverse end-diastolic flow in umbilical artery Doppler. Fetal Diagn Ther.
2010;28:160–166.
40. Valcamonico A, Danti L, Frusca T, et al. Absent end-diastolic velocity in umbilical artery: risk of
neonatal morbidity and brain damage. Am J Obstet Gynecol. 1994;170:796–801.
41. Trudinger BJ, Cook CM, Giles WB, et al. Fetal umbilical artery velocity waveforms and subsequent
neonatal outcome. Br J Obstet Gynaecol. 1991;98:378–384.
42. Yoon BH, Romero R, Roh CR, et al. Relationship between the fetal biophysical profile score,
umbilical artery Doppler velocimetry, and fetal blood acid-base status determined by cordocentesis.
Am J Obstet Gynecol. 1993;169:1586–1594.
43. Soregaroli M, Bonera R, Danti L, et al. Prognostic role of umbilical artery Doppler velocimetry in
growth-restricted fetuses. J Matern Fetal Neonatal Med. 2002;11:199–203.
44. Alfirevic Z, Stampalija T, Gyte GM. Fetal and umbilical Doppler ultrasound in high-risk pregnancies.
Cochrane Database Syst Rev. 2010;(1):CD007529.
45. Bricker L, Neilson JP. Routine Doppler ultrasound in pregnancy. Cochrane Database Syst Rev. 2000;
(2):CD001450.
46. Hankins GD, Miller DA. A review of the 2008 NICHD Research Planning Workshop:
recommendations for fetal heart rate terminology and interpretation. Clin Obstet Gynecol. 2011;54:3–
7.
47. Sholapurkar SL. Critical evaluation of American categorization of fetal heart rate (FHR) decelerations
and three tier classification—shortcomings, contradictions, remedies and need for debate. Open J
Obstet Gynecol. 2013;3:362–370.
48. Ugwumadu A. Are we (mis)guided by current guidelines on intrapartum fetal heart rate monitoring?
 Case for a more physiological approach to interpretation. BJOG. 2014;121:1063–1070.
49. Hill JB, Chauhan SP, Magann EF, et al. Intrapartum fetal surveillance: review of three national
guidelines. Am J Perinatol. 2012;29:539–550.
50. Higuchi H, Takagi S, Zhang K, et al. Effect of lateral tilt angle on the volume of the abdominal aorta
and inferior vena cava in pregnant and nonpregnant women determined by magnetic resonance
imaging. Anesthesiology. 2015;122:286–293.
51. Palmer CM. Tilting at aortocaval compression. Anesthesiology. 2015;122:231–232.
52. Alfirevic Z, Devane D, Gyte GM. Continuous cardiotocography (CTG) as a form of electronic fetal
monitoring (EFM) for fetal assessment during labour. Cochrane Database Syst Rev. 2013;
(5):CD006066.
53. Devane D, Lalor JG, Daly S, et al. Cardiotocography versus intermittent auscultation of fetal heart on
admission to labour ward for assessment of fetal wellbeing. Cochrane Database Syst Rev. 2012;
(2):CD005122.
54. Hill JB, Alexander JM, Sharma SK, et al. A comparison of the effects of epidural and meperidine
analgesia during labor on fetal heart rate. Obstet Gynecol. 2003;102:333–337.
55. Sekhavat L, Behdad S. The effects of meperidine analgesia during labor on fetal heart rate. Int J
Biomed Sci. 2009;5:59–62.
56. Nelson KE, Eisenach JC. Intravenous butorphanol, meperidine, and their combination relieve pain and
distress in women in labor. Anesthesiology. 2005;102:1008–1013.
57. Evron S, Glezerman M, Sadan O, et al. Remifentanil: a novel systemic analgesic for labor pain. Anesth
Analg. 2005;100:233–238.
58. Douma MR, Verwey RA, Kam-Endtz CE, et al. Obstetric analgesia: a comparison of patient-
controlled meperidine, remifentanil, and fentanyl in labour. Br J Anaesth. 2010;104:209–215.
59. Verdurmen KM, Renckens J, van Laar JO, et al. The influence of corticosteroids on fetal heart rate
variability: a systematic review of the literature. Obstet Gynecol Surv. 2013;68:811–824.
60. Duffy CR, Odibo AO, Roehl KA, et al. Effect of magnesium sulfate on fetal heart rate patterns in the
second stage of labor. Obstet Gynecol. 2012;119:1129–1136.
61. Hallak M, Martinez-Poyer J, Kruger ML, et al. The effect of magnesium sulfate on fetal heart rate
parameters: a randomized, placebo-controlled trial. Am J Obstet Gynecol. 1999;181:1122–1127.
62. Robins K, Lyons G. Supraventricular tachycardia in pregnancy. Br J Anaesth. 2004;92:140–143.
63. Chen RJ, Huang SC, Chow SN. Paroxysmal supraventricular tachycardia during pregnancy and
postpartum period. Int J Gynaecol Obstet. 1994;44:279–280.
64. Gowda RM, Khan IA, Mehta NJ, et al. Cardiac arrhythmias in pregnancy: clinical and therapeutic
considerations. Int J Cardiol. 2003;88:129–133.
65. Elkayam U, Goodwin TM. Adenosine therapy for supraventricular tachycardia during pregnancy. Am
J Cardiol. 1995;75:521–523.
66. Abdelhak Y, Roque H, Young BK. Terbutaline: effects on the fetal heart at term. J Perinat Med.
2011;40:69–71.
67. Clarke VT, Smiley RM, Finster M. Uterine hyperactivity after intrathecal injection of fentanyl for
analgesia during labor: a cause of fetal bradycardia? Anesthesiology. 1994;81:1083.
68. Gaiser RR, McHugh M, Cheek TG, et al. Predicting prolonged fetal heart rate deceleration following
intrathecal fentanyl/bupivacaine. Int J Obstet Anesth. 2005;14:208–211.
69. Patel NP, El-Wahab N, Fernando R, et al. Fetal effects of combined spinal-epidural vs epidural labour
analgesia: a prospective, randomised double-blind study. Anaesthesia. 2014;69:458–467.
70. Gambling DR, Bender M, Faron S, et al. Prophylactic intravenous ephedrine to minimize fetal
bradycardia after combined spinal-epidural analgesia: a randomized controlled study. Can J Anesth.
2015;62:1201–1208. doi:10.1007/s12630-015-0450-8.
71. Mardirosoff C, Dumont L, Boulvain M, et al. Fetal bradycardia due to intrathecal opioids for labour
analgesia: a systematic review. BJOG. 2002;109:274–281.
72. Abrão KC, Francisco RP, Miyadahira S, et al. Elevation of uterine basal tone and fetal heart rate
abnormalities after labor analgesia: a randomized controlled trial. Obstet Gynecol. 2009;113:41–47.
73. Van de Velde M, Teunkens A, Hanssens M, et al. Intrathecal sufentanil and fetal heart rate
abnormalities: a double-blind, double placebo-controlled trial comparing two forms of combined
spinal epidural analgesia with epidural analgesia in labor. Anesth Analg. 2004;98:1153–1159.
74. St. Amant MS, Koffel B, Malinow AM. The effects of epidural opioids on fetal heart rate variability
when coadministered with 0.25% bupivacaine for labor analgesia. Am J Perinatol. 1998;15:351–356.
75. Cigarini I, Kaba A, Bonnet F, et al. Epidural clonidine combined with bupivacaine for analgesia in
labor. Effects on mother and neonate. Reg Anesth. 1995;20:113–120.
76. Rosen MA. Paracervical block for labor analgesia: a brief historic review. Am J Obstet Gynecol.
2002;186:S127–S130.
77. Junttila EK, Karjalainen PK, Ohtonen PP, et al. A comparison of paracervical block with single-shot
spinal for labour analgesia in multiparous women: a randomised controlled trial. Int J Obstet Anesth.
2009;18:15–21.
78. LeFevre ML. Fetal heart rate pattern and postparacervical fetal bradycardia. Obstet Gynecol.
1984;64:343–346.
79. Palomäki O, Huhtala H, Kirkinen P. A comparative study of the safety of 0.25% levobupivacaine and
0.25% racemic bupivacaine for paracervical block in the first stage of labor. Acta Obstet Gynecol
Scand. 2005;84:956–961.
80. Clark RB, Brown MA, Lattin DL. Neostigmine, atropine, and glycopyrrolate: does neostigmine cross
the placenta? Anesthesiology. 1996;84:450–452.
 Maternal Infection and Fever
Rebecca D. Minehart, William Camann, and Scott Segal

I. Fever in pregnancy
A. General considerations
B. Neonatal outcome
II. Noninfectious fever in parturients
A. Noninfectious fever and epidural analgesia for labor
B. Mechanisms
III. Infectious causes of fever in parturients
A. Chorioamnionitis
B. Respiratory tract infection: pneumonia
C. Respiratory tract infection: influenza
D. Urinary tract infection
E. Postpartum infection (endometritis)
F. Group B streptococcus
G. Cytomegalovirus
H. Hepatitis
I. HIV
J. Herpes simplex virus (HSV-1 and HSV-2)
K. Miscellaneous infections
IV. Sepsis and septic shock
A. General considerations
B. Treatment
C. Anesthetic management
 V. Neuraxial anesthesia for the febrile parturient
A. Risk
B. IV antibiotics
C. Aseptic technique

KEYPOINTS
1. Whatever the cause of maternal fever, it is clear that higher maternal
temperatures can adversely impact neonatal outcomes.
2. Multiple studies of various designs have confirmed the excess fever in
women receiving epidural analgesia in labor.
3. The effect of epidural-associated fever, as opposed to infection, has not
been definitively linked to neonatal brain injury.
4. Postpartum, the anesthesia provider must be prepared to treat possible
uterine atony and hemorrhage, which can occur after vaginal delivery or
cesarean delivery (CD) in pregnancies complicated by chorioamnionitis.
5. If there are serious complications of influenza, supportive care is
warranted on an individual basis, paying particular attention to
intravascular volume status during neuraxial anesthesia because
dehydration may occur.
6. Without evidence of coagulopathy, neuraxial anesthesia can be
administered in parturients with hepatitis. However, in patients with
severe liver disease, metabolism of local anesthetics is also of concern
because of hepatic biotransformation of amino-amide local anesthetics.
7. One of the biggest concerns of administering neuraxial anesthesia to
patients with HIV infection is whether these patients are at increased risk
for infectious complications. Safe administration of neuraxial anesthesia
requires standard precautions and careful avoidance of needlestick injury.
8. Consensus is that neuraxial anesthesia is safe for secondary or re-
activated HSV infection, provided there are no active herpetic lesions at
the site of needle insertion.
9. Patients with varicella zoster may present challenges in pain management
 because the pain of zoster is difficult to control and requires careful
evaluation of all available modalities.
10. The Guidelines for the International Surviving Sepsis Campaign call for
administration of high-dose intravenous antibiotics within 1 hour of
admission for anyone with suspected sepsis.
11. Handwashing; jewelry removal; and use of sterile gloves (to supplement
handwashing and not as a substitute), fresh mask, and cap have been
shown to reduce the incidence of microbial contamination of the work
area but not directly to reduce nosocomial infection.

BODY TEMPERATURE IS TIGHTLY CONTROLLED by the hypothalamus and

normally varies from 36.5°C to 38.0°C (±0.5°C). Fever is defined as body
temperature above 38.0°C, which usually results from endogenous pyrogens,
secondary to an increased hypothalamic set point.1 Fever may be infectious or
noninfectious in origin, adding to diagnostic dilemmas.
I. Fever in pregnancy
A. General considerations
Fever increases basal metabolic rate, cardiac work, and oxygen
consumption. Fetal temperature is approximately 0.5°C higher
than maternal core temperature.2 A number of risk factors may
contribute to the predisposition of maternal fever, including
nulliparity, rupture of membranes for >24 hours, and a prolonged
latent phase of labor.3 Maternal fever results in increased
perinatal mortality (infection-related or otherwise), increased
neonatal sepsis workups, and increased neonatal central nervous
system (CNS) morbidity.4–7
B. Neonatal outcome
Intrapartum exposure of the neonate to hyperthermia may be
detrimental. The first observed effect was an indirect one. Reports
of a fourfold increase in sepsis evaluations of neonates whose
mothers received epidural analgesia initially elicited much
concern.8 Fortunately, there was no increased risk of documented
sepsis in neonates who underwent evaluation.8,9 Other centers,
 which do not evaluate neonates solely on the basis of maternal
temperature, failed to show any increase in women receiving
epidural analgesia.10 More directly, early neonatal condition may
be impaired, with increased need for neonatal resuscitation,
neonatal intensive care unit admission, and newborn seizures.5,6
More ominously, the fetal and neonatal brain may be injured by
maternal intrapartum fever. Impey et al.11 reported a tenfold
greater risk of neonatal encephalopathy in term infants who were
exposed to even low-grade (>37.5°C) maternal fever. A
prospective cohort study of 8,299 women investigated the
relationship between maternal intrapartum fever, neonatal
acidosis, and the risk of neonatal encephalopathy and found them
to be additive.12 An association between fever and cerebral palsy
has been known for more than a half-century, and recent analyses
suggest the risk may be increased by two- to ninefold.13,14 In
infants normal at birth, longer term sequelae may include lower
intelligence scores at school age15 and possibly development of
autism spectrum disorders.16 Whatever the cause of maternal
fever, it is clear that higher maternal temperatures can
adversely impact neonatal outcomes.

CLINICAL PEARL Maternal fever results in increased perinatal

mortality (infection-related or otherwise), increased neonatal sepsis
workups, and increased neonatal CNS morbidity.

II. Noninfectious fever in parturients

A. Noninfectious fever and epidural analgesia for labor
Unlike the situation in nonpregnant patients or pregnant patients
not in labor, epidural analgesia is associated with gradual
increases in average maternal core temperature when
administered to laboring women.17,18 More importantly, Goetzl et
al.19 concluded that most women do not become febrile after
epidural analgesia. Fever occurred in only 22% of the 99
 nulliparous women, with the greatest rise in temperature
occurring 1 hour after epidural administration. When averaged
with the nonfebrile cohort, the data recapitulated the slow gradual
rise seen in earlier studies, which appears to be an artifact of this
averaging. Multiple studies of various designs have confirmed the
excess fever in women receiving epidural analgesia in labor.
These include not only observational studies, which are subject to
selection bias (differences between women selecting and those
declining epidural analgesia), but also natural experiments (in
which epidural analgesia rapidly becomes available) and
randomized controlled trials (RCTs). All find fever to be
increased fourfold or more in women receiving epidurals.7
Subsequent studies have demonstrated that few variations in
epidural technique alter the incidence of epidural-associated
fever, including intermittent versus continuous drug infusions,
combined spinal-epidural (CSE) versus epidural techniques,
length of exposure to epidural analgesia, presence or absence of
systemic opioids, or intrathecal versus epidural techniques.20–23

CLINICAL PEARL Studies have demonstrated that few

variations in epidural technique alter the incidence of epidural-
associated fever, including intermittent versus continuous drug
infusions, CSE versus epidural techniques, length of exposure to
epidural analgesia, presence or absence of systemic opioids, or
intrathecal versus epidural techniques.

B. Mechanisms
1. The mechanisms for the increased temperature are
incompletely understood. Formerly, thermoregulatory
factors including ambient temperature, decreased sweating, or
decreased hyperventilation were implicated. However, with
the realization that the gradual rise in temperature is an
averaging artifact, it is likely that the relevant mechanisms are
 those that explain fever in the 20% to 30% of women who
develop it. The most likely cause is noninfectious (sterile)
inflammation, discussed in the following sections.
2. Inflammatory markers have been evaluated in parturients
with and without fever who received epidurals. Goetzl et al.24
demonstrated increased serum levels of inflammatory
cytokines (IL-6, IL-8) in maternal and fetal cord blood
samples in those with fever who had received epidural
analgesia. The levels were higher at baseline in those women
who eventually developed a fever, and the levels rose with
longer exposure to epidural analgesia.
3. Placental inflammation is consistently observed but is not
infectious. In reviewing placental findings in large cohorts of
women who self-selected epidural analgesia, placental
inflammation was consistently observed in the febrile
groups.25,26 More importantly, assiduous efforts to culture
bacteria or detect bacterial DNA failed to demonstrate
infection in all but rare cases.27 Similarly, prophylactic broad-
spectrum antibiotics did not alter placental inflammation or
maternal fever in a randomized trial.28
4. Anti-inflammatory agents moderate epidural-associated
fever. Goetzl et al.29 randomized women with epidural
analgesia to receive high-dose systemic methylprednisolone
or placebo. Steroid treatment prevented fever and increases in
maternal and fetal IL-6 but at the cost of nearly 10% neonatal
bacteremia. Similar effects were seen with epidural steroids30
but not with the weak anti-inflammatory agent. Prophylactic
acetamenophen is also ineffective in preventing maternal
fever.31
The effect of epidural-associated fever, as opposed to
infection, has not been definitively linked to neonatal brain
injury. Nonetheless, because the pathophysiology is likely
similar, and because maternal inflammation consistently
reproduces newborn brain injuries in experimental models,
 continued efforts to elucidate the mechanisms and potential
ways to modulate these effects are indicated.

CLINICAL PEARL The pathophysiology of epidural-related

fever and infection is likely similar. Because maternal inflammation
consistently reproduces newborn brain injuries in experimental
models, continued efforts to elucidate the mechanisms and potential
ways to modulate these effects are indicated.

III. Infectious causes of fever in parturients

The overall incidence of infection in parturients is approximately 3%,
but in some populations, it may be much higher. Even with a decrease
in maternal morbidity and mortality, infectious causes of fever still
account for the largest fraction of direct maternal deaths (due to
obstetric causes) and a substantial portion of indirect deaths (due to
preexisting maternal medical conditions).32
A. Chorioamnionitis
The most common cause of maternal intrapartum fever is
chorioamnionitis.33 Chorioamnionitis, or acute intraamniotic
infection, is associated with increased maternal and fetal
morbidity and mortality. The overall incidence of
chorioamnionitis in term gestations is thought to be 0.5% to
10.5%.34 In most cases, bacteria enter the amniotic cavity and
gain access to the fetus by ascending through the cervix after
rupture of membranes. In rare cases, bacteria from the maternal
circulation cross the placenta and gain access to the amniotic
cavity.
1. Causes
Chorioamnionitis is typically polymicrobial in origin, but in
most cases, bacteria that are normally present in the genital
tract are most often responsible for the infections. Although
Bacteroides, group B streptococcal species, and
Escherichia coli are most commonly isolated from amniotic
 fluid,34 Candida species can also be responsible for these
infections.35 In 7.5% to 12% of cases of clinical
chorioamnionitis, maternal bacteremia occurs.36,37 A recent
study, conversely, found that a significant proportion of
clinically diagnosed chorioamnionitis is in fact noninfectious
inflammation of the placenta, perhaps mediated by epidural
analgesia.38
2. Diagnosis
The diagnosis is often made on clinical grounds, based on
maternal fever >37.8°C or 38°C, maternal and/or fetal
tachycardia, uterine tenderness, foul-smelling amniotic fluid,
and other symptoms or signs of generalized infection.
However, the clinical presentation may not correlate with the
laboratory diagnosis. In a review of more than 500 women
with pathologically proven chorioamnionitis, only 10% of the
patients had abdominal tenderness and 1% had foul-smelling
amniotic fluid.39 Chorioamnionitis can be associated with:
a. Preterm labor
b. Postpartum hemorrhage
c. Postpartum infection
d. Sepsis and, in some instances, maternal or neonatal
death1,26
In addition to these complications, there is some
controversy whether chorioamnionitis negatively affects
uterine contractility and increases the risk of CD. Satin et
al.40 concluded in their study of 66 pregnancies complicated
by chorioamnionitis, “the impact of chorioamnionitis on the
course of labor can be divided into two clinical presentations.
That diagnosed before labor stimulation does not increase the
use of CD, whereas if diagnosed after oxytocin stimulation
may indicate abnormal labor, was and is associated with an
increase in CD for dystocia.”
3. Neonatal complications
There is some controversy regarding the pathophysiology of
 intraamniotic bacteremia in chorioamnionitis, suggesting
infection of the membranes may not be the cause but rather
the consequence of amniotic infection.41 Nonetheless, there
may be significant neonatal consequences, including:
a. Sepsis
b. Pneumonia/neonatal lung injury
The relationship between chorioamnionitis and neonatal
lung injury is complex. In preterm neonates, increased
inflammatory cytokines found in infected amniotic fluid
stimulate surfactant production, consequently reducing
the incidence of acute respiratory distress syndrome
(ARDS).42 However, there is evidence suggesting an
increased incidence of chronic lung disease in neonates
exposed to chorioamnionitis resulting from increased
inflammatory mediators.43
c. Cerebral palsy
Systematic reviews of published studies evaluating the
association between chorioamnionitis and cerebral palsy
have revealed risks of 1.9 to 4.7 in preterm and term
infants whose mothers had clinical evidence of
chorioamnionitis.13,44
d. Meningitis and, in some cases, neonatal death45

CLINICAL PEARL Although there is some controversy

regarding the pathophysiology of intraamniotic bacteremia in
chorioamnionitis, suggesting infection of the membranes may not
be the cause but rather the consequence of amniotic infection; there
may be significant adverse neonatal consequences.

4. Treatment of chorioamnionitis consists of prompt antibiotic

administration and expedited delivery, although this is still an
area of some controversy, with some studies finding duration
of chorioamnionitis before delivery correlating weakly with
 neonatal outcome.36,46 Nonetheless, there is no reason to
withhold antibiotics for fear of interfering with a sepsis
workup in the neonate.47
5. Neuraxial anesthesia and antibiotic therapy
There is no evidence to suggest that neuraxial anesthesia is
contraindicated in parturients with chorioamnionitis, but it is
contraindicated in patients with overt sepsis. Delaying
administration of neuraxial anesthetic techniques in patients
appearing ill enough to suspect the presence of early sepsis
until appropriate antibiotics are administered seems prudent
and has not proved injurious to parturients.48 Antepartum and
intrapartum antibiotic therapy has been shown to reduce both
maternal morbidity (i.e., shorter hospital stays, fewer days
with fever, lower peak postpartum temperatures) as well as
neonatal morbidity (i.e., decreased incidence of sepsis,
shorter hospital stays).
6. Complications
Postpartum, the anesthesia provider must be prepared to treat
possible uterine atony and hemorrhage, which can occur
after vaginal delivery or CD in pregnancies complicated by
chorioamnionitis.46
B. Respiratory tract infection: pneumonia
1. Risk during pregnancy
Respiratory tract infections are common during pregnancy but
not associated with complications as a rule. Physiologic
changes of the respiratory tract during pregnancy (see
Chapter 1) predispose pregnant women to more serious
respiratory tract infections with an increased likelihood of
maternal hypoxemia.49 The incidence of pneumonia is not
increased in pregnancy, but pneumonia in pregnancy is
preceded by upper respiratory tract infections in 50% of cases.
2. Pathogens are not identified in 41% to 60% of cases of
community-acquired pneumonias, but possible causes
include:
 a. Streptococcus pneumoniae
b. Haemophilus influenzae
c. Viral influenza (see next section)
d. Varicella zoster
3. Symptoms and diagnosis
Hallmarks of pneumonia include:
a. Fever
b. Dyspnea
c. Pleuritic chest pain
d. Cough
e. Rigors
f. Chills
Although the pulmonary examination can be relatively
insensitive and nonspecific, chest radiography must be
obtained for confirmation of suspected pneumonia.
4. Management includes antimicrobial therapy and may require
hospital admission for fetal monitoring and supplemental
oxygen administration. Fetal oxygenation decreases when the
maternal PaO2 is ≤65 mm Hg, or SpO2 is ≤90%; maternal
oxygenation should reach or surpass these levels.50 Up to
10% of parturients with pneumonia will require intensive care
unit (ICU) admission for optimization of their respiratory
status.
5. Anesthetic management
Although epidural analgesia during labor has been suggested
to attenuate increases in oxygen consumption in the parturient
with pneumonia, care must be taken to avoid high motor
block, which may further compromise pulmonary mechanics.
For CD, sensory levels of up to T2 may be necessary when
neuraxial anesthesia is used. The risk of a high anesthetic
level and potential respiratory embarrassment must be
weighed against administration of a general anesthetic, which
can result in a more rapid oxygen desaturation than in healthy
parturients already at risk for hypoxemia due to increased
 oxygen consumption and the decreased functional residual
capacity of pregnancy. If neuraxial anesthesia is
contemplated, it is important to establish adequate
intravenous (IV) antibiotic coverage in parturients with
suspected bacterial pneumonia before administration of the
anesthetic (see following section on regional anesthesia in
febrile or infected parturients).

CLINICAL PEARL In patients with pneumonia, the risk of a

high anesthetic level and potential respiratory embarrassment must
be weighed against administration of a general anesthetic, which
can result in even more rapid oxygen desaturation due to increased
oxygen consumption and decreased functional residual capacity of
pregnancy.

C. Respiratory tract infection: influenza

1. Transmission and clinical presentation. Influenza A and B
are the two primary viruses that cause human influenza.
Influenza is spread typically through respiratory secretions,
and common manifestations of infection are fever, myalgias,
headache, malaise, nonproductive cough, sore throat, and
rhinitis.
2. Serious complications from influenza include:
a. Primary viral pneumonia
b. Secondary bacterial pneumonia
c. Other less common complications:
(1) Encephalopathy
(2) Transverse myelitis
(3) Myositis
(4) Myocarditis
(5) Pericarditis
(6) Reye syndrome (rare)
3. Vaccination
 Complications from influenza are greatly increased in the
pregnant population because of the cardiac, respiratory,
and immunologic changes of pregnancy. For this reason,
pregnant women are encouraged to receive vaccinations
before influenza season. Two forms of vaccines exist: an
inactivated (killed) influenza vaccine that is typically given
intramuscularly (IM) and a live attenuated influenza vaccine
(LAIV) that is typically administered through intranasal spray,
typically given to children. To date, the inactivated influenza
vaccine has been shown to be safe when administered during
pregnancy.51 The fetus is passively protected through 20
weeks’ gestation, and maternal vaccination reduces fetal
deaths.52 If there are serious complications of influenza,
supportive care is warranted on an individual basis, paying
particular attention to intravascular volume status during
neuraxial anesthesia because dehydration may occur.
Aggressive use of antiviral drugs has been shown to be
effective in pregnancy and reduces complications.53
D. Urinary tract infection
1. General considerations
Urinary tract infection (UTI) is the most commonly
encountered bacterial infection in parturients. Infections
range from asymptomatic bacterial colonization of the urinary
tract to acute pyelonephritis. In a review of pregnancy-related
hospitalizations from 1999 to 2000,54 the most frequent cause
was a genitourinary complication. These complications may
result in preterm labor and delivery as well as significant
maternal morbidity and mortality.55 Pregnant women should
be screened for asymptomatic bacteriuria during early
pregnancy because increased concentrations of progesterone
cause relaxation of ureteral smooth muscle and the gravid
uterus causes partial ureteral obstruction. If bacteriuria is
present, there is strong scientific consensus and national
preventative task force recommendations that it should be
 treated to prevent pyelonephritis, which will otherwise
complicate 25% to 30% of cases.56
2. Symptoms of acute pyelonephritis typically include:
a. Acute onset of fever
b. Chills
c. Flank pain
d. Bacteriuria and possibly bacteremia
E. coli is the most commonly cultured pathogen, but other
gram-negative rods and group B streptococcus are also
encountered.
3. Treatment must include prompt initiation of IV antibiotics
and IV fluid replacement. Dysfunction of other organ
systems may occur and include:
a. Renal insufficiency, which occurs in up to 20% of
affected women (necessitating appropriate dose
adjustment of medications).
b. ARDS
c. Septic shock
The latter two conditions should be aggressively managed
by early measures to optimize pulmonary and hemodynamic
parameters. These include possible endotracheal intubation
and mechanical ventilation as well as IV volume
resuscitation, invasive monitoring, and vasopressor
therapy.

CLINICAL PEARL UTI is the most commonly encountered

bacterial infection in parturients. Infections range from
asymptomatic bacterial colonization of the urinary tract to acute
pyelonephritis.

E. Postpartum infection (endometritis)

1. General considerations
Sources of postpartum infection include genital tract,
 urinary tract, the breasts, and the respiratory tract, and
surgical sites in women after CD. Breast and intrauterine
infections are the most common infections.34
2. Postpartum uterine infection is the most common cause of
postpartum fever and is defined as infection of the decidua
with extension into the myometrium and parametrial tissues.
Commonly called endometritis, the infection actually includes
various surrounding tissues and terms for the disease include:
endomyometritis, or endoparametritis, and metritis with pelvic
cellulitis.
a. Diagnosis is usually based on clinical findings in the
setting of:
(1) Fever
(2) Lower abdominal pain or uterine tenderness
(3) Malaise
(4) Foul-smelling lochia
(5) Continued vaginal bleeding
b. Risk factors
The incidence of metritis varies with the mode of
delivery, but there is at least tenfold greater incidence
after CD. Prolonged rupture of membranes and
increased duration of labor, preterm, or previous
cesarean deliveries are other risk factors for these
infections.57 Prophylactic antibiotic administration is
known to reduce the risk of postpartum wound or uterine
infection in all women undergoing CD.58
c. Treatment
Most active infections are polymicrobial and respond well
to broad-spectrum antibiotics; gentamycin plus
clindamycin are the most effective regimens.59 Patients
rarely need surgical intervention; however, anesthetic
concerns include possible hemodynamic instability due to
continued vaginal bleeding and/or bacteremia. As with
any potential case of bacteremia, administration of
 appropriate IV antibiotics seems prudent before
placing a neuraxial anesthetic technique, provided
hemodynamic and respiratory status will not be
overtly compromised from the neuraxial block.
d. Other potential complications include:
(1) Abscess
(2) Peritonitis
(3) Septic thrombophlebitis
(4) Risk for uterine rupture in a subsequent pregnancy60
F. Group B streptococcus
Group B β-hemolytic streptococcus (GBS), or Streptococcus
agalactiae, is a commensal organism found in the gastrointestinal
or lower genital tract of some women. In the 1970s, it was
recognized as the most common causative agent associated
with neonatal and perinatal infections in the United States and
may be associated with a mortality rate of 5% in term neonates
(or as high as 25% in premature neonates), with significant
neurologic morbidity in surviving infants. In 1992, the American
College of Obstetricians and Gynecologists (ACOG)
recommended universal screening of pregnant women for GBS at
35 to 37 weeks’ gestation to more accurately reflect carrier
status at time of delivery and antibiotic treatment prior to
delivery, which significantly reduced neonatal infection. In 2010,
the Centers for Disease Control and Prevention updated (and the
ACOG subsequently endorsed) the guidelines for GBS screening
and prophylaxis to include more accurate screening methods and
more aggressive antibiotic regimens.61
G. Cytomegalovirus
Cytomegalovirus (CMV) infection in pregnancy may present as a
brief, self-limited, flu-like illness or it may be asymptomatic.
During pregnancy, prevalence of CMV ranges from 0.7% to 4%
for primary infections and up to 13.5% for recurrent infections.62
Although maternal CMV infection may be mild without sequelae,
congenital CMV infection is one of the most common causes of
 congenital hearing loss and neurodevelopmental problems in
children in high-resource countries.62 CMV infection is also one
of the AIDS-indicator conditions and is seen with other AIDS-
associated diseases. Although there is no therapy for either
maternal or fetal CMV infection, CMV prophylaxis is
recommended in patients with HIV infection. Because most
CMV disease is benign, routine screening is not recommended
during pregnancy by US, UK, and Australian guidelines
(although some European countries do employ it). Meta-analysis
of multiple trials suggests that hygiene and behavioral
interventions have some efficacy in preventing maternal
seroconversion, but adherence is problematic. Moreover, the
review found insufficient evidence to recommend use of
hyperimmune globulin or antiviral drugs.62 There is presently no
licensed CMV vaccine.
H. Hepatitis
1. Acute hepatitis
a. Infectious causes. Acute viral hepatitis is one of the
most serious infections of pregnant women and the
most common cause of jaundice in this patient population.
Hepatitis has a variety of rare causes (e.g., CMV, Epstein-
Barr virus, rubella, herpes simplex virus [HSV]).
However, the most common infectious causes are a family
of hepatitis viruses (A, B, C, D, E, and G).63 These
viruses have a particular affinity for hepatocytes and are
transmitted by several routes.
b. Transmission. Hepatitis A and E are transmitted through
fecal-oral routes and are generally self-limited. Hepatitis
B, C, and D are transmitted through bodily fluids and can
progress to chronic carrier states. Hepatitis G virus is
common in volunteer blood donors and can be transmitted
by blood transfusion.
c. Diagnosis. Although some acute illnesses are mild and
subclinical (including 70% of HBV), others present
 with acute illness and a few (0.5%) progress to
fulminant hepatic necrosis. Acute viral hepatitis is
characterized by fever, malaise, and epigastric or right
upper quadrant pain. Anorexia and nausea are also
common and may be accompanied by jaundice and
hepatomegaly. During acute infections, hepatic
transaminase enzymes increase markedly above baseline.
The diagnosis of acute viral hepatitis is confirmed by
serologic testing.64

CLINICAL PEARL Acute viral hepatitis is one of the most

serious infections of pregnant women and the most common cause
of jaundice in this patient population.

2. Chronic hepatitis
a. Importance of screening. Chronic hepatitis can be a
multisystem disorder with complications such as
cirrhosis, hepatic failure, hepatocellular carcinoma, or
even death. Parturients who are carriers or have a history
of chronic hepatitis should be fully examined (by both
physical examination and laboratory studies, including
liver function tests) to assess severity of the disease.
Specific vaccines and immunoglobulins are available for
hepatitis A and B. All pregnant women should undergo
screening for hepatitis B (as recommended by the
Centers for Disease Control and Prevention and the
ACOG65) because vertical transmission can lead to
neonatal hepatitis. HB immune globulin and antiviral
therapy with lamivudine have shown some promise in
reducing vertical transmission.
b. Neonatal transmission. In addition to these
considerations, neonatal immunoprophylaxis should be
administered to attenuate neonatal infection. Without
 prophylaxis, the risk of infection is 10% to 20% when the
mother is hepatitis B surface-antigen positive. If the
mother is hepatitis B virus core component e-antigen
positive, the risk of neonatal infection is approximately
85%.65 Maternal (i.e., vertical) transmission of
hepatitis B infection to the neonate remains an
important public health concern.
3. Anesthetic considerations
Anesthetic concerns typically involve assessment of
severity of the hepatitis, whether acute or chronic.
Parturients should be evaluated for clotting abnormalities in
the presence of severe liver dysfunction. Clotting factors
should be replaced before administration of neuraxial
anesthesia.
a. Neuraxial anesthesia
Without evidence of coagulopathy, neuraxial anesthesia
can be administered. In patients with severe liver disease,
metabolism of local anesthetics is also of concern
because of the hepatic biotransformation of amino-amide
local anesthetics. In patients with severe disease, there is
reduced blood flow to the liver and liver function is poor.
This may result in significantly higher blood levels of
amino-amide local anesthetics and reduced rate of
degradation. Hepatic pseudocholinesterase
concentrations can also be decreased in patients with
liver disease. This may decrease the clearance of 2-
chloroprocaine and other amino-ester local anesthetics.
Theoretically, engorgement of the epidural venous plexus
may be greater in the parturient with portal hypertension
and esophageal varices, compared to a normal pregnancy,
perhaps increasing the risk of intravascular placement,
enhanced local anesthetic spread, or epidural hematoma.
Experts generally recommend careful administration of
drugs usually administered during epidural anesthesia.64
 Theoretically, spinal anesthesia may be more
advantageous because of the small dose of local
anesthetic administered. However, there may be concerns
about rapid onset sympathetic blockade in the presence of
hypovolemia.

CLINICAL PEARL In cases of hepatitis, parturients should be

evaluated for clotting abnormalities in the presence of severe liver
dysfunction. Clotting factors should be replaced before
administration of neuraxial anesthesia.

b. General anesthesia
In cases complicated by coagulopathy, severe
hemorrhage, or umbilical cord prolapse, general
anesthesia may be necessary. The distribution and
metabolism of medications may be altered and should be
taken into account. Intravascular volume should be
evaluated with consideration for invasive monitoring
when ascites and/or cardiovascular compromise are
present. Rapid sequence induction can be facilitated
with a variety of induction agents, but the choice of agent
should be based on the patient’s hemodynamic status.
Although liver disease may affect pseudocholinesterase
concentrations and delay metabolism of
succinylcholine, this is of minimal clinical concern.
Because of potential delayed clearance of opioids, they
should be administered judiciously. Finally, it is important
to avoid hypoxia and reduced hepatic blood flow during
general anesthesia to not worsen liver function.64 (see
Chapter 27 for further detail on anesthetic considerations
for liver disease.)
I. Human immunodeficiency virus
1. General considerations
 In the early part of the 21st century, the fastest growing
population of newly infected individuals with HIV were
women of reproductive age, but fortunately, the rate of
infection in women decreased from 2009 to 2013, the most
recently reported data.66 In light of rapidly evolving standards
of care for HIV-infected individuals, a website
(aidsinfo.nih.gov) (last accessed April 8, 2015) has been
created and should be accessed by those caring for such
patients. Transmission of HIV from mother to fetus is
thought to occur 30% of the time in utero in women not
receiving antiretroviral medication. It is estimated that 70%
of cases of vertical transmission occur during labor and
delivery in nonbreastfed infants.67 Many women are given
antiretroviral treatments during labor to decrease this risk, and
women with high viral loads often undergo CD. This strategy
has been successful in preventing vertical transmission in
approximately 99% of cases.68,69
2. Systemic manifestations
With the widespread adoption of highly active antiretroviral
therapy (HAART), HIV and its progression to AIDS no
longer primarily manifests as opportunistic infection but still
can involve multiple organ systems. Common anesthetic
considerations include careful evaluation of all organ systems
affected. There may be abnormalities of pulmonary,
gastrointestinal, hematologic, cardiovascular, endocrine,
and/or renal systems. In addition, the conditions that led to
HIV infection in the parturient (most notably substance abuse)
may complicate anesthetic and obstetrical management. The
progression of disease in terms of CD4+ cell count or HIV-1
RNA levels may be helpful in predicting mortality after
surgery, although this relationship may be less valid in the era
of HAART.70
a. Neurologic disease
Neurologic involvement occurs early during primary
 HIV infection.71 During the initial infection, patients may
complain of headache, photophobia, and retro-orbital
pain. Cognitive or affective disorders may also be
observed. In addition, some cases may be complicated by
meningoencephalitis as well as cranial and peripheral
neuropathies. Others may be asymptomatic but still have
cerebral spinal fluid abnormalities. During the latent
phase of infection, patients may present with a
demyelinating neuropathy, similar to Guillain-Barré
syndrome. This is presumed to be autoimmune in nature.
It usually responds to IV immunoglobulin or
plasmapheresis. The late stages of HIV infection are
manifest by profound neurologic deterioration in
nearly all patients. These complications can include
meningitis, diffuse encephalopathy, focal brain disorders,
myelopathy, peripheral neuropathy, AIDS dementia
complex, inflammatory myopathy, and autonomic
neuropathy.72
b. Pulmonary complications are not caused directly by the
HIV but result from opportunistic infections associated
with the disease. The most common infective agent is
Pneumocystis jiroveci (formerly carinii). This fungal
pathogen is responsible for a pneumonia causing a clinical
presentation similar to adult respiratory distress syndrome
(i.e., severe hypoxemia and diffuse interstitial infiltrates
on chest radiograph). Respiratory failure requiring
intubation was formerly and nearly always fatal; in
the era of improved ICU care, mortality is still high
but has been reduced to approximately 50% overall
with a Pneumocystis mortality of approximately
10%.73,74 Other pulmonary diseases include reactivation
of latent tuberculosis (TB), bacterial infections (e.g., S.
pneumoniae, H. influenzae), and other fungal infections
(e.g., Aspergillus, Cryptococcus, Coccidiodes).
c. Gastrointestinal involvement
Large quantities of lymphoid tissue in the gut contribute
to viral replication in this organ system. Nearly all
patients with HIV infection complain of gastrointestinal
disturbances during the disease. These abnormalities can
include esophagitis, severe diarrhea, or hepatobiliary
disease. A variety of pathogens are responsible for these
disorders, including HSV, Candida albicans, CMV,
Mycobacterium avium, TB, and Cryptosporidia. HAART
toxicity also contributes to gastrointestinal symptoms.75
d. Hematologic disorders can result from HIV infection of
peripheral cell lines as well as antiretroviral agents that
produce hematologic toxicity. Cytopenias (most notably
leukopenia) are the most common abnormalities and may
manifest as anemia or thrombocytopenia. HAART has
been successful at preventing or reversing many of these
abnormalities.76
e. Cardiovascular disease
Although overt cardiovascular disease is uncommon in
these patients, lymphocytic infiltration of the myocardium
is present in up to 50% of cases.77 Pericarditis is the most
prevalent disorder, but others include pulmonary
hypertension, focal myocarditis, and infective
endocarditis.
f. Endocrine disorders typically result from HIV infection
of endocrine tissue, opportunistic infections, or
antiretroviral therapy.78 Involvement of the pituitary,
adrenal, and thyroid glands at autopsy is common, but
clinical evidence of disease is rare. Other endocrine
involvement can result in either hypoglycemia or
hyperglycemia from antiretroviral therapies (e.g., protease
inhibitors, pentamidine).
g. Renal disease
Sepsis, dehydration, and drug toxicity contribute to
 the risk of acute renal failure and chronic renal
insufficiency in these patients. In addition, patients with
HIV infection may develop renal failure from HIV-
associated immune complex nephropathy. Antiretroviral
drug therapy is associated with renal toxicity over time
and may be more common than direct HIV effects in the
HAART era.79
3. Anesthetic considerations
a. Neuraxial anesthesia
(1) Infectious risk. One of the biggest concerns of
administering neuraxial anesthesia to patients
with HIV infection is whether these patients are at
increased risk for infectious complications.
Although there is no evidence suggesting that these
patients are at increased risk for such complications,
strict aseptic technique must be maintained. Besides
adherence to the precautions for safe administration
of neuraxial anesthesia recommended by the
American Society of Regional Anesthesia (ASRA)
(see Chapter 10),80 the American Society of
Anesthesiologists (ASA) Subcommittee on
Infection Control has recommended use of standard
precautions and careful avoidance of needlestick
injury.81 Other concerns are related to the
administration of neuraxial anesthesia in patients who
may develop neurologic deficits in the future.
Although CNS involvement occurs very early in
the course of HIV disease and the deficits will not
likely be temporally related to the neuraxial
anesthetic, this should not be a concern when
contemplating neuraxial anesthesia.

CLINICAL PEARL Although there is no evidence suggesting

that these patients are at increased risk for infectious complications,
strict aseptic technique during the administration of regional
anesthesia must be maintained.

(2) Postdural puncture headache and epidural blood

patch. Despite the use of pencil-point needles for
spinal anesthesia and the occasional unintentional
dural puncture during attempted epidural placement,
postdural puncture headache (PDPH) still occurs. If
an HIV-infected parturient experiences a PDPH,
epidural blood patch can be considered if
conservative management fails. Only a small series of
such cases have been reported, all in the pre-HAART
era, but no neurologic complications attributable to
the blood patch were seen.82
b. General anesthesia
For general anesthesia, prior administration of the
antiretroviral drugs can alter anesthetic medication
effects (e.g., midazolam and fentanyl) through effects on
cytochrome P450 enzymes. Etomidate, atracurium,
remifentanil, and desflurane may be alternatives for use in
patients who receive long-term antiretroviral therapy
because they are not dependent on metabolism by the
cytochrome P450 system.83 Other concerns regarding
general anesthesia may be of unknown or theoretical
importance, such as temporary depression of immune
function after general anesthesia in healthy individuals,
difficulties in intubation due to pharyngeal lymphatic
hypertrophy in some patients, and the potential
introduction of pathogens into the pulmonary tree through
endotracheal intubation. In the situation of postpartum
hemorrhage, methylergonovine maleate (Methergine)
should be avoided in parturients who are on potent
CYP3A4 enzyme inhibitors (such as protease inhibitors
and the non-nucleoside reverse transcriptase inhibitors)
 because exaggerated vasoconstrictive responses have
been reported in these patients.84 Prostaglandins and
oxytocin are considered safe.
J. Herpes simplex virus (HSV-1 and HSV-2)
There are two major types of herpes simplex viruses: HSV-1 and
HSV-2. They are primarily responsible for nongenital (e.g.,
gingivostomatitis, keratoconjunctivitis) and genital lesions. HSV-
1 tends to be the causative agent in nongenital lesions and HSV-2
in genital lesions, although there is increasing crossover.85
Transmission occurs by direct contact with infected bodily
fluids (i.e., oral or genital secretions). There are two distinct
phases of HSV infection: primary and secondary (or reactivation).
1. Primary genital HSV can present with fever, myalgias,
headaches, genital lesions, and a transient viremia. However,
many patients may be asymptomatic and without
accompanying lesions. These factors make the diagnosis of
primary HSV infection difficult. However, the risk to the fetus
of vertical transmission is very high in this setting.86 There is
a theoretical concern of spreading HSV to the CNS via
neuraxial anesthesia due to the viremia that is possibly
present. The largest series of epidural and spinal anesthetics
given to women with HSV showed no permanent neurologic
sequelae, but nearly all cases were not primary infections.87
2. For secondary or reactivated HSV (the most common
presentation during pregnancy), the consensus is that
neuraxial anesthesia is safe, provided there are no active
lesions at the site of needle insertion. During secondary
infections, maternal antibodies prevent recurrence of viremia,
making neuraxial anesthesia less risky. A major concern is
vertical transmission of HSV from mother to neonate during
vaginal delivery in the presence of active genital lesions or
during asymptomatic viral shedding in the vagina. CD is
indicated as the standard of care because it reduces the rate of
vertical transmission when there are active genital lesions.88
 Neonatal mortality is high in HSV, especially in
disseminated disease.21 Acyclovir or valacyclovir prophylaxis
and treatment have been safely used in pregnancy and a meta-
analysis of multiple RCTs demonstrated reduction in active
lesions and need for CD.89 The use of epidural or spinal
opioids (especially morphine) has been associated with
reactivation of HSV-1 in perioral and thoracic regions.90,91
Previously postulated mechanisms included pruritus resulting
in scratching of the face, but immunologic activation of the
trigeminal nuclei by opioid binding is now thought to be the
primary mechanism.92 No such association has been drawn
between opioids and HSV-2 reactivation.

CLINICAL PEARL The use of epidural or spinal opioids

(especially morphine) has been associated with reactivation of
maternal HSV-1 in perioral and thoracic regions.

K. Miscellaneous infections
1. Lyme disease. Twelve strains of the spirochete Borrelia
burgdorferi sensu lato cause Lyme disease, which is the most
common vector-borne infection in the United States. It is
transmitted by the bites of deer ticks (Ixodes scapularis) as
well as Western black-legged ticks (Ixodes pacificus).
Common presentation of Lyme disease is a “bull’s-eye” rash
(erythema migrans) which spreads outward from the initial
site of inoculation and may be accompanied by fever, malaise,
fatigue, myalgias, arthralgias, and headaches. Some
parturients may be asymptomatic; however, others may
experience more serious cardiac and neurologic
manifestations. Fetal risk with maternal infection is largely
unknown and appears low, with no evidence of congenital
transmission.93 Antimicrobial treatment is warranted in
maternal Lyme disease, although the first-line drug,
 doxycycline is contraindicated in pregnancy and cefuroxime
or amoxicillin are the preferred alternatives.93 Anesthetic
considerations in the parturient with Lyme disease focus
on severity of disease, specifically cardiac and neurologic
involvement. If there are indications of central or
peripheral nervous system involvement, it may be wise to
avoid neuraxial anesthetic techniques, although there are
case reports of successful spinal anesthesia in infected
parturients.
2. Listeria. Listeria monocytogenes is the gram-positive rod
bacterium responsible for listeriosis. Listeriosis is rare in the
nonpregnant population, but infection is increased 20-fold
during pregnancy.94 Listeria survive at temperatures used
for refrigeration and may be transmitted in many ready-to-eat
food products that have been properly refrigerated.95 Many
parturients are advised to avoid such food products during
their pregnancy. Common signs and symptoms of listeriosis
include fever, headache, myalgias, and gastrointestinal
symptoms (including diarrhea). Rarely, severe maternal
complications (e.g., death) may occur from Listeria
infections but are mainly related to underlying
immunocompromised conditions. Fetal and neonatal
infection can be devastating, with a mortality rate of
approximately 20%.96 Prompt antimicrobial treatment must
be instituted to improve fetal survival.
3. Parvovirus B19 is the virus responsible for erythema
infectiosum (fifth disease) as well as transient aplastic crisis
in patients with hemoglobinopathies. Transmission is
primarily through hand-to-mouth contact and respiratory
secretions. Symptoms may include fever, sore throat, reticular
rash, and peripheral arthropathy, with the latter two occurring
up to several weeks after the initial infection. Disease can be
mild in parturients, even those who are additionally
immunocompromised.97 Fetal infection with parvovirus B19
 may result in fetal hydrops (due to myocarditis and/or
anemia) or fetal loss, especially if maternal infection occurs in
the first 20 weeks of gestation. Intrauterine transfusion of the
fetus may be required.97
4. Syphilis is caused by infection with the spirochete Treponema
pallidum, most commonly transmitted through sexual contact.
Syphilis infections are on the rise with increased HIV
infections and IV drug abuse. Eighty percent of women who
are currently infected are of reproductive age. Pregnancy
does not typically alter the course of syphilis, but syphilis
may be transmitted from mother to fetus, resulting in
intrauterine growth restriction, preterm birth, stillbirth,
neonatal death, and congenital infection.98 Serologic
testing during prenatal visits and treatment of syphilis with
penicillin helps to reduce the maternal–fetal transmission rate
from 70%–100% to 1%–2%.99 There are few specific
anesthetic considerations in parturients with syphilis
unless there is severe late stage disease affecting the CNS or
aorta. However, parturients presenting with syphilis often
have had no or poor prenatal care, and infection may be a
marker for cocaine use.100
5. Tuberculosis. Despite a decreasing prevalence in the United
States, TB continues to be a significant problem in urban
areas and among non–US-born populations.101,102 TB is
spread primarily through aerosolized droplets (typically
produced by coughing) that enter the respiratory system.
Although pregnancy does not appear to change the course of
TB, active TB and the emergence of multidrug-resistant M.
tuberculosis can pose serious problems to parturients,
neonates, and health care providers.102 In urban areas, it is
routine for pregnant women to be screened for TB by purified
protein derivative (PPD) skin testing during their prenatal
visits. A follow-up chest x-ray should be performed for
positive PPD results. This will document presence of active
 disease. Active TB should be treated during pregnancy with
first-line therapy including isoniazid, rifampin, and/or
ethambutol.103 All are considered to be safe for the fetus, but
isoniazid is associated with an increased incidence of hepatitis
during pregnancy; therefore, liver function tests must be
followed closely. It has been suggested that extrapulmonary
TB, possibly of the placenta, uterus, or genital tract, is
associated with increased maternal and fetal morbidity as well
as increased risk of congenital or neonatal TB.104 Caregivers
should take extra precautions to avoid exposure to infection in
the presence of active TB (such as placing the parturient in a
negative-pressure room and having exposed persons wear
N95 particulate respirator masks).
6. Varicella zoster virus (VZV) is a member of the herpes virus
family. There are two distinct forms of the disease. Varicella,
or chickenpox, is a febrile, systemic disease associated with
generalized pruritic vesicles, whereas herpes zoster (or
“shingles”) is a reactivation of the latent virus, which
resides in sensorineural ganglia. In cases of shingles, the
patient experiences eruption of painful vesicles in a unilateral
dermatomal distribution. Primary varicella can also present
with encephalitis or pneumonia (in 20% to 25% of primary
infections occurring as an adult), with occasional rapid
respiratory failure in the latter. If varicella pneumonia occurs,
it must be treated with IV acyclovir. Previously, varicella
pneumonia carried a 36% to 41% mortality rate in
parturients.However, introduction of antiviral agents (e.g.,
acyclovir) as well as earlier and improved recognition
have decreased maternal mortality to 13% to 14%.105 If
primary varicella occurs, the natural progression of both
neonatal varicella and varicella in the parturient may be
attenuated by administration of varicella zoster immune
globulin (VZIG), which must be administered within 96
hours of exposure to the virus. If acute primary varicella is
 present at the time of delivery, there is current debate about
how to best manage anesthesia. Because viremia may be
present for up to 2 weeks following onset of cutaneous
lesions, some authors recommend avoiding neuraxial
anesthesia. However, others would support its use due to the
high risk of varicella pneumonia during the course of the
disease, and there have been published case reports of
uneventful outcome after spinal anesthesia,106 perhaps after
administration of VZIG.88 If neuraxial anesthesia is
administered to a patient with primary or recurrent VZV
infection, spinal or epidural needles should probably not
be introduced through cutaneous lesions. Patients with
zoster may also present challenges in pain management
because the pain of zoster is difficult to control and requires
careful evaluation of all available modalities.

CLINICAL PEARL If neuraxial anesthesia is administered to a

patient with primary or recurrent VZV infection, spinal or epidural
needles should probably not be introduced through cutaneous
lesions.

7. Emerging infectious diseases and bioterrorism. Recent

experiences with emerging infectious diseases and the
potential for bioterrorism have required development of
response plans that include vaccines and medications for
which maternal and fetal effects are unknown. Diseases such
as severe acute respiratory syndrome (SARS), monkeypox,
smallpox, and anthrax pose threats to the parturient.107
Many of the vaccines and medications for potential
bioterrorism emergencies have been labeled as U.S. Food and
Drug Administration (FDA) pregnancy categories B through
X. Despite the ideal nature of limiting fetal exposure to
treatments that may be teratogenic, protecting the life of the
 mother is critical in protecting the fetus.
a. SARS is caused by a coronavirus and was initially treated
with ribavirin and corticosteroids, but the efficacy of these
agents is under investigation. In addition, SARS
treatments may be of concern for use in pregnant women
due to previous limited or untoward outcomes in
pregnancy.107
b. Monkeypox
The first outbreak of monkeypox in the United States in
2003 led to reintroduction of the smallpox vaccine
(vaccinia), which may be associated with preterm delivery
and fetal or neonatal death. Smallpox vaccine is generally
contraindicated in pregnant women or in women who
desire to become pregnant within 28 days of
administration. However, the high mortality of
monkeypox in Africa, as well as the high efficacy of
smallpox vaccination, led to the advisory of parturients
exposed to the monkeypox virus to receive the
vaccine.107 The risk of smallpox-related illness again
outweighs the risk of fetal vaccinia from a parturient
receiving smallpox vaccine; therefore, pregnant women
are advised to receive the vaccine.
c. Anthrax
During outbreaks of anthrax in 2001, ciprofloxacin
became the drug of choice for prophylactic therapy of
asymptomatic parturients exposed to Bacillus anthracis.
Despite the association between fluoroquinolones and
joint and cartilage malformations in animals, there
appears to be little risk in humans, and the risk of
penicillinase activity in B. anthracis leading to inadequate
treatment of the parturient outweighs this risk.

CLINICAL PEARL Recent experiences with emerging

infectious diseases (e.g., SARS, monkeypox, smallpox) and the
 potential for bioterrorism (e.g., anthrax) have required development
of response plans that include vaccines and medications for which
maternal and fetal effects are unknown.

IV. Sepsis and septic shock

Sepsis is one of the leading causes of preventable maternal death
worldwide.108 In the general population, septic shock, or organ
malperfusion associated with sepsis, carries a morbidity and mortality
rate of 25% and 50%, respectively. Although few in number, outcome
studies highlight the seriousness of these illnesses, and in these older
series, mortality was higher (perhaps reflecting the success of modern
intensive care for sepsis). In one of the series, 18 cases of septic shock
were reported over an 11-year period.109 The most common etiology
was pyelonephritis, followed by chorioamnionitis, endometritis, and
toxic shock syndrome. The authors reported a 28% mortality rate
associated with mild to severe myocardial depression in four of the
five fatal cases. Most obstetric patients may be healthier than the
average population, and sepsis mortality is now approximately 6%
overall,110 but septic shock in a parturient should always be
considered a life-threatening condition due to the high mortality
rate.109
A. General considerations
Systemic inflammatory response syndrome (SIRS), sepsis,
severe sepsis, and septic shock are thought to share a common
pathophysiology but are represented along a progressively
worsening continuum.111
1. SIRS is defined as the clinical response to infection
manifested by two or more of the following symptoms:
temperature ≥38°C or ≤36°C, pulse ≥90 beats per minute,
respirations of ≥20 breaths per minute or PaCO2 <32 mm Hg,
or white blood cell count ≥12,000 or ≤4,000, or >10%
immature neutrophils. The definition of sepsis is met when
SIRS criteria along with suspected or confirmed infection are
 present. Severe sepsis occurs along with dysfunction of at
least one organ system.
2. Septic shock is defined as sepsis with accompanying
hypotension (≤90 mm Hg systolic blood pressure [SBP])
despite fluid management. Hypotension may lead to
widespread tissue injury, hypoperfusion, and multisystem
organ failure. Most septic shock in parturients is associated
with bacterial infection, both gram-negative bacteremia as
well as gram-positive aerobic and anaerobic bacteremia.
Common organisms include E. coli, groups A and B
streptococcus, Klebsiella species, and Staphylococcus
aureus.111 Septic shock leads to massive inflammation and
coagulation when mediators (e.g., endotoxin, tumor necrosis
factor, interleukins, cyclooxygenase metabolites, tissue
factors, thrombin) are released from immune effector cells.112
All organ systems may be involved, but it is clear that
massive inflammation and coagulation disturbance often
lead to microthrombosis and organ failure. Most of the
pronounced changes are seen in the cardiovascular,
respiratory, hematologic, and metabolic organ systems.
B. Treatment
It is imperative that early, aggressive treatment strategies be
initiated in cases of septic shock to decrease maternal and fetal
morbidity. In cases where the pregnancy itself is the source of
maternal sepsis, delivery may be necessary before fetal viability,
otherwise the ACOG does not recommend delivery.113 Although
fetal well-being is an important consideration, treatment of the
mother is the first priority. Therapy is specifically aimed at
treating any underlying infectious cause (using broad-spectrum
antibiotics) as well as maximizing cardiovascular dynamics,
intravascular volume, and tissue oxygenation. Most authorities
recommend treatment similar to that in nonpregnant patients,
including following the surviving sepsis guidelines (see Table
8.1), although they have not been specifically evaluated in
 pregnant patients.114–116 Anesthesiologists may be called upon to
help care for these critically ill women, including airway and
ventilator management, fluid and hemodynamic support, and
implementation of invasive monitoring.

CLINICAL PEARL The Guidelines for the International

Surviving Sepsis Campaign call for administration of high-dose IV
antibiotics within 1 hour of admission for anyone with suspected
sepsis.

C. Anesthetic management
If delivery becomes necessary, neuraxial anesthetic techniques
may not be a viable choice due to aberrant hemodynamic,
respiratory, and coagulation parameters. When administering
general anesthesia, it is important to choose induction agents
which support the cardiovascular system, such as etomidate or
ketamine. These agents will not prolong the time from induction
 to delivery, avoiding further compromise to the fetus. In addition,
if a severe intraabdominal infection is suspected, it may be
prudent to avoid succinylcholine because it may cause
hyperkalemia in this setting.117 Rocuronium may be preferred for
rapid sequence induction due to its rapid onset of action. Up to
40% of pregnant patients with septic shock may need to undergo
surgery.109
V. Neuraxial anesthesia for the febrile parturient
Neuraxial anesthesia is generally preferred to general anesthesia in
obstetrics, with reduced mortality and serious morbidity compared to
general anesthesia. If general anesthesia is required for seriously
infected patients, the risk of hemodynamic instability, airway
compromise, and electrolyte abnormalities (discussed earlier) should
be considered. Neuraxial anesthesia in febrile patients poses
additional considerations.
A. Risk
There is some concern about causing infection while performing
neuraxial anesthetic techniques in febrile parturients. However, in
most cases, these techniques are safe when performed after
administration of appropriate antimicrobial agents. In a classic
paper by Carp and Bailey,118 treatment with a single dose of
gentamicin before dural puncture in rats with E. coli bacteremia
appeared to eliminate the risk of infection; however, it is unclear
if this applies to the febrile obstetric population. Most spinal or
epidural infections appear to be related to surgical procedures,
hematogenous spread of infectious agents, prolonged
catheterization, compromised immune status, and/or a lapse in
sterile technique, but many cases are spontaneous in origin. The
overall incidence of epidural abscess formation in parturients
receiving neuraxial anesthesia is unknown, largely due to the
rarity of occurrence and lack of centralized reporting.
However, two large prospectively collected audits, one in the
United Kingdom119 and one in the United States120 calculated the
risk between approximately 1:60,000 and 1:300,000, albeit with
 very wide confidence intervals given the rarity of the outcome.
The most common pathogens associated with spinal or epidural
abscesses are S. aureus (50%), various streptococci (15%), and
gram-negative rods (15% to 20%).121 Organisms cultured from
anesthesiologists’ nasopharynx or skin have been implicated in
some case reports.
B. IV antibiotics
It is reasonable to require administration of appropriate IV
antibiotics before placement of a neuraxial anesthetic in a
febrile parturient who appears ill and possibly bacteremic.122
However, the dose and timing of such treatment is currently
unknown. In addition, there are no current guidelines surrounding
maximum temperature, white blood cell counts, or other clinical
signs, which one would clearly contraindicate neuraxial
anesthesia. In a woman with florid sepsis, cardiovascular,
respiratory, and hematologic concerns may preclude the use of
neuraxial anesthesia, but the risks and benefits of alternatives
must be assessed and weighed individually.
C. Aseptic technique
11 The ideal aseptic technique for regional anesthesia is
controversial (see Chapter 10). There have been questions about
the use of maximal aseptic precautions that are similar to those
used during central venous access placement. Handwashing;
jewelry removal; and use of sterile gloves (to supplement
handwashing and not as a substitute), fresh mask, and cap have
been shown to reduce the incidence of microbial contamination of
the work area but not directly to reduce nosocomial infection. The
ASRA consensus statement80 and ASA Task Force report122
acknowledge the importance of these precautions.

REFERENCES
1. Kuczkowski KM, Reisner LS. Anesthetic management of the parturient with fever and infection. J
Clin Anesth. 2003;15:478–488.
2. Macaulay JH, Bond K, Steer PJ. Epidural analgesia in labor and fetal hyperthermia. Obstet Gynecol.
 1992;80:665–669.
3. Herbst A, Wølner-Hanssen P, Ingemarsson I. Risk factors for fever in labor. Obstet Gynecol.
1995;86:790–794.
4. Petrova A, Demissie K, Rhoads GG, et al. Association of maternal fever during labor with neonatal
and infant morbidity and mortality. Obstet Gynecol. 2001;98:20–27.
5. Lieberman E, Eichenwald E, Mathur G, et al. Intrapartum fever and unexplained seizures in term
infants. Pediatrics. 2000;106:983–988.
6. Lieberman E, Lang J, Richardson DK, et al. Intrapartum maternal fever and neonatal outcome.
Pediatrics. 2000;105:8–13.
7. Segal S. Labor epidural analgesia and maternal fever. Anesth Analg. 2010;111:1467–1475.
8. Lieberman E, Lang JM, Frigoletto F, et al. Epidural analgesia, intrapartum fever, and neonatal sepsis
evaluation. Pediatrics. 1997;99:415–419.
9. Philip J, Alexander JM, Sharma SK, et al. Epidural analgesia during labor and maternal fever.
Anesthesiology. 1999;90:1271–1275.
10. Kaul B, Vallejo M, Ramanathan S, et al. Epidural labor analgesia and neonatal sepsis evaluation rate: a
quality improvement study. Anesth Analg. 2001;93:986–990.
11. Impey L, Greenwood C, MacQuillan K, et al. Fever in labour and neonatal encephalopathy: a
prospective cohort study. BJOG. 2001;108:594–597.
12. Impey LW, Greenwood CE, Black RS, et al. The relationship between intrapartum maternal fever and
neonatal acidosis as risk factors for neonatal encephalopathy. Am J Obstet Gynecol. 2008;198:49.e41–
e46.
13. Wu YW, Escobar GJ, Grether JK, et al. Chorioamnionitis and cerebral palsy in term and near-term
infants. JAMA. 2003;290:2677–2684.
14. Wu YW, Colford JM Jr. Chorioamnionitis as a risk factor for cerebral palsy: a meta-analysis. JAMA.
2000;284:1417–1424.
15. Dammann O, Drescher J, Veelken N. Maternal fever at birth and non-verbal intelligence at age 9 years
in preterm infants. Dev Med Child Neurol. 2003;45:148–151.
16. Zerbo O, Iosif AM, Walker C, et al. Is maternal influenza or fever during pregnancy associated with
autism or developmental delays? Results from the CHARGE (CHildhood Autism Risks from Genetics
and Environment) study. J Autism Dev Disord. 2013;43:25–33.
17. Camann WR, Hortvet LA, Hughes N, et al. Maternal temperature regulation during extradural
analgesia for labour. Br J Anaesth. 1991;67:565–568.
18. Fusi L, Steer PJ, Maresh MJ, et al. Maternal pyrexia associated with the use of epidural analgesia in
labour. Lancet. 1989;1:1250–1252.
19. Goetzl L, Rivers J, Zighelboim I, et al. Intrapartum epidural analgesia and maternal temperature
regulation. Obstet Gynecol. 2007;109:687–690.
20. Mantha VR, Vallejo MC, Ramesh V, et al. Maternal and cord serum cytokine changes with continuous
and intermittent labor epidural analgesia: a randomized study. ScientificWorldJournal.
2012;2012:607938.
21. Mantha VR, Vallejo MC, Ramesh V, et al. The incidence of maternal fever during labor is less with
intermittent than with continuous epidural analgesia: a randomized controlled trial. Int J Obstet
Anesth. 2008;17:123–129.
22. Tian F, Wang K, Hu J, et al. Continuous spinal anesthesia with sufentanil in labor analgesia can induce
maternal febrile responses in puerperas. Int J Clin Exp Med. 2013;6:334–341.
23. Wong CA, Scavone BM, Peaceman AM, et al. The risk of cesarean delivery with neuraxial analgesia
given early versus late in labor. N Engl J Med. 2005;352:655–665.
24. Goetzl L, Evans T, Rivers J, et al. Elevated maternal and fetal serum interleukin-6 levels are associated
 with epidural fever. Am J Obstet Gynecol. 2002;187:834–838.
25. Dashe JS, Rogers BB, McIntire DD, et al. Epidural analgesia and intrapartum fever: placental
findings. Obstet Gynecol. 1999;93:341–344.
26. Vallejo MC, Kaul B, Adler LJ, et al. Chorioamnionitis, not epidural analgesia, is associated with
maternal fever during labour. Can J Anaesth. 2001;48:1122–1126.
27. Riley LE, Celi AC, Onderdonk AB, et al. Association of epidural-related fever and noninfectious
inflammation in term labor. Obstet Gynecol. 2011;117:588–595.
28. Sharma SK, Rogers BB, Alexander JM, et al. A randomized trial of the effects of antibiotic
prophylaxis on epidural-related fever in labor. Anesth Analg. 2014;118:604–610.
29. Goetzl L, Zighelboim I, Badell M, et al. Maternal corticosteroids to prevent intrauterine exposure to
hyperthermia and inflammation: a randomized, double-blind, placebo-controlled trial. Am J Obstet
Gynecol. 2006;195:1031–1037.
30. Wang LZ, Hu XX, Liu X, et al. Influence of epidural dexamethasone on maternal temperature and
serum cytokine concentration after labor epidural analgesia. Int J Gynaecol Obstet. 2011;113:40–43.
31. Goetzl L, Rivers J, Evans T, et al. Prophylactic acetaminophen does not prevent epidural fever in
nulliparous women: a double-blind placebo-controlled trial. J Perinatol. 2004;24:471–475.
32. Knight M, Kurinczuk J. Introduction and methodology. In: Knight M, Kenyon S, Brocklehurst P, et al.,
eds. Saving Lives, Improving Mothers’ Care: Lessons Learned to Inform Future Maternity Care from
the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2009-2012. Oxford,
United Kingdom: National Perinatal Epidemiology Unit, University of Oxford; 2014:1–8.
33. Newton ER. Chorioamnionitis and intraamniotic infection. Clin Obstet Gynecol. 1993;36:795–808.
34. Duff P, Gibbs RS, Sweet RL. Maternal and fetal infections. In: Creasy RK, Resnik R, Iams JD, et al.,
eds. Maternal-Fetal Medicine: Principles and Practice. 6th ed. Philadelphia, PA: Saunders-Elsevier;
2009:739–796.
35. Qureshi F, Jacques SM, Bendon RW, et al. Candida funisitis: a clinicopathologic study of 32 cases.
Pediatr Dev Pathol. 1998;1:118–124.
36. Gibbs RS, Castillo MS, Rodgers PJ. Management of acute chorioamnionitis. Am J Obstet Gynecol.
1980;136:709–713.
37. Yoder PR, Gibbs RS, Blanco JD, et al. A prospective, controlled study of maternal and perinatal
outcome after intra-amniotic infection at term. Am J Obstet Gynecol. 1983;145:695–701.
38. Roberts DJ, Celi AC, Riley LE, et al. Acute histologic chorioamnionitis at term: nearly always
noninfectious. PLoS One. 2012;7:e31819.
39. Goodman EJ, DeHorta E, Taguiam JM. Safety of spinal and epidural anesthesia in parturients with
chorioamnionitis. Reg Anesth. 1996;21:436–441.
40. Satin AJ, Maberry MC, Leveno KJ, et al. Chorioamnionitis: a harbinger of dystocia. Obstet Gynecol.
1992;79:913–915.
41. Kim MJ, Romero R, Gervasi MT, et al. Widespread microbial invasion of the chorioamniotic
membranes is a consequence and not a cause of intra-amniotic infection. Lab Invest. 2009;89:924–
936.
42. Shimoya K, Taniguchi T, Matsuzaki N, et al. Chorioamnionitis decreased incidence of respiratory
distress syndrome by elevating fetal interleukin-6 serum concentration. Hum Reprod. 2000;15:2234–
2240.
43. Van Marter LJ, Dammann O, Allred EN, et al. Chorioamnionitis, mechanical ventilation, and postnatal
sepsis as modulators of chronic lung disease in preterm infants. J Pediatr. 2002;140:171–176.
44. Wu YW. Systematic review of chorioamnionitis and cerebral palsy. Ment Retard Dev Disabil Res Rev.
2002;8:25–29.
45. Alexander JM, McIntire DM, Leveno KJ. Chorioamnionitis and the prognosis for term infants. Obstet
 Gynecol. 1999;94:274–278.
46. Rouse DJ, Landon M, Leveno KJ, et al. The Maternal-Fetal Medicine Units cesarean registry:
chorioamnionitis at term and its duration-relationship to outcomes. Am J Obstet Gynecol.
2004;191:211–216.
47. Sarkar SS, Bhagat I, Bhatt-Mehta V, et al. Does maternal intrapartum antibiotic treatment prolong the
incubation time required for blood cultures to become positive for infants with early-onset sepsis? Am
J Perinatol. 2015;32:357–362.
48. Bader AM, Gilbertson L, Kirz L, et al. Regional anesthesia in women with chorioamnionitis. Reg
Anesth. 1992;17:84–86.
49. Brito V, Niederman MS. Pneumonia complicating pregnancy. Clin Chest Med. 2011;32:121–132.
50. Benedetti TJ, Valle R, Ledger WJ. Antepartum pneumonia in pregnancy. Am J Obstet Gynecol.
1982;144:413–417.
51. Fiore AE, Shay DK, Broder K, et al. Prevention and control of seasonal influenza with vaccines:
recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm
Rep. 2009;58(RR-8):1–52.
52. Haberg SE, Trogstad L, Gunnes N, et al. Risk of fetal death after pandemic influenza virus infection or
vaccination. N Engl J Med. 2013;368:333–340.
53. Hansen C, Desai S, Bredfeldt C, et al. A large, population-based study of 2009 pandemic influenza A
virus subtype H1N1 infection diagnosis during pregnancy and outcomes for mothers and neonates. J
Infect Dis. 2012;206:1260–1268.
54. Bacak SJ, Callaghan WM, Dietz PM, et al. Pregnancy-associated hospitalizations in the United States,
1999–2000. Am J Obstet Gynecol. 2005;192:592–597.
55. Hill JB, Sheffield JS, McIntire DD, et al. Acute pyelonephritis in pregnancy. Obstet Gynecol.
2005;105:18–23.
56. Smaill F, Vazquez JC. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst
Rev. 2007;(2):CD000490.
57. Chaim W, Bashiri A, Bar-David J, et al. Prevalence and clinical significance of postpartum
endometritis and wound infection. Infect Dis Obstet Gynecol. 2000;8:77–82.
58. Smaill FM, Grivell RM. Antibiotic prophylaxis versus no prophylaxis for preventing infection after
cesarean section. Cochrane Database Syst Rev. 2014;(10):CD007482.
59. Mackeen AD, Packard RE, Ota E, et al. Antibiotic regimens for postpartum endometritis. Cochrane
Database Syst Rev. 2015;(2):CD001067.
60. Shipp TD, Zelop C, Cohen A, et al. Post-cesarean delivery fever and uterine rupture in a subsequent
trial of labor. Obstet Gynecol. 2003;101:136–139.
61. Verani JR, McGee L, Schrag SJ; Division of Bacterial Diseases, National Center for Immunization and
Respiratory Diseases, Centers for Disease Control and Prevention. Prevention of perinatal group B
streptococcal disease—revised guidelines from CDC, 2010. MMWR Recomm Rep. 2010;59(RR-10):1–
36.
62. Hamilton ST, van Zuylen W, Shand A, et al. Prevention of congenital cytomegalovirus complications
by maternal and neonatal treatments: a systematic review. Rev Med Virol. 2014;24:420–433.
63. Rac MW, Sheffield JS. Prevention and management of viral hepatitis in pregnancy. Obstet Gynecol
Clin North Am. 2014;41:573–592.
64. Wax DB, Beilin Y, Frolich M. Liver disease. In: Chestnut DH, Wong CA, Tsen LC, et al., eds.
Chestnut’s Obstetric Anesthesia: Principles and Practice. 5th ed. Philadelphia, PA: Elsevier;
2014:1068–1080.
65. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 86: viral hepatitis
in pregnancy. Obstet Gynecol. 2007;110:941–956.
66. Centers for Disease Control and Prevention. HIV surveillance report, vol. 25.
http://www.cdc.gov/hiv/library/reports/surveillance/2013/surveillance_Report_vol_25.html. Accessed
March 10, 2015.
67. De Cock KM, Fowler MG, Mercier E, et al. Prevention of mother-to-child HIV transmission in
resource-poor countries: translating research into policy and practice. JAMA. 2000;283:1175–1182.
68. Centers for Disease Control and Prevention. HIV among pregnant women, infants, and children.
http://www.cdc.gov/hiv/risk/gender/pregnantwomen/facts/index.html. Accessed March 10, 2015.
69. Siegfried N, van der Merwe L, Brocklehurst P, et al. Antiretrovirals for reducing the risk of mother-to-
child transmission of HIV infection. Cochrane Database Syst Rev. 2011;(7):CD003510.
70. King JT Jr, Perkal MF, Rosenthal RA, et al. Thirty-day postoperative mortality among individuals with
HIV infection receiving antiretroviral therapy and procedure-matched, uninfected comparators. JAMA
Surg. 2015;150:343–351. doi: 10.1001/jamasurg.2014.2257.
71. Michaels J, Sharer LR, Epstein LG. Human immunodeficiency virus type 1 (HIV-1) infection of the
nervous system: a review. Immunodefic Rev. 1988;1:71–104.
72. Spudich S, Gonzalez-Scarano F. HIV-1-related central nervous system disease: current issues in
pathogenesis, diagnosis, and treatment. Cold Spring Harb Perspect Med. 2012;2:a007120.
73. Miller RF, Huang L, Walzer PD. Pneumocystis pneumonia associated with human immunodeficiency
virus. Clin Chest Med. 2013;34:229–241.
74. Miller RF, Allen E, Copas A, et al. Improved survival for HIV infected patients with severe
Pneumocystis jirovecii pneumonia is independent of highly active antiretroviral therapy. Thorax.
2006;61:716–721.
75. Al Anazi AR. Gastrointestinal opportunistic infections in human immunodeficiency virus disease.
Saudi J Gastroenterol. 2009;15:95–99.
76. Choi SY, Kim I, Kim NJ, et al. Hematological manifestations of human immunodeficiency virus
infection and the effect of highly active antiretroviral therapy on cytopenia. Korean J Hematol.
2011;46:253–257.
77. Cheitlin M. Cardiovascular complications of HIV infection. In: Sande M, Volberding P, eds. The
Medical Management of AIDS. 5th ed. Philadelphia, PA: WB Saunders; 1999:275–284.
78. Kibirige D, Ssekitoleko R. Endocrine and metabolic abnormalities among HIV-infected patients: a
current review. Int J STD AIDS. 2013;24:603–611.
79. Rosenberg AZ, Naicker S, Winkler CA, et al. HIV-associated nephropathies: epidemiology, pathology,
mechanisms and treatment. Nat Rev Nephrol. 2015;11:150–160.
80. Hebl JR. The importance and implications of aseptic techniques during regional anesthesia. Reg
Anesth Pain Med. 2006;31:311–323.
81. American Society of Anesthesiologists Committee on Occupational Health Task Force on Infection
Control. Recommendations for infection control for the practice of anesthesiology (third edition).
https://www.asahq.org/~/media/sites/asahq/files/public/resources/asa committees/recommendations-
for-infection-control-for-the-practice-of-anesthesiology-%281%29.pdf?la=en. Accessed March 10,
2015.
82. Tom DJ, Gulevich SJ, Shapiro HM, et al. Epidural blood patch in the HIV-positive patient. Review of
clinical experience. San Diego HIV Neurobehavioral Research Center. Anesthesiology. 1992;76:943–
947.
83. Evron S, Glezerman M, Harow E, et al. Human immunodeficiency virus: anesthetic and obstetric
considerations. Anesth Analg. 2004;98:503–511.
84. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission.
Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal
health and interventions to reduce perinatal HIV transmission in the United States.
 http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf. Accessed March 10, 2015.
85. Roberts CM, Pfister JR, Spear SJ. Increasing proportion of herpes simplex virus type 1 as a cause of
genital herpes infection in college students. Sex Transm Dis. 2003;30:797–800.
86. Brown ZA, Vontver LA, Benedetti J, et al. Effects on infants of a first episode of genital herpes during
pregnancy. N Engl J Med. 1987;317:1246–1251.
87. Bader AM, Camann WR, Datta S. Anesthesia for cesarean delivery in patients with herpes simplex
virus type-2 infections. Reg Anesth. 1990;15:261–263.
88. Brown ZA, Wald A, Morrow RA, et al. Effect of serologic status and cesarean delivery on
transmission rates of herpes simplex virus from mother to infant. JAMA. 2003;289:203–209.
89. Hollier LM, Wendel GD. Third trimester antiviral prophylaxis for preventing maternal genital herpes
simplex virus (HSV) recurrences and neonatal infection. Cochrane Database Syst Rev. 2008;
(1):CD004946.
90. Davies PW, Vallejo MC, Shannon KT, et al. Oral herpes simplex reactivation after intrathecal
morphine: a prospective randomized trial in an obstetric population. Anesth Analg. 2005;100:1472–
1476.
91. Boyle RK. Herpes simplex labialis after epidural or parenteral morphine: a randomized prospective
trial in an Australian obstetric population. Anaesth Intensive Care. 1995;23:433–437.
92. Bauchat JR. Focused review: neuraxial morphine and oral herpes reactivation in the obstetric
population. Anesth Analg. 2010;111:1238–1241.
93. Shapiro ED. Clinical practice. Lyme disease. N Engl J Med. 2014;370:1724–1731.
94. Gellin BG, Broome CV, Bibb WF, et al. The epidemiology of listeriosis in the United States—1986.
Listeriosis Study Group. Am J Epidemiol. 1991;133:392–401.
95. Ramaswamy V, Cresence VM, Rejitha JS, et al. Listeria—review of epidemiology and pathogenesis. J
Microbiol Immunol Infect. 2007;40:4–13.
96. Allerberger F, Huhulescu S. Pregnancy related listeriosis: treatment and control. Expert Rev Anti Infect
Ther. 2015;13:395–403.
97. Crane J, Mundle W, Boucoiran I, et al. Parvovirus B19 infection in pregnancy. J Obstet Gynaecol Can.
2014;36:1107–1116.
98. Qin J, Yang T, Xiao S, et al. Reported estimates of adverse pregnancy outcomes among women with
and without syphilis: a systematic review and meta-analysis. PLoS One. 2014;9:e102203.
99. Hook EW III, Marra CM. Acquired syphilis in adults. N Engl J Med. 1992;326:1060–1069.
100. Nanda D, Feldman J, Delke I, et al. Syphilis among parturients at an inner city hospital: association
with cocaine use and implications for congenital syphilis rates. N Y State J Med. 1990;90:488–490.
101. Mathad JS, Gupta A. Tuberculosis in pregnant and postpartum women: epidemiology, management,
and research gaps. Clin Infect Dis. 2012;55:1532–1549.
102. Laibl VR, Sheffield JS. Tuberculosis in pregnancy. Clin Perinatol. 2005;32:739–747.
103. Loto OM, Awowole I. Tuberculosis in pregnancy: a review. J Preg. 2012;2012:379271.
104. Jana N, Vasishta K, Saha SC, et al. Obstetrical outcomes among women with extrapulmonary
tuberculosis. N Engl J Med. 1999;341:645–649.
105. Harger JH, Ernest JM, Thurnau GR, et al. Risk factors and outcome of varicella-zoster virus
pneumonia in pregnant women. J Infect Dis. 2002;185:422–427.
106. Brown NW, Parsons AP, Kam PC. Anaesthetic considerations in a parturient with varicella presenting
for caesarean section. Anaesthesia. 2003;58:1092–1095.
107. Cono J, Cragan JD, Jamieson DJ, et al. Prophylaxis and treatment of pregnant women for emerging
infections and bioterrorism emergencies. Emerg Infect Dis. 2006;12:1631–1637.
108. Maharaj D. Puerperal pyrexia: a review. Part I. Obstet Gynecol Surv. 2007;62:393–399.
109. Mabie WC, Barton JR, Sibai B. Septic shock in pregnancy. Obstet Gynecol. 1997;90:553–561.
110. Timezguid N, Das V, Hamdi A, et al. Maternal sepsis during pregnancy or the postpartum period
requiring intensive care admission. Int J Obstet Anesth. 2012;21:51–55.
111. Martin SR, Foley MR. Intensive care in obstetrics: an evidence-based review. Am J Obstet Gynecol.
2006;195:673–689.
112. Nduka OO, Parrillo JE. The pathophysiology of septic shock. Crit Care Clin. 2009;25:677–702.
113. American College of Obstetricians and Gynecologists. ACOG Technical Bulletin: septic shock.
Number 204. Int J Gynaecol Obstet. 1995;50:71–79.
114. Cantwell R, Clutton-Brock T, Cooper G, et al. Saving Mothers’ Lives: reviewing maternal deaths to
make motherhood safer: 2006-2008. The Eighth Report of the Confidential Enquiries into Maternal
Deaths in the United Kingdom. BJOG. 2011;118(suppl 1):1–203.
115. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for
management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41:580–637.
116. Lucas DN, Robinson PN, Nel MR. Sepsis in obstetrics and the role of the anaesthetist. Int J Obstet
Anesth. 2012;21:56–67.
117. Kohlschutter B, Baur H, Roth F. Suxamethonium-induced hyperkalaemia in patients with severe intra-
abdominal infections. Br J Anaesth. 1976;48:557–562.
118. Carp H, Bailey S. The association between meningitis and dural puncture in bacteremic rats.
Anesthesiology. 1992;76:739–742.
119. Cook TM, Counsell D, Wildsmith JA. Major complications of central neuraxial block: report on the
Third National Audit Project of the Royal College of Anaesthetists. Br J Anaesth. 2009;102:179–190.
120. D’Angelo R, Smiley RM, Riley ET, et al. Serious complications related to obstetric anesthesia: the
serious complication repository project of the Society for Obstetric Anesthesia and Perinatology.
Anesthesiology. 2014;120:1505–1512.
121. Schroeder TH, Krueger WA, Neeser E, et al. Spinal epidural abscess—a rare complication after
epidural analgesia for labour and delivery. Br J Anaesth. 2004;92:896–898.
122. American Society of Anesthesiologists Task Force on Infectious Complications Associated with
Neuraxial Techniques. Practice advisory for the prevention, diagnosis, and management of infectious
complications associated with neuraxial techniques: a report by the American Society of
Anesthesiologists Task Force on Infectious Complications Associated with Neuraxial Techniques.
Anesthesiology. 2010;112:530–545.
 Non-neuraxial Analgesic Techniques
Wint Mon, Roshan Fernando, and Geraldine O’Sullivan

I. Nonpharmacologic methods of pain relief in labor
A. Antenatal health education
B. Support during labor (birth partners and doulas)
C. Relaxation techniques—music and breathing exercises
D. Complementary therapies
E. Hydrotherapy
F. Transcutaneous electrical nerve stimulation
G. Sterile water injection
II. Non-neuraxial pharmacologic methods of pain relief
A. Inhalation techniques
B. Non-opioid analgesia and sedatives
C. Opioid analgesia

KEYPOINTS
1. Most women choose pain relief methods based on their expectations of
labor pain.
2. Pregnant women should have access to results from the best available
research about the effectiveness and possible side effects of both
pharmacologic and nonpharmacologic pain relief measures.
3. A calm, soothing environment should be provided to improve a woman’s
 laboring experience.
4. Lumbosacral massage has been shown to reduce back pain during labor.
5. Hypnobirthing has become a popular pain relief method in recent years,
although there is no current evidence to support its use as labor analgesia.
6. Acupuncture has been shown to reduce pain intensity during labor and
delivery.
7. When using inhalation analgesia, it is important that a woman remains
conscious to avoid regurgitation and aspiration of stomach contents.
8. Sedative anxiolytics are not recommended for use during labor because
they can readily cross the placenta and cause significant side effects for
both the mother and the neonate.
9. Systemic opioids can be given as nurse-controlled analgesia in the form
of intermittent intravenous or intramuscular boluses or as intravenous
patient-controlled analgesia (PCA).
10. Due to its fast onset and offset, remifentanil is suitable to treat the
cyclical pain of uterine contractions. However, continuous pulse oximetry
monitoring and one-to-one nursing care are essential when remifentanil is
in use.

MANY WOMEN EXPERIENCE SEVERE PAIN DURING LABOR. There are many forms
of pain relief available today, and these can be subdivided into neuraxial and
non-neuraxial analgesic techniques. Most women employ a number of ways to
cope with labor pain. Neuraxial analgesia techniques provide the most effective
pain relief and have the least systemic effects on the mother and the baby.
However, some women prefer to use less invasive techniques for pain relief.
Many women choose labor pain relief methods based on their expectations
of labor and labor pain.1 A systematic review by Hodnett2 specifically addressed
the issue of women’s views on the experience of childbirth in relation to
intrapartum analgesia. Four factors were found to be the most important for
women’s experiences of childbirth. These were (1) personal expectations, (2) the
amount of support from caregivers, (3) the quality of the caregiver–patient
relationship, and (4) the involvement in decision making. Therefore, it is
essential that maternity care providers have a discussion with women about their
expectation of birth and labor pain and provide them with evidence-based
information about all pain relief methods. In this chapter, we describe the
nonpharmacologic methods and the non-neuraxial pharmacologic methods of
pain relief in labor and current evidence surrounding their use.
I. Nonpharmacologic methods of pain relief in labor
A. Antenatal health education
1. Health education is an integral part of antenatal care. Delivery
of health education ranges from online resources to
classroom-style workshops designed to inform pregnant
women and their partners about labor, delivery, and care of
the newborn. A systematic survey of peer-reviewed studies
published between 1996 and 2006 found that women
preferred a small group learning environment where they
could talk to each other as well as the educator and relate
information to their individual circumstances.3
2. Antenatal classes cover aspects of labor pain, coping
strategies, and pain relief options available for pregnant
women. The first U.S. survey of women’s childbearing
experiences published in 2004 by the Maternity Center
Association suggested that women should have access to the
results of the best available research about the effectiveness
and possible side effects of both pharmacologic and
nonpharmacologic pain relief measures.4 In a randomized trial
carried out by Maimburg et al.,5 women who received health
education in the antenatal period were less likely to request
epidural analgesia in labor. However, they were still likely to
request some form of parenteral analgesia.
B. Support during labor (birth partners and doulas)
1. Most women choose to have a birthing partner during labor. A
birthing partner can be any close relative or friend. Some
women employ doulas for support during labor and delivery.
Doula originates from the ancient Greek word meaning
“female servant” and is a nonmedical person who supports a
woman during labor and after childbirth. Birth partners and
 doulas can not only give emotional support by listening and
giving reassurance to laboring women but also provide
physical support such as massage and help with positioning.
2. A Cochrane review by Hodnett et al.6 assessed the effects of
continuous, one-to-one intrapartum support compared to usual
care. Twenty-two trials involving 15,288 women were
included in the analysis. Women allocated to continuous
support were more likely to have a spontaneous vaginal birth
and were less likely to have intrapartum analgesia or report
dissatisfaction. Moreover, their labors were shorter and they
were less likely to have a cesarean delivery (CD) or an
instrumental vaginal birth. Women who had continuous
support were also less likely to have neuraxial analgesia or a
baby with a low 5-minute Apgar score.
C. Relaxation techniques—music and breathing exercises
1. Music
An increase in the use of mobile devices allows women to
listen to their music of choice in delivery rooms. Hosseini et
al.7 investigated the effect of music therapy on labor pain and
progress in primigravid parturients. The study showed that
music caused a statistically significant decrease in pain
scores. Another randomized trial also demonstrated that music
therapy during labor decreased postpartum anxiety and pain
and increased the satisfaction with childbirth experience.8

CLINICAL PEARL The provision of a calm, soothing

environment improves a woman’s experience of her labor, and
therefore, playing music of a woman’s choice during labor should
be encouraged.

2. Breathing exercises
Breathing exercises are widely discussed in antenatal classes.
Deep breathing, “belly” breathing, and patterned breathing are
 the examples of popular breathing techniques used during
labor and delivery. One controlled trial of breathing and
relaxation techniques was included in a systematic review of
complementary and alternative therapies for pain management
in labor.9 Women were randomly assigned to an experimental
group, who received “respiratory autogenic training”
(progressive muscle relaxation and focused slow breathing),
or a control group, who received a traditional
“psychoprophylaxis.” There was no difference between the
groups in women’s experience of pain, instrumental delivery
rate, augmentation with oxytocin, and neonatal Apgar scores.

CLINICAL PEARL Although there is a lack of evidence

currently to support respiratory autogenic training for labor pain,
women should not be discouraged from using breathing and
relaxation techniques in labor.

D. Complementary therapies
The use of complementary medicine has become popular with
many women, who are keen to avoid pharmacologic or invasive
methods of pain relief in labor. The Complementary Medicine
Field of the Cochrane Collaboration gives the definition of
complementary medicine as “practices and ideas which are
outside the domain of conventional medicine in several
countries.”10 The majority of the complementary therapies are
delivered by trained therapists, who may not be available in all
obstetric hospitals.
1. Massage and reflexology
a. Massage is commonly used to relax tense soft tissues and
calm the individual. In labor, a lumbosacral area massage
may be used for back pain and a light abdominal massage
may help during contraction. Many theories have been
proposed to explain the mechanisms by which massage
 relieves pain in labor. One of them is the gate control
theory of pain (see Fig. 9.1).11 It has also been suggested
that massage decreases the release of cortisol and
norepinephrine levels12 and increases the serotonin
level.13 A systematic review by Smith et al.14 included six
studies evaluating the effects of massage on labor pain. A
reduction in pain score was reported in the massage
therapy group when compared to the group who received
usual care during the first stage of labor (standardized
mean difference [SMD] −0.82; 95% confidence interval
[CI], −1.17 to −0.47; four trials; 225 women).

b. Reflexology involves the act of applying pressure to the

“reflex” points on the feet and palms. Reflexology has not
only been used for pain relief but also for treating nausea,
vomiting, and fatigue in pregnancy. There has been
relatively little research on the use of reflexology for labor
pain. Dolatian et al.15 carried out a randomized controlled
trial where parturients were randomly enrolled into three
different groups. The first group received 40 minutes of
reflexology at the beginning of the active phase. The
second group received emotional support for the same
duration at the same stage, and the third group received
routine standard care. Pain intensity was found to be
significantly lower in the reflexology group compared to
the other two groups.15
CLINICAL PEARL Current evidence suggests that massage
may be used as a pain relief measure in labor. More studies need to
be done to evaluate the efficacy of reflexology in labor.

2. Hypnosis
a. Hypnosis is the induction of a deeply relaxed state in
which a person loses the power of voluntary action and is
highly responsive to suggestions. Once in this state,
sometimes called a hypnotic trance, the patients are given
therapeutic suggestions to encourage changes in behavior
or relief of symptoms. “Hypnobirthing” has become a
popular trend in recent years. Hypnobirthing programs
teach women self-hypnosis, relaxation, and breathing
techniques to help manage the stress and pain associated
with labor. The anterior cingulate gyrus has been
demonstrated on positron emission tomography to be one
of the sites affected by the hypnotic modulation of pain.16
b. A Cochrane review of hypnosis included seven trials
involving a total of 1,213 women. Six of the seven trials
evaluated antenatal hypnotherapy. Only one trial provided
hypnotherapy during labor. There were no significant
differences between the hypnosis group and the control
group for the primary outcomes: use of pharmacologic
pain relief (average risk ratio [RR] 0.63; 95% CI, 0.39 to
1.01; six studies; 1,032 women), spontaneous vaginal
birth (average RR 1.35; 95% CI, 0.93 to 1.96; four
studies; 472 women), or satisfaction with pain relief (RR
1.06; 95% CI, 0.94 to 1.20; one study; 264 women).17 A
large randomized controlled, single-blinded trial (1,222
healthy nulliparous women), carried out in Denmark, also
did not find any differences in the use of epidural
analgesia or pain experience across three study groups: a
self-hypnosis group, a relaxation group, and a usual care
 group.18

CLINICAL PEARL Based on the current evidence, hypnosis

cannot be recommended as an effective pain relief method in labor.

3. Aromatherapy
a. Aromatherapy is a complementary therapy using essential
oils obtained from distillation of plant materials such as
roots, leaves, bark, seeds, and flowers. Essential oils can
be used through massage and aromatherapy diffusers or
vaporizers. The two commonly used oils in labor are
lavender and frankincense. Essential oils are thought to
increase the body’s own sedative, stimulant, and relaxing
substances.
b. A systematic review performed by Smith et al.19 included
two trials (535 women) evaluating the use of
aromatherapy in labor. The trials found no difference
between the aromatherapy and control groups for the
primary outcomes of pain intensity, assisted vaginal
delivery, CD, and admission to neonatal intensive care
unit.

CLINICAL PEARL There is currently no strong evidence to

support the effectiveness of aromatherapy in labor pain
management.

4. Acupuncture and acupressure

a. Acupuncture involves the insertion of various types of
needles into the skin and subcutaneous tissues at specific
points known as acupoints to correct the imbalance of
energy in the body. It has been used for more than 2,000
years in China. For acupressure, the therapists use their
hands and fingers to activate the same points as applied
 by acupuncture (see Fig. 9.2). Several theories have been
presented to explain how acupuncture and acupressure
may work. It has been proposed that acupuncture may
modify the perception of pain.20 Other theories suggest
that acupuncture stimulates the release of endorphins and
opioids.21,22 Intrapartum acupuncture is usually provided
by professional acupuncturists. In countries such as
Germany and Denmark, it is widely performed by
midwives.23

b. Chen et al.24 reviewed the studies on the use of

acupuncture in labor over a 10-year period (2002 to 2012)
in mainland China. There were 20 randomized controlled
trials and 2 nonrandomized controlled trials. All studies
found that acupuncture significantly relieved the pain
during delivery.24 A Cochrane review by Smith et al.25
included 13 trials involving 1,986 women for their meta-
analysis evaluating acupuncture or acupressure for the
labor pain management. Nine trials reported on
acupuncture and four trials studied acupressure. Reduced
pain intensity was found in the acupuncture group when
compared with the group which received no intervention
 (SMD −1.00; 95% CI, −1.33 to −0.67; one trial; 163
women). Another trial reported greater satisfaction with
pain relief compared to the placebo control group (RR
2.38; 95% CI, 1.78 to 3.19; 150 women). A reduction in
the use of pharmacologic analgesia was found in one trial,
which compared acupuncture with placebo (RR 0.72;
95% CI, 0.58 to 0.88; 136 women). Pain intensity was
reduced in the acupressure group when compared with the
placebo control group (SMD −0.55; 95% CI, −0.92 to
−0.19; one trial; 120 women) and the combined control
group (placebo and no treatment) (SMD −0.42; 95% CI,
−0.65 to −0.18; two trials; 322 women).25

CLINICAL PEARL Current evidence suggests that acupuncture

and acupressure may be useful for the management of labor pain.

E. Hydrotherapy
1. Hydrotherapy, in the form of immersion in the birthing pool
or bath, is used worldwide to promote relaxation and to
reduce pain and anxiety in laboring women. For women
without any antenatal or intrapartum complications,
hydrotherapy is deemed to be safe.26 Immersion is associated
with decreases in neuroendocrine responses in healthy adults.
At a thermoneutral temperature of 34.5°C, during rest and
exercise, immersion has been associated with decreases in
levels of plasma norepinephrine27 and epinephrine.28 The
National Institute for Health and Care Excellence29 guideline,
published in 2007, recommended that the temperature of the
woman and the water should be monitored every hour to
ensure that the woman is comfortable and not febrile. The
temperature of the water should not be above 37.5°C.
2. Nutter et al.30 published an integrated analysis of peer-
reviewed literature on water birth in 2014. Thirty-eight
 studies, including 2 randomized controlled trials and 36
observational studies, were reviewed. Their aggregate results
found that water birth was associated with high levels of
maternal satisfaction with pain relief. It was also linked to
decreased incidence of episiotomy and severe perineal tears.
Neonatal mortality rates were found to be low and similar in
women who used water immersion during labor and those
who did not use water immersion. Another review included
12 trials (3,243 women).31 Results for the first stage of labor
showed that there was a significant reduction in the epidural,
spinal, and paracervical analgesia use among the women
allocated to water immersion compared to the controls (478 of
1,254 vs. 529 of 1,245; RR 0.90; 95% CI, 0.82 to 0.99; six
trials). There were no differences in the rates of assisted
vaginal deliveries (RR 0.86; 95% CI, 0.71 to 1.05; seven
trials), cesarean deliveries (RR 1.21; 95% CI, 0.87 to 1.68;
eight trials), perineal trauma, or maternal infection. There
were also no differences for Apgar scores less than seven at 5
minutes (RR 1.58; 95% CI, 0.63 to 3.93; five trials), neonatal
unit admissions (RR 1.06; 95% CI, 0.71 to 1.57; three trials),
or neonatal infection rates (RR 2.00; 95% CI, 0.50 to 7.94;
five trials). However, there is considerable heterogeneity for
some outcomes in this review. Authors recommended further
research to be done.
F. Transcutaneous electrical nerve stimulation
1. Transcutaneous electrical nerve stimulation (TENS) is a
technique whereby low-voltage pulsatile electrical impulses,
varying in frequency and intensity, are administered through
electrodes. For pain in the first stage of labor, electrodes are
usually placed 2 cm over the T10–L1 dermatomes on either
side of the spinous processes. A second set of electrodes is
placed over the S2–S4 dermatomal areas for the pain relief in
the second stage. The mechanism of action of TENS is based
on the gate control theory of pain (see Fig. 9.1).11 It has also
 been reported that there are marked increases in β-endorphin
and met-enkephalin with low-frequency TENS.32
2. A review of 14 studies involving 1,256 women found that
there was little difference in satisfaction with pain relief or in
pain ratings between TENS and control groups. On the other
hand, women receiving TENS to acupuncture points were less
likely to report severe pain (RR 0.41; 95% CI, 0.32 to 0.55).33
In a Cochrane review involving 25 studies, Dowswell et al.34
reported that there was little difference in pain ratings
between the TENS and control groups. The majority of
women, who used TENS, reported that they would use it
again in a future labor.33

CLINICAL PEARL There is no current evidence that TENS has

any beneficial effect in treating labor pain.

G. Sterile water injection

1. A sterile water injection is a simple technique to treat back
pain in labor. It involves an intradermal injection of sterile
water in the lumbosacral area (see Fig. 9.3). A small bleb is
formed by injecting approximately 0.1 mL of sterile water.
The optimal number of injection(s) is unknown. The mode of
action is unclear. It is probably a form of counterirritation,
invoking the gate control theory of pain.11 It has also been
proposed that it may exert its effect through “physiologic
distraction.”35
 2. Derry et al.35 performed a systematic review evaluating seven
randomized, double-blind, controlled studies on the use of
intracutaneous or subcutaneous injection of sterile water for
labor pain. All studies reported a greater reduction in pain in
the sterile water injection group. However, due to the failure
to demonstrate a normal distribution for pain intensity or
relief and the use of different pain measurement scales, a
meta-analysis of available studies was deemed inappropriate.
One study found that significantly more women had “4/10 cm
or more reduction” in pain with sterile water (50% to 60%)
than with the placebo (20% to 25%). There was no significant
difference between sterile water and saline for rates of CD
(RR 0.58; 95% CI, 0.33 to 1.02), instrumental delivery (RR
1.31; 95% CI, 0.79 to 2.18), rescue analgesia (RR 0.86; 95%
CI, 0.44 to 1.69), timing of delivery, or Apgar scores.35

CLINICAL PEARL Sterile water injection should not be

recommended to women in active labor.

II. Non-neuraxial pharmacologic methods of pain relief

A. Inhalation techniques
Inhalational analgesia is provided by intermittent inhalation of
subanesthetic concentrations of volatile agents. The mother
should remain conscious with preservation of her laryngeal
reflexes, thereby avoiding regurgitation and aspiration of stomach
contents. The technique first achieved fame and later gained
widespread acceptance when John Snow administered chloroform
to Queen Victoria for the birth of her eighth and ninth children in
1853 and 1857. A variety of anesthetic agents have been used
over the years. Nitrous oxide has remained the most popular
inhalation agent for labor pain relief. Other volatile agents, such
as sevoflurane, have also been evaluated for the use in labor.
Inhalational agents can readily cross the placenta and the
concentration in fetal blood soon approaches that of the mother.
However, these agents are eliminated almost entirely through the
mother’s lungs. Environmental pollution from unscavenged gases
may be significant. The occupational risk of health care staff, who
have regular exposure to subanesthetic concentration of volatile
gases, is unknown.
1. Nitrous oxide
a. Nitrous oxide analgesia is administered as 50% nitrous
oxide in oxygen using a blender device or via a premixed
single cylinder. The blender device or cylinder is usually
attached to a demand valve, which in turn, is connected to
a face mask or mouthpiece. The demand valve only opens
when the user applies negative pressure by inhaling
through a mouthpiece or face mask (see Table 9.1). There
is no flow from the system when the device is not in use.
The incidence of its use for labor pain relief is 1% (or
less) in the United States, 43% in Canada, and 62% in the
United Kingdom.36 Obstetric anesthesiologists in the USA
have expressed concerns about the effect of nitrous oxide
on fetal neurodevelopment and its effects on the
environment.36 Nitrous oxide acts on several types of
receptors.37 It has an inhibitory action at N-methyl-D-
 aspartate (NMDA) glutamate receptors and has
stimulatory activity at dopaminergic, α1-and α2-
adrenergic, and opioid receptors. Common maternal side
effects include nausea, dizziness, paresthesias, and dry
mouth. It appears to be safe for the fetus.

b. Likis et al.38 published a systematic review evaluating the

use of nitrous oxide for the management of labor pain.
Although the authors identified 58 publications, only 2 of
them were of good quality. Nitrous oxide was found to be
less effective at relieving labor pain than epidural
analgesia. Many mothers reported unpleasant side effects
such as nausea, vomiting, dizziness, and drowsiness.
Apgar scores of the babies, who were born to the mothers
who used nitrous oxide, were not significantly different
from those whose mothers used other forms of labor
analgesia or no analgesia. Another review looked into the
use of inhaled analgesia for pain management in labor and
included 26 studies randomizing 2,959 women.39 Flurane
derivatives were found to offer superior pain relief when
compared to nitrous oxide in the first stage of labor as
measured by a lower pain intensity score. The incidence
of nausea was found to be higher in the nitrous oxide
group when compared with the flurane derivatives group
(RR 6.60; 95% CI, 1.85 to 23.52; two studies; 98
 women). Placebo or no treatment was found to offer less
pain relief compared to nitrous oxide (average RR 0.06;
95% CI, 0.01 to 0.34; two studies; 310 women). However,
the nitrous oxide group had more side effects such as
nausea (RR 43.10; 95% CI, 2.63 to 706.74; one study;
509 women), vomiting (RR 9.05; 95% CI, 1.18 to 69.32;
two studies; 619 women), dizziness (RR 113.98; 95% CI,
7.09 to 1833.69; one study; 509 women), and drowsiness
(RR 77.59; 95% CI, 4.80 to 1254.96; one study; 509
women) when compared with placebo or no treatment.

CLINICAL PEARL Current evidence suggests that nitrous oxide

is an effective form of pain relief when compared to placebo,
although many women will suffer unpleasant side effects. The
potential for an adverse impact of nitrous oxide on fetal
neurodevelopment, and on the environment, requires further
research.

2. Volatile anesthetic agents

Volatile anesthetic agents have been studied for labor
analgesia. They are more effective in reducing pain intensity
in labor when compared to nitrous oxide.39 However, there
has not been widespread use of these agents. Their routine use
is limited by the need for the anesthesiologist’s presence,
concerns for environmental pollution, potential for maternal
amnesia, and the loss of protective airway reflexes. All
volatile agents also cause dose-dependent uterine smooth
muscle relaxation.
a. Sevoflurane has a low blood gas partition coefficient
(0.65), allowing rapid onset and offset of action. It also
has a less unpleasant odor when compared with other
volatile anesthetic agents. Yeo et al.40 carried out an open-
labeled escalating-dose study involving 22 laboring
 women. Sevoflurane was self-administered using an
Oxford Miniature Vaporizer (OMV). The inspired
concentration was increased by 0.2% after each
contraction and decreased when sedation occurred. Pain
relief scores did not increase significantly above inspired
concentrations of 0.8% while sedation continued to
increase, with excessive sedation occurring at 1.2%
sevoflurane. The authors concluded that the optimal
inspired sevoflurane concentration for labor was 0.8%.
The same research group published a second study in
which they compared self-administered sevoflurane 0.8%
with nitrous oxide in 32 laboring women.41 Each
parturient underwent two open-label, three-part sequences
in oxygen (50:50 mix) in random order (nitrous
oxide/oxygen-sevoflurane-nitrous oxide/oxygen or
sevoflurane-nitrous oxide/oxygen-sevoflurane). Pain
relief scores were significantly higher for sevoflurane
(median 67, interquartile range [IQR] 55 to 74, total range
[TR] 33 to 100 mm) than for nitrous oxide/oxygen
(median 51, IQR 40 to 69.5, TR 13 to 100 mm, P < .037).
Nausea and vomiting were more common in the nitrous
oxide/oxygen group (relative risk 2.7; 95% CI, 1.3 to 5.7;
P = .004). No other adverse effects were observed in the
mothers or babies.
b. Enflurane. McGuinness and Rosen42 compared the
administration of 1% enflurane in air to nitrous oxide
during the first stage of labor. Lower pain scores and a
higher level of drowsiness were observed in the enflurane
group. There has not been any recent study evaluating the
effect of enflurane for labor analgesia.
c. Isoflurane. The use of 0.25% isoflurane and 50% nitrous
oxide mixture was studied in 221 laboring women. It was
found that nitrous oxide alone did not provide adequate
analgesia. Although none of the mothers became sedated,
 the requirement for neonatal resuscitation was higher in
mothers who had received systemic analgesia within 5
hours of birth in addition to the inhaled mixture.43
d. Desflurane. When the inhalation of 1% to 4.5% of
desflurane was compared with 30% to 60% of nitrous
oxide in oxygen in 80 healthy parturients, analgesia
scores were similar in both groups. However, the
incidence of amnesia was greater in the desflurane group
(23% vs. 0%; P < .05).44

CLINICAL PEARL Sevoflurane may be the best volatile agent

for inhalation analgesia because it has fast onset and offset times
and is also less irritating to the airway. However, like other volatile
agents, its use is limited by the requirement for specialized
equipment and trained personnel as well as its potential for causing
uterine smooth muscle relaxation.

B. Non-opioid analgesia and sedatives

Non-opioid analgesia and sedatives have been used in early labor
for mild to moderate pain. Due to maternal sedation and neonatal
depression, sedatives are used very infrequently.
1. Acetaminophen
a. Acetaminophen is a first-line treatment for mild pain and
pyrexia. It also plays an important role in multimodal
analgesia. Acetaminophen is a weak inhibitor of both
cyclooxygenase (COX)-1 and COX-2 receptors. Oral and
rectal administration can produce analgesic effects within
40 minutes, with a maximal effect at 1 hour. However,
bioavailability ranges from 63% to 89% for the oral form
and 24% to 98% for rectal administration. The
intravenous acetaminophen administration improves the
bioavailability and speed of onset.
b. A triple-blind, randomized, placebo-controlled trial,
 involving 120 low-risk laboring women, compared the
effect of 1,000 mg intravenous acetaminophen with
intravenous sterile water.45 When compared to the control
group, the acetaminophen group was associated with
lower visual analogue scale (VAS) score at 15 and 30
minutes after the start of medication. There was also a
lower need for rescue medication (8 of 57 [14%] vs. 49 of
59 [83.1%], P < .001) at 60 minutes. There were no
differences in the incidence of intrapartum fetal distress or
neonatal Apgar scores between two groups. Another study
involving 102 women compared the efficacy of
acetaminophen to that of meperidine and reported that the
reduction in pain was significantly greater in the
meperidine group only at 15 minutes. However, none of
the women in the acetaminophen group had adverse
effects, as compared with 64% of the meperidine group.46
In summary, acetaminophen is a safe analgesic drug to be
used for labor pain. However, more studies need to be
done to compare it with other forms of labor analgesia.
2. Ketamine
a. Ketamine is a phencyclidine derivative and acts primarily
by noncompetitive antagonism at the NMDA receptors. It
can be given either intravenously or intramuscularly.
When given intravenously, it has an onset of action within
30 seconds and duration of action between 5 and 10
minutes. If an intramuscular route is used, it has an onset
within 2 to 8 minutes with duration of action of 10 to 20
minutes. It is metabolized in the liver, and active
metabolites are excreted in the urine. Its use is limited by
its adverse psychological effects. It can also cause an
increase in heart rate and blood pressure. Therefore, it
should be avoided in parturients with preeclampsia or
hypertension.
b. There have not been many studies of ketamine for labor
 analgesia. Joel et al.47 performed a double-blind,
randomized, placebo-controlled trial, which compared
low-dose intravenous ketamine infusion with a normal
saline control infusion for labor pain. The study showed
that a low-dose ketamine infusion (loading dose of 0.2 mg
per kg delivered over 30 minutes, followed by an infusion
at 0.2 mg/kg/h) provided acceptable analgesia during
labor. Although there was no significant clinical change in
the maternal hemodynamics and fetal heart rate, 48.5% of
women had transient light-headedness in the ketamine
group. All the neonates in both groups were successfully
breastfed. The umbilical cord blood pH was between 7.1
and 7.2. Overall maternal satisfaction was found to be
significantly higher in the intervention group.47 There is a
need for more studies to be done to compare the efficacy
of ketamine with other conventional methods of pain
relief.
3. Sedatives
Sedative agents, such as benzodiazepines, phenothiazines, and
barbiturates, have been used in labor as adjuncts for pain
relief and as anxiolytics. Most of these agents can readily
cross the placenta and cause significant side effects for both
the mother and the neonate. Their use is generally not
recommended.
a. Benzodiazepines, such as diazepam, lorazepam, and
midazolam, have been used in labor as adjuncts for
analgesia.
(1) Benzodiazepines act by binding to a specific receptor
site on γ-aminobutyric acid (GABA) receptors,
facilitating their transmission. Midazolam has the
fastest elimination half-life, followed by lorazepam
and then diazepam (1 to 4 hours, 10 to 20 hours, and
20 to 45 hours, respectively). They cross the placenta
easily. They are associated with significant side
 effects for both the mother and the baby, such as
maternal and neonatal respiratory depression and
neonatal hypotonicity and impaired thermoregulation.
(2) McAuley et al.48 randomized 50 primigravid mothers
into a lorazepam (2 mg) group or placebo group.
Meperidine 100 mg was given as required. Analgesia
was significantly better in the lorazepam group.
However, there was a higher incidence of respiratory
depression in the neonates born to the mothers who
received lorazepam. A higher incidence of amnesia
was also observed in the mothers in the lorazepam
group. Evidence for the use of benzodiazepines is
limited. It is generally not advisable to use them as
adjuncts for pain relief in labor, but they can be
useful for women who have a severe panic attack
during labor.
b. Phenothiazines (e.g., promethazine and chlorpromazine)
have been used in the past for labor pain. They are
dopamine antagonists with sedative, antiemetic, and
antipsychotic properties. They can readily cross the
placenta. They have many unwanted side effects, such as
mild respiratory depression, hypotension, and
extrapyramidal movements in the mother and decreased
heart rate variability in the fetus.
c. Barbiturates are anesthetic agents that act mainly on
GABA receptors to cause sedation. They have been used
in early labor to reduce anxiety. They can readily cross the
placenta and cause neonatal depression.

CLINICAL PEARL Acetaminophen and ketamine have not been

adequately evaluated for labor analgesia. Sedatives are to be
avoided unless specifically indicated.
C. Opioid analgesia
Systemic opioids are the most widely used form of labor
analgesia worldwide. Even in the United States, where epidural
analgesia is widely available, opioids are a common form of
analgesia used in the obstetric population.49 They act on the
opioid receptors (μ-opioid peptide [MOP] receptor, κ-opioid
peptide [KOP] receptor, δ-opioid peptide [DOP] receptor, and
nociceptin/orphanin FQ peptide [NOP] receptor) to exert their
analgesic effects. Their main advantages are ease of
administration, low cost, and the lack of need for specialized
equipment and personnel. On the other hand, their major
disadvantages include failure to provide adequate analgesia for
labor pain and side effects, such as itching, nausea, vomiting, and
sedation for the mother and rapid placental transfer to the fetus.
Neonatal side effects include respiratory depression and
neurobehavioral changes. Systemic opioids can be given as nurse-
controlled analgesia in the form of intermittent intravenous or
intramuscular boluses or as intravenous patient-controlled
analgesia (PCA).
1. Nurse-controlled systemic opioid administration.
Intravenous and intramuscular routes are the most commonly
used methods for opioid administration during labor. An
intramuscular route has the advantage of easy administration;
however, it can be painful, and there is variable drug
absorption. The onset and duration depend on the site of
injection and local blood flow. On the other hand, an
intravenous administration of opioid has the advantages of
faster onset and the ability to titrate to effect. Intravenous
injections of opioids, however, need the presence of a
physician in many obstetric units.
2. Patient-controlled analgesia. The use of intravenous PCA
has increased in recent years for labor analgesia. The smaller
dosing and more frequent administration of opioid analgesia
provide a more stable plasma drug concentration and a more
 reliable analgesic effect when compared to nurse-controlled
intermittent boluses.50 However, it can be difficult to time the
peak effect of opioid with uterine contractions, and it may
become less effective as labor progresses.
3. Opioid analgesics
a. Meperidine
(1) Meperidine is a synthetic opioid derived from
phenylpiperidine. It is legal for midwives to use
meperidine without physicians’ supervision in the
United Kingdom. It is also the most extensively used
and investigated opioid analgesic in labor worldwide.
The dose is 50 to 100 mg intramuscularly, which can
be repeated every 4 hours. The onset takes 10 to 15
minutes, and it can take up to 45 minutes to reach
peak effect. The duration of action is between 2 and 3
hours. It is metabolized by the liver to an active
metabolite called normeperidine. Both meperidine
and normeperidine are more lipid-soluble than
morphine and cross the placenta readily. Meperidine
has many undesirable side effects. In mothers, it can
cause nausea, sedation, confusion, delayed gastric
emptying, and respiratory depression. There can be
reduced variability in the fetal heart rate, and it is also
known to cause neonatal respiratory depression.
(2) Meperidine versus diamorphine. Wee et al.51
carried out a two-center randomized, blinded,
controlled trial comparing intramuscular diamorphine
with intramuscular meperidine for labor analgesia.
Diamorphine provided modestly better pain relief at
60 minutes (mean difference [MD] of 1 cm on VAS;
95% CI, 0.5 to 1.5) and over the 3 hours of the study
(MD 0.7 cm; 95% CI, 0.3 to 1.1). However, average
length of labor in women receiving diamorphine was
82 minutes longer (95% CI, 39 to 124) when
 compared to the meperidine group. There were no
statistically significant differences in neonatal
outcomes.51
(3) Meperidine versus remifentanil. A systematic
review by Leong et al.52 compared remifentanil and
meperidine for labor analgesia. Only three studies
were suitable to be included in the meta-analysis (233
patients). Remifentanil was found to reduce the mean
VAS score at 1 hour by 25 mm more than meperidine
(95% CI, 19 to 31 mm; P < .001). There were
insufficient data for the authors to analyze the side
effect profile of remifentanil.52 Douma et al.53
compared patient-controlled meperidine,
remifentanil, and fentanyl in labor. Remifentanil PCA
was associated with the greatest decrease in pain
scores. However, the difference was only significant
at 1 hour. Significantly more parturients receiving
meperidine crossed over to epidural analgesia.
Overall satisfaction scores were higher with
remifentanil, but remifentanil produced more
sedation and itching. More periods of desaturation
(SaO2 <95%) were observed in the remifentanil and
fentanyl groups. There were no significant
differences in the fetal outcomes among three groups.
(4) The RESPITE trial, comparing intravenous
remifentanil PCA with intramuscular meperidine, is
taking place in the United Kingdom. Participating
women are randomly allocated into either meperidine
injection or remifentanil PCA groups during labor.
The primary outcome is the proportion of women that
go on to need epidural analgesia.

CLINICAL PEARL Systemic meperidine is the most widely

used opioid for labor analgesia worldwide despite providing poor
analgesia with significant side effects.

b. Diamorphine
(1) Diamorphine is a synthetic diacetylated analogue of
morphine. It is a prodrug and is hydrolyzed by
esterases in plasma, brain, and liver to active
metabolites, such as 6-monoacetylmorphine. The
latter is responsible for most of diamorphine’s
analgesic activity. Diamorphine is twice as potent as
morphine. It acts on the μ-opioid receptors to exert its
analgesic effects. It is usually given intramuscularly
for labor pain. The dose ranges from 5 to 10 mg. The
onset of action is 5 to 10 minutes after the
intramuscular injection. It lasts for approximately 90
minutes. It is more lipid-soluble than morphine and
readily crosses the placenta. It may cause euphoria
and respiratory depression in mothers and neonatal
respiratory depression when administered in high
doses.
(2) A UK-wide survey carried out by Tuckey et al.54
reported that 84.4% of responding units used
meperidine and 34.1% diamorphine. Prophylactic
antiemetics were coadministered in 73.7% of units.
McInnes et al.55 compared the intramuscular injection
of diamorphine with patient-controlled intravenous
diamorphine. Women in the patient-controlled
diamorphine group used significantly less
diamorphine than those in the intramuscular
diamorphine group. However, the PCA group was
significantly more likely to report that they were very
dissatisfied with the use of diamorphine and were
significantly more likely to opt out of the trial before
the birth of the baby.
CLINICAL PEARL More studies need to be done to compare
the efficacy and side effect profile of diamorphine with those of
other systemic opioids.

c. Morphine
(1) Morphine is a μ-opioid receptor agonist. It is now
infrequently used for labor analgesia. It can be given
every 4 hours intravenously (0.05 to 0.1 mg per kg)
or intramuscularly (0.1 to 0.2 mg per kg). If given
intravenously, its onset of action is 2 to 3 minutes
with a peak effect at 10 to 20 minutes. If an
intramuscular route is used, the onset of action takes
20 to 40 minutes with a peak effect at 1 to 2 hours.
Morphine is metabolized in the liver to an inactive
metabolite, morphine-3-glucuronide, and the active
metabolite, morphine-6-glucuronide. Both
metabolites are excreted by the kidneys and have
elimination half-lives of up to 4.5 hours. Like many
other opioids, morphine readily crosses the placenta.
The elimination half-life in neonates is a lot longer
than in adults. Morphine has predictable side effects,
such as respiratory depression, pruritus, nausea, and
vomiting. Respiratory depression can also be present
in the neonates.
(2) A Cochrane review by Ullman et al.56 included two
trials, which compared intravenous morphine and
intravenous meperidine. One of the studies reported
that the morphine group was less satisfied with pain
relief than the meperidine group (RR 0.87; 95% CI,
0.78 to 0.98). A second trial also reported that the
women in the intravenous morphine group were more
likely to request a second dose of analgesia when
compared to those in the meperidine group.
CLINICAL PEARL There is currently no evidence to support
the use of morphine for labor analgesia.

d. Fentanyl
(1) Fentanyl is a phenylpiperidine derivative, which is
highly selective for the μ-opioid receptor. It is known
to be 100 times as potent as morphine and 800 times
as potent as meperidine. In labor, fentanyl is usually
given intravenously in the form of PCA when
neuraxial analgesia is contraindicated or unavailable.
Its onset of action is 2 to 4 minutes with a short
duration of action (30 to 60 minutes). In small doses,
fentanyl undergoes rapid redistribution. However, in
repeated doses, the drug may accumulate. Fentanyl is
metabolized by the liver into inactive metabolites,
which are excreted by the kidneys. Its context-
sensitive half-life increases with an increase in the
duration of infusion. It can readily cross the placenta
and has a potential to cause neonatal respiratory
depression.
(2) Miyakoshi et al.57 performed a retrospective study
evaluating the use of patient-controlled intravenous
fentanyl in labor. Women who received fentanyl had
significantly longer labors and an increased need of
oxytocin augmentation when compared with the
women who received no analgesia. Neonatal
outcomes (i.e., Apgar score <7 at 1 minute or 5
minutes and umbilical artery pH <7.20) were
comparable between two groups irrespective of the
mode of delivery. Of the women who expressed their
satisfaction, 72% (48 of 67) exhibited “excellent” or
“good” for pain relief with patient-controlled
fentanyl.
CLINICAL PEARL Current evidence suggests that fentanyl
provides good pain relief in labor. Because its context-sensitive
half-life increases with prolonged use, both the mother and the baby
must be appropriately monitored for a period of time after stopping
a prolonged intravenous infusion.

e. Remifentanil
(1) Remifentanil is an ultrashort-acting anilidopiperidine
derivative. It acts selectively on the μ-opioid
receptors. Its onset of action is approximately 1
minute. It is hydrolyzed rapidly by tissue and plasma
esterases into inactive metabolites and has a context-
sensitive half-life of 3 minutes irrespective of the
duration of infusion. Due to its fast onset and offset,
remifentanil is suitable to treat the cyclical pain of
uterine contractions. It is typically administered in the
form of PCA when epidural analgesia is
contraindicated or unavailable. Bolus doses range
from 20 to 40 μg with a lockout time of 2 to 3
minutes. An example of a remifentanil PCA protocol
is described in Figure 9.4. The rapid elimination of
remifentanil reduces the risk of respiratory
depression; however, there have been case reports of
respiratory arrest and cardiovascular arrest in
laboring women who received remifentanil PCA.58,59
It is of paramount importance to monitor these
women closely with “one-to-one” midwifery or
nursing care. Continuous oxygen saturation
monitoring must be applied and means to give
supplementary oxygen with full resuscitation
equipment must be available. Clinical studies
evaluating the analgesic effect and maternal and fetal
outcomes of remifentanil are described in the
following text and in Tables 9.2 and 9.3.53,60–79
(2) Remifentanil versus other systemic opioids. A
meta-analysis carried out by Schnabel et al.60
included 12 randomized controlled trials. Women
who received remifentanil PCA had a significantly
lower rate of conversion to epidural analgesia, a
lower mean pain score at 1 hour, and a higher
 satisfaction score when compared to the women who
had meperidine. Serious maternal or fetal adverse
outcomes were not reported.
(3) Remifentanil patient-controlled analgesia versus
epidural analgesia. Liu et al.61 published a meta-
analysis of randomized controlled trials comparing
remifentanil PCA with epidural analgesia. Five
eligible studies were included in this meta-analysis.
The authors reported that women in the remifentanil
PCA group had higher VAS pain score when
compared to those in the epidural group at 1 hour and
2 hours. There was no statistical difference in the
incidence of nausea, vomiting, pruritus, and umbilical
artery pH values between the two groups. A
randomized controlled trial carried out by Stocki et
al.62 also reported that remifentanil PCA was inferior
to epidural analgesia for the provision of labor
analgesia. Mean respiratory rate was lower in the
remifentanil PCA group (18 ± 4 vs. 21 ± 4 breaths per
minute in the epidural group, P = .03). Mean SpO2
was also lower in the remifentanil PCA group (96.8%
± 1.4 vs. 98.4 ± 1.2 in the epidural group, P < .0001).
Moreover, nine apnea events occurred in five women
receiving remifentanil. Apgar scores and neonatal
respiratory outcomes were similar in both groups.62
This trial reinforces the safety concerns surrounding
the use of remifentanil PCA. Obstetric nurses should
be appropriately trained to recognize apnea and other
respiratory complications associated with
remifentanil use.
f. Alfentanil
(1) Alfentanil is a synthetic phenylpiperidine derivative,
which is structurally similar to fentanyl. It has 10% to
20% of fentanyl’s potency. It is highly bound to
 protein and is less lipophilic than fentanyl. The onset
of action is 1 minute, with a shorter duration than
fentanyl. Alfentanil is metabolized by the liver and
excreted in the urine. Context-sensitive half-life after
4 hours of infusion is 60 minutes. Bolus dose of 10
μg per kg is usually used. It is not frequently used for
labor analgesia.
(2) When alfentanil PCA was compared with fentanyl
PCA, women in the fentanyl group reported lower
pain scores on average, although the difference was
not statistically significant. There were no
statistically significant differences for any secondary
outcomes such as nausea, CD rate, and naloxone
administration.80

CLINICAL PEARL Currently, there is no strong evidence to

support the routine use of alfentanil for labor pain.

g. Sufentanil
(1) Sufentanil is also a synthetic phenylpiperidine
derivative. It is reported to be 6 to 10 times more
potent than fentanyl. It has a rapid onset and short
duration of action. It is mostly metabolized by the
liver, although a small proportion of drug is
metabolized in the small intestines. It is excreted in
the urine and feces. Its terminal half-life is
approximately 2.5 hours. Sufentanil is mainly used
for neuraxial analgesia and is infrequently used
parentally for labor pain. Bolus dose ranges from 1 to
3 μg per kg.
(2) Camann et al.81 compared the intrathecal, epidural,
and intravenous sufentanil for labor analgesia.
Twenty-four women were given sufentanil 10 μg
either intrathecally, epidurally, or intravenously
 during active labor. The median duration of analgesia
(median, IQR) was 84 (70 to 92) minutes in the
intrathecal group, 30 (23 to 32) minutes in the
epidural group, and 34 (17 to 30) minutes in the
intravenous route (P < .0001). The intrathecal group
also showed rapid and significant decrease in VAS
scores. The authors concluded that epidural and
intravenous administration of 10 μg of sufentanil did
not provide satisfactory analgesia.81

CLINICAL PEARL Currently, there is evidence to support the

routine use of sufentanil alone for labor pain.

h. Codeine phosphate
(1) Codeine phosphate is a naturally occurring opioid. It
is usually given orally or intramuscularly. Dose
ranges from 30 to 60 mg given every 6 hours. It
remains a popular analgesic drug during peripartum
period, especially in early labor and postpartum
period. The incidence of exposure to codeine during
pregnancy is 5% to 6%.82 Although it is a weaker
opioid than morphine, it can still predispose mothers
and babies to opioid-related side effects, such as
drowsiness and respiratory depression.
(2) Nezvalová-Henriksen et al.83 compared the
pregnancy outcomes of 2,666 women who used
codeine in pregnancy with the outcomes of 65,316
women who used no opioids in pregnancy. Codeine
use anytime during pregnancy was found to be
associated with an increased planned CD rate
(adjusted odds ratio [OR] 1.4; 95% CI, 1.2 to 1.7; P <
.0001). Third-trimester use was associated with an
increase in emergency CD rate (adjusted OR 1.5;
 95% CI, 1.3 to 1.8; P < .0001) and postpartum
hemorrhage (adjusted OR 1.3; 95% CI, 1.1 to 1.5; P
< .0001). No significant associations with other
adverse pregnancy outcomes were found.83 Because
more effective analgesic drugs are available, routine
use of codeine is not recommended for active labor.
(3) The U.S. Food and Drug Administration (FDA) has
issued a safety alert regarding codeine use in nursing
mothers and in young children. Respiratory
depression and death related to ultrarapid metabolism
of codeine to morphine have been reported in
children who received codeine in the postoperative
period following tonsillectomy and/or adenoidectomy
and had evidence of being ultrarapid metabolizers of
codeine. Moreover, deaths have also occurred in
nursing infants, who were exposed to high levels of
morphine in breast milk, because their mothers were
ultrarapid metabolizers of codeine. Some individuals
are ultrarapid metabolizers due to a specific CYP2D6
genotype. The prevalence of this CYP2D6 phenotype
varies widely among different ethnic groups. It has
been estimated at 0.5% to 1% in Chinese and
Japanese; 0.5% to 1% in Hispanics; 1% to 10% in
Caucasians; 3% in African Americans; and 16% to
28% in North Africans, Ethiopians, and Arabs.
Ultrarapid metabolizers convert codeine into its
active metabolite, morphine, more rapidly and
completely than other people. This rapid conversion
results in higher than expected serum morphine levels
predisposing them to life-threatening or fatal
respiratory depression or experience signs of
overdose. The FDA, therefore, advises that health
care providers should choose the lowest effective
dose for the shortest period of time and inform
 patients and caregivers about these risks and the signs
of morphine overdose when prescribing codeine-
containing drugs.84
i. Tramadol
(1) Tramadol is a synthetic analogue of codeine. It is
weak agonist at all opioid receptors with 20-fold
preference for μ-opioid receptors. It is also known to
inhibit neuronal reuptake of norepinephrine, and it
potentiates the release of serotonin. It is given orally,
intramuscularly, or intravenously in labor. Dose
ranges from 50 to 100 mg every 6 hours. It is
metabolized in the liver by demethylation. Its
elimination half-life is 4 to 6 hours. In equianalgesic
doses to morphine, tramadol causes less respiratory
and cardiovascular depression than morphine.
Tramadol is a proconvulsant and should be avoided
in patients with a history of epilepsy.
(2) Shetty et al.85 compared the efficacy of intramuscular
tramadol and pentazocine in the first stage of labor.
Sixty-five patients were divided into the pentazocine
group (30 mg pentazocine) and the tramadol group (1
mg per kg tramadol). There was no significant
difference in the analgesic effect between two groups.
Neither of the analgesics was effective toward the
end of the first stage. However, in the tramadol
group, the majority of women (55%) rated pain as
severe, whereas in the pentazocine group, the
majority of women (60%) rated pain as moderately
severe. There were not many side effects with either
of the drugs in the given dosage.85 Another
randomized controlled trial compared the efficacy of
intramuscular tramadol (100 mg) and meperidine (50
mg) in active labor. The duration of labor was shorter
in the tramadol group, for the first stage (190 vs. 140
 minutes, P < .0001) and for the second stage (33 vs.
25 minutes, P = .001). There were no differences in
VAS scores for pain at 10 minutes and 1 hour
between two groups. Women in the meperidine group
had lower VAS pain scores than those in the tramadol
group in the second stage of labor (8 vs. 9; P = .009).
There was a significantly higher incidence of nausea
and vomiting (35% vs. 15%; P = .003) and
drowsiness (80% vs. 29%; P < .0001) in the
meperidine group.86
j. Oxycodone
(1) Oxycodone is a μ-opioid receptor agonist. It has
increasingly been used to treat acute pain and can be
given orally or intravenously. Oral bioavailability
ranges from 60% to 87%. Its onset of action is
between 15 and 30 minutes, and it has duration of
action of 4 to 6 hours, although the analgesic effect of
controlled release formulations can last up to 12
hours. Most of the drug is metabolized in the liver,
whereas the rest is excreted by the kidneys. The
plasma half-life is 3 to 5 hours.
(2) Kokki et al.87 carried out an open-labeled study to
evaluate the maternal pharmacokinetic properties of
intravenous oxycodone in the first stage of labor.
Maternal plasma oxycodone concentration was found
to have a median half-life of 2.6 hours (ranges from
1.8 to 2.8). Oxycodone concentrations in the
umbilical plasma were similar to levels in maternal
plasma at the time of birth. The authors concluded
that maternal elimination half-life of intravenous
oxycodone was significantly shorter than the
elimination half-life reported in nonpregnant women
and that maternal plasma oxycodone correlated well
with neonatal umbilical concentrations at the time of
 birth.87 More studies need to be done to evaluate the
efficacy of oxycodone to treat labor pain.

CLINICAL PEARL Current evidence suggests that tramadol and

oxycodone do not offer significant benefit over other systemic
analgesia for labor pain.

k. Opioid partial agonists

(1) A partial agonist is a drug that has receptor affinity
but produces a submaximal effect compared with a
full agonist when given at very high doses. Opioid
partial agonists bind primarily to the μ-opioid
receptor and stimulate the production of endorphins
to a lesser extent than full agonists. They have a
ceiling to their analgesic effect. Increasing the dose
can potentially result in greater opioid side effects.
(2) Butorphanol is five times as potent as morphine.
Dose ranges from 1 to 2 mg for labor. It can be used
intravenously or intramuscularly. It is mostly
metabolized in the liver into inactive metabolites and
excreted in the urine. Like opioid agonists, it can also
cause undesirable side effects such as pruritus and
respiratory depression. Nelson and Eisenach88
compared the efficacy of meperidine versus
butorphanol when used for labor analgesia. Women
were randomly allocated to receive 50 mg
meperidine, 1 mg butorphanol, or 25 mg meperidine
plus 0.5 mg butorphanol (n = 15 per group). Overall,
only 29% of women reported clinically meaningful
pain relief with no difference among three groups.
There was no statistically significant difference in the
incidence of opioid-induced adverse effects among
three groups.
 (3) Nalbuphine is an agonist at κ-opioid receptors and a
partial agonist at μ-opioid receptors. It is given
intramuscularly, intravenously, or by subcutaneous
injection. Dose ranges from 10 to 20 mg every 4 to 6
hours. The onset of action takes 2 to 3 minutes from
the intravenous injection and longer if intramuscular
or subcutaneous routes are used. Duration of action is
between 3 to 6 hours. The drug is metabolized in the
liver to inactive compounds, which are then secreted
into bile and excreted in feces. Nalbuphine is known
to cause less respiratory depression when compared
to morphine. When Frank et al.89 compared
nalbuphine PCA (bolus 3 mg, lockout interval 10
minutes) with meperidine PCA (bolus 15 mg, lockout
interval of 10 minutes), the former was found to
provide better analgesia in nulliparous women. There
were no differences in maternal sedation scores and
neonatal outcome as assessed by Apgar scores.89

CLINICAL PEARL More research needs to be done to confirm

the efficacy and side effect profile of nalbuphine when used for
labor analgesia.

SUMMARY
It is essential to provide pain relief to laboring women in a timely manner. We
have described common nonpharmacologic and non-neuraxial pharmacologic
analgesic techniques and have cited the latest evidence supporting their use.
Neuraxial analgesia provides the most effective form of pain relief to laboring
women. The benefits and risks of non-neuraxial techniques should be discussed
with the parturient in whom either neuraxial analgesia is contraindicated or in
those who prefer a non-neuraxial technique.
REFERENCES
1. Lally JE, Murtagh MJ, Macphail S, et al. More in hope than expectation: a systematic review of
women’s expectations and experience of pain relief in labour. BMC Med. 2008;6:7.
2. Hodnett ED. Pain and women’s satisfaction with the experience of childbirth: a systematic review. Am
J Obstet Gynecol. 2002;186:S160–S172.
3. Nolan ML. Information giving and education in pregnancy: a review of qualitative studies. J Perinat
Educ. 2009;18:21–30.
4. Corry MP. Recommendations from Listening to Mothers: the first national U.S. survey of women’s
childbearing experiences. Birth. 2004;31:61–65.
5. Maimburg RD, Vaeth M, Dürr J, et al. Randomised trial of structured antenatal training sessions to
improve the birth process. BJOG. 2010;117:921–928.
6. Hodnett ED, Gates S, Hofmeyr GJ, et al. Continuous support for women during childbirth. Cochrane
Database Syst Rev. 2013;(7):CD003766.
7. Hosseini SE, Bagheri M, Honarparvaran N. Investigating the effect of music on labor pain and
progress in the active stage of first labor. Eur Rev Med Pharmacol Sci. 2013;17:1479–1487.
8. Simavli S, Kaygusuz I, Gumus I, et al. Effect of music therapy during vaginal delivery on postpartum
pain relief and mental health. J Affect Disord. 2014;156:194–199.
9. Smith CA, Collins CT, Cyna AM, et al. Complementary and alternative therapies for pain
management in labour. Cochrane Database Syst Rev. 2006;(4):CD003521.
10. Berman BM. Cochrane complementary medicine field. About the Cochrane Collaboration (Fields).
2006;(1):CE000052.
11. Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965;150:971–979.
12. Field T. Pregnancy and labor massage. Expert Rev Obstet Gynecol. 2010;5:177–181.
13. Field T. Massage therapy effects. Am Psychol. 1998;53:1270–1281.
14. Smith CA, Levett KM, Collins CT, et al. Massage, reflexology and other manual methods for pain
management in labour. Cochrane Database Syst Rev. 2012;(2):CD009290.
15. Dolatian M, Hasanpour A, Montazeri S, et al. The effect of reflexology on pain intensity and duration
of labor on primiparas. Iran Red Crescent Med J. 2011;13:475–479.
16. Faymonville ME, Laureys S, Degueldre C, et al. Neural mechanisms of antinociceptive effects of
hypnosis. Anesthesiology. 2000;92:1257–1267.
17. Madden K, Middleton P, Cyna AM, et al. Hypnosis for pain management during labour and childbirth.
Cochrane Database Syst Rev. 2012;(11):CD009356.
18. Werner A, Uldbjerg N, Zachariae R, et al. Self-hypnosis for coping with labour pain: a randomised
controlled trial. BJOG. 2013;120:346–353.
19. Smith CA, Collins CT, Crowther CA. Aromatherapy for pain management in labour. Cochrane
Database Syst Rev. 2011;(7):CD009215.
20. Stux G, Pomeranz B. Basics of Acupuncture. Berlin, Germany: Springer Verlag; 1995.
21. Pomeranz B, Stux G. Scientific Bases of Acupuncture. Berlin, Germany: Springer Verlag; 1989.
22. Ng LKY, Katims JJ, Lee MHM. Acupuncture: a neuromodulation technique for pain control. In:
Arnoff GM, ed. Evaluation and Treatment of Chronic Pain. 2nd ed. Baltimore, MD: Williams &
Wilkins; 1992:291–298.
23. Carr D, Lythgoe J. Use of acupuncture during labour. Pract Midwife. 2014;17:10, 12–15.
24. Chen Y, Zhang X, Fang Y, et al. Analyzing the study of using acupuncture in delivery in the past ten
years in China. Evid Based Complement Alternat Med. 2014;2014:672508.
25. Smith CA, Collins CT, Crowther CA, et al. Acupuncture or acupressure for pain management in
labour. Cochrane Database Syst Rev. 2011;(7):CD009232.
26. Benfield RD, Herman J, Katz VL, et al. Hydrotherapy in labor. Res Nurs Health. 2001;24:57–67.
27. Johansen LB, Pump B, Warberg J, et al. Preventing hemodilution abolishes natriuresis of water
immersion in humans. Am J Physiol. 1998;275:R879–R888.
28. Grossman E, Goldstein DS, Hoffman A, et al. Effects of water immersion on sympathoadrenal and
dopa-dopamine systems in humans. Am J Physiol. 1992;262:R993–R999.
29. National Institute for Health and Care Excellence. Intrapartum Care: Care of Healthy Women and
Their Babies during Childbirth. London, United Kingdom: National Institute for Health and Care
Excellence; 2007.
30. Nutter E, Meyer S, Shaw-Battista J, et al. Waterbirth: an integrative analysis of peer-reviewed
literature. J Midwifery Womens Health. 2014;59:286–319.
31. Cluett ER, Burns E. Immersion in water in labour and birth. Cochrane Database Syst Rev. 2009;
(2):CD000111.
32. Clement-Jones V, McLoughlin L, Tomlin S, et al. Increased beta-endorphin but not met-enkephalin
levels in human cerebrospinal fluid after acupuncture for recurrent pain. Lancet. 1980;2:946–949.
33. Bedwell C, Dowswell T, Neilson JP, et al. The use of transcutaneous electrical nerve stimulation
(TENS) for pain relief in labour: a review of the evidence. Midwifery. 2011;27:e141–e148.
34. Dowswell T, Bedwell C, Lavender T, et al. Transcutaneous electrical nerve stimulation (TENS) for
pain relief in labour. Cochrane Database Syst Rev. 2009;(2):CD007214.
35. Derry S, Straube S, Moore RA, et al. Intracutaneous or subcutaneous sterile water injection compared
with blinded controls for pain management in labour. Cochrane Database Syst Rev. 2012;
(1):CD009107.
36. King TL, Wong CA. Nitrous oxide for labor pain: is it a laughing matter? Anesth Analg. 2014;118:12–
14.
37. Maze MJ, Fujinaga M. Recent advances in understanding the actions and toxicity of nitrous oxide.
Anaesthesia. 2000;55:311–314.
38. Likis FE, Andrews JC, Collins MR, et al. Nitrous oxide for the management of labor pain: a
systematic review. Anesth Analg. 2014;118:153–167.
39. Klomp T, van Poppel M, Jones L, et al. Inhaled analgesia for pain management in labour. Cochrane
Database Syst Rev. 2012;(9):CD009351.
40. Yeo ST, Holdcroft A, Yentis SM, et al. Analgesia with sevoflurane during labour: I. Determination of
the optimum concentration. Br J Anaesth. 2007;98:105–109.
41. Yeo ST, Holdcroft A, Yentis SM, et al. Analgesia with sevoflurane during labour: II. Sevoflurane
compared with Entonox for labour analgesia. Br J Anaesth. 2007;98:110–115.
42. McGuinness C, Rosen M. Enflurane as an analgesic in labour. Anaesthesia. 1984;39:24–26.
43. Ross JA, Tunstall ME. Simulated use of premixed 0.25% isoflurane in 50% nitrous oxide and 50%
oxygen. Br J Anaesth. 2002;89:820–824.
44. Abboud TK, Swart F, Zhu J, et al. Desflurane analgesia for vaginal delivery. Acta Anaesthesiol Scand.
1995;39:259–261.
45. Abd-El-Maeboud KH, Elbohoty AE, Mohammed WE, et al. Intravenous infusion of paracetamol for
intrapartum analgesia. J Obstet Gynaecol Res. 2014;40:2152–2157.
46. Elbohoty AE, Abd-Elrazek H, Abd-El-Gawad M, et al. Intravenous infusion of paracetamol versus
intravenous pethidine as an intrapartum analgesic in the first stage of labor. Int J Gynaecol Obstet.
2012;118:7–10.
47. Joel S, Joselyn A, Cherian VT, et al. Low-dose ketamine infusion for labor analgesia: a double-blind,
randomized, placebo controlled clinical trial. Saudi J Anaesth. 2014;8:6–10.
48. McAuley DM, O’Neill MP, Moore J, et al. Lorazepam premedication for labour. Br J Obstet
Gynaecol. 1982;89:149–154.
49. Bucklin BA, Hawkins JL, Anderson JR, et al. Obstetric anesthesia workforce survey: twenty-year
update. Anesthesiology. 2005;103:645–653.
50. McIntosh DG, Rayburn WF. Patient-controlled analgesia in obstetrics and gynecology. Obstet
Gynecol. 1991;78:1129–1135.
51. Wee MY, Tuckey JP, Thomas PW, et al. A comparison of intramuscular diamorphine and
intramuscular pethidine for labour analgesia: a two-centre randomised blinded controlled trial. BJOG.
2014;121:447–456.
52. Leong WL, Sng BL, Sia AT. A comparison between remifentanil and meperidine for labor analgesia: a
systematic review. Anesth Analg. 2011;113:818–825.
53. Douma MR, Verwey RA, Kam-Endtz CE, et al. Obstetric analgesia: a comparison of patient-
controlled meperidine, remifentanil, and fentanyl in labour. Br J Anaesth. 2010;104:209–215.
54. Tuckey JP, Prout RE, Wee MY. Prescribing intramuscular opioids for labour analgesia in consultant-
led maternity units: a survey of UK practice. Int J Obstet Anesth. 2008;17:3–8.
55. McInnes RJ, Hillan E, Clark D, et al. Diamorphine for pain relief in labour: a randomised controlled
trial comparing intramuscular injection and patient-controlled analgesia. BJOG. 2004;111:1081–1089.
56. Ullman R, Smith LA, Burns E, et al. Parenteral opioids for maternal pain relief in labour. Cochrane
Database Syst Rev. 2010;(9):CD007396.
57. Miyakoshi K, Tanaka M, Morisaki H, et al. Perinatal outcomes: intravenous patient-controlled
fentanyl versus no analgesia in labor. J Obstet Gynaecol Res. 2013;39:783–789.
58. Bonner JC, McClymont W. Respiratory arrest in an obstetric patient using remifentanil patient-
controlled analgesia. Anaesthesia. 2012;67:538–540.
59. Marr R, Hyams J, Bythell V. Cardiac arrest in an obstetric patient using remifentanil patient-controlled
analgesia. Anaesthesia. 2013;68:283–287.
60. Schnabel A, Hahn N, Broscheit J, et al. Remifentanil for labour analgesia: a meta-analysis of
randomised controlled trials. Eur J Anaesthesiol. 2012;29:177–185.
61. Liu ZQ, Chen XB, Li HB, et al. A comparison of remifentanil parturient-controlled intravenous
analgesia with epidural analgesia: a meta-analysis of randomized controlled trials. Anesth Analg.
2014;118:598–603.
62. Stocki D, Matot I, Einav S, et al. A randomized controlled trial of the efficacy and respiratory effects
of patient-controlled intravenous remifentanil analgesia and patient-controlled epidural analgesia in
laboring women. Anesth Analg. 2014;118:589–597.
63. Volmanen P, Akural E, Raudaskoski T, et al. Comparison of remifentanil and nitrous oxide in labour
analgesia. Acta Anaesthesiol Scand. 2005;49:453–458.
64. Blair JM, Dobson GT, Hill DA, et al. Patient controlled analgesia for labour: a comparison of
remifentanil with pethidine. Anaesthesia. 2005;60:22–27.
65. Blair JM, Hill DA, Fee JP. Patient controlled analgesia for labour using remifentanil: a feasibility
study. Br J Anaesth. 2001;87:415–420.
66. Volmanen P, Akural EI, Raudaskoski T, et al. Remifentanil in obstetric analgesia: a dose-finding study.
Anesth Analg. 2002;94:913–917.
67. Thurlow JA, Laxton CH, Dick A, et al. Remifentanil by patient-controlled analgesia compared with
intramuscular meperidine for pain relief in labour. Br J Anaesth. 2002;88:374–378.
68. Volikas I, Butwick A, Wilkinson C, et al. Maternal and neonatal side-effects of remifentanil patient-
controlled analgesia in labour. Br J Anaesth. 2005;95:504–509.
69. Evron S, Glezerman M, Sadan O, et al. Remifentanil: a novel systemic analgesic for labor pain. Anesth
Analg. 2005;100:233–238.
70. Buehner U, Broadbent JR, Chesterfield B. Remifentanil patient-controlled analgesia for labour: a
complete audit cycle. Anaesth Intensive Care. 2011;39:666–670.
71. Jost A, Ban B, Kamenik M. Modified patient-controlled remifentanil bolus delivery regimen for
labour pain. Anaesthesia. 2013;68:245–252.
72. Balki M, Kasodekar S, Dhumne S, et al. Remifentanil patient-controlled analgesia for labour:
optimizing drug delivery regimens. Can J Anaesth. 2007;54:626–633.
73. Tveit TO, Halvorsen A, Seiler S, et al. Efficacy and side effects of intravenous remifentanil patient-
controlled analgesia used in a stepwise approach for labour: an observational study. Int J Obstet
Anaesth. 2013;22:19–25.
74. Ng TK, Cheng BC, Chan WS, et al. A double-blind randomised comparison of intravenous patient-
controlled remifentanil with intramuscular pethidine for labour analgesia. Anaesthesia. 2011;66:796–
801.
75. Volikas I, Male D. A comparison of pethidine and remifentanil patient-controlled analgesia in labour.
Int J Obstet Anesth. 2001;10:86–90.
76. Stourac P, Suchomelova H, Stodulkova M, et al. Comparison of parturient-controlled remifentanil
with epidural bupivacain and sufentanil for labour analgesia: randomised controlled trial. Biomed Pap
Med Fac Univ Palacky Olomouc Czech Repub. 2014;158:227–232.
77. Douma MR, Middledorp JM, Verwey RA, et al. A randomised comparison of intravenous remifentanil
patient-controlled analgesia with epidural ropivacaine/sufentanil during labour. Int J Obstet Anesth.
2011;20:118–123.
78. Volmanen P, Sarvela J, Akural EI, et al. Intravenous remifentanil vs. epidural levobupivacaine with
fentanyl for pain relief in early labour: a randomised, controlled, double-blinded study. Acta
Anaesthesiol Scand. 2008;52:249–255.
79. Marwah R, Hassan S, Carvalho JC, et al. Remifentanil versus fentanyl for intravenous patient-
controlled labour analgesia: an observational study. Can J Anaesth. 2012;59:246–254.
80. Morley-Forster PK, Reid DW, Vandeberghe H. A comparison of patient-controlled analgesia fentanyl
and alfentanil for labour analgesia. Can J Anaesth. 2000;47:113–119.
81. Camann WR, Denney RA, Holby ED, et al. A comparison of intrathecal, epidural, and intravenous
sufentanil for labor analgesia. Anesthesiology. 1992;77:884–887.
82. Palanisamy A, Bailey CR. Codeine in mothers and children: where are we now? Anaesthesia.
2014;69:655–660.
83. Nezvalová-Henriksen K, Spigset O, Nordeng H. Effects of codeine on pregnancy outcome: results
from a large population-based cohort study. Eur J Clin Pharmacol. 2011;67:1253–1261.
84. U.S. Food and Drug Administration. Codeine product labeling changes.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm356221.htm. Accessed July 25, 2015.
85. Shetty J, Vishalakshi A, Pandey D. Labour analgesia when epidural is not a choice: tramadol versus
pentazocine. ISRN Obstet Gynecol. 2014;2014:930349.
86. Khooshideh M, Shahriari A. A comparison of tramadol and pethidine analgesia on the duration of
labour: a randomised clinical trial. Aust N Z J Obstet Gynaecol. 2009;49:59–63.
87. Kokki M, Franco MG, Raatikainen K, et al. Intravenous oxycodone for pain relief in the first stage of
labour—maternal pharmacokinetics and neonatal exposure. Basic Clin Pharmacol Toxicol.
2012;111:182–188.
88. Nelson KE, Eisenach JC. Intravenous butorphanol, meperidine, and their combination relieve pain and
distress in women in labor. Anesthesiology. 2005;102:1008–1013.
89. Frank M, McAteer EJ, Cattermole R, et al. Nalbuphine for obstetric analgesia. A comparison of
nalbuphine with pethidine for pain relief in labour when administered by patient-controlled analgesia
(PCA). Anaesthesia. 1987;42:697–703.
 Choice of Neuraxial Analgesia and Local Anesthetics
Dominique Moffitt and Arvind Palanisamy

I. Pain pathways during labor
A. Severity of labor pain
B. First stage of labor
C. Second stage of labor
D. Effective blockade in both stages of labor
II. Neuraxial anatomy in pregnancy
A. Reduction in intervertebral gap
B. Widening and rotation of the pelvis
C. Higher level of the apex of thoracic kyphosis
D. Engorgement of epidural veins
E. Difficult identification of the ligamentum flavum
III. Techniques for neuraxial analgesia during labor
A. Indications
B. Contraindications
C. Rationale for choice of technique
D. Preparation
E. Description of technique
F. Epidural test dose
G. Choice of local anesthetics
H. Maintenance of analgesia
I. Analgesia for vaginal delivery
J. Ambulation during labor
 IV. Side effects and complications
A. Hypotension
B. Treatment for pruritus
C. Failed analgesia
D. Unintended dural puncture (“wet tap”)
E. Back pain
F. Excessive motor block, subdural, and high/total spinal block
G. Urinary retention
H. Maternal hyperthermia
I. Fetal heart rate abnormalities
J. Accidental IV injection
K. Meningitis
L. Epidural hematoma and abscess
M. Neurologic deficits

KEYPOINTS
1. Pain associated with labor is known to be the worst pain that a woman
can expect to experience in her lifetime.
2. Pain relief during labor and delivery is an essential part of good obstetric
care.
3. Anatomic and physiologic changes occur throughout pregnancy and add
to the complexity of administering neuraxial analgesia during labor.
4. Maternal request, in the absence of a medical contraindication, is
sufficient indication for initiation of labor analgesia.
5. Neuraxial analgesia is widely accepted as the most effective form of labor
analgesia.
6. Choice of neuraxial technique is at the discretion of the anesthesiologist
and is based on the patient’s medical history and clinical condition.
7. The goal of neuraxial analgesia is to provide effective and safe pain
control while improving patient satisfaction and without imposing a
 negative effect on obstetric outcomes.
8. Labor analgesia is generally safe, and the risk of serious complications is
extremely low.

I. Pain pathways during labor

A. Severity of labor pain. Labor pain, despite significant
interindividual variability, results in severe discomfort in most
parturients. Approximately 2.4 million women receive neuraxial
labor analgesia annually in the United States.1 Labor pain is likely
to be among the worst the parturient has ever experienced. It has
been assessed by the McGill Pain Questionnaire to be far worse
than pain associated with fractures, and in fact nearly as intense
as amputation of a digit.2 Achieving effective labor analgesia
requires a thorough understanding of the pain pathways involved
in parturition. Pain relief during labor and delivery is an essential
part of good obstetric care.
Progress of labor refers to increasing cervical dilation and
effacement combined with the descent of the presenting fetal part
in the pelvis. Relieving the pain generated by this process is one
of the most gratifying experiences in obstetric anesthesia practice.
Development of neuraxial techniques in the last several decades
has led to epidural administration of dilute concentrations of local
anesthetics with and without opioids (i.e., analgesia) versus
higher concentrations of local anesthetics (i.e., anesthesia).
Although these higher concentrations of local anesthetics
alleviated the pain of labor, it was at the expense of motor block
with effects on obstetric outcome (e.g., malpresentation). Newer
techniques allow active maternal participation with fewer effects
on labor and delivery. Achieving effective labor analgesia
requires a thorough understanding of the pain pathways involved
in parturition (see Fig. 10.1).
B. First stage of labor. Pain during the first stage of labor is
essentially visceral in nature and occurs due to a combination of
both uterine contractions and endocervical dilation. Although
uterine contractions likely result in myometrial ischemia causing
release of bradykinin, serotonin, histamine, and other mediators,
mechanoreceptors are also stimulated by stretching and distension
of the lower uterine segment and cervix. The noxious stimuli then
follow sensory nerve fibers that accompany sympathetic nerve
endings, traveling through the paracervical region as well as the
pelvic and hypogastric plexi to enter the lumbar sympathetic
chain. Visceral nociceptive fibers transmit these impulses to the
spinal cord through the posterior nerve roots of T10–L1.
The anatomic basis of pain produced during the first stage of
labor implies that the pain is amenable to blockade of peripheral
 afferents (by epidural block of T10–L1, paracervical block,
lumbar sympathetic block) or blockade of spinal cord
transmission by intrathecal injection of local anesthetics or
opioids.
C. Second stage of labor. Additional painful stimuli are added
during the second stage of labor. Beginning with fetal descent,
distension and transient ischemia of the vaginal canal, vulva and
perineum also occur. These painful somatic impulses are
transmitted by the afferent fibers of the pudendal nerve (S2–S4)
for subsequent relay in the spinal cord.
The anatomic basis of pain produced during the second stage of
labor implies that the pain is amenable to several techniques,
including saddle block spinal, pudendal nerve block and/or
extension of epidural blockade from T10–S4.
D. Effective blockade in both stages of labor. Pain signals from
both the first and second stage of labor are subjected to further
processing in the spinal cord, relayed to the supraspinal centers,
and ultimately projected to the sensory cortex. Effective
blockade of afferent transmission during both stages of labor
requires adequate coverage of neuraxial segments T10–S4.

CLINICAL PEARL Effective blockade of afferent transmission

during both stages of labor requires adequate coverage of neuraxial
segments T10–S4.

II. Neuraxial anatomy in pregnancy

A detailed discussion of lumbar anatomy is beyond the scope of this
chapter. Pregnancy, however, is known to induce a number of
anatomic changes in the spine. Both anatomic and physiologic
changes occur throughout pregnancy and add to the complexity of
administering neuraxial analgesia during labor.
A. Reduction in intervertebral gap. The lumbar lordosis is
exaggerated due to the parturient’s effort to stabilize her center of
 gravity. This alteration in lumbar anatomy reduces the dimensions
of the intervertebral space making it technically more difficult to
perform the procedure.
B. Widening and rotation of the pelvis. Effects of the hormones of
pregnancy and the mechanical strain imposed by the fetus result
in widening of the pelvis. This has two implications:
1. A head-down tilt results when the parturient is in the lateral
position. This can enhance rostral spread of local anesthetics
when injected intrathecally.
2. Forward rotation of the pelvis causes the line connecting the
iliac crests to cross the spine at a higher level (L3–L4
interspace) compared to nonpregnant patients (L4 body or
L4–L5 interspace). This can result in underestimation of the
level of needle placement (i.e., L2–L3 instead of L3–L4).

CLINICAL PEARL Forward rotation of the pelvis causes the

line connecting the iliac crests to cross the spine at a higher
level.This can result in underestimation of the level of needle
placement (i.e., L2–L3 instead of L3–L4).

C. Higher level of the apex of thoracic kyphosis. The apex of the

thoracic kyphosis is shifted to a higher level in pregnancy, from
T8–T6, which increases the possibility of increased rostral spread
of hyperbaric local anesthetics in the supine position (see Fig.
10.2).
 D. Engorgement of epidural veins. Compression of the inferior
vena cava and expansion of plasma volume lead to engorgement
of epidural veins, increasing the likelihood of vascular
cannulation during epidural placement.
E. Difficult identification of the ligamentum flavum. The
hormonal changes of pregnancy (i.e., edema) may make the
ligamentum flavum difficult to appreciate, increasing the risk of
accidental dural puncture.

CLINICAL PEARL The hormonal changes of pregnancy (i.e.,

edema) may make the ligamentum flavum difficult to appreciate,
increasing the risk of accidental dural puncture.

III. Techniques for neuraxial analgesia during labor

A. Indications
1. Maternal request. The American Society of
Anesthesiologists (ASA) and the American College of
Obstetricians and Gynecologists (ACOG) have jointly
endorsed a statement several times emphasizing that maternal
request per se is sufficient indication for analgesia:
 a. Labor results in severe pain for many women. In most
obstetric patients, the primary indication for epidural
analgesia is the patient’s desire for pain relief. There is no
other circumstance where it is considered acceptable for a
person to experience untreated severe pain, amenable to
safe intervention, while under a physician’s care. In the
absence of a medical contraindication, maternal request is
a sufficient medical indication for pain relief during
labor.3 Neuraxial analgesia is widely accepted as the most
effective form of labor analgesia.
b. ACOG directly endorses provision of neuraxial analgesia
without meeting arbitrary labor progress milestones in
this circumstance.
c. “American College of Obstetricians and Gynecologists
previously recommended that practitioners delay initiating
epidural analgesia in nulliparous women until the cervical
dilation reached 4–5 cm. However, more recent studies
have shown that epidural analgesia does not increase the
risks of cesarean delivery. . . . The fear of unnecessary
cesarean delivery should not influence the method of pain
relief that women can choose during labor.”4
2. Anticipation of operative delivery, including malpresentation
and multiple gestation
3. Obstetric disease (e.g., preeclampsia, nonreassuring fetal heart
rate [FHR] tracing) places the patient at high risk for
precipitous, high-risk, or emergency delivery.
4. Maternal conditions (e.g., morbid obesity, difficult airway,
malignant hyperthermia) complicating or contraindicating
general anesthesia
5. Maternal coexisting disease (e.g., severe cardiac or respiratory
disease) in which the physiologic consequences of
unmitigated pain need to be avoided

CLINICAL PEARL In most obstetric patients, the primary

indication for epidural analgesia is the patient’s desire for pain
relief. There is no other circumstance where it is considered
acceptable for a person to experience untreated severe pain,
amenable to safe intervention, while under a physician’s care.

B. Contraindications (see Table 10.1)

1. Absolute. Patient refusal, uncooperative patient, moderate or

severe bleeding diathesis, anticoagulation, uncontrolled
hemorrhage and severe hypovolemia, epidural site infection,
unskilled or inexperienced anesthesia provider
2. Relative. Elevated intracranial pressure (due to concern about
the potential consequences of accidental dural puncture),
documented local anesthetic allergy (although alternative
drugs may be considered), untreated systemic infection,
severe preexisting neurologic deficit, foreign language
without adequate interpretation, severe fetal depression,
severe maternal cardiac disease (e.g., Eisenmenger
syndrome), some skeletal anomalies and following some
types of back surgery
C. Rationale for choice of technique
Anesthesiologists may choose any of the three principal
techniques (epidural, combined spinal-epidural [CSE], continuous
spinal) for a number of reasons: maternal coexisting disease
 considerations, obstetric considerations, and anesthetic
considerations.
1. Maternal coexisting disease
Few maternal conditions clearly favor one neuraxial
technique over another. However, a conventional epidural
technique may be preferred in these situations:
a. Severe valvular heart disease, uncontrolled hypertension,
or other cardiovascular conditions in which central
volume changes would be poorly tolerated (e.g.,
pulmonary hypertension). The slowly titrated onset of an
epidural-induced sympathetic block may be
physiologically advantageous in such patients.
b. Intracranial mass lesions and other central neurologic
diseases (e.g., multiple sclerosis) lead some
anesthesiologists to avoid deliberate dural puncture, but
the effect of this strategy on outcome has not been
demonstrated.

CLINICAL PEARL Maternal coexisting disease, obstetric, and

anesthetic considerations will affect the choice of neuraxial
technique.

2. Obstetric considerations
a. When surgical intervention is very likely (e.g.,
nonreassuring fetal status), some anesthesiologists in the
past incorrectly favored the epidural technique for labor in
order to ensure the epidural catheter was functional in
order to avoid general anesthesia. A large retrospective
study confirmed that epidurals placed as part of a
CSE are more reliable than those placed alone.5 This
has been confirmed more recently by a large
randomized trial comparing CSE with traditional
epidural catheters.6
b. The choice of analgesic method in early labor is
controversial, but recent evidence favors the CSE
technique over systemic opioids or conventional epidural,
citing faster progress of labor as an advantage.7,8 The goal
of neuraxial analgesia is to provide effective and safe pain
control while improving patient satisfaction and without
imposing a negative effect on obstetric outcomes.
c. In active labor, CSE offers somewhat faster onset of
analgesia than a conventional epidural. A randomized
controlled trial in a private practice setting compared CSE
and traditional epidural analgesia in 800 term parturients.6
They found that patients receiving CSE had better pain
scores during the first stage of labor and required fewer
top-ups by the anesthesiologist, an important
consideration when anesthesia manpower is limited. In
contrast, a recent Cochrane Systematic Review concluded
that there is “little basis for offering CSE over epidurals in
labor, with no difference in overall maternal satisfaction
despite a slightly faster onset with CSE.”9 Collectively,
the effect may be relatively minimal when modern high-
volume, low-concentration epidural analgesia is used with
an overall advantage of the CSE of no more than 5 to 10
minutes.
d. In advanced labor, particularly in multiparous patients,
the CSE technique is often favored due to its rapid onset
of sacral analgesia.10
e. Ambulation may be facilitated by the CSE technique.
However, very low dose conventional epidurals have been
shown to confer similar motor strength and balance;
therefore, this advantage is minimal.
f. Preexisting fetal heart abnormalities may influence the
anesthesiologist to choose a conventional epidural
technique due to the association of intrathecal opioid
injections (and the CSE technique) with FHR
 abnormalities (e.g., fetal bradycardia).11
The issue of FHR patterns before and after CSE and
standard epidural techniques has been addressed in two
recent publications.12,13

CLINICAL PEARL In active labor, CSE offers faster onset of

analgesia than a conventional epidural. However, this difference is
less when high-volume, low-concentration epidural analgesia is
used.

3. Anesthetic considerations
a. Anticipated difficult airway may encourage early
placement of an indwelling epidural catheter. Poorly
functioning catheters should be replaced early during
labor and not waiting until the emergency cesarean
delivery (CD) has been called.
b. Early (i.e., before onset of labor or maternal request)
insertion of a spinal or epidural catheter for obstetric (e.g.,
twin gestation or preeclampsia) or anesthetic indications
(e.g., anticipated difficult airway or obesity) may be
advantageous to reduce the need for general anesthesia if
an emergent procedure becomes necessary.14 In addition,
cases of impending coagulopathy and decreasing platelet
counts (e.g., hemolysis, elevated liver enzymes, low
platelets [HELLP] syndrome) may warrant early
placement.
c. The rate of postdural puncture headache (PDPH) with
CSE is low, approximately 1% or less with modern
pencil-point needles. The overall risk of dural puncture
with an epidural needle may be reduced by the CSE
technique.5
d. Deliberate continuous spinal techniques are rarely used
due to the increased risk of PDPH. However, in extreme
 morbid obesity and selected other situations in which
slow-onset surgical anesthesia (e.g., aortic stenosis) is
desired, this technique may be appropriate. The inherent
dangers of having a woman labor with an indwelling
intrathecal catheter limit the use of this practice in many
hospitals. These dangers include mistakingly injecting a
dose of local anesthetic appropriate for an epidural into
the intrathecal space with the risk of high block leading to
respiratory arrest and cardiovascular collapse. These
catheters need to be well labeled and all care providers
informed that the catheter is intrathecal.

CLINICAL PEARL Early (i.e., before onset of labor or maternal

request) insertion of a spinal or epidural catheter for obstetric (e.g.,
twin gestation or preeclampsia) or anesthetic indications (e.g.,
anticipated difficult airway or obesity) may be advantageous to
reduce the need for general anesthesia if an emergent procedure
becomes necessary. Intrathecal catheters should be well labeled and
all caregivers informed.

D. Preparation (see Table 10.2)

Adequate preparation is the single most important determinant of

success with neuraxial techniques. The ASA’s recommendations
for neuraxial anesthesia in obstetrics are outlined in Chapter 33.14
1. Evaluation and consent. A focused history including all
relevant obstetric and anesthetic issues, a relevant physical
 examination (i.e., airway, heart, and lungs, consistent with the
ASA “Practice Advisory on Preanesthesia Evaluation”;
http://anesthesiology.pubs.asahq.org/article.aspx?
articleid=1933628), and determination of the timing of last
intake of solids are mandatory. One recent study demonstrates
that there are significant airway changes in women during
labor and delivery and that it is prudent to reexamine the
airway just before initiation of anesthesia during the
intrapartum or immediate postpartum period.15 The
advantages, potential side effects, and complications (e.g.,
infection, PDPH, neurologic injury) of neuraxial techniques
need to be specifically discussed before obtaining the
parturient’s signed consent. Initiating a discussion with the
obstetrician is useful in formulating a final plan of care. The
ASA practice guidelines reinforce the importance of
communication between obstetrician and anesthesiologist.
Specifically, “recognition of significant anesthetic or obstetric
risk factors should encourage consultation between the
obstetrician and the anesthesiologist.”14 It also gives an
opportunity for the anesthesiologist to establish rapport with
the labor and delivery nurse, an important resource in the
obstetric suite.
2. Aspiration prophylaxis. Restriction of oral intake to only
clear fluids is an intuitive precaution following neuraxial
blockade. However, the restriction of oral intake in labor is
controversial, and little evidence supports either very
restrictive or very liberal intake rules in the presence of
functional neuraxial block. The revised ASA guidelines for
obstetric anesthesia reflect this uncertainty, although the panel
recommends no intake of solid food during active labor.14
Patients with additional risk factors for aspiration (e.g.,
morbid obesity, diabetes, difficult airway) or patients at risk
for operative delivery (e.g., nonreassuring FHR pattern) may
have further restrictions of oral intake, determined on a case-
 by-case basis.
3. Intrapartum platelet counts and blood type and screen.
The anesthesiologist’s decision to obtain a platelet count
should be individualized based on a patient’s history, physical
examination, and clinical signs. A routine platelet count is
unnecessary in healthy parturients. A routine cross match is
unnecessary for uncomplicated parturients undergoing vaginal
or operative delivery. The decision to order or require a blood
type and screen or cross match should be based on maternal
history, anticipated hemorrhagic complications, and local
institutional policies.
4. Intravenous access. A good, functioning intravenous catheter
is required prior to epidural placement. Preloading or
coloading with IV fluids can be done according to the
prevailing department guidelines. However, a specified
volume is unnecessary and will not reliably prevent
hypotension.
5. Monitoring. Ensuring maternal and fetal well-being before,
during, and after epidural techniques is paramount to
successful management of laboring parturients.
a. Noninvasive blood pressure monitoring
Documentation of baseline noninvasive blood pressure
(NIBP) upon admission and immediately before epidural
placement is recommended. After administration of the
bolus dose, NIBP should be measured at least every 5
minutes for up to 20 minutes or until hemodynamic
stability is demonstrated. Periodic measurement of NIBP
is recommended for the duration of neuraxial analgesia,
although the optimal frequency of measurement has not
been established.
b. Electronic fetal monitoring. It is necessary to monitor
baseline FHR and identify FHR abnormalities during or
immediately after placement. The ASA Task Force
recommends monitoring before and after initiation of
 neuraxial analgesia but is equivocal on the need for
monitoring during the procedure itself and for continuous
monitoring thereafter.14
c. Other monitors. Electrocardiography and pulse oximetry
are not usually required. However, a pulse oximeter can
provide valuable information regarding maternal heart
rate during initiation of epidural analgesia and test dosing.
6. Positioning. Although both sitting and lateral positions are
suitable for epidural techniques, the ultimate decision depends
on the anesthesiologist’s preference. The advantages of the
sitting position include better perception of the midline and
increased maternal comfort. The lateral position may,
however, seem to have minimal effects on uteroplacental
perfusion and appears more suitable for FHR monitoring.
Some evidence supports fewer intravascular catheter
placements in the lateral position, during which the valveless
epidural veins are decompressed.16 However, for those who
use the sitting position routinely, intravascular catheter
placement is not a common event and is more often
influenced by the type of epidural catheter used.
7. Resuscitation drugs and equipment. Immediate availability
of resuscitation drugs, vasopressors such as ephedrine and
phenylephrine, airway equipment, and supplies are necessary
to administer a safe epidural anesthetic and manage
complications (e.g., hypotension, systemic toxicity, high
spinal anesthesia, respiratory depression). The
anesthesiologist must always be prepared to manage these
complications.
8. The Joint Commission 2015 National Patient Safety Goals.
The name, date of birth, and the proposed neuraxial technique
need to be verified with the parturient prior to initiation of the
procedure in accordance with The Joint Commission
recommendations for patient safety
(http://www.jointcommission.org/assets/1/6/2015_HAP_NPSG_ER.pdf
 date accessed: April 30, 2015).

CLINICAL PEARL Adequate preparation and optimal

positioning are important determinants of success with neuraxial
techniques.

E. Description of technique (see Table 10.3)

1. Epidural technique
a. The epidural tray. A commercial or self-prepared kit
should contain all materials needed for the block. Most
commercially available epidural kits contain a 17-G
epidural needle (either Tuohy or Weiss), a 19-G or 20-G
epidural catheter and ampules of saline and local
anesthetics (usually lidocaine 1% and lidocaine 1.5% with
epinephrine 1:200,000 for local infiltration and use as a
test dose, respectively), skin prep solutions (povidone-
iodine or chlorhexidine), sterile drape, gauze wipes, and
transparent dressing.
b. Sterile precautions. Hand washing, jewelry removal, and
the use of sterile gloves (to supplement hand washing, and
not as a substitute) are important sterile precautions, fresh
mask, and cap have been shown to reduce the incidence
of microbial contamination. Basic components of aseptic
technique are often breached. The American Society of
Regional Anesthesia (ASRA) consensus statement17 (see
Table 10.4) and ASA Taskforce in Obstetric Anesthesia14
acknowledge the importance of these procedures but
remain equivocal regarding the use of gowns. Alcohol-
based chlorhexidine solution has been convincingly
shown to provide superior germicidal properties
compared to povidone-iodine (Betadine) skin
preparation.17 Although it has been shown that
chlorhexidine solutions have faster and stronger
bactericidal effects than povidone-iodine, chlorhexidine is
not U.S. Food and Drug Administration (FDA)-approved
for use as a disinfectant solution before neuraxial
techniques due to controversy about neurotoxicity in
animal models; nevertheless, this agent is widely used for
skin preparation before neuraxial anesthesia.

c. Identification of the lumbar interspace. The ideal

lumbar interspaces for labor analgesia are usually L3–L4
or L2–L3. Traditionally, the line connecting the iliac
 crests is thought to cross the L4 vertebral body or the L4–
L5 interspace. It must be realized that identification of
such interspaces without radiologic guidance is at best a
“guesstimate” and is fraught with error.18,19 In patients
with difficult anatomic landmarks, such as the morbidly
obese, it is better to use the lowermost lumbar interspace
that can be easily located because of risk of
underestimating the interspace level. Although not
demonstrated in randomized trials, it appears that it is
more difficult to approach the epidural space at the L4–L5
interspace than at higher spaces.
Prepuncture ultrasonography may be useful to facilitate
epidural placement. Especially in obese parturients, the
distance to the epidural space is often underestimated
because of compression of the subcutaneous tissue that is
often required to compensate for poor visibility. A recent
study evaluated scanning in the paramedian sagittal
oblique (PSO) plane compared with the transverse median
(TM) plane to determine whether scanning in the PSO
plane resulted in a more precise estimate of the skin to
epidural space measurement.20 The authors concluded
that the estimates were comparable with PSO versus TM
and that the ability to use both estimates interchangeably
may prove useful in patients with poor visibility in the
TM plane.
After sterile preparation and draping, a liberal local
anesthetic infiltration (3 to 5 mL of 1% lidocaine) is
performed over the chosen interspace. The skin is then
punctured with the epidural needle and advanced until it
is firmly seated in the interspinous ligament. The stylet is
removed and the loss of resistance (LOR) syringe is
attached to the hub of the epidural needle.

CLINICAL PEARL Although not demonstrated in randomized

trials, it appears that it is more difficult to approach the epidural
space at the L4–L5 interspace than at higher spaces. Prepuncture
ultrasonography may be useful to facilitate epidural placement.

d. Techniques
(1) Loss of resistance. This commonly employed
method to identify the lumbar epidural space is based
on the tactile sensation of a sudden “give way” when
the soft tissue resistance offered by the ligamentum
flavum is overcome when the needle tip enters the
epidural space. A specially designed plastic or glass
LOR syringe, customized to reduce frictional and
resistive forces between the syringe and the plunger,
is attached to the hub of the epidural needle.
(a) Air versus saline. Although the
anesthesiologist’s preference may assume
primary importance, increasing evidence points
to the superiority of saline-based techniques
(saline alone, saline with a bubble of air) over air
for location of the epidural space.21 The cited
advantages include better sensory appreciation,
decreased incidence of patchy blocks, and
elimination of the risks of epidural venous air
embolism and pneumocephalus headache
(should an accidental dural puncture occur).
Some practitioners use air alone for the CSE
technique so that any clear fluid coming back
through the spinal needle can only be
cerebrospinal fluid (CSF); and not a depot of
saline or local anesthetic in the epidural space).
If using air, it is important not to empty the
syringe into the epidural space after LOR.
(b) Intermittent versus continuous pressure.
Application of “intermittent” or “continuous”
pressure to the syringe plunger is an integral
component of the LOR technique (see Fig. 10.3).
Purported advantages of the continuous
technique include faster identification of the
epidural space and possible reduced incidence of
accidental dural puncture. Purported advantages
of the intermittent technique include more
control over needle advancement (two hands on
the needle) and also reduced risk of dural
puncture.

The Episure (see Fig. 10.4) is a spring-

loaded syringe that uses saline and is designed to
automatically collapse upon entering the
epidural space. It offers the advantage of using
two hands on the needle with continuous
application of plunger pressure. A recent study
of experienced obstetric anesthesiologists
determined that the Episure syringe for LOR was
associated with a similar overall rate for
 establishing successful epidural labor analgesia
and a shorter elapsed time to epidural catheter
insertion.22

(2) Bevel orientation. It is common practice to orient the

bevel of the epidural needle cephalad. It may help
direct the catheter to its intended location (i.e., in the
vicinity of the T10–L2 segments). Insertion of the
needle with the bevel parallel to the long axis of the
back to reduce the risk of PDPH if dural puncture
occurs and rotating the needle within the epidural
space is not recommended. This maneuver is
associated with an increased risk of dural puncture.23
e. The epidural catheter
(1) Material. Most catheters are made of polyamide
(nylon). Most catheters are clearly marked in 1-cm
increments over the distal 20 cm. Wire-reinforced
epidural catheters are more flexible and have been
shown to reduce the incidence of paresthesias and
intravascular placement in obstetric patients
compared to use of more rigid catheters.24
(2) Multihole versus single hole. There is limited
evidence demonstrating the superiority of multiport
catheters over uniport catheters. Theoretically,
multiport catheters may be expected to provide better
quality of analgesia due to a more uniform spread of
local anesthetic, especially after bolus
administration.25 This advantage may be negated by
the current use of large-volume, low-concentration
mixtures for labor analgesia. In addition, inclusion of
opioids in the mixture may limit the theoretical
advantage even further, by providing excellent
quality segmental analgesia. Multicompartment
blocks (e.g., epidural, subdural, intrathecal, and
intravascular) have rarely been reported with use of
multiport catheters.
(3) Depth of catheter insertion. Increasing the depth of
the catheter (≥6 cm) in the epidural space increases
the incidence of coiling and unsatisfactory (i.e.,
unilateral) analgesia, whereas having a reduced
length (≤4 cm) increases the likelihood of catheter
dislodgement. Overall, inserting the catheter to a
depth of 4 to 5 cm appears to be optimal.26
In some cases, blood is noted in the catheter
during insertion or patients develop a persistent
paresthesia during insertion. When persistent
paresthesias occur, the catheter must be removed and
replaced. However, the catheter and epidural needle
must be withdrawn simultaneously. Otherwise,
withdrawing the catheter through the epidural needle
risks shearing of the catheter. If this occurs and the
broken catheter remains in the patient’s back, the
patient should be informed and a neurosurgeon
consulted. However, surgical removal is rarely
needed unless there are persistent neurologic
 symptoms.
If an IV catheter is detected on aspiration, the
catheter can be withdrawn 0.5 to 1 cm at the time
until blood is no longer aspirated. If the catheter tip
remains at an adequate depth and is no longer in the
vein, the catheter should be tested and secured. This
technique may salvage up to 50% of these catheters.
However, in some cases, the depth will be inadequate
and the catheter should be replaced.

CLINICAL PEARL When persistent paresthesias occur, the

epidural catheter must be removed and replaced.

f. If a test dose is used, it is recommended to administer it

before securing the catheter. The test dose will be
discussed at depth in a subsequent subsection of the
chapter.
2. Combined spinal-epidural technique
The CSE and conventional epidural techniques are similar,
with a few exceptions. The technique incorporates the
beneficial effects of intrathecal analgesia (i.e., rapid onset,
better quality, and increased sacral spread) to the flexibility
offered by an epidural catheter.
a. “Needle-through-needle” technique (see Fig. 10.5). The
procedure for locating the epidural space is the same as
described previously. Once the 17-G epidural needle is in
the epidural space, a 25- to 27-G pencil-point spinal
needle is inserted through the epidural needle and
advanced until a distinct “pop” is appreciated and CSF is
visualized in the spinal needle. The spinal needle is
stabilized and the intrathecal dose of local anesthetic (e.g.,
bupivacaine 1.5 to 3 mg) and/or opioid (e.g., fentanyl 5 to
15 μg) is administered when CSF appears at the hub.
 b. “Different interspaces” technique. The spinal needle is
placed first, intrathecal analgesia is then established, and
subsequently an epidural needle is placed. This technique
may be useful for those parturients who are extremely
distressed by labor pain such that immobility is difficult to
achieve. The epidural is subsequently placed one
interspace higher than the spinal. This technique helps
avoid placing an epidural in a “moving” target. However,
it risks placement of an epidural needle in a patient with
altered sensation.

CLINICAL PEARL The different interspaces technique involves

placement of the spinal needle first followed by injection of
intrathecal medication. An epidural needle is placed subsequently.
This technique may be useful for those parturients who are
extremely distressed by labor pain such that immobility is difficult
to achieve.

c. Aspiration of CSF may not be required for CSE analgesia

 because the epidural is available (as part of the CSE
technique) should spinal analgesia fail. In addition, it may
be difficult to aspirate CSF through a 27-G spinal needle,
and attempts at aspiration may result in accidental
dislodgement of the spinal needle.
d. Intrathecal medication. The commonly used intrathecal
dose consists of 2 to 3 mg of bupivacaine (as 1 to 1.2 mL
of 0.25% bupivacaine) and 5 to 15 μg of fentanyl. The
onset of analgesia is rapid, usually within the first few
minutes of injection and lasts between 60 and 90 minutes.
Bupivacaine lengthens the duration of effective
analgesia.27
Fentanyl-bupivacaine prepared in this fashion is
relatively hypobaric. If analgesia is asymmetric (i.e., less
anesthetized), placement of the painful (less blocked) side
in a nondependent position may improve analgesia.
e. Catheter placement. Immediately after the spinal
injection in the needle-through-needle technique, the
spinal needle is withdrawn and the epidural catheter is
threaded as usual to a depth of 4 to 5 cm into the epidural
space.
f. Securing the catheter. Before an epidural catheter is
secured, the catheter is inserted 5 cm into the epidural
space while the patient is in the sitting position.28 Before
taping, the patient moves to a lateral position. The
catheter is subsequently taped in place without adjusting
the catheter. Because the ligamentum flavum has a mild
grip on the epidural catheter, repositioning allows the
epidural catheter to be pulled into the subcutaneous fat,
sometimes by several centimeters.
g. Complications associated with the CSE technique are
similar to traditional epidural techniques.

CLINICAL PEARL Before an epidural catheter is secured, the

patient should assume a lateral position from the upright sitting
position before taping. Because the ligamentum flavum has a mild
grip on the epidural catheter, repositioning allows the epidural
catheter to be pulled into the subcutaneous fat, sometimes by
several centimeters.

3. Continuous spinal technique

a. This technique involves advancing an epidural needle into
the intrathecal space and an epidural catheter is placed.
Spinal catheter placement usually occurs following an
accidental dural puncture with an epidural needle and
only rarely as a primary technique. The catheter is
threaded to a depth of 5 cm in the intrathecal space.
b. Care must be taken to label the “spinal” catheter. All “top-
ups” must be administered with meticulous attention to
sterile technique. It is our custom to inform the patient
and the labor nurse of the intrathecal nature of the catheter
and place a sign on the patient’s room door to inform
colleagues of the intrathecal placement.
c. Analgesia can be initiated with solutions similar to those
employed during CSE analgesia (i.e., bupivacaine 1.25 to
2.5 mg and fentanyl 15 to 25 μg). Maintenance may be
accomplished with an infusion of a typical epidural
infusion, such as 0.8% to 0.125% bupivacaine with 1 to 2
μg per mL of fentanyl at a rate of 1 to 2 mL per hour.
d. It is prudent to aspirate the catheter for CSF and exclude
air bubbles in the syringe prior to any injections to
minimize the incidence of a pneumocephalus headache. It
is also important to remember that the catheter can have
up to 1 mL of dead space before any medication reaches
the subarachnoid space.
e. Intentional placement of continuous spinal catheters in
morbidly obese parturients or patients with known
 difficult airway has been reported. The possibility of
having a continuous mode of high-quality analgesia,
relative ease of conversion to anesthesia, and relatively
low incidence of PDPH in this population make it a
rational choice for such patients. Although it may be the
most rational choice for these patients, it should be
reserved for special cases because the catheter does
appear to be a “regular” epidural catheter and injection of
a large dose of local anesthetic can result in catastrophic
loss of the airway.
f. Continuous spinal analgesia (CSA) delivered by a 24- to
28-G microcatheter, placed via a thin spinal needle, was
briefly popular in the early 1990s. Reports of cauda
equina syndrome due to maldistribution of local
anesthetics injected through such catheters led to their
withdrawal from the market in the United States.
Investigations have been done with promising results
(<1% incidence of neurologic complications) that may
allow for the reintroduction of 28-G microcatheters for
labor analgesia in the future.29
g. A relatively new approach is the dural-puncture epidural
(DPE) technique,30 which is similar to the CSE with the
exception that no intrathecal medication is injected. This
technique offers the advantage of confirming midline
location by documenting presence of CSF flow, while
possibly avoiding the fetal adverse consequences that are
occasionally seen with the CSE technique. Dural puncture
before the initiation of epidural analgesia has also been
shown to improve sacral spread, onset, and bilateral pain
relief produced by analgesic concentrations of
bupivacaine with fentanyl. However, another study found
no benefit to using a dural puncture.31

CLINICAL PEARL CSA may be the most rational choice for

some patients (e.g., morbidly obese patients with difficult airway).
However, it should be reserved for special cases because the
catheter might appear to be a “regular” epidural catheter, and
injection of a large dose of local anesthetic could result in a
catastrophic outcome.

F. Epidural test dose

The rationale behind administering a “test dose” is to identify
intrathecal or intravascular placement of the epidural catheter
such that total spinal anesthesia or systemic local anesthetic
toxicity is prevented when large doses of local anesthetic are
administered.
Total spinal anesthesia can result from a miscalculated dose of
drug or unintentional subarachnoid injection during an epidural
block. The ASA Closed Claims Project analysis of obstetric
anesthesia liability claims found that the most common cause of
maternal death or brain damage in neuraxial anesthesia claims
was high block; 80% were associated with dosing epidural
anesthesia, and 20% involved spinal anesthesia.32
Intravascular placement complicates 5% to 10% of epidural
attempts. Adverse events due to local anesthetic toxicity have
decreased because of greater emphasis on incremental dosing and
use of a test dose, typically containing 15 μg of epinephrine to
exclude unintentional intravenous or subarachnoid catheter
placement. Cases of local anesthetic toxicity were absent from
most recent review of the ASA Closed Claims Project database.32
1. The ideal test dose must be safe for mother and baby, reliable,
and contain agents that can identify intravascular/intrathecal
location with high sensitivity and good positive predictive
value.
2. A test dose is important if administration of large volumes of
concentrated local anesthetics is contemplated (e.g., top ups
for operative delivery, epidural anesthesia for elective CD,
 and reactivation of epidural catheters for postpartum tubal
ligation). Some authorities have argued that test dosing is
unnecessary when moderate volumes of dilute local anesthetic
are administered (e.g., for labor analgesia).
3. The traditional test dose usually consists of a low-dose local
anesthetic (i.e., 3 to 5 mL of bupivacaine 0.25% [7.5 to 12.5
mg] or lidocaine 1.5% [45 to 60 mg] or 2-chloroprocaine 2%
[60 mg] and epinephrine [15 μg]). Development of a motor
block within 5 minutes of injection or an increase in the
baseline heart rate by 25 to 30 beats per minute (bpm) 20 to
40 seconds after injection is considered to be a positive test
dose and evidence of intrathecal or intravascular placement,
respectively.33
4. A “double test dose” can also be used and avoids the pitfalls
of administering an epinephrine-containing test dose. Two
doses of plain lidocaine 2% are administered: a 40 mg (2 mL)
intrathecal test dose followed in 5 minutes by a 100 mg (5
mL) IV test. This testing technique may be useful in cases
where it is imperative to have a functional epidural catheter in
patients at high risk for urgent operative delivery. Patients
must be observed after each injection to reduce maternal and
fetal risk.
5. For labor analgesia, however, use of a test dose is
controversial
a. Dilute local anesthetic solutions used for labor analgesia
have a low risk of systemic toxicity. However, if CD is
necessary, large amounts of concentrated local anesthetics
will be administered.
b. Theoretically, epinephrine can cause reduction in
uteroplacental blood flow, although the effect is
transient and does not affect fetal status in animal models.
Nor does it induce a clinically important change in
humans.
c. Specificity is reduced due the difficulty in distinguishing
 epinephrine-induced tachycardia from that induced by
painful maternal contractions. If a test dose is
administered, it should be injected between contractions.
d. Sensitivity is reduced due to the unpredictable rate of rise
of heart rate with epinephrine in parturients. Some have
advocated using the maximum rate seen in the 2 minutes
prior to injection as the baseline for comparison, and an
increase of 10 bpm rather than 25 to 30 bpm.34
e. After CSE, many anesthesiologists elect to start a dilute
epidural infusion immediately without using a test dose.
The value of a test dose in this setting has not been
established.

CLINICAL PEARL Because dilute local anesthetic solutions

used for labor analgesia have a low risk of systemic toxicity, the use
of a test dose is controversial. However, if CD is necessary, large
amounts of concentrated local anesthetics will be administered
increasing the risk of potential local anesthetic systemic toxicity.

6. Most anesthesiologists advocate routine fractionation of any

local anesthetic bolus and maintain frequent contact with the
patient to identify subjective symptoms (e.g., tinnitus, perioral
tingling). However, when dilute local anesthetic solutions are
administered, these symptoms may be absent. In this regard,
every dose must be considered a test dose.
7. Alternative test doses have been suggested33
a. Isoproterenol 5 μg produces a more reliable tachycardia
and less effect on uteroplacental blood flow when the test
dose is positive. However, human neurotoxicology studies
are lacking.
b. FHR Doppler probe placed over the maternal heart is
used to detect an IV epidural catheter following a bolus
injection of air (i.e., 1 to 2 mL) into the epidural catheter.
 However, there may be increased risk of “patchy” or
“spotty” block when air is administered epidurally.
c. Fentanyl, using subjective symptoms of lightheadedness
as a marker of intravenous versus epidural injection
d. Hyperbaric local anesthetic can also be used to better
identify intrathecal placements.
8. Special circumstances may further complicate use of a test
dose. These include treatment with β-blockers, as may be the
case in preeclampsia, and maternal coexisting disease that
might be worsened by tachycardia (e.g., stenotic valvular
heart disease).
G. Choice of local anesthetics (see Chapter 3)
1. Concentration and dose considerations
The ideal local anesthetic for labor should provide rapid onset
of action, long duration of analgesia, and excellent
sensorimotor differential blockade and cause minimal effects
on maternal and fetal physiology. Although none of the
available local anesthetics have all these properties, low
concentration bupivacaine has become the most popular.
a. Bupivacaine
Bupivacaine is an amide local anesthetic and a popular
choice for labor analgesia.
(1) Advantages
(a) Differential block. Bupivacaine demonstrates
good separation between its motor and sensory
effects at low concentrations. This may be
related to the sparing of the A-α motor neurons
with concentrations used for labor analgesia.
Because preservation of mobility greatly
enhances maternal satisfaction, bupivacaine is an
ideal choice for mobile, pain-free labor.
(b) Long duration of action. Among the
commonly used local anesthetics, bupivacaine
has the longest duration of action. A single bolus
 administration of 8 to 10 mL of 0.25%
bupivacaine provides approximately 90 to 120
minutes of analgesia.
(c) Lack of tachyphylaxis. This makes continuous
and repeated administration of bupivacaine, as in
a patient-controlled epidural analgesia (PCEA),
a viable option.
(d) Remarkable safety profile. With the exclusion
of 0.75% bupivacaine from obstetric practice
due to risk of cardiovascular toxicity (see
Chapter 3) and the preference for low
concentrations, PCEA/continuous infusion
devices over bolus administration of more
concentrated solutions, maternal mortality due to
bupivacaine toxicity is now almost nonexistent.
(e) Limited placental transfer. The umbilical
vein/maternal vein (UV/MV) ratio for
bupivacaine is about 0.3, one of the lowest for
local anesthetics. Although free drug UV/MV
ratios for all local anesthetics approach 1:1 at
equilibrium, extensive maternal protein binding
keeps the free drug concentration of bupivacaine
in maternal plasma very low, limiting
transplacental transfer.
(2) Disadvantages
(a) Slower onset time. Although full analgesic
effects may take 10 to 20 minutes to develop,
combining a high volume of dilute bupivacaine
with a lipophilic opioid provides an acceptable
speed of onset.
(b) Cardiovascular and neurologic toxicity.
Although deaths are rare, seizures and
cardiovascular instability and even cardiac arrest
have been reported when large volumes of
 concentrated bupivacaine are administered. The
ratio between the concentration producing
cardiovascular toxicity and that producing
central nervous system (CNS) toxicity is lower
than with other anesthetics, making it potentially
hazardous.
(3) Concentration and dose
(a) Labor analgesia is usually initiated with
incremental boluses of bupivacaine 0.0625% to
0.125% (total volume = 12 to 20 mL).
Concentrations as low as 0.04%, when combined
with fentanyl and epinephrine, have been used
successfully, at least for the first stage of labor.35
Concentrations as high as 0.25% (12 mL) are
sometimes used, although higher volumes of
lower concentrations are more popular now.14
(b) The ED50 for bupivacaine at a dose of 20 mL
(the median effective local anesthetic
concentration, or MLAC) is approximately
0.08%, but this can be reduced by the addition of
fentanyl. The bupivacaine concentration may be
increased during more advanced labor, or for
dysfunctional labor.36,37
b. Lidocaine
Despite the usefulness of lidocaine for surgical procedures
and test dosing, it is not routinely used for initiation or
maintenance of labor analgesia because of less
sensorimotor discrimination (i.e., increased motor block),
greater incidence of tachyphylaxis, and increased
transplacental transfer and ion trapping.
Apart from its popularity as an epidural test dose, there
are a few instances in which its quick onset of action may
be beneficial:
(1) Identifying a nonfunctional epidural catheter.
 Epidural administration of lidocaine without
epinephrine (5 to 10 mL of 2%) helps to delineate the
dermatomal sensory level in patients with inadequate
analgesia. This can facilitate making the decision to
replace such catheters.
(2) Need for rapid sacral analgesia. Lidocaine is
occasionally been used for rapid control of
breakthrough pain during the second stage of labor.
Low volumes (5 to 10 ml) of plain lidocaine (0.5% to
1.0%, without epinephrine) can be given and do not
produce significant motor block that might otherwise
interfere with maternal expulsive efforts.
(3) Supplemental analgesia for instrumental delivery and
perineal repair. Lidocaine 1.5% or 2% with or
without epinephrine (5 to 10 mL) can be used for
such procedures. Lidocaine with epinephrine
produces denser and longer lasting analgesia
compared to plain solutions.
c. 2-Chloroprocaine (see Chapter 3)
2-Chloroprocaine is an option when emergent
instrumental or operative delivery is necessary. It is an
ester local anesthetic that is rapidly metabolized with a
plasma half-life of approximately 30 seconds. 2-
Chloroprocaine is the least toxic of all local anesthetics.
(1) 3% 2-Chloroprocaine, an ester local anesthetic, is
widely used for rapid extension of surgical epidural
anesthesia for emergency CD (typically 20 mL).
(2) 2-Chloroprocaine is not favored for labor analgesia
due to its short duration of action and poor
sensorimotor discrimination (i.e., increased motor
block).
(3) 2-Chloroprocaine 2% to 3% provides effective
analgesia during extensive perineal repair.
(4) 2-Chloroprocaine has been shown to interfere with
 the action of bupivacaine and opioids administered
subsequently or in combination, although this effect
appears less pronounced with epidural administration
than with peripheral nerve blocks (see Chapter 3).38
(5) Association of back spasms with 2-chloroprocaine
use has been reported mainly in nonobstetric
literature, and this risk appears to be minimized by
the current preservative-free preparation.
d. Ropivacaine and levobupivacaine (see Chapter 3)
(1) Concerns with bupivacaine cardiotoxicity led to the
development of alternative local anesthetics that are
pure levo isomer preparations, notably ropivacaine
and levobupivacaine. At equal and equipotent
concentrations, both drugs are substantially less toxic
in animal and human models.
(2) Ropivacaine infusions of 0.1% to 0.2% produce
excellent analgesia comparable to bupivacaine. Early
results demonstrating less motor block with
comparable concentrations of ropivacaine versus
bupivacaine probably reflect the approximate 40%
lower potency of ropivacaine.39
(3) Currently in the United States, levobupivacaine is not
available commercially. However, it has analgesic
properties essentially indistinguishable from racemic
bupivacaine.
(4) When larger doses of more concentrated drug are
required (e.g., for CD), ropivacaine may offer a
safety advantage over bupivacaine. However,
lidocaine is equally effective, less expensive, and has
a long record of safety.
(5) Both levobupivacaine and ropivacaine are
considerably more expensive than bupivacaine.

CLINICAL PEARL The ideal local anesthetic for labor should

provide rapid onset of action, long duration of analgesia, excellent
sensorimotor differential blockade, and cause minimal effects on
maternal and fetal physiology.

2. Use of adjuvants in labor analgesia

a. Opioids. Extensive animal and human studies have
confirmed the synergism between opioids and local
anesthetics. Direct action at spinal and supraspinal opioid
receptors along with the facilitation of local anesthetic
effects makes opioids a useful adjunct in labor analgesia.
This results in a 20% to 30% overall reduction in local
anesthetic dose resulting in a decreased incidence of
toxicity and motor block.36
Lipophilic opioids (e.g., fentanyl, sufentanil, alfentanil)
are preferred over morphine due to a quick onset of
action, reduced incidence of side effects (e.g., pruritus,
nausea, and vomiting), and segmental nature of analgesia.
Fentanyl remains the most widely used and extensively
studied of all local anesthetic adjuncts. Sufentanil can also
be used but is four to five times more potent than
fentanyl. The side effects at equipotent doses are similar
with either drug; however, fentanyl remains a mainstay in
most practices (see Table 10.5).

The successful use of meperidine and butorphanol has

also been reported.
b. Epinephrine. Epinephrine-induced venoconstriction
reduces the clearance of epidurally administered local
anesthetics and opioids, prolonging and enhancing their
effects. It may also directly enhance analgesia by α2
 agonism.
The main disadvantages with epinephrine use in labor
are its ability to increase the density of motor block and
possible slowing of labor through β2 agonism (after
systemic absorption). Also, the higher incidence of
intravascular catheter placement/migration in parturients
may curtail the routine use of epinephrine in labor
analgesia.

CLINICAL PEARL The main disadvantages with epinephrine

use in labor are its ability to increase the density of motor block and
possible slowing of labor through β2 agonism (after systemic
absorption).

c. Clonidine. Isolated administration of clonidine only

provides moderate analgesia through α2-receptor agonism.
In combination with local anesthetics/opioids, however, it
prolongs the duration of analgesia. It does not increase the
intensity of motor block, unlike epinephrine.40
The main disadvantages of clonidine are sedation and
hemodynamic instability. Its use in the United States is
limited by an FDA “Black Box Warning” in obstetrics.
d. Neostigmine. Neostigmine is an anticholinesterase drug
that enhances analgesia by increasing levels of spinal
acetylcholine. Although preliminary reports in animal and
nonpregnant human studies were encouraging, more
recent work demonstrated that spinal neostigmine 10 μg
failed to augment labor analgesia and also produced
severe nausea.
H. Maintenance of analgesia
The usual methods of maintaining an epidural block for labor
analgesia include intermittent bolus injection, continuous epidural
infusion (CEI), and PCEA with or without background infusion.
Latest advances involve modifications in the traditional PCEA;
these include the use of automated intermittent boluses without a
patient-controlled option, a basal intermittent bolus along with
PCEA, and a computer-integrated PCEA.
1. Intermittent bolus injection
a. Periodic bolus injections (i.e., top-ups) with local
anesthetic, either in response to maternal discomfort or at
regular intervals depending on the duration of action of
the local anesthetic, can provide analgesia throughout
labor.
b. Historically, labor analgesia was provided by intermittent
top-ups, using approximately one-half of the initial
loading dose of 0.25% to 0.5% bupivacaine. This
technique mandates repeated administration of a test dose
to rule out intrathecal or intravascular migration of the
catheter. The major disadvantages of this technique
include maternal dissatisfaction due to lack of timely pain
control, unacceptably dense motor blockade, possibility of
hemodynamic instability with each bolus, and an
increased workload for the anesthesia provider.
c. Low-dose top-ups are inherently safer because less total
drug is employed. Bupivacaine 0.0625% to 0.125% (5 to
10 mL) in combination with fentanyl 2 μg per mL is often
used. Although such a technique may provide effective
analgesia, each bolus is not as long lasting because more
concentrated top-ups are often required for instrumental
vaginal delivery.
d. Some evidence supports the practice of scheduled
intermittent boluses of local anesthetic delivered by a
programmed infusion pump (as opposed to an equivalent
amount of drug delivered as a continuous infusion).
Advantages may include better dermatomal spread and
less total local anesthetic required.41
2. Continuous epidural infusion
 a. CEI is accomplished by administration of a continuous
infusion of a low-dose local anesthetic (with or without an
added opioid) via an infusion pump. Potential advantages
over intermittent physician-administered boluses include
maintenance of more stable levels of analgesia, less risk
of compromising sterility by repeatedly accessing the
epidural catheter, better hemodynamic stability, and
decreased anesthetic workload.
b. A pump with appropriate infusion settings must be
dedicated to the epidural infusion. The infusion tubing
must be labeled and ideally be color-coded and have no
side injection ports to prevent iatrogenic mishaps such as
unintentional injection of medications intended for IV
administration.
c. Appropriate dosing regimens include infusions of
bupivacaine 0.04% to 0.125% combined with a lipophilic
opioid (fentanyl 1 to 2 μg per mL or sufentanil 0.5 μg per
mL) to run at rates of 10 to 15 mL per hour.
d. The patient should be assessed at regular intervals (i.e.,
every 1 to 1.5 hour) for evidence of catheter migration
and adequacy of analgesia.
e. Additional physician-administered top-ups may be
required for second stage of labor, instrumental delivery,
or perineal repair, particularly if very low-dose infusions
are administered.
3. Patient-controlled epidural analgesia
a. A specially programmed infusion pump delivers boluses
of local anesthetic solution on demand from the patient,
analogous to patient-controlled IV administration (patient-
controlled analgesia [PCA]) of opioids. A background
infusion (CEI) is optional.
b. With PCEA, the parturient titrates the dose according to
her needs obviating the problem of interpatient variability.
It also provides psychological comfort because patients
 may feel more in control over the laboring process.
c. PCEA, even without a background infusion, produces a
significant decrease (almost 20%) in the requirement of
anesthesiologist-administered top-ups compared with
CEI. Moreover, it may reduce the total dose of drug
administered and subsequently may reduce the incidence
of motor block.42
d. The addition of a background infusion to PCEA is
controversial. Possible benefits include less requirement
for patient attentiveness to analgesic needs and fewer top-
ups overall. Potential disadvantages include greater total
drug use and probability of motor block. The literature is
equivocal on the relative merits of background infusions.
e. The potential disadvantages with PCEA include errors in
pump programming, cost, and use in unsuitable patients
(e.g., patients with cognitive deficits) and possibility of
nonpatient-initiated boluses. These disadvantages have
not reduced the enthusiasm for PCEA in North America,
where it is widely used.
f. Suitable regimens include bupivacaine/opioid
concentrations similar to those employed in CEI. A bolus
of 3 to 10 mL, a lockout interval of 10 to 20 minutes, and
an optional continuous infusion of 5 to 10 mL per hour
are appropriate. No clear consensus exists in the literature
regarding the optimal program, and it probably does not
matter as long as the patient has access to an adequate
hourly amount of drug mixture. We prefer a continuous
infusion of 6 mL per hour of 0.125% bupivacaine and
fentanyl 2 μg per mL with a 6 mL bolus of the same
solution and a 15-minute lockout interval. Suggested
PCEA regimens are listed in Table 10.6.
 g. A recent advance is the use of programmed intermittent
epidural bolus (PIEB) injection in lieu of the continuous
infusion. Reported advantages of such a technique include
a reduction in the overall local anesthetic consumption,
higher maternal satisfaction, less need for interventions,
lower incidence of motor block, and a decrease in
instrumental deliveries.41,43A recent study, presented at
the 2015 Society for Obstetric Anesthesia and
Perinatology (SOAP) meeting by a group in Seattle, was
unable to demonstrate those reported advantages of PIEB.
In the computer-integrated PCEA,44 patient’s hourly
analgesic needs are analyzed to constantly adjust the basal
infusion rate. So, more thorough studies are required to
clearly identify the advantages of these techniques, if any.

CLINICAL PEARL Latest advances in providing continuous

labor analgesia involve modifications in the traditional PCEA; these
include the use of automated intermittent boluses without a patient-
controlled option, a basal intermittent bolus along with PCEA, and
a computer-integrated PCEA.

4. Maintenance of continuous spinal analgesia

Whether placed intentionally or after an unintentional dural
puncture, analgesia for labor and vaginal delivery may be
successfully maintained by a continuous intrathecal infusion.
Clinical experience with CSE analgesia can be extended to
this form of labor analgesia.
a. The same caveats regarding CEI infusions must be kept in
 mind for CSA, especially safeguards against unintentional
injection of large amounts of local anesthetic appropriate
for epidural dosing or drugs intended for IV
administration.
b. We prefer to initiate analgesia with a standard CSE dose
(e.g., 15 to 25 μg fentanyl and 1 to 2.5 mg bupivacaine).
c. In order to maintain analgesia but avoid excessive sensory
and motor block, lipophilic opioids should generally be
part of a continuous infusion. We use (0.8% to 0.125%
bupivacaine and fentanyl 1 to 2 μg per mL at a rate of 1 to
1.5 mL per hour as a starting infusion rate and disconnect
the PCEA option as a safety measure.
d. Clinician-administered top-ups should generally include
fentanyl or sufentanil in doses one-half to one times those
used during initiation of CSE analgesia, combined with 1
to 2 mg bupivacaine. Use of bupivacaine solutions
without opioid is likely to produce excessive sensory and
motor block.
e. Care must be taken to label the “spinal catheter.” All top-
ups need to be administered with meticulous attention to
sterile technique.

CLINICAL PEARL Care must be taken to label the spinal

catheter. All top-ups need to be administered with meticulous
attention to sterile technique. All caregivers need to be aware of the
spinal catheter.

I. Analgesia for vaginal delivery

Pain during the second stage of labor is transmitted by somatic
nerve fibers that enter the spinal cord at S2–S4. Despite eventual
coverage of sacral segments with most neuraxial techniques,
supplementation of sacral analgesia may occasionally be required
to facilitate a vaginal delivery.
 1. Spontaneous vaginal delivery
a. Continuous infusions (CEI) usually provide adequate
analgesia for delivery if they have been in place for
several hours. More recently initiated infusions and
catheters exhibiting relative “sacral sparing” may benefit
from a perineal “top-up” dose. Although studies provide
no conclusive evidence, administering such a dose in the
sitting/semirecumbent position may provide a rapid onset
of perineal anesthesia while minimizing cephalad sensory
spread. Five to 10 mL of the infusion mix or 10 mL of
0.5% to 1.0% lidocaine with 100 μg fentanyl will usually
suffice to extend the block.
b. PCEA may often be used to extend sacral analgesia by
administering a demand dose while in the semisitting
position. Otherwise, the catheter may be treated as
described for CEI.
c. CSE generally provides superior sacral analgesia earlier in
labor.30 It has been shown to be effective even without
epidural supplementation when administered to
multiparas in advanced labor. Top-ups as described for
CEI are also suitable.
2. Instrumental vaginal delivery
a. Vacuum-assisted delivery can usually be performed with
regimens similar to those used for spontaneous vaginal
delivery.
b. Forceps delivery usually requires dense sacral analgesia.
A perineal top-up administered in the sitting position with
5 to 10 mL lidocaine 2% (with epinephrine if maximum
block is desired), bupivacaine 0.25%, or 2-chloroprocaine
3% will generally provide adequate analgesia without
eliminating maternal expulsive efforts.

CLINICAL PEARL Forceps delivery usually requires dense

sacral analgesia. A perineal top-up administered in the sitting
position with 5 to 10 mL lidocaine 2% (with epinephrine if
maximum block is desired), bupivacaine 0.25%, or 2-
chloroprocaine 3% will generally provide adequate analgesia
without eliminating maternal expulsive efforts.

J. Ambulation during labor (see Table 10.7)

Some obstetric providers and patients believe that allowing

mothers to ambulate may reduce the duration of first stage of
labor. Although carefully performed trials have not supported this
idea, the opportunity for ambulation in labor with neuraxial
analgesia remains a goal in many units.
1. Advantages
a. High maternal satisfaction and sense of autonomy. The
ability to ambulate, even if ambulation is not
accomplished or even attempted, may improve the labor
and birth experience.
b. Possible reduction in the incidence of dystocia by
improving fetal descent through the effect of gravity.
Although commonly asserted, especially by midwives and
the lay labor support community (e.g., doulas),
randomized studies have not confirmed this hypothesis.45
c. May decrease the incidence of deep vein thrombosis
(DVT) in parturients.
 2. Disadvantages
a. Subtle degrees of motor blockade and impaired
proprioception may affect the patient’s sense of balance.
Falls have been reported.
b. Postural hypotension may complicate attempts at
ambulation.
c. Need for another adult to accompany the parturient and
increased workload for the labor and delivery staff
d. More anesthetic interventions may be necessary.
e. Possible increased medicolegal risk

CLINICAL PEARL If patients ambulate during labor, there must

be clear guidelines for range of ambulation: for example, walking to
the bathroom, to the chair, walking in the hallway on labor and
delivery unit.

IV. Side effects and complications

Labor analgesia is generally very safe, and serious complications
(local anesthetic toxicity, infection, neurologic injury, high or total
spinal anesthesia) are extremely rare. More commonly, minor side
effects (e.g., hypotension, pruritus) and complications (e.g., failed or
incomplete block, PDPH) may complicate labor analgesia.
A. Hypotension (defined as systolic blood pressure [SBP] <90 mm
Hg or a decrease of 20% from the baseline)
1. One of the most common side effects of epidural analgesia,
affecting up to 80% of parturients
2. Hypotension occurs with approximately equal frequency
during CSE or immediately after a loading epidural bolus
dose.44
3. The sympathetic blockade induced by neuraxial block causes
peripheral vasodilatation, pooling of venous blood, and
decreased venous return to the heart. This results in a decrease
in maternal cardiac output and blood pressure (BP). Because
 uteroplacental perfusion is proportionate to BP, uncorrected
hypotension decreases uteroplacental perfusion and may
result in nonreassuring fetal status. Other symptoms may
include maternal dizziness, chest heaviness, and nausea.
4. The severity of hypotension can be partially mitigated by
fluid pre- or coloading, careful avoidance of aortocaval
compression, and prophylactic vasopressors.46 However, none
of these maneuvers eliminates hypotension, including fluid
boluses as large as 30 mL per kg and ephedrine doses as large
as up to 30 mg. Large doses of ephedrine can cause reactive
hypertension as well.
5. Hypotension is usually self-limited but requires prompt
treatment if maternal symptoms or fetal distress supervene.
Volume expansion, uterine displacement, and bolus doses of
IV phenylephrine 20 to 40 μg or ephedrine 5 to 10 mg may be
required.

CLINICAL PEARL Severity of hypotension can be partially

mitigated by fluid pre- or coloading but none of these maneuvers
eliminates hypotension, including fluid boluses as large as 30 mL
per kg and ephedrine doses as large as 30 mg.

B. Treatment for pruritus. Pruritus is a common side effect

following intrathecal opioid administration and less commonly,
epidural opioids. The incidence is somewhat dose related,
although even small intrathecal doses of lipophilic opioids cause
some pruritus in most patients. The effect is time-limited (usually
less than 90 minutes) and does not usually require pharmacologic
treatment. When required, we avoid diphenhydramine, which is
likely to sedate the patient. Although the literature is equivocal,
we believe that nalbuphine, 5 to 10 mg, or ondansetron, 8 mg, are
generally effective in reducing the severity of symptoms.
Ondansetron may be effective by occupation of 5-HT3 receptors
 that are stimulated by neuraxial administration of opioids.47
C. Failed analgesia
1. Labor analgesia may be inadequate due to a malpositioned
epidural catheter, subsequent migration after normal
positioning or altered epidural anatomy (e.g., scoliosis, back
surgery). Any of these can prevent uniform spread of the local
anesthetic within the epidural space.
2. A “failed epidural” describes a unilateral or asymmetric
block, a patchy block, a missed segment, or complete absence
of a block. Approximately 5% to 8% of epidurals will exhibit
some imperfection in the block. There is some evidence that
CSE results in fewer block failures.5 However, a recent
systematic review and meta-analysis determined that the risk
of failed conversion of labor epidural analgesia to anesthesia
was increased with an increasing number of top-ups
administered during labor.48
3. An asymmetric block can be managed by topping-up the
epidural with the painful side in a dependent position.
Withdrawing the catheter by 1 to 3 cm may be a prudent
measure if a longer length of the catheter (>5 cm) resides in
the epidural space. A larger volume (5 to 10 mL) of dilute
local anesthetic (0.0625% to 0.125% bupivacaine) solution is
preferred to ensure adequate spread.49
4. Missed segments may be managed in the same way as an
asymmetric block or sometimes by administering fentanyl 50
to 100 μg, usually diluted in normal saline or dilute local
anesthetic.
5. Complete absence of block may be assessed by administration
of 5 to 10 mL of 2% lidocaine (with or without epinephrine).
An absent sensory level 10 to 15 minutes after administration
mandates replacement of the epidural catheter. These
catheters should be considered IV catheters until proven
otherwise.
6. Recurrence of pain after a seemingly successful epidural
 placement may be due to several causes:
a. Displacement of the catheter due to patient movement
b. Disconnection or failure of the epidural maintenance
infusion
c. Migration of the catheter into an epidural vein
d. Changing pattern of painful stimuli: full bladder, descent
of the fetus with sacral stimulation, ruptured uterus, or
placental abruption
e. Sacral sparing
7. If there is any question about whether an epidural catheter can
be used for surgical anesthesia, it should be replaced.

CLINICAL PEARL Risk of failed conversion of labor epidural

analgesia to anesthesia is increased with an increasing number of
top-ups administered during labor.

D. Unintended dural puncture (“wet tap”) (see Chapter 19,

Postdural Puncture Headache)
The incidence of wet tap varies between 1% to 8% 50 and is
inversely related to the experience of the anesthesiologist. PDPH
complicates 50% to 80% of dural punctures with a 17-G epidural
needle. There are two basic strategies for management of dural
puncture: placement of an intrathecal catheter or replacing the
epidural at an alternate interspace. However a randomized study
evaluating both approaches to management, determined that
converting to spinal analgesia does not appear to affect the rate of
PDPH or epidural blood patch.50 Each case must be
individualized (e.g., difficult placement).
1. Intrathecal catheter
a. Advantages
(1) Highly reliable and excellent quality of analgesia
(2) No risk of another wet tap
(3) Reduced incidence of PDPH (controversial)
 b. Disadvantages
(1). Increased risk of introducing meningeal infection
(2). Increased incidence of iatrogenic mishaps from
unintentional injection of medications into the
intrathecal space
2. Repeating the epidural at an alternate interspace
a. Advantages
(1) No special precautions required
(2) Can be used for prophylactic blood patch
b. Disadvantages
(1) Risk of inducing another dural puncture
(2) Possibility of increased transdural flux of local
anesthetics with epidural boluses; doses should be
fractionated and possibly reduced.
(3) Threading of the epidural catheter into the intrathecal
space
E. Back pain
Forty percent of postpartum women will experience lower back
pain, regardless of choice of neuraxial or other analgesia. Older
studies linking epidural analgesia to back pain probably suffered
from recall bias because they relied on mail-in postpartum
questionnaires. Prospective studies have consistently found no
relationship.51
F. Excessive motor block, subdural, and high/total spinal block
The Serious Complication Repository Project of the SOAP
reported that high neuraxial block, respiratory arrest in labor and
delivery, and unrecognized spinal catheters were the most
frequently reported serious complications in more than 257,000
anesthetics over a 5-year study period.52 In the study, the
incidence of total spinal anesthesia after neuraxial blockade is 1
in 4,336. Risk factors for high block included obesity and spinal
anesthesia after failed epidural.
1. Motor block is generally less common with modern dilute
epidural infusions than in the past, but it may still complicate
 blocks in which multiple boluses have been given. Excessive
motor block can be managed by either decreasing or
discontinuing the epidural infusion. When PCEA is used, an
attractive option is to discontinue the background infusion
while allowing demand boluses, which allows the parturient
to prevent excessive regression of the block.
2. Subdural block can occur when the catheter is inadvertently
threaded between the dura and the arachnoid membrane. It
presents as a slow-onset, asymmetric, and patchy block that
may include cervical dermatomes and cause Horner’s
syndrome. Sparing of motor fibers to the lower extremities
may help differentiate a subdural block from a total spinal.
Apart from ineffective analgesia, a subdural block can
deteriorate to a high/total spinal with bolus administration due
to rupture of the arachnoid. Both these factors necessitate
prompt replacement of subdural catheters.
3. High spinal block or total spinal may occur due to
unidentified subarachnoid placement or due to subsequent
migration into the intrathecal space. Aspirating the catheter
and administering a test dose each time the catheter is bolused
can minimize the risk of a high spinal block. Treatment of
high or total spinal consists of respiratory and circulatory
support.
G. Urinary retention. Urinary retention commonly occurs during
epidural analgesia, and catheterization is routine on many labor
units. Very dilute infusions reduce the need for catheterization.
Postpartum urinary retention following regression of the epidural
block may be related to obstetric factors rather than the
anesthetic.53
H. Maternal hyperthermia. Observational and randomized studies
confirm that women with epidurals develop fever more often than
women without them. The exact mechanism by which this
phenomenon occurs has yet to be elucidated. Thermoregulatory
imbalance between heat producing and heat dissipating
 mechanisms, suppressive effect of systemic opioids in women
without epidurals, and inflammatory responses have all been
suggested as possible mechanisms. Current evidence favors the
latter as the dominant mechanism.54
I. Fetal heart rate abnormalities. Both epidural and CSE
techniques are associated with alterations in the FHR tracing
(decelerations, decrease in baseline) in approximately 6% to 8%
of cases. Severe bradycardia, but not emergency CD, is more
common with the CSE versus conventional epidural technique.11
The mechanisms responsible for FHR changes are not clear, but
increased uterine tone and transient uterine vasoconstriction, both
due to alterations in maternal catecholamines, are the most likely.
If there is either a tetanic uterine contraction or uterine
tachysystole after CSE or plain epidural analgesia and there is a
profound decrease in FHR, then sublingual nitroglycerin should
be used immediately. It should be readily available on labor and
delivery carts, and obstetric nurses and midwifes should be made
aware of the treatment algorithm for profound fetal bradycardia in
the presence of increased uterine tone after CSE.
J. Accidental IV of local anesthetic
The incidence of systemic local anesthetic toxicity (high blood
concentrations of local anesthetic) after obstetric lumbar epidural
analgesia is less than 1 in 250,000.52
1. This may occur if the catheter has migrated into an epidural
vein or if the catheter lies in close proximity to a punctured
epidural vein. The use of wire-reinforced flexible epidural
catheters has been shown to reduce the incidence of
intravascular placement and theoretically may reduce
intravascular migration.
2. Initial symptoms relate to the CNS: Dizziness, tinnitus,
perioral paresthesia, and complaints of restlessness or sudden
general malaise should alert the anesthesiologist at the time of
bolus administration. Seizures and loss of consciousness are
at the upper end of the continuum of CNS toxicity.
 3. Continued administration results in cardiovascular toxicity
characterized by cardiac dysrhythmias and hypotension
eventually causing cardiac arrest. Bupivacaine is the most
cardiotoxic of the commonly used local anesthetics in
obstetrics.
4. Treatment consists of supportive care of respiratory and
cardiovascular systems. Cardiopulmonary resuscitation (CPR)
and advanced cardiac life support (ACLS) protocols may be
needed. The use of an intravascular bolus of a lipid solution
(Intralipid) at a dose of 1 mL per kg of a 20% solution has
been shown to reverse cardiovascular toxicity in animal
models and in case reports in humans.55
K. Meningitis
Meningitis is one of the most serious neurologic complications
associated with neuraxial anesthesia. Although the overall risk
appears to be low, there are reports in the literature of this
potentially devastating complication.56 Bacterial meningitis is
probably the most common source of infection. The SOAP
Serious Complication Repository found the incidence of epidural
abscess or meningitis was 1 in 62,866 .52 Possible infectious
sources include:
1. Blood from the dural puncture
2. The anesthesiologist’s oral flora
3. Vaginal delivery
4. Manual removal of the placenta
5. Bacteremia
Fever, headache, photophobia, nausea, vomiting, and neck
stiffness are typical symptoms. The diagnosis can be mistaken
for PDPH but when the symptoms are accompanied by
confusion and/or lethargy, a diagnosis of meningitis must be
entertained.56 A full recovery can be expected with early
diagnosis and intervention.
L. Epidural hematoma and abscess. These devastating
complications occur with extremely low frequency, on the order
 of 1:100,000 cases. Symptoms of both include rapidly progressive
neurologic deficits; abscesses also present with severe back pain
and fever. Risk factors for hematoma include defects of
coagulation and possibly multiple attempts at epidural placement.
Risk factors for abscess are generally related to lapses in aseptic
technique. Treatment of both is aimed at rapid diagnosis with
magnetic resonance imaging (MRI), neurosurgical consultation,
and expeditious surgical decompression. In cases of hematoma
and abscess without spinal compression, it may be appropriate to
manage medically but only after a neurosurgical consultation (see
Chapter 20).
M. Neurologic deficits. Neurologic deficits after childbirth have
many causes, and all these events may occur spontaneously or
because of childbirth.57 The ASA32 Closed Claims Project
analysis of liability claims notes that the incidence of claims for
nerve injury has increased in their most recent review and is now
the most common cause of liability in obstetric anesthesia.
Serious neurologic injury occurs with an incidence of 1:35,923.52
Most postpartum neurologic complications are caused by nerve
compression during delivery, and both anesthesiologists and
obstetricians should be able to recognize common manifestations
of these neuropathies. One study suggests that transient
neurologic injuries are common and usually resolve within 1
year.58 In the study, few could clearly be linked unequivocally
with the epidural. They occurred at a rate of 1 in 4,300 women
(see Chapter 20).

REFERENCES
1. Traynor AJ, Tran ZV, Aragon M, et al. Obstetric anesthesia workforce survey: 30-year update. Anesth
Analg. In press.
2. Melzack R. The myth of painless childbirth (the John J. Bonica lecture). Pain. 1984;19:321–337.
3. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 295: pain
relief during labor. Obstet Gynecol. 2004;104:213.
4. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 339: analgesia
and cesarean delivery rates. Obstet Gynecol. 2006;107:1487–1488.
 5. Pan PH, Bogard TD, Owen MD. Incidence and characteristics of failures in obstetric neuraxial
analgesia and anesthesia: a retrospective analysis of 19,259 deliveries. Int J Obstet Anesth.
2004;13:227–233.
6. Gambling D, Berkowitz J, Farrell TR, et al. A randomized controlled comparison of epidural analgesia
and combined spinal-epidural analgesia in a private practice setting: pain scores during first and
second stages of labor and at delivery. Anesth Analg. 2013;116:636–643.
7. Wong CA, Scavone BM, Peaceman AM, et al. The risk of cesarean delivery with neuraxial analgesia
given early versus late in labor. N Engl J Med. 2005;352:655–665.
8. Tsen LC, Thue B, Datta S, et al. Is combined spinal-epidural analgesia associated with more rapid
cervical dilation in nulliparous patients when compared with conventional epidural analgesia?
Anesthesiology. 1999;91:920–925.
9. Simmons SW, Taghizadeh N, Dennis AT, et al. Combined spinal-epidural versus epidural analgesia in
labour. Cochrane Database Syst Rev. 2012;(10):CD003401.
10. Abouleish A, Abouleish E, Camann W. Combined spinal-epidural analgesia in advanced labour. Can J
Anaesth. 1994;41: 575–578.
11. Mardirosoff C, Dumont L, Boulvain M, et al. Fetal bradycardia due to intrathecal opioids for labour
analgesia: a systematic review. BJOG. 2002;109:274–281.
12. Patel NP, El-Wahab N, Fernando R, et al. Fetal effects of combined spinal-epidural vs epidural labour
analgesia: a prospective, randomised double-blind study. Anaesthesia. 2014;69:458–467.
13. Gambling DR, Bender M, Faron S, et al. Prophylactic intravenous ephedrine to minimize fetal
bradycardia after combined spinal-epidural labour analgesia: a randomized controlled study. Can J
Anaesth. 2015;62:1201–1208.
14. American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Practice guidelines for
obstetric anesthesia: an updated report by the American Society of Anesthesiologists Task Force on
Obstetric Anesthesia. Anesthesiology. 2007;106:843–863.
15. Kodali BS, Chandrasekhar S, Bulich LN, et al. Airway changes during labor and delivery.
Anesthesiology. 2008;108:357–362.
16. Harney D, Moran CA, Whitty R, et al. Influence of posture on the incidence of vein cannulation
during epidural catheter placement. Eur J Anaesthesiol. 2005;22:103–106.
17. Hebl JR. The importance and implications of aseptic techniques during regional anesthesia. Reg
Anesth Pain Med. 2006;31:311–323.
18. Broadbent CR, Maxwell WB, Ferrie R, et al. Ability of anaesthetists to identify a marked lumbar
interspace. Anaesthesia. 2000;55:1122–1126.
19. Chakraverty R, Pynsent P, Isaacs K. Which spinal levels are identified by palpation of the iliac crests
and the posterior superior iliac spines? J Anat. 2007;210:232–236.
20. Sahota JS, Carvalho JC, Balki M, et al. Ultrasound estimates for midline epidural punctures in the
obese parturient: paramedian sagittal oblique is comparable to transverse median plane. Anesth Analg.
2013;116:829–835.
21. Shenouda PE, Cunningham BJ. Assessing the superiority of saline versus air for use in the epidural
loss of resistance technique: a literature review. Reg Anesth Pain Med. 2003;28:48–53.
22. Carabuena JM, Mitani AM, Liu X, et al. The learning curve associated with the epidural technique
using the Episure AutoDetect™ versus conventional glass syringe: an open-label, randomized,
controlled, crossover trial of experienced anesthesiologists in obstetric patients. Anesth Analg.
2013;116:145–154.
23. Hollway TE, Telford RJ. Observations on deliberate dural puncture with a Tuohy needle: depth
measurements. Anaesthesia. 1991;46:722–724.
24. Jaime F, Mandell GL, Vallejo MC, et al. Uniport soft-tip, open-ended catheters versus multiport firm-
 tipped close-ended catheters for epidural labor analgesia: a quality assurance study. J Clin Anesth.
2000;12:89–93.
25. Segal S, Eappen S, Datta S. Superiority of multi-orifice over single-orifice epidural catheters for labor
analgesia and cesarean delivery. J Clin Anesth. 1997;9:109–112.
26. Beilin Y, Bernstein HH, Zucker-Pinchoff B. The optimal distance that a multiorifice epidural catheter
should be threaded into the epidural space. Anesth Analg. 1995;81:301–304.
27. Campbell DC, Camann WR, Datta S. The addition of bupivacaine to intrathecal sufentanil for labor
analgesia. Anesth Analg. 1995;81:305–309.
28. Hamilton CL, Riley ET, Cohen SE. Changes in the position of epidural catheters associated with
patient movement. Anesthesiology. 1997;86:778–784.
29. Arkoosh VA, Palmer CM, Yun EM, et al. A randomized, double-masked, multicenter comparison of
the safety of continuous intrathecal labor analgesia using a 28-gauge catheter versus continuous
epidural labor analgesia. Anesthesiology. 2008;108:286–298.
30. Cappiello E, O’Rourke N, Segal S, et al. A randomized trial of dural puncture epidural technique
compared with the standard epidural technique for labor analgesia. Anesth Analg. 2008;107:1646–
1651.
31. Thomas JA, Pan PH, Harris LC, et al. Dural puncture with a 27-gauge Whitacre needle as part of a
combined spinal-epidural technique does not improve labor epidural catheter function. Anesthesiology.
2005;103:1046–1051.
32. Davies JM, Posner KL, Lee LA, et al. Liability associated with obstetric anesthesia: a closed claims
analysis. Anesthesiology. 2009;110:131–139.
33. Guay J. The epidural test dose: a review. Anesth Analg. 2006;102:921–929.
34. Leighton BL, Norris MC, Sosis M, et al. Limitations of epinephrine as a marker of intravascular
injection in laboring women. Anesthesiology. 1987;66:688–691.
35. Breen TW, Shapiro T, Glass B, et al. Epidural anesthesia for labor in an ambulatory patient. Anesth
Analg. 1993;77:919–924.
36. Lyons G, Columb M, Hawthorne L, et al. Extradural pain relief in labour: bupivacaine sparing by
extradural fentanyl is dose dependent. Br J Anaesth. 1997;78:493–497.
37. Panni MK, Segal S. Local anesthetic requirements are greater in dystocia than in normal labor.
Anesthesiology. 2003;98:957–963.
38. Polley LS, Columb MO, Lyons G, et al. The effect of epidural fentanyl on the minimum local
analgesic concentration of epidural chloroprocaine in labor. Anesth Analg. 1996;83:987–990.
39. Polley LS, Columb MO, Naughton NN, et al. Relative analgesic potencies of ropivacaine and
bupivacaine for epidural analgesia in labor: implications for therapeutic indexes. Anesthesiology.
1999;90:944–950.
40. Roelants F, Lavand’homme PM, Mercier-Fuzier V. Epidural administration of neostigmine and
clonidine to induce labor analgesia: evaluation of efficacy and local anesthetic-sparing effect.
Anesthesiology. 2005;102:1205–1210.
41. Wong CA, Ratliff JT, Sullivan JT, et al. A randomized comparison of programmed intermittent
epidural bolus with continuous epidural infusion for labor analgesia. Anesth Analg. 2006;102:904–
909.
42. van der Vyver M, Halpern S, Joseph G. Patient-controlled epidural analgesia versus continuous
infusion for labour analgesia: a meta-analysis. Br J Anaesth. 2002;89:459–465.
43. Capogna G, Camorcia M, Stirparo S, et al. Programmed intermittent epidural bolus versus continuous
epidural infusion for labor analgesia: the effects on maternal motor function and labor outcome. A
randomized double-blind study in nulliparous women. Anesth Analg. 2011;113:826–831.
44. Lim Y, Sia AT, Ocampo CE. Comparison of computer integrated patient controlled epidural analgesia
 vs. conventional patient controlled epidural analgesia for pain relief in labour. Anaesthesia.
2006;61:339–344.
45. Vallejo MC, Firestone LL, Mandell GL, et al. Effect of epidural analgesia with ambulation on labor
duration. Anesthesiology. 2001;95:857–861.
46. Cyna AM, Andrew M, Emmett RS, et al. Techniques for preventing hypotension during spinal
anaesthesia for caesarean section. Cochrane Database Syst Rev. 2006;(4):CD002251.
47. Iatrou CA, Dragoumanis CK, Vogiatzaki TD, et al. Prophylactic intravenous ondansetron and
dolasetron in intrathecal morphine-induced pruritus: a randomized, double-blinded, placebo-controlled
study. Anesth Analg. 2005;101:1516–1520.
48. Bauer ME, Kountanis JA, Tsen LC, et al. Risk factors for failed conversion of labor epidural analgesia
to cesarean delivery anesthesia: a systematic review and meta-analysis of observational trials. Int J
Obstet Anesth. 2012;21:294–309.
49. Beilin Y, Zahn J, Bernstein HH, et al. Treatment of incomplete analgesia after placement of an
epidural catheter and administration of local anesthetic for women in labor. Anesthesiology.
1998;88:1502–1506.
50. Russell IF. A prospective controlled study of continuous spinal analgesia versus repeat epidural
analgesia after accidental dural puncture in labour. Int J Obstet Anesth. 2012;21:7–16.
51. Howell CJ, Dean T, Lucking L, et al. Randomised study of long term outcome after epidural versus
non-epidural analgesia during labour. BMJ. 2002;325:357.
52. D’Angelo R, Smiley RM, Riley E, et al. Serious complications related to obstetric anesthesia: the
Serious Complication Repository project of the Society for Obstetric Anesthesia and Perinatology.
Anesthesiology. 2014;120:1505–1512.
53. Liang CC, Wong SY, Tsay PT, et al. The effect of epidural analgesia on postpartum urinary retention in
women who deliver vaginally. Int J Obstet Anesth. 2002;11:164–169.
54. Goetzl L, Zighelboim I, Badell M, et al. Maternal corticosteroids to prevent intrauterine exposure to
hyperthermia and inflammation: a randomized, double-blind, placebo-controlled trial. Am J Obstet
Gynecol. 2006;195:1031–1037.
55. Weinberg G. Lipid rescue resuscitation from local anaesthetic cardiac toxicity. Toxicol Rev.
2006;25:139–145.
56. Baer ET. Post-dural puncture bacterial meningitis. Anesthesiology. 2006;105:381–393.
57. Wong CA. Nerve injuries after neuraxial anesthesia and their medicolegal implications. Best Pract Res
Clin Obstet Gynaecol. 2010;24:367–381.
58. Ruppen W, Derry S, McQuay H, et al. Incidence of epidural hematoma, infection, and neurologic
injury in obstetric patients with epidural analgesia/anesthesia. Anesthesiology. 2006;105:394–399.
 Ultrasound and Echocardiographic Techniques in
Obstetric Anesthesia
Laurie A. Chalifoux and John T. Sullivan

I. Introduction
II. Focused cardiac ultrasound
A. Introduction
B. Techniques
C. Clinical applications
D. FoCUS training, certification, and program maintenance
III. Pulmonary ultrasound
A. Introduction
B. Technique
C. Applications
IV. Ultrasound-guided neuraxial anesthesia
A. Introduction
B. Technique
C. Applications
V. Ultrasound-guided regional anesthesia (transversus abdominis
plane block)
A. Introduction
B. Technique
C. Application
VI. Intracranial pressure measurement (optic nerve sheath diameter)
A. Introduction
 B. Technique
C. Applications
VII. Gastric volume measurement
A. Introduction
B. Technique
C. Applications
VIII. Pelvic/abdominal ultrasound
A. Introduction
B. Technique
C. Applications
IX. Airway examination
A. Introduction
B. Technique
C. Applications
X. Lower extremity vein ultrasound
A. Introduction
B. Technique
C. Applications

KEYPOINTS
1. Applications of point of care ultrasound are rapidly expanding in
obstetric management.
2. Focused cardiac ultrasound can be used as a powerful extension of the
physical examination to evaluate a variety of clinical conditions including
hypotension, dyspnea, and cardiac arrest.
3. Pulmonary ultrasound can serve as a rapid and more sensitive measure of
lung water and pneumothorax than radiography, which can be used to
guide management.
4. Ultrasound-guided neuraxial blockade may improve efficiency of block
placement and has applications for training.
 5. Gastric ultrasound can be used to qualitatively assess gastric volume and
content, which may inform timing of decisions for nonelective obstetric
procedures.

I. Introduction
A. The application of ultrasound technology is rapidly changing the
practice of medicine in providing a safe, noninvasive tool to aid
in diagnosis, guide therapy, and assist with procedures.
B. Reduced costs and increased portability have led to increased
point of care applications of ultrasound.
C. Ultrasound has a long track record of safe use including in the
first trimester of pregnancy.1
D. The two principal skills required for point of care ultrasound are
image acquisition and interpretation. There is general agreement
that point of care ultrasound is valuable for qualitative assessment
for the purpose of rapidly narrowing differential diagnoses. There
is more debate about the appropriateness of quantitative
assessment in the domain of point of care ultrasound.
E. Ultrasound measurements have generally been demonstrated to be
accurate and reproducible.2 Point of care ultrasound is often
performed in less than ideal conditions (dynamic clinical
environment, patient movement, less training, and oversight) that
may compromise some quantitative validity.
F. With expansion of the use of ultrasound, there are challenges in
providing training to a broader group of users while ensuring
adequate quality of application.
G. Elements of a quality point of care ultrasound program include
using a structured approach to examination, documenting findings
in the medical record, storing images and videos, and maintaining
a quality assurance process.3
H. Most ultrasound machines have standard features to adjust gain,
scan depth, freeze images, and conduct basic measurements.
Additional available features include time-motion imaging (M-
 mode), color Doppler, and cardiac calculations.
I. In selecting ultrasound probes, it is important to understand the
relationship between frequency and image granularity/depth of
penetration. Deeper structures (>6 cm depth, e.g., abdomen and
chest) require low frequency ultrasound (2 to 5 MHz); however,
some imaging quality is sacrificed. Superficial structures (<6 cm
depth, e.g., pleura, peripheral nerves) can be imaged with higher
frequency ultrasound (5 to 8 MHz), resulting in sharp imaging.4
Choose an ultrasound probe based on intended structures to be
imaged (see Table 11.1).

II. Focused cardiac ultrasound

A. Introduction
1. Hemodynamic monitoring of the parturient, particularly those
with comorbidities or who are critically ill, is evolving
rapidly.
2. Changes in available technology, as well as perceptions of
complications and limited benefits with regard to outcomes
using invasive monitoring,5 have led to the growth of
ultrasound technology for hemodynamic monitoring.6
3. Cardiac ultrasonography as a diagnostic tool is particularly
well-suited to the pregnant woman.
a. Women are generally comfortable with ultrasound
examinations of their fetus throughout pregnancy.
b. The maternal anatomic changes of pregnancy are also
 favorable for cardiac ultrasound, with the gravid uterus
displacing the heart cephalad and laterally, bringing the
heart closer to the chest wall.
c. Parturients are often optimally positioned in left uterine
displacement or left lateral position, facilitating
parasternal and apical views.
d. Additionally, parturients are usually conscious and
mobile, making invasive monitoring less desirable.
4. Focused cardiac ultrasound (FoCUS) refers to the use of
ultrasound as an adjunct to physical examination to answer
specific clinical questions.7
5. FoCUS is unique among hemodynamic monitoring modalities
available to the clinician at bedside in providing
comprehensive anatomic and physiologic information that can
be obtained in real time and repeated to observe changes in
hemodynamics and responses to therapy.
6. FoCUS methodology involves point of care image acquisition
and interpretation by a physician with specific training, in
contrast to comprehensive echocardiography examination in
which image acquisition is obtained by an ultrasonographer
(i.e., technician) and interpretation performed by an
echocardiographer (i.e., specialist physician).
7. FoCUS combines image acquisition and interpretation skills
at the bedside, albeit with more limited expertise in both
domains. Anesthesiologists are particularly well suited to
adopt this technology given prevalent ultrasound skills in the
domains of vascular access and peripheral nerve blockade as
well as the cardiac image acquisition and interpretation skills
used for transesophageal echocardiography.

CLINICAL PEARL FoCUS provides real-time comprehensive

anatomic and physiologic information. It can be repeated to observe
changes in hemodynamics and responses to therapy.
B. Techniques
1. Basic FoCUS examination views. FoCUS incorporates
examination views commonly used in comprehensive
transthoracic echocardiography (TTE). Each of these views
provides different challenges and diagnostic advantages in the
parturient (see Fig. 11.1).

a. Subcostal long axis (SLAX)

b. Subcostal inferior vena cava (SIVC)
c. Parasternal long axis (PLAX)
d. Parasternal short axis (PSAX)
e. Apical 4-chamber (A4CH)
2. Intravascular volume
a. Intravascular volume assessment is a core application of
FoCUS.
b. Left ventricular end-diastolic diameter and/or area can
 easily be measured and compared using the basic FoCUS
views, including PSAX, PLAX, and A4CH to
demonstrate cardiac filling volumes or preload.
c. Normal values for left ventricular end-diastolic diameter
have been reported in pregnancy (3.0 to 5.6 cm).8
d. The SIVC view has also been shown to approximate
intravascular volume status.
e. Qualitatively, hypovolemia is associated with a
progressive narrowing of the IVC diameter and ultimately
collapse of >50% during inspiration with spontaneous
ventilation (see Fig. 11.2 and Table 11.2).

f. Obtaining the SIVC view can be challenging at term due

to uterine fundal height. This approach may be more
reliable in the postpartum setting.
 g. Regardless of the selected approach, the ability to rapidly
estimate volume status in the acute management of a
variety of clinical situations can be very valuable in
directing care.
h. Qualitative assessment of high or low intracardiac
volumes can guide the clinician in fluid management,
transfusion, or diuresis, whereas serial examinations can
serve to assess the response to treatment.
i. Estimations of right ventricular volume can be conducted
qualitatively using any cardiac view.
j. The A4CH provides the best perspective to compare right
and left ventricular size side by side.
k. In pathologic situations (acute embolism, pulmonary
hypertension, right heart failure), left and right ventricle
chamber sizes may equalize, the cardiac apex may
become shared, and the normal left to right
interventricular septal bowing may flatten.

CLINICAL PEARL FoCUS can be used to rapidly estimate

volume status in the acute management of a variety of clinical
situations and be very valuable in directing care.

3. Contractility
a. Biventricular systolic function can be determined
qualitatively using any cardiac view, but the parasternal
views are the most accessible in the pregnant patient.
b. Using the PSAX view, contractility of the concentric left
ventricle can be qualitatively assessed rapidly.
c. The PLAX provides another option for assessing
contractility including opportunities for more quantitative
measurements using ejection fraction calculations.
4. FoCUS protocols
a. A systematic approach to the FoCUS examination has
 been advocated to increase its accuracy and improve its
diagnostic capability.3
b. Several specific protocols and algorithms have been
developed for the peripartum patient, although no
individual protocol has been demonstrated to be
diagnostically superior or associated with improved
clinical outcomes.
c. Two commonly referenced protocols are the FoCUS
assessed transthoracic echocardiography (FATE)9 and
rapid obstetric screening echocardiography (ROSE).10
d. FATE was originally developed for critical care
application but has been adapted to a wide range of
clinical situations.9
e. The FATE examination includes the following steps: (1)
rule out obvious pathology, (2) assess wall thickness and
dimension of cardiac chamber, (3) assess contractility, (4)
assess pleura, and (5) relate these findings to the clinical
situation.9,11
f. Four basic views are utilized for FATE: SLAX, A4CH,
PSAX, and PLSX, with a basic pleural examination,
making FATE relatively simple and easy to learn.9,11
g. The ROSE scan was the first published FoCUS protocol
adapted to pregnant women.
h. The ROSE protocol incorporates qualitative and
quantitative evaluations using PSAX, PLAX, A4CH, and
A5CH views. The apical 5-chamber view (not shown in
Fig. 11.1) is a more anterior 4-chamber scan that includes
the left ventricular outflow tract.
i. The ROSE protocol also includes more advanced
quantitative elements of echocardiography such as cardiac
output, ventricular regional wall motion, valve
interrogation, and diastolic function that have been
deemed outside of the scope of basic FoCUS.3
C. Clinical applications
1. Hypotension
a. Unexplained hypotension is common in obstetric
anesthetic practice, and diagnosis can be difficult
considering the prevalence of both neuraxial anesthesia
and hemorrhage.
b. In other clinical domains, the use of FoCUS has been
shown to rapidly narrow broad differential diagnoses12
and reduce inappropriate therapy (e.g., fluid
administration in congestive heart failure [CHF])13 in
patients who are hypotensive.
c. One study of 184 patients presenting with nontraumatic,
undifferentiated hypotension were randomized to receive
early versus delayed “goal-directed cardiac ultrasound”
(i.e., FoCUS). Physicians who utilized FoCUS were able
to significantly narrow their differential diagnoses (see
Fig. 11.3) and were also more likely to choose the correct
final diagnosis as “most likely” on the differential list.12

d. In another randomized controlled trial, 240 hypotensive

 or tachycardic individuals were randomized to receive
either FoCUS in their primary trauma survey or standard
initial management (no FoCUS examination) in the
emergency department.13 They demonstrated reduced
intravenous fluid administration, shorter interval to the
operating room, and increased intensive care unit (ICU)
admission rate (80% vs. 67%, P = 0.04) in the group that
incorporated FoCUS into management.
e. In the parturient, the differential diagnosis for hypotension
is broad, ranging from hemorrhage to aortocaval
compression to embolic events. The unique
hemodynamics of the peripartum period also result in an
increased risk of rarer cardiovascular diseases such as
cardiomyopathy, myocardial infarction, and aortic
dissection.8

CLINICAL PEARL In some clinical domains, the use of FoCUS

has been shown to rapidly narrow broad differential diagnoses and
reduce inappropriate therapy (e.g., fluid administration in CHF) in
patients who are hypotensive.

2. Dyspnea
a. Symptoms of shortness of breath, tachypnea, oxygen
desaturation, or auscultative findings, alone or in
combination, are common in pregnancy or immediately
postpartum. FoCUS, preferably in combination with lung
ultrasound, may assist diagnosis and management.
b. FoCUS has been recommended as a first-line diagnostic
intervention for the pregnant patient with shortness of
breath or pulmonary edema.14
c. Differentiating pulmonary from cardiogenic pathology
may be of particular value. Qualitative, side-by-side
evaluation of left- and right-sided cardiac systolic
 function and filling volumes in this setting is useful to
rule out some diagnoses related to volume overload or
cardiac failure or diminish the likelihood of others such as
embolism.

CLINICAL PEARL FoCUS has been recommended as a first-

line diagnostic intervention for the pregnant patient with shortness
of breath or pulmonary edema.

3. Chest pain
a. There may be a limited role for FoCUS in the setting of
chest pain in pregnancy. As an adjunct to physical
examination, FoCUS can provide a rapid screening tool to
identify some rare, life-threatening causes such as
myocardial ischemia or infarction, pleural or pericardial
effusions, right ventricular strain associated with
pulmonary embolism, or aortic dissection.15
b. Comprehensive echocardiography is an American Society
of Echocardiography class I recommendation to evaluate
chest pain when electrocardiograms (the diagnostic gold
standard) are inconclusive.16 However, assessment of
segmental wall motion abnormalities is an advanced
echocardiographic skill and probably falls outside the
scope of FoCUS.3

CLINICAL PEARL Echocardiography is recommended to

evaluate chest pain when electrocardiograms (the diagnostic gold
standard) are inconclusive.

4. Cardiac arrest
a. Cardiac arrest in pregnancy occurs at a rate of
approximately 1 in 12,000 admissions,17 with the most
common etiologies being hemorrhage, heart failure,
 embolism, and sepsis.
b. FoCUS offers potential diagnostic and therapeutic
advantages in managing some of these conditions.
c. There is also evidence suggesting that FoCUS may aid
resuscitation management post-arrest in nonpregnant
patients by detecting potentially reversible mechanical
causes of cardiac arrest (e.g., profound hypovolemia,
embolism, tension pneumothorax, or tamponade) as well
as confirming cardiac standstill.
d. The subcostal 4-chamber view can be initiated during
advanced cardiac life support (ACLS) chest
compressions, with higher quality images acquired during
brief pauses to confirm pulses.
e. The use of FoCUS during cardiac arrest changes
management, is more accurate than physical examination
or electrocardiography in determining mechanical cardiac
function, and may facilitate better outcomes; however, its
use has not yet been shown to actually improve
outcomes.3

CLINICAL PEARL The use of FoCUS during cardiac arrest

changes management, is more accurate than physical examination
or electrocardiography in determining mechanical cardiac function,
and may facilitate better outcomes; however, its use has not yet
been shown to actually improve outcomes.

5. Preeclampsia and other potential future applications of

FoCUS
a. The use of FoCUS in obstetrics is still in a development
phase. Published reports have followed a pattern of proof
of feasibility,10 case reports of applications that redirected
care,8 and observational trials in high-risk patients such as
those with preeclampsia.18
b. The greatest opportunity in obstetrics and other domains
where FoCUS is being employed will be to link
applications to improved clinical outcomes.
c. Preeclampsia is an area with promise for potential
application of FoCUS. Hypertensive disorders of
pregnancy are important causes of maternal and fetal
morbidity and mortality affecting up to 10% of
pregnancies worldwide.19 The incidence has increased by
up to 30% over the past decade20 due to advanced
maternal age, increased use of alternative reproductive
techniques, along with prepregnancy comorbidities such
as obesity, diabetes, metabolic syndrome, and chronic
hypertension.21
d. The majority of maternal deaths from hypertensive
disorders are thought to be preventable,22 and
multidisciplinary groups have called for coordinated
efforts to improve outcomes.23
e. Reported hemodynamic observations have been
conflicting in women with preeclampsia, likely due to the
heterogeneity in the disease itself, as well as varied
research study designs, patient characteristics, and
presence or absence of therapeutic interventions.
f. Due to the heterogeneity of observed cardiovascular
dynamics of preeclampsia, the role of FoCUS in this
population may be best suited for early screening and
serial examination throughout the peripartum period.
g. Pulmonary edema, a major cause of ICU admission and
death in preeclampsia,24 could perhaps be reduced with
careful monitoring using FoCUS and timely therapeutic
interventions.
h. Diastolic dysfunction along with low colloid osmotic
pressure and increased intravascular hydrostatic pressure
are likely etiologies for pulmonary edema in
preeclampsia.24
 i. Although pushing the boundaries of the scope of FoCUS,
risk-stratifying patients by presence of diastolic
dysfunction may redirect management in high-risk
patients.
j. An important additional part of this evaluation includes
the use of pulmonary ultrasound to determine the
presence and degree of lung water (see “Dyspnea”
section). By employing this relatively simple lung
ultrasound technique in addition to FoCUS, clinicians can
further tailor intra- or postpartum fluid management
before the onset of acute hypoxia from pulmonary
edema.25
D. FoCUS training, certification, and program maintenance
It is unclear what optimal FoCUS skills training encompasses,
and this is an evolving field. The American Society of
Echocardiography has outlined optimal elements of this training,
which should include didactic training, hands-on imaging in
humans, and image interpretation experience.7 Many practitioners
are acquiring the skill set by taking one of the many established
courses in combination with local mentoring and guided practice.
The skill is likely best developed in an environment of
multidisciplinary collaboration and an established quality
assurance program. At the time of this publication, there is no
board certification process for FoCUS.

CLINICAL PEARL The majority of maternal deaths from

hypertensive disorders are thought to be preventable, and
multidisciplinary groups have called for coordinated efforts to
improve outcomes.

III. Pulmonary ultrasound

A. Introduction
1. The pulmonary ultrasound examination is relatively simple to
 perform and provides a sensitive and specific tool for
diagnosing pulmonary pathology including pleural effusions,
pulmonary edema, and pneumothorax.26
B. Technique
1. A high frequency rectilinear probe optimizes imaging of the
lung, although a low frequency, curvilinear probe can also
provide adequate imaging.27
2. The probe should be oriented cephalad to caudad and centered
over an appropriate intercostal space.
3. The anatomy of interest includes dependent lung parenchyma
if edema is being considered (e.g., midaxillary line in the
supine patient)28 or the nondependent pleural surfaces for
diagnosing pneumothoraces (e.g., midclavicular line in the
supine patient).29
4. Imaging at a depth of several centimeters is sufficient (enough
distance to traverse subcutaneous tissue and include pleura
and a representative sample of lung parenchyma).
5. M-mode (time-based imaging) may be useful as an additional
tool to assess the pleura and lung parenchyma to confirm
pneumothoraces.29
6. Lung imaging is focused on the parietal-visceral pleura
interface. The probe should be centered within an intercostal
space such that hypoechogenic rib shadows are evident
laterally.
7. Normal lung findings including hyperechogenic pleura and
“A line” reverberations visible over the lung parenchyma
parallel to the pleura, repeated with progressively decreasing
intensity at fixed intervals (see Fig. 11.4).
8. Moving ultrasound images of normal pleura demonstrate lung
sliding, specifically the movement of the visceral pleura along
the parietal pleura (zoom function may be valuable).
9. M-mode imaging presents linear pulmonary ultrasound
signals (y-axis) represented over time as a second dimension
(x-axis) and can be used to highlight the presence or absence
of lung sliding. A normal image has been described as
“seashore sign” with the granular “sand” (image distal to
probe) representing pulmonary parenchyma, the “shoreline”
 (mid-image) representing the pleural interface, and the “sky”
(proximal to probe) representing subcutaneous tissue.
10. Imaging consistent with a pneumothorax has been described
as “bar code sign” with horizontal linearity over the lung
parenchyma representing non-sliding lung over time27 (see
Fig. 11.5).

11. The extent of a pneumothorax can be determined by

interrogating the range of non-sliding lung from
nondependent to dependent fields and determining the point
where lung sliding reappears. This has been referred to as
“lung point”30 and should approximate the interface between
the pathologic air-filled intrapleural space and normal, non–
air-filled intrapleural potential space.
12. Air-filled normal lung parenchyma is a poor conductor of
sound waves, and resulting ultrasound images of lung tissue
per se are quite limited. However, lung water (extra-alveolar
and intra-alveolar) manifests ultrasonographically as vertical,
hypoechogenic “B lines” or “comet tails” extending from the
pleura over the area of lung parenchyma for the full depth of
the image and represent shadowing behind air-liquid
interfaces (see Fig. 11.4).4 The quantity and width of these
lines are proportional to the degree of lung water in
 nonpregnant patients.31
13. Lung ultrasonography has been reported to be more sensitive
than chest auscultation or radiography in detecting alveolar
consolidation (pulmonary edema is the most common form in
pregnant patients), pleural effusions, and alveolar-interstitial
syndrome in patients who are critically ill (see Table 11.3).32

14. Even in the hands of examiners with limited training, lung

ultrasound has been reported to be superior to radiography in
identifying pulmonary edema.28
15. The detection of pneumothorax with ultrasound has also been
reported to be superior to radiography, particularly partial
pneumothorax.26
C. Applications
1. The principal applications of pulmonary ultrasound during
pregnancy include investigating the causes of dyspnea and
hypoxemia.
2. The pulmonary examination can be used to identify
pulmonary pathology as described earlier and is particularly
powerful when combined with FoCUS to establish any
cardiogenic contributions.33
3. Common etiologies of pulmonary edema in the pregnant
patient include preexisting cardiac disease (26%), tocolysis
 (26%), iatrogenic fluid overload (22%), preeclampsia (18%),
and sepsis (8%).34
4. Point of care ultrasound findings can be combined with the
overall clinical presentation to guide fluid management, the
need for diuresis, and other interventions.
5. Pulmonary edema may be detected earlier in at-risk pregnant
populations (preeclampsia) than with the use of auscultation
alone.35 Serial examinations can be used to observe the
response to therapies.
6. The infrequency of pneumothorax in clinical practice may
represent a barrier to developing optimal accuracy in
diagnosis for many practitioners with ultrasound. However,
given the urgency that is frequently demanded in management
of pneumothorax, the efficiency of ultrasound (diagnosis can
be identified in minutes26) certainly is compelling.

CLINICAL PEARL Pulmonary ultrasound can be used to

identify pulmonary pathology and is particularly powerful when
combined with FoCUS to establish any cardiogenic contributions.

IV. Ultrasound-guided neuraxial anesthesia

A. Introduction
1. Neuraxial anesthesia is mostly practiced as a technique guided
by external anatomic landmarks.
2. Ultrasound applications have emerged in this domain that
may provide some technical benefits.
3. The bony anatomy of the spine presents some ultrasound
imaging challenges, particularly if concurrent imaging with
needle advancement is used. This is usually not a problem
during the imaging of predominately soft tissues during
peripheral nerve blockade. For this reason, much of
ultrasound-guided neuraxial techniques are performed with
sequential imaging followed by the procedure itself.
 4. Ultrasound in this domain provides the advantages of accurate
assessment of intervertebral space, depth of epidural space,
and potentially improves analgesic success.36
B. Technique
1. Ultrasound of the spine requires a low frequency probe to
achieve the required depth of signal penetration.
2. A curvilinear (abdominal) probe has been used in most
descriptions of the technique and may offer the best imaging
quality depending on equipment and preset software values.
Imaging can be approached with the probe longitudinal
(sagittal) or transverse to the axial skeleton, in either the
sitting or lateral position. The position used for imaging
should be used to perform the block (see Fig. 11.6).

3. The soft tissue should be compressed minimally.

4. Using the longitudinal approach, estimation of selected
intervertebral space can be determined with a greater degree
of certainty than anatomic estimation techniques.36
5. With a midline probe placement, the sacrum can be easily
identified by its length and fused segments.
6. Each lumbar interspace can be counted as the probe is moved
 cephalad to the desired intervertebral space. There may be
some advantage to evaluating the height of these interspaces
for ease of needle advance, although this may not necessarily
be superior to palpation.
7. Images obtained of the neuraxial skeleton with the
longitudinal approach will have several recognizable patterns
depending on the probe relationship to midline.37
a. When imaging laterally, hypoechogenic “fingers” can be
identified as shadows over the transverse processes (see
Fig. 11.7).

b. If the probe is moved toward the midline, the

interarticular processes become visible forming a “hump”
pattern (see Fig. 11.8).
c. If the probe is angulated in this position toward midline,
the interarticular surfaces change from a hump to a
“sawtooth” pattern (see Fig. 11.9). This view also
captures the “posterior complex” involving the
ligamentum flavum and dura. The widest intervertebral
space can be identified in this view and optimal mid-
interspace marked on the skin to guide needle insertion.
8. Rotating the probe 90 degrees into the transverse orientation
relative to the axial skeleton, the spinous processes appear as
the most superficial hypoechogenic shadows and should be
centered in the image.
a. Moving the probe into the middle of the intervertebral
space, the “flying bat” pattern is identifiable (see Fig.
11.10). It is valuable to position the probe to create
symmetry of the “bat ears” (articular process shadows) to
minimize angulation.
b. In this view, the posterior complex can be identified and
depth to the epidural space estimated by using a caliper to
measure distance from the skin to the anterior portion of
the posterior complex (ligamentum flavum) (see Figs.
11.11 and 11.12).
c. Midline can be marked on the skin and the intersection of
midline and midspace height marks serve as a reference
 for needle insertion.
9. Continuous imaging while advancing a spinal or epidural
needle is possible and has the advantages of needle
visualization relative to imaged anatomic structures.38
However, unlike peripheral nerve blockade, epidural
placement techniques (and to a lesser degree spinal anesthesia
techniques) generally require two hands, which, when
combined with the bony anatomy of the spine, has limited
wider application of this technique.
C. Applications
1. The use of ultrasound guidance in obstetric anesthesia for
epidural and spinal blockade has increased since 2001.39,40
2. When used for preprocedural imaging, the initial advantages
to its use were more precise definition of intervertebral space,
spinal midline, and depth to epidural space. Subsequent
investigations have demonstrated improved efficiency during
block insertion (reduced needle redirections and failed
epidural blockade) but not necessarily reduced complications
(e.g., unintended dural puncture).36
3. Ultrasound may be particularly advantageous in managing the
obese parturient or patients with anatomic abnormalities after
an initial learning curve of normal anatomy is mastered.
4. Ultrasound may also be helpful in teaching neuraxial
techniques and improve epidural block success (see Table
11.4).41
5. Ultrasound is more accurate in determining the location of
intervertebral space than using anatomic landmarks alone.42
There is excellent correlation between ultrasound estimation
of depth to the epidural space and needle insertion depth with
an average measurement error in most studies of
approximately 3 mm (see Fig. 11.13).36

a. Sources of error in this measurement may include (1)

incorrectly identifying the posterior complex, (2)
 differences in patient position or the position and angle of
the ultrasound image and the needle approach, and (3)
skin compression by the probe (ideally, the probe should
have good contact with the skin with the least amount of
force to acquire a quality image).
b. Some of these sources of error play a more important role
in obese women.43
6. Practitioners are appropriately concerned about incorporating
an additional time-consuming step into urgent neuraxial
procedures. However, the technique can be streamlined and in
skilled hands can be performed very rapidly. This time
invested may actually lead to efficiencies in complicated
patients where time could be wasted with multiple needle
redirections or, with epidural techniques, interruptions to
interrogate false losses of resistance.

CLINICAL PEARL The use of ultrasound for neuraxial block

placement is more accurate in determining the location of
intervertebral space than using anatomic landmarks alone.

V. Ultrasound-guided regional anesthesia (transversus abdominis

plane block)
A. Introduction
1. Transversus abdominis plane (TAP) blockade is one of the
few non-neuraxial regional anesthetic techniques commonly
used in obstetric anesthesia.
2. The technique takes advantage of the anatomic relationship of
anterior rami of T6–L1 segmental nerves transiting from the
spinal cord posteriorly to the anterolateral abdominal wall
within a confined fascial plane formed between the internal
abdominal oblique and transversus abdominis muscles.44
3. This block was originally introduced into obstetric practice
using a non-ultrasound technique relying on a palpable
 change of resistance as the needle traversed facial planes.45
4. Ultrasound has added precision to this technique specifically
in identifying the distinct anatomic layers as well as directly
observing the distribution of injected local anesthetic.
B. Technique
1. TAP blockade is best achieved at the level of T8–T10, lateral
on the abdominal wall (slightly anterior to the midaxillary
line) prior to division of nerve roots and transition out of the
interfacial plane.
2. A high frequency rectilinear probe provides optimal
resolution imaging for these generally superficial structures.
3. Morbidly obese parturients may require scanning depths
beyond what is optimal with a high frequency probe (6 cm),
in which case a low frequency curvilinear abdominal probe
may be substituted.
4. TAP blockade requires identification of the three abdominal
wall muscle layers as well as the peritoneum to avoid passage
of the needle into the intraabdominal space.
5. Ideal position of the needle tip between the internal
abdominal oblique and transversus abdominis muscles can be
enhanced by injecting small volumes of saline to dissect this
fascial plane prior to injecting the local anesthetic.
6. Successful blockade and reducing the risk of local anesthetic
toxicity is dependent on administering the majority of the
local anesthetic into this plane. This is likely enhanced by
observing appropriate plane dissection during injection (see
Fig. 11.14).46,47
 7. The optimal selection of local anesthetic, adjuvant drugs, and
volumes or doses of these medications has not been
determined for TAP blockade.
8. Practitioners should be cautioned about total local anesthetic
dose administered because TAP blockade has been associated
with relatively high systemic local anesthetic levels48 and
case reports of systemic local anesthetic toxicity.49
9. The prior administration of other local anesthetic (e.g., recent
epidural anesthetic dosing) should be considered before
performing a TAP block. Appropriate monitoring is needed to
observe for signs of local anesthetic toxicity so that therapy
can be instituted if needed.
10. Peak systemic levels of local anesthetic have been measured
approximately 30 minutes following TAP blockade,
suggesting that patients should be monitored carefully within
this time period.48
C. Application
1. TAP blockade using ultrasound guidance is likely the
preferred technique by most practitioners with access to
 ultrasound equipment. The ability to identify the location of
the needle tip during advancement and local anesthetic
administration most likely improves blockade effectiveness
and avoids complications.
2. Preliminary evidence with TAP blockade in obstetric practice
is supportive of ultrasound-guided practice.50 Although no
studies have directly compared this blockade with and without
ultrasound guidance, direct observation of deposition of the
local anesthetic into the intended TAP will reassure the
anesthesiologist of correct placement of the block.

CLINICAL PEARL Practitioners should be cautioned about

total local anesthetic dose administered because TAP blockade has
been associated with relatively high systemic local anesthetic levels
and case reports of systemic local anesthetic toxicity.

VI. Intracranial pressure measurement (optic nerve sheath

diameter)
A. Introduction
1. Noninvasive, accurate measurement of intracranial pressure
can be obtained by taking advantage of the anatomic
continuity of the distensible subdural space along the optic
nerve and the favorable acoustic coupling across the eye and
retroocular sulcus.51
2. The optic nerve sheath diameter (ONSD) has been reported to
closely correlate with invasive intracranial pressure
transduction.52
B. Technique
1. ONSD measurement can be obtained using a high frequency,
rectilinear probe using low energy setting (ophthalmic
examination). Although the lack of thermal and vibratory
damage due to ultrasound is well established, an additional
degree of safety is mandated with use across the more delicate
 structures of the eye.
2. ONSD can be measured at the insertion of the optic nerve into
the posterior retina (see Fig. 11.15).

3. Measuring ONSD at a standardized distance (3 mm) behind

the retina optimizes reproducibility, particularly with serial
measurements in the same patient.
4. ONSD in normal pregnant patients has been reported to 4.3 to
4.8 mm.53
C. Applications
1. Cerebral pathology can occur in preeclampsia with severe
features, eclampsia, and stroke. Cerebral edema, severe
headache, and visual disturbances may precede a seizure,
CVA, or posterior reversible encephalopathy syndrome
(PRES).54
2. Preeclamptic cerebral pathophysiology is complex and not
completely understood, but noninvasive measurement of
intracranial hypertension may serve as a valuable screening
tool to guide care.
3. ONSD measurements are increased in women with
preeclampsia as compared with normal term pregnant
patients.53 This increase will lessen in the first week
postpartum approaching normal levels (see Fig. 11.16).
Although these results are preliminary, the ability to measure
intracranial pressure noninvasively may lead to clinical trials
aimed at stratifying higher risk patients and evaluating
therapeutic interventions for treatment.

4. Theoretical applications of this measurement include

managing parturients with other reasons for elevated
intracranial pressure. The management of parturients with a
history of intracranial hypertension or masses presents
substantial challenges to the obstetric team with regard to
labor management decisions and analgesic options. The
management of both groups of patients focuses on avoiding
extreme increases in intracranial pressure, which can
 compromise cerebral perfusion as well as avoiding the
development of pressure gradients across the foramen
magnum potentially causing cerebellar tonsillar herniation.
a. Some of the reasons for intracranial hypertension lead to
alterations in obstetric delivery decisions (cesarean
delivery [CD] or vaginal delivery with assisted second
stage to avoid pushing) as well as avoiding neuraxial
anesthesia.
b. Optic nerve sheath measurement may provide diagnostic
information to guide these decisions. For example,
measurements in the normal range may be reassuring to
clinicians and lead to pursuing less cautious plans during
delivery (e.g., pushing during the second stage of labor
and use of neuraxial anesthesia).
c. Decision-making in patients with intracranial lesions has
historically been guided by anatomic information from
imaging studies, although physiologic information
(pressure) may be more relevant. In addition, ultrasound
may also provide immediate information, whereas
imaging information, even if recent, may not accurately
reflect current conditions.

CLINICAL PEARL Preliminary results suggest that ONSD

measurements are increased in women with preeclampsia as
compared with those with a normal term pregnancy.

VII. Gastric volume measurement

A. Introduction
1. Pregnant women are among those at highest risk for
perioperative aspiration, and assessment of the degree of risk
has been mostly based on the timing and content of recent
oral intake.55
2. Due to the limited scientific evidence on which the American
 Society of Anesthesiologists (ASA) guideline
recommendations were based, controversy remains on
optimal fasting times for liquids and solids.
3. There are likely shortcomings of applying data from
nonpregnant patients to pregnant women and applying data
obtained from population studies to individual patients.
4. There is also considerable debate about the impact of diet
restriction on patient satisfaction and numerous obstetric
outcomes.56
5. Ultrasound may offer an opportunity to optimize practice by
directly measuring gastric volume.
B. Technique
1. Gastric scanning is performed with the patient in
semirecumbent position (45 degrees head of bed elevation),
first supine and then full lateral position using a low
frequency, curvilinear probe.57
2. The anatomic structure of interest for determining
intraluminal volume is the gastric antrum because of its
consistent shape, ease of imaging, and absence of air. The
antrum can be viewed in a sagittal to right parasagittal plane
between the left lobe of the liver and the pancreas at
approximately the level of the aorta or inferior vena cava (see
Fig. 11.17).57
3. An empty stomach antrum appears flat (antral walls in close
proximity) or has a “bull’s eye” appearance (see Fig. 11.17); a
stomach full of clear liquids has a “starry night” appearance
(see Fig. 11.18); and a stomach full of solids has a “frosted
glass” appearance (see Fig. 11.19).57
 4. Further quantification of stomach liquid contents can be made
by comparing images obtained in the supine and full lateral
positions. The lowest gastric volumes correlate with empty
appearance both supine and lateral, intermediate volumes
appear empty when supine but distended when lateral, the
fullest volumes have distended antra supine and lateral.58
C. Applications
1. More routine use of gastric ultrasound may likely increase our
understanding of pregnant digestive physiology and perhaps
alter routine management of diet in the peripartum period.
2. Although use of this technique for qualitative assessment of
gastric content has been reported to be reasonably accurate
and reproducible,58 it would be very difficult to investigate
the correlation of ultrasound findings to aspiration risk, due to
 its rarity. At this point, using gastric imaging for clinical
decision-making should still be considered experimental and
its use should not replace fasting guidelines.
However, circumstances exist where estimating individual
risk for aspiration by estimating gastric volume may be
beneficial. These include making decisions about when to
initiate several nonemergent obstetric procedures where the
estimated aspiration risk is weighed against the risk of
procedure delay (examples may include CD for breech with
rupture of membranes or circumstances where there is
uncertainty about NPO status).

CLINICAL PEARL The use of gastric imaging for clinical

decision-making should still be considered experimental. Its use
should not replace fasting guidelines.

VIII. Pelvic/abdominal ultrasound

A. Introduction
1. Abdominal ultrasound has been used extensively in the
domains of trauma surgery and emergency medicine to
rapidly determine the degree of intraabdominal hemorrhage.59
2. The technique has been extended to other clinical domains
including nontraumatic abdominal surgery and, more recently,
the management of obstetric hemorrhage.60 This adds to
already commonly employed use of ultrasound by
obstetricians to examine the intrauterine cavity for retained
placenta.
3. The utility of this ultrasound application may be limited by its
low sensitivity and specificity.
B. Technique
1. A low frequency, curvilinear probe is used for abdominal
scanning.
2. The focused abdominal sonogram for trauma (FAST) directs
 examination to four areas: right upper abdominal quadrant,
left upper abdominal quadrant, pelvis, and pericardium.59
3. Obstetric applications have emphasized the pelvis and right
upper abdominal quadrant.60 The specific anatomic areas to
examine for post-obstetric surgical bleeding include Douglas’
pouch (posterior to the uterus) and Morrison’s pouch
(between the liver and right kidney).
4. To examine for bleeding in the pelvis, orient the probe in the
sagittal plane immediately cephalad to the pubic symphysis
and aim the ultrasound beam posteriorly and slightly caudad
to image behind the uterus. Hemorrhage into the pelvis can be
identified by hypoechogenicity between the bladder and the
uterus or posterior to the uterus (see Fig. 11.20).

5. To examine the right upper abdominal quadrant (Morrison’s

pouch), place the probe in the right midaxillary line
immediately below the costal margin, in a cephalad–caudal
orientation. Some adjustment may be needed to find the
hepatorenal interface depending on the relationship of the
costal margin to organ interspace.61
6. Hyperechogenicity in either of these potential spaces
 represents intraabdominal fluid, likely hemoperitoneum.
Some degree of fluid in these spaces may be normal
postoperatively,62 but the degree of hyperechogenicity (>2
mm width of the distended potential space) combined with the
clinical presentation may confirm intraabdominal hemorrhage
requiring an intervention.
7. Scoring systems have been developed in trauma patients,
which combine FAST scan findings and have been correlated
with need for subsequent surgical exploration.59 However, no
scoring system or treatment algorithm exists for obstetric
hemorrhage.
C. Applications
1. Applications of pelvic and abdominal ultrasound can be used
to guide management including the confirmation of
hemorrhage and the need to pursue medical management,
uterine artery embolization, or reexplore the abdomen
surgically.
2. The most relevant clinical scenario would be to evaluate an
unstable postcesarean patient or one with a high risk or
suspicion for surgical bleeding.63
3. Alternative evaluations for pelvic and intraabdominal
hemorrhage include computed tomography (CT) scanning and
clinical judgment. The logistics involved in patient transport
to the radiology suite raise concerns about vigilance and
treatment options should a patient’s condition deteriorate
while in route, making CT scanning less attractive.
4. However, it is likely that pelvic and abdominal ultrasound
may be insensitive in identifying hemoperitoneum, and it is
unclear how much blood is required to distend pelvic
anatomic potential spaces. In addition, it is possible that this
methodology could lead to false-positive diagnoses of
hemoperitoneum. Hyperechogenicity in the pelvis and right
upper quadrant is present in some stable patients post-CD (0%
to 1.4% of patients in some observational studies).60,62
 5. Given some of the uncertainty with regard to the relationship
between ultrasound findings and clinical outcomes, serial
examinations to establish trends should be used, and the
results interpreted in the context of the clinical presentation
should be emphasized.

CLINICAL PEARL Although applications of pelvic and

abdominal ultrasound can be used to guide management including
the confirmation of hemorrhage and the need to pursue medical
management, uterine artery embolization, or reexplore the abdomen
surgically, serial examinations should be used with an emphasis on
results interpreted within the context of the clinical presentation.

IX. Airway examination

A. Introduction
1. Ultrasound applications for airway management have been
developed for predicting difficult laryngoscopy and
confirming appropriate endotracheal tube placement.
2. Airway ultrasound (i.e., sublingual approach) may add power
to traditionally used physical examination methods (e.g.,
Mallampati scoring) for predicting airway management
difficulty.64
3. Pulmonary and tracheal ultrasound can be used as secondary
tests to confirm proper endotracheal tube position. These
techniques may be superior for ruling out endobronchial
intubation.65
4. Tracheal ultrasound may be a useful tool to predict
esophageal intubation in situations where capnography is not
immediately available or may be unreliable (i.e., cardiac
arrest). It may also suggest esophageal intubation before
initiating ventilation, thus decreasing the amount of gastric
air.66
B. Technique
1. A high frequency, rectilinear ultrasound probe is optimal for
all airway applications.
2. Pre-intubation assessment has been described using a range of
screening techniques (e.g., measuring anterior neck thickness)
to specific interrogation of known pharyngeal and laryngeal
pathology (e.g., tumors, abscesses, epiglottitis).67
3. Alternative confirmation for correct endotracheal placement
and bilateral ventilation can be achieved by using pulmonary
ultrasound to observe lung sliding in any lung field during
ventilation (see Section III).65
4. In some circumstances, the endotracheal tube can be
visualized directly within the trachea either by retaining a
stylet with the tube or injecting air into a saline filled
endotracheal cuff.67 Alternatively, the trachea and esophagus
can be imaged in cross section to evaluate for tube placement
(see Fig. 11.21).
C. Applications
1. Standard confirmation of correct endotracheal tube placement
within the trachea relies on capnography and auscultation of
lung fields. There are circumstances where capnography is
unavailable and auscultation is equivocal (e.g., morbid
obesity, pulmonary disease). Ultrasound confirmation of lung
sliding is easy to achieve in almost all patients.
 2. Regarding endobronchial intubation, capnography is an
insensitive measure, and bronchoscopy is invasive and may
involve interruption of ventilation. Lung ultrasound is
technically easy, and the presence of unilateral lung sliding,
which becomes bilateral with incremental endotracheal tube
withdrawal, provides definitive evidence of tube position
relative to the carina.

CLINICAL PEARL Pre-intubation assessment has been

described using a range of screening techniques (e.g., measuring
anterior neck thickness) including specific interrogation of known
pharyngeal and laryngeal pathology (e.g., tumors, abscesses,
epiglottitis).

X. Lower extremity vein ultrasound

A. Introduction
1. Pregnant patients are at high risk for pulmonary
thromboembolism with an estimated prevalence of deep
venous thrombosis of 1.4% in the third trimester.68
2. Evaluations of dyspnea or chest pain may be aided by
determining the presence of lower extremity deep venous
thromboses.
B. Technique
1. Bilateral femoral vein scanning is best accomplished with a
high frequency probe.
2. The femoral vein can be identified lateral to the pulsatile
femoral artery immediately caudad to the inguinal ligament.
Color-flow Doppler can be used to distinguish artery from
vein. Noncompressibility of the vein is consistent with the
presence of a thrombus69 (see Fig. 11.22).
 3. The popliteal vein can also be interrogated for compression at
the popliteal crease superficial and lateral to the popliteal
artery.
4. Although compression ultrasonography is generally viewed as
safe, care should be taken in performing this examination
because excessive compression could theoretically dislodge a
thrombus.
C. Applications
1. The primary application for ultrasound examination of the
lower extremity veins is to determine the presence of deep
venous thrombosis and need for pharmacologic management
and embolism workup.
2. Bilateral femoral vein scanning alone may serve as a
reasonable, highly sensitive screening process for patients at
high-risk for lower extremity deep venous thrombosis.69

CLINICAL PEARL Although lower extremity compression

ultrasonography is generally viewed as safe, care should be taken in
performing this examination because excessive compression could
theoretically dislodge a thrombus.

REFERENCES
1. Barnett SB. Routine ultrasound scanning in first trimester: what are the risks? Semin Ultrasound CT
MR. 2002;23:387–391.
2. Belfort MA, Rokey R, Saade GR, et al. Rapid echocardiographic assessment of left and right heart
hemodynamics in critically ill obstetric patients. Am J Obstet Gynecol. 1994;171:884–892.
3. Via G, Hussain A, Wells M, et al. International evidence-based recommendations for focused cardiac
ultrasound. J Am Soc Echocardiogr. 2014;27:683.e1–e33.
4. Moore CL, Copel JA. Point-of-care ultrasonography. N Engl J Med. 2011;364:749–757.
5. Sandham JD, Hull RD, Brant RF, et al. A randomized, controlled trial of the use of pulmonary-artery
catheters in high-risk surgical patients. N Engl J Med. 2003;348:5–14.
6. Berenholtz SM, Lubomski LH, Weeks K, et al. Eliminating central line-associated bloodstream
infections: a national patient safety imperative. Infect Control Hosp Epidemiol. 2014;35:56–62.
7. Spencer KT, Kimura BJ, Korcarz CE, et al. Focused cardiac ultrasound: recommendations from the
American Society of Echocardiography. J Am Soc Echocardiogr. 2013;26:567–581.
8. Dennis A, Stenson A. The use of transthoracic echocardiography in postpartum hypotension. Anesth
Analg. 2012;115: 1033–1037.
9. Jensen MB, Sloth E, Larsen KM, et al. Transthoracic echocardiography for cardiopulmonary
monitoring in intensive care. Eur J Anaesthesiol. 2004;21:700–707.
10. Dennis AT. Transthoracic echocardiography in obstetric anaesthesia and obstetric critical illness. Int J
Obstet Anesth. 2011;20:160–168.
11. Holm JH, Frederiksen CA, Juhl-Olsen P, et al. Perioperative use of focus assessed transthoracic
echocardiography (FATE). Anesth Analg. 2012;115:1029–1032.
12. Jones AE, Tayal VS, Sullivan DM, et al. Randomized, controlled trial of immediate versus delayed
goal-directed ultrasound to identify the cause of nontraumatic hypotension in emergency department
patients. Crit Care Med. 2004;32: 1703–1708.
13. Ferrada P, Evans D, Wolfe L, et al. Findings of a randomized controlled trial using limited
transthoracic echocardiogram (LTTE) as a hemodynamic monitoring tool in the trauma bay. J Trauma
Acute Care Surg. 2014;76:31–37; discussion 37–38.
14. Cantwell R, Clutton-Brock T, Cooper G, et al. Saving Mothers’ Lives: reviewing maternal deaths to
make motherhood safer: 2006-2008. The Eighth Report of the Confidential Enquiries into Maternal
Deaths in the United Kingdom. BJOG. 2011;118(suppl 1):1–203.
15. Labovitz AJ, Noble VE, Bierig M, et al. Focused cardiac ultrasound in the emergent setting: a
consensus statement of the American Society of Echocardiography and American College of
Emergency Physicians. J Am Soc Echocardiogr. 2010;23:1225–1230.
16. Douglas PS, Khandheria B, Stainback RF, et al. ACCF/ASE/ACEP/ASNC/SCAI/SCCT/SCMR 2007
appropriateness criteria for transthoracic and transesophageal echocardiography: a report of the
American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness
Criteria Working Group, American Society of Echocardiography, American College of Emergency
Physicians, American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and
Interventions, Society of Cardiovascular Computed Tomography, and the Society for Cardiovascular
 Magnetic Resonance endorsed by the American College of Chest Physicians and the Society of
Critical Care Medicine. J Am Coll Cardiol. 2007;50:187–204.
17. Mhyre JM, Tsen LC, Einav S, et al. Cardiac arrest during hospitalization for delivery in the United
States, 1998-2011. Anesthesiology. 2014;120:810–818.
18. Dennis AT, Castro J, Carr C, et al. Haemodynamics in women with untreated pre-eclampsia.
Anaesthesia. 2012;67: 1105–1118.
19. World Health Organization Guidelines Review Committee. WHO Recommendations for Prevention
and Treatment of Pre-Eclampsia and Eclampsia. Geneva, Switzerland: World Health Organization;
2011.
20. Kuklina EV, Ayala C, Callaghan WM. Hypertensive disorders and severe obstetric morbidity in the
United States. Obstet Gynecol. 2009;113:1299–1306.
21. Berg CJ, Mackay AP, Qin C, et al. Overview of maternal morbidity during hospitalization for labor
and delivery in the United States: 1993-1997 and 2001-2005. Obstet Gynecol. 2009;113:1075–1081.
22. Campbell OM, Graham WJ, Lancet Maternal Survival Series steering group. Strategies for reducing
maternal mortality: getting on with what works. Lancet. 2006;368:1284–1299.
23. Druzin MS, Shields L, Peterson, N. Preeclampsia Toolkit: Improving health care response to
preeclampsia: a California toolkit to transform maternity care.
https://www.cmqcc.org/preeclampsia_toolkit. Accessed December 2, 2014.
24. Dennis AT, Solnordal CB. Acute pulmonary oedema in pregnant women. Anaesthesia. 2012;67:646–
659.
25. Zieleskiewicz L, Contargyris C, Brun C, et al. Lung ultrasound predicts interstitial syndrome and
hemodynamic profile in parturients with severe preeclampsia. Anesthesiology. 2014;120:906–914.
26. Zhang M, Liu ZH, Yang JX, et al. Rapid detection of pneumothorax by ultrasonography in patients
with multiple trauma. Crit Care. 2006;10:R112.
27. Bouhemad B, Zhang M, Lu Q, et al. Clinical review: bedside lung ultrasound in critical care practice.
Crit Care. 2007;11:205.
28. Martindale JL, Noble VE, Liteplo A. Diagnosing pulmonary edema: lung ultrasound versus chest
radiography. Eur J Emerg Med. 2013;20:356–360.
29. Lichtenstein DA, Mezière G, Lascols N, et al. Ultrasound diagnosis of occult pneumothorax. Crit Care
Med. 2005;33: 1231–1238.
30. Lichtenstein D, Mezière G, Biderman P, et al. The “lung point”: an ultrasound sign specific to
pneumothorax. Intensive Care Med. 2000;26:1434–1440.
31. Facchini C, Malfatto G, Giglio A, et al. Lung ultrasound and transthoracic impedance for noninvasive
evaluation of pulmonary congestion in heart failure [published online ahead of print January 7, 2015].
J Cardiovasc Med. doi:10.2459/JCM.0000000000000226.
32. Lichtenstein D, Goldstein I, Mourgeon E, et al. Comparative diagnostic performances of auscultation,
chest radiography, and lung ultrasonography in acute respiratory distress syndrome. Anesthesiology.
2004;100:9–15.
33. Liteplo AS, Marill KA, Villen T, et al. Emergency thoracic ultrasound in the differentiation of the
etiology of shortness of breath (ETUDES): sonographic B-lines and N-terminal pro-brain-type
natriuretic peptide in diagnosing congestive heart failure. Acad Emerg Med. 2009;16:201–210.
34. Sciscione AC, Ivester T, Largoza M, et al. Acute pulmonary edema in pregnancy. Obstet Gynecol.
2003;101:511–515.
35. Zieleskiewicz L, Lagier D, Contargyris C, et al. Lung ultrasound-guided management of acute
breathlessness during pregnancy. Anaesthesia. 2013;68:97–101.
36. Perlas A, Chaparro LE, Chin KJ. Lumbar neuraxial ultrasound for spinal and epidural anesthesia: a
systematic review and meta-analysis [published online ahead of print December 9, 2014]. Reg Anesth
 Pain Med. doi:10.1097/AAP.0000000000000184.
37. Chin KJ, Perlas A, Chan V, et al. Ultrasound imaging facilitates spinal anesthesia in adults with
difficult surface anatomic landmarks. Anesthesiology. 2011;115:94–101.
38. Karmakar MK, Li X, Ho AM, et al. Real-time ultrasound-guided paramedian epidural access:
evaluation of a novel in-plane technique. Br J Anaesth. 2009;102:845–854.
39. Grau T, Leipold RW, Conradi R, et al. Ultrasound imaging facilitates localization of the epidural space
during combined spinal and epidural anesthesia. Reg Anesth Pain Med. 2001;26:64–67.
40. Chin KJ, Chan V. Ultrasonography as a preoperative assessment tool: predicting the feasibility of
central neuraxial blockade. Anesth Analg. 2010;110:252–253.
41. Vallejo MC, Phelps AL, Singh S, et al. Ultrasound decreases the failed labor epidural rate in resident
trainees. Int J Obstet Anesth. 2010;19:373–378.
42. Halpern SH, Banerjee A, Stocche R, et al. The use of ultrasound for lumbar spinous process
identification: a pilot study. Can J Anaesth. 2010;57:817–822.
43. Balki M, Lee Y, Halpern S, et al. Ultrasound imaging of the lumbar spine in the transverse plane: the
correlation between estimated and actual depth to the epidural space in obese parturients. Anesth
Analg. 2009;108:1876–1881.
44. Petersen PL, Mathiesen O, Torup H, et al. The transversus abdominis plane block: a valuable option
for postoperative analgesia? A topical review. Acta Anaesthesiol Scand. 2010;54:529–535.
45. McDonnell JG, Curley G, Carney J, et al. The analgesic efficacy of transversus abdominis plane block
after cesarean delivery: a randomized controlled trial. Anesth Analg. 2008;106:186–191.
46. Costello JF, Moore AR, Wieczorek PM, et al. The transversus abdominis plane block, when used as
part of a multimodal regimen inclusive of intrathecal morphine, does not improve analgesia after
cesarean delivery. Reg Anesth Pain Med. 2009;34:586–589.
47. Belavy D, Cowlishaw PJ, Howes M, et al. Ultrasound-guided transversus abdominis plane block for
analgesia after caesarean delivery. Br J Anaesth. 2009;103:726–730.
48. Griffiths JD, Barron FA, Grant S, et al. Plasma ropivacaine concentrations after ultrasound-guided
transversus abdominis plane block. Br J Anaesth. 2010;105:853–856.
49. Weiss E, Jolly C, Dumoulin JL, et al. Convulsions in 2 patients after bilateral ultrasound-guided
transversus abdominis plane blocks for cesarean analgesia. Reg Anesth Pain Med. 2014;39:248–251.
50. Kelly SMC, Malhotra RK. Ultrasound-guided transversus abdominis plane blocks for analgesia post
cesarean section. J Com Eff Res. 2011;1:35–38.
51. Hansen HC, Helmke K. Validation of the optic nerve sheath response to changing cerebrospinal fluid
pressure: ultrasound findings during intrathecal infusion tests. J Neurosurg. 1997;87:34–40.
52. Dubourg J, Javouhey E, Geeraerts T, et al. Ultrasonography of optic nerve sheath diameter for
detection of raised intracranial pressure: a systematic review and meta-analysis. Intensive Care Med.
2011;37:1059–1068.
53. Dubost C, Le Gouez A, Jouffroy V, et al. Optic nerve sheath diameter used as ultrasonographic
assessment of the incidence of raised intracranial pressure in preeclampsia: a pilot study.
Anesthesiology. 2012;116:1066–1071.
54. Frontera JA, Ahmed W. Neurocritical care complications of pregnancy and puerperum. J Crit Care.
2014;29:1069–1081.
55. American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Practice guidelines for
obstetric anesthesia: an updated report by the American Society of Anesthesiologists Task Force on
Obstetric Anesthesia. Anesthesiology. 2007;106:843–863.
56. O’Sullivan G, Liu B, Hart D, et al. Effect of food intake during labour on obstetric outcome:
randomised controlled trial. BMJ. 2009;338:b784.
57. Cubillos J, Tse C, Chan VW, et al. Bedside ultrasound assessment of gastric content: an observational
 study. Can J Anaesth. 2012;59:416–423.
58. Arzola C, Cubillos J, Perlas A, et al. Interrater reliability of qualitative ultrasound assessment of
gastric content in the third trimester of pregnancy. Br J Anaesth. 2014;113:1018–1023.
59. Scalea TM, Rodriguez A, Chiu WC, et al. Focused Assessment with Sonography for Trauma (FAST):
results from an international consensus conference. J Trauma. 1999;46:466–472.
60. Antonelli E, Morales MA, Dumps P, et al. Sonographic detection of fluid collections and postoperative
morbidity following cesarean section and hysterectomy. Ultrasound Obstet Gynecol. 2004;23:388–
392.
61. Ashar T, Ladner H. Trauma: the FAST approach: an introduction to bedside trauma ultrasound. Isr J
Emerg Med. 2006;6: 43–51.
62. Koskas M, Nizard J, Salomon LJ, et al. Abdominal and pelvic ultrasound findings within 24 hours
following uneventful cesarean section. Ultrasound Obstet Gynecol. 2008;32:520–526.
63. Lousquy R, Morel O, Soyer P, et al. Routine use of abdominopelvic ultrasonography in severe
postpartum hemorrhage: retrospective evaluation in 125 patients. Am J Obstet Gynecol.
2011;204:232.e1–e6.
64. Hui CM, Tsui BC. Sublingual ultrasound as an assessment method for predicting difficult intubation: a
pilot study. Anaesthesia. 2014;69:314–319.
65. Hsieh KS, Lee CL, Lin CC, et al. Secondary confirmation of endotracheal tube position by ultrasound
image. Crit Care Med. 2004;32(suppl 9):S374–S377.
66. Werner SL, Smith CE, Goldstein JR, et al. Pilot study to evaluate the accuracy of ultrasonography in
confirming endotracheal tube placement. Ann Emerg Med. 2007;49:75–80.
67. Sustić A, Kovac D, Zgaljardić Z, et al. Ultrasound-guided percutaneous dilatational tracheostomy: a
safe method to avoid cranial misplacement of the tracheostomy tube. Intensive Care Med.
2000;26:1379–1381.
68. Heit JA, Kobbervig CE, James AH, et al. Trends in the incidence of venous thromboembolism during
pregnancy or postpartum: a 30-year population-based study. Ann Intern Med. 2005;143:697–706.
69. Blaivas M. Ultrasound in the detection of venous thromboembolism. Crit Care Med. 2007;35(suppl
5):S224–S234.
 Impact of Neuraxial Analgesia on Obstetric Outcomes
Christopher R. Cambic and Cynthia A. Wong

I.Introduction
II.Effects of neuraxial analgesia on the progress of labor
III. Duration of the first stage of labor
IV. Duration of the second stage of labor
V. Instrumental vaginal delivery
VI. Cesarean delivery
VII. Influence of oxytocin augmentation and ambulation on labor
outcomes
VIII. Impact of neuraxial analgesia on maternal fever rates
IX. Impact of neuraxial analgesia on breastfeeding success rates
X. Conclusion

KEYPOINTS
1. Neuraxial analgesia is the most effective form of labor analgesia.
Additionally, it provides physiologic and safety benefits to both mother
and fetus.
2. Effective neuraxial analgesia may increase the risk of instrumental
vaginal delivery and prolong the second stage of labor. The impact of
these outcomes on maternal and fetal well-being remains unclear.
3. Neuraxial analgesia does not increase the risk of cesarean delivery
 compared with systemic opioid analgesia. Moreover, the initiation of
labor analgesia during the latent phase of labor does not increase the risk
of cesarean delivery or prolong the duration of labor.
4. Neuraxial labor analgesia is associated with maternal temperature
elevation in some women. The etiology is unclear and further research is
indicated.
5. The impact of neuraxial labor analgesia on breastfeeding success rates is
not clear and warrants further inquiry.

I. Introduction
A. Neuraxial analgesia is the most effective form of pain relief
during labor in current clinical practice.1
B. The use of neuraxial labor analgesia has increased since the
1970s.2
1. In the United States, 2008 data from 27 states demonstrated
that 61% of women who underwent a singleton vaginal
delivery received neuraxial analgesia.3
2. In the United Kingdom, approximately 34% of parturients
received neuraxial analgesia or anesthesia for delivery in 2012
to 2013.4
C. Factors influencing the rate of neuraxial analgesia include3,5:
1. Availability of anesthesia providers
2. Race/ethnicity
3. Personal and cultural expectations
4. Information and advice provided to pregnant women by other
health care providers
5. Obstetric complications
D. Neuraxial analgesia provides benefits to the mother, fetus/neonate,
and the parturient’s partner (see Table 12.1).6–13
 CLINICAL PEARL Neuraxial analgesia provides superior pain
relief to the mother during labor and delivery and conveys other
significant benefits.

II. Effects of neuraxial analgesia on the progress of labor

A. Observational data demonstrate that neuraxial analgesia is
associated with increased cesarean and instrumental vaginal
delivery rates, and prolonged duration of labor. However,
controversy exists as to whether this association is causal.
B. Ideally, one would conduct a randomized, double-blind, placebo-
controlled trial to determine the true effect of neuraxial analgesia
on the progress and outcome of labor. However, designing and
conducting such a study is fraught with several difficulties:
1. Ideally, the control group would receive no analgesia; this is
unethical.
2. Most controlled trials have utilized systemic opioids or
inhaled analgesia (e.g., nitrous oxide) as the control group,
but these modes of analgesia also have limitations:
a. Neuraxial analgesia is significantly superior to other
 forms of analgesia, making blinding of patient and
provider virtually impossible.
b. Patients may be unwilling to enroll in a study knowing
they might be randomized to an inferior form of labor
analgesia, resulting in difficulties with achieving an
adequate sample size.
c. The marked superiority of neuraxial labor analgesia
contributes to a high crossover rate between study groups,
preventing meaningful interpretation of the data.
d. The effect of systemic opioids on labor outcomes has not
been well studied and opioids may differ on their effects
on uterine muscle contractility.13
3. The external validity of these studies may be questioned
because many women have already made a decision regarding
labor analgesia before the onset of labor and may be unwilling
to let random chance determine the type of analgesia they will
receive.
4. There is difficulty in controlling for other factors that are
known to affect the progress and outcome of labor, including:
a. Induction of labor
b. Artificial rupture of membranes
c. Parity
d. Payer status
e. Obstetric provider management (e.g., labor augmentation)
5. Selection bias
a. Women who are at higher risk for prolonged labor and
operative delivery are more likely to request and receive
neuraxial analgesia than women who undergo rapid,
uncomplicated labor.8
b. Greater pain during labor appears to be associated with an
increased risk for operative delivery.
(1) Women who received continuous infusion, low-
concentration bupivacaine/fentanyl epidural
analgesia, and who required three or more manual
 epidural boluses to treat breakthrough pain during
labor (top-up doses), were more than twice as likely
to undergo cesarean delivery (CD) than women who
required fewer boluses.14
(2) The rate of CD was 14% in women who gave
themselves 50 mg per hour or more of meperidine via
patient-controlled intravenous analgesia (PCIA)
compared to 1.4% in those who gave themselves less
than 50 mg per hour.15

CLINICAL PEARL Although observational studies show that

neuraxial analgesia is associated with increased rate of CD and a
prolongation of labor, these findings have not been confirmed in
properly constructed, randomized controlled trials.

III. Duration of the first stage of labor

A. No randomized controlled trials to date have investigated the
effect of neuraxial analgesia on the duration of the first stage of
labor as a primary outcome.
B. Studies that have investigated the impact of neuraxial labor
analgesia on the duration of the first stage of labor as a secondary
outcome have conflicting results.
1. Randomized controlled trials investigating the impact of
initiation of labor analgesia during the latent phase of labor
have demonstrated no difference or a shorter duration in
the first stage of labor for women randomized to early
neuraxial analgesia compared to those assigned to receive
systemic opioid analgesia in latent labor.12,16,17
2. Systematic reviews have demonstrated no difference or a
longer duration (~30 minutes) in the first stage of labor
between women randomly assigned to receive epidural
analgesia and systemic opioid analgesia.18,19
3. Effect of neuraxial technique
 a. Combined spinal-epidural (CSE) versus epidural
analgesia: Randomized controlled trials have
demonstrated no difference or a shorter first stage
duration in women randomized to receive CSE
analgesia.20,21
b. Choice of local anesthetic: No differences in the rate of
cervical dilation or duration of the first stage of labor
were observed between women randomized to receive
0.08% bupivacaine/fentanyl 2 μg per mL and 0.08%
ropivacaine/fentanyl 2 μg per mL via patient-controlled
epidural analgesia (PCEA).22
c. Maintenance of analgesia
(1) Continuous infusion versus PCEA: a 2002 meta-
analysis of nine studies reported no difference in the
duration of the first stage of labor between patients
randomized to continuous epidural infusion and
PCEA.23
(2) Continuous infusion versus programmed intermittent
bolus (infusion pump is programmed to administer
regular bolus doses): a 2013 meta-analysis of eight
studies demonstrated that women who received
programmed intermittent scheduled boluses of
epidural medication reported no difference in the
duration of first stage of labor compared to women
who received a continuous infusion with or without
PCEA.24
d. Local anesthetic concentration: a 2013 meta-analysis of
11 studies demonstrated no difference in the duration of
first stage of labor between women who received low
concentrations of epidural local anesthetic (defined as
≤0.1% bupivacaine or ≤0.17% ropivacaine) and those
who received higher concentrations.25
4. Difficulty with assessment—differences in outcomes among
these studies are likely due to variations in study design,
differences in neuraxial analgesic techniques and medications,
and the impact of confounding factors influencing uterine
activity.
a. Assessment of duration: documentation of start and end
times
(1) The definition of start time differs among studies but
is usually consistent within a study.
(2) End time is clearly defined at 10 cm cervical dilation,
which can only be assessed via manual cervical
examinations. Studies differ in frequency and/or
requirement of regular cervical examinations,
increasing intra-study variation in determining full
cervical dilation.
(3) Women with effective neuraxial analgesia will likely
have an artificially prolonged duration of the first
stage of labor because these patients will complain of
rectal pressure (and subsequently be examined and
verified to be at complete cervical dilation) at a later
time compared to those who have received systemic
opioid analgesia.
b. Direct effects of local anesthetics on uterine tone and
contractility
(1) In vitro studies in human myometrium demonstrate
increased tone but decreased rate and strength of
contractions when exposed to high concentrations of
local anesthetics.26
(2) In vitro studies in human myometrium exposed to
clinically relevant local anesthetic concentrations
showed no effect on uterine activity or tone.27
c. Effect on plasma catecholamine levels
(1) Initiation of neuraxial analgesia is associated with a
rapid decrease in maternal plasma concentrations of
epinephrine. In turn, this is hypothesized to cause an
increase in uterine activity secondary to decreased β-
 adrenergic receptor activation.10
(2) Studies have demonstrated an increased incidence of
uterine tachysystole in women who received CSE
technique for labor analgesia compared to traditional
epidural analgesia.28,29 Two important limitations of
these studies are (1) plasma epinephrine levels were
not measured or correlated with the occurrence of
uterine tachysystole, and (2) the duration of the first
stage of labor was not assessed as an outcome to
determine if this increased uterine activity affected
the progress of labor. This increase in uterine
tachysystole may not be associated with higher
rates of abnormal fetal heart rate tracings or
adverse neonatal outcomes.30
(3) Additional studies have suggested that the epidural
administration of dilute concentrations of
epinephrine (1.25 to 5 μg per mL) with local
anesthetic does not affect the progress of labor.31,32
d. Effect on oxytocin concentration
(1) Fluid boluses: Bolus administration of 1-L of
crystalloid solution (but not 0.5-L or maintenance
fluid alone) has been shown to decrease uterine
activity, possibly by decreased production and release
of antidiuretic hormone and oxytocin, both of which
originate from the posterior pituitary gland.33
(2) Rahm et al.34 demonstrated lower plasma oxytocin
concentrations 60 minutes after initiation of epidural
analgesia (bupivacaine with sufentanil) compared to
women without epidural analgesia.
e. Genetic polymorphisms
(1) New evidence suggests polymorphisms in the β2-
adrenergic receptor (ADRB2) and catechol-O-
methyltransferase (COMT), and oxytocin receptor
(OXTR) genes may affect the progress of labor.35,36
 (2) Further studies are needed to elucidate the interaction
of these and other genotypes with neuraxial analgesia
and their impact on labor progress.
5. Summary of evidence for the effect of neuraxial labor
analgesia on the duration of the first stage of labor
a. The available evidence suggests that neuraxial analgesia
has a variable effect on the duration of the first stage of
labor: It may prolong it in some patients, whereas
shortening it in others.
b. These inconsistent results are likely a result of the
influence of several factors known to affect uterine
activity and duration of the first stage of labor, including
management of labor, as well as differences in neuraxial
analgesic techniques and medications.

CLINICAL PEARL Studies investigating the effect of neuraxial

analgesia on the length of the first stage of labor report varying
results. Differences in analgesic technique, study design, and
obstetric management are the most likely reasons.

IV. Duration of the second stage of labor

A. Effective neuraxial analgesia prolongs the second stage of
labor.
1. Meta-analyses of randomized controlled trials demonstrates
that the median duration of the second stage of labor is 15 to
20 minutes longer in women who receive neuraxial analgesia
compared to those who received systemic opioids.18,19
2. Recent data suggest that labor curves developed in the 1950s
by Friedman may not reflect the pattern of modern labor.37
a. There are several factors which may explain these
changes in labor patterns in modern obstetrics:
(1) Parturients are heavier and older, two factors that are
known to affect the progress of labor.38
 (2) Operative vaginal deliveries are being performed at a
lower rate, which may increase the CD rate.38
(3) The use of neuraxial labor analgesia is more
prevalent.2,3,38
b. Zhang et al.37 performed a secondary analysis of data
from the Consortium on Safe Labor, a multicenter study
involving more than 62,000 patients demonstrating:
(1) The time to progress from 4 to 6 cm cervical dilation
was much longer than previously described by the
Friedman labor curves.
(2) Nulliparous and multiparous patients progressed at a
similar rate of cervical dilation before 6 cm dilation,
after which multiparous women progressed much
faster. This suggests the transition to active phase of
labor might occur at approximately 6 cm instead of 4
cm as previously thought.
(3) The 95th percentiles for the duration of the second
stage of labor in nulliparous women with and without
neuraxial analgesia were 3.6 hours and 2.8 hours,
respectively.
c. Cheng et al.39 demonstrated in a retrospective cohort
study that the 95th percentile duration of the second stage
was prolonged by more than 2 hours in women who
received epidural analgesia.
3. The American College of Obstetricians and Gynecologists
(ACOG) has specific definitions for a prolonged second stage
of labor, depending on parity and presence or absence of
neuraxial analgesia. However, new criteria for defining
second stage arrest have been proposed, which are concordant
with more recent data (see Table 12.2).
4. Effect of prolonged second stage duration on maternal and
neonatal outcomes.
a. Rouse et al.40, in a secondary analysis of data from a
multicenter study involving nulliparous women,
demonstrated that long (≥3 hours) compared to short
second stage labor duration was associated with:
(1) Decreased rates of spontaneous vaginal delivery and
increased rates of instrumental vaginal delivery
(2) Increased risk of chorioamnionitis, uterine atony, and
third- or fourth-degree perineal laceration
(3) No increased risk of adverse neonatal outcomes (after
adjusting for mode of delivery)
b. Laughon et al.41 conducted a multicenter retrospective
cohort study involving more than 100,000 parturients of
mixed parity. The authors demonstrated that prolonged
second stage, as defined by ACOG guidelines, was
associated with:
(1) Decreased rates of spontaneous vaginal delivery and
increased rates of operative vaginal delivery
(2) Increased risk of chorioamnionitis and third- or
fourth-degree perineal lacerations
(3) Increased risk of neonatal asphyxia in nulliparous
women with epidural analgesia (the absolute rate for
this outcome was low at 0.3%)
(4) Sixfold increased risk of perinatal mortality in
parturients without epidural analgesia regardless of
parity
 (5) No increased risk of hypoxic-ischemic
encephalopathy in parturients with epidural analgesia
regardless of parity
c. Summary of evidence for maternal and neonatal outcomes
with prolonged second stage of labor
(1) It is unclear whether the longer second stage of labor
caused by neuraxial analgesia also causes other
adverse outcomes (e.g., chorioamnionitis, lacerations)
or whether these outcomes are independently
associated with prolonged second stage.
(2) The need for intervention (instrumental or
surgical) should not be mandated solely based on
second stage duration, especially if progress is being
made and maternal/fetal status remains reassuring.42
By extending the duration of the second stage, more
women will be able to deliver vaginally, thereby
reducing the rate of CD.
B. Immediate versus delayed pushing
1. The impact of immediate versus delayed pushing on second
stage labor duration, mode of delivery, and maternal/neonatal
outcomes is controversial.
a. The Pushing Early or Pushing Late with Epidural
(PEOPLE) study was a randomized, multicenter
controlled trial, which demonstrated that compared to
immediate pushing, women who were randomized to
delayed pushing had43:
(1) Higher rate of spontaneous vaginal delivery
(2) Shorter duration of pushing
(3) Lower rate of mid-rotational forceps
(4) Longer duration of second stage of labor
b. Tuuli et al.44 performed a meta-analysis that included
more than 3,000 parturients from nine high-quality and
three low-quality randomized controlled trials. When only
the high-quality studies were analyzed, the authors found
 that delayed pushing:
(1) Did not increase spontaneous vaginal delivery rates
(2) Did not decrease operative delivery rates
(3) Was associated with longer duration of second stage
of labor but shorter duration of pushing
(4) Differences in the definition of maternal and neonatal
outcomes precluded meta-analysis.
2. Despite no clear advantages to delayed pushing, the potential
for maternal exhaustion from prolonged pushing makes it
unreasonable to require parturients to begin pushing from a
high fetal station.

CLINICAL PEARL Neuraxial analgesia prolongs the second

stage of labor. The clinical impact of this prolongation on maternal
and fetal outcomes is unclear.

V. Instrumental vaginal delivery

A. Observational data suggest an association between neuraxial
labor analgesia and increased rate of instrumental vaginal
delivery, that is, vacuum or forceps delivery.
B. No randomized controlled trial has assessed the effect of
neuraxial analgesia on the rate of instrumental vaginal delivery as
its primary outcome, although multiple trials have assessed it as a
secondary outcome variable.45–47
C. Most randomized controlled trials and systematic reviews of
randomized controlled trials comparing neuraxial to systemic
opioid analgesia, in which the rate of CD was the primary
outcome, have concluded that effective neuraxial analgesia is
associated with an increased risk of instrumental vaginal
delivery.18,19,46,47
1. Sharma et al.19, in an individual patient meta-analysis of
studies performed at a single institution involving more than
2,700 patients, reported an adjusted odds ratio of 1.86 (95%
 confidence interval [CI], 1.43 to 2.40).
2. A meta-analysis involving 23 studies calculated a risk ratio
for instrumental vaginal delivery for women randomized to
epidural analgesia or systemic opioid analgesia of 1.42 (95%
CI, 1.28 to 1.57).18
3. A systematic review of five randomized controlled trials
comparing early (defined as cervical dilation of 3 cm or less)
compared with later (>3 cm cervical dilation) labor initiation
of neuraxial analgesia showed no increase in instrumental
vaginal delivery rates in women receiving early analgesia
(risk ratio 0.94; 95% CI, 0.87 to 1.02).48
D. Impact studies, also known as before–after studies, are designed
to assess the incidence of a patient outcome before and after the
implementation of a specific treatment (e.g., implementation of a
neuraxial analgesia service).
1. In contrast to randomized controlled trials comparing
neuraxial to systemic opioid analgesia, most impact studies
have demonstrated no difference in instrumental vaginal
delivery between the control and study time periods.
a. Impey et al.49 found no increase in the instrumental
vaginal delivery rate at the National Maternity Hospital in
Dublin despite a fivefold increase in the epidural
analgesia rate over a 7-year period.
b. At Tripler Army Medical Center, Yancey et al.50 reported
no change in the instrumental vaginal delivery rate
(11.1% vs. 11.9%) despite an increase in the epidural
analgesia rate from 1% to 80% in a 1-year period.
c. A systematic review of seven impact studies involving
more than 28,000 patients showed no difference in
instrumental vaginal delivery rates (mean change, 0.76%;
95% CI, −1.2 to 2.8).51
E. These conflicting results emphasize the potential impact of
multiple confounding factors on data interpretation regarding the
influence of neuraxial analgesia on instrumental vaginal delivery
 rates. The contribution of these factors to the outcome of second
stage of labor is not only poorly understood, but also poorly
controlled in many studies. Some of these factors include:
1. Neuraxial analgesia–induced motor blockade
2. Maternal pain and the urge to bear down
3. Fetal station and position
4. Definition of prolonged second stage and indications for
instrumental vaginal delivery

CLINICAL PEARL Randomized controlled trials and

observational and impact studies conflict over whether neuraxial
analgesia increases the risk of instrumental delivery. How neuraxial
analgesia impacts factors that may affect the second stage of labor
is not well understood.

F. The density of neuraxial analgesia may significantly influence

the outcome of the second stage of labor.
1. Dense sensory blockade of the uterus and birth canal can
decrease the ability to coordinate maternal expulsive efforts
with uterine contractions.
2. Motor blockade secondary to high doses/concentrations of
epidural local anesthetic may result in:
a. Relaxation of abdominal wall musculature causing
decreased effectiveness of maternal expulsive efforts
b. Relaxation of the pelvic musculature, which may interfere
with fetal rotation during descent
3. Obstetricians are more likely to perform instrumental vaginal
delivery in patients with effective second stage analgesia.
4. The specific neuraxial analgesia technique, local anesthetic
concentrations used, and method of maintenance of epidural
analgesia influence the density of neuraxial analgesia, which
may influence the risk of instrumental vaginal delivery.
a. Results from randomized controlled trials and systematic
 reviews investigating the impact of neuraxial technique on
instrumental vaginal delivery are conflicting.
(1) Collis et al.52 found no difference in instrumental
vaginal delivery rates between parturients
randomized to receive “low-dose” CSE analgesia
(intrathecal bupivacaine/fentanyl followed by
intermittent boluses of epidural 0.1%
bupivacaine/fentanyl 2 μg per mL) and traditional
“high-dose” epidural analgesia (0.25% bupivacaine).
(2) In contrast, the Comparative Obstetric Mobile
Epidural Trial (COMET) study group reported a
lower rate of instrumental vaginal delivery in the
groups randomized to either low-dose epidural or
CSE techniques (0.1% bupivacaine/fentanyl 2 μg per
mL) compared with the high-dose epidural technique
(0.25% bupivacaine).47
(3) A 2012 meta-analysis demonstrated no difference in
the rate of instrumental vaginal delivery between
low-dose epidural and CSE techniques (risk ratio
1.07; 95% CI, 0.88 to 1.30) but did find an increased
risk of instrumental vaginal delivery between high-
dose epidural and CSE techniques (risk ratio 0.81;
95% CI, 0.67 to 0.97).53
b. Multiple studies have demonstrated that lower
concentrations of bupivacaine are associated with a
lower risk for instrumental vaginal delivery.
(1) James et al.54 noted that women randomly assigned
to receive epidural 0.1% bupivacaine/fentanyl 2 μg
per mL had a lower incidence of instrumental
vaginal delivery than women who received epidural
0.25% bupivacaine (6% vs. 24%; P = .03).
(2) A 2013 systematic review involving 11 studies (n =
1,997) demonstrated lower risk of assisted vaginal
delivery (odds ratio 0.70; 95% CI, 0.56 to 0.86)
 when lower concentrations of bupivacaine (≤0.1%) or
ropivacaine (≤0.17%) are used compared with higher
concentrations. The authors also determined that use
of the lower concentration of epidural local anesthetic
would result in 14 people needing to be treated to
prevent one assisted vaginal delivery (95% CI, 9 to
25).25
c. Maintenance of labor analgesia with an intermittent bolus
compared with a continuous infusion technique is, in
general, associated with a lower dose of bupivacaine,
which in turn, is associated with a lower degree of motor
blockade. However, the relationship between motor
blockade and instrumental vaginal delivery is
inconsistent.
(1) Capogna et al.55 randomized women to a
programmed intermittent bolus technique versus
continuous epidural infusion, with PCEA for
breakthrough pain, and found a significant increase
in the instrumental delivery rate (7% vs. 20%, P =
.03) and higher incidence of motor block (2.7% vs.
37%, P < .001) in the continuous infusion group.
(2) However, the COMET study demonstrated no
difference in the instrumental vaginal delivery
rate between the low-dose epidural group
(maintained by continuous infusion) and CSE group
(maintained by intermittent boluses) despite a
significantly lower total bupivacaine dose in the CSE
group than the epidural group.47
(3) Additionally, a systematic review of eight studies (n
= 652) comparing programmed intermittent epidural
bolus versus continuous epidural infusion resulted in
no difference in the risk of instrumental vaginal
delivery between these two modes of maintaining
epidural analgesia (odds ratio 0.59; 95% CI, 0.35 to
 1.00).24
G. Fetal malposition
1. Motor blockade may increase the risk of malrotation of the
vertex fetal position. However, the association between
epidural analgesia and fetal malposition is controversial.
a. Lieberman et al.56 performed a prospective cohort study
demonstrating, via serial ultrasonographic examinations, a
higher incidence of occiput position at delivery in
women with epidural analgesia (13% vs. 3%, P < .002).
Despite an increase in fetal malposition at delivery, there
was no increase in instrumental vaginal delivery
between groups.
b. A systematic analysis of four studies (n = 673) also
demonstrated no difference in the incidence of fetal
malposition between women who received epidural
analgesia and nonepidural analgesia (risk ratio 1.40; 95%
CI, 0.98 to 1.99).18
2. Interpretation of these results need to be made with caution
because confounding factors exist, which are poorly
controlled in several studies:
a. Women with fetal occiput posterior presentation may be
more likely to request neuraxial analgesia due to the
extreme pain of “back labor” typically seen with this
presentation.
b. Greater pain during labor, subsequent breakthrough pain
during neuraxial analgesia, and the resulting need for
supplemental bolus (top-up) doses may result in maternal
motor blockade. However, it is unclear if this motor
blockade results in fetal malpositioning, or if fetal
malpositioning results in increased pain during labor and
need for higher local anesthetic doses.
H. Maternal perineal injury
1. Operative vaginal delivery may increase the risk of maternal
perineal injury (i.e., third- and fourth-degree vaginal
 lacerations).
2. If effective epidural analgesia prolongs the duration of the
second stage of labor and potentially increases the risk of
operative vaginal delivery, one might assume that epidural
analgesia may have an effect on the incidence of maternal
perineal injury. Although studies investigating the role of
epidural analgesia in the occurrence of obstetric anal sphincter
injury are conflicting, most population-based studies
demonstrate no difference or even a protective effect of
epidural analgesia on the development of maternal perineal
injury.57,58
a. In a large population-based study (n = 214,256), epidural
analgesia was found to decrease the risk of obstetric
anal sphincter injury compared to no neuraxial analgesia
(adjusted odds ratio 0.84; 95% CI, 0.81 to 0.88).59
I. Summary
1. The overall available evidence suggests that effective
neuraxial analgesia in the second stage of labor results in
an increased risk of instrumental vaginal delivery.
2. Neuraxial labor analgesia is not generic; differences in
techniques may differentially affect outcomes. Differences in
local anesthetic doses/concentrations and modes of
maintaining epidural analgesia affect the density of neuraxial
analgesia during the second stage, which may influence the
mode of delivery.
3. Lower concentrations of epidural local anesthetics are
associated with a decreased incidence of instrumental
vaginal delivery.
4. The impact of neuraxial analgesia on fetal malrotation is
unclear, but likely depends on degree of maternal motor
block.
5. Despite an increased risk of instrumental vaginal delivery,
epidural analgesia has been shown in most population-based
studies to have no effect or even a protective effect on the
 occurrence of maternal perineal injury.

CLINICAL PEARL Lower concentrations of epidural local

anesthetic are associated with a decrease in instrumental deliveries.
This may be related to a decrease in associated maternal motor
blockade and fetal malrotation.

VI. Cesarean delivery

A. Observational data uniformly suggest that use of neuraxial labor
analgesia is associated with increased risk of CD, but more
scientifically rigorous studies demonstrate that a cause-and-effect
relationship is unlikely.
B. Impact studies demonstrate no increase in CD rates despite an
increase in epidural analgesia rate.
1. Impey et al.49 compared obstetric outcomes for the first 1,000
nulliparous, term, spontaneously laboring parturients who
delivered at the Dublin National Maternity Hospital in 1987
with similar groups of women who delivered in 1992 and
1994. During this time period, the epidural analgesia rate
increased (10% in 1987, 45% in 1992, and 57% in 1994), yet
the CD rate remained unchanged (4% in 1987, 5% in 1992,
and 4% in 1994; P = NS).
2. Despite an increase in epidural analgesia use from 1% to 80%
over a 1-year period in 1993 at Tripler Army Hospital, Yancey
et al.50 demonstrated no change in the CD rate (14.4% before
vs. 12.1% after introduction of neuraxial analgesia; adjusted
risk ratio 0.8; 95% CI, 0.6 to 1.2).
3. In a systematic analysis involving nine impact studies (n =
37,753), Segal et al.51 found no increase in the rate of CD
during a period of increased use of epidural analgesia
compared with a historical control period.
C. Multiple randomized controlled trials and meta-analyses have
also found no increase in CD rates between women randomized
 to neuraxial and systemic opioid analgesia for labor.
1. Parkland Hospital in Dallas performed four randomized
controlled trials and one individual patient meta-analysis
comparing neuraxial with systemic opioid labor analgesia.
a. Parkland Hospital had a unique organizational setup that
eliminated several factors known to confound results of
similar studies, for example, patient and obstetric provider
variability and differences in labor management.
b. Three of the four randomized controlled trials
demonstrated no difference in CD rates between women
randomized to neuraxial labor analgesia (epidural or CSE)
and systemic meperidine analgesia.45,46,60
(1) The single study that demonstrated a difference in
CD rates (9.0% in the epidural group vs. 3.9% in the
meperidine group) had a high crossover rate, and the
analysis of data was not appropriate (intent-to-treat
analysis was not used).61
(2) When an intent-to-treat analysis was performed in a
subsequent secondary analysis of the data, the CD
rate was 6% for both groups.62
c. A large individual patient meta-analysis (n = 4,465)
comparing CD rates in women randomized to epidural
analgesia versus systemic opioids demonstrated an odds
ratio for CD of 1.04 (95% CI, 0.81 to 1.34).19
2. Despite differences in several variables among included
studies (e.g., type and density of neuraxial analgesia, route of
administration of systemic analgesia, parity, crossover rate,
and obstetric management), a 2012 meta-analysis of 27
studies (n = 8,417) found no difference in CD rate between
women randomized to epidural analgesia and nonepidural
analgesia (risk ratio 1.10; 95% CI, 0.97 to 1.25).18
D. Effect of mode and density of neuraxial analgesia
1. Initiation of neuraxial analgesia
a. A 2012 meta-analysis of six studies (n = 1,015)
 randomizing women to CSE versus epidural analgesia
found no increased risk of CD between the two
techniques (risk ratio 1.06; 95% CI, 0.85 to 1.32).53
2. Maintenance of neuraxial analgesia
a. A 2013 meta-analysis of eight studies (n = 652)
demonstrated no difference in CD risk between women
whose epidural labor analgesia was maintained with
continuous epidural infusion and programmed
intermittent epidural boluses (odds ratio 0.87; 95% CI,
0.56 to 1.35).24
3. Density of neuraxial analgesia
a. The COMET study found no difference in CD rates
when women were randomized to one of three labor
analgesia regimens47:
(1) Low-dose CSE analgesia—intrathecal 0.25%
bupivacaine/fentanyl 25 μg, followed by intermittent
boluses of 0.1% bupivacaine/fentanyl 2 μg per mL
(2) Low-dose epidural analgesia—intermittent boluses of
0.1% bupivacaine/fentanyl 2 μg per mL
(3) High-dose epidural analgesia—intermittent boluses
of 0.25% bupivacaine
b. A 2013 systematic review of 11 studies (including the
COMET study) involving more than 1,900 patients also
demonstrated no increase in CD rate (odds ratio 1.05;
95% CI, 0.82 to 1.33) in women who received epidural
bupivacaine ≤0.1% or ropivacaine ≤0.17%, compared to
those who received higher epidural bupivacaine or
ropivacaine concentrations.25

CLINICAL PEARL Randomized controlled trials and impact

studies have shown that effective neuraxial analgesia does not
increase rates of CD. The risk of CD is unrelated to the technique
chosen for the initiation and maintenance of neuraxial analgesia.
 E. Timing of initiation of neuraxial analgesia
1. Observational data suggest an association between CD and
the early initiation of neuraxial analgesia during early labor
(usually defined as cervical dilation less than 4 to 5 cm).63
2. Randomized controlled trials and meta-analyses have
examined the timing of neuraxial analgesia during labor and
have demonstrated no increase in CD rates between women
who receive neuraxial analgesia earlier and later.
3. Wong et al.12 and Ohel et al.16 demonstrated no difference in
CD rates between women randomized to neuraxial labor
analgesia early in labor (median cervical dilation was 2 cm)
and systemic opioid analgesia. Differences in these two
studies included mode of neuraxial analgesia (CSE technique
in the first study12 vs. epidural technique in the second16) and
use of oxytocin augmentation (94% vs. 29%).
a. Wang et al.17 conducted a 5-year randomized controlled
trial involving more than 12,000 subjects. There was no
increase in CD rate in patients randomized to receive
epidural analgesia in the latent phase compared to active
phase of labor (23.2% vs. 22.8%, P = .51).
b. In a meta-analysis involving five studies (n = 14,836),
Wassen et al.48 found no difference in the CD rate (risk
ratio, 1.02; 95% CI, 0.96 to 1.08) when neuraxial
analgesia was initiated at a cervical dilation <4 cm
compared to women who received neuraxial analgesia at
cervical dilation ≥4 cm.
4. Current ACOG recommendations reflect the evidence that
timing of neuraxial analgesia has no impact on risk of CD.64

CLINICAL PEARL The timing of neuraxial analgesia has no

impact on the risk of CD.

VII. Influence of oxytocin augmentation and ambulation on labor

outcomes
A. Oxytocin augmentation
1. Randomized controlled trials comparing neuraxial and
systemic opioid analgesia on labor outcomes demonstrate
increased use of oxytocin augmentation in women
randomized to receive neuraxial analgesia.
a. The individual patient meta-analysis by Sharma et al.19
found more women with neuraxial analgesia required
oxytocin augmentation than those who received
meperidine (48% vs. 40%, P < .001). This occurred
despite a decrease in the concentration of the epidural
bupivacaine infusion from 0.125% to 0.0625% over the 7-
year study period.
b. A systematic review of 13 randomized trials also
demonstrated an increased risk of oxytocin augmentation
in patients who received neuraxial versus systemic opioid
analgesia (risk ratio 1.19; 95% CI, 1.03 to 1.39).18
c. None of the studies are blinded; thus, the possibility of
bias cannot be excluded.
2. The relationship between mode of neuraxial analgesia (i.e.,
CSE versus epidural technique) and need for oxytocin
augmentation does not favor one technique over another. A
meta-analysis of 883 patients randomized to CSE versus
epidural analgesia showed a risk ratio of 0.95 (95% CI, 0.84
to 1.09).53
3. Randomized controlled trials investigating early versus late
initiation of neuraxial analgesia have utilized different rates of
oxytocin augmentation, but report no adverse labor outcomes
with the early initiation of neuraxial analgesia.
a. Despite a 94% oxytocin usage rate in both groups, Wong
et al.12 reported a lower maximum oxytocin rate in the
early CSE group and shorter median duration of labor.
b. Ohel et al.16 not only reported a 29% rate of oxytocin use,
but also reported a shorter duration of labor in the early
 epidural group.
c. These results suggest that oxytocin use was not a factor in
labor outcomes in these studies.
B. Ambulation
1. Ambulation and upright positioning during labor has been
shown to have potential benefits on labor outcomes in women
without neuraxial analgesia.
a. A 2013 Cochrane systematic review demonstrated that
compared to recumbent positions, ambulant and upright
positions during the first stage of labor were associated
with65:
(1) Shorter duration of first stage of labor by 1.37 hours
(weighted mean difference −1.36; 95% CI, −2.22 to
−0.51)
(2) Decreased risk of CD (risk ratio 0.71; 95% CI, 0.54
to 0.94)
b. A 2012 meta-analysis comparing upright or lateral versus
supine or lithotomy positioning in women during the
second stage of labor showed66:
(1) A decreased incidence of instrumental vaginal
delivery (risk ratio 0.78; 95% CI, 0.68 to 0.90)
(2) No difference in the second stage of labor
2. However, studies of the effects of ambulation and upright
positioning during labor in women with neuraxial analgesia
show no difference in duration of labor or mode of
delivery compared to recumbent, supine, or lithotomy
positioning.65,67

CLINICAL PEARL Oxytocin augmentation for labor is

increased in women who receive neuraxial analgesia but is
unaffected by the choice of neuraxial technique.

VIII. Impact of neuraxial analgesia on maternal fever rates (see

Chapter 8, Maternal Infection and Fever)
A. Although there are several causes for intrapartum fever, women
who receive neuraxial analgesia for labor are more likely to
have an increase in body temperature and overt fever
compared to women who choose systemic or no analgesia.68 It
is unclear why some women develop fever, but most do
not.69–71
B. The primary etiology for epidural-associated fever appears to be
maternal noninfectious inflammation,although the mechanism
by which epidural analgesia induces or augments inflammation
remains unclear. Biomarkers for inflammation, such as
interleukin 6, are more likely to be elevated in women who
develop fever after epidural analgesia72,73 and neutrophilic
placental infiltration is increased.74 However, antibiotic
administration does not reduce neutrophil inflammation or the
incidence of fever.75
C. Although epidural-associated fever may increase maternal
sympathetic stimulation and oxygen consumption, these changes
are usually well tolerated. The rates of antibiotic administration
may be increased76 and the presence of fever may alter obstetric
management.62
D. Although the risk of neonatal sepsis is not increased,62 the
frequency of neonatal sepsis evaluations may increase.77
Randomized trials of epidural use versus nonepidural analgesia
have consistently shown no differences in short term neonatal
outcome,18 but hyperthermia in women may be associated with
an increased risk of short-term neonatal adverse effects.78 Long-
term neonatal effects in absence of maternal infection have not
been evaluated.68
E. Further research is necessary to determine the exact association
between epidural analgesia, maternal fever and inflammation, and
neonatal outcomes. Meanwhile, when maternal fever occurs,
clinical practice should be directed to lowering maternal
temperature and treating maternal infection, if presumed present.
 CLINICAL PEARL Epidural analgesia increases rates of
noninfectious maternal fever.

IX. Impact of neuraxial analgesia on breastfeeding success rates

A. It has been hypothesized that intrapartum neuraxial analgesia is
associated with decreased breastfeeding success. Proposed
mechanisms include:
1. Lipophilic neuraxial opioids cross the neonatal blood–brain
barrier resulting in depressed neonatal feeding behaviors.79
2. Women with neuraxial analgesia have decreased acute stress
levels, which may affect neuro organizing behaviors in utero,
resulting in a decreased immediate need for neonates to
organize neurobehaviors (including breastfeeding) during the
postpartum period.64
B. Studies are conflicting regarding the impact of neuraxial
analgesia on breastfeeding success rates. These conflicting results
are primarily due to deficiencies in study design, including lack
of control of factors known to affect breastfeeding outcomes.
1. Limitations in study designs include:
a. Nonstandardization of breastfeeding scoring systems
among studies
b. Variability in dose and type of opioids and local
anesthetics within and among studies
c. Differences among institutions with types of breastfeeding
support programs in place
d. Lack of randomization
e. Failure to control for body mass index because women
with obesity are more likely to have breastfeeding failure
f. Failure to control for oxytocin augmentation of labor
2. Wieczorek et al.80 performed a prospective, observational,
cohort study in women who previously breastfed successfully
for >6 weeks and found no relationship between epidural
fentanyl dose and breastfeeding rates at 6 weeks’
 postpartum. However, this study was likely underpowered to
detect any difference because the authors reported high
breastfeeding success rates (92% to 98%).
3. Beilin et al.81 performed a double-blind study in women who
previously breastfed successfully. Subjects were randomized
to receive epidural analgesia with bupivacaine and one of
three fentanyl doses: no fentanyl, intermediate-dose (1 to 150
μg) or high-dose fentanyl (>150 μg). The authors found:
a. No difference among the three groups in the incidence of
difficulty with breastfeeding 24-hour postpartum.
However, this study was likely underpowered to detect a
difference.
b. When the data were reanalyzed based on the actual
amount of fentanyl the patient received (rather than group
assignment), women who received >150 μg fentanyl had
more difficulty with breastfeeding at 24 hours compared
to those who received an intermediate dose or no fentanyl.
c. At 6 weeks’ postpartum, mothers who were assigned
and/or received >150 μg were more likely to have stopped
breastfeeding compared to the other two groups.
C. These conflicting results demonstrate that:
1. Breastfeeding is a complex process that has several social,
cultural, and medical factors, which may impact success rates.
2. More randomized controlled trials, controlling for factors
known to affect breastfeeding success rates, are needed before
any evidence-based recommendations can be made.

CLINICAL PEARL The effects of neuraxial analgesia on

breastfeeding have not been determined.

X. Conclusion
A. Neuraxial analgesia has the potential to positively and negatively
affect labor outcomes.
B. No single medication or technique exists that can universally
 manage labor pain for all patients and circumstances. Anesthesia
providers need to assess each patient’s individual needs in order
to provide safe and effective labor analgesia.

REFERENCES
1. Jones L, Othman M, Dowswell T, et al. Pain management for women in labour: an overview of
systematic reviews. Cochrane Database Syst Rev. 2012;(3):CD009234.
2. Bucklin BA, Hawkins JL, Anderson JR, et al. Obstetric anesthesia workforce survey: twenty-year
update. Anesthesiology. 2005;103:645–653.
3. Osterman MJ, Martin JA. Epidural and spinal anesthesia use during labor: 27-state reporting area,
2008. Natl Vital Stat Rep. 2011;59:1–16.
4. Philip J, Alexander JM, Sharma SK, et al. Epidural analgesia during labor and maternal fever.
Anesthesiology. 1999;90:1271–1275.
5. Paech MJ. The King Edward Memorial Hospital 1,000 mother survey of methods of pain relief in
labour. Anaesth Intensive Care. 1991;19:393–399.
6. Capogna G, Camorcia M, Stirparo S. Expectant fathers’ experience during labor with or without
epidural analgesia. Int J Obstet Anesth. 2007;16:110–115.
7. Levinson G, Shnider SM, DeLorimier AA, et al. Effects of maternal hyperventilation on uterine blood
flow and fetal oxygenation and acid-base status. Anesthesiology. 1974;40:340–347.
8. Noble AD, Craft IL, Bootes JA, et al. Continuous lumbar epidural analgesia using bupivicaine: a study
of the fetus and newborn child. J Obstet Gynaecol Br Commonw. 1971;78:559–563.
9. Peabody JL. Transcutaneous oxygen measurement to evaluate drug effects. Clin Perinatol.
1979;6:109–121.
10. Shnider SM, Abboud TK, Artal R, et al. Maternal catecholamines decrease during labor after lumbar
epidural anesthesia. Am J Obstet Gynecol. 1983;147:13–15.
11. Smith CV, Rayburn WF, Allen KV, et al. Influence of intravenous fentanyl on fetal biophysical
parameters during labor. J Matern Fetal Med. 1996;5:89–92.
12. Wong CA, Scavone BM, Peaceman AM, et al. The risk of cesarean delivery with neuraxial analgesia
given early versus late in labor. N Engl J Med. 2005;352:655–665.
13. Yoo KY, Lee J, Kim HS, et al. The effects of opioids on isolated human pregnant uterine muscles.
Anesth Analg. 2001;92:1006–1009.
14. Hess PE, Pratt SD, Soni AK, et al. An association between severe labor pain and cesarean delivery.
Anesth Analg. 2000;90:881–886.
15. Alexander JM, Sharma SK, McIntire DD, et al. Intensity of labor pain and cesarean delivery. Anesth
Analg. 2001;92:1524–1528.
16. Ohel G, Gonen R, Vaida S, et al. Early versus late initiation of epidural analgesia in labor: does it
increase the risk of cesarean section? A randomized trial. Am J Obstet Gynecol. 2006;194:600–605.
17. Wang F, Shen X, Guo X, et al. Epidural analgesia in the latent phase of labor and the risk of cesarean
delivery: a five-year randomized controlled trial. Anesthesiology. 2009;111:871–880.
18. Anim-Somuah M, Smyth RM, Jones L. Epidural versus non-epidural or no analgesia in labour.
Cochrane Database Syst Rev. 2011;(12):CD000331.
19. Sharma SK, McIntire DD, Wiley J, et al. Labor analgesia and cesarean delivery: an individual patient
meta-analysis of nulliparous women. Anesthesiology. 2004;100:142–148.
20. Gambling D, Berkowitz J, Farrell TR, et al. A randomized controlled comparison of epidural analgesia
 and combined spinal-epidural analgesia in a private practice setting: pain scores during first and
second stages of labor and at delivery. Anesth Analg. 2013;116:636–643.
21. Tsen LC, Thue B, Datta S, et al. Is combined spinal-epidural analgesia associated with more rapid
cervical dilation in nulliparous patients when compared with conventional epidural analgesia?
Anesthesiology. 1999;91:920–925.
22. Campbell DC, Zwack RM, Crone LA, et al. Ambulatory labor epidural analgesia: bupivacaine versus
ropivacaine. Anesth Analg. 2000;90:1384–1389.
23. van der Vyver M, Halpern S, Joseph G. Patient-controlled epidural analgesia versus continuous
infusion for labour analgesia: a meta-analysis. Br J Anaesth. 2002;89:459–465.
24. George RB, Allen TK, Habib AS. Intermittent epidural bolus compared with continuous epidural
infusions for labor analgesia: a systematic review and meta-analysis. Anesth Analg. 2013;116:133–
144.
25. Sultan P, Murphy C, Halpern S, et al. The effect of low concentrations versus high concentrations of
local anesthetics for labour analgesia on obstetric and anesthetic outcomes: a meta-analysis. Can J
Anaesth. 2013;60:840–854.
26. McGaughey HS Jr, Corey EL, Eastwood D, et al. Effect of synthetic anesthetics on the spontaneous
motility of human uterine muscle in vitro. Obstet Gynecol. 1962;19:233–240.
27. Fanning RA, Campion DP, Collins CB, et al. A comparison of the inhibitory effects of bupivacaine
and levobupivacaine on isolated human pregnant myometrium contractility. Anesth Analg.
2008;107:1303–1307.
28. Abrão KC, Francisco RP, Miyadahira S, et al. Elevation of uterine basal tone and fetal heart rate
abnormalities after labor analgesia: a randomized controlled trial. Obstet Gynecol. 2009;113:41–47.
29. Van de Velde M, Teunkens A, Hanssens M, et al. Intrathecal sufentanil and fetal heart rate
abnormalities: a double-blind, double placebo-controlled trial comparing two forms of combined
spinal epidural analgesia with epidural analgesia in labor. Anesth Analg. 2004;98:1153–1159.
30. Patel NP, El-Wahab N, Fernando R, et al. Fetal effects of combined spinal-epidural vs epidural labour
analgesia: a prospective, randomised double-blind study. Anaesthesia. 2014;69:458–467.
31. Abboud TK, David S, Nagappala S, et al. Maternal, fetal, and neonatal effects of lidocaine with and
without epinephrine for epidural anesthesia in obstetrics. Anesth Analg. 1984;63:973–979.
32. Craft JB Jr, Epstein BS, Coakley CS. Effect of lidocaine with epinephrine versus lidocaine (plain) on
induced labor. Anesth Analg. 1972;51:243–246.
33. Cheek TG, Samuels P, Miller F, et al. Normal saline i.v. fluid load decreases uterine activity in active
labour. Br J Anaesth. 1996;77:632–635.
34. Rahm VA, Hallgren A, Högberg H, et al. Plasma oxytocin levels in women during labor with or
without epidural analgesia: a prospective study. Acta Obstet Gynecol Scand. 2002;81:1033–1039.
35. Reitman E, Conell-Price J, Evansmith J, et al. β2-adrenergic receptor genotype and other variables that
contribute to labor pain and progress. Anesthesiology. 2011;114:927–939.
36. Terkawi AS, Jackson WM, Thiet MP, et al. Oxytocin and catechol-O-methyltransferase receptor
genotype predict the length of the first stage of labor. Am J Obstet Gynecol. 2012;207:184.e1–184.e8.
37. Zhang J, Landy HJ, Branch DW, et al. Contemporary patterns of spontaneous labor with normal
neonatal outcomes. Obstet Gynecol. 2010;116:1281–1287.
38. Laughon SK, Branch DW, Beaver J, et al. Changes in labor patterns over 50 years. Am J Obstet
Gynecol. 2012;206:419.e1–419.e9.
39. Cheng YW, Shaffer BL, Nicholson JM, et al. Second stage of labor and epidural use: a larger effect
than previously suggested. Obstet Gynecol. 2014;123:527–535.
40. Rouse DJ, Weiner SJ, Bloom SL, et al. Second-stage labor duration in nulliparous women: relationship
to maternal and perinatal outcomes. Am J Obstet Gynecol. 2009;201:357.e1–351.e7.
41. Laughon SK, Berghella V, Reddy UM, et al. Neonatal and maternal outcomes with prolonged second
stage of labor. Obstet Gynecol. 2014;124:57–67.
42. American College of Obstetrics and Gynecology Committee on Practice Bulletins—Obstetrics. ACOG
Practice Bulletin Number 49, December 2003: Dystocia and augmentation of labor. Obstet Gynecol.
2003;102:1445–1454.
43. Fraser WD, Marcoux S, Krauss I, et al. Multicenter, randomized, controlled trial of delayed pushing
for nulliparous women in the second stage of labor with continuous epidural analgesia. The PEOPLE
(Pushing Early or Pushing Late with Epidural) Study Group. Am J Obstet Gynecol. 2000;182:1165–
1172.
44. Tuuli MG, Frey HA, Odibo AO, et al. Immediate compared with delayed pushing in the second stage
of labor: a systematic review and meta-analysis. Obstet Gynecol. 2012;120:660–668.
45. Gambling DR, Sharma SK, Ramin SM, et al. A randomized study of combined spinal-epidural
analgesia versus intravenous meperidine during labor: impact on cesarean delivery rate.
Anesthesiology. 1998;89:1336–1344.
46. Sharma SK, Alexander JM, Messick G, et al. Cesarean delivery: a randomized trial of epidural
analgesia versus intravenous meperidine analgesia during labor in nulliparous women. Anesthesiology.
2002;96:546–551.
47. Comparative Obstetric Mobile Epidural Trial Study Group UK. Effect of low-dose mobile versus
traditional epidural techniques on mode of delivery: a randomised controlled trial. Lancet.
2001;358:19–23.
48. Wassen MM, Zuijlen J, Roumen FJ, et al. Early versus late epidural analgesia and risk of instrumental
delivery in nulliparous women: a systematic review. BJOG. 2011;118:655–661.
49. Impey L, MacQuillan K, Robson M. Epidural analgesia need not increase operative delivery rates. Am
J Obstet Gynecol. 2000;182:358–363.
50. Yancey MK, Pierce B, Schweitzer D, et al. Observations on labor epidural analgesia and operative
delivery rates. Am J Obstet Gynecol. 1999;180:353–359.
51. Segal S, Su M, Gilbert P. The effect of a rapid change in availability of epidural analgesia on the
cesarean delivery rate: a meta-analysis. Am J Obstet Gynecol. 2000;183:974–978.
52. Collis RE, Davies DW, Aveling W. Randomised comparison of combined spinal-epidural and standard
epidural analgesia in labour. Lancet. 1995;345:1413–1416.
53. Simmons SW, Taghizadeh N, Dennis AT, et al. Combined spinal-epidural versus epidural analgesia in
labour. Cochrane Database Syst Rev. 2012;(10):CD003401.
54. James KS, McGrady E, Quasim I, et al. Comparison of epidural bolus administration of 0.25%
bupivacaine and 0.1% bupivacaine with 0.0002% fentanyl for analgesia during labour. Br J Anaesth.
1998;81:507–510.
55. Capogna G, Camorcia M, Stirparo S, et al. Programmed intermittent epidural bolus versus continuous
epidural infusion for labor analgesia: the effects on maternal motor function and labor outcome. A
randomized double-blind study in nulliparous women. Anesth Analg. 2011;113:826–831.
56. Lieberman E, Davidson K, Lee-Parritz A, et al. Changes in fetal position during labor and their
association with epidural analgesia. Obstet Gynecol. 2005;105:974–982.
57. Baghestan E, Irgens LM, Børdahl PE, et al. Trends in risk factors for obstetric anal sphincter injuries
in Norway. Obstet Gynecol. 2010;116:25–34.
58. Richter HE, Brumfield CG, Cliver SP, et al. Risk factors associated with anal sphincter tear: a
comparison of primiparous patients, vaginal births after cesarean deliveries, and patients with previous
vaginal delivery. Am J Obstet Gynecol. 2002;187:1194–1198.
59. Jangö H, Langhoff-Roos J, Rosthøj S, et al. Modifiable risk factors of obstetric anal sphincter injury in
primiparous women: a population-based cohort study. Am J Obstet Gynecol. 2014;210:59.e1–59.e6.
60. Sharma SK, Sidawi JE, Ramin SM, et al. Cesarean delivery: a randomized trial of epidural versus
patient-controlled meperidine analgesia during labor. Anesthesiology. 1997;87:487–494.
61. Ramin SM, Gambling DR, Lucas MJ, et al. Randomized trial of epidural versus intravenous analgesia
during labor. Obstet Gynecol. 1995;86:783–789.
62. Lieberman E, Cohen A, Lang J, et al. Maternal intrapartum temperature elevation as a risk factor for
cesarean delivery and assisted vaginal delivery. Am J Public Health. 1999;89:506–510.
63. Thorp JA, Hu DH, Albin RM, et al. The effect of intrapartum epidural analgesia on nulliparous labor:
a randomized, controlled, prospective trial. Am J Obstet Gynecol. 1993;169:851–858.
64. Bell AF, White-Traut R, Medoff-Cooper B. Neonatal neurobehavioral organization after exposure to
maternal epidural analgesia in labor. J Obstet Gynecol Neonatal Nurs. 2010;39:178–190.
65. Lawrence A, Lewis L, Hofmeyr GJ, et al. Maternal positions and mobility during first stage labour.
Cochrane Database Syst Rev. 2013;(8):CD003934.
66. Gupta JK, Hofmeyr GJ, Shehmar M. Position in the second stage of labour for women without
epidural anaesthesia. Cochrane Database Syst Rev. 2012;(5):CD002006.
67. Kemp E, Kingswood CJ, Kibuka M, et al. Position in the second stage of labour for women with
epidural anaesthesia. Cochrane Database Syst Rev. 2013;(1):CD008070.
68. Segal S. Labor epidural analgesia and maternal fever. Anesth Analg. 2010;111:1467–1475.
69. Goetzl L, Rivers J, Zighelboim I, et al. Intrapartum epidural analgesia and maternal temperature
regulation. Obstet Gynecol. 2007;109:687–690.
70. Herbst A, Wølner-Hanssen P, Ingemarsson I. Risk factors for fever in labor. Obstet Gynecol.
1995;86:790–794.
71. Soper DE, Mayhall CG, Dalton HP. Risk factors for intraamniotic infection: a prospective
epidemiologic study. Am J Obstet Gynecol. 1989;161:562–566.
72. Goetzl L, Evans T, Rivers J, et al. Elevated maternal and fetal serum interleukin-6 levels are associated
with epidural fever. Am J Obstet Gynecol. 2002;187:834–838.
73. Goetzl L, Zighelboim I, Badell M, et al. Maternal corticosteroids to prevent intrauterine exposure to
hyperthermia and inflammation: a randomized, double-blind, placebo-controlled trial. Am J Obstet
Gynecol. 2006;195:1031–1037.
74. Riley LE, Celi AC, Onderdonk AB, et al. Association of epidural-related fever and noninfectious
inflammation in term labor. Obstet Gynecol. 2011;117:588–595.
75. Sharma SK, Rogers BB, Alexander JM, et al. A randomized trial of the effects of antibiotic
prophylaxis on epidural-related fever in labor. Anesth Analg. 2014;118:604–610.
76. Goetzl L, Cohen A, Frigoletto F Jr, et al. Maternal epidural analgesia and rates of maternal antibiotic
treatment in a low-risk nulliparous population. J Perinatol. 2003;23:457–461.
77. Lieberman E, Lang JM, Frigoletto F Jr, et al. Epidural analgesia, intrapartum fever, and neonatal
sepsis evaluation. Pediatrics. 1997;99:415–419.
78. Greenwell EA, Wyshak G, Ringer SA, et al. Intrapartum temperature elevation, epidural use, and
adverse outcome in term infants. Pediatrics. 2012;129:e447–e454.
79. Loftus JR, Hill H, Cohen SE. Placental transfer and neonatal effects of epidural sufentanil and fentanyl
administered with bupivacaine during labor. Anesthesiology. 1995;83:300–308.
80. Wieczorek PM, Guest S, Balki M, et al. Breastfeeding success rate after vaginal delivery can be high
despite the use of epidural fentanyl: an observational cohort study. Int J Obstet Anesth. 2010;19:273–
277.
81. Beilin Y, Bodian CA, Weiser J, et al. Effect of labor epidural analgesia with and without fentanyl on
infant breast-feeding: a prospective, randomized, double-blind study. Anesthesiology. 2005;103:1211–
1217.
 Anesthetic Considerations for Women Receiving
Cesarean Delivery
Robert R. Gaiser

I. Background
II. Indications for cesarean delivery
III. Surgical considerations
A. Technical aspects
IV. Complications of cesarean delivery
A. Anesthetic complications
B. Surgical complications
C. Subsequent pregnancy risk
V. Preoperative considerations
A. Preoperative assessment
B. Consent
C. Blood products
D. Aspiration prophylaxis
E. Supplemental oxygen
F. Other preparation
G. Intraoperative medications
VI. Anesthetic techniques
A. Basic considerations
B. Epidural anesthesia for cesarean delivery
C. Spinal anesthesia for cesarean delivery
D. Combined spinal-epidural anesthesia for cesarean delivery
 E. General anesthesia for cesarean delivery
VII. Postoperative management
VIII. Conclusions

KEYPOINTS
1. Cesarean delivery (CD) is the most commonly performed surgical
procedure.
2. In women receiving neuraxial anesthesia, high neuraxial block is a
leading cause of maternal mortality.
3. Hemorrhage, heart failure, amniotic fluid embolism, and sepsis are
common etiologies for cardiac arrest during hospitalization for delivery.
4. Obstetric blood loss is often underestimated.
5. Maternal history and risk of hemorrhage should guide decision making
about whether a type and screen or a type and cross match should be
obtained prior to CD.
6. Before cesarean delivery, practitioners should consider the timely
administration of nonparticulate antacids, H2-receptor antagonists, and/or
metoclopramide for aspiration prophylaxis.1
7. Uncomplicated patients who are scheduled for elective cesarean delivery
may have moderate amounts of clear fluids 2 hours and greater prior to
induction of anesthesia.1
8. The patient undergoing elective cesarean delivery or postpartum tubal
sterilization should not eat solid food for 6-8 hours beforehand,
depending on the composition of the food (e.g., fat content).1
9. Antibiotic prophylaxis should be administered within 1 hour of the
surgical incision.
10. Although phenylephrine is associated with fewer metabolic effects on the
fetus, either phenylephrine or ephedrine may be used for the prevention
and treatment of hypotension associated with anesthetic administration.
11. The decision to use a specific anesthetic technique for CD depends on the
situation and patient factors such as severe thrombocytopenia. The
 obstetrician determines the urgency of the case.
12. Regardless of the anesthetic technique, all patients are maintained in left
uterine displacement until delivery of the neonate.
13. The administration of a bolus of crystalloid intravenously prior to and
during the initiation of neuraxial anesthesia may decrease the incidence
of hypotension but does not reliably prevent hypotension.
14. Combined spinal-epidural anesthesia may be advantageous when the
duration of CD is expected to outlast the spinal anesthetic.
15. Failed intubation, failed ventilation and oxygenation, and pulmonary
aspiration of gastric contents remain leading anesthesia-related causes of
maternal death, but there are new concerns of hypoventilation or airway
obstruction during extubation, emergence, or recovery.

I. Background
A. Cesarean delivery (CD) remains the most frequently performed
surgical procedure in the United States.
1. Beginning in 1998, the CD rate has increased every year until
2009. In 2009, it peaked at 32.9% of all births. The total rate
declined in 2010 to 32.8% and remained stable for 2011 and
2012.2
2. Recently, the American College of Obstetricians and
Gynecologists (ACOG) and the Society for Maternal and
Fetal Medicine issued a joint consensus statement: “The rapid
increase in the rate of cesarean births without evidence of
concomitant decreases in maternal or neonatal morbidity or
mortality raises significant concern that cesarean delivery is
overused. Therefore, it is important for health care providers
to understand . . . the safe and appropriate opportunities to
prevent overuse of cesarean delivery, particularly primary
cesarean delivery.” 3
This document includes 19 recommendations to decrease the
CD rate.
3. Approximately 60% of all CDs are primary (first-time CD).
 Although in many cases, a prior cesarean does not necessitate
a subsequent CD; rates of trial of labor after cesarean
(TOLAC) have declined in recent years.
4. In 2012, the states with the lowest CD rate were Utah and
Idaho, whereas Louisiana and Florida had the highest rates.2
5. The increase in the use of epidural analgesia for labor is not
the reason for this increase in the incidence of CD, even if
administered early in the course of labor.4
B. Although CD rates have increased worldwide, rates vary by
country and are related to maternal, fetal, medicolegal,
socioeconomic, and obstetric factors.
C. Cesarean delivery on maternal request (CDMR) is a recent
consideration in obstetric practice. It is defined as a primary
prelabor CD on maternal request in the absence of any maternal
or fetal indications. Estimates suggest that these requests do not
contribute substantially to the increased CD rates. The ACOG
Committee on Obstetric Practice has concluded “that in the
absence of maternal or fetal indications for cesarean delivery, a
plan for vaginal delivery is safe and appropriate and should be
recommended to patients. In cases in which cesarean delivery on
maternal request is planned, delivery should not be performed
before a gestational age of 39 weeks. Cesarean delivery on
maternal request should not be motivated by the unavailability of
effective pain management. Cesarean delivery on maternal
request particularly is not recommended for women desiring
several children, given that the risks of placenta previa, placenta
accreta, and gravid hysterectomy increase with each cesarean
delivery.”5
D. “Obstetricians may accede to a patient’s request for CDMR.
However, obstetricians are not obliged ethically or professionally
to do so, and if the patient and clinician cannot agree on an
intended route of delivery, ACOG indicates that referral to
another health care practitioner is appropriate.”6
E. As compared to planned vaginal delivery, planned CD without
 obstetric or fetal indications may be associated with lower rates of
hemorrhage and transfusion, surgical complications, and maternal
incontinence in the first year following delivery. However, it is
associated with a higher rate of neonatal respiratory morbidity
compared with vaginal delivery when delivery is earlier than 39
to 40 weeks of gestation.5
F. A recent meta-analysis of 157 eligible randomized controlled
trials (n = 31,085) evaluated whether the risk of cesarean was
higher following induction of labor. The results suggested that the
risk of CD was 12% lower when induction occurred in term and
post-term gestations. In addition, the risk of fetal death or
admission to the neonatal intensive care unit was decreased and
there was no impact on maternal death.7

CLINICAL PEARL CD on maternal request should not be

motivated by the unavailability of effective pain management.

II. Indications for cesarean delivery

CD may be performed for either maternal or fetal indications (see
Table 13.1).
 III. Surgical considerations
A. Technical aspects
1. CD involves the delivery of the fetus through an incision
created in the maternal abdomen. For CD, either neuraxial or
general anesthesia is used. Anesthetic choice depends on the
urgency of the procedure and maternal comorbidities.
2. To perform a CD, the obstetrician may perform either
transverse or vertical skin incision.
a. There are two types of transverse incisions:
(1) Pfannenstiel incision. An incision that is slightly
curved 2 to 3 cm above the symphysis pubis with the
midportion of the incision within the shaved area of
the pubic hair. By using a curved incision, there is
less cutting of the nerves of the anterior abdominal
wall.
(2) Maylard incision. An incision that is straight and is
located 3 cm below the line that joins the anterior
superior iliac spines. This incision is slightly more
 cephalad than the Pfannenstiel incision. It also
involves transection of the anterior rectus sheath and
the rectus muscle bilaterally. Despite transection of
the rectus muscle, this incision has been shown not to
affect abdominal wall strength.
b. A vertical skin incision extends from the umbilicus to
the pubic symphysis. It allows for rapid access to the
uterus but is associated with a higher incidence of
development of an umbilical hernia later in life.
c. Transverse incision versus vertical uterine incisions
The decision of whether to perform a transverse versus
vertical incision is based solely on the expediency in
which delivery must occur. Transverse incisions are less
painful and are associated with a decreased risk of
developing an umbilical hernia. Once the abdomen has
been entered, the obstetrician must create an incision in
the uterus for delivery of the infant. There are three types
of uterine incisions.
(1) A low transverse incision (Kerr) is used in the
majority of cases. It carries less risk of entry into the
upper uterine segment and less bladder dissection.
Vaginal birth with a subsequent pregnancy is possible
after this incision, and it is associated with a low
incidence (0.8%) of uterine rupture.8
(2) A low vertical incision involves an incision in the
lower uterine segment. This incision may easily be
extended upward, both deliberately and accidentally.
Given this concern for accidental extension, a low
vertical incision is not frequently performed. The risk
of rupture with this incision (1.0%) is not as great as
with a classical (vertical) uterine incision but is
greater than with a low transverse incision.8
(3) A classical incision involves the upper uterine
segment. This incision has a greater risk of adhesion
 formation and greater risk of uterine rupture or
dehiscence with subsequent pregnancies
(approximately 10%). A classical incision in the
uterus is a contraindication to subsequent vaginal
delivery.8
d. There is safety and benefit to delayed cord clamping at
delivery.9 It should be considered routine in order to:
(1) Stabilize the transitional circulation, decrease the
need for inotropes and blood transfusions, and reduce
the risk of necrotizing enterocolitis and
intraventricular hemorrhage in preterm neonates.
(2) Decrease the incidence of iron deficiency anemia and
increase iron stores in term neonates.
e. After delivery of the infant, skin-to-skin contact may be
initiated for the infant. Skin-to-skin contact involves the
infant lying prone on the mother’s bare chest, with the
infant covered by a blanket. Early contact is associated
with better thermoregulation of the newborn and
improved breastfeeding. Skin-to-skin contact is possible
with CD in selected patients and will depend on local
protocols, which vary from institution to institution.10
f. The obstetrician may or may not close the peritoneum
after delivery of the infant. There is no difference in
adhesion formation with or without closure of the
peritoneum. Closure of the peritoneum increases surgical
time.11

CLINICAL PEARL A vertical uterine incision is a

contraindication to subsequent vaginal delivery.

IV. Complications of cesarean delivery

Complications of CD are either surgical or anesthesia related.
However, CD can also increase the risk in subsequent pregnancies.
 A. Anesthetic complications include hypotension, dyspnea, local
anesthetic toxicity, total or high spinal, spinal headache, failed
intubation, aspiration, awareness and recall, and death.
1. The risk of anesthetic-related maternal mortality continues to
decline. Most anesthesia-related maternal deaths are
preventable (see Chapter 32, Maternal Morbidity and
Mortality).
a. When comparing anesthesia-related deaths from 1979–
1990 to 1991–2002, anesthetic-related maternal mortality
has declined 60%.12 This is attributed to the increased use
of neuraxial anesthesia. Anesthetic complications account
for 0.3% of all pregnancy-related deaths in the United
States.13
b. The leading cause of maternal death in women receiving
neuraxial blockade for CD was a high block in a recent
survey of U.S. maternal mortality.12 High blocks can also
be related to unrecognized intrathecal catheters as well as
spinal local anesthetic administration after failed epidural
anesthesia.
c. In addition, lethal infectious complications of neuraxial
blockade, hypotensive cardiac arrest, reflex-mediated
bradycardia, and respiratory arrest are other potential
causes of anesthetic-related maternal mortality.
2. A recent report analyzing data from the Nationwide Inpatient
Sample during the years 1998 through 2011 determined that
cardiac arrest complicated 8.5 per 100,000 hospitalizations for
delivery (99% confidence interval [CI], 7.7 to 9.3 per
100,000).14 Hemorrhage, heart failure, amniotic fluid
embolism, and sepsis were identified as etiologies for the
cardiac arrests. Although survival depended on the etiology of
the arrest, nearly 60% of patients survived to hospital
discharge.

CLINICAL PEARL High neuraxial block is a leading cause of

maternal mortality. Unrecognized intrathecal catheters as well as
local anesthetic administration after failed epidural anesthesia are
important contributors.

B. Surgical complications
1. Intraoperative surgical complications occur in 12% to 15% of
CDs.15
a. The most common complication is hemorrhage.
Hemorrhage results from uterine atony, uterine
lacerations, or broad ligament hematomas.
b. The incidence of transfusion for primary CD is 3.2%,
with the median transfused volume being 2 units. The
majority of blood for primary CD is transfused
postoperatively. The incidence of transfusion for repeat
CD is 2.2%, with the majority of transfusions occurring
postoperatively. The median amount of blood transfused
is 2 units. Risk factors for transfusion include placenta
previa and preoperative anemia.16
c. The need for transfusion is not great due to the increase in
blood volume accompanying pregnancy, but an atonic
uterus can lose up to 2 L of blood in 5 minutes.
Furthermore, obstetric blood loss is often underestimated.
d. General anesthesia for CD is associated with a higher
blood loss than neuraxial anesthesia. However, this
increase in blood loss is NOT associated with an increase
in the need for blood transfusion.17
e. Table 13.2 lists the suggested resources that should be
available for management of obstetric hemorrhage.
 f. Uterine or uterocervical lacerations are the next most
common complications.
g. Other complications include bladder laceration, fetal
laceration, and hysterectomy.
2. Postoperative complications include anemia, fever, urinary
tract infection, urinary retention, endometritis, thrombosis,
ileus, and wound infection.18

CLINICAL PEARL The most common surgical complication of

CD is hemorrhage (see Chapter 16, Obstetric Emergencies).

C. Subsequent pregnancy risk

1. CD increases the risk of placental abruption in subsequent
pregnancies. The uterine scar from the CD leads to impaired
placental perfusion, which increases the risk of placental
abruption by approximately 24-fold. Placental abruption
refers to separation of the placenta after 20 weeks of gestation
but before the birth of the fetus.
2. CD increases the risk of placenta previa in subsequent
pregnancies. The uterine scar may lead to low implantation of
the placenta. Placenta previa occurs when the placenta
overlies the cervical os or is proximate to the internal os of the
cervix. Placenta accreta is defined as a placenta that invades
the uterine wall and is inseparable from it. This placental
 abnormality gives rise to three situations: (1) placenta accreta
adheres directly to the myometrium; (2) placenta increta
invades the myometrium; and (3) placenta percreta invades
through the myometrium into the serosa and potentially into
adjacent organs (e.g., bowel, bladder) (see Fig. 13.1). In a
multicenter study of more than 30,000 patients who had CD
without labor, the risk of placenta accreta was 0.2%, 0.6%,
2.1%, 2.3%, and 7.7% for women experiencing their first
through sixth CDs, respectively. In patients with placenta
previa in the current pregnancy, the risk of placenta accreta
was 3%, 11%, 40%, 61%, and 67% for those undergoing their
first through their fifth or greater CD, respectively. In patients
with placenta previa and placenta accreta, massive
intraoperative blood loss is common, averaging 2 to 3 L.19

CLINICAL PEARL CD increases the risk of placental abruption

and placenta previa in subsequent pregnancies.
3. Cesarean deliveries that require hysterectomy to control
hemorrhage are associated with significant maternal
hemorrhage. Blood loss may exceed 3 L, with the majority of
patients requiring intraoperative transfusion. Although it is
possible to accomplish these cases with neuraxial anesthesia,
general anesthesia is preferred. Early intubation removes the
concern of intubation in the setting of hemodynamic
instability and edema of the patient’s airway. When patients
require intraoperative hysterectomy, many will develop
postoperative infection, and 8% of these patients will have
urologic injury. After a cesarean hysterectomy, some women
may require blood vessel embolization in the interventional
radiology department in order to treat persistent postoperative
bleeding.
4. A prior CD does not necessitate a subsequent CD. TOLAC
(which is called vaginal birth after cesarean [VBAC] if
successful) is possible following a low transverse uterine
incision. The risk of uterine rupture is small, approximately
0.5%. Obstetric practice patterns and resources affect the
ability to offer TOLAC. In New Mexico, the number of
counties offering it decreased from 100% to 41%, citing
anesthesia availability, hospital and malpractice policies,
malpractice costs, and obstetrician availability as the top
reasons for not offering trial of labor after CD.20 Prior to
1980, it was felt that once a patient had a CD, she should
always have a CD with subsequent deliveries. From 1980 to
2000, there was increased enthusiasm for TOLAC. However,
this enthusiasm declined with the publication of a
retrospective cohort study that showed a uterine rupture
incidence of 2.5% in women with previous CD who were
being induced with prostaglandins.21 Data suggest that three
of five women who attempt TOLAC will be successful.
However, maternal obesity, history of dystocia, and induction
of labor reduce the likelihood for successful VBAC. The
 ACOG states that anesthesia personnel must be immediately
available if a laboring parturient is attempting TOLAC. This
requirement is difficult for many groups to accomplish,
removing TOLAC as an option for many patients.

CLINICAL PEARL Data suggest that three out of five women

who attempt TOLAC will be successful.

V. Preoperative considerations
A. Preoperative assessment
All patients who will undergo CD require a detailed history and
physical examination. The physical examination must be as
comprehensive as necessary but particular attention should be
paid to examination of the airway and the back. According to the
American Society of Anesthesiologists (ASA) Practice
Guidelines for Obstetric Anesthesia, “The anesthesiologist should
conduct a focused history and physical examination before
providing anesthesia care.”1

CLINICAL PEARL The anesthesiologist should conduct a

focused history and physical examination before providing
anesthesia care.

B. Consent (see Chapter 5, Ethical and Legal Considerations in

Obstetric Anesthesia)
Obtaining informed medical consent from a patient is a process
by which the risks, benefits, and alternatives are explained by the
anesthesia provider. The following elements are required.
1. The patient is competent to make decisions regarding her
health care.
2. The anesthesia provider discloses the anesthetic risks in a
noncoercive manner.
3. The patient comprehends the information.
 4. The patient authorizes consent voluntarily.
C. Blood products
1. Postpartum hemorrhage is a leading cause of maternal
mortality. Although there is no difference in the risk of
hemorrhage in patients undergoing elective CD and
uncomplicated vaginal delivery, patients undergoing CD
during labor are at greater risk for hemorrhage.
2. There is no consensus about whether a type and screen or a
type and cross match should be obtained prior to CD.1
Maternal history and risk of hemorrhage should guide
decision making.
3. Blood should be readily available for high-risk cases (e.g.,
placenta accreta).

CLINICAL PEARL Patients undergoing CD during labor are at

greater risk for hemorrhage.

D. Aspiration prophylaxis
1. All parturients undergoing CD should receive aspiration
prophylaxis preoperatively including an H2-receptor blocker,
metoclopramide, and a nonparticulate antacid.1 Aspiration
prophylaxis is a recommendation of the ASA Practice
Guidelines for Obstetric Anesthesia.1
2. Parturients in labor are at an increased risk for aspiration
during general anesthesia. Gastric emptying is slowed with
the onset of painful contractions and parenteral opioids.
Epidural and intrathecal fentanyl can also impair gastric
emptying. If a patient aspirates, the patient is at risk for the
development of pneumonitis. In 1946, Mendelson reported 66
cases of aspiration of stomach contents during obstetric
anesthesia.22 Of these patients, 5 patients aspirated solid
material; 21 patients were subsequently diagnosed as having
aspirated; and 40 patients aspirated liquid material. The
 aspiration of solid materials definitely increases the risk of
aspiration pneumonitis. For liquid material, the risk of
aspiration pneumonitis is dependent on the pH of the solution
(increased if pH<2.5) and volume of the solution (increased if
the volume is >25 mL). The administration of above
mentioned aspiration prophylaxis is thought to reduce the risk
for aspiration pneumonitis.23
3. “The oral intake of modest amounts of clear liquids may be
allowed for uncomplicated laboring patients. The
uncomplicated patient undergoing elective cesarean delivery
may have modest amounts of clear liquids up to 2 h before
induction of anesthesia. Examples of clear liquids include, but
are not limited to, water, fruit juices without pulp, carbonated
beverages, clear tea, black coffee, and sports drinks. The
volume of liquid ingested is less important than the presence
of particulate matter in the liquid ingested. However, patients
with additional risk factors for aspiration (e.g., morbid
obesity, diabetes, difficult airway) or patients at increased risk
for operative delivery (e.g., nonreassuring fetal heart rate
pattern) may have further restrictions of oral intake,
determined on a case-by-case basis.”1
4. “Solid foods should be avoided in laboring patients. The
patient undergoing elective surgery (e.g., scheduled cesarean
delivery or postpartum tubal ligation) should undergo a
fasting period for solids of 6–8 h depending on the type of
food ingested (e.g., fat content).”1

CLINICAL PEARL Gastric emptying is slowed with the onset

of painful contractions and parenteral opioids. Epidural and
intrathecal fentanyl can also impair gastric emptying.

E. Supplemental oxygen
The routine administration of supplemental oxygen during CD
 has been questioned because there is evidence that it may be
ineffective and, in some cases, detrimental because of the
conversion of oxygen to free radical oxygen species. Current
evidence suggests that supplementary oxygen given to healthy
term pregnant women during elective CD under neuraxial
anesthesia is associated with higher maternal and neonatal oxygen
levels (maternal SpO2, PaO2, UaPO2, and UvPO2) and higher
levels of oxygen free radicals. However, the intervention appears
neither beneficial or harmful to the neonate’s short-term clinical
outcome as assessed by Apgar scores.24
F. Other preparation
The ASA Practice Guidelines for Obstetric Anesthesia state that
the operating room for CD must have the same equipment as for
regular surgery.1 The ASA standards for basic monitoring apply
to the care of patients undergoing CD. The incidence of failed
intubation for CD is 1:224 general anesthetics. Whether the use of
videolaryngoscopy on the incidence of failed intubation is
unclear.25 A difficult airway cart as well as supplies for massive
hemorrhage and malignant hyperthermia should also be readily
available (see Chapter 14, Difficult Airway Management in the
Pregnant Patient).
G. Intraoperative medications
1. Prophylactic antibiotics are administered to reduce the risk
of endometritis, wound infections, urinary tract infections,
and fever. ACOG recommends administration of a first-
generation cephalosporin or other narrow-spectrum antibiotic
within 1 hour of the surgical incision.26 However, a recent
database review of over 1 million women who underwent CD
examined rates of antibiotic use and determined that only
60% of patients received antibiotics on the day of surgery.27
The study revealed a large variation by geographic region but
no influence of age, race, or insurance status.

CLINICAL PEARL A first-generation cephalosporin or other

narrow-spectrum antibiotic should be administered within 1 hour of
the surgical incision.

2. Vasopressor administration
a. A vasopressor must be readily available. Either
phenylephrine or ephedrine is an acceptable choice.
b. The initial thought that ephedrine was the preferred agent
for the treatment of hypotension during CD was based on
animal models in which α-agonists decreased uterine
blood flow but mixed agonists had no effect. Subsequent
studies did not demonstrate an effect on uterine blood
flow from α-agonists.
c. A statistically significant difference in improved umbilical
arterial pH was found for phenylephrine, but the clinical
importance of this small difference is uncertain. The
difference is not due to an effect on uterine blood flow but
because ephedrine crosses the placenta and stimulates the
release of fetal catecholamines. The increase in
catecholamine levels leads to an increase in oxygen
consumption and an increase in lactate concentration.28
d. The effect of ephedrine on umbilical arterial pH may also
be a result of genetic susceptibility in certain fetuses.
Those infants who do develop an acidosis tend to have
similar genetics.29
e. Phenylephrine is typically administered by continuous
infusion, especially when spinal anesthesia is
administered. The infusion is initiated at the time of
administration of the intrathecal medications. There is no
difference in umbilical arterial pH when phenylephrine is
administered as a continuous infusion or as intermittent
boluses. With a continuous infusion, there is a lower
incidence of maternal nausea and vomiting.30
f. Either phenylephrine or ephedrine is an acceptable choice
for the treatment of hypotension. If multiple doses are
 required, phenylephrine is the preferred drug. If the
maternal heart rate is low, as may occur with spinal
anesthesia with a T1–T2 sensory level, ephedrine is the
better choice as phenylephrine may slow the maternal
heart rate further. Rather than the choice of drug, the most
important factor is the rapid correction of hypotension
because uteroplacental perfusion is proportionate to blood
pressure. However, this has recently been questioned. In
one study of 919 mothers who underwent CD, over 30%
of patients who experienced a ≤30% decrease in maternal
mean arterial pressure for greater than 5 minutes had no
adverse effect on the neonate.31
g. In another quantitative, systematic review of studies
comparing phenylephrine and ephedrine was conducted, 7
randomized controlled trials were identified for a total of
292 patients. There was no difference between
phenylephrine and ephedrine in the ability to correct
maternal hypotension, but a higher incidence of maternal
bradycardia occurred if phenylephrine was used. In regard
to the neonate, there was no difference in the incidence of
true fetal acidosis, but neonates whose mothers received
phenylephrine had higher umbilical arterial pH values.32
h. Most recently, one study has suggested that
norepinephrine may be useful in this setting.33

CLINICAL PEARL Either phenylephrine or ephedrine is an

acceptable choice for the treatment of hypotension. If multiple
doses are required, phenylephrine is the preferred drug.

3. Treatment of uterine atony

ACOG recommends prophylactic administration of uterotonic
agents to prevent uterine atony.34 Although oxytocin is a first-
line agent for prophylaxis and treatment of uterine atony,
 methylergonovine, 15-methylprostaglandin F2α, and
misoprostol should be readily available for cases of refractory
uterine atony.
VI. Anesthetic techniques
A. Basic considerations
1. Anesthetic choice for CD includes epidural, spinal, combined
spinal-epidural, or general anesthesia.
2. Induction to delivery time is shortest for general anesthesia.
There is little impact of surgical incision to delivery and
uterine incision to delivery on the neonate.35
3. Hypotension is more often associated with epidural or spinal
anesthesia as compared to general anesthesia.
4. The literature is equivocal regarding the difference in
umbilical pH with regard to anesthetic technique.
5. Apgar scores are lowest for general anesthesia compared to
regional anesthesia, most likely secondary to transplacental
passage of the anesthetic agents. This effect is exemplified in
the lower 1-minute Apgar score with little difference
compared with other techniques in the 5-minute Apgar score.
In addition, general anesthesia is administered when there are
time constraints or neuraxial anesthesia is contraindicated or
has failed.
6. Maternal complications, specifically related to the airway, are
greatest for general anesthesia. Other complications that are
increased with general anesthesia as compared to neuraxial
anesthesia include awareness, postdelivery hemorrhage, and
surgical site infection.
7. The decision to use a specific technique for CD depends on
the situation. The obstetrician determines the urgency of the
case. There are several classifications for the urgency of CD
with each system having advantages and disadvantages.36 To
assist in determining the urgency, the obstetrician will classify
the fetal heart rate into one of three categories (see Table
13.3).
a. After the obstetrician determines the urgency of the CD,
the anesthesiologist evaluates the safety of each technique
based on history, physical examination, and laboratory
values. Although the patient will also indicate her
preference, all of the aforementioned considerations will
be used in deciding on a specific technique.
b. Regardless of the technique chosen, all patients are
maintained in left uterine displacement for the surgical
procedure. In the supine position, the gravid uterus
obstructs venous return from the vena cava. This decrease
in venous return results in decreased preload and
decreased cardiac output. In the nonanesthetized state, the
parturient will compensate for this decrease in cardiac
output with sympathetic stimulation. With general or
neuraxial anesthesia, the sympathetic response is
attenuated, resulting in no compensation. All parturients
who receive anesthesia should be positioned with left
uterine displacement until delivery of the infant. Left
uterine displacement may be obtained by tilting the table
 to the left or, preferably, by placing a wedge under the
right hip.

CLINICAL PEARL The decision to use a specific technique for

CD depends on the situation and patient factors such as severe
thrombocytopenia. The obstetrician determines the urgency of the
case.

B. Epidural anesthesia for cesarean delivery

1. In 1973, it was demonstrated that an epidural catheter placed
for labor could be used for CD.
2. Epidural anesthesia involves the injection of local anesthetic
into the epidural space. The extent of the block is dependent
on the volume of local anesthetic injected, whereas the
density of the blockade is related to the total mass of the drug.
When local anesthetic is injected epidurally, it travels both
cephalad and caudad. The extent of sensory block does not
depend on the density of the local anesthetic or on gravity;
rather, it depends on the volume of the injected local
anesthetic.
3. A sensory level of T4 is required for CD. The sensory level
may be determined by pin pick, temperature, or light touch. A
sensory level of T4 using light touch has been shown to result
in the lowest incidence of requirement for intraoperative
supplementation.37 The recommended sensory blockade for
CD varies from T8 to T2, depending on whether the uterus is
to be exteriorized for repair. Although exteriorization of the
uterus facilitates repair of the uterine incision, it has been
associated with increased rates of intraoperative nausea,
vomiting, venous air embolus, as well as postoperative pain.
a. Pain sensations from pelvic organs enter the spinal cord at
T10–L1, but more extensive blockade is required for CD
because other intraabdominal structures such as the
 peritoneum are innervated by sensory afferents that enter
the spinal cord as far cephalad as T2.
b. The lower extent of sensory blockade is also important
for patient comfort. Blocking of the large nerve roots of
L5–S4 is necessary to prevent discomfort from traction on
the uterosacral ligaments or bladder. Sacral nerve roots
are difficult to block due to the large volume of the sacral
epidural space and the larger diameter of these nerves.
c. With an epidural catheter, the block may be adjusted,
prolonged, and even reinitiated as the clinical situation
demands. These points are especially important when the
length of the procedure is unclear, as may occur with a
repeat CD.
4. The gradual onset of blockade with epidural anesthesia is
advantageous in instances when sudden decreases of blood
pressure should be avoided, such as maternal cardiovascular
disease.
5. As compared to spinal anesthesia, onset of the dense sensory
blockade required for CD takes longer with epidural
anesthesia.
6. Contraindications to epidural anesthesia are presented in
Table 13.4.

7. Potential complications of epidural anesthesia

a. Hypotension following epidural anesthesia is a result of
sympathetic blockade. The administration of a bolus of
 crystalloid intravenously prior to and during the initiation
of the block may decrease the incidence of hypotension
but does not reliably prevent it. Hypotension decreases
uterine blood flow and must be treated.
b. High block may result from excessive administration of
local anesthetic. The patient often requires vasopressor
therapy and may require assistance with ventilation.
c. Total spinal anesthesia results when the epidural catheter
is located intrathecally or when accidental dural puncture
occurs and the catheter is resited in another interspace. A
total spinal is not possible when the catheter is located in
the epidural space. The upper boundary of the epidural
space is the foramen magnum, which limits the cephalad
spread. It is not possible to anesthetize the cranial nerves
from a properly placed epidural catheter.
d. Local anesthetic toxicity results from intravascular
injection of local anesthetic. Test dosing, aspirating the
catheter, and fractionating the local anesthetic decreases
the risk of local anesthetic toxicity. Part of the treatment
for local anesthetic toxicity is intravenous (IV) intralipid.
Intralipid 20% is administered as a bolus 1.5 mL per kg
following by 0.25 mL/kg/min for 30 to 60 minutes
depending on the severity of local anesthetic toxicity.
Additional boluses of 20% intralipid may be indicated if
symptoms persist (see Chapter 3, Local Anesthetics and
Toxicity).
e. Nerve injury can result from a persistent paresthesia
during epidural catheter placement. If a persistent
paresthesia is encountered during epidural catheter
placement, the epidural needle and catheter should be
removed and redirected to prevent permanent injury.38
f. Postdural puncture headache results from dural puncture
during epidural needle insertion. The International
Headache Society has defined a postdural puncture
 headache as a bilateral frontal and occipital headache that
develops within 7 days after lumbar puncture and
disappears within 14 days after the lumbar puncture. The
headache worsens within 15 minutes of assuming the
upright position and disappears or improves within 30
minutes of assuming the recumbent position. The
headache might coexist with one of the following
symptoms: tinnitus, neck stiffness, hypoacusis,
photophobia, or nausea. Although the headache generally
occurs within 24 to 48 hours of the dural puncture, it may
occur later than 3 days in 25% of the cases. A larger
gauge needle puts the patient at increased risk for the
development of this headache. The headache is not easily
prevented but is treated with an epidural blood patch.39 It
was thought that placement of the epidural catheter
intrathecally would decrease the chance of the
development of a headache. In a randomized study of
parturients who experienced accidental dural puncture
with a 17-gauge Tuohy needle, there was no difference in
the incidence of headache if the catheter was inserted
intrathecally versus resiting the catheter at another
interspace. A reason to thread a catheter intrathecally is to
prevent a repeat dural puncture at another interspace,
especially if the first attempt was difficult40 (see Chapter
19, Management of Postdural Puncture Headache).
g. Neuraxial infection (meningitis, epidural abscess) was the
most common cause of obstetric-related neuraxial injuries
in the 1980 to 1999 Closed Claims Database.41 To prevent
neuraxial infection, epidural catheters must be inserted
aseptically. At a minimum, the operator must wear a
mask, hat, and sterile gloves. The site may be prepped
with iodine or chlorhexidine, but chlorhexidine has the
better antibacterial activity. Although chlorhexidine is not
approved by the U.S. Food and Drug Administration
 (FDA), it is recommended as the first line antiseptic in
this setting by most anesthetic societies.
h. Backache has been associated with epidural anesthesia.
However, this has not been proven in prospective studies.
There is no difference in backache between those who
select epidural anesthesia for their delivery and those who
do not.42
8. Local anesthetics for epidural anesthesia (see Chapter 3,
Local Anesthetics and Toxicity)
a. Lidocaine 1.5% to 2.0% is frequently used for epidural
anesthesia for CD. It offers the advantage of rapid onset
of blockade. Its duration of action is 1 to 1.5 hours.
b. Bupivacaine 0.5% is used less frequently for epidural
anesthesia. In addition to prolonged onset, the concern of
cardiac toxicity has decreased its use. Pregnancy does not
enhance the cardiac toxicity of bupivacaine.
c. Ropivacaine 0.5% has the advantage of decreased cardiac
toxicity. Ropivacaine is prepared solely as the s-isomer.
The r-isomer has the greater cardiac toxicity. The onset is
not as fast as lidocaine, but it has a longer duration of
action of 2 to 2.5 hours. Although the use of ropivacaine
has increased, the cost of ropivacaine is increased over
other comparable local anesthetics.
d. 2-Chloroprocaine 3.0% has a short duration of action,
approximately 45 minutes. Due to its rapid metabolism in
the maternal serum by pseudocholinesterase, the concern
of local anesthetic toxicity is not as great as for other local
anesthetics, allowing for the administration of larger
doses. Its onset is rapid, especially when sodium
bicarbonate has been added to the solution. It is frequently
used for urgent/emergent CDs because a sensory level
may be obtained within 2 minutes of completing the
injection. The use of 2-choroprocaine may decrease the
effectiveness of epidural morphine43; however, this is
 controversial. Originally, 2-chloroprocaine was associated
with back pain; this back pain was attributed to its
preservative. 2-Chloroprocaine is now prepared as a
preservative-free solution.
9. Adjuvants to the local anesthetics for epidural anesthesia
a. Sodium bicarbonate is frequently added to the local
anesthetic solution to increase the speed of onset. It has
been shown to improve the onset time for lidocaine and 2-
chloroprocaine (dose 1 mL sodium bicarbonate for every
10 mL local anesthetic). It is not added to bupivacaine or
ropivacaine due to its ability to precipitate the local
anesthetic.
b. Epinephrine
(1) When epinephrine (1:200,000) is added to lidocaine
1.5% in combination with aspiration of the catheter it
is highly effective in detecting incorrect placement of
an epidural catheter. If the catheter is intrathecal, this
drug combination requires approximately 2 minutes
to obtain a sensory level. For the detection of an
intravascular catheter, a positive test dose would be a
sudden increase in maternal heart rate of 10 beats per
minute within 1 minute after the injection. It should
not be administered during a uterine contraction
because labor pain may trigger a maternal
tachycardic response. This test dose has been
extensively studied and is safe both for mother and
fetus.44
(2) Epinephrine is added to local anesthetic to increase
the density of blockade. It is usually added to
lidocaine at a concentration of 1:200,000 and
infrequently added to 2-chloroprocaine, bupivacaine,
and ropivacaine. Epinephrine increases the duration
and density of a block. In a study of 40 patients
receiving either plain 2% lidocaine or 2% lidocaine
 with epinephrine, patients receiving plain lidocaine
experienced more intraoperative pain.45
(3) Epinephrine may provide analgesia by activation of
the α2 receptor.
(4) Epinephrine should not be used in patients who have
a contraindication to maternal tachycardia (e.g.,
cardiac disease).
10. Opioids
a. Epidural fentanyl or sufentanil administration improves
the quality of intraoperative anesthesia without adversely
affecting the neonate or the mother. The usual dose is 50
to 100 μg fentanyl or 10 to 20 μg sufentanil.
b. Epidural morphine provides prolonged analgesia
postoperatively. The optimal dose is 4 mg.46
(1) Epidural morphine increases the possibility of
reactivation of herpes simplex I virus.47
(2) Side effects of epidural opioids include respiratory
depression (if concomitant, IV opioids are used) and
pruritus. Treatment of the pruritus is with nalbuphine
or naloxone, whereas treatment for respiratory
depression is ONLY with naloxone.

CLINICAL PEARL As compared to spinal anesthesia, the dense

sensory block required for CD takes longer to establish with
epidural anesthesia.

C. Spinal anesthesia for cesarean delivery

1. Spinal anesthesia results from the injection of local anesthetic
into the cerebrospinal fluid (CSF). Given that the medication
is administered into the fluid around the spinal cord, the speed
of onset of blockade is quicker and more reliable compared to
epidural anesthesia.
2. Access to CSF is by lumbar puncture. Because the spinal cord
 ends at the L2 level in 99% of the population, lumbar
punctures are not done above this location. The subarachnoid
space is entered via a midline or paramedian approach.
3. A pencil-point spinal needle is used for lumbar puncture. This
type of spinal needle has a dull tip rather than a sharp, cutting
tip. The incidence of postdural puncture headache is
significantly reduced by the use of pencil-point spinal
needles. The ASA Practice Guidelines for Obstetric
Anesthesia state that only a pencil-point spinal needle should
be used in the obstetric patient.1 Examples of the pencil-point
needle include the Sprotte, Whitacre, European, and Gertie
Marx. The differences among these needles are in the size and
the location of the lateral orifice48 (see Fig. 13.2).

4. The extent of blockade for spinal anesthesia depends on the

baricity of the local anesthetic solution and the position of the
 patient after injection of the local anesthetic. The baricity of a
local anesthetic solution is the ratio of its density to the
density of the CSF at the same temperature. Local anesthetic
solutions with densities at 37°C greater than 1.008 gm per mL
are described as hyperbaric, those with densities between
0.998 and 1.007 gm per mL are considered to be isobaric, and
those with densities less than 0.997 gm per mL are hypobaric.
Local anesthetics prepared in dextrose are hyperbaric; in CSF
or isotonic saline, isobaric; in dilute solution with water,
hypobaric. The dose of the drug, the baricity of the local
anesthetic solution, and the position of the patient during and
after injection largely determine the distribution of the local
anesthetic and the sensory level of the anesthesia.

CLINICAL PEARL The dose of the drug, the baricity of the

local anesthetic solution and the position of the patient during and
after injection largely determine the distribution of the local
anesthetic and the sensory level of the anesthesia.

5. Both intrathecal hyperbaric and isobaric local anesthetic

solutions are used for CD.
6. As the local anesthetic is injected directly into the CSF, sacral
sparing is not a concern with spinal anesthesia.
7. Spinal anesthesia offers the advantage of rapid onset and
reliability. Also, spinal anesthesia is technically easier to
perform. However, spinal anesthesia is of limited duration,
and the lack of a catheter removes the ability to redose the
anesthetic. While some individuals place catheters
intrathecally, the current size of the needle required to place
an intrathecal catheter increases the risk of postdural puncture
headache.
8. Due to its rapid onset of sympathetic blockade, many
practitioners concluded that spinal anesthesia was
 contraindicated in the severe preeclamptic patient. These
individuals were concerned with the profound hypotension
and the risk of pulmonary edema from the fluid administered
to treat the hypotension. Randomized studies do not confirm
these concerns. Spinal anesthesia is not contraindicated in the
severely preeclamptic parturient.49
9. There is a higher incidence of failed spinal anesthesia in the
morbidly obese parturient. It has been hypothesized that the
dose of anesthesia for spinal anesthesia should be reduced in
morbidly obese parturients due to decreased CSF volume in
the lumbar area. This assumption is incorrect. The dose for
the morbidly obese parturient should be the same as the
nonobese parturient.50
10. Contraindications to spinal anesthesia are presented in Table
13.4.
11. Potential complications of spinal anesthesia
a. Hypotension
(1) The rapid onset of sympathetic blockade results in
hypotension. The hypotension is easily treated with
ephedrine or phenylephrine (see previous discussion
of vasopressors). Fluid preloading or coloading with
colloid solutions prior to spinal anesthesia decreases
the incidence of hypotension. However, colloid
solutions are more expensive and have a greater risk
of anaphylaxis.51
(2) A meta-analysis compared spinal anesthesia to
epidural anesthesia with regard to the effect on the
neonate. Umbilical cord pH was significantly lower
for spinal anesthesia. Spinal anesthesia was
associated with a larger base deficit, probably due to
the higher incidence of hypotension.52 The ASA
Practice Guidelines for Obstetric Anesthesia
concluded that the literature was equivocal regarding
the differences in umbilical artery pH values.1 The
 data reinforces the importance of the timely treatment
of hypotension. For the treatment of hypotension,
large doses of ephedrine should be avoided.
b. High spinal anesthesia
(1) Patients with high sensory levels may complain of
breathlessness. The most likely etiology is cerebral
hypoperfusion from hypotension.
(2) High levels (C3–C5) with phrenic nerve paralysis
require assisted ventilation.
c. Postdural puncture headache
(1) While spinal anesthesia involves dura and arachnoid
mater puncture, the incidence of headache is low if a
pencil-point spinal needle is used.
(2) Use of a cutting needle (e.g., Quincke) increases
headache risk.

CLINICAL PEARL The incidence of headache is low if a

pencil-point spinal needle is used.

d. Paresthesia
(1) Spinal anesthesia is performed at interspaces lower
than L2 to prevent trauma to the spinal cord. A
paresthesia may occur during placement of the spinal
needle or injection of the anesthetic as the needle
contacts the cauda equina. Patients may complain of
pain or a shock shooting into the lower extremity.
(2) For persistent paresthesias, the needle should be
removed and placed at another interspace.
e. Cardiac arrest
(1) Unexpected cardiac arrest has been reported in
patients receiving spinal anesthesia. It generally
occurs in patients with high sensory levels in which
the cardiac accelerator fibers (T1–T4) have been
blocked.
 (2) The early use of epinephrine in the resuscitation of
patients experiencing cardiac arrest from spinal
anesthesia improves survival.53

CLINICAL PEARL The early use of epinephrine in the

resuscitation of patients experiencing cardiac arrest from spinal
anesthesia improves survival.

12. Local anesthetics for spinal anesthesia

a. 5% lidocaine
(1) Use of hyperbaric 5% lidocaine has decreased due to
the concern of transient neurologic syndrome (TNS).
(2) TNS occurs when the patient experiences pain in the
legs and back for 24 to 48 hours following the
administration of the spinal anesthetic. There is an
increased risk with the use of intrathecal lidocaine
during lithotomy positioning. TNS is not increased in
patients undergoing CD.54
b. 0.5% or 0.75% bupivacaine. Spinal bupivacaine is the
local anesthetic of choice for CD because of its ability to
produce a dense block of long duration.
c. 0.5% ropivacaine has not been approved by the FDA for
use in the United States. Furthermore, studies have
suggested that the duration of sensory and motor blockade
was of shorter duration compared to bupivacaine.
13. Additives to local anesthetics
a. Epinephrine at a dose of 100 μg prolongs the duration of
the block.
b. Opioids
(1) Fentanyl 10 μg improves the quality of the sensory
anesthesia but does not provide prolonged
postoperative analgesia.
(2) Preservative-free morphine 0.1 to 0.15 mg provides
 postoperative analgesia of a duration of 10 to 24
hours. Side effects are similar to epidural opioids and
include pruritus and respiratory depression.55 When
adding these small doses to the local anesthetic, it is
best to draw them up in a 1 mL tuberculin syringe to
improve dosing accuracy.
c. Neostigmine and clonidine remain under clinical
investigation.
14. Spinal anesthesia after a failed epidural
The concern with spinal anesthesia after failed epidural
anesthesia is the development of a high or total spinal block.
The postulated mechanism for the high block is compression
of the intrathecal space by the epidural solution, causing an
increased cephalad movement of intrathecally injected
medication. Case reports suggest that a high spinal is a
possibility when large amounts of local anesthetic are injected
epidurally. If a bilateral sensory level is not achieved with 10
mL of epidural local anesthetic (will be lower than a sensory
level of T4 but should be bilateral), the administration of
additional local anesthetic will be most likely be ineffective.
Consideration should be given to the placement of spinal
anesthesia at this point, with a reduction of the spinal
anesthetic dose by 30%.56 If the failed block involves no
evidence of a residual sensory level, then it would be
reasonable to use a full subarachnoid dose.

CLINICAL PEARL The concern with spinal anesthesia after

failed epidural anesthesia is the development of a high or total
spinal block.

D. Combined spinal-epidural anesthesia for cesarean delivery

1. Combined spinal-epidural (CSE) anesthesia involves
advancing a long spinal needle through the epidural needle
 once the epidural needle is in the epidural space. This
technique combines the rapid onset and density of spinal
anesthesia with the ability to prolong the block with the
placement of an epidural catheter.
2. According to the Practice Guidelines for Obstetric Anesthesia,
CSE anesthesia does not improve anesthesia compared to
spinal anesthesia.1 It does shorten time to skin incision
compared to epidural anesthesia.
3. Although CSE anesthesia does not decrease maternal side
effects, it may be advantageous when the duration of CD is
expected to outlast the spinal anesthetic.
E. General anesthesia for cesarean delivery
1. General anesthetic agents cross the placenta and may result in
neonatal depression.
2. The time to skin incision from induction is the shortest for
general anesthesia. General anesthesia is not induced until the
maternal abdomen is prepped and draped and the surgeon is
ready for surgical incision.
3. Indications for general anesthesia
a. Profound fetal bradycardia. The rapid delivery of the fetus
from an unfavorable uterine environment makes general
anesthesia an ideal option.
b. Maternal hemorrhage. If the mother is experiencing
hemorrhage, one may not want to induce sympathetic
blockade from neuraxial anesthesia.
c. Neuraxial anesthesia is not possible. The mother may
have a coagulopathy or severe thrombocytopenia, which
may increase the risk of epidural hematoma. Two other
reasons would be previous maternal spinal surgery or
infection in the lumbar area.
4. Induction of general anesthesia is via rapid sequence.
Following preoxygenation, an induction agent such as
propofol, ketamine, or etomidate is administered and followed
immediately (in rapid sequence) by succinylcholine. The
 choice of induction agent depends on the maternal condition.
In instances of profound hemorrhage, ketamine may be used.
Etomidate may be a good choice when there is maternal
cardiac disease. Propofol is the induction agent used most
frequently for general anesthesia.
5. In a review of options to prevent hypertension and risk of
cerebral vascular accident in patients with preeclampsia,
anesthesia providers should consider administering propofol,
esmolol (1.5 mg per kg), and labetalol.57 Nitroglycerin (2 μg
per kg), nicardipine, fentanyl, and remifentanil can also be
considered.
6. An assistant places pressure on the cricoid cartilage following
loss of consciousness and maintains the pressure until an
endotracheal tube is placed and confirmed to be in the correct
place by capnography.
7. Following intubation, anesthesia is maintained with a volatile
agent. Nitrous oxide may be added depending on the
condition of the fetus. Most practitioners prefer to use 100%
oxygen until delivery of the fetus. Volatile agents provide
uterine relaxation. Following delivery of the infant, the
concentration of the volatile agent should be decreased to 0.5
minimum alveolar concentration (MAC) or less with the
addition of nitrous oxide and opioid. In most cases, IV
administration of oxytocin is able to overcome the uterine
relaxant effects of the volatile agents if they are kept to 0.5
MAC. However, postpartum bleeding is greater when general
anesthesia is used.
8. Pregnancy decreases MAC. However, MAC is a spinal reflex
and does not measure the extent of the effect of anesthetics on
the central nervous system. When comparing pregnant to
nonpregnant women, there is no difference in the amount of
anesthesia necessary to affect the electroencephalography
(EEG). As such, there is no difference in the amount of
anesthesia necessary to prevent awareness in a pregnant
 woman as compared to a nonpregnant woman.58
9. If a patient is receiving magnesium sulfate for seizure
prophylaxis accompanying preeclampsia, nondepolarizing
neuromuscular blockers should be avoided because
magnesium sulfate increases the sensitivity of the parturient to
nondepolarizing muscle relaxants.
10. Opioids are withheld until delivery of the fetus to prevent
transplacental passage. Following delivery, most practitioners
convert to nitrous oxide/oxygen/opioid technique with a small
amount of inhalation agent to prevent awareness.
11. Postoperative analgesia consists of IV patient-controlled
analgesia.
12. For patients who received general anesthesia, a transversus
abdominis plane (TAP) block may be beneficial. It involves
the injection of local anesthetic between the transversus
abdominis and the internal oblique muscles. It is typically
performed using ultrasound guidance. It is not used with
neuraxial anesthesia because the TAP block does not provide
any additional analgesia if neuraxial morphine is used.
13. Mortality from anesthesia during CD is highest for general
anesthesia. The majority of deaths during general anesthesia
result from difficulty with intubation, failed oxygenation and
ventilation, or pulmonary aspiration. However, there are
newer concerns about hypoventilation or airway obstruction
during extubation, emergence, or recovery.59
Videolaryngoscopy has decreased the incidence of failed
intubation but has no effect on the incidence of aspiration.
14. The ACOG has recognized the importance of identifying
women at risk for possible difficult intubation in Guidelines
for Perinatal Care, 7th edition. The obstetric care team
should be alert to the presence of risk factors that place the
parturient at increased risk for complications from general
anesthesia. For those patients at risk, consideration should be
given to the planned placement in early labor of an epidural
 catheter with confirmation that the catheter is functional.60
VII. Postoperative management (see Chapter 18, Postcesarean
Analgesia)
Postoperative pain management is best accomplished with multimodal
analgesic techniques, including systemic nonsteroidal anti-
inflammatory drugs, IV acetaminophen, and neuraxial opioids and/or
local anesthetics. TAP blocks have been described but intrathecal
morphine has been shown to provide superior and longer lasting
analgesia.61 Patient-controlled epidural analgesia using dilute
solutions of local anesthetic and opioid has also been described after
epidural anesthesia. When neuraxial techniques are utilized for CD,
postoperative pain control (12 to 24 hours) is most often provided by
intrathecal morphine (100 to 150 μg) or epidural morphine (3.5 to 4.0
mg). Although delayed respiratory depression is a known side effect
of neuraxial morphine, other side effects include nausea, vomiting,
and pruritus. Because of the risk of respiratory depression, patients
must be monitored in the postoperative period, especially morbidly
obese women who may be at higher risk for respiratory depression.62

CLINICAL PEARL Patients must be monitored in the

postoperative period following neuraxial opioid administration,
especially morbidly obese women who may be at higher risk for
respiratory depression.

VIII. Conclusions
A. The number of CDs in the United States has stabilized. However,
with a CD rate of one-third of all births in the United States, it
represents the most commonly performed surgical procedure.
B. Epidural analgesia does not increase the risk of CD. If an epidural
catheter had been placed for labor, it may be used for CD. If the
catheter appears to be nonfunctional, it is important to stop
injecting the catheter before large volumes are administered to
prevent a high sensory level from administration of spinal
 anesthetic.
C. If general anesthesia is chosen, rapid sequence induction should
be used because parturients are at risk for aspiration. Parturients
require the same amount of anesthesia as nonpregnant individuals
to prevent awareness. Postpartum bleeding is greater with general
anesthesia, although there is no difference in the need for
transfusion.
D. General, spinal, epidural, and CSE anesthesia are used for CD.
Each has advantages and disadvantages. The decision to use a
particular anesthetic must be individualized and will, in part, be
dependent on the institution and the level of training of the
surgeons. In addition, the choice will be dependent on the
urgency of the situation and the maternal condition.

REFERENCES
1. American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Practice guidelines for
obstetric anesthesia: an updated report by the American Society of Anesthesiologists Task Force on
Obstetric Anesthesia. Anesthesiology. 2007;106:843–863.
2. Osterman MJ, Martin JA. Primary cesarean delivery rates, by state: results from the revised birth
certificate: 2006-2012. Natl Vital Stat Rep. 2014;63:1–11.
3. American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine. Obstetric
Care Consensus No. 1: safe prevention of the primary cesarean delivery. Obstet Gynecol.
2014;123:693–711.
4. Wong CA, Scavone BM, Peaceman AM, et al. The risk of cesarean delivery with neuraxial analgesia
given early versus late in labor. N Engl J Med. 2005;352:655–665.
5. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 559: cesarean
delivery on maternal request. Obstet Gynecol. 2013;121:904–907.
6. Ecker J. Elective cesarean delivery on maternal request. JAMA. 2013;309:1930–1936.
7. Mishanina E, Rogozinska E, Thatthi T, et al. Use of labour induction and risk of cesarean delivery: a
systematic review and meta-analysis. CMAJ. 2014;186:665–673.
8. Osterman MJ, Martin JA. Changes in cesarean delivery rates by gestational age: United States, 1996-
2011. NCHS Data Brief. 2013;124:1–8.
9. McAdams RM. Time to implement delayed cord clamping. Obstet Gynecol. 2014;123:549–552.
10. Hung KJ, Berg O. Early skin-to-skin after cesarean to improve breastfeeding. MCN Am J Matern
Child Nurs. 2011;36:318–324.
11. Bamigboye AA, Hofmeyr GJ. Closure versus non-closure of the peritoneum at caesarean section:
short- and long-term outcomes. Cochrane Database Syst Rev. 2014;8:CD000163.
12. Hawkins JL, Chang J, Palmer SK, et al. Anesthesia-related maternal mortality in the United States:
1979-2002. Obstet Gynecol. 2011;117:69–74.
13. Creanga AA, Berg CJ, Syverson C, et al. Pregnancy-related mortality in the United States, 2006-2010.
 Obstet Gynecol. 2015;125:5–12.
14. Mhyre JM, Tsen LC, Einav S, et al. Cardiac arrest during hospitalization for delivery in the United
States, 1998-2011. Anesthesiology. 2014;120:810–818.
15. Hammad IA, Chauhan SP, Magann EF, et al. Peripartum complications with cesarean delivery: a
review of Maternal-Fetal Medicine Units Network publications. J Mat Fetal Neonatal Med.
2014;27:463–474.
16. Rouse DJ, MacPherson C, Landon M, et al. Blood transfusion and cesarean delivery. Obstet Gynecol.
2006;108:891–897.
17. Heesen M, Hofmann T, Klöhr S, et al. Is general anaesthesia for caesarean section associated with
postpartum haemorrhage? Systematic review and meta-analysis. Acta Anaesthesiol Scand.
2013;57:1092–1102.
18. Zelop C, Heffner LJ. The downside of cesarean delivery: short- and long-term complications. Clin
Obstet Gynecol. 2004;47:386–393.
19. Silver RM, Landon MB, Rouse DJ, et al. Maternal morbidity associated with multiple repeat cesarean
deliveries. Obstet Gynecol. 2006;107:1226–1232.
20. Leeman LM, Beagle M, Espey E, et al. Diminishing availability of trial of labor after cesarean
delivery in New Mexico hospitals. Obstet Gynecol. 2013;122:242–247.
21. Lydon-Rochelle M, Holt VL, Easterling TR, et al. Risk of uterine rupture during labor among women
with a prior cesarean delivery. N Engl J Med. 2001;345:3–8.
22. Mendelson CL. The aspiration of stomach contents into the lungs during obstetric anesthesia. Am J
Obstet Gynecol. 1946;52:191–205.
23. Paranjothy S, Griffiths JD, Broughton HK, et al. Interventions at caesarean section for reducing the
risk of aspiration pneumonitis. Cochrane Database Syst Rev. 2014;2:CD004943.
24. Chatmongkolchart S, Prathep S. Supplemental oxygen for caesarean section during regional
anesthesia. Cochrane Database Syst Rev. 2013;6:CD006161.
25. Quinn AC, Milne D, Columb M, et al. Failed tracheal intubation in obstetric anaesthesia: 2 yr national
case-control study in the UK. Br J Anaesth. 2013;110:74–80.
26. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 120: use of
prophylactic antibiotics in labor and delivery. Obstet Gynecol. 2011;117:1472–1483.
27. Brubaker SG, Friedman AM, Cleary KL, et al. Patterns of use and predictors of receipt of antibiotics
in women undergoing cesarean delivery. Obstet Gynecol. 2014;124:338–344.
28. Saravanan S, Kocarev M, Wilson RC, et al. Equivalent dose of ephedrine and phenylephrine in the
prevention of post-spinal hypotension in caesarean section. Br J Anaesth. 2006;96:95–99.
29. Landau R, Liu SK, Blouin JL, et al. The effect of maternal and fetal beta2-adrenoceptor and nitric
oxide synthase genotype on vasopressor requirement and fetal acid-base status during spinal
anesthesia for cesarean delivery. Anesth Analg. 2011;112:1432–1437.
30. Doherty A, Ohashi Y, Downey K, et al. Phenylephrine infusion versus bolus regimens during cesarean
delivery under spinal anesthesia: a double-blind randomized clinical trial to assess hemodynamic
changes. Anesth Analg. 2012;115:1343–1350.
31. Maayan-Metzger A, Schushan-Eisen I, Todris L, et al. Maternal hypotension during elective cesarean
section and short-term neonatal outcome. Am J Obstet Gynecol. 2010;202:56.e1–e5.
32. Lee A, Ngan Kee WD, Gin T. A quantitative, systematic review of randomized controlled trials of
ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for
cesarean delivery. Anesth Analg. 2002;94:920–926.
33. Ngan Kee WD, Lee SW, Ng FF, et al. Randomized double-blinded comparison of norepinephrine and
phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery.
Anesthesiology. 2015;122:736–745.
34. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin: Clinical Management
Guidelines for Obstetrician-Gynecologists Number 76, October 2006: postpartum hemorrhage. Obstet
Gynecol. 2006;108:1039–1047.
35. Maayan-Metzger A, Schushan-Eisen I, Todris L, et al. The effect of time intervals on neonatal
outcome in elective cesarean delivery at term under regional anesthesia. Int J Gynaecol Obstet.
2010;111:224–228.
36. Torloni MR, Betran AP, Souza JP, et al. Classifications for cesarean section: a systematic review. PLoS
One. 2011;6:e14566.
37. Nor NM, Russell IF. Assessing blocks after spinal anaesthesia for elective caesarean section: how
different questions affect findings from the same stimulus. Int J Obstet Anesth. 2013;22:294–297.
38. Auroy Y, Benhamou D, Bargues L, et al. Major complications of regional anesthesia in France: the
SOS regional anesthesia hotline service. Anesthesiology. 2002;97:1274–1280.
39. Evans RW, Armon C, Frohman EM, et al. Assessment: prevention of post-lumbar puncture headaches:
report of the Therapeutics and Technology Assessment Subcommittee of the Academy of Neurology.
Neurology. 2000;55:909–914.
40. Russell IF. A prospective controlled study of continuous spinal analgesia versus repeat epidural
analgesia after accidental dural puncture in labour. Int J Obstet Anesth. 2012;21:7–16.
41. Lee LA, Posner KL, Domino KB, et al. Injuries associated with regional anesthesia in the 1980s and
1990s: a closed claims analysis. Anesthesiology. 2004;101:143–152.
42. Howell CJ, Dean T, Lucking L, et al. Randomised study of long term outcome after epidural versus
non-epidural analgesia during labour. BMJ. 2002;325:357.
43. Karambelkar DJ, Ramanathan S. 2-Chloroporcoaine antagonism of epidural morphine analgesia. Acta
Anaesthesiol Scand. 1997;41:774–778.
44. Colonna-Romano P, Lingaraju N, Godfrey SD, et al. Epidural test dose and intravascular injection in
obstetrics: sensitivity, specificity, and lowest effective dose. Anesth Analg. 1992;75:372–376.
45. Brose WG, Cohen SE. Epidural lidocaine for cesarean section: effect of varying epinephrine
concentration. Anesthesiology. 1988;69:936–940.
46. Palmer CM, Nogami WM, Van Maren G, et al. Postcesarean epidural morphine: a dose-response
study. Anesth Analg. 2000;90:887–891.
47. Boyle RK. A review of anatomical and immunological links between epidural morphine and herpes
simplex labialis in obstetric patients. Anaesth Intensive Care. 1995;23:425–432.
48. Lambert DH, Hurley RJ, Hertwig L, et al. Role of needle gauge and tip configuration in the production
of lumbar puncture headache. Reg Anesth. 1997;22:66–72.
49. Visalyaputra S, Rodanant O, Somboonviboon W, et al. Spinal versus epidural anesthesia for cesarean
delivery in severe preeclampsia: a prospective randomized, multicenter study. Anesth Analg.
2005;101:862–868.
50. Carvalho B, Collins J, Drover DR, et al. ED(50) and ED(95) of intrathecal bupivacaine in morbidly
obese patients undergoing cesarean delivery. Anesthesiology. 2011;114:529–535.
51. Dyer RA, Farina Z, Jouber IA, et al. Crystalloid preload versus rapid crystalloid administration after
induction of spinal anesthesia (coload) for elective caesarean section. Anaesth Intensive Care.
2004;32:351–357.
52. Reynolds F, Seed PT. Anaesthesia for caesarean section and neonatal acid-base status: a meta-analysis.
Anaesthesia. 2005;60:636–653.
53. Kopp SL, Horlocker TT, Warner ME, et al. Cardiac arrest during neuraxial anesthesia: frequency and
predisposing factors associated with survival. Anesth Analg. 2005;100:855–865.
54. Aouad MT, Siddik SS, Jalbout MI, et al. Does pregnancy protect against intrathecal lidocaine-induced
transient neurologic symptoms? Anesth Analg. 2001;92:401–404.
55. Palmer CM, Emerson S, Volgoropolous D, et al. Dose-response relationship of intrathecal morphine
for postcesarean analgesia. Anesthesiology. 1999;90:437–444.
56. Blumgart CH, Ryall D, Dennison B, et al. Mechanism of extension of spinal anaesthesia by extradural
injection of local anaesthetic. Br J Anaesth. 1992;69:457–460.
57. Pant M, Fong R, Scavone B. Prevention of peri-induction hypertension in preeclamptic patients: a
focused review. Anesth Analg. 2014;119:1350–1356.
58. Mhyre JM, Riesner MN, Polley LS, et al. A series of anesthesia-related maternal deaths in Michigan,
1985-2003. Anesthesiology. 2007;106:1096–1104.
59. Ueyama H, Hagihira S, Takashina M, et al. Pregnancy does not enhance volatile anesthetic sensitivity
on the brain: an electroencephalographic analysis study. Anesthesiology. 2010;113:577–584.
60. American College of Obstetricians and Gynecologists. Guidelines for Perinatal Care. 7th ed.
Washington, DC: American College of Obstetricians and Gynecologists; 2012:109–110, 160, 192–
194, 248.
61. McMorrow RC, Ni Mhuircheartaigh RJ, Ahmed KA, et al. Comparison of transversus abdominis
plane block vs spinal morphine for pain relief after caesarean section. Br J Anaesth. 2011;106:706–
712.
62. Horlocker TT, Burton AW, Connis RT, et al. Practice guidelines for the prevention, detection, and
management of respiratory depression associated with neuraxial opioid administration.
Anesthesiology. 2009;110:218–230.
 Difficult Airway Management in the Pregnant Patient
Uma Munnur and Maya S. Suresh

I. Introduction
II. Definitions
A. Difficult airway
B. Difficult face mask ventilation or supraglottic airway
ventilation
C. Difficult supraglottic airway placement
D. Difficult laryngoscopy
E. Difficult tracheal intubation
F. Failed intubation
III. Goals and preparation for airway management during pregnancy
A. Goals to eliminate airway-related mortality
B. Preparation
IV. Incidence of difficult and failed intubation
A. Risk of failed intubation in obstetric patients
B. Factors contributing to the difficult airway
V. Anesthesia-related morbidity and mortality
A. Experience in the United States
B. Experience in the United Kingdom
VI. Maternal deaths and airway-related issues following emergence
A. US data
B. Data from the United Kingdom
VII. Anatomic and physiologic changes during pregnancy contributing
 in difficult airway management
A. Airway changes
B. Respiratory changes
C. Cardiovascular changes
D. Gastrointestinal changes
E. Recommendations for airway management: implications of
the physiologic changes of pregnancy
VIII. Airway assessment
A. History
B. Physical examination
C. Specific individual tests for assessment of difficult tracheal
intubation
IX. Morbid obesity in pregnancy and the airway
A. Prevalence of morbid obesity
B. Technical challenges
C. Increased anesthetic risk
X. Aspiration of gastric contents
A. Aspiration-related death
B. Risk of difficult mask ventilation and aspiration after repeat
attempts at intubation
XI. Anesthetic management in obstetric patients with a predicted
difficult airway
A. American Society of Anesthesiologists practice guidelines
B. Management of the parturient with a predicted difficult
airway undergoing labor or operative delivery, where airway
management is not necessary
C. Management of the predicted difficult airway in obstetric
patient where airway management is needed: emphasis on
awake intubation
XII. Management of pregnant patient with an unanticipated difficult
airway
A. Step 1: first attempt at tracheal intubation
 B. Step 2: second tracheal intubation/best attempt—difficult
laryngoscopy/difficult intubation
C. Step 3: maintenance of oxygenation/ventilation—failed
intubation
D. Step 4: management of the “cannot intubate/cannot ventilate”
situation
E. Step 5: management of pregnant patients with a critical
airway (increasing hypoxemia)
XIII. Extubation and postanesthesia care unit airway issues
XIV. Conclusion

KEYPOINTS
1. Airway-related complications associated with failed endotracheal
intubation and the inability to oxygenate/ventilate after induction of
general anesthesia for cesarean delivery are associated with increased
rates of maternal morbidity and mortality.
2. Attention should be focused on history, physical examination, and airway
evaluation for predictors of difficult intubation and difficult ventilation.
3. Heightened awareness of general anesthesia–related maternal morbidity
and mortality has led to a widespread adoption of neuraxial techniques
for both labor and cesarean delivery, and improvements in the
management of difficult airway has led to a significant decrease in
airway-related deaths.
4. Emergency airway management following failed tracheal intubation in
obstetrics presents challenges for the anesthesia provider.
5. A well-thought-out airway rescue plan, within the framework of a
predetermined difficult airway algorithm, is required prior to the
induction of anesthesia in the parturient.
6. Protocols to reduce anesthesia risks for women undergoing labor, during
induction of general anesthesia for cesarean delivery, during anesthetic
emergence, and postoperatively should be established by each institution
 where obstetric anesthesia is provided.
7. All anesthesia providers should acquire and maintain advanced airway
management skills including cricothyroidotomy.

I. Introduction
Airway-related complications associated with failed endotracheal
intubation and the inability to ventilate/oxygenate after induction of
general anesthesia (GA) for cesarean delivery (CD) are associated
with increased rates of maternal morbidity and mortality. Anatomic
and physiologic changes during pregnancy place the parturient at
higher risk for airway-related complications; therefore, the parturient
undergoing GA is at greater risk for airway-related problems
compared to the nonpregnant patient. Obesity, estimated to affect over
50% of the pregnant population, also increases the risk for difficult
intubation and ventilation. As the prevalence of high-risk obstetric
patients increases, anesthesia providers will likely encounter more
clinical situations where neuraxial anesthesia may be exceedingly
difficult or contraindicated, making airway management exceedingly
challenging. In many countries, the recognition that adverse maternal
anesthetic outcomes are often associated with difficult airway
management has led to a dramatic decline in the use of GA for both
elective and emergency CD.
Increased focus on improving patient safety in anesthesia by
anesthesiologists has led to tremendous advances in airway
management in recent years. These include (1) introduction and
revision of the American Society of Anesthesiologists (ASA) Task
Force on Difficult Airway Management (DAM)—recommendations
for management of the difficult airway,1 (2) considerable advances in
comprehensive airway management, (3) improvement and increases
in the number of airway devices available to aid in airway
management, and (4) an increase in publications worldwide
concerning advanced airway management. These improvements have
led to a decline in the incidence of airway-related perioperative
morbidity during anesthesia and surgery in the general surgical and
 obstetrical populations.2
II. Definitions. There is no consensus on a standard definition of the
difficult airway in the available literature. The following are
definitions used by the ASA Task Force on Difficult Airway
Management1:
A. Difficult airway. Clinical situation in which a conventionally
trained anesthesiologist experiences difficulty with face mask
ventilation of the upper airway, difficulty with tracheal intubation,
or both leading to hypoxemia.
B. Difficult face mask ventilation or supraglottic airway
ventilation
1. Successful face mask ventilation provides anesthesia
providers with a rescue technique during unsuccessful
attempts at laryngoscopy and unanticipated difficult airway
situations.
2. A grading scale for mask ventilation consisting of four
categories (Grades 1 to 4): Grade 1: easy ventilation by mask,
Grade 2: ventilation by mask with oral airway/adjuvant with
or without muscle relaxant, Grade 3: difficult ventilation
(inadequate, unstable, or requiring two providers) with or
without muscle relaxant, Grade 4: unable to mask ventilate
with or without muscle relaxant. Grades 3 and 4 define
difficult mask ventilation and impossible mask ventilation,
respectively.
3. Supraglottic airway (SGA) equipment includes the laryngeal
mask airway (LMA), intubating LMA (ILMA), and laryngeal
tubes.
4. Difficult SGA ventilation
a. “Difficult SGA” ventilation occurs when the
anesthesiologist is unable to provide adequate ventilation
because of one or more of the following problems: (1)
inadequate mask or SGA seal, (2) excessive gas leak, or
(3) excessive resistance to the ingress or egress of gas.
b. Signs of inadequate ventilation include (but are not
 limited to) absent or inadequate chest movement, absent
or inadequate breath sounds, auscultatory signs of severe
obstruction, cyanosis, gastric air entry or dilatation,
decreasing or inadequate oxygen saturation (SpO2),
absent or inadequate exhaled carbon dioxide as detected
by end-tidal carbon dioxide (ETCO2) monitoring, absent
or inadequate spirometry measures of exhaled gas flow,
and hemodynamic changes associated with hypoxemia or
hypercarbia (e.g., hypertension, tachycardia,
dysrhythmia).
C. Difficult supraglottic airway placement. SGA placement that
requires multiple attempts.
D. Difficult laryngoscopy. It is not possible to visualize any portion
of the vocal cords after multiple attempts at conventional
laryngoscopy.
E. Difficult tracheal intubation. The ASA Task Force describes
difficult intubation as requiring multiple attempts.
F. Failed intubation. This has occurred when placement of the
endotracheal tube (ETT) fails after multiple attempts. The ASA
Task Force on Difficult Airway Management definition may not
be applicable in the obstetrical patient undergoing CD in which
GA is used for urgent delivery of the neonate. A common practice
in such obstetrical patients is to induce GA in a rapid sequence
manner using a single dose of succinylcholine to accomplish the
intubation. A more appropriate definition of failed intubation in
obstetrical patients may be an inability to secure the airway after
administration of a single dose of succinylcholine followed by no
more than two attempts at intubation using conventional
laryngoscopy or an alternative device to assist with the tracheal
intubation.
III. Goals and preparation for airway management during
pregnancy
A. Goals to eliminate airway-related mortality. The impact of
 adverse maternal and fetal outcomes due to anesthesia-related
airway mishap or suboptimal management can have devastating
effects on the patient’s family and result in financial liability for
anesthesia providers. Recently announced safe motherhood
initiatives and United Nations Millennium Development Goals,
which emphasize improved maternal health, focus on eliminating
anesthesia-related maternal mortality, particularly airway-related
mortality. Obstetric anesthesia providers should:
1. Understand the impact of anatomic and physiologic changes
during pregnancy and the impact on airway management (see
Chapter 1).
2. Balance the urgency of delivering the baby while ensuring
maternal safety.
3. Understand the importance of prioritizing and establishing
oxygenation and ventilation, using a number of airway rescue
devices.
4. Prevent pulmonary aspiration, particularly during the use of
SGA devices.
5. Recognize a difficult airway and have effective strategies to
manage a parturient with a difficult airway undergoing labor
or CD. The ultimate goal as stated in the Safe Motherhood
Initiatives is to prevent and eliminate all maternal deaths,
including deaths associated with difficult airway management.
B. Preparation. With these goals in mind, the obstetric anesthesia
provider should implement the following steps:
1. Learn the predictors of difficult airway management.
2. Assess a patient for risk factors that predispose to airway-
related complications.
3. Have a well-thought-out airway rescue plan, within the
framework of a predetermined difficult airway algorithm.
4. Have a difficult airway cart immediately available in the labor
and delivery area.
5. Understand the importance of preventing aspiration of gastric
contents when using an SGA.
 6. Acquire and maintain advanced airway management skills
including cricothyroidotomy.

CLINICAL PEARL All anesthesia providers should acquire

advanced skills in managing difficult airway situations in obstetric
patients.

IV. Incidence of difficult and failed intubation

Although maternal morbidity and mortality secondary to airway-
related complications have declined, the incidence of difficult tracheal
intubation has remained unchanged because of the anatomic and
physiologic changes of pregnancy.2
A. Risk of failed intubation in obstetric patients. The incidence of
failed intubation in obstetric patients averages 1:300, compared to
1:2,230 in the general surgical population3,4 (see Table 14.1).
Therefore, there is a seven-to eightfold increased risk for failed
intubation in obstetric patients.
 B. Factors contributing to the difficult airway. Difficult mask
ventilation, difficult laryngoscopy, and difficult intubation are
factors that contribute to a difficult airway.
1. Difficult mask ventilation and difficult laryngoscopy occurs in
5% and 5.8% of patients undergoing GA for surgical
procedures, respectively.5
2. A combination of difficulty mask ventilation and difficult
laryngoscopy increases the risk for hypoxemia.
a. A recent trial determined the incidence of difficult mask
ventilation combined with difficult laryngoscopy to be
0.4% and identified 12 independent predictors: (1) age
>46 years, (2) body mass index (BMI) >30 kg per m2, (3)
male sex, (4) Mallampati class III or IV, (5) neck mass or
prior neck radiation therapy, (6) limited thyromental
distance, (7) sleep apnea, (8) prominent teeth, (9) beard,
(10) thick neck, (11) limited cervical spine mobility, and
(12) limited jaw protrusion.5
b. The incidence of simultaneous difficult mask ventilation
and difficult intubation in obstetrical population is
unknown. Two studies show that failure of mask
ventilation or SGA devices to rescue the airway in
obstetrical patients can result in a high incidence of
cannot intubate, cannot ventilate situations with an
estimated incidence ranging from 1:95 to 1:500.6 In one
recent review of GA for CD, there was one encounter of a
cannot intubate, cannot ventilate situation following failed
attempts at intubation and placement of an SGA, which
required emergent cricothyroidotomy resulting in good
outcomes in both mother and baby.6

CLINICAL PEARL Rates of difficult mask ventilation and

difficult tracheal intubation are increased in obstetric patients.
 V. Anesthesia-related morbidity and mortality
Recent reviews of anesthesia-related maternal mortality have
improved anesthesiologists’ awareness of potential airway problems
in obstetric patients. The increased use of neuraxial anesthesia and
advances in airway management have resulted in a decrease in the
incidence of maternal brain death and mortality.2 However, cases of
difficult or failed intubation are still reported, some in association
with the administration of neuraxial anesthesia. An anesthesia
provider must provide effective airway management when using
either neuraxial or general anesthesia for CD.
A. Experience in the United States
1. In the last three decades, GA-related complications related to
airway management resulting in maternal mortality have
declined in the United States. Declines in anesthesia-related
maternal mortality7 in the United States and the United
Kingdom are similar.
a. Hawkins et al. published the first national study of
anesthesia-related maternal mortality in the United States
in 1997 and reported a 16.7 relative risk increase in
mortality in mothers who received GA as compared with
those who received neuraxial anesthesia.8 Eighty-two
percent of the deaths took place during CD and most often
resulted from difficult or failed intubation, inability to
ventilate and oxygenate, pulmonary aspiration, and
respiratory complications. The death rates during GA for
CD increased from 20 per million during the interval
1979 to 1984 to 32.3 per million for the interval 1985 to
1990. The relative risk ratio of GA associated mortality
was 2.3 times higher as compared to neuraxial anesthesia-
related deaths. The evidence-based data hastened the
change in anesthesia for pregnant patients away from GA
to predominantly neuraxial anesthesia for CDs.
b. In a follow-up report, Hawkins et. al.9 reexamined and
estimated trends of anesthesia-related maternal deaths in
 the 12 years from 1991 to 2002 and compared it to the
anesthesia-related deaths from 1979 to 1990. The case
fatality for GA declined from 16.8 in 1991 to 1996 to 6.5
per million in 1997 to 2002. Although the data was
encouraging, 56 maternal deaths occurred during CD.
Anesthesia-related mortality was most associated with
complications during anesthetic induction, failure of
tracheal intubation, respiratory failure, or high spinal or
epidural block followed by respiratory failure.
c. Currently, anesthetic-related deaths occur in 1 of 1 million
live births.9 Although the reasons for the reductions in
anesthesia-related deaths are not fully understood, the
improved patterns of anesthesia practice, enhanced
awareness, use of protocols and difficult airway
algorithms during management, and utilization of
alternate airway technologies are likely responsible for the
noted improvement in outcomes.
2. According to a recent ASA closed claims analysis, pulmonary
aspiration in association with difficult intubation in obstetric
patients may occur more often than in nonobstetric patients.
The greater proportion of obstetric claims in which pulmonary
aspiration was identified as the primary damaging event is
noteworthy because it occurred in 15 out of the 17 patients
who received GA. A strong association with difficult
intubation or the sequelae of esophageal intubation was
noted.10
B. Experience in the United Kingdom
1. The Confidential Enquiries into Maternal Deaths is published
every 3 years in the United Kingdom. The reports show that
since the early 1980s, there has been a dramatic reduction in
anesthesia-related maternal deaths. Increased use of neuraxial
anesthesia, aspiration prophylaxis for CD, and improvement
in airway training has likely contributed to this decrease.11
a. In 1967 to 1969, there were 35 deaths directly attributed
 to anesthesia; in the last three reports, including the 2003
to 2005 report, an average of six deaths were considered
to be a direct result of anesthetic management and
associated with difficult tracheal intubation.
b. In the 2003 to 2005 report, all six GA-related deaths were
deemed due to suboptimal airway management.
Additionally, reviewers expressed concern regarding the
proficiency of junior anesthesia practitioners in providing
GA for emergency CD without supervision and discussed
the need for the participation of consultants in emergency
cases.11
2. Using the UK Obstetric Surveillance System (UKOSS) of
data collection, a recent survey found the incidence of failed
tracheal intubation in obstetric anesthesia to be 1:224. Higher
maternal age, obesity, and Mallampati score >1 were
significant independent predictors of failure.12
3. The Fourth National Audit Project (NAP4) of the Royal
College of Anesthetists and the Difficult Airway Society were
designed to study the incidence of major complications of
airway management in hospitals in the United Kingdom and
perform a quantitative and qualitative analysis. Four events in
pregnant women, who had problems at the time of intubation
during emergency CD, were examined. All of these cases took
place outside of normal working hours, involved complex
patients, and were managed by senior anesthetists. The airway
complications noted were aspiration, a failed
cricothyroidotomy attempt, and one successful surgical
airway. All patients were admitted to the intensive care unit
(ICU) and made a full recovery13 (see Table 14.2).
 CLINICAL PEARL Although maternal morbidity and mortality
due to GA and inadequate airway management have declined in
recent decades, most anesthetic-related deaths are still associated
with difficult airway management.

VI. Maternal deaths and airway-related issues following emergence

A. United States data
1. In earlier reports of airway-attributed maternal death, failed
ventilation or pulmonary aspiration associated with difficult
intubation at the induction of anesthesia were more commonly
reported. More recent reports note the events are increasingly
associated with tracheal extubation or occur in the early
postoperative period.
2. A review of anesthesia-related maternal deaths in Michigan
(1985 to 2003) reported that obesity and African American
race were important risk factors for anesthesia-related
maternal mortality.14 Most deaths resulted from
hypoventilation or airway obstruction during emergence,
extubation, or recovery. Vigilance in monitoring oxygenation
and ventilation throughout the entire perioperative period is
important.
B. Data from the United Kingdom
1. In the Confidential Enquiry into Maternal Deaths from 2003
to 2005, there were six maternal deaths related to anesthesia, a
number similar to that reported during the previous triennium.
Of the six deaths, one resulted from respiratory distress after
 tracheal extubation and two from postoperative respiratory
insufficiency. No deaths resulted from airway management
during induction of GA.
2. Seven anesthesia-attributed deaths were reported in the
triennium 2006 to 2008 and only two of the deaths were
airway related. One of the deaths was due to persistent
attempts to intubate the trachea despite adequate ventilation
through a laryngeal mask, and the other was the result of
pulmonary aspiration following extubation of the trachea after
emergency CD in a woman with a full stomach.15

CLINICAL PEARL Extubation and the postanesthetic period

convey the same risk for airway-related morbidity and mortality as
airway management during anesthetic induction.

VII. Anatomic and physiologic changes during pregnancy

contributing in difficult airway management
Anatomic and physiologic factors alter the airway during pregnancy,
placing the parturient at risk for difficult mask ventilation, difficult
laryngoscopy, and difficult intubation. Difficult mask ventilation and
difficult laryngoscopy may be due to excessive maternal weight gain,
increased upper airway edema (further increased in preeclampsia),
and breast enlargement. The respiratory (decreased functional residual
capacity [FRC]) and circulatory changes during pregnancy increase
the risk for hypoxemia. Gastrointestinal changes place the parturient
at risk for pulmonary and respiratory-related complications.
A. Airway changes
1. The hormonal changes in pregnancy, particularly the increase
in estrogen, increase the ground substance of maternal airway
connective tissue, circulating blood volume, and total body
water. Hypervascularity and edema of the oropharynx,
nasopharynx, and respiratory tract are the result. Mallampati
scores have been shown to increase during pregnancy, labor,
 and delivery.16
2. Excessive weight gain during pregnancy, preeclampsia,
iatrogenic fluid overload, and bearing down efforts during
labor can lead to increased mucosal edema.
3. Due to the increased vascularity of the respiratory mucosa and
swelling of the airway, the parturient is at increased risk for
epistaxis following manipulation of nasopharynx.
B. Respiratory changes
1. The gravid uterus displaces the diaphragm cephalad with
progression of pregnancy and leads to a 20% decrease in
FRC, which is exacerbated in the supine position.
2. Oxygen consumption and carbon dioxide production are
increased by 20% to 40% secondary to the metabolic needs of
the growing fetus, uterus, and placenta.
3. The decrease in FRC, along with increased oxygen
consumption, shortens the safe apnea time in a parturient
compared to a nonpregnant patient.
C. Cardiovascular changes
1. The gravid uterus compresses the inferior vena cava in the
supine position resulting in a decrease in venous return and
cardiac output. The decrease in cardiac output and the
resulting hypoxemia during a difficult/failed intubation
predispose the mother to the risks of myocardial hypoxemia,
compromised uteroplacental perfusion, and cardiovascular
arrest.
2. Left uterine displacement, establishing an airway with
adequate oxygenation and ventilation in a timely manner, and
maintenance of adequate perfusion in mother and baby
through periods of cardiovascular stability are important in
creating a safe outcome.
D. Gastrointestinal changes
1. Risk is increased for gastric regurgitation and pulmonary
aspiration during a GA.
2. Decreases in gastric pH and increases in intragastric pressure
 are associated with an increasingly incompetent
gastroesophageal sphincter and a predisposition to pulmonary
aspiration.
3. The updated 2007 ASA Practice Guidelines for Obstetric
Anesthesia recommend that practitioners should consider the
timely administration of nonparticulate antacids, H2-receptor
antagonists, and/or metoclopramide for aspiration prophylaxis
in parturients undergoing CD.17
E. Recommendations for airway management: implications of
the physiologic changes of pregnancy
1. Careful attention is required when evaluating and managing a
parturient’s airway. Placing a nasal airway or nasotracheal
tube can lead to brisk epistaxis; therefore, manipulation of the
nasopharynx must be avoided if possible. The mucosal
swelling decreases the area of the glottic opening and smaller
size ETTs are recommended. Attempts at intubation should be
gentle because the airway is more vulnerable to trauma and
hemorrhage.
2. Increased weight gain during pregnancy and enlarged breasts
can hinder laryngoscopy and result in difficult intubation. In
the recumbent position, the enlarged breasts tend to fall
against the neck, hindering laryngoscopy. Solutions to
minimize direct laryngoscopy in these patients include (1)
taping of breasts laterally and caudad, (2) use of the proper
sniffing position, facilitated by the use of blankets or sheets,
to create a ramp under the shoulders, and (3) use of a short
laryngoscope handle.
3. The aim of proper positioning is to ensure that an imaginary
horizontal line connects the external auditory meatus to the
sternal notch so that the patient’s head is above the level of
the chest to facilitate face mask ventilation, optimal
laryngoscopy, and tracheal intubation (see Fig. 14.1).
 VIII. Airway assessment
A. History. An airway history should be obtained, whenever
possible, and previous anesthetic records can yield useful
information regarding prior airway management.
B. Physical examination. The ASA Practice Guidelines for
Obstetric Anesthesia recommend physical examination of the
airway prior to initiation of anesthetic care and airway
management in all patients.17
C. Specific individual tests for assessment of difficult tracheal
intubation. The airway examination of the airway should focus
on the following six items to assess the difficulty of tracheal
intubation: (1) Mallampati classification, (2) jaw protrusion or
mandibular protrusion test, (3) atlanto-occipital joint extension,
(4) mouth opening, (5) thyromental distance, and (6) mentohyoid
distance.
1. Mallampati classification (see Fig. 14.2)
a. The Mallampati classification has been used either as a
single univariate predictor, or as a part of multivariate
analysis, to predict difficult tracheal intubation. Changes
in Mallampati classification during pregnancy illustrate
the airway changes during pregnancy and highlight the
importance of preoperative assessment of the airway.
Pilkington and colleagues18 photographed women at 12
and 38 weeks of pregnancy and found that there was an
increase in Mallampati class at 38 weeks. Increases were
correlated with increases in body weight and advanced
gestation, as well as increases in airway connective tissue
and increased vascularity.
b. Kodali and colleagues16 performed a two-part study to
evaluate Mallampati changes during labor and delivery. In
the first part of the study, the airway was photographed at
onset and at the end of labor and the Samsoon
modification of the Mallampati classification was used to
measure airway change. In the second part of the study,
upper airway volumes were measured using acoustic
reflectometry at the onset and conclusion of labor. In the
first part of the study, there was a significant increase in
the Mallampati class from pre- to postlabor. In the second
 part of the study, there were significant decreases in oral
volume and pharyngeal volume area after labor and
delivery.
2. Jaw protrusion or mandibular protrusion test. The ability
to slide the lower incisors in front of the upper ones may be
classified as A, B, or C (see Fig. 14.3). Class C protrusion is
often associated with difficult laryngoscopy and difficult
mask ventilation, whereas Class A protrusion is rarely
associated with any difficulty.19,20 Limited jaw protrusion can
help predict both difficult mask ventilation and difficult
laryngoscopy as a jaw thrust is required for adequate mask
ventilation and movement of the mandible to expand the
submental space for the tongue to ensure adequate
laryngoscopy.5,19

3. Atlanto-occipital joint extension. The sniffing position

depends on adequate atlanto-occipital joint extension and is
considered the “optimal” position of the head and neck for
facilitating tracheal intubation. To measure this, the patient is
asked to face directly to the front, hold their head erect,
extend the head maximally, and the examiner estimates the
angle traversed by the occlusal surface of the upper teeth.
Normal atlanto-occipital joint extension is a 35-degree
 extension of the head over the neck (see Fig. 14.4). Any
reduction in the extension helps predict difficulty with
laryngoscopy and intubation.

4. Mouth opening. The interincisor distance is the distance

between the upper and lower incisors. The normal distance is
>4.6 cm; a distance <3 cm or <2 fingerbreadths is
nonreassuring and may predict difficult laryngoscopy. A
distance of <1 fingerbreadths will impair insertion of a regular
LMA, whereas a distance of 2 cm is needed to insert an
ILMA.
5. Thyromental distance. Thyromental distance is the distance
from the chin (mentum) to the top of the notch of the thyroid
cartilage, when the head is fully extended. This distance gives
an estimate of the mandibular space into which the tongue is
displaced during direct laryngoscopy and also helps to
determine how readily the laryngeal axis will align with the
pharyngeal axis when the atlanto-occipital joint is extended
(see Fig. 14.5).
 a. Thyromental distance >6.5 cm: This indicates easy
intubation if no other abnormalities is present.
b. Thyromental distance 6.0 to 6.5 cm: There can be
difficulty with laryngoscopy and intubation but is usually
possible with the use of adjuncts for intubation such as
gum elastic bougie or optical stylette.
c. Thyromental distance <6 cm: This indicates that
laryngoscopy and intubation may be impossible.
6. Mentohyoid distance. Measurement of the mandibular length
from the chin (mentum) to hyoid should be at least 4 cm.21 If
the vertical distance between the mandible and the hyoid bone
is increased, direct laryngoscopy may be encountered.
7. All of these tests have high sensitivity, but low specificity, and
only moderate interobserver reliability. The low specificity of
these tests, when combined with the low incidence of difficult
airway, leads to a poor positive predictive value. However, a
combination of these tests can predict a difficult airway more
accurately.
8. Gupta and colleagues22 used a combination of Mallampati
classification and the Wilson risk sum23 to predict difficult
intubation in 372 obstetric patients undergoing elective and
emergency CD.22 The Wilson risk sum score is calculated by
adding scores of five factors, three objective, and two
 subjective criteria (weight, head and neck movement, jaw
movement/jaw protrusion, receding mandible, and buck
teeth). Combining the Mallampati classification and Wilson
risk sum has been shown to improve the sensitivity,
specificity, and positive predictive value for prediction of
difficult airway in obstetric patients.22
9. The “LEMON” mnemonic (developed by the U.S. National
Emergency Airway Management course) labels a combination
of tests to predict difficult intubation. Application is simple,
quick, and can be performed on any emergency patient and
has proven to have high predictive value.24 The LEMON
method is an acronym for Look-Evaluate-Mallampati-
Obstruction-Neck, which represents five elements for
preanesthetic assessment shown in Table 14.3 and Figure
14.6.
 10. Eighty-seven percent of emergency or urgent CDs can be
anticipated by regular preoperative evaluation of patients
admitted to the labor and delivery suite.25 The ASA
recommends that all parturients undergoing an operative
delivery should have a preanesthetic evaluation with
emphasis on the airway examination.1 The parturient should
also be evaluated for difficulty in mask ventilation (i.e., BMI
>35 kg per m2, absence of teeth, snoring, etc.).26 Selection of
anesthetic techniques, airway devices, and procedures will
depend on airway evaluation and patient safety.
11. According to a recent obstetric anesthesia–related difficult
airway survey comparing academic and private hospitals,
68% of respondents in academic institutions perform a
preanesthetic evaluation on most patients in labor and
delivery suite versus 39% of respondents in private
hospitals.27

CLINICAL PEARL Combining the use of multiple tests of

airway assessment will improve the ability of the anesthesiologist to
assess the risk for difficult airway management compared to the use
of single tests alone.
 IX. Morbid obesity in pregnancy and the airway
A. Prevalence of morbid obesity. The prevalence of morbid obesity
in pregnancy has increased significantly over the last decade, with
a significant impact on maternal morbidity and mortality (see Fig.
14.7). In 2005 to 2006, the U.S. Centers for Disease Control and
Prevention reported that 34.3% of adults in the United States had
a BMI above 30 kg per m2.

B. Technical challenges. Obese women pose technical challenges to

obstetricians. Morbidly obese parturients are at increased risk for
postpartum hemorrhage, cephalopelvic disproportion resulting in
CD, hypertension, and gestational diabetes when compared with
nonobese parturients.
C. Increased anesthetic risk. Obese parturients have increased
anesthetic risks compared to nonobese parturients.
1. A study by Shiga et al.28 found that the incidence of difficult
intubation by direct laryngoscopy increased threefold to
15.8% in patients with BMI above 30 kg per m2.
2. Obese parturients have an increased risk of difficult intubation
and increased difficulty in maintaining adequate mask
ventilation and are at risk for airway complications.26,29 In
addition, these patients are also at risk for cardiopulmonary
dysfunction and perioperative morbidity and mortality.30,31
3. In the supine position, breasts and chest wall soft tissue can
hinder chest wall excursion, decrease compliance, hinder
laryngoscopy, and result in difficult intubation. These
problems are encountered more frequently in morbidly obese
parturients (>130 kg).13,32
4. Most of the increased risk is from failed intubation and gastric
aspiration during procedures that require GA.33,34 As noted
earlier, a review of anesthesia-related maternal mortality from
Michigan showed that obesity was a major risk factor for
maternal mortality.14 Furthermore, four of the six deaths
directly attributable to anesthesia from the 2003 to 2005
Confidential Enquiries into Maternal Deaths in the United
Kingdom occurred in obese parturients, two of whom were
morbidly obese (BMI >35 kg per m2).11
5. The ASA obstetric anesthesia closed claims files indicate that
damaging events related to the respiratory system were
significantly more common among obese (32%) than
nonobese (7%) parturients. Furthermore, mortality was more
common among obese parturients. The data illustrate the
importance of increased awareness, caution, and immediate
availability of resources (i.e., difficult airway algorithm) and
equipment on all labor and delivery suites.10
6. The American College of Obstetricians and Gynecologists
(ACOG) Committee Opinion No. 315 on Obesity in
Pregnancy recommends that an anesthesiologist should be
consulted before delivery when an obese parturient is
identified.35 Anesthesia for both elective and emergency
situations should be planned in advance with a difficult
airway cart immediately available.
 7. Positioning is very important to optimize the conditions for
laryngoscopy and intubation in the morbidly obese parturient.
Use of a ramp pillow or blankets under the shoulders to
elevate the head, upper body, and shoulder above the level of
the chest is strongly recommended (see Fig. 14.1).

CLINICAL PEARL Most surveys of maternal morbidity and

mortality suggest that most difficult airway situations leading to
poor outcomes occur in obese patients.

X. Aspiration of gastric contents

A. Aspiration-related death. Aspiration-related deaths may occur
from difficult or failed endotracheal intubation and from
inadvertent esophageal intubation.37 Although maternal mortality
from aspiration has decreased dramatically over recent decades,
NAP4 in the United Kingdom identified aspiration of blood or
gastric contents as the most common cause of death after GA
among surgical patients.13
1. Patients at greatest risk for aspiration are obese parturients
who have eaten after the onset of labor or within 6 to 8 hours
of delivery.
2. The technique of rapid sequence induction (RSI) with cricoid
pressure and endotracheal intubation was introduced in
obstetric anesthesia practice to protect the airway from
aspiration of gastric contents. Improper application of cricoid
pressure can lead to problems with intubation.
B. Risk of difficult mask ventilation and aspiration after repeat
attempts at intubation. Following failed intubation and repeated
attempts at intubation, the risk for difficult mask ventilation is
increased. Difficult mask ventilation increases the risk of stomach
distension, thereby increasing the possibility of aspiration of
gastric contents.38
1. In the recent national survey by Quinn and colleagues,12 there
 were four cases of aspiration in the failed intubation group
and one in the control group.
2. The NAP4 in the United Kingdom reported a death
consequent to a massive aspiration of gastric contents
following extubation.13
XI. Anesthetic management in obstetric patients with a predicted
difficult airway
Management of the difficult airway has emerged as one of the most
important safety issues in obstetric population. Emergency airway
management following failed tracheal intubation in obstetrics presents
challenges for the anesthesia provider. Analysis of the serious airway
complications in the NAP4 study identified repeated gaps in care that
included (1) poor identification of at-risk patients, (2) poor or
incomplete planning, (3) inadequate provision of skilled staff and
equipment to manage the events successfully, (4) delayed recognition
of events, (5) and failed rescue due to lack of or failure of
interpretation of capnography. The lessons learned from the
prospective NAP4 project findings suggest that proper planning and
preformulated strategies can prevent deaths due to airway
complications.13 ASA Practice Guidelines help guide practice in this
situation.
A. American Society of Anesthesiologists practice guidelines. The
ASA Guidelines for Obstetric Anesthesia published in 2007 have
specific recommendations to decrease maternal and fetal
complications. The recommendations for the anesthetic
management of parturients with predicted difficult airway
include:
1. Consultation between the anesthesia and obstetric provider
when a parturient with morbid obesity, severe preeclampsia,
or a difficult airway is encountered.
2. Development of a strategy to avoid instrumentation of the
airway in patients at risk for difficult intubation or difficult
mask ventilation while the patient is in early labor.
3. Implementation of a plan to place a neuraxial catheter early in
 labor in high-risk parturients and patients attempting trial of
labor after cesarean delivery (TOLAC). Early placement of a
functioning neuraxial catheter can be for obstetric or
anesthetic indications (predicted difficult airway, obesity, or at
high risk for CD).
4. Development of a preformulated strategy for the immediate
availability of personnel and equipment to manage airway
emergencies and a means to provide oxygenation and
ventilation, or to manage a critical airway in the patient with
increasing hypoxemia, if it becomes necessary.
B. Management of the parturient with a predicted difficult
airway undergoing labor or operative delivery, where airway
management is not necessary
Communication and a collaborative approach between
obstetricians and anesthesiologists facilitate optimal patient care,
which may improve patient outcomes. The National Confidential
Enquiry into Maternal Deaths identified “lack of communication
and teamwork” as a substantial component that resulted in
substandard care in many of their analyses.39 The obstetric care
team should be alerted by the anesthesia team to the presence of
risk factors that place the parturient at increased risk for
complications from GA. In addition, the obstetric care team
should routinely assess patients for risk factors that place the
parturient at increased risk for difficult airway management and
when such risk factors are identified, the anesthesiologist should
be notified.40
1. Labor
a. Incorporating “best practices” in the anesthetic
management of the parturient will help to eliminate
airway-related maternal morbidity and mortality.
(1) Best practice involves the immediate availability of
anesthesia services to evaluate and provide
consultative services to all parturients on the labor
floor, which allows for better planning and decreases
 the likelihood of an anesthesia provider being
unaware of a patient with a difficult airway.
Anesthesiologists should become involved earlier in
labor rather than later, especially in high-risk patients.
Examples include (1) preeclampsia, (2) morbid
obesity, (3) TOLAC. The National Confidential
Enquiry into Maternal Deaths identified “lack of
communication and teamwork” resulting in
substandard care.39
(2) Close communication and collaboration between the
obstetrician and anesthesia provider when caring for
“at-risk” parturients allows for development of a
cogent plan of action to facilitate optimal patient
care.
(3) Educating and training obstetric residents in the
evaluation of a difficult airway, and the potential
complications with GA in such a patient, has shown
to improve their acceptance of labor analgesia.41
b. Based on the ASA Practice Guidelines for Obstetric
Anesthesia, parturients in labor should undergo a
thorough preanesthetic evaluation.
(1) Because the incidence of difficult tracheal intubation
is significantly higher in the obstetric patient during
emergency CD and especially in emergencies that
occur during nights and weekends, the best strategy is
to avoid instrumentation of the airway in patients
who are at risk for difficult intubation or difficult
mask ventilation particularly, if there are other safe
choices available. Prior planning is required while the
patient is in labor prior to operative delivery and is
especially important in those patients identified as
high risk for potential emergent CD. Such high-risk
cases include women who are obese, those with
severe preeclampsia, and patients attempting
 TOLAC.
(2) In these patients, early placement of an epidural
catheter should be considered. Adoption of a policy
of placing an epidural catheter early in labor in
women who are considered to be at high risk for CD
reduces the risk of unanticipated GA.17 This practice
has been validated in large population studies.6

CLINICAL PEARL Parturients with known difficult airways

especially those with obstetric conditions that place them at high
risk for operative delivery should have early epidural catheter
placement for labor and delivery.

2. Cesarean delivery
a. Neuraxial anesthesia
(1) Neuraxial anesthesia is the most common mode of
anesthesia utilized for CD in developed countries. For
elective or urgent CD in women with a known
difficult airway and no prior neuraxial block,
neuraxial anesthesia is usually preferable, provided
there is adequate time, no acute maternal or fetal
compromise, and no contraindication to neuraxial
anesthesia. Neuraxial techniques are safe and
predictable in women with difficult airways,8
especially for the elective or emergent CD if airway
intervention is deemed unnecessary. A single-shot
spinal, continuous epidural anesthesia, combined
spinal-epidural (CSE), or continuous spinal
anesthesia (CSA) can be used.42
(2) The use of neuraxial anesthesia in patients with a
recognized difficult airway does not always eliminate
the problem of difficult airway management. The
danger of neuraxial anesthesia in a patient with
 known or suspected difficult airway is that failure to
provide an adequate block, prolonged surgery, or
uncontrolled hemorrhage could result in the need for
immediate induction of GA under suboptimal
conditions. In such a situation, airway equipment to
help manage the airway should be immediately
available.
b. Spinal anesthesia. Spinal anesthesia is often
administered for a CD regardless of airway status. With
administration of an appropriate dose of local anesthetic
for spinal anesthesia, a high motor block with respiratory
insufficiency can almost always be avoided.
c. Epidural anesthesia
(1) When a CD is nonemergent, epidural anesthesia can
be used. The advantages of epidural anesthesia
include gradual titration of block, avoidance of major
hemodynamic and respiratory compromise, and the
ability to extend the anesthetic until surgery is
completed.
(2) In a patient with an epidural catheter in situ, adequate
function of the catheter must be confirmed before
surgery. If anesthesia is inadequate, and if time
permits, the epidural catheter should be replaced.
Bloom et al.43 reported that failed neuraxial
anesthesia requiring conversion to GA occurred more
commonly with an epidural than spinal or CSE (4.3%
vs. 2.1% and 1.7%, respectively).
d. Spinal anesthesia after failed epidural blockade. The
administration of spinal anesthesia after a failed epidural
is associated with an increased risk for high or total spinal
anesthesia. However, with adequate precautions, the use
of spinal anesthesia in this setting has several advantages,
including rapid onset and reliable surgical anesthesia. The
recommended precautions, when spinal anesthesia is
 planned after a failed epidural, are (1) no epidural bolus
administered in the 30 minutes preceding spinal
anesthesia, (2) decrease the dose of intrathecal local
anesthetic by 20% to 30%, and (3) maintain the sitting
position for 1 to 2 minutes after intrathecal injection
followed by supine positioning with left uterine
displacement.44,45

CLINICAL PEARL The risk of high motor block during spinal

anesthesia is increased following failed epidural anesthesia for CD.

C. Management of the predicted difficult airway in obstetric

patient where airway management is needed: emphasis on
awake intubation
GA is chosen for CD if there are contraindications to neuraxial
anesthesia (e.g., patient refusal, severe hemorrhage,
coagulopathy). The anesthesiologist’s preplanned strategy for
intubation of the difficult airway should include identification of
the patient who requires an awake intubation or who can be
adequately ventilated, but who may be difficult to intubate. In
addition, an approach for managing the can’t intubate, can’t
ventilate situation (e.g., the super morbidly obese parturient)
should be developed. When GA is planned and difficult airway is
suspected, an awake intubation is the safest option. Successful
awake endotracheal intubation requires proper preparation of the
patient. There are several advantages of securing an airway awake
in a parturient with difficult airway: (1) maintenance of protective
airway reflexes, (2) uncompromised gas exchange and
oxygenation, and (3) maintenance of normal muscle tone, which
helps identify anatomic landmarks. All these factors contribute to
safe patient outcomes.
1. Indications for awake intubation. Flexible fiberoptic
intubation should be a skill practiced by all anesthesiologists.
Indications for awake tracheal intubation in patients
 undergoing CD include previous difficult/failed intubation,
cervical spine abnormalities, severe rheumatoid arthritis with
airway pathology, osteogenesis imperfecta, acromegaly,
lingular tonsillar hyperplasia, severe morbid obesity with
obstructive sleep apnea, predicted difficult or impossible
mask ventilation.
2. Preparation for fiberoptic intubation
a. Psychological preparation. Appropriate psychological
preparation will increase the likelihood of success by
ensuring an alert and cooperative patient.
b. Pharmacologic preparation. Administration of an
antisialogogue, preferably glycopyrrolate 3 to 4 μg per kg
or 0.2 mg intravenously (IV), should occur 15 to 60
minutes before administration of local anesthesia. This
will dry the oral mucosa and allows for better absorption
of local anesthetic and superior anesthesia of the airway.
It will also improve the view through the fiberoptic
bronchoscope. An advantage of glycopyrrolate over
atropine administration is that it does not cross the
placental barrier and thus has no adverse effect on fetal
heart rate.
c. Sedation. Intravenous sedation with midazolam 15 to 30
μg per kg and fentanyl 1.5 μg per kg IV will relax the
patient and help depress airway reflexes during
instrumentation of the airway. Intravenous
dexmedetomidine is an alternative for sedation; it does
not cause respiratory depression and helps to maintain a
patent airway. It does not cross the placenta and maintains
stable maternal hemodynamics. Administer
dexmedetomidine at a loading dose of 1 μg per kg over 10
minutes. After 10 minutes, continue a maintenance
infusion at 0.7 μg per kg per hour. Assess the sedation
level 15 minutes after initiating the dexmedetomidine
infusion, and every 3 minutes thereafter. The Ramsay
 Sedation Score should be at 2; a Ramsay Sedation Score
of 2 indicates a patient who is cooperative, oriented, and
tranquil.
d. Tips for anesthetizing the airway. Adequate
topicalization of the oral airway or selective nerve
blockade is required to depress the pharyngeal, laryngeal,
and tracheobronchial reflexes.46
(1) Topicalization for combined pharyngeal,
periepiglottic, and periglottic anesthesia. Have the
patient gargle with 4% viscous lidocaine (2 to 4 mL)
intermittently for 5 minutes and spit it out. Have an
assistant pull the tongue gently anterior with a gauze
padded finger and thumb, and apply lidocaine gel 2%
with a tongue blade to the tip of the tongue, both
sides of the tongue, and follow with application to the
base of the tongue. Place 1 inch of 2% to 5%
lidocaine ointment on a tongue blade and place it like
a lollipop midline as far as posterior on the tongue as
tolerated, ask the patient to bite on the tongue blade,
and allow the ointment to melt for 5 to 10 minutes.
Another method is to use an atomizer and spray 2%
to 4% lidocaine solution on the palate, tonsillar
fossae, vallecular, epiglottis, and larynx.
(2) Glossopharyngeal nerve block
(a) Employ a tongue depressor on the lateral surface
to shift the tongue medially and spray 4%
lidocaine on the palate, base of the tongue,
uvula, posterior pharyngeal wall, and the
anterior/posterior tonsillar pillars.
(b) The MADgic atomizer (Wolfe Tory Medical,
Inc., Salt Lake City, Utah) works well for the
local anesthetic spray because the droplet size is
very small.46,47
(c) Apply gauze pledget balls, with a string attached
 and soaked with 4% lidocaine, using a
Bayonet/Krause forceps to the pyriform fossa for
<5 minutes. Eliminating the gag reflex is critical
for a successful awake intubation, which means
applying topical local anesthesia to the base of
the tongue, uvula, and the peritonsillar pillars to
block the glossopharyngeal nerve.
(d) Assess adequate topicalization by stimulating
the uvula, tongue, and bilateral posterior
pharyngopalatine fauces with a wooden tongue
blade. Use a catheter to clear secretions and to
test for reaction (e.g., gag and cough).
(3) Superior laryngeal and recurrent laryngeal nerve
blocks
During the actual fiberoptic intubation technique, the
“spray as you go” technique is utilized to topicalize
periepiglottic and periglottic areas. Using the side
port of the fiberoptic broncoscope preloaded with a 5-
mL Luer slip syringe containing 2% to 4% lidocaine,
spray 2 to 3 mL on the anterior and superior aspects
of the epiglottis in order to block the superior
laryngeal nerve, the posterior and inferior aspects of
the epiglottis, the vocal cords, and upper trachea to
block the recurrent laryngeal nerve.48
(4) It has been suggested that injecting local anesthetic
below the vocal cords might increase the risk of
aspiration by eliminating protective airway reflexes.
However, Ovassapian et al.47 showed no adverse
outcomes in patients at high risk for aspiration
undergoing awake fiberoptic intubation after sedation
and topicalization of the upper and lower airway.
3. Oral fiberoptic intubation technique
a. Administer O2 via nasal cannula; use SaO2 as indicator of
sedation level. If needed, have an assistant provide jaw
 thrust or chin lift while keeping an intraoral airway
midline.
b. Before advancing the fiberoptic bronchoscope, measure
the distance from the corner of the mouth to the ear; that
is, the distance from mouth opening to the glottis. An
intubation oral airway (e.g., Ovassapian, Berman, Patil-
Syracuse, WIlliams, or MADgic Airway) can be placed
before introducing the scope. It is usually well-tolerated
following adequate topicalization.
c. Use the nondominant hand for the fiberoptic
bronchoscope controls and connect an ETT syringe with
lidocaine to the fiberoptic bronchoscope port to spray as
needed.
d. Keep the fiberoptic bronchoscope straight, in the midline,
and utilize a step stool if needed. Place the lubricated ETT
over the fiberoptic bronchoscope.
e. Insert the preferred intraoral airway device (e.g.,
Ovassapian, Berman, Patil-Syracuse, Williams). Insert the
distal tip of fiberoptic bronchoscope through the intraoral
airway, advance slowly, and make small movements with
the lever as you advance the fiberoptic bronchoscope
while recognizing the structures, uvula, and epiglottis.
Spray lidocaine when epiglottis is in view.
f. Once the vocal cords are visualized, advance the fiberoptic
bronchoscope through the vocal cords and spray once
below the vocal cords. Advance the fiberoptic
bronchoscope to three rings above the carina and then
advance the ETT over the fiberoptic bronchoscope under
visual control of fiberoptic bronchoscope.
g. Remove the fiberoptic bronchoscope, stabilize the ETT
with one hand and inflate the cuff, connect the ETT to the
anesthesia circuit, and confirm ETCO2 by capnography
and bilateral breath sounds by auscultation before
anesthetizing the patient.
 4. The use of fiberoptic intubation is the gold standard for awake
intubation; however, with adequate topicalization of the
airway, recent reports show that successful awake intubation
can be achieved with video laryngoscopes.48–50 One study
compared awake intubation utilizing fiberoptic intubation
versus the GlideScope video laryngoscope utilizing mild
sedation in nonobstetric patients showed shorter intubation
times and reduced stress response with the GlideScope video
laryngoscope.50
5. With the low rate of GA in most obstetric units, it can be
difficult to maintain proficiency in advanced airway
techniques. The use of simulators and intubation mannequins
during training workshops as well as the elective utilization of
fiberoptic techniques in nonobstetric patients will help ensure
that obstetric anesthesia providers will maintain fiberoptic
intubation skills.

CLINICAL PEARL The skills needed for successful fiberoptic

intubation can be practiced in anesthetized general surgical patients
to prepare the anesthesiologist for their use in emergency situations
involving obstetrical patients.

XII. Management of pregnant patient with an unanticipated difficult

airway
The anesthesiologist/anesthesia provider must have a clear, concise
plan for managing an unanticipated difficult airway during an
emergent CD. We include a simple, logical, and linear five-step
approach in Figure 14.8 based on the ASA Difficult Airway
Algorithm and the UK Difficult Airway Society guidelines. Each step
should not exceed 45 seconds so that the decision to proceed to
emergency invasive airway management in the “emergency pathway
critical airway” scenario should occur within 5 minutes of initial
presentation.51 First attempt at tracheal intubation is critical in the
parturient because this can influence the final outcome for both
mother and baby.

A. Step 1: first attempt at tracheal intubation (see Step 1, Fig.

14.8)
1. RSI of anesthesia with cricoid pressure and intubation of the
trachea is routinely performed for GA during a CD. The
 considerations to improve and obtain the best view during
laryngoscopy and best attempt at intubation require the
following:
a. Patient in the optimal sniffing position
b. External laryngeal manipulation (backward, upward,
rightward pressure [BURP] maneuver) during intubation
attempts
c. Use of a single change in laryngoscope blade/handle
d. Attempt at passage of an Eschmann bougie
e. Easing of cricoid pressure when needed because excess or
improperly applied cricoid pressure can obscure the
glottic view.
2. If the first attempt at tracheal intubation is successful, verify
intubation with breath sounds and capnography and proceed
with CD or proceed to Step 2.
B. Step 2: second tracheal intubation/best attempt—difficult
laryngoscopy/difficult intubation (see Step 2, Fig. 14.8)
1. Following direct laryngoscopy and the intubation is deemed
difficult during the first attempt, the focus should be to ensure
adequate oxygenation and ventilation. The recommendations
are as follows:
a. Maintain cricoid pressure but consider releasing
transiently during the second attempt.
b. Attempt bag and mask ventilation.
c. Change laryngoscope blade type and size.
d. Consider using Eschmann bougie, optical stylette, or a
video laryngoscope.
e. Have the most experienced person available make the
second attempt, use BURP maneuver; BURP maneuver
often improves the laryngoscopic view by an entire grade.
f. Consider awakening the patient and returning to
spontaneous ventilation.
2. The second attempt should be well optimized and should be
the best attempt at intubation. A review of the ASA obstetric
 closed claims data suggests that repeated attempts at
intubation may result in progressively difficult ventilation that
ultimately leads to complete airway obstruction.2 As the
number of laryngoscopies increase, there can be
complications, which can result in hypoxemia, regurgitation
of gastric contents, aspiration, and aspiration of gastric
contents, bradycardia, and cardiac arrest (see Fig. 14.9).

3. GlideScope, C-MAC video laryngoscope, and Airtraq

laryngoscopes
Meta-analyses of randomized controlled trials comparing
video-assisted laryngoscopy with direct laryngoscopy in
patients with predicted or simulated difficult airways report
improved laryngeal views, higher frequency of successful
intubations, and a higher frequency of first attempt
intubations with video-assisted laryngoscopy.1 So, it could be
argued that a video laryngoscope should be used as the first
option for all CD under general endotracheal anesthesia
(GETA).
a. The GlideScope video laryngoscope can be a very useful
tool in patients with difficult airways. This device utilizes
a video camera embedded into a plastic laryngoscope
blade. The configuration of the laryngoscope blade
 provides a less obstructed view of the glottis compared to
that obtained with a conventional laryngoscope, allowing
the user to “see around the corner” of the tongue.
b. C-MAC video laryngoscope improves the glottic view
and increases the success rate of tracheal intubation in
cases of unanticipated difficult intubations with
conventional laryngoscopy. A recent study in surgical
patients showed that C-MAC video laryngoscope was
successfully utilized as the primary rescue device in
patients where conventional laryngoscopy with a
Macintosh blade had failed.52 There are no published case
reports of C-MAC intubations in obstetrics. We used the
CMAC in 15 morbidly pregnant women in our institution
as the primary airway device with success.
c. The Airtraq video laryngoscope (Prodol Meditec S. A.,
Vizcaya, Spain) is a new disposable intubating device,
designed to provide a view of the glottis without
alignment of the oral and pharyngeal axes. Dhonneur et
al.53 recently reported two cases of rapid tracheal
intubation with this device after failed direct laryngoscopy
in morbidly obese parturients undergoing emergency CD
(see Table 14.4).

C. Step 3: maintenance of oxygenation/ventilation—failed

intubation (see Step 3, Fig. 14.8)
Airway management from this point onward is critical to avoid
adverse respiratory, cardiac, or neurologic complications.
Providing maternal oxygenation, prevention of gastric
regurgitation and aspiration, and allowing delivery of the fetus are
the goals, usually by providing mask ventilation.
1. If mask ventilation is not achieved by one person, two-person
mask ventilation should be performed by either the primary
provider holding the mask with two hands while
simultaneously providing chin elevation/jaw lift and the
assistant compressing the reservoir bag, or by the primary
provider holding the mask in the left hand while
simultaneously compressing the reservoir bag with the right
hand and with the assistant helping with chin elevation and
jaw lift. Caution should be used to prevent gastric
insufflation/regurgitation.
2. Difficult oxygenation/ventilation: use of a supraglottic
airway
The use of nonsurgical airway devices to establish
oxygenation and ventilation is critical. These airway devices
include SGA devices such as the classic LMA, the ProSeal
LMA, and intubating ILMA (Fastrach).
a. Laryngeal mask airway
The LMA is now a recognized part of the ASA Difficult
Airway Algorithm and should be part of every obstetric
anesthesiologists’ plan for managing difficult airways.
(1) The LMA has been found to be a lifesaving device in
obstetric patients who could not be ventilated or
intubated by conventional techniques during
emergency CD. Han et al.54 reported the successful
use of the LMA as a ventilatory device in 1,060 of
1,067 patients undergoing elective CD.
(2) If the classic LMA is used for ventilation following
failed intubation during urgent/emergent CD,
oxygenation can be restored and adequate anesthetic
depth ensured to avoid coughing. Obstetricians
should be notified to avoid fundal pressure to prevent
aspiration, particularly in an unprotected airway.
Once the fetus is delivered, the trachea can be
 intubated through the classic LMA using a
fiberscope. The classic LMA with the tracheal tube
can be left in place until the surgery is completed and
removed at the end of surgery.
(3) If prolonged intubation is required for postoperative
ventilation, another option is to intubate the trachea
through the classic LMA with the aid of fiberoptic
scope and the Cook Aintree catheter. The fiberoptic
scope is loaded with the Cook Aintree catheter and
passed into the trachea through the aperture bars and
through the vocal cords. The Aintree catheter is left
in place and the fiberoptic scope, along with the
LMA, is removed. The Aintree catheter serves as an
airway exchange catheter and the tracheal tube can be
placed over it. When the tracheal tube is in place, the
Aintree™ catheter can be removed.
b. LMA ProSeal
(1) LMA ProSeal is a modification of the classic LMA,
providing a better seal and better airway protection. It
has a second lumen so that an orogastric tube can be
placed to vent any regurgitated esophageal contents;
malposition is detected more readily. The LMA
ProSeal allows positive pressure ventilation at much
higher pressures and has its own built-in bite block.
(2) The LMA ProSeal has been used successfully in
parturients after failed intubation during RSI and in
cases where postoperative respiratory support is
needed.38,55,56 It has been recently used in two failed
obstetric intubation scenarios and served to provide a
patent airway.57 It has also been used during
electroconvulsive therapy in a parturient at 20 to 22
weeks’ gestation with a known difficult airway.58
c. LMA Supreme The new LMA Supreme, a disposable
version of the LMA ProSeal, may be useful as a rescue
 device in a similar obstetrical situation. It is a single-use,
SGA device designed as an alternative to conventional,
tracheal intubation, and it provides a good seal for
positive pressure ventilation.
(1) It has features that are similar to both the ILMA and
the ProSeal LMA, with a shorter stem and handle to
allow manipulation as per the ILMA (but not
designed as a conduit for a tracheal tube) and similar
to the ProSeal LMA, with a built-in drain tube
designed to channel fluids and gas away from the
airway. The elliptical shape and integrated bite block
facilitate proper placement and prevent kinking.
d. LMA Fastrach
The LMA Fastrach has been designed to increase the
success rate of tracheal intubation compared with a
regular LMA. The LMA Fastrach differs from a regular
LMA in that the ILMA has a more rigid shaft. This shaft
acts as an insertion tool for the ETT to allow an
atraumatic intubation when the mask aperture is in
alignment with the glottic opening. LMA Fastrach has
been used in parturients when failed intubation
occurs.59,60 In our institution, LMA Fastrach has been
used in two parturients in a CICV situation during CD.
D. Step 4: management of the “cannot intubate/cannot ventilate”
situation (see Step 4, Fig. 14.8)
According to the ASA Difficult Airway Algorithm, following
failed intubation, if face mask ventilation and LMA ventilation
are ineffective in maintaining oxygenation, immediate rescue
ventilation with other noninvasive devices, such as Combitube or
King LTS/LTS-D should be used.
1. Combitube
a. The Combitube can be used when mask ventilation and
intubation have failed. The Combitube can be placed
easily, rapidly, and without extensive preparation. It can
 be placed blindly or by direct laryngoscopy. Ventilation is
possible when the Combitube is placed either in the
trachea or esophagus. When properly positioned, it
protects against regurgitation. It also allows subsequent
attempts at intubation after deflating the pharyngeal cuff
while the inflated esophageal cuff maintains airway
protection. There is the potential for esophageal trauma
with its use. In 1993, Wissler61 recommended the use of
the Combitube in managing difficult airway situations in
obstetric anesthesia. However, with the recent
introduction of video laryngoscopes and SGAs into
clinical practice, its use is limited to a few enthusiasts at
present.
b. Surgery typically can be completed using a Combitube.
However, replacement of the Combitube with a tracheal
tube is required for prolonged postoperative ventilation.
An FOB is introduced through the mouth to expose the
inflated pharyngeal balloon of the Combitube. The
pharyngeal balloon is deflated, and with the aid of a
laryngoscope and Magill forceps, the FOB is advanced
toward the larynx. The FOB is passed through the glottis
into the trachea. The tracheal tube is passed over the FOB
into the trachea.
2. King LTS/LTS-D
a. The King LTS is the double lumen version of the King
LT; similar to the Combitube, but smaller, shorter, and
softer. It has a nonlatex oropharyngeal cuff and dedicated
channels for ventilation and esophageal/gastric access. It
is designed for easy placement, it uses a low pressure
cuff, and few complications with its use have been
reported.62 The King LTS simultaneously isolates the
esophagus from the airway by allowing passage of an 18-
Fr orogastric tube via the posteriorly placed gastric
drainage lumen to aspirate stomach contents. King LTS
 allows passage of an FOB to facilitate intubation with a
tracheal tube to establish a definitive airway.
b. The King LTS has been successfully used to establish
oxygenation and ventilation, after failed intubation,
during emergency CD.63 The King LTS-D is the
disposable version of King LTS.
3. If ventilation is impossible with nonsurgical devices, then
cricothyroidotomy, transtracheal jet ventilation (TTJV), or
surgical tracheostomy should be performed as a lifesaving
maneuver.
4. A thorough working knowledge of devices available for the
management of the difficult airway and recommended rescue
strategies is essential in avoiding airway complications. The
use of airway equipment for the first time during a failed
intubation scenario is unlikely to be successful.
E. Step 5: management of pregnant patients with a critical
airway (increasing hypoxemia)
Steps 1 through 4 mentioned earlier should be time limited, no
more than 30 to 45 seconds per step (total ≤5 minutes). If
hypoxemia occurs in a can’t intubate, can’t ventilate situation,
then direct surgical or percutaneous access to the trachea through
the neck is indicated. A case report describes can’t intubate, can’t
ventilate in a pregnant patient where surgical cricothyroidotomy
was performed within 5 minutes of anesthesia induction with a
successful outcome. If hypoxemia during can’t intubate, can’t
ventilate leads to cardiac arrest, cardiopulmonary resuscitation
(CPR) should be initiated and an abdominal delivery performed
as soon as possible. Perimortem CD guidelines recommend
making an incision at 4 minutes in order to deliver the fetus
within 5 minutes after the start of a maternal cardiac arrest.64 The
three procedures that might be considered in an emergency
airway setting include (1) surgical cricothyroidotomy (traditional
four steps or percutaneous tracheostomy), (2) needle
cricothyroidotomy, with or without transtracheal jet ventilation, or
(3) a formal tracheostomy in the can’t intubate, can’t ventilate
situation.
1. Emergency percutaneous cricothyroidotomy
a. Emergent percutaneous cricothyroidotomy is not easily
practiced in real life situations. Initial training and skill
improvement can occur by using simulators.65,66 The
complication rate for emergent cricothyroidotomy ranges
from 10% to 40% of cases.67
b. Percutaneous cricothyroidotomy requires knowledge of
neck anatomy. The cricothyroid membrane, which has
vertical height of 8 to 19 mm and a width of 9 to 19 mm,
is located between the thyroid and cricoid cartilages.
Branches of the thyroid arteries pierce the cricothyroid
membrane in its upper third; it is recommended to
approach the access at its lower third. Identifying the
midline of the structure is extremely important because
roughly 30% of the population have large-caliber veins
within 1 cm of the midline, whereas only 10% have veins
greater than 2 mm in diameter that cross the midline. In
patients in whom landmarks are difficult to identify, the
membrane is usually 4 finger breadths from the sternal
notch.
2. Surgical cricothyroidotomy
a. An easy and rapid four-step surgical cricothyroidotomy
technique, which can be performed in 30 seconds,
involves:
(1) Identifying the cricothyroid membrane
(2) Performing a horizontal stab incision through skin
and cricothyroid membrane
(3) Applying caudad traction on cricothyroid membrane
with a tracheal hook
(4) Inserting a cricothyroidotomy tube into the trachea68
(5) Establishing ventilation and oxygenation through the
cricothyroidotomy tube
 b. Many commercial surgical cricothyroidotomy kits are
available, including the Melker guidewire kit with a
cuffed cricothyroidotomy tube. The Eschmann stylette has
been used as an introducer to facilitate insertion of the
cricothyroidotomy tube in the obese patient.69
3. Transtracheal jet ventilation
Inability to provide adequate oxygenation by routine methods
is the primary indication for the use of transtracheal jet
ventilation. Needle cricothyroidotomy is faster than
conventional tracheotomy and is probably the most rapid
technique for oxygenating an apneic patient. The technique is
not popular because it is an invasive procedure and can
produce complications such as pneumomediastinum,
pneumothorax, and subcutaneous emphysema.70
a. Percutaneous insertion of a 12- to 14-G IV catheter
through the cricothyroid membrane is simple, quick, and
relatively safe in most patients.
b. When performing transtracheal jet ventilation, it is
essential to allow for adequate exhalation to avoid
barotrauma.
c. Oxygenation by transtracheal jet ventilation is only a
temporary measure, and in order to avoid barotrauma, it is
mandatory to have a dedicated person assigned to firmly
hold the catheter in place at the patient’s neck.
d. Experience gained with the use of newer airway devices
in elective surgeries make nonsurgical devices preferable
to transtracheal jet ventilation.

CLINICAL PEARL An airway algorithm should be adopted by

all obstetric anesthesiologists and each step practiced before the
algorithm is followed during emergency airway management.

XIII. Extubation and postanesthesia care unit airway issues

 Although the management of tracheal intubation receives much
attention during difficult airway scenarios, there has been very little
emphasis and research on complications following tracheal extubation
and emergence issues in postanesthesia care unit (PACU). The ASA
Task Force on the Management of the Difficult Airway regards the
concept of extubation strategy as a logical extension of the intubation
process in order to avoid airway catastrophes during emergence.1
Airway misadventure in PACU is associated with increased maternal
morbidity and mortality compared with intubation attempts in the
operating room.14
XIV. Conclusion
Failed intubations often occur during emergency surgeries and at
night. Teams need to train for these emergencies using manikin-based
simulation in order to improve success during real rescue.71
Simulation-based training should be a mandatory part of obstetric
anesthesia training. Anesthesiologists/anesthesia providers play a
critical role in providing safe anesthetic care and also to acquire and
maintain advanced airway management skills.

REFERENCES
1. Apfelbaum JL, Hagberg CA, Caplan RA, et al. Practice guidelines for management of the difficult
airway: an updated report by the American Society of Anesthesiologists Task Force on Management
of the Difficult Airway. Anesthesiology. 2013;118:251–270.
2. Davies JM, Posner KL, Lee LA, et al. Liability associated with obstetric anesthesia: a closed claims
analysis. Anesthesiology. 2009;110:131–139.
3. Lyons G. Failed intubation: six years’ experience in a teaching maternity unit. Anaesthesia.
1985;40:759–762.
4. Samsoon GL, Young JR. Difficult tracheal intubation: a retrospective study. Anaesthesia.
1987;42:487–490.
5. Kheterpal S, Healy D, Aziz MF, et al. Incidence, predictors, and outcome of difficult mask ventilation
combined with difficult laryngoscopy: a report from the multicenter perioperative outcomes group.
Anesthesiology. 2013;119:1360–1369.
6. Palanisamy A, Mitani AA, Tsen LC. General anesthesia for cesarean delivery at a tertiary care hospital
from 2000 to 2005: a retrospective analysis and 10-year update. Int J Obstet Anesth. 2011;20:10–16.
7. Bucklin BA. Gerard W. Ostheimer “what’s new in obstetric anesthesia” lecture. Anesthesiology.
2006;104:865–871.
8. Hawkins JL, Koonin LM, Palmer SK, et al. Anesthesia-related deaths during obstetric delivery in the
 United States: 1979–1990. Anesthesiology. 1997;86:277–284.
9. Hawkins JL, Chang J, Palmer SK, et al. Anesthesia-related maternal mortality in the United States:
1979–2002. Obstet Gynecol. 2011;117:69–74.
10. Chadwick HS. Obstetric anesthesia closed claims update II.
http://depts.washington.edu/asaccp/sites/default/files/pdf /Click%20here%20for%20_74.pdf Accessed
November 4, 2015.
11. Cooper GM, McClure JH. Anaesthesia chapter from Saving Mothers’ Lives: reviewing maternal
deaths to make pregnancy safer. Br J Anaesth. 2008;100:17–22.
12. Quinn AC, Milne D, Columb M, et al. Failed tracheal intubation in obstetric anaesthesia: 2 yr national
case-control study in the UK. Br J Anaesth. 2013;110:74–80.
13. Cook TM, Woodall N, Harper J, et al; for the Fourth National Audit Project. Major complications of
airway management in the UK: results of the Fourth National Audit Project of the Royal College of
Anaesthetists and the Difficult Airway Society, part 2: intensive care and emergency departments. Br J
Anaesth. 2011;106:632–642.
14. Mhyre JM, Riesner MN, Polley LS, et al. A series of anesthesia-related maternal deaths in Michigan:
1985–2003. Anesthesiology. 2007;106:1096–1104.
15. McClure JH, Cooper GM, Clutton-Brock TH; for Centre for Maternal and Child Enquiries. Saving
Mothers’ Lives: reviewing maternal deaths to make motherhood safer: 2006–2008: a review. Br J
Anaesth. 2011;107:127–132.
16. Kodali BS, Chandrasekhar S, Bulich LN, et al. Airway changes during labor and delivery.
Anesthesiology. 2008;108: 357–362.
17. American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Practice guidelines for
obstetric anesthesia: an updated report by the American Society of Anesthesiologists Task Force on
Obstetric Anesthesia. Anesthesiology. 2007;106:843–863.
18. Pilkington S, Carli F, Dakin MJ, et al. Increase in Mallampati score during pregnancy. Br J Anaesth.
1995;74:638–642.
19. Takenaka I, Aoyama K, Kadoya T. Mandibular protrusion test for prediction of difficult mask
ventilation. Anesthesiology. 2001;94:935.
20. Calder I, Calder J, Crockard HA. Difficult direct laryngoscopy in patients with cervical spine disease.
Anaesthesia. 1995;50:756–763.
21. Chou HC, Wu TL. Mandibulohyoid distance in difficult laryngoscopy. Br J Anaesth. 1993;71:335–
339.
22. Gupta S, Pareek S, Dulara SC. Comparison of two methods for predicting difficult intubation in
obstetric patients. Middle East J Anesthesiol. 2003;17:275–285.
23. Wilson ME, Spiegelhalter D, Robertson JA, et al. Predicting difficult intubation. Br J Anaesth.
1988;61:211–216.
24. Murphy MF, Walls RM. The difficult and failed airway. In: Walls RA, ed. Manual of Emergency
Airway Management. Philadelphia, PA: Lippincott Williams & Wilkins; 2000:31–39.
25. Morgan BM, Magni V, Goroszenuik T. Anaesthesia for emergency caesarean section. Br J Obstet
Gynaecol. 1990;97: 420–424.
26. Langeron O, Masso E, Huraux C, et al. Prediction of difficult mask ventilation. Anesthesiology.
2000;92:1229–1236.
27. Felton E, Suresh M, Wali A. Survey questionnaire: difficult airway management during emergent
cesarean section and availability of difficult airway equipment in the labor and delivery suite: a
comparison between academic and private practice hospitals. Anesthesiology. 2005;103:A583.
28. Shiga T, Wajima Z, Inoue T, et al. Predicting difficult intubation in apparently normal patients: a meta-
analysis of bedside screening test performance. Anesthesiology. 2005;103:429–437.
29. Kheterpal S, Han R, Tremper KK, et al. Incidence and predictors of difficult and impossible mask
ventilation. Anesthesiology. 2006;105:885–891.
30. Pathi A, Esen U, Hildreth A. A comparison of complications of pregnancy and delivery in morbidly
obese and non-obese women. J Obstet Gynaecol. 2006;26:527–530.
31. Saravanakumar K, Rao SG, Cooper GM. The challenges of obesity and obstetric anaesthesia. Curr
Opin Obstet Gynecol. 2006;18:631–635.
32. Hood DD, Dewan DM. Anesthetic and obstetric outcome in morbidly obese parturients.
Anesthesiology. 1993;79:1210–1218.
33. Adams JP, Murphy PG. Obesity in anaesthesia and intensive care. Br J Anaesth. 2000;85:91–108.
34. Endler GC, Mariona FG, Sokol RJ, et al. Anesthesia-related maternal mortality in Michigan: 1972 to
1984. Am J Obstet Gynecol. 1988;159:187–193.
35. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 315: obesity in
pregnancy. Obstet Gynecol. 2005;106:671–675.
36. Brodsky JB, Lemmens HJ, Brock-Utne JG, et al. Anesthetic considerations for bariatric surgery:
proper positioning is important for laryngoscopy. Anesth Analg. 2003;96:1841–1842.
37. Hawkins JL. Anesthesia-related maternal mortality. Clin Obstet Gynecol. 2003;46:679–687.
38. Awan R, Nolan JP, Cook TM. Use of a ProSeal laryngeal mask airway for airway maintenance during
emergency caesarean section after failed tracheal intubation. Br J Anaesth. 2004;92:144–146.
39. Morgan PJ, Pittini R, Regehr G, et al. Evaluating teamwork in a simulated obstetric environment.
Anesthesiology. 2007;106:907–915.
40. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 104:
anesthesia for emergency deliveries. Int J Gynaecol Obstet. 1992;39:148.
41. Gaiser RR, McGonigal ET, Litts P, et al. Obstetricians’ ability to assess the airway. Obstet Gynecol.
1999;93:648–652.
42. Wong CA. Epidural and spinal analgesia/anesthesia for labor and vaginal delivery. In: Chestnut DH,
ed. Chestnut’s Obstetric Anesthesia Principles and Practice. 4th ed. Philadelphia, PA: Mosby Elsevier;
2009:429.
43. Bloom SL, Spong CY, Weiner SJ, et al. Complications of anesthesia for cesarean delivery. Obstet
Gynecol. 2005;106:281–287.
44. Dadarkar P, Philip J, Weidner C, et al. Spinal anesthesia for cesarean section following inadequate
labor epidural analgesia: a retrospective audit. Int J Obstet Anesth. 2004;13:239–243.
45. Portnoy D, Vadhera RB. Mechanisms and management of an incomplete epidural block for cesarean
section. Anesthesiol Clin North America. 2003;21:39–57.
46. Wheeler M, Ovassapian A. Fiberoptic endoscopy-aided techniques. In: Hagberg C, ed. Benumof’s
Airway Management. 2nd ed. Philadelphia, PA: Mosby Elsevier; 2007:399–438.
47. Ovassapian A, Krejcie TC, Yelich SJ, et al. Awake fibreoptic intubation in the patient at high risk of
aspiration. Br J Anaesth. 1989;62:13–16.
48. Trevisan P. Fibre-optic awake intubation for caesarean section in a parturient with predicted difficult
airway. Minerva Anesthesiol. 2002;68:775–781.
49. Doyle DJ. Awake intubation using the Glidescope video laryngoscope: initial experience in four cases.
Can J Anaesth. 2004;51:520–521.
50. Jakushenko N, Kopeika U, Nagobade D, et al. Comparison of awake endotracheal intubation with
GlideScope videolaryngoscope and fibreoptic bronchoscope in patients with difficult airway. Eur J
Anaesth. 2010;27:264.
51. Suresh MS, Wali A, Crosby ET. Difficult and failed intubation: strategies, prevention and management
of airway-related catastrophes in obstetrical patients. In: Suresh MS, Segal BS, Preston RL, et al., eds.
Shnider and Levison’s Anesthesia for Obstetrics. 5th ed. Philadelphia, PA: Lippincott Williams &
 Wilkins; 2013:363–403.
52. Kilicaslan A, Topal A, Tavlan A, et al. Effectiveness of the C-MAC video laryngoscope in the
management of unexpected failed intubations. Braz J Anesthesiol. 2014;64:62–65.
53. Dhonneur G, Ndoko S, Amathieu R, et al. Tracheal intubation using the Airtraq in morbid obese
patients undergoing emergency cesarean delivery. Anesthesiology. 2007;106:629–630.
54. Han TH, Brimacombe J, Lee EJ, et al. The laryngeal mask airway is effective (and probably safe) in
selected healthy parturients for elective cesarean section: a prospective study of 1067 cases. Can J
Anaesth. 2001;48:1117–1121.
55. Cook TM, Brooks TS, Van der Westhuizen J, et al. The ProSeal LMA is a useful rescue device during
failed rapid sequence intubation: two additional cases. Can J Anaesth. 2005;52:630–633.
56. Keller C, Brimacombe J, Lirk P, et al. Failed obstetric tracheal intubation and postoperative respiratory
support with the ProSeal laryngeal mask airway. Anesth Analg. 2004;98:1467–1470.
57. Sharma B, Sahai C, Sood J, et al. The ProSeal laryngeal mask airway in two failed obstetric tracheal
intubation scenarios. Int J Obstet Anesth. 2006;15:338–339.
58. Brown NI, Mack PF, Mitera DM, et al. Use of the ProSeal laryngeal mask airway in a pregnant patient
with a difficult airway during electroconvulsive therapy. Br J Anaesth. 2003;91:752–754.
59. González GG, Marenco de la Fuente ML, Cornejo MB. Fastrach mask to resolve a difficult airway
during emergency cesarean section [in Spanish]. Rev Esp Anestesiol Reanim. 2005;52:56–57.
60. Minville V, N’guyen L, Coustet B, et al. Difficult airway in obstetric using Ilma-Fastrach. Anesth
Analg. 2004;99:1873.
61. Wissler RN. The esophageal-tracheal combitube. Anesthesiol Rev. 1993;20:147–152.
62. Dorges V, Ocker H, Wenzel V, et al. The laryngeal tube: a new simple airway device. Anesth Analg.
2000;90:1220–1222.
63. Zand F, Amini A. Use of the laryngeal tube-S for airway management and prevention of aspiration
after a failed tracheal intubation in a parturient. Anesthesiology. 2005;102:481–483.
64. Lipman S, Cohen S, Einav S, et al. The Society for Obstetric Anesthesia and Perinatology consensus
statement on the management of cardiac arrest in pregnancy. Anesth Analg. 2014;118:1003–1016.
65. Wong DT, Prabhu AJ, Coloma M, et al. What is the minimum training required for successful
cricothyroidotomy?: a study in mannequins. Anesthesiology. 2003;98:349–353.
66. Vadodaria BS, Gandhi SD, McIndoe AK. Comparison of four different emergency airway access
equipment sets on a human patient simulator. Anaesthesia. 2004;59:73–79.
67. DeLaurier GA, Hawkins ML, Treat RC, et al. Acute airway management: role of cricothyroidotomy.
Am Surg. 1990;56: 12–15.
68. Brofeldt BT, Panacek EA, Richards JR. An easy cricothyrotomy approach: the rapid four-step
technique. Acad Emerg Med. 1996;3:1060–1063.
69. Morris A, Lockey D, Coats T. Fat necks: modification of a standard surgical airway protocol in the
pre-hospital environmental. Resuscitation. 1997;35:253–254.
70. Gambling DR, Shay DC. The mother of all breathing problems. J Clin Anesth. 2003;15:491–494.
71. Baker DP, Day R, Salas E. Teamwork as an essential component of high-reliability organizations.
Health Serv Res. 2006;41:1576–1598.
 Anesthesia for Multiple Gestation and Breech
Presentation
Carolyn F. Weiniger

ANESTHESIA FOR MULTIPLE GESTATION
I. Introduction
II. National Guidelines
A. Practice guidelines for obstetric anesthesia: an updated report
by the American Society of Anesthesiologists Task Force on
Obstetric Anesthesia
B. American College of Obstetricians and Gynecologists 2014
Practice Bulletin 144: multiple gestation—complicated twin,
triplet, and high-order multifetal pregnancy
C. American College of Obstetricians and Gynecologists 2013
Committee Opinion 560: medically indicated late-preterm and
early-term deliveries
D. American College of Obstetricians and Gynecologists 2013
Committee Opinion 573: magnesium sulfate use in obstetrics
III. Maternal adaptation to multiple gestation pregnancy
A. Cardiovascular system
B. Respiratory system
C. Central nervous system
D. Hematologic changes
IV. Obstetric conditions and concerns for multiple gestation pregnancy
A. Preeclampsia
 B. Maternal hemorrhage
C. Fetal surgery
D. Maternal morbidity
E. Other concerns
V. Timing of delivery for multiple gestation pregnancy
A. Overview
B. Medically indicated delivery timing
C. Preventing multiple gestation preterm birth
VI. Preterm birth in multiple gestation pregnancy
A. Predicting preterm birth
B. Interventions to prevent preterm birth
C. Pharmacologic therapies to prevent preterm birth
D. Anesthesia for multiple gestation preterm birth
VII. Delivery route for multiple gestation pregnancy
A. Overview
B. Delivery route
C. Cephalic-cephalic presenting twins
D. Cephalic-noncephalic presenting twins
VIII. Anesthesia for vaginal delivery in multiple gestation pregnancy
A. Labor patterns
B. Unplanned operative delivery
IX. Anesthesia for cesarean delivery in multiple gestation pregnancy
A. Cesarean delivery
B. Unplanned cesarean delivery
X. Pharmacologic therapies for multiple gestation pregnancy
A. Corticosteroids
B. Magnesium sulfate
XI. Costs of multiple gestation pregnancy

ANESTHESIA FOR BREECH PRESENTATION
I. Introduction
II. American College of Obstetricians and Gynecologists Committee
 Opinion 2006: breech presentation management
III. Historical perspective for breech presentation management
IV. Demographics for breech presentation
A. Incidence
B. Risk factors
V. Obstetric management for breech presentation
A. Historical perspective
B. Vaginal breech delivery
C. Anesthesia for vaginal breech delivery
D. Uterine relaxation for vaginal breech delivery
VI. Complications of vaginal breech delivery
A. Preterm breech delivery
B. Umbilical cord prolapse
C. Fetal head entrapment
D. Anesthesia for fetal head entrapment
E. Emergent cesarean delivery (Zavanelli maneuver)
F. Emergent anesthesia for breech cesarean delivery
VII. Cesarean delivery for breech presentation
A. Overview
B. Anesthesia for planned breech cesarean delivery
C. Risks
D. Anesthesia for urgent cesarean delivery
VIII. External cephalic version for breech presentation
A. Overview
B. Maternal and fetal indications for external cephalic version
C. Utilization of external cephalic version
D. Success of external cephalic version
E. Risks of external cephalic version
IX. Labor following external cephalic version
A. Successful vaginal delivery
B. Neonatal outcomes following external cephalic version
C. Labor augmentation
 X. Anesthesia for external cephalic version in breech presentation
A. Overview
B. Anesthesia and external cephalic version success
C. Conversion of neuraxial technique for subsequent use
D. Emergency preparations
XI. Costs for external cephalic version
XII. Neonatal resuscitation in breech presentation delivery

KEYPOINTS
1. Multiple gestation pregnancies have become considerably more frequent
in past decades, although the twin pregnancy rate appears to have peaked,
and non-twin multiple gestations are decreasing. Multiple gestation
delivery is high risk, associated with cesarean delivery (CD), preterm
birth, and an increased incidence of concurrent medical and obstetric
conditions, such as preeclampsia.
2. Postpartum hemorrhage should be anticipated due to the distended uterus
in multiple gestation pregnancy. Protocols can guide management of this
potentially life-threatening disaster.
3. The majority of twin pregnancies will deliver before 37 weeks. Multiple
gestation is associated with an increased incidence of fetal
malpresentation and congenital anomalies. These factors may impact
delivery route choice.
4. Perinatal mortality is significantly increased following vaginal breech
delivery, and CD is the prevalent delivery mode for breech presentation.
5. Women should be offered external cephalic version (ECV) if possible,
and anesthesia may increase the success of ECV, in turn enabling vaginal
delivery.

ANESTHESIA FOR MULTIPLE GESTATION

 I. Introduction
Multiple gestation delivery is high risk, and is associated with
cesarean delivery (CD), preterm birth, and obstetric conditions such
as preeclampsia.1,2 Multiple gestation pregnancy is associated with
higher maternal age and assisted reproductive techniques. Although in
past decades multiple gestation pregnancies have become more
frequent,3 the twin pregnancy rate appears to have peaked and rates of
non-twin multiple gestations are decreasing (see Fig. 15.1).4 In 2012,
twins comprised 33.1 per 100,000 pregnancies, but the triplet birth
rate decreased to a reported 124.4 per 1,000 births. Decreases were
also observed with quintuplet or higher order births in the United
States during that year.5 Most multiple gestation pregnancies are twin
gestations and mothers are usually older, with associated
comorbidities such as hypertension and anemia.6

CLINICAL PEARL Multiple gestation delivery is high risk,

associated with CD, preterm birth, and obstetric conditions such as
preeclampsia.

II. National Guidelines

These U.S. guidelines present practice recommendations related to
current evidence for multiple gestation, anesthetic management, and
pharmacologic therapies. The pertinent topics in these guidelines are
summarized and further expanded throughout this chapter.
A. Practice guidelines for obstetric anesthesia: an updated report
by the American Society of Anesthesiologists Task Force on
Obstetric Anesthesia.7 These American Society of
Anesthesiologists (ASA) 2007 guidelines, updated from 1998,
refer to management of anesthesia for multiple gestation
pregnancy labor and delivery.
1. Platelet count. Maternal anesthetic complications, such as
neuraxial hematoma, may be reduced by checking a platelet
count prior to placement of epidural anesthesia in patients
with preeclampsia. A routine platelet count will not reduce
complications associated with neuraxial block placement.
However, a low platelet count seen in hemolysis, elevated
liver enzymes, low platelets (HELLP) syndrome, a variant of
preeclampsia, is more common in multiple gestation
pregnancies.
2. Early epidural placement. This is recommended for multiple
gestation and for preeclampsia. The potential for CD and to
avoid unplanned general anesthesia are the reasons behind
this plan. Placement of labor epidural catheters should be
encouraged before labor or in early labor.
B. American College of Obstetricians and Gynecologists 2014
Practice Bulletin 144: multiple gestation—complicated twin,
triplet, and high-order multifetal pregnancy.8 This 2014
American College of Obstetricians and Gynecologists (ACOG)
Practice Bulletin, updated from 2004, acknowledges a rise in
multiple gestation pregnancies. The increase is attributed to
advanced maternal age (associated with spontaneous multiple
gestation pregnancy) and assisted reproductive technology.
C. American College of Obstetricians and Gynecologists 2013
Committee Opinion 560: medically indicated late-preterm
and early-term deliveries.9 This document summarizes
 recommended delivery timing for twin pregnancies, dependent on
concurrent obstetric conditions (see Section V.B. in the following
text).
D. American College of Obstetricians and Gynecologists 2013
Committee Opinion 573: magnesium sulfate use in
obstetrics10
1. Magnesium administration for fetal neuroprotection is
indicated if delivery is anticipated before 32 weeks gestational
age.
2. Women may receive magnesium sulfate for up to 48 hours
during the period of antenatal corticosteroid administration, if
they are between 24 and 34 weeks’ gestation and at risk for
preterm delivery within 7 days.
III. Maternal adaptation to multiple gestation pregnancy
The wide-ranging maternal physiologic adaptations of pregnancy are
presented in Chapter 1. Multiple gestation pregnancy exaggerates
many of these changes, with implications for anesthetic management
and maternal safety (see Table 15.1).

A. Cardiovascular system
Many of the cardiovascular changes associated with singleton
pregnancy have been described in the past decade using
echocardiography. Cardiac output increases with gestational age
 along with stroke volume; these changes are more dramatic than
with singleton pregnancy. Cardiac output is 20% greater—a
consequence of exaggerated responses of stroke volume and heart
rate.11 Preload is further increased above singleton pregnancy
after 20 weeks. Aortocaval compression, seen from 20 weeks in
singleton pregnancy, is exaggerated in twin pregnancy and may
present earlier.12,13 Preeclampsia is more common in multiple
gestations pregnancies.11,14 Gestational hypertension presenting
during twin pregnancy progresses more frequently to
preeclampsia than in singleton pregnancy.15
B. Respiratory system
The greater abdominal size with multiple gestation pregnancies
compounds respiratory changes and may cause dyspnea.16
However, respiratory function does not appear to differ markedly
compared to singleton pregnancies.17 Nevertheless, the enlarged
abdomen and elevated serum progesterone levels may impact
respiration in multiple gestation pregnancy.18
C. Central nervous system
The mechanism for enhanced effect of spinal drug in multiple
gestation pregnancy may be related to aortocaval compression.12
Spinal anesthesia drug spread is greater compared to singleton
pregnancy and is reportedly two dermatomes higher. Another
explanation relates to higher cerebrospinal fluid progesterone
levels that contribute to a neural sensitizing effect with lower
doses achieving a denser block.19 Hemodynamic instability after
spinal anesthesia is not greater in multiple gestation pregnancies,
as expressed by vasopressor requirements during CD.20 Spinal
anesthesia has been reported to be safe in triplet21 and quadruplet
pregnancies.22
D. Hematologic changes
Blood volumes increase more in twin pregnancy compared with
singletons.23 Morbidity and mortality are increased in multiple
gestation pregnancy and in an advanced age population.24 Aside
from thrombocytopenia associated with HELLP syndrome,
 multiple gestation pregnancies frequently feature gestational
thrombocytopenia. Morikawa et al.25 reported a count below
100,000 in 43% of triplet pregnancies compared with 4.3% for
twin pregnancy. Triplet pregnancies are associated with further
increased risk for HELLP and acute fatty liver disease compared
with twin pregnancies. Regarding platelet counts that may impact
neuraxial anesthesia, 3.2% of women carrying triplets had platelet
counts <70,000 per mcL,26 and thrombocytopenia frequently
preceded the diagnosis of preeclampsia.
IV. Obstetric conditions and concerns for multiple gestation
pregnancy
Complications of multiple gestation pregnancy are listed in Table
15.2.

A. Preeclampsia
Hypertension is more frequent in twin pregnancy than singletons.
In a perinatal database case-control study from 1982 to 1987, the
likelihood of hypertension was 2.5 times higher among 1,253
twin versus 5,119 singleton pregnancies (odds ratio [OR], 2.5;
95% confidence interval [CI], 2.1 to 3.1).6 Preeclampsia may be
more prevalent in multiple gestation pregnancies. Foo et al.15
reported that multiple gestation pregnancies with de novo
hypertensive disorders were more likely to progress to
preeclampsia than singletons (24 per 70 [34%] vs. 279 per 1,881
[15%], P < .001). A similar finding was reported for progression
of chronic hypertension to preeclampsia in twins (53%) versus
singletons (18%), P < .01. The initial hypertensive-related
disorder diagnosed in twin pregnancies was more likely to be
 preeclampsia rather than gestational hypertension.
B. Maternal hemorrhage
1. Multiple gestation pregnancy has a greater blood loss (>900
mL)—similar to that seen in CD and double that seen
following singleton delivery.23 Placental abruption is three
times more likely among twin pregnancies compared with
singletons (OR, 3.0; 95% CI, 1.9 to 4.7) and the frequency is
more apparent after adjustment for maternal age and weight
gain (OR, 3.7; 95% CI, 2.6 to 3.5).6
2. The rate of postpartum hemorrhage (PPH) is doubled in
multiple gestation pregnancies and occurs in approximately
9% of deliveries, in part due to the increased abruption rate.27
The distended uterus may also become atonic. Independent
risk factors for PPH in twin pregnancies were reported in a 9-
year Japanese cohort. When the gestational age was >41
weeks, the risk of PPH was over 8 times more likely
compared to a singleton pregnancy. Hypertensive disorders
were over 5 times more likely to be associated with PPH.28
3. PPH protocols can guide management of this potentially life-
threatening event. PPH should be anticipated in multiple
gestation deliveries.29 Airway considerations, readily
available equipment (e.g., intravenous [IV] access, rapid
infusers, warming blankets), massive transfusion protocols,
uterotonics (e.g., oxytocin, Methergine, misoprostol, and
Hemabate), and regular protocol drills are all important.30,31

CLINICAL PEARL Many centers use strategies such as massive

transfusion protocols (MTPs) to efficiently manage transfusion for
PPH. Practice drills may improve the implementation of these
MTPs and other institution-specific strategies. Visual aids placed in
the labor and delivery suites may act as reminders for the PPH
algorithm when massive hemorrhage occurs.
 C. Fetal surgery. Monochorionic twins comprise 20% of twin
pregnancies,32 and up to 20% of these will develop twin-to-twin
transfusion syndrome (TTTS). Recent advances in management
of TTTS make it likely that fetoscopic laser therapy may be
performed. One potential maternal complication of TTTS is
“mirror syndrome” causing maternal hydrops with edema,
oliguria, and hemodilution.33 Mirror syndrome may be mistaken
for preeclampsia, but the presence of fetal hydrops may direct the
diagnosis. Management of the mother with mirror syndrome
includes consideration of her volume status, cardiovascular
function, and use of appropriate hemodynamic monitoring;
neuraxial anesthesia is a suitable option. However, general
anesthesia may be necessary and airway edema may increase the
risk of difficult airway management.34 Traditionally, fetal surgery
for TTTS was performed 17 to 26 weeks’ gestation. However,
recent data suggest that fetoscopic surgery may be performed in
the third trimester, with good fetal survival and rates of maternal
complications (e.g., intensive care unit [ICU] admission,
pulmonary edema, mirror syndrome, hemorrhage requiring
transfusion) similar to earlier procedures.35 Maternal outcomes
for fetal surgery are not widely reported. Among 53 fetal
procedures performed for cardiac indications, 1 unrelated PPH
occurred. However, maternal morbidity (e.g., anesthesia
complications such as aspiration, anaphylaxis, cardiovascular
complications, airway injuries, awareness, or hypoxic injury) was
absent.36 Fetal reduction may be performed early in pregnancy to
reduce the incidence of preterm birth. Fetal reduction may also
attenuate obstetric-related conditions, such as gestational
hypertension.37

CLINICAL PEARL Fetal surgery is not performed at all

institutions. However, because more centers are introducing fetal
surgery, special training and multidisciplinary protocols may be
 required for institution-specific anesthetic strategies.

D. Maternal morbidity. There is an increased incidence of

concurrent medical and obstetric conditions. Anemia,
hemorrhage, hypertension, and preeclampsia are more common in
multiple gestation pregnancies. The precipitous rise in multiple
gestation pregnancy, in particular among women of advanced
age,23 contributes to the recent observation of rising maternal
mortality. Multiple gestation pregnancies are associated with a
mortality risk ratio of 3.6 (95% CI, 3.1 to 4.1) compared to
singleton pregnancies.38 Specific conditions such as
thromboembolism, hemorrhage, and hypertensive disease are
associated with multiple gestation pregnancy.39 African American
twin and high-order multiple pregnancies have a higher incidence
of death compared to whites.39

CLINICAL PEARL Multiple gestation pregnancies and

associated maternal morbidities are contributing to the rising rate of
maternal mortality. Women with multiple gestation pregnancy
should be closely monitored and cared for by a multidisciplinary
team, and morbidities should be anticipated.

E. Other concerns. Multiple gestation pregnancy is more likely than

singleton pregnancy to be delivered by CD. Multiple gestation
may be associated with postpartum depression.
V. Timing of delivery for multiple gestation pregnancy
A. Overview
Multiple gestation pregnancies are associated with maternal
morbidity, neonatal morbidity, and prematurity, all of which may
be difficult to prevent. Multiple gestation pregnancies deliver
earlier than singletons, and twin gestation pregnancy lasts, on
average, 35 weeks.40 Birth weights are smaller for twin
 pregnancies6 and one study suggests better outcomes when
elective twin delivery is performed at 37 weeks rather than
expectant care (from 38 weeks to later).41 The majority of twin
pregnancies will deliver before 37 weeks. Among 138,660 twin
births reported in one survey, almost 60% were delivered before
the 37th week.40
B. Medically indicated delivery timing. Uncomplicated
dichorionic-diamniotic twins can be delivered at 37 to 38 weeks’
gestation.42 ACOG recommends delivery in the 38th week in
uncomplicated dichorionic-diamniotic twin pregnancy.9 Earlier
delivery has been recommended for monochorionic-diamniotic
twins (34 to 37 weeks)9,42 and many US practitioners deliver
monoamniotic-monochorionic twins by 34 weeks because of the
risk of perinatal morbidity and mortality.43
C. Preventing multiple gestation preterm birth. There are no
currently effective treatments to avoid preterm delivery in
multiple gestations pregnancies. 17-α hydroxyprogesterone
caproate44 and vaginal progesterone45 do not prevent preterm
twin birth. Cerclage may be harmful.46
VI. Preterm birth in multiple gestation pregnancy
A. Predicting preterm birth. Cervical length, fetal fibronectin,
home uterine monitoring, and digital examination are modalities
used to predict preterm birth. However, these modalities are not
recommended for asymptomatic multiple gestation because they
do not prevent spontaneous preterm birth. Even for symptomatic
multiple gestation, their use is not exclusively recommended.
B. Interventions to prevent preterm birth, such as cerclage,
bedrest, and prophylactic tocolytics, are not recommended in
multiple gestation because they fail to prevent preterm birth. 17α-
Hydroxyprogesterone caproate may increase multiple gestation
midtrimester fetal loss and is not associated with reductions in
maternal morbidity.
C. Pharmacologic therapies to prevent preterm birth may be
 combined with corticosteroids.
1. Corticosteroids may not be beneficial in multiple gestation
pregnancies at risk for preterm birth. Expert opinion
recommends the administration of a single course of
corticosteroid between 24 and 34 weeks’ gestation in
singleton pregnancies, when the pregnancy is at risk for
preterm delivery within 7 days.47
2. Tocolytics to prevent uterine contractions (β-agonists such as
ritodrine, terbutaline, or calcium channel blockers) may cause
maternal tachycardia, hypotension, and electrolyte
abnormalities, such as hyperglycemia and hyperkalemia.
Combination therapies may be used despite a paucity of
evidence for maternal or neonatal advantage.48 Pulmonary
edema may result from tocolytic therapy. One therapy to
consider is epidural anesthesia to relieve cardiac efforts
associated with this condition.49
3. Magnesium therapy. Recent evidence from preeclampsia
studies showed magnesium sulfate therapy generates a fetal
neuroprotective effect for preterm birth up to 32 weeks.47
Magnesium has not been proven to be as beneficial as it has
for singleton pregnancies; however, its use is recommended
for multiple gestation pregnancies. Magnesium sulfate
administration for up to 48 hours prior to preterm labor may
have maternal consequences. Although there were no serious
maternal adverse effects (e.g., death, cardiac arrest,
respiratory arrest) reported in the IRIS trial, arm discomfort
and warmth over the body were reported in over two-thirds of
the women receiving magnesium for fetal neuroprotection in
the first hour regardless of the loading time (20 minutes vs. 1
hour).50 The use of magnesium for neonatal neuroprotection
or seizure prophylaxis can prolong maternal neuromuscular
blockade.
D. Anesthesia for multiple gestation preterm birth. CD is more
likely in preterm delivery of multiple gestation. Anesthesia modes
 for preterm birth delivery are not frequently reported but
neuraxial techniques are most frequently employed in most
centers. Epidural analgesia can optimize vaginal delivery
conditions for the premature neonate, moderated through pelvic
floor relaxation, which may reduce maternal expulsive efforts.51
VII. Delivery route for multiple gestation pregnancy
A. Overview. The decision for twin delivery route is based on fetal
lie, ability to monitor the fetus through labor, and maternal–fetal
well-being, according to the ACOG Practice Bulletin.8 Multiple
gestation is associated with an increased incidence of fetal
malpresentation and congenital anomalies. These conditions may
impact delivery choice.52
B. Delivery route. Vaginal birth is suitable for vertex-presenting
twin pregnancy. Non-twin multiple gestation pregnancies will be
delivered by CD. Monoamniotic twins are often delivered by CD
because of the risk of perinatal mortality.
C. Cephalic-cephalic presenting twins have the best chance of
vaginal delivery (and comprise 40% of twin deliveries).53 The
likelihood of CD is 6.3%; the likelihood of operative vaginal
delivery is 8.3% following successful cephalic primary twin
delivery.54 CD may be the necessary delivery option for the
second twin in an emergency, for example, fetal distress and cord
prolapse.54 Neonatal morbidity for the second twin is highest
after failed vaginal delivery. If it is likely that the second twin will
fail to delivery vaginally, CD for both twins is the best delivery
route.55
D. Cephalic-noncephalic presenting twin have a high chance of
successful vaginal delivery after version of the noncephalic
second twin, although the most likely reason for CD is
malpresentation.56 A randomized controlled trial (RCT) of
vaginal versus planned CD for 2,800 twin gestations (vertex-
presenting twin), between 32 and 38 weeks’ gestation,
demonstrated similar outcomes for severe maternal and neonatal
 morbidity, regardless of delivery mode.57 The incidence of the
primary outcome (i.e., a neonatal morbidity composite) was
similar for planned CD versus vaginal delivery (2.2% vs. 1.9%,
respectively; OR, 1.16; 95% CI, 0.77 to 1.74), thus supporting the
practice of vaginal delivery for twin pregnancies with cephalic-
presenting fetus.
VIII. Anesthesia for vaginal delivery in multiple gestation pregnancy
A. Labor patterns are prolonged compared with singletons,58 and
epidural use for twin delivery may improve maternal relaxation to
avoid premature pushing, enable breech extraction, and can be
extended if operative vaginal or CD is required.51
B. Unplanned operative delivery. Due to the potential for
unplanned operative delivery in twins attempting vaginal
delivery, there is debate surrounding the optimal location for twin
delivery. Limited resources and logistics may limit the routine
availability for an operating room for vaginal twin delivery. On
the other hand, need for rapid delivery conditions may make
operating room delivery safer. In addition, the mandatory
presence of the anesthesia provider during twin delivery may be
beneficial to ensure adequate labor analgesic levels, uterine
relaxation for fetal manipulation such as internal podalic version,
or provide rapid surgical anesthesia.51 Carvalho et al.51 surveyed
California hospitals regarding practice for twin delivery and there
was no consensus: 64% perform vaginal twin delivery in the
operating room, 55% provide an anesthesiologist during the
delivery, and a strong association exists between these two
factors. Conversely, there was no association between hospital
characteristics (type, location, delivery rate) and the delivery
location.

CLINICAL PEARL There is no specific recommendation that

twins should be delivered in the operating suite or that anesthesia
providers should be present at the delivery. For anesthesia personnel
 attending a twin delivery, preparations for emergency transfer to the
operating room and emergency CD considerations may be required.
Although there is a valid argument supporting vaginal twin delivery
in the operating room, there may be logistic limitations such as
operating room availability.

IX. Anesthesia for cesarean delivery in multiple gestation pregnancy

A. Cesarean delivery for multiple gestation is frequently performed.
In a study of 12 Finnish delivery units, multiple gestation was the
cause of up to 80% of CD.59 Based on current guidelines from the
ASA, a neuraxial anesthesia technique is the recommended route
for women undergoing CD.60 Rates of anesthesia-related maternal
morbidity have decreased, concurrent with a rise in neuraxial
anesthesia use for CD.61,62 Left lateral tilt should be used as in all
pregnancies because aortocaval compression following neuraxial
anesthesia is more exaggerated in multiple gestation pregnancy.18
B. Unplanned cesarean delivery (vertex second twin) may be
associated with emergency indications, such as cord prolapse and
fetal bradycardia, both necessitating rapid surgical intervention.54
CD is preferentially chosen over vaginal operative delivery for a
second vertex twin delivery in cephalopelvic disproportion, fetal
bradycardia, and cord prolapse. Ideally, an epidural catheter
placed for twin delivery can be extended to provide suitable and
timely surgical conditions. However, epidural failure or urgent
surgery may necessitate general anesthesia.63,64 Complications
from general anesthesia, such as aspiration and airway
management disasters, can be avoided by using a neuraxial
technique.65

CLINICAL PEARL CD is preferentially chosen over vaginal

operative delivery for second vertex twin delivery in cephalopelvic
disproportion, fetal bradycardia, and cord prolapse.
 X. Pharmacologic therapies for multiple gestation pregnancy
A. Corticosteroids. Unless there are contraindications, multiple
gestation pregnancies should receive antenatal corticosteroids,
especially when there is risk of delivery, such as following
premature rupture of membranes <32 weeks’ gestation. Lung
maturity may occur earlier in twin pregnancies—around 32
weeks.66
B. Magnesium sulfate. This has been shown to reduce the incidence
of cerebral palsy in preterm birth. The risk of cerebral palsy
increases from 1.6 per 1,000 live births for singleton pregnancy to
7 per 1,000 for twins and 28 per 1,000 for triplets.
XI. Costs of multiple gestation pregnancy. Higher associated delivery
costs related to multiple gestation are primarily related to premature
birth.

ANESTHESIA FOR BREECH PRESENTATION

I. Introduction
Breech presentation accounts for 3% to 5% of term singleton
pregnancies.67,68 Over the past two decades, the safest delivery route
for the neonate is CD for the breech-presenting fetus. This is due to
reports of associated increased maternal and neonatal morbidity
following vaginal breech delivery. However, for the mother, vaginal
vertex delivery is the safest route.
Anesthesia may be used to moderate the risks of delivery of a
breech-presenting fetus and may also enable a reduction in the
incidence of breech presentation at term via external cephalic version
(ECV) to convert to a vertex presentation.
II. American College of Obstetricians and Gynecologists Committee
Opinion 2006: breech presentation management69
A. Perinatal mortality is significantly increased following vaginal
breech delivery.
B. Women should be offered ECV if possible.
 C. Women should be informed of the risks associated with vaginal
breech delivery.
D. Suitable hospitals with guidelines for management of vaginal
breech delivery may elect to perform planned vaginal breech
delivery.
III. Historical perspective for breech presentation management
In the early to mid-1900s, the neonatal mortality during breech
presentation delivery was reportedly 10%.70 ECV to convert the fetus
to cephalic presentation was one option used to address this problem.
By the 1960s, although vaginal breech delivery was still performed,
the increasingly acceptable alternative became CD. Toward the end of
the last millennium, a further shift away from vaginal breech delivery
occurred, as highlighted by the Term Breech Trial in 2000 and
subsequent ACOG guidelines in 2001 that almost contraindicated
vaginal breech delivery.71,72 A backlash ensued, supporting vaginal
breech delivery as a viable option.73 In 2006, ACOG revised their
Committee Opinion to support vaginal breech delivery in suitable
circumstances.69 Due to lack of skilled operators, vaginal breech
delivery is reserved for special cases in the United States. However, in
Europe, it is a more accepted technique.74 ACOG recommended ECV
as routine therapy for the breech-presenting fetus.
IV. Demographics for breech presentation
A. Incidence
1. The incidence of term breech presentation is approximately
3–5% of all term deliveries.
2. At 28 weeks, 24.4% of singleton pregnancies are breech
presenting.68
3. Malpresentation is suggested clinically if the fetal head is not
in the pelvis, although the definitive diagnosis is made by
ultrasound.75
4. Frank, complete, or footling breech presentation describe the
breech position in utero; each is defined according to the
relationship between the buttocks and the legs in the maternal
 pelvis (see Fig. 15.2). Frank breech presentation has the lower
extremities flexed at the hips, but extended at the knees, so
the feet lie up with the head. A complete breech presentation
has at least one or both knees flexed. An incomplete breech
presentation is where one or both hips are not flexed and one
or both feet or knees lie below the breech, and will be the
lowest presenting part. For example, a footling breech is an
incomplete breech with one or both feet below the breech.76
Incomplete breech has the highest risk of umbilical cord
prolapse.

B. Risk factors. A number of maternal conditions are associated

with breech presentation, predominantly multiple gestation and
grandmultiparity.77 Among singleton births, nulliparity, uterine
abnormality, advanced maternal age, maternal diabetes, smoking
during pregnancy, and late or no prenatal care are associated with
breech presentation. Neonatal characteristics associated with
breech presentation include low birth weight, hydrocephalus, and
congenital malformations (see Table 15.3).67,77
 V. Obstetric management for breech presentation
A. Historical perspective
1. Vaginal breech presentation delivery was associated with a
high mortality rate (10%), yet nevertheless, was the usual
delivery mode for breech presentation. Only 10% of breech
deliveries were performed by CD in 195678 with a small
increase to 11.6% by 1970. By 1999, CD was performed for
84.5% of breech presentations in the United States.72
2. In the past 20 years, neonatal safety concerns have motivated
almost routine use of CD for breech presentation.69 Recent
data report that malpresentation is responsible for almost one-
fifth of elective79 and primary80 CD. Many recent reviews and
studies lament this trend away from vaginal breech delivery.73
However, lack of skilled personnel to assist with vaginal
breech delivery makes it unlikely that this practice will
become more widespread.
3. ECV was described almost two millennia ago by Hippocrates
as a technique to facilitate vaginal cephalic presentation.
Subsequently, ECV was described in the 1950s to enable
vaginal cephalic delivery.70,81 However, reportedly high
complications of ECV in this era, lacking ultrasound and
other suitable fetal monitors, limited its usefulness. ECV is
currently an accepted technique to reduce term breech
presentation.69,75
B. Vaginal breech delivery
1. Vaginal breech delivery is not often performed. The rate of
vaginal breech delivery has declined over the past two
decades, spurred by a number of studies demonstrating
negative neonatal outcomes compared with CD.
2. Three extraction approaches for vaginal delivery of the
breech-presenting fetus may be encountered: (1) spontaneous
breech delivery, in which the mother expels the fetus without
any need for assistance; (2) partial breech extraction where
the fetus is spontaneously out to the umbilicus, at which point
 manipulations, such as traction, aid the maternal expulsive
efforts; (3) total breech extraction where manipulations and
maneuvers are used to extract the fetus from the uterus.

CLINICAL PEARL Emergency induction of general anesthesia

may be required at any stage during the fetal extraction.
Preparations for IV drug administration, maternal hemorrhage from
lacerations, or uterine atony should be considered prior to the
delivery.

3. Planned vaginal delivery is a suitable management strategy

for the term singleton fetus, within specific institutional
guidelines.
4. Most practitioners will justify CD for singleton breech
delivery based on anticipated neonatal morbidities. Table 15.4
outlines the indications for breech CD in singleton pregnancy.

5. Women should be informed of the risks of vaginal breech

delivery, particularly the increased neonatal morbidities in the
short-term versus elective-planned CD.
C. Anesthesia for vaginal breech delivery
1. Historically, labor epidural analgesia was performed with
caution because of theoretical risks of prolonged labor.82
2. There are potential benefits for the use of epidural analgesia
for breech labor.83,84 These include a decrease in maternal
expulsive efforts prior to full dilation, potentially reducing
 head entrapment and pelvic floor relaxation.
3. An epidural catheter can be used to rapidly extend the block
for unplanned CD.
4. Labor analgesia is not mentioned in the ACOG Committee
Opinion; however, vaginal breech delivery is considered a
strong indication for early epidural analgesia during labor.

CLINICAL PEARL Vaginal breech delivery is rarely performed

in many institutions. Most women who attempt to deliver a breech-
presenting fetus should receive early labor epidural analgesia.

D. Uterine relaxation for vaginal breech delivery

1. The obstetrician may request pelvic floor, cervical, or uterine
relaxation to facilitate delivery of the head. Nitroglycerin
(NTG) or inhaled anesthetic agents can be used to assist
uterine relaxation for breech delivery.
2. Anesthesia for breech extraction should provide sufficient
relaxation to allow intrauterine manipulations. Neuraxial
block may enable fetal manipulations; however, despite
administration of NTG and β-mimetic tocolytics, increased
uterine tone can hinder these efforts. General anesthesia with
a volatile agent may be necessary as an adjunct for uterine
relaxation in addition to analgesia.

CLINICAL PEARL Suitable agents for uterine relaxation should

be readily available in the labor suite when a vaginal breech
delivery is anticipated or planned. This can facilitate delivery of the
after-coming head. Anesthesia providers should be prepared to
administer general anesthesia if required.

VI. Complications of vaginal breech delivery (see Table 15.5)

 A. Preterm breech delivery is associated with increased peripartum
complications compared with preterm vertex presentation.75 It is
unclear whether vaginal breech delivery is associated with
increased complications in very low birth weight infants. CD is
the preferred mode of delivery for preterm breech presentation.
B. Umbilical cord prolapse is the most common life-threatening
complication of vaginal breech delivery, with an incidence of up
to 28.5%. Cord prolapse is particularly associated with footling or
incomplete breech, a small fetus, and multiparity.69,85 Umbilical
cord prolapse is considered an emergency situation where the
fetus is in danger of asphyxia, with a high mortality rate 38.5%.85
Rapid spinal anesthesia has been described in this setting, in a
patient with an anticipated difficult airway.86

CLINICAL PEARL Women presenting with umbilical cord

prolapse may require immediate CD under general anesthesia with a
rapid sequence induction technique. A suitable antenatal
assessment, however brief, must include consideration of
equipment for safe airway management.

C. Fetal head entrapment

1. As the head is extracted, the cervix may constrict the neck and
block the delivery of the fetal head. This is rare, but more
likely with a small preterm fetus and an incompletely dilated
cervix. This is an emergency situation because there may be
total umbilical cord compression. A number of obstetric
 management strategies may be employed in such cases of
fetal head entrapment or shoulder dystocia.
2. Dührssen incisions. These incisions enlarge the cervical
aperture; however, they may be technically challenging
because the fetus blocks the vagina. In addition, they may
cause hemorrhage that may be concealed in the vagina or
peritoneal cavity.
3. In order to relieve fetal head entrapment, the anesthesia
provider may be asked to facilitate uterine relaxation with IV
NTG—typically 100 µg. Sublingual NTG is another suitable
option (1–2 puffs)
4. NTG, a potent smooth muscle relaxant, may facilitate
extraction of a trapped head during vaginal breech delivery.
NTG may be used for extraction of retained placenta, internal
version of the nonvertex second twin, and extraction of twins
at CD complicated by a tight uterine contraction, and
facilitates extraction of an entrapped head during cesarean
breech delivery.
5. Doses of 50 to 100 µg of IV NTG provide rapid uterine
relaxation within 30 to 90 seconds. An IV bolus of up to 1 mg
has been described without evidence of significant maternal
hypotension87; however, hypotension can occur with smaller
doses, and vasopressor treatment should be readily available.
6. Cervical relaxation may be less readily managed with NTG
because the cervix comprises only 15% smooth muscle,
unlike the uterus.
D. Anesthesia for fetal head entrapment
1. Labor epidural analgesia can facilitate Dührssen incisions or
induce pelvic floor relaxation to increase the chance of
vaginal delivery.
2. Inhalation anesthetic agents may be required because they are
potent uterine relaxants.
E. Emergent cesarean delivery (Zavanelli maneuver)
1. This involves cephalic replacement by the obstetrician
 followed by immediate CD. In some published cases, there
were delays up to 75 minutes for performance of the CD.
2. Although Sandberg reviewed 103 published attempts at the
Zavanelli maneuver and demonstrated a remarkably high
success rate (92%), with relatively few complications, the
Zavanelli maneuver is considered to be a last resort
intervention.88
3. Major maternal and fetal morbidity have also been reported,
including cervical spine dislocation, clavicular and humeral
fracture, and anoxia in the fetus and uterine rupture in the
mother.88
F. Emergent anesthesia for breech cesarean delivery. The
anesthesia provider may need to provide emergent anesthesia for
the Zavanelli maneuver.
VII. Cesarean delivery for breech presentation
A. Overview. CD is associated with significant maternal morbidity
and mortality.89 There are also neonatal risks, such as fetal head
entrapment. The risk can be mitigated by using an extended
uterine incision, pharmacologic myometrial relaxation (NTG, 50
to 100 mg), or inhaled anesthetic agents.
B. Anesthesia for planned breech cesarean delivery. Neuraxial
anesthetic techniques are commonly used for CD for breech
presentation. Since the use of neuraxial anesthesia for CD has
increased, rates of anesthetic-related maternal morbidity have
decreased.61,62 Complications of general anesthesia, such as
aspiration and airway management disasters, can be avoided by
using a neuraxial technique.65 Avoiding general anesthesia is
beneficial to enable participation of the mother and her partner in
the delivery.
C. Risks
1. Several obstetric conditions associated with breech
presentation (e.g., polyhydramnios, uterine anomalies, etc.)
may increase the risk of PPH.
2. As with vaginal breech delivery, there is a higher incidence of
 neonatal depression and the need for resuscitation in the
breech CD.
3. Fetal head entrapment has been described during cesarean
breech delivery. As stated earlier, NTG has been successfully
used to relax the uterus and facilitate delivery.
D. Anesthesia for urgent cesarean delivery. Breech presentation
may be associated with unplanned CD in a number of situations:
Breech is associated with umbilical cord prolapse or footling
presentation. ECV may cause placental abruption or acute fetal
bradycardia; vaginal breech delivery is also associated with fetal
head entrapment. Immediate surgical delivery may be required,
and such situations may necessitate general anesthesia.
VIII. External cephalic version for breech presentation
A. Overview
1. ACOG suggests that ECV should be offered to all women
with breech presentation “wherever possible.”
2. ECV may be the only option for vaginal delivery in current
practice for women with breech presentation. Review and
guidelines since the 1990s and more recent ones recommend
ECV to decrease the incidence of breech presentation at
term.69,90,91 However, current data suggest that CD is the
routine delivery mode, despite guidelines recommending ECV
for all suitable women.69
3. ECV should be performed with “ready access” to facilities to
perform an emergency CD.
B. Maternal and fetal indications for external cephalic version. A
number of contraindications have been reported for ECV; none is
absolute. Prior CD, uterine anomaly, preeclampsia/hypertension,
cardiac disease, and fetal factors (growth restriction, abnormality
of cardiotocography, fetal macrosomia [>4 kg], fetal head
hyperextension, restrictive nuchal cord, and unstable lie) have all
been suggested as contraindications, but have not been
definitively associated with increased ECV risks.92,93 Reported
obstetric contraindications to ECV include ruptured membranes,
 antepartum bleeding, history of placental abruption from previous
pregnancies, restrictive nuchal cord, active labor, and
oligohydramnios.92
C. Utilization of external cephalic version. Women may prefer CD
over ECV, especially if ECV is considered painful or may fail.94
Educational strategies to increase knowledge regarding ECV and
the potential benefits, such as decreased likelihood of CD, may
increase ECV utilization,95 but are not routinely used.96 Women’s
preference for CD appears to be rising with declining rates of
ECV.97 Obstetricians may decline to inform women about ECV. A
diagnosis of breech presentation should be made early to enable
discussion of options; however, if no one explains the
considerations of ECV, women may not actively pursue this
option.95,98
D. Success of external cephalic version. Several reviews and
individual institutional reports have reported a wide range of
success rates with ECV, from 35% to 86%. Factors associated
with ECV failure are presented in Table 15.6. Higher rates of
ECV success are associated with (1) a palpable fetal head, (2)
nonengaged breech, (3) nonanterior placenta, and (4) amniotic
fluid index above 7 to 10 cm.99 ECV success rates are also higher
in multiparas and in women with BMI <65 kg.100–102 Uterine
relaxation can be achieved with adjuvant tocolytics and is
associated with increased ECV success rates.103

E. Risks of external cephalic version. ECV is generally safe for

 both mother and fetus, although serious complications have been
reported. Transient fetal bradycardia is the most common adverse
event associated with ECV, reported in up to 47% of cases and
occurs approximately 5.7% of the time. 99 Non-reassuring fetal
heart rate changes may necessitate emergent delivery in 0.35% to
1.1% of cases.99,104 Other reported complications include
placental abruption, fetomaternal transfusion, vaginal bleeding,
umbilical cord prolapse, fetal femur fracture, cervical cord
transaction, intracranial hemorrhage, and even fetal death.99,104

CLINICAL PEARL Although there is no specific

recommendation that ECV should be performed in the operating
room, some practitioners may prefer to perform ECV in the
operating room due to the potential for complications. ACOG
recommends that ECV should be performed in an area where
facilities for CD can be readily accessed. Some authorities
recommend that ECV be performed in the labor and delivery unit,
with an operating room available for emergency CD if required.
There are considerations such as fasting prior to the ECV
procedure, IV access, preparation for maternal hemorrhage,
anesthesia for emergent CD, and availability of anesthesia
personnel if needed. It is prudent to ensure suitable institutional
strategies for women undergoing ECV.

IX. Labor following external cephalic version

A. Successful vaginal delivery. Vaginal delivery rates following
ECV vary widely (35% to 100%).105–109 Following successful
ECV, the parturient appears to have associated increased risk for
labor complications and CD.106 The control group used for these
comparisons is usually singleton spontaneous labors.
B. Neonatal outcomes following external cephalic version.
Balayla et al.110 recently reported neonatal risks for ECV among
 183,323 singleton breech deliveries during the year 2006, 4.3% of
all births. These were compared according to ECV success, ECV
failure, and no ECV performed, using data from the “Birth Data
Files” of the National Center for Health Statistics (Centers for
Disease Control and Prevention). ECV was performed in 3.4% of
the singleton breech deliveries and was successful in 72.5%
(4,470 per 6,165) cases. In their regression analysis with
adjustment for potential confounders, failed ECV was associated
with abnormal fetal heart tracing, lower Apgar scores, and need
for ventilator support at birth compared with successful ECV and
no ECV. However, the authors suspect a high degree of
misclassification for the failed ECV group.
C. Labor augmentation. The need for labor augmentation and
instrumental vaginal delivery is also increased after ECV.
X. Anesthesia for external cephalic version in breech presentation
A. Overview
1. Pain is a major reason for women who decline ECV.
Anesthesia may provide analgesia, and through uterine
relaxation, increase ECV success rates.
2. In the 1940s and 1950s, general anesthesia with IV and
inhalational agents was used to increase ECV success rates, as
well as provide muscle relaxation. Maternal uterine atony and
placental abruption were common. During this period when
routine fetal monitors were not available, rates of fetal demise
approached 1.6%.
3. The feedback of pain when pressing on the uterus may guide
obstetricians to limit the downward force applied. Recent
investigations have suggested that the pressure applied is not
excessive during ECV with anesthesia.111
B. Anesthesia and external cephalic version success
1. Retrospective reviews have reported that epidural analgesia is
associated with improved success of ECV and can facilitate
successful ECV after an initial failed attempt.112
2. Six prospective RCTs, using neuraxial block for ECV,
 reported varying success rates.113–117 Lavoie et al.118
categorized these RCTs according to depth of anesthesia.
Anesthesia was associated with significantly increased
success rates for ECV, whether spinal or epidural. Spinal
anesthesia used 7.5 mg bupivacaine and epidural blockade
used 2% lidocaine to a sensory level of T6.113–116
3. Using lower dose of spinal analgesia was not associated with
increased ECV success rates; however, the pain scores were
improved in one study.117
4. To date, the use of neuraxial anesthesia has not been
associated with significant fetal complications.112
5. The optimum dose for neuraxial block in ECV has not yet
been identified. It may be prudent to consider a combined
spinal-epidural technique.

CLINICAL PEARL Combined spinal-epidural technique is

versatile for extension of anesthesia if required for CD or labor
epidural analgesia, if ECV is successful. In order to avoid the need
for intrathecal morphine in case of CD following the ECV attempt,
the epidural catheter can be used for cesarean anesthesia and
postoperative epidural morphine analgesia.

C. Conversion of neuraxial technique for subsequent use

1. Conversion for unplanned cesarean delivery. There are no
guidelines regarding the optimal location for performing ECV
under neuraxial blockade. Many units will perform neuraxial
anesthesia in the labor suite or in the operating room. ECV is
associated with an approximately 1% incidence of fetal
bradycardia requiring emergent delivery. A functioning
epidural can rapidly be extended to provide surgical
anesthesia.

CLINICAL PEARL ECV may be performed without anesthesia

 provider support or presence, and women may not be fasted.
Transfer of the patient to the operating room and availability of the
anesthesia provider are issues to consider in each individual
institution.

2. If vaginal delivery is to follow immediately following

successful ECV, an indwelling epidural catheter can be used
to provide labor analgesia.
D. Emergency preparations
1. Ensure the patient is fasting.
2. Women undergoing ECV should be evaluated by an
anesthesia provider, even if neuraxial anesthesia is not
performed.
3. Following ECV the anesthesiologist must be prepared to
administer anesthesia urgently.
4. If a combined spinal-epidural technique is used, the spinal
drug should include local anesthetic, and if required, a short-
acting opioid to obtain a suitable anesthetic level. A long-
acting opioid, such as morphine, should be reserved for
administration via the epidural catheter if CD is performed.
XI. Costs for external cephalic version
Each successful ECV can result in a cost saving of up to $720 if
neuraxial block is used.119 In an inner city hospital setting without
neuraxial anesthesia, an examination of Medicaid billing costs
suggested that up to a $3,000 savings could be realized when ECV
was attempted.120 The magnitude of the cost savings was dependent
upon a low CD rate following successful ECV.
XII. Neonatal resuscitation in breech presentation delivery
Regardless of the mode of delivery, the obstetric team must be
prepared to resuscitate the newborn. An increase rate of fetal
anomalies associated with breech presentation (e.g., hydrocephalus,
growth restriction) may increase the need for resuscitation. Breech
presentation is associated with lower Apgar scores and increased
 neonatal morbidity and mortality, probably because of increased rates
of associated umbilical cord prolapse, fetal head entrapment, and
placental abruption.

REFERENCES
1. Martin JA, Hamilton BE, Osterman MJ. Three decades of twin births in the United States, 1980-2009.
NCHS Data Brief. 2012:1–8.
2. Lee YM. Delivery of twins. Semin Perinatol. 2012;36:195–200.
3. Martin JA, Hamilton BE, Sutton PD, et al. Births: final data for 2002. Natl Vital Stat Rep. 2003;52:1–
113.
4. Martin JA, Hamilton BE, Sutton PD, et al. Births: final data for 2005. Natl Vital Stat Rep. 2007;56:1–
103.
5. Martin JA, Hamilton BE, Osterman MJ, et al. Births: final data for 2012. Natl Vital Stat Rep.
2013;62:1–68.
6. Spellacy WN, Handler A, Ferre CD. A case-control study of 1253 twin pregnancies from a 1982-1987
perinatal data base. Obstet Gynecol. 1990;75:168–171.
7. American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Practice guidelines for
obstetric anesthesia: an updated report by the American Society of Anesthesiologists Task Force on
Obstetric Anesthesia. Anesthesiology. 2007;106:843–863.
8. American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine. ACOG
Practice Bulletin No. 144: multifetal gestations: twin, triplet, and higher-order multifetal pregnancies.
Obstet Gynecol. 2014;123:1118–1132.
9. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 560: medically
indicated late-preterm and early-term deliveries. Obstet Gynecol. 2013;121:908–910.
10. American College of Obstetricians and Gynecologists Committee on Obstetric Practice. ACOG
Committee Opinion No. 573: magnesium sulfate use in obstetrics. Obstet Gynecol. 2013;122:727–
728.
11. Kametas NA, McAuliffe F, Krampl E, et al. Maternal cardiac function in twin pregnancy. Obstet
Gynecol. 2003;102:806–815.
12. Barclay DL, Renegar OJ, Nelson EW Jr. The influence of inferior vena cava compression on the level
of spinal anesthesia. Am J Obstet Gynecol. 1968;101:792–800.
13. Kim YI, Chandra P, Marx GF. Successful management of severe aortocaval compression in twin
pregnancy. Obstet Gynecol. 1975;46:362–364.
14. Coonrod DV, Hickok DE, Zhu K, et al. Risk factors for preeclampsia in twin pregnancies: a
population-based cohort study. Obstet Gynecol. 1995;85:645–650.
15. Foo JY, Mangos GJ, Brown MA. Characteristics of hypertensive disorders in twin versus singleton
pregnancies. Pregnancy Hypertens. 2013;3:3–9.
16. Milne JA, Howie AD, Pack AI. Dyspnoea during normal pregnancy. BJOG. 1978;85:260–263.
17. McAuliffe F, Kametas N, Costello J, et al. Respiratory function in singleton and twin pregnancy.
BJOG. 2002;109:765–769.
18. Craft JB, Levinson G, Shnider SM. Anaesthetic considerations in caesarean section for quadruplets.
Can Anaesth Soc J. 1978;25:236–239.
19. Hirabayashi Y, Shimizu R, Saitoh K, et al. Cerebrospinal fluid progesterone in pregnant women. Br J
Anaesth. 1995;75:683–687.
20. Ngan Kee WD, Khaw KS, Ng FF, et al. A prospective comparison of vasopressor requirement and
hemodynamic changes during spinal anesthesia for cesarean delivery in patients with multiple
gestation versus singleton pregnancy. Anesth Analg. 2007;104:407–411.
21. Marino T, Goudas LC, Steinbok V, et al. The anesthetic management of triplet cesarean delivery: a
retrospective case series of maternal outcomes. Anesth Analg. 2001;93:991–995.
22. Elliott JP, Radin TG. Quadruplet pregnancy: contemporary management and outcome. Obstet
Gynecol. 1992;80:421–424.
23. Pritchard JA. Changes in the blood volume during pregnancy and delivery. Anesthesiology.
1965;26:393–399.
24. Mhyre JM. Maternal mortality. Curr Opin Anaesthesiol. 2012;25:277–285.
25. Morikawa M, Yamada T, Kataoka S, et al. Changes in antithrombin activity and platelet counts in the
late stage of twin and triplet pregnancies. Semin Thromb Hemost. 2005;31:290–296.
26. Al-Kouatly HB, Chasen ST, Kalish RB, et al. Causes of thrombocytopenia in triplet gestations. Am J
Obstet Gynecol. 2003;189:177–180.
27. Ananth CV, Demissie K, Smulian JC, et al. Placenta previa in singleton and twin births in the United
States, 1989 through 1998: a comparison of risk factor profiles and associated conditions. Am J Obstet
Gynecol. 2003;188:275–281.
28. Suzuki S, Hiraizumi Y, Miyake H. Risk factors for postpartum hemorrhage requiring transfusion in
cesarean deliveries for Japanese twins: comparison with those for singletons. Arch Gynecol Obstet.
2012;286:1363–1367.
29. Shields LE, Wiesner S, Fulton J, et al. Comprehensive maternal hemorrhage protocols reduce the use
of blood products and improve patient safety. Am J Obstet Gynecol. 2015;212:272–280.
30. Einerson BD, Miller ES, Grobman WA. Does a postpartum hemorrhage patient safety program result
in sustained changes in management and outcomes? Am J Obstet Gynecol. 2015;212:140–144.
31. Daniels K, Clark A, Lipman S, et al. Multidisciplinary simulation drills improve efficiency of
emergency medication retrieval. Obstet Gynecol. 2014;123(suppl 1):143s–144s.
32. D’Alton ME, Simpson LL. Syndromes in twins. Semin Perinatol. 1995;19:375–386.
33. Chang YL, Chao AS, Chang SD, et al. Mirror syndrome after fetoscopic laser therapy for twin-twin
transfusion syndrome due to transient donor hydrops that resolved before delivery. A case report. J
Reprod Med. 2014;59:90–92.
34. Tayler E, DeSimone C. Anesthetic management of maternal Mirror syndrome. Int J Obstet Anesth.
2014;23:386–389.
35. Baud D, Windrim R, Keunen J, et al. Fetoscopic laser therapy for twin-twin transfusion syndrome
before 17 and after 26 weeks’ gestation. Am J Obstet Gynecol. 2013;208:197.e1–e7.
36. Wohlmuth C, Tulzer G, Arzt W, et al. Maternal aspects of fetal cardiac intervention. Ultrasound
Obstet Gynecol. 2014;44:532–537.
37. Haas J, Hourvitz A, Dor J, et al. Perinatal outcome of twin pregnancies after early transvaginal
multifetal pregnancy reduction. Fertil Steril. 2014;101:1344–1348.
38. Hogan MC, Foreman KJ, Naghavi M, et al. Maternal mortality for 181 countries, 1980-2008: a
systematic analysis of progress towards Millennium Development Goal 5. Lancet. 2010;375:1609–
1623.
39. Lang CT, King JC. Maternal mortality in the United States. Best Pract Res Clin Obstet Gynaecol.
2008;22:517–531.
40. Martin JA, Hamilton BE, Sutton PD, et al. Births: final data for 2008. Natl Vital Stat Rep. 2010;59:1,
3–71.
41. Dodd JM, Crowther CA, Haslam RR, et al. Elective birth at 37 weeks of gestation versus standard care
for women with an uncomplicated twin pregnancy at term: the twins timing of birth randomised trial.
 BJOG. 2012;119:964–973.
42. Barrett JF. Twin delivery: method, timing and conduct. Best Pract Res Clin Obstet Gynaecol.
2014;28:327–338.
43. Desai N, Lewis D, Sunday S, et al. Current antenatal management of monoamniotic twins: a survey of
maternal-fetal medicine specialists. J Matern Fetal Neonatal Med. 2012;25:1913–1916.
44. Durnwald CP, Momirova V, Rouse DJ, et al. Second trimester cervical length and risk of preterm birth
in women with twin gestations treated with 17-α hydroxyprogesterone caproate. J Matern Fetal
Neonatal Med. 2010;23:1360–1364.
45. Norman JE, Mackenzie F, Owen P, et al. Progesterone for the prevention of preterm birth in twin
pregnancy (STOPPIT): a randomised, double-blind, placebo-controlled study and meta-analysis.
Lancet. 2009;373:2034–2040.
46. Berghella V, Odibo AO, To MS, et al. Cerclage for short cervix on ultrasonography: meta-analysis of
trials using individual patient-level data. Obstet Gynecol. 2005;106:181–189.
47. American College of Obstetricians and Gynecologists, Committee on Practice Bulletins—Obstetrics.
ACOG Practice Bulletin No. 127: management of preterm labor. Obstet Gynecol. 2012;119:1308–
1317.
48. Vogel JP, Nardin JM, Dowswell T, et al. Combination of tocolytic agents for inhibiting preterm labour.
Cochrane Database Syst Rev. 2014;(7):CD006169.
49. Marks RJ, De Chazal RC. Ritodrine-induced pulmonary oedema in labour. Successful management
using epidural anaesthesia. Anaesthesia. 1984;39:1012–1014.
50. Bain ES, Middleton PF, Yelland LN, et al. Maternal adverse effects with different loading infusion
rates of antenatal magnesium sulphate for preterm fetal neuroprotection: the IRIS randomised trial.
BJOG. 2014;121:595–603.
51. Carvalho B, Saxena A, Butwick A, et al. Vaginal twin delivery: a survey and review of location,
anesthesia coverage and interventions. Int J Obstet Anesth. 2008;17:212–216.
52. Conde-Agudelo A, Belizán JM, Lindmark G. Maternal morbidity and mortality associated with
multiple gestations. Obstet Gynecol. 2000;95:899–904.
53. Chasen ST, Spiro SJ, Kalish RB, et al. Changes in fetal presentation in twin pregnancies. J Matern
Fetal Neonatal Med. 2005;17:45–48.
54. Yang Q, Wen SW, Chen Y, et al. Occurrence and clinical predictors of operative delivery for the vertex
second twin after normal vaginal delivery of the first twin. Am J Obstet Gynecol. 2005;192:178–184.
55. Rossi AC, Mullin PM, Chmait RH. Neonatal outcomes of twins according to birth order, presentation
and mode of delivery: a systematic review and meta-analysis. BJOG. 2011;118:523–532.
56. Wen SW, Fung KF, Oppenheimer L, et al. Occurrence and predictors of cesarean delivery for the
second twin after vaginal delivery of the first twin. Obstet Gynecol. 2004;103:413–419.
57. Barrett JF, Hannah ME, Hutton EK, et al. A randomized trial of planned cesarean or vaginal delivery
for twin pregnancy. N Engl J Med. 2013;369:1295–1305.
58. Leftwich HK, Zaki MN, Wilkins I, et al. Labor patterns in twin gestations. Am J Obstet Gynecol.
2013;209:254.e1–e5.
59. Pallasmaa N, Alanen A, Ekblad U, et al. Variation in cesarean section rates is not related to maternal
and neonatal outcomes. Acta Obstet Gynecol Scand. 2013;92:1168–1174.
60. Nicholls K, Ayers S. Childbirth-related post-traumatic stress disorder in couples: a qualitative study.
Br J Health Psychol. 2007;12:491–509.
61. Wanderer JP, Leffert LR, Mhyre JM, et al. Epidemiology of obstetric-related ICU admissions in
Maryland: 1999-2008. Crit Care Med. 2013;41:1844–1852.
62. Kuklina EV, Meikle SF, Jamieson DJ, et al. Severe obstetric morbidity in the United States: 1998-
2005. Obstet Gynecol. 2009;113:293–299.
63. Kathirgamanathan A, Douglas MJ, Tyler J, et al. Speed of spinal vs general anaesthesia for category-1
caesarean section: a simulation and clinical observation-based study. Anaesthesia. 2013;68:753–759.
64. Bauer ME, Kountanis JA, Tsen LC, et al. Risk factors for failed conversion of labor epidural analgesia
to cesarean delivery anesthesia: a systematic review and meta-analysis of observational trials. Int J
Obstet Anesth. 2012;21:294–309.
65. Hawkins JL, Chang J, Palmer SK, et al. Anesthesia-related maternal mortality in the United States:
1979-2002. Obstet Gynecol. 2011;117:69–74.
66. Leveno KJ, Quirk JG, Whalley PJ, et al. Fetal lung maturation in twin gestation. Am J Obstet Gynecol.
1984;148:405–411.
67. Fruscalzo A, Londero AP, Salvador S, et al. New and old predictive factors for breech presentation:
our experience in 14 433 singleton pregnancies and a literature review. J Matern Fetal Neonatal Med.
2014;27:167–172.
68. Hill LM. Prevalence of breech presentation by gestational age. Am J Perinatol. 1990;7:92–93.
69. American College of Obstetricians and Gynecologists Committee on Obstetric Practice. ACOG
Committee Opinion No. 340. Mode of term singleton breech delivery. Obstet Gynecol. 2006;108:235–
237.
70. Siegel IA, McNally HB. Primary breech presentation and external cephalic version; the management
of 308 primary breech presentations. South Med J. 1951;44:942–950.
71. Hannah ME, Hannah WJ, Hewson SA, et al. Planned caesarean section versus planned vaginal birth
for breech presentation at term: a randomised multicentre trial. Lancet. 2000;356:1375–1383.
72. Committee on Obstetric Practice. ACOG Committee Opinion: Number 265, December 2001. Mode of
term single breech delivery. Obstet Gynecol. 2001;98:1189–1190.
73. van Roosmalen J, Meguid T. The dilemma of vaginal breech delivery worldwide. Lancet.
2014;383:1863–1864.
74. Azria E, Le Meaux JP, Khoshnood B, et al. Factors associated with adverse perinatal outcomes for
term breech fetuses with planned vaginal delivery. Am J Obstet Gynecol. 2012;207:285.e1–e9.
75. Eller DP, VanDorsten JP. Route of delivery for the breech presentation: a conundrum. Am J Obstet
Gynecol. 1995;173:393–398.
76. Beilin Y, Bernstein HH. Fetal malpresentation and multiple birth. In: MC Norris, ed. Obstetric
Anesthesia. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1999:666–673.
77. George RT, Singh N, Yentis SM. External cephalic version—the bad, the good and the what now? Int
J Obstet Anesth. 2014;23:4–7.
78. Hall JE, Kohl S. Breech presentation: a study of 1,456 cases. Am J Obstet Gynecol. 1956;72:977–990.
79. Bragg F, Cromwell DA, Edozien LC, et al. Variation in rates of caesarean section among English NHS
trusts after accounting for maternal and clinical risk: cross sectional study. Br Med J. 2010;341:c5065.
80. Caughey AB, Cahill AG, Guise JM, et al. Safe prevention of the primary cesarean delivery. Am J
Obstet Gynecol. 2014;210:179–193.
81. Freeth D, MacVine JS. The value of external cephalic version under anaesthesia. Br Med J.
1951;2:881–884.
82. Crawford JS. Continuous lumbar epidural analgesia for labour and delivery. Br Med J. 1979;1:1560–
1561.
83. Breeson AJ, Kovacs GT, Pickles BG, et al. Extradural analgesia—the preferred method of analgesia
for vaginal breech delivery. Br J Anaesth. 1978;50:1227–1230.
84. Darby S, Hunter DJ. Extradural analgesia in labour when the breech presents. BJOG. 1976;83:35–38.
85. Cheng M, Hannah M. Breech delivery at term: a critical review of the literature. Obstet Gynecol.
1993;82:605–618.
86. Ginosar Y, Weiniger C, Elchalal U, et al. Emergency cesarean delivery for umbilical cord prolapse: the
 head-down, knee-chest prone position for spinal anesthesia. Can J Anaesth. 2008;55:612–615.
87. Vinatier D, Dufour P, Bérard J. Utilization of intravenous nitroglycerin for obstetrical emergencies. Int
J Gynaecol Obstet. 1996;55:129–134.
88. Sandberg EC. The Zavanelli maneuver: 12 years of recorded experience. Obstet Gynecol.
1999;93:312–317.
89. Flamm BL, Newman LA, Thomas SJ, et al. Vaginal birth after cesarean delivery: results of a 5-year
multicenter collaborative study. Obstet Gynecol. 1990;76:750–754.
90. Weiner CP. Vaginal breech delivery in the 1990s. Clin Obstet Gynecol. 1992;35:559–569.
91. Royal College of Obstetricians and Gynaecologists. External Cephalic Version and Reducing the
Incidence of Breech Presentation (Guideline No. 20a). London, United Kingdom: Royal College of
Obstetricians and Gynaecologists; 2006.
92. Burgos J, Cobos P, Rodríguez L, et al. Is external cephalic version at term contraindicated in previous
caesarean section? A prospective comparative cohort study. BJOG. 2014;121:230–235.
93. Rosman AN, Guijt A, Vlemmix F, et al. Contraindications for external cephalic version in breech
position at term: a systematic review. Acta Obstet Gynecol Scand. 2013;92:137–142.
94. Vlemmix F, Kuitert M, Bais J, et al. Patient’s willingness to opt for external cephalic version. J
Psychosom Obstet Gynaecol. 2013;34:15–21.
95. Say R, Thomson R, Robson S, et al. A qualitative interview study exploring pregnant women’s and
health professionals’ attitudes to external cephalic version. BMC Pregnancy and Childbirth.
2013;13:4.
96. Maier B, Georgoulopoulos A, Zajc M, et al. Fetal outcome for infants in breech by method of
delivery: experiences with a stand-by service system of senior obstetricians and women’s choices of
mode of delivery. J Perinat Med. 2011;39:385–390.
97. Yogev Y, Horowitz E, Ben-Haroush A, et al. Changing attitudes toward mode of delivery and external
cephalic version in breech presentations. Int J Gynaecol Obstet. 2002;79:221–224.
98. Rosman AN, Vlemmix F, Beuckens A, et al. Facilitators and barriers to external cephalic version for
breech presentation at term among health care providers in the Netherlands: a quantitative analysis.
Midwifery. 2014;30:e145–e150.
99. Collaris RJ, Oei SG. External cephalic version: a safe procedure? A systematic review of version-
related risks. Acta Obstet Gynecol Scand. 2004;83:511–518.
100. Gottvall T, Ginstman C. External cephalic version of non-cephalic presentation; is it worthwhile? Acta
Obstet Gynecol Scand. 2011;90:1443–1445.
101. De Hundt M, Vlemmix F, Kok M, et al. External validation of a prediction model for successful
external cephalic version. Am J Perinatol. 2012;29:231–236.
102. Burgos J, Cobos P, Rodriguez L, et al. Clinical score for the outcome of external cephalic version: a
two-phase prospective study. Aust N Z J Obstet Gynaecol. 2012;52:59–61.
103. Cluver C, Gyte GM, Sinclair M, et al. Interventions for helping to turn term breech babies to head first
presentation when using external cephalic version. Cochrane Database Syst Rev. 2015;(2):CD000184.
104. Zhang J, Bowes WA Jr, Fortney JA. Efficacy of external cephalic version: a review. Obstet Gynecol.
1993;82:306–312.
105. Clock C, Kurtzman J, White J, et al. Cesarean risk after successful external cephalic version: a
matched, retrospective analysis. J Perinatol. 2009;29:96–100.
106. de Hundt M, Velzel J, de Groot CJ, et al. Mode of delivery after successful external cephalic version: a
systematic review and meta-analysis. Obstet Gynecol. 2014;123:1327–1334.
107. Policiano C, Costa A, Valentim-Lourenço A, et al. Route of delivery following successful external
cephalic version. Int J Gynaecol Obstet. 2014;126:272–274.
108. Jain S, Mulligama C, Tagwira V, et al. Labour outcome of women with successful external cephalic
 version: a prospective study. J Obstet Gynaecol. 2010;30:13–16.
109. Ben-Haroush A, Perri T, Bar J, et al. Mode of delivery following successful external cephalic version.
Am J Perinatol. 2002;19:355–360.
110. Balayla J, Dahdouh EM, Villeneuve S, et al. Obstetrical and neonatal outcomes following unsuccessful
external cephalic version: a stratified analysis amongst failures, successes, and controls. J Matern
Fetal Neonatal Med. 2015;28:605–610.
111. Suen SS, Khaw KS, Law LW, et al. The force applied to successfully turn a foetus during reattempts of
external cephalic version is substantially reduced when performed under spinal analgesia. J Matern
Fetal Neonatal Med. 2012;25:719–722.
112. Sultan P, Carvalho B. Neuraxial blockade for external cephalic version: a systematic review. Int J
Obstet Anesth. 2011;20:299–306.
113. Weiniger CF, Ginosar Y, Elchalal U, et al. Randomized controlled trial of external cephalic version in
term multiparae with or without spinal analgesia. Br J Anaesth. 2010;104:613–618.
114. Weiniger CF, Ginosar Y, Elchalal U, et al. External cephalic version for breech presentation with or
without spinal analgesia in nulliparous women at term: a randomized controlled trial. Obstet Gynecol.
2007;110:1343–1350.
115. Mancuso KM, Yancey MK, Murphy JA, et al. Epidural analgesia for cephalic version: a randomized
trial. Obstet Gynecol. 2000;95:648–651.
116. Schorr SJ, Speights SE, Ross EL, et al. A randomized trial of epidural anesthesia to improve external
cephalic version success. Am J Obstet Gynecol. 1997;177:1133–1137.
117. Sullivan JT, Grobman WA, Bauchat JR, et al. A randomized controlled trial of the effect of combined
spinal-epidural analgesia on the success of external cephalic version for breech presentation. Int J
Obstet Anesth. 2009;18:328–334.
118. Lavoie A, Guay J. Anesthetic dose neuraxial blockade increases the success rate of external fetal
version: a meta-analysis. Can J Anaesth. 2010;57:408–414.
119. Carvalho B, Tan JM, Macario A, et al. Brief report: a cost analysis of neuraxial anesthesia to facilitate
external cephalic version for breech fetal presentation. Anesth Analg. 2013;117:155–159.
120. Adams EK, Mauldin PD, Mauldin JG, et al. Determining cost savings from attempted cephalic version
in an inner city delivering population. Health Care Manag Sci. 2000;3:185–192.
 Obstetric Emergencies
Michael Frölich and Brenda A. Bucklin

I. Nonreassuring fetal status
A. Pathophysiology
B. Diagnosis
C. Treatment
II. Peripartum bleeding
A. Management of obstetric hemorrhage
B. Antepartum hemorrhage
C. Postpartum hemorrhage
III. Intrapartum emergencies
A. Preterm labor and delivery
B. Shoulder dystocia
C. Umbilical cord compression/prolapse
D. Amniotic fluid embolism

KEYPOINTS
1. Management of the pregnant patient includes the assessment and
screening of pregnant patients, perioperative management, and
postoperative care as appropriate. When managing the obstetric patient
both maternal and fetal well-being must be considered.
2. Intrauterine asphyxia is an uncommon cause of newborn depression.
 3. A neonate who has experienced hypoxia proximate to delivery severe
enough to result in hypoxic encephalopathy will demonstrate other signs
of hypoxic damage, such as a profound metabolic or mixed acidemia (pH
<7.00), a low Apgar score of 0 to 3 for more than 5 minutes, and
evidence of neonatal neurologic sequelae.
4. Obstetric emergencies contribute significantly to maternal morbidity and
mortality.
5. Recent developments in the management of medical emergencies
emphasize the value of a protocol-based team approach and regular
simulation-based rehearsal of management algorithms.
6. Obstetric blood loss is often underestimated. However, visual aids can be
used to objectively and subjectively improve estimation of blood loss.
7. “Never treat ‘postpartum hemorrhage’ without simultaneously pursuing
an actual clinical diagnosis” because postpartum hemorrhage is a
“clinical sign of an underlying condition that is amenable to diagnosis.”1

MOST OBSTETRIC EMERGENCIES CAN BE divided into two categories: potential

injury to the fetus and maternal hemorrhage. In such cases, communication and
prompt intervention by the obstetrician and anesthesiologist are essential for
ensuring maternal and fetal safety. This chapter reviews obstetric emergencies
including (1) nonreassuring fetal status, (2) peripartum hemorrhage, and (3)
intrapartum emergencies. Management of the pregnant patient with an obstetric
emergency includes assessment and screening, perioperative management, and
postoperative care. When managing the obstetric patient, both maternal and fetal
well-being must be considered.
I. Nonreassuring fetal status
For many years, the term fetal distress described a fetal status that
was worrisome to the obstetrician. In 2005, the Committee on
Obstetric Practice of the American College of Obstetricians and
Gynecologists (ACOG) expressed concern about the continued use of
the term fetal distress as either an antepartum or intrapartum
diagnosis and birth asphyxia as a neonatal diagnosis.2 The term fetal
distress has a low positive predictive value even in high-risk
populations and is usually associated with an infant who is in good
condition at birth as determined by the Apgar score or umbilical cord
blood gas analysis or both. ACOG recommended replacing the term
fetal distress with nonreassuring fetal status, followed by a further
description of findings (e.g., repetitive variable decelerations, fetal
bradycardia, or biophysical profile score of <4). Fetal distress
implies a significantly compromised fetus; only a few fetal heart
rate (FHR) tracings fall into this category (e.g., repetitive late or
variable decelerations without variability) reflecting the
clinician’s interpretation of data regarding fetal status.
Intrauterine asphyxia is an uncommon cause of newborn
depression. Asphyxia has been defined as a condition of impaired
blood gas exchange leading, if it persists, to progressive hypoxemia
and hypercapnia.3 The term asphyxia should be reserved for the
description of damaging acidemia, hypoxia, and metabolic acidosis.
This definition fails to include conditions that are not readily
recognized clinically, such as occult abruption, but is probably correct
in a majority of cases.4 A neonate who has experienced hypoxia
proximate to delivery severe enough to result in hypoxic
encephalopathy will demonstrate other signs of hypoxic damage, such
as a profound metabolic or mixed acidemia (pH <7.00), a low Apgar
score of 0 to 3 for more than 5 minutes, and evidence of neonatal
neurologic sequelae. The primary insult relates to the duration of the
period lacking oxygenation, leading to death if not reestablished.
Reoxygenation leads to a secondary insult, related to a cascade of
biochemical events required for restoring proper function.5 These
sequelae may include seizures, coma, hypotonia, and one or more of
the following: cardiovascular, gastrointestinal, hematologic,
pulmonary, or renal system dysfunction. The International Task
Force on Cerebral Palsy6,7 published the following criteria
necessary for an acute intrapartum event sufficient to cause
neurologic abnormalities:
Essential criteria (must meet all four):
• Evidence of a metabolic acidosis in fetal umbilical cord arterial
 blood obtained at delivery (pH <7 and base deficit ≥12 mmol per L)
• Early onset of severe or moderate neonatal encephalopathy in
infants born at 34 or more weeks of gestation
• Cerebral palsy of the spastic quadriplegic or dyskinetic type
• Exclusion of other identifiable etiologies such as trauma,
coagulation disorder, infectious conditions, or genetic disorders
Nonspecific criteria suggesting an intrapartum event occurring in
close proximity to labor and delivery:
• A sentinel hypoxic event occurring immediately before or during
labor
• A sudden and sustained fetal bradycardia or the absence of FHR
variability in the presence of persistent, late, or variable
decelerations, usually after a hypoxic sentinel event when the
pattern was previously normal
• Apgar scores of 0 to 3 beyond 5 minutes
• Onset of multisystem involvement within 72 hours of birth
• Early imaging study demonstrating evidence of acute nonfocal
cerebral abnormality

CLINICAL PEARL Intrauterine asphyxia is an uncommon

cause of newborn depression.

A. Pathophysiology
Epidemiologic studies have demonstrated that <20% of cases of
neonatal encephalopathy meet nonstringent criteria for
intrapartum hypoxia with another 10% demonstrating an
association with intrapartum hypoxia. These studies concluded
that approximately 70% of cases of neonatal encephalopathy
result from events arising before the onset of labor. Although it is
difficult to distinguish between birth asphyxia, newborn asphyxia,
and hypoxic-ischemic encephalopathy of the newborn, the overall
incidence of neonatal encephalopathy attributable to intrapartum
hypoxia in the absence of any other preconception or antepartum
abnormalities is estimated to be approximately 1.6 per 10,000.7
The ACOG has suggested abandoning the term birth asphyxia.2
1. Causes of fetal asphyxia. There are several mechanisms by
which a fetus can experience intrapartum asphyxia (see Table
16.1).

a. Decreased maternal O2 tension is an uncommon cause

of intrapartum fetal asphyxia. Clinical situations that may
result in decreased maternal O2 tension and fetal hypoxia
include anemia, pulmonary edema, smoking, maternal
apnea, pulmonary embolus, severe asthma, cyanotic heart
disease, and amniotic fluid embolus. High altitude is
another cause of decreased maternal O2 tension.
b. Interrupted umbilical blood flow prevents O2 delivery
from the placenta to the fetus. When the umbilical cord is
occluded (e.g., cord prolapse), fetal afterload increases,
initiating a vagal response that produces fetal bradycardia.
If the occlusion is intermittent in an otherwise healthy
fetus, the bradycardia may become intermittent in the
form of variable decelerations.
c. Inadequate uterine blood flow results in impaired fetal
O2 uptake. Uterine blood flow is not autoregulated and is
a major determinant of O2 delivery across the placenta.
Because uteroplacental perfusion is proportionate to blood
pressure (BP), reduction below a certain threshold results
in inadequate fetal O2 uptake. Examples of acute
reductions in uterine blood flow include hypotension
associated with neuraxial anesthesia or abruptio placentae.
Uteroplacental insufficiency produced by hypertensive
 disorders (e.g., preeclampsia) is an example of chronic
insufficiency. Intermittent reductions in blood flow can
also result from maternal supine positioning secondary to
aortocaval compression and uterine contractions.
d. Fetal pathology is an uncommon cause of fetal asphyxia.
Examples include (1) fetus with increased metabolic rate
(e.g., pyrexia) or (2) decreased O2 carrying capacity (e.g.,
anemia).

CLINICAL PEARL The overall incidence of neonatal

encephalopathy attributable to intrapartum hypoxia in the absence
of any other preconception or antepartum abnormalities is estimated
to be approximately 1.6 per 10,000.

2. Fetal acid–base balance and asphyxia. The umbilical artery

cord blood pH, PaO2, PacO2, and the calculated base excess are
the most objective determinations of the fetal metabolic
condition at the time of delivery.8 However, the definitions of
normal umbilical cord blood gases and base deficit is unclear
because vigorous infant with Apgar scores >7 at 5 minutes
can be born with umbilical arterial pH of <7.1 with base
excess of 11 mEq per L. During asphyxia, there is a
continuum of decreasing PaO2, accompanied by increasing
PacO2, and decreasing pH. Despite the low PaO2, tissues
continue to consume O2. In the presence of very low PaO2,
anaerobic metabolism results, producing metabolic acidosis.
This is partially buffered by bicarbonate in the blood.
If fetal hypoxia occurs just before birth, there may be
lactic acid in the tissues that has not yet reached the central
circulation. The diagnosis of intrapartum fetal asphyxia
requires a blood gas and acid–base assessment. The
important question for the clinician is what is the
threshold of metabolic acidosis beyond which fetal
 morbidity or mortality may occur.8
3. Fetal response to asphyxia. Fetal anoxia evolves at varying
rates, and severe asphyxia can be lethal in <10 minutes.9 It is
clinically important to realize that fetal cardiac output is
maintained early in asphyxia, but its distribution changes
markedly as the process progresses. The healthy term fetus is
able to mount a series of compensatory mechanisms that
protect the brain from hypoxia-related damage. Fetal cerebral
metabolic responses to acute hypoxia include reducing energy
consumption, increasing oxygen extraction, and maximizing
substrate delivery.10 During the advanced stages of asphyxia,
O2 delivery to the brain and heart decreases and the
myocardium consumes glycogen reserves. Evolving lactic
acidosis and the progressively lower PaO2 and pH lead to
myocardial dysfunction and redistribution of blood flow to
vital organs. Generally, myocardial failure does not occur
until both pH and PaO2 are extremely low, approximately 6.9
and 20 mm Hg, respectively. Although human studies make it
clear that an isolated severe hypoxic–ischemic insult can lead
directly to fetal brain injury, they also suggest that this is a
rare event and that many cases of encephalopathy are
associated with preceding or coexisting factors.11 The
difference between a hypoxic insult that leads to
fetal/neonatal death versus that causing significant fetal stress
with a normal long-term neurologic outcome is probably very
small.
B. Diagnosis
1. Fetal heart rate monitoring was introduced over four decades
ago, but the interpretation and management of FHR patterns
during labor remains one of the most problematic issues in
obstetrics. FHR monitoring is one of the few tools available
for assessing fetal status and oxygenation during labor and
delivery. The relative merits of FHR monitoring have
nevertheless been the subject of substantial debate. Central to
the conflict are issues regarding interpretation, reproducibility
of interpretation, and management of abnormal patterns.
Disappointing outcomes associated with electronic FHR
monitoring may be related to the observations that many cases
of asphyxial damage begin before labor and intrapartum FHR
monitoring will not detect antepartum events that would
otherwise prompt intrapartum interventions. Fetal and
neonatal outcomes are not improved with the use of
continuous electronic FHR monitoring compared to
intermittent FHR electronic auscultation.12 The incidence of
cerebral palsy has not decreased in the last 30 years!
a. Fetal heart rate pattern. Because of the lack of
agreement about pattern interpretation as well as the high
number of false-positive tracings, a Eunice Kennedy
Shriver National Institute of Child Health and Human
Development (NICHD) consensus panel in 2008 proposed
a uniform system of terminology in which any FHR
pattern is classified as category I, II, or III, based on the
presence or absence of well-defined aspects of the FHR.13
With this in mind, subsequent recommendations have
been developed by the ACOG for the management of
category I (normal) and category III (pathologically
abnormal) FHR patterns. The management of category II
FHR patterns remains the most important and challenging
issue in the field of FHR monitoring, but
recommendations regarding the clinical management have
been developed.14
b. Interpretation of fetal heart rate. It is generally
accepted that decreased baseline FHR variability is the
single most reliable predictor of fetal compromise. During
asphyxia, FHR variability decreases and then disappears
before significant fetal depression or death occurs in
utero. Decreased variability correlates clinically with
decreased central nervous system (CNS) function and is
 thought to precede CNS damage. In cases where
variability is absent and/or the FHR is persistently <80
beats per minute (bpm) (category III), there is no time to
reduce fetal stress and immediate delivery is indicated.
Patients with category II (all FHR patterns not classified
as category I or III) tracings should be evaluated for
factors that may reduce fetal oxygenation but most
importantly take into account associated clinical
circumstances.

CLINICAL PEARL Fetal and neonatal outcomes are not

improved with the use of continuous electronic FHR monitoring
compared to intermittent FHR electronic auscultation.

2. Presence of meconium
Meconium staining has often been associated with neonatal
depression. In a recent prospective cohort study, the presence
of meconium was associated with higher risk of the composite
morbidity.15 However, in most cases, the finding is not of
serious importance because it is not necessarily indicative of
intrauterine asphyxia. Historically, the presence of meconium-
stained amniotic fluid during labor was a potentially ominous
sign, but controversy exists over its relative impact on fetal
status. Data indicate that timing and quantity of meconium
passage are critical variables for assessing the significance of
this occurrence on fetal well-being. Presumably, these two
aspects of meconium passage correlate with the duration and
severity of the intrauterine insult. If meconium staining is
present in combination with an abnormal FHR tracing or
another risk factor (e.g., intrauterine growth restriction
[IUGR], postdates), there is an increased likelihood of
neonatal depression. More important, aspiration of
meconium-stained fluid can lead to serious neonatal
 morbidity and mortality.

CLINICAL PEARL In most cases of meconium staining, the

finding is not of serious importance because it is not necessarily
indicative of intrauterine asphyxia.

3. Umbilical cord gases

a. American College of Obstetricians and Gynecologists
recommendation for umbilical cord blood gas
sampling. The determination of pH, blood gases, and
base deficit in umbilical cord blood is commonly
performed to assess the metabolic status of the newborn
in conjunction with Apgar scores and the neonatal clinical
course. In 2006, ACOG recommended selective sampling
only if a serious abnormality arises in the delivery process
or a problem occurs in the newborn period.8 Fetal
acidemia is often considered a sign of more permanent
neonatal morbidity and is used as an indicator of risk for
adverse neonatal outcome. Although the degree of
asphyxia can be determined by the extent of acidemia, it
does not necessarily reflect the duration of the insult.
b. Umbilical cord gas limits. Previously, a normal
umbilical cord pH was at least 7.2. However, these limits
have been challenged because they do not distinguish
between differences in arterial and venous blood samples.
These limits have been challenged even further by
differences in blood samples obtained following labor as
well as those obtained from premature infant deliveries.
For example, if a fetus has been subjected to the stress of
labor, acidemia should be defined as an umbilical artery
pH <7.15 or an umbilical vein pH <7.2. By definition,
acidemia refers to increased hydrogen ion concentration
in the blood. Acidosis occurs when there is increased
 hydrogen ion concentration in the tissues. Asphyxia
includes both hypoxia (i.e., decreased pO2 in tissues) as
well as CO2 retention. The combination of these may lead
to acidosis. However, in most cases, the term birth
asphyxia should be avoided because there are no precise
clinical or biochemical indicators that have a high positive
predictive value for perinatal asphyxia.

CLINICAL PEARL In most cases, the term birth asphyxia

should be avoided because there are no precise clinical or
biochemical indicators that have a high positive predictive value for
perinatal asphyxia.

4. Doppler ultrasound
Doppler ultrasound is used to assess blood flow in the fetal
arterial and venous systems. It is as an important tool used in
antenatal surveillance for the management and timing of
delivery in pregnancies associated with IUGR. Evaluation of
the umbilical arteries provides information on placental
resistance. Placental resistance is elevated in uteroplacental
insufficiency. This leads to a reduction in forward umbilical
artery flow and is reflected by a relative reduction in diastolic
as compared to systolic velocities. Absent or reversed end
diastolic flow in the umbilical artery is known to be
associated with an 80-fold increased risk of perinatal
mortality.16 Neonatal intracranial volume and cerebral cortical
gray matter, as measured by magnetic resonance imaging
(MRI), were also reduced in infants born from pregnancies
complicated by fetal growth restriction and abnormal
umbilical artery Doppler studies compared with matched
infants of the same gestational age but with appropriate
intrauterine growth.17
The measurement of blood flow velocities in umbilical
 and fetal cerebral arteries is a valuable tool in antepartum
surveillance.

CLINICAL PEARL The ideal time for delivery is when

abnormalities exist only in the umbilical and venous circulations
and before abnormalities are observed in the FHR tracing.
However, this may be influenced by gestational age.

C. Treatment
1. Obstetric management
Type II and type III FHR patterns warrant active medical
intervention. When there is an unresolved, prolonged severe
bradycardia (class III FHR pattern), emergency cesarean
delivery (CD) will be necessary to minimize fetal risk. The
management of a class II FHR pattern will depend on the
presence or absence of moderate variability or accelerations,
the response of the FHR to contractions and the progress and
stage of labor. With a category II FHR pattern, several
maneuvers can be utilized to resuscitate the fetus in utero (see
Table 16.2). Fetal O2 content and saturation can be improved
by administering supplemental O2 and by placing the mother
in the left lateral position to reduce compression of the vena
cava. Uterine stimulants (i.e., oxytocin infusion) should also
be discontinued. Tocolysis should be considered to achieve
uterine relaxation if the mother is hemodynamically stable
and there is no evidence of abruptio placentae. Terbutaline,
0.25 mg administered subcutaneously (SQ) or intravenously
(IV) has been found to be superior to placebo and to
magnesium sulfate in relieving decelerations. Sublingual
nitroglycerin spray can achieve more rapid uterine relaxation,
but its use may cause hypotension and maternal headache. IV
hydration should be considered if the volume status is in
question. Maternal hypotension resulting from neuraxial
 anesthesia should also be corrected. A vaginal examination
should be performed to rule out rapid cervical change and
fetal descent as well as cord prolapse. If there is evidence of
cord compression by the presence of repetitive, moderate to
severe variable decelerations, amnioinfusion should be
considered. If the FHR abnormalities do not resolve with the
earlier mentioned measures, CD or operative vaginal delivery
is indicated. Maternal fever can lead to increased fetal oxygen
consumption and is associated with increased risk of poorer
neonatal outcome. Treatment with acetaminophen and cooling
measures should be instituted.

CLINICAL PEARL Anesthetic considerations for category II

FHR patterns include administration of supplemental O2, left uterine
displacement, IV hydration, correction of hypotension resulting
from neuraxial anesthesia, treating uterine overstimulation, and
preparation for cesarean or operative vaginal delivery.

2. Anesthetic management
Anesthesia for CD of a distressed fetus must provide proper
operating conditions for the obstetrician within a short time
period without compromising maternal or fetal safety. The
obstetrician determines the timing and speed with which
the procedure must be performed. The choice of general,
spinal, or extension of an existing epidural anesthetic
depends on the clinical circumstances. Although general
anesthesia (GA) may be indicated in some cases of FHR
abnormality, the severity of the abnormality should be
considered before incurring risk associated with GA.18
a. Interpretation of the 30-minute rule
Clinicians have attempted to provide guidance on the time
frame when an emergent CD should be initiated. In 1982,
ACOG proposed a 15-minute interval between the time of
decision for a CD to its start. These guidelines, however,
were revised in 1989, and the 15-minute recommendation
was extended to 30 minutes.19
A 30-minute interval is reported to be adequate for
most CD. The Optimal Goals for Anesthesia Care in
Obstetrics emphasize the “Availability of anesthesia and
surgical personnel to permit the start of a cesarean
delivery within 30 minutes of the decision to perform the
procedure”20; in cases of vaginal birth after cesarean
(VBAC), appropriate facilities and personnel, including
obstetric anesthesia, nursing personnel, and a physician
capable of monitoring labor and performing CD,
immediately available during active labor to perform
emergency CD. “The definition of immediate availability
of personnel and facilities remains a local decision, based
on each institution’s available resources and geographic
location.”20 Although there are early reports of evidence
for increased risk of fetal loss if the “alarm to surgery”
interval exceeds 20 minutes21 and another report
suggested that permanent fetal CNS damage may begin
after approximately 10 minutes of fetal anoxia,22 most
cases of fetal asphyxia are not the result of fetal anoxia. In
cases where complete fetal anoxia is suspected, delivery
should occur as soon as possible. Because these
emergencies may occur at any time, the anesthesia
provider must always be prepared for emergent operative
delivery.
CLINICAL PEARL “Availability of anesthesia and surgical
personnel to permit the start of a cesarean delivery within 30
minutes of the decision to perform the procedure”; in cases of
VBAC, appropriate facilities and personnel, including obstetric
anesthesia, nursing personnel, and a physician capable of
monitoring labor and performing CD, immediately available during
active labor to perform emergency CD. “The definition of
immediate availability of personnel and facilities remains a local
decision, based on each institution’s available resources and
geographic location.”20

b. Anesthetic choice
Every woman admitted to labor and delivery has the
potential to develop an obstetric emergency as a result of
nonreassuring fetal status. When choosing an anesthetic,
the anesthesia provider must communicate with the
obstetrician to determine the urgency of the situation. “A
communication system should be in place to encourage
early and ongoing contact between obstetric providers,
anesthesiologists, and other members of the
multidisciplinary team.”23
Because most anesthesiologists and other anesthesia
providers are not experts in FHR monitoring, it is up to
the obstetrician to determine the severity of the FHR
abnormality. Emergency CD is performed when the
situation is life threatening for either the mother or fetus.
In cases of abnormal FHR patterns, emergency CD is
indicated for prolonged fetal bradycardia, late
decelerations without FHR variability, and cord prolapse
with bradycardia.
“The decision to use a particular anesthetic
technique for cesarean delivery should be
 individualized, based on several factors. These include
anesthetic, obstetric, or fetal risk factors (e.g., elective vs.
emergency), the preferences of the patient, and the
judgment of the anesthesiologist. Neuraxial techniques
are preferred to GA for most cesarean deliveries. An
indwelling epidural catheter may provide equivalent onset
of anesthesia compared to initiation of spinal anesthesia
for urgent cesarean delivery. . . . However, GA may be
the most appropriate choice in some circumstances
(e.g., profound fetal bradycardia, ruptured uterus,
severe hemorrhage, severe placental abruption)”23 but
the risk of a difficult airway (and availability of
backup and advanced airway equipment) should
always be considered.

CLINICAL PEARL The obstetrician determines the severity of

the FHR abnormality. Emergency CD is performed when the
situation is life threatening for either the mother or fetus. Neuraxial
techniques are preferred to GA for most CD.

(1) Local anesthetics and fetal acidosis

The use of 2% lidocaine with or without epinephrine
may be associated with fetal ion trapping of the local
anesthetic in the presence of severe fetal acidosis.
The balance of ionized and nonionized forms of a
local anesthetic is shifted toward the ionized, poorly
lipid-soluble form in the acidotic environment. This
imbalance has led many investigators to believe that
local anesthetics (in particular, lidocaine) may
accumulate in the acidotic environment. Despite this
theoretical concern, pH adjusted 2% lidocaine with
epinephrine is commonly used in practice. In some
situations, 3% 2-chloroprocaine can be used because
 it is almost completely hydrolyzed by maternal
plasma esterases before it reaches the fetal
circulation.
c. Maternal safety
Complications related to anesthesia remain an important
and often preventable cause of obstetric-related mortality.
Although maternal mortality has declined significantly in
the last 50 years, the rate of decline stabilized from 1980
to 2000. The most recent report from the Centers of
Disease Control and Prevention indicates that pregnancy-
related deaths in the United States have steadily increased
from 7.2 deaths per 100,000 live births in 1987 to a high
of 17.8 deaths per 100,000 live births in 2009 and 2011.24
Although the reasons for the overall increase in
pregnancy-related deaths are unclear, numbers of
pregnant women with chronic diseases (hypertension,
obesity, diabetes, chronic heart disease) are increasing and
likely contributory to the increased mortality rates.
Anesthesia-related maternal mortality in the United
States is estimated at 1.7 per 1,000,000 live births.25
During the 1970s and 1980s, 17 women died as a result of
GA for every one that died from neuraxial anesthesia. By
the early 1990s, this had improved to six GA deaths for
every neuraxial anesthetic death. More recently, the
serious complication repository project of the Society for
Obstetric Anesthesia and Perinatology captured data on
more than 250,000 anesthetics, including 3,000 general
anesthetics.26 Although serious complications occurred in
only 1:3,000 obstetric anesthetics, high neuraxial block,
respiratory arrest in labor and delivery, and unrecognized
spinal catheters were the most frequent complications
identified. Leading causes of death were hemorrhage and
preexisting cardiac disease. Another recent report of
maternal deaths at a tertiary care center identified
 hypertensive disease and thromboembolic events as the
leading causes of death. Access to a tertiary care center
(distance of residence to the hospital) appeared to be the
primary factor associated with maternal deaths.27 Despite
advances in obstetric and anesthesia care, catastrophic
complications do occur. These reports further emphasize
the need for clear communication between obstetrician,
anesthesia providers, and nursing staff as well as
implementation of a “disaster” plan.
II. Peripartum bleeding
Obstetric emergencies contribute significantly to maternal morbidity
and mortality. In a review of closed anesthesia malpractice claims,
obstetric hemorrhage accounted for more than 30% of the hemorrhage
claims, and lapses in communication contributed to 60% of the cases.
Recent developments in the management of medical emergencies
emphasize the value of a protocol-based team approach and regular
simulation-based rehearsal of the management algorithms.28
A. Management of obstetric hemorrhage
1. Fundamentals of obstetric hemorrhage
Hemorrhagic shock is a condition in which inadequate
perfusion of organs results in insufficient availability of O2 to
satisfy the metabolic needs of the tissues. A catabolic state
develops. The consequences of these changes are
inflammation, endothelial dysfunction, and disruption of
normal metabolic processes in vital organs. The initial
assessment of the patient with blood loss requires only basic
clinical evaluations. Monitoring of BP, pulse, capillary refill,
mental status, and urinary output is sufficient to judge the
amount and the rate of blood loss and to plan therapy.
Scrupulous attention to these indices is important because
visual estimates of obstetric blood loss are notoriously
unreliable, and the failure to recognize early signs of
hypovolemia can lead to irretrievable complications.
Pregnant patients tolerate blood loss of up to 15% of their
blood volume (approximately 1 L in a 70 kg woman at
term) without symptoms or alterations in vital signs.
When blood loss exceeds about 1,500 mL, hemodynamic
changes (e.g., tachycardia, hypotension) begin to occur
(see Table 16.3).

Tachycardia develops, often with a narrowing of pulse

pressure; systolic blood pressure (SBP) may remain normal.
Capillary refill may also be delayed. At this point, the patient
often becomes anxious. Failure to recognize anxiety and
restlessness in a postoperative or postpartum patient as early
signs of hypoperfusion is a common error with potentially
fatal consequences. As blood loss continues, tachypnea
develops and urine output falls substantially. If untreated, the
patient’s restlessness progresses to confusion. With massive
losses (>3,000 mL), the pulse is often >140 bpm, BP is
markedly decreased, capillary refill absent, and marked
oliguria develops. The patient becomes lethargic and,
eventually, comatose.29 The Joint Commission30 and the
Society of Maternal Fetal Medicine recommended the
adoption of protocols to address maternal death and morbidity
that are associated with postpartum hemorrhage (PPH).28
Within a large health care system, the application of a
standardized method to address maternal hemorrhage
 significantly reduced maternal morbidity, based on the need
for maternal transfusion and peripartum hysterectomy.31
2. Key management considerations include
a. Hypotension is a late sign of hypovolemia because of the
increased blood volume associated with pregnancy.
Obstetric blood loss is often underestimated. Blood loss
can be underestimated by 50% with the reliability of
visual estimation decreasing as blood loss increases.32
Visual aids can be used to objectively and subjectively
improve estimation of blood loss.33 Ongoing blood loss
should be addressed without delay.
b. Because of the risk of considerable blood loss, large bore
IV access should be obtained early during resuscitative
efforts.
c. Either crystalloid or colloid can be used to assist in
restoring blood volume because an atonic uterus can lose
up to 2 L of blood in 5 minutes. In addition, more than 1 L
of blood can be sequestered in an atonic uterus. This
degree of blood loss occurs because nearly 15% of the
cardiac output perfuses the uterus at term. Because
pregnancy expands blood volume, hemorrhage may go
undetected until the patient becomes hypotensive and
tachycardic.
d. An arterial line is often useful for beat-to-beat monitoring
of the BP and for obtaining hemoglobin, blood gases, and
coagulation studies.
e. Anesthesia providers should for transfusion of blood
products. If the institution has a massive transfusion
protocol, it should be activated when there is substantial
blood loss. If coagulopathy is likely, it is prudent to give
blood products before coagulation studies deteriorate.
f. If medical interventions fail, other interventions may be
necessary including intrauterine balloon (or gauze)
tamponade and uterine compression sutures. Next steps
 include radiologic embolization or pelvic
devascularization. Hysterectomy is reserved for refractory
cases.
3. Transfusion in obstetric hemorrhage
The ASA Practice Guidelines for Obstetric Anesthesia
state that a routine blood cross match is not necessary for
vaginal or operative delivery. The decision whether to order
or require a blood type and screen, or cross match, should be
based on maternal history, anticipated hemorrhagic
complications (e.g., placenta accreta in a patient with placenta
previa and previous uterine surgery), and local institutional
policies.23 In addition, the ASA Task Force on Obstetric
Anesthesia and the ACOG recommend that all facilities
providing obstetric care be prepared to manage
hemorrhagic emergencies.23,34 Response to hemorrhage
takes a coordinated effort between clinicians and the blood
bank. It is helpful to have a massive hemorrhage protocol
outline before an emergency occurs. Facilities should also
consider writing and posting such a protocol in addition to
initiating clinical drills on obstetric hemorrhage
scenarios.31
4. Transfusion thresholds: when to transfuse
Determining the point when a parturient should be
transfused is often difficult because blood loss during and
after delivery is often underestimated. In these situations,
blood loss arises from several areas and amniotic fluid is also
present. Vital signs, ongoing hemorrhage, and coexisting
disease should be considered. Signs and symptoms of
inadequate perfusion resulting from hypovolemia include
tachycardia, decreased pulse pressure, tachypnea, decreased
urine output, and altered mental status. Although the
physiologic changes of pregnancy help mitigate the
parturient’s response to hemorrhage and vital signs may
not change until more than 1,500 mL of blood loss has
 occurred, patients should be transfused when there are
signs of significant hypoperfusion.
The purpose of packed red blood cell (PRBC)
administration is to increase the O2 carrying capacity of
blood. In the past, the goal of transfusion therapy was a
hemoglobin concentration of 10 g per dL. Recently, this
threshold was challenged by a study reporting decreased
mortality rates in critically ill patients who were transfused at
lower thresholds (<7 g per dL).35 However, in obstetric
patients, Karpati et al.36 reported an approximately 50%
incidence of myocardial ischemia in the intensive care unit
(ICU) patients who were admitted with a diagnosis of PPH
and hypovolemic shock. Risk factors for myocardial ischemia
in these patients included a hemoglobin concentration of ≤6.0
g per dL, SBP ≤88 mm Hg, diastolic BP ≤50 mm Hg, and a
heart rate (HR) >115 bpm. Interestingly, a recent survey of
anesthesiologists and obstetricians determined that the
transfusion threshold for PRBCs for most providers was
between 7.0 and 8.0 g per dL with anesthesiologists
transfusing at a lower threshold (i.e., 7.5 g per dL) compared
to obstetricians (i.e., 8.0 g per dL).37 The ASA Task Force on
Blood Replacement has concluded that PRBC
administration is rarely indicated when the hemoglobin
concentration is >10 g per dL but is almost always
indicated when the hemoglobin level is ≤6 g per dL.38 In
some centers, an arterial blood gas is used to guide
transfusion therapy. If the base deficit is >15 mEq per L, in
the presence of significant and ongoing blood loss, then blood
should be administered.
5. Antepartum donation/autologous transfusion
Obstetric cases receive approximately 5% of blood
components used annually throughout the United States. One
potential method for reducing the need for homologous blood
transfusions is autologous transfusion of the patient’s donated
 blood. Normally, blood center programs schedule donors once
per week for up to 6 weeks preceding surgery. In some cases,
erythropoietin is administered before surgery in an attempt to
reduce the amount of homologous blood transfused.
Unfortunately, with few exceptions, the results are
disappointing. Most trials of erythropoietin given prior to
surgery do not result in reduction of homologous blood
transfused, although most have documented a positive impact
on reticulocyte count and preoperative hematocrit.39
Routine autologous blood donation is not utilized for
routine obstetric deliveries because of concern about cost-
effectiveness.40 However, it is a reasonable option for patients
at risk for peripartum hemorrhage, especially those with rare
antibodies who may be difficult to transfuse with compatible
homologous blood. Autologous donation during pregnancy
has been shown to have minimal maternal hemodynamic
effects.
Yamada et al.41 published an analysis of 82 patients with
placenta previa after implementation of an autologous blood
donation protocol. The authors reported that women who did
not donate blood prepartum had a four times greater rate (12%
versus 3.1%) of peripartum homologous blood transfusion.
They recommended beginning blood donation at 32 weeks’
gestation with removal of 400 mL per week to achieve a total
stored volume of 1,200 to 1,500 mL. Patients who donated
autologous blood had a higher overall rate of blood
transfusion, with 71% receiving blood peripartum compared
with 12% of patients who received homologous blood.
Although autologous blood has a slightly smaller risk of
bacterial contamination, the risk of ABO mismatching is
similar for both autologous and homologous blood.
Consequently, the indications for transfusion of autologous
blood are the same as banked blood.
6. Intraoperative cell salvage
 Another alternative to homologous-banked blood is the use of
an intraoperative cell salvage device, or cell saver. This
technique involves suctioning of blood from the operative
field followed by cell washing, suspension in saline, and
reinfusion to the patient. Concerns about its possible
association with amniotic fluid embolism (AFE) have made
this technique controversial in the past but now it is used in
most major centers.42
The cause of the coagulopathy and cardiovascular
collapse associated with AFE is unclear. Contaminants
including tissue factor, fetal squamous cells, meconium, and
other particulates are present in amniotic fluid and may play a
role in the development of AFE.43 Waters and colleagues44
demonstrated that when cells are washed and a leukocyte
depletion filter is used, the resulting blood has a concentration
of fetal squamous cells similar to a preoperative maternal
blood sample. Another potential concern is that fetal
hemoglobin is present in the processed cell saver blood,
raising concerns about maternal alloimmunization and the
potential for problems with subsequent pregnancies. Rh
mismatch is particularly important and anti-D immune
globulin should be administered to Rh-negative mothers who
receive salvaged blood.
Cell salvage has been used safely in many patients and
should be considered in patients at high risk for
hemorrhage who would be difficult to cross match, object
to blood transfusion (e.g., a Jehovah’s Witness with a
known placenta accreta), or as a lifesaving measure.
However, equipment and skilled personnel must be available.
7. Acute normovolemic hemodilution
Acute normovolemic hemodilution is a technique involving
collection of autologous blood immediately prior to surgery or
delivery. Normovolemia is maintained by IV fluid
administration with colloid or crystalloid. The volume of
 colloid administered should be equal to the volume of blood
withdrawn. When crystalloid is administered, the volume
should be three times the volume of blood removed. When
blood is subsequently lost, it has less red blood cell mass and
the blood removed can be returned to the patient as needed.
Because the blood is collected and stored at the bedside
for immediate reinfusion, the risks of bacterial contamination
and administrative error associated with autologous blood
storage are significantly reduced. This technique has been
successfully reported in patients at risk for blood loss during
CD, with an average of 1,000 mL of blood collected just prior
to the surgery.45 In this study, no patients experienced
symptoms of nausea, vomiting, dizziness, or light-headedness,
and there were no abnormalities in vital signs or FHR.
8. Complications
The risks of blood transfusion are summarized in Table 16.4.
9. Massive blood loss and transfusion
a. Definition
Massive transfusion is defined by administration of
greater than 10 units of PRBCs. When massive blood
loss occurs in obstetric patients, it is important to notify
the blood bank. Communication between personnel,
especially the obstetrician, anesthesiologist, and nursing
staff regarding continued blood loss and the ongoing need
for blood products, is important. A “code-white” or
massive hemorrhage protocol is particularly helpful to
outline responsibilities of nursing staff and personnel who
are transporting blood products to the labor and delivery
suite.46 Despite a recommendation for implementation of
PPH protocols in every labor and delivery unit in the
United States from the National Partnership for Maternal
Safety,47 at least 20% of United States academic obstetric
anesthesia units are without PPH protocols.48
b. Monitoring
Adequate fluid resuscitation, appropriate monitoring,
and therapy guided by laboratory tests are of prime
importance in the management of obstetric
hemorrhage. During massive blood loss, the patient
must be reassessed frequently to evaluate effectiveness
of treatment as well as to monitor for potential
complications. At a minimum, two large cannulae (size 14
to 16 gauge) should be inserted. Fluid should be warmed
to prevent hypothermia and this typically requires a blood
infusion device with adequate warming capacity at high
infusion rates. The goal of initial fluid resuscitation is to
return the BP to low normal to ensure adequate tissue
perfusion. The urine output and central venous pressure
(CVP) are used to determine the adequacy of circulating
volume. Urine output should be maintained at least at 0.5
mL/kg/hour and the CVP at 4 to 8 cm H2O. The
anesthesiologist should keep in mind that CVP reflects
right atrial filling pressure but is an inaccurate indicator of
the left heart filling when the patient has cardiac or
pulmonary disease. Thromboelastography (TEG) or
rotational thromboelastometry (ROTEM) provide faster
results than standard laboratory testing, which is
advantageous in the setting of ongoing obstetric
hemorrhage. Figure 16.1 presents an illustration of
expected TEG tracings in obstetric coagulopathy.
However, laboratory analyses (platelet count, activated
partial thromboplastin time, prothrombin time, fibrinogen,
antithrombin, and D-dimer) show greater differences in
coagulation variables and may correlate better with
estimated blood loss.49
c. Electrolyte balance
Electrolyte imbalance is common in hemorrhagic shock
and requires attention. Hypokalemia is not unusual and is
probably the consequence of a dramatic increase in
catecholamine release during shock. This causes
potassium to be transported into cells and is a temporary
change that will self-correct if perfusion is restored.
Treatment is generally not required unless the serum
potassium concentration is <2.5 mEq per L or cardiac
dysrhythmias are present. Hypocalcemia is often observed
in patients who receive multiple blood product
transfusions because the citrate anticoagulant chelates
 calcium. In addition, shock can result in failure of cellular
ion pumps that export calcium from cells. The high
intracellular calcium levels disrupt adenosine triphosphate
(ATP) synthesis and myocardial contractility. Treatment
should be considered if the ionized calcium level falls
below approximately 1.5 mEq per L or if Q-T
prolongation is seen on the electrocardiogram (ECG).
Similarly, if hypomagnesemia occurs, replacement should
be considered.
d. Dilutional coagulopathy
Patients with massive hemorrhage (greater than one blood
volume) usually develop a dilutional coagulopathy from
factor deficiency after IV crystalloid and/or colloid
resuscitation. Fibrinogen levels decrease initially; the
critical level of 1.0 g per L is likely to be reached after
150% blood volume loss, followed by a decrease of other
labile coagulation factors to 25% activity after a 200%
blood loss. Prolongation of the activated partial
thromboplastin time (aPTT) and prothrombin time (PT) to
1·5 times the mean normal value is correlated with
increased risk of clinical coagulopathy. Infusion of fresh
frozen plasma (FFP) should be considered after blood
volume is lost. The dose should be large enough to
maintain coagulation factors well above the critical level.
Experts advise that the platelet count should not be
allowed to fall below the critical level of 50 to 100 × 109
per L in an acutely bleeding patient.
Treatment of dilutional coagulopathy is challenging and
the primary monitoring tools are measurement of PT,
aPTT, platelet count, and fibrinogen. Dilutional
coagulopathy can also be detected by the use of
thromboelastographic measurements (decreased
maximum amplitude and/or α angle) and its use in
obstetrics has been described.50,51 Calcium binding by the
 citrate preservative of blood products can become
clinically significant in massive transfusion, leading to
cardiac depression and hypotension. Patients often require
calcium replacement to restore normal plasma levels.
Studies of women with PPH have reported lower mean
plasma fibrinogen levels (≤2 g per L) in women who go
on to develop more severe PPH.52 The low fibrinogen
concentrations in FFP limit its utility as a source of
fibrinogen in transfusion.53 Cryoprecipitate has higher
concentrations of fibrinogen54 but does not undergo viral
inactivation procedures and carries the potential risk of
patient exposure to blood-borne pathogens.55 In treating
dilutional coagulopathy, the goal is for the platelet count
to be higher than 50 × 109 per L and fibrinogen level >2 g
per L.
e. Disseminated intravascular coagulation
Disseminated intravascular coagulation (DIC) results
from an underlying disease process (e.g., placental
abruption, dead fetus syndrome, AFE, gram-negative
sepsis, eclampsia, and retained products of conception)
that initiates biodegradation of fibrinogen and clotting
factors. This results in hemorrhage as well as
microvascular thrombosis. Laboratory findings of DIC are
listed in Table 16.5. Management includes treatment of
the underlying disease with ongoing administration of
blood products (i.e., PRBCs, platelets, clotting factors).
f. Activated recombinant factor VII
In life-threatening PPH, recombinant activated factor
VII (rFVIIa) may be used as an adjunct to other surgical
treatments, but there are no data to support the optimal
timing of its use or recommended dose. A commonly used
dose is 90 μg per kg, repeated once if no clinical response
within 15 to 30 minutes. Adequate levels of platelet and
fibrinogen are essential for rFVIIa to be effective,56 and
these variables should be checked and corrected before
administration of rFVIIa. This drug is also less effective
in the presence of hypothermia and acidosis. The rFVIIa
was originally developed to prevent or control bleeding in
patients with hemophilia A or B with inhibitors to factors
VIII or IX, but several reports have suggested decreased
blood product requirements in surgical and trauma
patients receiving rFVIIa during uncontrolled
hemorrhage.
The rFVIIa augments the intrinsic clotting pathway by
binding with tissue factor and directly activating factors
IX and X. The dose is 50 to 100 µg per kg IV every 2
hours until there is evidence of hemostasis. Most patients
require only one dose, but it is important to ensure
adequate levels of platelets and other clotting factors
because rFVIIa increases clotting by acting on these
substrates. The optimal timing for administration has not
been described, but rFVIIa should only be considered in
life-threatening obstetric hemorrhage when other
management strategies have failed. Most complications
resulting from rFVIIa are associated with thrombosis,
myocardial infarction, pulmonary embolism, and clotting
of vascular access devices.
g. Tranexamic acid is an antifibrinolytic agent.
Investigations have been conducted to determine if it is
useful for both prevention and treatment of PPH because
 its hypothesized mechanism of action is to supplement
uterotonics and because it has been proved to reduce
blood loss in elective surgery and bleeding in trauma
patients. Although results are promising in the treatment
of PPH after vaginal delivery or CD, large multicentre
randomized controlled trials will be required before
widespread use can be recommended.57
B. Antepartum hemorrhage
Antepartum hemorrhage complicates nearly 10% of all
pregnancies. Although most of these cases are not serious and
result from minor complications (e.g., cervicitis), others result
from abnormal placentation (e.g., placenta previa, placental
abruption). These more serious causes of hemorrhage are a threat
to fetal and maternal well-being.
Obstetricians ask the following questions when evaluating
patients with antepartum hemorrhage:
• Does the bleeding threaten the life of mother and/or fetus?
• What is the cause of hemorrhage?
• When and how should the fetus be delivered?
1. Placenta previa
a. Definition
The placenta normally implants in the upper uterine
segment. In placenta previa, the placenta either totally or
partially implants over or very near the internal os.
Because it presents before the fetal presenting part, it
obstructs fetal descent. This condition affects
approximately 0.5% of pregnancies.
b. Epidemiology
Placenta previa complicates 4.8 per 1,000 deliveries
annually and is fatal in approximately 0.03% of cases.
The exact cause is uncertain, but prior uterine surgery
is a common factor in most cases. Risk factors include
(1) advanced maternal age, (2) multiparity, (3)
smoking history, (4) prior CD or other uterine surgery
 (e.g., myomectomy), and (5) previous placenta previa.
Women with placenta previa are at an increased risk for
abruptio placentae (relative risk [RR], 13.8), CD (RR,
3.9), fetal malpresentation (RR, 2.8), and PPH (RR,
1.7).58 Women with placenta previa and a prior history of
CD are also at increased risk for placenta accreta59 (see
Table 16.6).

c. Diagnosis
The diagnosis of placenta previa has shifted from clinical
examination of the dilated cervix to sonographic
assessment of the closed internal os, resulting in
confusing terminology. Placenta previa is classified
according to the extent of encroachment of the placenta
(see Fig. 16.2):
 (1) A low-lying placenta encroaches the lower segment
of the uterus but does not infringe on the cervical os.
(2) Marginal placenta touches but does not cover the top
of the cervix.
(3) Partial placenta previa partially covers the cervix.
(4) Complete placenta previa covers the top of the
cervix entirely.
Placenta previa often presents as painless bleeding in
the late second or early third trimester. All vaginal
bleeding in the third trimester should be considered to
be placenta previa until proven otherwise. Some
cases will not bleed until labor begins, but the
majority of cases are diagnosed during routine
ultrasonography in asymptomatic women, usually
during the second trimester. Transvaginal
ultrasonography appears to be superior to
transabdominal ultrasonography for diagnosis.

CLINICAL PEARL Women with placenta previa and a prior

history of CD are at increased risk for placenta accreta.

d. Obstetric management
Obstetric management depends on the degree of blood
loss as well as fetal maturity and status. In such cases, the
fetus is at risk for compromise because of placental
separation resulting in uteroplacental insufficiency or
premature delivery. CD is recommended if the placenta
reaches the cervical margin at time of delivery, and this
entity may be grouped with placenta previa.60 In these
patients, bleeding may stop spontaneously or be sudden
and severe. If the bleeding is ongoing, an urgent CD is
indicated. However, if bleeding has abated and the fetus is
preterm, obstetric management is “expectant” (i.e., bed
rest). There are reports of tocolytic administration in
women who have a preterm fetus and are contracting with
placenta previa. Judicious tocolytic administration is
reasonable if both mother and fetus are stable.61 Steroids
should be administered in women between 24 and 34
weeks of gestation, generally at the time of admission for
bleeding, to promote fetal lung maturation. In women
who have a history of CD or prior uterine surgery,
detailed ultrasonography should be performed to exclude
placenta accreta. As the fetus approaches “term,” fetal
maturity will be assessed (usually be amniocentesis) and
an elective CD will be performed when fetal lung
maturity is confirmed.
e. Anesthetic management
Anesthetic management is dependent on the urgency of
the situation as well as maternal hemodynamic (i.e.,
degree and rate of hemorrhage) status. If there is rapid
or massive hemorrhage, then GA is the most expedient
way to deliver the fetus and stabilize the mother. It may
not be possible to fully resuscitate the mother prior to
 delivery because bleeding will continue until after
delivery of both the fetus and placenta (unless there is no
evidence of placenta accreta). The importance of adequate
IV access cannot be overemphasized in patients with
active bleeding. Flow through an IV cannula is directly
proportional to the fourth power of the radius and
inversely proportional to length. Consequently, one or
more short, large bore peripheral IV catheters are often
preferable to central venous access with longer catheters
(i.e., double-or triple-lumen catheters). An arterial line
can be extremely helpful during a hemorrhagic
emergency, both for beat-to-beat monitoring of BP and for
obtaining frequent laboratory tests.
The ASA Task Force on Obstetric Anesthesia and
the ACOG recommend that all facilities providing
obstetric care be prepared to manage hemorrhagic
emergencies.23 Hand-inflated pressure bags, an automatic
rapid infusion system, a fluid warmer, and a forced-air
warming device are recommended. Because all hospitals
have different capabilities, it is paramount to have
knowledge about blood bank resources for managing
hemorrhage. In cases where the bleeding has stopped
spontaneously, neuraxial anesthesia can be used after
careful assessment of maternal volume status (HR, BP,
urine output). Neuraxial anesthesia may decrease the
estimated blood loss.62 However, hypovolemia is a
relative contraindication to neuraxial anesthesia.

CLINICAL PEARL Anesthetic management is dependent on the

urgency of the situation as well as maternal hemodynamic (i.e.,
degree and rate of hemorrhage) status.

2. Vasa previa
Vasa previa, if undiagnosed, is associated with perinatal
mortality rates of approximately 60% because rupture of
fetal vessels can lead to exsanguination of the fetus and is
often disastrous for fetal well-being.63
a. Definition
Vasa previa occurs when the fetal vessels cross the
membranes ahead of the fetal presenting part.
Consequently, fetal vessels are unprotected by either the
placenta or umbilical cord, resulting in shearing of the
fetal vessels if rupture of membranes occurs.
b. Epidemiology
Vasa previa is a rare obstetric complication with an
estimated incidence of approximately 1 in 2,500
deliveries. Vasa previa is most commonly diagnosed when
vaginal bleeding and fetal bradycardia, or fetal death
accompany rupture of the membranes. Although vasa
previa does not endanger the mother’s life, achieving
optimal fetal outcomes depends on prenatal diagnosis and
appropriate management at the time of delivery.63
Advances in ultrasonography have made it possible to
diagnose vasa previa with reasonable accuracy. Such
diagnostic capabilities allow for proper delivery planning
and management.
c. Obstetric management
The primary obstetric treatment goal is fetal survival. A
ruptured vasa previa is a true obstetric emergency
requiring immediate CD. If diagnosed in early pregnancy,
these patients can be managed in an antenatal unit with
bed rest and frequent monitoring of fetal status. Elective
CD is then performed when fetal maturity has improved
(approximately 34 weeks estimated gestational age
[EGA]).
d. Anesthetic management
Anesthetic management is dependent on the urgency of
 the situation. In cases of ruptured vasa previa, GA is often
required.

CLINICAL PEARL Vasa previa, if undiagnosed, is associated

with high rates of perinatal mortality because rupture of fetal
vessels can lead to exsanguination of the fetus and is often
disastrous for fetal well-being.

3. Abruptio placentae
a. Definition
Abruptio placentae (placental abruption) is defined as
premature separation of a normally implanted placenta
from the decidua basalis after 20 weeks of gestation and
prior to birth. During a normal delivery, maternal blood
loss is limited by constriction of the spiral arteries
following delivery of the placenta. In acute cases of
abruption, bleeding results from exposure of decidual
vessels because the uterus is unable to selectively
constrict the area of abruption. The separation can be a
complete or partial and associated with maternal
hemorrhage. The hemorrhage may be concealed or
present as vaginal bleeding. Loss of placental-uterine
surface area reduces gas exchange and can result in a
distressed fetus and/or fetal asphyxia. Many cases involve
a premature infant and at least half occur prior to the onset
of labor.
b. Epidemiology
Placental abruption occurs in approximately 1% of
pregnancies worldwide with a fetal mortality rate of up to
20% to 40% depending on the degree of separation.
Placental abruption can contribute to maternal mortality64
and may be implicated in up to 10% of preterm births.65
Perinatal mortality is estimated to be 12% among
 pregnancies complicated by abruption.66 Risk factors
include (1) advanced maternal age, (2) multiparity, (3)
hypertension, (4) smoking, (5) trauma, (6) premature
rupture of membranes, (7) trauma, and (8) cocaine
abuse.67 Uterotonic drugs do not increase the risk of
abruptio placentae.68
c. Obstetric considerations
(1) Signs and symptoms
The classically described symptoms of placental
abruption are vaginal bleeding and abdominal pain.
Typically, there is uterine hypertonus associated with
frequent uterine contractions. The uterus is frequently
tender and tense to palpation. Breakthrough pain in a
patient with an otherwise effective labor epidural
may indicate acute abruption. Decidual bleeding with
subsequent hematoma formation leads to progressive
placental separation. Blood may also force its way
through the uterine wall into the serosa, a condition
known as Couvelaire uterus. Up to 90% of abruptions
are mild to moderate without fetal compromise,
maternal hypotension, or coagulopathy. However,
vaginal blood loss is often underestimated and
misleading. In some cases, as much as 3,000 mL of
blood can be sequestered behind the placenta (i.e.,
“concealed bleeding”) without evidence of vaginal
bleeding. Consequently, the amount of vaginal
bleeding can grossly underestimate the volume
status because of the concealed retroplacental
hematoma formation. The primary risk to the
mother is hypovolemic shock due to acute blood loss.

CLINICAL PEARL In cases of placental abruption, the amount

of vaginal bleeding can grossly underestimate the volume status
because of the concealed retroplacental hematoma formation.
 A consumptive coagulopathy can result both
from release of tissue factor into maternal blood
and ongoing blood loss. Thrombocytopenia,
hypofibrinogenemia, and decreased factors V and
VIII are common in such cases. In severe cases, there
may be DIC with evidence of fibrin degradation
products in the blood as well as oozing from IV and
operative sites. This results from either activation of
circulating plasminogen or placental thromboplastin
triggering activation of the extrinsic clotting pathway.
(2) Classification
Abruptions are classified by (1) grade 1—
asymptomatic, associated with vaginal bleeding with
mild uterine tenderness, no distress of mother or
fetus; (2) grade 2—symptomatic mother and some
evidence of fetal compromise; or (3) grade 3—severe
bleeding (which may be occult) leading to maternal
shock and fetal death.
(3) Diagnosis
The diagnosis is generally a clinical diagnosis with
the aid of ultrasound guidance. The
ultrasonographic appearance of abruption depends to
a large extent on the size and location of the bleed as
well as the time frame between the abruption and
time of the ultrasonographic examination. The
Kleihauer-Betke test is sometimes performed in
women when abruption is suspected to quantify
fetomaternal transfusion and guide dosing of Rh-
immune globulin in Rh-negative women.
(4) Obstetric management
The definitive treatment is delivery of the fetus
and placenta. However, the degree of maternal and
fetal compromise will determine the timing and mode
 of delivery. FHR monitoring should be initiated.
Treatment depends on the amount of blood loss and
fetal status. In a case–control study examining the
relationship between decision-to-delivery interval and
perinatal outcome in 33 patients with severe
abruption and fetal bradycardia, Kayani et al.69
determined that longer decision-to-delivery intervals
were associated with poorer perinatal outcomes. In
instances of significant abruption with fetal
bradycardia, minutes may make a difference between
fetal death and survival.
d. Anesthetic management
(1) Anesthetic management is based on the severity of
the abruption and degree of maternal and fetal
compromise. In many cases, the abruption will be
mild or moderate. Vaginal delivery may be the
preferred route of delivery if the FHR is
reassuring without evidence of maternal
hypovolemia, coagulopathy, or ongoing blood loss.
Neuraxial analgesia should be considered when
hypovolemia has been treated, the coagulation status
is normal, and there is no evidence of ongoing
maternal or fetal compromise. When cases of
abruption are complicated by coagulopathy,
laboratories should be obtained including an Hb/Hct,
platelet count, fibrinogen, fibrin degradation
products, thrombelastography (if available), as well
as a type and cross match. In some cases, IV patient
controlled analgesia (PCA) opioid analgesia may be
the only option for pain control.
(2) Anesthetic considerations are similar for CD.
Neuraxial anesthesia can be considered if (1)
maternal status is stable, (2) fetal status is reassuring,
(3) volume status is normal, and (4) coagulation
 studies are normal. Either spinal, epidural, or
combined spinal–epidural (CSE) can be administered.
(3) If the abruption is severe, an emergent CD may be
necessary. GA may be required because patients
typically present with a severely distressed fetus and
maternal hemodynamic instability. In such cases, GA
allows the anesthesia provider to secure the airway,
provide surgical conditions in an expeditious manner,
as well as avoid the stress of managing massive
hemorrhage in a conscious patient. These cases can
be complicated by massive blood loss. The maternal
volume status should be carefully evaluated. Large
bore IVs should be in place because the initial blood
loss may require aggressive fluid resuscitation with
PRBC and blood component therapy. In addition, an
arterial catheter should be inserted when there is
severe hemorrhage and coagulopathy to monitor beat-
to-beat BPs and obtain frequent blood samples for
monitoring of laboratories, including coagulation
status. Some cases may be complicated by uterine
atony and/or coagulopathy. Uterotonics should be
readily available and administered in cases of
persistent atony. In rare cases, hysterectomy may be
necessary to control the blood loss.

CLINICAL PEARL When there is placental abruption, neuraxial

anesthesia can be considered if (1) maternal status is stable, (2) fetal
status is reassuring, (3) volume status is normal, and (4) coagulation
studies are normal.

4. Uterine rupture
Uterine rupture is a potentially catastrophic complication for
mother and fetus. Even though it occurs most commonly in
patients with prior uterine scars (e.g., CD, myomectomy), the
overall risk is low.
a. Definition
Uterine rupture refers to separation of a uterine scar that is
clinically apparent and results in fetal distress and
maternal hemorrhage requiring emergency CD or
postpartum laparotomy. Uterine rupture has also been
reported in women with an unscarred uterus; it is
sometimes related to trauma.70
b. Epidemiology
Uterine rupture is a potentially catastrophic event in
which the integrity of the myometrial wall is breached.
However, in most patients with a prior uterine scar,
the risk of rupture is <1%. Defects may occur
antepartum, intrapartum, or postpartum. The most
common type of defect is uterine scar separation or
dehiscence. Most of these cases are asymptomatic and do
not result in maternal or fetal morbidity. However, actual
uterine rupture is a defect of the uterine wall that is
profound enough to cause fetal compromise and/or
maternal hemorrhage resulting in CD or laparotomy.
Conditions associated with uterine rupture include
(1) separation of a prior uterine scar (e.g., CD,
myomectomy), (2) rapid labor, (3) prolonged labor
associated with oxytocin infusion, (4) traumatic
rupture, (5) weakened uterine musculature (e.g., grand
multiparity, polyhydramnios, connective tissue
disorders), (6) excessive fundal pressure, and (7)
forceps delivery. However, the single most important risk
factor is prior uterine surgery. Rupture of a classical
uterine incision scar (i.e., vertical incision) is associated
with the greatest morbidity and mortality. Compared to a
low transverse uterine scar, the vertical scar involves a
more vascular area and is often the site of placental
 implantation. A retrospective analysis of more than
20,000 deliveries in women with one prior CD
determined that the risk of uterine rupture was (1) 1.6 per
1,000 in nonlaboring women; (2) 5.2 per 1,000 in women
with spontaneous labor; (3) 7.7 per 1,000 in women
undergoing induction of labor; and (4) 24.5 per 1,000
among women undergoing a prostaglandin induction.71
Risk of rupture increases in patients undergoing an
induction of labor, particularly in the presence of an
unfavorable cervix or high fetal station. This practice is
discouraged by the ACOG.72 Maternal mortality is
increased in patients without a prior uterine scar or if
the rupture is traumatic.
c. Diagnosis
Although the diagnosis can be difficult because of
variable presentation, the most consistent clinical feature
of uterine rupture is fetal bradycardia in approximately
70% of patients.73,74 Other signs and symptoms may
include vaginal bleeding, severe abdominal pain, shoulder
pain, and/or hypotension. If rupture is diagnosed
intrapartum, prompt management is essential, and if there
is hypovolemia, fluid resuscitation should begin before
inducing GA and laparotomy. In more severe cases, the
fetus will already be expelled from the uterus into the
abdomen. This is a situation in which the fetus rarely
survives. Serious maternal and fetal morbidity and
mortality occur in 10% to 25% of cases of uterine
rupture.75 Maternal morbidity is associated with gravid
hysterectomy and a high rate of blood loss and
transfusion.
d. Obstetric management
Because most cases of uterine rupture are associated with
trial of labor after cesarean (TOLAC) attempts, this has
been a controversial area of obstetric practice. Despite an
 increasing CD rate, the TOLAC rate has declined
substantially. The most recent ACOG Practice Bulletin on
TOLAC states, “A trial of labor after previous cesarean
delivery should be undertaken at facilities capable of
emergency deliveries.”76 The recommendations further
indicated that “TOLAC is not contraindicated for women
with previous cesarean delivery with an unknown uterine
scar type unless there is a high clinical suspicion of a
previous classical uterine incision.” The ASA Optimal
Goals are also consistent and state that “in cases of
TOLAC, appropriate facilities and personnel, including
obstetric anesthesia, nursing personnel, and a physician
capable of monitoring labor and performing CD,
immediately available during active labor to perform
emergency CD. The definition of immediate availability
of personnel and facilities remains a local decision, based
on each institution’s available resources and geographic
location.”77
When uterine rupture is an incidental finding after
vaginal delivery, the obstetrician must carefully monitor
the patient for concealed bleeding. Close observation is
appropriate in this circumstance. However, when uterine
rupture occurs during labor, explorative laparotomy and
hysterectomy may be required to manage bleeding. The
treatment must be individualized based on maternal and
fetal considerations.
e. Anesthetic considerations
In patients attempting TOLAC, the major signs of
intrapartum rupture are a change in uterine tone or
contraction pattern and FHR abnormalities. Epidural
analgesia is not contraindicated in patients attempting
TOLAC because epidural analgesia with low
concentrations of local anesthetic will not mask the
pain of uterine rupture. Success rates for TOLAC are
 similar to women who do or do not receive epidural
analgesia.76 In these cases, the lowest concentration
possible of local anesthetic with opioid should be used to
ensure adequate analgesia. If the trial of labor is
unsuccessful and both mother and fetus are stable, the
epidural block may be extended and used for CD.
However, in a true emergency where the uterine scar is
ruptured and the fetus is distressed or there is maternal
cardiovascular instability, GA for emergent CD is
indicated. In such cases, invasive hemodynamic
monitoring, volume resuscitation, and transfusion may be
necessary. Hemorrhage may be uncontrollable and
hysterectomy is necessary.
C. Postpartum hemorrhage
PPH is often defined as the loss of more than 500 mL of blood
after vaginal delivery or 1,000 mL after CD within the first 24
hours following delivery. Severe hemorrhage is the primary cause
of maternal death worldwide78 with >50% of these deaths
occurring within 24 hours of delivery. In the United States, it is an
important contributor to maternal morbidity and mortality.79,80
Morbidity results in coagulopathy, shock, adult respiratory
distress syndrome, loss of fertility, and pituitary necrosis.46
Recently, Clark and Hankins1 stated to “ never treat ‘postpartum
hemorrhage’ without simultaneously pursuing an actual clinical
diagnosis” because PPH is a “clinical sign of an underlying
condition that is amenable to diagnosis.”
1. Uterine atony
a. Epidemiology
Uterine atony is the most common cause of PPH.79 It
complicates up to 10% of deliveries and is the most
common cause of serious obstetric hemorrhage. Although
rates of PPH from uterine atony are increasing, this is not
explained by changes in rates of CD, TOLAC, maternal
age, multiple births, hypertension, or diabetes mellitus.79
 Uterine atony manifests as a noncontracted uterus with
severe bleeding. Risk factors include (1) rapid or
protracted delivery, (2) tocolysis, (3) overdistention of the
uterus (e.g., multiple gestations, macrosomia,
polyhydramnios), (4) high parity, (5) prolonged oxytocin
infusion (i.e., either induced labor or augmented labor),
(6) chorioamnionitis, (7) retained placenta, (8) operative
assisted vaginal delivery, (9) GA with volatile agents, and
(10) previous or current gestational trophoblastic disease,
(11) hypertensive disease, (12) diabetes, and (13)
advanced maternal age.
b. Medical management
The initial treatment of uterine atony is medical
management, including the active management of the
third stage of labor (i.e., oxytocin administration and
uterine massage). The ACOG recommends prophylactic
uterotonic administration to stimulate uterine contraction
and prevent uterine atony.34
(1) These uterotonic agents include:
(a) Oxytocin. Oxytocin is an effective first-line
treatment for PPH. Oxytocin is usually
administered by rapid IV infusion with 20 to 40
U added per 1 L normal saline (NS) or Ringer’s
lactate (LR) solution.81 Many practitioners avoid
bolus dosing because oxytocin is a systemic
vasodilator and may aggravate hypotension,
especially during severe hemorrhage.
(b) Methylergonovine. When oxytocin fails,
prostaglandins and ergot alkaloids are
considered second-and third-line treatments.
They enhance uterine contractility and cause
vasoconstriction. Methylergonovine
(Methergine) is an ergot alkaloid that causes
generalized smooth muscle contraction in which
 the upper and lower segments of the uterus
contract simultaneously. Because ergot alkaloid
agents increase BP, they are relatively
contraindicated in women with preeclampsia or
hypertension. Other relative contraindications
include peripheral vascular disease and coronary
artery disease. Methergine should not be
administered IV, but intramuscularly (IM) at a
dose of 0.2 mg. Other adverse effects include
nausea, vomiting, and in rare cases, pulmonary
edema. Recent evidence suggests that the risk of
myocardial ischemia is negligible.82
(c) 15-Methyl prostaglandin F2α. The
prostaglandin most commonly used is 15-methyl
prostaglandin F2α, or carboprost (Hemabate). It
can be administered intramyometrially or IM in
a dose of 0.25 mg; this dose can be repeated
every 15 minutes for a total dose of up to 2 mg.
Carboprost has been proved to control
hemorrhage in up to 87% of patients and may
control hemorrhage when other medical
treatments fail.83 Despite the success of this
medication, it should be used cautiously in
asthmatic patients. It is known to cause
abnormal ventilation–perfusion ratios, increased
pulmonary shunt fraction, and hypoxemia.
Relative contraindications include hepatic,
cardiac, and renal disease. It is also known to
produce tachycardia, diarrhea, and fever.
(d) Misoprostol (PGE1, Cytotec). Prostaglandins
have been used for PPH when other measures
fail.84 Misoprostol, is an inexpensive
prostaglandin E1 analog and has been suggested
as an alternative for routine management of the
 third stage of labor. When administered rectally
(800 to 1,000 μg), misoprostol has been effective
in treating PPH when other medical treatments
fail. There are few, if any, side effects.
Misoprostol does not require refrigeration for
storage, thus making it attractive for use in
underdeveloped countries.

CLINICAL PEARL The initial treatment of uterine atony is

medical management, including the active management of the third
stage of labor (i.e., oxytocin administration and uterine massage).
The ACOG recommends prophylactic uterotonic administration to
stimulate uterine contraction and prevent uterine atony.

c. Invasive therapy
Conservative therapy sometimes fails to treat uterine
atony.
(1) Uterine atony unresponsive to medical therapy is
treated with tamponade techniques (e.g., Sengstaken-
Blakemore tube, Bakri balloon) or surgical
procedures (e.g., uterine curettage, uterine artery
ligation, B-Lynch suture, hypogastric artery
ligation, hysterectomy),46 whereas fluid
resuscitation is initiated as necessary to prevent
obstetric shock. Invasive management is aimed at
preventing uterine atony by compressive methods
(i.e., uterus hemostatic suture by B-Lynch or uterine
Z-suture) or achieving selective uterine
devascularization (e.g., vascular ligation of uterine
arteries, ovarian arteries, and hypogastric arteries;
and/or selective transarterial embolization of uterine
arteries) to prevent hemorrhage.
(2) In some cases, arterial embolization is used to
 reduce hemorrhage. It is a procedure that is available
in a number of centers that are staffed with
appropriately trained interventional radiologists. The
catheter is introduced via the femoral artery and is
advanced above the bifurcation of the aorta where the
bleeding point is identified by contrast injection. The
feeder artery is catheterized and embolized with
absorbable gelatin sponge, which is usually resorbed
in about 10 days. However, “angiographic
embolization is not meant to be used for acute,
massive postpartum hemorrhage.”1
(3) Hysterectomy is the last resort in the management
of PPH due to uterine causes. In most instances, a
subtotal hysterectomy, which is rapid, simple, safe,
and associated with less blood loss, is effective. Total
hysterectomy is necessary in cases where bleeding
occurs in the lower segment such as placenta previa
with accreta and tears into the lower segment.
Hysterectomy is reserved when all other treatments
available have been exhausted, bleeding continues,
and when further delay may compromise a patient
who is in severe shock. It is also the definitive
treatment in cases of coagulopathy when no
replacement blood products are available.19
2. Retained placenta
The third stage of labor is delivery of the placenta. The
retroplacental myometrium must contract to allow the
placenta to shear away from its bed and be expelled.
a. Epidemiology
Retained placenta complicates approximately 1% of
deliveries worldwide and is a significant cause of
maternal mortality and morbidity. In the developing
world, the associated mortality approaches 10% from
resulting PPH. However, not all cases of retained placenta
 result in PPH. If the uterus contracts despite retained
fragments, little or no hemorrhage occurs. Risk factors
include previous history of retained placenta, previous
injury to uterus, preterm delivery, induced labor, and
multiparity.
b. Obstetric management
Oxytocics cause myometrial contraction, which generates
a shearing force that detaches the placenta from the
uterine wall. However, after placental detachment,
cervical constriction may trap the placenta within the
uterus. Manual removal of the placenta is standard
treatment. After removal, the placenta should be inspected
to ensure that there are no other retained fragments. In
addition, uterine tone should be assessed for evidence of
uterine atony and ongoing hemorrhage. Uterine curettage
will be necessary in some cases.
c. Anesthetic management
(1) Analgesia or anesthesia is often necessary in cases of
retained placenta because the obstetrician must
explore a uterus that is often partially contracted. In
some patients who have not received a neuraxial
block prior to delivery, IV analgesia with ketamine
(0.1 mg per kg), benzodiazepines, and judicious
administration of opioids (e.g., fentanyl) may be
adequate. However, it is essential to prevent
excessive sedation and loss of the maternal airway.
(2) If sedation is inadequate, the choice of anesthetic
technique depends largely on the degree of
hemorrhage. Spinal anesthesia is a reasonable choice
for patients who are hemodynamically stable with
little evidence of hemorrhage. However, in patients
with profound hemorrhage, GA is a better choice
because of the risk of hypotension resulting from
sympathetic blockade in a patient with hypovolemia
 who has just received spinal anesthesia. In cases
where there is an indwelling neuraxial catheter and
the patient is hemodynamically stable, the addition of
more concentrated local anesthetic (e.g., 3% 2-
chloroprocaine) may be necessary to achieve
adequate anesthesia for uterine exploration.
(3) Obstetricians may request uterine relaxation for
removal of retained placenta. In the past, GA with
volatile anesthetic provided such relaxation. More
recently, reports consistently suggest that modest
incremental doses of IV nitroglycerin (25 to 50 µg)
are effective in producing adequate uterine relaxation
without major side effects. Nitroglycerin spray has
also been administered sublingually as an effective
uterine relaxant.

CLINICAL PEARL Analgesia or anesthesia is often necessary

in cases of retained placenta because the obstetrician must explore a
uterus that is often partially contracted.

3. Placenta accreta
Placenta accreta is a potentially life-threatening pregnancy-
related complication. Although the incidence of placenta
accreta has increased over the past 20 to 30 years,85,86
estimates suggest that the complication occurs between 1 and
90 per 10,000 deliveries and is dependent on the frequency of
CD.87 A recent retrospective cohort study using data from the
Canadian Institute for Health Information of more than
570,000 deliveries from 2009 to 2010 determined that there
was a strong association between placenta accreta and PPH
with hysterectomy.88
a. Definition
Placenta accreta refers to a placenta that is abnormally
 attached to the uterus. When the placenta invades the
myometrium, the term placenta increta is used, whereas
placenta percreta refers to a placenta that has invaded
through the myometrium and serosa, sometimes into
adjacent organs, such as the bladder (see Fig. 16.2). The
term placenta accreta is often used interchangeably as a
general term to describe all of these conditions. These
conditions can all cause maternal hemorrhage.
b. Epidemiology
Prior CD and presence of placenta previa in the current
pregnancy are important risk factors. In a multicenter
study of more than 30,000 patients who underwent CD
without labor, the risk of placenta accreta was
approximately 0.2%, 0.3%, 0.6%, 2.1%, and 7.7% for
women experiencing their first through sixth CD,
respectively. In patients with placenta previa, the risk of
accreta was 3%, 11%, 40%, 61%, and 67% for those
undergoing their first through their fifth or greater CD,
respectively.59 Other risk factors include (1) placenta
previa with or without prior uterine surgery, (2) prior
myomectomy, (3) prior CD, (4) Asherman syndrome, (5)
submucous leiomyomata, and (6) maternal age older than
35 years. Placenta accreta accounts for up to 50% of
all cesarean hysterectomies, most of which are
unplanned.
c. Diagnosis
There should be a high degree of clinical suspicion in
women with placenta previa or a history of CD or other
uterine surgery. Vigilance is particularly indicated when
the placenta is anterior and overlies the cesarean scar.
Ultrasonography is the primary imaging modality for
diagnosing accreta and is readily available in most
centers. Color Doppler techniques may also be helpful in
the diagnosis.34 Although most studies have suggested
 reasonable diagnostic accuracy of MRI for placenta
accreta, it appears that MRI is no more sensitive than
ultrasonography for diagnosing placenta accreta.89
However, MRI may be more useful in the diagnosis of
cases when the placenta is situated posteriorly.
d. Obstetric management
(1) The ACOG suggests that the following measures
be taken when there is a strong suspicion of
placenta accreta before delivery:34
(a) The patient should be counseled about the
likelihood of hysterectomy and blood
transfusion.
(b) Blood products and clotting factors should be
available.
(c) Cell saver technology should be considered if
available.
(d) The appropriate location and timing for delivery
should be considered to allow access to adequate
surgical personnel and equipment.
(e) A preoperative anesthesia assessment should be
obtained.
(2) The area and depth of the abnormal attachment will
determine the obstetric treatment (i.e., curettage,
wedge resection, medical management, or
hysterectomy). When there is a small focal area of
abnormal attachment, conservative treatment may be
effective. However, in many cases, abdominal
hysterectomy is the definitive treatment approach.
e. Anesthetic management
(1) The role of experienced anesthesiology personnel
who are skilled in obstetric anesthesia cannot be
overemphasized, and they should be involved in
preoperative assessment of the patient.
(2) In cases of unexpected placenta accreta during
 elective CD, GA is often necessary to protect the
patient’s airway. In all cases of placenta accreta, the
anesthesia provider should be prepared for massive
hemorrhage with adequate IV access and large
amounts of crystalloid, colloid, and blood products.
(3) In patients who are hemodynamically stable and
euvolemic, but are at risk for placenta accreta and
hysterectomy, a continuous catheter neuraxial
technique has been shown to be a reasonable
option.90,91 However, the neuraxial technique may
fail because (1) extended operative time predisposes
the patient to restlessness and fatigue, (2) surgical
retraction exceeds that required by CD alone, and (3)
a quiet operative field is necessary for dissection.90
When patients are candidates for neuraxial
anesthesia, they should be counseled about the risks
and benefits of such techniques, specifically that the
neuraxial technique might be inadequate and require
conversion to GA. When an epidural is in place but
GA becomes necessary, the epidural anesthetic
reduces volatile anesthetic requirements and can be
used for postoperative analgesia.
f. Interventional radiology techniques
Although controversial, preoperative placement of
internal iliac artery balloon catheters and ureteral stents
may be helpful to control hemorrhage during CD and
subsequent hysterectomy. In the largest of studies,
placement of balloon catheters preoperatively reduced (1)
the mean estimated blood loss, (2) the number of cases
with blood loss more than 2.5 L, and (3) the number of
massive transfusions.92 However, there can be
complications related to placement (e.g., fetal
bradycardia) and postoperatively (e.g., lower extremity
ischemia) (see Table 16.7). The Society of Maternal-Fetal
 Medicine recommends prophylactic intra-arterial balloon
catheters for women who (1) have a desire to preserve
fertility, (2) decline blood products, and (3) who have
unresectable placenta percreta.93 In cases where
embolization techniques are unsuccessful, hysterectomy
will be necessary and the anesthesia provider should be
prepared for significant hemorrhage and transfusion
requirements.

CLINICAL PEARL In all cases of placenta accreta, the

anesthesia provider should be prepared for massive hemorrhage
with adequate IV access and large amounts of crystalloid, colloid,
and blood products.

4. Uterine inversion
a. Definition
Uterine inversion is a “turning inside out” of the uterus.
Although rare, it has potentially serious consequences. It
is classified as complete if the fundus passes through the
cervix, or incomplete if it remains above this level. The
underlying causes are not completely understood94 but
risk factors include (1) overzealous fundal pressure, (2)
excessive umbilical cord traction, (3) uterine
anomalies, (4) uterine atony, and (5) placenta accreta.
b. Diagnosis
Cases of uterine inversion are often obvious because of
 hemorrhage and a mass in the vagina. In the past,
obstetricians have suggested that the degree of
hemorrhage was disproportionate to the degree of shock.
However, an atonic, inverted uterus will contribute to
severe hemorrhage and shock.
c. Obstetric management
Management of uterine inversion has two important
components: the immediate treatment of hemorrhagic
shock and replacement of the uterus. Atony usually
resolves after replacement followed by medical treatment
(e.g., oxytocin infusion).
d. Anesthetic management
Resuscitation should begin immediately while attempts
are made to replace the uterus manually because
hypotension and bradycardia may occur. In most cases,
neuraxial analgesia does not provide adequate relaxation
but may be helpful in providing analgesia. Reports
suggest that nitroglycerin may obviate the need for GA,
although GA with a volatile halogenated agent may be
necessary for uterine relaxation. Other anecdotal reports
suggest terbutaline as well as magnesium sulfate tocolytic
therapies. Severe cases require laparotomy.

CLINICAL PEARL Management of uterine inversion has two

important components: the immediate treatment of hemorrhagic
shock and replacement of the uterus.

III. Intrapartum emergencies

A. Preterm labor and delivery
Preterm delivery is defined as a delivery that occurs before 37
weeks’ gestation. In the United States, it occurs in up to 13% of
all pregnancies, whereas in other developed countries, the
incidence is between 5% and 9%.95 Preterm delivery is a
significant cause of neonatal morbidity and mortality with
estimates suggesting that preterm delivery is responsible for up to
80% of neonatal deaths.96
1. Risk factors. Although many factors have been associated
with preterm labor, multiple gestations, history of preterm
delivery, and non-Hispanic black race are the most significant
risk factors.
2. Anesthetic management
Patients in preterm labor will often request neuraxial
analgesia for labor and vaginal delivery. Some patients will
require urgent CD, especially for abnormal presentations with
advanced cervical dilation and nonreassuring fetal status.
These clinical conditions will often present as obstetric
emergencies. Although there is a theoretical concern that the
preterm fetus is vulnerable to the depressant effects of
anesthetic agents, studies evaluating fetal pharmacokinetics
and pharmacodynamics of anesthetic agents are limited.
a. Vaginal delivery. Neuraxial analgesia is frequently
requested for its profound analgesic effects and the ability
to convert a labor epidural to a surgical anesthetic if CD
becomes necessary. However, timing of neuraxial
placement can be difficult because the parturient may not
be in active labor and if she is, labor may proceed rapidly.
In many cases, it is prudent to place the labor epidural
before the onset of labor.
b. Cesarean delivery. Neuraxial anesthesia, either spinal,
CSE, or epidural is preferred for CD in order to prevent
the depressant effects of GA. The concern with
administration of GA is the potential risk of brain-cell
apoptosis in the developing fetal/neonatal brain following
administration of propofol, ketamine, and inhalational
agents.97,98 However, the duration of exposure to these
agents in these animal models was considerably longer
than in a CD in humans. So although there are theoretical
 concerns about the use of GA in this situation, there is no
current evidence that the anesthetic technique must be
altered because of the gestational age.
c. Tocolytics and their interactions
(1) Calcium-entry blocking drugs (e.g., nifedipine) have
a low incidence of maternal and fetal side effects.
However, when nifedipine is administered in addition
to volatile anesthetics, it can potentially cause
vasodilation, hypotension, myocardial depression,
and cardiac conduction abnormalities.99 Calcium-
entry blocking drugs are often used as first-line
treatment for preterm labor.100
(2) Cyclooxygenase inhibitors (e.g., indomethacin) have
been found to be effective in the treatment of preterm
labor. Although these agents do not cause alternations
in BP or HR, their administration is limited to less
than 72 hours because of conflicting data regarding
adverse neonatal outcomes associated with calcium-
entry blocking drug therapy.101 Calcium-entry
blocking drug therapy is not a contraindication to
neuraxial anesthesia.
(3) Magnesium sulfate is considered beneficial for
neuroprotection in preterm neonates and is used less
frequently for treatment of preterm labor. Maternal
side effects include (1) flushing, (2) sedation, (3)
chest pain, (4) blurred vision, (5) hypotension, and
(6) pulmonary edema.102,103 In some cases,
pulmonary edema can be life threatening. Because
magnesium sulfate administration may increase the
risk of hypotension during neuraxial anesthetic
administration, the anesthesia provider must be aware
and administer vasopressor therapy when indicated.
Because magnesium also potentiates the action of
depolarizing and nondepolarizing neuromuscular
 blocking agents104 by (1) limiting the release of
succinylcholine at the neuromuscular endplate, (2)
decreasing membrane excitability, and (3) reducing
the sensitivity of the neuromuscular endplate to
acetylcholine, judicious use of both depolarizing and
nondepolarizing neuromuscular blocking agents is
recommended.
(4) Beta-adrenergic receptor agonists (e.g., terbutaline)
were used in the past for treatment of preterm labor;
however, because of the associated fetal and maternal
side effects such as (1) tachycardia, (2) hypotension,
(3) myocardial ischemia, (4) dysrhythmias, (5)
pulmonary edema, (6) hypokalemia, and (7)
hyperglycemia, their use has markedly declined.105
(5) Oxytocin antagonists (e.g., atosiban) have been
shown to be effective without increasing the risk of
postpartum uterine atony and hemorrhage.106
Although not currently available in the United States,
oxytocin antagonists are widely used in Europe
because of the favorable side effect profile for mother
and fetus.
B. Shoulder dystocia
1. Diagnosis and recognition
Shoulder dystocia, or impacted shoulder, represents the failure
of delivery of the fetal shoulder(s). It is rare and occurs in
0.2% to 3.0% of all deliveries. Nevertheless, it is one of the
primary causes of birth trauma and in severe cases can be
associated with significant perinatal (e.g., fetal asphyxia,
damage to the brachial plexus) and maternal morbidity. This
complication is often unexpected and may be difficult to
predict, but numerous risk factors have been proposed for the
occurrence of the event.
During labor, as the fetus descends into the pelvis, the
shoulders assume an anterior–posterior alignment. Then, the
 shoulders rotate into an oblique position. Failed rotation of the
fetal trunk and shoulders can result in entrapment of the
anterior shoulder beneath the pubic symphysis causing
shoulder dystocia. Mild shoulder dystocia may not require
ancillary obstetric maneuvers. However, if there is severe
shoulder dystocia, and the interval between delivery of the
head and delivery of the shoulders is extended beyond several
minutes, the fetal blood supply may be compromised by
umbilical cord compression.
2. Risk factors
Risk factors cannot always be identified before labor and
delivery. However, fetal macrosomia, maternal diabetes
mellitus, delayed active phase of labor, prolonged second
stage of labor, gestational age greater than 40 weeks, maternal
weight, and instrumental delivery are all potential risk factors
for shoulder dystocia.107
3. Obstetric management
It is important that the obstetrician recognizes the warning
signs of shoulder dystocia before and during delivery. With
respect to making a decision for CD without labor, Rouse and
colleagues108 constructed a decision analytic model to
compare three policies in both diabetic and nondiabetic
patients: (1) management without ultrasound, (2) ultrasound
and elective CD for estimated fetal weight of 4,000 g or more,
and (3) ultrasound and elective CD for estimated fetal weight
of 4,500 g or more. The authors determined that for diabetic
patients, a policy for elective CD for ultrasonographically
diagnosed fetal macrosomia was favorable for both CD and
reduction of cost per permanent injury. During delivery,
retraction of the head (i.e., “turtle sign”) after initial delivery
occurs because the anterior shoulder is entrapped below the
symphysis pubis; it is one of the warning signs associated
with shoulder dystocia. It is imperative that the obstetrician
examine whether there is ample time to safely deliver the
fetus without injury. Several maneuvers have been described
for the successful alleviation of shoulder dystocia.60
a. Suprapubic pressure
Suprapubic pressure, commonly administered by nursing
personnel, is directed toward the pelvic floor and is
performed in conjunction with gentle traction on the fetal
head. If successful, this maneuver dislodges the anterior
shoulder from above the public symphysis. Other
described techniques for suprapubic pressure have
included lateral application from either side of the
maternal abdomen or alternating between sides using a
rocking pressure.
b. McRoberts maneuver
If suprapubic pressure is unsuccessful in delivering the
shoulders, the McRoberts maneuver is performed in rapid
succession by sharply flexing the maternal thighs onto the
abdomen. This results in a straightening of the maternal
sacrum relative to the lumbar spine with subsequent
cephalic rotation of the symphysis pubis. The McRoberts
maneuver is associated with a significant degree of
success in relieving shoulder dystocia. Care should be
taken to avoid prolonged or overly aggressive application
of the McRoberts maneuver because the
fibrocartilaginous articular surfaces of the symphysis
pubis and surrounding ligaments may be unduly stretched.
c. Intravaginal pressure on the posterior shoulder
If the McRoberts maneuver is unsuccessful, the
practitioner attempts to abduct the posterior shoulder by
exerting intravaginal pressure onto the anterior surface of
the posterior shoulder (i.e., Woods corkscrew maneuver).
The physician places at least two fingers on the anterior
aspect of the fetal posterior shoulder, applying upward
pressure around the circumference. This maneuver may
be combined to increase torque forces by using two
 fingers behind the fetal anterior shoulder and two fingers
in front of the fetal posterior shoulder.
d. Delivery of the posterior arm
Delivery of the posterior arm involves placing the
physician’s hand in the vagina and locating the fetal arm,
which sometimes is displaced behind the fetus and must
be nudged anteriorly. The physician’s hand, wrist, and
forearm may need to enter the vagina, necessitating an
episiotomy or extension. The fetal elbow is then flexed,
and the forearm is delivered in a sweeping motion over
the anterior chest wall of the fetus.
e. The Zavanelli maneuver109
The Zavanelli maneuver involves replacement of the
head into the vagina followed by immediate CD. It
requires reversal of the cardinal movements of labor:
internal rotation, flexion, and subsequent manual
replacement of the fetal vertex into the vagina.
Performing this maneuver is often complicated by the
provider’s lack of clinical experience, emergent
conditions, and potential for significant maternal and
neonatal complications. However in Sandberg’s109 review
encompassing 12 years of recorded experience, the
Zavanelli maneuver successfully returned 84/92 (92%)
fetuses into the vagina. In this series, there were no
reports of injury to the fetus resulting from the Zavanelli
maneuver.
4. Anesthetic management
Although neuraxial anesthesia is very helpful in these
situations, it is not essential. Early recognition of a shoulder
dystocia is imperative, and if an epidural catheter is in place,
the anesthesia provider should administer 10 to 15 mL of
either 3% 2-choloroprocaine or 2% lidocaine with bicarbonate
to enhance pelvic relaxation. If all options for obstetric
management of shoulder dystocia have been exhausted and
 the Zavanelli maneuver is necessary, the anesthesia provider
should administer IV nitroglycerin to facilitate replacement of
the fetal head into the vagina prior to CD. In patients without
a neuraxial catheter, GA for emergency CD will be necessary.

CLINICAL PEARL Early recognition of a shoulder dystocia is

imperative, and if an epidural catheter is in place, the anesthesia
provider should administer 10 to 15 mL of either 3% 2-
choloroprocaine or 2% lidocaine with bicarbonate to enhance pelvic
relaxation.

C. Umbilical cord compression/prolapse

1. Diagnosis
Umbilical cord prolapse is another complication that can
cause fetal asphyxia and is stressful for patients and their
attendants. In recent retrospective survey, the incidence of
cord prolapse has decreased from 6.4 per 1,000 live births in
the 1940s to 1.7 per 1,000 live births in the last decade.110
Perinatal survival increased from 46% to 94% in the same
period of time. This trend was explained by the higher use of
CD.
2. Obstetric management
Several techniques have been described to reduce the pressure
of the presenting part on the umbilical cord during
contractions. Whether the umbilical cord compression is
partial or complete may be difficult to determine but depends
on the station of the presenting part. Although manual
reduction or manual head elevation and subsequent CD are
the primary obstetric treatments used, Katz et al.111 described
the successful use of retrograde bladder filling with 500 to
600 mL of saline in combination with IV ritodrine. The
bladder filling may reduce the pressure on the umbilical cord
by displacement and elevation of the presenting part.
 However, if umbilical cord prolapse is associated with
refractory fetal bradycardia, a CD should be performed
immediately.
3. Anesthetic considerations
If emergency CD is required because of prolonged fetal
bradycardia resulting from umbilical cord prolapse, GA is
usually necessary unless there is an existing neuraxial
catheter. The decision to use either GA or the existing
neuraxial catheter is dependent on the anesthesia provider’s
assessment of the time required to achieve adequate neuraxial
anesthesia and the anticipated difficulty for GA as well as the
obstetrician’s assessment of fetal reserve. As in all obstetric
emergencies, communication between the care providers is
essential.

CLINICAL PEARL If emergency CD is required because of

prolonged fetal bradycardia resulting from umbilical cord prolapse,
GA is usually necessary unless there is an existing neuraxial
catheter.

D. Amniotic fluid embolism112

AFE is a rare complication of pregnancy that presents with signs
and symptoms similar to other obstetric complications (see Table
16.8). Although diagnosis is often challenging and difficult,
estimates suggest an incidence ranging from 2.0 to 7.7 per
100,000 in developed countries.113–116 However, data is sparse
from lesser developed countries. Data from the United Kingdom
suggest that based on their surveillance system, 56% of cases
occurred before and during delivery, whereas 44% occurred after
delivery.114 It is frequently a diagnosis of exclusion.
1. Risk factors. Many risk factors (e.g., CD, instrumented
delivery, placenta previa, placental abruption, eclampsia) for
AFE have been suggested, but in five developed countries
(United States, Canada, United Kingdom, Australia,
Netherlands), only induction of labor and maternal age >35
were identified among studies in these countries.117
2. Pathophysiology. Although there have been many proposed
mechanisms, the pathogenesis remains unclear. Most agree
that AFE is an immune-mediated response resulting from
entry of amniotic fluid into the maternal circulation by a break
in the maternal/fetal interface. Amniotic fluid contains several
vasoactive substances (e.g., leukotrienes, arachidonic acid,
bradykinin, and cytokines), which potentially trigger DIC—a
common complication occurring with AFE.118 In addition,
complement likely plays a role in development of the
disorder. The syndrome is likely not due to an embolic event
or caused by amniotic fluid, so the label is a misnomer.119
3. Clinical presentation. Diagnosis of AFE is based on the
clinical presentation.112 Common signs and symptoms include
the sudden onset of dyspnea and oxygen desaturation. Severe
hypotension, cardiac dysrhythmias, cardiovascular collapse,
and cardiac arrest commonly follow the onset of respiratory
 signs and symptoms. Sudden cardiovascular collapse is
attributed to profound vasospasm of the pulmonary
vasculature resulting in severe pulmonary hypertension and
right ventricular dysfunction. If GA is administered, there will
be a decrease in end-tidal carbon dioxide. In up to 50% of
cases, there is a rapid onset of DIC. Diagnosis is based on
these signs and symptoms, but other maternal conditions as
well as other obstetric and anesthetic complications must be
considered (see Table 16.8).
4. Management
a. Obstetric management. If AFE occurs before delivery and
cardiac arrest occurs, advanced cardiac life support
(ACLS) must be initiated immediately along with uterine
displacement. Fetal viability should not be confirmed.
Guidelines for resuscitation during cardiac arrest
recommend rapid delivery of the fetus by CD within 5
minutes of the arrest.120,121 This approach aims to
improve maternal outcomes during resuscitation and
increase the chances of neonatal survival with minimal
neurologic damage. In addition to effective chest
compressions and early defibrillation, drug dosages and
recommendations for defibrillation are unchanged from
nonpregnant individuals.120,121 If the woman is
undelivered and a perimortem CD performed, it is prudent
to activate a massive transfusion protocol because of
expected coagulopathy and hemorrhage. In most cases,
hysterectomy will be necessary for management of
associated hemorrhage.
b. Anesthetic management. Goals of anesthetic management
include correction of (1) hemodynamic instability, (2)
hypoxemia, and (3) coagulopathy. “The effectiveness of
replacement and supportive therapy should be
continuously monitored by the signs and symptoms of
adequate oxygen delivery and tissue perfusion.”122
(1) Hemodynamic instability is often treated with
aggressive IV fluid administration, vasopressor
therapy, and inotropic support. Placement of an intra-
arterial catheter should occur early in management to
monitor beat-to-beat BPs as well as facilitate analysis
of blood gases and laboratories. A pulmonary artery
catheter may be considered. However, in most cases,
patients require intubation, and if available,
transesophageal echocardiography will assess cardiac
function as well as guide fluid management and
vasopressor therapy.123
(2) Early intubation and ventilatory support are the most
effective measures to improve ventilation and
oxygenation.
(3) Coagulopathy is frequently accompanied by
hemorrhage. Treatment involves administration of
PRBCs, FFP, platelets, and cryoprecipitate.
Activation of a massive transfusion protocol should
be considered early in management.124 The
transfusion ratio in those cases will be 1:1 PRBC to
FFP. Although there are reports of the successful use
of rFVIIa in cases where coagulopathy could not be
corrected, a recent systematic review concluded that
88% of patients receiving rFVIIa had worse
outcomes (i.e., permanent disability, death) compared
to the 39% who did not receive the therapy.125 The
authors concluded that rFVIIa should only be used as
a last resort to treat coagulopathy and hemorrhage
associated with AFE.
(4) If all else fails, there are reports of (1) inhaled nitric
oxide administration, (2) prostacyclin administration,
(3) exchange transfusion, (4) plasma exchange, (5)
cardiopulmonary bypass, (6) extracorporeal
membrane oxygenation, and (7) right ventricular
 assist device placement.
5. Outcome. Although a report from 1979 estimated that 86% of
AFE cases resulted in maternal mortality,126 more recent large
population-based studies from developed countries have
reported maternal mortality rates between 13% and
35%.113–116,127 Rates of maternal death associated with AFE
appear to have improved, but the reasons for improvement are
unclear. Unfortunately, AFE is a leading cause of death in the
United States, and survivors often report major adverse
outcome including neurologic injury.114

REFERENCES
1. Clark SL, Hankins GD. Preventing maternal death: 10 clinical diamonds. Obstet Gynecol.
2012;119:360–364.
2. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 326:
inappropriate use of the terms fetal distress and birth asphyxia. Obstet Gynecol. 2005;106:1469–1470.
3. Bax M, Nelson KB. Birth asphyxia: a statement. Dev Med Child Neurol. 1993;35:1022–1024.
4. American College of Obstetricians and Gynecologists Task Force on Neonatal Encephalopathy and
Cerebral Palsy, American Academy of Pediatrics. Neonatal Encephalopathy and Cerebral Palsy:
Defining the Pathogenesis and Pathophysiology. Washington, DC: American College of Obstetricians
and Gynecologists; 2003.
5. Herrera-Marschitz M, Neira-Pena T, Rojas-Mancilla E, et al. Perinatal asphyxia: CNS development
and deficits with delayed onset. Front Nuerosci. 2014;8:47.
6. MacLennan A. A template for defining a causal relation between acute intrapartum events and cerebral
palsy: international consensus statement. BMJ. 1999;319:1054–1059.
7. American College of Obstetricians and Gynecologists. Neonatal encephalopathy and cerebral palsy:
executive summary. Obstet Gynecol. 2004;103:780–781.
8. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 348: umbilical
cord blood gas and acid-base analysis. Obstet Gynecol. 2006;108:1319–1322.
9. Dawes GS. Sudden death in babies: physiology of the fetus and newborn. Am J Cardiol. 1968;22:469–
478.
10. Fetal physiology and cell biology. In: American College of Obstetricians and Gynecologists, American
Academy of Pediatrics, eds. Neonatal Encephalopathy and Neurologic Outcome. 2nd ed. Washington,
DC: American College of Obstetricians and Gynecologists; 2014:21–36.
11. Badawi N, Kurinczuk JJ, Keogh JM, et al. Antepartum risk factors for newborn encephalopathy: the
Western Australian case-control study. BMJ. 1998;317:1549–1553.
12. Leveno KJ, Cunningham FG, Nelson S, et al. A prospective comparison of selective and universal
electronic fetal monitoring in 34,995 pregnancies. N Engl J Med. 1986;315:615–619.
13. Macones GA, Hankins GD, Spong CY, et al. The 2008 National Institute of Child Health and Human
Development workshop report on electronic fetal monitoring: update on definitions, interpretation,
and research guidelines. Obstet Gynecol. 2008;112:661–666.
14. Clark SL, Nageotte MP, Garite TJ, et al. Intrapartum management of category II fetal heart rate
tracings: towards standardization of care. Am J Obstet Gynecol. 2013;209:89–97.
15. Graham EM, Adami RR, McKenney SL, et al. Diagnostic accuracy of fetal heart rate monitoring in
the identification of neonatal encephalopathy. Obstet Gynecol. 2014;124:507–513.
16. Alfirevic Z, Neilson JP. Doppler ultrasonography in high-risk pregnancies: systematic review with
meta-analysis. Am J Obstet Gynecol. 1995;172:1379–1387.
17. Tolsa CB, Zimine S, Warfield SK, et al. Early alteration of structural and functional brain development
in premature infants born with intrauterine growth restriction. Pediatr Res. 2004;56:132–138.
18. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 36: obstetric
analgesia and anesthesia. Int J Gynaecol Obstet. 2002;78:321–335.
19. American College of Obstetricians and Gynecologists. Standards of Obstetric-Gynecologic Services.
7th ed. Washington, DC: American College of Obstetricians and Gynecologists; 1989:39.
20. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 433: optimal
goals for anesthesia care in obstetrics. Obstet Gynecol. 2009;113:1197–1199.
21. Korhonen J, Kariniemi V. Emergency cesarean section: the effect of delay on umbilical arterial gas
balance and Apgar scores. Acta Obstet Gynecol Scand. 1994;73:782–786.
22. Myers RE. Two patterns of perinatal brain damage and their conditions of occurrence. Am J Obstet
Gynecol. 1972;112:246–276.
23. American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Practice guidelines for
obstetric anesthesia: an updated report by the American Society of Anesthesiologists Task Force on
Obstetric Anesthesia. Anesthesiology. 2007;106:843–863.
24. Centers for Disease Control and Prevention. Pregnancy mortality surveillance system.
http://www.cdc.gov/reproductivehealth/maternalinfanthealth/pmss.html. Accessed March 22, 2015.
25. Hawkins JL, Koonin LM, Palmer SK, et al. Anesthesia-related deaths during obstetric delivery in the
United States, 1979–1990. Anesthesiology. 1997;86:277–284.
26. D’Angelo R, Smiley RM, Riley ET, et al. Serious complications related to obstetric anesthesia: the
serious complication repository project of the Society for Obstetric Anesthesia and Perinatology.
Anesthesiology. 2014;120:1505–1512.
27. Frölich MA, Banks C, Brooks A, et al. Why do pregnant women die? A review of maternal deaths
from 1990 to 2010 at the University of Alabama at Birmingham. Anesth Analg. 2014;119:1135–1139.
28. Shields LE, Smalarz K, Reffigee L, et al. Comprehensive maternal hemorrhage protocols improve
patient safety and reduce utilization of blood products. Am J Obstet Gynecol. 2011;205:368.e1–
368.e8.
29. Reiss RF. Hemostatic defects in massive transfusion: rapid diagnosis and management. Am J Crit
Care. 2000;9:158–165.
30. The Joint Commission. Preventing maternal death. Sentinel Event Alert. 2010;44:1–4.
31. Shields LE, Wiesner S, Fulton J, et al. Comprehensive maternal hemorrhage protocols reduce the use
of blood products and improve patient safety. Am J Obstet Gynecol. 2015;212:272–280.
32. Scavone BM, Tung A. The transfusion dilemma: more, less, or more organized? Anesthesiology.
2014;121:439–441.
33. Zuckerwise LC, Pettker CM, Illuzzi J, et al. Use of a novel visual aid to improve estimation of
obstetric blood loss. Obstet Gynecol. 2014;123:982–986.
34. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin: Clinical Management
Guidelines for Obstetrician-Gynecologists No. 76: postpartum hemorrhage. Obstet Gynecol.
2006;108:1039–1047.
35. Hébert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of
transfusion requirements in critical care. Transfusion requirements in critical care investigators,
 Canadian Critical Care Trials Group. N Engl J Med. 1999;340:409–417.
36. Karpati PCJ, Rossignol M, Pirot M, et al. High incidence of myocardial ischemia during postpartum
hemorrhage. Anesthesiology. 2004;100:30–36.
37. Matot I, Einav S, Goodman S, et al. A survey of physicians’ attitudes toward blood transfusion in
patients undergoing cesarean section. Am J Obstet Gynecol. 2004;190:462–467.
38. American Society of Anesthesiologists Task Force on Perioperative Blood Management. Practice
guidelines for perioperative blood management: an updated report by the American Society of
Anesthesiologists Task Force on Perioperative Blood Management. Anesthesiology. 2015;122:241–
275.
39. Vanderlinde ES, Heal JM, Blumberg N. Autologous transfusion. BMJ. 2002;324:772–775.
40. Goodnough LT, Brecher ME, Kanter MH, et al. Transfusion medicine. Second of two parts—blood
conservation. N Engl J Med. 1999;340:525–533.
41. Yamada T, Mori H, Ueki M. Autologous blood transfusion in patients with placenta previa. Acta
Obstet Gynecol Scand. 2005;84:255–259.
42. Allam J, Cox M, Yentis SM. Cell salvage in obstetrics. Int J Obstet Anesth. 2008;17:37–45.
43. Petroianu GA, Altmannsberger SH, Maleck WH, et al. Meconium and amniotic fluid embolism:
effects on coagulation in pregnant mini-pigs. Crit Care Med. 1999;27:348–355.
44. Waters JH, Biscotti C, Potter PS, et al. Amniotic fluid removal during cell salvage in the cesarean
section patient. Anesthesiology. 2000;92:1531–1536.
45. Grange CS, Douglas MJ, Adams TJ, et al. The use of acute hemodilution in parturients undergoing
cesarean section. Am J Obstet Gynecol. 1998;178:156–160.
46. Malone DL, Hess JR, Fingerhut A. Massive transfusion practices around the globe and a suggestion
for a common massive transfusion protocol. J Trauma. 2006;60:S91–S96.
47. Mhyre JM, D’Oria R, Hameed AB, et al. The maternal early warning criteria: a proposal from the
national partnership for maternal safety. Obstet Gynecol. 2014;124:782–786.
48. Kacmar RM, Mhyre JM, Scavone BM, et al. The use of postpartum hemorrhage protocols in United
States academic obstetric anesthesia units. Anesth Analg. 2014;119:906–910.
49. Karlsson O, Jeppsson A, Hellgren M. Major obstetric haemorrhage: monitoring with
thromboelastography, laboratory analyses or both? Int J Obstet Anesth. 2014;23:10–17.
50. Sharma SK, Philip J, Whitten CW, et al. Assessment of changes in coagulation in parturients with
preeclampsia using thromboelastography. Anesthesiology. 1999;90:385–390.
51. Sharma SK, Philip J, Wiley J. Thromboelastographic changes in healthy parturients and postpartum
women. Anesth Analg. 1997;85:94–98.
52. Cortet M, Deneux-Tharaux C, Dupont C, et al. Association between fibrinogen level and severity of
postpartum haemorrhage: secondary analysis of a prospective trial. Br J Anaesthesia. 2012;108:984–
989.
53. Theusinger OM, Baulig W, Seifert B, et al. Relative concentrations of haemostatic factors and
cytokines in solvent/detergent-treated and fresh-frozen plasma. Br J Anaesth. 2011;106:505–511.
54. Caudill JSC, Nichols WL, Plumhoff EA, et al. Comparison of coagulation factor XIII content and
concentration in cryoprecipitate and fresh-frozen plasma. Transfusion. 2009;49:765–770.
55. Levy JH, Szlam F, Tanaka KA, et al. Fibrinogen and hemostasis: a primary hemostatic target for the
management of acquired bleeding. Anesth Analg. 2012;114:261–274.
56. Lewis NR, Brunker P, Lemire SJ, et al. Failure of recombinant factor VIIa to correct the coagulopathy
in a case of severe postpartum hemorrhage. Transfusion. 2009;49:689–695.
57. Sentilhes L, Lasocki S, Ducloy-Bouthors AS, et al. Tranexamic acid for the prevention and treatment
of postpartum haemorrhage. Br J Anaesth. 2015;114:576–587.
58. Iyasu S, Saftlas AK, Rowley DL, et al. The epidemiology of placenta previa in the United States, 1979
 through 1987. Am J Obstet Gynecol. 1993;168:1424–1429.
59. Silver RM, Landon MB, Rouse DJ, et al. Maternal morbidity associated with multiple repeat cesarean
deliveries. Obstet Gynecol. 2006;107:1226–1232.
60. Dashe JS. Toward consistent terminology of placental location. Semin Perinatol. 2013;37:375–379.
61. Sharma A, Suri V, Gupta I. Tocolytic therapy in conservative management of symptomatic placenta
previa. Int J Gynaecol Obstet. 2004;84:109–113.
62. Bonner SM, Haynes SR, Ryall D. The anaesthetic management of caesarean section for placenta
praevia: a questionnaire survey. Anaesthesia. 1995;50:992–994.
63. Oyelese Y, Catanzarite V, Prefumo F, et al. Vasa previa: the impact of prenatal diagnosis on outcomes.
Obstet Gynecol. 2004;103:937–942.
64. Sheiner E, Shoham-Vardi I, Hallak M, et al. Placental abruption in term pregnancies: clinical
significance and obstetric risk factors. J Matern Fetal Neonatal Med. 2003;13:45–49.
65. Ananth CV, Oyelese Y, Yeo L, et al. Placental abruption in the United States, 1979 through 2001:
temporal trends and potential determinants. Am J Obstet Gynecol. 2005;192:191–198.
66. Ananth CV, Wilcox AJ. Placental abruption and perinatal mortality in the United States. Am J
Epidemiol. 2001;153: 332–337.
67. Tikkanen M, Nuutila M, Hiilesmaa V, et al. Clinical presentation and risk factors of placental
abruption. Acta Obstet Gynecol Scand. 2006;85:700–705.
68. Morikawa M, Cho K, Yamada T, et al. Do uterotonic drugs increase risk of abruptio placentae and
eclampsia? Arch Gynecol Obstet. 2014;289:987–991.
69. Kayani SI, Walkinshaw SA, Preston C. Pregnancy outcome in severe placental abruption. BJOG.
2003;110:679–683.
70. Walsh CA, Baxi LV. Rupture of the primigravid uterus: a review of the literature. Obstet Gynecol Surv.
2007;62:327–334.
71. Lydon-Rochelle M, Holt VL, Easterling TR, et al. Risk of uterine rupture during labor among women
with a prior cesarean delivery. N Engl J Med. 2001;345:3–8.
72. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 342: induction
of labor for vaginal birth after cesarean delivery. Obstet Gynecol. 2006;108:465–468.
73. Eden RD, Parker RT, Gall SA. Rupture of the pregnant uterus: a 53-year review. Obstet Gynecol.
1986;68:671–674.
74. Scavone B. Antepartum and postpartum hemorrhage. In: Chestnut DH, Wong CA, Tsen LC, et al, eds.
Chestnut’s Obstetric Anesthesia: Principles and Practice. 5th ed. Philadelphia, Pa: Elsevier Saunders;
2014:881–914.
75. Stalnaker BL, Maher JE, Kleinman GE, et al. Characteristics of successful claims for payment by the
Florida Neurologic Injury Compensation Association Fund. Am J Obstet Gynecol. 1997;177:268–271.
76. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 115: vaginal birth
after previous cesarean delivery. Obstet Gynecol. 2010;116:450–463.
77. American Society of Anesthesiologists. Optimal goals for anesthesia care in obstetrics.
http://www.asahq.org/publications AndServices/standards/24.html. Accessed April 7, 2015.
78. World Health Organization. World Health Organization recommendations for the prevention and
treatment of postpartum haemorrhage.
http://apps.who.int/iris/bitstream/10665/75411/1/9789241548502_eng.pdf. Accessed March 22, 2015.
79. Callaghan WM, Kuklina EV, Berg CJ. Trends in postpartum hemorrhage: United States, 1994–2006.
Am J Obstet Gynecol. 2010;202:353.e351–353.e356.
80. Mhyre JM. Maternal mortality. Curr Opin Anaesthesiol. 2012;25:277–285.
81. Tita ATN, Szychowski JM, Rouse DJ, et al. Higher-dose oxytocin and hemorrhage after vaginal
delivery: a randomized controlled trial. Obstet Gynecol. 2012;119:293–300.
 82. Bateman BT, Huybrechts KF, Hernandez-Diaz S, et al. Methylergonovine maleate and the risk of
myocardial ischemia and infarction. Am J Obstet Gynecol. 2013;209:459.e1–459.e13.
83. Oleen MA, Mariano JP. Controlling refractory atonic postpartum hemorrhage with Hemabate sterile
solution. Am J Obstet Gynecol. 1990;162:205–208.
84. Gülmezoglu AM, Forna F, Villar J, et al. Prostaglandins for preventing postpartum haemorrhage.
Cochrane Database Syst Rev. 2007;3:CD000494.
85. Timor-Tritsch IE, Monteagudo A. Unforeseen consequences of the increasing rate of cesarean
deliveries: early placenta accreta and cesarean scar pregnancy. A review. Am J Obstet Gynecol.
2012;207:14–29.
86. Wu S, Kocherginsky M, Hibbard JU. Abnormal placentation: twenty-year analysis. Am J Obstet
Gynecol. 2005;192: 1458–1461.
87. Gielchinsky Y, Rojansky N, Fasouliotis SJ, et al. Placenta accreta—summary of 10 years: a survey of
310 cases. Placenta. 2002;23:210–214.
88. Mehrabadi A, Hutcheon JA, Liu S, et al. Contribution of placenta accreta to the incidence of
postpartum hemorrhage and severe postpartum hemorrhage. Obstet Gynecol. 2015;125:814–821.
89. Palacios Jaraquemada JM, Bruno CH. Magnetic resonance imaging in 300 cases of placenta accreta:
surgical correlation of new findings. Acta Obstet Gynecol Scand. 2005;84:716–724.
90. Chestnut DH, Redick LF. Continuous epidural anesthesia for elective cesarean hysterectomy. South
Med J. 1985;78: 1168–1169.
91. Chestnut DH, Dewan DM, Redick LF, et al. Anesthetic management for obstetric hysterectomy: a
multi-institutional study. Anesthesiology. 1989;70:607–610.
92. Ballas J, Hull AD, Saenz C, et al. Preoperative intravascular balloon catheters and surgical outcomes
in pregnancies complicated by placenta accreta: a management paradox. Am J Obstet Gynecol.
2012;207:216.e211–216.e215.
93. Belfort MA. Placenta accreta. Am J Obstet Gynecol. 2010;203:430–439.
94. Wendel PJ, Cox SM. Emergent obstetric management of uterine inversion. Obstet Gynecol Clin North
Am. 1995;22: 261–274.
95. Goldenberg RL, Culhane JF, Iams JD, et al. Epidemiology and causes of preterm birth. Lancet.
2008;371:75–84.
96. Eichenwald EC, Stark AR. Management and outcomes of very low birth weight. N Engl J Med.
2008;358:1700–1711.
97. Patel P, Sun L. Update on neonatal anesthetic neurotoxicity: insight into molecular mechanisms and
relevance to humans. Anesthesiology. 2009;110:703–708.
98. Palanisamy A. Maternal anesthesia and fetal neurodevelopment. Int J Obstet Anesth. 2012;21:152–
162.
99. Yamasato K, Burlingame J, Kaneshiro B. Hemodynamic effects of nifedipine tocolysis. J Obstet
Gynaecol Res. 2015;41:17–22.
100. van Vliet EO, Boormans EM, de Lange TS, et al. Preterm labor: current pharmacotherapy options for
tocolysis. Expert Opin Pharmacother. 2014;15:787–797.
101. Loe SM, Sanchez-Ramos L, Kaunitz AM. Assessing the neonatal safety of indomethacin tocolysis: a
systematic review with meta-analysis. Obstet Gynecol. 2005;106:173–179.
102. Chau AC, Gabert HA, Miller JM Jr. A prospective comparison of terbutaline and magnesium for
tocolysis. Obstet Gynecol. 1992;80:847–851.
103. Hollander DI, Nagey DA, Pupkin MJ. Magnesium sulfate and ritodrine hydrochloride: a randomized
comparison. Am J Obstet Gynecol. 1987;156:631–637.
104. DeVore JS, Asrani R. Magnesium sulfate prevents succinylcholine-induced fasciculations in toxemic
parturients. Anesthesiology. 1980;52:76–77.
105. Neilson JP, West HM, Dowswell T. Betamimetics for inhibiting preterm labour. Cochrane Database
Syst Rev. 2014;2: CD004352.
106. Flenady V, Reinebrant HE, Liley HG, et al. Oxytocin receptor antagonists for inhibiting preterm
labour. Cochrane Database Syst Rev. 2014;6:CD004452.
107. Beall MH, Spong C, McKay J, et al. Objective definition of shoulder dystocia: a prospective
evaluation. Am J Obstet Gynecol. 1998;179:934–937.
108. Rouse DJ, Owen J, Goldenberg RL, et al. The effectiveness and costs of elective cesarean delivery for
fetal macrosomia diagnosed by ultrasound. JAMA. 1996;276:1480–1486.
109. Sandberg EC. The Zavanelli maneuver: 12 years of recorded experience. Obstet Gynecol.
1999;93:312–317.
110. Gibbons C, O’Herlihy C, Murphy JF. Umbilical cord prolapse—changing patterns and improved
outcomes: a retrospective cohort study. BJOG. 2014;121:1705–1708.
111. Katz Z, Shoham Z, Lancet M, et al. Management of labor with umbilical cord prolapse: a 5-year study.
Obstet Gynecol. 1988;72:278–281.
112. McDonnell NJ, Percival V, Paech MJ. Amniotic fluid embolism: a leading cause of maternal death yet
still a medical conundrum. Int J Obstet Anesth. 2013;22:329–336.
113. Abenhaim HA, Azoulay L, Kramer MS, et al. Incidence and risk factors of amniotic fluid embolisms:
a population-based study on 3 million births in the United States. Am J Obstet Gynecol.
2008;199:49.e1–49.e8.
114. Knight M, Tuffnell D, Brocklehurst P, et al. Incidence and risk factors for amniotic-fluid embolism.
Obstet Gynecol. 2010;115:910–917.
115. Kramer MS, Rouleau J, Baskett TF, et al. Amniotic-fluid embolism and medical induction of labour: a
retrospective, population-based cohort study. Lancet. 2006;368:1444–1448.
116. Roberts CL, Algert CS, Knight M, et al. Amniotic fluid embolism in an Australian population-based
cohort. BJOG. 2010;117:1417–1421.
117. Knight M, Berg C, Brocklehurst P, et al. Amniotic fluid embolism incidence, risk factors and
outcomes: a review and recommendations. BMC Pregnancy Childbirth. 2012;12:7.
118. Dean LS, Rogers RP III, Harley RA, et al. Case scenario: amniotic fluid embolism. Anesthesiology.
2012;116:186–192.
119. Clark SL. Amniotic fluid embolism. Obstet Gynecol. 2014;123:337–348.
120. Vanden Hoek TL, Morrison LJ, Shuster M, et al. Part 12: cardiac arrest in special situations: 2010
American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency
Cardiovascular Care. Circulation. 2010;122:S829–S861.
121. Farinelli CK, Hameed AB. Cardiopulmonary resuscitation in pregnancy. Cardiol Clin. 2012;30:453–
461.
122. Paterson-Brown S, Bamber J. Prevention and treatment of haemorrhage. In: Knight M, Kenyon S,
Brocklehurst P, et al, eds. Saving Lives, Improving Mothers’ Care : Lessons Learned to Inform Future
Maternity Care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity
2009-2012. Oxford, United Kingdom: University of Oxford; 2014:45–55.
123. Conde-Agudelo A, Romero R. Amniotic fluid embolism: an evidence-based review. Am J Obstet
Gynecol. 2009;201:445.e1–455.e13.
124. Girard T, Mörtl M, Schlembach D. New approaches to obstetric hemorrhage: the postpartum
hemorrhage consensus algorithm. Curr Opin Anaesthesiol. 2014;27:267–274.
125. Leighton BL, Wall MH, Lockhart EM, et al. Use of recombinant factor VIIa in patients with amniotic
fluid embolism: a systematic review of cases. Anesthesiology. 2011;115:1201–1208.
126. Morgan M. Amniotic fluid embolism. Anaesthesia. 1979;34:20–32.
127. Kramer MS, Rouleau J, Liu S, et al. Amniotic fluid embolism: incidence, risk factors, and impact on
perinatal outcome. BJOG. 2012;119:874–879.
 Newborn Resuscitation
Richard A. Month

I. Neonatal adaptations to extrauterine life
A. Fetal cardiovascular and pulmonary physiology
B. Normal peripartum transition to extrauterine life
C. Prolonged hypoxemia/acidosis and failure of transition
II. Anticipating the depressed newborn
A. Antepartum evaluation
B. Intrapartum evaluation
III. Evaluating the neonate
A. Apgar score
B. Umbilical cord blood gas measurements
IV. Resuscitation of the neonate
A. Preparation for resuscitation
B. The resuscitation algorithm
C. Initial resuscitation
D. Maintain normothermia
E. Assisted ventilation
F. Considerations for establishing ventilation
G. Oxygen administration
H. Chest compressions
I. Umbilical vein catheterization
J. Medications
K. Discontinuation of resuscitative efforts
 V. Special resuscitation circumstances
A. Meconium-stained amniotic fluid
B. Premature infants
C. Opioid-induced respiratory depression
D. Magnesium toxicity

KEYPOINTS
1. The transition from intrauterine to extrauterine life requires a reduction in
neonatal pulmonary vascular resistance and an increase in systemic
vascular resistance that accompanies the onset of breathing.
2. Prolonged acidosis and hypoxia after delivery can prevent this transition.
3. Most cases of neonatal depression can be predicted by antepartum and
intrapartum fetal assessment.
4. The Apgar score gives practitioners a guide to the need for resuscitation.
It is not a good predictor of poor neurologic outcome following delivery.
5. The primary responsibility of the anesthesia provider is to the mother. A
second individual skilled in neonatal resuscitation should be immediately
available to resuscitate the neonate when possible.
6. Assisted ventilation is indicated 30 seconds after delivery in the neonate
who has ineffective breathing following initial resuscitative measures.
7. The administration of 100% oxygen during assisted ventilation is no
longer routinely recommended. However, the optimal inspired oxygen
concentration has not been established.
8. Hypovolemia is rarely a cause of neonatal cardiopulmonary depression.
The administration of large volumes of fluid to a normovolemic neonate
is associated with significant adverse effects.
9. Intrapartum oropharyngeal and tracheal suctioning of a vigorous neonate
born through meconium-stained fluid is not recommended.
10. Initial treatment of the neonate with opioid-induced respiratory
depression is with assisted ventilation, not naloxone administration.
A SUCCESSFUL TRANSITION FROM THE INTRAUTERINE TO EXTRAUTERINE
ENVIRONMENT requires numerous complex physiologic changes. Approximately
10% of newborns will require assistance with ventilation at birth, and 1% will
need extensive resuscitative measures.1 Worldwide, an estimated 5 to 10 million
interventions will be required annually; it is imperative that all providers
working in labor and delivery suites understand the neonatal adaptions to
extrauterine life, recognize the need for resuscitation, and have the expertise to
respond appropriately.
I. Neonatal adaptations to extrauterine life
A. Fetal cardiovascular and pulmonary physiology
1. Unlike the adult, where pulmonary and systemic circulations
operate in parallel, the fetal circulation operates in series
(see Fig. 17.1).2 Oxygenated blood from the placenta returns
via the umbilical vein and is shunted through the ductus
venosus into the inferior vena cava (IVC). Upon return to the
heart, nearly 40% of IVC flow is directed across the foramen
ovale and through the left heart and ascending aorta in order
to perfuse the fetal heart and brain with maximally
oxygenated blood.3 Deoxygenated blood from the head and
upper extremities enters the heart through the superior vena
cava (SVC). This blood is preferentially directed into the right
ventricle where it mixes with the remainder of the maximally
oxygenated IVC return. High pulmonary vascular resistance
(PVR) ensures that 90% of right ventricular outflow shunts
across the ductus arteriosus to the descending aorta to perfuse
the abdomen, pelvis, and lower extremities.4 This creates a
substantial right-to-left cardiac shunt. Forty percent of
cardiac output flows through the umbilical arteries to the
placenta; due to the large total cross sectional area of the
placenta, it has low resistance and contributes little to fetal
systemic vascular resistance (SVR).
2. Fetal lung development takes place throughout pregnancy,
and lung maturation continues well into the neonatal period.
The pulmonary transition that occurs in the fetus is initiated
before labor begins. Cortisol production increases in the third
trimester to begin multisystem organ preparation for the
newborn transition, including preparation for pulmonary
maturation. In addition, surfactant production increases to
reduce alveolar surface tension, promote alveolar expansion,
 foster gas exchange, and stimulate fetal lung development.5
B. Normal peripartum transition to extrauterine life
1. Delivery leads to rapid and profound changes in neonatal
hemodynamics and pulmonary mechanics. During
development, the fetal airways contain approximately 30 mL
per kg of fluid. This fluid, an ultrafiltrate of fetal plasma,
begins to reabsorb during labor.3 During vaginal delivery,
compression of the thorax expels further fluid from the mouth
and upper airways.2 With the first breaths, the lungs fill with
air, surfactant is released, and oxygenation increases
dramatically.6 This increase in oxygen tension and blood flow
increases the release of nitric oxide in the pulmonary
vasculature resulting in pulmonary vasodilation and a
substantial decrease in PVR.7 Simultaneously, clamping of the
umbilical cord removes the low-resistance placenta from the
systemic circulation increasing SVR. Functional closure of
the foramen ovale occurs rapidly after birth as left atrial
pressures exceed right atrial pressures.
2. The right-to-left shunt across the foramen ovale and ductus
arteriosus is substantially reduced within the first few minutes
of life.

CLINICAL PEARL The substantial right-to-left shunting of

oxygenated blood in the fetal circulation is dramatically reduced at
birth by reductions in PVR and increases in SVR. These changes
are primarily due to the neonate’s first breaths and umbilical cord
clamping.

C. Prolonged hypoxemia/acidosis and failure of transition

1. Transient hypoxemia and acidosis are typically well
tolerated in the normal newborn; prompt resuscitation of a
depressed newborn should prevent permanent physiologic
alterations. However, prolonged neonatal hypoxemia and
 acidosis impede the normal transition from fetal to neonatal
physiology. Hypoxemia maintains patency of the ductus
arteriosus and continued right-to-left shunting as ductal
smooth muscle constriction depends on an increase in blood
oxygen tension. Hypoxemia promotes hypoxic pulmonary
vasoconstriction and increases the risk of significant
pulmonary hypertension. Pulmonary hypertension causes an
elevation of right atrial pressure, maintaining the right-to-left
shunt across the foramen ovale. Blood flowing through the
patent ductus arteriosus and foramen ovale is therefore not
oxygenated, contributing to increasing hypoxemia and
continued deterioration.4
2. Both the fetus and neonate respond to hypoxemia with a
“diving” reflex (known as such due to its similarity to seal
physiology during a dive): Blood flow is diverted centrally to
the heart, brain, and adrenal glands, and tissue oxygen
extraction increases.
3. Neonatal circulation initially exhibits a hypertensive response
because additional oxygen cannot be extracted by the neonate.
As a result, myocardial contractility and cardiac output
decrease leading to systemic hypotension.4
4. Neonatal ventilation during hypoxia is initially rapid and
regular (see Fig. 17.2). However, as hypoxia continues,
respirations stop in a stage known as primary apnea.
Stimulation of the neonate during primary apnea will lead to
reinitiation of respiratory effort. If hypoxia continues through
primary apnea, the neonate will begin to attempt irregular,
grunting respirations, followed by secondary or terminal
apnea. Stimulation will not reverse secondary apnea because
respiratory drive has been reduced by both central nervous
system and direct diaphragmatic depression.8 The net result of
these physiologic responses is a neonate with persistent
pulmonary hypertension and little or no ventilatory drive.
Ideally, prompt resuscitation prevents these physiologic
 perturbations.

CLINICAL PEARL Transient hypoxemia and acidosis are well

tolerated by the normal newborn. However, prolonged hypoxemia
and acidosis lead to depressed hemodynamics, persistent pulmonary
hypertension, and poor ventilatory drive.

II. Anticipating the depressed newborn

Neonatal resuscitation can be anticipated in about 80% of cases.1,9
A. Antepartum evaluation (see Chapter 7 Fetal Assessment and
Monitoring)
The advent of fetal heart rate (FHR) evaluation by
cardiotocography has allowed for development of protocols to
identify the at-risk fetus and, if necessary, effect delivery and
outcome. The nonstress test (NST), contraction stress test (CST),
and the biophysical profile (BPP) are all used to assess fetal well-
being10–15 (see Chapter 7). Many of the antepartum factors
related to increased likelihood for neonatal resuscitation are listed
in Table 17.1.
B. Intrapartum evaluation (see Chapter 7)
Many intrapartum events increase the likelihood for neonatal
resuscitation (see Table 17.2).

1. The primary method for intrapartum evaluation of the fetus is

FHR monitoring by cardiotocography. Although this is a
reliable method of confirming fetal well-being and is highly
predictive of the need for immediate postpartum resuscitative
efforts,9,16 a reassuring FHR pattern does not necessarily
guarantee a neonate who does not need resuscitation at birth;
50% of babies born by cesarean delivery (CD) with prior
reassuring FHR patterns will require some resuscitation.9
2. Intrapartum fetal monitoring utilizes FHR measurement (by
external Doppler ultrasound or internal fetal scalp electrode)
combined with measurement of contraction pattern (by
external tocodynamometry or intrauterine pressure
transducer). These two parameters together can suggest fetal
well-being or foretell fetal asphyxia. Four parameters are
evaluated when assessing the FHR tracing: baseline,
 variability, accelerations, and decelerations.17 Using these
four parameters, FHR tracings can be placed into three
categories, as identified in Table 17.3. Category I tracings are
classified as normal and are indicative of fetal well-being.
Category II tracings are classified as indeterminate and are
neither indicative of fetal well-being nor predictive of
abnormal fetal acid–base status. Category III tracings are
abnormal and are highly predictive of abnormal fetal acid–
base status and should be met with prompt evaluation and
intervention.17 In the past, fetal scalp sampling has also been
used to help confirm the need for expedited delivery
(indicated if the fetal capillary pH was below 7.20).18
However, the examination is invasive and has been replaced
by fetal scalp stimulation. An FHR acceleration of 10 beats
per minute (bpm) for 10 seconds or longer after stimulation is
highly predictive of a fetal pH greater than 7.20.19

CLINICAL PEARL A majority of neonates who will require

resuscitation can be anticipated by ante-and intrapartum fetal
assessment; however, resources should be available to resuscitate a
neonate at every delivery, if required.
 III. Evaluating the neonate
A. Apgar score. Historically, the Apgar score was the first
standardized approach to neonatal evaluation following delivery.
The score, first published by anesthesiologist Virginia Apgar in
1953, uses five signs: heart rate, respiratory effort, reflex
irritability, muscle tone, and color, each on a 0-to-2-point scale,
for a maximum score of 10, measured at 1 and 5 minutes
postpartum.20 The individual parameters are listed in Table 17.4.
The Apgar score contains the major elements used in more
current algorithms to guide therapy of the depressed neonate
following delivery.21

1. In addition, the Apgar score has repeatedly proven useful in

predicting neonatal mortality; the term infant with a 5-minute
Apgar score of 0 to 3 is more likely to die in the neonatal
period than the term infant with a score of 7 to 10.21,22
2. Use of the Apgar score is not without concerns. There is high
interobserver variation in scoring, both in the total score and
in each of the subcategories.23 In addition, the scores have
been used incorrectly in an attempt to identify long-term
outcomes beyond the increased risk of neonatal death
(including long-term neurologic function, cerebral palsy, and
even future intelligence). This has led to concerns of
increased medicolegal liability based on a scoring system that,
although shown to correlate with neonatal death, is not “a
conclusive marker . . . of an acute intrapartum hypoxic event”
 according to the American Academy of Pediatrics (AAP) and
the American College of Obstetricians and Gynecologists
(ACOG).24
B. Umbilical cord blood gas measurements. Umbilical cord blood
gas measurements can be used to evaluate the intrauterine
environment of the fetus prior to delivery. Normal umbilical
arterial and venous blood gas measurements are found in Table
17.5.

CLINICAL PEARL Elements of the Apgar score can be used to

guide resuscitation of the neonate following delivery.

IV. Resuscitation of the neonate

All anesthesia providers working within labor and delivery units must
be familiar with neonatal resuscitation. Given the urgent nature of
neonatal resuscitation, preparation is imperative.
A. Preparation for resuscitation
Neonatal resuscitation equipment and medications should be
organized in a central location, checked frequently for proper
function and expiration, and replenished immediately after use
(see Table 17.6). At least one provider whose primary
responsibility is resuscitation of the newborn should attend every
delivery. Both the American Society of Anesthesiologists (ASA)
and the ACOG have published optimal goals for neonatal
resuscitation endorsing that the anesthesiologist’s primary
responsibility is care of the mother.25 However, the
 anesthesiologist may provide brief neonatal assistance only if care
of the mother is not compromised. In addition, the joint statement
recommends that individuals demonstrate proficiency in
evaluating the neonatal condition, knowledge of the
pathophysiology of neonatal depression, and skill in airway
management and drug administration. Additional qualified
personnel are recommended for deliveries where fetal
compromise is anticipated.

CLINICAL PEARL The primary responsibility of the

anesthesiologist is to care for the mother. A second individual
skilled in neonatal resuscitation should be present, if possible, when
neonatal resuscitation is anticipated or needed.

B. The resuscitation algorithm

The American Heart Association (AHA) and AAP endorse a
neonatal resuscitation protocol based on frequent assessment of
the newborn and escalating levels of intervention (see Fig. 17.3).1
The algorithm is organized into 30-second intervals during which
an intervention is completed, the neonate is reassessed, and the
decision to proceed, or not, is made. Assessment of the neonate
 focuses on evaluation of the heart rate, respirations, and
oxygenation. Successful completion of the previous step is a
prerequisite to proceeding to the next intervention.

C. Initial resuscitation
The general condition of the neonate is quickly assessed with four
screening questions addressed immediately following delivery
(see Fig. 17.3): (1) Is the infant full-term? (2) Is the amniotic fluid
 clear? (3) Is the newborn breathing or crying? (4) Does the infant
have good muscle tone? Routine care is provided for full-term
newborns with clear amniotic fluid, good muscle tone, and
breathing without distress. Neonates with difficulty making the
transition to extrauterine life should be warmed, gently
stimulated, and placed in the “sniffing position” to open their
airways. Suctioning of the pharynx and nose should be brief and
gentle because prolonged or vigorous suctioning may result in
breath holding, laryngospasm, or bradycardia.
D. Maintain normothermia
Minimizing heat loss is an integral part of neonatal resuscitation.
All infants have an unstable thermal regulatory system and this is
enhanced in depressed or asphyxiated neonates. The large surface
area to body mass ratio of the neonate facilitates rapid heat loss
by conduction, convection, evaporation, and radiation. The term
neonate’s primary defense against hypothermia is nonshivering
thermogenesis through catecholamine-mediated metabolism of
brown fat. This, in turn, leads to an increase in oxygen
consumption, calorie utilization, and metabolic rate.26 The
resulting hypoxemia, hypercarbia, and hypoglycemia promote
persistence of the fetal circulation and hinder resuscitation.
E. Assisted ventilation
Spontaneously breathing infants should make their first
respiratory effort seconds after delivery of the thorax, generating
a negative intrathoracic pressure of 60 to 100 cm H2O and
inspiring a tidal volume of approximately 80 mL. The majority of
this first breath is retained within the lungs as part of the
functional residual capacity.27 Infants who fail to initiate
respirations with gentle stimulation, warming, and airway
suctioning require further intervention to ensure adequate
ventilation.
1. Assisted ventilation is required in about 3% to 5% of all
newborn infants. Positive pressure ventilation is indicated in
neonates who remain apneic, have ineffective or gasping
 ventilation, or a heart rate less than 100 bpm more than 30
seconds after delivery (see Fig. 17.3). Assisted ventilation can
be initiated via a bag valve mask device, a laryngeal mask
airway (LMA), or an endotracheal tube. Ventilation is usually
first established with a bag valve mask device followed by
endotracheal intubation in the absence of clinical
improvement.
2. Common indications for endotracheal intubation include
tracheal suctioning for meconium, ineffective or prolonged
bag valve mask ventilation, or endotracheal administration of
medications (although this practice is now strongly
discouraged). For ideal intubating conditions, the infant’s
head is placed in a neutral “sniffing position” (see Fig. 17.4).
A small straight blade, such as a Miller 0 or 1, provides the
best visualization of the neonatal larynx given its unique
anatomic characteristics. Specifically, the newborn larynx is
more anterior than the adult and at the level of the third
cervical vertebra rather than the sixth. A small air leak with
positive pressure ventilation indicates the uncuffed
endotracheal tube is appropriately sized (see Table 17.7). An
oversized endotracheal tube may cause subglottic stenosis,
whereas an undersized endotracheal tube can impede
adequate ventilation and may become easily occluded. The
endotracheal tube is inserted 2 cm past the vocal cords, and
tracheal placement is confirmed via detection of end tidal
CO2, bilateral breath sounds, and symmetric chest rise.
3. Both bag valve mask and endotracheal ventilation are known
to produce significant morbidity. Prolonged bag valve mask
ventilation can result in distention of the stomach and/or
ocular or facial abrasions from pressure applied to the mask.
On the other hand, direct laryngoscopy can be accompanied
by a significant hypertensive response contributing to cerebral
hemorrhage. In addition, intubation can be challenging in
neonates. A recent survey found that intubation by third-year
 pediatric residents was successful only 62% of the time on the
first or second attempt.28
4. Given some of the limitations of bag valve mask and
endotracheal ventilation, some advocate for the use of LMAs
in neonatal resuscitation.29–31 LMAs have been used
successfully in resuscitation of both full-term and preterm
infants and may have significant advantages over
endotracheal intubation, including ease of use and decreased
hemodynamic response. Both novice and experienced
providers have had success with LMA use in the neonate. One
study reported the successful resuscitation of 20 neonates with
the LMA as a conduit for positive pressure ventilation by
novice providers.29 Another trial found no significant
difference between the LMA and endotracheal intubation
during resuscitation of infants by experienced providers after
CD.31 Although endotracheal intubation is still preferred in
situations requiring ventilation with high peak airway
pressures, tracheal suctioning, or administration of
endotracheal medications, the LMA can be lifesaving in
neonates with difficult airways, specifically in conditions with
a congenital hypoplastic mandible, such as Pierre-Robin and
Treacher-Collins syndromes.

CLINICAL PEARL Neonatal respiratory depression at birth will

often respond to stimulation, warming, and gentle suctioning.
Assisted ventilation with bag and mask should be performed in
those who do not respond to those interventions.

F. Considerations for establishing ventilation

The optimal inflation pressure, time, and flow rate to establish
ventilation in the neonate have yet to be determined. With
assisted ventilation, pressures of 30 to 40 cm H2O are often
necessary for the first few breaths to establish lung expansion
 with the use of higher inflation pressures carrying the risk of
iatrogenic pneumothorax. After initial inflation, pressures of 12 to
20 cm H2O are usually sufficient to deliver tidal volumes of 5 to 7
mL per kg. If positive pressure ventilation fails to initiate
spontaneous respiration, ventilation should be continued at a rate
of 30 breaths per minute. Consideration should be given to the
application of positive end-expiratory pressure (PEEP) because it
may protect against lung injury and improve lung compliance and
gas exchange.32 Regardless of the mode of ventilation, adequate
oxygenation is confirmed by an improvement in heart rate, color,
and body tone.
G. Oxygen administration
The administration of oxygen has historically been a fundamental
aspect of neonatal resuscitation; however, recent evidence
challenges the use of 100% oxygen in neonatal resuscitation.33–37
In fact, in the most recent guidelines, the AHA and AAP support
the use of room air during initial resuscitative efforts for the full-
term infant.1
1. The growing interest in room air resuscitation began with a
report by Ramji et al.33 that room air was as effective as 100%
oxygen in neonatal resuscitation. Follow-up investigations
reported a decreased neonatal mortality rate (13.9% vs. 19%)
in infants resuscitated with room air instead of 100%
oxygen,34 although no significant differences in neurologic
evaluation, somatic growth, or developmental milestones at
18 to 24 months were found between the two groups of
infants.35 A recent report from Spain demonstrated a
reduction in mortality from 3.5% in the 100% oxygen group
to 0.5% in the room air group, suggesting the reduction in
mortality is not exclusive in studies conducted in third world
environments.37 The benefits of room air neonatal
resuscitation, including a significantly lower neonatal
mortality, shorter time to first breath, and higher 5-minute
Apgar scores in the room air group, were recently
 summarized in a meta-analysis encompassing randomized or
pseudo-randomized trials of neonatal resuscitation with room
air versus 100% oxygen.36
2. Despite growing evidence that resuscitation with 100%
oxygen may be harmful, it remains unclear that ventilation
with room air is ideal; further studies of the effect of inspired
oxygen tension on neonates after resuscitation have reported
differing results.38–42 In a neonatal piglet model of
intermittent apnea, selective regions of the brain (striatum and
hippocampus) were better protected from apoptotic injury
when resuscitation was conducted with 100% rather than 21%
oxygen.38 Other studies have suggested that resuscitation with
100% oxygen leads to reperfusion injury in the developing
brain, lungs, myocardium, and kidneys secondary to excessive
production of reactive oxygen species.39–41 In addition,
exposure to even brief periods of hyperoxia following
delivery has been associated with decreases in cerebral blood
flow in term and preterm infants.42
3. It remains unclear what oxygen fraction is optimal to achieve
a balance between the toxic effects of oxygen and the
deleterious effects of hypoxemia.

CLINICAL PEARL Although the use of 100% inspired oxygen

during resuscitation has been recently challenged, the optimal
inspired oxygen fraction has not yet been determined.

H. Chest compressions
Regardless of the fraction of inspired oxygen used during initial
resuscitative efforts, if the heart rate remains less than 60 bpm
after 30 seconds of positive pressure ventilation, then chest
compressions are indicated (see Fig. 17.3). Neonatal cardiac
arrest occurs in less than 0.1% of term deliveries and is most
commonly associated with respiratory failure because hypoxemia
and tissue acidosis lead to bradycardia, decreased cardiac
contractility, and eventually cardiac arrest.
1. Chest compressions should be initiated at a ratio of 3:1 with
90 compressions and 30 breaths per minute, by one of two
compressive techniques (see Fig. 17.5). With the “thumb
compression technique,” both thumbs are positioned at the
lower third of the sternum and the fingers encircle the chest
and support the back; this method generates higher peak
systolic and coronary perfusion pressures and is generally
recommended over the “two-finger technique.”43 The “two-
finger technique,” with the tips of the middle and index
fingers positioned perpendicular to the chest and a second
hand supporting the back, facilitates simultaneous
interventions on the neonate and may be preferred in
situations where access to the umbilical vessels is necessary.
Regardless of the technique, the sternum is displaced one-
third the anterior–posterior chest diameter with each
compression. An improvement in the neonate’s oxygenation
and/or color and the presence of a palpable pulse confirms the
adequacy of cardiac output. Chest compressions can be
paused every 2 minutes for evaluation of the endogenous
heart rate.
 2. Discontinuation of chest compressions is indicated when the
heart rate is greater than 80 bpm and the pulse remains
palpable.
I. Umbilical vein catheterization
Cannulation of the umbilical vessels allows for both prompt
administration of resuscitation drugs and hemodynamic
monitoring. In addition, they provide a reliable conduit for the
administration of epinephrine and/or fluids. The umbilical artery
can be cannulated when frequent assessment of systemic blood
pressure or arterial blood gases is necessary.
1. A 3.5 or 5 French catheter is sterilely inserted into the vein at
the stump of the umbilical cord. The catheter is advanced 2 to
3 cm, at which point aspiration of blood should be possible.
The catheter must remain infrahepatic because hepatic
infusion of drugs or hypertonic solutions can cause hepatic
necrosis or portal vein thrombosis.
2. The tip of the umbilical artery catheter should be positioned
above the bifurcation of the aorta and below the celiac, renal,
and mesenteric arteries. In a term infant, advancement of the
catheter between 9 and 12 cm generally allows for optimal
positioning. Radiographic verification of the tip position is
 indicated if the catheter is to remain in place for an extended
period.
J. Medications
1. Epinephrine
In approximately 1 in 2,000 deliveries where the heart rate
remains less than 60 bpm despite adequate ventilation and 30
seconds of chest compressions, epinephrine is the vasopressor
of choice (see Fig. 17.3). Administration of epinephrine leads
to increased myocardial blood flow from α-adrenergic-
mediated vasoconstriction and a subsequent increase in
coronary perfusion pressure.
a. Intravascular epinephrine is given at doses of 0.01 to 0.03
mg per kg and can be repeated every 3 to 5 minutes until
the heart rate is greater than 60 bpm (see Table 17.8).
Adequate ventilation must be established prior to its
administration because the α-and β-adrenergic activity of
epinephrine increases oxygen consumption and can lead
to myocardial damage in the setting of hypoxemia.

b. The endotracheal route for epinephrine administration is

controversial. In one report, only 32% of neonates
experienced a return of spontaneous circulation after
administration of endotracheal epinephrine.44 Several
factors may impede neonatal alveolar drug absorption,
including the persistence of the fetal circulation, dilution
of the drug due to alveolar fluid remaining in the lungs
after delivery, and reduction of pulmonary blood flow due
to pulmonary vasoconstriction. Although some animal
studies demonstrate a positive result with high-dose
endotracheal epinephrine,45 more conventional doses fail
 to show an effect.46 These higher doses of epinephrine are
associated with exaggerated hypertension, a decrease in
myocardial function, and poor neurologic outcome.
Because the use of medications during neonatal
resuscitation is an uncommon event, determination of the
most effective epinephrine regimen has been difficult.

CLINICAL PEARL Adequate ventilation is required before

epinephrine can be administered. Administration via an
endotracheal tube is controversial.

2. Volume expanders for the treatment of shock

Although neonatal cardiorespiratory depression is most often
secondary to hypoxemia and acidosis, in rare situations, it is
the result of significant hypovolemia.
a. The most common cause of neonatal shock is acute
compression of the umbilical cord. A tight nuchal cord
may result in placental trapping of fetal blood as flow
continues through the rigid, muscular umbilical arteries
but is inhibited through the compliant umbilical vein.
Less frequent causes of neonatal hypovolemia include
placental abruption, placenta previa, vasa previa, and
fetomaternal hemorrhage.
b. Despite the various potential causes of neonatal blood
loss during delivery, volume infusions are rarely indicated
and in many situations are detrimental. In a recent
retrospective study of approximately 38,000 deliveries,
only 1:12,000 term infants needed volume therapy after
birth.47 According to the current AHA guidelines, volume
expansion may be indicated if the infant is not responding
to intensive resuscitation and there is evidence of blood
loss.1 In the presence of hypovolemia, volume expansion
may be achieved with either isotonic crystalloid or O-
 negative blood. An initial dose of 10 mL per kg over 5 to
10 minutes may be repeated, if necessary (see Table 17.8).
There is no benefit of albumin over isotonic crystalloid
for the treatment of hypotension in neonates.48
c. The inappropriate infusion of fluid may contribute to
continued cardiac and neurologic compromise.
Unfortunately, in the absence of obvious blood loss, it is
difficult to distinguish a hypovolemic infant from a
normovolemic, asphyxiated infant. Both will exhibit
cyanosis, weak pulses, and delayed capillary refill.
Because the neonatal heart has a relatively fixed stroke
volume, increased preload can be detrimental in a
normovolemic, asphyxiated infant with decreased
myocardial function and reduced cardiac output.
Furthermore, the cerebral microcirculation of an
asphyxiated neonate is particularly vulnerable to injury
from rapid volume expansion. Infants receiving volume
infusions early during cardiopulmonary resuscitation have
shown decreased Apgar scores at 10 minutes, lower cord
arterial pH, larger base deficits, and longer resuscitation
periods.47

CLINICAL PEARL Hypovolemia is a rare cause of neonatal

acidosis. The administration of large volumes of fluid is detrimental
in the normovolemic depressed neonate.

3. Sodium bicarbonate
Although acidemia impairs myocardial performance and may
attenuate the hemodynamic response to catecholamines, the
benefit of sodium bicarbonate infusions has been refuted by
several studies in adults and neonates.49
a. Among 19 retrospective adult studies examining mortality
rates and other outcomes, none demonstrated benefit: 11
 showed no difference in outcomes, and 8 suggested a
deleterious effect of sodium bicarbonate administration
during cardiopulmonary resuscitation.50 One randomized
controlled trial of sodium bicarbonate use in neonatal
resuscitation demonstrated no difference in mortality rates
or neurologic outcomes.51 Recent AHA guidelines
highlight the adverse neurologic and cardiac effects linked
to bicarbonate administration.52
b. Exogenously administered sodium bicarbonate is readily
converted into carbon dioxide. It diffuses into myocardial
and cerebral cells and paradoxically contributes to
intracellular acidosis and reduced cellular function. The
extracellular alkalosis created by sodium bicarbonate
shifts the oxyhemoglobin saturation curve, further
worsening the intracellular acidosis by impeding oxygen
release to the tissues. Sodium bicarbonate infusions also
hinder cerebral and coronary perfusion by reducing SVR.
The strong relationship between intracranial hemorrhage
and rapid infusions of hyperosmolar sodium bicarbonate
further argue against its routine use. The administration of
sodium bicarbonate is no longer recommended during
initial neonatal resuscitation.

CLINICAL PEARL The administration of sodium bicarbonate

during initial resuscitation is not recommended.

K. Discontinuation of resuscitative efforts

In addition to providing guidelines for neonatal resuscitation, the
AHA has recommendations on when it is appropriate to terminate
resuscitative efforts.1 Most infants with Apgar scores of 0 after 10
minutes after adequate resuscitative measures will expire during
the immediate neonatal period from multiorgan failure; those who
survive will almost invariably suffer severe hypoxic-ischemic
 encephalopathy and devastating neurologic sequelae.53 It is
therefore acceptable to withhold or interrupt resuscitation after 10
minutes if the neonate shows no evidence of life.
V. Special resuscitation circumstances
A. Meconium-stained amniotic fluid
Meconium is the breakdown product of amniotic fluid,
gastrointestinal cells, and intestinal secretions. Passage of
meconium normally occurs after delivery; however, intrapartum
fetal distress can stimulate colonic activity, resulting in
meconium-stained amniotic fluid (MSAF) in 10% to 15% of all
deliveries.54 Intrapartum hypoxic stress may trigger deep, agonal
gasping, leading to meconium aspiration and the development of
meconium aspiration syndrome (MAS) in 5% of infants delivered
through MSAF.55 The consequences of severe MAS include
inflammation of lung tissue, obstruction of the small airways,
release of vasoactive substances stimulating pulmonary
vasoconstriction, and inhibition of surfactant function. MAS may
be complicated by the need for prolonged mechanical ventilation,
the development of pulmonary air leaks, or persistent pulmonary
hypertension. This severe respiratory compromise results in a
mortality rate among infants with MAS as high as 5%.55
1. The management of infants delivered through MSAF has
evolved over the past several decades.
a. In the 1970s, MAS was presumed to be a postnatal event
initiated by the aspiration of meconium at the time of the
first breath. Early investigations suggested that
meticulous suctioning of the fetal oropharynx and trachea
at delivery decreased the rate of MAS.56,57 With reports
of 100% survival in infants born through MSAF who
subsequently underwent tracheal intubation and
suctioning,56 a combined approach was introduced
involving suctioning of the upper airway at the perineum
followed by tracheal suctioning after delivery.57 Although
 the clinical significance of these earlier studies was
questionable, until recently, the combined two-step
approach was universally adopted.
b. MAS is no longer considered to be an exclusively
postnatal disorder. Recent studies suggest aspiration of
meconium by itself is insufficient to produce the
histologic or physiologic changes of severe MAS.58,59
Evidence of long-standing stress in infants with MAS,
including pulmonary hypertension and vascular
hypertrophy, suggests this is a complex, multifactorial
disorder with antenatal as well as intrapartum factors. It is
likely that aspiration of meconium is an event predating
labor, and severe MAS is caused by pathologic processes
occurring in utero, primarily chronic asphyxia and
infection.60
c. Therapeutic interventions that have traditionally been
advocated, including oropharyngeal suctioning prior to
delivery of the thorax and tracheal suctioning after
delivery, have questionable benefit in altering the
outcome of severe MAS.61–64 In an international,
prospective randomized controlled trial involving 2,514
infants, suctioning of the oropharynx and nasopharynx
prior to delivery of the thorax caused no difference in the
incidence of MAS, mechanical ventilation, duration of
supplemental oxygen use, or mortality.61 Other
investigators have found that vigorous, meconium-stained
infants with a heart rate >100 bpm, spontaneous
ventilation, and reasonable muscle tone do not benefit
from tracheal suctioning.62,63 The benefit of tracheal
suctioning in depressed infants born through MSAF has
yet to be determined.
d. It is imperative to recognize that tracheal suctioning may
actually cause complications, including: (1) vagal
stimulation resulting in bradycardia and apnea; (2)
 irritation to mucous membranes, causing increased mucus
production and nasal congestion; (3) tissue trauma,
resulting in a break in the natural barrier against infection,
thereby increasing the risk of transmission of infection.65
2. The Neonatal Resuscitation Program (NRP) and the ACOG
no longer recommend routine intrapartum oropharyngeal and
nasopharyngeal suctioning in the presence of MSAF; in
vigorous infants, tracheal suctioning is advocated only for
depressed neonates (see Fig. 17.6).

CLINICAL PEARL Intrapartum oropharyngeal and tracheal

suctioning is recommended only for the depressed infant born with
MSAF.

B. Premature infants
Although the survival rate of premature infants has steadily
increased over the past few decades,66,67 long-term morbidity and
mortality is still common in neonates less than 28 weeks’
gestational age.68 Appropriate resuscitation of this subset of
newborns requires an understanding of their unique physiologic
limitations. Although premature infants are at higher risk for
problems with multiple organ systems, the pulmonary and
cerebral systems deserve special consideration.
1. Fetal lung development during the third trimester is
characterized by the saccular development of terminal
bronchioles and the formation of surfactant by type II
pneumocytes. The reduction in pulmonary surface area and
surfactant production characteristic of immature lungs
contributes to difficulty in ventilation and increases
vulnerability to barotrauma during positive pressure
ventilation. In addition, the antioxidant defense system
develops late in gestation, and premature neonates may be
more susceptible to the adverse effects of excess oxygen. In
one study, preterm infants resuscitated with 30% oxygen had
less oxidative stress, inflammation, and chronic lung disease
compared to those resuscitated with 100% oxygen.69
However, room air appears to be insufficient for the
resuscitation of most neonates born at less than 28 weeks’
gestation.70–72 In another study, attempts to titrate oxygen
concentrations in preterm infants initially receiving room air
left several babies with uncertain or dangerously low levels of
oxygenation at 9 minutes of life.72 In an attempt to ensure
oxygenation while avoiding the complications of hyperoxia,
neonates <34 weeks should initially be resuscitated with 30%
oxygen. If oxygen saturation (SaO2) is less than 70% at 5
minutes of age or the heart rate is not increasing satisfactorily,
additional oxygen should be given.73
2. The cerebral architecture is often insufficiently developed in
the premature infant. Although the survival rate of infants
weighing less than 1,500 g is approximately 85%,74 a large
number of these infants display neurologic deficits later in
life. From 5% to 10% of very low birth weight infants
develop cerebral palsy and 25% to 50% exhibit behavioral
and cognitive deficits.75,76 The fragility of the immature
subependymal germinal matrix predisposes preterm neonates
to intraventricular hemorrhage (IVH), which is an early
 marker for brain injury. Antenatal interventions, such as
corticosteroids and magnesium sulfate,77–79 and postnatal
management strategies can decrease the risk of IVH and
improve neurologic outcome in the premature infant.
Establishing adequate ventilation helps maintain the integrity
of the cerebral vasculature. Hypoxemia and hypercarbia have
been linked to disruption of cerebrovascular autoregulation
and the development of pressure-passive cerebral
circulation.76 In addition, the rapid infusion of volume
expanders and hypertonic solutions, such as sodium
bicarbonate during neonatal resuscitation has been shown to
increase the risk of IVH and thus neurologic injury.76
3. Hypothermia can also cause significant morbidity and
mortality in the premature infant. Preterm neonates are prone
to thermoregulatory problems. Thin skin and a large body
surface area contribute to rapid heat loss, whereas inadequate
brown fat stores limit nonshivering thermogenesis. Cold stress
in this population leads to increased oxygen consumption,
hypoglycemia, and metabolic acidosis, which hinders
resuscitative efforts. Additional warming techniques,
including wrapping in polyethylene bags and radiant warmers,
are recommended in preterm, low birth weight infants to
prevent hypothermia.80

CLINICAL PEARL The deleterious effects of hypoxemia,

acidosis, and hypothermia on outcomes are greater in preterm,
compared to term, neonates.

C. Opioid-induced respiratory depression

Opioids administered for labor analgesia may contribute to
significant neonatal depression following delivery. The incidence
of respiratory depression in the neonate is related to cumulative
maternal opioid exposure and the elapsed time from last dosage.
 Narcotized infants are characterized by hypoventilation and poor
response to stimuli.
1. The AAP81 states naloxone should not be routinely
administered to infants exposed to opioids. These neonates
should be initially resuscitated with assisted ventilation. There
are currently no studies that have examined the use of
naloxone in infants with severe respiratory depression from
maternal opioid exposure. Naloxone (0.1 mg per kg) is
reserved as an adjunctive therapy in the small subset of
opioid-exposed infants who remain significantly depressed
with irregular respirations following a period of ventilation.81
2. Many experts have expressed concern about the potential
consequences of naloxone administration in this setting.81,82
Naloxone has been reported to cause acute withdrawal
symptoms including cardiac dysrhythmias, hypertension,
noncardiogenic pulmonary edema, and seizures. In addition,
there is some suggestion that neonatal administration of
naloxone may interfere with critical functions of endogenous
opioids and affect long-term behavior.81

CLINICAL PEARL Naloxone should not be used as a first-line

therapy in the neonate with depressed ventilation due to opioids.
Assisted ventilation should be used initially.

D. Magnesium toxicity
Hypermagnesemia may be encountered in neonates born to
mothers treated with large doses of magnesium for preeclampsia
and eclampsia. Magnesium easily crosses the placenta and can
influence the neuromuscular and cardiac systems of newborns.
Specifically, hypermagnesemic infants are generally flushed,
hypotensive, hypotonic, and peripherally vasodilated. In rare
circumstances, hypermagnesemic infants require intubation and
mechanical ventilation because of poor respiratory effort. In the
 presence of adequate renal function, magnesium levels normalize
over 24 to 48 hours. If severe hypotension is present, calcium can
be used as an antidote. The blood pressure of hypermagnesemic
neonates should increase with a bolus of 100 to 200 mg per kg of
calcium gluconate given over 5 minutes.

REFERENCES
1. American Heart Association. 2005 American Heart Association (AHA) guidelines for
cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC) of pediatric and
neonatal patients: neonatal resuscitation guidelines. Pediatrics. 2006;117:e1029–e1038.
2. Ostheimer GW. Anaesthetists’ role in neonatal resuscitation and care of the newborn. Can J Anaesth.
1993;40:R50–R62.
3. Rudolph AM, Heyman MA. Fetal and neonatal circulation and respiration. Annu Rev Physiol.
1974;36:187–207.
4. Wimmer JE Jr. Neonatal resuscitation. Pediatr Rev. 1994;15:255–265.
5. Swanson JR, Sinkin RA. Transition from fetus to newborn. Pediatr Clin North Am. 2015;62:329–343.
6. Lawson EE, Birdwell RL, Huang PS, et al. Augmentation of pulmonary surfactant secretion by lung
expansion at birth. Pediatr Res. 1979;13:611–614.
7. Lakshminrusimha S, Steinhorn RH. Pulmonary vascular biology during neonatal transition. Clin
Perinatol. 1999;26: 601–619.
8. Dawes G. Foetal and Neonatal Physiology: A Comparative Study of the Changes at Birth. Chicago,
IL: Year Book Medical; 1968:141–157.
9. Posen R, Friedlich P, Chan L, et al. Relationship between fetal monitoring and resuscitative needs:
fetal distress versus routine cesarean deliveries. J Perinatol. 2000;20:101–104.
10. Ray M, Freeman R, Pine S, et al. Clinical experience with the oxytocin challenge test. Am J Obstet
Gynecol. 1972;114:1–9.
11. Lagrew DC Jr. The contraction stress test. Clin Obstet Gynecol. 1995;38:11–25.
12. Manning FA, Platt LD, Sipos L. Antepartum fetal evaluation: development of a fetal biophysical
profile. Am J Obstet Gynecol. 1980;136:787–795.
13. Freeman RK, Anderson G, Dorchester W. A prospective multi-institutional study of antepartum fetal
heart rate monitoring. I. Risk of perinatal mortality and morbidity according to antepartum fetal heart
rate test results. Am J Obstet Gynecol. 1982;143:771–777.
14. Nageotte MP, Towers CV, Asrat T, et al. Perinatal outcome with the modified biophysical profile. Am J
Obstet Gynecol. 1994;170:1672–1676.
15. Vintzileos AM, Knuppel RA. Multiple parameter biophysical testing in the prediction of fetal acid-
base status. Clin Perinatol. 1994;21:823–848.
16. Schifrin BS, Dame L. Fetal heart rate patterns. Prediction of Apgar score. JAMA. 1972;219:1322–
1325.
17. Macones GA, Hankins GD, Spong CY, et al. The 2008 National Institute of Child Health and Human
Development workshop report on electronic fetal monitoring: update on definitions, interpretation,
and research guidelines. Obstet Gynecol. 2008;112:661–666.
18. Saling E. A new method for examination of the child during labor. Introduction, technic and principles
[in German]. Arch Gynakol. 1962;197:108–122.
19. Skupski DW, Rosenberg CR, Eglinton GS. Intrapartum fetal stimulation tests: a meta-analysis. Obstet
Gynecol. 2002;99:129–134.
20. Apgar V. A proposal for a new method of evaluation of the newborn infant. Curr Res Anesth Analg.
1953;32:260–267.
21. Casey BM, McIntire DD, Leveno KJ. The continuing value of the Apgar score for the assessment of
newborn infants. N Engl J Med. 2001;344:467–471.
22. Moster D, Lie RT, Irgens LM, et al. The association of Apgar score with subsequent death and cerebral
palsy: a population-based study in term infants. J Pediatr. 2001;138:798–803.
23. O’Donnell CP, Kamlin CO, Davis PG, et al. Interobserver variability of the 5-minute Apgar score. J
Pediatr. 2006;149: 486–489.
24. American Academy of Pediatrics, Committee on Fetus and Newborn, American College of
Obstetricians and Gynecologists, Committee on Obstetric Practice. The Apgar score. Pediatrics.
2006;117:1444–1447.
25. American College of Obstetricians and Gynecologists Committee on Obstetric Practice. ACOG
Committee Opinion No. 433: optimal goals for anesthesia care in obstetrics. Obstet Gynecol.
2009;113:1197–1199.
26. Adamson SK Jr, Gandy GM, James LS. The influence of thermal factors upon oxygen consumption of
the newborn human infant. J Pediatr. 1965;66:495–508.
27. Karlberg P. The breaths of life. In: Gluck L, ed. Modern Perinatal Medicine. Chicago, IL: Year Book
Medical; 1974:391–408.
28. Falck AJ, Escobedo MB, Baillargeon JG, et al. Proficiency of pediatric residents in performing
neonatal endotracheal intubation. Pediatrics. 2003;112:1242–1247.
29. Paterson SJ, Byrne PJ, Molesky MG, et al. Neonatal resuscitation using the laryngeal mask airway.
Anesthesiology. 1994;80:1248–1253.
30. Trevisanuto D, Micaglio M, Ferrarese P, et al. The laryngeal mask airway: potential applications in
neonates. Arch Dis Child Fetal Neonatal Ed. 2004;89:F485–F489.
31. Esmail N, Saleh M, Ali A. Laryngeal mask airway versus endotracheal intubation for Apgar score
improvement in neonatal resuscitation. Eg J Anaesth. 2002;18:115–121.
32. Probyn ME, Hooper SB, Dargaville PA, et al. Positive end expiratory pressure during resuscitation of
premature lambs rapidly improves blood gases without adversely affecting arterial pressure. Pediatr
Res. 2004;56:198–204.
33. Ramji S, Ahuja S, Thirupuram S, et al. Resuscitation of asphyxic newborn infants with room air or
100% oxygen. Pediatr Res. 1993;34:809–812.
34. Saugstad OD, Rootwelt T, Aalen O. Resuscitation of asphyxiated newborn infants with room air or
oxygen: an international controlled trial: the Resair 2 study. Pediatrics. 1998;102:e1.
35. Saugstad OD, Ramji S, Irani SF, et al. Resuscitation of newborn infants with 21% or 100% oxygen:
follow-up at 18 to 24 months. Pediatrics. 2003;112:296–300.
36. Saugstad OD, Ramji S, Vento M. Resuscitation of depressed newborn infants with ambient air or pure
oxygen: a meta-analysis. Biol Neonate. 2005;87:27–34.
37. Ramji S, Saugstad OD. Use of 100% oxygen or room air in neonatal resuscitation. Neoreviews.
2005;6:e172–e196.
38. Mendoza-Paredes A, Liu H, Schears G, et al. Resuscitation with 100%, compared with 21%, oxygen
following brief, repeated periods of apnea can protect vulnerable neonatal brain regions from
apoptotic injury. Resuscitation. 2008;76:261–270.
39. House JT, Schultetus RR, Gravenstein N. Continuous neonatal evaluation in the delivery room by
pulse oximetry. J Clin Monit. 1987;3:96–100.
40. Vento M, Asensi M, Sastre J, et al. Resuscitation with room air instead of 100% oxygen prevents
 oxidative stress in moderately asphyxiated term neonates. Pediatrics. 2001;107:642–647.
41. Ten VS, Matsiukevich D. Room air or 100% oxygen for resuscitation of infants with perinatal
depression. Curr Opin Pediatr. 2009;21:188–193.
42. Niijima S, Shortland DB, Levene MI, et al. Transient hyperoxia and cerebral blood flow velocity in
infants born prematurely and at full term. Arch Dis Child. 1988;63:1126–1130.
43. Menegazzi JJ, Auble TE, Nicklas KA, et al. Two-thumb versus two-finger chest compression during
CRP in a swine infant model of cardiac arrest. Ann Emerg Med. 1993;22:240–243.
44. Barber CA, Wyckoff MH. Use and efficacy of endotracheal versus intravenous epinephrine during
neonatal cardiopulmonary resuscitation in the delivery room. Pediatrics. 2006;118:1028–1034.
45. Ralston SH, Voorhees WD, Babbs CF. Intrapulmonary epinephrine during prolonged cardiopulmonary
resuscitation: improved regional blood flow and resuscitation in dogs. Ann Emerg Med. 1984;13:79–
86.
46. Kleinman ME, Oh W, Stonestreet BS. Comparison of intravenous and endotracheal epinephrine during
cardiopulmonary resuscitation in newborn piglets. Crit Care Med. 1999;27:2748–2754.
47. Wyckoff MH, Perlman JM, Laptook AR. Use of volume expansion during delivery room resuscitation
in near-term and term infants. Pediatrics. 2005;115:950–955.
48. Oca MJ, Nelson M, Donn SM. Randomized trial of normal saline versus 5% albumin for the treatment
of neonatal hypotension. J Perinatol. 2003;23:473–476.
49. Aschner JL, Poland RL. Sodium bicarbonate: basically useless therapy. Pediatrics. 2008;122:831–835.
50. Levy MM. An evidence-based evaluation of the use of sodium bicarbonate during cardiopulmonary
resuscitation. Crit Care Clin. 1998;14:457–483.
51. Lokesh L, Kumar P, Murki S, et al. A randomized controlled trial of sodium bicarbonate in neonatal
resuscitation-effect on immediate outcome. Resuscitation. 2004;60:219–223.
52. Emergency Cardiovascular Care Committee. Subcommittees and Task Forces of the American Heart
Association. 2005 American Heart Association guidelines for cardiopulmonary resuscitation and
emergency cardiovascular care. Circulation. 2005;112:1–203.
53. Harrington DJ, Redman CW, Moulden M, et al. The long-term outcome in surviving infants with
Apgar zero at 10 minutes: a systematic review of the literature and hospital-based cohort. Am J Obstet
Gynecol. 2007;196:463.e1–463.e5.
54. Wiswell TE, Bent RC. Meconium staining and the meconium aspiration syndrome. Unresolved issues.
Pediatr Clin North Am. 1993;40:955–981.
55. Wiswell TE, Tuggle JM, Turner BS. Meconium aspiration syndrome: have we made a difference?
Pediatrics. 1990;85:715–721.
56. Gregory GA, Gooding CA, Phibbs RH, et al. Meconium aspiration in infants—a prospective study. J
Pediatr. 1974;85:848–852.
57. Carson BS, Losey RW, Bowes WA Jr, et al. Combined obstetric and pediatric approach to prevent
meconium aspiration syndrome. Am J Obstet Gynecol. 1976;126:712–715.
58. Jovanovic R, Nguyen HT. Experimental meconium aspiration in guinea pigs. Obstet Gynecol.
1989;73:652–656.
59. Cornish JD, Dreyer GL, Snyder GE, et al. Failure of acute perinatal asphyxia or meconium aspiration
to produce persistent pulmonary hypertension in a neonatal baboon model. Am J Obstet Gynecol.
1994;171:43–49.
60. Ghidini A, Spong CY. Severe meconium aspiration syndrome is not caused by aspiration of
meconium. Am J Obstet Gynecol. 2001;185:931–938.
61. Vain NE, Szyld EG, Prudent LM, et al. Oropharyngeal and nasopharyngeal suctioning of meconium-
stained neonates before delivery of their shoulders: multicentre, randomised controlled trial. Lancet.
2004;364:597–602.
62. Wiswell TE, Gannon CM, Jacob J, et al. Delivery room management of the apparently vigorous
meconium-stained neonate: results of the multicenter, international collaborative trial. Pediatrics.
2000;105:1–7.
63. Linder N, Aranda JV, Tsur M, et al. Need for endotracheal intubation and suction in meconium-stained
neonates. J Pediatr. 1988;112:613–615.
64. Falciglia HS, Henderschott C, Potter P, et al. Does DeLee suction at the perineum prevent meconium
aspiration syndrome? Am J Obstet Gynecol. 1992;167:1243–1249.
65. Velaphi S, Vidyasagar D. The pros and cons of suctioning at the perineum (intrapartum) and post-
delivery with and without meconium. Semin Fetal Neonatal Med. 2008;13:375–382.
66. Markestad T, Kaaresen PI, Rønnestad A, et al. Early death, morbidity, and need of treatment among
extremely premature infants. Pediatrics. 2005;115:1289–1298.
67. Fanaroff AA, Stoll BJ, Wright LL, et al. Trends in neonatal morbidity and mortality for very low
birthweight infants. Am J Obstet Gynecol. 2007;196:147.e1–147.e8.
68. Landmann E, Misselwitz B, Steiss JO, et al. Mortality and morbidity of neonates born at <26 weeks of
gestation (1998–2003). A population-based study. J Perinat Med. 2008;36:168–174.
69. Vento M, Moro M, Escrig R, et al. Preterm resuscitation with low oxygen causes less oxidative stress,
inflammation, and chronic lung disease. Pediatrics. 2009;124:e439–e449.
70. Wang CL, Anderson C, Leone TA, et al. Resuscitation of preterm neonates by using room air or 100%
oxygen. Pediatrics. 2008;121:1083–1089.
71. Escrig R, Arruza L, Izquierdo I, et al. Achievement of targeted saturation values in extremely low
gestational age neonates resuscitated with low or high oxygen concentrations: a prospective,
randomized trial. Pediatrics. 2008;121:875–881.
72. Dawson JA, Kamlin CO, Wong C, et al. Oxygen saturation and heart rate during delivery room
resuscitation of infants <30 weeks’ gestation with air or 100% oxygen. Arch Dis Child Fetal Neonatal
Ed. 2009;94:F87–F91.
73. Vento M, Saugstad OD. Resuscitation of the term and preterm infant. Semin Fetal Neonatal Med.
2010;15:216–222.
74. Hamilton BE, Miniño AM, Martin JA, et al. Annual summary of vital statistics: 2005. Pediatrics.
2007;119:345–360.
75. Wolke D, Meyer R. Cognitive status, language attainment, and prereading skills of 6-year-old very
preterm children and their peers: the Bavarian longitudinal study. Dev Med Child Neurol. 1999;41:94–
109.
76. Volpe JJ. Neurology of the Newborn. 5th ed. Philadelphia, PA: Saunders Elsevier; 2008.
77. Moïse AA, Wearden ME, Kozinetz CA, et al. Antenatal steroids are associated with less need for
blood pressure support in extremely premature infants. Pediatrics. 1995;95:845–850.
78. Nelson KB, Grether JK. Can magnesium sulfate reduce the risk of cerebral palsy in very low
birthweight infants? Pediatrics. 1995;95:263–269.
79. Hirtz DG, Nelson K. Magnesium sulfate and cerebral palsy in premature infants. Curr Opin Pediatr.
1998;10:131–137.
80. Watkinson M. Temperature control of premature infants in the delivery room. Clin Perinatol.
2006;33:43–53.
81. American Academy of Pediatrics. Committee on drugs. Naloxone use in newborns. Pediatrics.
1980;65:667–669.
82. Herschel M, Khoshnood B, Lass NA. Role of naloxone in newborn resuscitation. Pediatrics.
2000;106:831–834.
Postpartum Issues
 Postcesarean Analgesia
Richard N.Wissler

I. Introduction
II. Multimodal therapy
A. Goals
B. Components of multimodal therapy
III. Medications: oral, systemic, neuraxial, and regional administration
A. Opioids
B. Local anesthetics
C. Nonsteroidal anti-inflammatory drugs
D. Acetaminophen
E. Other medications
F. Medications in breast milk
IV. Summary

KEYPOINTS
1. The use of multimodal analgesia and differing routes of administration
will increase overall postcesarean delivery (post-CD) analgesia and
reduce the incidence of unwanted side effects.
2. Opioids are the mainstay of post-CD analgesia. Intravenous patient-
controlled analgesia (PCA) opioid administration provides superior pain
relief compared to intermittent caregiver administration and may have
 analgesic effectiveness comparable to neuraxial opioid administration.
3. Neuraxial opioids are the gold standard in providing post-CD analgesia
by decreasing overall opioid consumption, improving ambulation,
allowing earlier return of bowel function, and improving reductions in
breast milk levels of opioids compared to systemically administered
opioids.
4. Neuraxial opioids are associated with nausea, vomiting, urinary retention,
respiratory depression, and pruritus.
5. Continuous wound infiltration with local anesthetic using catheter
techniques may offer significant post-CD analgesia. The use of
transversus abdominis blockade does not offer significant analgesic
advantage when added to neuraxial opioid administration.
6. Nonsteroidal anti-inflammatory drugs, when administered orally or
intravenously and when added to local anesthetics used in neuraxial
blockade, are useful analgesic adjuncts to opioids. Acetaminophen may
offer significant analgesia and is safe for mother and child.
7. Predicting the effects of maternally administered medications that appear
in breast milk is complex. Consulting the published guidelines written by
professional organizations is recommended

I. Introduction
Pain relief after cesarean delivery (CD) has many of the same clinical
considerations as analgesia following other forms of abdominal
surgery. Additional concerns in the post-CD population include the
goal of minimizing maternal sedation to facilitate interactions with the
newborn, family, and friends; transfer of analgesic medications in
breast milk; and reducing time to discharge to home. CD is a very
common surgical procedure, and anesthesiologists should be familiar
with current post-CD analgesic techniques. More than 1.28 million
CD were performed in the United States in 2013, representing
32.7% of all births.1 As seen in the subsequent text, the anesthetic
method used for CD often influences the choices for postcesarean
analgesia. Both scheduled and unplanned CD have similar acute
 postoperative pain scores and analgesic requirements.2
Acute postoperative or nociceptive pain following CD is a
combination of visceral pain from the uterus and somatic pain
from the abdominal wall. Recent research has focused on the
subsequent development of chronic neuropathic pain at the abdominal
incision site. Retrospective and prospective studies of chronic pain
after CD report an incidence range of 1% to 18%.3 At this time,
modifications of post-CD analgesia to decrease the incidence of
chronic incisional pain are investigational only. This chapter focuses
on current analgesic strategies for acute nociceptive post-CD pain.
However, some data suggest that effective treatment of acute
postoperative pain may minimize the development of chronic pain in
these patients.4
Effective post-CD analgesia is an attainable goal recommended
by several national professional organizations.5,6 One prospective
written survey of pregnant patients before delivery demonstrates that
pain during and after CD are the two most concerning anesthesia
outcomes.7 A prospective study of healthy parturients shows that
preoperative questions about anxiety, expected postoperative pain,
and expected needs of postoperative analgesic medications are
moderately predictive of post-CD analgesic requirements.8 However,
the practical application of preoperative questionnaires for routine
clinical practice is not clear.
II. Multimodal therapy
A. Goals. Utilizing several medications and/or routes of
administration that complement each other.5,9 The goals are:
1. Increasing the effectiveness of analgesia
2. Decreasing medication side effects by decreasing doses of
individual medications
B. Components of multimodal therapy. Examples of multimodal
therapy for post-CD analgesia include different combinations of
the following:
1. Systemic opioids
 2. Systemic nonsteroidal anti-inflammatory drugs (NSAIDs)
3. Epidural medications
a. Opioids
b. Adjuncts
c. Local anesthetics
4. Intrathecal (IT) medications
a. Opioids
b. Adjuncts
5. Direct wound site treatments
a. Local anesthetics
b. NSAIDs

CLINICAL PEARL A multimodal approach to post-CD

analgesia will improve overall analgesia and reduce side effects.

III. Medications: oral, systemic, neuraxial, and regional

administration
A. Opioids. They have historically been and remain the mainstay of
post-CD and analgesic medications.
1. Reported routes of administration include intramuscular (IM),
intravenous (IV), epidural, IT, oral (PO), rectal, and rarely,
intranasal.
2. Systemic opioids
a. Specific medications studied include morphine,
meperidine, hydromorphone, fentanyl, sufentanil,
oxymorphone, butorphanol, and diamorphine. Choice of
opioid is influenced by its overall direct effects, time of
onset, duration of action, and the frequency and nature of
side effects.
b. IV meperidine is seldom used for post-CD analgesia
due to concerns about infant sedation by the active
metabolite, normeperidine.10 However, patient-
controlled epidural analgesia (PCEA) with meperidine
results in lower maternal systemic doses that should be
 compatible with neonatal safety during breastfeeding.11
c. Diamorphine (heroin) is a Drug Enforcement
Administration (DEA) Schedule I medication and not
available for clinical use in the United States, although it
has enjoyed widespread epidural and IT use in the United
Kingdom and other parts of Europe.
d. IV opioid administration, particularly by patient-
controlled analgesia (PCA), provides superior post-CD
analgesia compared to the IM route.12
e. Direct comparisons of demand-only IV PCA with IV PCA
and continuous basal infusion are limited in women after
CD.13 In the absence of a definite overall advantage of
basal infusion IV PCA, along with safety concerns
regarding respiratory depression associated with the basal
infusion rates in other postsurgical populations,14 the
author recommends the demand-only mode of IV PCA
in post-CD patients.
f. Table 18.1 lists the IV PCA doses for several opioids. The
effectiveness of IV PCA as an analgesic modality
requires adequate loading doses.

g. The demand-only IV PCA incorporates several safety

features to minimize the possibility of a patient
receiving unsafe doses of IV opioid. First, the PCA
pump is programmed to limit the amount of opioid per
patient request and per hour. Second, if the patient is very
sedated, she will be unable to push the PCA demand
button and the current opioid effect will diminish.
Unfortunately, even with these safeguards, adverse
 outcomes have occurred with IV PCA in post-CD
patients. Examples include visitors activating the PCA
demand button for the patient (i.e., PCA by proxy) and
medication and programming errors.15,16

CLINICAL PEARL IV PCA opioid administration offers

superior pain relief compared to intermittent administration by
health care workers. Its safety is maximized if given by patient
demand only without use of a low-dose baseline infusion.

3. Epidural opioids
a. Specific medications studied include morphine,
meperidine, hydromorphone, fentanyl, sufentanil,
oxymorphone, methadone, nalbuphine, butorphanol,
buprenorphine, and diamorphine (not available in the
United States).
b. The rationale for neuraxial (i.e., epidural or spinal)
administration of opioids is to improve the analgesic
efficacy while minimizing the side effects of the opioids
when administered by other routes. These side effects
include sedation, respiratory depression, nausea and
vomiting, itching, and urinary retention. However, all
these side effects can occur with either systemic or
neuraxial opioids.
c. A single dose of epidural morphine:
(1) Provides better post-CD analgesia than a saline
placebo17 or IM opioids12,18
(2) Has similar analgesic efficacy and patient
satisfaction compared to IV PCA morphine12,18
(3) Is associated with more pruritus than IV PCA or
IM morphine
(4) May be less effective than if given by continuous
infusion19
d. Studies of PCEA in patients receiving post-CD analgesia
with fentanyl, sufentanil, or hydromorphone demonstrate:
(1) Better pain relief, less medication administration, and
more pruritus compared to IV PCA opioids20,21
(2) No benefit of continuous basal infusion PCEA versus
demand-only PCEA22,23
e. A single dose of epidural fentanyl should be diluted to an
injection volume of at least 10 mL for the best effect.24
However, injection volume variations with single doses of
epidural morphine do not have a significant effect on
post-CD analgesic efficacy.25
f. Extended-release epidural morphine
(1) It was approved by the U.S. Food and Drug
Administration (FDA) in 2004 for postoperative
analgesia, with the trade name of DepoDur.26
(2) Two prospective randomized studies have compared
DepoDur® to conventional morphine for post-CD
epidural analgesia.27,28 The patients who received
DepoDur had improved pain scores at rest and with
movement as well as improved functional ability. The
differences between DepoDur and conventional
morphine were restricted to the 24 to 48 hour
postoperative time frame, but the magnitude of
those differences was clinically modest.
(3) Although it is approved for clinical use, it is currently
not being produced by the pharmaceutical company,
Pacira, who currently own the license. They are using
the carrier, DepoFoam to manufacture the long acting
local anesthetic preparation, Exparel.
g. Table 18.2 lists the recommended single doses of
conventional epidural opioids, based on prospective
randomized studies.
 h. Adjuncts and epidural opioids
(1) Clonidine (75 to 150 µg) improves post-CD
analgesia when added to single epidural doses of
fentanyl or morphine.29,30 However, there is an FDA
black box warning for clonidine. “Duraclon®
(epidural clonidine) is not recommended for
obstetric, postpartum, or perioperative pain
management . . . ” Use of clonidine alone does not
offer significant analgesic improvement over
neuraxial opioid use, and the associated side effects
of frequent sedation and hypotension mitigate against
its routine use.
(2) Epinephrine has demonstrated inconsistent effects in
improving analgesia and reducing side effects when
added to single doses of epidural opioids.
(3) The use of N-methyl-D-aspartate (NMDA)
antagonists (e.g., ketamine, magnesium), although
safe and effective in producing analgesia in a very
limited number of studies, should be considered
experimental at present.
4. Intrathecal Opioids
a. Specific medications studied include morphine,
meperidine, fentanyl, sufentanil, nalbuphine, butorphanol,
and buprenorphine.
b. In contrast to systemic and epidural routes of
administration, IT administration of opioids does not
lead to clinically significant maternal serum
concentrations of these agents.31,32
c. In most circumstances, IT opioid administration implies a
“single-shot” opioid delivery as part of a spinal or
combined spinal-epidural (CSE) anesthetic. A number of
IT local anesthetics have been combined successfully with
IT opioids including lidocaine, bupivacaine, tetracaine,
mepivacaine, and ropivacaine.
d. Direct comparisons of the IT and epidural routes of
administration for single-dose morphine show similar
efficacy for post-CD analgesia.31,32 However, the
recommended dose is reduced by approximately 20-fold
in the IT space.
e. In many instances, pruritus is more prevalent and intense
with IT opioids, compared with either epidural or
systemic administration.
f. Table 18.3 lists the recommended single doses of IT
opioids based on the best available evidence.

g. Adjuncts and IT opioids

(1) Clonidine (60 to 150 µg) improves postcesarean
analgesia when added to a single IT dose of morphine
or sufentanil.33–35 IT clonidine is likely to increase
the duration of the spinal anesthetic as well as
maternal intraoperative sedation.34,35 Refer to section
III.A.3.h.(1) for the FDA “black box” warning on
neuraxial clonidine.
(2) Neostigmine (12.5 μg) improves post-CD analgesia
and may reduce side effects when added to a
subtherapeutic dose of IT morphine.36 Its short
 duration of action and side effect profile do not
convey significant benefit over use of neuraxial
opioids.
(3) Epinephrine does not seem to improve post-CD
analgesia when used with IT opioids.
(4) IT ketamine and magnesium use should be
considered experimental.

CLINICAL PEARL Neuraxial administered morphine offers

superior analgesia of long duration. The use of adjunct medications
does not appear to offer significant advantages when added to
single-shot neuraxial morphine.

5. Opioid side effects

a. Respiratory depression, with the risk of apnea and
hypoxic injury or death, is the most serious side effect
of opioids. This complication is encountered in
postoperative patients after opioid administration by
any route. The American Society of Anesthesiologists
developed a practice guideline focused on potential
respiratory depression after neuraxial opioid
administration.37 Some recommendations included in this
document are:
(1) The anesthesiologist should conduct a focused
history and physical examination to identify patient
characteristics associated with a risk of respiratory
depression (obesity, obstructive sleep apnea,
coexisting respiratory disease).
(2) Although neuraxial opioids may be safely used in
place of parenteral opioids without increasing the risk
of respiratory depression, the concomitant
administration of parenteral opioids and other
sedatives requires increased monitoring due to
 increased risk.
(3) All patients receiving neuraxial opioids should be
monitored for the adequacy of ventilation (respiratory
rate, depth of breathing), oxygenation (pulse
oximetry depending on patient condition), and level
of consciousness, without disturbing a sleeping
patient.
(4) After a single injection of lipophilic opioid,
monitoring should continue for a minimum of 2
hours, after which the patient’s overall clinical
condition should guide monitoring. After a single
injection of a hydrophilic opioid, monitoring should
be performed for a period of 24 hours, with
monitoring at hourly intervals for the first 12 hours
and every 2 hours for the next 12 hours.
(5) Supplemental oxygen should be available to all
patients and administered to those with signs of
respiratory depression or hypoxemia. An IV line
should be maintained for administration of reversal
agents if needed.
(6) Women after CD may be at lower risk for respiratory
depression after neuraxial opioid use compared to
other surgical patients. A recent retrospective study of
women after CD treated with common doses of
epidural or spinal morphine found no instances of
respiratory depression in more than 5,000 patients.38
b. Pruritus is a common side effect of neuraxial opioid
treatment. In many instances, it seems to worsen with
increasing doses of a given opioid and may be more
intense with IT as opposed to epidural administration. A
number of therapies have been proposed.39
(1) Opioid antagonists. The most consistent treatment
is with opioid antagonist medications, either a pure
antagonist (e.g., naloxone40) or a mixed agonist–
 antagonist (e.g., nalbuphine41).
(2) Diphenhydramine. Diphenhydramine 25 mg IV can
be helpful in the treatment of pruritus. Although its
mechanism of action in this setting is unknown, it can
produce profound sedation. Because opioid-induced
pruritus does not appear to be mediated by histamine
release, the antihistamine-effects of diphenhydramine
do not appear to play a significant role in reducing
pruritus.
(3) 5-HT3 receptor antagonists. Because morphine is
known to activate 5-HT3 receptors by a mechanism
independent of opioid receptors, morphine may
directly stimulate 5-HT3 receptors and cause IT
morphine-induced pruritus. Consequently, occupation
of 5-HT3 receptors by a 5-HT3 receptor antagonist
potentially prevents the pruritus. Both ondansetron
and dolasetron have been administered
prophylactically in the treatment of IT morphine-
induced pruritus with variable results.
c. Nausea and vomiting has a multifactorial etiology after
CD.39 Clearly, opioids can contribute significantly to this
problem. As with pruritus, one strategy has been to
minimize opioid doses whenever possible through
multimodal therapy. There is little consensus about
specific therapies to prevent or treat postcesarean nausea
and vomiting. Table 18.4 provides suggested prophylactic
and therapeutic interventions for nausea and vomiting.

CLINICAL PEARL Opioid agonist/antagonist drugs are

effective in treating the pruritus associated with neuraxially
administered opioids. Nausea and vomiting are effectively treated
with a variety of medications because many factors affect its
incidence and severity.

B. Local anesthetics
1. Epidural
a. Local anesthetics, alone or in combination with opioids,
may be infused by the lumbar epidural route for post-CD
analgesia. The infusion strategy may be continuous or by
PCEA, analogous to postoperative analgesia regimens for
other lower abdominal surgeries.5
b. Adding a local anesthetic to an epidural opioid infusion
may have a dose-sparing effect,42 but it can result in
lower extremity motor block and delayed ambulation in
women after CD.43
2. Iliohypogastric and ilioinguinal peripheral nerve blocks
a. These two peripheral nerves originate from the L1 spinal
nerve root and innervate the abdominal wall region that
corresponds to a lower transverse cesarean incision. The
blocks need to be performed bilaterally.
b. The existing literature with single-shot nerve blocks
presents conflicting results about the effectiveness of
perioperative placement of these blocks in decreasing
subsequent supplemental opioid use after low transverse
CD.44–46
c. A case series of ultrasound-guided continuous ilioinguinal
and iliohypogastric nerve blocks in post-CD patients
describes apparent opioid-sparing in the postoperative
period.47
3. Transversus abdominis plane blocks
a. A transversus abdominis plane (TAP) block is a lower
abdominal wall block accomplished by placing local
 anesthetic medications in the fascial plane between the
internal oblique and the transversus abdominis muscles. It
must be performed bilaterally and uses approximately 20
mL of local anesthetic per side. Although initially
described using surface anatomy landmarks, it is now
placed with real-time ultrasound guidance.
b. When used after spinal anesthesia for CD, the TAP block
adds value only when IT morphine is omitted from a
multimodal analgesic regimen.48,49 A prospective direct
comparison study in post-CD patients demonstrates that
IT morphine is a more effective analgesic technique
compared to a TAP block, but with a higher side effect
profile.50 A case series in this patient population describes
a continuous bilateral TAP block technique using 20
gauge epidural catheters placed with ultrasound
guidance.51
c. The role of TAP blocks in for post-CD analgesia is
evolving. Their best use maybe in treating pain after
general anesthesia or as rescue treatment after spinal
anesthesia52 when neuraxial opioids have failed or are not
indicated. Adding 75 µg of clonidine to each side of a
post-CD local anesthetic TAP block did not improve its
performance in a multimodal analgesic regimen that
included IT morphine.53
4. Surgical wound infiltration
a. Single-injection direct surgical wound infiltration with 20
mL of bupivacaine 0.5% at wound closure does not
significantly change postoperative supplemental analgesic
use after low transverse CD54,55; however, injection of
local anesthetic at the fascial level during wound closure
decreases opioid requirements during the first 12 hours of
recovery.56
b. Postoperative wound infusion, using a catheter
inserted at the time of surgery, is an effective post-CD
 analgesic technique.57,58 Direct comparisons show
postoperative wound infusions with local anesthetics are
more effective than epidural morphine and similar to
systemic diclofenac.58,59 Catheter infusions are most
effective when located deep to the fascia at the time of
wound closure60 and should be placed using ultrasound
guidance to improve success.
c. Postoperative wound infusions with local anesthesia affect
specific inflammatory mediators measured in wound
exudates, suggesting an interaction with the wound
healing process.61
d. It remains to be seen if infiltration of the wound with
Exparel®, the long acting local anesthetic product,
improves post-CD analgesia, especially on day 2
postoperatively

CLINICAL PEARL TAP blocks do not offer improved analgesia

when added to single-shot neuraxially administered morphine.
Continuous catheter techniques can improve analgesia but should
be placed under ultrasound guidance.

C. Nonsteroidal anti-inflammatory drugs

1. Many different NSAIDs have been used successfully for
postcesarean analgesia. They are the most common class of
drugs used in conjunction with opioids as components of
multimodal analgesic regimens. In a study of non-pregnant
women after laparotomy, NSAID administration had
analgesic effects similar to codeine-acetaminophen
combinations.62
2. NSAIDs are typically administered by the PO, IV, or rectal
routes. Recent studies have described direct postoperative
wound infiltration with NSAIDs, using a continuous infusion
through a wound catheter inserted at CD. In one study,
 diclofenac was as effective as ropivacaine for wound
infiltration and more effective than systemic diclofenac.63 A
second study described the effects of adding ketorolac (0.6
mg per hour) to bupivacaine for continuous wound
infiltration.64 In this regimen, ketorolac improved analgesia
and altered inflammatory mediators in wound exudates. The
authors concluded that NSAID administration directly into a
surgical wound is a strategy to accomplish the analgesia of
NSAIDs while minimizing their systemic side effects.
3. Relative contraindications to the use of NSAIDs in post-CD
analgesia include:
a. History of renal disease
b. History of upper gastrointestinal ulcers
c. Prior sensitivity to NSAIDs
d. Coagulation deficits
e. Problems with surgical hemostasis
4. The benefits of using selective cyclooxygenase 2 inhibitors as
opposed to other NSAIDs has not been demonstrated for post-
CD analgesia.
D. Acetaminophen
1. Acetaminophen may be administered by the PO, rectal, or IV
routes. As a component of multimodal postoperative
analgesia, acetaminophen has been most commonly
prescribed in combination with oral opioids such as codeine,
oxycodone, or hydrocodone. Following spinal anesthesia for
CD without IT morphine, patients receiving oral oxycodone-
acetaminophen had slightly better pain scores than patients
with IV PCA morphine.65
2. The current clinical interest in acetaminophen as a component
of post-CD multimodal analgesia is driven by two issues:
a. Unpredictable factors during CD (such as impaired
hemostasis) may preclude the use of NSAIDs in the
postoperative period.
b. Recent approval in the United States of an IV formulation
 of acetaminophen
3. Following spinal anesthesia for CD without IT morphine,
patients had similar postoperative analgesia with either 1 g IV
acetaminophen every 6 hours or 400 mg oral ibuprofen every
4 hours.66
4. Current controversies with acetaminophen include the clinical
efficacy and cost-effectiveness of IV acetaminophen
compared to other routes of administration. Also, the large IV
doses of acetaminophen raise concerns about unintended toxic
doses when combined with the oral formulations, particularly
when patients are transferred between clinical services or
units.

CLINICAL PEARL NSAIDs can be administered orally, IV, and

as adjuncts to local anesthetic neuraxial block for analgesic effects.
Whether acetaminophen has significant analgesic properties is
unclear, but it has very few reported side effects and thus a very
good safety profile.

E. Other medications
1. Ketamine
CD patients who received IV ketamine in subhypnotic doses
during either spinal or general anesthesia had only transient
small decreases in postoperative pain or none at all.67–69 One
study described a modest decrease in pain scores 2 weeks
after surgery in the ketamine group.69
2. Gabapentin
Perioperative oral dosing with gabapentin does not produce
clinically meaningful post-CD analgesia. In addition, it is
associated with increased sedation.70,71
3. Magnesium when administered intravenously demonstrates
minimal reduction in pain scores and modest reduction in
opioid use in non-pregnant women after surgery but has not
 been evaluated in women after CD.72

CLINICAL PEARL The routine use of NMDA receptor

antagonist drugs (e.g., magnesium, ketamine) and gabapentinoids
for postcesarean analgesia is not currently recommended.

F. Medications in breast milk

1. The pharmacokinetics of medications and breast milk are
complex, and data are incomplete for many medications.
Breast milk is a combined solution and suspension, and the
composition changes over the first week postdelivery as the
colostrum transitions to mature milk. These factors make it
difficult for health care providers to predict whether
individual medications will be present in breast milk in
sufficient concentrations to cause a clinically significant
effect in the infant.
2. Recent case series and studies have expressed concern over
the variations between individuals in activity of the hepatic
cytochrome P450 enzyme 2D6 (CYP2D6). This enzyme
metabolizes codeine to its active form (morphine) and
oxycodone to oxymorphone. Individuals with excess
CYP2D6 activity (i.e., ultra-rapid metabolizers) may generate
excess maternal opioid activity, increasing the transfer to the
infant through breast milk. This situation can cause sedation
in the mother and baby, but rare fatalities have been
reported.73–75
3. This author’s recommendation is to utilize an
authoritative source for decisions about medications and
breastfeeding. There are two guidelines from professional
organizations76,77 and three textbooks78–80 listed in the
reference section of this chapter. Ready access to these
publications will facilitate clinical decision making and
patient communication; this is particularly important
 because of common maternal concerns regarding the
effects of maternal analgesia on the nursing newborn. The
recommendations are not identical, but in general, the
commonly used opioids and NSAIDs for post-CD
analgesia are compatible with breastfeeding. The
exceptions among the opioids are meperidine, codeine, and
oxycodone.

CLINICAL PEARL The effects of maternally administered

drugs is complex and unpredictable. The use of published
guidelines is recommended.

IV. Summary
A. Multimodal therapy is the current and future direction for post-
CD analgesia.
B. Opioids have been, and continue to be, the dominant medications
for pain relief after CD despite concerns about patient safety.
C. IM route of administration should be considered only as a last
resort.
D. NSAIDs have a widespread role in post-CD analgesia, frequently
in addition to opioids.
E. Acetaminophen’s use as a postoperative medication continues to
evolve, particularly in reference to IV versus other routes of
administration. The total dose in different formulations needs to
be appreciated to minimize the risk of toxicity.
F. Patient-controlled catheter infusions are promising techniques and
can be used for postoperative wound infiltration with a local
anesthetic and/or NSAID.
G. Analgesic medications are mostly compatible with breastfeeding.
As discussed earlier, some concerns have been expressed
concerning the administration of meperidine, codeine, or
oxycodone to patients who are breastfeeding, based on different
mechanisms of drug metabolism.
 H. In general, postoperative pain management is an opportunity for
anesthesiologists to collaborate with obstetricians and obstetric
nurses. We have expertise to share that will improve the
postoperative experience for many patients after CD. New
initiatives for post-CD analgesia are unlikely to succeed without
the prior knowledge and support of our clinical obstetric and
nursing colleagues. Also, in the current regulatory climate,
hospitals will appreciate assistance in improving patient
satisfaction scores.

REFERENCES
1. Martin JA, Hamilton BE, Osterman MJ, et al. Births: final data for 2013. Natl Vital Stat Rep. 2015;
64:1–65.
2. Carvalho B, Coleman L, Saxena A, et al. Analgesic requirements and postoperative recovery after
scheduled compared to unplanned cesarean delivery: a retrospective chart review. Int J Obstet Anesth.
2010;19:10–15.
3. Landau R, Bollag L, Ortner C. Chronic pain after childbirth. Int J Obstet Anesth. 2013;22:133–145.
4. Eisenach JC, Pan P, Smiley RM, et al. Resolution of pain after childbirth. Anesthesiology.
2013;118:143–151.
5. American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for
acute pain management in the perioperative setting: an updated report by the American Society of
Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012;116:248–273.
6. American College of Obstetricians and Gynecologists. Guidelines for Perinatal Care. 7th ed.
Washington, DC: American College of Obstetricians and Gynecologists; 2012.
7. Carvalho B, Cohen SE, Lipman SS, et al. Patient preferences for anesthesia outcomes associated with
cesarean delivery. Anesth Analg. 2005;101:1182–1187.
8. Pan PH, Tonidandel AM, Aschenbrenner CA, et al. Predicting acute pain after cesarean delivery using
three simple questions. Anesthesiology. 2013;118:1170–1179.
9. Tan M, Law LS, Gan TJ. Optimizing pain management to facilitate enhanced recovery after surgery
pathways. Can J Anaesth. 2015;62:203–218.
10. Wittels B, Scott DT, Sinatra RS. Exogenous opioids in human breast milk and acute neonatal
neurobehavior: a preliminary study. Anesthesiology. 1990;73:864–869.
11. Al-Tamimi Y, Ilett KF, Paech MJ, et al. Estimation of infant dose and exposure to pethidine and
norpethidine via breast milk following patient-controlled epidural pethidine for analgesia post
cesarean delivery. Int J Obstet Anesth. 2011;20:128–134.
12. Eisenach JC, Grice SC, Dewan DM. Patient-controlled analgesia following cesarean section: a
comparison with epidural and intramuscular narcotics. Anesthesiology. 1988;68:444–448.
13. Sinatra R, Chung KS, Silverman DG, et al. An evaluation of morphine and oxymorphone administered
via patient-controlled analgesia (PCA) or PCA plus basal infusion in postcesarean-delivery patients.
Anesthesiology. 1989;71:502–507.
14. Parker RK, Holtmann B, White PF. Effects of a nighttime opioid infusion with PCA therapy on patient
 comfort and analgesic requirements after abdominal hysterectomy. Anesthesiology. 1992;76:362–367.
15. Lam FY. Patient-controlled analgesia by proxy. Br J Anaesth. 1993;70:113.
16. Vicente KJ, Kada-Bekhaled K, Hillel G, et al. Programming errors contribute to death from patient-
controlled analgesia: case report and estimate of probability. Can J Anaesth. 2003;50:328–332.
17. Binsted RJ. Epidural morphine after caesarean section. Anaesth Intensive Care. 1983;11:130–134.
18. Harrison DM, Sinatra R, Morgese L, et al. Epidural narcotic and patient-controlled analgesia for post-
cesarean section pain relief. Anesthesiology. 1988;68:454–457.
19. Rauck RL, Raj PP, Knarr DC, et al. Comparison of the efficacy of epidural morphine given by
intermittent injection or continuous infusion for the management of postoperative pain. Reg Anesth.
1994;19:316–324.
20. Cooper DW, Ryall DM, Desira WR. Extradural fentanyl for postoperative analgesia: predominant
spinal or systemic action? Br J Anaesth. 1995;74:184–187.
21. Ngan Kee WD, Lam KK, Chen PP, et al. Comparison of patient-controlled epidural analgesia with
patient-controlled intravenous analgesia using pethidine or fentanyl. Anaesth Intensive Care.
1997;25:126–132.
22. Parker RK, Sawaki Y, White PF. Epidural patient-controlled analgesia: influence of bupivacaine and
hydromorphone basal infusion on pain control after cesarean delivery. Anesth Analg. 1992;75:740–
746.
23. Vercauteren MP, Coppejans HC, ten Broecke PW, et al. Epidural sufentanil for postoperative patient-
controlled analgesia (PCA) with or without background infusion: a double-blind comparison. Anesth
Analg. 1995;80:76–80.
24. Birnbach DJ, Johnson MD, Arcario T, et al. Effect of diluent volume on analgesia produced by
epidural fentanyl. Anesth Analg. 1989;68:808–810.
25. Asantila R, Eklund P, Rosenberg PH. Epidural analgesia with 4 mg of morphine following caesarean
section: effect of injected volume. Acta Anaesthesiol Scand. 1993;37:764–767.
26. U.S. Food and Drug Administration. Product label for DepoDur.
www.accessdata.fda.gov/drugsatfda_docs/label/2009/021671s020lbl.pdf. Accessed April 30, 2015.
27. Carvalho B, Riley E, Cohen SE, et al. Single-dose, sustained-release epidural morphine in the
management of postoperative pain after elective cesarean delivery: results of a multicenter randomized
controlled study. Anesth Analg. 2005;100: 1150–1158.
28. Carvalho B, Roland LM, Chu LF, et al. Single-dose, extended-release epidural morphine (DepoDur)
compared to conventional epidural morphine for post-cesarean pain. Anesth Analg. 2007;105:176–
183.
29. Eisenach JC, D’Angelo R, Taylor C, et al. An isobolographic study of epidural clonidine and fentanyl
after cesarean section. Anesth Analg. 1994;79:285–290.
30. Capogna G, Celleno D, Zangrillo A, et al. Addition of clonidine to epidural morphine enhances
postoperative analgesia after cesarean delivery. Reg Anesth. 1995;20:57–61.
31. Sarvela J, Halonen P, Soikkeli A, et al. A double-blinded, randomized comparison of intrathecal and
epidural morphine for elective cesarean delivery. Anesth Analg. 2002; 95:436–440.
32. Dualé C, Frey C, Bolandard F, et al. Epidural versus intrathecal morphine for postoperative analgesia
after caesarean section. Br J Anaesth. 2003;91:690–694.
33. Paech MJ, Pavy TJ, Orlikowski CE, et al. Postcesarean analgesia with spinal morphine, clonidine, or
their combination. Anesth Analg. 2004;98:1460–1466.
34. Lavand’homme PM, Roelants F, Waterloos H, et al. An evaluation of the postoperative
antihyperalgesic and analgesic effects of intrathecal clonidine administered during elective cesarean
delivery. Anesth Analg. 2008;107:948–955.
35. van Tuijl I, van Klei WA, van der Werff DB, et al. The effect of addition of intrathecal clonidine to
 hyperbaric bupivacaine on postoperative pain and morphine requirements after cesarean section: a
randomized controlled trial. Br J Anaesth. 2006;97:365–370.
36. Chung CJ, Kim JS, Park HS, et al. The efficacy of intrathecal neostigmine, intrathecal morphine, and
their combination for post-cesarean section analgesia. Anesth Analg. 1998;87:341–346.
37. American Society of Anesthesiologists Task Force on Neuraxial Opioids, Horlocker TT, Burton AW,
et al. Practice guidelines for the prevention, detection, and management of respiratory depression
associated with neuraxial opioid administration. Anesthesiology. 2009;110:218–230.
38. Crowgey TR, Dominguez JE, Peterson-Layne C, et al. A retrospective assessment of the incidence of
respiratory depression after neuraxial morphine administration for postcesarean delivery analgesia.
Anesth Analg. 2013;117:1368–1370.
39. Dominguez JE, Habib AS. Prophylaxis and treatment of the side-effects of neuraxial morphine
analgesia following cesarean delivery. Curr Opin Anesthesiol. 2013;26:288–295.
40. Luthman JA, Kay NH, White JB. Intrathecal morphine for post cesarean section analgesia: does
naloxone reduce the incidence of pruritus? Int J Obstet Anesth. 1992;1:191–194.
41. Charuluxananan S, Kyokong O, Somboonviboon W, et al. Nalbuphine versus propofol for treatment of
intrathecal morphine-induced pruritus after cesarean delivery. Anesth Analg. 2001;93:162–165.
42. Cooper DW, Ryall DM, McHardy FE, et al. Patient-controlled extradural analgesia with bupivacaine,
fentanyl, or a mixture of both, after caesarean section. Br J Anaesth. 1996;76:611–615.
43. Cohen S, Amar D, Pantuck CB, et al. Adverse effects of epidural 0.03% bupivacaine during analgesia
after cesarean section. Anesth Analg. 1992;75:753–756.
44. Huffnagle HJ, Norris MC, Leighton BL, et al. Ilioinguinal iliohypogastric nerve blocks—before or
after cesarean delivery under spinal anesthesia? Anesth Analg. 1996;82:8–12.
45. Bell EA, Jones BP, Olufolabi AJ, et al. Iliohypogastric-ilioinguinal peripheral nerve block for post-
cesarean delivery analgesia decreases morphine use but not opioid-related side effects. Can J Anaesth.
2002;49:694–700.
46. Vallejo MC, Steen TL, Cobb BT, et al. Efficacy of the bilateral ilioinguinal-iliohypogastric block with
intrathecal morphine for postoperative cesarean delivery analgesia. Sci World J. 2012;2012:107316.
doi: 10.1100/2012/107316.
47. Gucev G, Yasui GM, Chang TY, et al. Bilateral ultrasound-guided continuous ilioinguinal-
iliohypogastric block for pain relief after cesarean delivery. Anesth Analg. 2008;106:1220–1222.
48. McDonnell JG, Curley G, Carney J, et al. The analgesic efficacy of transversus abdominis plane block
after cesarean delivery: a randomized controlled trial. Anesth Analg. 2008;106:186–191.
49. Costello JF, Moore AR, Wieczorek PM, et al. The transversus abdominis plane block, when used as
part of a multimodal regimen inclusive of intrathecal morphine, does not improve analgesia after
cesarean delivery. Reg Anesth Pain Med. 2009;34:586–589.
50. Kanazi GE, Aouad MT, Abdallah FW, et al. The analgesic efficacy of subarachnoid morphine in
comparison with ultrasound-guided transversus abdominis plane block after cesarean delivery: a
randomized controlled trial. Anesth Analg. 2010;111:475–481.
51. Bollag L, Richebe P, Ortner C, et al. Transversus abdominis plane catheters for post-cesarean delivery
analgesia: a series of five cases. Int J Obstet Anesth. 2012;21:176-180.
52. Mirza F, Carvalho B. Transversus abdominis plane blocks for rescue analgesia following cesarean
delivery: a case series. Can J Anaesth. 2013;60:299–303.
53. Bollag L, Richebe P, Siaulys M, et al. Effect of transversus abdominis plane block with and without
clonidine on post-cesarean delivery wound hyperalgesia and pain. Reg Anesth Pain Med.
2012;37:508–514.
54. Trotter TN, Hayes-Gregson P, Robinson S, et al. Wound infiltration of local anesthetic after lower
segment caesarean section. Anaesthesia. 1991;46:404–407.
55. Pavy T, Gambling D, Kliffer P, et al. Effect of preoperative skin infiltration with 0.5% bupivacaine on
postoperative pain following cesarean section under spinal anesthesia. Int J Obstet Anesth.
1994;3:199–202.
56. Niklasson B, Borjesson A, Carmnes UB, et al. Intraoperative injection of bupivacaine-adrenaline close
to the fascia reduces morphine requirements after cesarean section: a randomized controlled trial. Acta
Obstet Gynecol Scand. 2012;91: 1433–1439.
57. Ranta PO, Ala-Kokko TI, Kukkonen JE, et al. Incisional and epidural analgesia after caesarean
delivery: a prospective, placebo-controlled, randomised clinical study. Int J Obstet Anesth.
2006;15:189–194.
58. O’Neill P, Duarte F, Ribeiro I, et al. Ropivacaine continuous wound infusion versus epidural morphine
for postoperative analgesia after cesarean delivery: a randomized controlled trial. Anesth Analg.
2012;114:179–185.
59. Zohar E, Shapiro A, Eidinov A, et al. Postcesarean analgesia: the efficacy of bupivacaine wound
installation with and without supplemental diclofenac. J Clin Anesth. 2006;18:415–421.
60. Rackelboom T, Le Strat S, Silvera S, et al. Improving continuous wound infusion effectiveness for
postoperative analgesia after cesarean delivery: a randomized controlled trial. Obstet Gynecol.
2010;116:893–900.
61. Carvalho B, Clark DJ, Yeomans DC, et al. Continuous subcutaneous instillation of bupivacaine
compared to saline reduces interleukin 10 and increases substance P in surgical wounds after cesarean
delivery. Anesth Analg. 2010;111:1452–1459.
62. Nauta M, Landsmeer MLA, Koren G. Codeine-acetaminophen versus nonsteroidal anti-inflammatory
drugs in the treatment of post-abdominal surgery pain: a systemic review of randomized trials. Am J
Surg. 2009;198:256–261.
63. Lavand’homme PM, Roelants F, Waterloos H, et al. Postoperative analgesic effects of continuous
wound infiltration with diclofenac after elective cesarean delivery. Anesthesiology. 2007;106:1220–
1225.
64. Carvalho B, Lemmens HJ, Ting V, et al. Postoperative subcutaneous instillation of low-dose ketorolac
but not hydromorphone reduces wound exudate concentrations of interleukin-6 and interleukin-10 and
improves analgesia following cesarean delivery. J Pain. 2013;14:48–56.
65. Davis KM, Esposito MA, Meyer BA. Oral analgesia compared with intravenous patient-controlled
analgesia for pain after cesarean delivery: a randomized controlled trial. Am J Obstet Gynecol.
2006;194:967–971.
66. Alhashemi JA, Alotaibi QA, Mashaat MS, et al. Intravenous acetaminophen vs oral ibuprofen in
combination with morphine PCIA after cesarean delivery. Can J Anaesth. 2006;53:1200–1206.
67. Menkiti ID, Desalu I, Kushimo OT. Low-dose intravenous ketamine improves postoperative analgesia
after caesarean delivery with spinal bupivacaine in African parturients. Int J Obstet Anesth.
2012;21:217–221.
68. Reza FM, Zahra F, Esmaeel F, et al. Preemptive analgesic effect of ketamine in patients undergoing
elective cesarean section. Clin J Pain. 2010;26:223–226.
69. Bauchat JR, Higgins N, Wojciechowski KG, et al. Low-dose ketamine with multimodal postcesarean
delivery analgesia: a randomized controlled trial. Int J Obstet Anesth. 2011;20:3–9.
70. Monks DT, Hoppe DW, Downey K, et al. A perioperative course of gabapentin does not produce a
clinically meaningful improvement in analgesia after cesarean delivery: a randomized controlled trial.
Anesthesiology. 2015;123:320–326. doi:10.1097/ALN.0000000000000722.
71. Short J, Downey K, Bernstein P, et al. A single preoperative dose of gabapentin does not improve
postcesarean delivery pain management: a randomized, double-blind, placebo-controlled dose-finding
trial. Anesth Analg. 2012;115:1336–1342.
72. De Oliveria GS, Castro-Alves LJ, Khan JH, et al. Perioperative systemic magnesium to minimize
postoperative pain: a meta-analysis of randomized controlled trials. Anesthesiology. 2013;119:178–
190.
73. Madadi P, Shirazi F, Walter FG, et al. Establishing causality of CNS depression in breastfed infants
following maternal codeine use. Paediatr Drugs. 2008;10:399–404.
74. VanderVaart S, Berger H, Sistonen J, et al. CYP2D6 polymorphisms and codeine analgesia in
postpartum pain management: a pilot study. Ther Drug Monit. 2011;33:425–432.
75. Lam J, Kelly L, Matok I, et al. Putative association of ABCB1 2677G>T/A with oxycodone-induced
central nervous system depression in breastfeeding mothers. Ther Drug Monit. 2013;35:466–472.
76. American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into
human milk. Pediatrics. 2001;108:776–789.
77. Montgomery A, Hale TW, Academy of Breastfeeding Medicine Protocol Committee. ABM clinical
protocol #15: analgesia and anesthesia for the breastfeeding mother. Breastfeed Med. 2006;1:271–277.
78. Lawrence RA, Lawrence RM. Breastfeeding: A Guide for the Medical Profession. 7th ed.
Philadelphia, PA: Saunders; 2010.
79. Briggs GG, Freeman RK. Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and
Neonatal Risk. 10th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2014.
80. Weiner CP, Buhimschi C. Drugs for Pregnant and Lactating Women. 2nd ed. Philadelphia, PA:
Saunders; 2009.
 Management of Postdural Puncture Headache
David Wlody

I. Scope of the problem
II. Pathophysiology
A. Meningeal traction
B. Cerebral vasodilation
III. Risk factors for postdural puncture headache
A. Unmodifiable risk factors
B. Modifiable risk factors
IV. Diagnosis of postdural puncture headache
A. Occurrence of postdural puncture headache
B. Clinical characteristics
V. Differential diagnosis of postpartum headache
A. Migraine
B. Tension headache
C. Intracranial hemorrhage
D. Cerebral venous and sinus thrombosis
E. Neoplasm
F. Medications/substance withdrawal
G. Preeclampsia
H. Meningitis
I. Posterior reversible leukoencephalopathy syndrome
J. Benign intracranial hypertension (pseudotumor cerebri)
K. Spontaneous intracranial hypotension
 L. Lactation headache
VI. Prevention and treatment of postdural puncture headache after
accidental dural puncture
A. Bed rest
B. Hydration
C. Prone position
D. Abdominal binder
E. Caffeine
F. Serotonin agonists
G. Corticosteroids/adrenocorticotropic hormone
H. Pregabalin and gabapentin
I. Acupuncture
J. Intrathecal saline
K. Intrathecal catheter
L. Epidural morphine
M. Epidural saline
N. Epidural blood patch
O. Prophylactic epidural blood patch
P. Epidural colloids
VII. Recommendations
A. Ambulation
B. Hydration
C. Analgesics
D. Pharmacologic therapy
E. Epidural blood patch
F. Prevention after known accidental dural puncture
Summary

KEYPOINTS
 1. Far from being a minor complication, postdural puncture headache
(PDPH) can significantly increase the cost of hospitalization, can have an
extremely negative impact on patient satisfaction with a consequent
increase in the risk of litigation, and can lead to significant increases in
both short-and long-term maternal morbidity.
2. When evaluating patients with presumed PDPH, it is critically important
to rule out other potentially life-threatening causes of headache.
3. Numerous pharmacologic treatments for PDPH have been proposed, but
there is little evidence to support the routine use of a specific drug.
4. Although evidence supporting the practice is inconclusive, placement of
an intrathecal catheter after accidental dural puncture may decrease the
risk of developing PDPH.
5. Although not without its own complications, epidural blood patch (EBP)
represents the gold standard for treatment of established PDPH. The
routine use of prophylactic EBP and the optimal timing of EBP remain
controversial.

I. Scope of the problem

Despite advances in neuraxial anesthetic techniques, postdural
puncture headache (PDPH) remains a persistent problem. Even in
experienced hands, the risk of accidental dural puncture with an
epidural needle is approximately 1 in 200, but in many teaching
hospitals, the rate is between 1% and 4%. When it occurs, PDPH is
often mild in intensity and brief in duration (i.e., 3 to 7 days).
However, PDPH is occasionally severe enough to leave patients
bedridden and can delay hospital discharge. Symptoms of PDPH have
been reported to last months or even years in rare cases.1 Untreated
PDPH can lead to the development of persistent cranial nerve palsies
and intracranial hemorrhage.2,3 Finally, despite a widespread belief
among physicians that PDPH is merely a nuisance, it is a frequent and
sometimes costly source of litigation.4 It is undoubtedly, in the words
of Sachs and Smiley,5 “the worst common complication in obstetric
anesthesia.”
 A wide range of conservative and invasive treatments for PDPH
has been described in the literature, often with minimal supporting
evidence. In this chapter, we review the presumed pathophysiologic
mechanisms underlying PDPH as well as the risk factors for PDPH,
both those that can be modified and those that cannot. The diagnosis
of PDPH is described as well as the other types of headache that are
common in the parturient. The rationale for the commonly used
methods for preventing and treating PDPH is discussed on the basis of
our current understanding of the mechanisms of PDPH. The evidence
supporting these techniques will be described when such evidence
exists. There are few rigorous, well-controlled studies of the treatment
of PDPH, so many of the treatment recommendations will be based
on case reports, observational studies, and the author’s experience.
More than 100 years after August Bier6 first described PDPH, its
optimal management is a question that remains unanswered.
II. Pathophysiology
It is well accepted that the proximal cause of PDPH is persistent loss
of cerebrospinal fluid (CSF) through a dural, or more accurately, an
arachnoid puncture. This leakage leads to headache through one of
two presumed mechanisms.
A. Meningeal traction
Continued leak of CSF from a lumbar–dural puncture leads to
loss of fluid from the intracranial compartment. The loss of a
cushioning effect from CSF allows the brain to sag within the
skull, placing traction on the pain-sensitive meninges, an effect
that becomes most apparent in the upright position. This suggests
that the treatment of PDPH should be based on minimizing CSF
leakage, increasing CSF production, or translocating CSF from
the spinal to the intracranial compartment.
B. Cerebral vasodilation
The second theory is based on the Monro-Kellie hypothesis,
which states that the sum of brain tissue, CSF, and intracranial
blood is constant. Thus, a decrease in intracranial CSF will lead
to an increase in intracranial blood, mediated through
 compensatory cerebral vasodilation. This suggests that PDPH is
similar to migraine headache, a theory supported by the similarly
increased incidence of migraine and PDPH in women, and also
by magnetic resonance imaging (MRI) studies that demonstrate
enhanced cerebral blood flow in PDPH.7 This theory suggests not
only that PDPH will be relieved by restoration of intracranial CSF
volume but also that cerebral vasoconstrictors might provide
symptomatic relief.
III. Risk factors for postdural puncture headache
A. Unmodifiable risk factors
1. Age. Headache is uncommon in elderly patients. The highest
risk group appears to be patients younger than 40 years of
age, an age range typical for most parturients.
2. Gender. A recent meta-analysis concluded that nonpregnant
females are more likely to develop PDPH than males, despite
the fact that the women studied were considerably older, a
difference which would be expected to decrease the incidence
of PDPH in that group.8
3. Pregnancy. Pregnant women are more likely to develop
PDPH than age-matched, nonpregnant female controls. It has
been suggested that it may not be pregnancy per se but rather
vaginal delivery (particularly vigorous expulsive efforts in the
second stage of labor) that leads to this increased incidence,
perhaps due to increased CSF loss. The evidence for this is
inconclusive.9,10
4. Previous postdural puncture headache. A history of prior
PDPH is a risk factor for headache after spinal anesthesia.11

CLINICAL PEARL Pregnancy and a prior history of PDPH

convey greater risk for the development of PDPH.

B. Modifiable risk factors

1. Needle size. Numerous studies show that there is a consistent
 decrease in the incidence of PDPH as the needle diameter gets
smaller. With needles <27 gauge, the increasing technical
difficulty of needle placement limits the usefulness of further
decreases in diameter.
2. Needle shape. For any needle diameter, the use of conical or
“pencil-point” needles (e.g., Whitacre, Sprotte, Gertie Marx)
consistently decreases the incidence of PDPH compared to
cutting-bevel (e.g., Quincke) needles.12
3. Orientation of needle bevel. When a cutting-bevel needle is
used, insertion of the needle with the bevel parallel to the
longitudinal axis of the body will significantly decrease the
risk of headache.13
4. Paramedian approach. Although used infrequently in
obstetrics, subarachnoid block performed through the
paramedian approach appears to significantly decrease the
incidence of PDPH.14
5. Morbid obesity. It has long been thought that the incidence
of PDPH is decreased in morbidly obese parturients.15 A
recent study, adds further evidence that obesity provides
protection against the development of PDPH.16

CLINICAL PEARL The use of small pencil-point spinal

needles, with the bevel of a cutting needle oriented parallel to the
spinal axis, and a paramedian approach reduces the risk of PDPH.

IV. Diagnosis of postdural puncture headache

A. Occurrence of postdural puncture headache. PDPH may occur
immediately after dural puncture or it may not appear for as long
as 5 to 7 days. The great majority, however, develop within 48 to
72 hours.
B. Clinical characteristics
1. Posture. The sine qua non of PDPH is exacerbation by
upright position and diminution of symptoms with
 recumbency. Absence of a postural component must cast
doubt on the diagnosis of PDPH. The onset of headache
may be delayed by as long as 15 minutes after assuming the
upright position; however, the absence of a headache
immediately after positional change does not rule out PDPH.
2. Location. Typically, headache is distributed in the frontal and
occipital regions, with radiation to the neck and shoulders.
Pain in the interscapular region of the upper back may be
observed.
3. Auditory disturbances. Decreased CSF pressure is
transmitted to the cochlea, often producing auditory
symptoms such as decreased acuity, tinnitus, and what is often
described as a “hollow” sound.
4. Visual disturbances. Diplopia is common, typically due to
paresis of lateral gaze due to compression of cranial nerve VI
along its long course in the middle fossa by the sagging brain.

CLINICAL PEARL The onset of headache in a patient with

PDPH may be delayed by as much as 15 minutes after assuming the
upright position.

V. Differential diagnosis of postpartum headache

It is important to rule out other possible causes for headache in the
postpartum period (see Table 19.1), both to prevent the unnecessary
use of invasive treatments, such as epidural blood patch (EBP), to
treat benign and self-limiting conditions and, more importantly, to
ensure that potentially life-threatening intracranial pathology is not
overlooked.17,18
A. Migraine. Headaches caused by migraine are divided into two
subtypes: migraine with aura and migraine without aura. In
the former, reversible neurologic symptoms, typically visual but
often involving facial numbness or motor deficits in the arms or
legs, develop over 5 to 20 minutes and resolve within 1 hour.
Both subtypes are characterized by unilateral, pulsating pain,
worsened by activity, and often associated with nausea and
photophobia. Migraine usually begins in adolescence, is more
common in women, often improves during pregnancy, but also
frequently recurs in the early postpartum period. New onset of
migraine during pregnancy or postpartum is unusual and warrants
investigation.
B. Tension headache. Tension headache is the most common type
of headache and is more common in women. In contrast to
migraine, tension headaches seldom begin in adolescence and are
more likely to occur in middle age. These headaches are of mild-
to-moderate intensity and are usually bilateral, nonpulsating, and
unaffected by activity. Nausea and photophobia are absent.
Pregnancy appears to increase the incidence of tension headache.
C. Intracranial hemorrhage. Headache due to intracranial
hemorrhage is characterized by sudden onset, intense severity,
and the presence of focal neurologic signs or alterations in the
level of consciousness.
1. Subarachnoid hemorrhage. The incidence of SAH does not
 appear to be increased during pregnancy. Approximately 75%
are due to a ruptured aneurysm; however, the remainder arises
from arteriovenous malformations. Hypertension and
proteinuria are common, and SAH may be confused with
preeclampsia.19
2. Intracerebral hemorrhage is usually seen in the setting of
severe preeclampsia or other hypertensive states such as
cocaine intoxication.
3. As mentioned previously, subdural hematoma has been
reported in the setting of PDPH; decreased intracranial
pressure presumably leads to rupture of stretched bridging
veins. PDPH does not exclude headache due to subdural
hematoma; both may exist simultaneously. This should be
considered when the character of a PDPH changes after
several days or when EBP fails to provide relief.
D. Cerebral venous and sinus thrombosis
1. Cerebral venous thrombosis is estimated to occur in 10 to 20
per 100,000 deliveries.20 The hypercoagulable state produced
by pregnancy is a contributing factor, and these patients
should also be evaluated for the presence of a hereditary
thrombophilia. Approximately 80% of cases occur during the
first 2 postpartum weeks, but cerebral venous thrombosis has
been reported as late as the third postpartum month.
2. Features of headache secondary to intracranial thrombosis
vary depending on whether a large sinus or an isolated
cortical vein is thrombosed.
a. With thrombosis of a dural sinus, headache, seizures,
intracranial hypertension (due to impaired absorption of
CSF), and alterations in the level of consciousness are
common.
b. When a cortical vein is thrombosed, focal motor and
sensory deficits and seizures are more likely to be
observed.
3. There are several reported cases of intracranial thrombosis
 that were initially treated as PDPH.18,20 Dural puncture may
in fact be a risk factor for the development of cerebral venous
thrombosis.21 The presence of signs and symptoms suggesting
intracranial hypertension should lead to a more thorough
evaluation before EBP is performed (i.e., MRI or magnetic
resonance angiography).
4. Venous thrombotic occlusion leads to increased capillary
pressure, often causing hemorrhagic infarcts. With
recanalization of the vessel, capillary pressure decreases and
further hemorrhage is prevented. Heparin prevents further
thrombus formation; therefore, its use is indicated, even in
patients with preexisting hemorrhage.
E. Neoplasm
1. Headache associated with intracranial neoplasm is typically
diffuse; nonpulsating; associated with nausea and vomiting;
and worsened by physical activity, Valsalva maneuver,
coughing, and sneezing.
2. Focal signs may be present, influenced by location and size of
the tumor as well as by the presence of elevated intracranial
pressure.
3. The incidence of intracranial neoplasms is unaffected by
pregnancy, but it is not unusual for symptomatology to first
appear at this time due to increased extracellular fluid
accumulation. There is a significant hormonal influence on
certain tumors, such as pituitary adenomas and meningiomas,
which leads to increased growth during pregnancy.
F. Medications/substance withdrawal
1. Magnesium sulfate therapy is associated with headache,
particularly during administration of a loading dose.
2. Cessation of caffeine intake in patients with a chronic intake
of >200 mg per day will lead to a headache that is rapidly
reversed by administration of caffeine.
3. Abrupt termination of chronic opioid therapy, corticosteroids,
tricyclic antidepressants, and nonsteroidal anti-inflammatory
 drugs may lead to headache.
G. Preeclampsia
1. Headache is one of the diagnostic criteria for severe
preeclampsia. Headache associated with preeclampsia is
characterized by bilateral, pulsating pain, aggravated by
physical activity, and accompanied by hypertension and
proteinuria. Visual disturbances, including blurred vision and
scotomata, may be present. It is not unusual to be asked by
an obstetrician to evaluate a woman with headache 4 to 5
days postpartum, with a presumed diagnosis of PDPH,
who, upon careful history, does not require an EBP but
requires immediate magnesium therapy and additional
management of severe preeclampsia.
2. As noted earlier, severe hypertension may lead to intracranial
hemorrhage in preeclampsia.
H. Meningitis
Meningitis is an exceedingly rare complication of neuraxial
anesthesia, but the failure to diagnose and treat it in a timely
manner can have catastrophic consequences.
1. Headache due to meningitis is characterized by diffuse,
progressively worsening pain. In addition, there is often fever,
nuchal rigidity, nausea and vomiting, and photophobia.
2. PDPH shares many characteristics with headache due to
meningitis. Diagnostic lumbar puncture should be considered
in patients with presumed PDPH accompanied by fever,
leukocytosis, and meningismus.
I. Posterior reversible leukoencephalopathy syndrome
This disorder presents with headache, seizures, alterations in
consciousness, changes in vision, and other focal neurologic
deficits.22 It occurs most often postpartum and distinguishing it
from preeclampsia/eclampsia can be difficult because the
symptoms and signs are similar. MRI scanning is required to
make the diagnosis, which should be made as early as possible.22
Outcome is improved when treatment to control hypertension and
 to reverse the vasogenic edema of brain white matter is instituted
as soon as possible.23
J. Benign intracranial hypertension (pseudotumor cerebri)
Parturients with pseudotumor cerebri usually present with
symptoms prepartum and the headache symptoms are usually the
same postpartum. Treatment is usually that used antepartum with
diuretics, corticosteroids, carbonic anhydrase inhibitors, or
drainage of CSF.24 There is a case report of EBP treatment for
PDPH in a patient with the disorder.25
K. Spontaneous intracranial hypotension
The presentation is the same as in patients with PDPH but
without a history of prior regional anesthesia.26 Dural tears,
which are the presumed etiology, most often occur in thoracic
dermatomes. The diagnosis is confirmed by CT myelography,
which can also help identify the level of the CSF leak.27
L. Lactation headache
Headache in association with lactation has most often been
described in women with prior migrainous headache.28 Increased
vasopressin levels that accompanied breastfeeding has been
described in a woman who had repeated headaches while nursing,
suggesting that the hormonal changes associated with
breastfeeding may be causative.29 Headache has been described
in association with postpartum breast engorgement.28

CLINICAL PEARL Not all postdelivery headaches are due to

dural puncture in patients who have received neuraxial anesthesia.
A neurologic examination should be performed before therapy for
PDPH is instituted and an abnormality should prompt an evaluation
to rule out other intracranial pathology.

VI. Prevention and treatment of postdural puncture headache after

accidental dural puncture
A. Bed rest. Bed rest will provide symptomatic relief of PDPH.
 However, a recent review of the literature demonstrated that bed
rest after dural puncture does not reduce the risk of developing a
headache; in fact, this review showed a trend toward increased
headache in patients placed at rest.30 There is no evidence that
prolonging the duration of bed rest after dural puncture
decreases the likelihood of headache. Early ambulation after
dural puncture should be encouraged, and patients with an
established headache should ambulate as much as possible
due to the risk of thrombotic disease in the pregnant patient.
B. Hydration. Despite the widespread enthusiasm for aggressive
hydration after dural puncture, there is only one study of fluid
supplementation after dural puncture that showed no evidence
that it decreased the incidence of PDPH.31
C. Prone position. The prone position can relieve headache in some
patients with PDPH, but there are no published studies supporting
this practice. Presumably, increased intraabdominal pressure
translocates CSF from the lumbar spine to the intracranial
compartment. The prone position may be worthwhile in patients
whose surgical incision does not prevent this position.
D. Abdominal binder. A single study suggested that an abdominal
binder prevents the development of PDPH.32 It may provide
symptomatic relief by the same mechanism as prone positioning.
Again, this may not be feasible in patients with an abdominal
incision.
E. Caffeine. A study of 41 patients with headache unresponsive to
conservative measures demonstrated that IV caffeine 500 mg led
to permanent resolution of symptoms in 70% of subjects.33 The
small size of the study and the lack of a control group cast doubt
on the effectiveness of this therapy. Additionally, caffeine is
freely excreted into breast milk but is not associated with reports
of adverse neonatal outcomes. It has been linked to maternal
toxicity, including seizures and cardiac dysrhythmias. Because IV
caffeine is unavailable in many hospitals, the use of oral caffeine
has been proposed as a substitute. However, the widespread
 endorsement of caffeine to prevent and treat PDPH is not
supported by the available clinical evidence.34
F. Serotonin agonists. These agents are cerebral vasoconstrictors
used in the treatment of migraine. The similar vascular
mechanisms underlying this disorder and PDPH suggest that a
drug effective in the treatment of migraine might have similar
beneficial effects in PDPH. One study reported relief of PDPH in
four of six patients treated with 6 mg subcutaneous sumatriptan.35
A subsequent study did not replicate these results.36 A single
study suggested that frovatriptan was effective in preventing
PDPH, but this result has not been replicated either.37 Hence, the
routine use of sumatriptan and similar agents is not
recommended.
G. Corticosteroids/adrenocorticotropic hormone. A number of
case reports have suggested a therapeutic role for corticosteroids
or ACTH. A single randomized study demonstrated that high-
dose hydrocortisone reduced the severity of PDPH compared to
placebo.38 Another randomized study could not demonstrate any
benefit from ACTH administration.39 A recent review concluded
that cosyntropin reduced the incidence of PDPH of any severity
by nearly half, based on the results of only one randomized
trial.40
H. Pregabalin and gabapentin. Both agents were shown to provide
more effective relief than acetaminophen in a series of orthopedic
surgery patients that developed PDPH; pregabalin 100 mg
administered every 8 hours was the most effective agent.41
I. Acupuncture. In a recent study, five patients with PDPH
unresponsive to conservative measures were successfully treated
with acupuncture. None required EBP.42
J. Intrathecal saline. Injection of 10 mL preservative-free saline
through the Tuohy needle after accidental dural puncture has been
shown to decrease the incidence of headache from 62% to 32%.
Injection of normal saline through an intrathecal catheter, placed
after accidental dural puncture, appeared to decrease headache as
 well, but the number of patients studied in the catheter group was
too small to achieve statistical significance.43
K. Intrathecal catheter. After accidental dural puncture during
attempted epidural placement, a catheter can be placed into the
subarachnoid space to provide continuous spinal anesthesia.
Some studies have suggested that this technique will reduce the
incidence of subsequent PDPH.44 This result has not been
demonstrated consistently, perhaps because of differing durations
of subarachnoid catheterization in the various studies.45 One
study showed an improvement when the catheter remained in
place for 24 hours after delivery.46 Subsequent studies have
shown no effect47 or a decreased incidence of PDPH48,49 after
subarachnoid catheterization. Although the effect of subarachnoid
catheterization on subsequent development of PDPH may be
unclear, this will eliminate the possibility of a second accidental
dural puncture during an attempt to resite the epidural at another
level. If a spinal catheter is placed, it is critical to maintain the
sterility of the catheter. It is also imperative that all anesthetic
providers are aware of the presence of a labeled subarachnoid
catheter to prevent the injection of large (epidural) doses of
local anesthetic and high or total spinal anesthesia.
L. Epidural morphine. A single randomized controlled study of
parturients with PDPH revealed that administration of two doses
of epidural morphine 3 mg, 24 hours apart, decreased the
incidence of PDPH by 75%.40,50
M. Epidural saline. Continuous epidural infusion of normal saline
has been reported to prevent or relieve the symptoms of PDPH
after accidental dural puncture during epidural placement.51
Unfortunately, discontinuation of the infusion usually leads to
recurrence of the headache. This technique may be useful in
patients who refuse EBP, providing symptomatic relief until the
dural puncture resolves spontaneously.
N. Epidural blood patch. The gold standard for the treatment of
PDPH is EBP, with early reports suggesting a success rate
 (permanent and complete relief of headache) of as high as 95%.
However, a recent meta-analysis suggests that evidence for the
efficacy of EBP is lacking.52 Additionally, more recent reports
suggest that the success rate of EBP may be as low as 65%.53
Patients with a large dural puncture have the least success from
EBP and these are the patients in whom headache is most likely
to be severe and persistent. In patients with recurrence of
headache after EBP, a repeat procedure is usually successful.
Failure of a second EBP should encourage a search for other
possible causes of the headache.
O. Prophylactic epidural blood patch. A blood patch administered
through an epidural catheter placed after the accidental dural
puncture has been reported to decrease the incidence of PDPH by
anywhere from 30% to 70%.54 More recently, others have
suggested that the usefulness of prophylactic EBP has been
overstated.55 Although there is evidence that prophylactic EBP
does not prevent headache, it may decrease its duration.56
Although a subsequent study suggested significant benefit to
prophylactic EBP, methodologic differences from the earlier
studies make it difficult to generalize these results.57,58 Because
not all patients develop PDPH after a dural puncture, prophylactic
EBP could expose some women to unnecessary risks. Therefore,
it is important that patients be fully informed of the potential
complications of EBP and that every effort is made to prevent
those complications, particularly infection.
P. Epidural colloid administration. In patients who cannot receive
EBP because of fever or who refuse EBP because of religious
reasons, epidural dextran has been used with some success.59 This
treatment has not been studied in a prospective manner, and
concerns about the potential for neurotoxicity and the risk of
allergic reaction remain. Hydroxyethyl starch has been used in a
similar fashion.60 Epidural colloid infusion must be considered a
nonstandard therapy at this time.
CLINICAL PEARL Prophylactic and therapeutic noninvasive
and pharmacologic therapies for PDPH are mostly ineffective,
although the use of cosyntropin and neuraxial morphine have not
been fully evaluated. An EBP is most often effective, but failure of
a second EBP should prompt investigation for a cause of headache
other than prior dural puncture.

VII. Recommendations
PDPH can be debilitating, can cause serious morbidity, and may result
in litigation. In view of the consequences of PDPH, the
anesthesiologist should make every effort to minimize the risk of
headache by optimizing the factors that can be controlled, namely
needle size and shape. Despite all efforts, however, PDPH will
continue to occur, and anesthesia providers will continue to be called
upon to manage them. Unfortunately, despite many years of research,
the optimal treatment of PDPH is unclear. What follows then is one
suggested management approach based on a summary of the literature
and also on personal experience.
A. Ambulation. In patients who develop spinal headache,
ambulation should not be restricted because bed rest has no
demonstrated effect on the duration of spinal headache, while at
the same time increasing the risk of thromboembolism in patients
who are already at high risk for that complication. Patients should
be encouraged to ambulate as much as they can tolerate.
B. Hydration. Although forced hydration is unlikely to augment
CSF production to any significant degree, dehydration will
worsen the headache, and IV fluids should be provided to
patients who are unable to maintain adequate oral intake.
C. Analgesics. Oral analgesics should be made available; in
severe headache, opioid analgesics may be required and should be
provided.
D. Pharmacologic therapy. In patients who decline or who cannot
receive an EBP, pharmacologic therapy should be considered.
 Caffeine can be given; if the IV preparation is available, one or
two doses of caffeine benzoate 500 mg should be administered.
Otherwise, 300 mg of oral caffeine can be administered every 6
hours. In many patients, headache will return after cessation of
caffeine therapy; thus, more definitive treatment will often be
necessary. Other pharmacologic therapies such as gabapentin,
cosyntropin, and serotonin agonists are of unproven utility but
may be considered in patients who are unresponsive to or
intolerant of caffeine and who remain unwilling or unable to
undergo more definitive therapy (EBP). The administration of
either intrathecal or epidural morphine might be of benefit.
E. Epidural blood patch
1. My practice is to wait at least 24 hours after the onset of
symptoms before considering a blood patch, because some
headaches may resolve by that time, and I would prefer to
avoid the possible complications of EBP in headaches that
resolve so quickly. There are exceptions: In patients with a
debilitating headache due to accidental dural puncture with a
large epidural needle, the likelihood of rapid spontaneous
resolution is small, and I will perform EBP soon after the
development of symptoms. It should be remembered,
however, that EBP performed within 24 hours of dural
puncture has a lower success rate; whether this is because
headaches treated within 24 hours are more severe, and
therefore more likely to lead to failed blood patch, or because
there is an intrinsic increased failure rate with early blood
patch, is unclear.

CLINICAL PEARL An EBP performed within 24 hours of dural

puncture has a lower success rate; however, this consideration
should not delay the performance of an EBP in a severely
symptomatic patient.
 2. There are technical aspects of a blood patch that increase the
likelihood of its success. The spinal interspace chosen for the
blood patch should be as close as possible to the initial
puncture site, preferably below that site, because cephalad
spread of injected blood is typically greater than caudad. If
significant back pain does not develop during injection, a
volume of 20 mL of blood is optimal. The success rate of
EBP is improved if the patient is allowed to remain supine for
at least 1 hour and possibly as long as 2 hours.61 The patient
should be advised to avoid heavy lifting or straining for at
least 48 hours because a forceful Valsalva maneuver may
dislodge the patch leading to recurrence of headache.
F. Prevention after known accidental dural puncture
1. The evidence for placing an intrathecal catheter through a
dural puncture to reduce headache risk is inconsistent, so the
decision to use a continuous spinal catheter should be made
on other considerations, such as difficult airway or morbid
obesity. If this is done, as stated earlier, it is important for all
caregivers to be notified of the intrathecal location of the
catheter.
2. If a catheter is placed in the epidural space subsequent to a
dural puncture, an infusion of epidural saline (20 to 30 mL per
hour) may prevent a headache from developing; however, a
headache usually develops after the infusion is stopped.
3. Finally, an immediate blood patch performed through an
epidural catheter may prevent the development of a headache.
However, as many as 50% of patients with a dural puncture
(even from a 17-gauge epidural needle) will not develop a
headache, and these patients would be treated unnecessarily.
For this reason, I reserve immediate EBP for those patients in
whom I suspect a repeated epidural procedure would be
technically difficult. I also reserve immediate blood patch for
those patients whose epidural catheters were treated in strict
sterile manner after the initial dural puncture because the
 consequences of injecting blood through a contaminated
catheter are potentially catastrophic.

SUMMARY
Dural puncture is only one of many causes of postpartum headache. Patients
with PDPH have a strong postural component to the headache. The supine
position is associated with relief or improvement of headache, whereas sitting up
or standing up is associated with a worsening of the headache. The headache is
classically frontal and occipital, with radiation to the neck and shoulders, and
photophobia and/or tinnitus can occur with severe PDPH. Initial therapy should
be conservative, aimed at maintaining adequate levels of hydration and by
administering oral or IV analgesics. The administration of caffeine, cosyntropin,
and neuraxial morphine can be considered as well. For persistent or severe
headaches, an EBP will provide a definitive treatment for most women; however,
EBP can fail and may need to be repeated.

RECOMMENDED READING
Baysinger CL. Accidental dural puncture and postdural puncture headache management. Int Anesthesiol
Clin. 2014;52:18–39.
Bradbury CL, Singh SI, Badder SR, et al. Prevention of post-dural puncture headache in parturients: a
systematic review and meta-analysis. Acta Anaesthesiol Scand. 2013;57:417–430.
Sachs A, Smiley R. Post-dural puncture headache: the worst common complication in obstetric anesthesia.
Semin Perinatol. 2014;38:386–394.
Turnbull DK, Shepherd DB. Post-dural puncture headache: pathogenesis, prevention and treatment. Br J
Anaesth. 2003;91: 718–729.

REFERENCES
1. Gerritse BM, Gielen MJ. Seven months delay for epidural blood patch in post-dural puncture
headache. Eur J Anaesthesiol. 1999;16:650–651.
2. Béchard P, Perron G, Larochelle D, et al. Case report: epidural blood patch in the treatment of
abducens palsy after a dural puncture. Can J Anaesth. 2007;54:146–150.
3. Zeidan A, Farhat O, Maaliki H, et al. Does postdural puncture headache left untreated lead to subdural
hematoma? Case report and a review of the literature. Int J Obstet Anesth. 2006;15:50–58.
4. Davies JM, Posner KL, Lee LA, et al. Liability associated with obstetric anesthesia: a closed claims
analysis. Anesthesiology. 2009;110:131–139.
5. Sachs A, Smiley R. Post-dural puncture headache: the worst common complication in obstetric
 anesthesia. Semin Perinatol. 2014;38:386–394.
6. Bier A. Versuche über Cocainisirung des Rückenmarkes [in German]. Dtsch Zeitschr f Chir.
1899;51:361–369.
7. Bakshi R, Mechtler LL, Kamran S, et al. MRI findings in lumbar puncture headache syndrome:
abnormal dural-meningeal and dural venous sinus enhancement. Clin Imaging. 1999;23:73–76.
8. Wu CL, Rowlingson AJ, Cohen SR, et al. Gender and post-dural puncture headache. Anesthesiology.
2006;105:613–618.
9. Stride PC, Cooper GM. Dural taps revisited: a 20-year survey from Birmingham Maternity Hospital.
Anaesthesia. 1993;48:247–255.
10. Angle P, Thompson D, Halpern S, et al. Second stage pushing correlates with headache after
unintentional dural puncture in parturients. Can J Anaesth. 1999;46:861–866.
11. Lybecker H, Møller JT, May O, et al. Incidence and prediction of postdural puncture headache: a
prospective study of 1,021 spinal anesthetics. Anesth Analg. 1990;70:389–394.
12. Santanen U, Rautoma P, Luurila H, et al. Comparison of 27-gauge (0.41-mm) Whitacre and Quincke
spinal needles with respect to post-dural puncture headache and non-dural puncture headache. Acta
Anaesthesiol Scand. 2004;48:474–479.
13. Richman JM, Joe EM, Cohen SR, et al. Bevel direction and postdural puncture headache: a meta-
analysis. Neurologist. 2006;12:224–228.
14. Hatfalvi BI. Postulated mechanisms for postdural puncture headache and review of laboratory models:
clinical experience. Reg Anesth. 1995;20:329–336.
15. Faure E, Moreno R, Thisted R. Incidence of postdural puncture headache in morbidly obese
parturients. Reg Anesth. 1994;19:361–363.
16. Peralta F, Higgins N, Lange E, et al. The relationship of body mass index with the incidence of
postdural puncture headache in parturients. Anesth Analg. 2015;121:451–456
17. Wlody DJ. Postpartum headache other than post-dural puncture headache. In: Atlee J, ed.
Complications in Anesthesia. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.
18. Headache Classification Subcommittee of the International Headache Society. The international
classification of headache disorders. 2nd ed. Cephalalgia. 2004;24(suppl 1):1–150.
19. Dias MS, Sekhar LN. Intracranial hemorrhage from aneurysms and arteriovenous malformations
during pregnancy and the puerperium. Neurosurgery. 1990;27:855–865.
20. Lockhart EM, Baysinger CL. Intracranial venous thrombosis in the parturient. Anesthesiology.
2007;107:652–658.
21. Guner D, Tiftikcioglu BI, Uludag IF, et al. Dural puncture: an overlooked cause of cerebral venous
thrombosis. Acta Neurol Belg. 2015;115:53–57.
22. Altinkaya SO, Nergiz S, Küçük M, et al. Posterior reversible encephalopathy syndrome in obstetric
patients: report of three cases with literature review. Clin Exp Obstet Gynecol. 2014;41:730–733.
23. Alhilali LM, Reynolds AR, Fakhran S. A multi-disciplinary model of risk factors for fatal outcome in
posterior reversible encephalopathy syndrome. J Neurol Sci. 2014;15;347:59–65.
24. Kesler A, Kupferminc M. Idiopathic intracranial hypertension and pregnancy. Clin Obstet Gynecol.
2013;56:389–396.
25. Lussos SA, Loeffler C. Epidural blood patch improves postdural puncture headache in a patient with
benign intracranial hypertension. Reg Anesth. 1993;18:315–317.
26. Singh T, Schroeder F, Pereira A, et al. Antenatal blood patch in a pregnant woman with spontaneous
intracranial hypotension. Int J Obstet Anesth. 2009;18:165–168.
27. Roll JD, Larson TC III, Soriano MM. Cerebral angiographic findings of spontaneous intracranial
hypotension. AJNR Am J Neuroradiol. 2003;24:707–708.
28. MacGregor EA. Headache in pregnancy. Neurol Clin. 2012;30:835–866.
29. Askmark H, Lundberg PO. Lactation headache—a new form of headache? Cephalalgia. 1989;9:119–
122.
30. Sudlow C, Warlow C. Posture and fluids for preventing post-dural puncture headache. Cochrane
Database Syst Rev. 2002;(2):CD001790.
31. Dieterich M, Brandt T. Incidence of post-lumbar puncture headache is independent of daily fluid
intake. Eur Arch Psychiatry Neurol Sci. 1988;237:194–196.
32. Mosavy SH, Shafei M. Prevention of headache consequent upon dural puncture in obstetric patient.
Anaesthesia. 1975;30:807–809.
33. Sechzer PH, Abel L. Post-spinal anesthesia headache treated with caffeine: evaluation with demand
method: part I. Curr Ther Res. 1978;24:307–312.
34. Halker RB, Demaerschalk BM, Wellik KE, et al. Caffeine for the prevention and treatment of
postdural puncture headache: debunking the myth. Neurologist. 2007;13:323–327.
35. Carp H, Singh PJ, Vadhera R, et al. Effects of the serotonin-receptor agonist sumatriptan on postdural
puncture headache: report of six cases. Anesth Analg. 1994;79:180–182.
36. Connelly NR, Parker RK, Rahimi A, et al. Sumatriptan in patients with postdural puncture headache.
Headache. 2000;40:316–319.
37. Bussone G, Tullo V, d’Onofrio F, et al. Frovatriptan for the prevention of postdural puncture headache.
Cephalalgia. 2007;27:809–813.
38. Noyan Ashraf MA, Sadeghi A, Azarbakht Z, et al. Hydrocortisone in post-dural puncture headache.
Middle East J Anesthesiol. 2007;19:415–422.
39. Rucklidge MW, Yentis SM, Paech MJ. Synacthen depot for the treatment of postdural puncture
headache. Anaesthesia. 2004;59:138–141.
40. Basurto Ona X, Uriona Tuma SM, Martínez García L, et al. Drug therapy for preventing post-dural
puncture headache. Cochrane Database Syst Rev. 2013;(2):CD001792.
41. Mahoori A, Noroozinia H, Hasani E, et al. Comparing the effect of pregabalin, gabapentin, and
acetaminophen on post-dural puncture headache. Saudi J Anesth. 2014;8:374–377.
42. Dietzel J, Witstruck T, Adler S, et al. Acupuncture for treatment of therapy-resistant post-dural
puncture headache: a retrospective case series. Br J Anaesth. 2013;111:847–849.
43. Charsley MM, Abram SE. The injection of intrathecal normal saline reduces the severity of postdural
puncture headache. Reg Anesth Pain Med. 2001;26:301–305.
44. Dennehy KC, Rosaeg OP. Intrathecal catheter insertion during labour reduces the risk of post-dural
puncture headache. Can J Anaesth. 1998;45:42–45.
45. Liu N, Montefiore A, Kermarec N, et al. Prolonged placement of spinal catheters does not prevent
postdural puncture headache. Reg Anesth. 1993;18:110–113.
46. Ayad S, Demian Y, Narouze SN, et al. Subarachnoid catheter placement after wet tap for analgesia in
labor: influence on the risk of headache in obstetric patients. Reg Anesth Pain Med. 2003;28:512–515.
47. Russell IF. A prospective controlled study of continuous spinal analgesia versus repeat epidural
analgesia after accidental dural puncture in labour. Int J Obstet Anesth. 2012;21:7–16.
48. Heesen M, Klöhr S, Rossaint R, et al. Insertion of an intrathecal catheter following accidental dural
puncture: a meta-analysis. Int J Obstet Anesth. 2013;22:26–30.
49. Verstraete S, Walters MA, Devroe S, et al. Lower incidence of post-dural puncture headache with
spinal catheterization after accidental dural puncture in obstetric patients. Acta Anaesthesiol Scand.
2014;58:1233–1239.
50. Al-metwalli RR. Epidural morphine injections for prevention of post dural puncture headache.
Anaesthesia. 2008;63:847–850.
51. Shah JL. Epidural pressure during infusion of saline in the parturient. Int J Obstet Anesth. 1993;2:190–
192.
52. Sudlow C, Warlow C. Epidural blood patching for preventing and treating post-dural puncture
headache. Cochrane Database Syst Rev. 2002;(2):CD001791.
53. Safa-Tisseront V, Thormann F, Malassiné P, et al. Effectiveness of epidural blood patch in the
management of post-dural puncture headache. Anesthesiology. 2001;95:334–339.
54. Cheek TG, Banner R, Sauter J, et al. Prophylactic extradural blood patch is effective: a preliminary
communication. Br J Anaesth. 1988;61:340–342.
55. Vasdev GM, Southern PA. Postdural puncture headache: the role of prophylactic epidural blood patch.
Curr Pain Headache Rep. 2001;5:281–283.
56. Scavone BM, Wong CA, Sullivan JT, et al. Efficacy of a prophylactic epidural blood patch in
preventing post dural puncture headache in parturients after inadvertent dural puncture.
Anesthesiology. 2004;101:1422–1427.
57. Stein MH, Cohen S, Mohiuddin MA, et al. Prophylactic vs therapeutic blood patch for obstetric
patients with accidental dural puncture—a randomised controlled trial. Anaesthesia. 2014;69:320–326.
58. Scavone BM. Timing of epidural blood patch: clearing up the confusion. Anaesthesia. 2015;70:119–
121.
59. Barrios-Alarcon J, Aldrete JA, Paragas-Tapia D. Relief of post-lumbar puncture headache with
epidural dextran 40: a preliminary report. Reg Anesth. 1989;14:78–80.
60. Vassal O, Baud MC, Bolandard F, et al. Epidural injection of hydroxyethyl starch in the management
of postdural puncture headache. Int J Obstet Anesth. 2013;22:153–155.
61. Martin R, Jourdain S, Clairoux M, et al. Duration of decubitus position after epidural blood patch. Can
J Anaesth. 1994;41:23–25.
 Neurologic Deficits Following Labor and Delivery
Mark I. Zakowski and Andrew Geller

I. Neurologic injury
A. Incidence
II. History and initial evaluation
A. Relevant questions during evaluation
B. The causes of postpartum neurologic injury
C. The extent of the injury
III. Basic anatomy
A. The lumbar plexus
B. The sacral plexus
C. Trauma caused by the fetal head
IV. Common obstetric neuropathies
A. The lateral femoral cutaneous nerve of the thigh
B. The femoral nerve
C. The obturator nerve
D. The sciatic nerve
V. Ischemic injury to the spinal cord
A. Blood supply to the spinal cord
B. The artery of Adamkiewicz
C. The lumbar arteries
D. Diagnosis of spinal cord ischemia
VI. Types of lesions
A. Chemical injury
 B. Direct nerve trauma
VII. Diagnosis and treatment of neuropathies
A. Electromyography
B. Nerve conduction studies
C. Timing of electrophysiologic studies
VIII. Approach to patients with peripheral nerve injuries
A. Preexisting causes
B. Neurologist consultation and imaging studies
C. Plexus injury versus spinal cord injury
IX. Complications related to spinal fluid leakage
A. Postdural puncture headache
B. Characteristics of postdural puncture headache
C. Imaging studies
D. Autologous epidural blood patch
E. Complications of epidural blood patch
F. Managing an unintended postdural puncture headache
G. Prophylactic epidural blood patch
H. Intracranial hematomas
I. Seizures
J. Spontaneous intracranial hypotension
X. Infectious complications of neuraxial blocks
A. Postdural puncture meningitis
B. Epidural abscess
XI. Epidural hematoma
A. Predisposing factors
B. Symptoms
C. Diagnosis
D. Treatment
E. Catheter removal causing epidural hematoma
F. Guidelines for administering neuraxial blocks
XII. Recommendations


KEYPOINTS
1. Neuraxial anesthesia for labor and delivery is extremely safe with a
prolonged complication rate of 1:2,000 to 1:13,000. Most neurologic
injuries are a result of birth trauma and not from neuraxial anesthesia.
2. Permanent nerve injuries are extremely rare but need to be expeditiously
evaluated with a complete history and physical exam. The neurologic
complaint may need to be further evaluated with appropriate diagnostic
testing and consultations.
3. Understanding the anatomy and nerve innervations is crucial in
diagnosing nerve injuries.
4. Careful procedural technique, including sterile precautions, with diligent
monitoring of patients can help reduce neurologic complications from
neuraxial anesthesia.

LUMBAR EPIDURAL AND SUBARACHNOID BLOCK enjoy widespread popularity for

obstetric analgesia and anesthesia1 with a reported 61% utilization rate during
singleton vaginal deliveries in 2008.2 Although under most circumstances these
blocks are extremely safe, there are occasions in which they may lead to serious
complications. The complications may be acute in onset, such as systemic
hypotension and cardiorespiratory collapse, or they may appear several hours to
days after delivery. Delayed complications include epidural abscess, peripheral
neuropathy, or damage to the spinal cord itself. This chapter will focus on the
neurologic complications of neuraxial anesthesia.
I. Neurologic injury
A. Incidence
1. Neuraxial blocks for pain relief during childbirth are
associated with a low, prolonged complication rate of 1:2,000
to 1:13,000.3–8 The Society for Obstetric Anesthesia and
Perinatology (SOAP) constructed a self-reporting
complication repository, with 30 institutions contributing
information over a 5-year period, including over 256,000
obstetrical anesthetics. Serious complications occurred at a
 rate of about 1:3,000 (see Table 20.1).4,9,10 In another study,
Pitkanen et al.10 conducted a national survey from 2000 to
2008 of 1,400,000 patients in Finland who underwent
neuraxial anesthesia. Permanent injuries from neuraxial
anesthesia were identified in only 41 of the 1.4 million
patients who were surveyed. Of laboring women receiving
epidural anesthesia, the only permanent injury was one
fatality, giving a rate of 1/144,000. These rare complications
may occur even if proper precautions are taken to avoid
mishaps (see Table 20.2 for a summary of studies reporting
neurologic injuries). Persistent neurologic deficits more
commonly arise from obstetric trauma sustained during the
passage of the fetus through the birth canal.6,8

2. Despite the very low incidence of neurologic injury, it

represents a significant contributor to malpractice litigation.
Davies et al.11 performed an obstetric anesthesia closed
claims analysis of 426 claims from 1990 to 2003. Regional
 anesthesia was involved in nearly 80% of the claims, whereas
general anesthesia was involved in 17%. Headaches
accounted for 10% of the claims, back pain 8%, and nerve
injury 20%. Nerve injury payments averaged $126,000. Lee et
al.9 performed a closed claims analysis of 1,005 regional
anesthesia claims from 1990 to 2004. Cardiac arrest
associated with neuraxial block was the primary damaging
event in 32% of obstetric claims involving death or brain
damage. Although, obstetric anesthesia claims are
predominately associated with minor injuries, cardiac arrest
associated with neuraxial anesthesia and neuraxial hematomas
associated with coagulopathy are the main sources of high-
severity injuries.
3. Hayes et al.12 collected self-reported patient symptoms
following discharge. At this single institution in Ireland from
2004 to 2007, 15,033 deliveries occurred with 46.5%
receiving neuraxial anesthesia. Only 1.4% (98) patients
contacted the investigators with new complaints. Of these,
headache was the most common complaint (44% of
complaints), presenting 5 to 9 days (interquartile range)
postpartum with only 4 of the 43 patients receiving an
epidural blood patch (EBP). Sensorimotor symptoms were
self-reported in 34% of patients who self-reported, with a
median time reporting on day 8 postpartum. The incidence of
late, self-reported obstetric nerve palsies was 1:15,033.
4. Horlocker et al.13 reported their experience with 4,220
epidurals inserted for postoperative analgesia in nonobstetric
patients. These patients were anesthetized before insertion of
the neuraxial catheter and therefore could not report
paresthesias. One epidural catheter broke during removal and
a segment was retained; there were no other major problems.
Six patients developed new neurologic symptoms or
postoperative worsening of a previous neurologic condition
unrelated to epidural catheterization. There was one death due
 to anterior spinal artery syndrome. The patient had a
prolonged aortic cross-clamp time, which might have
predisposed to spinal cord ischemia. The authors concluded
that the risk of neurologic complications associated with
lumbar epidural catheter placement in anesthetized patients is
small.
5. Wong et al.21 studied 6,057 women who delivered liveborn
infants; 6,048 were interviewed and 56 had a confirmed new
nerve injury to a lower extremity peripheral nerve, an
incidence of 0.92%. Factors found by logistic regression
analysis to be associated with nerve injury were nulliparity
and prolonged second stage of labor. Women with nerve
injury spent more time pushing in the semi-Fowler–lithotomy
position compared to women without injury. The median
duration of symptoms was 2 months. Contrary to the
previously described studies, this study reports a much higher
incidence of neurologic injury. However, the injuries reported
in this study seem to be related to childbirth and not due to the
anesthetic technique per se.
6. A review by Brull et al.,22 of 32 studies published over 10
years, suggests that the rate of neurologic complications after
central nerve blockade is <4:10,000 or 0.04%. This review
also suggests that spinal anesthesia carries a higher risk of
radiculopathy or peripheral neuropathy (3.78:10,000)
compared to epidural anesthesia (2.19:10,000) (see Fig. 20.1).
However, permanent neurologic injury after neuraxial
anesthesia is a rare occurrence in contemporary anesthetic
practice.
 CLINICAL PEARL Neurologic injury following neuraxial
blockade in obstetrics is very rare but contributes to 80% of patient
claims for injury associated with obstetric anesthesia.

II. History and initial evaluation

When evaluating a patient with postpartum neuropathy, it is important
to remember that the etiology of neuropathy may be totally unrelated
to anesthesia and may be secondary to nerve injury sustained by the
patient during the birth process. Nerve injury may occur during
vaginal birth or cesarean delivery (CD); however, mode of delivery
does not seem to carry a different risk of neurologic injury.3
A. Relevant questions during evaluation. The most pertinent
questions to ask when evaluating a patient with postpartum
neuropathy are6–8:
1. What was the duration of labor?
2. How long did the patient push?
3. Was the patient placed in exaggerated lithotomy position
while pushing?
 4. Were forceps or vacuum used?
5. What was the weight of the infant?
6. What was the position of the presenting part (i.e., occiput
posterior)?
7. Did the patient have any history of back problems or
preexisting neurologic disorder (e.g., multiple sclerosis [MS],
HIV infection, diabetes, obesity)?
8. What was the type and amount of local anesthetic used?
9. Did the patient ever recover sensory and motor function
completely before the onset of symptoms?
10. What type of anesthetic was delivered and its duration?
B. The causes of postpartum neurologic injury
Neuraxial anesthesia is only one of many possible etiologies of
neurologic injury.23 These injuries are often the result of direct
trauma caused by the fetal head, or obstetric forceps, to the major
nerve trunks that supply the lower extremities. Direct ischemic
injury of the lower spinal cord is also possible when the fetal head
compresses the ascending spinal branch of the internal iliac
artery.8 One should also consider the possibility of epidural
hematoma. When extensive neurologic deficits are noted, a
neurologist or neurosurgeon must be consulted. Bilateral leg
weakness may be due to spinal cord compression (e.g. epidural
hematoma), and magnetic resonance imaging (MRI) or computed
tomography (CT) scan of the spinal cord must be performed
without delay. Neurologic deficits due to spinal cord compression
may be reversible if diagnosed early, and decompression occurs
within the first 6 to 12 hours.
C. The extent of the injury
Neurologic injuries associated with childbirth may involve many
disparate areas, including the lumbosacral plexus, anterior tibial
nerve, femoral nerve, obturator nerve, and lateral femoral
cutaneous nerve, and may rarely result in cauda equina
syndrome.6–8 Obviously, involvement of a major nerve plexus
may result in extensive injury that can take weeks or months to
 resolve. Rarely, piriformis syndrome, an inflammation of muscle
fascia affecting the sciatic nerve, may occur.24,25 The basic
anatomy of neural and vascular structures of the pelvis will be
reviewed because injury to these structures can result in serious
neurologic complications.26
III. Basic anatomy
A. The lumbar plexus
1. The lumbar plexus and its branches (see Fig. 20.2) may be
compressed by the fetal head. The lumbar plexus is formed by
the communication of the upper four lumbar nerves.27 The
lumbar plexus is connected to the sacral plexus by the
lumbosacral trunk. The plexus assembles in the substance of
the psoas major muscle, anterior to the transverse processes of
the lumbar vertebrae.

2. The branches of the lumbar plexus include the

iliohypogastric, ilioinguinal, genitofemoral, lateral cutaneous,
femoral, and obturator nerves, and branches to the psoas
major and minor, iliacus, and quadratus lumborum muscles.
B. The sacral plexus
The sacral plexus (see Fig. 20.2) is formed by the contribution of
 nerves from L4, L5, S1–S3, and a part of S4. The coccygeal
plexus receives the remainder of the S4 and S5 nerve roots and
the coccygeal nerve. The roots of the lumbosacral plexus unite to
form two major divisions, the sciatic and the pudendal nerves.
The plexus lies on the posterior wall of the pelvic cavity, behind
the pelvic fascia, and on the anterior surface of the piriformis
muscle.
C. Trauma caused by the fetal head
As the fetal head crosses the ala of the sacrum (posterior brim of
the pelvis), it can compress the lumbosacral plexus (see Fig.
20.2).8 This type of injury can be unilateral (75%) or bilateral
(25%), and occurs more commonly in nulliparous parturients with
a platypelloid pelvis, large fetus, cephalopelvic disproportion,
vertex presentation, and forceps delivery.28,29 These compressive
nerve injuries may involve multiple root levels and can present as
injuries to the femoral or the obturator nerve, with sensory
impairment of L4–L5 dermatomes. The incidence of obstetrical
lumbosacral plexopathy occurs in 1.5 to 5/10,000 deliveries.3
IV. Common obstetric neuropathies
The anatomic features of some nerves make them especially
vulnerable to damage during delivery. The distinguishing clinical
picture of damage to these nerves is listed in Tables 20.3 and 20.4.
A. The lateral femoral cutaneous nerve of the thigh. This nerve
(L2–L3) exits the pelvis 1 to 2 cm medial to the anterior superior
iliac spine, under or through a split in the lateral end of the
inguinal ligament. This nerve is purely sensory providing
innervation to the anterior aspect of the thigh (see Tables 20.3 and
20.4 and Fig. 20.3). Relapses of MS may often affect this nerve.30
Decreased sensation of the anterior aspect of the thigh occurs as a
result of compression of this nerve and is called meralgia
paresthetica. In <2% of women, the lateral femoral cutaneous
nerve arises from the femoral nerve and penetrates the inguinal
ligament to exit the pelvis in which case, meralgia paresthetica is
more likely to occur during pregnancy.31 The nerve is more likely
to sustain trauma when the hyperextended lithotomy position is
used. Pressure from the fetal head or from the handle of a
retractor held by a surgical assistant during a CD may also lead to
injury. In one prospective study, the lateral femoral cutaneous
nerve was the most common obstetric nerve palsy, accounting for
30% of nerve injuries.5 This injury does not require treatment and
typically recovers within 6 weeks.
B. The femoral nerve. The femoral nerve is composed of the nerve
roots from L2, L3, and L4, exits beneath the inguinal ligament,
and travels one fingerbreadth lateral to the femoral artery (see
Fig. 20.2).31 The intermediate and medial cutaneous branches
innervate the thigh, and it innervates the quadriceps femoris as
well. The femoral nerve supplies the muscles and skin of the
anterior compartment of the thigh, the psoas, and iliacus muscles.
 When this nerve is affected, hip flexion and knee extension
become difficult. Because the hips are actively flexed during the
second stage of labor, the inguinal ligament compresses the
femoral nerve. Extreme or prolonged flexion of the hips during
pushing should be avoided and the legs rested between
contractions/pushing. The use of a squatting bar, to keep the hips
hyperflexed during second stage of labor, has resulted in femoral
nerve injury.6,7,31 Weak hip flexion suggests an injury to the
femoral nerve at the level of the inguinal ligament. This may also
occur due to compression of the lumbosacral plexus by the fetal
head.
C. The obturator nerve. The obturator nerve (L2–L4)31 emerges at
the medial border of the psoas at the pelvic brim. After passing
through the obturator canal at the lateral wall of the pelvis
(common locations of injury), it supplies the adductor muscles of
the thigh along with the sciatic nerve. The adductor magnus
muscle receives dual innervations by the obturator as well as by
the sciatic nerve. When the obturator nerve is involved, thigh
adduction is weakened with loss of sensation on the medial aspect
of the thigh (see Tables 20.3 and 20.4 and Fig. 20.3).
D. The sciatic nerve. The sciatic nerve (L4, L5, S1–S3)31 is the
largest peripheral nerve in the body (see Tables 20.3 and 20.4,
and Fig. 20.2 and 20.3). It leaves the pelvis through the greater
sciatic foramen and divides into the larger tibial and smaller
peroneal trunks. After exiting the sciatic foramen, it either exits
inferior and through, or cranial to, the piriformis muscle, and then
curves around the ischial spine and descends. The sciatic nerve
innervates the adductor magnus and biceps femoris muscles and
divides into medial (anterior tibial) and lateral popliteal (common
peroneal) nerves in the popliteal triangle. The medial popliteal
nerve supplies cutaneous (sural nerve) and muscular branches to
the gastrocnemius and soleus muscles. The common peroneal
nerve (L4, L5, S1, S2) winds around the neck of the fibula, where
it is the only palpable nerve in the lower extremity (see Fig. 20.4).
The nerve supplies both sensory and motor innervation to the leg.
Owing to its superficial location, it is one of the more frequently
injured nerves. Damage to this nerve causes paralysis of the ankle
and foot, resulting in foot drop and inversion with sensory
impairment of the anterior aspect of the foot (see Tables 20.3 and
20.4 and Fig. 20.3).32 Occasionally, inflammation of the
piriformis muscle can lead to sciatic nerve irritation (piriformis
syndrome) and cause gluteal and hip pain radiating down to the
knee. Pain occurs when the extended thigh is rotated internally
(Friedberg test).26,33 Prolonged sitting and excessive weight
bearing during pregnancy, or injury during labor, can lead to
irritation and spasm of the piriformis muscle. The peroneal
portion of the sciatic nerve has a greater susceptibility to injury
than the tibial division because the peroneal division travels more
superficially in the bundle, has fewer and larger fascicles, less
epineurium, and little blood supply. The peroneal nerve is fixed at
two points, the sciatic foramen and the fibular head; sciatic
neuropathy at the hip may appear similar to the more distal
common peroneal nerve injury, with symptoms of foot drop and
denervation of the anterolateral leg muscle. For suspected
peroneal nerve injury, an MRI of the nerve at both the hip and
knee should be performed.3 An MRI usually shows a
hyperintense signal in the piriformis region.25,26
Electrophysiologic studies may be of assistance in diagnosis, but
difficult to obtain given the deep location of the injury.
 CLINICAL PEARL Most neurologic deficits can be diagnosed
with a careful history and physical examination.

V. Ischemic injury to the spinal cord

A. Blood supply to the spinal cord. The blood supply to the spinal
cord (see Fig. 20.5) can be precarious and subject to major
anatomic variations.34–37 One anterior and two posterior spinal
arteries supply the cord. The anterior spinal artery arises from the
vertebral arteries and extends from the level of the lower
brainstem to the tip of the conus medullaris. It supplies the ventral
surface of the medulla and the anterior two-thirds of the spinal
cord. The posterior spinal arteries supply the dorsal third of the
spinal cord and also originate from the vertebral arteries.
B. The artery of Adamkiewicz. At certain sites along the spinal
cord, there are a number of sources of additional blood flow from
other arteries: the thyrocervical trunk, intercostal arteries, and the
artery of Adamkiewicz (arteria radicularis magna [ARM]).8,38
The ARM, which supplies the lower spinal cord, originates
usually from the left side from one or two of the thoracolumbar
segmental arteries. In most people, the origination is found
between segments T9–L2.36 The ARM travels to the ventral
surface of the spinal cord and fuses with the anterior spinal artery
and makes a hairpin turn to course downward. This artery is often
implicated in ischemic injuries to the lower portion of the spinal
cord. The conus medullaris can also receive blood supply from
 one of the lumbar arteries originating from the internal iliac artery
at the level of L5 or S1.8 However, the bulk of the conus
medullaris blood supply comes from the ARM.
C. The lumbar arteries. In approximately 15% of cases, the ARM
originates from spinal segments as high as the T5 level (high
takeoff; see Fig. 20.5).8 In these patients, the major part of blood
supply of the lower spinal cord is provided by a lumbar branch,
which lies in front of the ala of the sacrum and enters the spinal
cord through the L5–S1 intervertebral foramen. This branch can
be compressed by the fetal head, which can lead to ischemia of
the conus medullaris.
D. Diagnosis of spinal cord ischemia. Acute spinal cord ischemia is
often undetectable with conventional MRI. Echoplanar diffusion-
weighted MRI (DWI)8,38–40 has been used to diagnose acute
spinal cord ischemia. Early DWI reveals areas of hyperintense
signal indicating decreased diffusion. Follow-up MRI shows high
signal on T2-weighted images and contrast enhancement at the
expected levels. Echoplanar DWI38,40 may be helpful for
confirmation of spinal cord ischemia in the acute stage, but
follow-up images have superior spatial resolution and correlation
with clinical findings. Although MRI studies within 24 hours of
acute spinal cord ischemia typically are often normal, after 1 to 2
days an MRI generally shows focal cord enlargement and
hyperintensity, whereas spinal cord enhancement takes 2 to 11
days.41 The MRI is also valuable in diagnosing space-occupying
lesions, such as epidural hematoma or epidural abscess, or
intervertebral disk herniation. CT scan is also of value in
detecting space-occupying lesions and disk herniation.

CLINICAL PEARL Most serious neuropathies that occur during

labor and delivery are due to the birthing process and are not the
result of neuraxial blockade.
 VI. Types of lesions
A. Chemical injury
Chemical injury usually results from accidental injection of an
irritant into the epidural or subarachnoid space. Preservatives,
such as sodium bisulfite, have been implicated in producing
adhesive arachnoiditis and cauda equina syndrome. Neurologic
injury may also occur as a result of local anesthetic
neurotoxicity.24,30 The subarachnoid space may become
obliterated from such injuries. Cauda equina syndrome has been
reported to occur following the use of spinal microcatheters (28 to
32 G) for continuous spinal anesthesia. In this setting, toxicity is
believed to be the result of poor mixing of concentrated local
anesthetic (i.e., lidocaine 5%) with the cerebrospinal fluid (CSF),
with subsequent toxic drug concentrations at the nerve roots. The
U.S. Food and Drug Administration (FDA) has removed spinal
microcatheters from the US market.42 Cauda equina syndrome
may also occur as a result of acute intervertebral disk herniation
requiring immediate surgical intervention.43
B. Direct nerve trauma
1. Paresthesia. Nerve trauma during neuraxial anesthesia is an
uncommon cause of neurologic deficits. If a paresthesia with
involuntary leg movement occurs, the needle or the catheter
should be withdrawn immediately. Transient paresthesias
perceived with dural puncture, spinal needle insertion, or
epidural catheter threading are common, occuring in 5% to
20% of neuraxial blocks, with one study reporting an
incidence of 14% with pencil-point needles.44 Epidural
catheters with a soft polyurethane tip are associated with
fewer paresthesias than the stiffer nylon catheters.45 Spinal
anesthesia is associated with neurologic injury more
frequently than epidural anesthesia.13,23 The anesthesiologist
should document the severity and location of paresthesias. It
may take 48 hours to 3 months for complete recovery from
neuropathy resulting from a direct nerve trauma.7
2. Direct trauma with spinal and epidural blocks to nervous
tissue may occur at the level of the spinal cord, nerve root, or
peripheral nerve. Epidural placement is most likely to
traumatize a nerve root. A spinal needle may contact a nerve
root inside or outside the subarachnoid space, or directly
injure the spinal cord. The spinal cord usually ends at the
level of first lumbar intervertebral disk, but occasionally, it
may extend to the L2–L3 intervertebral disk. Although the
superior iliac crest denotes the L4 spinous process or L4–L5
interspace in 79% of patients, this landmark has been reported
to be as high as the L3–L4 interspace in 4% of subjects.29 In
pregnancy, Tuffier’s line may often be perceived as more
cephalad than in nonpregnant patients. In one study,
experienced anesthesiologists correctly identified the precise
interspace only 29% of the time by palpation, as validated by
MRI.5 In a series of >103,000 neuraxial anesthetics performed
in France, two-thirds of neurologic sequelae were associated
with paresthesia or pain during drug injection, suggesting
direct nerve trauma; 29 of 34 neurologic complications had
transient sequelae, with recovery occurring between 48 hours
and 3 months.17 Intraneural injection of local anesthetics was
more likely to result in prolonged neurologic deficits.
3. Spinal cord injury with spinal needles. The study from
France also reported that spinal anesthesia was significantly
more likely to result in both neurologic injury (5.9/10,000 vs.
2/10,000) and radiculopathy (4.7/10,000 vs. 1.7/10,000)
compared to epidural anesthesia. All radicular deficits related
to paresthesia from neuraxial anesthesia resolved except
one.17 Combined spinal-epidural (CSE) anesthesia can be
associated with minor paresthesias, but may occasionally
result in severe paresthesias. Pencil-point spinal needles seem
less likely to traumatize a nerve root. Reynolds46 summarized
the findings from seven patients who sustained an injury to
the conus medullaris during spinal anesthesia or CSE, with
 persistent neurologic sequelae. There was MRI evidence of
spinal cord injury, and neurologic symptoms included pain,
sensory deficit, foot drop, and bladder symptoms. Reynolds46
concluded that the operator inserted the spinal needle at an
intervertebral space higher than L2.
4. Different degrees of nerve injury. With mild nerve injuries,
only a block in conduction occurs through the damaged
segment of the nerve (neuropraxia). Severe injuries lead to
axonal degeneration, and axonal regeneration may never be
complete, leading to total or partial loss of function in the
affected area. Axonotmesis is said to occur when the axons
are damaged, and neurotmesis signifies disruption of
epineurium as well. Surgical repair is necessary to correct
neurotmesis, and recovery may not be complete.47 The patient
must be informed of the prognosis for recovery and that
resolution may take several weeks, depending on the severity
of initial symptoms.

CLINICAL PEARL Spinal anesthesia has a higher incidence of

neurologic injury than epidural anesthesia.

VII. Diagnosis and treatment of neuropathies (see Fig. 20.5 and Table
20.5)
A. Electromyography. Electromyography (EMG) is extremely
useful in diagnosing the extent of injury to a peripheral nerve (see
Fig. 20.6).48 However, the timing of the test is critical. The
presence of abnormal spontaneous activity in a resting muscle
(fibrillation potentials; see Fig. 20.6) and increased activity
induced by the insertion of the recording needle into the muscle
(insertion activity) suggest differing duration of injury. Insertion
activity becomes noticeable on the EMG within a few days,
whereas fibrillation potentials take 2 to 4 weeks to develop (see
Fig. 20.6).48 A progressive increase in the recruitment of more
motor units, when a muscle is stimulated, is an important
finding.48 In a completely denervated muscle, no recruitment
occurs, whereas partial recruitment may occur when the nerve is
damaged slightly, causing decreased conduction velocity (see Fig.
20.6). EMG is also useful in diagnosing whether the clinical
deficit involves a nerve injury, the extent of the injury, and if
there is evidence of plexus or nerve root injury. EMG studies can
be helpful to differentiate a radiculopathy from a plexopathy;
however, almost half of the patients with a radiculopathy may
have a false-negative paraspinous EMG. EMG can optimally
detect nerve injury between 3 weeks and 6 months following the
inciting event. Fibrillations that identify radiculopathy are seen
most commonly in the paraspinous muscle 1 week after injury
and after 3 to 6 weeks in the distal limb muscles. An early EMG
showing immediate fibrillations (test performed <1 week after
injury) indicates preexisting disease.
B. Nerve conduction studies
1. Both motor and sensory functions of a nerve can be assessed
using evoked potential responses (see Fig. 20.6 and Table
20.5).48 For motor nerve function, the nerve is stimulated at
two points and the compound action potential is recorded
from one of the muscles it innervates. Conduction velocity, as
well as the size of the evoked action potential from the
muscle, is obtained by stimulating the nerve at a point
presumed to be proximal to the site of injury and a point distal
to the site of injury. An abnormality in either of the
parameters recorded may indicate an injury. Similarly, sensory
conduction velocity may be studied by stimulating the nerve
at one point and studying the action potential at another
rostral point on the nerve. When attempting to differentiate
lesions at the level of the spinal root from a peripheral nerve
injury, EMG studies of the paraspinal muscles may help
because the short posterior branch of the spinal root
innervates them, and any combined EMG abnormality of a
lower limb muscle and the paraspinal muscles usually
 indicates a lesion at the root level.48–50 If only the peripheral
muscle shows an abnormal EMG pattern, it usually indicates a
peripheral nerve lesion. Paraspinal EMG alone without a
peripheral muscle EMG may lack specificity and sensitivity to
differentiate between spinal root and peripheral nerve
lesions.50,51
2. Usefulness of nerve conduction studies48,49
a. Nerve conduction studies evaluate the functional integrity
of the nerve.
b. They can help localize the lesion. It may not be possible
for the clinician to pinpoint the nerve involved when a
serious clinical sign or symptom occurs. For instance, a
foot drop may be the result of sciatic, common peroneal,
or a lumbar root involvement, and only an
electrophysiologic study will be able to differentiate
between them. This type of study will also determine the
extent of the involvement based on conduction velocity
and muscle action potentials.
c. Evoked potential measurements, in combination with
needle EMG, can delineate the extent of injury and
thereby help to determine the prognosis.
d. Such studies help to determine whether a given clinical
picture results from injury to a single abnormal nerve or
represents an underlying multiple nerve involvement.
e. In lesions where axonal loss has occurred, nerve
conduction studies reveal smaller than usual amplitude for
sensory and muscular compounded action potentials, with
near normal conduction velocities.
f. Demyelination is associated with drastically slowed
conduction velocities with mild to moderate conduction
block.
C. Timing of electrophysiologic studies
Electrophysiologic (EP) examination performed within the first 2
days of injury may provide useful information.48 Any motor
 action potential recorded from the muscle indicates only partial
damage. Fibrillation potentials suggest a long-standing lesion,
which may have occurred before the anesthetic and delivery.
Studies done 4 weeks later can be useful in assessing the severity
of the lesion and progress of regeneration.52 For example, if
fibrillation potentials are recorded with no action potential from a
muscle after a month, it indicates a poor prognosis and surgical
exploration of the involved nerve may be necessary.
VIII. Approach to patients with peripheral nerve injuries
A. Preexisting causes. During the assessment of patients with
postpartum neurologic deficits, other preexisting causes of
neuropathy, such as diabetes mellitus, obesity, HIV infection, and
MS, should be considered.53 Although most clinicians are
familiar with diabetic neuropathy, neuropathy associated with
HIV is often unrecognized.54 Peripheral neuropathy is the most
frequent neurologic complication associated with HIV infection.
Polyneuropathies may also occur secondary to the neurotoxicity
of antiretroviral treatment. The anesthesiologist should document
in the preoperative evaluation all preexisting neurologic
abnormalities in patients with systemic diseases to avoid future
medicolegal problems. MS is particularly prone to relapse in the
postpartum period54 and often involves the lateral cutaneous
nerve of the thigh.
B. Neurologist consultation and imaging studies. In the initial
evaluation, the anesthesiologist should document all sensory and
motor deficits. It is important to consult a neurologist who is
familiar with obstetric nerve injuries. Appropriate investigations
may include an MRI, CT scan, and EP studies which should be
performed without delay. Depending on the type and severity of
the lesion, it may take up to 8 weeks for the neurologic lesion to
resolve completely. A repeat EP study may be required to assess
progress of the lesion. A consultation from a physiotherapist may
be valuable to decide on the best rehabilitation procedures to
prevent muscle atrophy. A splint may be required in patients with
 a significant foot drop to prevent permanent deformity. If epidural
hematoma is suspected, an MRI or CT scan followed by an
immediate decompressive laminectomy within 6 to 12 hours from
the onset of symptoms offers the best chance for a return of
neurologic function.
C. Plexus injury versus spinal cord injury. Sometimes, an
extensive injury to the lumbosacral plexus may be difficult to
distinguish from an injury to the spinal cord. With spinal cord
injury, EP studies will indicate a lesion at the root level or higher.
In patients with spinal cord ischemia, the ischemic episode may
be caused by compression of the lumbar spinal artery (which may
supply the conus) at the level of the sacrum. MRI findings
suggesting ischemia may be delayed. The possible causes of
prolonged neurologic deficits in parturients are listed in Table
20.6.
 CLINICAL PEARL Electromyography and nerve conduction
studies can help identify the level of neurologic deficit and its
timing.

IX. Complications related to spinal fluid leakage

A. Postdural puncture headache (see Chapter 19). Postdural
puncture headache (PDPH) may occur as a result of either an
accidental dural puncture with an epidural needle or after a spinal
anesthetic. The size of the needle used for lumbar puncture and
the age of the patient are factors that influence the incidence of
headache. Pencil-point needles (e.g., Gertie Marx, Sprotte,
 Whitacre) are associated with decreased incidence of PDPH
compared to cutting needles (e.g., Quincke).55 The use of pencil-
point needles is also associated with decreased requirement for a
therapeutic EBP (see Fig. 20.7). ASA1 Practice Guidelines for
Obstetric Anesthesia strongly recommend the use of pencil-point
needles. The influence of obesity on the incidence of PDPH is
controversial. A recent retrospective study by Miu et al.56 in
obstetric patients did not find a significant relationship between
the incidence of PDPH and need for blood patch and body mass
index.

B. Characteristics of postdural puncture headache. The headache

is classically postural and localized to the frontal or occipital
region or the neck (see Fig. 20.8).57 Although the postural nature
has been the hallmark of PDPH, a recent retrospective study
suggests that 5.6% of patients may exhibit an “atypical,”
nonpositional headache.58 Nausea, dizziness, photophobia,
diplopia, and tinnitus may also occur. Diplopia is thought to occur
as a result of stretching compression of cranial nerve VI. Tinnitus
may result from decreased endolymphatic pressure within the
cochlea due to communication with the subarachnoid space.59
Although low-frequency hearing loss has been reported in elderly
patients after spinal anesthesia, Yousry et al.60 found no such
 hearing loss in women undergoing CD under spinal anesthesia.
Although the time course for PDPH varies from 2 days to 2
months, 1 week is average. Fortunately, spontaneous resolution of
PDPH eventually occurs; it may therefore be appropriate to delay
autologous EBP in patients who report a decrease in the severity
of their symptoms because this may herald spontaneous recovery.

C. Imaging studies. Imaging studies done in patients with

intracranial hypotension with CSF leakage have shown spinal
hygroma (collection of fluid).60 In patients with postural
headache, MRI reveals dilation of the anterior internal vertebral
venous plexus (85%), subdural hygromas (70%), and extraspinal
fluid collections at the C1–C2 level (50%). The origin of the
retrospinal fluid collections may be the result of transudation and
not extravasation. Taken together, all three signs could be the
result of, and the response to, a decreased CSF volume.
Regression of these signs parallels regression of the postural
headache. The presence of cervical spinal hygroma may be the
etiology of neck pain seen in PDPH syndrome.
D. Autologous epidural blood patch. Autologous epidural blood
patch is the treatment of choice, for severe PDPH. Untreated
PDPH typically resolves within a week but occasionally may
persist for months. EBP may be curative even after a year.61 If a
patient develops severe diplopia or other cranial nerve symptoms,
EBP should be performed without delay. If diplopia persists after
a blood patch, neurologic and/or an ophthalmologic consultation
must be obtained. The recommended timing of EBP is greater
than 24 hours after initial dural puncture. The efficacy of
prophylactic or early EBP (<24 hours) has been questioned
because only 50% had relief in one recent retrospective study.
That study also showed that an EBP performed 48 hours after
dural puncture may be more efficacious than those performed
earlier, with 89% of patients receiving initial relief with
permanent results in 76%.62 See Fig. 20.9 for MRI brain images
with CSF leak before and after EBP.63
E. Complications of epidural blood patch. The complications are
few, mild, and transient, with the most common being backache.
Major complications or persistent neurologic deficits are rare.
During an EBP, it is possible to inject the blood into the
subarachnoid space. Kalina et al.64 presented a case of intrathecal
injection of blood. The literature concerning this complication is
scarce. Subarachnoid injection of blood may result in chemical or
infectious meningitis, arachnoiditis, and pain or paresthesias.
 However, patients usually recover fully. These patients should be
followed up by MRI to gauge the resolution of the intrathecal
hematoma.65 We do not perform EBP if the patient is actively
febrile (≥38°C) due to the possibility of bacterial seeding from
infected blood.
F. Managing an unintended postdural puncture headache. If a
dural puncture occurs during an epidural placement, one can
either redo the epidural at the same spinal level, another level, or
introduce the epidural catheter into the intrathecal space and
utilize a continuous spinal catheter technique. Ayad et al.66 have
reported that leaving the intrathecal catheter in situ for at least 24
hours decreases the incidence of PDPH. These results were
duplicated in a study by Verstraete et al.,67 where an epidural
catheter was threaded into the intrathecal space after a known
dural puncture with a reduction in the incidence of PDPH (odds
ratio 2.3). However, this approach poses additional risk for severe
complications: incorrect dosing (an epidural dose given
intrathecally resulting in a high or total spinal), injection of drugs
with the potential for neurotoxicity into the subarachnoid space,
and a potential increased risk of neuraxial infection. Strict sterile
technique is essential, and all providers must be made aware of
the subarachnoid location of the catheter. Additional randomized
blinded trials are needed before this method can be recommended
for routine use.
G. Prophylactic epidural blood patch. If the epidural catheter is
resited into the epidural space following a wet tap, a prophylactic
EBP may be considered. Twenty milliliters of autologous blood
are injected into the epidural space through the epidural catheter
after the patient has delivered, and residual sensory and motor
block has receded. Injecting blood through an epidural catheter in
a patient with residual block may cause the anesthetic level to
rise.65 The efficacy of prophylactic EBP is controversial. In one
study, prophylactic EBP did not decrease the incidence of PDPH
or the need for therapeutic EBP.68 However, prophylactic EBP did
 shorten the length and decrease the severity of PDPH symptoms.
Although there may be a role for prophylactic EBP, especially in
patients in whom initial epidural placement was difficult, the
popularity has decreased.
H. Intracranial hematomas. Very rarely, an untreated PDPH may
be associated with a subdural hematoma (see Fig. 20.10) and,
rarely, an intracerebral hematoma. The etiology is believed to be
due to the stretching of the bridging veins that drain into dural
sinuses that are adherent to the inner table of the skull which
results in vessel damage.69 These blood vessels are short and
straight and located between the periosteal and investing layers of
the cranial dura matter. When intracranial hypotension develops,
the brain may be displaced downward, thereby creating a negative
pressure between the two layers of the dura, which leads to
tearing of these blood vessels. Intracranial hematoma (ICH) is
associated with a nonpostural headache and rapid deterioration of
the level of consciousness. Any long-lasting PDPH that loses its
postural characteristic, and is associated with new onset of nausea
and vomiting, must arouse suspicion of an intracranial event.
Cranial imaging and a neurology consult must be immediately
obtained. If ICH is detected, surgical consultation for surgical
evacuation must occur. The potential for developing a subdural
hematoma may be higher in women with preeclampsia. Zeidan et
al.69 reviewed 46 cases of ICH that were associated with PDPH.
Both subdural and intracerebral hematomas were reported, and
both spinal anesthesia and epidural blocks with accidental dural
puncture were implicated. Epidural-related subdural hematomas
were almost exclusively noted in pregnant women, whereas
spinal-related hematomas were noted in pregnant and
nonpregnant subjects.
 I. Seizures. Patients with intracranial hypotension may develop
seizures.70 Patients with PDPH and seizure activity must be
evaluated by a neurologist without delay. Besides ICH, other
diagnoses include cortical vein thrombosis and eclampsia (more
likely if maternal blood pressure is elevated).
J. Spontaneous intracranial hypotension. Occasionally, an
orthostatic headache clinically similar to PDPH may occur in
patients without any history of neuraxial block or spinal or cranial
trauma (i.e., spontaneous intracranial hypotension). This
condition is twice as common in women in their fourth decade of
life as compared to men63 and is said to be associated with
connective tissue disorders such as Marfan syndrome, Ehlers-
Danlos syndrome, and polycystic kidney disease. These
headaches may respond to a blood patch, although there is no
consensus as to its efficacy in this setting.71–73

CLINICAL PEARL Although the diagnosis of postdural

puncture headache is usually easily made in the parturient with
prior dural puncture, other diagnoses for headache should be
 considered in the patient who has other new neurologic deficits or a
headache that changes in character over time.

X. Infectious complications of neuraxial blocks

A. Postdural puncture meningitis. One of the most feared
complications of neuraxial block is meningitis. Baer74 reported a
fatal case of Streptococcus viridans meningitis and reviewed
several cases of postdural puncture meningitis. Various strains of
S. viridans (a mouth commensal) were the causative organisms,
isolated in 49% of the 179 reported cases. Other pathogens
included Staphylococcus aureus, Pseudomonas aeruginosa, and
Enterococcus faecalis. In 64 cases, no pathogen was isolated,
leading to a diagnosis of aseptic meningitis. In 2007, the
Healthcare Infection Control Practice Advisory Committee of the
Centers for Disease Control and Prevention (CDC) recommended
the use of surgical masks by the proceduralist for placement of
spinal anesthesia to minimize the transmission of oral flora.
During the period 2008 to 2009, five cases of Streptococcus
salivarius meningitis from neuraxial anesthesia were identified in
postpartum women. Investigation of these infections
demonstrated droplet transmission from the anesthesiologist as
the cause of meningitis.75 Nucleic acid amplification (NATs) and
polymerase chain reaction (PCR) tests may also be useful in
identifying the bacteria. These tests are becoming more readily
available, but the clinician should initiate empiric antibiotic
therapy without waiting for results.76 Meningitis has been
reported to occur following single-injection spinals, accidental
dural puncture, myelography, CSE, continuous spinal anesthesia,
and even uncomplicated epidural analgesia.76–79 There have been
three reported deaths due to iatrogenic meningitis and all of them
were young obstetric patients; technical difficulties during
neuraxial block placement were reported in all three.
1. The diagnosis of bacterial meningitis is confirmed using
CSF examination. CSF chemistry, Gram stain, and culture and
 sensitivity testing must be performed. In many cases, the CSF
may appear cloudy, confirming an infectious origin. The
recommended guidelines for diagnosing bacterial meningitis
are80:
a. CSF–blood glucose ratio ≤0.4
b. CSF white blood cell count ≥500 per μL
c. CSF lactate level ≤31.5 mg per dL
2. Prevention of bacterial meningitis. Viral upper respiratory
infection increases the bacterial load and shedding of oral
commensal pathogens. Numerous measures have been
proposed to prevent droplet infection. The use of cap, mask
(changed between procedures), sterile gloves, and large sterile
drapes should be considered the standard of care. Hand
washing is simple and effective in reducing infectious
complications.81,82 The commonly used povidone-iodine prep
solution must be allowed to dry to exert its complete
disinfecting action. Alcohol-based chlorhexidine (which dries
more quickly) is now the agent of choice for skin
disinfection.83 Both povidone-iodine and alcohol-based
chlorhexidine are neurotoxic, and need to dry completely
before needle insertion to minimize chances of arachnoiditis
and neurotoxicity. The use of sterile gowns is not common
among US obstetric anesthesia providers while performing
neuraxial anesthesia; their usefulness in preventing central
venous catheter infections has not been duplicated for
infection after neuraxial procedures.81,84 The authors of this
chapter use all the precautions except a sterile gown.
3. The symptoms and signs of meningitis include neck pain,
nuchal rigidity, high fever, vomiting, severe photophobia,
altered sensorium, seizures, and coma.85 Early administration
of antibiotic therapy is vital to assure a good outcome.
Pending specific bacterial identification and sensitivity
studies, vancomycin (to cover β-lactam-resistant bacteria),
plus a third-generation cephalosporin, are recommended.
B. Epidural abscess
1. Etiology and incidence. This devastating complication of
epidural anesthesia may be more common than was once
suspected.86 Various studies report an incidence of 1:160,000
to 1:505,000. The SOAP serious complication registry
reported an incidence of epidural abscess/meningitis of
1:62,868.4 In a general surgical population, the predisposing
factors are compromised immunity, preexisting source of
infection (e.g., urinary tract infection), diabetes mellitus,
degenerative disease of the spine, substance abuse, and
neuraxial block.87 In obstetric populations, no preexisting
patient-related risk factors have been identified; however, if
the previously discussed risk factors are present, then the
index of suspicion for epidural abscess should be increased.
Bacteria can enter the epidural space during epidural catheter
placement, through contaminated local anesthetic solutions,
by colonization, or hematogenous spread. However, Reihsaus
et al.88 report that only 5.5% of epidural abscesses are
associated with epidural anesthesia.
The spectrum of organisms causing epidural anesthesia–
associated abscesses is similar to those causing a spontaneous
abscess. Of 26 cases associated with an epidural catheter, the
organisms were S. aureus, Staphylococcus epidermidis, P.
aeruginosa, coagulase-negative Staphylococci, and
Pyocyaneus.89 S. aureus and Pseudomonas were causative
organisms in nine patients who had received single-injection
epidural or spinal anesthetics.
2. Clinical signs and symptoms of epidural abscess include
fever, meningismus, back pain, radicular pain, neurologic
deficits, incontinence, and ultimately paraplegia. The onset of
symptoms typically occurs a few days to weeks after epidural
instrumentation. Occasionally, the classical signs of fever,
back pain, and radiculopathy are absent, and patients may
only complain of nonspecific malaise.87,89 Neurologic
 deficits, including weakness, sensory loss, and diminished or
absent reflexes, develop progressively. The appearance of
neurologic deficit with back pain and fever is highly
suggestive of epidural abscess. Flexion often is more painful
than extension of the back. MRI is considered the technique
of choice for diagnosis (see Fig. 20.11). MRI is as effective as
myelography in diagnosing an epidural abscess. Involvement
of the intervertebral disk, vertebral body, and the paraspinal
regions may also be noted.84 As in the case of epidural
hematoma, early diagnosis the key to a positive outcome.

3. In most cases, treatment of an epidural abscess consists of

surgical evacuation through a laminectomy. Percutaneous
aspiration of the abscess has also been described. The
mortality rate associated with an epidural abscess is declining,
with a currently reported rate of 13% to 16%. The antibiotic
used for treating an epidural abscess must be able to penetrate
bone tissue to eradicate spondylodiscitis, and therapy may be
necessary for several weeks.89 The choice of antibiotics
depends on the institutional preference and must be based on
culture and sensitivity studies.
 4. Precautions to prevent epidural abscess. The precautions
described previously in the section on meningitis should be
routinely utilized when performing neuraxial blockade.
Evidence suggests that alcohol-based solutions are more
effective than povidone-iodine at penetrating lipid barriers in
hair follicles and the stratum corneum.90 If povidone-iodine is
used to disinfect the skin, sufficient time must be allowed for
the solution to dry.87
XI. Epidural hematoma
A. Predisposing factors. Epidural hematomas are very rare, with an
incidence of approximately 1:200,000 blocks. The SOAP Serious
Complication Repository (SCORE) project recently reported an
incidence for epidural hematoma of 1:251,463.4 This
complication occurs more frequently after epidural than spinal
anesthesia.87 In a series reported by Vandermeulen et al.,89 5 of
61 spinal hematomas involved parturients. The introduction of
new anticoagulants, such as low molecular weight heparin
(LMWH) and antiplatelet medications, has increased the risk of
this catastrophic complication. Epidural hematoma is often
associated with a preexisting coagulation disorder or
anticoagulant therapy. Risk factors include the intensity of the
anticoagulant effect, increased age, female gender, history of
gastrointestinal bleeding, concomitant aspirin use, the duration of
therapy, and traumatic epidural placement.91
In obstetric patients, anticoagulant therapy, typically LMWH,
may be used to prevent abnormal clotting associated with
thrombophilias (e.g., factor V Leiden mutation). Current trends
suggest that there will be an increased use of LMWH during
pregnancy. However, an epidural hematoma may occur in patients
without any predisposing factors, including LMWH use. There is
no consensus as to the volume of blood accumulated within the
epidural space that is necessary to produce a mass effect.
Thrombocytopenia related to preeclampsia is presumed to
increase the risk of epidural hematoma. Although an absolute
 minimum acceptable platelet count for neuraxial anesthesia
cannot be determined with certainty, a platelet count is mandatory
if the diagnosis of preeclampsia has been made; the decision
regarding the acceptability of a platelet count in a particular
patient must be made on a case-by-case basis.
Thromboelastogram studies may provide additional insight in
determining acceptable coagulation profiles for safe epidural
anesthesia placement.92
Spontaneous epidural hematoma may occur without any
antecedent trauma to the epidural blood vessels,93,94 and it may
affect all regions of the spinal column. A preexisting
coagulopathy or anticoagulant therapy is not always present in
these patients.
B. Symptoms. The symptoms of an acute epidural hematoma
include muscle weakness, back pain, radicular pain, sensory
deficit, and urinary retention. The diagnosis is typically suspected
in the patient whose neuraxial block fails to resolve. Other
symptoms typically occur within the first few days following
neuraxial blockade. Paraplegia can develop over 24 to 48 hours.
Postdelivery failure of the sensory or motor block to resolve
within the expected time should arouse suspicion.
C. Diagnosis. The diagnosis of epidural hematoma is confirmed
with imaging studies including MRI or CT scan. Decompression
must occur within 8 to 12 hours to maximize the potential for
complete recovery of function.95
D. Treatment. In most patients with good recovery of neurologic
function, surgery was performed within 8 hours of the
development of paraplegia. Identification of the spinal hematoma
and the subsequent decision to perform emergency surgery was
significantly delayed in most patients who experienced poor
neurologic recovery and eventually died (more than 24 hours
after the appearance of paraplegia).95
E. Catheter removal causing epidural hematoma. Approximately
50% of epidural hematomas are associated with catheter
 removal.91,95 Therefore, timing of the removal of the catheter in
relation to LMWH dosing is as important as the time of insertion.
If LMWH is administered twice daily in the postoperative period,
the dosing regimen of LMWH should be changed to once daily
and the epidural catheter removed during the trough of the
anticoagulant effect of the LMWH, and preferably 24 hours after
the preceding LMWH dose. LMWH may be restarted 2 hours
after epidural catheter removal.96,97 These rules also apply to
patients who are receiving higher doses of LMWH (1
mg/kg/dose), regardless of the frequency. In patients receiving a
0.5 mg/kg/dose, a 12-hour delay before catheter removal may be
sufficient.96,98 In women with preeclampsia, thrombocytopenia
may actually worsen in the postpartum period before recovery
begins. A platelet count must be repeated before catheter removal
to ensure adequate hemostasis.
F. Guidelines for administering neuraxial blocks (see Chapter 24,
Thrombophilias/Coagulopathies). The guidelines for
administering neuraxial blocks to patients on anticoagulant
therapy are available from American Society of Regional
Anesthesia.96,99 The basic guidelines pertaining to unfractionated
heparin and LMWH therapy are summarized in Table 20.7.96 In
patients receiving higher doses of LMWH (1 mg per kg once
daily or 0.5 mg per kg twice daily), a 24-hour wait is necessary
before a neuraxial block can be performed. When patients receive
0.5 mg per kg once daily, a 12-hour wait is sufficient.
 Anticoagulation therapy with warfarin is an absolute
contraindication to neuraxial anesthesia. In some patients,
anticoagulation therapy cannot be interrupted because of concerns
regarding clot formation and embolism (e.g., prosthetic heart
valves, deep vein thrombosis, atrial fibrillation). These patients
are better managed without neuraxial anesthesia.

CLINICAL PEARL Successful outcome in the patient who

develops an epidural hematoma or abscess depends on a high index
of suspicion, diagnosis with corroborating imaging studies within 6
to 12 hours, and surgical consultation for possible neuraxial
decompression once the diagnosis is made.

XII. Recommendations
The description of the serious complications in this chapter might
give the impression that neuraxial anesthesia is associated with
significant dangers for the parturient and, therefore, must be avoided.
However, when practiced judiciously, neuraxial anesthesia is
associated with a much smaller incidence of overall anesthetic
complications compared to general anesthesia. Maternal
anesthesia–related mortality was 1.7 times higher with general than
 with neuraxial anesthesia in the most recently reported survey of U.S.
patients, although the rate has decreased and is very low, 1 per 1
million live births.100 Obstetric analgesia and anesthesia must be
administered by properly trained individuals. A thorough
understanding of maternal and fetal physiology, attention to technical
details, use of sterile precautions, and a comprehensive vigilant
approach are critical to minimize the incidence of complications.
When a complication occurs, the patient must be informed, followed
closely, and appropriate consultations must be obtained. The care of
patients in the postanesthesia care unit is important. It cannot be
overemphasized that the anesthesiologist or health care provider must
ensure that the block has receded before the patient is discharged to
her room, and that nursing staff continue to monitor block resolution
until complete. In the setting of a compressive lesion within the spinal
canal, timely intervention is essential to ensure recovery without
residual neurologic dysfunction.

REFERENCES
1. American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Practice guidelines for
obstetric anesthesia: an updated report by the American Society of Anesthesiologists Task Force on
Obstetric Anesthesia. Anesthesiology. 2007;106:843–863.
2. Osterman MJ, Martin JA. Epidural and spinal anesthesia use during labor: 27-state reporting area,
2008. Natl Vital Stat Rep. 2011;59:1–13.
3. Zakowski MI. Obstetric-related neurological complications. Int Anesthesiol Clin. 2014;52:40–60.
4. D’Angelo R, Smiley RM, Riley ET, et al. Serious complications related to obstetric anesthesia: the
Serious Complication Repository Project of the Society for Obstetric Anesthesia and Perinatology.
Anesthesiology. 2014;120:1505–1512.
5. Wong CA. Nerve injuries after neuraxial anaesthesia and their medicolegal implications. Best Pract
Res Clin Obstet Gynaecol. 2010;24:367–381.
6. Zakowski M. Postoperative neurologic complication associated with regional anesthesia in the
parturient. In: Norris M, ed. Obstetric Anesthesia. 2nd ed. Philadelphia, PA: Lippincott Williams &
Wilkins; 1999:723–748.
7. Zakowski M. Complications associated with regional anesthesia in the obstetric patient. Semin
Perinatol. 2002;26:154–168.
8. Bromage PR. Neurologic complications of regional anesthesia in obstetrics. In: Hughes SC, Levinson
G, Rosen MA, eds. Schnider and Levinson’s Anesthesia for Obstetrics. 4th ed. Philadelphia, PA:
Lippincott Williams & Wilkins; 2002:409–428.
9. Lee LA, Posner KL, Domino KB, et al. Injuries associated with regional anesthesia in the 1980s and
1990s: a closed claims analysis. Anesthesiology. 2004;101:143–152.
10. Pitkänen MT, Aromaa U, Cozanitis DA, et al. Serious complications associated with spinal and
epidural anaesthesia in Finland from 2000 to 2009. Acta Anaesthesiol Scand. 2013;57:553–564.
11. Davies JM, Posner KL, Lee LA, et al. Liability associated with obstetric anesthesia: a closed claims
analysis. Anesthesiology. 2009;110:131–139.
12. Hayes NE, Wheelahan JM, Ross A. Self-reported post-discharge symptoms following obstetric
neuraxial blockade. Int J Obstet Anesth. 2010;19:405–409.
13. Horlocker TT, Abel MD, Messick JM Jr, et al. Small risk of serious neurologic complications related
to lumbar epidural catheter placement in anesthetized patients. Anesth Analg. 2003;96:1547–1552.
14. Cook TM, Counsell D, Wildsmith JA. Major complications of central neuraxial block: report on the
Third National Audit Project of the Royal College of Anaesthetists. Br J Anaesth. 2009;102:179–190.
15. Ruppen W, Derry S, McQuay H, et al. Incidence of epidural hematoma, infection, and neurologic
injury in obstetric patients with epidural analgesia/anesthesia. Anesthesiology. 2006;105:394–399.
16. Moen V, Dahlgren N, Irestedt L. Severe neurological complications after central neuraxial blockades
in Sweden 1990-1999. Anesthesiology. 2004;101:950–959.
17. Auroy Y, Narchi P, Messiah A, et al. Serious complications related to regional anesthesia: results of a
prospective survey in France. Anesthesiology. 1997;87:479–486.
18. Scott DB, Tunstall ME. Serious complications associated with epidural/spinal blockade in obstetrics: a
two-year prospective study. Int J Obstet Anesth. 1995;4:133–139.
19. Scott DB, Hibbard BM. Serious non-fatal complications associated with extradural block in obstetric
practice. Br J Anaesth. 1990;64:537–541.
20. Usubiaga JE. Neurological complications following epidural anesthesia. Int Anesthesiol Clin.
1975;13:1–153.
21. Wong CA, Scavone BM, Dugan S, et al. Incidence of postpartum lumbosacral spine and lower
extremity nerve injuries. Obstet Gynecol. 2003;101:279–288.
22. Brull R, McCartney CJ, Chan VW, et al. Neurological complications after regional anesthesia:
contemporary estimates of risk. Anesth Analg. 2007;104:965–974.
23. Kuczkowski KM. Neurologic complication of labor analgesia: facts and fiction. Obstet Gynecol Surv.
2004;59:47–51.
24. Lee EY, Margherita AJ, Gierada DS, et al. MRI of piriformis syndrome. AJR Am J Roentgenol.
2004;183:63–64.
25. Vallejo MC, Mariano DJ, Kaul B, et al. Piriformis syndrome in a patient after cesarean section under
spinal anesthesia. Reg Anesth Pain Med. 2004;29:364–367.
26. Redick L. Maternal perinatal nerve palsies. Postgrad Obstet Gynecol. 1992;12:1–6.
27. Grant JCB. Grant’s Atlas of Anatomy, by Regions. 6th ed. Baltimore, MD: Williams & Wilkins; 1972.
28. Cole JT. Maternal obstetric paralysis. Am J Obstet Gynecol. 1946;52:372–386.
29. Graham JG. Neurological complications of pregnancy and anaesthesia. Clin Obstet Gynaecol.
1982;9:333–350.
30. Ellis H, Feldman H. Anatomy for Anaesthetists. 3rd ed. London, United Kingdom: Blackwell Science;
1977:159–331.
31. Papadopoulos EC, Kahn SN. Piriformis syndrome and low back pain: a new classification and review
of the literature. Orthop Clin North Am. 2004;35:65–71.
32. Katirji B. Peroneal neuropathy. Neurol Clin. 1999;17:567–591.
33. Ramanathan S, Chalon J, Richards M, et al. Prolonged spinal nerve involvement after epidural
anesthesia with etidocaine. Anesth Analg. 1978;57:361–364.
34. Berlit P, Klötzsch G, Röther J, et al. Spinal cord infarction: MRI and MEP findings in three cases. J
Spinal Disord. 1992; 5:212–216.
35. Biglioli P, Roberto M, Cannata A, et al. Upper and lower spinal cord blood supply: the continuity of
 the anterior spinal artery and the relevance of the lumbar arteries. J Thorac Cardiovasc Surg.
2004;127:1188–1192.
36. Dimakakos P, Arkadopoulos N. Spinal cord ischaemia. Eur J Vasc Endovasc Surg. 1999;17:544–545.
37. Masson C, Leys D, Meder JF, et al. Spinal cord ischemia. J Neuroradiol. 2004;31:35–46.
38. Castro-Moure F, Kupsky W, Goshgarian HG. Pathophysiological classification of human spinal cord
ischemia. J Spinal Cord Med. 1997;20:74–87.
39. Loher TJ, Bassetti CL, Lövblad KO, et al. Diffusion-weighted MRI in acute spinal cord ischaemia.
Neuroradiology. 2003;45:557–561.
40. Stepper F, Lövblad KO. Anterior spinal artery stroke demonstrated by echo-planar DWI. Eur Radiol.
2001;11:2607–2610.
41. Alblas Cl, Bouvy WH, Lycklama à Nijeholt GJ, et al. Acute spinal-cord ischemia: evolution of MRI
findings. J Clin Neurol. 2012;8:218–223.
42. Faccenda KA, Finucane BT. Complications of regional anaesthesia. Incidence and prevention. Drug
Saf. 2001;24:413–442.
43. Hussain SA, Gullan RW, Chitnavis BP. Cauda equina syndrome: outcome and implications for
management. Br J Neurosurg. 2003;17:164–167.
44. Pong RP, Gmelch BS, Bernards CM. Does a paresthesia during spinal needle insertion indicate
intrathecal needle placement? Reg Anesth Pain Med. 2009;34:29–32.
45. Jaime F, Mandell GL, Vallejo MC, et al. Uniport soft-tip, open-ended catheters versus multiport firm-
tipped close-ended catheters for epidural labor analgesia: a quality assurance study. J Clin Anesth.
2000;12:89–93.
46. Reynolds F. Damage to the conus medullaris following spinal anaesthesia. Anaesthesia. 2001;56:238–
247.
47. Aminoff MJ. Electrophysiologic testing for the diagnosis of peripheral nerve injuries. Anesthesiology.
2004;100:1298–1303.
48. Krarup C. An update on electrophysiological studies in neuropathy. Curr Opin Neurol. 2003;16:603–
612.
49. Czyrny JJ, Lawrence J. The importance of paraspinal muscle EMG in cervical and lumbosacral
radiculopathy: review of 100 cases. Electromyogr Clin Neurophysiol. 1996;36:503–508.
50. Bojović V, Berisavac I, Rasulic L. Significance of sensory evoked potentials in determination of the
level of brachial plexus injuries [in Serbian]. Acta Chir Iugosl. 2003;50:15–22.
51. Haig AJ, Levine JW, Ruan C, et al. Describing paraspinal EMG findings: inadequacy of the single 0-
4+ score. Am J Phys Med Rehabil. 2000;79:133–137.
52. Lalive PH, Truffert A, Magistris MR. Lombosacral radiculopathy (L3-S1) and specificity of multifidus
EMG [in French]. Neurophysiol Clin. 2004;34:41–47.
53. Wulff EA, Wang AK, Simpson DM. HIV-associated peripheral neuropathy: epidemiology,
pathophysiology and treatment. Drugs. 2000;59:1251–1260.
54. Confavreux C, Hutchinson M, Hours MM, et al. Rate of pregnancy-related relapse in multiple
sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J Med. 1998;339:285–291.
55. Vallejo MC, Mandell GL, Sabo DP, et al. Postdural puncture headache: a randomized comparison of
five spinal needles in obstetric patients. Anesth Analg. 2000;91:916–920.
56. Miu M, Paech MJ, Nathan E. The relationship between body mass index and post-dural puncture
headache in obstetric patients. Int J Obstet Anesth. 2014;23:371–375.
57. Vilming ST, Kloster R. Pain location and associated symptoms in post-lumbar puncture headache.
Cephalalgia. 1998;18:697–703.
58. Loures V, Savoldelli G, Kern K, et al. Atypical headache following dural puncture in obstetrics. Int J
Obstet Anesth. 2014;23:246–252.
59. Finegold H, Mandell G, Vallejo MC, et al. Does spinal anesthesia cause hearing loss in the obstetric
population? Anesth Analg. 2002;95:198–203.
60. Yousry I, Förderreuther S, Moriggl B, et al. Cervical MR imaging in postural headache: MR signs and
pathophysiological implications. AJNR Am J Neuroradiol. 2001;22:1239–1250.
61. Gaiser R. Postdural puncture headache. Curr Opin Anaesthesiol. 2006;19:249–253.
62. Kokki M, Sjövall S, Keinänen M, et al. The influence of timing on the effectiveness of epidural blood
patches in parturients. Int J Obstet Anesth. 2013;22:303–309.
63. Schievink WI. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA.
2006;295:2286–2296.
64. Kalina P, Craigo P, Weingarten T. Intrathecal injection of epidural blood patch: a case report and
review of the literature. Emerg Radiol. 2004;11:56–59.
65. Leivers D. Total spinal anesthesia following early prophylactic epidural blood patch. Anesthesiology.
1990;73:1287–1289.
66. Ayad S, Demian Y, Narouze SN, et al. Subarachnoid catheter placement after wet tap for analgesia in
labor: influence on the risk of headache in obstetric patients. Reg Anesth Pain Med. 2003;28:512–515.
67. Verstraete S, Walters MA, Devroe S, et al. Lower incidence of post-dural puncture headache with
spinal catheterization after accidental dural puncture in obstetric patients. Acta Anaesthesiol Scand.
2014;58:1233–1239.
68. Scavone BM, Wong CA, Sullivan JT, et al. Efficacy of a prophylactic epidural blood patch in
preventing post dural puncture headache in parturients after inadvertent dural puncture.
Anesthesiology. 2004;101:1422–1427.
69. Zeidan A, Farhat O, Maaliki H, et al. Does postdural puncture headache left untreated lead to subdural
hematoma? Case report and review of the literature. Middle East J Anaesthesiol. 2010;20:483–492.
70. Agrawal D, Durity FA. Seizure as a manifestation of intracranial hypotension in a shunted patient.
Pediatr Neurosurg. 2006;42:165–167.
71. Warwick WI, Neal JM. Beyond spinal headache: prophylaxis and treatment of low-pressure headache
syndromes. Reg Anesth Pain Med. 2007;32:455–461.
72. Zada G, Pezeshkian P, Giannotta S. Spontaneous intracranial hypotension and immediate
improvement following epidural blood patch placement demonstrated by intracranial pressure
monitoring. Case report. J Neurosurg. 2007;106:1089–1090.
73. Diaz JH. Treatment outcomes in spontaneous intracranial hypotension: do epidural blood patches stop
the leaks? Pain Pract. 2004;4:295–302.
74. Baer ET. Post-dural puncture bacterial meningitis. Anesthesiology. 2006;105:381–393.
75. Centers for Disease Control and Prevention. Bacterial meningitis after intrapartum spinal anesthesia—
New York and Ohio, 2008–2009. MMWR Morb Mortal Wkly Rep. 2010;59:65–69.
76. Wedel DJ, Horlocker TT. Risks of regional anesthesia—infectious, septic. Reg Anesth. 1996;21(suppl
6):57–61.
77. Kasai T, Yaegashi K, Hirose M, et al. Aseptic meningitis during combined continuous spinal and
epidural analgesia. Acta Anaesthesiol Scand. 2003;47:775–776.
78. Reynolds F. Infection as a complication of neuraxial blockade. Int J Obstet Anesth. 2005;14:183–188.
79. Horlocker TT, McGregor DG, Matsushige DK, et al. Neurologic complications of 603 consecutive
continuous spinal anesthetics using macrocatheter and microcatheter techniques. Perioperative
Outcomes Group. Anesth Analg. 1997;84:1063–1070.
80. Straus SE, Thorpe KE, Holroyd-Leduc J. How do I perform a lumbar puncture and analyze the results
to diagnose bacterial meningitis? JAMA. 2006;296:2012–2022.
81. American Society of Anesthesiologists Task Force on Infectious Complications Associated with
Neuraxial Techniques. Practice advisory for the prevention, diagnosis, and management of infectious
 complications associated with neuraxial techniques: a report by the American Society of
Anesthesiologists Task Force on Infectious Complications Associated with Neuraxial Techniques.
Anesthesiology. 2010;112:530–545.
82. Videira RL, Ruiz-Neto PP, Brandao Neto M. Post spinal meningitis and asepsis. Acta Anaesthesiol
Scand. 2002;46:639–646.
83. Hepner DL. Gloved and masked—will gowns be next? The role of asepsis during neuraxial
instrumentation. Anesthesiology. 2006;105:241–243.
84. Kowalski TJ, Layton KF, Berbari EF, et al. Follow-up MR imaging in patients with pyogenic spine
infections: lack of correlation with clinical features. AJNR Am J Neuroradiol. 2007;28:693–699.
85. Cohen S, Hunter CW, Sakr A, et al. Meningitis following intrathecal catheter placement after
accidental dural puncture. Int J Obstet Anesth. 2006;15:172.
86. Grewal S, Hocking G, Wildsmith JA. Epidural abscesses. Br J Anaesth. 2006;96:292–302.
87. Horlocker TT. What’s a nice patient like you doing with a complication like this? Diagnosis, prognosis
and prevention of spinal hematoma. Can J Anaesth. 2004;51:527–534.
88. Reihsaus, E, Waldbaur H, Seeling W. Spinal epidural abscess: a meta-analysis of 915 patients.
Neurosurg Rev. 2000;23: 175–204.
89. Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesth
Analg. 1994;79: 1165–1177.
90. Sato S, Sakuragi T, Dan K. Human skin flora as a potential source of epidural abscess. Anesthesiology.
1996;85:1276–1282.
91. Sidiropoulou T, Pompeo E, Bozzao A, et al. Epidural hematoma after thoracic epidural catheter
removal in the absence of risk factors. Reg Anesth Pain Med. 2003;28:531–534.
92. Huang J, McKenna N, Babins N. Utility of thromboelastography during neuraxial blockade in the
parturient with thrombocytopenia. AANA J. 2014;82:127–130.
93. Groen RJ, Ponssen H. The spontaneous spinal epidural hematoma. A study of the etiology. J Neurol
Sci. 1990;98:121–138.
94. Groen RJ. Non-operative treatment of spontaneous spinal epidural hematomas: a review of the
literature and a comparison with operative cases. Acta Neurochir (Wien). 2004;146:103–110.
95. Horlocker TT, Heit JA. Low molecular weight heparin: biochemistry, pharmacology, perioperative
prophylaxis regimens, and guidelines for regional anesthetic management. Anesth Analg.
1997;85:874–885.
96. Horlocker TT, Wedel DJ, Rowlingson JC, et al. Regional anesthesia in the patient receiving
antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine
Evidence-Based Guidelines (Third Edition). Reg Anesth Pain Med. 2010;35:64–101.
97. Douketis JD, Kinnon K, Crowther MA. Anticoagulant effect at the time of epidural catheter removal
in patients receiving twice-daily or once-daily low-molecular-weight heparin and continuous epidural
analgesia after orthopedic surgery. Thromb Haemost. 2002;88:37–40.
98. Wu CL. Regional anesthesia and anticoagulation. J Clin Anesth. 2001;13:49–58.
99. Horlocker TT, Wedel DJ, Benzon H, et al. Regional anesthesia in the anticoagulated patient: defining
the risks (the second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation).
Reg Anesth Pain Med. 2003;28:172–197.
100. Hawkins JL, Chang J, Palmer SK, et al. Anesthesia-related maternal mortality in the United States:
1979-2002. Obstet Gynecol. 2011;117:69–74.
 Postpartum Tubal Ligation
Brenda A. Bucklin

I. American Society of Anesthesiologists Practice Guidelines for
Obstetric Anesthesia: recommendations for postpartum
sterilization
II. Postpartum anatomic and physiologic changes
A. Cardiovascular changes
B. Gastrointestinal changes
III. Timing of postpartum tubal sterilization
A. Interval versus postpartum tubal sterilization
B. Timing from the obstetrician’s perspective
IV. Surgical considerations relevant to the anesthesiologist
A. Tubal sterilization
B. The overweight or obese patient
V. Anesthetic considerations
A. Anesthetic risk
B. Preoperative assessment
C. Aspiration risk and prophylaxis
D. Breastfeeding and anesthesia
E. Which neuraxial anesthetic is best for postpartum tubal
sterilization?
F. Anesthetic choice: general
G. Anesthetic choice: local
H. Postoperative analgesia
 I. Summary of anesthetic considerations

KEYPOINTS
1. Although postpartum tubal ligation is considered an “urgent” procedure1
because of the consequences of failure to sterilize, the procedure should
not be attempted when it could compromise other aspects of patient care.2
2. Timing of the procedure should be based on anesthetic and obstetric risk
factors as well as patient preferences.
3. If postpartum tubal sterilization is anticipated within 8 hours of delivery,
neuraxial anesthesia should be encouraged during labor and delivery.
4. There should be no oral intake of solid foods within 6 to 8 hours of
surgery.
5. Aspiration prophylaxis should be considered.
6. Neuraxial techniques are preferred.
7. Epidural catheters placed for labor may be more likely to fail with longer
postdelivery time intervals.

POSTPARTUM TUBAL LIGATION (PPTL) also known as postpartum tubal

sterilization, is a common and effective form of birth control used in the United
States. It ranks after the oral contraceptive pill as the second most common form
of birth control method used by women today.3 Although estimates suggest that
it is performed in approximately 10% of hospital deliveries,3 only 50% of the
women who request postpartum sterilization at the time of contraception
counseling receive the procedure. Postpartum sterilization is technically easier
for obstetricians and avoids the inconvenience and cost of a second hospital
visit. Although the procedure should not compromise other aspects of patient
care,2 there is a significant cost to the patient and health care system when the
request for sterilization is unfulfilled.4 PPTL is considered an “urgent” procedure
by the American College of Obstetricians and Gynecologists (ACOG)1 because
of the consequences of failure to sterilize. However, both obstetric and anesthetic
considerations can influence the timing of tubal sterilization. This chapter
reviews timing as well as surgical and anesthetic considerations of PPTL.
I. American Society of Anesthesiologists Practice Guidelines for
Obstetric Anesthesia: recommendations for postpartum
sterilization
The American Society of Anesthesiologists (ASA) Task Force on
Obstetric Anesthesia has published Practice Guidelines for Obstetric
Anesthesia, which include recommendations for postpartum
sterilization (see Table 21.1).2

II. Postpartum anatomic and physiologic changes

A. Cardiovascular changes. Cardiovascular changes occur
immediately after delivery.
1. For several days following delivery, there is a period of
relative hypervolemia, increased venous return, and a shift of
fluid from the interstitium into the circulation. The
hypervolemia and increased venous return result from release
of vena caval compression and reduced lower extremity
venous pressure. Removal of the placenta results in (i.e.,
volume returned to the circulation exceeding blood loss).
2. In the immediate postpartum period, cardiac output and
stroke volume increase as much as 75% above predelivery
levels. Within 1 hour, both stroke volume and heart rate
decrease, reducing cardiac output to approximately 30% of
prelabor values. Cardiac output decreases to prelabor values
within 48 hours of delivery. Heart rate decreases rapidly
immediately after delivery and reaches a prepregnant rate 2
 weeks following delivery. Stroke volume is elevated above
prelabor levels for 48 hours and gradually declines over the
next 24 weeks.
3. Doppler and M-mode echocardiographic evaluations of
postpartum patients have determined that left ventricular wall
thickness and mass remain elevated up to 24 weeks’
postpartum. However, multiparous patients (more than four
pregnancies) who were studied approximately 13 years after
their last pregnancy demonstrated complete reversibility of
all changes (e.g., left ventricular mass, cardiac chamber size,
diastolic and systolic function) when compared with age-
matched nulliparous controls.5
B. Gastrointestinal changes. Gastrointestinal changes during
pregnancy predispose parturients to reflux of gastric contents.
Reflux is a well-known risk factor for acid aspiration. Do these
changes persist in the postpartum period and increase risk for
aspiration?
1. Anesthesiologists have been concerned about the risk of
maternal aspiration associated with PPTL in the postpartum
period. However, a review of anesthetic-related maternal
mortality determined that there were no maternal deaths
associated with maternal aspiration during PPTL.6
2. Several factors contribute to lower esophageal sphincter tone
and reflux during pregnancy. However, many of these changes
resolve soon after delivery.
a. During pregnancy, plasma progesterone concentrations
increase resulting in relaxation of the lower esophageal
sphincter and reflux. Because progesterone is produced
primarily by the placenta, progesterone concentrations
decline rapidly in the first 2 hours after delivery and
approach levels seen during the luteal phase of the
menstrual cycle by 24 hours postpartum.7
b. During pregnancy, the gravid uterus alters the position of
the stomach, displacing the esophagus into the thorax.
 This mechanical change reduces lower esophageal
sphincter tone resulting in reflux before delivery.
3. Several studies have assessed gastric emptying during labor
and postpartum.8 Parturients who are >18 hours postpartum
demonstrate gastric emptying, volume, and pH similar to
nonpregnant women. However, data is limited on the first 8
hours postpartum.
a. All parturients demonstrate delayed gastric emptying of
solids during labor.
b. Parenteral, intrathecal, and bolus-dose epidural
opioids can delay gastric emptying during labor. These
effects likely continue into the early postpartum period.
c. Gastric emptying of clear liquids, including isotonic
sports drinks, does not appear to be delayed unless
opioids have been administered.
4. The preponderance of evidence suggests that if only
pregnancy-induced changes in gastrointestinal function are
considered, postpartum patients are not at increased risk of
aspiration.

CLINICAL PEARL Major anatomic and physiologic changes

occur during pregnancy and labor and delivery. Some changes
extend into the postpartum period and can affect timing and choice
of anesthetic for tubal sterilization.

III. Timing of postpartum tubal sterilization

A. Interval versus postpartum tubal sterilization. The timing of
PPTL can be affected by medical and nonmedical issues (see
Table 21.2). Women who request PPTL and do not receive it are
more likely to become pregnant within 1 year of delivery (47%)
compared to women who did not request the procedure (22%).9
An immediate tubal sterilization performed within 8 hours of
delivery may decrease length and cost of hospital stay but there
may be reasons to delay the PPTL beyond the 8-hour time period.

1. Consent. Tubal sterilization is considered a permanent form

of contraception. A patient’s desire for permanent sterilization
is often discussed with her obstetrician before labor and
delivery, but some patients request tubal sterilization during
labor and delivery or the early postpartum period. Medicaid
Title XIX requirements, state laws, and insurance
regulations may require a specific time interval between
the tubal sterilization and when the obstetrician obtains
consent. Such requirements may limit access to tubal
sterilization in low-income and underserved groups, but
recently, these regulations have been questioned10 and the
ACOG Committee on Health Care for Underserved Women
has recommended revising the Medicaid Title XIX
requirements to establish fair and equitable access to
sterilization procedures.1 Currently, specific Medicaid Title
XIX requirements include11:
a. The patient must be 21 years of age and mentally
competent when the consent is signed.
b. Consent must be obtained 30 days prior to sterilization. A
signed copy of the consent form must be available or
verified at the time of the procedure.
c. In cases of preterm delivery or emergency abdominal
surgery, the 30-day waiting period may be waived.
However, 72 hours must lapse between the time of the
consent and procedure.
d. The consent is valid for 180 days after the consent is
obtained.
 e. Consent is invalid if it is obtained during childbirth or
while the patient is in labor.
f. Consent must not be obtained while the patient is
undergoing abortion or is under the influence.
2. Patient uncertainty. Patients may be unsure about
postpartum sterilization. These patients should be aware that
many factors affect the incidence of successful pregnancy
following tubal sterilization. In such cases, reanastomosis
and/or extracorporeal fertilization may be required unless
there are medical, financial, or religious considerations.
3. Patient regret. In addition to these considerations, there are
other concerns that may affect a woman’s decision to proceed
with postpartum tubal sterilization. Patients with postpartum
sterilization have reported increased rates of menstrual
dysfunction and subsequent hysterectomy compared with
nonsterilized women. In these cases, sterilized women may
choose hysterectomy as a therapeutic alternative more
frequently than nonsterilized women. Patient regret (i.e.,
dissatisfaction with permanent sterilization) is also a
recognized long-term concern. Although the risk of regret is
increased when patients are younger (aged 20 to 24 years), the
odds of regret are similar in women who have undergone
postpartum sterilization (1 year after sterilization) compared
to women who undergo interval sterilization.12 In all cases,
the patient needs to be appropriately counseled and committed
to her decision. This requires prenatal dialogue between the
patient and her physician.
4. Sterilization failure. Despite these concerns, patients should
also be aware that tubal sterilization failures do occur at a
rate of 7.5 pregnancies per 1,000 sterilizations. Postpartum
sterilizations have the lowest failure rate of any other method
of tubal sterilization, especially if fallopian tube resection
occurs.13
5. The anesthesiologist should consider the following factors
 when immediate tubal ligation is planned within 8 hours
of delivery:
a. The decision to administer general anesthesia within 8
hours of delivery should be considered carefully.
b. What is the duration of the fast for solids?
c. Did the patient receive opioids during labor?
d. Is a functional epidural catheter in place?
B. Timing from the obstetrician’s perspective
1. Obstetricians often prefer postpartum sterilization because
interval procedures require laparoscopic visualization of
the fallopian tubes. However, hysteroscopic Essure™ tubal
sterilization is now very popular and avoids the laparoscopic
approach for tubal sterilization remote from delivery. This
approach also avoids abdominal incisions and the procedure
can be performed in an office-based setting with paracervical
block and sedation. However, a recent review of all
randomized controlled trials determined that for hysteroscopic
Essure™ tubal sterilization overall pain scores were not
significantly reduced by either paracervical block with
lidocaine or conscious sedation.14
a. Laparoscopic interval complications. Postpartum
procedures are technically easier, require less equipment,
and are associated with fewer serious complications (e.g.,
subcutaneous emphysema, pneumothorax,
pneumomediastinum, venous gas emboli) compared
with laparoscopic interval sterilization.
b. Postpartum tubal complications are rare and include:
(1) Difficult identification and mobilization of the
tube, skin infections, intraoperative bleeding, or
delayed hemorrhage.
(2) Delayed hemorrhage can result in retroperitoneal
hematoma, but this is an infrequent complication.
(3) Other rare but serious complications include bowel
laceration and vascular injury.
2. Two important considerations may affect the decision to
proceed with postpartum sterilization.
a. Uterine atony and hemorrhage. Although multiparous
patients are more likely to request these procedures, they
are at increased risk for uterine atony and associated
postpartum hemorrhage. Fortunately, atony usually
subsides within 12 hours of delivery, making postpartum
sterilization possible if the hematocrit is stable and within
normal limits.
b. Newborn assessment. A major obstetric disadvantage
of an early postpartum procedure is inadequate time to
assess the newborn. If newborn resuscitation is necessary
or the newborn is transferred to the intensive care unit,
postpartum sterilization may be delayed.
3. High-risk patients. If patients have serious medical
comorbidities (e.g., cardiovascular disease) or complicated
obstetric histories, an obstetric concern is the risk of
subsequent pregnancy. If the obstetrician fears that a patient
may not return for interval sterilization 6 weeks’ postpartum,
the decision to proceed with tubal sterilization in such a high-
risk patient must be weighed against the risk of a subsequent
pregnancy. Because of continuing resolution of the
physiologic changes of pregnancy in the early postpartum
period, some women with serious medical comorbidities may
benefit from interval sterilization. However, general
anesthesia, obesity, diabetes mellitus, and a previous
history of abdominal or pelvic surgery have been identified
as independent predictors for complications in women
undergoing interval sterilization.15
4. The ASA Practice Guidelines for Obstetrical Anesthesia state
that a PPTL should not be attempted when it might
compromise other aspects of care.2 However, PPTL is
considered an “urgent” procedure1 because of the
consequences of failure to sterilize.
 a. Timing of the tubal sterilization will depend on the
adequacy of labor and delivery staffing.
b. Patients should be aware that tubal sterilization cannot be
guaranteed despite the best attempts of the hospital team.
c. To avoid rescheduling and interval sterilization, hospitals
may employ temporary mechanisms to increase staffing
when labor and delivery is busy and a tubal sterilization is
requested.

CLINICAL PEARL The timing of the procedure should be

individualized and based on anesthetic risk factors (e.g., delayed
gastric emptying in patients who have received opioids during
labor), obstetric risk factors (e.g., maternal fever, chorioamnionitis,
sepsis, blood loss, hemodynamic instability), and patient
preferences.2

IV. Surgical considerations relevant to the anesthesiologist

A. Tubal sterilization is frequently considered to be a minor
procedure by both patients and health care providers. However,
manipulation and ligation of the fallopian tubes often produces
intense surgical stimulation. Although the incision is small,
peritoneal stimulation may correspond to the pain levels
experienced by parturients at cesarean delivery (CD). When
neuraxial anesthesia is administered and deemed inadequate, the
patient may initiate a Valsalva maneuver making identification
and ligation of the fallopian tubes difficult. This may necessitate a
larger surgical incision or placement of intraperitoneal packs.
Although some marginal, spinal, and epidural anesthetics can be
salvaged with 0.5% to 1% lidocaine injected over the peritoneal
surfaces and tubes, some patients will require conversion to
general anesthesia.
B. The overweight or obese patient. In the United States, more
than one-third of all women are obese, more than 50% of
pregnant women are overweight or obese, and nearly 10% of
women of reproductive age are extremely obese.16 The obese
patient is another challenge for the obstetrician and
anesthesiologist.
1. Type of incision. Although the fallopian tubes are more
easily accessible in the postpartum patient because of
altered anatomy produced by the enlarged uterus, obese
patients may require a vertical supraumbilical incision at the
level of the uterine fundus for adequate surgical exposure. In
these cases, achieving an adequate level of anesthesia with a
neuraxial technique may be difficult.
2. Surgical approach. Although there are several surgical
approaches performed using minilaparotomy, most
obstetricians use some type of partial salpingectomy
technique (e.g., Pomeroy method) (see Fig. 21.1). In cases
where exposure is difficult due to excessive subcutaneous
tissue, titanium clips (see Fig. 21.2) may be used to decrease
surgical manipulation and reduce operative time. However,
because of increased risk of pregnancy at 24 months after use
of the titanium clip compared with postpartum partial
salpingectomy, routine use of the titanium clip is not
recommended.17 General anesthesia may be required, and
in some cases, the risk-benefit ratio of early tubal sterilization
must be reassessed.
CLINICAL PEARL There should be close communication
between the obstetrician and anesthesiologist because the type of
 incision and ligation method may increase surgical time and affect
the anesthetic technique and agent.

V. Anesthetic considerations
A. Anesthetic risk
1. Although the true anesthetic risk for postpartum sterilization
performed within 8 hours of delivery is unknown, neuraxial
anesthesia should be encouraged during labor and delivery.
a. Early epidemiologic records only contain data from
laparoscopic and laparotomy sterilizations performed after
the 8-hour postpartum period.18,19 These reports indicated
that complication rates were five times higher when
general anesthesia was administered compared to local
anesthetic techniques (i.e., local, epidural, or spinal).
However, these reports occurred prior to the use of pulse
oximetry and capnography and do not reflect modern
anesthetic practice.
b. Reports of anesthetic-related mortality during obstetric
delivery in the United States do not identify PPTL as a
risk for anesthetic-related complications.6
c. Similarly, there are no reports of anesthetic-related
mortality associated with tubal sterilization in the
Reports of Confidential Enquiries into Maternal Deaths.20
These detailed reports of maternal deaths are published
every 3 years in the United Kingdom and make
recommendations for improvement in patient care.

CLINICAL PEARL Collectively, reports suggest low rates of

anesthetic complication associated with tubal sterilization.

2. Many tubal sterilizations are performed with neuraxial

anesthesia. In the event of failure of a neuraxial technique in
the immediate postpartum period, it may be prudent to wait
 until the following day so that a spinal anesthetic can be
administered instead of a general anesthesia.
a. Airway mishaps and failed intubation in obstetrics are
most often associated with CD.21 Because CDs with
general anesthesia are often emergent, the clinical
circumstances between tubal sterilization and CD are very
different (elective vs. emergent). Emergency surgery
for CD has been identified as a risk factor for anesthesia-
related mortality.22 The urgency of the situation may
contribute to overall airway difficulty.
b. However, there are anecdotal reports suggesting that
airway changes can persist for an unspecified time
period following delivery resulting from maternal
expulsive efforts. Residual laryngeal edema may
contribute to airway difficulty if general anesthesia is
necessary for postpartum tubal sterilization.

CLINICAL PEARL Neuraxial techniques are preferred to

general anesthesia for most postpartum tubal sterilizations.2

B. Preoperative assessment. The anesthesiologist should pay

particular attention to the preanesthetic assessment and the
events of labor and delivery and early postpartum. Every
physiologic system is altered during pregnancy (and especially
during labor and delivery), but these changes mostly resolve in
the early postpartum period. However, the anesthesiologist should
still bear these physiologic alterations in mind.
1. Blood loss and uterine atony can be limiting factors for early
postpartum sterilization. Because blood loss in obstetrics is
often underestimated, careful assessment of uterine tone and
blood loss are helpful in determining the appropriateness of
early postpartum sterilization.
2. In most cases of postpartum sterilization performed within 8
hours of delivery, an immediate postpartum hematocrit is
 not required, if the antenatal hematocrit was normal and
blood loss during labor and delivery was not excessive.
3. If the surgery is performed the following day, the obstetricians
usually obtain a hematocrit. This laboratory value is
compared with the antenatal hematocrit.
4. Although there is no specific hematocrit that will cause a
surgical delay, obvious signs of hemodynamic instability (i.e.,
orthostasis) or excessive blood loss will delay surgery.
5. Some high-risk patients may benefit from interval sterilization
6 to 8 weeks’ postpartum. However, the safety of postpartum
tubal sterilization has been reported in patients with
uncomplicated preeclampsia or gestational hypertension.23
Similar hemodynamic outcomes were reported in
hypertensive patients undergoing spinal anesthesia during
postpartum sterilization compared with patients who had
uncomplicated pregnancies. However, refractory
hypertension or severe diseases complicated by oliguria or
pulmonary edema are indications for delayed interval
sterilization.
C. Aspiration risk and prophylaxis. Although the true anesthetic
risk of postpartum sterilization is unknown, there are few reports
of complications.
1. Immediately postpartum, gastrointestinal changes of
pregnancy resolve rapidly but complete resolution may take
up to 6 weeks.
2. Although aspiration prophylaxis will not prevent gastric
contents from entering the lung if aspiration occurs, it may
lessen the severity of the aspiration and its consequences.
3. No time interval will guarantee a postpartum patient risk-
free for aspiration.
4. Patients should have no oral intake of solid food within 6 to
8 hours of surgery, depending on the type of food ingested
(i.e., fat content).2
5. Several medications are used for aspiration prophylaxis in
 obstetrics. A clear non-particulate antacid, H2-receptor
antagonist, and metoclopramide are mainstays of aspiration
prophylaxis.
a. A clear nonparticulate antacid is administered before
going to the operating room to rapidly increase the pH of
stomach contents. Side effects of these antacids include
nausea, increased potential for emesis, and variable
duration of action.
b. The H2-receptor antagonists inhibit gastric acid
secretion and reduce gastric volume, but their usefulness
can be limited by delayed onset.
c. Metoclopramide, a dopamine receptor antagonist, is
described as a gastrointestinal prokinetic drug because it
increases lower esophageal sphincter tone, increases
gastric emptying, and thereby decreases gastric volume.
Dystonia is a reported side effect; however, it is rare.
d. Although the nonparticulate antacids have an immediate
effect, both the H2-receptor antagonists and
metoclopramide can take up to 2 hours for a maximal
effect. Administration of all three agents should be
considered when the risk of aspiration is increased (e.g.,
diabetes mellitus).

CLINICAL PEARL No time interval will guarantee a

postpartum patient risk-free for aspiration. Before postpartum tubal
sterilization, patients should have no oral intake of solid food within
6 to 8 hours of surgery, depending on the type of food ingested (i.e.,
fat content). Aspiration prophylaxis should be considered.2

D. Breastfeeding and anesthesia. The American Academy of

Pediatrics identifies breastfeeding as the ideal method of
feeding and nurturing infants.24 It also recognizes
breastfeeding as primary in achieving the best possible health as
 well as the best developmental and psychosocial outcomes for
infants. Because many women are breastfeeding at time of
discharge from the hospital, there is increasing concern about the
effects of drugs on breastfeeding and neonatal safety.
1. Drug transfer in the neonate is dependent on lipid solubility,
degree of ionization, molecular weight, degree of protein
binding, and secretion into breast milk. Although the
amount of drug detected in breast milk is proportionate to the
maternal drug dose, the amount of drug reaching the neonate
is usually subtherapeutic. The average fetal dose is
approximately 1% to 2% of the maternal dose.
Furthermore, during the first few days’ postpartum, the infant
receives only a small amount of colostrum. Colostrum
contains only a very small amount of drug, making it unlikely
that drug transfer will adversely affect the neonate.
2. For many years, there has been concern about the role of
peripartum medications and breastfeeding success. Although
randomized trials evaluating this issue are limited, short-term
administration of commonly administered sedatives and
analgesics (e.g., midazolam, propofol, fentanyl) result in
minute breast milk doses.25 Because there are many factors
that can limit breastfeeding success, identification of the
safest available medication in a specific category as well as
review of the AAP list of drugs that are compatible with
breastfeeding should be considered.26
3. The U.S. Department of Health and Human Services has
concluded that following anesthesia and sedation, “mothers
with normal term or older infants can generally resume
breastfeeding as soon as they are awake, stable, and alert.
Resumption of normal mentation is a hallmark that these
medications have redistributed from the plasma compartment
(and thus generally the milk compartment) and entered
adipose and muscle tissue where they are slowly released.”27
E. Which neuraxial anesthetic is best for postpartum tubal
sterilization?
1. Both spinal and epidural anesthesia are effective for tubal
sterilization and can reduce the risk of airway mishaps.
Neuraxial techniques are preferred to general anesthesia
for most postpartum tubal sterilizations.2
a. A T4 sensory level is required to block pain effectively
during fallopian tube manipulation and ligation.
b. Patient preference, presence of a functional epidural
catheter, delivery to tubal sterilization interval, and
technical factors all influence the decision to perform a
particular neuraxial technique.
c. Although many epidural catheters are adequate for labor
and delivery, some will fail during operative procedures.
2. Epidural reactivation
a. Several factors should be considered before attempting
epidural catheter reactivation (see Table 21.3):

b. The Practice Guidelines for Obstetric Anesthesia suggest

that epidural catheters placed for labor may be more likely
to fail with longer postdelivery time intervals.2
(1) An important factor affecting the success of epidural
catheter reactivation is the interval from delivery to
tubal ligation. Studies of epidural reactivation have
produced conflicting results with regard to a specific
time interval for activation and subsequent success,
but catheters are more likely to fail when PPTL is
performed more than 10 hours after delivery.
(2) Other factors that may influence the success of
reactivation are ambulation during labor and
 postpartum as well as the method of securing the
catheter. Catheters should be secured when the
patient is in a deflexed position.28
c. Epidural catheter reactivations have also been associated
with increased anesthesia provider times and patient
charges when compared with spinal anesthetics,
especially if reactivation fails (see Fig. 21.3).29

d. If postpartum tubal sterilization is anticipated within

several hours of delivery and the epidural catheter
provided adequate labor analgesia, it is reasonable to
attempt epidural reactivation.
e. Choice of local anesthetic. Three percent 2-
chloroprocaine is a reasonable choice for epidural
reactivation for postpartum tubal sterilization unless a
prolonged procedure is anticipated (e.g., morbidly obese
patient). In those cases, 2% lidocaine with epinephrine is
 the anesthetic of choice. The addition of fentanyl 50 to
100 μg to the local anesthetic will reduce peritoneal
discomfort associated with visceral traction.
f. Technical considerations can also affect the likelihood of
epidural reactivation.
(1) Depth of catheter insertion. Because catheter
dislodgement is one such consideration, depth of
catheter placement at time of insertion is important.
Although catheters inserted >6 cm into the epidural
space are more likely to remain functional for
prolonged periods compared to catheters inserted 2 to
4 cm, the risk of intravascular cannulation is also
increased. The highest incidence of “satisfactory”
analgesia is associated with an insertion depth of 4
to 6 cm.30
(2) Type of catheter. Multiorifice catheters have also
been shown to provide superior analgesia and
require less manipulation compared to single-orifice
epidural catheters.31
(3) The walking epidural. Although walking epidurals
and postpartum ambulation may increase the
likelihood of epidural catheter dislodgement and
subsequent reactivation failure, no evaluations of this
as a possible causative factor have been reported.
g. When early postpartum tubal sterilization is anticipated,
epidural labor analgesia is ideal to avoid intrapartum
parenteral opioid administration. Parenteral opioids can
delay gastric emptying for an unspecified time period
and potentially increase the risk of aspiration if general
anesthesia becomes necessary.
h. Inadequate epidural anesthesia after reactivation.
Although some inadequate epidural anesthetics can be
rescued with subcuticular and/or intraperitoneal
lidocaine infiltration as well as parenteral sedation,
 other patients will require spinal anesthesia, epidural
catheter replacement, or general anesthesia.
(1) When activation is attempted and there is
question of adequate anesthesia, spinal anesthesia
is one anesthetic option. However, if large amounts
of local anesthetic have been administered epidurally,
there is a chance of high or total spinal anesthesia32
resulting from a physical effect of the fluid volume in
the epidural space. Some anesthesia providers will
administer a reduced-dose spinal anesthetic in this
situation,33 although there is no specific formula used
to predict the height of spinal anesthesia once a large
volume of local anesthetic has been injected into the
epidural space.
(2) When reactivation fails, other alternatives include:
(a) Allowing the inadequate epidural block to
recede followed by administration of a single-
injection spinal anesthetic
(b) Repeating the epidural anesthetic with a short-
acting local anesthetic (e.g., 3% 2-
chloroprocaine)
(c) Combined spinal-epidural anesthesia
(d) General anesthesia
(3) Anesthesia providers must consider that epidural
reactivations can be time consuming (i.e.,
reactivation may require more time than the surgical
procedure) and costly. In the interest of time, it may
be prudent to remove the epidural catheter and
initiate spinal anesthesia before attempting epidural
activation.

CLINICAL PEARL An epidural catheter placed for labor

may be more likely to fail with longer postdelivery time intervals.2
 3. Spinal anesthesia is the preferred technique for patients
undergoing delayed PPTL or for immediate procedures when
an epidural catheter was not used during labor. It is reliable,
simple to perform, provides sensory and motor blockade,
and is rapid in onset.
a. Both spinal and epidural anesthetic requirements
decrease during pregnancy, but requirements return to
prepregnancy levels by 36 to 48 hours postpartum. A 30%
increase in local anesthetic requirements may be observed
8 to 24 hours postpartum.34 This rapid increase is most
likely due to a decrease in progesterone levels after
delivery.
b. Although hyperbaric lidocaine and bupivacaine are often
administered for tubal ligation, many anesthesiologists
have discontinued hyperbaric spinal lidocaine
administration because of concern about transient
neurologic symptoms (TNS) and potential neurotoxicity.
Although there are few reports of TNS in obstetrics,35
there is still insufficient evidence to recommend the
routine use of hyperbaric lidocaine in obstetrics.36
F. Anesthetic choice: general
Neuraxial techniques are preferred to general anesthesia for tubal
sterilization,2 but some patients will request or require general
anesthesia. Because no time interval will guarantee a
postpartum patient risk-free for aspiration, general
anesthesia with rapid sequence intubation and cricoid
pressure is recommended. The decision to perform tubal
sterilization using general anesthesia within 8 hours of delivery
should be considered carefully.
1. Induction agents. Although propofol is often used for
induction of anesthesia because of its antiemetic properties
and rapid awakening, other agents (e.g., etomidate) have a
long history of safety and efficacy.
2. Muscle relaxants. Alterations in the activity of both
 nondepolarizing and depolarizing muscle relaxants have been
observed during the postpartum period.
a. Succinylcholine is the mainstay for tracheal intubation in
obstetrics unless there is a specific contraindication.
Although pseudocholinesterase levels decrease during
pregnancy and postpartum, these changes do not have a
clinically important effect on the duration of
succinylcholine. Reports suggest that metoclopramide
may increase the duration of succinylcholine postpartum
because of its inhibition of plasma cholinesterase.37
Plasma cholinesterase activity or the duration of action of
succinylcholine are not affected by ranitidine.38
b. Prolonged neuromuscular blockade after rocuronium,
vecuronium, and mivacurium administration has been
reported. Decreased plasma cholinesterase activity is
responsible for the increased duration of mivacurium.
Increased hormonal effects as well as alterations in
hepatic blood flow explain the increased duration of
rocuronium and vecuronium. However, if lean body mass
instead of total body weight is used to calculate the dose
of rocuronium, the duration of action of rocuronium is not
prolonged in postpartum women.39 No change in
duration of atracurium has been observed but
decreased duration has been reported with
cisatracurium. Taken together, these changes are rarely
clinically significant. However, neuromuscular blockade
should be monitored if a nondepolarizing muscle relaxant
is used.
3. Inhalation agents. During pregnancy, the minimal alveolar
concentration (MAC) for volatile anesthetics decreases by
one-third. During the postpartum period, MAC is decreased
during the first 12 hours but returns to near normal 12 to 24
hours postpartum.40 One important consideration when
administering volatile anesthetics postpartum is the risk of
 uterine atony. High concentrations of volatile anesthetics are
known to impair uterine activity in postpartum patients.
Cautious administration of these agents is necessary to
prevent postpartum uterine atony and hemorrhage.
Concomitant use of intravenous oxytocin will decrease the
risk of uterine atony.
G. Anesthetic choice: local
Tubal sterilization has been performed under local anesthesia
because of easy surgical access to the fallopian tubes in the early
postpartum period. One hazard of this technique is that the
amount of intravenous sedation needed may blunt airway reflexes
and increase the risk of aspiration. Although PPTL can be
performed with intraperitoneal lidocaine injection and
intravenous sedation, the Practice Guidelines for Obstetric
Anesthesia question the effectiveness of this technique.2 The
editors do not recommend this approach other than in exceptional
circumstances.
H. Postoperative analgesia. Typically, patients experience modest
pain of short duration after PPTL
Although several postoperative pain control methods have been
suggested, the anesthesiologist must consider that these patients
may be discharged soon after the procedure. In addition,
prevention of bothersome side effects (e.g., nausea, vomiting,
sedation) is important to encourage bonding and caring for the
infant.
1. Postoperatively, patients usually require a single dose of
parenteral opioid followed by an oral analgesic.
2. Ibuprofen is often used to supplement the parenteral opioid.
3. Ketorolac may also be administered as an adjunct. It is
considered “compatible with breastfeeding” by the
American Academy of Pediatrics.26
4. Although expensive, acetaminophen (IV) is another option
for postoperative pain control.
5. Other methods of postoperative pain control have been
 reported.
a. Both intrathecal and epidural morphine have
successfully alleviated pain after tubal ligation.41,42
However, the risk of delayed respiratory depression
following neuraxial morphine administration is an
important consideration, especially if the patient is to be
discharged from the hospital that same day.
b. Others have reduced postoperative pain after tubal
sterilization by infiltrating the skin and fallopian tubes
with 0.5% bupivacaine during the procedure. A recent
systematic review and meta-analysis concluded that
during interval sterilization with either rings or clips, use
of topical or injectable local anesthetic decreased
postoperative pain substantially for up to 8 hours
postoperatively.43 However, comparative studies
assessing postoperative pain control after tubal ligation
with cautery versus rings or clips did not meet eligibility
requirements.
c. One percent lidocaine has also been administered
intraperitoneally for adequate pain control.
d. Finally, patients receiving infiltration of sufentanil into
the fallopian tube and mesosalpinx demonstrated
significant pain relief postoperatively.44

CLINICAL PEARL Both intrathecal and epidural morphine

have been used for postoperative pain control. However, the risk of
delayed respiratory depression should be considered, especially if
the patient is to be discharged from the hospital that same day.

I. Summary of anesthetic considerations

In many patients, PPTL is performed safely within 8 hours of
delivery. High-risk patients may benefit from delayed
sterilization, but the medical risks of a subsequent pregnancy
 must be weighed against those of a PPTL. Practice Guidelines for
Obstetric Anesthesia suggest that spinal, epidural, or general
anesthesia can be provided without affecting maternal
complications.2 Although reports of complications are rare and
the true anesthetic risk of postpartum tubal sterilization is
unknown, many procedures are performed within 8 hours of
delivery. Solid food consumption, parenteral, epidural, and
intraspinal opioid administration can contribute to delays in
gastric emptying in postpartum patients. Despite the scarcity of
literature comparing the various anesthetic techniques, the timing
of the procedure and the decision to use a particular anesthetic
technique should be individualized and based on anesthetic and/or
obstetric risk factors and patient preference.

REFERENCES
1. Committee on Health Care for Underserved Women. Committee Opinion No. 530: access to
postpartum sterilization. Obstet Gynecol. 2012;120:212–215.
2. American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Practice guidelines for
obstetric anesthesia: an updated report by the American Society of Anesthesiologists Task Force on
Obstetric Anesthesia. Anesthesiology. 2007;106:843–863.
3. Mosher WD, Jones J. Use of contraception in the United States: 1982-2008. Vital Health Stat 23.
2010;29:1–44.
4. Rodriguez MI, Edelman A, Wallace N, et al. Denying postpartum sterilization to women with
Emergency Medicaid does not reduce hospital charges. Contraception. 2008;78:232–236.
5. Sadaniantz A, Saint Laurent L, Parisi AF. Long-term effects of multiple pregnancies on cardiac
dimensions and systolic and diastolic function. Am J Obstet Gynecol. 1996;174:1061–1064.
6. Hawkins JL, Chang J, Palmer SK, et al. Anesthesia-related maternal mortality in the United States:
1979-2002. Obstet Gynecol. 2011;117:69–74.
7. Löfgren M, Bäckström T. Serum concentrations of progesterone and 5 alpha-pregnane-3,20-dione
during labor and early post partum. Acta Obstet Gynecol Scand. 1990;69:123–126.
8. Hawkins JL. Postpartum tubal sterilization. In: Chestnut DH, Wong CA, Tsen LC, et al., eds.
Chestnut’s Obstetric Anesthesia: Principles and Practice. 5th ed. Philadelphia, PA: Elsevier; 2014:30–
42.
9. Thurman AR, Janecek T. One-year follow-up of women with unfulfilled postpartum sterilization
requests. Obstet Gynecol. 2010;116:1071–1077.
10. Borrero S, Zite N, Potter JE, et al. Medicaid policy on sterilization—anachronistic or still relevant? N
Engl J Med. 2014;370:102–104.
11. Colorado medicaid sterilization consent form (MED-178). Colorado Web site.
https://www.colorado.gov/pacific/sites /default/files/MED-178_092713.pdf. Accessed November 6,
2014.
12. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 133: benefits and
risks of sterilization. Obstet Gynecol. 2013;121:392–404.
13. Peterson HB, Xia Z, Hughes JM, et al. The risk of pregnancy after tubal sterilization: findings from
the U.S. Collaborative Review of Sterilization. Am J Obstet Gynecol. 1996;174:1161–1168.
14. Kaneshiro B, Grimes DA, Lopez LM. Pain management for tubal sterilization by hysteroscopy.
Cochrane Database System Rev. 2012:(8)CD009251.
15. Jamieson DJ, Hillis SD, Duerr A, et al. Complications of interval laparoscopic tubal sterilization:
findings from the United States Collaborative Review of Sterilization. Obstet Gynecol. 2000;96:997–
1002.
16. Flegal KM, Carroll MD, Kit BK, et al. Prevalence of obesity and trends in the distribution of body
mass index among US adults, 1999-2010. JAMA. 2012;307:491–497.
17. Rodriguez MI, Edelman AB, Kapp N. Postpartum sterilization with the titanium clip: a systematic
review. Obstet Gynecol. 2011;118:143–147.
18. Peterson HB, DeStefano F, Rubin GL, et al. Deaths attributable to tubal sterilization in the United
States, 1977 to 1981. Am J Obstet Gynecol. 1983;146:131–136.
19. Peterson HB, Greenspan JR, DeStefano F, et al. Deaths associated with laparoscopic sterilization in
the United States, 1977-79. J Reprod Med. 1982;27:345–347.
20. Cantwell R, Clutton-Brock T, Cooper G, et al. Saving mothers’ lives: reviewing maternal deaths to
make motherhood safer: 2006-2008. The eighth report of the Confidential Enquiries into Maternal
Deaths in the United Kingdom. BJOG. 2011;118:1–203.
21. Quinn AC, Milne D, Columb M, et al. Failed tracheal intubation in obstetric anaesthesia: 2 yr national
case-control study in the UK. Br J Anaesth. 2013;110:74–80.
22. Endler GC, Mariona FG, Sokol RJ, et al. Anesthesia-related maternal mortality in Michigan, 1972 to
1984. Am J Obstet Gynecol. 1988;159:187–193.
23. Suelto MD, Vincent RD Jr, Larmon JE, et al. Spinal anesthesia for postpartum tubal ligation after
pregnancy complicated by preeclampsia or gestational hypertension. Reg Anesth Pain Med.
2000;25:170–173.
24. American Academy of Pediatrics. AAP reaffirms breastfeeding guidelines. http://www.aap.org/en-
us/about-the-aap/aap-press-room/Pages/AAP-Reaffirms-Breastfeeding-Guidelines.aspx. Accessed
November 6, 2014.
25. Nitsun M, Szokol JW, Saleh HJ, et al. Pharmacokinetics of midazolam, propofol, and fentanyl transfer
to human breast milk. Clin Pharmacol Ther. 2006;79:549–557.
26. American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into
human milk. Pediatrics. 2001;108:776–789.
27. U.S. Department of Health and Human Services. Analgesia and anesthesia for the breastfeeding
mother, revised 2012. http://www.guideline.gov/content.aspx?id=39271. Accessed November 6, 2014.
28. Hamilton CL, Riley ET, Cohen SE. Changes in the position of epidural catheters associated with
patient movement. Anesthesiology. 1997;86:778–784.
29. Viscomi CM, Rathmell JP. Labor epidural catheter reactivation or spinal anesthesia for delayed
postpartum tubal ligation: a cost comparison. J Clin Anesth. 1995;7:380–383.
30. Beilin Y, Bernstein HH, Zucker-Pinchoff B. The optimal distance that a multiorifice epidural catheter
should be threaded into the epidural space. Anesth Analg. 1995;81:301–304.
31. D’Angelo R, Foss ML, Livesay CH. A comparison of multiport and uniport epidural catheters in
laboring patients. Anesth Analg. 1997;84:1276–1279.
32. Mets B, Broccoli E, Brown AR. Is spinal anesthesia after failed epidural anesthesia contraindicated for
cesarean section? Anesth Analg. 1993;77:629–631.
33. Dadarkar P, Philip J, Weidner C, et al. Spinal anesthesia for cesarean section following inadequate
 labor epidural analgesia: a retrospective audit. Int J Obstet Anesth. 2004;13:239–243.
34. Abouleish EI. Postpartum tubal ligation requires more bupivacaine for spinal anesthesia than does
cesarean section. Anesth Analg. 1986;65:897–900.
35. Philip J, Sharma SK, Gottumukkala VN, et al. Transient neurologic symptoms after spinal anesthesia
with lidocaine in obstetric patients. Anesth Analg. 2001;92:405–409.
36. Schneider MC, Birnbach DJ. Lidocaine neurotoxicity in the obstetric patient: is the water safe? Anesth
Analg. 2001;92:287–290.
37. Kao YJ, Turner DR. Prolongation of succinylcholine block by metoclopramide. Anesthesiology.
1989;70:905–908.
38. Woodworth GE, Sears DH, Grove TM, et al. The effect of cimetidine and ranitidine on the duration of
action of succinylcholine. Anesth Analg. 1989;68:295–297.
39. Gin T, Chan MT, Chan KL, et al. Prolonged neuromuscular block after rocuronium in postpartum
patients. Anesth Analg. 2002;94:686–689.
40. Zhou HH, Norman P, DeLima LG, et al. The minimum alveolar concentration of isoflurane in patients
undergoing bilateral tubal ligation in the postpartum period. Anesthesiology. 1995;82:1364–1368.
41. Habib AS, Muir HA, White WD, et al. Intrathecal morphine for analgesia after postpartum bilateral
tubal ligation. Anesth Analg. 2005;100:239–243.
42. Marcus RJ, Wong CA, Lehor A, et al. Postoperative epidural morphine for postpartum tubal ligation
analgesia. Anesth Analg. 2005;101:876–881.
43. Harrison MS, DiNapoli MN, Westhoff CL. Reducing postoperative pain after tubal ligation with rings
or clips: a systematic review and meta-analysis. Obstet Gynecol. 2014;124:68–75.
44. Rorarius M, Suominen P, Baer G, et al. Peripherally administered sufentanil inhibits pain perception
after postpartum tubal ligation. Pain. 1999;79:83–88.
Disease States
 Hypertensive Disorders of Pregnancy
Yelena Spitzer and Yaakov Beilin

I. Differential diagnosis and definitions
A. Gestational hypertension
B. Chronic hypertension
C. Preeclampsia
D. Chronic hypertension with superimposed preeclampsia
II. Epidemiology
A. Incidence
B. Maternal mortality
C. Neonatal mortality
III. Risk factors
A. Positive predictors
B. Protective factors
IV. Etiology
A. Decreased placental perfusion
B. Outcome of placental ischemia
C. Inflammatory mediators
D. Oxidative stress
E. Vasoactive substances
F. Antioxidants
G. Lifestyle modifications
H. Genetic influences
I. Prostaglandin imbalance
 V. Pathophysiology
A. Central nervous system
B. Cardiovascular system
C. Respiratory system
D. Coagulation system
E. Genitourinary/renal system
F. Hepatobiliary system
G. Fetus and placenta
VI. Obstetric management
A. Prediction and prevention of preeclampsia
B. Timing and route of delivery
C. Seizure prophylaxis
D. Blood pressure control
VII. Anesthetic considerations
A. Assessment of volume status
B. Controlling blood pressure
C. Coagulation
VIII. Mode of delivery and anesthetic technique
A. Vaginal delivery
B. Cesarean delivery
IX. Postpartum care
A. Analgesia
B. Seizure prophylaxis
C. Blood pressure control
D. Fluid balance
E. Long-term sequelae

KEYPOINTS
1. Hypertensive disorders of pregnancy complicate 6% to 8% of all
 pregnancies in the United States and result in a significant risk of
maternal and fetal morbidity and mortality.
2. In 2013, the Task Force on Hypertension in Pregnancy changed the
definition of preeclampsia. Given the dynamic nature of the disease,
preeclampsia is no longer classified as mild or severe but rather as
preeclampsia and preeclampsia with severe features.
3. Preeclampsia with severe features is a major contributor to neonatal
morbidity and mortality, due to impaired uteroplacental perfusion,
placental abruption, and iatrogenic prematurity due to delivery remote
from term.
4. Delivery of the fetus is the only definitive cure and the timing of the
delivery must take into account both maternal and fetal conditions.
5. Neuraxial anesthesia is the preferred mode of analgesia for labor and
anesthesia for cesarean delivery, and the choice is based on an assessment
of the intravascular volume, blood pressure, and coagulation status.

HYPERTENSIVE DISORDERS OF PREGNANCY complicate 6% to 8% of all

pregnancies in the United States and result in a significant risk of maternal and
fetal morbidity and mortality.1–3 The obstetric anesthesiologist is a vital part of
the labor and delivery team and must have a thorough working knowledge of
these disorders. The anesthesiologist should understand the changes in maternal
physiology and how they interact with the pathophysiology of the various
hypertensive disorders of pregnancy. Thorough knowledge of the changes will
allow the anesthesiologist to administer safe and effective analgesia and
anesthesia to the mother, with minimal effect on the fetus. The etiology,
treatment, and management of the hypertensive disorders of pregnancy are
discussed here.
I. Differential diagnosis and definitions
Previous nomenclatures of the hypertensive disorders of pregnancy
have focused on each disorder specifically. In 2000, the National High
Blood Pressure Education Program standardized these terms as they
relate to pregnancy.2 In 2013, the Task Force on Hypertension in
Pregnancy modified some of the components of the classification but
maintained the four categories.3
A. Gestational hypertension. Gestational hypertension, previously
known as transient hypertension
1. Blood pressure (BP) >140/90 mm Hg diagnosed for the first
time after the 20th week of pregnancy.
2. Proteinuria and other manifestations of preeclampsia are
absent with this entity.
3. Gestational hypertension usually resolves by 12 weeks’
postpartum.
4. Gestational hypertension may progress to preeclampsia,
eclampsia, or the hemolysis, elevated liver enzymes, low
platelets (HELLP) syndrome.
5. Gestational hypertension may be a predictor of future chronic
hypertension. It is an important marker regarding follow-up
and preventive medicine decisions.
B. Chronic hypertension. Chronic hypertension is defined as a BP
>140/90 mm Hg diagnosed before the 20th week of gestation
and/or persisting beyond 12 weeks postpartum.
1. Most parturients with chronic hypertension have a known
history of essential hypertension. Diagnosing chronic
hypertension may be difficult if the patient presents late in
pregnancy for prenatal care.
2. Other end-organ damage may be manifest in the patient with
chronic hypertension. Left ventricular hypertrophy, retinal
changes, and renal disease are potential future comorbidities
in this patient population.3 The pregnant patient with chronic
hypertension may take medications for BP control that have
an adverse effect on the fetus. For example, angiotensin-
converting enzyme inhibitors, although not teratogenic in the
first trimester, can lead to fetal renal failure, oligohydramnios,
and pulmonary hypoplasia when administered later in
pregnancy.
C. Preeclampsia. Preeclampsia is rarely diagnosed before the 20th
week of gestation except in the setting of gestational trophoblastic
neoplasia. Women with early onset of preeclampsia (prior to 34
weeks) often have more progressive disease and worse outcome
as compared to those with late onset preeclampsia. Previously, a
diagnostic triad of proteinuria, hypertension, and edema was
necessary to make the diagnosis. Edema was eliminated as a
criterion for preeclampsia in 2000 due to its unreliability as a
prognostic indicator and the pervasiveness among pregnant
women.2 Edema, however, is important to the obstetric
anesthesiologist because it may portend airway compromise
during general anesthesia. Given the dynamic nature of
preeclampsia, the Task Force on Hypertension in Pregnancy
changed the definition of the disease and no longer classified
preeclampsia as mild or severe, but rather as preeclampsia and
preeclampsia with severe features.3
1. Diagnostic criteria for preeclampsia (see Table 22.1) include a
BP ≥140/90 mm Hg on two occasions at least 4 hours apart;
proteinuria ≥300 mg in a 24-hour urine collection; urine
protein/creatinine ratio ≥0.3, or a urine dipstick reading of 1+.
Dipstick tests for diagnosis are discouraged unless other
approaches are unavailable. Recent studies have indicated
little relationship between quantity of urinary protein and
pregnancy outcome in pregnancy. Therefore, massive
proteinuria ≥5 g in a 24-hour urine collection has been
eliminated from the consideration of severe preeclampsia.
2. Severe features of preeclampsia include BP ≥160/100 mm Hg
on two occasions at least 4 hours apart; thrombocytopenia
(platelet count <100,000 per μL); impaired liver function;
severe persistent right upper quadrant or epigastric pain;
progressive renal insufficiency (serum creatinine >1.1 mg per
dL or a doubling of serum creatinine in the absence of other
renal disease); pulmonary edema; new onset cerebral or visual
disturbances. Another change is the removal of intrauterine
growth restriction as a feature of severe preeclampsia because
it is a very common finding.
3. HELLP syndrome is often considered a subtype of severe
preeclampsia, although it may be a related but unique
condition. Alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) may be significantly elevated in this
disorder. The platelet count is generally <100,000 per mm3.
BP may be normal (15% of cases) in the HELLP syndrome,
which will occasionally delay the diagnosis. Management and
treatment are the same as for preeclampsia with severe
features.
4. Eclampsia is the onset of seizure activity not attributable to
another cause in a pregnant woman. Any seizure in a pregnant
patient with hypertension after the 20th week of gestation
 should be assumed to be eclampsia until proved otherwise.
Seizures may occur as late as 2 weeks’ postpartum.4
Headaches and visual disturbances are common prodromal
symptoms before the onset of seizures.
D. Chronic hypertension with superimposed preeclampsia. This
is the manifestation of preeclampsia in patients with chronic
hypertension regardless of the cause.
1. Patients with chronic hypertension are at increased risk for the
development of preeclampsia. It is vital that the pregnant
patient with chronic hypertension seek early prenatal care,
and even preconception counselling, when possible. Early
assessment of renal function is key to diagnosis and
monitoring of patients with superimposed preeclampsia.
2. Comorbidities that may exist with hypertension include
connective tissue disorders, such as systemic lupus
erythematosus and scleroderma, and severe renal disease,
such as acute or chronic glomerulonephritis.
3. Preexisting renal disease in the setting of chronic
hypertension may make the diagnosis of superimposed
preeclampsia difficult, if not impossible. Following trends in
proteinuria of a 24-hour timed specimen may be the only
means to make this diagnosis.

CLINICAL PEARL The differential diagnosis of hypertension

during pregnancy includes gestational hypertension, chronic
hypertension, preeclampsia, and chronic hypertension with
superimposed preeclampsia.

II. Epidemiology
Preeclampsia and gestational hypertension are primarily disorders of
older nulliparous women. Because assisted reproductive technology
allows the older patient to achieve a successful pregnancy who may
also have other comorbidities such as hypertension and diabetes, the
 incidence of these disorders will continue to rise.
A. Incidence. Preeclampsia affects 6% to 8% of all pregnancies, of
which 25% have preeclampsia with severe features.5
1. HELLP syndrome occurs in 10% of women with
preeclampsia with severe features.
2. The rate of preeclampsia in the United States is on the rise.
For preeclampsia overall, the rate has increased from 3.4% in
1980 to 3.8% in 2010. The increase in preeclampsia with
severe features accounts for the overall increase. In 1980,
severe preeclampsia accounted for 0.3% of the cases
compared to 1.4% in 2010.5
B. Maternal mortality. Preeclampsia and its sequelae, one of the
three leading causes of maternal mortality, account for more than
25% of all cases of maternal mortality in the United States. Most
of the deaths related to preeclampsia are due to pulmonary
complications (e.g., pulmonary edema) and intracranial
hemorrhage.
C. Neonatal mortality. Preeclampsia with severe features is a major
contributor to neonatal morbidity and mortality, due to impaired
uteroplacental perfusion, placental abruption, and iatrogenic
prematurity due to onset of preeclampsia remote from term.
III. Risk factors (see Table 22.2)

A. Positive predictors. There are multiple risk factors for the

 development of preeclampsia. Preeclampsia frequently occurs
during the first pregnancy and in those with a family history of
preeclampsia. Advanced maternal age (older than 35 years) is
now also recognized as an independent risk factor. Young age and
low socioeconomic status may not play as great a role as
previously thought.6
B. Protective factors. Cigarette smoking has been reported to be a
protective factor against the development of preeclampsia,
perhaps due to reduced secretion of soluble fms-like tyrosine
kinase-1 (sFlt-1), a major mediator of preeclampsia.7
IV. Etiology
The true etiology of preeclampsia remains unknown. However,
vascular endothelial injury is a consistent finding and leads to the
clinical manifestations of preeclampsia.
A. Decreased placental perfusion. Owing to trophoblastic invasion,
uterine spiral arteries vasodilate in a normal pregnancy to accept
the increases in blood flow during late pregnancy. In
preeclampsia, these changes do not occur. This abnormal
angiogenesis results in superficial placentation that later in
pregnancy causes release of soluble fms-like tyrosine kinase-1
(sFlt-1) and soluble endoglin (sEng), both placentally derived
antiangiogenic factors. Increased levels of sFlt-1 and sEng reduce
the placental release of vascular endothelial growth factor
(VEGF) and placental growth factor (PlGF) both required for
normal angiogenesis. Without VEGF and PlGF, placental
ischemia and endothelial dysfunction occur and leads to the signs
and symptoms of preeclampsia.8
B. Outcome of placental ischemia. Placental ischemia triggers the
maternal systemic endothelial alterations that result in proteinuria,
hypertension, and occasionally liver dysfunction.
C. Inflammatory mediators. Inflammatory mediators such as
prostaglandins, interleukins, and endothelins, all of which have
vasoactive properties, may trigger endothelial cell activation and
dysfunction. An abnormal response to nitric oxide has been
 proposed as a factor in the development of preeclampsia.
D. Oxidative stress. Oxidative stress that results in membrane
damage and lipid peroxidation due to free radical formation has
been described as a potential mediator of endothelial cell
dysfunction and activation in preeclampsia.
E. Vasoactive substances. Abnormal responses to vasoactive
substances such as norepinephrine and angiotensin II may also
play a role in the pathogenesis of preeclampsia. For example, a
normotensive pregnant patient is usually refractory to the effects
of an infusion of norepinephrine or angiotensin II. However, the
preeclamptic patient with preeclampsia lacks this refractoriness.9
F. Antioxidants. Dietary deficiencies of antioxidants such as β-
carotene and vitamin E have been reported in preeclampsia. There
was initial enthusiasm for dietary supplementation of these
antioxidants for prevention of preeclampsia. However, large
randomized, placebo-controlled trials conducted during
pregnancy found that supplementation with vitamins C and E did
not reduce the risk of preeclampsia or improve maternal or fetal
outcome.
G. Lifestyle modifications. Obesity due to dietary excess is still one
of the most important risk factors in the development of
preeclampsia. Protein and calorie restriction for obese pregnant
women does not reduce the risk of preeclampsia or gestational
hypertension and may increase the risk of intrauterine growth
restriction and should be avoided.3 Exercise for prevention of
preeclampsia has been investigated. Moderate exercise has been
hypothesized to stimulate placental angiogenesis and improve
maternal endothelial dysfunction. Small clinical trials have been
unable to make any conclusions about the efficacy of moderate
exercise in improving endothelial dysfunction. Large randomized
trials are necessary.3
H. Genetic influences. Genetic influences have been reported in
preeclampsia. Polymorphisms in the genes controlling the
expression of inflammatory mediators such as interleukins have
 been described.10
I. Prostaglandin imbalance. A consistent finding in preeclampsia
is a predominance of thromboxane, relative to prostacyclin,
perhaps related to the endothelial injury.
1. Thromboxane is associated with vasoconstriction, platelet
aggregation, decreased uterine blood flow, and increased
uterine activity. Prostacyclin is associated with the opposite
effects.
2. Aspirin, which inhibits the production of thromboxane, has
been proposed as a means of preventing the development or
decreasing the severity of preeclampsia. Although the routine
use of this agent in all pregnant women does not appear to be
indicated, there is a possibility that aspirin (81 mg daily) may
be useful in women at high risk of developing early onset
severe disease.11,12
V. Pathophysiology. The pathophysiology of preeclampsia can involve
every maternal organ system, as well as the fetus (see Table 22.3).
A. Central nervous system
In normal patients, cerebral perfusion is autoregulated within a
mean arterial pressure of 50 to 160 mm Hg. One study has
described abnormal autoregulation of cerebral blood flow in
patients with preeclampsia.13 Clinical manifestations include
hyperreflexia, headaches, visual changes including cortical
 blindness, and seizures. Headache is a marker for end-organ
involvement and is a criterion for the diagnosis of preeclampsia
with severe features. Severe retro-orbital headache is considered a
premonitory symptom for eclampsia.13
1. A hyperdynamic and hyperperfused state has been described
in the cerebral circulation of patients with preeclampsia,
similar to patients with hypertensive encephalopathy. This is
particularly true in patients with headaches as a manifestation
of their preeclampsia. These findings have been documented
by magnetic resonance imaging (MRI) studies.14
2. Generalized cerebral edema, which frequently presents in
imaging studies of the brain, is a poor prognostic sign and
may precede herniation of the brainstem through the foramen
magnum.
3. Postmortem brain findings in patients with preeclampsia
include edema, hyperemia, thrombosis, and bleeding ranging
from petechiae to large cerebral hemorrhages. Intracranial
hemorrhage, particularly subarachnoid hemorrhage, is a
common cause of maternal mortality.
4. Electroencephalogram (EEG) findings are usually nonspecific
in patients with preeclampsia.
5. Imaging studies of the brain may demonstrate areas of
infarction that will often resolve spontaneously on serial
examination but may persist in some women even after
delivery.
B. Cardiovascular system
Preeclampsia is a dynamic disease process with hemodynamic
changes characterized by increased vascular tone and increased
sensitivity to vasoconstrictors occurring during the course of the
disease and its treatment. Many of these changes are associated
with endothelial cell dysfunction as described previously.
1. Studies reporting the use of invasive hemodynamic
monitoring have had conflicting results, in large part because
of the range of responses and the difficulty of interpreting
 data from patients who were treated with vasodilators or
anticonvulsants.15
2. Preload is generally decreased due to a relative depletion of
intravascular volume (third spacing effects). Preload may be
augmented with intravenous (IV) administration of crystalloid
or colloid solutions.
3. A hyperdynamic response to volume expansion may occur in
the patient with preeclampsia.16 This is probably related to the
increased release of atrial natriuretic peptide (ANP) compared
to normal controls.17 Cardiac output may rise to three to four
times that of baseline when blood volume is expanded.
4. Afterload is almost universally increased two- to threefold
above baseline values. The increase in afterload is primarily
responsible for the increase in BP seen in preeclampsia. With
increases in afterload, the left ventricle may fail.
5. Volume contraction increases the sensitivity of the patient
with preeclampsia to blood loss. Hemoconcentration leads to
an elevated hematocrit.
C. Respiratory system
1. Increased airway edema as a result of third spacing can lead
to difficult tracheal intubation. This also predisposes the
patient with preeclampsia to mucosal injury and profuse
hemorrhage during airway instrumentation.
2. Pulmonary edema (affects 3% of all preeclamptic women)
may occur on a noncardiogenic basis due to endothelial
capillary leakage.
D. Coagulation system
1. Platelets are affected by preeclampsia. The abnormality can
be both quantitative and qualitative. Thrombocytopenia is the
most common hematologic disorder in women with
preeclampsia. A decrease in the platelet count is generally the
first index of coagulation to become abnormal but it is below
100,000 in fewer than 10% of patients with severe features.
Because platelets adhere to the damaged arterial walls,
 platelets release thromboxane and other factors resulting in
platelet activation.18
2. Signs and symptoms of disseminated intravascular
coagulation (DIC), such as a low fibrinogen and prolonged
prothrombin time (PT) and partial thromboplastin time (PTT),
rarely occur until the platelet count falls below 100,000 per
mm3.19 Unless the platelet count is <100,000, or there is a
precipitous decrease in platelet count within a short time
period (i.e., 1 to 2 hours) and/or there are signs of clinical
bleeding (e.g., ecchymosis at BP sites), a full coagulation
profile is unnecessary before neuraxial anesthesia placement.
3. In HELLP syndrome, prolonged PT/PTT should be
anticipated and a full coagulation profile obtained for all
patients.
E. Genitourinary/renal system
1. Proteinuria is a hallmark of preeclampsia and is an indicator
of renal dysfunction. It is a product of endothelial cell damage
and a “leaky” capillary state.
2. Normally, glomerular filtration rate (GFR) dramatically
increases during pregnancy. Women with preeclampsia have
diminished GFR, and renal function will worsen as the
process becomes severe. This can lead to renal insufficiency
and oliguria.
3. Elevated blood uric acid levels were once considered a
predictor of decreased renal function; however, the uric acid
level is not a good monitor of onset or offset of preeclampsia.
Elevated uric acid levels correspond to decreased GFR or may
indicate increased tubular reabsorption.20 The blood urea
nitrogen (BUN) level also rises in patients with preeclampsia.
4. Acute tubular necrosis is rare, but may occur in the severely
volume constricted patient and in the face of severe blood loss
and inadequate volume replacement.
F. Hepatobiliary system
1. Hepatic changes associated with preeclampsia may range
 from a mild elevation in liver function tests to a syndrome
similar to acute fatty liver of pregnancy. Hepatic rupture has
been reported but is fortunately rare.
2. Large subcapsular hematomas have been reported in patients
with severe preeclampsia and are often manifested by right
upper quadrant pain. These can usually be managed without
surgical intervention, but severe subcapsular
hemorrhage/hematoma can cause intraperitoneal hemorrhage.
This requires emergency laparotomy and if unrecognized can
result in maternal death. Early treatment by interventional
radiologists using stents is very successful in limiting the
morbidity associated with subcapsular hematomas and,
indeed, may be lifesaving.
G. Fetus and placenta
1. Preeclamptic women have decreased uteroplacental perfusion,
leading to fetal growth restriction and oligohydramnios.
Because uteroplacental blood flow is proportionate to BP,
hypotension during neuraxial analgesia/anesthesia must be
avoided.

CLINICAL PEARL Every organ system is affected by

preeclampsia and the anesthesiologist must pay particular attention
to the cardiac, respiratory, and coagulation systems. Additionally,
airway edema can make tracheal intubation difficult.

VI. Obstetric management

A. Prediction and prevention of preeclampsia. Currently, there is
no single test that predicts the development of preeclampsia in the
pregnant patient. The use of uterine artery Doppler for prediction
of preeclampsia has been investigated with no effect on maternal
or fetal outcome.21 Similarly, the predictive potential of several
angiogenesis related biomarkers, including sFlt-1, PlGF, and sEng
have been investigated but have not proven to be reliably
 predictive of preeclampsia for clinical use.3 Efforts at prevention,
such as dietary supplementation of calcium,22 low-dose aspirin
therapy,10 and antioxidant23 therapy have all been tried in an
effort to forestall the onset of preeclampsia but without consistent
success. Delivery is the definitive treatment of preeclampsia.
Until delivery, the major goals of therapy are BP control and
prevention of seizures.
B. Timing and route of delivery. The timing of the delivery
depends on the gestational age of the fetus and the severity of the
preeclampsia. In mild preeclampsia, delivery should occur at 37
weeks. In severe preeclampsia, delivery management with
administration of steroids to mature the fetal lungs should
commence with planned delivery at 34 weeks. However, with
worsening symptoms, for example, thrombocytopenia or elevated
liver function tests, delivery should occur prior to 34 weeks.
1. If the fetus is preterm and the mother’s condition is stable,
corticosteroids should be given over 24 to 48 hours to
enhance fetal lung maturity. Until delivery, close monitoring
of BP, renal and hepatic function, and platelet count are
mandatory. Also, serial assessment of fetal well-being is
important. Useful tools of fetal assessment may include
Doppler velocimetry of umbilical arterial blood flow,
nonstress test, and biophysical profile. Monitoring can occur
as an inpatient or outpatient in women with mild
preeclampsia.
2. Indications for immediate delivery include term gestation,
nonreassuring fetal status, previable or nonviable fetus or any
signs of preeclampsia progression, including severe refractory
hypertension, progressive thrombocytopenia, liver
dysfunction, severe renal dysfunction, pulmonary edema, or
seizures.24
3. The route of delivery depends on the condition of the cervix,
fetal presentation, and maternal and fetal status. Cesarean
delivery (CD) may be necessary to expedite delivery in
 worsening preeclampsia with an unfavorable cervix.
Nonreassuring fetal status is a frequent indication for CD.
C. Seizure prophylaxis
1. Eclampsia is heralded by the onset of generalized tonic-clonic
seizures. Seizure prevention is paramount in the treatment of
preeclampsia.
2. Magnesium sulfate (MgSO4) is the anticonvulsant of choice
in the United States for the prevention of seizures in women
with preeclampsia. Diazepam and phenytoin have been used
in Europe. In the United Kingdom, MgSO4 has largely
replaced diazepam as the anticonvulsant of choice, and
several randomized controlled studies support its use over
other anticonvulsants.25 Magnesium may improve neonatal
neurologic outcome when administered prior to delivery in
preterm (<32 weeks) babies.
a. MgSO4 acts to prevent seizures by stabilizing neurons in
the cerebral cortex. It also inhibits the release of
acetylcholine and decreases excitability of muscle
membranes. Because of its effect on acetylcholine,
MgSO4 may prolong the effect of both depolarizing and
nondepolarizing muscle relaxants.
b. MgSO4 is a mild vasodilator with effects in multiple
vascular beds, including the cerebral circulation, where it
may reduce ischemia. It improves hepatic and renal blood
flow. However, MgSO4 may blunt the compensatory
hemodynamic response to hemorrhage.
c. MgSO4 is excreted by the kidneys and must be used with
caution in patients with known or suspected renal failure.
Should renal function deteriorate, the infusion rate of
MgSO4 will need to be adjusted in order to prevent
toxicity.
d. MgSO4 is administered as a 4 to 6 g intravenous loading
dose over 15 to 20 minutes. A continuous intravenous
 infusion is initiated at 2 g per hour. Serial magnesium
levels are monitored, with the goal of maintaining levels
within the therapeutic range of 4 to 8 mEq per L. Toxic
levels of MgSO4 can lead to respiratory and, possibly,
cardiac arrest (see Table 22.4). Toxicity should be treated
with IV administration of calcium chloride 300 mg or
calcium gluconate 1 g.

e. Because magnesium crosses the placenta, the neonate can

also exhibit signs of magnesium toxicity. Signs of
magnesium toxicity in the newborn include respiratory
depression, apnea, and decreased muscle tone.
Magnesium toxicity in the newborn and the mother can be
reversed with calcium administration.
f. Seizures that are not controlled with MgSO4 may require
other anticonvulsants. Midazolam, lorazepam, phenytoin,
and phenobarbital have all been used for seizure control
in patients unresponsive to MgSO4. Persistent seizures
unresponsive to treatment should initiate a search for
other causes (e.g., intracranial neoplasm).
CLINICAL PEARL MgSO4 is the preferred drug for seizure
prophylaxis in preeclampsia.

D. Blood pressure control (see Table 22.5)

Acute onset systolic and/or diastolic hypertension can occur

during pregnancy and postpartum. The degree of systolic
hypertension may be the most important predictor of cerebral
injury and infarction. Antihypertensive therapy should be
administered within 15 minutes when a systolic BP of ≥160 mm
Hg or a diastolic BP of ≥110 mm Hg persists.26 Labetalol,
hydralizine, or nifedipine can be used for the initial treatment of
hypertension. The BP should not be reduced to “normal” but
rather to a diastolic BP of ≤100 mm Hg and systolic pressure of
≤160 mm Hg to reduce the risk of cerebral hemorrhage,
myocardial ischemia, and placental abruption. Reducing BP to the
normal range can lead to reduced uteroplacental perfusion
because placental and uterine blood flow are not autoregulated.
1. Hydralazine is a direct-acting arteriolar vasodilator that
reduces afterload. It is available in oral and parenteral forms.
Hydralazine is administered in 2.5 to 10 mg boluses IV, with a
maximum dose of 20 mg, and has a peak onset of
approximately 10 to 15 minutes. It should not be used in
patients with known or suspected coronary artery disease
because hydralazine can decrease coronary artery perfusion
 by causing reflex tachycardia. Hydralazine also selectively
vasodilates the uterine and renal vasculature, making it
particularly useful in preeclampsia.
2. Labetalol is a selective α1 and nonselective β-antagonist. This
agent, like hydralazine, is available in both oral and IV forms.
Labetalol has a rapid onset of action of approximately 3 to 5
minutes and, unlike hydralazine, does not cause reflex
tachycardia. The dosage is 5 to 10 mg IV to a maximum of
220 mg.
a. There is intense interest in labetalol as an alternative to
MgSO4 in the prevention of eclampsia. Labetalol
decreases cerebral vasospasm and corrects those
intracranial hemodynamic disturbances that are associated
with eclampsia.27,28
3. Nifedipine is the most common calcium channel blocker used
for treating hypertension in pregnancy. It inhibits the influx of
extracellular calcium into smooth muscle through slow
channels with effects in arteriolar and arterial smooth muscle
beds. The magnitude of BP reduction is related to the
pretreatment pressures; the higher the mean arterial pressure,
the greater the effect. An exaggerated hypotensive response
can occur, especially when the sublingual route is utilized,
which may lead to nonreassuring fetal status.29 The
hypotensive response may also be exaggerated with the
concomitant administration of MgSO4.30 Dosage is 10 mg
every 20 minutes up to a maximum dose of 50 mg.
4. Potent antihypertensive agents, such as sodium nitroprusside
and nitroglycerin, are used for acute hypertensive crisis,
intractable hypertension unresponsive to other agents, and to
prevent the hypertensive response to laryngoscopy. Use of
these agents requires continuous intra-arterial pressure
monitoring.
a. Sodium nitroprusside is a potent arteriolar dilator with a
rapid onset and short duration. Therapy is initiated at a
 dose of 0.25 μg/kg/minute, to a maximum dose of 5
μg/kg/minute. Side effects include tachyphylaxis with
prolonged use and metabolic acidosis. Cyanide toxicity
(maternal and fetal) has also been reported and most often
related to high-dose (≥4 μg/kg/minute) and/or prolonged
infusions. The fetus is at particular risk, due to the limited
ability of the fetal liver to metabolize cyanide. However,
low doses (≤2 μg/kg/minute) for short periods are unlikely
to lead to cyanide toxicity. Should prolonged
administration be required, some measure of fetal well-
being should be utilized (e.g., fetal heart rate monitoring
or, when possible, fetal scalp pH).
b. Nitroglycerin is a venodilator that reduces cardiac filling
pressure by acting on capacitance vessels. It is less potent
than nitroprusside but does not carry the risk of cyanide
toxicity. Infusion should begin at 0.5 to 1 μg/kg/minute,
increasing by increments of 0.5 μg/kg/minute until a
satisfactory response is obtained. Like sodium
nitroprusside, there is a risk of abrupt hypotension.
Nitroglycerin is typically used for short-term BP control
(i.e., at the time of tracheal intubation).

CLINICAL PEARL BP should be treated when the systolic is

>160 mm Hg or the diastolic is ≥110. BP should not be reduced to
normal but only to approximately 140/90 to prevent intracerebral
hemorrhage.

VII. Anesthetic considerations

Before initiation of neuraxial anesthesia for labor and delivery, the
anesthesiologist should assess intravascular volume status, ensure
adequate BP control, and confirm normal coagulation status.
A. Assessment of volume status. This is critical because volume
depletion occurs often in women with preeclampsia.
 1. Volume assessment should start with an evaluation of urine
output. If urine output has been adequate over several hours,
then it is probably safe to proceed with a neuraxial anesthetic.
2. If the patient with preeclampsia is oliguric or anuric, a fluid
bolus of 500 to 1,000 mL should be administered. Invasive
monitoring should be considered if repeat fluid boluses do not
result in adequate urine output of 0.5 to 1 mL/kg/hour.
3. The lack of correlation between right- and left-sided cardiac
filling pressures has led some to suggest that when invasive
monitoring is deemed necessary, a pulmonary artery catheter
should be placed in preference to a central venous catheter
(CVC).31 However, because low central venous pressures are
seldom associated with high pulmonary capillary wedge
pressures, the use of a CVC to guide fluid replacement is
unlikely to lead to fluid overload and is an acceptable
alternative. In any event, the use of invasive monitoring in
severe preeclampsia has become less common among
practicing anesthesiologists, but may be of value in a
individual patient after a risk/benefit analysis. The use of
transthoracic echocardiography, which is noninvasive, can
also be considered.
B. Controlling blood pressure
1. Ideally, neuraxial anesthesia should not be initiated until BP
is adequately controlled. Generally, noninvasive BP
monitoring is adequate, but in severe cases, intra-arterial
monitoring should be considered.
2. Neuraxial analgesia should not be utilized as an
antihypertensive therapy. Severely elevated BP generally
indicates the patient is dehydrated, and placing a neuraxial
anesthetic can lead to profound hypotension.
C. Coagulation
1. Coagulation function plays a major role in anesthetic
management of women with preeclampsia. The
anesthesiologist must understand the implications and the
 limitations of coagulation studies in this decision-making
process.
2. Preeclampsia is primarily a disease of platelet aggregation, so
a platelet count must be checked before neuraxial anesthesia
is administered. In addition to affecting platelet count,
preeclampsia may also alter platelet function; the clinical
implications of this dysfunction are unclear, and tests of
platelet function are not recommended.
3. Evaluation of other tests of coagulation such as PT, PTT,
fibrinogen, and D-dimers should be reserved for those cases
complicated by a platelet count ≤100,000 per mm3 or those
with the HELLP syndrome.
4. Ancillary tests to assess platelet function such as bleeding
time, thromboelastography, or the platelet function analyzer
have not been found to be useful in assessing the risk of
epidural hematoma and are not used by the authors.32,33
5. There is no absolute platelet count below which a neuraxial
anesthetic is contraindicated. Many anesthesiologists will not
place an epidural anesthetic when the platelet count is 80,000
per mm3 or less (e.g., 60,000 per mm3)34 but many others
will, and the decision to do so must be individualized to each
patient. A thorough bleeding history should be taken, and both
the absolute platelet count as well as the trend in platelet
count should be considered.
6. Preeclampsia is a dynamic disease and the platelet count can
fall rapidly. Repeat values are recommended.
7. If the decision is made to place an epidural catheter, the
catheter should not be removed until a platelet count is
rechecked to ensure it has not decreased since epidural
placement. In a large review of the incidence of epidural
hematomas, the complication was found to occur either
during catheter placement or removal.35

CLINICAL PEARL Thrombocytopenia is the primary

 coagulation defect in preeclampsia and a platelet count must be
checked close to epidural placement because the platelet count can
drop rapidly.

VIII. Mode of delivery and anesthetic technique

A. Vaginal delivery
1. Epidural analgesia is the preferred mode of analgesia for
vaginal delivery. Systemic opioids are best avoided due to
their limited analgesic efficacy as well as the risk of
producing both maternal and neonatal respiratory depression.
a. Epidural neuraxial block provides excellent labor
analgesia.
b. Epidural anesthesia also may facilitate BP control by
eliminating labor pain, although it should not be used as
the sole means of BP control.
c. Epidural analgesia decreases circulating maternal stress-
induced catecholamines36 and improves intervillous blood
flow.37
d. Low-dose concentrations of local anesthetics should be
used. An initial epidural bolus of 0.0625% bupivacaine
with 2 μg per mL fentanyl, 15 mL in divided doses, can be
used to provide initial pain relief. This dosage, in the
author’s experience, has been found to have minimal
impact on maternal hemodynamics when given slowly in
divided aliquots of 5 mL. An epidural infusion of 10 mL
per hour of the same solution is then initiated, or patient-
controlled epidural analgesia (PCEA) is started at rates
used commonly in the institution.
e. Combined spinal-epidural analgesia has been used with
good success and minimal morbidity in patients with
preeclampsia.38
B. Cesarean delivery
1. CD can be accomplished with spinal, epidural, or general
 anesthesia. Neuraxial anesthesia is preferred.
a. The airway in the preeclamptic woman can be edematous,
leading to difficult tracheal intubation.
b. Hemodynamic and neuroendocrine responses are
abolished with epidural and spinal anesthesia as compared
with general anesthesia, especially during tracheal
intubation and extubation.
c. Despite the potential for hypotension, maternal and
neonatal outcome is similar when neuraxial anesthesia is
used as compared to general anesthesia.39
2. Either spinal or epidural anesthesia can be used safely.
a. The incidence of hypotension is similar in patients with
severe preeclampsia who receive either epidural or spinal
anesthesia, and the incidence of hypotension does not
appear to be increased, and may be lower, in preeclamptic
women with severe features compared to normal
controls.40,41
b. Spinal anesthesia has a more rapid onset and provides
superior anesthesia compared to epidural anesthesia,
making it a useful technique, especially in the urgent or
emergent situation. The authors utilize spinal anesthesia
almost exclusively for CD in preeclampsia.
3. General anesthesia should be reserved for emergent delivery,
the patient with a coagulopathy or other contraindication to
neuraxial anesthesia, or patients refusing neuraxial
techniques.
a. Tracheal intubation can be particularly difficult in the
woman with preeclampsia due to airway edema. Airway
adjuncts such as the laryngeal mask airway, GlideScope™,
and fiberoptic intubation devices should be available.
b. A plan should be available in case of difficult tracheal
intubation (see Fig. 22.1).
c. All should receive 0.3M sodium citrate with or without an
H2 blocker before general anesthesia. Metoclopramide (10
 mg IV) should be given to facilitate gastric emptying.
d. One must be ready to control the hypertensive response to
laryngoscopy which can lead to pulmonary edema,
cerebral edema, or intracranial hemorrhage—the latter
being most common cause of death in women with
preeclampsia.
(1) Labetalol or hydralazine administration should be
considered before tracheal intubation.42
(2) Nitroprusside and nitroglycerin can be used for acute
increases in maternal BP.43
(3) BP monitoring with an intra-arterial catheter should
be utilized in patients with poorly controlled
hypertension undergoing CD under general
anesthesia.
e. Induction of general anesthesia may be performed with
propofol, or etomidate. Ketamine is generally avoided
because it can precipitate hypertension. A dose of 1.5 mg
per kg of succinylcholine is administered to facilitate
tracheal intubation.
(1) The duration of action of both the depolarizing and
nondepolarizing muscle relaxants may be prolonged
in patients receiving MgSO4. Because even a small
dose of nondepolarizing muscle relaxant can lead to
significant weakness, and fasciculations are rare in
women receiving magnesium, a defasciculating dose
is not recommended. Succinylcholine can be used
safely in the usual doses because any prolongation of
effect will not be clinically important.

CLINICAL PEARL Neuraxial anesthesia is the preferred

technique for cesarean delivery and either spinal or epidural
anesthesia can be safely used. General anesthesia should be
reserved for the patient with coagulopathy or for severe
 dehydration.

IX. Postpartum care

Although delivery is the ultimate treatment, signs and symptoms of
preeclampsia do not resolve immediately and care is required into the
postpartum period.
A. Analgesia
1. Intrathecal or epidural opioids provide excellent pain relief in
patients who have received neuraxial anesthesia for CD.
2. IV patient-controlled analgesia (PCA) with morphine or
fentanyl is used in patients who received general anesthesia.
B. Seizure prophylaxis
1. Although delivery is the definitive treatment for preeclampsia,
seizure prophylaxis with MgSO4 is typically continued for 24
hours, although some authors recommend only 12 hours of
therapy.44 Premature discontinuation of magnesium in the
postpartum period has led to a longer period of administration
 may be safer. eclampsia in some patients, so (24 to 48 hours).
C. Blood pressure control
1. BP control is much the same as in the antepartum and
perioperative periods. Consideration of oral antihypertensive
therapy should be given if the BP remains elevated after
diuresis occurs.
D. Fluid balance
1. With mobilization of third space fluids, the patient is at
highest risk for pulmonary edema following delivery. Fluid
restriction should continue until a brisk diuresis occurs.
E. Long-term sequelae
1. Women with preeclampsia have an increased incidence of
hypertension and cardiovascular disease later in life.45,46
2. Also, they may have a decreased incidence of breast cancer.47

REFERENCES
1. Martin JA, Hamilton BE, Sutton PD, et al. Births: final data for 2005. Natl Vital Stat Rep. 2007;56:1–
103.
2. National High Blood Pressure Education Program. Report of the National High Blood Pressure
Education Program working group on high blood pressure in pregnancy. Am J Obstet Gynecol.
2000;183:S1–S22.
3. American College of Obstetricians and Gynecologists. Hypertension in pregnancy. Report of the
American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy.
Obstet Gynecol. 2013;122:1122–1131.
4. Matthys LA, Coppage KH, Lambers DS, et al. Delayed postpartum preeclampsia: an experience of
151 cases. Am J Obstet Gynecol. 2004;190:1464–1466.
5. Hauth JC, Ewell MG, Levine RJ, et al. Pregnancy outcomes in healthy nulliparas who developed
hypertension. Calcium for Preeclampsia Prevention Study group. Obstet Gynecol. 2000;95:24–28.
6. American College of Obstetricians and Gynecologists Committee on Obstetric Practice. ACOG
practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January
2002. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 2002;77:67–75.
7. Mehendale R, Hibbard J, Fazleabas A, et al. Placental angiogenesis markers sFlt-1 and PIGF: response
to cigarette smoke. Am J Obstet Gynecol. 2007;197:363.e1–363.e5.
8. Lyall F. Priming and remodeling of human placental bed spiral arteries during pregnancy—a review.
Placenta. 2005;26 (suppl A):S31–S36.
9. Shah DM. Preeclampsia: new insights. Curr Opin Nephrol Hypertens. 2007;16:213–220.
10. Hefler LA, Tempfer CB, Gregg AR. Polymorphisms within the interleukin-1 beta gene cluster and
preeclampsia. Obstet Gynecol. 2001;97:664–668.
11. Collaborative Low-dose Aspirin Study in Pregnancy Collaborative Group. CLASP: a randomized trial
 of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9,364 pregnant women.
Lancet. 1994;343:619–629.
12. Duley L, Henderson-Smart DJ, Meher S, et al. Antiplatelet agents for preventing preeclampsia and its
complications. Cochrane Database Syst Rev. 2007;(2):CD004659.
doi:10.1002/14651858.CD004659.pub2
13. Belfort MA, Saade GR, Grunewald C, et al. Association of cerebral perfusion with headache in
women with preeclampsia. Br J Obstet Gynaecol. 1999;106:814–821.
14. Zeeman GG, Hatab MR, Twickler DM. Increased cerebral blood flow in preeclampsia with magnetic
resonance imaging. Am J Obstet Gynecol. 2004;191:1425–1429.
15. Cotton DB, Lee W, Huhta JC, et al. Hemodynamic profile of severe pregnancy-induced hypertension.
Am J Obstet Gynecol. 1988;158:523–529.
16. Phelan JP, Yurth DA. Severe preeclampsia. I. Peripartum hemodynamic observations. Am J Obstet
Gynecol. 1982;144:17–22.
17. Pouta A, Karinen J, Vuolteenaho O, et al. Preeclampsia: the effect of intravenous fluid preload on
atrial natriuretic peptide secretion during caesarean section under spinal anaesthesia. Acta
Anaesthesiol Scand. 1996;40:1203–1209.
18. Pritchard JA, Cunningham FG, Mason RA. Coagulation changes in eclampsia: their frequency and
pathogenesis. Am J Obstet Gynecol. 1976;124:855–864.
19. Leduc L, Wheeler JM, Kirshon B, et al. Coagulation profile in severe preeclampsia. Obstet Gynecol.
1992;79:14–18.
20. Taufield PA, Ales KL, Resnick LM, et al. Hypocalciuria in preeclampsia. N Engl J Med.
1987;316:715–718.
21. Myatt L, Clifton RG, Roberts JM, et al. The utility of uterine artery Doppler velocimetry in prediction
of preeclampsia in a low-risk population. Obstet Gynecol. 2012;120:815–822.
22. Trumbo PR, Ellwood KC. Supplemental calcium and risk reduction of hypertension, pregnancy-
induced hypertension, and preeclampsia: an evidence-based review by the US Food and Drug
Administration. Nutr Rev. 2007;65:78–87.
23. Spinnato JA, Livingston JC. Prevention of preeclampsia with antioxidants: evidence from randomized
trials. Clin Obstet Gynecol. 2005;48:416–429.
24. Haddad B, Deis S, Goffinet F, et al. Maternal and perinatal outcomes during expectant management of
239 severe preeclamptic women between 24 and 33 weeks’ gestation. Am J Obstet Gynecol.
2004;190:1590–1595.
25. Lucas MJ, Leveno KJ, Cunningham FG. A comparison of magnesium sulfate with phenytoin for the
prevention of eclampsia. N Engl J Med. 1995;333:201–205.
26. American College of Obstetricians and Gynecologists. Committee Opinion No. 623: emergent therapy
for the acute-onset, severe hypertension during pregnancy and the postpartum period. Obstet Gynecol.
2015;125:521–525.
27. Belfort MA, Clark SL, Sibai B. Cerebral hemodynamics in preeclampsia: cerebral perfusion and the
rationale for an alternative to magnesium sulfate. Obstet Gynecol Surv. 2006;61:655–665.
28. Belfort MA, Tooke-Miller C, Allen JC Jr, et al. Labetalol decreases cerebral perfusion pressure
without negatively affecting cerebral blood flow in hypertensive gravidas. Hypertens Pregnancy.
2002;21:185–197.
29. Impey L. Severe hypotension and fetal distress following sublingual administration of nifedipine to a
patient with severe pregnancy induced hypertension at 33 weeks. Br J Obstet Gynaecol.
1993;100:959–961.
30. Neustein S, Dimich I, Shiang H, et al. Cardiovascular consequences of the concomitant administration
of nifedipine and magnesium sulfate in pigs. Int J Obstet Anesth. 1998;7:247–250.
31. Bolte AC, Dekker GA, van Eyck J, et al. Lack of agreement between central venous pressure and
pulmonary capillary wedge pressure in preeclampsia. Hypertens Pregnancy. 2000;19:261–271.
32. Rodgers RP, Levin J. A critical reappraisal of the bleeding time. Semin Thromb Hemost. 1990;16:1–20.
33. Beilin Y, Arnold I, Hossain S. Evaluation of the platelet function analyzer (PFA-100) vs. the
thromboelastogram (TEG) in the parturient. Int J Obstet Anesth. 2006;15:7–12.
34. Beilin Y, Zahn J, Comerford M. Safe epidural analgesia in thirty parturients with platelet counts
between 69,000 and 98,000 mm(−3). Anesth Analg. 1997;85:385–388.
35. Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesth
Analg. 1994;79:1165–1177.
36. Abboud T, Artal R, Sarkis F, et al. Sympathoadrenal activity, maternal, fetal, and neonatal responses
after epidural anesthesia in the preeclamptic patient. Am J Obstet Gynecol. 1982;144:915–918.
37. Jouppila P, Jouppila R, Hollmén A, et al. Lumbar epidural analgesia to improve intervillous blood
flow during labor in severe preeclampsia. Obstet Gynecol. 1982;59:158–161.
38. Ramanathan J, Vaddadi AK, Arheart KL. Combined spinal and epidural anesthesia with low doses of
intrathecal bupivacaine in women with severe preeclampsia: a preliminary report. Reg Anesth Pain
Med. 2001;26:46–51.
39. Wallace DH, Leveno KJ, Cunningham FG, et al. Randomized comparison of general and regional
anesthesia for cesarean delivery in pregnancies complicated by severe preeclampsia. Obstet Gynecol.
1995;86:193–199.
40. Hood DD, Curry R. Spinal versus epidural anesthesia for cesarean section in severely preeclamptic
patients: a retrospective survey. Anesthesiology. 1999;90:1276–1282.
41. Aya AG, Vialles N, Tanoubi I, et al. Spinal anesthesia-induced hypotension: a risk comparison
between patients with severe preeclampsia and healthy women undergoing preterm cesarean delivery.
Anesth Analg. 2005;101:869–875.
42. Ramanathan J, Sibai BM, Mabie WC, et al. The use of labetalol for the attenuation of the hypertensive
response to endotracheal intubation in preeclampsia. Am J Obstet Gynecol. 1988;159:650–654.
43. Cetin A, Yurtcu N, Guvenal T, et al. The effect of glyceryl trinitrate on hypertension in women with
severe preeclampsia, HELLP syndrome, and eclampsia. Hypertens Pregnancy. 2004;23:37–46.
44. Isler CM, Barrilleaux PS, Rinehart BK, et al. Postpartum seizure prophylaxis: using clinical
parameters to guide therapy. Obstet Gynecol. 2003;101:66–69.
45. Harskamp RE, Zeeman GG. Preeclampsia: at risk for remote cardiovascular disease. Am J Med Sci.
2007;334:291–295.
46. Wenger, NK. Recognizing pregnancy-associated cardiovascular risk factors. Am J Cardiol.
2014;113:406–409.
47. Innes KE, Byers TE. First pregnancy characteristics and subsequent breast cancer risk among young
women. Int J Cancer. 2004;112:306–311.
 Endocrine Disorders
Jessica Booth, Peter H. Pan, Janine Malcolm, and Erin J. Keely

I. Diabetes mellitus
A. Introduction
B. Effect of pregnancy on diabetes mellitus
C. Effect of diabetes mellitus on pregnancy
D. Management of diabetes mellitus during pregnancy
E. Management during labor and delivery
II. Thyroid disorders
A. Introduction
B. Thyroid physiology
C. Hyperthyroidism
D. Hypothyroidism
III. Pituitary disorders
A. Introduction
B. Pituitary adenomas
C. Pituitary insufficiency during pregnancy
IV. Adrenal disorders
A. Primary adrenal insufficiency
B. Cushing disease and syndrome
C. Pheochromocytoma
V. Conclusion


KEYPOINTS
1. Diabetes and thyroid disease are the most common endocrine disorders
associated with pregnancy.
2. Neonatal macrosomia and/or shoulder dystocia occur with increased
frequency in pregnancy complicated by all types of diabetes mellitus.
3. Appropriate maternal glycemic control with oral hypoglycemic agents or
insulin is necessary to reduce fetal and maternal complications when diet
modification alone is insufficient.
4. A preanesthetic evaluation of the obstetric patient with thyroid disease
should include an evaluation of current symptoms, presence of goiter,
adequacy of treatment, and cardiovascular symptoms.
5. Early diagnosis and appropriate treatment of maternal
pheochromocytoma is critical to reduce maternal and fetal mortality.

I. Diabetes mellitus
A. Introduction
The prevalence of diabetes mellitus (DM) in pregnancy is
estimated to be 6% to 7%.1 Gestational diabetes is typically
defined as glucose intolerance with onset during the second or
third trimester of pregnancy. Overt or pregestational diabetes
is diagnosed using American Diabetes Association criteria of a
screening fasting blood glucose >125 mg per dL or by
combining the results of other standard diagnostic tests
including elevated hemoglobin A1c and elevated random
blood glucose.2 Screening for gestational diabetes is typically
performed at 24 to 28 weeks’ gestation with a 1-hour diagnostic
oral glucose tolerance test. Patients with a blood glucose >135 to
140 mg per dL after the 50-g 1-hour glucose screening test will
undergo a 100-g, 3-hour diagnostic oral glucose tolerance test.
Alternatively, some national organizations recommend a one-step
2-hour 75-g test.1
A pregnancy complicated by DM requires multidisciplinary
cooperation among obstetricians, internists/endocrinologists,
anesthesia providers, nurse educators, and dietitians to facilitate a
healthy outcome for mother and child. A woman may have a
known type 1 or type 2 DM (e.g., pregestational DM) or be
identified during pregnancy with gestational diabetes mellitus
(GDM). A small percentage of women will present with new-
onset, previously unidentified type 1 or type 2 DM during
pregnancy, which may be difficult to separate from GDM until
after delivery. Although the clinical management and risks of
types 1 and 2 DM during pregnancy are similar, there are
important differences in pathogenesis and associated conditions.
1. Type 1 DM results from the destruction of insulin-secreting
cells by an immune-mediated process leading to absolute
insulin deficiency. It represents 5% to 10% of all types of
DM. Some patients will be identified as having type 1 disease
by a sudden onset of diabetic ketoacidosis (DKA). However,
others, especially those who present in adulthood, may have a
more insidious onset. These women may be misidentified as
having type 2 DM until they develop DKA under stressful
situations such as pregnancy.
2. Type 2 DM is part of the metabolic syndrome, which includes
insulin resistance, visceral adiposity, dyslipidemia,
hypertension, accelerated cardiovascular disease, and
polycystic ovary disease. The prevalence of type 2 DM in the
pregnant population is rising as the incidence of maternal
obesity and advanced maternal age increases. Individuals with
DM, identified before pregnancy, may become pregnant while
being treated with diet and exercise, oral hypoglycemic
agents, or insulin. Obesity and hypertension often
associated with DM bring additional risk to the pregnancy
that must be identified and managed. Tight glycemic
control is required for optimal management.
3. GDM is defined as any degree of glucose intolerance with
onset during pregnancy, but does not exclude the possibility
of pregestational DM. It accounts for approximately 90% of
 DM during pregnancy. The purpose of screening for GDM is
to identify pregnancies at increased risk for poor perinatal
outcomes and also to identify a cohort of women at increased
lifetime risk for type 2 DM. Although controversy continues
concerning screening and treatment strategies, most expert
groups recommend universal screening for all pregnant
women. Obesity, advanced maternal age, family history, and
glucose intolerance with prior pregnancy, are risk factors for
gestational diabetes in the United States.3 Women of color are
also at increased risk. Although most women are screened for
GDM at 24 to 28 weeks’ gestation, earlier screening may be
warranted in obese women with a body mass index (BMI)
≥30, women with a prior history of GDM, or women with a
known history of impaired glucose metabolism.1
B. Effect of pregnancy on diabetes mellitus
1. Glycemic control
Three important physiologic changes in glucose
metabolism occur during pregnancy: (a) increased risk of
fasting hypoglycemia and associated hypoglycemia
unawareness, (b) insulin resistance, and (c) accelerated
starvation resulting in increased lipolysis and ketone
production. Hypoglycemia unawareness is more prevalent
due to lack of autonomic warning from reduced
catecholamine production.4 Insulin sensitivity is decreased
by approximately 50% by the third trimester; insulin dosages
of two or three times the prepregnancy dose are often needed
during the second and third trimesters in insulin dependent
women.1 There is immediate onset of a rapid return of insulin
sensitivity postpartum, necessitating a marked reduction in
insulin dose (typically to two-thirds of the dose used
prepregnancy) immediately following delivery of the
placenta. The accelerated starvation state of pregnancy
produces lower fasting glucose levels and increased ketone
production, predisposing women to ketoacidosis. Other
 stressors such as hyperemesis and corticosteroid use to
promote fetal lung maturity also predispose to keotacidosis.
2. Complications of diabetes mellitus
a. Women with type 1 or type 2 DM may have significant
microvascular disease and rarely macrovascular
disease. Approximately 34% to 50% of women with type
1 and 3% of women with type 2 DM will have evidence
of retinopathy. The presence and degree of diabetic
retinopathy are associated with the duration of DM and
long term glycemic control. Most studies show some
worsening of retinopathy during pregnancy.5
b. Diabetic nephropathy represents a spectrum of disease
ranging from microalbuminuria (microalbumin, 30 to 300
mg per dL or a microalbumin-to-creatinine ratio .2 mg per
μmol) to overt nephropathy (.300 mg of protein per 24
hours) to end-stage renal failure. Nephropathy
complicates approximately 4% of diabetic pregnancies
and is associated with increased maternal and perinatal
morbidity rates. Pregnancy may worsen the degree of
proteinuria, causing progression of renal insufficiency
which aggravates hypertension. In most cases, renal
function will return to baseline values postpartum;
however, in women with severe nephropathy or serum
creatinine >1.4 mg per dL, there is risk of a permanent
decline in GFR.6 One retrospective study further
suggested that diabetic parturients with moderate-to-
severe renal dysfunction at pregnancy onset had increased
risk of requiring dialysis about 36 months earlier than
predicted by prepregnancy estimates based on linear
decline in GFR.7

CLINICAL PEARL The hyperglycemia associated with DM in

pregnancy is due both to inadequate insulin supply and insulin
resistance exacerbated by the physiologic changes of pregnancy.
C. Effect of diabetes mellitus on pregnancy
1. The impact that DM has on pregnancy outcomes is
dependent on the type of DM, level of glycemic control,
and associated complications. White’s8 classification
scheme was developed to emphasize the relationship of
disease duration, vascular complications, and poor fetal
outcome in women with type 1 DM. This classification
system has undergone modification and, although is used by
many clinicians caring for pregnant diabetics in the United
States, its utility has declined with shifting emphasis on
adequacy of control and identification whether diabetes
existed before pregnancy.
2. The presence of hyperglycemia in first trimester increases the
risk of first-trimester fetal loss and congenital malformations,
with congenital heart disease and musculoskeletal anomalies
being the most common. These risks are directly related to
glycemic control and preventable by obtaining near-normal
blood sugars at the time of conception. Significant
hyperglycemia during the period of organogenesis during
the first 5 to 8 weeks of gestation is contributory to the
higher rates of congenital malformations seen in patients
with DM. Perinatal mortality has been reported to be higher
with all types of DM during pregnancy, although more
recently, this has not been confirmed with GDM.9 However,
there is an approximate fourfold increase in perinatal
mortality in both type 1 and type 2 DM.10 Neonatal
macrosomia and/or shoulder dystocia occur with increased
frequency in all types of DM. Infant mortality rates increase
significantly in infants >5,000 g.11 Excess fetal growth is
partly due to fetal hyperinsulinemia in response to maternal
hyperglycemia. In all women with diabetes, maternal
prepregnancy weight and maternal weight gain during
pregnancy are most predictive of macrosomia.11
 Paradoxically, the risk for growth restriction is also increased,
especially in the setting of maternal vascular disease and
hypertension. Excessively tight glycemic control may
predispose to intrauterine growth restriction (IUGR) as well.12
Neonatal hypoglycemia (defined as plasma glucose <2
μmol per L) is the most clinically significant neonatal
morbidity. The incidence of clinically significant neonatal
hypoglycemia is related to the tightness of third-trimester
glycemic control.
3. Recent evidence has shown that treatment of GDM reduces
macrosomia and large for gestational age (LGA) births.13 In
addition, the incidence of preeclampsia and hypertensive
disorders of pregnancy can be reduced by adequate treatment
of GDM. The prevention of these morbid maternal medical
conditions can have significant short- and long-term impacts
on both maternal and fetal outcomes.13

CLINICAL PEARL Macrosomia (neonatal birth weight >4,500

g) is the most common adverse outcome in term infants.

4. The effects of poorly controlled maternal hyperglycemia may

have long-term effects on the newborn. The effect of diabetes
exposure during pregnancy on childhood obesity and
subsequent risk for type 2 diabetes has been examined in a
short-and long-term follow-up study. It demonstrated a
predisposition to increased weight and impaired glucose
tolerance or prevalence of type 2 diabetes during childhood.
This predisposition to long-term effect is similar between
types of maternal diabetes and exists after adjusting for the
presence of diabetes in the father and obesity in the offspring.
This suggests a nongenetic role in the fetal response to the
intrauterine environment.14
CLINICAL PEARL The risk for childhood obesity and
prevalence of type 2 DM is increased in the children of diabetic
mothers regardless of the type of DM.

D. Management of diabetes mellitus during pregnancy

The treatment of DM during pregnancy should focus on
excellent glycemic control, avoidance of severe hypoglycemia,
the stabilization and monitoring of complications, and fetal
surveillance. Self-monitoring of blood glucose is essential for
glycemic control. Measurements should be obtained before meals
to aid with insulin corrections for hyperglycemia and postprandial
to assess effectiveness of insulin therapy in preventing
postprandial hyperglycemia. The target values for capillary
glucose measurement during pregnancy are a fasting (premeal)
value of 3.8 to 5.2 μmol per L (65 to 95 mg per dL), a 1-hour
postmeal value of 5.5 to 7.7 μmol per L (100 to 140 mg per dL),
and/or a 2-hour postmeal value of 5.0 to 6.6 μmol per L (90 to
120 mg per dL).15 The risk for serious hypoglycemia may limit
the achievement of the glycemic targets, especially in women
with type 1 DM.
1. Insulin
In general, multiple doses of insulin are required to achieve
good glycemic control including basal intermediate- or long-
acting insulin and preprandial short- or rapid-acting insulin
(see Table 23.1).16 Insulin dosage is adjusted based on
anticipation of carbohydrate intake, exercise, and for the
glucose level. The conventional starting dose of insulin is
0.25 to 0.5 units/kg/day in divided doses.1 Insulin analogs are
being used more frequently in patients with DM. Their action
profiles result in better glycemic control with less frequent
episodes of hypoglycemia.17 Although there is little data it is
unlikely that insulin analogs cross the placenta, similar to
insulin; however, there is only published data on placental
 transfer of insulin lispro. The rapid-acting analogs, insulin
lispro and aspart, offer better glucose control than regular
insulin. Comparisons of NPH insulin and long-acting analog
detemir have determined that detemir improves fasting
plasma glucose concentrations, without fetal benefit. Recent
studies have confirmed that aspart, detemir, and glargine can
be safely used during pregnancy without an increase in
maternal or fetal complications. However, caution is advised
with the use of lispro insulin because it is associated with
higher fetal birth weight and an increased incidence of LGA
deliveries despite a lower incidence of critical maternal
hypoglycemia.18

2. Oral hypoglycemic agents

a. Women with pregestational type 2 DM who require oral
agents for glucose control should ideally be changed to
insulin before pregnancy. Although there is no evidence to
suggest that metformin and glyburide are teratogenic, the
marked increase in insulin resistance during pregnancy
usually results in women with type 2 DM requiring
insulin for glycemic control and potential reduction of
perinatal mortality.19 Data on the long-term effects of
 meglitinides, thiazolidinediones, dipeptidyl peptidase-4
(DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1)
analogues, and sodium-glucose co-transporter-2 (SGLT-2)
antagonists are lacking in pregnancy.
b. Most clinicians prefer to find an optimal insulin regimen
before pregnancy to avoid unstable glycemic control
during organogenesis. Oral hypoglycemic agents should
not be discontinued in women who conceive while
receiving oral hypoglycemic agents, until insulin therapy
is initiated as hyperglycemia is potentially much more
teratogenic than any of the currently available oral
therapies used to treat DM. Current data has shown that
the use of oral diabetic medications during pregnancy has
not resulted in harmful, short-term effects, but evidence is
lacking on the effects of long-term use.1
c. GDM is a milder metabolic derangement more easily
controlled by oral hypoglycemic agents such as
glyburide and metformin. Although the U.S. Food and
Drug Administration has not approved these oral agents
for treatment of GDM, current evidence from several
trials have demonstrated good glycemic control with
glyburide or metformin, although there is some concern
for an increased risk for hypoglycemia with glyburide
use; up to 50% of women will need insulin
supplementation as well. Data do not show an increased
risk of unfavorable short-term maternal or neonatal
outcomes with the use of glyburide or metformin.20,21
Although glyburide has been reported to cross the
placenta in one study, another study was unable to detect
glyburide levels in umbilical cord blood analyses.2 Thus,
women with GDM should be counselled on the risks
versus benefits of oral hypoglycemic agents versus insulin
for glycemic control when diet modification alone is
insufficient.
3. Diabetic ketoacidosis in pregnancy
a. DKA is the triad of hyperglycemia, ketosis, and
metabolic acidosis that is usually accompanied by
significant intravascular volume and total body
potassium depletion. It most often occurs in women with
type I diabetes. The metabolic changes that accompany
pregnancy make the pregnant woman more prone to DKA
and include (i) insulin resistance, (ii) accelerated
starvation, (iii) hyperemesis-associated dehydration, and
(iv) need to compensate for a progesterone-induced
respiratory alkalosis with renal excretion of bicarbonate.22
DKA is most common in second and third trimesters.
Precipitating events for DKA include omission of insulin
in insulin requiring pregnancies (often an inappropriate
reaction to hyperemesis), infection, and corticosteroid use
to promote lung maturity. DKA may also occur in type 2
DM, albeit rarely, especially in the African American
population. Women with type 2 diabetes may be more
likely to develop a hyperosmolar hyperglycemic
nonketotic state (HHNS) portrayed by hyperglycemia,
serum hyperosmolality (>360 mOsm per L), and severe
hypovolemia without ketonemia.23
b. The presentation of DKA is similar in nonpregnant and
pregnant patients, although the glucose levels may be
much lower than in nonpregnant patients with DKA.22
The physiologic respiratory alkalosis of pregnancy results
in lowered buffering capacity allowing more rapid
changes in pH, and the high GFR in pregnancy causes
continued renal excretion of glucose. Therefore, acidosis
is more pronounced at lower serum glucose levels.22
c. DKA in pregnancy is a medical emergency that requires
immediate treatment. A high fetal mortality rate is
associated with DKA, although it has decreased from
27% (from 1950 to 1979) to 9% (from 1985 to 1995).22
 Treatment requires prompt recognition, maternal
stabilization, rehydration, intravenous (IV) insulin
therapy, and electrolyte replacement as in the nonpregnant
patient. Precipitating factors should be investigated and
treated. Continuous fetal monitoring and full fetal
assessment should be utilized. Urgent cesarean delivery
(CD) while the mother is still acidotic is not
recommended due to higher maternal risk with minimal
benefit to the fetus. Fetal compromise may improve once
the maternal metabolic condition reverses.

CLINICAL PEARL The incidence of DKA in women with DM

prior to pregnancy is 5% to 10%. DKA can be present with only
mildly increased glucose levels in pregnant women; thus, the
diagnosis requires a high index of suspicion.

4. Assessment and surveillance for complications

a. Renal disease. Women with known nephropathy must
be closely followed for increasing proteinuria, renal
insufficiency, and hypertension. It is very difficult, and
at times impossible, to differentiate worsening
nephropathy from superimposed preeclampsia. A
microalbumin per creatinine ratio or 24-hour urine
collection for creatinine clearance (CrCl) and protein
excretion (including microalbumin levels) should be
obtained in each trimester and more often if progression is
seen. The mean increase in protein excretion is
approximately 3 g per 24 hours throughout gestation.24
Microalbuminuria usually increases but rarely to the level
of overt nephropathy. Postpartum renal function will
return to prepregnancy levels in most cases.6 For
women with moderate-to-severe renal impairment (serum
creatinine level >124 μmol per L or CrCl <70 mL per
 minute) before conception, there is a 45% risk of
pregnancy-related permanent decline in GFR.7
Hypertension is seen in 30% of women with diabetic
nephropathy in the first trimester and in 75% by the third
trimester. Deteriorating renal function and superimposed
preeclampsia are responsible for the high rates of preterm
delivery (>50%), low birth weight, and CD.
b. Retinopathy. The baseline severity of retinopathy is
highly predictive of its progression during pregnancy.
Frequent ophthalmology assessments are necessary
throughout gestation, if significant retinopathy is present.
Many practitioners recommend an assisted vaginal
delivery due to the increased risk of retinal bleeding;
however, there is little evidence to support this
recommendation.
E. Management during labor and delivery
1. Timing of delivery
Optimal timing of delivery for the woman with DM
requires balancing the risks of prematurity with the risks
of worsening maternal and fetal health. Patients with well-
controlled DM, in the absence of worsening complications
and no evidence of nonreassuring fetal status, may go to their
expected date of delivery but generally not past 40 weeks.15 A
pregnancy complicated by macrosomia is at greater risk for
maternal and infant birth trauma, which may be an indication
for earlier delivery with an estimated fetal weight of >4,500 g.
However, the indications for induction for vaginal delivery
and elective CD in pregnancies complicated by
macrosomia are controversial, and outcome studies are
sparse.25 Decreasing insulin requirements in late gestation,
not related to a decrease in carbohydrate intake, may be a sign
of placental failure. Although not well validated, many
practitioners will proceed with delivery if there has been a
significant decrease in insulin dosage unrelated to diet.
 Other indications for intervention in these women include
worsening diabetic nephropathy, superimposed preeclampsia,
and evidence of nonreassuring fetal status. Nonstress testing
and Doppler measurements are often used to assess the fetal
status.
2. Glucose management
Women with GDM will generally not require insulin
during labor, whereas women with type 1 and type 2 will
require careful monitoring and adjustment of insulin. The
goals are to avoid maternal hyperglycemia and reduce risk
of maternal and neonatal hypoglycemia while incorporating
patient preference for autonomy of care. Maintaining the
intrapartum maternal glucose level <120 mg per dL may
reduce neonatal hypoglycemia26; however, many women
will develop hypoglycemia. Changing oral intake, stress of
labor, and the change in insulin sensitivity after placental
delivery make glycemic control challenging. In general,
subcutaneous (SQ) insulin can be continued until the
woman is in active labor or is unable to eat. Then, IV
insulin should be initiated with the dose adjusted based on
hourly glucose monitoring. IV insulin protocols should be
developed locally with input from all care providers to
reduce risk of medication error. Women who use a
continuous SQ insulin infusion (pump) can continue to use
the pump throughout labor and delivery, provided they are
willing to take responsibility for adjusting doses during
delivery.
3. Anesthetic management
Anesthesiologists can expect to care for diabetic parturients in
a variety of patient care settings including premature labor,
uncomplicated labor and vaginal delivery, complicated
obstetric disorders (e.g., preeclampsia), as well as elective or
emergent CD. Maternal, fetal, and neonatal complications
can be expected in this patient population; therefore, early
preanesthetic evaluation is essential. This will include
careful airway examination (e.g. to rule out stiff joint
syndrome), assessment of blood glucose control and renal
function, as well as documentation of the presence or absence
of peripheral neuropathy. This assessment is helpful in the
detection of the chronic complications of diabetes due to
microvascular disease.
a. Labor analgesia
Parenteral opioids can be used in early labor for pain
control in uncomplicated diabetic patients, but early
epidural analgesia offers many benefits. Labor epidural
analgesia not only provides superior pain relief but also
reduces maternal endogenous catecholamine levels,
resulting in improved placental perfusion and reduced
insulin requirements. Because many diabetic mothers
are at increased risk for urgent or emergent CD, a
functioning epidural catheter allows for rapid
induction of anesthesia, and avoids the need for
general anesthesia.
After noting baseline maternal vital signs and fetal
heart rate (FHR), either epidural or combined spinal-
epidural (CSE) analgesia can be administered safely.
Although some practitioners prefer epidural analgesia
because of the ability to titrate the block and confirm the
block level, CSE techniques have been shown to be as
reliable as epidural only techniques. Regardless of the
technique, a well-conducted epidural or CSE should be
administered with care, paying particular attention to
maintenance of uterine displacement, avoiding
hypotension and administration of non–dextrose-
containing fluids. Hypotension unresponsive to IV fluids
should be treated promptly with either ephedrine or
phenylephrine because even minor degrees of
hypotension may worsen uteroplacental insufficiency in
 diabetic parturients. Women with overt nephropathy are at
risk for volume overload; therefore, IV fluid
administration should be closely monitored.
b. Cesarean delivery
Anesthetic considerations for CD in the diabetic parturient
are similar to those for labor analgesia: (i) avoid
hypotension, (ii) administer non–dextrose-containing IV
fluids, and (iii) maintain uterine displacement. Spinal,
epidural, or general anesthesia can be administered safely
but the chosen technique should be individualized based
on several factors, including anesthetic, obstetric, or fetal
risk factors (e.g., elective vs. emergency); the preferences
of the patient; and the judgment of the anesthesiologist.
Neuraxial techniques are preferred to general anesthesia
for most CD. However, general anesthesia may be the
most appropriate choice in some circumstances (e.g.,
profound fetal bradycardia, ruptured uterus, severe
hemorrhage, and severe placental abruption).

CLINICAL PEARL Anesthetic management should focus on

maintaining appropriate glucose control, modification based on the
presence and severity of preexisting end organ disease, and
maintaining an optimal fetal environment.

4. Postpartum care
a. Insulin requirements. Following delivery of the
placenta, insulin sensitivity returns immediately.
Maternal hypoglycemia should be avoided. A reduction of
insulin dosage to two-thirds of the prepregnancy
requirement is prudent. For women with type 1 DM, the
first SQ dose of insulin should be administered before
discontinuing an IV infusion due to the short half-life of
IV insulin. For women on oral agents or diet before
 pregnancy, insulin should be used only if the patient
clearly has postpartum hyperglycemia.
b. Neonatal hypoglycemia must be anticipated and local
protocols established. In general, infants born to these
mothers should have frequent capillary glucose
measurements and, if the blood glucose level is <2 μmol
per L (<36 mg per dL), early oral feeding or the use of IV
dextrose should be implemented. Other neonatal
complications include (a) hypocalcemia, (b) jaundice, (c)
polycythemia, (d) septal hypertrophy, (e) sacral agenesis,
and (f) respiratory distress syndrome.

CLINICAL PEARL The risk for neonatal hypoglycemia

following delivery may be minimized by good maternal glucose
control during labor and vaginal and operative delivery.

II. Thyroid disorders

A. Introduction
Thyroid disorders are common in women of childbearing age
with an incidence estimated at 4% to 5%. Women may (a)
have previously diagnosed thyroid disease that requires
monitoring during pregnancy, (b) have unrecognized thyroid
disease that exacerbates during pregnancy, or (c) develop
pregnancy-induced thyroid dysfunction during or after pregnancy.
Depending on the underlying cause of the thyroid disorder and
severity of change in thyroid hormone levels, there can be
detrimental consequences for both maternal and fetal health.
B. Thyroid physiology
1. Pregnancy is associated with significant but reversible
changes in maternal thyroid physiology. There are two
forms of thyroid hormone—thyroxine (T4) and
triiodothyronine (T3). Most circulating hormone is T4, of
which only 0.04% is unbound (“free T4”) and physiologically
 active. The remainder is bound to circulating transport
proteins. T4 is converted intracellularly to T3, which is
required for in biologic action. Thyroid-stimulating hormone
(TSH) is the primary regulator of thyroid function; it
increases synthesis and release of thyroid hormone.
2. The pregnant woman makes 50% more thyroid hormone
during pregnancy to compensate for increased levels of
binding hormone and increased clearance of hormone through
placental degradation. The fetal thyroid gland begins to
synthesize thyroid hormone at 12 weeks’ gestation, but
remains dependent on maternal thyroid hormone until the
thyroid–pituitary axis begins functioning at 18 weeks.
3. There are normal, physiologic changes in thyroid hormone
levels during pregnancy. The rising levels of human
chorionic gonadotropin (hCG) in the first trimester result in
a transient increase in T4 production and suppression of TSH.
It is therefore “normal” to have a slightly suppressed TSH and
slightly elevated free T4 during the first trimester (see
subsequent text). TSH will return to normal nonpregnant
levels once hCG levels fall. Most studies have demonstrated a
mild decrease in free T4 and slight increase in TSH in the
third trimester, usually within the normal range.
4. Most thyroid disorders are autoimmune in nature. The
thyroid-stimulating hormone receptor antibodies (TSHrAbs)
associated with Graves disease have been shown to decrease
substantially during pregnancy, allowing discontinuation of
medical treatment for many women. In those women who
continue to have high antibody titers during pregnancy,
passive placental transfer can lead to fetal thyroid disorders
after 18 weeks. Antibody titers will increase postpartum and
are responsible for flares of Graves disease and appearance of
postpartum thyroiditis.27
5. Some, but not all, clinical practice guidelines/expert panels
recommend routine thyroid screening preconceptually, or
 when pregnancy is identified, due to an increased risk for
impaired brain development in children of mothers with
abnormal thyroid function during pregnancy.28 Table 23.2
compares the overall changes in thyroid function tests in
normal pregnancy versus thyroid disease states.

CLINICAL PEARL Normal pregnancy requires an increase in

thyroid production by the maternal thyroid gland, which can be
insufficient due to a variety of causes.

C. Hyperthyroidism
1. Definition and pathophysiology
Hyperthyroidism is defined by excessive thyroid hormone
production. It can be subclinical (suppressed TSH, normal
T4 and T3) or overt (suppressed TSH and elevated T4 and/or
T3). Severe thyrotoxicosis is associated with poor obstetric
outcomes. Women with uncontrolled hyperthyroidism have a
fivefold greater risk of developing severe preeclampsia.27
There is also an increased risk of fetal loss, low birth weight,
prematurity, and placental abruption, which appear to be
directly related to the blood level of maternal T4. Women who
are appropriately treated and euthyroid before pregnancy do
not have increased risk for these poor outcomes.28
2. Physiology of hyperthyroidism
In the first trimester, 10% to 20% of normal women will
 have a suppressed TSH due to the effect of hCG. Some
women, especially those with high hCG levels associated with
hyperemesis, molar pregnancy, and twins will have
gestational thyrotoxicosis, also referred to as first-trimester
thyrotoxicosis and hCG-related thyrotoxicosis. This temporary
condition improves as hCG levels decrease and does not
usually require medical intervention. The most common cause
of preexisting hyperthyroidism is Graves disease, an
autoimmune hyperthyroidism secondary to stimulation of the
thyroid gland by TSHrAb. Other causes include (a) toxic
solitary nodule, (b) multiple nodular goiter, (c) ingestions
(e.g., exogenous thyroid hormone, amiodarone, excess
iodine), and (d) subacute thyroiditis (see Table 23.3).

3. Clinical presentation of hyperthyroidism

a. The clinical presentation of hyperthyroidism in
pregnancy will depend on the underlying cause and
severity of the thyrotoxicosis. All causes of thyrotoxicosis
may present with adrenergic symptoms including (i)
nervousness, (ii) heat intolerance, (iii) weight loss, (iv)
diarrhea, (v) palpitations, (vi) anxiety, (vii) lid
retraction, and (viii) stare. Features specific to the
 underlying cause may be detected on the thyroid
examination. The diffuse, symmetric, soft goiter may
have an audible bruit and may be a feature of Graves
disease. Symptoms are often exacerbated in the first
trimester of pregnancy and improve as the pregnancy
advances.29 In the setting of subacute thyroiditis, there
may be a palpable nodule associated with nodular disease
(usually >3 cm) and tenderness.
b. Autoimmune manifestations such as (i) orbitopathy
(proptosis, soft tissue periorbital swelling, and
extraocular muscle dysfunction), (ii) pretibial
myxedema, and (iii) clubbing may be present and are
exclusive to Graves disease. If clinical findings are
inconclusive, it is helpful to measure TSHrAb provided
that the results are available in a timely manner; however,
TSHrAbs are positive only in 80% of patients with
Graves disease.30
4. Management
The goal of management in all cases of thyrotoxicosis is to
normalize, but not suppress, thyroid hormone levels and
to treat bothersome symptoms. In the nonpregnant state,
three treatment options exist for hyperthyroidism: (a)
antithyroid medication, (b) radioactive iodine to partially
ablate the thyroid gland, and (c) near-total thyroidectomy. The
biochemical status of women who have chosen radioactive
iodine or surgery before pregnancy, no longer reflects their
autoimmune status. Women with Graves disease who
previously received ablative therapy (iodine 131 [131I] or
thyroidectomy) have a continued risk of fetal Graves disease
if the antibody titer is still significantly elevated.
Propylthiouracil (PTU) and methimazole are both used as
medical therapy for Graves disease. PTU is generally
preferred due to concern over congenital anomalies reported
with methimazole use.31,32
 5. Fetal outcome
a. Fetal risk depends on the degree of thyrotoxicosis, the
underlying cause of the thyrotoxicosis, and the
treatment modality used. In most cases, the neonate of a
hyperthyroid mother is euthyroid. Hyper- or
hypothyroidism may occur and either condition can
develop with or without a neonatal goiter. Neonatal hyper-
and hypothyroidism that is secondary to maternal thyroid
dysfunction is usually transient and will respond to
therapy within 1 to 2 weeks.
b. Placental transfer of TSHrAb can cause excessive
stimulation of the fetal thyroid gland resulting in fetal or
neonatal Graves disease. This occurs after 16 weeks of
gestation with (i) fetal tachycardia, (ii) high-output
cardiac failure, (iii) hydrops, (iv) craniosynostosis, (v)
IUGR, and (vi) fetal goiter. Fetal goiter can also be caused
by placental transfer of maternally administered
thioamides. In this situation, the fetus is hypothyroid.
c. Chronic exposure to hyperthyroidism from inadequately
treated maternal hyperthyroidism may impair maturation
of the fetal hypothalamic-pituitary-thyroid axis. This can
lead to central congenital hypothyroidism in the infant.

CLINICAL PEARL Thyrotoxicosis is associated with increased

rates of spontaneous abortion, preeclampsia, and preterm delivery.
Only Graves disease–related thyrotoxicosis is associated with
neonatal Graves disease.

6. Antepartum considerations
a. Medications. The treatment goal is a free T4 level in
the high normal range using the lowest dose of
thioamide possible. For symptom relief, β-blockers can
be used until the free T4 levels come into the normal
 range. Table 23.433 summarizes the common drugs and
their action of mechanism for treatment of
hyperthyroidism. Excessive use of antithyroid medication
can result in fetal hypothyroidism and fetal goiter and
must be avoided. Gestational thyrotoxicosis is self-
limiting and does not require thioamide treatment. For
individuals who develop adverse reactions to
thioamides, especially significant leukopenia, or liver
abnormalities, a thyroidectomy in pregnancy may be
required.

b. Fetal goiter/Graves disease. In women medically treated

 for Graves disease, fetal goiter can occur from thioamide-
induced fetal hypothyroidism or fetal Graves disease.
Women who receive radioactive iodine or a
thyroidectomy may continue to produce high titers of
TSHrAb and place their fetuses at risk for Graves disease.
For women not on antithyroid medication and who have
negative TSHrAb, no additional fetal monitoring is
required.34 Fetal monitoring should include assessment
for tachycardia, fetal growth, and goiter size by
ultrasonography starting at 20 weeks’ gestation and
repeated monthly. If there is no evidence of fetal goiter,
significant fetal thyroid dysfunction is unlikely. Rapid
resolution of the fetal goiter is possible with in utero
therapy.
7. Thyroid storm. Pregnancy is a potential rare cause of
thyroid storm and is associated with a very high mortality
rate of 25%.35 Diagnosis is by clinical detection of a rapid-
onset, severe, life-threatening exacerbation of thyrotoxicosis
that usually occurs in the presence of significant goiter. Other
life-threatening illnesses (sepsis, hypoglycemia,
pheochromocytoma, and cocaine toxicity) may mimic thyroid
storm.
a. The classic features are (i) fever, (ii) tachycardia with
atrial fibrillation, (iii) nausea/vomiting, (iv) abdominal
pain, (v) delirium/coma, (vi) systolic hypertension with
wide pulse pressure, and (vii) high output cardiac
failure.36 Pregnant women may be more vulnerable to
heart failure with severe thyrotoxicosis due to the
already increased cardiac output, diminished vascular
resistance, and hypervolemia of pregnancy.37
Hyperglycemia, hypercalcemia, and abnormal liver
function tests may also be present. The severity of the
clinical picture is not directly related to the circulating
level of free T4 or T3. Any patient suspected of thyroid
 storm requires immediate admission to an intensive care
unit (ICU) for invasive hemodynamic monitoring and
administration of immediate therapy without waiting for
confirmatory laboratory results.
b. Treatment is aimed at (i) blocking the peripheral effect
of excess thyroid hormone, (ii) halting thyroid hormone
synthesis, (iii) preventing release of preformed hormone,
and (iv) reducing peripheral conversion of T4 to T3 (see
Table 23.4).33 Adequate adrenergic blockade is
essential and requires high doses of β-blockers
administered at short intervals because hyperthyroidism
increases both the number of β-receptors that need to be
blocked and drug metabolism. Propranolol has been the
treatment of choice because it decreases T4 to T3
conversion; however, esmolol has also been used
successfully.38 PTU should be administered as soon as the
diagnosis is made. An initial dose of 300 mg q6h should
be administered by mouth or nasogastric tube. The use of
inorganic iodine (four to eight drops of Lugol solution
every 6 to 8 hours or five drops saturated solution of
potassium iodide [SSKI] q6h) or iodinated contrast agents
(sodium ipodate 1 mg q8h for 24 hours then 500 mg
q12h) are standard therapies in the nonpregnant patient.34
When administered after the first dose of PTU, both are
very effective at preventing release of thyroid hormone.
Very little information is available on the consequences of
large amounts of iodine on the developing fetus; however,
the risk to the fetus during uncontrolled, severe maternal
thyrotoxicosis likely outweighs the potential risks of fetal
iodine exposure. Glucocorticoids may be administered to
inhibit peripheral conversion of T4 to T3 and help prevent
relative adrenal insufficiency.

CLINICAL PEARL Thyroid storm conveys a high risk of

maternal and fetal death.

8. Intrapartum and anesthetic considerations

a. The major concerns at delivery are the degree of
thyrotoxicosis, presence of maternal goiter, and
presence of fetal goiter. Although pregnant women with
well-controlled hyperthyroidism generally tolerate labor
and delivery without complications, anesthesiologists
should be aware of several potential physiologic changes
associated with hyperthyroidism that may affect
anesthetic management: (i) airway obstruction resulting
from an enlarged thyroid gland, (ii) respiratory muscle
weakness, (iii) a hyperdynamic cardiovascular system
with possible cardiomyopathy, (iv) excessive sympathetic
stimulation resulting from pain and anxiety, (v) increased
β-adrenergic receptor populations, (vi) electrolyte
abnormalities, and (vii) coagulation test abnormalities
with increased risk of thrombosis or bleeding depending
on severity of thyroid diseases. Ideally, the goal of
preoperative preparation is a euthyroid patient;
however, minimizing the risk of thyroid storm is most
important. In poorly controlled patients, labor and
delivery can evoke thyroid storm, and anesthesia
providers should be prepared to treat this complication.
For those who remain severely thyrotoxic, assessment
of maternal cardiac status and monitoring during
delivery are important. Preoperative preparation may
include the administration of PTU, glucocorticoids,
sodium iodide, and a β-blocker.
b. Labor analgesia
Excessive anxiety and inadequate pain control during
labor can activate the sympathetic nervous system. Either
epidural or CSE analgesia should be initiated early in
labor. Continuous infusion epidural techniques or patient-
 controlled epidural anesthesia (PCEA) can be used to
maintain analgesia and minimize the risk for thyroid
storm. Labetalol, commonly available and familiar to
labor and delivery room staff, can be used for β-
blockade.39 In addition to the usual management
considerations during labor analgesia administration (e.g.,
left uterine displacement), hypotension can be treated
with a combination of crystalloid administration and
vasopressor therapy, but judicious dosing of
vasopressors is recommended to avoid possible
exaggerated hypertensive responses.
c. Cesarean delivery
(1) Anesthetic choice. Spinal, epidural, or general
anesthesia is acceptable, but in most cases,
neuraxial anesthesia is preferred to general
anesthesia; however, no studies have evaluated the
effectiveness or safety of a particular technique in
this patient population. In awake patients with
adequate neuraxial anesthesia, excessive anxiety and
sympathetic nervous system activation can be
problematic. Although there has been some concern
about the administration of epinephrine-containing
local anesthetic solutions in patients with
hyperthyroidism, due to fear of exaggerated
circulatory responses, most agree that it is safe to
administer these local anesthetics to minimize
uptake and reduce risk of local anesthetic toxicity.
Hypotension should be treated with IV crystalloid
and judicious vasopressor therapy. If general
anesthesia is necessary, drugs that stimulate the
sympathetic nervous system (e.g., ketamine) or cause
maternal tachycardia (e.g., atropine, glycopyrrolate,
β-mimetics for tocolysis, and pancuronium) should
be avoided, if possible. Midazolam, 1 to 2 mg IV, can
 be used to reduce maternal anxiety.
(2) Ex utero intrapartum treatment procedure. If
fetal goiter is identified and not resolved through
treatment in utero, the delivery plan must be
discussed by a multidisciplinary team that includes
obstetricians, neonatologists, and anesthesiologists.
An ex utero intrapartum treatment (EXIT) procedure
should be considered when there is concern for fetal
airway compromise.40
D. Hypothyroidism
1. Pathophysiology
Hypothyroidism is caused by inadequate thyroid hormone
production. The prevalence of hypothyroidism during
pregnancy is approximately 2% to 3%, although this is likely
an underestimate.41 Hypothyroidism may be overt (i.e.,
elevated TSH and low free T4) or subclinical (i.e., elevated
TSH, free T4 in normal reference range).
a. In the developed countries, autoimmune destruction
(Hashimoto thyroiditis) is the most common cause.
b. Iodine deficiency remains the leading cause globally with
up to 30% of the world’s population at risk.
Other causes include:
c. Ablation with radioactive iodine following treatment for
Graves disease or thyroid nodule.
d. Thyroidectomy (partial or near complete for treatment of
benign or malignant neoplasm, Graves disease).
e. Medications (e.g., lithium, amiodarone).
f. Transient inflammatory thyroiditis.
g. Central hypothyroidism is rare in prepregnancy and can
be due to inadequate stimulation of the thyroid gland
because of a defect at the level of the pituitary or
hypothalamus.
2. Clinical presentation
The clinical manifestations of mild to moderate
 hypothyroidism are vague and often insidious in onset,
making it often difficult to differentiate the disease from the
normal signs and symptoms of pregnancy. These include (a)
fatigue, (b) constipation, (c) cold intolerance, (d) weight gain,
(e) carpal tunnel syndrome, (f) hair loss, (g) voice changes,
(h) reduced memory, (i) muscle cramps, and (j) dry skin.
Women who report these over the previous year are more
likely to have overt thyroid disease.41 The presence or
absence of a pathologically enlarged thyroid gland depends on
the etiology of hypothyroidism. Women in areas of endemic
iodine deficiency, or those with Hashimoto thyroiditis, are
more likely to have a goiter.
3. Treatment
The goal of treatment in pregnant women with overt
hypothyroidism is clinical and biochemical euthyroidism at
the time of conception and throughout pregnancy.
Levothyroxine sodium (thyroxine) is the treatment of choice
for routine management of hypothyroidism. The long half-life
of thyroxine (7 days) does not permit rapid dosage titration.
Most women with hypothyroidism will require an increased
dose once pregnant due to increased hepatic-binding protein
production secondary to estrogen stimulation, fetal transfer,
and placental clearance.
4. Obstetric risk and complications depend on the severity and
cause of the hypothyroidism.
a. Fetal risk
Iodine deficiency results in inadequate fetal thyroid
hormone production throughout gestation resulting in
profound fetal hypothyroidism. This results in: (i)
significant neurodevelopmental delay, (ii) deafness, (iii)
stunted growth, and (iv) increased risk of neonatal
mortality. Although modest but significant changes in
psychomotor and IQ testing among children exposed to
mild maternal hypothyroidism have been reported,
 neonatal thyroid function is normal.
b. Obstetric complications
The fetal thyroid gland does not start making thyroid
hormone until 14 weeks’ gestation, so maternal
hypothyroidism during the first trimester of pregnancy is
particularly detrimental.41 Obstetric complications from
mild hypothyroidism include (i) increased risk of
stillbirth, (ii) preterm delivery, (iii) preeclampsia, (iv)
placental abruption, (v) breech presentation, and (vi) low
birth weight.42 Women who have been rendered
hypothyroid following radioactive iodine or
thyroidectomy for their underlying Graves disease may
continue to make TSHrAb, which puts the fetus at risk for
fetal Graves disease.
5. Antenatal care
a. Women with known thyroid disease should have a serum
TSH at their first prenatal visit. A low normal TSH (<2.5
mU per mL) should be the goal during pregnancy. In the
first trimester, a slightly suppressed TSH is normal and
the dose of Levothyroxine (L)-thyroxine should not be
altered. Almost half of these women will require an
increase in thyroid replacement during pregnancy.
When dose adjustments are made, the TSH should be
repeated every 4 to 6 weeks, and then every 8 to 12
weeks, when stable.
b. Severe, undiagnosed hypothyroidism is extremely rare
in pregnancy because it tends to lead to infertility.
However, there are several case reports of women
presenting with myxedematous coma in pregnancy.43
Severe hypothyroidism may be precipitated by (i)
infection, (ii) medications including sedatives and
opioids, and (iii) cardiovascular events.
c. The clinical presentation of severe hypothyroidism
includes (i) alteration in cognitive function, (ii)
 depression, (iii) hypothermia, (iv) bradycardia, (v)
hypotension, (vi) hypercapnia, and (vii) hyponatremia.
d. Therapy should involve (i) electrocardiogram (ECG)
monitoring, (ii) thyroxine replacement, (iii) external
warming, (iv) judicious fluid replacement, and (v)
glucocorticoid therapy.
6. Intrapartum and anesthetic considerations
a. Although prior thyroid surgery or medical therapy should
alert providers about possible hypothyroidism, primary
hypothyroidism is often undiagnosed. Anesthetic
management of the parturient with untreated
hypothyroidism focuses on (i) increased myocardial and
hemodynamic effects of depressant drugs (e.g., volatile
anesthetics), (ii) risk of coronary artery disease, (iii)
altered metabolism and inactivation of drugs, (iv)
monitoring for the respiratory depression with opioid
administration, (v) detection of obstructive sleep apnea,
(vi) recognition of skeletal and respiratory muscle
dysfunction, (vii) monitoring for altered ventilatory
responses to hypoxemia, (viii) obtaining tests for adrenal
insufficiency, (ix) detecting electrolyte abnormalities, (x)
observing for altered consciousness, and (xi) monitoring
for abnormal platelet count and coagulation factors.
b. Anesthesia for labor and delivery
Patients who are not euthyroid are at increased risk for
impaired baroreceptor responses as well as decreased
intravascular volume. During labor, neuraxial analgesic
techniques are preferred to parenteral techniques because
of risk of opioid-induced respiratory depression. Labor
can induce a stress response, precipitating decreased
adrenal cortical function. In these patients, glucocorticoid
replacement will be necessary. Although there are no
special considerations for administration of neuraxial
analgesic techniques in patients who are hypothyroid,
 hypothyroidism may be associated with qualitative
platelet dysfunction. In patients with overt disease, it
may be prudent to verify normal coagulation before
proceeding with neuraxial techniques, although there are
no documented cases of a neuraxial hematoma in patients
with thyroid disease. Responses to vasopressor therapy
are normal.
c. Anesthesia for cesarean delivery
Although neuraxial anesthesia is the preferred technique
for CD, some parturients will require general anesthesia.
In such cases, particular attention should be paid to the
airway examination if a large goiter is present. In
addition, cardiorespiratory depressant drugs should be
used cautiously. Rapid sequence induction can be
accomplished with minimal doses of induction agent (e.g.,
thiopental or ketamine). Etomidate may also be
considered but may suppress serum cortisol. In these
patients, the physiologic responses to hypercarbia and
hypoxia are abnormal. Judicious benzodiazepine and
opioid administration are required. Volatile anesthetics
should also be administered with caution due to their
cardiac depressant effects. If muscle relaxation is
necessary beyond an intubating dose of succinylcholine,
administration of nondepolarizing muscle relaxants
should be guided with the use of a nerve stimulator due to
abnormal skeletal and respiratory muscle function.

CLINICAL PEARL Both regional and general anesthesia are

safe alternatives for anesthesia of the parturient with adequately
controlled thyroid disease.

III. Pituitary disorders

A. Introduction
 Pregnancy is unusual in women with significant preexisting
pituitary disease because normal pituitary function is required for
both conception and maintenance of early pregnancy. Pituitary
disease may result in hormonal hypersecretion with resulting
syndromes (i.e., prolactinoma) or pituitary insufficiency due to
destruction of the functioning gland. There may also be space-
occupying effects that produce visual field compromise. Rare
disorders specific to pregnancy such as Sheehan syndrome or
lymphocytic hypophysitis may also alter pituitary function. The
most common pituitary disorders in pregnancy are due to
pituitary adenomas.44
B. Pituitary adenomas
1. Classification
Pituitary adenomas are classified on the basis of hormone
secretion and size: (a) microadenomas <10 mm and (b)
macroadenomas >10 mm. The size of an adenoma may alter
management in pregnancy as the clinical behavior of
macroadenomas and microadenomas differ considerably
during pregnancy.
2. Clinical considerations
a. Prolactinomas are the most commonly diagnosed
pituitary lesion in pregnancy. The associated
hyperprolactinemia is easily treated with dopamine
agonists and restores fertility in these women.45 Women
with pituitary prolactinomas are usually diagnosed before
pregnancy because they are often infertile. However,
some women initially present in pregnancy with
symptoms of tumor expansion.
b. Clinically, macroadenoma expansion presents as (i)
headache, (ii) visual field defects, (iii) rhinorrhea, (iv)
cranial nerve palsies, (v) diabetes insipidus, and (vi)
pituitary apoplexy.
c. Acromegaly and nonfunctioning pituitary adenomas are
other rare causes of pituitary adenomas found in pregnant
 patients. Because most of these pituitary tumors are
macroadenomas, fertility is often impaired due to
impaired gonadotropin secretion or hyperprolactinemia
caused by neoplastic compression of the pituitary stalk.45
Ideally, patients with acromegaly should have their
disease optimally managed before pregnancy (i.e.,
suppression of growth hormone levels and normalization
of insulin-like growth factor-1 [IGF-1]). Hypertension
and DM should be screened for and managed
appropriately.
3. Management
a. Management of pregnant patients with prolactinoma is
dependent on the size of the adenoma. Dopamine agonist
therapy is usually discontinued in women with
microadenoma once pregnancy is confirmed because the
risk of pituitary expansion during pregnancy is low.
Routine visual field testing is not required and should be
reserved for the woman with symptoms of tumor
expansion. Routine measurement of prolactin is of no
benefit because prolactin levels normally increase with
pregnancy and may not rise further with tumor expansion.
b. Therapeutic management for prolactin-secreting
macroadenomas is less clear. Options include (i)
discontinuation of bromocriptine once pregnancy is
documented, with careful monitoring of the patient for
tumor expansion; (ii) prepregnancy surgical debulking; or
(iii) continuation of bromocriptine throughout pregnancy
because this has been suggested to decrease tumor
enlargement. A screen for function of other pituitary
hormones (i.e., cortisol and thyroid) should be
performed. Baseline visual field testing and imaging of
the pituitary is crucial for women with macroadenoma
who must be monitored throughout gestation for evidence
of tumor expansion. If evidence of tumor expansion
 occurs, reinstitution of bromocriptine should be
considered. Surgery or early delivery may be necessary
for patients who do not respond to medical therapy.46
4. Antepartum maternal risks
a. Maternal complications
The main maternal complication from a pituitary
adenoma is tumor expansion. In patients with a
prolactinoma, the marked increase in estrogen during
pregnancy has a stimulatory effect on prolactin secretion
that can cause tumor growth.45 Microadenomas and
macroadenomas have different risks for growth
during pregnancy. Microadenomas are associated with a
1.4% risk of expansion, whereas macroadenomas carry a
risk of expansion in 26% of patients who have not
undergone prior surgery or irradiation.44 Tumor growth
has also been seen in patients with acromegaly,
particularly in those who had not been previously treated
or who have received only pharmacologic therapy before
pregnancy. These patients should also be screened for
tumor growth during pregnancy. Women with
acromegaly may have maternal DM, hypertension, and
left ventricular hypertrophy.
b. Risk of expansion
In patients with a nonfunctioning pituitary adenoma,
hyperplasia normally associated with pregnancy might
cause headaches or visual disturbances, but this potential
complication has not been reported; one case of expansion
of a nonfunctioning pituitary adenoma has been
reported.46 In such cases, transsphenoidal surgery is
recommended, if bromocriptine therapy fails to provide
timely improvement.
c. Pituitary insufficiency
Women with pituitary macroadenomas are at risk for
pituitary insufficiency, particularly if tumor expansion
 occurs. Patients should be screened for cortisol and
thyroid deficiency, and high doses of corticosteroids may
be required at times of stress such as labor or operative
delivery.

CLINICAL PEARL Differentiating women with pituitary

microadenomas versus those with macroadenomas is important due
to the increased risk of a mass effect with the latter.

5. Intrapartum considerations
Most patients with pituitary disease require no special
anesthetic considerations during labor and delivery.
However, Valsalva maneuvers associated with labor and
delivery may increase intracranial pressure and potentially
increase the risk of pituitary apoplexy in patients with
pituitary macroadenomas. An assisted vaginal delivery
should also be considered. Women should therefore be
monitored for signs and symptoms such as severe headache
and hemodynamic compromise. Stress-dose corticosteroids
may be required in patients with macroadenomas during labor
and delivery. This dose should be discontinued over 2 to 3
days following delivery.
C. Pituitary insufficiency during pregnancy
1. Diagnosis
Pituitary insufficiency is difficult to diagnose during
pregnancy because the symptoms may be attributed to
pregnancy alone. Also, dynamic testing is difficult. Pituitary
insufficiency may be caused by a number of disorders (see
Table 23.5) and can present before pregnancy, or become
clinically significant during pregnancy (i.e., lymphocytic
hypophysitis, diabetes insipidus), or postpartum (i.e.,
Sheehan syndrome).
2. Pathophysiology
In cases of hypopituitarism present before conception, the
destruction of the pituitary results in impairment of its ability
to secrete some or all of the releasing hormones. Deficiencies
of cortisol, thyroid hormone, follicle-stimulating hormone
(FSH), luteinizing hormone (LH), and vasopressin can
result. These women usually present before pregnancy with
infertility. Management of patients with preexisting pituitary
insufficiency should include a review of medications and a
detailed surveillance plan outlined for pregnancy. If the
hormonal deficiency is partial, screening for deficiencies of
other pituitary hormones should be completed. Hormonal
replacement should be optimized. Increased thyroid hormone
may be needed during gestation to meet the increased
requirements for thyroxine during pregnancy. In this case,
measurement of TSH is unhelpful because it will always be
low in patients with hypopituitarism. The free T4 level should
be monitored and kept within the normal range. Cortisol
replacement should be maintained at prepregnancy
replacement doses, unless there is an additional illness or
stress such as hyperemesis, fever, or labor. Periodic
measurements of electrolytes and blood pressure (BP) may
be helpful in determining the adequacy of cortisol
replacement.
a. Lymphocytic hypophysitis
Lymphocytic hypophysitis is an autoimmune disease
causing infiltration of lymphocytes and plasma cells
leading to destruction of the pituitary. Women may
present in pregnancy with signs of an expanding
intrasellar mass (e.g., visual field changes, cranial nerve
palsies, or headache) or hypopituitarism. Immediate
surgical intervention is unnecessary (unless there is
evidence of visual field defects, intractable headaches, or
radiologic evidence of an expanding mass) because
women may undergo a spontaneous regression of the
mass and restoration of pituitary function.47 A short
course of high-dose corticosteroids may produce dramatic
resolution of visual field defects in some women.48
b. Diabetes insipidus
Diabetes insipidus (DI) occurs rarely during pregnancy
with an incidence of 0.004% Polyuria, polydipsia,
extreme thirst, and dehydration are symptoms. The
diagnosis of DI is often made clinically, with laboratory
confirmation. A high urine output, low urine osmolality
<275 mOsm per kg, and high serum osmolality (>290
mOsm per kg) are the hallmarks of DI. Gestational DI is
thought to be caused by increased vasopressinase (a
placental enzyme that metabolizes endogenous arginine-
vasopressin (AVP) but not synthetic DDAVP) activity
with lower renal receptiveness to AVP. Gestational DI has
been associated with preeclampsia, the hemolysis,
elevated liver enzymes, low platelets (HELLP) syndrome,
and fatty liver of pregnancy, likely because the liver is
partially responsible for the metabolism of
 vasopressinase. Electrolytes and volume status in
pregnant women with DI should be carefully monitored.49
c. Sheehan syndrome
The pathogenesis of Sheehan syndrome is unclear, but is
felt to be secondary to ischemia of the pituitary gland. The
acute diagnosis of Sheehan syndrome should be
considered in women with postpartum hemorrhage who
are unresponsive to fluid resuscitation. Prolactin levels
that are normally high during pregnancy may be low. An
adrenocorticotropic hormone (ACTH) stimulation test
may be normal as the adrenals have not yet had the time
to atrophy as in other patients with pituitary insufficiency.
Acute pituitary insufficiency, as in the case of acute
Sheehan syndrome, is a medical emergency with
potentially fatal outcomes for both mother and fetus.
Baseline laboratory studies should be obtained, but
therapy should be initiated while awaiting results. Fluid
resuscitation in combination with stress-dose
corticosteroids (i.e., hydrocortisone 100 mg IV every 8
hours) is required. IV glucose may be necessary for
treatment of hypoglycemia. It is important to observe for
polyuria following administration of corticosteroids
because their administration may unmask diabetes
insipidus. If this occurs, an evaluation for DI should be
performed. Thyroid hormone replacement may be
instituted if levels are found to be low.
3. Antepartum risks
Untreated and partially treated hypopituitarism increases the
risk of maternal hypotension and hypoglycemia. Rates of
operative delivery may be increased. Small for gestational
age infants, preterm birth, and intrauterine fetal death have
been reported in patients with preexisting hypopituitarism.
Poorer outcomes may be related to inadequate hormonal
replacement in the mother. Congenital malformations have
 not been reported.
4. Intrapartum considerations
Stress corticosteroids will be required for labor and delivery.
Hydrocortisone 100 mg IV q8h should be administered and
decreased to replacement doses over 2 to 3 days following
delivery or postpartum.

CLINICAL PEARL Laboring parturients with pituitary

insufficiency should be monitored for hypoglycemia, receive stress-
dose steroids, and are at increased risk for hypotension.

IV. Adrenal disorders

A. Primary adrenal insufficiency
1. Pathophysiology
a. Primary adrenocortical insufficiency. Primary
adrenocortical insufficiency usually results from
autoimmune destruction of the adrenal cortex (Addison
disease). There is deficiency of all adrenal steroids
(cortisol and aldosterone), and ACTH levels are
elevated. The diagnosis of adrenocortical insufficiency in
pregnancy is challenging because many of its symptoms
are identical to the normal symptoms of pregnancy
(e.g., nausea, vomiting, fatigue, orthostatic hypotension,
and hyperpigmentation). Clues to help differentiate
normal from pathologic processes include (a) excessive
nausea, anorexia, and vomiting after the first trimester; (b)
weakness; and (c) new pigmentation in the mucous
membranes, extensor surfaces, and scars. Decreased
extracellular volume and electrolyte disturbances (e.g.,
hyponatremia and hyperkalemia) may indicate
aldosterone deficiency.
b. Addisonian crisis. Acute adrenal insufficiency
(Addisonian crisis) can occur in undiagnosed or
 undertreated patients with chronic insufficiency in times
of stress such as preeclampsia, postpartum hemorrhage,
and systemic infections. It generally presents with fever,
vomiting, confusion, hypotension, hypoglycemia, and
hyponatremia. Flank pain may accompany adrenal
infarction or hemorrhage. Maternal baseline cortisol
levels may be higher than expected in the nonpregnant
state because of the physiologic increase observed during
pregnancy. Definitive diagnosis requires an ACTH
stimulation test. Basal serum cortisol levels should
double within 30 minutes of 250 μg of cosyntropin
(Cortrosyn) (synthetic ACTH) administered IV. If this
does not occur, adrenal insufficiency is present, and the
ACTH level should be measured to distinguish primary
from secondary causes. If the clinical picture strongly
suggests adrenal insufficiency, diagnostic and therapeutic
studies should be done simultaneously.
2. Antepartum considerations
a. Maternal complications
The main maternal risks of the disease during pregnancy
are inadequate steroid hormone replacement or failure
to diagnose the disorder. Undiagnosed Addison disease
may be life threatening. If replacement therapy is
appropriate, pregnancy should be uneventful. During
pregnancy, dosing requirements of mineralocorticoids and
glucocorticoids do not differ from those in the
nonpregnant population. Hydrocortisone and prednisone
are the agents of choice because of their lower risk of fetal
exposure.
Parenteral steroids in stress doses are required at
times of severe hyperemesis, labor and delivery, surgical
procedures, and other situations of severe stress.
Glucocorticoid therapy in human pregnancies is not
associated with congenital anomalies, although cleft
 palate has been reported in animal studies.50 Long-term
studies have shown no changes in neurologic
development or somatic growth.
b. Fetal considerations
Fetal growth restriction, neonatal hypoglycemia, and
low birth weight have been documented, but most of
these cases occurred in women with either inadequate or
no steroid replacement. In women with adequate
replacement, there should be no increased fetal
morbidity.
3. Intrapartum and anesthetic considerations
a. Stress-dose steroids. The stress of labor or operative
delivery necessitates parenteral steroids in stress doses.
Hydrocortisone 100 mg q8h should be administered
parenterally while the patient is in active labor or before
CD. Postpartum, steroids should be decreased
incrementally, returning to the patient’s normal
replacement dose over 2 to 3 days.
b. Unexplained hypotension. Most women tolerate labor
and delivery well with the addition of supplemental
corticosteroids. Although there are no specific
recommendations for the administration of neuraxial
anesthetics, unexplained hypotension requires
confirmation of adequate corticosteroid and
mineralocorticoid replacement. Adrenal insufficiency is
associated with the potential for hypotension and
circulatory collapse.
c. Emergency situations. Some emergency situations will
require hydrocortisone infusions and IV fluid
management that is guided by invasive hemodynamic
monitoring. Although neuraxial anesthesia is preferred
in most CDs, some require general anesthesia. In these
cases, judicious dosing of anesthetics is essential because
of the risk of drug-induced myocardial depression.
 Glucose and electrolyte levels must also be measured
perioperatively. If neuromuscular blockade is necessary,
small incremental doses of muscle relaxant should be
administered with the use of a nerve stimulator.

CLINICAL PEARL Glucocorticoid and mineralocorticoid

steroid administration may be required in parturients with adrenal
insufficiency during times of stress.

B. Cushing disease and syndrome

1. Pathophysiology
a. Cushing disease. Cushing disease is caused by
overproduction of ACTH from a pituitary adenoma.
Excess ACTH stimulates the adrenal glands, leading to
overproduction of cortisol. Cushing syndrome refers to
symptoms that result from excessive exposure to steroid
hormones. Pregnancy is rare in patients with Cushing
syndrome because of infertility resulting from
anovulation. Other complications include (a) spontaneous
abortion, (b) preeclampsia, (c) gestational diabetes, and
(d) hypertension.51
b. Cushing syndrome. Cushing syndrome can result from
excessive plasma corticotropin concentrations that
stimulate the adrenal cortex to produce markedly
elevated cortisol levels (i.e., ACTH-dependent) or
excessive production of cortisol by abnormal
adrenocortical tissue that suppresses the secretion of
both corticotropin-releasing hormone (CRH) and
corticotrophin (i.e., corticotropin-independent).52 In a
review of 58 cases of Cushing syndrome during
pregnancy since 1990, 40% resulted from benign adrenal
adenoma, 41% developed adrenal hyperplasia from
elevated ACTH of either pituitary or placental origin, and
 adrenal carcinoma was responsible for 10% of cases.
Other cases resulted from indeterminate causes; one
patient presented with ectopic ACTH from an ACTH-
secreting pheochromocytoma.53
2. Antepartum considerations
a. Clinical presentation. The clinical presentation includes
(i) weight gain, (ii) weakness, (iii) muscle atrophy, (iv)
abdominal striae, (v) easy bruising, (vi) edema, (vii)
hyperpigmentation, (viii) thinning of the skin, (ix)
pathologic fractures, and (x) glucose intolerance. In some
patients, the diagnosis may be delayed because the signs
and symptoms may be attributed to preeclampsia, DM, or
normal pregnancy.51
b. Laboratory studies and imaging. In normal pregnancy,
cortisol levels are elevated two- to threefold. Much of this
cortisol is protein bound, thereby potentially making the
diagnosis difficult. However, women with Cushing
syndrome demonstrate a loss of diurnal variation in
cortisol levels as well as increased urinary free cortisol.
Patients with corticotropin-dependent Cushing syndrome
show marked suppression of free cortisol and 17-
hydroxycorticosteroid levels following a dexamethasone
suppression test. In addition, patients with corticotropin-
independent Cushing syndrome will fail to demonstrate
suppression of baseline corticosteroid levels.
Ultrasonography, computed tomography (CT), or
magnetic resonance imaging (MRI) may be helpful in
ruling out an adenoma or locating a pituitary or adrenal
mass.
c. Maternal and fetal considerations. Cushing syndrome
is associated with significant morbidity and mortality
for mother and fetus.53 In a series of 67 pregnancies,
only 34% resulted in term birth. Pregnancy
complications included (i) spontaneous abortion, (ii)
 stillbirth, (iii) preterm birth, and (iv) IUGR. Maternal
complications included (i) hypertensive disorders, (ii)
glucose intolerance, (iii) congestive heart failure (CHF),
(iv) impaired wound healing, (v) pulmonary embolism,
and (vi) maternal death.53,54
d. Antepartum management. Adrenalectomy, pituitary
irradiation, or medical therapy with metyrapone or
cyproheptadine are associated with fewer stillbirths
and premature births compared to supportive therapy
alone.54 Surgery is the preferred treatment in women with
severe symptoms. There are reports of successful
laparoscopic or open adrenalectomy during the second
and third trimesters. Transsphenoidal hypophysectomy
has been successfully reported during midpregnancy. In
women who are not surgical candidates, medications can
be administered to inhibit cortisol secretion (e.g.,
metyrapone, 5-hydroxytryptamine [HT] antagonist
cyproheptadine, ketoconazole). All these medications
cross the placenta and may cause fetal adrenal
suppression.
3. Anesthetic considerations
a. Preanesthetic considerations. Although severe
hypertension is the most significant complication
encountered during labor and delivery, coagulation,
cardiovascular function, plasma glucose, electrolytes,
and acid–base status should be evaluated before
administering either neuraxial or general anesthesia.
Frequent BP monitoring should be implemented.
Hypertension should be treated promptly because severe
hypertension can be associated with cardiac failure in
these patients. BP control can be achieved with
hydralazine or labetalol. Other complications include (i)
polyuria, (ii) DM, (iii) fluid retention, (iv) hypokalemia,
and (v) alkalosis.
b. Neuraxial anesthesia can be contraindicated because of
coagulation abnormalities. Block placement can be
complicated by a variety of technical problems (e.g.,
central obesity, muscle wasting, bruising of skin,
osteoporosis with vertebral body collapse).55
Hemodynamic responses from vasopressors,
endogenous catecholamines, or sympathectomy may
be exaggerated. Hypotension is best avoided by
incremental administration of local anesthetics, adequate
uterine displacement, and fluid administration.
c. Anesthetic management for operative delivery. Many
of these women will require operative delivery. Either
neuraxial or general anesthesia is an acceptable
technique, with increased awareness for potential
exaggerated hemodynamic responses. In some cases
(e.g., cardiac failure), invasive hemodynamic monitoring
will be necessary to manage complications. The physical
findings of Cushing disease (central obesity, buffalo
hump, increased adipose tissue in the neck and sternal
areas, increased mucosal friability) may all contribute to
difficult airway management.55 In such cases, awake
fiberoptic intubation should be considered.
Neuromuscular blocking agents should be administered
with caution due to muscle weakness. Use of a peripheral
nerve stimulator is essential.
d. Management of severe hypertension. Severe
hypertension can be treated with either hydralazine or
labetalol. BP should be reduced to 160 mm Hg systolic
and 90 to 100 mm Hg diastolic. Before induction of
general anesthesia, nitroglycerin in bolus doses of 50 mg
will help maintain BP in an acceptable range. IV lidocaine
will also attenuate the sympathetic response to intubation.
IV opioids after cord clamping will reduce, but not
eliminate, the release of cortisol from surgical stimulation.
CLINICAL PEARL Severe hypertension is the most common
complication encountered during anesthetic management of the
parturient with Cushing syndrome.

C. Pheochromocytoma
Pheochromocytoma is a rare cause of hypertension with an
incidence of approximately 0.1% in the general population.56
Reported prevalence in pregnancy is 0.02%.57 Despite its rarity in
pregnancy, pheochromocytoma is potentially lethal for both
mother and fetus with mortality rates of up to 17% and 40%,
respectively, if untreated; however, prenatal diagnosis with
appropriate therapy dramatically reduces the maternal and fetal
mortality rate to <1% and <15%, respectively.58
Pheochromocytoma should therefore be considered as part of the
differential diagnosis of hypertension during pregnancy.
1. Maternal and fetal risks
a. Maternal risks include hypertensive crisis, which can
lead to (i) myocardial infarction (MI), (ii) stroke, (iii)
dysrhythmias, (iv) CHF, and (v) death. Hypertensive
crisis may be precipitated by general anesthesia, vaginal
delivery, and/or mechanical compression of the tumor
caused by an enlarging uterus.
b. Fetal risks are increased because of severe maternal
hypertension that may lead to IUGR, uteroplacental
insufficiency, fetal hypoxia, and death.
2. When to suspect a pheochromocytoma
Signs that differentiate pheochromocytoma from pregnancy-
related hypertension include (i) paroxysmal nature of the
hypertension; (ii) lack of proteinuria, ankle edema, or elevated
plasma uric acid level; (iii) presence of hypertensive
complications such as heart failure and pulmonary edema; and
(iv) presence of unexplained orthostatic hypotension.58 BP
might paradoxically worsen if a predominately β-blocking
 drug such as labetalol were given due to unopposed alpha
adrenergic effect. Women with pheochromocytoma generally
present with labile and difficult to control hypertension. A
20% incidence of proteinuria is seen with
pheochromocytoma, making it difficult to distinguish from
preeclampsia. Pheochromocytoma should be suspected in
women with paroxysmal symptoms such as headache,
tremors, or sweating. Severe and intermittent hypertension,
lack of edema, development of hypertension before 20 weeks,
and the coexistence of GDM may be other clues to the
diagnosis. Most pheochromocytomas are sporadic. However,
there are several familial neuroendocrine disorders of
which pheochromocytoma is a part. These include multiple
endocrine neoplasia (MEN) type 2A, MEN type 2B, von
Hippel-Lindau disease, and neurofibromatosis. Family history
should be obtained and the patient examined for clinical
features of these syndromes.
3. Diagnosis of pheochromocytoma
a. The most sensitive diagnostic test for pheochromocytoma
is differential measurement of metanephrines in urine
or in plasma because these measurements are unaffected
by pregnancy. A baseline 24-hour urine collection should
be obtained. If this sample is normal, a 24-hour collection
starting at the onset of a clinical episode should be
obtained. In general, a value greater than two times
normal indicates pheochromocytoma.
b. Several pharmacologic agents interfere with
measurement of catecholamine levels. These include (i)
tricyclic antidepressants, (ii) labetalol, (iii) methyldopa,
(iv) ethanol, and (v) benzodiazepines, all of which
increase catecholamine values. Use of agents that
interfere with catecholamine measurement should be
discontinued 7 to 14 days before sample collection.59
c. Anatomic localization of the tumor should be performed
 by MRI because this imaging modality is not associated
with harm to the fetus. MRI has a sensitivity of close to
100% for lesions >1.5 cm and can be used to document
extraadrenal lesions. Other imaging modalities have been
used, but CT scanning requires ionizing radiation and
contrast dye. Ultrasonography lacks sensitivity.
Metaiodobenzylguanidine (MIBG) scanning is
contraindicated in pregnancy.

CLINICAL PEARL The clinical diagnosis of

pheochromocytoma can be difficult to differentiate from the
parturient with preeclampsia or illicit drug abuse, even in the patient
with the classic triad of paroxysmal hypertension, headache, and
sweating with palpitations.

4. Medical therapy for pheochromocytoma

A skilled multidisciplinary team consisting of
anesthesiologists, internists, obstetricians, and neonatologists
is required for management of this disorder. A care plan
agreed on by all members of the team should be created.
Medical therapy, in the form of a-blockade, should be
initiated once a biochemical diagnosis is made, even if
localization procedures are not complete. The treatment of
choice in pregnancy is phenoxybenzamine, an irreversible α-
blocker. The benefits of α-blockade in pregnancy outweigh
any potential unknown teratogenic or long-term effects. β-
Blockade should be instituted after α-blockade is achieved
in order to avoid tachyarrhythmias. The dose should be
titrated to achieve a maternal heart rate of 80 to 100 beats per
minute. The potential fetal risks of β-blockade include
decreased FHR, neonatal hypoglycemia, neonatal
hyperbilirubinemia, and apnea.
5. Timing of surgery for pheochromocytoma
 After adequate medical therapy and localization of the
tumor, surgery can be considered. The optimal timing of
surgery in pregnancy depends on gestational age, adequacy
of a-blockade, and accessibility of the tumor. It is generally
agreed that if the tumor is diagnosed in the first two
trimesters, the tumor should be surgically removed after
adequate α-blockade. If the pheochromocytoma is discovered
in the third trimester, surgery should be delayed until
delivery if the mother can be managed adequately with
medications. After 24 weeks’ gestation, the size of the uterus
makes abdominal exploration difficult unless the fetus is
delivered first. CD has been suggested as the delivery method
of choice because it is associated with a lower incidence of
maternal death compared with labor and vaginal delivery.60
Optimal preoperative values for patients with
pheochromocytoma include BP values <165/90 mm Hg for 48
hours before surgery, the presence of orthostatic hypotension
(but not <80/45 mm Hg), the absence of new ST-T changes on
ECG, and <1 premature ventricular contraction (PVC) every 5
minutes.61

CLINICAL PEARL CD is preferred over a vaginal delivery due

to a decreased risk for maternal catecholamine release during labor
and maternal mortality.

6. Intrapartum and surgical considerations

CD is the preferred method of delivery in patients with
pheochromocytoma. This method of delivery minimizes the
increased pressure on the tumor that may occur during active
labor.
7. Anesthetic considerations
The goal of anesthetic management of the pregnant patient
with pheochromocytoma is to avoid medications and
situations that will result in stimulation of the sympathetic
nervous system.
a. Monitoring. Monitoring should allow early detection of
a catecholamine surge and should include invasive
arterial BP monitoring. Continuous ECG, pulse oximeter,
capnograph, temperature, and urinary output should also
be monitored during labor for vaginal deliveries as well as
cesarean deliveries.
b. General anesthetic considerations
(1) Laryngoscopy and tracheal intubation may trigger
an acute hypertensive crisis leading to
cerebrovascular accident (CVA), MI, uteroplacental
insufficiency, and fetal death. Therefore, surgical
depth of anesthesia should be achieved before
attempts at laryngoscopy and endotracheal intubation.
An IV lidocaine bolus may attenuate catecholamine-
induced responses such as dysrhythmias and
hypertension. IV nitroprusside or remifentanil can
be administered before intubation to assist in blunting
the hypertensive response to intubation.62 Ketamine
should be avoided as an induction agent because of
its association with sympathetic nervous system
stimulation. IV infusions of magnesium sulfate
throughout surgery and delivery have been used
successfully in pregnancy.63,64 Magnesium has a
number of benefits that make it an ideal agent,
including (i) inhibition of catecholamine release from
both the adrenal medulla and the peripheral
adrenergic terminals, (ii) reduction of postsynaptic α-
adrenergic receptors, and (iii) peripheral
vasodilation.63 In addition to nitroprusside and
magnesium sulfate, phentolamine, nitroglycerin,
trimethaphan, and propranolol have all been used
successfully to control intraoperative hypertension
 and tachycardia in pregnant patients with
pheochromocytoma.
(2) Maintenance of anesthesia is most often achieved by
a combination of volatile anesthetic, nitrous oxide,
and opioid. Isoflurane is often preferred because of
its vasodilatory properties. It also provides excellent
anesthesia and does not sensitize the myocardium to
catecholamines.65 Desflurane should be avoided
because of the catecholamine release associated with
its use during rapid administration at high
concentrations.
(3) Medications. Some medications should be avoided
perioperatively because they may directly or
indirectly increase catecholamine release by the
tumor. They include (a) atracurium, (b) droperidol,
(c) halothane, (d) metoclopramide, (e) morphine, (f)
pancuronium, (g) pentazocine, (h) succinylcholine,
and (i) vancomycin.

CLINICAL PEARL Steps to blunt the hypertensive and

tachycardic responses to the induction of anesthesia and
endotracheal intubation are required during general anesthesia for
CD.

c. Neuraxial anesthesia
Epidural anesthesia has been used successfully for
both excisions of pheochromocytoma and CD in
pregnant patients.66 Spinal anesthesia can produce
sudden hemodynamic changes that require vasopressor
therapy and therefore epidural anesthesia is preferred
for most cases. Adequate preoperative α-blockade and
reexpansion of plasma volume are essential before
initiating anesthesia. The use of a combined epidural
 technique with general anesthesia must be balanced
against the risk of hypertension during epidural
placement. In addition, sympathetic blockade resulting
from epidural anesthesia does not protect against
catecholamine release during tumor manipulation.67
8. Fetal considerations
Transient neonatal hypotension may be seen in the neonate
following delivery due to transplacental passage of
phenoxybenzamine. Magnesium use can cause neonatal
hypotonia.
V. Conclusion
DM and other endocrine disorders carry significant maternal and fetal
risks during pregnancy. However, the risks can be greatly reduced by
timely diagnosis, optimizing treatment, and involving a
multidisciplinary team in patient care. Communication between
obstetrician, anesthesiologist, and endocrinologist is of utmost
importance. Clear coordinated care plans that are well
documented will aid in producing positive obstetric outcomes for
the affected mothers and their newborns.

REFERENCES
1. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 137: gestational
diabetes mellitus. Obstet Gynecol. 2013;122:406–416.
2. Hedderson MM, Gunderson EP, Ferrara A. Gestational weight gain and risk of gestational diabetes
mellitus. Obstet Gynecol. 2010;115:597–604.
3. Ferrara A. Increasing prevalence of gestational diabetes mellitus: a public health perspective. Diabetes
Care. 2007;30(suppl 2): S141–S146.
4. Kimmerle R, Heinemann L, Delecki A, et al. Severe hypoglycemia incidence and predisposing factors
in 85 pregnancies of type 1 diabetic women. Diabetes Care. 1992;15:1034–1037.
5. Best RM, Chakravarthy U. Diabetic retinopathy in pregnancy. Br J Ophthalmol. 1997;81:249–251.
6. Miodovnik M, Rosenn BM, Khoury JC, et al. Does pregnancy increase the risk for development and
progression of diabetic nephropathy? Am J Obstet Gynecol. 1996;174:1180–1191.
7. Purdy LP, Hantsch CE, Molitch ME, et al. Effect of pregnancy on renal function in patients with
moderate-to-severe diabetic renal insufficiency. Diabetes Care. 1996;19:1067–1074.
8. White P. Classification of obstetric diabetes. Am J Obstet Gynecol. 1978;130:228–230.
9. Casey BM, Lucas MJ, Mcintire DD, et al. Pregnancy outcomes in women with gestational diabetes
compared with the general obstetric population. Obstet Gynecol. 1997;90:869–873.
10. Macintosh MC, Fleming KM, Bailey JA, et al. Perinatal mortality and congenital anomalies in babies
of women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based
study. BMJ. 2006;333:177.
11. Boulet SL, Alexander GR, Salihu HM, et al. Macrosomic births in the United States: determinants,
outcomes, and proposed grades of risk. Am J Obstet Gynecol. 2003;188:1372–1378.
12. Langer O, Levy J, Brutsman L, et al. Glycemic control in gestational diabetes mellitus—how tight is
tight enough: small for gestational age versus large for gestational age? Am J Obstet Gynecol.
1989;161:646–653.
13. Falavigna M, Schmidt MI, Trujillo J, et al. Effectiveness of gestational diabetes treatment: a
systematic review with quality of evidence assessment. Diabetes Res Clin Pract. 2012;98:396–405.
14. Dabelea D. The predisposition to obesity and diabetes in offspring of diabetic mothers. Diabetes Care.
2007;30(suppl 2): S169–S174.
15. American College of Obstetricians and Gynecologists Committee on Practice Bulletins—Obstetrics.
ACOG Practice Bulletin: clinical management guidelines for obstetricians-gynecologists: number 60,
March 2005: pregestational diabetes mellitus. Obstet Gynecol. 2005;105:675–685.
16. Mathiesen ER, Kinsley B, Amiel SA, et al. Maternal glycemic control and hypoglycemia in type 1
diabetic pregnancy: a randomized trial of insulin aspart versus human insulin in 322 pregnant women.
Diabetes Care. 2007;30:771–776.
17. Hirsch IB. Insulin analogues. N Engl J Med. 2005;352:174–183.
18. Lv S, Wang J, Xu Y. Safety of insulin analogs during pregnancy: a meta-analysis. Arch Gynecol
Obstet. 2015. http://www.ncbi.nlm.nih.gov/pubmed/25855052. Accessed May 5, 2015.
19. Ekpebegh CO, Coetzee EJ, van der Merwe L, et al. A 10-year retrospective analysis of pregnancy
outcome in pregestational type 2 diabetes: comparison of insulin and oral glucose-lowering agents.
Diabetic Med. 2007;24:253–258.
20. Su DF, Wang XY. Metformin vs insulin in the management of gestational diabetes: a systematic
review and meta-analysis. Diabetes Res Clin Pract. 2014;104:353–357.
21. Langer O, Yogev Y, Xenakis EM, et al. Insulin and glyburide therapy: dosage, severity level of
gestational diabetes, and pregnancy outcome. Am J Obstet Gynecol. 2005;192:134–139.
22. Carroll MA, Yeomans ER. Diabetic ketoacidosis in pregnancy. Crit Care Med. 2005;33(suppl
10):S347–S353.
23. Nayak S, Lippes HA, Lee RV. Hyperglycemic hyperosmolar syndrome (HHS) during pregnancy. J
Obstet Gynaecol. 2005;25:599–601.
24. Gordon M, Landon MB, Samuels P, et al. Perinatal outcome and long-term follow-up associated with
modern management of diabetic nephropathy. Obstet Gynecol. 1996;87:401–409.
25. Boulvain M, Stan C, Irion O. Elective delivery in diabetic pregnant women. Cochrane Database Syst
Rev. 2001;(2):CD001997.
26. Mendiola J, Grylack LJ, Scanlon JW. Effects of intrapartum maternal glucose infusion on the normal
fetus and newborn. Anesth Analg. 1982;61:32–35.
27. Millar LK, Wing DA, Leung AS, et al. Low birth weight and preeclampsia in pregnancies complicated
by hyperthyroidism. Obstet Gynecol. 1994;84:946–949.
28. Gyamfi C, Wapner RJ, D’Alton ME. Thyroid dysfunction in pregnancy: the basic science and clinical
evidence surrounding the controversy in management. Obstet Gynecol. 2009;113:702–707.
29. Mestman JH. Hyperthyroidism in pregnancy. Curr Opin Endocrinol Diabetes Obes. 2012;19:394–401.
30. Laurberg P, Nygaard B, Glinoer D, et al. Guidelines for TSH-receptor antibody measurements in
pregnancy: results of an evidence-based symposium organized by the European Thyroid Association.
Eur J Endocrinol. 1998;139:584–586.
31. Mandel SJ, Cooper DS. The use of antithyroid drugs in pregnancy and lactation. J Clin Endocrinol
 Metab. 2001;86:2354–2359.
32. Mestman JH. Hyperthyroidism in pregnancy. Best Pract Res Clin Endocrinol Metab. 2004;18:267–
288.
33. Pan PH, Tonidandel AM. Anesthesia for pregnant patients with endocrine disorders. In: Suresh MS,
Segal BS, Preston R, et al, eds. Shnider and Levinson’s Anesthesia for Obstetrics. 5th ed. Philadelphia,
PA: Lippincott Williams & Wilkins; 2013: 462–484.
34. Luton D, Le Gac I, Vuillard E, et al. Management of Graves’ disease during pregnancy: the key role of
fetal thyroid gland monitoring. J Clin Endocrinol Metab. 2005;90:6093–6098.
35. Pugh S, Lalwani K, Awal A. Thyroid storm as a cause of loss of consciousness following anaesthesia
for emergency caesarean section. Anaesthesia. 1994;49:35–37.
36. Nayak B, Burman K. Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am.
2006;35:663–686.
37. Sheffield JS, Cunningham FG. Thyrotoxicosis and heart failure that complicate pregnancy. Am J
Obstet Gynecol. 2004;190:211–217.
38. Duggal J, Singh S, Kuchinic P, et al. Utility of esmolol in thyroid crisis. Can J Clin Pharmacol.
2006;13:e292–e295.
39. Bowman ML, Bergmann M, Smith JF. Intrapartum labetalol for the treatment of maternal and fetal
thyrotoxicosis. Thyroid. 1998;8:795–796.
40. Zadra N, Giusti F, Midrio P. Ex utero intrapartum surgery (EXIT): indications and anaesthetic
management. Best Pract Res Clin Anaesthesiol. 2004;18:259–271.
41. Casey BM, Leveno KJ. Thyroid disease in pregnancy. Obstet Gynecol. 2006;108:1283–1292.
42. Leung AS, Millar LK, Koonings PP, et al. Perinatal outcome in hypothyroid pregnancies. Obstet
Gynecol. 1993;81:349–353.
43. Wartofsky L. Myxedema coma. Endocrinol Metab Clin North Am. 2006;35:687–698.
44. Chandraharan E, Arulkumaran S. Pituitary and adrenal disorders complicating pregnancy. Curr Opin
Obstet Gynecol. 2003;15:101–106.
45. Molitch ME. Medical management of prolactin-secreting pituitary adenomas. Pituitary. 2002;5:55–65.
46. Kupersmith MJ, Rosenberg C, Kleinberg D. Visual loss in pregnant women with pituitary adenomas.
Ann Intern Med. 1994;121:473–477.
47. McGrail KM, Beyerl BD, Balck PM, et al. Lymphocytic adenohypophysitis of pregnancy with
complete recovery. Neurosurgery. 1987;20:791–793.
48. Reusch JE, Kleinschmidt-DeMasters BK, Lillehei KO, et al. Preoperative diagnosis of lymphocytic
hypophysitis (adenohypophysitis) unresponsive to short course of dexamethasone: case report.
Neurosurgery. 1992;30:268–272.
49. Kalelioglu I, Kubat Uzum A, Yildirim A, et al. Transient gestational diabetes insipidus diagnosed in
successive pregnancies: review of pathophysiology, diagnosis, treatment, and management of delivery.
Pituitary. 2007;10:87–93.
50. Czeizel AE, Rockenbauer M. Population-based case-control study of teratogenic potential of
corticosteroids. Teratology. 1997;56:335–340.
51. Delibasi T, Ustun I, Aydin Y, et al. Early severe pre-eclamptic findings in a patient with Cushing’s
syndrome. Gynecol Endocrinol. 2006;22:710–712.
52. Orth DN. Cushing’s syndrome. N Engl J Med. 1995;332:791–803.
53. Aron DC, Schnall AM, Sheeler LR. Cushing’s syndrome and pregnancy. Am J Obstet Gynecol.
1990;162:244–252.
54. Buescher MA, McClamrock HD, Adashi EY. Cushing syndrome in pregnancy. Obstet Gynecol.
1992;79:130–137.
55. Glassford J, Eagle C, McMorland GH. Caesarean section in a patient with Cushing’s syndrome. Can
 Anaesth Soc J. 1984;31:447–450.
56. Mannelli M, Bemporad D. Diagnosis and management of pheochromocytoma during pregnancy. J
Endocrinol Invest. 2002;25:567–571.
57. Harper MA, Murnaghan GA, Kennedy L, et al. Phaeochromocytoma in pregnancy: five cases and a
review of the literature. Br J Obstet Gynaecol. 1989;96:594–606.
58. Kamoun M, Mnif MF, Charfi N, et al. Adrenal diseases during pregnancy: pathophysiology, diagnosis,
and management strategies. Am J Med Sci. 2014;347:64–73.
59. Young WF Jr. Pheochromocytoma and primary aldosteronism: diagnostic approaches. Endocrinol
Metab Clin North Am. 1997;26:801–827.
60. Botchan A, Hauser R, Kupfermine M, et al. Pheochromocytoma in pregnancy: case report and review
of the literature. Obstet Gynecol Surv. 1995;50:321–327.
61. Fleisher LA, Mythen M. Anesthetic implications of concurrent diseases. In: Miller RD, ed. Miller’s
Anesthesia. 8th ed. Philadelphia, PA: Elsevier; 2015:1156–1225.
62. Dugas G, Fuller J, Singh S, et al. Pheochromocytoma and pregnancy: a case report and review of
anesthetic management. Can J Anaesth. 2004;51:134–138.
63. James MF, Huddle KR, Owen AD, et al. Use of magnesium sulphate in the anaesthetic management of
phaeochromocytoma in pregnancy. Can J Anaesth. 1988;35:178–182.
64. Hudsmith JG, Thomas CE, Browne DA. Undiagnosed phaeochromocytoma mimicking severe
preeclampsia in a pregnant woman at term. Int J Obstet Anesth. 2006;15:240–245.
65. Pullerits J, Ein S, Balfe JW. Anaesthesia for phaeochromocytoma. Can J Anaesth. 1988;35:526–534.
66. Stonham J, Wakefield C. Phaeochromocytoma in pregnancy: caesarean section under epidural
analgesia. Anaesthesia. 1983;38:654–658.
67. Kinney MA, Narr BJ, Warner MA. Perioperative management of pheochromocytoma. J Cardiothorac
Vasc Anesth. 2002;16:359–369.
 Thrombophilias/Coagulopathies
James P.R. Brown and M. Joanne Douglas

I. Overview of normal hemostatic coagulation
II. Physiologic changes of coagulation in pregnancy
A. Platelets
B. Coagulation factors
C. Thrombotic control
D. Fibrinolysis
III. Measurements of coagulation in pregnancy
A. Routine tests
B. Bleeding time
C. Near patient testing
IV. Thrombophilia
A. Risk factors for thromboembolic disease in pregnancy
B. Inherited thrombophilias
C. Management of parturients with suspected thrombophilia
D. Acquired thrombophilias
E. Anesthetic implications: neuraxial anesthesia and
anticoagulants
V. Disorders of coagulation
A. Inherited disorders of coagulation
B. Acquired disorders of coagulation
C. Disseminated intravascular coagulation
Summary


KEYPOINTS
1. Hypercoagulability. Normal parturients are hypercoagulable at term.
Parturients are at risk for venous thromboembolic events (VTEs) during
pregnancy and up to 6 weeks’ postpartum.
2. Predicting bleeding risk. No single blood test can predict the risk of
clinically significant bleeding, for example, neuraxial hematoma from
epidural anesthesia or postpartum hemorrhage.
3. Thromboembolic risk reduction. Management of anticoagulation
during pregnancy should be tailored to individual risk. Considerations
include inherited thrombophilias, family, and personal history of previous
VTE.
4. Anesthetic management. When considering neuraxial anesthesia, there
should be an individual assessment of risk versus benefit. Peripartum
management requires multidisciplinary input (obstetrician,
anesthesiologist, hematologist).

TO MINIMIZE BLOOD LOSS AT birth, physiologic adaptations during normal

pregnancy result in a hypercoagulable state. These physiologic adaptations
include an increase in certain coagulation factors and a decrease in some
fibrinolytic factors. Although protective against hemorrhage, the
hypercoagulable state increases parturients’ risk of venous thromboembolic
events (VTEs).1 Disorders of coagulation during pregnancy are associated with
significant morbidity and mortality. Important related anesthetic considerations
are reducing occurrence of VTE, assessing safety of neuraxial anesthesia, and
managing obstetric hemorrhage.
I. Overview of normal hemostatic coagulation
Hemostasis is achieved through a complex interaction between blood
cells, clotting factors, and vascular endothelium. Procoagulant effects
are balanced by antithrombotic mechanisms, limiting the hemostatic
process to the site of injury.
The cell-based theory of coagulation (see Figs. 24.1 to 24.5) has
replaced the classically described clotting cascade. Cell-based theory
emphasizes the role of cell surfaces in providing an environment
(organizing surface) for the reactions required to achieve hemostasis.
 Vascular spasm, mediated by vasoconstrictor substances released
from platelets, reduces blood flow and occurs in the first stages of
hemostasis. Damaged endothelium attracts platelets, which adhere to
it, forming a platelet plug. A clot forms as the platelet plug is
stabilized with fibrin.
Hemostasis occurs in several phases.
II. Physiologic changes of coagulation in pregnancy
In general, there is an increase in most coagulation factors and a
decrease in native anticoagulants and fibrinolytics. As a result, normal
pregnancy is associated with a sixfold increase in VTE. Incidence is
highest in the third trimester and postpartum. Because of the
physiologic changes that occur in coagulation with pregnancy,
reference ranges are different from the normal population. Changes at
term are summarized in Table 24.1.
A. Platelets2
1. Platelet count decreases throughout pregnancy, is lowest at
term, and normalizes 4 to 6 weeks postpartum
2. Decrease is due to the destruction by the uteroplacental unit
and dilution by expanded plasma volume
3. Production and function are normal, lifespan is decreased, and
mean volume increased.
B. Coagulation factors3
1. FVIII, X, XII, and von Willebrand factor (vWF) increase.
2. FVII may increase by up to tenfold.
3. Fibrinogen can double.
4. FXIII increases in the first trimester, but falls to half of
prepregnancy levels by term.
5. Reports on FIX and FXI levels are conflicting.
C. Thrombotic control3
1. Protein C (PC) levels remain stable or slightly increased.
2. Protein S (PS) levels decrease.
3. Antithrombin levels are unchanged.
D. Fibrinolysis3
1. Tissue plasminogen activity (tPA) is reduced.
2. The decrease is the result of increased plasminogen activator
inhibitor-1 and -2 (PAI-1 and PAI-2); PAI-2 is primarily
 produced by placenta
3. Thrombin-activatable fibrinolysis inhibitor (TAFI) is
increased by term.
III. Measurements of coagulation in pregnancy
A. Routine tests
When combined with a clinical history, routine tests act as a
screening tool to exclude coagulopathies. As highlighted by the
cell-based model, these routine tests may not represent what is
happening in vivo.
1. Platelet count as part of a complete blood count (CBC)
2. Prothrombin time (PT) or international normalized ratio
(INR) measures the extrinsic and common pathways (see Fig.
24.6).

3. Activated partial thromboplastin time (aPTT) measures the

 intrinsic and common pathways (see Fig. 24.6).
4. Fibrinogen. There has been recent interest in the fibrinogen
level taken at first diagnosis of postpartum hemorrhage (PPH)
as a predictive marker of the severity of PPH. If fibrinogen is
<2 g per L, the adjusted odds ratio for severe PPH is 12.4
B. Bleeding time
Although an in vivo measure of hemostasis, its clinical use is
limited. It is invasive, and the results are operator dependent. It is
nonspecific and nonsensitive at predicting perioperative
bleeding.5
C. Near patient testing
1. Proposed roles of near patient testing:
a. Replace formal CBC for emergent surgery where
neuraxial anesthesia is considered.
b. Assess platelet function in parturients with
thrombocytopenia.
c. Screen for suspected platelet dysfunction, for example,
those with a history of easy bruising/bleeding.
d. Assess anticoagulant status, for example, after stopping
heparin therapy.
e. Guide blood product replacement in obstetric hemorrhage.
2. Currently, there is no evidence to support the ability of near
patient testing to predict risk of clinical bleeding, for example,
the risk of epidural hematoma with neuraxial anesthesia.
a. Thromboelastography6–8 or thromboelastometry9–11
(1) Dynamic viscoelastic tests: provide a visual
representation of hemostasis: clot initiation,
formation, stability, breakdown
(2) Global assay of whole blood
(3) Platelet function is represented by maximum
amplitude (MA); MA is also influenced by fibrinogen
levels.
(4) MA is increased in normal pregnancy, representing
the hypercoagulable state.8
 (5) Disadvantage: the tests do not detect effect of
antiplatelet therapy, for example, aspirin
b. Platelet function analyzer (PFA 100)6,7,12
(1) Represents primary hemostasis as closure time (CT):
the time taken for platelet plug to form in an aperture
when whole blood is placed on a collagen sheet
(2) One study supporting PFA as a test for platelet
quality and quantity suggested CT increases in
healthy parturients with a platelet count <80 × 109. l
−1 and was more sensitive than thromboelastography

(TEG) at identifying platelet dysfunction associated

with preeclampsia in those with a normal platelet
count.7
IV. Thrombophilia
Thrombophilia is associated with the following thromboembolic
complications:13
• Arterial and VTEs
• Recurrent fetal loss
• Intrauterine growth restriction
• Preeclampsia with severe features
• Placental abruption
A. Risk factors for thromboembolic disease in pregnancy
1. Virchow’s triad: the causes of thrombosis
a. Hypercoagulability
(1) Hemostatic changes of pregnancy (Table 24.1)
(2) Inherited thrombophilia (see Section IV.B.)
(3) Acquired thrombophilia
(a) Antiphospholipid syndrome (APS)
(b) Nephrotic syndrome (antithrombin loss)
b. Stasis
(1) Venous distension
(2) Mechanical obstruction to venous return from lower
limbs by the gravid uterus
(3) Bed rest
 c. Endothelial injury
(1) Cesarean delivery
(2) Traumatic vaginal delivery
2. Additional risk factors
a. Obesity
b. Age >35 years
c. Infection
3. Although risk factors increase the incidence of VTE, events
frequently occur in parturients without risk factors.14

CLINICAL PEARL Postpartum anticoagulation

Because VTE is a major cause of maternal morbidity and mortality,
particularly after operative delivery, a way to improve patient
outcome is to assess the risk of VTE in all patients undergoing
cesarean delivery and anticoagulate those at high risk. Specific
protocols should prompt physicians to assess the postpartum VTE
risk for each parturient and include dosing and timing schedules for
low molecular weight heparin (LMWH) relative to time of
neuraxial procedures (including neuraxial catheter removal) and
surgery. One approach to ensure that anticoagulation is considered
after operative delivery is to include VTE risk and anticoagulation
as part of the Surgical Safety Checklist.

B. Inherited thrombophilias
Inherited thrombophilias are responsible for 30% of maternal
VTE; half of these are a result of either Factor V (FV) Leiden or
prothrombin gene abnormalities.15,16 Genes associated with
increased VTE risk are carried by 15% of the Caucasian
population.17
1. Factor V Leiden
a. Most prevalent inherited thrombophilia13
b. Prevalence highest in European Caucasian populations
 c. Mutation in FV gene, rendering FV resistant to
inactivation by activated PC (Fig. 24.4). This leads to
slower breakdown of FV, increased thrombin production,
and a prothrombotic state.
d. Heterozygous state common: rarely leads to VTE unless
combined with another risk factor, such as pregnancy
e. Homozygous state increases VTE risk by up to 80
times.17
2. Prothrombin gene mutation
a. Point mutation (G20210A)
b. Increases the circulation of functionally normal
prothrombin
c. Most VTEs occur in those patients with additional risk
factors
d. Commonly inherited with FV Leiden. With both
mutations: 100-fold increase in VTE.16
3. Antithrombin deficiency
a. Previously known as antithrombin (AT) III deficiency
b. Most severe of the inherited thrombophilias
c. AT is a natural anticoagulant that binds and deactivates
thrombin: AT decreases the production and half-life of
thrombin. It also binds and deactivates Factors IXa, Xa,
XIa, and XIIa (Fig. 24.4).
d. Parturients with normal AT activity, but decreased
quantity, have a 400 times increased risk of VTE.15
e. There are greater than 250 mutations that either reduce
quantity or quality of AT production
f. Homozygous individuals are rare: most die in utero.
g. AT deficiency can be acquired, for example, liver disease,
malnutrition, or consumptive coagulopathy.
4. Protein C deficiency
a. Natural anticoagulant, degrades FVa and FVIIIa
b. Strong inhibitor of coagulation, activated by the
thrombin/thrombomodulin complex in the presence of
 protein S (a cofactor)18 (Fig. 24.4)
c. PC deficiency results from more than 160 distinct
mutations, with variable quality and quantity of PC
produced.13
5. Protein S deficiency
a. Is a cofactor for activated PC
b. Also directly inactivates FVa and FXa
c. Normal pregnancy increases protein binding of PS,
reducing the availability of unbound active PS.
(1) Individuals homozygous for either PC or PS
deficiency present with neonatal purpura fulminans
and require lifelong anticoagulation.13
C. Management of parturients with suspected thrombophilia
1. Screening for thrombophilia
a. Screening results guide individual risk assessment and
decisions about anticoagulation. Testing for all genetic
mutations listed in Table 24.2 should take place prior to
pregnancy in parturients with:

(1) Previous history of a VTE

(2) First-degree relative with a history of thrombophilia
b. Pregnancy, recent thrombosis, and anticoagulation
treatment can affect test results.13
2. Treatment
a. Extent of anticoagulation therapy based on an individual
risk assessment depending on:
(1) Prior personal and family history of VTE
(2) Presence of genetic mutation
(3) Additional risk factors, for example, immobility,
obesity, cesarean delivery13
b. VTE risk is greater in the first 6 weeks postpartum than
during pregnancy: Anticoagulation needs to be continued,
or increased, postpartum.
c. Inherited thrombophilias are divided into low and high
risk; this guides anticoagulation management (Table
24.3).13

(1) Low-risk thrombophilias. Heterozygous FV Leiden

or prothrombin gene mutation, PC, or PS deficiency
(2) High-risk thrombophilias. AT deficiency,
homozygous FV Leiden, or prothrombin gene
 mutation, combination of heterozygous disorders
(a) Anticoagulation therapy employs either
unfractionated heparin (UFH) or LMWH and
can be divided into prophylactic, intermediate,
or therapeutic dosing (Table 24.4).

(b) Dose of therapeutic UFH is monitored and

adjusted according to aPTT.
(c) Therapeutic LMWH is prescribed according to
patient weight.
(d) Serum anti-Xa levels can guide dosing of
therapeutic LMWH, but is typically performed
only in individuals with extremes of weight or
significant renal impairment.
(e) Warfarin, UFH, and LMWH are not
contraindicated in breastfeeding.
D. Acquired thrombophilias
1. Antiphospholipid syndrome (APS)20,21
a. Autoimmune cause of hypercoagulability
b. Defined by the presence of circulating antiphospholipid
antibodies (APLA) and clinical manifestations of
thrombotic disease
c. Clinical manifestations: either venous (65% to 70%) or
 arterial thrombosis or pregnancy morbidity, that is, ≥3
early pregnancy losses
d. Can be primary (occurring in isolation) or secondary
(associated with connective tissue diseases such as
systemic lupus erythematosus)
e. Three APLA contribute to the syndrome: lupus
anticoagulant, anticardiolipin, and anti-β2-glycoprotein I
(1) APLA can bind to platelets and block target proteins,
including PC and tPA, interfering with thrombotic
control and fibrinolysis, leading to a procoagulant
state.
(2) APLA have prothrombotic effect in maternal–
placental circulation.
f. APS is associated with several obstetric complications
(1) Recurrent pregnancy loss
(2) Preeclampsia
(3) Intrauterine growth restriction
(4) Complications are probably related to thrombosis of
the uteroplacental vasculature and placental
infarction; other mechanisms may contribute
(5) APLA influences trophoblastic invasion and hormone
production.20
g. Forty percent to 50% of patients with APS also develop
autoimmune thrombocytopenia.21
h. Expert opinion for the management of APS:21
(1) History of VTE: recommend prophylactic antepartum
and postpartum anticoagulation.
(2) Without prior VTE: women may benefit from
prophylactic antepartum and postpartum
anticoagulation
(3) With a history of recurrent pregnancy loss:
Anticoagulation may be combined with low-dose
aspirin.
2. Thrombotic microangiopathies
 a. Cause pathologic occlusion of the microvasculature by
disseminated microthrombi22
b. Most prominent pregnancy-associated thrombotic
microangiopathies are hemolysis, elevated liver enzymes,
low platelets (HELLP) syndrome, thrombotic
thrombocytopenic purpura (TTP), and hemolytic uremic
syndrome (HUS). These conditions are frequently
associated with consumptive thrombocytopenia (see
Section V.B.).
E. Anesthetic implications: neuraxial anesthesia and
anticoagulants
1. Heparin is the most common anticoagulant used in pregnancy
because it does not cross the placenta and lacks teratogenicity.
Warfarin is teratogenic in the first trimester but on occasion is
used later in pregnancy in women who cannot tolerate
heparin. It is important to plan the timing of administration of
anticoagulation peripartum, balancing the opportunity for
neuraxial anesthesia with reducing incidence of PPH and
managing VTE risk. Neuraxial hematoma as a complication
of neuraxial anesthesia is rare in the absence of coagulopathy,
approximately 1:150,000 following epidural and 1:220,000
after spinal anesthesia.19,23
2. The American Society of Regional Anesthesia (ASRA) has
published guidelines regarding neuraxial anesthesia in
anticoagulated patients:19
a. Convert oral anticoagulation to LMWH or UFH by 36
weeks.
b. At least 36 hours prior to induction of labor or cesarean
delivery, discontinue LMWH or subcutaneous UFH.
c. Stop intravenous UFH 4 to 6 hours prior to anticipated
delivery.
d. Advise the parturient to withhold LMWH if labor is
suspected.
e. Where possible, schedule an induction of labor or
 cesarean delivery.
f. Plan restarting anticoagulation postpartum.
g. Perform neurologic monitoring postneuraxial block to
ensure full recovery
3. Relevant recommendations in terms of timing of neuraxial
anesthesia for the obstetric anesthesiologist are summarized in
Table 24.5.

CLINICAL PEARL Multidisciplinary team

A multidisciplinary team, including obstetrics, hematology, and
anesthesiology, should develop a care plan for parturients at high
risk for thromboembolic events. This plan should document the
 antepartum, intrapartum, and postpartum management of
anticoagulation, labor analgesia, and anesthesia for elective or
emergency cesarean delivery. The aim is to reduce the risk of PPH
and maximize the possibility of performing a neuraxial technique
while reducing the risk period that the parturient is not
anticoagulated.

V. Disorders of coagulation
A. Inherited disorders of coagulation
1. Common factor deficiencies. The anesthetic management of
parturients with common inherited disorders of coagulation is
summarized in Table 24.6 and Table 24.7.
a. von Willebrand disease
(1) Autosomal dominant condition
(2) Most common inherited bleeding disorder
(prevalence 1%)
(3) vWF required for adhesion of platelets to injured
endothelium and also prevents breakdown of
circulating FVIII.
(4) Classified into 3 types25
(a) Quantitative (type I: 75% of cases)
(b) Qualitative (type II)
(c) Complete absence (type III)
(5) vWF levels rise during pregnancy
(a) Patients with type I usually achieve normal
levels by the third trimester.3
(b) vWF levels and activity rarely improve in
 patients with types II or III.
(6) A rapid decline in factor levels occurs postpartum
which increases the risk of PPH. Patients with von
Willebrand disease (vWD) are 15 to 20 times more
likely to suffer from delayed (>24 hours) PPH than
normal parturients.26
b. Hemophilia A (FVIII deficiency) and B (FIX
deficiency)
(1) Sex-linked autosomal recessive
(2) Occurs in 1 in 5,000 to 30,000 live male births
(3) Hemophilia A is characterized by deficient or
defective FVIII (activity <35%)3
(4) Hemophilia B (Christmas disease) is characterized by
a deficiency of FIX activity
(5) Female carriers of both conditions have 50% of the
respective factor levels; they are usually
asymptomatic.
(6) FVIII levels significantly increase in pregnancy; FIX
levels do not.
(7) Parturient carriers of hemophilia A or B are at risk for
primary and secondary PPH.
2. Rare factor deficiencies. A review of the management of
inherited bleeding disorders during pregnancy is provided by
the United Kingdom Haemophilia Doctors’ Organization
(UKHCDO).27,28 The suitability of neuraxial anesthesia for
such parturients should be considered on an individual basis,
in discussion with a hematologist. Case reports of successful
neuraxial procedures are described for most deficiencies with
appropriate factor replacement, but individual absolute risk is
difficult to quantify.3

CLINICAL PEARL Hematology

Communication with hematology is essential in parturients with
coagulopathies. The hematologist can advise on treatment options
and coordinate with the blood bank to ensure products are
immediately available when required; specific treatments or clotting
factors often require hematology approval prior to release, for
example, recombinant Factor VIIa or fibrinogen.

B. Acquired disorders of coagulation

1. Thrombocytopenia.29 Thrombocytopenia is the most
common hematologic disorder of pregnancy.
a. Gestational thrombocytopenia30
(1) Accounts for 75% of all pregnancy-associated
thrombocytopenia
(2) Occurs in 5% to 10% of all pregnancies
(3) Platelet count is generally >75 × 109 per L
(4) Not associated with PPH risk: is not a
contraindication to neuraxial anesthesia
b. Idiopathic thrombocytopenic purpura
(1) Most common cause for first trimester
thrombocytopenia
(2) Is an autoimmune disease; an autoantibody response
is mounted against platelets
(3) Increases platelet destruction: platelet function is
normal or improved; platelets on peripheral blood
film are large and well-granulated.
(4) Symptomatic patients, or those with extremely low
platelet counts (<20 × 109 per L), may be treated
with:
(a) Intravenous immunoglobulin (IVIg)
(b) Corticosteroids (prednisolone 1 mg.kg−1)
(c) Treatment may take several days to increase the
platelet count, and the effect may last up to 6
weeks.3
(d) Rarely, splenectomy is required; is best
 performed in the second trimester.31
(e) In the context of acute hemorrhage and extreme
low platelet count, a platelet transfusion may be
necessary.
2. Pregnancy-induced hypertension
a. Preeclampsia. Twenty-one percent of parturients with
thrombocytopenia have preeclampsia: 50% of patients
with preeclampsia are thrombocytopenic.32
b. Hemolysis, elevated liver enzymes, low platelets
syndrome. A consumptive coagulopathy results in
thrombocytopenia, abnormal coagulation tests (aPTT,
PT), and reduced fibrinogen. Thrombocytopenia may be
severe.
c. Thrombotic thrombocytopenic purpura and hemolytic
uremic syndrome
(1) Previously considered as separate syndromes:
however the pathophysiology of these conditions is
identical.
(2) Both are characterized by:
(a) Microangiopathic hemolytic anemia
(b) Thrombocytopenia
(c) Fever
(d) End organ damage
(3) Central nervous system is primarily affected with
TTP.
(4) Renal system is primarily affected in HUS.
(5) TTP typically occurs in the second trimester and
HUS postpartum.
(6) Delivery of baby does not alter course of the disease.
(7) Treatment for both TTP and HUS is supportive
management with plasma exchange and renal
replacement therapy.33
d. Neuraxial anesthesia management of patient with
thrombocytopenia
Neuraxial hematoma and secondary neurologic
impairment is the risk of most concern when performing
neuraxial anesthesia in parturients with
thrombocytopenia. In a literature review, Horlocker et
al.19 report 16 cases of neuraxial hematoma (13 following
epidural anesthesia; one following spinal anesthesia; two
cases technique not reported). Half of these were
thrombocytopenic or coagulopathic at the time of the
procedure and one had altered clotting when the epidural
catheter was removed. Approximately a third recovered
completely, a third had partial recovery, and a third had
permanent neurologic deficits.19 The incidence of
spontaneous neuraxial hematoma in healthy parturients
peripartum is unknown.19 As neuraxial hematoma is a
rare complication, there is no good evidence for platelet
count limits or coagulation test results above or below
which neuraxial procedures are safe. The decision to
proceed with neuraxial anesthesia should be made on an
individual risk/benefit analysis based on patient history,
preexisting medical conditions, anticoagulant history, and
blood test results. The following questions and principles
may help in decision making:
(1) Platelet count
(a) >100 × 109 per L with a stable count, neuraxial
anesthesia is generally considered safe, unless
bleeding history to suggest abnormal platelet
function
(b) >80 × 109.l−1 and <100 × 109 per L, consider the
rate of fall?
(i) A stable count is more reassuring. A
precipitously falling platelet count is
indicative of worsening pathology and
increasing risk with neuraxial procedures.
Disseminated intravascular coagulation
 (DIC) should be considered as a possible
cause.
(ii) A stable count is likely to be either
gestational thrombocytopenia or idiopathic
thrombocytopenic purpura (ITP); platelet
function is normal in both conditions.
(c) >50 × 109 per L and <80 × 109 per L: unless ITP
or gestational thrombocytopenia are present,
where the risks of neuraxial anesthesia are
probably increased.
(d) <50 × 109 per L. In most cases, the risks
probably outweigh the benefits of neuraxial
anesthesia.
(2) Platelet function
(a) Is there a history of easy bruising or bleeding?
(i) For example, is there evidence of petechiae,
ecchymosis with minimal trauma (e.g.,
blood pressure cuff)?
(ii) For example, is there evidence of gum
bleeding when cleaning teeth or excessive
bleeding from intravenous sites?
(3) Risks of alternative methods of
analgesia/anesthesia
(a) What is the individual risk/benefit analysis?
(i) Are there predictors of difficult intubation
or ventilation? For example, morbid obesity
(4) Can the patient’s condition be optimized?
(a) Discuss optimization with a hematologist (e.g.,
IVIg or corticosteroids for ITP; platelet
transfusion).
(5) If the decision is made to proceed with neuraxial
anesthesia
(a) Discuss and document risks of neuraxial
anesthesia and alternative techniques.
 (b) Single-shot spinal anesthesia presents a lower
risk than epidural because there is less risk of
damaging epidural blood vessels as the needle is
smaller.
(c) Ensure coagulation is normal prior to epidural
catheter removal (same as insertion). Timing
may require clinical judgment, for example, with
HELLP, the platelet count may continue to fall
for 24 to 48 hours or longer. Arguably, leaving
an epidural catheter in situ, while waiting several
days for the platelet count to recover, carries as
much risk of traumatizing an epidural blood
vessel as removing the catheter early.34 If
clinical evidence of a coagulopathy, or the
patient is heparinized, then removal of the
catheter is not recommended.
(d) If the patient is thrombocytopenic, consider
withholding nonsteroidal anti-inflammatory
drugs (NSAIDs) postpartum.
(e) Assess lower limb neurologic assessment in
patients postpartum to exclude signs/symptoms
of neuraxial hematoma.

CLINICAL PEARL General anesthesia

Anesthesiologists often feel pressure to avoid general anesthesia
due to the potential risk of a difficult intubation and risk of
pulmonary aspiration syndrome. However, in parturients with
possible underlying coagulopathy or borderline thrombocytopenia,
the risk versus the benefit may favor the use of general anesthesia
for cesarean delivery. Communication with the obstetrician and the
patient is essential in this situation and that discussion should be
documented on the chart.
C. Disseminated intravascular coagulation
Obstetric patients may be predisposed to DIC because of the
hypercoagulable physiologic changes of normal pregnancy.35 DIC
is the result of widespread activation of the coagulation system,
leading to pathologic fibrin deposition and a consumptive
coagulopathy. The resulting low fibrinogen and
thrombocytopenia place patients at risk for hemorrhagic
complications. Table 24.8 lists precipitating causes in pregnancy.
No single blood test is sensitive or specific for DIC: Serial
coagulation and platelet counts often demonstrate a progressively
worsening picture. Fibrinogen is typically low <1.5 g per L. D-
dimers are raised in normal pregnancy, but very high levels may
contribute to the diagnosis of DIC. Critical care support is often
needed. Treatment is targeted at removing the precipitating cause,
correcting coagulopathy, and managing massive hemorrhage, if
present. Suggested product replacement includes:36

1. 15 mL per kg of fresh frozen plasma (contains all clotting

products present in plasma, including fibrinogen). This
equates to 4 units for a 70-kg patient. Repeat until INR and
 aPPT <1.5 times normal.37
2. Cryoprecipitate or fibrinogen concentrate to maintain
fibrinogen >1 g per L. Cryoprecipitate is packaged in pools of
6 to 10 units (each donated by different individuals). One dose
in a 70-kg patient will increase fibrinogen by approximately
0.75 g per L.37
3. Platelet transfusion: keep >50 × 109 per L. In case of ongoing
DIC and massive hemorrhage, a target of >75 × 109 per L is
suggested. Pragmatically, this means transfusing as soon as
levels fall below 100 × 109 per L because the count will have
fallen because blood was taken, and thus the result will be
historical.36 Platelet units can be from a single donor, or
contain pools from several donors, and are the equivalent of 6
units of whole blood. One unit raises the platelet count of a
70-kg patient by approximately 40 to 50 × 109 per L.37
4. The role of recombinant Factor VIIa (rFVIIa) in parturients
with DIC and massive hemorrhage is controversial; it is
reported to be effective but is associated with an increased
risk of VTE.38 In keeping with the cell-based model of
coagulation, it is suggested that therapy with platelets, FFP,
and cryoprecipitate/fibrinogen should be optimized, in
addition to physiologic maximization (correction of acidosis,
hypothermia, hypocalcemia), prior to giving rFVIIa in a dose
of 90 μg per kg.36,39
5. In discussion with a hematologist, blood product replacement
should be tailored to the individual’s evolving situation. Near
patient testing, such as TEG, can guide therapy. DIC has a
significant mortality rate and needs to be managed
aggressively.
SUMMARY
Parturients with a coagulopathy or thrombophilia receiving
anticoagulant treatment are a challenge to the anesthesiologist and
obstetrician. The risk of neuraxial hematoma in these patients, when
 undergoing neuraxial blockade, is not fully quantified. The risks of
performing a neuraxial procedure in the setting of the parturient’s
particular circumstances should be fully discussed, allowing informed
consent. Guidelines set by organizations, such as ASRA and
UKHCDO, represent expert opinion based on current evidence. They
aim to minimize the occurrence of adverse events without denying
pregnant women the benefits of neuraxial analgesia and anesthesia.

REFERENCES
1. Holmes VA, Wallace JM. Haemostasis in normal pregnancy: a balancing act? Biochem Soc Trans.
2005;33:428–432.
2. Clark P. Changes of hemostasis variables during pregnancy. Semin Vasc Med. 2003;3:13–24.
3. Thornton P, Douglas J. Coagulation in pregnancy. Best Pract Res Clin Obstet Gynaecol. 2010;24:339–
352.
4. Cortet M, Deneux-Tharaux C, Dupont C, et al. Association between fibrinogen level and severity of
postpartum haemorrhage: secondary analysis of a prospective trial. Br J Anaesth. 2012;108:984–989.
5. Samama C, Simon L. Detecting coagulation disorders of pregnancy: bleeding time or platelet count?
Can J Anaesth. 2001;48:515–518.
6. Beilin Y, Arnold I, Hossain S. Evaluation of the platelet function analyzer (PFA-100) vs. the
thromboelastogram (TEG) in the parturient. Int J Obstet Anesth. 2006;15:7–12.
7. Davies JR, Fernando R, Hallworth SP. Hemostatic function in healthy pregnant and preeclamptic
women: an assessment using the platelet function analyzer (PFA-100) and thromboelastograph. Anesth
Analg. 2007;104:416–420.
8. Sharma S, Philip J, Wiley J. Thromboelastographic changes in healthy parturients and postpartum
women. Anesth Analg. 1997;85:94–98.
9. Armstrong S, Fernando R, Ashpole K, et al. Assessment of coagulation in the obstetric population
using ROTEM thromboelastometry. Int J Obstet Anesth. 2011;20:293–298.
10. Huissoud C, Carrabin N, Benchaib M, et al. Coagulation assessment by rotation thrombelastometry in
normal pregnancy. Thromb Haemost. 2009;101:755–761.
11. Oudghiri M, Keita H, Kouamou E, et al. Reference values for rotation thromboelastometry (ROTEM)
parameters following non-haemorrhagic deliveries. Correlations with standard haemostasis
parameters. Thromb Haemost. 2011;106:176–178.
12. Vincelot A, Nathan N, Collet D, et al. Platelet function during pregnancy: an evaluation using the
PFA-100 analyser. Br J Anaesth. 2001;87:890–893.
13. American College of Obstetricians and Gynecologists Women’s Health Care Physicians. ACOG
Practice Bulletin No. 138: inherited thrombophilias in pregnancy. Obstet Gynecol. 2013;122:706–717.
14. Kent N, Leduc L, Crane J, et al. Prevention and treatment of venous thromboembolism (VTE) in
obstetrics. J SOGC. 2000;22:736–749.
15. Kobayashi T. Antithrombin abnormalities and perinatal management. Curr Drug Targets. 2005;6:559–
566.
16. Franchini M, Veneri D, Salvagno GL, et al. Inherited thrombophilia. Crit Rev Clin Lab Sci.
2006;43:249–290.
17. Calderwood CJ, Greer IA. The role of factor V Leiden in maternal health and the outcome of
pregnancy. Curr Drug Targets. 2005;6:567–576.
18. Sugiura M. Pregnancy and delivery in protein C-deficiency. Curr Drug Targets. 2005;6:577–583.
19. Horlocker T, Wedel D, Rowlingson J, et al. Regional anesthesia in the patient receiving antithrombotic
or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-
Based Guidelines (Third Edition).Reg Anesth Pain Med. 2010;35:64–101.
20. Derksen R, de Groot P. The obstetric antiphospholipid syndrome. J Reprod Immunol. 2008;77:41–50.
21. American College of Obstetricians and Gynecologists. Practice Bulletin No. 132: antiphospholipid
syndrome. Obstet Gynecol. 2012;120:1514–1521.
22. Franchini M. Haemostasis and pregnancy. Thromb Haemost. 2006;95:401–413.
23. Ruppen W, Derry S, McQuay H, et al. Incidence of epidural hematoma, infection, and neurologic
injury in obstetric patients with epidural analgesia/anesthesia. Anesthesiology. 2006;105:394–399.
24. U.S. Food and Drug Administration. FDA Drug Safety Communication: updated recommendations to
decrease risk of spinal column bleeding and paralysis in patients on low molecular weight heparins.
http://www.fda.gov/Drugs/DrugSafety/ucm373595.htm. Accessed August 2014.
25. Kujovich JL. von Willebrand disease and pregnancy. J Thromb Haemost. 2005;3:246–253.
26. James AH. Von Willebrand disease. Obstet Gynecol Surv. 2006;61:136–145.
27. Bolton-Maggs P, Perry D, Chalmers EA, et al. The rare coagulation disorders—review with guidelines
from the United Kingdom Haemophilia Centre Doctors’ Organisation. Haemophilia. 2004;10:593–
628.
28. Lee CA, Chi C, Pavord SR, et al. The obstetric and gynaecological management of women with
inherited bleeding disorders—review with guidelines produced by a taskforce of UK Haemophilia
Centre Doctors’ Organisation. Haemophilia. 2006;12:301–336.
29. McCrae KR. Thrombocytopenia in pregnancy: differential diagnosis, pathogenesis, and management.
Blood Rev. 2003;17:7–14.
30. Boehlen F, Hohlfeld P, Extermann P, et al. Platelet count at term pregnancy: a reappraisal of the
threshold. Obstet Gynecol. 2000;95:29–33.
31. Felbinger TW, Posner M, Eltzschig HK, et al. Laparoscopic splenectomy in a pregnant patient with
immune thrombocytopenic purpura. Int J Obstet Anesth. 2007;16:281–283.
32. Kam PC, Thompson SA, Liew AC. Thrombocytopenia in the parturient. Anaesthesia. 2004;59:255–
264.
33. George JN. The association of pregnancy with thrombotic thrombocytopenic purpura-hemolytic
uremic syndrome. Curr Opin Hematol. 2003;10:339–344. 34. Douglas MJ. Platelets, the parturient
and regional anesthesia. Int J Obstet Anesth. 2001;10:113–120.
35. Montagnana M, Franchi M, Danese E, et al. Disseminated intravascular coagulation in obstetric and
gynecologic disorders. Semin Thromb Hemost. 2010;36:404–418.
36. Stainsby D, MacLennan S, Thomas D, et al. Guidelines on the management of massive blood loss. Br
J Haematol. 2006;135:634–641.
37. Fuller AJ, Bucklin BA. Blood product replacement for postpartum hemorrhage. Clin Obstet Gynecol.
2010;53:196–208.
38. Phillips LE, McLintock C, Pollock W, et al. Recombinant activated factor VII in obstetric hemorrhage:
experiences from the Australian and New Zealand Haemostasis Registry. Anesth Analg.
2009;109:1908–1915.
39. Franchini M, Franchi F, Bergamini V, et al. The use of recombinant activated FVII in postpartum
hemorrhage. Clin Obstet Gynecol. 2010;53:219–227.
40. Levi M. Pathogenesis and management of peripartum coagulopathic calamities (disseminated
intravascular coagulation and amniotic fluid embolism). Thromb Res. 2013;131(suppl 1):S32–S34.
 Cardiac Disease in the Obstetric Patient
Nathaen S. Weitzel and Bryan S. Ahlgren

I. Overview
A. Physiology
B. General anesthetic considerations
C. Neonatal risk
D. Obstetric delivery considerations
II. Valvular heart disease: congenital and acquired
A. Mitral stenosis
B. Aortic stenosis
C. Mitral regurgitation
D. Mitral valve prolapse
E. Aortic insufficiency
III. Congenital heart disease in the adult parturient
A. General peripartum considerations
B. Cyanotic lesions
C. Left-to-right shunting
D. Aortic defects
IV. Primary pulmonary hypertension
A. Peripartum considerations
B. Anesthetic management
C. Invasive monitoring
V. Cardiomyopathy
A. Peripartum cardiomyopathy
 B. Idiopathic dilated cardiomyopathy
C. Hypertrophic obstructive cardiomyopathy
D. Obstetric care after cardiac transplantation
VI. Ischemic heart disease in pregnancy
A. Peripartum considerations
B. Anesthetic management
VII. Cardiac dysrhythmias and pregnancy
A. Treatment limited to rhythms with hemodynamic
consequences
B. Therapy for dysrhythmias
VIII. Cardiopulmonary resuscitation in the obstetric patient
A. Fetal viability influences therapy
B. Treatment of cardiac arrest from suspected LAST

KEYPOINTS
1. Cardiac disease is present in up to 4% of parturients with 80% of these
cases being congenital in origin.
2. Regardless of origin of cardiac disease, presence of reduced left
ventricular ejection fraction, left-sided obstructive lesions, New York
Heart Association functional class (NYHC) >II, or history of prior
cardiac event are all risk factors for cardiac events in pregnancy.
3. Parturients with a history of congenital heart disease and have received
definitive surgical repair as a child and have good functional results after
surgery will often tolerate pregnancy well. These patients can often be
managed like a normal parturient. Patients presenting with partial
correction, palliative procedures, uncorrected lesions, and residual
cardiac defects need to be managed according to their current
cardiovascular physiology.
4. Peripartum cardiomyopathy is a rare disorder affecting between 1 in
3,000 and 1 in 4,000 live births and has a mortality of up to 20%. Once
 identified, anesthetic management should reflect principles for any
patient presenting with advanced heart failure.

I. Overview. During the past century, the care of the parturient with
cardiac disease has changed dramatically. Cardiac disease is present
in up to 4% of total pregnancies with overall cardiac-related mortality
rates estimated to be between 0.5% and 2.7%.1–6 Congenital heart
disease (CHD) is the leading etiology of cardiac disease in pregnancy
in the Western world, owing to advances in early medical and surgical
management and improved survival in women of childbearing age.
CHD accounts for an estimated 80% of parturients with cardiac
disease, yet this number is much lower outside Europe and North
America (<20%).6 In certain subsets of cardiac patients, such as
severe pulmonary hypertension, mortality rates continue to approach
50%.7 Despite advances in care, cardiac disease remains the most
common nonobstetric cause of death among parturients, and it
presents one of the most challenging clinical scenarios for
anesthesiologists to manage.8
A. Physiology. Previous chapters discuss the physiologic changes of
pregnancy, but critical elements for patients with cardiac disease
include1:
1. Increased blood volume of 50%, elevated cardiac output by
40%, and increased heart rate (HR) by 25% to approximately
80 to 100 beats per minute (bpm) (measurements peak by the
end of the second trimester)
2. Reduced systemic vascular resistance (SVR) and pulmonary
vascular resistance (PVR)
3. Labor and delivery itself imposes nearly a 50% increase in
myocardial oxygen demand and cardiac output.
B. General anesthetic considerations. Numerous reports describe
risk factors for cardiac events in pregnancy. Siu et al.3 reported a
prospective trial of 562 patients (CAREPREG Trial) investigating
the relationship between cardiac events during pregnancy and
concomitant cardiac disease. These authors identified four main
predictors of cardiac events3:
1. Prior cardiac event (e.g., heart failure, transient ischemic
attack, stroke, or dysrhythmias)
2. Baseline New York Heart Association (NYHA) functional
class >II or the presence of cyanosis (see Table 25.1)

3. Left heart obstruction (mitral valve area <2 cm2, aortic

valve area <1.5 cm2, or peak left ventricular outflow tract
gradient >30 mm Hg by echocardiography)
4. Reduced left ventricular function (ejection fraction <40%)
Risk estimation was done by assigning one point for each
predictor. The estimated risks for a cardiac event with 0, 1, and
>1 points are 5%, 27%, and 75%, respectively, and this risk
prediction model is the most widely used to date.6 Cardiac events
were defined as pulmonary edema, sustained tachyarrhythmia, or
bradyarrhythmia requiring treatment, stroke, cardiac arrest, or
cardiac death.
In 2011, the European Society of Cardiology (ESC) generated
a report from the Task Force on the Management of
Cardiovascular Diseases during Pregnancy, which considers both
acquired cardiac disease and CHD. Table 25.2 is a summary of
risk classification from this report using the World Health
Organization (WHO) classification system.6 A 2014 prospective
validation study indicated that the WHO classification system
 more accurately predicted events than either the CAREPREG or
ZAHARA risk models.9

C. Neonatal risk
Considerations must be made for both the risk of neonatal disease
and for failure of the pregnancy. Figure 25.1 indicates the
distribution of completed pregnancies, elective abortions, and
miscarriages by specific maternal congenital cardiac defect.
Incidence of preterm delivery of neonates born to mothers with
CHD is elevated, with an incidence of 16% to 19%. Rates of
neonatal intensive care unit admission, intraventricular
hemorrhage, small for gestational age, and neonatal mortality are
also all elevated.10,11 Neonates born from mothers with CHD
 have a tenfold elevated risk of suffering CHD with an incidence
of 3% to 10%.12 Genetic testing may be useful in select patients
with increased risk profile.

D. Obstetric delivery considerations

1. Vaginal delivery is typically preferred over cesarean delivery
(CD) because of lesser blood loss and fluid shifts, a lower
incidence of postoperative infections and pulmonary
complications, as well as reduced metabolic demands and
stress response.8
2. CD has been suggested for the following cardiac conditions:
Marfan syndrome with aortic root involvement, severe aortic
stenosis, aortic dissection, recent myocardial infarction, and
severe heart failure during a previous delivery.13,14 The
principal rationale for these recommendations is avoidance of
the hemodynamic stress of labor and delivery, although one
could speculate that the afterload and hemodynamic stress
reduction associated with epidural analgesia might be
favorable for situations such as Marfan syndrome with aortic
 insufficiency and aortic dissection.
II. Valvular heart disease: congenital and acquired
Valvular heart disease accounts for approximately 15% of cardiac
disease among parturients, with rheumatic heart disease being most
prevalent.15 Stenotic abnormalities carry the highest risk for both the
mother and developing fetus.1,15 Regurgitant lesions are better
tolerated, but can worsen to the point of increasing the NYHA class.
The severity of the valvular lesion and underlying cardiac function
correlate with the risk of cardiac complications during pregnancy and
delivery.3 Echocardiography constitutes the gold standard for both
diagnosis and grading the severity of valvular lesions.16
A. Mitral stenosis
Mitral stenosis (MS) remains fairly common worldwide and
most often follows childhood rheumatic fever. However, the
incidence of MS has declined significantly in developed nations
as a result of recognition and treatment of streptococcal disease.13
The natural history of MS is a slow progression of disease and
symptoms over 20 to 30 years. The mitral valve leaflets thicken,
calcify, and fuse near the chordae or commissures (see Fig. 25.2)
to induce a stenotic flow pattern.

1. Pathophysiology
 a. Typical symptoms or signs of severe MS include chest
pain, dyspnea, palpitations, pulmonary edema,
hemoptysis, and thromboembolism.
b. The stenotic valve prevents normal left ventricle filling
and leads to enlargement of the left atria, elevated
pulmonary venous and arterial pressures, and eventually
to right-sided heart failure often with associated tricuspid
valvular insufficiency.
c. Left ventricular stroke volume decreases along with the
cardiac output.
d. Severity is judged by mitral valve area obtained by
echocardiography.16 Normal mitral valve area is 4 to 6
cm2 with mild stenosis typically defined as a valve area of
1.5 to 3 cm2, moderate stenosis as 1.1 to 1.5 cm2, and
severe stenosis as <1.0 cm2. Severe lesions typically
require surgery, which can usually be done at a relatively
low risk to both mother and fetus during the first trimester
of pregnancy.
2. Peripartum considerations. The “hyperdynamic” cardiac
state of pregnancy is poorly tolerated by women with severe
MS.16
a. Increased plasma volume can cause pulmonary edema
and worsen left atrial enlargement.
b. Tachycardia decreases left ventricular diastolic filling
time through the stenotic valve.
c. Atrial fibrillation (AF) is common in MS, and this can be
highly detrimental because the atrial “kick” may account
for as much as 30% of the left ventricular stroke volume
in patients with MS.16 Medical management of AF
typically includes ventricular rate control by using β-
adrenergic blocking agents, unless there is a
contraindication; yet, a resting HR of approximately 90 to
100 bpm is considered normal during pregnancy.
d. Patients with severe disease have improved outcomes
 with intervention prior to pregnancy. Typical interventions
include surgical mitral valve commissurotomy, valve
replacement, or percutaneous mitral
commissurotomy.16–19
3. Anesthetic management
Management should be based on the severity of the lesion,
which depends on the mitral valve area and the
hemodynamic stability of the patient.19 Most obstetric
anesthesiologists advocate early pain control using either IV
opioids or epidural analgesia for labor and vaginal
delivery.20–22 Second stage of labor increases cardiac preload
and cardiac output as a result of autotransfusion from the
uterus and relief of aortocaval compression. These alterations
in hemodynamics and cardiac preload can cause acute
pulmonary edema.
Combined spinal-epidural (CSE) technique, where
intrathecal opiates are given early in the first stage of labor
followed by gradual titration of dilute epidural local
anesthetic as labor progresses to the second stage (to cover
T10–S4), provides an excellent hemodynamic profile for most
patients.19
a. Epidural anesthesia is ideal for prolonged second stage
vaginal deliveries where instrumentation is required.
Often the epidural infusion during labor will provide
adequate anesthesia for forceps placement. If the epidural
block is inadequate, administration of epidural fentanyl
along with small doses of 2% lidocaine or 3% 2-
chloroprocaine can provide surgical blockade in a timely
and safe manner.19
b. Reductions in SVR from sympathetic blockade should be
treated preferentially with cautiously titrated
phenylephrine and judicious volume expansion, unless the
patient is relatively bradycardic (HR <70 bpm). In this
situation, ephedrine may be preferable.
4. For CD, epidural anesthesia is the preferred approach if time
allows.1,19
a. “Single-shot” spinal techniques should be avoided in both
moderate and severe MS because abrupt changes in SVR
are poorly tolerated.
b. Slow titration of 2% lidocaine combined with fentanyl
through the epidural catheter will produce surgical
blockade (T4–T6 level). Titration of small doses of
phenylephrine (50 to 100 μg) as needed will counteract
the expected hypotension from sympathectomy. Systolic
BP should ideally exceed 100 mm Hg, although the
potential exists to exacerbate pulmonary hypertension. If
echocardiography in the second or third trimester suggests
pulmonary hypertension or signs of right heart “overload”
(i.e., dilation of right ventricle and/or atrium, often with
tricuspid regurgitation), then placement of a pulmonary
artery catheter (PAC) for labor and delivery should be
considered.
c. The blood volume reduction that accompanies vaginal
delivery and CD are beneficial to the patient with MS, as
long as adequate cardiac preload is maintained.
5. General anesthesia. Consideration of the above
hemodynamic goals should be used in choosing induction and
maintenance anesthetics.1,19
a. Stress response suppression during induction and through
the predelivery period, using opiates such as remifentanil
(0.5 to 1 μg/kg) and a short-acting β-adrenergic blocker
such as esmolol (30 to 50 μg/kg) at induction, should be
considered. Etomidate 0.2 to 0.3 mg/kg is a good choice
for induction, typically accompanied by succinylcholine 1
to 1.5 mg/kg in a rapid-sequence technique accompanied
by cricoid pressure.
b. Drugs that may produce tachycardia should probably be
avoided (e.g., glycopyrrolate, atropine, meperidine,
 pancuronium, ketamine).
c. Full stomach and aspiration prophylaxis are the same as
for CD under general anesthesia without mitral stenosis.
d. Methergine, prostaglandins, and oxytocin should be used
cautiously because these drugs may alter systemic or
pulmonary pressures leading to hemodynamic
compromise.22
6. Invasive monitoring including arterial and central venous or
pulmonary arterial pressure monitoring should be considered
for high-risk patients. The risks of placing a PAC, especially
dysrhythmias, are significant, but the information gained in
patients with severe MS may be beneficial to management
during labor.19,20,23 If general anesthesia is selected,
consideration should be given to the use of transesophageal
echocardiography to facilitate decision making about fluid
replacement and/or inotropes and vasopressors.

CLINICAL PEARL Anesthetic and hemodynamic goals in

MS:
• Maintain hemodynamics close to the patient’s normal state. This goal is
facilitated by adequate pain control and by avoiding hypoxia, hypercarbia,
and acidosis.
• Preserve sinus rhythm (if present) and treat AF aggressively.
• Avoid aortocaval compression. Monitor and maintain adequate cardiac
preload without causing pulmonary edema.
• Provide supplemental oxygen.
• Avoid reductions in SVR.

B. Aortic stenosis
Severe aortic stenosis (AS) is rare among parturients. Rheumatic
heart disease is the most common acquired cause of AS, whereas
a bicuspid aortic valve is the most common congenital cause (see
Fig. 25.3). Left ventricular hypertrophy compensates for AS by
offsetting the increase in left ventricular wall tension imposed by
increased left ventricular pressures. Unlike MS, symptoms of AS
appear late in the course of disease and lead to high mortality.14,24
Patients with severe AS should have surgical correction prior to
pregnancy.1,21

1. Pathophysiology
a. Symptoms of severe AS include syncope, dyspnea, angina
pectoris, and fatigue.1
b. Patients are usually asymptomatic until the valve area is
reduced to 1.0 cm2, which is roughly one third the normal
valve area of 3 to 4 cm2.16,25
c. Severe AS is often defined as a valve area less than 0.7
cm2, which typically is associated with a transvalvular
mean pressure gradient greater than 50 mm Hg derived
from echocardiographic measurements.16,25
2. Peripartum considerations
a. Pregnancy is usually tolerated by women with mild to
moderate AS.8,14
b. Patients with severe AS are unable to accommodate
increased blood volume and tachycardia, and often
experience worsening of symptoms including angina
pectoris and dyspnea. These women have little cardiac
 reserve during pregnancy and have a high mortality rate
of 15% to 17%.1,14,24
3. Anesthetic management1,22,24
Vaginal delivery is preferred for mild and moderate AS,
whereas CD is often chosen for patients with severe AS.
Keeping the HR below 90 bpm improves ventricular
emptying against a fixed obstruction, although lower HRs
may be required to avoid subendocardial ischemia in patients
with severe AS and marked LVH. Tachycardia can induce left
ventricular subendocardial ischemia, reduce left ventricular
ejection fraction, and increase myocardial oxygen
consumption. These women also have a limited capacity to
increase left ventricular stroke volume, so the usual LV
preload augmentation that accompanies slower HRs is
impaired. Consequently, an HR below 70 bpm may place
these patients at risk for critically low cardiac output. Left
ventricular hypertrophy places the myocardium at risk for
ischemia under situations of high myocardial oxygen demand
(typically manifested in AS as excessively high left
ventricular systolic pressures or tachycardia) or when SVR is
reduced and coronary perfusion pressure (i.e., diastolic blood
pressure minus left ventricular diastolic pressure) is
compromised.
a. Single-shot spinal anesthesia is contraindicated for
women with severe AS and relatively contraindicated for
those with moderate AS.22
b. Epidural or continuous spinal approaches for labor have
been successfully carried out with slow titration of both
an opioid and a local anesthetic agent.26 Epinephrine
should be avoided because of the risk of causing
tachycardia with intravascular injection.
c. As in MS, early analgesia is beneficial. CSE with an
intrathecal opioid followed by epidural titration of a dilute
local anesthetic solution as labor progresses is ideal.
 Management of prolonged second stage instrumented
deliveries is the same as for MS.
4. For general anesthesia, slow titration of opioids and use of
etomidate constitute an excellent approach. As with MS,
avoiding tachycardia is important, so glycopyrrolate, atropine,
pancuronium, and ketamine should be avoided. Propofol
should be used cautiously, if at all, due to reductions in SVR,
cardiac preload, and myocardial depression.14
5. CD considerations are similar to MS except that AS patients
are more afterload dependent and may tolerate the
sympathectomy induced by spinal or epidural anesthesia even
more poorly than MS patients. Both MS and AS patients also
tolerate preload reduction poorly, but AS patients are
probably more likely to experience it, and this may become
clinically significant even with slow onset of an epidural
anesthetic.
6. Invasive monitors
a. Consider arterial catheter placement to closely monitor
changes in blood pressure.
b. Central venous pressure or pulmonary artery catheter.
Use of PAC monitoring is controversial, and placement
decisions should be made on a case-by-case
basis.1,7,14,15,22 Tight volume control is recommended in
these patients, but introduction of the PAC creates some
risk of dysrhythmias, which can be life threatening.
Hypovolemia should probably induce greater concern
with moderate or severe AS than pulmonary edema
because preload reduction can severely reduce cardiac
output. Central venous pressure (CVP) monitoring may be
an adequate substitute for the PAC to help monitor the
volume status in the setting of moderate to severe
disease.1,8 Attempts should be made to keep CVP in the
high normal to slightly elevated range (8 to 12 mm Hg).
With severe AS, neither CVP nor pulmonary artery
 occlusion pressures reliably reflect left ventricular
preload, and the use of transesophageal echocardiography
(TEE) should be considered for this purpose if general
anesthesia is utilized.

CLINICAL PEARL Anesthetic and hemodynamic goals in AS

during labor and delivery:
• Maintain hemodynamics close to the patient’s normal state. Adequate pain
control helps avoid alterations in hemodynamics.
• Avoid tachycardia. Maintenance of sinus rhythm is critical.
• Avoid reductions in SVR and maintain preload to the heart. Aortocaval
compression is not well tolerated.
• Avoid myocardial depressant agents during general anesthesia.

C. Mitral regurgitation
Consideration of mitral regurgitation (MR) requires division into
acute MR and chronic MR. The most common causes of acute
MR during pregnancy are bacterial endocarditis, trauma, papillary
muscle rupture (see Fig. 25.4), and prosthetic valve dysfunction.
Chronic MR is more common and usually results from
myxomatous degeneration or rheumatic disease.
Echocardiographic imaging is the standard diagnostic modality,
and a case of moderate to severe MR is shown in Figure 25.5. MS
and MR may coexist in pregnant patients. Women with severe
symptomatic MR should consider mitral valve repair prior to
conception.21
1. Pathophysiology
a. Acute MR results in an acute volume load into the left
atrium across the incompetent mitral valve. This results in
elevated pulmonary pressures and reduction in forward
flow. If the patient survives the acute insult, pulmonary
edema and right heart failure may occur and emergency
valve surgery is often required.22
b. With chronic MR, the lesion develops over time and the
left atrium and pulmonary venous system are able to
accommodate the increased blood volume by enlarging.
 This predisposes the patient to atrial fibrillation. Elevated
pulmonary pressures are much less common in chronic
MR compared with acute MR, but certainly can occur
with severe chronic MR. Pulmonary congestion is
common.22
c. AF is better tolerated in MR as compared to either MS or
AS because left ventricular preload is better
maintained.8,15
2. Peripartum considerations. MR is well tolerated in
pregnancy, unless the patient has severe MR or is
symptomatic before pregnancy.3
a. Afterload reduction is the treatment for MR, so the
decreased SVR that accompanies pregnancy is helpful.
Moderate tachycardia is also helpful because it limits the
time for regurgitation, so the increase in HR seen with
pregnancy is similarly helpful.
b. Hypertension during pregnancy should be aggressively
treated because increased afterload will increase the
regurgitant fraction.24
c. The risk of thrombus formation is increased as a result of
the enlarged left atrium and the hypercoagulability of
pregnancy. Thrombus is found in up to 20% of patients.1
D. Mitral valve prolapse
Mitral valve prolapse (MVP) is a subset of mitral valve disease
that most often involves early myxomatous degeneration with
minimal MR in women of childbearing age, but advanced disease
with severe MR is possible. This lesion is quite common and is
found in 12% to 17% of women.24 MVP may predispose the
patient to dysrhythmias and may be associated with other
systemic diseases such as Marfan syndrome. In the absence of
concomitant disease, there are no specific alterations in the
anesthetic management of these patients because there are rarely
any cardiac complications that arise from prolapse alone.24 In
contrast to patients with most forms of advanced MR, patients
 with early MVP typically have less MR in the presence of high
preload, high afterload, and low HR.
E. Aortic insufficiency
Aortic insufficiency (AI) occurs more commonly than AS, and
rheumatic disease is the causative agent in the majority of
patients. Patients with rheumatic AI often have concomitant
mitral valve disease. AI can also be present in patients with
congenital bicuspid valve disease or with collagen vascular
disorders.24 Acute AI can result from endocarditis, or rarely from
trauma. These patients are critically ill and typically require
urgent surgical correction. There have been reported cases of
medical management of acute AI until CD could be performed,
but it is rare for those patients to survive.27
1. Pathophysiology
a. AI increases left ventricular diastolic volume. Over time,
this causes significant ventricular dilation and eccentric
hypertrophy. This typically precedes the onset of
symptoms, which include dyspnea, diminished exercise
ability, pounding in the chest, and orthopnea.1
b. Progression of disease causes left ventricular failure,
reduced ejection fraction, and further increases in end-
diastolic ventricular volume.
c. In the absence of pregnancy, symptoms typically occur 10
to 20 years after the onset of rheumatic disease.24
2. Peripartum considerations. Mild to moderate AI is well
tolerated during pregnancy.
a. The tachycardia associated with pregnancy reduces the
regurgitant fraction and left ventricular diastolic volume.
The reduction of SVR associated with pregnancy also
promotes forward flow out of the left ventricle.
b. Patients with severe AI who have symptoms of heart
failure prior to pregnancy have diminished cardiac
reserve. Onset of pregnancy-related hypertension or signs
of congenital heart failure (CHF) should prompt treatment
 with afterload reduction, diuretics, and/or inotropic
agents.21,24

CLINICAL PEARL Anesthetic and hemodynamic goals in

MR and AI:
• Afterload reduction is beneficial. Avoid increases in SVR, so early and
effective analgesia during labor is recommended.
• Avoid and treat atrial fibrillation aggressively.
• Slight tachycardia is preferred (target HR of 80 to 100). Bradycardia is
poorly tolerated.
• Maintain preload and avoid aortocaval compression.
• Myocardial depression should be avoided.

3. Anesthetic management (management of both MR and AI).

Patients with regurgitant lesions can be managed safely using
either general or neuraxial anesthesia.
a. Epidural analgesia or CSE for labor is preferred by
many because early administration during the first stage
of labor permits titration with a combination of an opiate
and local anesthetic agent, which facilitates cautious and
titrated hemodynamic management.1
b. Early analgesia helps prevent pain-induced elevation in
catecholamine levels that will increase SVR and therefore
increase the regurgitant fraction.
c. Invasive monitoring should be reserved for those patients
with severe and symptomatic MR or AI because risk of
placement may outweigh the benefit.1 TEE should be
considered with severe MR or AI if general anesthesia is
used.
4. Cesarean delivery. Epidural anesthesia for CD is preferred,
but spinal or general anesthesia may be acceptable
alternatives.1,24
a. Spinal anesthesia can be used, but the abrupt changes in
 hemodynamics may not be tolerated by patients with
more severe disease.
b. Bradycardia is poorly tolerated and can push the patient
into cardiovascular compromise. Treatment of
hypotension should be carried out preferentially with
ephedrine to avoid bradycardia, and promote slight
tachycardia.
c. Avoiding increased PVR in severe MR is important (see
Table 25.3). Acute increases in PVR can reduce forward
flow and induce right ventricular failure.

5. General anesthesia. Overall hemodynamic goals are similar,

and the agents used should ideally promote slight tachycardia
and reduce SVR without producing myocardial depression.1,24
a. Induction with ketamine and use of glycopyrrolate to
prevent or treat bradycardia.
b. Agents such as propofol can be used, but slow titration is
recommended to avoid significant myocardial depression
or preload reduction.
c. AF should be avoided and aggressively treated.
III. Congenital heart disease in the adult parturient
Adult patients with CHD now represent the majority (60% to 80%) of
obstetric patients with cardiac disease.28 Significant improvements
in surgical techniques have allowed many patients (85% of children
with CHD) to not only survive to adulthood, but also have relatively
normal function. In 2000, the 32nd Bethesda Conference report
generated from the American College of Cardiology indicated that
approximately 85% of patients with surgical repair and CHD survive
to adulthood.29 It was estimated that 800,000 patients with adult
congenital heart disease (ACHD) were living in the United States in
2000, with an additional 8,500 corrected each year.30,31 This report
highlighted the importance of developing a model for seamless
transitions of care for patients who are cared for at pediatric heart
centers who now must transition into the adult population and adult
hospitals.
This population can pose obstetric and anesthetic challenges as the
physiology of pregnancy interacts with each patient’s corrected or
uncorrected cardiac pathology. Figure 25.1 demonstrates the
distribution of completed pregnancies, elective abortions, and
miscarriages by congenital cardiac lesion.6 A full discussion about
pre-pregnancy risk assessment and counseling exceeds the scope of
this chapter, and typically, the anesthesiologist will not be involved
with these aspects of care. However, when the patient with CHD
presents in labor, it is important to have an understanding of the
relative risks for the different lesions (see Table 25.2). CHD lesions
will be discussed in two broad categories: cyanotic lesions and lesions
resulting in left-to-right shunts.
A. General peripartum considerations. For patients with either
cyanotic lesions (often with right-to-left shunts) or lesions with
left-to-right shunts, who received definitive surgical repair as a
child and have good functional results from the surgery,
pregnancy is often well tolerated and can be managed like a
normal parturient. Those patients presenting with partial
correction, palliative procedures, uncorrected lesions, and
residual cardiac defects need to be managed according to their
current cardiovascular physiology. Some key considerations for
determining the level of concern when approaching CHD patients
are as follows32–40:
1. Evidence of congestive heart failure (even if compensated).
If present, 30% of patients will have functional decline during
pregnancy compared to 5% in those without CHF.
2. Presence of cyanosis. If cyanotic (oxygen saturation less than
90%), more than 50% of patients will deteriorate during
pregnancy, whereas only 15% of acyanotic patients will show
signs of cardiovascular deterioration.
3. Pulmonary hypertension. These patients are in the highest
risk category for death or severe cardiac complications with
pregnancy.
4. Presence of dysrhythmias. Ventricular and atrial
dysrhythmias are extremely common in ACHD patients and
account for nearly 50% of emergency hospitalizations.41
Dysrhythmias in this population may be treated with anti-
arrhythmics, implantable devices, ablative procedures, or
combinations of the earlier mentioned. Table 25.4 outlines
incidence of dysrhythmia based on a specific congenital
lesion.
5. Corrected single ventricle or systemic right ventricle.
These patients should be considered at intermediate to high
risk, and level of concern should be based on functional
ability and type of surgical correction prior to pregnancy.
6. Presence of residual ventricular septal defect. Changes in
SVR during pregnancy can alter the shunt physiology in an
asymptomatic patient, typically by decreasing SVR to lessen a
left-to-right shunt, or to potentially convert a left-to-right
shunt or incipient Eisenmenger complex to a right-to-left
shunt with cyanosis.
Severity and functional ability impact the type of anesthetic
chosen. These patients will usually be followed by a cardiologist,
and consultation should be obtained to gain information on the
functional ability and cardiac status. After determining functional
status and possible residual cardiac pathology, the
anesthesiologist can tailor the individual anesthetic to achieve the
appropriate hemodynamic goals.32 Current echocardiographic
data should be sought to gain information on current cardiac
 function and anatomy.
B. Cyanotic lesions
1. General considerations. Some broad principles apply to
anesthetic management of cyanotic congenital heart lesions,
particularly those with residual defects.2,32–34,38–40
a. Cyanotic lesions have some element of right-to-left
shunt even after surgical repair. The degree of this shunt
determines the level of cyanosis present. Caution should
be taken with sedative medicines because decreasing
ventilation can increase PVR and exacerbate cyanosis by
increasing right-to-left shunt.
(1) Right-to-left shunting reduces the uptake of
inhalational anesthetics and prolongs inhalation
induction. Conversely, the onset of IV induction
hastens.
(2) Nitrous oxide may elevate pulmonary artery pressure
and should be used cautiously.
b. Risk of air embolus. Extreme care should be taken to
avoid an air embolus. Saline should be used for loss of
resistance during epidural placement, not air, because air
entrainment into an epidural vein can easily cross into the
systemic circulation. IV lines should be aggressively de-
aired and monitored.
c. Systemic vascular resistance. Changes in SVR disrupt
the balance between pulmonary and systemic circulations
to change the shunt. All anesthetic medications should
be slowly titrated to prevent rapid changes. This holds
true for both neuraxial and general anesthetics.
(1) Single-shot spinal anesthetic techniques are generally
contraindicated because the quick onset of
sympathectomy is poorly tolerated.
(2) Administration of antibiotics (e.g., vancomycin) may
reduce SVR, particularly if administered quickly.
(3) Choice of anesthetic induction drug is not as
 important as the manner and vigilance used by the
anesthesiologist in managing hemodynamics.
(4) Phenylephrine is generally the vasopressor of choice
unless it is highly likely that the primary cause for
hypotension is myocardial depression, in which case
ephedrine or epinephrine should be considered.
(5) Interventions that could decrease PVR, such as
increases in mixed venous O2 (typically via high Fio2)
and modest degrees of respiratory alkalosis, are
encouraged to reduce shunting.
d. Invasive monitoring
(1) Previous surgical procedures, such as Blalock-
Taussig shunts using the subclavian artery,
compromise blood flow to the ipsilateral upper
extremity and will affect the location for arterial line
placement.
(2) Central venous catheters should be reserved for the
most symptomatic patients because an increased risk
of thrombus and stroke PACs are anatomically
difficult or impossible to place and are seldom
helpful in patients with cyanotic cardiac lesions.
(3) TEE may be the most useful real-time monitor of
cardiovascular status, especially when administering
general anesthesia.
e. Aortopulmonary collaterals. Unrepaired complex
cyanotic patients often develop aortopulmonary
collaterals via the bronchial arteries. This causes a left-to-
right shunt through the pulmonary circulation, which can
potentially compete with the coronary arteries and
compromise myocardial perfusion.40 Situations causing
increased SVR, such as pain during labor, may increase
this left-to-right shunt.
f. Prolonged second stage labor. Earlier transition to
instrumented delivery may help to reduce the
 hemodynamic stress on an already abnormal
cardiovascular system.42 Slowly and carefully titrated
epidural analgesia for labor supplemented by pudendal
nerve blockade for delivery (to avoid excessive epidural
spread and decreased SVR) may optimize pain control
without enhancing cyanosis. Vaginal delivery is preferred
over CD when feasible, because of the lesser
hemodynamic stress if adequate analgesia is provided.
2. Tetralogy of Fallot—“blue baby syndrome.” Tetralogy of
Fallot (ToF) is the most common cyanotic lesion, accounting
for 10% of CHD.
a. Features of ToF include33,43: (see Fig. 25.6)

(1) Ventricular septal defect

(2) Pulmonic stenosis/right ventricular outflow tract
obstruction
(3) Overriding aorta
(4) Right ventricular hypertrophy
 There is great variability in the extent of these defects
ranging from small ventricular septal defect (VSD) and
overriding aorta with minimal pulmonary stenosis to severe
pulmonary stenosis and large VSD. Unrepaired, only 30% of
children will reach the age of 10 years. However, with current
surgical repair techniques, there is a 36-year survival of nearly
86%.36
b. Pathophysiology. ToF can cause right-to-left shunt and
cyanosis, with the degree of shunting proportionate to the
severity of the right ventricular outflow tract obstruction
(RVOTO) and SVR.39,44
(1) Palliative shunts (e.g., Blalock-Taussig, Waterston,
or Potts) were the initial surgical solutions developed.
They all involve systemic arterial (i.e., aorta or
subclavian artery) to pulmonary artery anastomoses.
They provided temporary relief of symptoms, but
often had long-term sequelae.36,37,39
(2) Definitive surgical repair involves closure of the
VSD and relief of RVOTO using resection and
reconstruction with Gore-Tex patch grafting across
the RVOTO or conduits to bypass the RVOTO.44
(3) Common reasons for reoperation following definitive
repair include residual VSD or recurrence of the VSD
(10% to 20%), residual RVOTO or stenosis (10%)
leading to right heart failure,39 and rarely RV failure
caused by pulmonic insufficiency from the RVOTO
patch.
(4) Additional management concerns include a higher
risk of sudden cardiac death compared with age-
matched controls, elevated risk of dysrhythmias
(especially atrial fibrillation), right bundle branch
block, pulmonary regurgitation, and right ventricular
aneurysms.
c. Peripartum considerations. ToF patients with definitive
 surgical repair tolerate pregnancy well and can be
managed as a typical obstetric patient.
(1) Patients with mild ToF may present unrepaired for
management during the peripartum period. A review
of Mayo Clinic data looking at 43 ToF patients found
8 with unrepaired ToF who delivered successfully.
This study also confirmed results of two previous
case series indicating that patients with repaired ToF
are not at increased maternal risk with pregnancy.42
The authors found that the presence of underlying
cardiac dysfunction or residual cardiac defects after
repair were associated with adverse cardiac events
during pregnancy.
(2) Echocardiography should be utilized during
pregnancy to monitor maternal cardiac function and
adaptation to pregnancy (see Fig. 25.7).

(3) The increased blood volume and decreased SVR can

either produce new right-to-left shunting, exacerbate
preexisting right-to-left shunting across a patent
VSD, and induce cyanosis or heart failure.
d. Anesthetic management2,40,42
 (1) Epidural or CSE is an excellent option for pain
control early in the first stage of labor, using
intrathecal opioid followed by slow epidural titration
of dilute bupivacaine. This allows slow equilibration
to prevent rapid changes in SVR, preserving the
shunt fraction.
(2) Treatment of hypotension should be immediate and
most often should be done with phenylephrine.
Phenylephrine may cause elevations in PVR, which
can be a problem with residual VSD in the absence of
RVOTO. In those situations, carefully titrated
ephedrine is probably a better choice. In the presence
of RVOTO and right-to-left shunting, phenylephrine
is preferred because it will increase SVR and
decrease shunting.
(3) Patients with pulmonary stenosis or significant
pulmonic valvular regurgitation are more likely to
develop right heart failure. Avoiding elevated PVR
and maintaining high-normal filling pressures are
critical in patients with pulmonic valvular
regurgitation.40
(4) Cesarean deliveries can be managed with epidural
anesthesia using a slow titration of local anesthetic
while avoiding large decreases in cardiac preload.
(5) General anesthesia. Choice of induction agents
should be tailored to achieve the mentioned
hemodynamic goals based on the underlying cardiac
function.
(6) If an arterial catheter is placed, patients with Blalock-
Taussig shunts will require cannulation in the
contralateral arm or in either leg.

CLINICAL PEARL Anesthetic and hemodynamic goals in

ToF:
• Avoid changes (especially decreases) in SVR to prevent altering existing
shunt.
• Avoid increases in PVR by preventing hypoxia, hypercarbia, acidosis, and
providing supplemental oxygen (see Table 25.3).
• Maintain normal to elevated cardiac filling pressures, especially in patients
with right ventricular impairment. Avoid aortocaval compression.
• Continuous electrocardiogram (ECG) monitoring is advisable due to high
incidence of both atrial and ventricular dysrhythmias.
• Tachycardia and increases in myocardial contractility should be avoided in
situations where there is residual RVOTO because this may exacerbate the
obstruction and cause right-to-left shunting.

3. Transposition of great vessels

Transposition of great vessels (TGV) is relatively rare,
representing 1% to 5% of congenital heart defects (see Fig.
25.8 A–C). Two main types are congenitally corrected TGV
(L-TGV) and complete TGV (D-TGV). Without surgical
intervention, survival in D-TGV to 6 months is less than
10%.39,40 L-TGV allows survival, albeit typically at the cost
of early adult heart failure.
a. D-TGV is described as blood flow in a parallel system,
such that systemic venous return flows to the right atrium
and right ventricle, which then ejects blood into the aorta.
Pulmonary venous blood flow proceeds to the left atrium,
left ventricle, and then into the pulmonary artery. Without
additional communication from septal defects or a patent
 ductus arteriosus (PDA), there is no connection between
blood oxygenated in the lungs and systemic arteries, and
survival is impossible. 39,40
(1) Atrial switch operations (see Fig. 25.8B), such as the
Mustard or Senning procedure, create an atrial baffle
that causes venous blood to cross at the atrial level
into the appropriate ventricle. Because the
morphologic right ventricle then continues to eject
blood into the aorta, these patients experience a
higher risk of heart failure as a result of that
ventricle’s impaired capacity to chronically pump
against systemic arterial pressures.
(2) The arterial switch (see Figure 25.8C), known as the
Jatene procedure, switches the pulmonary artery and
aorta with re-implantation of the coronary vessels.
This requires a left ventricle of sufficient size to
provide systemic flows. These patients often have
relatively normal physiology following surgical
repair.
b. L-TGV is described as blood flowing from right atrium
to a morphologic left ventricle and then into the
pulmonary artery. Pulmonary venous blood flows into the
left atrium, a morphologic right ventricle, and then into
the aorta. L-TGV allows for physiologic blood flow, but
as with the Mustard and Senning procedures, a
morphologic right ventricle must chronically eject blood
into the aorta and the risk of heart failure is increased. L-
TGV is associated with concomitant defects (e.g., VSD,
ASD) that will increase the risk of heart failure
symptoms. In that situation, surgical repair is indicated to
close any symptomatic defects.39,40,45
c. Peripartum considerations
(1) Pregnancy is well tolerated in patients who have
undergone arterial switch procedures. Parturients who
 received the atrial switch repair will be at much
higher risk for heart failure as a result of the
physiologic changes of pregnancy, partly because of
the systemic right ventricle, and partly because the
atrial baffles sometimes obstruct blood flow.45
(2) L-TGV patients often reach childbearing age, and the
risks associated with pregnancy are based on degree
of heart failure.43
(3) Due to surgical interventions, patients are at higher
risk for dysrhythmias.
(4) Invasive monitors should be used selectively. Central
venous catheters may be useful for vascular access
and monitoring in patients with heart failure, but
PACs are probably ill advised in patients who have
undergone atrial switch procedures. Preoperative
information from recent echocardiograms can be
invaluable for symptomatic patients.
d. Anesthetic management
(1) Patients with arterial switch procedures can be
considered as a normal. These patients will likely
tolerate spinal anesthetics; however, in patients with
either L-TGV or the atrial switch palliation, single-
shot spinal anesthesia for CD is probably
contraindicated due to extreme preload dependence.40
(2) Those with evidence of heart failure must be treated
carefully because they are in an intermediate to high-
risk category; the biggest concern is volume shifts.46
(3) Epidural anesthesia with slow titration of local
anesthetic will minimize abrupt alterations in
hemodynamics.
(4) For CD, neuraxial or general anesthesia may be
selected, but either technique should be specifically
tailored based on cardiac status. If heart failure is
present, refer to the “Cardiomyopathy” section for
 further management discussion. These patients may
be more sensitive to volume changes, so blood loss
should be monitored closely and appropriate fluid
replacement given.

CLINICAL PEARL Anesthetic and hemodynamic goals for

TGV:
• Avoid aortocaval compression.
• Consider an arterial catheter and/or CVP catheter. Avoid excessive fluids in
patients with evidence of heart failure.
• Avoid negative inotropic agents.
• Monitor for dysrhythmias and treat as indicated.

4. Tricuspid atresia and hypoplastic left heart syndrome

a. Tricuspid atresia (TA) is the third most common
cyanotic congenital heart lesion and involves agenesis of
the tricuspid valve and hypoplasia or absence of the right
ventricle. Survival depends on the completeness of the
lesion, compensating defects such as atrial and ventricular
septal defects, degree of cyanosis, and the ability to
surgically improve the pathophysiology.
(1) Pathophysiology. TA creates a situation where blood
must pass from the right atrium to the left atrium via
an atrial septal defect (ASD), where it mixes with
pulmonary venous return. Blood flow is then directed
to both the pulmonary artery and the aorta by various
routes.
(2) Regardless of the type of lesion in TA, blood flow
depends entirely on the left ventricle for cardiac
output (see Fig. 25.9).
b. Hypoplastic left heart syndrome
Hypoplastic left heart syndrome (HLHS) is a group of
related disorders that involve hypoplasia of left-sided
aortic tract structures. The incidence of HLHS is
approximately 1.2% to 1.5% of all congenital heart
defects.47 Without intervention, this group of disorders is
 90% fatal within the first month of life because the ductus
arteriosus spontaneously closes. Thanks to surgical
advances with palliative procedures, almost 70% of
neonates born with HLHS will now reach adulthood.47
(1) Pathophysiology. HLHS creates a situation in which
inadequate blood flow is able to pass through the
hypoplastic left ventricle and hypoplastic aortic arch.
Mitral and/or aortic valves may be too small to allow
adequate systemic blood flow or completely atretic
allowing no left-sided cardiac output. Neonatal
systemic circulation is almost completely dependent
on the right ventricular pumping of blood shunted
though the ductus arteriosus.
(2) Today, most children afflicted with HLHS in the
developed world undergo a series of three palliative
operations completed by the age of 4 years. The end
result is much the same as with TA—a single
ventricle supplying the entirety of systemic blood
flow along with a total caval–pulmonary connection
returning de-oxygenated blood to the lungs (i.e.,
Fontan circulation).
(3) An important distinction with HLHS compared to TA
is that unlike TA, HLHS survivors are left with a
morphologic right ventricle to supply systemic blood
flow. Many of these patients will suffer from right
ventricular failure later in life and may require heart
transplantation.47 Anesthetic management of this
group of patients is among the most challenging in an
adult anesthetic practice.40
c. Surgical correction. Because of the similarity in
approach for palliation of both TA and HLHS, surgical
correction for both disorders is discussed together. The
Fontan procedure is the definitive palliative surgical
approach that creates a univentricular circulation via a
 cavopulmonary anastomosis. The Fontan procedure
consists of creation of a classical or bidirectional Glenn
shunt (i.e., superior vena cava to pulmonary artery
connection), closure of the ASD, ligation of the proximal
pulmonary artery, and creation of right atrial-to-
pulmonary artery connection (see Fig. 25.9). Multiple
variations of the Fontan procedure exist; however, the
same general physiologic principles apply to most
situations:21,29,33
(1) Blood flow to the pulmonary arteries is passive.
Elevations in PVR will therefore reduce pulmonary
flow, and hence decrease cardiac output, by
reducing the gradient between the vena cava and the
pulmonary artery.
(2) Hemodynamic stability is highly dependent on
maintaining high systemic venous pressures and
right atrial preload. Decreased right atrial preload
causes dramatic declines in pulmonary blood flow
and cardiac output. Peripheral edema often results
from the high systemic venous pressures.
(3) Spontaneous respiration assists forward flow by
keeping PVR low. Any compromise in pulmonary
function can be detrimental by increasing PVR.
(4) The single ventricle is prone to failure leading to
pulmonary edema. The atrial contribution to flow is
significant, but dysrhythmias are common and poorly
tolerated.
(5) Progressive hepatic failure is widely prevalent due to
altered hepatic circulation from increased systemic
venous pressures. This can present as bleeding
increased clotting, or as a mixed clinical picture.
Pulmonary embolism and stroke are common late
complications.
d. Peripartum considerations. Pregnancy presents a major
 challenge for patients with Fontan circulations. Small case
series report pregnancy and delivery in patients with
Fontan physiology.48,49
(1) Patients had an increased incidence of cardiac
complications, but there were no reported maternal
deaths. Heart failure, dysrhythmias, and stroke were
the most common complications.
e. Anesthetic management
(1) Vaginal delivery utilizing epidural anesthesia is the
best approach. Slow titration of epidural local
anesthetics (e.g., ropivacaine ≤0.2%, bupivacaine
≤0.125%, or lidocaine 1%) with opioids early in first
stage of labor will minimize alterations in SVR and
preload. Single-shot spinal anesthesia is
contraindicated.
(2) As a result of embolic risk, many patients will be
chronically anticoagulated; therefore, coagulation
studies and platelet counts should be obtained prior to
neuraxial blockade.
(3) Supplemental oxygen should be provided. Avoid
mechanical ventilation if possible.
(4) CD should ideally be managed with epidural
anesthesia as spontaneous respiration is preserved.
(5) If general anesthesia is required, agents should be
selected to provide a smooth hemodynamic profile.
Etomidate and ketamine are excellent induction
agents, and moderate doses of an opioid such as
fentanyl, sufentanil, or remifentanil will reduce the
stress response with an acceptable risk of fetal
respiratory depression. A muscle relaxant with
minimal hemodynamic effects (e.g., succinylcholine
or rocuronium) is desirable. Large fluid shifts from
blood loss are not well tolerated. Utmost attention
should be paid to avoiding increases in PVR or
 decreases in systemic venous pressure.
f. Invasive monitoring can be problematic and may be
unnecessary in all but the most hemodynamically unstable
patients. Central venous catheter placement probably
carries a higher risk of thromboembolic events, but may
nevertheless be appropriate for short-term use. CVP
measurements as high as 25 to 30 mm Hg are not
unexpected and may be essential to drive blood through
the pulmonary circulation. Attempts to place PACs are not
advised. If general anesthesia is administered, TEE should
be strongly considered for intraoperative monitoring.

CLINICAL PEARL Anesthetic and hemodynamic goals for

patients with Fontan circulations:
• Maintain preload. Avoid aortocaval compression.
• Avoid elevation in PVR by preventing acidosis, hypoxemia and
hypercarbia.
• Maintain sinus rhythm.
• Maintain spontaneous respiration. Avoid sedative medications.
• Avoid myocardial depressants.

5. Eisenmenger syndrome
Eisenmenger syndrome (ES) represents the most severe form
of pulmonary artery hypertension seen in adults with CHD.
Chronic high-volume systemic to pulmonary shunting of any
congenital defect results in right ventricular hypertrophy,
elevated PVR, and significant ventricular and arterial
remodeling on the right side of the heart. Eventually,
remodeling and elevation of PVR leads to reversal of shunt
flow and hypoxia. 50 ES carries a maternal mortality ranging
from 30% to 50% along with a high incidence of fetal demise,
so patients are usually counseled against pregnancy (see Fig.
25.1).6,33 Sudden death is common and may be due to stroke,
dysrhythmia, brain abscesses, or heart failure. Twenty-five-
year survival after diagnosis of ES is reported to be 42% in
the absence of pregnancy.39
a. Pathophysiology. ES is defined by a PVR greater than
800 dyn·s/cm5 along with right-to-left or bidirectional
shunt flow.33 Early correction of the shunt may resolve
the progression to pulmonary hypertension, but once
pulmonary arteriolar remodeling (i.e., medial
hypertrophy) develops, the elevated PVR is irreversible,
differentiating ES from primary pulmonary hypertension
(PPH).1
(1) Symptoms: fatigue, dyspnea, cyanosis, edema,
clubbing, and polycythemia
(2) Elevated stroke risk: The underlying right-to-left
shunt, hyperviscosity from polycythemia, and the
development of heart failure promote thrombus
formation and embolization.
b. Peripartum considerations. Patients with ES are often
unable to accommodate the increased oxygen demands of
pregnancy.
(1) Reduced SVR from pregnancy coupled with the
irreversible elevated PVR of Eisenmenger increases
right-to-left shunting and cyanosis.
(2) Reduction in functional residual capacity adds to the
hypoxemia, further reducing oxygen delivery to the
fetus and increasing the risk of fetal demise.1
(3) Management of patients who desire to remain
pregnant should be carried out utilizing a
multidisciplinary approach among obstetricians,
cardiologists, and anesthesiologists trained in high-
risk pregnancies.
c. Anesthetic management for labor. Historically,
neuraxial anesthesia was contraindicated, and general
anesthesia was the standard. A review of cases of
 noncardiac surgery including labor and CD in
Eisenmenger syndrome indicates that neuraxial anesthesia
is safe for these patients.51 In addition, it has been shown
that general anesthesia confers a near fourfold increased
risk of maternal mortality in patients with severe PH.52
Regardless of the type of anesthetic, this population
requires utmost vigilance to maintain the aforementioned
hemodynamic goals. Vaginal deliveries will often require
an assisted second stage to reduce cardiac stress. 50,53
d. Labor. Early and effective analgesia is critical to maintain
the balance of SVR and PVR by avoiding catecholamine
surges from pain. Intrathecal opioid administration (CSE)
in first stage of labor is ideal; however, if anticoagulation
is a concern, then a low-dose remifentanil infusion or
patient-controlled analgesia are good options.6
(1) Slow titration of local anesthetic with aggressive
treatment for any reduction in SVR (i.e., systemic
hypotension) using phenylephrine will provide good
results for second stage of labor as well as
instrumental delivery.51
(2) Maintenance of intravascular volume status using
carefully titrated fluid boluses along with use of
phenylephrine for decreased SVR should be used to
prevent onset or exacerbation of cyanosis.
(3) Pudendal blockade may also be employed to avoid
the risk of extending the epidural blockade (and
decreasing SVR) to “cover” stage 2 of labor and for
delivery.
(4) Oxytocin, methergine, and prostaglandins should be
used with extreme caution because of systemic and
pulmonary vascular side effects.
e. Anesthesia for cesarean delivery
(1) Slowly titrated epidural anesthetics maybe preferable
to general anesthesia.
 (2) Slow titrated doses of local anesthetic to obtain a
surgical block can be safely used.
(3) Single-shot spinal anesthesia is contraindicated.
(4) Tight hemodynamic monitoring and control is of
utmost importance.51 Avoiding elevations in PVR is
critical (see Table 25.3).
f. For general anesthesia, slow titration of induction agents
is preferred because rapid sequence inductions carry a
high risk of SVR alterations and subsequent
hemodynamic collapse. This places the patient at
increased risk for aspiration, so strict NPO guidelines, use
of pharmacologic prophylaxis against aspiration (e.g.,
sodium citrate, H2-blockade), and mask ventilation using
cricoid pressure are recommended. Propofol should be
avoided or used with extreme caution due to marked
reductions in SVR, whereas ketamine and etomidate seem
appropriate. Inhalational agents should be used with
caution because of their propensity to decrease SVR.
Nitrous oxide should be avoided because of its likelihood
to increase PVR. Maintenance of anesthesia may be
accomplished using careful titration of intravenous agents
such as nondepolarizing neuromuscular blockers, opioids,
and sedative-hypnotic agents (e.g., midazolam or
ketamine) as well as “topping off” with potent
inhalational agents used at concentrations of less than 0.5
MAC.
g. Monitoring
(1) Pulse oximetry may be the most important monitor
because changes in saturation directly correlate with
alterations in shunt flow.1
(2) Intra-arterial monitoring is generally employed and
is used to closely monitor blood pressure.
(3) Central venous catheters are controversial. CVP
catheter placement carries a risk of air embolus,
 thrombus, and pneumothorax, which can be
devastating in these patients; however, information
regarding cardiac filling pressures can be useful.
(4) PACs are contraindicated in obstetric patients with
ES for a number of reasons. The anatomic
abnormality causing ES typically renders flow-
directed flotation of PA catheters difficult or
impossible. The risk of dysrhythmia, pulmonary
artery rupture, and thromboembolism are also
elevated. Cardiac output measurements will be
inaccurate due to the large shunt.
(5) If general anesthesia is administered, TEE may
provide the best real-time monitor of cardiac preload
and of the status of right-to-left shunting.
h. Advanced pulmonary artery hypertension therapies
(1) Inhaled nitric oxide. Inhaled nitric oxid (iNO) is a
direct-acting pulmonary vasodilator that avoids
systemic vasodilation, thus reducing shunt flow and
hypoxia. Evidence for use of iNO for labor in
Eisenmenger patients is limited, but several case
reports indicate improvement in oxygenation and
reduced pulmonary pressures.46
(2) Prostacyclin analogues. Prostacyclin analogues act
like iNO and are direct pulmonary vasodilators.
However, their use in pregnancy is not well defined.
As with iNO, it is probably best to institute treatment
prior to hemodynamic collapse and right ventricular
failure.52
(3) Endothelin receptor antagonists. Endothelin
receptor antagonists (ERAs), such as bosentan, work
by competitively binding at the endothelin-A and B
receptors in pulmonary vasculature, limiting vascular
constriction. Animal studies have shown that
bosentan may have teratogenic effects; therefore, its
 use in pregnancy is limited.54
(4) Phosphodiesterase inhibitors. Phosphodiesterase
inhibitors (PDE5) such as sildenafil act by inhibiting
the degradation of cGMP, causing pulmonary
vasodilation. Sildenafil’s use in pregnancy and ES is
not well defined. Sildenafil has not been shown to be
teratogenic in animal studies, although its safety
profile is not well elucidated in humans. Patients
presenting on sildenafil therapy probably should be
maintained on the drug during pregnancy.52

CLINICAL PEARL Anesthetic and hemodynamic goals for

Eisenmenger syndrome:
• Avoid elevations in PVR. Prevent hypoxemia, acidosis, hypercarbia, and
pain. Provide supplemental oxygen at all times.
• Maintain SVR. Reductions in SVR will increase right-to-left shunting.
• Avoid myocardial depressants and maintain myocardial contractility.
• Maintain preload. Avoid aortocaval compression.
• Maintain sinus rhythm.

C. Left-to-right shunting
1. General considerations. There are some general anesthetic
considerations that apply to lesions causing left-to-right
shunts, particularly in patients with residual defects.32,33,39
a. Left-to-right shunts include defects such as ASD, VSD,
or PDA. Large defects require surgical repair, which, if
done early, result in normal cardiac physiology. These
patients can be managed as typical obstetric patients.
Patients with repaired or small defects tend to tolerate the
physiologic changes of pregnancy well.4
b. Effects of chronic shunting. The balance between SVR
and PVR determines the shunt fraction and the direction
of shunting. Causes of chronic left-to-right shunting
 include:
(1) Excessive pulmonary blood flow, which can lead to
pulmonary edema or pulmonary hypertension. As a
result of elevated pulmonary blood flow, PVR
increases over time, which reduces left-to-right
shunting. This eventually causes equilibration of left
and right ventricular pressures and conversion of the
left-to-right shunt into a right-to-left shunt to produce
Eisenmenger physiology.
(2) Once Eisenmenger complex develops, cyanosis
ensues along with variable degrees of heart failure,
which places patients in the highest risk category for
pregnancy (see Table 25.2).
(3) Even without Eisenmenger complex, these patients
may experience heart failure as a result of the high
RV and pulmonary blood flow, which may be as
much as four times systemic blood flow.
c. SVR. Acute changes in SVR from anesthetic
administration or pain can result in alteration or reversal
of the shunt, leading to heart failure or cyanosis. These
alterations depend on where the patient is in the evolution
from large left-to-right shunt into the right-to-left shunting
of Eisenmenger physiology. Overall, anesthetic goals
should be to maintain physiologic balance and avoid
abrupt hemodynamic alterations.
d. Supplemental oxygen should be provided to avoid
hypoxemia and elevation of PVR.
e. Air embolus. Extreme care to avoid an air embolus is
required. Epidural catheter placement should use saline
for loss of resistance, not air, because air entrainment into
an epidural vein can cross to the left sided circulation. IV
lines should be aggressively de-aired and monitored.
f. Single-shot spinal anesthesia is contraindicated for
patients who have or are approaching Eisenmenger
 physiology. Spinal anesthesia is theoretically beneficial
for patients with large left-to-right shunts and normal, or
only slightly elevated PVR, that remains far below SVR.
g. Inhalational agents. Uptake should not be affected by
left-to-right shunting. Right-to-left shunting prolongs
inhalation inductions, but this is rarely clinically relevant.
h. Invasive monitors. Central venous or arterial catheters
should be considered in patients with symptomatic heart
failure. PA catheters are considered to be contraindicated
by some because of the difficulty encountered in placing
them and the possibility of increased risk of pulmonary
artery rupture, but this area of practice lacks evidence-
based information.
i. Anticoagulation during pregnancy is common due to
elevated thromboembolic risk, so coagulation status
should be tested prior to neuraxial blockade.
2. Atrial septal defect
ASDs account for nearly one-third of congenital heart defects
and are found in women more commonly than men.39 Small
defects (less than 5 mm) are hemodynamically insignificant,
but large defects (greater than 20 mm) can have severe
hemodynamic consequences.33,34 ASDs do not typically close
spontaneously and are commonly associated with additional
cardiac defects. Modern interventional techniques permit
ASD closure through percutaneous methods with a high rate
of success in long-term outcome studies.55–58
a. Pathophysiology. The overall effect is a left-to-right
shunt along the pressure gradient. This leads to right atrial
and ventricular dilation, increased pulmonary blood flow,
and potentially to pulmonary edema (high-output failure)
and pulmonary hypertension (usually <500 dyn·s/cm5).
The likelihood for development of Eisenmenger complex
over time is much lower for a VSD with similar initial
pulmonary blood flows, but this can also occur.
 (1) Development of right heart failure can occur without
repair.
(2) Patients are at risk for dysrhythmias and paradoxical
embolus leading to stroke.
(3) Endocarditis risk is increased, so antibiotic
prophylaxis is required.
3. Ventricular septal defect
This is the most common congenital heart lesion in children,
although nearly 90% close spontaneously by age 10 years.
Those patients with large lesions and who are symptomatic at
birth will usually be surgically corrected, whereas
asymptomatic patients will often be closely monitored for
evidence of spontaneous closure.34,39 Surgical closure
typically involves a right ventricular incision, and this carries
a significant risk of interventricular and atrioventricular
conduction abnormalities. Interventional closure techniques
show definite promise, but lack long-term outcome studies to
support their use.38,39,59
4. Patent ductus arteriosus
PDA accounts for roughly 10% of congenital heart defects
and occurs in females in a ratio of 2:1.34,39 In utero, the
ductus arteriosus connects the aorta and pulmonary artery
allowing fetal circulation to bypass the lungs. Failure of the
ductus arteriosus to close shortly after birth results in a left-to-
right shunt that behaves much like a VSD. If present after
infancy, PDA closure rarely occurs spontaneously and closure
can be accomplished surgically without cardiopulmonary
bypass (CPB). Newer interventional approaches permit PDA
closure in the interventional radiology suite, thus avoiding
surgery and demonstrate >95% clinical success.60
a. Pathophysiology (ventricular septal defect and patent
ductus arteriosus). The predominant effect of left-to-
right shunting depends on the size and the resistance
between the systemic and pulmonary systems. In contrast
 to ASD, both VSD and PDA will result in left ventricular
volume overload and dilation.
(1) PVR eventually increases in response to chronic
exposure to aortic pressures, and eventually the flow
equalizes and then converts to a right-to-left shunt to
produce Eisenmenger physiology.
(2) Shunt flow depends on the balance between SVR and
PVR, so acute changes in either of these can alter the
shunt, induce cyanosis, and pulmonary circulatory
and left ventricular volume overload.
b. Anesthetic management. Refer to the general guidelines
at the start of this section. Epidural anesthesia is the
preferred approach for patients with significant shunt
because it reduces alterations in SVR when titrated
slowly.
(1) Either vaginal or CD are acceptable; however, in
patients with severe shunting, vaginal delivery may
provide more stable hemodynamics as a result of
reduced blood loss.
(2) Patients with reduced cardiac function may benefit
from assisted second stage of labor (i.e., assistance
with forceps or vacuum extraction) to reduce the
duration of labor and stress on the cardiovascular
system.
c. General anesthesia can safely be administered in these
patients with close attention to the hemodynamic goals
outlined earlier. Titration of induction agents and careful
ventilatory management minimizes changes in SVR and
PVR (see Table 25.3).
D. Aortic defects
1. Coarctation of the aorta
Coarctation of the aorta is a congenital lesion affecting males
more often than females. It is caused by a constricting band
impinging on the aortic lumen and is most often located just
distal to the left subclavian artery in the area of the
ligamentum arteriosum. Extensive collateral circulation
develops through axillary, subclavian, intercostal, and
scapular arteries. Associated defects include VSD, ASD,
PDA, bicuspid aortic valve, circle of Willis aneurysms, and
mitral valve abnormalities.39,61
a. Pathophysiology. Systolic and mean arterial blood
pressure differences are noted between the upper and
lower extremities, although diastolic pressures are usually
similar. Physiologic consequences include hypertension
proximal to the coarctation, left ventricular hypertrophy
and failure, coronary arterial occlusive disease, stroke,
aortic dissection, and an elevated risk of endocarditis.39
Severity is determined by the gradient across the
coarctation. Surgical repair is typically indicated for mean
arterial pressure gradients greater than 30 mm Hg.
b. Peripartum considerations. Pregnancy is usually well
tolerated in patients with both corrected and uncorrected
lesions, as reported by Beauchesne et al.61 in a series of
118 pregnancies in 50 women. There was one death in
this group from acute aortic dissection. A higher
incidence of CD was also noted.
(1) Significant hypertension above the coarctation can
adversely affect the fetus.61,62 Blood pressure control
is used to reduce the risk of aortic dissection, with β-
adrenergic blockers serving as first-line
antihypertensive drugs. Treatment of hypertension
theoretically serves as a two-edged sword because
adequate uterine perfusion pressure may depend on
high driving pressures above the coarctation,
especially if arterial collaterals are poorly developed.
(2) Alterations in cardiac output and blood volume can
precipitate heart failure.
c. Anesthetic management. Early analgesic administration
 reduces hemodynamic stress and theoretically helps
prevent aortic dissection. Vaginal delivery is preferred,
often with a forceps-assisted second stage to reduce risk
of prolonged labor.
(1) For corrected or uncorrected but mild coarctation,
epidural anesthesia is an acceptable approach using
careful titration of opioid and local anesthetic to
avoid large reductions in SVR, which could
compromise uterine perfusion pressure.
(2) Single-shot spinal anesthesia is contraindicated.
(3) Uncorrected coarctation represents one subset of
patients where epidural anesthesia is relatively
contraindicated. In the setting of a high arterial
pressure gradient, placental perfusion pressure can be
reduced significantly following epidural anesthesia.
General anesthesia is preferred in severe coarctation,
with emphasis on hemodynamic stability and
avoidance of tachycardia.
(4) In addition to prevention of substantial reductions in
blood pressure, one should also avoid large increases
in blood pressure because the risk of aortic dissection
and cerebral aneurysm rupture appears to be elevated
in this group of patients.
(5) As in all pregnant women, aortocaval compression
should be avoided and fetal monitoring used because
reduced placental perfusion occur with any chosen
anesthetic.
2. Marfan syndrome
Marfan syndrome (MFS) is a hereditary collagen vascular
disorder that presents diversely in the skeletal, ocular, and
cardiovascular systems, among others.6,21 The increased
stress on the cardiovascular system during pregnancy can
cause aortic dilation or dissection in MFS, which has been
associated with increased mortality during pregnancy. Recent
outcomes studies confirm that MFS continues to carry
increased risk for both the developing fetus and the
mother.63–65
a. Pathophysiology. Development of aortic dissection is the
primary reason for high mortality during pregnancy.
Aortic dissection begins as a tear in the intima, allowing a
path for blood to flow between the intima and media or
adventitia. This creates a false lumen that can spread
distally or proximally along the aorta or into its branch
arteries. Dissections fall into three categories:
(1) Type I dissections involve the ascending aorta, aortic
arch, and descending aorta, whereas Type II
dissections are confined to the ascending aorta. Type
III dissections begin in the descending aorta and
spread distally from there.
(2) Aortic rupture can occur in MFS and is nearly always
fatal.
(3) When the root of the ascending aorta is dilated from
MFS, as can occur even without dissection because
of laxity in the aortic wall, aortic insufficiency (AI)
can occur. This AI can range from asymptomatic and
mild to severe enough to induce left ventricular (LV)
failure even without pregnancy. When Type I or Type
II dissections occur, acute AI often results.
b. Peripartum considerations. Pregnancy presents a
challenge for MFS patients who have significant aortic
involvement and frequently causes increased aortic
dilation or dissection.
(1) If the aortic root diameter (at or distal to the
sinotubular junction) is less than 40 mm, pregnancy
is generally well tolerated.6 A prospective cohort
study from 1995 reported a 1% maternal mortality in
this specific group.65,66 The authors recommend
serial echocardiographic monitoring of aortic size as
 well as prophylactic β-adrenergic blockade, which is
a mainstay in MFS both with and without dissection.
(2) The maternal mortality risk is 30% to 40% with a
history of dissection, aortic root size >40 mm, or
aortic valve involvement causing AI.1,3 These
patients are often counseled against pregnancy, and if
pregnancy is attempted, CD is recommended.6
(3) In acute aortic dissection, case reports describe aortic
root repair utilizing normothermic CPB with selective
cerebral perfusion resulting in survival of mother and
fetus.67,68
(4) Data for the management of aortic dissections in
pregnancy is sparse, so no consensus
recommendations exist. Type III dissections should
be managed medically (tight BP and HR control), and
type I or II dissections are managed surgically if the
situation allows.6,64,68
(5) Advances in interventional endovascular
management of aortic pathology are occurring
rapidly. Thoracic Endovascular Aortic Repair
(TEVAR) now has a defined role in the treatment of
thoracic aortic pathology and should be considered
for its management.69 Recently, reports of use of
TEVAR for aortic dissection during pregnancy have
indicated success, however large-scale studies are
lacking.70,71
c. Anesthetic considerations. The main goals for anesthetic
management of labor and delivery are reduction in
cardiovascular stress and afterload reduction.
Currently, there is no consensus on an optimal anesthetic
approach because good outcomes have been reported with
either general or epidural anesthesia.65,72
(1) Epidural placement early in labor can provide a
smooth hemodynamic course and accomplish the
 mentioned goals. Prolonged labor and maternal
expulsive efforts during stage II may predispose to
aortic dilation or dissection, so either forceps-assisted
delivery using an epidural catheter to produce solid
perineal anesthesia or CD may be needed.
Communication with the obstetrician is important to
help develop a complete management plan. Spinal
anesthesia is an acceptable and perhaps the most
desirable choice for CD.
d. Acute aortic dissection is a high-risk situation. If the
fetus is mature enough for delivery in the presence of a
Type I or Type II dissection, then a combined CD of the
fetus and aortic repair can be employed using general
anesthesia with full hemodynamic monitoring including
TEE. If the dissection is small and stable and there is a
question of fetal maturity, then medical management with
afterload reduction and β-adrenergic blockade may be the
best option until CD can be performed which conveys a
reasonable expectation of maternal and fetal survival. The
anesthetic technique should emphasize reduction in
cardiovascular stress response and afterload
reduction.65,72
IV. Primary pulmonary hypertension
Although not considered a congenital defect, peripartum management
for PPH is similar to ES. PPH is defined as a syndrome with elevated
pulmonary artery pressures (mean PAP >25 mm Hg at rest) in the
absence of primary cardiac pathology.6,46 PPH is associated with
reduced nitric oxide and prostacyclin synthesis, as well as with
increased thromboxane production. Histologic features include medial
thickening and intimal fibrosis. PPH typically involves pulmonary
vasculature that remains responsive to vasodilators, whereas ES is
characterized by an unresponsive pulmonary vasculature.22
A. Peripartum considerations. Mortality and morbidity is high in
PPH and many authors consider pregnancy to be contraindicated.
 Risk for maternal mortality is nearly 30% for PPH.
1. Pregnancy can induce right heart dilation or failure and many
cases of maternal death occur in the initial week postpartum.
2. Thromboembolic events are also common and most patients
require anticoagulation.
B. Anesthetic management.22 Refer to the hemodynamic goals for
ES, with one caveat: Reduction in SVR will not alter the shunt
fraction for PPH patients because there is no defect, but will
cause a marked decrease in cardiac output due to relatively
fixed right-sided pressures. Experience in the management of
these patients is increasing, but reported cases are still quite low.
Consensus recommendations are limited.
1. Vaginal delivery is preferred using epidural anesthesia (or
CSE) with an assisted second stage labor (i.e., forceps
delivery) to minimize stress on the right ventricle.
2. Oxytocin has been used successfully both for induction of
labor and to increase uterine tone postpartum. Careful titration
is required because it can decrease SVR and elevate PVR to
decrease both coronary perfusion pressure and forward flow.
It is important to avoid carboprost and methergine because of
bronchoconstrictive and vasoconstrictive side effects,
respectively.
3. CD has been associated with increased mortality; however,
patients with severe disease causing right heart failure may
require operative delivery.73 The anesthetic should be tailored
to each patient’s underlying cardiac function because epidural
and general anesthesia have similar outcomes.
4. iNO has been used successfully during labor (see discussion
under “Eisenmenger syndrome” section).74 Other therapeutic
agents that are useful in the management of ES are potentially
useful in patients with PPH.
C. Invasive monitoring. Arterial and PACs are generally employed.
The PAC can help guide the vasodilator therapy as well as
monitor the volume status of the patient. Although the risks of
 placement discussed in previous sections apply to this subset of
patients, the information gained may outweigh the risk of
placement. TEE should be considered in the setting of general
anesthesia (see Fig. 25.10).

V. Cardiomyopathy
Cardiomyopathy constitutes a rare but devastating cardiac
complication for pregnant women. Etiologies include peripartum
cardiomyopathy, idiopathic dilated cardiomyopathy, and hypertrophic
obstructive cardiomyopathy (HOCM).
A. Peripartum cardiomyopathy. Peripartum cardiomyopathy
(PPCM) occurs with a general incidence of 1:3,000 to 1:4,000
live births.6,75 The current accepted definition is: an idiopathic
cardiomyopathy presenting with heart failure secondary to LV
systolic dysfunction towards the end of pregnancy or in the
months following delivery. It is a diagnosis of exclusion when no
other cause of heart failure is found. The LV may not be dilated,
but the EF is nearly always reduced below 45%.6,76 Recent trends
in the United States suggest an actual incidence of 8.5 to 11 per
10,000 live births, with a major adverse event rate of 13.5%.77
Echocardiography confirms the diagnosis by the presence of
reduced LV ejection fraction (<45%), decreased fractional
shortening (<30%), and/or elevated end diastolic LV diameter
(see Figs. 25.11 and 25.12).
1. Pathophysiology. Symptoms of fatigue, shortness of breath,
and peripheral edema are typical in pregnancy; however,
progressive deterioration and increased severity along with
chest pain, palpitations, and pulmonary edema can indicate
developing heart failure.
a. The etiology of PPCM is unknown, but myocarditis,
maladaptive response to the hemodynamic challenges of
pregnancy, abnormal immune response to pregnancy, and
prolonged tocolysis have been implicated.72,75
b. PPCM is associated with multiple gestations,
preeclampsia, obesity, advanced maternal age, and
coronary vascular disease.
c. Standard therapeutic measures for heart failure should be
 initiated including salt and water restrictions, diuretics,
afterload reduction, and inotropic support as needed.75,78
2. Peripartum considerations. Once the diagnosis is made,
collaboration among the cardiologist, obstetrician, and
anesthesiologist is critical for timely decisions about care.
Maternal mortality is nearly 20% with some patients
surviving only if a heart transplant is available.75 There may
be a role for immunosuppressive therapy if myocarditis is
confirmed by biopsy and the patient’s condition is
deteriorating.6,75,78
a. In the setting of heart failure with a fetus that is near term,
delivery should occur because this reduces stress on the
heart.
b. Anticoagulation may be needed to decrease
thromboembolic risk.
c. Standard therapy for heart failure includes angiotensin-
converting enzyme (ACE) inhibitors; however, this needs
to be delayed until after birth because of
teratogenicity.75,78 β-adrenergic blockade, hydralazine,
and nitrates may help allay symptoms during pregnancy,
and there is the potential need for inotropic or “inodilator”
support using drugs such as dobutamine or milrinone.
d. Prognosis depends on the degree of recovery of left
ventricular function by 6 to 12 months postpartum.
Presence of heart failure symptoms at this time indicates
irreversible damage.75 Approximately 50% of women will
recover normal or near-normal cardiac function, but 5-
year mortality with persistent dysfunction can reach
85%.75
e. Repeated pregnancy carries a mortality risk of 1% to 15%
in various populations, with up to 50% of patients
demonstrating recurrance of PPCM.6
3. Anesthetic management should reflect principles for any
patient with heart failure. These patients will have extreme
 sensitivity to myocardial depressants including those typically
used for general anesthesia. In this context, even volatile
anesthetics that typically induce vasodilation as their
predominant hemodynamic effect may cause myocardial
depression and decompensation; careful titration and low
concentrations (<0.5 MAC) are recommended if those agents
are chosen.
a. Epidural anesthesia using slow titration of a dilute local
anesthetic solution and an opioid will gently reduce SVR,
so this is a good choice. This should be employed early in
first stage of labor, and often a forceps-assisted delivery
will likely reduce hemodynamic stress on the heart by
expediting delivery.6
b. Coagulation studies should be checked (especially before
epidural placement) because anticoagulation therapy is
common.
4. CD can be managed with epidural anesthesia provided there
is time to slowly titrate the local anesthetic. If general
anesthesia is required, myocardial depressants, such as
inhalational agents, and propofol should be avoided or titrated
cautiously in low doses. Generous use of opioids will reduce
the stress response and remifentanil may be the best choice
because of its short duration of action and low likelihood of
inducing prolonged fetal respiratory depression. Cautious use
of β-adrenergic blockade (e.g., esmolol) can prevent dramatic
increases in HR. Careful attention to intravascular volume and
blood loss is required because both hypovolemia and
hypervolemia are poorly tolerated.
5. Invasive monitors. Arterial catheters should be strongly
considered for patients with PPCM. The decision to place
central venous and PACs should be made on a case-by-case
basis, but they are generally reserved for NYHA class III and
IV patients. In the setting of general anesthesia, TEE provides
rapid, real-time evaluation of cardiac function.
B. Idiopathic dilated cardiomyopathy. Dilated cardiomyopathy
(DCM) is extremely rare in pregnancy with an estimated
incidence of 5:100,000 births per year and has a similar
presentation, risk, and treatment as PPCM. Symptoms are the
same as for PPCM, but the onset of idiopathic dilated
cardiomyopathy (IDC) is not limited to the later stages of
pregnancy. Possible etiologies include idiopathic,
familial/genetic, viral, immune, alcoholic, or toxic causes.79
Treatment goals are the same as for PPCM.
C. Hypertrophic obstructive cardiomyopathy. HOCM is a genetic
disorder causing hypertrophy of the left ventricle and varying
degrees of left ventricular outflow tract obstruction (LVOTO).
The hypertrophy causes a noncompliant or “stiff” ventricle with
varying degrees of diastolic dysfunction, reduction in left
ventricular volumes, and outflow obstruction (see Fig. 25.13).

1. Peripartum considerations. The physiologic changes of

pregnancy are typically well tolerated because the decreased
SVR is offset to some degree by the elevation in blood
volume. Tachycardia is poorly tolerated and patients are often
treated with β blockade.80 Maternal mortality with HOCM is
approximately 10 per 1000 live births and appears to be
directly related to the presence of heart failure symptoms
 prior to pregnancy.80–82
2. Anesthetic management. Dynamic obstruction of LV
outflow characterizes cardiac function in HOCM. LVOTO
with HOCM is exacerbated by increases in LV contractility
and HR and by reductions in LV preload and afterload.6 Labor
analgesia is important to avoid tachycardia and elevated
cardiac output; however, neuraxial anesthesia has been
considered by some to be contraindicated because of the
potential reduction in SVR leading to increased LVOTO.
a. Epidural anesthesia has been successfully administered
for both vaginal and CD, but the consensus is that
neuraxial blockade should be used cautiously and that
single-shot spinal anesthetics should be avoided.82 Some
authors recommend that epidural anesthesia be used only
with arterial and PAC monitoring to assist in the titration
of local anesthetics while maintaining tight control of
SVR,46 although this approach appears overly
interventional unless LVOTO is severe as judged by a
high pressure gradient diagnosed by echocardiogram or
ongoing pulmonary congestion resulting from LV failure.
b. General anesthesia should utilize similar precautions and
be tailored to the mentioned hemodynamic goals.
Avoiding tachycardia, maintaining normal to slightly
reduced myocardial contractility, and ensuring normal to
elevated SVR and a “full tank” are primary hemodynamic
goals. For these reasons, hypotension should usually be
treated first with phenylephrine. Consensus guidelines for
HOCM have been recently revised and provide a more in-
depth discussion.81,82

CLINICAL PEARL Anesthetic and hemodynamic goals for

HOCM:
1. Avoid decreased preload.
2. Avoid decreased SVR.
3. Avoid tachycardia.
4. Avoid positive cardiac inotropy because it can increase dynamic
obstruction.

D. Obstetric care after cardiac transplantation

The first successful pregnancy in a patient with a transplanted
heart was reported in 1988.83,84 Since that time, 12,900 cardiac
transplants have been performed in female patients, with an
expected 5-year survival of 69%.83 The number of cardiac
transplant operations performed annually in the United States
trends very closely to available organs, which has been around
2,200 per year since 1988 based on the national Organ
Procurement and Transplantation Network database. Initially,
cardiac transplant patients were discouraged from pregnancy;
however, there is increasing evidence that pregnancy is typically
well tolerated, providing the mother has stable cardiovascular and
renal function prior to pregnancy.85,86 There are a number of
considerations in pre-pregnancy planning, which are beyond the
scope of this chapter, but well described by Cowan et al.83
1. Pathophysiology. The transplanted heart relies on intrinsic
adrenergic receptors because it has no afferent or efferent
autonomic innervation. This results in an upregulation of the
adrenergic receptors, making these patients more sensitive to
sympathomimetic agents.
a. Lack of vagal innervation causes a high resting HR,
usually around 100 bpm. The heart is usually
unresponsive to agents such as atropine that function via
vagal effects.
b. These patients experience accelerated coronary artery
disease, various degrees of rejection impairing cardiac
function, hypertension, and possible immunosuppressive
drug side effects.
2. Peripartum considerations. In the setting of good graft (i.e.,
 cardiac) function, pregnancy is well tolerated, but if cardiac
function is questionable, then cardiac risk increases.84
a. Pregnancy places the patient at increased risk for
rejection, fetal growth restriction, preterm delivery,
hypertension, preeclampsia, and dysrhythmias.85
b. Immunosuppressive drug regimens may need to be
altered due to changing blood volume and hormonal
changes.
c. Cardiac functional studies usually are obtained by the
cardiologist and may include recent echocardiography,
cardiac catheterization, and myocardial biopsy to assess
rejection.85
d. CD should be performed for the usual obstetric
indications.
3. Anesthetic management. There have successful reports of
spinal, epidural, and general anesthetic management in
postcardiac transplant parturients.83,85 Epidural anesthesia is
the recommended approach, with slow titration to avoid large
reductions in SVR. In the setting of good graft function, these
patients should tolerate the hemodynamic effects of anesthesia
quite well. Some key points are as follows:
a. Patients may have hypersensitivity to sympathomimetics.
Consider avoiding epinephrine-containing local
anesthetics for epidural administration because there are
reports of profound tachycardia.
b. Bradycardia requires treatment with direct acting agents
such as isoproterenol or possibly epinephrine.
c. Phenylephrine can be safely administered for
hypotension. Ephedrine’s cardiac effects should be
attenuated but not eliminated as a result of cardiac
denervation.
d. Invasive monitoring is generally not required and carries
a higher risk of infection because of immunosuppression.
e. Epidural placement should be done with utmost vigilance
 for sterile technique.
f. Stress-dose steroids are generally required if the patient is
receiving corticosteroid immunosuppression.
4. General anesthesia. Should general anesthesia be chosen,
induction should focus on the mentioned hemodynamic goals.

CLINICAL PEARL Anesthetic and hemodynamic goals for

the cardiac transplant parturient:
• Maintain normal filling pressures. Avoid aortocaval compression.
• Aseptic technique is critical. Patients are at high risk for infection.
• If there are signs of coronary artery disease, treat the patient
accordingly: avoid tachycardia and hypertension.
• If there are signs of rejection, myocardial function may be impaired, so
avoid myocardial depressants.

VI. Ischemic heart disease in pregnancy

The overall incidence of acute myocardial infarction (AMI) in
pregnancy is low at 0.6 to 1 in 10,000 deliveries.87 It is estimated that
in patients with preexisting coronary artery disease or who have
previously suffered acute coronary syndrome (ACS)/myocardial
infarction (MI), the risk of serious adverse maternal cardiac risks is
approximately 10%.88 Risk factors for MI during pregnancy include
hypertension, diabetes, advanced maternal age, and severe
preeclampsia.87 The classical risk factors independent of pregnancy
include preexisting evidence of coronary artery disease, tobacco
smoking, diabetes mellitus, hypertension, family history of cardiac
disease, hyperlipidemia, and oral contraceptive use.87,89
A. Peripartum considerations. AMI during pregnancy should be
managed with aspirin, β blockade, and nitrates. Coronary artery
stenting can be employed as well as thrombolytic therapy,
provided the patient is not about to deliver vaginally, undergo a
CD, or is immediately postpartum because the risk of hemorrhage
is high.89
 1. Many cases of AMI during pregnancy are probably caused by
coronary artery spasm because up to 47% of coronary
angiography studies have been normal.
2. There is an association between coronary artery spasm and
the use of prostaglandins or methergine. Patients with risk
factors for AMI should not be treated with methergine for
postpartum hemorrhage because this may precipitate coronary
spasm. If coronary spasm is suspected, then rapid treatment
with nitrates may help avoid AMI. However nitrates should
be also used with caution because they can exacerbate
postpartum hemorrhage.
B. Anesthetic management. Anesthetic management should be
tailored to achieve the goals for any patient with cardiac disease.
Labor and delivery place a large stress on the heart. Early
analgesia in labor, typically using an epidural catheter, will help
reduce HR and the hemodynamic stress (i.e., hypertension,
increased venous return with contractions) of labor. Slower HRs
are desirable and can be facilitated with β-adrenergic blockade.
The type of anesthetic is not as important as how it is delivered,
with an emphasis on stable hemodynamics.
VII. Cardiac dysrhythmias and pregnancy. Cardiac dysrhythmias are
common during pregnancy, labor, and delivery. Associated factors
include hormone effects, alterations in autonomic tone, hemodynamic
changes, hypokalemia of pregnancy, and underlying structural heart
disease.6
A. Treatment limited to rhythms with hemodynamic
consequences. Treatment should be limited to rhythms with
hemodynamic consequences because most lack significant
effects. Paroxysmal supraventricular tachycardia (PSVT) and
ventricular tachycardia can result in hemodynamic compromise,
which can affect uterine perfusion and depress the fetus, hence
requiring aggressive treatment.
B. Therapy for dysrhythmias. Therapy for dysrhythmias during
pregnancy is the same as for the nonobstetric patient but special
considerations are needed to avoid adverse effects on the fetus.
Figure 25.14 is a summary of recommendations from the ESC
consensus guidelines on management of cardiac disease in the
pregnant patient. These guidelines provide a clear structure of
these management details.

1. Initial therapy for most tachyarrhythmias includes avoiding

agents such as tobacco, caffeine, alcohol, and stimulants such
as amphetamines.
 2. Pharmaceutical therapy is limited to agents that are safe
during pregnancy as rated by the U.S. Food and Drug
Administration (FDA) (see Chapter 2).
3. Electrical cardioversion is safe and can be considered when
hemodynamic compromise has occurred with rhythm
changes.
4. PSVT can be treated with vagal maneuvers, and if this fails,
then adenosine (FDA pregnancy class C) or β-adrenergic
blockers (class B/C) can be employed.
5. Ventricular dysrhythmias can often be terminated by using
lidocaine, procainamide, or electrical cardioversion.90
Amiodarone’s use should be based on perceived need despite
possible risk to the fetus.
6. The goal for treatment of AF is to regain sinus rhythm or to
achieve ventricular rate control (typically less than 120 bpm).
β-adrenergic blockade with metoprolol or digoxin can be
used.
VIII. Cardiopulmonary resuscitation in the obstetric patient
The incidence of sudden cardiac arrest has risen slightly from the
previous estimate of 1:30,000 pregnancies to 1:20,000.91 Patients with
cardiac disease, especially in high-risk groups (see Table 25.2), have a
greater risk of cardiac arrest. Cardiac arrest often occurs late in
pregnancy. A wide range of etiologies may be the cause, including
dysrhythmias, hemorrhage, amniotic fluid embolism, pulmonary
embolism, MI, heart failure, and iatrogenic causes such as
pharmaceuticals or hypoxia from failed intubation attempts.
A. Fetal viability influences therapy. Prior to 24 weeks’ gestation,
therapy should be directed only at saving the mother. After 24
weeks, fetal viability is a concern and American Heart
Association (AHA) guidelines for CPR in pregnancy suggest that
the best therapy for the fetus is to administer the best therapy to
the mother.91
1. When a cardiac arrest occurs, the advanced cardiac life
support (ACLS) protocol should be initiated with
 defibrillation, airway control, and chest compressions. A
wedge should be placed under the right side to prevent
aortocaval compression and improve blood flow during chest
compressions. Electrical cardioversion should be used if
indicated, along with appropriate pharmaceutical therapy as
guided by the ACLS protocol.
2. Search for etiology of arrest: BEAU-CHOPS is the AHA
acronym to consider:91
a. Bleeding
b. Embolism (pulmonary, coronary, amniotic fluid)
c. Anesthetic complications (e.g., local anesthetic systemic
toxicity [LAST])
d. Uterine atony
e. Cardiac disease
f. Hypertension/preecclampsia
g. Other: Follow standard ACLS differential diagnostic
criteria.
h. Placental abruption/previa
i. Sepsis
3. If initial attempts at resuscitation are unsuccessful, immediate
delivery of the fetus within 4 minutes of the arrest is indicated
because this may save the life of the fetus and help resuscitate
the mother. Fetal resuscitation from hypoxia, acidosis, and
possible preterm delivery is usually needed.
4. More invasive measures may be considered including
thoracotomy with open heart massage or initiation of CPB,
although this is typically only considered in cases of
pulmonary embolism or bupivacaine toxicity where CPB can
provide support while the bupivacaine slowly dissipates from
sodium channels.
B. Treatment of cardiac arrest from suspected LAST. For cardiac
arrest from suspected LAST, management with current ACLS
protocol must be adjusted (see Chapter 3).
REFERENCES
1. Vidovich M. Cardiovascular disease. In: Chestnut DH, Wong C, Tsen LC, et al, eds. Chestnut’s
Obstetric Anesthesia: Principles and Practice. 5th ed. Philadelphia, PA: Elsevier Saunders; 2014;960–
1002.
2. Ortman AJ. The pregnant patient with congenital heart disease. Semin Cardiothorac Vasc Anesth.
2012;16:220–234.
3. Siu SC, Sermer M, Colman JM, et al. Prospective multicenter study of pregnancy outcomes in women
with heart disease. Circulation. 2001;104:515–521.
4. Kuklina E, Callaghan W. Chronic heart disease and severe obstetric morbidity among hospitalisations
for pregnancy in the USA: 1995-2006. BJOG. 2011;118:345–352.
5. Klein LL, Galan HL. Cardiac disease in pregnancy. Obstet Gynecol Clin North Am. 2004;31:429–459.
6. Regitz-Zagrosek V, Blomstrom Lundqvist C, Borghi C, et al. ESC guidelines on the management of
cardiovascular diseases during pregnancy: the Task Force on the Management of Cardiovascular
Diseases during Pregnancy of the European Society of Cardiology (ESC). Eur Heart J. 2011;32:3147–
3197.
7. Lupton M, Oteng-Ntim E, Ayida G, et al. Cardiac disease in pregnancy. Curr Opin Obstet Gynecol.
2002;14:137–143.
8. van Mook WN, Peeters L. Severe cardiac disease in pregnancy, part I: hemodynamic changes and
complaints during pregnancy, and general management of cardiac disease in pregnancy. Curr Opin
Crit Care. 2005;11:430–434.
9. Balci A, Sollie-Szarynska KM, van der Bijl AG, et al. Prospective validation and assessment of
cardiovascular and offspring risk models for pregnant women with congenital heart disease. Heart.
2014;100:1373–1381.
10. Drenthen W, Pieper PG, Roos-Hesselink JW, et al. Outcome of pregnancy in women with congenital
heart disease: a literature review. J Am Coll Cardiol. 2007;49:2303–2311.
11. Ford AA, Wylie BJ, Waksmonski CA, et al. Maternal congenital cardiac disease: outcomes of
pregnancy in a single tertiary care center. Obstet Gynecol. 2008;112:828–833.
12. Burn J, Brennan P, Little J, et al. Recurrence risks in offspring of adults with major heart defects:
results from first cohort of British collaborative study. Lancet. 1998;351:311–316.
13. van Mook WN, Peeters L. Severe cardiac disease in pregnancy, part II: impact of congenital and
acquired cardiac diseases during pregnancy. Curr Opin Crit Care. 2005;11:435–448.
14. Wolff GA, Weitzel NS. Management of acquired cardiac disease in the obstetric patient. Semin
Cardiothorac Vasc Anesth. 2011;15:85–97.
15. Ayoub CM, Jalbout MI, Baraka AS. The pregnant cardiac woman. Curr Opin Anaesthesiol.
2002;15:285–291.
16. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients
with valvular heart disease: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines. Circulation. 2014;129:e521–e643.
17. Martínez-Ríos MA, Tovar S, Luna J, et al. Percutaneous mitral commissurotomy. Cardiol Rev.
1999;7:108–116.
18. Silversides CK, Colman JM, Sermer M, et al. Cardiac risk in pregnant women with rheumatic mitral
stenosis. Am J Cardiol. 2003;91:1382–1385.
19. Pan PH, D’Angelo R. Anesthetic and analgesic management of mitral stenosis during pregnancy. Reg
Anesth Pain Med. 2004;29:610–615.
20. Clark SL, Phelan JP, Greenspoon J, et al. Labor and delivery in the presence of mitral stenosis: central
hemodynamic observations. Am J Obstet Gynecol. 1985;152:984–988.
21. Siu SC, Colman JM. Heart disease and pregnancy. Heart. 2001;85:710–715.
22. Ray P, Murphy G, Shutt L. Recognition and management of maternal cardiac disease in pregnancy. Br
J Anaesth. 2004;93:428–439.
23. Hemmings GT, Whalley DG, O’Connor PJ, et al. Invasive monitoring and anaesthetic management of
a parturient with mitral stenosis. Can J Anaesth. 1987;34:182–185.
24. Ramsey PS, Ramin KD, Ramin SM. Cardiac disease in pregnancy. Am J Perinatol. 2001;18:245–266.
25. Bonow RO, Carabello BA, Kanu C, et al. ACC/AHA 2006 guidelines for the management of patients
with valvular heart disease: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for
the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society
of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and
Interventions and the Society of Thoracic Surgeons. Circulation. 2006;114:e84–e231.
26. Van de Velde M, Budts W, Vandermeersch E, et al. Continuous spinal analgesia for labor pain in a
parturient with aortic stenosis. Int J Obstet Anesth. 2003;12:51–54.
27. Paulus DA, Layon AJ, Mayfield WR, et al. Intrauterine pregnancy and aortic valve replacement. J
Clin Anesth. 1995;7:338–346.
28. Williams RG, Pearson GD, Barst RJ, et al. Report of the National Heart, Lung, and Blood Institute
Working Group on research in adult congenital heart disease. J Am Coll Cardiol. 2006;47:701–707.
29. Webb GD, Williams RG. 32nd Bethesda Conference: “Care of the adult with congenital heart
disease”. J Am Coll Cardiol. 2001;37:1162.
30. van der Bom T, Zomer AC, Zwinderman AH, et al. The changing epidemiology of congenital heart
disease. Nat Rev Cardiol. 2011;8:50–60.
31. Connelly MS, Webb GD, Somerville J, et al. Canadian Consensus Conference on Adult Congenital
Heart Disease 1996. Can J Cardiol. 1998;14:395–452.
32. Skorton DJ, Garson A Jr, Allen HD, et al. Task force 5: adults with congenital heart disease: access to
care. J Am Coll Cardiol. 2001;37:1193–1198.
33. Lovell AT. Anaesthetic implications of grown-up congenital heart disease. Br J Anaesth. 2004;93:129–
139.
34. Moodie DS. Diagnosis and management of congenital heart disease in the adult. Cardiol Rev.
2001;9:276–281.
35. Deanfield J, Thaulow E, Warnes C, et al. Management of grown up congenital heart disease. Eur
Heart J. 2003;24:1035–1084.
36. Nollert G, Fischlein T, Bouterwek S, et al. Long-term survival in patients with repair of tetralogy of
Fallot: 36-year follow-up of 490 survivors of the first year after surgical repair. J Am Coll Cardiol.
1997;30:1374–1383.
37. Touati GD, Vouhé PR, Amodeo A, et al. Primary repair of tetralogy of Fallot in infancy. J Thorac
Cardiovasc Surg. 1990;99:396–402.
38. Brickner ME, Hillis LD, Lange RA. Congenital heart disease in adults. First of two parts. N Engl J
Med. 2000;342:256–263.
39. Brickner ME, Hillis LD, Lange RA. Congenital heart disease in adults. Second of two parts. N Engl J
Med. 2000;342:334–342.
40. Heggie J, Karski J. The anesthesiologist’s role in adults with congenital heart disease. Cardiol Clin.
2006;24:571–585.
41. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 guidelines for the management of
adults with congenital heart disease: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines on the
Management of Adults With Congenital Heart Disease). Developed in collaboration with the
 American Society of Echocardiography, Heart Rhythm Society, International Society for Adult
Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of
Thoracic Surgeons. J Am Coll Cardiol. 2008;52:e143–e263.
42. Veldtman GR, Connolly HM, Grogan M, et al. Outcomes of pregnancy in women with tetralogy of
Fallot. J Am Coll Cardiol. 2004;44:174–180.
43. Motta P, Miller-Hance WC. Transesophageal echocardiography in tetralogy of Fallot. Semin
Cardiothorac Vasc Anesth. 2012;16:70–87.
44. Twite MD, Ing RJ. Tetralogy of Fallot: perioperative anesthetic management of children and adults.
Semin Cardiothorac Vasc Anesth. 2012;16:97–105.
45. Connolly HM, Grogan M, Warnes CA. Pregnancy among women with congenitally corrected
transposition of great arteries. J Am Coll Cardiol. 1999;33:1692–1695.
46. Ray P, Murphy GJ, Shutt LE. Recognition and management of maternal cardiac disease in pregnancy.
Br J Anaesth. 2004;93:428–439.
47. Twite MD. Congenital cardiac forum: hypoplastic left heart syndrome. Semin Cardiothorac Vasc
Anesth. 2013;17:90–91.
48. Walker F. Pregnancy and the various forms of the Fontan circulation. Heart. 2007;93:152–154.
49. Drenthen W, Pieper PG, Roos-Hesselink JW, et al. Pregnancy and delivery in women after Fontan
palliation. Heart. 2006;92:1290–1294.
50. Galiè N, Beghetti M, Gatzoulis MA, et al. Bosentan therapy in patients with Eisenmenger syndrome: a
multicenter, double-blind, randomized, placebo-controlled study. Circulation. 2006;114:48–54.
51. Martin JT, Tautz TJ, Antognini JF. Safety of regional anesthesia in Eisenmenger’s syndrome. Reg
Anesth Pain Med. 2002;27:509–513.
52. Bédard E, Dimopoulos K, Gatzoulis MA. Has there been any progress made on pregnancy outcomes
among women with pulmonary arterial hypertension? Eur Heart J. 2009;30:256–265.
53. Correale M, D’Amato N, D’Agostino C, et al. Eisenmenger’s syndrome in pregnancy. J Cardiovasc
Med. 2013;14:384–387.
54. Madsen KM, Neerhof MG, Wessale JL, et al. Influence of ET(B) receptor antagonism on pregnancy
outcome in rats. J Soc Gynecol Investig. 2001;8:239–244.
55. Michel-Behnke I, Ewert P, Koch A, et al. Device closure of ventricular septal defects by hybrid
procedures: a multicenter retrospective study. Catheter Cardiovasc Interv. 2011;77:242–251.
56. Sadiq M, Kazmi T, Rehman AU, et al. Device closure of atrial septal defect: medium-term outcome
with special reference to complications. Cardiol Young. 2011;22:71–78.
57. Tomar M, Khatri S, Radhakrishnan S, et al. Intermediate and long-term followup of percutaneous
device closure of fossa ovalis atrial septal defect by the Amplatzer septal occluder in a cohort of 529
patients. Ann Pediatr Cardiol. 2011;4:22–27.
58. Guo JJ, Luo YK, Chen ZY, et al. Long-term outcomes of device closure of very large secundum atrial
septal defects: a comparison of transcatheter vs intraoperative approaches. Clin Cardiol. 2012;35:626–
631.
59. Kanaan M, Ewert P, Berger F, et al. Follow-up of patients with interventional closure of ventricular
septal defects with Amplatzer Duct Occluder II. Pediatr Cardiol. 2015;36:379–385.
60. Moore JW, Greene J, Palomares S, et al. Results of the combined U.S. Multicenter Pivotal Study and
the Continuing Access Study of the Nit-Occlud PDA device for percutaneous closure of patent ductus
arteriosus. JACC Cardiovasc Interv. 2014;7:1430–1436.
61. Beauchesne LM, Connolly HM, Ammash NM, et al. Coarctation of the aorta: outcome of pregnancy. J
Am Coll Cardiol. 2001;38:1728–1733.
62. Head CE, Thorne SA. Congenital heart disease in pregnancy. Postgrad Med J. 2005;81:292–298.
63. Curry RA, Gelson E, Swan L, et al. Marfan syndrome and pregnancy: maternal and neonatal
 outcomes. BJOG. 2014;121:610–617.
64. Hassan N, Patenaude V, Oddy L, et al. Pregnancy outcomes in Marfan syndrome: a retrospective
cohort study. Obstet Gynecol. 2014;123:(suppl 1):148S.
65. Rossiter JP, Repke JT, Morales AJ, et al. A prospective longitudinal evaluation of pregnancy in the
Marfan syndrome. Am J Obstet Gynecol. 1995;173:1599–1606.
66. Matsuda H, Ogino H, Neki R, et al. Hemiarch replacement during pregnancy (19 weeks) utilizing
normothermic selective cerebral perfusion. Eur J Cardiothorac Surg. 2006;29:1061–1063.
67. Sakaguchi M, Kitahara H, Seto T, et al. Surgery for acute type A aortic dissection in pregnant patients
with Marfan syndrome. Eur J Cardiothorac Surg. 2005;28:280–283.
68. Brar HB. Anaesthetic management of a caesarean section in a patient with Marfan’s syndrome and
aortic dissection. Anaesth Intensive Care. 2001;29:67–70.
69. Grabenwöger M, Alfonso F, Bachet J, et al. Thoracic Endovascular Aortic Repair (TEVAR) for the
treatment of aortic diseases: a position statement from the European Association for Cardio-Thoracic
Surgery (EACTS) and the European Society of Cardiology (ESC), in collaboration with the European
Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur J Cardiothorac Surg.
2012;42:17–24.
70. Chahwala V, Tashiro J, Baqai A, et al. Endovascular repair of a thoracic aortic aneurysm in pregnancy
at 22 weeks of gestation [published online ahead of print May 23, 2014]. J Vasc Surg.
71. Shu C, Fang K, Dardik A, et al. Pregnancy-associated type B aortic dissection treated with thoracic
endovascular aneurysm repair. Ann Thorac Surg. 2014;97:582–587.
72. Abbas AE, Lester SJ, Connolly H. Pregnancy and the cardiovascular system. Int J Cardiol.
2005;98:179–189.
73. Weiss BM, Zemp L, Seifert B, et al. Outcome of pulmonary vascular disease in pregnancy: a
systematic overview from 1978 through 1996. J Am Coll Cardiol. 1998;31:1650–1657.
74. Decoene C, Bourzoufi K, Moreau D, et al. Use of inhaled nitric oxide for emergency cesarean section
in a woman with unexpected primary pulmonary hypertension. Can J Anaest. 2001;48:584–587.
75. Pearson GD, Veille JC, Rahimtoola S, et al. Peripartum cardiomyopathy: National Heart, Lung, and
Blood Institute and Office of Rare Diseases (National Institutes of Health) workshop
recommendations and review. JAMA. 2000;283:1183–1188.
76. Sliwa K, Hilfiker-Kleiner D, Petrie MC, et al. Current state of knowledge on aetiology, diagnosis,
management, and therapy of peripartum cardiomyopathy: a position statement from the Heart Failure
Association of the European Society of Cardiology Working Group on Peripartum Cardiomyopathy.
Eur J Heart Fail. 2010;12:767–778.
77. Kolte D, Khera S, Aronow WS, et al. Temporal trends in incidence and outcomes of peripartum
cardiomyopathy in the United States: a nationwide population-based study. J Am Heart Assoc.
2014;3:e001056.
78. Sliwa K, Fett J, Elkayam U. Peripartum cardiomyopathy. Lancet. 2006;368:687–693.
79. Nishimura RA, Otto C. 2014 ACC/AHA valve guidelines: earlier intervention for chronic mitral
regurgitation. Heart. 2014;100:905–907.
80. Autore C, Conte MR, Piccininno M, et al. Risk associated with pregnancy in hypertrophic
cardiomyopathy. J Am Coll Cardiol. 2002;40:1864–1869.
81. Maron BJ, McKenna WJ, Danielson GK, et al. American College of Cardiology/European Society of
Cardiology clinical expert consensus document on hypertrophic cardiomyopathy. A report of the
American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents
and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol.
2003;42:1687–1713.
82. Elliott PM, Anastasakis A, Borger MA, et al. 2014 ESC guidelines on diagnosis and management of
 hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic
Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J. 2014;35:2733–2779.
83. Cowan SW, Davison JM, Doria C, et al. Pregnancy after cardiac transplantation. Cardiol Clin.
2012;30:441–452.
84. Abdalla M, Mancini DM. Management of pregnancy in the post-cardiac transplant patient. Semin
Perinatol. 2014;38:318–325.
85. McKay DB, Josephson MA, Armenti VT, et al. Reproduction and transplantation: report on the AST
Consensus Conference on Reproductive Issues and Transplantation. Am J Transplant. 2005;5:1592–
1599.
86. Coscia LA, Constantinescu S, Moritz MJ, et al. Report from the National Transplantation Pregnancy
Registry (NTPR): outcomes of pregnancy after transplantation. Clin Transpl. 2010:65–85.
87. El-Deeb M, El-Menyar A, Gehani A, et al. Acute coronary syndrome in pregnant women. Expert Rev
Cardiovasc Ther. 2011;9:505–515.
88. Burchill LJ, Lameijer H, Roos-Hesselink JW, et al. Pregnancy risks in women with pre-existing
coronary artery disease, or following acute coronary syndrome. Heart. 2015;101:525–529.
89. Pacheco LD, Saade GR, Hankins GD. Acute myocardial infarction during pregnancy. Clin Obstet
Gynecol. 2014;57:835–843.
90. Gowda RM, Khan IA, Mehta NJ, et al. Cardiac arrhythmias in pregnancy: clinical and therapeutic
considerations. Int J Cardiol. 2003;88:129–133.
91. Vanden Hoek TL, Morrison LJ, Shuster M, et al. Part 12: cardiac arrest in special situations: 2010
American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency
Cardiovascular Care. Circulation. 2010;122:S829–S861.
92. Neal JM, Mulroy MF, Weinberg GL; for the American Society of Regional Anesthesia and Pain
Medicine. American Society of Regional Anesthesia and Pain Medicine checklist for managing local
anesthetic systemic toxicity: 2012 version. Reg Anesth Pain Med. 2012;37:16–18.
93. Thorne S, MacGregor A, Nelson-Piercy C. Risks of contraception and pregnancy in heart disease.
Heart. 2006;92:1520–1525.
 Neurologic and Neuromuscular Disease
Tammy Y. Euliano and Mary A. Herman

I. Anatomic disease
A. Scoliosis
B. Spinal surgery
C. Spinal cord injury
D. Spina bifida
E. Intracranial neoplasms
F. Idiopathic intracranial hypertension (pseudotumor cerebri)
G. Maternal central nervous system shunts
II. Vascular disease
A. Intracranial hemorrhage
B. Cortical vein thrombosis
III. Immunologic disease
A. Multiple sclerosis
B. Myasthenia gravis
C. Landry-Guillain-Barré syndrome
IV. Epilepsy
A. Obstetric management
B. Anesthetic management
V. Conclusion

KEYPOINTS
1. In patients with a neurologic condition, thorough preanesthetic
neurologic testing and documentation of preexisting deficits are essential.
2. In the patient with elevated intracranial pressure (ICP), neuraxial
procedures must be considered carefully. Although dural puncture could
cause brainstem herniation, infusion of epidural fluid could also acutely
increase ICP.
3. Although there is no evidence of neuraxial analgesia/anesthesia altering
the course of any neurologic disease, including chronic back pain, a
discussion of the natural history of the patient’s condition should be
included in the preanesthetic evaluation.

I. Anatomic disease
A. Scoliosis
Anesthesiologists seldom encounter parturients with severe
curvature of the spine, due in large part to screening programs
and early intervention. It is more common for patients to have a
vague history and mild curvature that complicates epidural
placement. In addition, patients may have had surgical correction
of the scoliosis with instrumentation, further complicating, but
rarely contraindicating, neuraxial analgesia/anesthesia (see
Section B. Spinal Surgery in subsequent text).
1. Clinical issues
a. Scoliotic curves involve both lateral deviation of the
vertebral column as well as axial rotation of the vertebral
bodies (see Fig. 26.1).
(1) The Cobb angle measures the degree of spinal
curvature (see Fig. 26.2). Minor curves (10 to 20
degrees) occur in approximately 2% of adolescents in
the United States. These are benign and require no
therapy. Curves <40 degrees rarely require fusion, but
thoracic curves >65 degrees will require fusion and,
if untreated, can result in a restrictive respiratory
pattern limiting ventilatory reserve.1
 (2) Nonstructural curves are the result of leg length
discrepancies or posture. The spine remains mobile
and the curve is not progressive. Structural curves
are more commonly idiopathic and can result from a
variety of conditions (see Table 26.1).

b. Surgical correction involves decortication of the

vertebrae with fusion and instrumentation. During fusion
and instrumentation, the spinal muscles are dissected
 away from the curved vertebrae. Once exposed, the
spinous processes and interspinous ligaments are removed
to allow “straightening” of the curve. The vertebrae are
then decorticated and subsequently fused.
2. Obstetric management
a. Mild curves are not affected by pregnancy. Parturients
with corrected or mild scoliosis tolerate pregnancy and
delivery well and require no special considerations.
Patients with curves >25 degrees that have not been
stabilized may experience clinical deterioration due to the
mechanical and hormonal effects of pregnancy (see Table
26.2).

b. In patients with severe disease, all of these can

contribute to deterioration of cardiopulmonary
function. In addition, those patients with severe disease
or preexisting cardiopulmonary compromise may not
tolerate the physiologic changes of advanced labor.
c. Patients with kyphoscoliosis of the lumbar spine may also
have funnel-shaped distortion of the pelvis. These
deformities often result in abnormal fetal presentations.
Indications for cesarean delivery (CD) are outlined
below.2
(1) Maternal decompensation
(2) Pelvic abnormalities
(3) Malpresentation
(4) Inadequate labor
3. Anesthetic considerations
a. Antepartum care
(1) Pathophysiology. Preanesthetic evaluation should
 be obtained in patients who have undergone
corrective surgery or have a Cobb angle >30 degrees.
The anesthesiologist should determine if there are
associated disorders (e.g., spina bifida, Marfan
syndrome) as well as determine the extent of
cardiopulmonary disease. Because scoliosis can
interfere with formation, growth, and development of
the lungs, especially in patients with disease
occurring before age 8, the number of alveoli will be
reduced. The pulmonary vasculature develops in
parallel to alveolar formation. If these processes are
interrupted, increased pulmonary vascular resistance
can produce pulmonary hypertension and right-sided
heart failure.
(2) Respiratory function. Mechanical function can also
be impaired by vertebral and rib cage abnormalities.
The most common pulmonary function abnormality
is a restrictive pattern. This occurs in patients with
curves >65 degrees. In these patients, the functional
residual capacity (FRC) is also reduced, causing
airway closure during normal tidal breathing. The
most common blood gas abnormality is a reduced
PaO2, normal PaCO2, and increased alveolar-to-arterial
oxygen gradient. These findings result from
venoarterial shunting and altered regional perfusion.
Pulmonary function tests and blood gas analysis will
be helpful in symptomatic patients to determine if the
patient will tolerate the demands of labor and
delivery.
(3) Other neuromuscular disorders and scoliosis. In
addition to the skeletal deformity, patients with
scoliosis resulting from neuromuscular disorders can
also suffer from respiratory compromise produced by
abnormalities of central control of respiration and
 supraspinal innervation of respiratory muscles. These
patients may be at risk for aspiration pneumonitis
resulting from compromised protective airway
reflexes.
(4) Preanesthetic consultation. A preanesthetic
consultation gives the anesthesiologist an opportunity
to review prepregnancy radiographs as well as
operative records. In cases where such radiographs
are unavailable, it is desirable to obtain a
radiograph at term to identify the extent and
location of instrumentation. A preanesthetic
consultation also allows for discussion of the
advantages and disadvantages of neuraxial anesthesia
before the patient experiences pain. The natural
history of scoliosis is for back pain to increase over
time. Although there is a lack of evidence suggesting
that neuraxial anesthetic techniques worsen back pain
in this population, it is important for this to be part
of the discussion. In those who have undergone
instrumentation, it is helpful to detail the caudal
extent of instrumentation. In approximately 20% of
patients, the instrumentation extends to a level of L4–
L5. Patients with evidence of cardiopulmonary
disease may require subspecialty referrals for
optimization and delivery planning.
b. Intrapartum management
Patients with scoliosis, particularly those who have
undergone instrumentation, are at increased risk for
difficult epidural placement and complications (see
Table 26.3).3
(1) Inadequate block. Inadequate or unsatisfactory
block can be expected in up to 50% of patients with
instrumentation. However, recent advances in
instrumentation may lessen the incidence of poor-
quality block.
(2) Anatomic considerations. Some practitioners
consider corrective spinal surgery a relative
contraindication to neuraxial anesthesia. However, in
many patients, a neuraxial catheter may be
inserted below the level of instrumentation and
preferably in the least affected part of the spine.
Ultrasound may be helpful in identifying the caudal
extent of instrumentation.4 Patients with a Cobb
angle >40 degrees will also have a vertebral
deformity resulting in vertebral bodies that are
shorter with thinner pedicles and laminae. This
deformity causes a narrower vertebral column on the
concave side.
(3) Technical considerations. The rotational component
of scoliosis frequently requires placement of a
laterally directed needle (i.e., from the palpable
spinous process toward the convexity of the curve)
(see Fig. 26.3).5 The actual angle varies with the
degree of curvature and is best determined by
identification of the ligaments during advancement of
the needle. Also, the degree of lateral deviation is
determined by the severity of the curvature. Consider
a bevel direction of the epidural needle parallel to the
 long axis of the back (i.e., parallel to the dural fibers)
to reduce the risk of headache in the event of dural
puncture.6 Indeed, due to the increased incidence of
“spotty” or “patchy” blocks, intentional dural
puncture and use of a continuous spinal may be
considered, particularly in patients at increased risk
for CD.7,8 Other possible analgesic modalities
include (i) intraspinal opioids, (ii) caudal analgesia,
(iii) intravenous (IV), and (iv) patient-controlled
analgesia (PCA). If dural puncture has occurred and
the patient develops a postdural puncture headache
(PDPH), Gerancher et al.9 report the successful
placement of a caudal blood patch in a patient with
Harrington rod instrumentation. However, most
obstetric anesthesiologists are not experienced in the
caudal approach so care should be exercised if
considering this option.

CLINICAL PEARL The rotational component of scoliosis

frequently requires placement of the needle lateral to the apparent
midline and directed toward the convexity of the curve.
 (4) Anesthesia for cesarean delivery. For CD, neuraxial
techniques are preferred. However, in some patients
positioning may be difficult and neuraxial placement
is impossible or the technique fails. In addition,
patients with severe disease may not tolerate supine
positioning. In such cases, general anesthesia will be
necessary to ensure airway control and adequate
ventilation. Invasive monitoring is rarely indicated
in patients with scoliosis, but in cases where there is
severe respiratory compromise and evidence of
impending respiratory failure, an arterial line will be
helpful for assessing ventilatory management in the
operating room as well as postoperatively.
B. Spinal surgery
1. Clinical issues
Corrective surgery for scoliosis, including instrumentation,
represents the most common spinal surgery in patients
presenting for obstetric care (see preceding text). Because of
early detection and intervention, the number of patients with
uncorrected curves is reduced from previous decades, limiting
the number of patients with cardiopulmonary complications.
Occasionally, patients will present having sustained trauma or
after laminectomy or other procedures for herniated discs.
2. Obstetric management
Obstetric management is rarely affected, except that these
patients will occasionally have continuing back pain that
requires chronic opioid therapy. In these cases, the care team
should be reminded of the risk of withdrawal symptoms and
that such patients will benefit from early anesthetic
consultation to assist in managing chronic opioid doses as
well as adding agonist–antagonist opioid agents during the
peripartum period.
3. Anesthetic management
 Several published studies and case reports describe epidural
or continuous spinal analgesia/anesthesia for labor and
delivery in women with spinal instrumentation. There is no
contraindication and no long-term sequelae from neuraxial
techniques. The risks of neuraxial block are listed in Table
26.3. These risks are substantially lower for those patients
who have undergone only discectomy or simple fusion.10
Neuraxial blocks should be placed above or below the level of
the surgery, and conservative dosing should be used,
recognizing that the smaller epidural space may require less
local anesthetic. A continuous spinal catheter may improve
success,8 although current equipment in the United States
results in an unacceptable rate of PDPH.

CLINICAL PEARL The risks and benefits of neuraxial block

must be discussed, particularly the natural progression of chronic
back pain that is likely unaltered by the neuraxial anesthetic.

C. Spinal cord injury

The annual incidence of SCI is 4.5 per 100,000 population in the
United States.11 More than half of these occur in the cervical
region.12 Improvements in acute care and rehabilitation have
enabled more women with SCI to become pregnant. Both the
level of injury and its duration impact the care of these patients.
1. Clinical issues
a. Duration of injury
(1) Acute phase
During the initial spinal shock phase, the patient
suffers flaccid motor paralysis, areflexia, and
sympathetic denervation below the level of the lesion.
This results in vasodilation that can compromise
both temperature regulation and hemodynamic
stability to a degree commensurate with the level of
 the lesion. If the lesion is above T1, there may be
relative bradycardia due to unopposed
parasympathetic innervation. Lower systemic
vascular resistance results in venous pooling,
decreased venous return, and hypotension. In fact,
anything that results in vagal stimulation (e.g.,
Valsalva, tracheal suctioning) may cause profound
bradycardia, which may require external or chemical
pacing with a direct-acting catecholamine agonist.
During this phase, respiratory complications are
common due to paralysis of the intercostal muscles,
poor cough, and decreased respiratory reserve. These
complications are further compounded during
pregnancy by upward displacement of the diaphragm
by the gravid uterus and “thoracic” breathing.
(2) Chronic phase
After a period of several weeks, a chronic state of
paralysis, muscle spasticity, and disuse atrophy
ensues. In addition, cardiovascular reflexes attempt to
compensate for the loss of sympathetic tone with
variable success. During this period, orthostatic
hypotension is common. Meanwhile, some of the
motor reflex activity returns, often pathologically.
The mass motor reflex occurs when a stimulus that
normally causes contraction of a small number of
fibers, produces widespread spasm.
Thermoregulation is also impaired in these patients.
Other related problems include (i) anemia, (ii)
chronic urinary tract infections, and (iii) decubitus
ulcers.
b. Level of injury
(1) Women with cord injuries below S2 have
involvement of bladder, bowel, and sexual function.
(2) Women with lesions above T10 will not experience
 labor pain and, although they are not at particular
risk for preterm labor, they may not present until
labor is advanced.
(3) Above T6, patients are at risk for autonomic
hyperreflexia (see subsequent text) and respiratory
compromise. Estimates suggest that more than two-
thirds of parturients with a lesion above T6 will
develop autonomic hyperreflexia in response to
distension of the uterus, bladder, or rectum.
(4) When lesions are above T1, patients lose
sympathetic innervation to the heart,
compromising the reflexive response to
hypotension.
c. Other complications
Additional medical complications can include respiratory
compromise, from lesions above T5, due to a loss of FRC.
With the addition of pregnancy, patients have an increased
likelihood of respiratory failure. Impaired
thermoregulation due to vasodilation, impaired sweating,
and autonomic hyperreflexia are also possible. Urinary
tract infections occur at a much higher rate as well.
d. Autonomic hyperreflexia
This potentially life-threatening complication results from
lack of central inhibition of the sympathetic neurons
present in the spinal cord below the level of injury.
Painful visceral or cutaneous stimuli (e.g., uterine
contractions or bladder distension) below the level of the
spinal cord lesion stimulate sympathetic afferents in the
sympathetic chain. Although inhibitory neurons in the
intact individual limit the spread of this impulse, patients
with SCI respond with an impulse that propagates up and
down the sympathetic chain, resulting in massive
sympathetic stimulation and vasoconstriction. With
lesions below T6, compensatory vasodilation in the intact
 portion of the cardiovascular system prevents critical
hypertension. If the lesion is above T6, there is
insufficient innervated vasculature to adequately
compensate. This results in profound hypertension.

CLINICAL PEARL SCI above a T6 level warrants neuraxial

anesthesia to prevent autonomic hyperreflexia; close hemodynamic
monitoring is required.

(1) Signs and symptoms of autonomic hyperreflexia

(see Table 26.4)

(2) Prevention/treatment
(a) Prevention is paramount. Early administration
of combined spinal-epidural (CSE), or epidural
analgesia with local anesthetics and opioids can
prevent autonomic hyperreflexia caused by
uterine contractions. Neuraxial analgesia
prevents the reflex by interrupting noxious
sensory input from the viscera. A Foley catheter
should be placed to prevent bladder distension.
(b) Treatment of a hypertensive emergency
includes removal of the offending stimulus, if
possible (e.g., consider bladder catheterization),
and administration of IV nitroprusside,
sublingual nitroglycerin, and/or phentolamine.
2. Obstetric management13,14
a. Traumatic SCI occurring during pregnancy may result in
spontaneous abortion or preterm delivery. For the first
several months after injury, the patient is at increased risk
for deep vein thrombosis (DVT) and pulmonary
embolism. Prophylaxis against these complications may
impact plans for neuraxial anesthesia. Guidelines for
administration of neuraxial anesthesia in patients
receiving anticoagulants can be found at
http://www.asra.com.
b. Patients with SCI who have lesions above T10 will have
painless labor and are at risk for preterm labor and
delivery. Before term, they are monitored closely to
prevent home delivery. Because of inadequate expulsive
efforts in the second stage, assisted delivery may be
necessary.
c. Antepartum consultation in a high-risk obstetric
anesthesia clinic, with delivery at a tertiary care center
that includes appropriate anesthesia coverage, is
recommended.
d. For those at risk for autonomic hyperreflexia,
antihypertensive medications should be available at
the bedside and labor analgesia should be instituted
early. Autonomic hyperreflexia can also confound the
diagnosis of preeclampsia.
e. Temperature should be measured at regular intervals
because hyperthermia (in the absence of infection) can
occur as a result of altered thermoregulation.
f. Patient position should be changed regularly to prevent
decubitus ulcer formation.
g. The American College of Obstetricians and Gynecologists
(ACOG) concluded in their 2002 Committee Opinion:
Obstetric management of patients with spinal cord
injuries, that obstetricians should be aware of the specific
problems related to SCIs. Autonomic dysreflexia is the
 most significant medical complication seen in women
with SCIs and precautions should be taken to avoid
stimuli that can lead to this potentially fatal syndrome.
Women with SCIs may give birth vaginally, but when CD
is indicated, adequate anesthesia (spinal or epidural, if
possible) is needed.15
3. Anesthetic management
a. Neuraxial analgesia is the most common approach for the
prevention and treatment of autonomic hyperreflexia.
Although either CSE or epidural analgesia is a good
choice, CSE may be preferable for its rapid onset. Labor
analgesia differs in these patients by (i) need for initiation
very early in labor, (ii) a typical test dose that will not
identify unintentional subarachnoid catheter placement,
and (iii) difficult assessment of level of analgesia. If
neuraxial block placement is impossible, other measures
for treating autonomic hyperreflexia should be at the
bedside (e.g., nitroglycerin, nitroprusside).
b. Sensory levels can only be reliably assessed if the level of
block is more cephalad than the spinal cord lesion.
However, a limited assessment can be made by stroking
the abdomen above and below the umbilicus. If there is
contraction of the abdominal muscles, the level of sensory
block is below that level because sensory blockade will
abolish this reflex.
c. Placement of an arterial catheter may be indicated to
allow beat-to-beat monitoring of blood pressure (BP)
because many of these patients have low baseline BP and
are prone to hemodynamic instability. Pulse oximetry may
also be prudent.
d. For CD, spinal anesthesia is preferable because it
provides better protection from autonomic hyperreflexia
compared to epidural anesthesia.13 If neuraxial anesthesia
is technically impossible, or if the level of cord injury
 produces respiratory embarrassment when supine, general
anesthesia will be necessary. During the period of
denervation (i.e., 24 hours to 1 year after injury),
succinylcholine should not be administered due to the risk
of hyperkalemic cardiac arrest, due to the potential for
massive potassium release from postsynaptic and
extrajunctional receptors. However, some have suggested
that succinylcholine should always be avoided in these
patients, and that nondepolarizing muscle relaxants
should be used to facilitate laryngoscopy and intubation,
if necessary.16
D. Spina bifida
Spina bifida results from failure of the vertebrae to fuse
completely around the neural tube contents. There are two major
categories:
1. Spina bifida occulta describes failed fusion of the arch
without herniation of the meninges or spinal cord. Failure
at a single level (usually L5 or S1) is common and occurs in
up to one-third of the population. It is considered to be a
normal variant by some.17 There is a wide range of
presentations, from asymptomatic radiographic findings to
chronic back pain with posterior disc herniation and minor
neurologic problems. In patients who have superficial
stigmata (e.g., tuft of hair or lipoma), there is an increased
likelihood of an underlying occult spinal dysraphism (i.e.,
cord abnormality). Most of these are asymptomatic but there
may be a higher risk for disc herniation.
a. Obstetric management is uncomplicated in patients with
spina bifida occulta.
b. Anesthetic management
(1) Most patients carrying this diagnosis present little
concern, but preanesthetic assessment should include
examination of the back with clear documentation
of neurologic status.18 The patient should also be
 informed that analgesia could be incomplete during
delivery because the epidural space may not be
continuous across the defect. There is an increased
risk of dural puncture because of abnormal lamina
and ligamentum flavum formation, especially when
placement is attempted at the site of the lesion. This
risk can be reduced by inserting the needle in a
position remote from the level of the lesion. Most
neuraxial anesthetics are uncomplicated because the
level of the lesion is typically below most neuraxial
needle placements (i.e., L5–S1). In addition, most are
midline defects of the lamina that rarely interfere
with needle placement.
(2) Presence of neurologic deficits or cutaneous
manifestations should concern the
anesthesiologist, particularly for the risk of
tethered cord.19 Tethered cord results from
attachment of the spinal cord to an area of the lumbar
spine. Reports suggest that the incidence of tethered
cord in cases of spinal bifida occulta is low, but
nearly all patients with spina bifida cystica and
meningomyelocele have tethering. If there are
neurologic deficits or cutaneous manifestations,
radiographs, preferably existing ones, should be
obtained.
(3) In a patient with tethered cord who declined
neuraxial analgesia, fentanyl IV PCA with an adjunct
infusion of dexmedetomidine (an α2-agonist with
negligible placental transfer) provided adequate
analgesia without respiratory depression.20
2. Spina bifida cystica (or aperta) includes meningocele (i.e.,
failed closure of the neural arch with herniation of the
meninges) and myelomeningocele (i.e., herniation of both
meninges and neural elements through a vertebral defect).
These cases are much less common (<5 per 1,000 births).
Prenatal folate supplementation has further reduced the
incidence by as much as 50%.21 Improved surgical and
medical care has increased the likelihood that affected women
will present for obstetric interventions. Numerous anomalies
may coexist including Chiari II malformation (i.e., downward
displacement of the medulla, fourth ventricle, and cerebellum
into the cervical spinal canal), hydrocephalus with shunt
placement, and tethered cord. Many of these patients develop
progressive spinal deformities, including kyphoscoliosis.
a. Obstetric management
Recurrent urinary tract infections are the most common
complication, resulting in preterm labor. Patients with
severe kyphoscoliosis may experience respiratory
compromise due to the expanding uterus. CD is reserved
for obstetric indications (e.g., inadequate pelvic
dimensions).
b. Anesthetic management
(1) Preanesthesia consultation. Preanesthetic
consultation helps determine anesthetic options. The
anesthesiologist should determine the level of the
lesion and whether the patient has residual neurologic
function. Most patients with these disorders have
undergone imaging studies to determine the spinal
abnormalities. These will facilitate anesthetic
assessment.
(2) Technical concerns. Parturients with lesions above
T10 are unlikely to experience labor pain, but those
with higher lesions are at risk for autonomic
hyperreflexia (see Section C. Spinal Cord Injury).
Because neuraxial anesthesia is not contraindicated in
these patients,17 such techniques should be utilized
whenever possible to prevent autonomic
hyperreflexia and to avoid the risk of general
 anesthesia. However, attempts at identifying the
epidural space can result in dural puncture due to
incomplete formation of the ligamentum flavum. If
epidural placement is successful, one must consider
that the epidural anesthetic may be inadequate due to
discontinuity of the epidural space. In patients with
negligible function below the lesion, concerns for
cord damage are reduced and continuous spinal
anesthesia should be considered.
(3) Other considerations. If a patient has a
ventricular shunt, its function should be assessed.
Symptoms of shunt malfunction or infection include
headache, fever, drowsiness, and convulsions.
Patients with severe kyphoscoliosis may also require
pulmonary function testing. Patients with spina bifida
who lack bladder control often self-catheterize and
are at increased risk (approximately 25%) for latex
sensitivity.22

CLINICAL PEARL Patients with spina bifida are at increased

risk for latex sensitivity.

E. Intracranial neoplasms
The incidence of brain tumors in pregnant patients does not differ
from the age-matched nonpregnant population nor does the
distribution of types: (i) glioma, 38%; (ii) meningioma, 28%; (iii)
acoustic neuroma, 14%; and (iv) pituitary adenoma, 7%. These
tumors may be asymptomatic until hormonal and physiologic
changes of pregnancy (e.g., increased plasma volume) worsen
symptoms through peritumoral edema formation.23 In addition,
some meningiomas contain progesterone receptors, and their
growth can be accelerated during pregnancy.
Metastatic disease to the central nervous system (CNS) from
breast, lung, and skin tumors represents another important source
of intracranial tumors. Hematogenous spread leads to
macroscopic tumor formation in brain parenchyma with increased
edema and breakdown of the blood–brain barrier. Prognosis of
such cases is dependent on the tumor origin.
1. Clinical issues23
Signs and symptoms of an intracranial neoplasm (see Table
26.5)

a. Headache is the most common presenting symptom.

Although frequently encountered in pregnant patients,
headache exacerbation with maneuvers that increase
intracranial pressure (ICP) helps differentiate from a more
benign cause.
b. Nausea and vomiting may be attributed to morning
sickness, but persistence into the second and third
trimesters merits further investigation.
c. New-onset seizure activity during the third trimester
most likely results from eclampsia, but a seizure may be
the initial presenting sign of neoplasm in 20% of patients.
d. Focal neurologic deficits occur with tumor invasion or
mass effect, even if the tumor is benign.
e. Neuroimaging studies can be obtained safely throughout
pregnancy, using creativity to minimize risk.24 Magnetic
resonance imaging (MRI) is preferable to computed
tomographic (CT) scanning due to reduced radiation
exposure. Gadolinium, the MRI contrast agent, is also
safer in pregnancy than agents used for CT imaging.
f. Risk for herniation must be evaluated in any patient with
an intracranial mass.
2. Obstetric management depends on (i) location of the tumor,
(ii) tumor size (i.e., mass effect), and (iii) potential for
 malignancy.
a. Each case must be evaluated individually and a care
plan developed. In some patients with aggressive
neoplasms, intractable seizures, or severe visual
impairment, neurosurgical intervention may be necessary
during pregnancy. However, surgery can be delayed in
others with more benign tumors (e.g., meningioma). In
cases associated with elevated ICP, efforts should be made
to reduce ICP until surgery is feasible.
b. Expulsive efforts during the second stage of labor can
increase ICP as much as 70 cm H2O above baseline,25
consequently increasing risk of cerebral herniation in
patients with decreased intracranial compliance. During
the first stage of labor, maternal “bearing down” resulting
from pain will increase ICP. Depending on the patient,
either CD or assisted vaginal birth to avoid pushing is
appropriate.
3. Anesthetic management
a. Neuraxial anesthetic considerations
(1) ICP changes during labor must be considered when
choosing an analgesic technique for labor and vaginal
delivery in parturients with increased ICP. Parenteral
analgesia risks respiratory depression and
hypercarbia with subsequent elevation of the ICP.
Proponents of epidural analgesia argue that it will
attenuate the increased ICP resulting from painful
contractions and produce a pain-free second stage
during instrumental vaginal delivery and avoid
pushing.

CLINICAL PEARL Injection of fluid into the epidural space can

increase ICP for up to 5 minutes.26
 (2) Inadvertent dural puncture is always a risk with
epidural placement and can cause potentially
disastrous changes in transtentorial pressure gradient
and fatal brain herniation.27 For these reasons, any
type of dural puncture (associated with either
intrathecal or CSE labor analgesia) is contraindicated
in patients with increased ICP.
b. Choice of anesthetic for cesarean delivery. General,
epidural, and spinal anesthesia have all been administered
successfully to patients with intracranial neoplasms.
Many anesthesiologists favor general anesthesia for (i)
BP control, (ii) hyperventilation to decrease ICP, and (iii)
ability of induction agents (e.g., thiopental, propofol) to
decrease ICP. However, aggressive hyperventilation can
result in uteroplacental vasoconstriction and a
compromised fetus.
c. General anesthetic administration. The risks of
increased ICP during laryngoscopy and intubation, as well
as the risk of regurgitation and aspiration, must be
considered. IV lidocaine and/or fentanyl can be
administered to attenuate the sympathetic responses to
intubation. Many anesthesiologists argue against the use
of succinylcholine because of its ability to increase ICP,
and favor a nondepolarizing muscle relaxant instead.
Anesthesia can be maintained with a combination of low
dose (<1 minimum alveolar concentration [of a volatile
anesthetic] [MAC]) volatile anesthetic and fentanyl. High-
dose sevoflurane may lower seizure threshold under
hypocapnic conditions. Nitrous oxide administration in
such patients is controversial. In all cases, anesthetic
management for CD in patients with increased ICP
must be individualized.
F. Idiopathic intracranial hypertension (pseudotumor cerebri)
Formerly called benign intracranial hypertension, idiopathic
intracranial hypertension (IIH) is a chronic and potentially
debilitating condition that produces persistent elevations in ICP
without an identifiable cause (e.g., mass lesion, obstruction of
cerebrospinal fluid [CSF] outflow, or infection). It is more
common in obese women aged 20 to 30 years. The diagnostic
criteria, although currently undergoing revision, remain the
modified Dandy criteria:28
• Signs/symptoms of elevated ICP (e.g., headache, visual
changes, papilledema)
• No localizing neurologic signs except for sixth nerve palsies
• Increased CSF opening pressure but normal CSF
composition
• No evidence of hydrocephalus, mass, structural, or
vascular lesion on neuroimaging
• No other cause of increased ICP identified
1. Clinical issues
a. The incidence of idiopathic intracranial hypertension is
not increased during pregnancy, but it is a disorder of
obese women of childbearing age. This suggests that
hormonal factors may be implicated in the
pathophysiology. Symptoms (e.g., headache,
nausea/vomiting, visual disturbance) worsen during
pregnancy in approximately half of these patients, but
often improve after delivery. Maternal and perinatal
outcome are unaffected by the disorder.
b. Treatment is directed at preserving the patient’s vision
and improving symptoms. It commonly includes repeat
lumbar puncture and CSF drainage. Steroids,
acetazolamide (a carbonic anhydrase inhibitor that
reduces CSF production), and lumbar-peritoneal (LP)
shunting are reserved for refractory cases.
2. Obstetric management
Although ICP will increase during labor and delivery, the
equalization of pressure throughout the CNS limits the risk of
 herniation. In patients with severe symptoms, shunt placement
results in symptomatic improvement and normal perinatal
outcome. Labor and vaginal delivery are not contraindicated,
but an elective instrumental vaginal delivery will minimize
the surge in ICP that accompanies pushing. In most cases, CD
should be performed for obstetric indications only.
3. Anesthetic management
a. Epidural techniques are preferred for labor analgesia
because they avoid the hypercarbia and respiratory
depression associated with parenteral opioids. However,
in patients with untreated IIH, large volumes of epidural
anesthetic can worsen symptoms resulting from increased
ICP. In patients without ICP gradient or focal
neurologic deficits, spinal techniques (such as the
therapeutic dural puncture) are safe because of the
generalized increase in ICP. In a case report, a spinal
catheter was used for labor analgesia and temporary
control of ICP.29 Both epidural and spinal anesthesia have
been used successfully in women with IIH; however, in
patients with an LP shunt, care must be taken to avoid
puncture of the shunt by avoiding the level of the scar
from catheter placement. Concern that drug would be lost
to the intraperitoneal space appears to be unfounded.
Although there are potential maternal and fetal concerns
about radiography during pregnancy, it has been used for
shunt identification before neuraxial analgesia/anesthesia
in patients at term.

CLINICAL PEARL Neurologic symptoms in patients with

untreated idiopathic intracranial hypertension may worsen if large
volumes of epidural anesthetic are administered; spinal techniques
are safe.
 b. General anesthesia (GA) may be a suboptimal choice in
these patients because (i) airway manipulation can
increase ICP; (ii) obesity can complicate airway
management; (iii) succinylcholine may increase ICP,
although less likely in pregnancy where fasciculations are
limited; (iv) decreased mean arterial pressure (MAP) may
impair cerebral perfusion and with GA, mentation cannot
be assessed.
c. Keeping in mind these caveats, spinal, epidural, and
general anesthesia have all been used successfully for CD
in patients with IIH.30
G. Maternal central nervous system shunts
Treatment of hydrocephalus often requires shunting of CSF out of
the brain. In these patients, catheters are tunneled under the skin
either into the heart or peritoneal cavity. Patients may have had
shunts placed for a variety of reasons including (i) IIH, (ii)
intracerebral hemorrhage, (iii) aqueductal stenosis, (iv) Arnold-
Chiari malformation, and (v) Dandy-Walker syndrome.
Ventriculoperitoneal or ventriculoatrial shunt catheters are the
treatment for many of these disorders. Advances in neonatal and
neurosurgical care have resulted in more of these women reaching
childbearing age.
1. Obstetric management
Obstetric management is unaffected by a well-functioning
shunt, but also depends on associated disorders. Many of
these patients will develop neurologic complications (e.g.,
headache, shunt malfunction, increased ICP). If the patient
develops signs of increased ICP, neurosurgical evaluation of
the shunt is indicated. In most cases, CD should only be
performed for obstetric indications, but severe symptoms or
neurologic deficits may warrant CD. Prophylactic antibiotics
are often administered to prevent shunt infection, but there is
little evidence to support this practice.
2. Anesthetic management
 In patients without symptoms of elevated ICP, there are few
anesthetic management considerations, although prophylactic
antibiotics may be considered. If the shunt originates in the
lumbar spine, the risk of shunt trauma and/or drainage of
intrathecal medications into the peritoneal cavity or atrium
(resulting in inadequate anesthesia) should be considered.
Performing the neuraxial block at least one level above or
below the scar should be sufficient.
II. Vascular disease
A. Intracranial hemorrhage
Intracranial hemorrhage (ICH) during pregnancy is most common
in the peridelivery/postpartum period. The most common causes
are hypertensive disorders,31 highlighting the imperative to
aggressively control hypertension in a timely manner.32 Here, we
will focus on aneurysm and arteriovenous malformation (AVM).
Other, less common, causes of ICH include (i) Moyamoya
disease, (ii) posterior reversible encephalopathy syndrome, (iii)
coagulation disorders, (iv) mycotic aneurysm rupture, and (v)
postpartum cerebral thrombosis. Regardless of the cause, ICH is a
serious complication with mortality rates of up to 35% in patients
with a ruptured aneurysm and 30% after AVM rupture.

CLINICAL PEARL Aggressive, timely treatment of severe

hypertension is required in parturients to prevent ICH.

1. Clinical issues
a. Cerebral angiography can be performed with abdominal
shielding.
b. Despite increased blood volume, it is unclear whether the
risk of aneurysmal bleeding is increased during
pregnancy. However, once a bleed has occurred, early
surgical intervention may improve both maternal and
fetal outcome.33 Cases of endovascular embolization
 have also been reported during pregnancy. In some
patients, this approach avoids craniotomy.
c. Similarly, intervention for an AVM that has bled may
reduce the risk of serious hemorrhage.34
2. Obstetric management
Surgically corrected lesions present no special
considerations. Patients with untreated aneurysms or AVMs,
however, require careful management of BP because of the
risk of rebleeding. Although CD should be reserved for
obstetric indications, hypertension, and increased ICP
resulting from expulsive efforts during second stage labor
should be avoided. Excellent labor analgesia with neuraxial
techniques and an instrumental vaginal delivery are
indicated in these patients.35 Cesarean delivery does not
have a definite advantage over vaginal delivery.
3. Anesthetic management
In patients who have undergone surgical repair of either a
cerebral aneurysm or AVM, anesthetic management is not
different from other obstetric patients. However, if the
patient has an uncorrected aneurysm or AVM and vaginal
delivery is expected, epidural analgesia can prevent pain-
induced hypertension and facilitate assisted vaginal delivery.
An arterial line can also be helpful for beat-to-beat monitoring
of the BP. Either spinal or epidural anesthesia are reasonable
choices for CD. In women with elevated ICP, the risk of dural
puncture and brainstem herniation must also be considered
(see preceding text). If general anesthesia is necessary,
anesthetic considerations are similar to nonpregnant patients
undergoing intracranial surgery. In women with a viable fetus,
a combined neurovascular procedure and CD may be
required. Anesthetic management should follow
recommendations for pregnant women undergoing
nonobstetric surgery.
B. Cortical vein thrombosis
 1. Cortical vein thrombosis (CVT), although rare, is increased
during pregnancy, particularly the puerperium. It is related to
obstruction of blood flow from the cavernous, sagittal,
cortical, or lateral sinuses. Although the etiology is unclear,
the risk of CVT is increased because of (i) intracerebral blood
flow stasis, (ii) endothelial capillary injury during the second
stage of labor, (iii) dehydration, and (iv) hypercoagulability.
Most cases occur acutely during the second or third week
postpartum.
2. Clinical issues36
a. Risk factors include (i) inherited thrombophilias; (ii)
systemic disease (e.g., lupus); (iii) neoplasia; (iv)
infection, especially locally (e.g., otitis); and (v) use of
oral contraceptives prior to pregnancy. Dural puncture and
intracranial hypotension may also predispose to CVT.
b. Headache is a common presenting symptom, often
associated with nausea and vomiting. The headache may
be constant or positional and cannot be easily
distinguished from a PDPH. A changing character of the
headache over time is more characteristic of CVT.
Patients should undergo a brief neurologic examination
prior to epidural blood patch. Epidural blood patch (EBP)
in a patient with CVT may improve symptoms briefly. In
this setting, imaging may be warranted.37

CLINICAL PEARL The headache from CVT may be positional

in character and mimics that of PDPH but usually changes over
time.

c. Severe symptoms can include (i) focal seizures, (ii)

neurologic deficits, (iii) lethargy, and (iv) confusion.
Papilledema is frequently present.
d. MRI is preferred for diagnosis, whereas magnetic
 resonance venography helps to detect the nonvisualized
segment of the clotted vessel. Angiography is not
necessary.36
e. Treatment includes anticonvulsants and, in patients
without evidence of hemorrhage, anticoagulant
therapy. If the neurologic condition is refractory to full
anticoagulant doses of low molecular weight heparin
(LMWH) or vitamin K antagonists, a microcatheter can
be positioned in the sinus and thrombolytic therapy
attempted.36
f. Predictors of poor outcome include altered consciousness
and associated ICH. In a recent study of 19 patients
appropriately treated with anticoagulants, there were no
deaths.36
III. Immunologic disease
A. Multiple sclerosis
Multiple sclerosis (MS) is a major cause of disability. It has a
prevalence of approximately 3 to 8 per 1,000 in the United States
and Canada and is twice as common in women. Because the peak
age of onset is during the childbearing years, obstetric
anesthesiologists may be required to manage parturients with
MS.11
1. Clinical issues
a. Symptoms and diagnosis. Although the etiology is
unclear, the pathophysiology involves immune-mediated
inflammatory demyelination of white matter
throughout the CNS. Symptoms include (i) ataxia, (ii)
spasticity, (iii) diplopia, (iv) dysesthesias, and (v)
sphincter dysfunction. Multiple diagnostic criteria have
been proposed, but no single laboratory test is diagnostic.
MRI studies often demonstrate white matter plaques,
whereas CSF laboratory studies demonstrate increased
immunoglobulin (Ig) and lymphocyte concentrations.
Two major types of disease are described: (i)
 exacerbating remitting and (ii) chronic progressive. In
exacerbating remitting disease, attacks appear abruptly
and resolve over several months.
b. Relapse. Symptoms during relapse include exacerbation
of previous deficits, as well as cerebellar, brainstem,
and/or extrapyramidal symptoms. Exacerbations are often
related to stress, infection, and/or increases in core body
temperature. There is a decrease in relapse rate during
pregnancy. However, in the postpartum period, disease
relapse is increased—42% in the first year.38 Loss of
antenatal immunosuppression and declining hormonal
levels likely contribute to this increase. Over time,
neurologic deficits are usually progressive and
debilitating, but pregnancy does not appear to change the
lifelong course of the disease.
c. Treatment. Treatment of the nonpregnant patient includes
immunomodulating agents (e.g., β-interferon, intravenous
immunoglobulin [IVIG]), glatiramer (a synthetic myelin
basic protein), mitoxantrone (with cumulative cardiac
toxicity, maximum 100 mg per m2), azathioprine, and
methotrexate. Newer immunosuppressants include
dimethyl fumarate, fingolimod, and teriflunomide.
Monoclonal antibody therapies are second-line agents in
those with relapsing disease.39 However, during
pregnancy and lactation, only corticosteroids,
glatiramer,39 and IVIG are considered safe.40
2. Obstetric management
a. MS does not alter fertility or pregnancy. Pregnancy, labor,
and delivery outcomes are unaffected by the disease.
b. Increased body temperature is associated with relapse;
therefore, maintaining a cool labor room is advisable.
Stress also increases risk of relapse.

CLINICAL PEARL Maintaining a cool environment for the

laboring patient with MS is advisable.

c. The relapse rate after delivery is 30% in the first 3 months

postpartum and 50% in the first 6 months.41
3. Anesthetic management
a. Preoperative evaluation. Preoperative anesthetic
evaluation should include a well-documented neurologic
examination describing the extent of deficits as well as
other physical impairments. Special attention should be
paid to the respiratory system including the ability to
cough.
b. Neuraxial anesthesia. Historically controversial,
neuraxial techniques for labor and delivery are not
associated with an increased risk for CNS damage.
Concern over potential effects of local anesthetics on
demyelinated tissue in the neuraxis appears unwarranted.
Still, the lowest effective concentration of local anesthetic
and opioid is recommended.35
c. Risk of relapse. Patients should be cautioned that
relapse is common in the postpartum period
regardless of the type of anesthetic administered. The
relationship of relapse to spinal anesthesia as well as other
conditions (e.g., stress, hyperpyrexia) known to
exacerbate the disease is uncertain.
d. General anesthesia and MS. General anesthesia does
not exacerbate MS. Anesthetic induction agents and
inhaled gases have no demonstrable effects on nerve
conduction and do not contribute to the progression of
this disorder. Succinylcholine carries a theoretical risk
in all patients with MS; however, in patients with
profound neurologic deficits, upregulation of motor
end-plate acetylcholine receptors can result in a
hyperkalemic response to depolarization. In such
cases, succinylcholine should be avoided.
B. Myasthenia gravis
Myasthenia gravis (MG), although rare at 1:10,000, strikes
primarily during the second and third decades of life, the prime
childbearing years. This autoimmune disorder causes fatigue and
progressive muscular weakness through immunoglobulin G (IgG)
antibodies that target nicotinic acetylcholine receptors. The
contractile ability of muscle is exhausted by repetitive activity,
but is restored with rest. This disease can be classified by the
presence or absence of antibodies to the acetylcholine receptor
(AchR), by the severity of the disease, and by the etiology.
Approximately 85% of patients are seropositive for AchR
antibodies. Ten percent to 20% of patients with acquired MG do
not have antibodies targeted to AchR. Ocular muscles are the
first to be involved, followed by bulbar, proximal limb, and
respiratory musculature. Smooth and cardiac muscle are
unaffected by the disease.
1. Clinical issues
Disease severity is classified as follows:
• I: ocular myasthenia
• IIA: mild generalized myasthenia with slow progression,
no crises, drug responsive
• IIB: moderate generalized myasthenia with severe skeletal
and bulbar involvement, no crises but inadequate drug
response
• III: acute, rapidly progressive disease with respiratory
compromise, poor drug response, increased mortality
• IV: late severe myasthenia with progression of disease >2
years from class I or II
Precipitants of MG include physical or emotional stress,
systemic illness, infections, hypothyroidism, hyperthyroidism,
and pregnancy. Therapy includes immunosuppressive
medications, pyridostigmine (an acetylcholinesterase
inhibitor), plasmapheresis, IVIG, and surgical thymectomy.
2. Obstetric management42
a. Approximately one-third of patients with MG experience
a worsening of symptoms during pregnancy, usually
during the first trimester. Improvement may occur later in
pregnancy due to immunosuppression and the inhibitory
effect of α-fetoprotein on the antibodies, but exacerbation
commonly occurs during delivery and postpartum.
Myasthenic crisis may present with (i) an acute increase
in acetylcholinesterase inhibitor requirements, (ii)
resistance to medication, and (iii) cholinergic crisis due to
excessive medication.
b. Pregnancy outcome. Although most patients can expect
a favorable pregnancy outcome, pregnancy may be
complicated by fetal loss, preterm labor, and maternal
morbidity and mortality.
c. Treatment. Pyridostigmine can be administered safely
during pregnancy because cholinesterase inhibitors are
quaternary amine compounds that do not cross the
placenta. IV administration, however, has been associated
with premature labor because of its oxytocic effects.
During pregnancy, the dose of anticholinesterase may be
altered because of increased blood volume.
Corticosteroids are also considered safe. Myasthenic
crisis (i.e., severe weakness and respiratory compromise)
can be treated with plasmapheresis and/or IVIG during
pregnancy.
d. Magnesium sulfate administration. Magnesium sulfate
should be administered with extreme caution in women
with MG due to its effects on the neuromuscular junction.
It will increase muscle weakness and may precipitate
respiratory compromise.
e. Duration of labor. Because uterine smooth muscle is
unaffected by MG, contractility is unimpaired, and the
length of the first stage of labor is unaffected.
However, striated muscle is required for the expulsive
 efforts during second stage labor. In some cases,
instrumental delivery is needed when there is maternal
fatigue.
f. Anesthetic choice. Respiratory status should be
monitored throughout labor. Parenteral analgesic
techniques may increase the risk of respiratory
compromise. Neuraxial techniques are preferred for labor
and vaginal delivery.
g. Method of delivery. CD should be performed only for
obstetric indications and can be associated with
exacerbation. Neuraxial anesthesia is preferred unless
there is significant respiratory or bulbar involvement.
h. Medications. Many medications are known to exacerbate
myasthenic symptoms and are listed in Table 26.6.

i. Neonatal myasthenia gravis. Transitory neonatal

myasthenia gravis (TNMG) occurs during the first few
days of life in approximately 20% of infants born to
mothers with MG. Maternal IgG readily crosses the
placenta causing generalized weakness, hypotonia, weak
cry, and respiratory distress in some infants. Treatment
with acetylcholinesterase inhibitors and ventilatory
support may be necessary. Surprisingly, the incidence of
TNMG is not related to maternal disease severity.
Resolution usually occurs in a few weeks but may take
several months.
j. Arthrogryposis multiplex congenita. Infants born to
mothers with MG may develop this rare complication.
It consists of multiple congenital joint contractures,
 pulmonary hypoplasia, and polyhydramnios. Many of
these babies do not survive. Mothers with MG must be
counseled regarding the high recurrence rate with
subsequent pregnancies.
3. Anesthetic management35
a. Preanesthetic evaluation. Patients should receive an
early anesthetic consultation. The history should pay
particular attention to chewing and swallowing
difficulties. Swallowing difficulties suggest bulbar
involvement, which indicates more severe disease. The
physical examination should look for evidence of ptosis,
an indicator of active disease, even if the patient is
receiving anticholinesterase therapy. Dysphonia results
from laryngeal weakness. Weakness of the intercostal
muscles and diaphragm can cause dyspnea on exertion, on
lying flat, or at rest. Paradoxical breathing is an important
sign of neuromuscular respiratory failure. Pulmonary
function testing is recommended in patients with
respiratory compromise and/or bulbar involvement. Deep
tendon reflexes (DTRs) and sensory examination are
often normal. Up to 13% of patients with MG have
thyroid abnormalities including hyperthyroidism,
hypothyroidism, and nonfunctioning goiter. Other
autoimmune diseases are associated with MG including
systemic lupus erythematosus (SLE), sarcoidosis,
polymyositis, and ulcerative colitis.
b. Anesthesia for labor and delivery. In laboring patients,
judicious dosing of parenteral opioids will avoid
respiratory depression. In patients with severe symptoms,
intrathecal opioids should also be administered with
caution.
c. Anesthesia for cesarean delivery. Neuraxial anesthesia
for labor or CD should be utilized, if the patient can
tolerate weakness of the intercostal muscles secondary to
 a high anesthetic level. In patients with profound bulbar
symptoms or respiratory compromise, general anesthesia
is recommended for CD.
d. Muscle relaxants. Nondepolarizing muscle relaxants
may have a prolonged effect in patients with MG and
should be avoided if possible or used in smaller doses
(one-half normal). These women may be relatively
resistant to succinylcholine, but normal dosing of
succinylcholine is recommended.43 The muscle relaxant
properties of volatile anesthetics are likely sufficient and
obviate the need for supplemental muscle relaxation after
intubation.

CLINICAL PEARL The use of nondepolarizing muscle

relaxants is not recommended in the patient with MG.

e. Postoperative care. Patients should be monitored closely

in the postoperative period because of risk from a sudden
exacerbation of disease. The following risk factors are
associated with a need for postoperative mechanical
ventilation:
(1) Duration of MG >6 years
(2) History of chronic respiratory disease
(3) Pyridostigmine dose >750 mg per day
(4) Vital capacity <2.9 L
C. Landry-Guillain-Barré syndrome
Landry-Guillain-Barré (LGB) syndrome is an acute inflammatory
demyelinating polyneuritis that produces inflammation of
peripheral nerves and nerve roots. With a reported incidence of
approximately 1 case per 100,000 persons per year, it occurs most
commonly after a bacterial or viral infection. The risk for LGB is
lower during pregnancy and increases after delivery.44 Patients
experience a progressive, ascending, symmetrical weakness
with loss of sensation and reflexes. Autonomic dysfunction may
produce BP instability and some patients experience significant
muscle pain. In severe cases, respiratory insufficiency and/or
failure result from involvement of the accessory and intercostal
muscles, as well as the diaphragm. Most LGB-related deaths
occur as a result of respiratory failure.
1. Clinical issues16
a. Diagnosis. Diagnosis requires exclusion of other causes
of weakness. Nerve conduction studies are useful and will
demonstrate reduced velocities and delayed distal
latencies.
b. Outcome. The course is self-limited, with maximum
deficit occurring at approximately 30 days. Most patients
experience complete recovery; however, 10% of patients
experience severe residual disability.
c. Treatment. Treatment is supportive, although if the
diagnosis is early, plasmapheresis may decrease the
severity and length of illness. IVIG can be useful in the
treatment of this disease, but in some women a second
course of IVIG is required. Steroids are ineffective. Pain
should be treated with nonsteroidal anti-inflammatory
drugs (NSAIDs), with consideration given to
thromboembolic prophylaxis, physical therapy, and
nutrition.
d. Monitoring disease progression. Forced vital capacity
(FVC) and forced expiratory volume may be used to
assess respiratory function. These tests are more sensitive
indicators of respiratory insufficiency than arterial blood
gases (ABGs) because changes in the ABG may not be
observed until there is profound respiratory weakness.
The degree of respiratory compromise may necessitate
(perhaps lengthy) mechanical ventilation.
2. Obstetric management45
a. This syndrome seems to occur less frequently in pregnant
women than in nonpregnant women. If the course is
 uncomplicated, pregnancy is unaffected. Termination of
pregnancy does not hasten recovery or improve
outcome. Uterine activity is unaffected by LGB
syndrome and CD should be reserved for obstetric
indications only.
b. The fetus/neonate is unaffected.
3. Anesthetic management
a. Neuraxial analgesia has been administered to patients
with LGB syndrome during labor, but the implications are
uncertain. In at least one recent case, the labor epidural
was implicated in a progressive course of disease.46 Early
obstetric anesthesia consultation and discussions with the
patient are advised. In most cases, the benefits of labor
analgesia will likely outweigh the risks.45
b. Potential autonomic dysfunction requires adequate fluid
loading and careful titration of anesthetics and
vasopressors.
c. If general anesthesia is required for CD, upregulation of
AchRs is a contraindication to the use of
succinylcholine because of risk of hyperkalemia.
Resistance to nondepolarizing muscle relaxants has
also been reported.
IV. Epilepsy
The most common neurologic condition in pregnancy, epilepsy affects
approximately 1 in 200 parturients. Classification of seizures has
changed over recent years (see Table 26.7). Epileptic seizures occur
independent of metabolic disturbances or acute cerebral pathology.
A. Obstetric management47,48
1. Outcome. Epilepsy itself does not increase the risk of
congenital malformations, but these patients have a higher
risk of preterm labor and delivery (especially if they smoke),
gestational hypertension (but not preeclampsia), and CD.
About one-third of patients experience an increase in seizure
activity, and those with seizures during pregnancy have a
higher incidence of small for gestational age infants.
Preconception counseling is recommended. Sleep deprivation
and hormonal fluctuations in the peripartum period can
increase the risk of seizure, but the overall incidence during
labor is less than 5%.
2. Generalized tonic-clonic seizures can result in maternal
hypoxia and acidosis, with potential devastating
consequences for the fetus, including death. A seizure
during delivery, which occurs with a frequency of 1% to 2%,
often results in decreased fetal heart rate (FHR) and potential
for urgent delivery. Fetal bradycardia, transient late
decelerations, decreased beat-to-beat variability, and
compensatory tachycardia are thought to be caused by
 maternal hypoxia. These fetal hemodynamic changes often
resolve within 10 minutes after the seizure terminates.49
Seizures may also induce trauma to the fetus or fetal
membranes.
3. Status epilepticus. Status epilepticus is a true obstetric
emergency. It requires immediate IV access, O2
administration, ventilation, aspiration prevention, and uterine
displacement. Treatment includes anticonvulsant therapy
(e.g., benzodiazepine, propofol, thiopental).
4. Treatment. Physiologic changes of pregnancy (increased
plasma volume and drug clearance), as well as the risk of
teratogenicity from antiepileptic drugs, require attention to
pharmacotherapy. Polytherapy clearly increases the risk for
teratogenicity. Valproate, phenobarbital, carbamazepine, and
topiramate have been linked to a high risk of fetal
malformations.49 Newer second-line medications (e.g.,
lamotrigine and levetiracetam) are preferable during
pregnancy. Infants of mothers who used antiepileptic drugs,
and especially multiple agents, during pregnancy have a
higher risk of impaired fine motor skills at 6 months of age.
5. Breastfeeding. Breastfeeding is still recommended due to the
low excretion of anticonvulsants in breast milk.
B. Anesthetic management35
1. Choice of anesthetic should be based on the maternal and fetal
condition, urgency of the procedure, patient preference, and
skill of the anesthesiologist. Neuraxial analgesia/anesthesia is
not contraindicated for labor or CD.
2. A small dose of propofol or a benzodiazepine will usually
“break” a seizure, but airway protection and emergent
delivery may be required if fetal bradycardia occurs and is
persistent.
3. If general anesthesia is necessary, propofol is preferable to
other induction agents. Despite conflicting information in the
literature, propofol is anticonvulsant in the epileptic patient,
 whereas ketamine and etomidate can be proconvulsant.
Following an induction with propofol and succinylcholine,
anesthesia can be maintained with fentanyl and a mixture of
O2, N2O, and isoflurane. Sevoflurane may be proconvulsant
in the presence of hypocapnia or at high concentration. If
nondepolarizing muscle relaxants are needed, the degree of
muscle relaxation should be monitored carefully.
Anticonvulsants can increase hepatic enzyme activity
resulting in more rapid metabolism. Drugs such as meperidine
and ketamine are not ideal in patients with epilepsy because
they or their metabolites can lower the seizure threshold. In
the intubated patient, hyperventilation with resultant
hypocarbia can also lower the seizure threshold.
Electroencephalogram may be useful to ascertain if an
unresponsive patient remains in status epilepticus following a
seizure.
V. Conclusion
Neuromuscular disorders are uncommonly encountered during
pregnancy, but can be challenging for both the obstetrician and
anesthesiologist. Early consultation and communication is essential
for developing a care plan to ensure good maternal and neonatal
outcomes.

REFERENCES
1. Asher MA, Burton DC. Adolescent idiopathic scoliosis: natural history and long term treatment
effects. Scoliosis. 2006;1:2.
2. Crosby ET. Disorders of the vertebral column. In: Gambling DR, Douglas MJ, McKay RSF, eds.
Obstetric Anesthesia and Uncommon Disorders. 2nd ed. Cambridge, United Kingdom: Cambridge
University Press; 2008:129–144.
3. Kuczkowski KM. Labor analgesia for the parturient with prior spinal surgery: what does an
obstetrician need to know? Arch Gynecol Obstet. 2006;274:373–375.
4. Yeo ST, French R. Combined spinal-epidural in the obstetric patient with Harrington rods assisted by
ultrasonography. Br J Anaesth. 1999;83:670–672.
5. Ko JY, Leffert LR. Clinical implications of neuraxial anesthesia in the parturient with scoliosis. Anesth
Analg. 2009;109: 1930–1934.
6. Norris MC, Leighton BL, DeSimone CA. Needle bevel direction and headache after inadvertent dural
 puncture. Anesthesiology. 1989;70:729–731.
7. Okutomi T, Saito M, Koura M, et al. Spinal anesthesia using a continuous spinal catheter for cesarean
section in a parturient with prior surgical correction of scoliosis. J Anesth. 2006;20:223–226.
8. Smith PS, Wilson RC, Robinson AP, et al. Regional blockade for delivery in women with scoliosis or
previous spinal surgery. Int J Obstet Anesth. 2003;12:17–22.
9. Gerancher JC, D’Angelo R, Carpenter R. Caudal epidural blood patch for the treatment of postdural
puncture headache. Anesth Analg. 1998;87:394–395.
10. Russell R, Comara S. Regional blocks for delivery in women with scoliosis or previous spinal surgery.
Int J Obstet Anesth. 2003;12:308–310.
11. Hirtz D, Thurman DJ, Gwinn-Hardy K, et al. How common are the “common” neurologic disorders?
Neurology. 2007;68: 326–337.
12. Sekhon LH, Fehlings MG. Epidemiology, demographics, and pathophysiology of acute spinal cord
injury. Spine. 2001; 26:S2–S12.
13. Pereira L. Obstetric management of the patient with spinal cord injury. Obstet Gynecol Surv.
2003;58:678–687.
14. Kuczkowski KM. Labor analgesia for the parturient with spinal cord injury: what does an obstetrician
need to know? Arch Gynecol Obstet. 2006;274:108–112.
15. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 275: obstetric
management of patients with spinal cord injuries. Obstet Gynecol. 2002;100:625–627.
16. Briggs ED, Kirsch JR. Anesthetic implications of neuromuscular disease. J Anesth. 2003;17:177–185.
17. Avrahami E, Frishman E, Fridman Z, et al. Spina bifida occulta of S1 is not an innocent finding. Spine.
1994;19:12–15.
18. Tidmarsh MD, May AE. Epidural anaesthesia and neural tube defects. Int J Obstet Anesth.
1998;7:111–114.
19. Ali L, Stocks GM. Spina bifida, tethered cord and regional anaesthesia. Anaesthesia. 2005;60:1149–
1150.
20. Palanisamy A, Klickovich RJ, Ramsay M, et al. Intravenous dexmedetomidine as an adjunct for labor
analgesia and cesarean delivery anesthesia in a parturient with a tethered spinal cord. Int J Obstet
Anesth. 2009;18:258–261.
21. Pitkin RM. Folate and neural tube defects. Am J Clin Nutr. 2007;85:285S–288S.
22. Bernardini R, Novembre E, Lombardi E, et al. Risk factors for latex allergy in patients with spina
bifida and latex sensitization. Clin Exp Allergy. 1999;29:681–686.
23. Stevenson CB, Thompson RC. The clinical management of intracranial neoplasms in pregnancy. Clin
Obstet Gynecol. 2005;48:24–37.
24. Alvis JS, Hicks RJ. Pregnancy-induced acute neurologic emergencies and neurologic conditions
encountered in pregnancy. Semin Ultrasound CT MR. 2012;33:46–54.
25. Marx GF, Zemaitis MT, Orkin LR. Cerebrospinal fluid pressures during labor and obstetrical
anesthesia. Anesthesiology. 1961;22:348–354.
26. Hilt H, Gramm HJ, Link J. Changes in intracranial pressure associated with extradural anaesthesia. Br
J Anaesth. 1986;58: 676–680.
27. Su TM, Lan CM, Yang LC, et al. Brain tumor presenting with fatal herniation following delivery
under epidural anesthesia. Anesthesiology. 2002;96:508–509.
28. Thurtell MJ, Wall M. Idiopathic intracranial hypertension (pseudotumor cerebri): recognition,
treatment, and ongoing management. Curr Treat Options Neurol. 2013;15:1–12.
29. Aly EE, Lawther BK. Anaesthetic management of uncontrolled idiopathic intracranial hypertension
during labour and delivery using an intrathecal catheter. Anaesthesia. 2007;62:178–181.
30. Karmaniolou I, Petropoulos G, Theodoraki K. Management of idiopathic intracranial hypertension in
 parturients: anesthetic considerations. Can J Anaesth. 2011;58:650–657.
31. Bateman BT, Olbrecht VA, Berman MF, et al. Peripartum subarachnoid hemorrhage nationwide data
and institutional experience. Anesthesiology. 2012;116:324–333.
32. Clark SL, Christmas JT, Frye DR, et al. Maternal mortality in the United States: predictability and the
impact of protocols on fatal postcesarean pulmonary embolism and hypertension-related intracranial
hemorrhage. Am J Obstet Gynecol. 2014;211:32.e1–32.e9.
33. Dias MS, Sekhar LN. Intracranial hemorrhage from aneurysms and arteriovenous malformations
during pregnancy and the puerperium. Neurosurgery. 1990;27:855–865.
34. Magann EF, Doherty DA, Chauhan SP, et al. Pregnancy, obesity, gestational weight gain, and parity as
predictors of peripartum complications. Arch Gynecol Obstet. 2011;284:827–836.
35. Kuczkowski KM. Labor analgesia for the parturient with neurological disease: what does an
obstetrician need to know? Arch Gynecol Obstet. 2006;274:41–46.
36. Demir CF, Inci MF, Özkan F, et al. Clinical and radiological management and outcome of pregnancies
complicated by cerebral venous thrombosis: a review of 19 cases. J Stroke Cerebrovasc.
2013;22:1252–1257.
37. Lockhart EM, Baysinger CL. Intracranial venous thrombosis in the parturient. Anesthesiology.
2007;107:652–658.
38. Portaccio E, Ghezzi A, Hakiki B, et al; for the MS Study Group of the Italian Neurological Society.
Postpartum relapses increase the risk of disability progression in multiple sclerosis: the role of disease
modifying drugs. J Neurol Neurosurg Psychiatry. 2014;85:845–850.
39. Carrithers MD. Update on disease-modifying treatments for multiple sclerosis. Clin Ther.
2014;36:1938–1945.
40. Stangel M, Gold R, Gass A, et al. Current issues in immunomodulatory treatment of multiple sclerosis
—a practical approach. J Neurol. 2006;253(suppl 1):I32–I36.
41. Confavreux C, Hutchinson M, Hours MM, et al; for the Pregnancy Multiple Sclerosis Group. Rate of
pregnancy-related relapse in multiple sclerosis. N Eng J Med. 1998;339:285–291.
42. Ciafaloni E, Massey JM. The management of myasthenia gravis in pregnancy. Semin Neurol.
2004;24:95–100.
43. Levitan R. Safety of succinylcholine in myasthenia gravis. Ann Emerg Med. 2005;45:225–226.
44. Jiang GX, de Pedro-Cuesta J, Strigård K, et al. Pregnancy and Guillain-Barré syndrome: a nationwide
register cohort study. Neuroepidemiology. 1996;15:192–200.
45. Chan LY, Tsui MH, Leung TN. Guillain-Barré syndrome in pregnancy. Acta Obstet Gynecol Scand.
2004;83:319–325.
46. Wiertlewski S, Magot A, Drapier S, et al. Worsening of neurologic symptoms after epidural anesthesia
for labor in a Guillain-Barré patient. Anesth Analg. 2004;98:825–827.
47. Pennell PB. Pregnancy in women who have epilepsy. Neurol Clin. 2004;22:799–820.
48. Shehata HA, Okosun H. Neurological disorders in pregnancy. Curr Opin Obstet Gynecol.
2004;16:117–122.
49. Harden CL. Pregnancy and epilepsy. Continuum. 2014;20:60–79.
 Renal and Hepatic Disease in the Pregnant Patient
Quisqueya T. Palacios and M. Susan Mandell

I. Introduction
A. Renal and liver diseases in parturients
B. Multidisciplinary team
II. Renal disease during pregnancy
A. Renal anatomy
B. Renal physiology
C. Assessment of renal function during pregnancy
D. Categories of renal dysfunction and influence on pregnancy
E. Systemic effects of renal disease and prognosis
F. Etiology of renal disease
G. General management strategies
H. Anesthetic implications of renal disease
I. Renal failure associated with pregnancy
J. Renal disease, dialysis, and pregnancy outcomes
III. Liver disease
A. Characteristics of hepatic disease during pregnancy
B. Changes in hepatic anatomy and physiology during pregnancy
C. Assessment of hepatic function
D. Diagnosis of liver disease in pregnancy
E. Anesthetics and hepatic disease
F. Hepatic diseases unique to pregnancy
G. Hepatic diseases exacerbated by pregnancy


KEYPOINTS
1. The incidence of renal disease during pregnancy is 0.1%.
2. Renal disease during pregnancy may be secondary to acute kidney injury
during pregnancy or preexisting chronic renal disease.
3. Pregnancy is associated with hormonally induced anatomic and
physiologic changes in the kidney that directly and indirectly affect renal
function.
4. Maternal and fetal outcomes depend on the degree of renal impairment
and the severity of hypertension and proteinuria. Timely diagnosis and
management of parturients with preexisting chronic renal disease is key
to outcome.
5. Causes of chronic renal disease include diabetes, hypertension, and
systemic lupus erythematosus (SLE).
6. Early management and treatment of preeclampsia, hypertension, sepsis,
and hemorrhage are associated with better outcomes.
7. Careful use of neuraxial techniques and knowledge of systemic effects of
chronic renal disease and safety implications of anesthetic drugs with
dose adjustments are imperative in parturients with renal disease.
8. Causes of acute kidney injury may include hyperemesis gravidarum,
severe preeclampsia, and acute fatty liver of pregnancy (AFLP).
9. Liver disease can be a coincidental finding or caused by the pregnancy.
10. Use of gestational age of the pregnancy is a good guide to the differential
diagnosis of liver disease. For example, hyperemesis gravidarum occurs
mainly in the first trimester, whereas intrahepatic cholestasis occurs in the
third trimester.
11. Liver disease is present in approximately 3% of all pregnancies.
12. In general, mild liver disease has little effect on drug action and
metabolism, whereas advanced liver dysfunction has complex effects on
drug handling.
13. Many patients with hepatic disease also have defects in renal function
 marked by a reduction in glomerular filtration and therefore clearance of
renally excreted drugs.
14. Neuraxial and general anesthesia and intraabdominal surgery can
decrease hepatic blood flow by 20% to 30%, which can further prolong
drug activity.
15. Cerebral edema is a leading cause of death in patients with fulminant
hepatic failure of any cause.
16. Acute viral hepatitis is the most common cause of jaundice during
pregnancy.

I. Introduction
Nonobstetric medical disorders (e.g., cardiac and hypertensive
disease, pulmonary disease, and hepatorenal disease) can lead to
increased maternal morbidity and peripartum intensive care unit
(ICU) admission as well as maternal and fetal mortality. Early
diagnosis of associated medical disorders, optimization of preexisting
diseases, and timely delivery of the fetus can improve outcome.
Although maternal mortality rates in the United States are very low,
over the last 30 years, other developed nations have continued to
decrease maternal mortality rates. However, the maternal mortality
rate in the United States has increased when compared to other
developed nations. Many of the causes of maternal mortality are
preventable.1 The overall maternal mortality rate was estimated at
11.5 maternal deaths per 100,000 live births during 1991 to 1997.2 In
2008, maternal mortality rate in the United States has increased and
was estimated at 17 maternal deaths per 100,000 births. In addition,
the increased rates of obesity, hypertension, diabetes, renal disease,
and cesarean delivery (CD) have contributed to increased maternal
morbidity.3

CLINICAL PEARL Early diagnosis of nonobstetric medical

disorders, optimization of preexisting diseases, and timely delivery
of the fetus can improve outcome.
A. Renal and liver diseases in parturients
The physiologic changes of pregnancy may alter the expected
signs and symptoms of common medical disorders.
Approximately 7.4 million people in the United States are
affected by renal disease, and at least 400,000 have chronic liver
disease. The onset of many of these diseases occurs during the
childbearing years in women. Therefore, renal and liver diseases
are not uncommon in parturients. This chapter will outline the
more common renal and liver diseases that are seen during
pregnancy. The special considerations for treatment that might
affect anesthetic management are discussed.
1. The incidence of renal disease during pregnancy is 0.1%.4
Renal disease during pregnancy may be secondary to acute
kidney injury during pregnancy or preexisting chronic renal
disease. Comorbidities, such as obesity, hypertension, and
diabetes, are risk factors leading to chronic renal disease. In
addition, chronic renal disease occurring prior to pregnancy
may be a consequence of intrinsic renal disease, such as
glomerulonephritis. However, preexisting diabetic and
hypertensive nephropathies and nephropathies associated with
extrinsic medical disease, such as systemic lupus
erythematosus (SLE), lead to chronic renal disease during
pregnancy. The incidence of chronic renal disease during
pregnancy is 0.03% to 0.12%. Parturients with chronic renal
disease have a fivefold higher incidence of morbidity,
including gestational hypertension, preeclampsia, eclampsia,
and maternal mortality, when compared to parturients with
normal pregnancies. Adverse perinatal outcomes are two
times greater in parturients with chronic renal disease.5
However, acute renal disease during pregnancy may result
from an increased risk of urinary tract infection and
pyelonephritis, obstetric complications associated with
preeclampsia, or in association with acute fatty liver of
pregnancy but is typically associated with acute blood loss or
 trauma. The overall incidence of acute renal failure (ARF)
during pregnancy is 1 per 15,000 to 1 per 20,000.
2. The incidence of hepatic dysfunction causing jaundice during
normal pregnancy is between 1:1,500 and 1:5,000. Viral
hepatitis accounts for 50% of cases.
3. Although this is a small proportion of all ICU admissions,
renal and liver failure are the fourth and fifth most common
reasons for which parturients require critical care
management.
4. Renal and/or hepatic diseases account for a large proportion
of the maternal deaths in the United States with mortality
rates ranging from <10% to approximately 80%. Renal and
liver diseases have an even greater impact on maternal and
infant mortality in developing countries.

CLINICAL PEARL Comorbidities, such as obesity,

hypertension, and diabetes, are risk factors leading to chronic renal
disease. Renal and hepatic dysfunction contribute to a significant
number of maternal deaths in the United States.

B. Multidisciplinary team
Most critically ill parturients with liver or renal disease will
benefit from the care provided by a multidisciplinary team.
These team members often include a maternal–fetal medicine
specialist, nephrologist or hepatologist, critical care specialist, an
obstetric anesthesiologist, and neonatologist. A combination of
thorough antenatal and intrapartum obstetric anesthesia care,
systematic assessment of peripartum anesthetic considerations, as
well as neonatal intensive care preparation will provide
comprehensive care that can reduce maternal and neonatal
morbidity and mortality.6

CLINICAL PEARL Most critically ill parturients with liver or

 renal disease will benefit from the care provided by a
multidisciplinary team.

II. Renal disease during pregnancy

A. Renal anatomy
The kidneys undergo anatomic and physiologic changes during
pregnancy in response to increasing filtration and elimination
demands of the fetus. These changes directly and indirectly affect
renal function. A number of important physiologic changes are
outlined in Chapter 1.
B. Renal physiology
1. Hormonal factors (i.e., progesterone, prostaglandin E1
[PGE1]) and compression of the ureters at the pelvic brim
cause the kidney to dilate. These physiologic changes produce
hydronephrosis as well as an increased incidence of
vesicoureteric reflux. These changes predispose to a higher
incidence of asymptomatic bacteriuria, which, if inadequately
treated, can lead to pyelonephritis and urinary tract infection
during pregnancy. Changes can persist up to 4 months
postpartum.
2. Renal blood flow (RBF) is autoregulated at a mean arterial
pressure between 80 and 180 mm Hg and controlled through
neural and hormonal influences including myogenic,
tubuloglomerular feedback, sympathetic tone, the renin-
angiotensin-aldosterone axis, and prostaglandin E (PGE). The
glomerulus filters 20% of renal plasma flow (RPF), and the
glomerular filtration rate (GFR) is 180 L per day or 120 mL
per minute. The filtrate is determined by balance of
hydrostatic and oncotic forces and is essentially protein free.
An increase in total RBF during a normal pregnancy causes
the GFR to increase by 40% to 50% from a nonpregnant
baseline of 100 to 150 mL per minute. By the second
trimester, there is a concomitant 40% to 50% decrease in
 serum urea, creatinine, and uric acid. The upper limits of
normal for blood urea nitrogen (BUN) and serum creatinine
are therefore reduced to 6 to 9 mg per dL and 0.4 to 0.6 mg
per dL, respectively, during normal pregnancy. At the end of
the third trimester, GFR and RBF return to nonpregnant
values.
3. Parturients in the supine position may have an immediate
decrease in GFR despite a normal blood pressure. Decreases
in GFR are caused by increased capsular hydrostatic pressure
associated with obstructive disease such as ureteric and renal
calculi, increased capillary oncotic pressure associated with
increased plasma proteins, and decreased glomerular
hydrostatic pressure associated with hypotension.
Furthermore, angiotensin II (ANG II) is decreased, and there
is increased sympathetic tone and vasoconstriction. There
may be a decreased ultrafiltration coefficient (Kf) associated
with diabetes and hypertension. The fall in GFR is due to
compression of the renal arteries and veins by the gravid
uterus with a compensatory decrease in total RBF.

CLINICAL PEARL RBF is autoregulated at a mean arterial

pressure between 80 and 180 mm Hg. Parturients in the supine
position may have an immediate decrease in GFR despite a normal
blood pressure.

4. An increase in intravascular volume and changes in renal

solute clearance cause a decrease in plasma osmolality
during early pregnancy. Plasma osmolality is 270 mOsm per
kg during pregnancy. Plasma sodium and potassium
concentrations decrease from 10 to 28 weeks of gestation and
remain stable throughout pregnancy. Serum sodium and
potassium are typically 135 mEq per L and 3.8 mEq per L,
respectively. The osmotic thresholds for the sensation of thirst
 and the secretion of antidiuretic hormone decrease in parallel.
The lower osmotic trigger for thirst leads to increased water
intake and solute dilution. Arginine vasopressin is not
inhibited and encourages the retention of extra free water.7
Despite these changes, pregnancy does not change daily urine
output significantly.
5. There is a change in urinary solutes during pregnancy
Proteinuria of up to 300 mg per day and glucosuria of 1 to 10
g per day are considered within normal limits and not
necessarily associated with pathology. Urinary protein of
>300 mg per day is above the 95th percentile and used to be
accepted as a single criterion for the diagnosis of mild
preeclampsia.8 However, the 2013 American Society of
Obstetrics and Gynecology Task Force on Hypertension in
Pregnancy state that proteinuria is longer required for the
diagnosis of preeclampsia unless other severe preeclampsia
features are present.9 Proteinuria >3 g per day is a sign of
systemic and renal disease.
An increase in glomerular filtration reduces the resorption
of glucose, and glycosuria often occurs. There is an increased
production of serum acids resulting in part from fetal waste.
Uric acid is 2 to 3 mg per dL during pregnancy. This relative
acidemia causes an increase in minute ventilation in order to
normalize the pH. To neutralize the pH, the kidneys excrete
bicarbonate. Serum bicarbonate levels during pregnancy are
18 to 20 mEq per L.10 Table. 27.1 reviews the renal changes
associated with pregnancy.
C. Assessment of renal function during pregnancy
1. Renal function is commonly assessed by two techniques. The
first measures serum levels of creatinine and BUN. However,
these serum values will not increase until approximately 60%
of renal function is lost. The second technique measures the
loss of solute in the urine over time. The solute concentration
is used to calculate GFR [(urine concentration of solute ×
urine flow) / (plasma concentration of solute)]. The GFR is a
sensitive indicator of renal function. GFR increases 40% to
50% in normal pregnancy. A GFR and serum creatinine value
considered normal in the nonpregnant population may
represent renal function 40% to 50% of normal in the
parturient.10
2. Many studies use serum creatinine to calculate GFR and
renal function using an equation that includes age and
body mass. However, creatinine clearance does not always
correlate with GFR, and this technique requires a timed urine
collection.
3. Serum markers used in research (e.g., cystatin C) require
further testing in pregnancy before they can be used to
routinely measure renal function. Placental production of
cystatin C, in addition to selective decreased glomerular
filtration of cystatin C, affects this test’s accuracy during
pregnancy. Therefore, creatinine clearance by 24-hour urine
collection is the best method to calculate GFR during
pregnancy.10
 4. Prediction formulas. Modification of Diet in Renal Disease
(MDRD) underestimates GFR during pregnancy and is less
accurate than creatinine clearance. It is not recommended for
use as a screening test for renal disease during pregnancy.11

CLINICAL PEARL Serum creatinine will not increase until

approximately 60% of renal function is lost.

D. Categories of renal dysfunction and influence on pregnancy

1. The severity of renal disease is categorized by the GFR.12
The GFR is quoted in the units of mL/minute/1.73 m 2 to
normalize to body mass index. The five stages of renal
disease are shown in Table. 27.2. A referral to a nephrologist
is recommended when i) GFR is <30 mL per minute, ii) a
urine–creatinine ratio >60 mg per mmol, or iii) proteinuria >1
g per day.13

CLINICAL PEARL The severity of renal disease is categorized

by the GFR.

a. Preserved renal function with no hypertension is

associated with GFR >90 (approximate serum creatinine
levels of <125 μmol per L or <1.4 mg per dL). Pregnancy
has a minimal effect on renal function and is not
independently associated with postpartum deterioration or
development of end-stage renal disease (ESRD).
b. Mild renal impairment with a GFR of 60 to 89
(approximate serum creatinine levels between 125 and
170 μmol per L or >1.4 mg per dL) is associated with
minimal symptoms during pregnancy and postpartum.14
c. Moderate renal impairment with a GFR of 30 to 59
(serum creatinine approximately between 170 and 220
μmol per L or >2.4 mg per dL) is usually associated with
hypertension. Postpartum loss of renal function is
accelerated when moderate renal failure is associated with
proteinuria of >1 g per day.15
d. Severe renal impairment is defined by a GFR between 15
and 29 (approximate creatinine >265 μmol per L or >3.0
mg per dL). Patients with hypertensive disorders
associated with pregnancy are at risk for loss of renal
function. In one study, women with hypertensive
disorders in pregnancy had a risk of ESRD that was 11
times greater than women without hypertension. The risk
was highest in women with a history of preeclampsia
superimposed on chronic hypertension. Women with
gestational hypertension also had a higher risk of ESRD
than did women without hypertensive disorders in
pregnancy. Fetal mortality was increased and low birth
weight common.16
e. Patients with end-stage, dialysis-dependent renal
failure often have amenorrhea and infertility. Only 1%
to 7% of women with established renal failure become
pregnant, and less than half will reach full-term gestation,
most ending in abortion. Dialysis parameters may need
adjustment during pregnancy due to the change in
intravascular volume and electrolytes. Erythropoietin dose
requirements for treatment of anemia are also increased.
Table 27.2 reviews the “Renal Disease Outcome Quality
Initiative” classification of renal disease.
CLINICAL PEARL Only 1% to 7% of women with established
renal failure become pregnant, and less than half will reach full-
term gestation, most ending in abortion.

2. Patients with ESRD can have unstable blood pressures.

Hypertension and rapid changes in intravascular volume and
electrolytes are common during dialysis. Maternal
hypotension is a common complication of hemodialysis. This
can cause changes in the pulsatility index of the umbilical
artery, leading to nonreassuring fetal heart rate patterns and
urgent CD.
3. Pregnancy outcome and end-stage renal disease
Physiologic changes caused by ESRD contribute to an
increase in fetal morbidity and mortality. The rapid changes in
electrolytes, acid–base abnormalities, intravascular volume,
anemia of chronic disease, and the need for anticoagulation
are associated with increased risk of maternal mortality and
fetal loss. Other complications of chronic renal disease (CRD)
during pregnancy include intrauterine growth restriction
(IUGR), preterm delivery, low birth weight, and stillbirth.
E. Systemic effects of renal disease and prognosis
CRD in pregnancy is uncommon and occurs in only 0.03% to
0.12% of parturients.
1. Hypertension tends to worsen and preeclampsia develops in
10% of these women.

CLINICAL PEARL Hypertension is associated with an

increased risk of abruption, peripartum bleeding, and anemia.

2. Uremia has many negative systemic effects (see Table. 27.3).

 3. The two most important factors affecting prognosis are the
degree of renal dysfunction and the presence of hypertension
at conception. Pregnancy does not appear to accelerate the
loss of kidney function or affect fetal outcome if (a) the GFR
is >40 and there is <1 g per day proteinuria and (b) the patient
does not have poorly controlled hypertension or other risk
factors for renal failure.17 Renal function and blood pressure
should be monitored during pregnancy (see Table. 27.4).

CLINICAL PEARL Patients with ESRD can have unstable

blood pressures. Hypertension and rapid changes in intravascular
volume and electrolytes are common during dialysis. Maternal
hypotension is a common complication of hemodialysis.

F. Etiology of renal disease

1. Primary renal diseases
Two common groups of renal disorders are (a) glomerular and
(b) tubulointerstitial diseases. Patients with both disorders
often demonstrate proteinuria and microscopic hematuria.
Although they can remain asymptomatic for many years,
these disorders are responsible for most cases of chronic renal
failure.
a. Glomerular diseases are a group of disorders with varied
pathologies. Usually, the microvascular network of the
renal cortex that ultrafiltrates blood is damaged by drugs,
toxins, or the deposition of antigen–antibody complexes.
Therefore, autoimmune diseases such as SLE are common
causes of glomerular disease. This can cause a nephritic
syndrome producing glomerular inflammatory or
necrotizing lesions. Nephritic syndrome is characterized
by microscopic debris of red and white blood cells and
cortical cells in the urinary sediment. Protein
accumulation in the glomeruli from diseases such as
amyloidosis or diabetes mellitus can cause a different
presentation of renal disease called nephrotic syndrome.
Although the primary abnormality involves an increased
loss of protein through the glomerular vessels rather than
cellular debris, there is considerable overlap between
nephritic and nephrotic syndromes.
b. Tubulointerstitial diseases
Renal glomeruli ultrafiltrates blood, whereas renal tubules
modify the filtered fluid via resorption and secretion of
various molecules. These specific actions determine the
final composition of the urine. The renal tubules can be
selectively affected by a variety of diseases. In general,
urine concentration and composition are abnormal in
tubular disease but GFR is preserved until late in the
course of the disease. These diseases are commonly
characterized by electrolyte imbalance.
CLINICAL PEARL Patients with glomerular and
tubulointerstitial diseases often demonstrate proteinuria and
microscopic hematuria.

2. Diabetes mellitus and hypertension can produce renal

dysfunction in pregnancy. Diabetes is the most common
cause of ESRD in the United States. Renal failure develops in
up to 25% to 30% of women with type 2 diabetes mellitus
after 15 years of disease. African Americans, Hispanics, and
Native Americans with diabetes are at greatest risk for renal
failure. The rate of gestational diabetes increases with
maternal age, preexisting hypertension, urinary tract infection,
and multiple pregnancies. Furthermore, the risk of
preeclampsia, urinary tract infection, premature delivery, liver
disease, and chronic renal disease is greater in parturients with
gestational diabetes and preexisting diabetes. Preexisting
diabetes and gestational diabetes are associated with increases
in pregnancy-related complications, longer hospital days, and
medical cost. The risk of venous thromboembolism,
peripartum hemorrhage, shoulder dystocia, and placental
abnormalities are greater in parturients with preexisting
diabetes but not in parturients with gestational diabetes.18
Pregnancy does not affect the progression of diabetic
nephropathy provided the GFR is >40. However, there is an
increased risk of infection and preeclampsia.19

CLINICAL PEARL Hypertension and diabetes are two systemic

diseases that can produce renal dysfunction.

3. Collagen vascular diseases (e.g., SLE, rheumatoid arthritis,

and scleroderma) are associated with pregnancy-related renal
disease. SLE is the most common collagen vascular disease in
pregnancy with an incidence of 1 in 1,660. In general,
 pregnancy does not increase the severity of SLE or other
collagen vascular diseases, although there may be some
increase in disease activity during the first month of
pregnancy. Koh et al.20 noted that pregnancies with
preexisting lupus nephritis had a greater frequency of adverse
obstetric outcomes and maternal comorbidity. Renal flares (an
increase in serum creatinine or urine protein) occurred in 50%
of pregnancies with preexisting lupus nephritis, 90% of which
were reactivations. Active preexisting lupus neprhitis and
eGFR <90 mL/minute/1.73 m2 prior to pregnancy are
associated with renal flares during pregnancy. Persistent lupus
nephritis 1 year after delivery occurred in 33.3% of
pregnancies, and chronic renal disease occurred in 20% of
pregnancies with renal flare. There is no reason why women
with SLE should avoid pregnancy unless they have advanced
end-organ damage. The key to successful outcome is careful
monitoring.20
4. Renal transplant patients benefit from preconception
planning to discuss specific steps that will improve the
likelihood of a successful pregnancy outcome. ESRD results
in menstrual irregularities, anovulation, and infertility. Kidney
transplantation increases fertility in patients with chronic
renal disease. However, assisted reproductive technologies
may be required for patients with persistent luteal
insufficiency and premature ovarian failure syndrome.21 The
National Kidney Foundation suggests that patients wait at
least 1 year between the time of transplantation and
pregnancy. Pregnancy has no deleterious effect on graft
function.22 The incidence of acute renal rejection during
pregnancy is 3% to 14%. However, pregnancy does not
increase the risk of renal graft loss as long as patients are
maintained on their antirejection drugs. Although most
antirejection medications do not seem to have a negative
effect on the fetus, mycophenolate, mofetil (Cellcept), and
 rapamycin (Sirolimus) should be discontinued at least 6
months before conception. Changes in blood volume and
metabolism during pregnancy and in the postpartum period
may affect the blood levels of antirejection medication and
increase the risk of acute rejection. This may require
adjustments in the dose or type of immune suppressants
administered. Localization of the graft in the pelvis does not
preclude the possibility of vaginal delivery. The incidence of
prematurity and malformations (e.g., cleft lip/palate, cardiac
abnormalities, congenital hydronephrosis, and undescended
testicles) are increased, and perinatal mortality is 2% to 5%.

CLINICAL PEARL Renal transplant patients benefit from

preconception planning to discuss specific steps that will improve
the likelihood of a successful pregnancy outcome.

G. General management strategies

1. The primary goal for the anesthesiologist is primum non
nocere that means “first do no harm,” which also applies
when caring for parturients with borderline renal function or
CRD. There are many conditions that can precipitate acute
kidney injury (AKI) in obstetric patients with renal
dysfunction. These conditions should be quickly and
aggressively treated to ensure better outcomes. It is
imperative to treat complications that can cause renal injury
(e.g., hypotension, hemorrhage, hypovolemia, sepsis). Timely
restoration of renal perfusion and renal function will help
limit the extent of injury and prevent irreversible renal failure.
Table. 27.5 reviews the signs and symptoms of acute renal
decompensation.
 2. The use of loop diuretics does not reduce maternal
mortality by converting oliguric to nonoliguric AKI and is
reserved for cases of volume overload. Anemia is usually
well tolerated due to a shift in the oxyhemoglobin dissociation
curve favoring oxygen delivery. However, anemia,
hyperkalemia, and metabolic acidosis should be treated,
particularly if clinical signs of uremia, such as pulmonary
edema, pericarditis, neuropathy, and uremic encephalopathy,
are present. Kidney function is best preserved by maintenance
of euvolemia, normal blood pressure, and by avoiding renal
toxins.23 Therapeutic use of osmotic diuretics for renal failure
is associated with decreases in GFR and maintenance of urine
flow by increasing proximal tubular water reabsorption and
decreasing urinary excretion. The potential toxic effects of
osmotic diuretics include increased intravascular fluid
volume, hypersensitivity reactions, hyperglycemia, and
glycosuria. All preclude the use of osmotic diuretics except
when indicated for reduction in CSF and intraocular pressure
and CSF volume during pregnancy. Additional side effects
may include headaches, nausea, and vomiting.

CLINICAL PEARL The use of loop diuretics does not reduce

maternal mortality by converting oliguric to nonoliguric AKI and is
reserved for cases of volume overload.

H. Anesthetic implications of renal disease

1. Altered responses to drugs
Patients with CRD may have altered responses to
medications.
a. The volume of distribution of water-soluble drugs can
change when intravascular volume is adjusted during
dialysis. A fall in serum proteins can increase the active
concentration of protein-bound drugs, and the volume of
distribution of lipid-soluble drugs is often less.
Furthermore, there are changes in central nervous system
receptors and drug metabolism that can increase the
response to sedatives, hypnotics, and analgesics. The
changes in drug distribution and activity may result in
hypoventilation and an inability of the patient to protect
the airway. All patients with renal failure have
gastroparesis and aspiration risk.
b. Serum concentration of drugs, which are excreted through
the kidneys, such as magnesium sulfate, should be
monitored frequently and maintenance infusion rates
lowered when necessary. Drugs that are eliminated by the
kidney can have prolonged action because their clearance
is decreased by systemic acidosis and alterations in the
volume of distribution. The loading dose of many drugs is
not changed, but maintenance doses are reduced. This
explains why the dose of etomidate and propofol appear
to be unchanged by renal failure. However,
benzodiazepines are highly protein bound and may have
an increased effect when the serum protein is reduced.
The initial dose of such medications should be decreased.
In addition, active metabolites can rapidly accumulate
with repeat doses in patients with moderate to severe renal
failure.
c. Prolonged respiratory depression may be avoided with the
use of shorter acting opioids that do not require renal
elimination (e.g., fentanyl, remifentanil).
d. Opioids, barbiturates, propofol, and benzodiazepines are
associated with mild reductions in GFR. Transplant
 patients are at risk for hypertension, diabetes, CD, preterm
labor, and anemia. Despite this, one recent observational
study noted there were no anesthetic complications
associated with either general or neuraxial
anesthesia.24
e. When utilizing neuraxial techniques, sterile technique
should be maintained and hypotension should be treated
with vasopressors to maintain renal perfusion.24

CLINICAL PEARL Patients with chronic renal disease may

have changes in central nervous system receptors and drug
metabolism that can increase the response to sedatives, hypnotics,
and analgesics. The changes in drug distribution and activity may
result in hypoventilation and an inability of the patient to protect the
airway.

2. Potential nephrotoxins
a. There are several potential nephrotoxins that should be
used with caution in parturients with renal insufficiency
(e.g., nonsteroidal anti-inflammatory drugs [NSAIDs],
aminoglycosides, anticholinergics, radiocontrast agents).
NSAIDs, in particular, reduce RBF and should be used
with caution in patients with renal dysfunction.
b. Some inhaled anesthetics (e.g., sevoflurane) increase
inorganic fluoride levels. Although sevoflurane is
metabolized to the nephrotoxic compound A, this has not
been found to be clinically significant.
3. Preoperative preparation and laboratory studies
a. Preoperative evaluation of a parturient with preexisting
renal disease should include a thorough history and
physical examination, paying particular attention to
complications associated with renal disease and any signs
or symptoms of inadequate dialysis, such as uremia and
 fluid overload. Table. 27.6 reviews the effects of chronic
renal disease on organ systems.

b. Laboratory studies should focus on the detection of

anemia, abnormalities of coagulation and electrolytes,
and urinary infection. Therefore, it is reasonable to
obtain a complete blood count, coagulation profile, and
electrolyte panel in all patients with renal disease. The
serum magnesium level can be high in patients with renal
disease. A routine magnesium level may be indicated in
this patient population. Routine urinalysis may detect
proteinuria associated with preeclampsia, progression of
renal disease or previously undetected chronic renal
disease, hematuria, and urinary tract infection (see Table.
27.4).
c. Preoperative preparation should include adequate IV
access and judicious hydration. Aspiration prophylaxis
should be consistent with the American Society of
Anesthesiologists’ (ASA)25 Practice Guidelines for
Obstetric Anesthesia. Besides routine monitoring, fetal
heart tones should also be monitored. Invasive monitoring
is reserved for cases with severe renal disease, worsening
renal function, and hypertension. Extremities with
hemodialysis fistulas should be padded carefully to
prevent thrombosis. Blood pressure cuffs should not be
placed on these extremities.
 CLINICAL PEARL Laboratory studies should focus on the
detection of anemia, abnormalities of coagulation and electrolytes,
and urinary tract infection.

4. Anesthetic management
Anesthetic management aims to optimize the medical
condition of the patient before labor and delivery. This
includes balancing intravascular volume as well as avoiding
hypotension, renal toxic drugs, and anesthetic complications.
The advantages of neuraxial anesthesia have been discussed
previously (see Chapter 12). Although neuraxial anesthesia
offers many advantages for labor and delivery, the decision to
use a particular anesthetic technique should be based on the
relative risks and benefits. Spinal anesthesia has been used
successfully in parturients with chronic renal disease with
normal coagulation profile for elective CD.26 Relative
contraindications to neuraxial anesthesia may include volume
contraction due to dialysis, hypotension, and coagulation
abnormalities. Serum potassium should be determined before
induction of general anesthesia in patients with renal failure.
Succinylcholine administration increases the serum potassium
level by as much as 0.7 mEq per L. If a patient is already
hyperkalemic, further elevations in potassium could cause
asystole or ventricular dysrhythmia.

CLINICAL PEARL Relative contraindications to neuraxial

anesthesia may include volume contraction due to dialysis,
hypotension, and coagulation abnormalities.

I. Renal failure associated with pregnancy

1. Women with chronic renal disease may be unable to adapt to
the increases in intravascular volume and the increased
demand for excretion of waste products by the mother and
 fetus. These demands may exceed the capacity of the maternal
kidney to provide homeostasis and may cause a decline in
preexisting renal function or precipitate ARF. Renal
dysfunction may be covert until the demands of pregnancy
exceed the capacity of the kidney.
2. Acute kidney injury during pregnancy
a. AKI is a precipitous decline in renal function that is
measured by a decrease in urine output and/or GFR.27
AKI occurs rarely during pregnancy with an incidence of
1 in 10,000 but is associated with a high mortality.28 The
term acute renal failure is no longer used because it
does not capture the marked increase in mortality
associated with modest increases in creatinine or
declines in GFR. Therefore, a working definition of AKI
was developed so that physicians could detect and treat
renal injury at an early stage.29 Because early intervention
improves outcome, it is important that a definition of AKI
is sensitive and multifaceted. The aim is to identify
patients at risk for renal injury in addition to those who
have established renal failure. With this task, the Acute
Dialysis Quality Initiative (ADQI) developed the RIFLE
classification of AKI (kidney Risk, Injury, Failure, and
Loss and End-stage renal failure). This classification uses
diagnostic definitions for stages of AKI, which can be
treated (risk), stages of renal damage (injury), and
established renal failure (loss and failure). The RIFLE
score has been tested clinically in a wide variety of patient
populations and has been shown to be predictive of renal
outcome.
b. An increased risk of renal failure is defined by i) an
increase of serum creatinine of 50% and ii) a decrease in
GFR, relative to baseline, of >25% or iii) a urine output of
<0.5 mL/kg/hour for >6 hours. Outcome studies show that
these simple criteria can distinguish between patients who
 have temporary inadequate renal perfusion compared to
those who have the early stages of kidney injury. Kidney
injury is defined by a doubling of serum creatinine or a
urinary output below 0.5 mL/kg/hour for at least 12 hours.
More than 50% of patients who develop injury according
to these criteria will progress to develop established renal
failure.30

CLINICAL PEARL Risk of renal injury is defined by the

following criteria: (a) an increase of serum creatinine by 50% and
(b) a decrease in GFR, relative to baseline, of >25% or (c) a urine
output of <0.5 mL/kg/hour for >6 hours.

3. Historically, AKI was classified as prerenal, intrarenal, or

postrenal.28 The newer RIFLE classification does not
distinguish between prerenal, renal, and postrenal causes of
AKI. Although this classification is no longer used, it still
helps to explain the common types of physiologic insults that
cause AKI. Table. 27.7 reviews the etiology and laboratory
findings of AKI according to the older classification. None of
the three categories are exclusive, and one type of physiologic
insult often overlaps with another.

a. Prerenal failure is the most common form of AKI.

Prerenal causes of AKI usually result from inadequate
RBF. Common causes are hypovolemia, severe blood
 loss, or heart failure. Prerenal AKI can cause intrinsic
renal damage if RBF is not normalized within as little as
48 hours.
b. Intrinsic renal disease
(1) The loss of urinary concentrating ability is an early
sign of intrinsic renal disease, most likely reflecting
failure of the energy requiring electrolyte exchange in
the renal tubules. Intrinsic causes of AKI are
associated with high rates of morbidity and mortality.
(2) The causes of intrinsic renal injury are complex and
can be related to drugs (e.g., NSAIDs) or toxins (e.g.,
radiocontrast) or specific comorbid diseases (e.g.,
SLE). In addition, significant changes in prerenal or
postrenal function may cause or contribute to
profound renal injury.
c. Postrenal failure is associated with hydronephrosis and
varying degrees of obstructive uropathy, which, if
complete, may lead to renal failure. Postrenal obstruction
may be confirmed with the use of ultrasonography,
computed tomographic (CT) scan, or retrograde
pyelography. However, return of renal function depends
on the duration of obstruction.
4. There are several diseases that cause intrinsic renal
dysfunction during pregnancy. Some are rare; however,
they have important clinical implications and are discussed in
subsequent text.31 Table. 27.8 reviews the causes of AKI in
pregnancy.
a. Preeclampsia
(1) Preeclampsia is a leading cause of maternal mortality
in the United States and worldwide. In addition, the
rate of preeclampsia in the United States has
increased 25% in the last two decades and contributes
to significant morbidity associated with preterm
delivery, severe hypertension, hemorrhagic stroke,
and seizures.
(2) Prior to 2013, preeclampsia was diagnosed when a
parturient developed hypertension and proteinuria
(>300 mg protein in a 24-hour urine collection) with
or without generalized edema after the 20th week of
pregnancy. In order to expedite the diagnosis and
early treatment of preeclampsia, the Task Force
Report on Hypertension in Pregnancy by the
American College of Obstetricians and Gynecologists
(ACOG)9 in 2013 made the recommendation to no
longer require proteinuria for the diagnosis of
preeclampsia. The Task Force Report also included
recommendations and guidelines for managing and
treating preeclampsia, chronic hypertension, and
superimposed preeclampsia. In February 2015,
ACOG32 released recommendations regarding
emergent therapy for acute-onset, severe
hypertension during pregnancy and the postpartum
 period based on standardized evidence-based clinical
guidelines associated with risk reduction in order to
improve maternal outcomes.
(3) Hypertension complicates approximately 5% to 8%
of all pregnancies and is a leading cause of maternal
and fetal morbidity, especially when hypertension is
due to preeclampsia or when superimposed on
chronic hypertension.33 Preeclampsia occurs with
greater frequency in patients with chronic
hypertension, obesity, diabetes, renal disease, and
autoimmune disease (see Chapter 22). The incidence
of preeclampsia is increased in patients with renal
disease. The incidence is related to the severity of the
underlying renal disease. For example, preeclampsia
occurs in 50% of parturients with a serum creatinine
>2 mg per dL. Patients receiving dialysis have a 40%
to 80% risk of developing preeclampsia. However,
patients with a renal transplant have a reduced risk of
preeclampsia (~20% to 30%).

CLINICAL PEARL The rate of preeclampsia in the United

States has increased by 25% in the last two decades and contributes
to significant morbidity associated with preterm delivery, severe
hypertension, hemorrhagic stroke, and seizures.

(4) Pathophysiology of renal disease caused by

preeclampsia
Preeclampsia is caused by the release of
vasoconstrictors into the circulation, which results in
hypertension and a decrease in blood supply to vital
organs such as the kidney. Intense vasoconstriction
causes ischemic injury to the blood vessels of the
kidney.
(5) Management of hypertension and renal function
in preeclampsia
Control of hypertension (see Chapter 22) and early
delivery of the neonate are the principal treatments
for preeclampsia. Patients with preeclampsia are at
increased risk for developing AKI. Rates of obstetric
ARF in Canada increased 61% between 2003 and
2010 (from 1.66 to 2.68 per 10,000 deliveries).34 In
this retrospective cohort study, the observed increase
in obstetric ARF was prevalent in women with
hypertensive disorders and was most pronounced
among women with preeclampsia. In a large study
from Norway, preeclampsia was a clinical marker for
an increased risk of ESRD. The risk was greater if a
preeclamptic pregnancy resulted in a preterm or a low
birth weight infant or if preeclampsia occurred in
more than one pregnancy.35 Patients with known
preeclampsia require blood pressure control and close
monitoring of urinary protein. Patients who show
signs of AKI may require admission to the ICU for
close observation. In a retrospective multicenter
study in France of patients admitted to ICU for
postpartum complications, AKI occurred in 37% and
29% required dialysis. Twelve percent developed
chronic renal disease due to cortical necrosis.
Maternal mortality rates due to obstetric AKI range
between 12.5% and 24% and are associated with poor
access to antenatal care and multiparity. Hemolysis,
elevated liver enzymes, low platelets syndrome
associated with postpartum hemorrhage is associated
with a high risk of ARF.36 Placental abruption and
associated severe anemia is the most common cause
of obstetric AKI. Management with blood component
transfusions, early dialysis, and avoidance of
 nephrotoxic drugs are associated with better
outcomes.37
b. Pyelonephritis
Symptomatic reflux hydronephrosis during pregnancy
occurs in 0.5% of parturients. In addition, loss of ureteral
sphincter tone associated with elevated progesterone
levels may lead to pyelonephritis with colonization of the
kidney with gram-negative bacteria. Most symptomatic
patients are diagnosed after the first trimester and up to
20% fail conservative treatment, which can lead to AKI.
Pyelonephritis is a serious complication of pregnancy that
can lead to systemic sepsis. Approximately 2% of women
with antepartum pyelonephritis develop pulmonary edema
requiring mechanical ventilation.38 Therefore, pregnancy
predisposes women to an increased risk of pyelonephritis
and sepsis resulting in intensive care admission during
pregnancy.39
c. Renal colic
Ultrasound confirmed the diagnosis of renal colic in 96%
of cases parturients hospitalized for back pain during
pregnancy in one study.40 Only 4% of cases required the
use of MRI or low-dose CT for diagnosis of renal colic.
Most patients with renal colic had dilatation of renal
cavities. However, 28% of patients with renal colic had
urinary tract infection. Symptomatic treatment and
management included analgesics and antibiotics. Urinary
diversion by a double J stent may be required in cases of
failed antibiotic therapy and progressive sepsis.
Ureteroscopy during pregnancy has been successful in
removing renal calculi.40
d. Hemolytic uremic syndrome (HUS) is a rare (1 in
25,000) but important cause of renal failure that can occur
in late term pregnancy and the postpartum period. HUS is
characterized by hemolytic anemia, thrombocytopenia,
 and renal failure. Most cases are sporadic and due to an
abnormal immune response to bacterial infections.
Platelet agglutination in the arterial microvasculature
results in consumptive thrombocytopenia, intravascular
hemolysis, and nephritic syndrome. HUS is often
confused with another rare disease called thrombotic
thrombocytopenic purpura (TTP). Both diseases can
present with thrombocytopenia, oliguria, and
hypertension. However, TTP often causes cerebral
ischemia with neurologic dysfunction, as opposed to
HUS, which does not. Early diagnosis and the immediate
use of plasmapheresis within 48 hours of presentation
have improved mortality rates from TTP and HUS from
90% to 10%–20%. Recovery of renal function occurs
rarely in patients requiring dialysis for more than 28 days.
Multisystem organ failure and left ventricular failure
contribute to increased maternal mortality. Perinatal
mortality remains high at 30% to 80%. Delivery of the
fetus does not provide any clear benefit.41
e. Acute fatty liver of pregnancy (AFLP) is a rare and
potentially fatal complication of late pregnancy with an
incidence of 0.1%. AFLP is associated with
microvesicular fatty infiltration of hepatocytes, without
inflammation or necrosis, leading to liver failure,
hypoglycemia, and renal failure. Although AFLP is
primarily associated with liver failure, it can also induce
acute renal failure in 80% of cases, and 10% of these
cases may result in maternal death. In addition, neonatal
prematurity occurs in up to 50% of cases and rates of
neonatal mortality reach 85%. Prompt perioperative
management, expeditious delivery, and intensive
supportive care are key to improving prognosis. In cases
involving significant coagulopathy, general anesthesia
with rapid sequence induction is the technique of choice.
 However, neuraxial techniques can be utilized when there
is no evidence of coagulopathy.42

CLINICAL PEARL The differential diagnosis of renal

dysfunction during pregnancy is extensive.43 Although AFLP is
primarily associated with liver failure, ARF complicates 80% of
cases, and 10% of these cases may cause maternal death.

f. SLE is a serious autoimmune disease that primarily

affects women of childbearing age. At least 50% of
patients with SLE have evidence of renal injury.
g. Hyperemesis gravidarum
In rare circumstances, nausea and vomiting due to
pregnancy can become so protracted that patients become
dehydrated and develop electrolyte abnormalities. If left
uncorrected, this can place parturients at risk for AKI.
J. Renal disease, dialysis, and pregnancy outcomes
1. Maternal and fetal outcomes in women with renal disease
depend on the degree of renal dysfunction at conception, the
underlying cause of renal dysfunction, amount of proteinuria,
and hypertension. Renal dysfunction may occur during
pregnancy in women without preexisting renal problems,
particularly in the context of preeclampsia. Women with
underlying chronic renal insufficiency (GFR <40) have a
significantly increased risk of pregnancy-related loss of renal
function (43%) and poor fetal outcome.
2. Although the indications for dialysis during pregnancy are
similar to those in the general population, there is a lower
threshold in order to limit fetal exposure to uremia. Initiation
of daily dialysis sessions, limitation of teratogenic drugs, and
management of anemia and hypertension are recommended
for improved prognosis. Although prognosis has significantly
improved, dialysis patients have a significant risk for
 unfavorable maternal outcome associated with preeclampsia,
eclampsia and preterm birth, intrauterine growth restriction,
and stillbirth. The incidence of prematurity is 85% versus
10% in the general population. If renal replacement therapy is
required prior to 24 weeks’ gestation, fetal survival is poor.
The incidence of perinatal mortality is 18%. Hemodialysis
during pregnancy is better tolerated especially in patients with
hemodynamic stability. Positive pregnancy outcomes can
occur in women receiving chronic hemodialysis, but
pregnancy during dialysis is rare (~1.5%). Peritoneal dialysis
during pregnancy is also possible with modification of the
exchange protocol and reducing volumes.44 Risk for adverse
pregnancy outcomes was not affected by hyperfiltration.45

CLINICAL PEARL Maternal and fetal outcomes in women with

renal disease depend on the degree of renal dysfunction at
conception, the underlying cause of renal dysfunction, amount of
proteinuria, and severity of hypertension.

III. Liver disease

A. Characteristics of hepatic disease during pregnancy
Liver disease can have a significant effect on both maternal and
fetal outcome. Liver disease can be a coincidental finding or
caused by the pregnancy.46
The differential diagnosis, management, treatment, and severity
of these diseases are guided by an understanding of the
interaction between the type of liver disease and gestational age
of pregnancy. Table. 27.9 reviews the characteristics of liver
disease in pregnancy.
CLINICAL PEARL The differential diagnosis, management,
treatment, and severity of liver diseases are guided by an
understanding of the interaction between the type of disease and
gestational age of pregnancy.

B. Changes in hepatic anatomy and physiology during

pregnancy
The size of the liver does not usually increase during normal
pregnancy and is rarely palpable. Hepatic blood flow falls from
approximately 35% to 28% of the cardiac output (CO) and
although the relative amount of hepatic blood flow decreases
during pregnancy, pressure in the portal and esophageal veins
increases in the third trimester. This is caused by pressure of the
gravid uterus on the intraabdominal venous system.
Telangiectasia and palmar erythema, signs suggestive of liver
disease, may appear in up to 60% of normal pregnancies,
although these patients have no evidence of liver dysfunction (see
Chapter 1).
C. Assessment of hepatic function
During normal pregnancy, serum transaminases can be slightly
increased (see Chapter 1). Liver function tests are usually not
affected by pregnancy except for the alkaline phosphatase (ALP).
Fetal and placental production of ALP increases maternal serum
 levels and makes interpretation of these laboratory results
difficult.
D. Diagnosis of liver disease in pregnancy
1. Liver disease is present in approximately 3% of all
pregnancies. Elevated aminotransferase occurs in 24% of
parturients with mild preeclampsia, 50% with severe
preeclampsia and Hemolysis, Elevated Liver enzymes, Low
Platelets (HELLP) syndrome, and 84% with eclampsia. It is
rare for these diseases to progress to acute liver failure.
However, AFLP and acute infection with viral hepatitis
(hepatitis A, B, and E) can lead to death from fulminant
hepatic failure.47 Early diagnosis is the first step in the
successful management of liver failure during pregnancy.
2. There are two recommendations that are critical for the timely
differential diagnosis of liver disease:
a. The signs and symptoms that are associated with
hepatobiliary disease should be compared to those
occurring during normal pregnancy.
b. In general, specific diseases are far more likely to occur in
certain trimesters. Therefore, use of gestational age of the
pregnancy is a good guide to the differential diagnosis of
liver disease. For example, hyperemesis gravidarum
occurs mainly in the first trimester, whereas intrahepatic
cholestasis occurs in the third trimester (see Table. 27.9).

CLINICAL PEARL Elevated aminotransferase occurs in 24% of

parturients with mild preeclampsia, 50% with severe preeclampsia
and HELLP syndrome, and 84% with eclampsia.

E. Anesthetics and hepatic disease

The effects of IV anesthetic agents are influenced by the severity
of the liver disease.
1. In general, mild liver disease has little effect on drug action
 and metabolism, whereas advanced liver dysfunction has
complex effects on drug handling. As liver disease progresses,
the kidney increases sodium and water resorption. This
expands the intravascular volume, which then increases the
volume of distribution. Therefore, patients with liver disease
often require relatively normal doses of drugs used for the
induction of anesthesia, especially those that are water soluble
such as neuromuscular blockers.
2. Patients with advanced liver disease may have changes in
neurologic function necessitating a reduction in the dose of
sedative-hypnotic drugs. Furthermore, drug activity is
enhanced in advanced liver disease by a reduction in total
serum protein. This will increase the amount of unbound drug
to interact with receptors. Drugs that are metabolized
primarily by the liver usually have prolonged action in more
advanced liver disease.
3. Many patients with hepatic disease also have defects in renal
function, marked by a reduction in glomerular filtration and
therefore clearance of renally excreted medications; hence,
drugs that are metabolized by Hoffman elimination or other
plasma-based enzymes will have the most predictive time
course of activity.
4. Neuraxial and general anesthesia and intraabdominal surgery
can decrease hepatic blood flow by 20% to 30%, which can
further prolong drug activity. For general anesthesia, hepatic
blood flow is relatively well maintained with isoflurane and
desflurane. The latter two volatile anesthetics also have the
lowest incidence of drug-induced hepatitis.

CLINICAL PEARL Patients with advanced liver disease may

have changes in neurologic function necessitating a reduction in the
dose of sedative-hypnotic drugs.
F. Hepatic diseases unique to pregnancy
Table. 27.10 reviews the causes of hepatic dysfunction in
obstetric patients.

1. Hyperemesis gravidarum
Most pregnant women experience nausea and vomiting in the
first trimester, usually resolving by 12 to 16 weeks’ gestation.
In rare cases, pregnant women develop a persistent severe
form of nausea and vomiting called hyperemesis gravidarum.
HG occurs in 0.5 to 10 per 1,000 pregnancies and is the only
pregnancy-induced hepatic disease occurring during the first
trimester of pregnancy. Differential diagnoses include bile
duct stones, cholecystitis, and viral hepatitis.
a. Laboratory evaluation
Mild elevation in the serum transaminases develops in
25% to 67% of cases. In rare circumstances, there is
severe dehydration with marked increases in serum
transaminases of up to 300%, indicating ischemic
hepatocellular injury. Serum unconjugated bilirubin and
ALP rise slightly, whereas serum albumin and
international normalized ratio (INR) remain normal.
These biochemical abnormalities normalize with
treatment.
b. Management and anesthetic implications
Hospitalization for IV hydration, antiemetics, and
monitoring may be required. Initial IV therapy is initiated
for 24 to 48 hours to correct dehydration, electrolyte, and
any acid–base imbalance. Thiamine should be added to
 glucose-containing IV solutions when HG is severe and
associated with abnormal hepatic function or in cases
lasting more than 3 weeks.
c. Outcome
Outcomes are usually good with no adverse maternal and
fetal effects (e.g., prematurity, birth defects), provided that
symptoms are adequately treated. The serum
transaminases return to normal with proper supportive
care, and there is rarely any permanent hepatic injury.
Most cases resolve by 20 weeks’ gestation, regardless of
therapy.

CLINICAL PEARL Hyperemesis gravidarum occurs in 0.5 to 10

per 1,000 pregnancies and is the only pregnancy-induced hepatic
disease occurring during the first trimester of pregnancy.

2. Cholestasis of pregnancy
a. Intrahepatic cholestasis of pregnancy (ICP) is a rare and
serious complication of pregnancy. It is associated with
fetal mortality rates of 11% to 20% if left untreated. The
cause is unknown, but it is thought that increasing levels
of estrogen during pregnancy play a role in genetically
susceptible patients. Estrogen influences transport across
the bile ducts. Patients usually present with moderate to
severe itching in the third trimester of pregnancy.
Approximately 80% have pruritus alone, whereas 20%
will develop jaundice in addition to itching. The
incidence of ICP is 1 to 2 per 1,000 pregnancies in North
America. Risk factors include older, multiparous women
with multiple gestations, a positive family history of
cholestasis of pregnancy, and cholestasis while on oral
contraceptives. ICP must be distinguished from other
common causes of cholestasis. A careful evaluation by a
 medical specialist helps to exclude infectious and
autoimmune causes of cholestasis, which are common in
women of childbearing age.48
b. Laboratory evaluation
The key diagnostic laboratory finding is an increase in
serum bile acids from 10 to 100 times the normal value.
Bilirubin levels rarely exceed 6 mg per dL. The
transaminases can be increased in ICP.
c. Management and anesthetic implications
Patients with ICP can have severe excoriations. This can
cause infection and may make IV access and neuraxial
needle placement difficult. Treatment aims to provide
symptomatic relief from itching. Mild pruritus may
respond to emollients, topical antipruritics, and
antihistamines. Ursodeoxycholic acid (UDCA) is an
effective therapy that provides relief in patients with
moderate or severe pruritus.49 There is rapid resolution
following delivery.
d. Outcomes
ICP is associated with an increase in preterm delivery,
perinatal mortality, and meconium staining. Therefore,
obstetric management involves close fetal surveillance.49
All maternal symptoms resolve rapidly following
delivery. Women with cholestasis of pregnancy have a
60% recurrence in subsequent pregnancies.50

CLINICAL PEARL Intrahepatic cholestasis of pregnancy must

be distinguished from other common causes of cholestasis. A
careful evaluation by a medical specialist helps to exclude
infectious and autoimmune causes of cholestasis, which are
common in women of childbearing age.

3. Acute fatty liver of pregnancy

 AFLP is a rare and potentially fatal complication that presents
in the third trimester of pregnancy or immediately
postpartum. Incidence of AFLP is 1 in 7,000 to 15,000
pregnancies.51 Patients at risk include primiparous women
(50%) with multiple gestations (10% to 15%) and a male
fetus. AFLP appears to affect women of all races, ethnicities,
and age-groups. Severe preeclampsia appears to increase the
risk of AFLP. The use of NSAIDs is also associated with an
increased risk of developing AFLP.

CLINICAL PEARL AFLP is a rare and potentially fatal

complication that presents in the third trimester of pregnancy or
immediately postpartum. It is associated with significant maternal
and perinatal mortality.

a. Diagnosis
The modified Swansea criteria are used for diagnosis.
Liver biopsy studies show that the criteria have a
sensitivity of 100% and specificity of 57%. The positive
and negative predictive values are 85% and 100%,
respectively. The criteria are shown in Table. 27.11.

(1) Initially, patients complain of vague abdominal pain,

malaise, fatigue, anorexia, nausea and vomiting, and
fever. Rapid clinical deterioration may occur with
progressive fatty infiltration of the liver leading to
fulminant liver failure. Hepatic encephalopathy is a
 late sign and is associated with a poor outcome.
(2) The changes in coagulation are consistent with
disseminated intravascular coagulation. Up to 50% of
patients will also have signs suggestive of
preeclampsia and HELLP. Although a definitive
diagnosis is made by liver biopsy, it is often
unnecessary because acute fatty liver is distinguished
by a marked increase in the serum bilirubin.
b. Obstetric management
(1) Delivery should be prompt and is the treatment of
choice for AFLP. The decision for CD should be
made based on severity of maternal illness and fetal
maturity. AFLP can be a medical and obstetric
emergency that requires immediate treatment of liver
failure and prompt delivery of the fetus to prevent
intrauterine fetal death and further maternal
deterioration. Symptomatic treatment is provided for
the complications of liver disease including acidosis,
hypoglycemia, and renal failure.52 Coagulation
abnormalities associated with bleeding require
correction.

CLINICAL PEARL Delivery should be prompt and is the

treatment of choice for AFLP.

(2) Cerebral edema is a leading cause of death in

patients with fulminant hepatic failure of any cause.
Therapy is identical to other causes of increased
intracranial pressure and consists of hyperventilation,
osmotic agents, and sedative drugs.
c. Anesthetic implications
(1) Anesthetic choices for labor and delivery are often
limited due to coagulation abnormalities. In mild,
stable cases of AFLP with normal or corrected
 coagulation, neuraxial anesthesia may be considered
for delivery.53 The opinion of the second American
Society of Regional Anesthesia Consensus
Conference on Neuraxial Anesthesia and
Anticoagulation is that neuraxial anesthesia may be
performed if the INR is <1.5.54 However, neuraxial
anesthesia is contraindicated in cases of coagulopathy
and sepsis because of increased risk of epidural
hematoma and abscess.
(2) General anesthesia is usually required for CD in
cases of severe AFLP with rapidly progressive
hepatic failure because patients have significant
defects in coagulation and may have an altered level
of consciousness. All patients need aspiration
prophylaxis prior to the induction of general
anesthesia, and a rapid sequence induction should
be performed. Anesthetic drugs should be selected
based on their ability to maintain hemodynamic
stability and be rapidly cleared from the circulation.
Propofol and etomidate are acceptable choices for
induction because they are rapidly metabolized. In
very ill patients, the duration of action of
succinylcholine may be prolonged due to plasma
cholinesterase deficiency. Drugs that are metabolized
by plasma enzymes such as atracurium and
remifentanil have a predictable duration of action.
Remifentanil crosses the placenta but appears to be
quickly metabolized and redistributed to mother and
the fetus. Although other opioids (e.g., fentanyl or
alfentanil) may be associated with prolonged
respiratory depression, the risk of neonatal muscle
rigidity and respiratory depression with remifentanil
is short lived. The action of other drugs, including
neuromuscular blockers, can be prolonged by a
 reduction in hepatic metabolism or urinary clearance.

CLINICAL PEARL The action of other drugs, including

neuromuscular blockers, can be prolonged by a reduction in hepatic
metabolism or urinary clearance.

d. Outcome
(1) In the absence of fulminant liver failure, liver
function improves rapidly after delivery. Since the
1980s, maternal mortality rates have decreased to
approximately 10% to 20% with early diagnosis,
treatment, and prompt delivery. However, fetal
mortality rates remain high at 23%. With aggressive
therapy, one study reported 100% survival in two
U.S. hospitals over a 15-year period.55
(2) Patients who fail to rapidly emerge from general
anesthesia should be carefully evaluated for
progressive encephalopathy or increased intracranial
pressure. These two conditions are associated with a
poor maternal outcome.51
4. Hemolysis, elevated liver enzymes, low platelets syndrome
HELLP syndrome was previously considered to be a severe
form of preeclampsia. Although many think that HELLP is a
distinct disease, the presentation is very similar to
preeclampsia; there is generalized vasoconstriction and
activation of the coagulation cascade resulting in
thrombocytopenia. This causes microangiopathic hemolytic
anemia and hepatic necrosis. The incidence of HELLP is
approximately 1 in 1,000 pregnancies.52

CLINICAL PEARL Many think that HELLP is a distinct

disease, but the presentation is very similar to preeclampsia; there is
generalized vasoconstriction and activation of the coagulation
cascade resulting in thrombocytopenia.

a. Diagnosis
Women complain of pain in the right upper quadrant,
nausea and vomiting, and weight gain. Some patients may
also present with symptoms of preeclampsia (elevated
blood pressure and proteinuria). Laboratory testing shows
(i) hemolysis, (ii) increase in total bilirubin and lactate
dehydrogenase (LDH), (iii) moderately elevated
transaminases, and (iv) thrombocytopenia. Patients can
develop a microangiopathic hemolytic anemia due to
activation of the coagulation cascade. This can cause
disseminated intravascular coagulation with an increased
risk of bleeding and thrombotic complications. These
findings are useful to distinguish HELLP from other
serious medical conditions with a similar presentation
such as AFLP and SLE. Table. 27.12 reviews the signs
and symptoms of HELLP.

b. Management of hemolysis, elevated liver enzymes, low

platelets syndrome
The most effective treatment for HELLP syndrome is to
deliver the fetus. Physicians try to ensure fetal lung
maturity before delivery; however, refractory maternal
hypertension, worsening coagulopathy, rapid deterioration
of liver function, or nonreassuring fetal status are
indications for emergent delivery. Corticosteroids are
often used before 32 weeks’ gestation to promote lung
maturity of the fetus. Even patients who have stable
 HELLP syndrome can have a rapid progression in
symptoms leading to both maternal and fetal compromise.
Treatment aims to control high blood pressure in the 90%
of patients who experience hypertension together with
HELLP syndrome. Surveillance is used to diagnose and
follow the progress of HELLP syndrome. Liver function
tests and platelet count are routinely monitored in these
cases.
c. Outcome
Most patients with HELLP syndrome recover by 6 days
postpartum. However, HELLP may rarely lead to
fulminant hepatic failure and liver transplantation.
Hepatic infarct, hematoma, and rupture are also rare and
potentially fatal complications of HELLP syndrome. The
incidence of liver rupture is 1 in 45,000 to 225,000
(0.002% to 0.0004%) deliveries and 2% of cases of
HELLP. Maternal mortality is 18% to 35%.
G. Hepatic diseases exacerbated by pregnancy
1. Viral hepatitis
Acute viral hepatitis is the most common cause of jaundice
during pregnancy. Risk factors include IV drug use, sexual
activity, potential contact with infected persons, and travel to
hepatitis-endemic countries. Although acute viral hepatitis
carries a potential high risk for both mother and fetus, the
course of hepatitis A, B, C, and D is usually unaffected by
pregnancy.56–58 Hepatitis E occurs in 4% to 29% of the
general population. It was previously more common in third-
world countries but now has the same prevalence worldwide.
It is usually a mild disease but can be life threatening in
pregnancy. Furthermore, transplacental transmission can
occur during the third trimester resulting in late fetal
mortality.
2. Autoimmune hepatitis
Autoimmune liver disease is rare, occurring in only 0.1% of
 the population. However, there is a predilection for female
gender and pregnancy can precipitate onset in previously
asymptomatic patients. The presentation can be fulminant and
is an important consideration in the differential diagnosis of
acute liver failure. The diagnosis can be one of exclusion
because autoantibodies (antinuclear and smooth muscle
antibodies) only have moderate specificity but high sensitivity
in diagnosing the disease. Increased fetal mortality has been
reported; however, close medical management significantly
improves both maternal and fetal outcome.59
3. Pregnancy outcome following organ transplantation
a. Epidemiology
The National Transplantation Pregnancy Registry (NTPR)
was established in 1991 to report outcomes of pregnancies
in female and male transplant recipients in the United
States.60 Female renal transplant recipients were the
largest cohort within the NTPR.
b. Obstetric complications
There are more maternal complications in kidney
compared to liver transplant recipients.61 Placental
arteries show an increase in atherosclerotic lesions that
interfere with placental blood exchange. Preexisting
hypertension has been documented in up to 50% of
kidney transplant recipients, and the rate of diabetes is
increased. CD is more common in kidney transplant
recipients for preeclampsia, fetal distress, HELLP
syndrome, and defects in placentation.
c. Fetal outcomes
Live births were reported in 76% of pregnancies of the
NTPR kidney recipients. In contrast, there was a much
higher rate of live births in liver transplant recipients. The
incidence of birth defects in both liver and kidney
recipients was similar to the general population except for
a 23% increase in patients who received mycophenolate
 mofetil. There is little effect on pregnancy outcome in
fathers who received mycophenolate following
transplantation.
More than one-third of all babies were born before 38
weeks’ gestation. Gestational age and birth weight were
greater in liver compared to kidney transplant recipients.

REFERENCES
1. Lang CT, King JC. Maternal mortality in the United States. Best Pract Res Clin Obstet Gynaecol.
2008;22:517–531.
2. Centers for Disease Control and Prevention. Maternal mortality—United States, 1982-1996. MMWR
Morb Mortal Wkly Rep. 1998;47:705–707.
3. Hankins GD, Clark SL, Pacheco LD, et al. Maternal mortality, near misses, and severe morbidity:
lowering rates through designated levels of maternity care. Obstet Gynecol. 2012;120:929–934.
4. Chinnappa V, Ankichetty S, Angle P, et al. Chronic kidney disease in pregnancy. Int J Obstet Anesth.
2013;22:223–230.
5. Nevis IF, Reitsma A, Dominic A, et al. Pregnancy outcomes in women with chronic kidney disease: a
systematic review. Clin J Am Soc Nephrol. 2011;6:2587–2598.
6. Dhir S, Fuller J. Case report: pregnancy in hemodialysis-dependent end-stage renal disease: anesthetic
considerations. Can J Anaesth. 2007;54:556–560.
7. Lindheimer MD, Davison JM. Osmoregulation, the secretion of arginine vasopressin and its
metabolism during pregnancy. Eur J Endocrinol. 1995;132:133–143.
8. Higby K, Suiter CR, Phelps JY, et al. Normal values of urinary albumin and total protein excretion
during pregnancy. Am J Obstet Gynecol. 1994;171:984–989.
9. American College of Obstetricians and Gynecologists. Ob-Gyns Issue Task Force Report on
Hypertension in Pregnancy: preeclampsia diagnosis no longer requires presence of proteinuria.
http://www.acog.org/About-ACOG/News-Room/News-Releases/2013/Ob-Gyns-Issue-Task-Force-
Report-on-Hypertension-in-Pregnancy. Accessed June 19, 2015.
10. Cheung AN, Luk SC. The importance of extensive sampling and examination of cervix in suspected
cases of amniotic fluid embolism. Arch Gynecol Obstet. 1994;255:101–105.
11. Smith MC, Moran P, Ward MK, et al. Assessment of glomerular filtration rate during pregnancy using
the MDRD formula. BJOG. 2008;115:109–112.
12. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease:
evaluation, classification, and stratification. Am J Kidney Dis. 2002;39:S1–S266.
13. Podymow T, August P, Akbari A. Management of renal disease in pregnancy. Obstet Gynecol Clin
North Am. 2010;37:195–210.
14. Jones DC, Hayslett JP. Outcome of pregnancy in women with moderate or severe renal insufficiency.
N Engl J Med. 1996;335:226–232.
15. Imbasciati E, Gregorini G, Cabiddu G, et al. Pregnancy in CKD stages 3 to 5: fetal and maternal
outcomes. Am J Kidney Dis. 2007;49:753–762.
16. Wu CC, Chen SH, Ho CH, et al. End-stage renal disease after hypertensive disorders in pregnancy. Am
J Obstet Gynecol. 2014;210:147.e1–147.e8.
17. Fischer MJ. Chronic kidney disease and pregnancy: maternal and fetal outcomes. Adv Chronic Kidney
Dis. 2007;14:132–145.
18. Son KH, Lim NK, Lee JW, et al. Comparison of maternal morbidity and medical costs during
pregnancy and delivery between patients with gestational diabetes and patients with pre-existing
diabetes. Diabet Med. 2015;32:477–486.
19. Landon MB. Diabetic nephropathy and pregnancy. Clin Obstet Gynecol. 2007;50:998–1006.
20. Koh JH, Ko HS, Lee J, et al. Pregnancy and patients with preexisting lupus nephritis: 15 years of
experience at a single center in Korea. Lupus. 2015;24:764–772.
21. Delesalle AS, Robin G, Provôt F, et al. Impact of end-stage renal disease and kidney transplantation on
the reproductive system. Gynecol Obstet Fertil. 2015;43:33–40.
22. López LF, Martínez CJ, Castañeda DA, et al. Pregnancy and kidney transplantation, triple hazard?
Current concepts and algorithm for approach of preconception and perinatal care of the patient with
kidney transplantation. Transplant Proc. 2014;46:3027–3031.
23. Friedrich AD. The controversy of “renal-dose dopamine.” Int Anesthesiol Clin. 2001;39:127–139.
24. Ioscovich A, Orbach-Zinger S, Zemzov D, et al. Peripartum anesthetic management of renal transplant
patients—a multicenter cohort study. J Matern Fetal Neonatal Med. 2014;27:484–487.
25. American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Practice guidelines for
obstetric anesthesia: an updated report by the American Society of Anesthesiologists Task Force on
Obstetric Anesthesia. Anesthesiology. 2007;106:843–863.
26. Modi M, Vora K, Parikh G, et al. Anesthetic management in parturients with chronic kidney disease
undergoing elective caesarean delivery: our experience of nine cases. Indian J Nephrol. 2014;24:20–
23.
27. Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care. 2007;13:638–
644.
28. Gammill HS, Jeyabalan A. Acute renal failure in pregnancy. Crit Care Med. 2005;33:S372–S384.
29. Lameire N, Van Biesen W, Vanholder R. Acute renal failure. Lancet. 2005;365:417–430.
30. Hoste EA, Kellum JA. Acute kidney injury: epidemiology and diagnostic criteria. Curr Opin Crit
Care. 2006;12:531–537.
31. Nwoko R, Plecas D, Garovic VD. Acute kidney injury in the pregnant patient. Clin Nephrol.
2012;78:478–486.
32. American College of Obstetricians and Gynecologists Committee on Obstetric Practice. Committee
Opinion No. 623: emergent therapy for acute-onset, severe hypertension during pregnancy and the
postpartum period. Obstet Gynecol. 2015;125:521–525.
33. Lindheimer MD, Taler SJ, Cunningham FG; for the American Society of Hypertension. ASH position
paper: hypertension in pregnancy. J Clin Hypertens. 2009;11:214–225.
34. Mehrabadi A, Liu S, Bartholomew S, et al. Hypertensive disorders of pregnancy and the recent
increase in obstetric acute renal failure in Canada: population based retrospective cohort study. BMJ.
2014;349:g4731.
35. Vikse BE, Irgens LM, Leivestad T, et al. Preeclampsia and the risk of end-stage renal disease. N Engl J
Med. 2008;359:800–809.
36. Jonard M, Ducloy-Bouthors AS, Boyle E, et al. Postpartum acute renal failure: a multicenter study of
risk factors in patients admitted to ICU. Ann Intensive Care. 2014;4:36.
37. Dambal A, Lakshmi KS, Gorikhan G, et al. Obstetric acute kidney injury; a three year experience at a
medical college hospital in North Karnataka, India. J Clin Diagn Res. 2015;9:OC01–OC04.
38. Zeeman GG. Obstetric critical care: a blueprint for improved outcomes. Crit Care Med.
2006;34:S208–S214.
39. Neligan PJ, Laffey JG. Clinical review: special populations—critical illness and pregnancy. Crit Care.
 2011;15:227.
40. Fontaine-Poitrineau C, Brachereau J, Rigaud J, et al. Renal colic in pregnant women: study of a series
of one hundred and three cases [in French]. Prog Urol. 2014;5:294–300.
41. Elliott MA, Nichols WL. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.
Mayo Clin Proc. 2001;76:1154–1162.
42. McDonald SD, Malinowski A, Zhou Q, et al. Cardiovascular sequelae of preeclampsia/eclampsia: a
systematic review and meta-analyses. Am Heart J. 2008;156:918–930.
43. Hussein W, Lafayette RA. Renal function in normal and disordered pregnancy. Curr Opin Nephrol
Hypertens. 2014;23:46–53.
44. Panaye M, Jolivot A, Lemoine S, et al. Pregnancies in hemodialysis and in patients with end-stage
chronic kidney disease: epidemiology, management and prognosis. Nephrol Ther. 2014;10:485–491.
45. Piccoli GB, Attini R, Vigotti FN, et al. Is renal hyperfiltration protective in chronic kidney disease-
stage 1 pregnancies? A step forward unravelling the mystery of the effect of stage 1 chronic kidney
disease on pregnancy outcomes. Nephrology. 2015;20:201–208.
46. Almashhrawi AA, Ahmed KT, Rahman RN, et al. Liver diseases in pregnancy: diseases not unique to
pregnancy. World J Gastroenterol. 2013;19:7630–7638.
47. Bose PD, Das BC, Hazam RK, et al. Evidence of extrahepatic replication of hepatitis E virus in human
placenta. J Gen Virol. 2014;95:1266–1271.
48. Arrese M. Cholestasis during pregnancy: rare hepatic diseases unmasked by pregnancy. Ann Hepatol.
2006;5:216–218.
49. Caughey AB. Cholestasis of pregnancy: in need of a more rapid diagnosis. J Perinatol. 2006;26:525–
526.
50. Schutt VA, Minuk GY. Liver diseases unique to pregnancy. Best Pract Res Clin Gastroenterol.
2007;21:771–792.
51. Holzman RS, Riley LE, Aron E, et al. Perioperative care of a patient with acute fatty liver of
pregnancy. Anesth Analg. 2001;92:1268–1270.
52. Sibai BM. Imitators of severe preeclampsia. Obstet Gynecol. 2007;109:956–966.
53. Gregory TL, Hughes S, Coleman MA, et al. Acute fatty liver of pregnancy; three cases and discussion
of analgesia and anaesthesia. Int J Obstet Anesth. 2007;16:175–179.
54. Horlocker TT, Wedel DJ, Benzon H, et al. Regional anesthesia in the anticoagulated patient: defining
the risks (the second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation).
Reg Anesth Pain Med. 2003;28:172–197.
55. Castro MA, Goodwin TM, Shaw KJ, et al. Disseminated intravascular coagulation and antithrombin
III depression in acute fatty liver of pregnancy. Am J Obstet Gynecol. 1996;174:211–216.
56. Riley C. Liver disease in the pregnant patient. Am J Gastroenterol. 1999;94:1728–1732.
57. Guntupalli SR, Steingrub J. Hepatic disease and pregnancy: an overview of diagnosis and
management. Crit Care Med. 2005;33:S332–S339.
58. Soubra SH, Guntupalli KK. Critical illness in pregnancy: an overview. Crit Care Med. 2005;33:S248–
S255.
59. Czaja AJ. Review article: the management of autoimmune hepatitis beyond consensus guidelines.
Aliment Pharmacol Ther. 2013;38:343–364.
60. Coscia LA, Constantinescu S, Moritz MJ, et al. Report from the National Transplantation Pregnancy
Registry (NTPR): outcomes of pregnancy after transplantation. Clin Transpl. 2010:65–85.
61. Blume C, Sensoy A, Gross MM, et al. A comparison of the outcome of pregnancies after liver and
kidney transplantation. Transplantation. 2013;95:222–227.
 Obstetric Anesthesia for Parturients with Respiratory
Diseases
Suzanne K.W. Mankowitz and Stephanie R. Goodman

I. Introduction
II. Asthma
A. Introduction
B. Effect of pregnancy on asthma
C. Effect of asthma on pregnancy
D. Asthma classification and control
E. Medical management
F. Labor management
G. Anesthesia for cesarean delivery
III. Pulmonary embolism during pregnancy
A. Introduction
B. Pregnancy effects on venous thromboembolism
C. Symptoms of venous thromboembolism and pulmonary
embolism
D. Risk factors for venous thromboembolism
E. Imaging studies
F. Treatment
G. Anesthetic implications of venous thromboembolism treatment
IV. Amniotic fluid embolism
A. Background
B. Timing
 C. Symptoms and presentation
D. Risk factors
E. Pathophysiology
F. Diagnosis
G. Treatment
V. Venous air embolism
A. Description
B. Timing
C. Symptoms
D. Risk factors
E. Monitoring
F. Treatment
VI. Smoking
A. Pregnancy effects
B. Neonatal effects
C. Offspring effects
D. Pulmonary complications
VII. Obstructive sleep apnea
A. Background
B. Effect on pregnancy
C. Diagnosis
D. Treatment
E. Analgesia and anesthesia
VIII. Sarcoidosis
A. Description
B. Pulmonary sarcoidosis
C. Effect of sarcoidosis on pregnancy
D. Effect of pregnancy on sarcoidosis
E. Diagnosis and treatment
IX. Aspiration pneumonitis
A. Definition
B. Aspiration in parturients
 C. Pathophysiology
D. Treatment
E. Prophylaxis
F. Anesthetic management
X. Cystic fibrosis
A. Background
B. Effect of pregnancy on cystic fibrosis
C. Effect of cystic fibrosis on pregnancy
D. Medical management
E. Anesthetic management
XI. Lung transplantation
A. Transplantation and pregnancy
B. Medications
C. Preterm delivery
D. Surveillance
E. Anesthetic management
XII. Restrictive lung disease
A. Pregnancy
B. Spinal cord injury and kyphoscoliosis
C. Evaluation
D. Management
XIII. Acute respiratory distress syndrome and respiratory failure
A. Diagnostic criteria
B. Clinical presentation
C. Causes of acute respiratory distress syndrome
D. Treatment
E. Alternative treatments
F. Effect of acute respiratory distress syndrome on pregnancy
G. Obstetric management
Summary


KEYPOINTS
1. Diagnosis and presentation. Many respiratory diseases are difficult to
diagnose during pregnancy because the normal physiologic changes of
pregnancy resemble the pathologic states seen in these diseases. For
example, embolic disease may present with dyspnea and tachycardia.
Overlapping presentations of respiratory diseases further complicate the
diagnosis. Venous thromboembolism (VTE), amniotic fluid embolism
(AFE), venous air embolism (VAE), obstructive sleep apnea (OSA),
aspiration, severe restrictive lung disease (RLD), cystic fibrosis (CF), and
pulmonary sarcoidosis share similar signs and symptoms.
2. Physiologic changes of pregnancy and disease progression. The
physiologic changes of pregnancy may predispose to respiratory disease
development or exacerbate preexisting disease. For example, the
hematologic changes which occur during pregnancy increase the risk of
VTE. The gastrointestinal and airway changes increase the likelihood of
pulmonary aspiration. OSA symptoms often worsen during pregnancy.
Decreased functional residual capacity and increased tidal volume,
respiratory rate, and blood volume exacerbate disease in patients with
severe RLD, CF, and sarcoidosis.
3. Effect of pregnancy on disease states. Pregnancy may be beneficial to
some parturients with respiratory disease, particularly those with
sarcoidosis and asthma. Other parturients are more likely to suffer
complications during pregnancy, such as lung transplant recipients.
Generally, severe disease prior to pregnancy usually worsens during
pregnancy, particularly in patients with severe asthma, advanced
sarcoidosis, CF, and RLD. Patients with severe cardiorespiratory
compromise from pulmonary embolism (PE), AFE, VTE, and acute
respiratory distress syndrome (ARDS) may require intensive care
admission and may not survive the pregnancy.
4. Perinatal complications and medications. Many respiratory diseases
seen during pregnancy result in perinatal complications. This may result
in maternal pregnancy complications particularly in women with asthma,
smokers, and parturients with OSA. Neonatal complications can also
 occur in women with asthma, smokers, lung transplant recipients, and in
parturients with CF and OSA. In addition, the medications which are
administered for the treatment of respiratory disease may have
detrimental fetal effects. However, the overall benefit of medication
administration exceeds their risk in women with severe asthma, transplant
recipients, critically ill patients with ARDS, and after an embolic event.
Sometimes, administered medications may complicate regional anesthetic
management.
5. Anesthetic management. General endotracheal anesthesia is best
avoided in patients with respiratory disease. Neuraxial analgesia during
labor should be encouraged, and neuraxial anesthesia should be used for
most surgical procedures.

I. Introduction. Patients who are pregnant and have respiratory disease

present many challenges to the anesthesiologist. Respiratory diseases
may be affected by pregnancy, such that the parturient may become
worse or better. The disease itself may adversely affect maternal and
fetal well-being. Some pulmonary diseases, such as amniotic fluid
embolism (AFE), are unique to pregnancy. This chapter describes a
number of respiratory diseases and their impact on pregnancy and
delivery. There are physiologic changes of pregnancy that affect the
respiratory system, which are outlined in the following text in Figure
28.1 and Table 28.1.
 II. Asthma
A. Introduction
1. Asthma presentation and symptoms. Asthma causes
episodic partially reversible airway obstruction resulting from
bronchoconstriction, inflammation, hyperresponsiveness, and
mucous plugging. Symptoms include wheezing, chest
tightness, difficulty breathing, and coughing. These symptoms
may be exacerbated by exercise, viral infections, weather,
pain, stress, and exposure to various allergens.
 2. Epidemiology. Asthma affects up to 12% of pregnant women
worldwide and the prevalence is rising. It is one of the most
common medical conditions complicating pregnancy and the
most common respiratory disease affecting parturients.1
B. Effect of pregnancy on asthma. The asthmatic patient may be
adversely affected by the physiologic changes in pregnancy.
These include decreased functional residual capacity (FRC),
increased minute ventilation, increased oxygen consumption, and
elevation of the diaphragm by the gravid uterus.
1. Exacerbations. Approximately 20% to 40% of parturients
with asthma experience exacerbations or increased severity,
which require medical intervention.1,2 Women with severe
asthma tend to have a higher exacerbation rate.3
a. Timing of exacerbations. Exacerbations usually occur in
the late second trimester.1
b. Risk factors. Risk factors for exacerbation most
commonly include viral infections and noncompliance
with medication use.1,4,5
2. Improved or unchanged symptoms. Approximately 23% to
30% of patients have an improvement in asthma severity.
Maselli et al.2 reported that 30% of patients had no change in
their symptoms.
3. Symptoms during labor and delivery. Acute attacks during
labor and delivery are not common.1 If they do occur, they
tend to be mild. Women with severe asthma are more likely to
suffer symptoms during labor than women with mild asthma.
C. Effect of asthma on pregnancy
1. Asthma and maternal pregnancy complications. Asthma
has been associated with a number of adverse pregnancy
complications.
a. A large recent review and meta-analysis estimated a 31%
increased risk for cesarean delivery (CD) and a 40%
increased risk for gestational diabetes.6 Another study
found that the incidence of preeclampsia was increased by
 50% in women with asthma.7 Not all authors agree on
particular maternal complications, but those frequently
cited include preeclampsia, gestational diabetes,
hemorrhage, placental abruption, premature rupture of
membranes (PROM), increased CD rates, placenta previa,
preterm labor (PTL), and preterm delivery (PTD).3,4,6,7
b. Maternal complications and asthma severity. Some
maternal and placental complications are attributed to
asthma severity.6–8 In a large recent review and meta-
analysis, moderate to severe asthma was associated with
an increased pregnancy risk, whereas optimal
management decreased the risk.4,6
2. Fetal and neonatal complications. Neonatal complications
associated with asthma include increased perinatal morbidity
and mortality, PTL, PTD, low birth weight (LBW), small for
gestational age (SGA) infants, and possible increase in fetal
congenital malformations.4,7
a. Congenital malformations. There are some reports of
congenital malformations of the cardiac, respiratory,
nervous, digestive, and dermatologic systems in the
offspring of parturients with asthma.9 Murphy et al.,5 in a
large review and meta-analysis, reported that women with
asthma are 11% more likely to have fetal congenital
malformations. These malformations were not associated
with exacerbations or the use of inhaled bronchodilators.
Further studies will be needed to confirm these findings
and to understand the mechanism.
b. Neonatal complications and asthma severity. Some
neonatal complications correlate with asthma severity and
exacerbations.1,4,7,8,10 For example, in a large review and
meta-analysis, there was an increased risk for LBW and
SGA infants in moderate to severe, compared to
parturients with mild asthma. Women with asthma with
acute exacerbations were at greater risk for PTD and
 LBW infants. Many neonatal risks can be reduced to
nonsignificant levels with active asthma management.7
D. Asthma classification and control
1. Pulmonary function tests. Forced expiratory volume in 1
second (FEV1), forced vital capacity (FVC), the FEV1/ FVC
ratio, peak expiratory flow rate (PEFR), and the mean forced
expiratory flow (FEF) during the middle half of FVC (FEF25–
75) are all useful measurements in the management of
pregnant women with asthma. Typically, asthma control is
assessed by FEV1 and PEFR. More recently, the fraction of
exhaled nitric oxide has been used successfully to guide
management.2
2. Asthma severity classification. The definition of asthma
class (severity) and control according to the National Asthma
Education and Prevention Program (NAEPP) is summarized
in Table 28.2. Asthma severity is classified by symptom
frequency and measurement of FEV1 and PEFR for patients
on or off medications for asthma control.11

3. Remove triggers. As mentioned earlier, exacerbations tend to

occur in patients who discontinue medications and in those
with severe disease.3,8 It is important to remove
environmental triggers, treat infections, control allergic
rhinitis and gastroesophageal reflux (GERD), and institute
medical management.1
 4. Obstetric testing. In addition to good control of asthma
symptoms with medications, obstetric management will
require serial ultrasonography and other antenatal testing.
Pulmonary function tests (PFTs) and PEFR should be
followed regularly.
E. Medical management. Asthma control is necessary to improve
both maternal and fetal outcomes.2–4
1. Medication use in pregnancy. Medications should be
administered when necessary and are considered to be safe
during pregnancy.2,3,10 There is some controversy over oral
corticosteroid use during the first trimester and an increased
incidence of LBW and cleft lip, with or without cleft palate.3
Corticosteroids may be lifesaving for the severe asthmatic and
should be given when needed.

CLINICAL PEARL In general, the benefits of asthma

medication use in pregnancy outweigh the risk of exacerbations and
other complications from asthma or from the use of asthma
medication itself.

2. Step approach to treatment. The NAEPP recommends that

patients be treated in a step-up fashion, adding medications
depending on asthma severity. The most commonly
prescribed medications are anti-inflammatory inhaled
corticosteroids and inhaled β2-agonists. See Figure 28.2 for
the step approach to treatment recommended by the NAEPP.
F. Labor management. See Figure 28.3 for the management of an
acute exacerbation of asthma during labor or delivery.2
1. Induction of labor. Cervical ripening with prostaglandins for
the induction of labor should be undertaken with caution.
Prostaglandin F2α is a bronchoconstrictor and its use during
labor has been associated with bronchospasm. Prostaglandin
E2 has been associated with bronchodilation and
bronchoconstriction.12 β-Adrenergic receptor blockade can
cause bronchospasm and should be used with caution.13
2. Anesthetic goals. Anesthetic goals include good analgesia,
prevention of stress and increased minute ventilation, and
avoidance of a high sensory or motor block. The latter might
interfere with the muscles of respiration and could also lead to
unopposed parasympathetic-induced bronchoconstriction.13
3. Analgesia for labor
a. Opioids. Opioids should be administered carefully to
 patients with active asthma, given the potential for
respiratory depression and bronchoconstriction.
Histamine-releasing opioids such as morphine and
meperidine should be used with caution. Fentanyl and
remifentanil may be better choices.13
b. Neuraxial analgesia. Pudendal and paracervical blocks
can be helpful, but neuraxial analgesia has many
advantages. Hyperventilation, pain, and stress can
aggravate asthma during labor.
(1) Benefits. Neuraxial analgesia benefits the asthmatic
parturient by decreasing oxygen consumption, work
of breathing, stress, and minute ventilation during
labor. In addition, an epidural can be extended for CD
in an emergency so that manipulation of the airway,
and resultant bronchospasm, can be avoided.13,14
(2) Pulmonary effects. A dilute solution of epidural
local anesthetic and opioid to a T10 level for labor
should have minimal motor block and a small effect
on respiratory function.15 Lumbar epidural analgesia
for labor is unlikely to adversely affect respiration.
There are reports of only a 3% decrease in vital
capacity (VC) with a motor block to approximately
T8, which is a higher level and denser blockade than
would be required for labor.14
G. Anesthesia for cesarean delivery
1. Neuraxial anesthesia. Neuraxial anesthesia is preferable to
general endotracheal anesthesia (GETA) given the risk of
provoking bronchospasm with GETA. This is especially
important during general anesthesia where a rapid sequence
induction (RSI) is required and there is a tendency to give less
volatile anesthetic after delivery, which could result in lighter
levels of anesthesia and precipitate bronchospasm.15
a. Anesthetic level and asthma exacerbation. There is
concern that high levels of blockade may impair
 accessory respiratory muscle function in women with
severe asthma and that a sympathectomy could lead to
unopposed parasympathetic tone and bronchospasm.14,15
A carefully titrated epidural or a low-dose combined
spinal-epidural may be preferable to a spinal anesthetic in
patients with severe asthma.15 Although there are
concerns about the adverse pulmonary effects from a high
thoracic blockade, such a block appears safe and to have
minimal effects on pulmonary function in patients with
chronic obstructive pulmonary disease (COPD).
b. Effects of thoracic neuraxial anesthesia. In normal
parturients, high thoracic epidural anesthesia reduces VC
by 6%, total lung capacity (TLC) by 3.5%, and FEV1 by
5%. The ratio of FEV1 /FVC does not change. There is no
change in tidal volume (TV), gas exchange, arterial blood
gases (ABGs), the ventilatory response to hypoxemia or
hypercarbia, or bronchial tone. There does appear to be a
decrease in PEFR after spinal anesthesia in parturients
and a decrease in peak expiratory pressure (PEP) after
epidural anesthesia, although this depends on the density
of the thoracic motor block and does not seem to affect
patients with COPD.16 Respiratory impairment from high
thoracic neuraxial anesthesia appears to be minimal in
patients with COPD.14,16 See Figure 28.4 for a summary
of these findings.
 c. Postoperative management. Patients having neuraxial
anesthesia can enjoy improved postoperative pain
management via epidural analgesia or with long-acting
neuraxial opioids, such as preservative-free morphine.
This could lead to less postoperative pulmonary
dysfunction than after GETA.13,14
2. General endotracheal anesthesia. Should GETA become
necessary, inhaled β2-agonists and intravenous (IV) lidocaine
may reduce airway hyperactivity, but the former may decrease
uterine tone.13,14
a. Induction agents. Ketamine is the preferred induction
agent because of its sympathomimetic bronchodilating
properties; however, it does increase secretions. Propofol
decreases the response to airway manipulation and may
have direct airway smooth muscle relaxant activity,
making it a good alternative.15
 b. Muscle relaxants. Neuromuscular blocking agents that
release histamine, such as curare and atracurium, should
not be used. Most of the muscle relaxants in use today
will not cause bronchospasm; however, neuromuscular
blocking agents are common medications implicated in
allergic reactions in the operating room.13
c. Reversal agents. Reversal agents such as neostigmine
may cause bronchospasm and increase airway secretions.
They should be used carefully and after administration of
an anticholinergic agent.13,15
d. Aspiration risk. Although inhalational induction by
mask ventilation and deep extubation are sometimes
performed in women with severe asthma, the risk of
pulmonary aspiration is increased in parturients. Thus,
parturients with asthma should typically be extubated
awake. The risk of bronchospasm must be weighed
against the risk of aspiration.
3. Postpartum hemorrhage. Postpartum hemorrhage (PPH) is
best treated with oxytocin. Ergot alkaloids have been linked to
bronchospasm, and prostaglandin F2α is relatively
contraindicated because it can precipitate bronchospasm.
Prostaglandin E2 aerosols can provoke bronchospasm as well.
Prostaglandin E1 appears to be safer. Other means of
controlling hemorrhage, such as embolization and arterial
ligation, should be considered.10,15

CLINICAL PEARL Drugs that can precipitate bronchospasm

include opioids, β-blockers, histamine-releasing neuromuscular
blockers, reversal agents, ergot alkaloids, and prostaglandin F2α.

III. Pulmonary embolism during pregnancy

A. Introduction. Embolic diseases during pregnancy include
pulmonary thromboembolism (PE), AFE, and venous air
 embolism (VAE). Approximately one-fifth of deaths in the United
States are due to embolic disease and constitute obstetric
emergencies.17 PE is one of the most common causes of maternal
mortality worldwide. Venous thromboembolism (VTE) manifests
as deep vein thrombosis (DVT) and PE. DVT is more common
(75% to 80% of VTE) than PE (20% to 25%).18,19
1. Venous thromboembolism prevalence and mortality. VTE
occurs in approximately 0.6% to 1.8% per 1,000 pregnancies
and accounts for 1.1 to 1.6 deaths per 100,000 births.20,21
Recent studies report that 10.2% of pregnancy-related deaths
in the United States are due to VTE; however, some report a
mortality rate as high as 20% to 25% in the United States.22
PE alone occurs in 0.4 to 0.5 per 1,000 births,23 and 80% of
women with PE will have evidence of a DVT. Early suspicion
is critical as up to 65% of fatalities occur within 1 hour of the
onset of a PE symptom.24
2. Venous thromboembolism morbidity. There is also
significant morbidity associated with VTE such as pulmonary
hypertension, venous insufficiency, and postthrombotic
syndrome.19
B. Pregnancy effects on venous thromboembolism
1. Venous thromboembolism risk. The risk of VTE is greatly
increased during pregnancy with an estimated 5 to 10 times
greater incidence than outside of pregnancy.21,25,26
2. Venous thromboembolism timing. VTE can occur at any
time during gestation, although the incidence increases in the
third trimester and peaks following delivery, declining to
prepregnancy levels within 12 weeks. The highest risk may be
in the first week postpartum.18 The overall risk is at least 20
times greater in the first 6 weeks postpartum than in the
nongravid state.18,19,25
3. Venous thromboembolism and hematologic changes in
pregnancy. Pregnancy increases the risk of PE due to a
combination of factors, such as hypercoagulability,
 hemodynamic changes, and endothelial injury. During
pregnancy, there is an increase in venous stasis, increased
production of coagulation factors including fibrinogen and
von Willebrand factor (vWF), decreased production of
inhibitors of coagulation, and a suppressed fibrinolytic state.27

CLINICAL PEARL Hematologic changes in pregnancy

contribute to the risk of VTE. These include higher levels of
fibrinogen; vWF; and factors V, VII, VIII, IX, X, and XII.
Additionally, the anticoagulant activity of protein S is decreased
and activated protein C resistance increases. Thrombolysis is
decreased as a result of increased activity of plasminogen activator
inhibitor types 1 and 2 and decreased activity of tissue plasminogen
activator. Early suspicion for VTE is critical because as many as
65% of fatalities occur within 1 hour of the onset of a PE symptom.

C. Symptoms of venous thromboembolism and pulmonary

embolism
1. Similarity of pregnancy and pulmonary embolism
symptoms. The diagnosis of PE requires a high index of
suspicion because the symptoms of PE resemble the normal
changes of pregnancy, such as shortness of breath, dyspnea on
exertion, and a slightly increased heart rate. For this reason,
the diagnosis of PE is frequently missed in parturients. If one
suspects PE, it is important to evaluate and treat promptly.20
2. Venous thromboembolism symptoms. The symptoms of
DVT are leg pain and redness. During pregnancy, the left leg
and the proximal deep veins (iliac and femoral) are most
commonly involved.26 Symptoms of PE may include dyspnea,
palpitations, anxiety, cough, and chest pain. Common
presenting signs include tachypnea, respiratory rales, and
tachycardia. A large acute PE can increase pulmonary artery
pressure, leading to right ventricular failure, decreased cardiac
 output, increased ventilation/perfusion ( ) mismatch, and
arterial hypoxemia. This could result in cardiovascular and
respiratory collapse with syncope, hypotension, pulseless
electrical activity, and death.26
D. Risk factors for venous thromboembolism. There are many risk
factors, in addition to pregnancy itself, which increase the
incidence of PE. It is important to offer prophylactic therapy to
patients at increased risk. Risk factors for VTE development
include a history of a previous DVT, thrombophilias (deficiencies
of antithrombin and proteins C and S, factor V Leiden, and
prothrombin gene mutation), the presence of a lupus
anticoagulant and anticardiolipin/β2 glycoprotein 1 antibodies,
obesity, CD, surgical procedures during pregnancy, and advanced
maternal age.20,26
E. Imaging studies. A combination of lower limb compression
Doppler ultrasonography (CUS), chest X-ray (CXR), nuclear
scanning, and computed tomography pulmonary angiogram
(CTPA) is used to make the diagnosis of PE. The order of studies
varies among practitioners. If there is a high clinical suspicion,
and/or a positive CUS or high-probability scan or CTPA,
treatment should begin or continue.
1. Ultrasonography. This can diagnose a DVT without any
radiation exposure and allows prompt treatment if positive. It
has a 97% sensitivity and 94% specificity for a lower
extremity DVT, but is less reliable for pelvic DVTs.26 A
proximal thrombus is found in only 23% to 52% of pregnant
women with confirmed PE.26
2. Chest x-ray. If the CUS is negative, a CXR, which confers
negligible risk to the fetus, may help identify other etiologies
or reveal pulmonary edema, effusions, focal opacities, and
atelectasis.19,28 Frequently, the CXR is normal (50%) and
further workup will be required.26 If there is an abnormality
on CXR, a CTPA is done. If the CXR is normal, either a
CTPA or scan can be performed.
3. Ventilation/perfusion scan versus computed tomography
pulmonary angiogram. The decision to proceed with either a
scan or CTPA is controversial.28
a. Ventilation/perfusion scans. Some practitioners prefer
scans, especially after a normal CXR, because of the
high negative predictive value, infrequent comorbid
pulmonary disease in parturients, and lower maternal
radiation exposure.19 However, scanning in pregnancy
is inconclusive in 25% of patients, which might
necessitate further testing and radiation exposure.29
b. Computed tomography pulmonary angiogram. CTPA
delivers less radiation to the fetus than scanning and
has a decreased lifetime cancer risk than scanning
(<1:1 million vs. 1:280,000, respectively). However,
CTPA delivers higher doses of radiation to maternal breast
tissue and increases the risk of breast cancer by as much
as 14%.19–21,26 Nonetheless, CTPA allows visualization of
the lung, mediastinum, and chest wall such that other
etiologies can be excluded. CTPA is the preferred test for
unstable patients and has a better sensitivity and
specificity than a scan and fewer undergo further
scans. If nuclear testing is positive, treatment should be
continued. Nondiagnostic nuclear imaging will require
workup with pulmonary angiogram/serial CUS and
magnetic resonance imaging (MRI) studies.20 See Figure
28.5 for PE demonstrated on CTPA.
4. Ventilation/perfusion single photon emission computed
tomography. The ventilation/perfusion single photon
emission computed tomography (  SPECT) is a new three-
dimensional imaging modality that has gained popularity and
has a higher sensitivity and specificity compared to planar
scanning (97% and 91% compared to 76% and 85%,
respectively). In addition, the radiation dose is about 35% to
40% less than CTPA, with much less radiation to maternal
breast tissue.21
 5. Echocardiography. Echocardiography helps to visualize a
massive centrally located PE, particularly in patients who are
hemodynamically unstable. In addition, there could be signs
of pressure overload of the right ventricle (RV), such as RV
dilation and hypokinesis, tricuspid regurgitation, pulmonary
hypertension, flattening and paradoxical motion of the
septum, and lack of inspiratory collapse of the inferior vena
cava.26,28
6. D-dimer. D-dimers indicate recent thrombus formation; they
are plasma breakdown products of cross-linked fibrin. D-
dimers increase in pregnancy, and by the third trimester, very
few parturients will have a negative D-dimer. However, a low
level would be suggestive that there is no PE. (i.e., has good
negative predictive value).20
F. Treatment. Typically, patients who are not pregnant are treated
with low molecular weight heparin (LMWH) in the acute period
followed by chronic warfarin therapy. Warfarin cannot be used in
pregnancy because it crosses the placenta leading to an
embryopathy early in pregnancy and has been associated with
intraventricular hemorrhage and schizencephaly later in
pregnancy.21 LMWH and unfractionated heparin (UFH) do not
cross the placenta. Further benefits include weight-based dosing,
lack of need for monitoring blood values, decreased risk of
thrombocytopenia, and decreased risk of osteoporotic fractures
compared to UFH. UFH used to be the standard of care for acute
embolism, but this has changed to LMWH for the treatment of
DVT and PE.20,25

CLINICAL PEARL LMWH does not cross the placenta.

Warfarin is contraindicated in pregnancy. Warfarin early in
pregnancy causes an embryopathy. Later in pregnancy, warfarin
increases the risk of fetal intracranial bleeding, stillbirth, ventricular
septal defect (VSD), and growth retardation.
 1. Optimum dosing. The physiologic changes of pregnancy,
such as increased renal clearance and plasma volume, lead to
a shorter half-life of LMWH. Further testing to determine the
optimum dosing during pregnancy for the treatment of
DVT/PE may be needed.21
2. Unfractionated heparin. UFH is used for life-threatening PE
treatment.
3. Thrombolysis. In patients with hemodynamic compromise,
thrombolysis may be beneficial in decreasing the clot burden
and improving hemodynamics. There is an increased risk of
maternal bleeding and fetal loss. Some fibrinolytics such as
streptokinase do not cross the placenta.26,28
4. Embolectomy. If a patient remains hemodynamically
unstable after medical management, emergency thoracotomy
with embolectomy has been lifesaving.22
5. Extracorporeal membrane oxygenation. In patients with a
massive PE resulting in RV failure and hypoxemia,
extracorporeal membrane oxygenation (ECMO) has been
used as a bridge to embolectomy, or to stabilize the patient so
that she can benefit from anticoagulation.
6. Vena cava filter. Experience with venacaval filters in
pregnancy is limited, but they may be helpful if delivery is
eminent.20
G. Anesthetic implications of venous thromboembolism
treatment. Closer to delivery, most practitioners switch from
LMWH to subcutaneous (SQ) heparin in order to avoid bleeding,
and so that patients can benefit from neuraxial analgesia and
anesthesia. This typically occurs at 36 weeks’ gestation.
1. Therapeutic low molecular weight heparin and neuraxial
analgesia. If a patient on LMWH is in labor, no further
LMWH should be administered. Typically, epidural analgesia
and spinal anesthesia can be performed 24 hours after
therapeutic doses of LMWH. The LMWH should not be
restarted until at least 2 hours after epidural catheter removal.
 However, if a patient undergoes a surgical procedure, then
LMWH should not be administered regardless of anesthetic
technique for 24 hours. If blood is encountered during
neuraxial placement, the administration of LMWH should be
delayed for 24 hours postoperatively.30
2. Prophylactic low molecular weight heparin and neuraxial
analgesia. If the patient is on once-a-day prophylactic dose of
LMWH, neuraxial anesthesia and analgesia can be
administered 12 hours after the last dose. LMWH dosing
should not resume for 2 hours after catheter removal.
However, removal should occur at least 12 hours after the last
dose of LMWH. After a surgical procedure in patients on
prophylactic therapy, LMWH use should wait for 6 to 8
hours.30
3. Unfractionated heparin. Recommendations on IV UFH are
lacking. Typically, UFH is discontinued and laboratory testing
done to confirm a normal coagulation profile. SQ UFH in
prophylactic doses does not contraindicate neuraxial analgesia
or anesthesia. Higher doses should prompt laboratory
investigation before placing a block.30
4. Neurologic checks. Even when you follow the recommended
guidelines, the patient should be observed postpartum for
signs of epidural hematoma.

CLINICAL PEARL Neuraxial analgesia and anesthesia should

not be administered until 24 hours after the last dose of therapeutic
LMWH, 1.5 mg per kg daily or 1 mg per kg twice a day. Neuraxial
analgesia and anesthesia can be administered 12 hours after
therapeutic dosing, usually 40 mg SQ daily. LMWH should not be
given before 2 hours after catheter removal, assuming that the last
dose was 12 or 24 hours prior to catheter removal for prophylactic
and therapeutic dosing respectively.
 IV. Amniotic fluid embolism
A. Background. AFE is a rare disease specific to pregnancy that has
an acute onset of cardiac and pulmonary distress and carries a
high mortality. The etiology is poorly understood. AFE may even
be a misnomer in that the symptoms may not be due directly to
amniotic fluid or from an embolic event.31 The incidence of, and
mortality rates from, AFE reported in industrialized countries
vary widely depending on study methodology. In the United
States, the incidence has been reported as 7.7 per 100,000
deliveries.32 Some report that the case fatality rate ranges from
13.5% to 44% in developed countries,33 whereas others have
pointed to a mortality rate as high as 60%.31 In the United States,
AFE accounts for 7.5% to 14% of maternal deaths.24,32 Perinatal
mortality after maternal AFE ranges from 7% to 38%.33
Survivors are often affected by significant morbidity such as
permanent neurologic sequelae and 34% to 50% of surviving
children have deficits.33
B. Timing. AFE can occur at any time during pregnancy and in the
immediate postpartum period, but typically has been reported in
the peripartum period.34 One report suggested that AFE usually
occurs between 2 hours before delivery and 4 hours postpartum,
56% occur before or at delivery, and of these, 73% are in women
who have CD.35
C. Symptoms and presentation. Patients often have sudden acute
dyspnea, which quickly progresses to cardiac and respiratory
arrest.31–33 Symptoms may be preceded in 30% of cases by
nonspecific premonitory symptoms such as agitation, impending
doom, light-headedness, and chills.35 The classic triad of AFE
involves sudden hypoxia, hypotension, and coagulopathy during
labor or after delivery.31 See Table 28.3 for common symptoms of
AFE.
 1. Phases of presentation
a. Early phase. The early phase occurs in the first 30 to 60
minutes and is depicted by intense pulmonary
vasoconstriction, pulmonary hypotension, acute right
ventricular failure, severe tricuspid regurgitation,
hypoxemia, and respiratory failure.33–35
b. The second or late phase. This phase involves left
ventricular failure and pulmonary edema (51% to 100%)
in survivors of the early phase. Many parturients do not
survive the first phase.33
2. Disseminated intravascular coagulation. Coagulopathy
occurs in more than 80% of cases and may be the presenting
feature.35 This may occur within 10 to 30 minutes of the onset
of symptoms, but presents within 4 hours in 50% of cases or
as late as 9 hours after onset. The cause of disseminated
intravascular coagulation (DIC) is not fully understood, but is
likely due to both hyperfibrinolysis and procoagulant
substances in amniotic fluid which can cause cytokine or
complement activation.33,35
3. Mortality. Causes of death in women who survive the first
phase include sudden cardiac arrest, severe hemorrhage from
DIC, acute respiratory distress syndrome (ARDS), and
multiple organ failure.
D. Risk factors. AFE pregnancy risk factors include advanced age,
race, amnioinfusion, induction of delivery, CD (classical more
than low transverse), postpartum hemorrhage, abruption, placenta
previa, chorioamnionitis, polyhydramnios, multiple pregnancy,
stillbirth, and preeclampsia (eclampsia much more than mild
preeclampsia). Diseases associated with AFE include
 cardiomyopathy, cerebrovascular accidents, renal disease, urinary
tract infection, and hypertensive disorders. Some of these pose
significant risk. For example, cardiac disease carries an odds ratio
of 70 for AFE.32–34
E. Pathophysiology. The pathophysiology of AFE is not well
understood.
1. Barrier interruption. A break may occur between maternal
and fetal barriers such that amniotic fluid leaks through
endocervical veins, areas of uterine trauma, and placental
attachment sites.32
2. Causes of cardiopulmonary arrest. Early research proposed
a mechanical obstruction of the pulmonary vessels by fluid
components, alveolar capillary leak due to microemboli which
caused an ARDS-like picture, and an anaphylactoid reaction
from the maternal exposure to fetal antigen.34
3. Humoral and immunologic etiology. More current theories
have focused on the expression of humoral and immunologic
factors resulting from activation of inflammatory meditators
found in amniotic fluid (cytokines, bradykinin, thromboxane,
leukotrienes, and arachidonic acid). Complement activation
and/or procoagulants found in amniotic fluid (e.g., platelet-
activating factor, tissue factor, tissue factor pathway inhibitor)
have been implicated in causing the DIC of AFE. Thus, there
is both activation of proinflammatory mediators and the
coagulation cascade in response to fetal antigen
exposure.31,33,35
F. Diagnosis. Diagnosis is by clinical suspicion. AFE is primarily
diagnosed by clinical presentation rather than laboratory findings.
Diagnosis is one of exclusion; other diseases must be ruled
out.31,34
1. Fetal squamous cells. The presence of fetal squamous cells
in the maternal circulation is no longer pathognomonic for
AFE. Many parturients have fetal cells in their circulation.
There are no tests to confirm the diagnosis.
 2. Histologic evidence. There may be histologic evidence of
AFE at autopsy. Formed components (e.g., lamellar epithelial
squames, meconium components, mucin, and lanugo hairs) of
amniotic fluid may be seen in the pulmonary circulation.
Fibrin thrombi are usually detected in the pulmonary
arterioles and capillaries.33

CLINICAL PEARL The diagnosis of AFE is one of exclusion.

Other common causes of cardiac and pulmonary arrest and DIC
must be considered. This includes total spinal, local anesthetic
toxicity, sepsis, anaphylaxis, VTE, VAE, myocardial
ischemia/infarct, aspiration, placental abruption, hemolysis,
elevated liver enzymes, low platelets (HELLP) syndrome, and
uterine rupture.

G. Treatment. Treatment is supportive. Prompt resuscitation

requires airway and hemodynamic support. This includes
measures to improve oxygenation including intubation and
mechanical ventilation, infusion of crystalloid for volume
replacement, and early administration of vasopressor therapy.
Transesophageal echocardiography (TEE) is helpful in managing
inotropes and vasopressors. Advanced life support protocols
should be applied as needed. Invasive monitoring should be
placed as indicated.33
1. Blood products. Coagulation tests, cross-matched blood, and
ABGs should be obtained. Blood products (red blood cells,
fresh frozen plasma, platelets, and cryoprecipitate) may be
necessary in the setting of DIC and hemorrhage. Tranexamic
acid, aprotinin, and fibrinogen concentrate have been useful to
treat DIC. Factor VIIa has been used, but may be complicated
by thrombosis and worse outcomes.31,34
Thromboelastography can be a useful tool in the management
of DIC.33,35
 2. Emergency delivery. Emergency CD should be initiated
within 4 to 5 minutes of cardiac arrest or life-threatening
dysrhythmia. This might improve both maternal and neonatal
outcomes. However, mothers who suffer a cardiac arrest carry
a poor prognosis for recovery.31,34
3. Hysterectomy and other modalities. Hysterectomy is
advised in the setting of uterine atony or hemorrhage.33 Other
modalities which have been employed include pelvic
embolization, cardiopulmonary bypass, pulmonary artery
thrombectomy, thrombolysis, ECMO, intra-aortic balloon
counterpulsation, exchange transfusions, and
hemofiltration.34,35
V. Venous air embolism
A. Description. VAE involves the presence of air emboli in the
pulmonary circulation and typically occurs during a surgical
procedure. There must be entrainment of air from open veins to
the circulation producing embolism to the right heart or
pulmonary veins. A pressure gradient of −5 cm H2O between the
operating field and the right heart permits entrainment of a
significant amount of air into the circulation. VAE accounts for
1% of maternal deaths.36 The incidence varies greatly, reportedly
between 10% to 60% by Doppler monitoring in patients
undergoing CD.37
B. Timing. VAE typically occurs during CD. However, VAE has
been reported during labor and delivery (vaginal and cesarean
delivery), vaginal exams, orogenital sex, and during other surgical
procedures.23 The amount and rate of entrapment determine the
symptoms and outcome of VAE.
C. Symptoms. Symptoms largely depend on the size of the VAE.
Typically, the venous injection of more than 3 mL per kg of air
can be fatal in humans. It is likely that subclinical VAE is
common, whereas massive VAE is not. Clinically significant VAE
may cause chest pain, dyspnea, tachypnea, dysrhythmias, and
 desaturation. A massive VAE causes sudden hypotension and
respiratory and cardiovascular collapse as the air occludes
pulmonary vessels. This results in acute right ventricular failure
followed by decreased cardiac output and cardiac arrest.37
Cerebral involvement could occur if there is an intracardiac shunt.
In patients under general anesthesia, there may be a sudden
decrease in end-tidal (ET) CO2, hypotension, and hypoxemia. See
Figure 28.6 for a description of the symptoms seen with varying
amounts of air.38

D. Risk factors. Risk factor for VAE include placenta previa,

placental abruption, manual placental extraction, exteriorization
of the uterus, hemorrhage, and operating in the Trendelenburg
position with a 15-degree tilt.23,36,37
 E. Monitoring
1. Transesophageal echocardiography. TEE is the most
sensitive monitor and detects as little as 0.02 mL per kg of air.
Echocardiography assists with the detection of the severity of
the VAE as well as determining cardiac function and the
presence of an intracardiac defect that might allow
paradoxical embolization.38
2. Doppler. Precordial Doppler ultrasound can detect as little as
0.05 mL per kg of air and has a high sensitivity.38
3. Pulmonary artery catheter, end-tidal N2, and end-tidal
CO2. Other monitors that could be useful, but are not
typically used in patients having neuraxial anesthesia, include
pulmonary artery catheter (PAC), ETN2, and ETCO2
monitoring. A PAC has a high sensitivity and can detect as
little as 0.25 mL per kg of air. ETN2 and expired ETCO2
monitoring detects 0.5 mL per kg of air.38 A “mill wheel
murmur” auscultated by esophageal stethoscope, oxygen
saturation, and electrocardiogram (ECG) changes have low
sensitivities and are late findings.38
4. Chest x-ray and arterial blood gas. A CXR may reveal an
air–fluid level in the pulmonary vessels, and an ABG may
show hypoxemia and hypercarbia.36,37

CLINICAL PEARL The most sensitive monitors for VAE based

on the mL per kg of air detected are TEE 0.02 mL per kg, precordial
Doppler 0.05 mL per kg, and PAC 0.25 mL per kg.

F. Treatment36,39
1. Reverse the pressure gradient. Treatment involves reversing
the pressure gradient between the right atrium and the uterus
by increasing right atrial pressure. In order to trap the air in
the right atrium, it is recommended to place the patient in a
left lateral tilt with a 5-degree head-down position.36,37
 However, this has not been effective in animal models and
may not be effective in humans.
2. Flood the field. It is also important to flood the field with
fluid such as normal saline and, if possible, eliminate the site
of air entry.
3. Discontinue nitrous oxide. Nitrous oxide should not be used,
and 100% oxygen should be delivered.
4. Central venous catheter. A central venous catheter or PAC
can be used to aspirate air from the heart. As much as 50% of
entrained air can be aspirated via a multiorifice catheter
placed in the right atrium.
5. Positive end-expiratory pressure. The use of positive end-
expiratory pressure (PEEP) and the Valsalva maneuver could
result in a paradoxical embolism.
6. Supportive care. Vasopressors, inotropes, and pulmonary
vasodilators may be necessary.
7. Hyperbaric oxygen. Hyperbaric oxygen therapy has been
useful especially after paradoxical air embolism with cerebral
air embolism.
VI. Smoking. Approximately 14% of women in the United States smoke
during pregnancy. Both perinatal and pregnancy-related
complications occur as a result of smoking.40
A. Pregnancy effects. There are number of pregnancy complications
associated with smoking.40 These include infertility, ectopic
pregnancy, spontaneous abortion (20% to 80% higher in women
who smoke), placental abruption, placenta previa, fetal growth
restriction, and PTD.
B. Neonatal effects. Several fetal malformations have been reported.
In a large meta-analysis, moderate increases in the rates of limb,
cardiac, and musculoskeletal defects were reported. Larger effects
were noted for orofacial clefts, clubfoot, limb, eye, and
gastrointestinal defects.41 These results need to be confirmed in
further studies.
C. Offspring effects. Offspring effects include increased rates of
 sudden infant death syndrome and evidence of increased rates of
childhood respiratory disease, such as asthma, as well as
behavioral problems, such as attention deficit disorder has been
reported.

CLINICAL PEARL Smoking cessation reduces carbon

monoxide and nicotine levels within 12 to 24 hours, decreases
sputum production within 1 to 2 weeks, and, by 8 to 12 weeks,
reduces postoperative morbidity and mortality.

D. Pulmonary complications. Smoking causes significant

morbidity and should be stopped prior to pregnancy.
Perioperative pulmonary complications include laryngospasm,
bronchospasm, aspiration, hypoxemia, hypoventilation,
reintubation, and the need for postoperative admission.42 See
Table 28.4 for some of the adverse effects of smoking.42 Given
the risk of pulmonary complications in patients who smoke,
neuraxial analgesia and anesthesia should be encouraged. Airway
morbidity can be minimized with its use.

VII. Obstructive sleep apnea

A. Background. Obstructive sleep apnea (OSA) is characterized by
periodic upper airway obstruction during sleep, which results in
hypoxemia, hypercapnia, and disordered sleep. OSA frequently
results in hypertension, cardiac disease, and metabolic syndrome.
1. Incidence. The incidence of OSA in pregnancy is unknown,
 largely because of insufficient data. The incidence in obese
parturients may be as high as 15.4%.43 The physiologic
changes that occur during pregnancy, as well as the obesity
epidemic, probably precipitate and exacerbate OSA.44
2. Pathophysiology. OSA causes sympathetic system activation,
increased oxidative stress, and an inflammatory response,
which results in endothelial dysfunction.45,46
B. Effect on pregnancy. There is growing evidence that OSA may
be associated with adverse maternal and fetal consequences.43
1. Maternal complications. OSA has been associated with
gestational hypertension, preeclampsia, and diabetes.44,45
2. Fetal effects. Fetal growth restriction resulting in SGA and
LBW infants, lower Apgar scores, and PTD have been
reported in parturients with OSA.44
3. Data. Most studies have not been able to adjust for
confounding variables or achieve sufficient power. Further
investigation is warranted.
C. Diagnosis. Diagnosis is by plethysmography. Reports of snoring,
daytime somnolence, disrupted sleep and irritability, especially in
women with obesity, should prompt further investigation. Several
questionnaires, such as the Berlin, Epworth sleepiness scale, and
the STOPBang scoring system, have been used to help diagnose
OSA. These scales may not to be sensitive or specific in
parturients.44
D. Treatment. The treatment for OSA consists of nasal continuous
positive airway pressure (CPAP). Women who use CPAP prior to
pregnancy should continue CPAP during pregnancy.
1. Continuous positive airway pressure in pregnancy. CPAP
appears to be safe and effective in pregnancy. There is
evidence that CPAP decreases both systolic and diastolic
blood pressures in parturients.44,46
2. Continuous positive airway pressure compliance. CPAP
may need to be adjusted as gestational age increases.
Compliance may be compromised given its propensity to
 cause nasal congestion and discomfort.43,44
E. Analgesia and anesthesia
1. Epidural analgesia. Neuraxial analgesia should be
encouraged and placed early in labor. Parturients with OSA
are often obese, which has been associated with both more
painful labors and CD.44 Placing neuraxial analgesia in
women with obesity with OSA may pose a technical
challenge; however, neuraxial analgesia results in less opioid
consumption and less sedation and respiratory depression than
alternative forms of analgesia. In addition, the epidural
catheter can be used to extend the block for CD, if necessary.
2. Neuraxial anesthesia. Careful airway examinations should
be performed. Women with obesity may have an eight times
higher incidence of failed intubation than parturients with a
normal BMI.44 These patients pose challenges with both
ventilation and intubation. Airway equipment for difficult
airway management should be readily available. Neuraxial
anesthesia avoids potential airway misadventure, apnea,
aspiration risk, sedation, and the need for postoperative
patient-controlled analgesia (PCA) with opioids, which can
cause respiratory depression. The epidural could be used for
postoperative pain management to avoid respiratory
depression. These patients require careful postoperative
monitoring. They should also be observed for VTE and
wound infection.44
3. General endotracheal anesthesia. If GETA becomes
necessary, preoxygenation is critically important, with the
application of CPAP by mask prior to induction. Aspiration
prophylaxis should be administered. A difficult airway cart
should be available, and a Troop elevation pillow may
facilitate intubation. Induction may be accomplished in the
head-up or sitting position, prior to lying supine for
intubation. Short-acting anesthetic drugs and less soluble
inhalation anesthetics should be used with careful titration of
 opioids and other sedatives. The patient should be extubated
awake after full reversal of neuromuscular blockade. Some
patients require CPAP after extubation of the trachea. If
possible, either postoperative intrathecal opioid or epidural
analgesia should be considered. If PCA is necessary, a basal
infusion rate should not be administered. Extreme vigilance
must be used in the postoperative period. These patients
should recover in a sitting position and have continuous
cardiopulmonary monitoring for a prolonged period of time.
CPAP or auto-PAP can be employed. CPAP may decrease
airway obstruction, postoperative complications, and the
length of admission.44
VIII. Sarcoidosis
A. Description. Sarcoidosis is a multisystem granulomatous disease
that causes tissue injury and granuloma formation. The lungs are
affected in more than 90% of cases.47 There can also be
dermatologic, lymph node, ocular, and liver involvement and less
commonly, neurologic, endocrine, laryngeal, renal, and muscle
involvement.47–49 The etiology is unknown. A recent study
reports a prevalence of 9.6 cases per 100,000 births.39
B. Pulmonary sarcoidosis. Possible pulmonary manifestations
include restrictive lung disease (RLD), fibrosis, bronchiectasis,
emphysema, cavitary lung disease with mycetomas, and
pulmonary hypertension.47
C. Effect of sarcoidosis on pregnancy. Although most authors
report no adverse pregnancy outcomes in parturients with
sarcoidosis,48 others suggest an increased risk of various
complications such as preeclampsia, PE, and PTD.39
D. Effect of pregnancy on sarcoidosis
1. Benign course. Pregnancy does not typically affect patients
with stable or inactive disease. Patients with active disease,
that is present before pregnancy, may improve, perhaps due to
increased circulating cortisol levels.50
 2. Disease progression. Parturients with advanced radiographic
stage, parenchymal infiltrates on CXR, extrapulmonary
disease, and/or the need for second-line medications may
suffer disease progression during pregnancy.48,49
3. Postpartum relapse or the development of new manifestations
at 3 to 6 months is common.49,50
E. Diagnosis and treatment
1. Diagnosis. Diagnosis requires compatible clinical, radiologic,
and histologic findings of noncaseating granulomas in more
than one organ after other diseases have been excluded.
2. Medication treatment. Corticosteroids are used to treat
sarcoidosis. Second-line agents used in the treatment of
sarcoidosis include azathioprine, chloroquine, and
hydroxychloroquine. Many cytotoxic medications, such as
methotrexate and cyclophosphamide, are contraindicated
during pregnancy.48,50
3. Benign course during pregnancy. Because sarcoidosis is
typically benign during pregnancy, anesthetic management
involves good analgesia to facilitate decreased oxygen
consumption. However, the presence of extrapulmonary
disease or severe restrictive and other lung disease dictates
individualized anesthetic management plans.
IX. Aspiration pneumonitis
A. Definition. Aspiration pneumonitis is defined as the inhalation of
oropharyngeal or gastric contents into the larynx and/or lower
respiratory tract. Aspiration pneumonitis is an acute lung injury
that occurs after the inhalation of regurgitated gastric contents.
There has been a significant decrease in the number of maternal
deaths from pulmonary aspiration over the last several decades
concurrent with an increase in the use of neuraxial anesthesia for
CD. However, pulmonary aspiration is a significant complication
of anesthesia due to its increased risk of morbidity and
mortality.51
B. Aspiration in parturients. Pregnant women have long been
 considered at high risk for pulmonary aspiration. Historically,
gastric fluid with a pH <2.5 and a gastric volume >25 mL have
been considered factors increasing the risk of lung injury.52
Emergency surgery, obesity, GERD, and airway problems during
general anesthesia increase the risk of aspiration and are
commonly seen in pregnant women.53 Gastric emptying does not
decrease during pregnancy until labor begins. Delayed gastric
emptying to water has not been demonstrated in obese,
nonlaboring parturients.54 Pain and opioids are also associated
with delayed gastric emptying.

CLINICAL PEARL Gastric emptying has been shown to be

similar in pregnant women who are not in active labor compared to
nonpregnant patients. The American Society of Anesthesiologists’
Practice Guidelines for Obstetric Anesthesia allow clear liquids for
up to 2 hours before anesthesia induction in uncomplicated patients
having elective CD. The recommended time for fasting of solid
foods remains 6 to 8 hours.

C. Pathophysiology. Aspiration of acidic liquid causes injury to the

alveolar epithelium. This leads to decreased pulmonary
compliance, increased alveolar water, and intrapulmonary
shunting. Pulmonary edema and intrapulmonary shunting cause
hypoxemia and bronchospasm. Cellular debris or aspiration of
large solid particles can cause bronchial obstruction. An initial
CXR may appear normal, but most patients develop a right lower
lobe infiltrate within 12 to 24 hours of aspiration.55
D. Treatment. Hypoxemia is treated with CPAP in patients who are
breathing spontaneously or with PEEP in those who are
mechanically ventilated. There is no role for the use of
prophylactic antibiotics.
E. Prophylaxis. Several medications can be used to minimize the
risk of regurgitation of stomach contents and pulmonary
 aspiration. Nonparticulate antacids (e.g., sodium citrate) are used
to increase gastric pH. These are used routinely in patients
undergoing CD. Sodium citrate is only efficacious for
approximately 30 minutes after administration and increases the
incidence of nausea.56 H2-receptor antagonists decrease gastric
acid production and gastric volume. Given intravenously, onset
occurs within 30 minutes, but does not reach maximal effect for
60 to 90 minutes. Cimetidine and ranitidine are effective for 4 to
8 hours. Proton pump inhibitors, such as omeprazole, inhibit
gastric acid production. They have few side effects and are useful
in reducing gastric acidity; however, they have been found most
effective if given in two successive doses, the evening before and
the morning of surgery. For this reason, they may be useful only
for elective CD.52 Metoclopramide increases lower esophageal
sphincter tone and gastric peristalsis. Ten milligrams administered
IV decreases gastric volume within 15 minutes. Metoclopramide
has the potential to cause extrapyramidal side effects and should
be injected slowly to reduce the risk.

CLINICAL PEARL The combination of antacids and H2-

receptor antagonists are more effective than no intervention and is
better than antacids alone in providing a higher gastric pH at the
time of direct laryngoscopy.

F. Anesthetic management. The use of neuraxial anesthesia

decreases the incidence of aspiration and should be provided
whenever possible. If GETA is planned, a thorough evaluation of
the airway is essential. An awake fiberoptic intubation should be
considered for patients with a difficult airway. If an easy
intubation is anticipated, then an RSI with GETA is
recommended. Cricoid pressure (Sellick maneuver) should be
maintained until tracheal intubation is confirmed. Avoidance of
mask ventilation decreases gastric insufflation, and the
 application of cricoid pressure will reduce the risk of passive
regurgitation of stomach contents into the airway. Application of
cricoid pressure is somewhat controversial; cricoid pressure is
often applied incorrectly and without the appropriate amount of
force. Cricoid pressure may also make laryngoscopy more
difficult.57 A cuffed endotracheal tube remains the standard of
care for airway protection during mechanical ventilation. Other
airway devices, such as the laryngeal mask airway (LMA) may be
useful in emergency situations, but they do not protect the airway
from aspiration.52 There is a growing body of literature
describing the use of LMA in elective CD. In one report, 1,067
fasted, parturients with a normal BMI received general anesthesia
with an LMA with no reported aspiration.58
X. Cystic fibrosis
A. Background. Cystic fibrosis (CF) is an autosomal recessive
disorder. Mutations in the chloride channel in epithelial cells
result in the production of thick, mucous secretions by the lungs,
pancreas, and sweat glands. This results in respiratory,
gastrointestinal, and reproductive dysfunction.59 Progressive,
chronic bronchial pulmonary disease is the usual cause of
morbidity and mortality in most CF patients. CF patients are at
risk for chronic infections, inflammation, plugging and
obstructive lung disease, bronchiectasis, hemoptysis, fibrosis and
RLD, distal airway hyperinflation, and pneumothorax. These
changes result in mismatch and chronic hypoxemia, which
ultimately leads to pulmonary hypertension, cor pulmonale, and
progressive respiratory failure. Pancreatic insufficiency results in
malabsorption and impaired digestion. Many patients develop
diabetes mellitus, and end-stage disease may be marked by biliary
cirrhosis and portal hypertension.
B. Effect of pregnancy on cystic fibrosis. Patients with severe
disease may not be able to tolerate the physiologic changes
associated with pregnancy. These include decreased residual
volume, decreased expiratory reserve capacity, decreased FRC,
 increased work of breathing, and increased circulating blood
volume.60 Deterioration during pregnancy usually correlates with
the severity of the pulmonary disease before pregnancy. Pregnant
CF patients use more therapies and receive more intense
monitoring during their pregnancy compared to healthy
patients.59 Improvements in the medical care and survival of
patients with CF mean that more patients with CF are becoming
pregnant.61
C. Effect of cystic fibrosis on pregnancy. Patients with severe
pulmonary dysfunction have an increased incidence of perinatal
complications and PTD.60 This is likely related to arterial
hypoxemia and poor nutritional status. In addition to pulmonary
function impairment, other factors such as an increased rate of
diabetes mellitus, infection with Burkholderia cepacia, and
frequent infectious exacerbations have all been implicated in poor
maternal outcome.62 Recent studies emphasize that most patients
do well, particularly patients with milder CF, good nutritional
status, and less impairment of lung function. The degree of FEV1
decrease during pregnancy correlates with poorer pregnancy
outcomes.59
D. Medical management.15,63 Patients with severe prepregnancy
disease should be counseled about the potential for adverse
maternal and fetal outcomes. Pregnancy remains hazardous in
women with preexisting severe lung disease complicated by
pulmonary hypertension and cor pulmonale. Care of these
patients requires a coordinated team effort with pulmonologists,
maternal–fetal medicine specialists, anesthesiologists,
neonatologists, physiotherapists, and dietitians.59,61 Patients
should be offered genetic and nutritional counseling. Enzyme
replacement and caloric supplementation should be provided.
Bronchodilators, mucolytics, steroids, antibiotics, and continuous
oxygen therapy may be indicated. Aerosolized deoxyribonuclease
I reduces the viscosity of lung secretions. Serial ultrasonography
and prenatal testing are advised to ensure proper fetal growth and
 well-being. Emerging therapies, such as lung transplantation and
gene therapy, may be recommended. Other promising therapies
include drugs which act on various chloride channels, such as
those regulated by cystic fibrosis transmembrane regulator
(CFTR), to improve chloride conductance.
E. Anesthetic management15,61,64
1. The preanesthetic evaluation should include PFTs, cardiac
evaluation, and ABGs. Respiratory involvement is often the
primary issue facing the anesthesiologist. Continuous pulse
oximetry will guide the use of supplemental oxygen.
Parenteral opioids for analgesia are best avoided because they
may lead to suppression of the cough reflex and respiratory
depression.
2. Early epidural analgesia is advantageous for the patient in
labor because of the increased ventilatory demands of labor.
Neuraxial analgesia for labor results in decreased
hyperventilation, work of breathing, and oxygen requirements
and helps prevent respiratory decompensation. High motor
blockade and thoracic sensory levels should be avoided
because they may lead to respiratory distress. A dilute local
anesthetic solution to achieve a T10 sensory level is
recommended.
3. The recommended anesthetic for CD is an epidural, rather
than a spinal, in order to titrate the anesthetic level slowly so
as not to impair ventilation and the capacity to clear secretions
by coughing. A T6 upper sensory level is advised. There are
several case reports of successful use of a low-dose
intrathecal dose with epidural extension when a combined
spinal-epidural technique is used for CD.61,63 The advantage
of this technique is the predictable block from the spinal
combined with the ability to extend the block as needed.
General anesthesia may pose problems such as bronchospasm,
pneumothorax, endotracheal tube obstruction by secretions,
and mismatch. Nitrous oxide should be avoided because
 of the risk of pneumothorax from ruptured bullae. Gases
should be humidified and frequent suctioning should be
performed. A longer exhalation time is needed to prevent air
trapping during positive pressure ventilation. Anticholinergic
medications should be avoided because they promote drying
and can worsen inspissation of airway secretions.59 Chest
physiotherapy and good postoperative pain management by
epidural or parenteral means should be provided after
delivery.
XI. Lung transplantation
A. Transplantation and pregnancy. Compared to other solid organ
transplant patients, such as kidney, liver, and heart, very few
patients have become pregnant after lung transplantation. Patients
are usually counseled against pregnancy after transplant due to
the complexities of immunosuppression, which is required for
graft survival, and the effect of this on the fetus. It is
recommended that pregnancy be avoided for at least 1 to 2 years
posttransplant to minimize the risks to allograft function and fetal
well-being.65 Of the recipients who become pregnant, patients
may suffer from a decline in lung function, often from infection
or rejection. Many parturients with transplanted lungs appear to
do worse than after other solid organ transplants. The National
Transplantation Pregnancy Registry (NTPR) reported 48% of
patients experienced loss of graft function within 2 years of
delivery, which represents a 36% greater risk of graft rejection
compared to other solid organ recipients.60 One study of
transplanted parturients with CF noted that all patients suffered
progressive decline of lung function and died of chronic rejection
within 38 months of delivery.66 A recent study of 16 lung
transplant patients who had been pregnant found only 8
successful births out of 19 pregnancies. Six of these patients died
after pregnancy, one with rapidly progressive bronchiolitis
obliterans.67 Other complications reported in parturients after
transplantation include pregnancy-induced hypertension,
 preeclampsia, anemia, and gestational diabetes.65 Recent studies
have not found changes in PFTs during pregnancy in lung
transplant recipients. A decline in PFTs likely represents
pathology, such that infection and rejection should be
considered.67
B. Medications. The mother should be counseled about potential
drug toxicity to the fetus and infection risk. Toxoplasmosis, other
infections (congenital syphilis and viruses), rubella,
cytomegalovirus, and herpes simplex virus (TORCH) syndromes
could affect the fetus.68 Exposure to higher levels of
immunosuppression that are required immediately
postoperatively can be avoided by waiting for 1 to 2 years before
attempting pregnancy.67 The U.S. Food and Drug Administration
(FDA) classifies commonly used immunosuppressive drugs as
either class C (cannot rule out fetal risk) or D (evidence of fetal
risk exists). Maintenance of immunosuppression is recommended,
but may be changed or titrated during pregnancy. A calcineurin
inhibitor (CNI), prednisone, and azathioprine are generally
continued during pregnancy. Mycophenolate mofetil and
mammalian target of rapamycin inhibitors (mTORi) are typically
stopped.65 Immunosuppression must be regularly monitored and
dosing adjusted to avoid graft rejection.
C. Preterm delivery. An increased rate of preterm delivery (<37
weeks) and LBW occurs in parturients who have had a transplant.
The NTPR reported complications in >70% of neonates. There
were no deaths, and most neonates proceeded to develop well.60
D. Surveillance. These patients must be monitored for rejection,
preeclampsia, hypertension, renal dysfunction, and viremia,
particularly from cytomegalovirus and herpes simplex virus.
Surveillance for graft function by PFTs and, if necessary, by
bronchoscopy is important. Patients should be evaluated every 4
weeks during pregnancy until 32 weeks’ gestation, biweekly until
36 weeks, and weekly thereafter until delivery. Management is
best in specialized multidisciplinary transplant centers.65
 E. Anesthetic management.69 Strict attention to asepsis must be
followed, as well as adjusting steroids dosing and administering
prophylactic antibiotics. Neuraxial analgesia for labor is
recommended. For CD, both epidural and combined spinal-
epidural are reasonable options; a slowly titrated block might be
preferred if there is pulmonary impairment. Poor lymphatic
drainage may predispose the patient to pulmonary edema;
Therefore, careful fluid management is indicated. If a double-lung
transplant has been carried out with denervation of the carina, the
patient may be at increased risk for aspiration if GETA is used.
These patients may have poor or even absent cough reflex.65 If
GETA is provided, care must be taken not to disrupt the tracheal
suture lines during intubation.
XII. Restrictive lung disease. Patients with RLD have decreased FRC,
TLC, and VC. FVC, FEV1, and inspiratory capacity (IC) all decrease
as well. Patients may also have microatelectasis and decreased lung
and chest wall compliance.70 Larger transpulmonary gradients are
needed to achieve airflow. More respiratory effort is needed to expand
the lungs, but most patients compensate by breathing with smaller
lung volumes at a faster rate. This increases dead space ventilation.
As respiratory work increases, the potential for respiratory failure also
increases. It is sometimes difficult to distinguish between the
physiologic dyspnea of normal pregnancy and the pathologic dyspnea
that can occur with RLD. Pathologic dyspnea is usually progressive,
extreme, and can limit normal daily activities.71

CLINICAL PEARL Progesterone normally causes an increase in

minute ventilation during pregnancy. RLD may limit this, causing
hypercapnic respiratory failure. The effects of mild to moderate
hypercapnia in pregnancy are unclear, although respiratory alkalosis
does cause uterine vasoconstriction, which may adversely affect
fetal oxygenation.
A. Pregnancy. RLD is uncommon in pregnancy. If antenatal lung
volumes exceed 50% of predicted on PFTs, pregnancy is usually
well tolerated. In a small study of patients with an FVC <70%, all
parturients survived, but some required supplemental oxygen or
assisted ventilation.72
B. Spinal cord injury and kyphoscoliosis. Spinal cord injury and
kyphoscoliosis are commonly associated causes of restrictive
patterns of lung disease in pregnant women.
1. Spinal cord injury. Patients with spinal cord injury (SCI)
have respiratory muscle weakness, which causes decreased
lung volumes and flow rates, especially with spinal injury
above T10. Patients with acute lesions at C2–C4 usually
require chronic ventilatory support, whereas lower cervical
lesions create paralysis of the intercostal and abdominal
muscles, but the diaphragm remains intact. Patients with high
thoracic levels of injury may have a decreased cough reflex
and are therefore susceptible to recurrent infections.73 The
enlarging uterus decreases the excursion of the diaphragm.
This is especially important if the patient with SCI is entirely
dependent on the diaphragm for respiratory function. Some
patients may need ventilator assistance during late
pregnancy.70
2. Scoliosis. Patients with scoliosis and thoracic curves of >65
degrees have vertebral and rib cage deformities that lead to
the respiratory changes of RLD. With scoliosis and
pregnancy, greater decreases in FRC can be seen, which are
associated with mismatch and hypoxia. Dyspnea on
exertion is uncommon with curvatures <70 degrees but is
common if >100 degrees.70
C. Evaluation. Patients with RLD require evaluation of their
pulmonary function before conception to determine if pregnancy
will be well tolerated. PFTs and ABG measurements should be
obtained. Consultation with a pulmonologist is advised if there is
evidence of pulmonary compromise. Echocardiogram is useful to
 evaluate for pulmonary hypertension.72 Periodic reevaluation
should occur to ensure that the patient is tolerating the increased
physiologic demands of pregnancy. Antepartum anesthetic
consultation is useful.73
D. Management. Labor and delivery normally puts an added
demand on ventilation and may cause diaphragmatic fatigue. If
the patient experiences pain during labor, she may not be able to
tolerate the increased minute ventilation that results. These
patients may ultimately suffer respiratory failure. Some patients
with SCI do not experience painful labor.73 CD should be
reserved for obstetric indications only. Careful titration of
neuraxial analgesia and anesthesia is important to avoid
worsening respiratory function with accessory muscle paralysis
from local anesthetics.70
XIII. Acute respiratory distress syndrome and respiratory failure
A. Diagnostic criteria. ARDS is a form of respiratory failure which
is characterized by acute hypoxemia and increased alveolar
capillary permeability. The cause is diffuse pulmonary
inflammation. Diagnostic criteria include acute onset, a PaO2/FIO2
ratio of ≤200 (regardless of PEEP level), bilateral infiltrates on
CXR, a pulmonary artery occlusion pressure of ≤18 mm Hg, and
the absence of clinical evidence of left atrial hypertension.74
Different definitions have been used for obstetric-related ARDS,
but ARDS that occurs during pregnancy usually results from an
obstetric cause or is otherwise modified by an obstetric-related
factor.
B. Clinical presentation. Clinically, patients experience acute
hypoxemic respiratory failure and often suffer from dyspnea,
tachypnea, and tachycardia. Diffuse bibasilar crackles or
wheezing can be heard on auscultation. Pulmonary hypertension
and multiple organ dysfunction syndrome (MODS) may
develop.75
C. Causes of acute respiratory distress syndrome. There are
 numerous causes of ARDS in pregnancy (see Table 28.5). Some
involve direct injury to the lung, whereas others are mediated by
systemic inflammation. Some etiologies are unaffected by
pregnancy, some are modified by pregnancy, and some are unique
to pregnancy.75

D. Treatment. The best treatment for the fetus is maintaining a good

intrauterine environment and supporting the mother’s respiratory
function.
1. Adequate fetal oxygenation requires a maternal PaO2 of ≥70
mm Hg. The maternal PaCO2 should be <45 mm Hg. The
overall goal, as in nonparturients, is to manage blood gas
variables while avoiding ventilator-associated barotrauma.
Criteria for endotracheal intubation include increased work of
breathing, deterioration of mental status, hemodynamic
instability, and inability to protect the airway or manage
secretions.
2. Lower tidal volumes (6 mL per kg) and plateau pressures
(<30 cm H2O) are recommended for mechanical ventilation to
avoid barotrauma. Studies of nonpregnant patients
demonstrate improved survival at lower tidal volumes
compared to 12 mL per kg.74 This permissive hypercapnia
strategy may not be well tolerated during pregnancy:
however, there are reports of maternal PaCO2 maintained
below 50 mm Hg without adverse fetal effects.76 FIO2 should
 be maintained <60% when possible to avoid oxygen toxicity.
The addition of PEEP can improve oxygenation. This has not
been studied specifically in pregnant patients with ARDS but
is thought to improve survival in nonpregnant patients as
oxygenation improves. A noninvasive ventilatory mode may
be an alternative treatment if the patient has mild ARDS and
is hemodynamically stable.74 A pulmonary artery catheter
may be helpful in optimizing fluid status, which can be
challenging given the increased blood volume of pregnancy
and the effect of PEEP on cardiac output.77

CLINICAL PEARL A normal PaCO2 value in nonpregnant

patients is a sign of impending respiratory distress in a parturient.
PaCO2 decreases to approximately 32 mm Hg during pregnancy.

E. Alternative treatments. There are several alternative approaches

for the treatment of women with severe illness.
1. Different ventilator modalities that have been useful for
improving oxygenation include the use of airway pressure
release ventilation and high-frequency oscillatory ventilation.
A lung recruitment maneuver using a brief (30 to 60 seconds)
but sustained inflation at relatively high pressures (40 to 50
cm H2O) may be useful. Placing the patient in the prone
position improves oxygenation. However, prone ventilation is
not achieved easily and is associated with a unique set of
practical problems.78
2. Inhaled nitric oxide, prostacyclin, and surfactant have
been used to improve oxygenation with limited results. These
interventions have not been shown to decrease death rates or
complications from ARDS.77 Corticosteroids are
controversial, especially in terms of dosing and timing. Some
studies show improvements in oxygenation and other
outcomes, but they may have no effect in ARDS caused by
 influenza A (H1N1) pneumonia.74
3. Improvements in ECMO during the last decade have
allowed its use as a treatment for ARDS. In 2009, the
influenza A (H1N1) pandemic caused an increase in the
number of parturients with ARDS. Several recent reports
describe the use of ECMO in the treatment of severe ARDS.
The major complications are severe bleeding and clotting.79
F. Effect of acute respiratory distress syndrome on pregnancy.
Impaired maternal oxygenation can cause fetal distress. Uterine
irritability and PTL may be precipitated by hypoxia. Magnesium
sulfate and β-agonists should be used cautiously due to the risk of
increased pulmonary capillary permeability. Nonsteroidal anti-
inflammatory drugs are preferred alternatives for the treatment of
PTL.77 Sedatives for maternal comfort during intubation and
mechanical ventilation may lead to decreased fetal activity.76
G. Obstetric management. Delivery decisions will be influenced
by the gestational age, fetal status, and maternal status. Generally,
the premature fetus is better supported in utero until 32 to 34
weeks of gestation. However, if the mother is unstable or the
precipitating cause is related to the pregnancy, immediate delivery
may be indicated. Before viability, termination of pregnancy is an
option. Delivery may slightly improve the maternal status in
ventilated women with ARDS, but delivery should be for
obstetric indications and not to improve pulmonary ventilation.
Neither induction of labor nor CD is without risk in patients with
ARDS; thus, the indications for delivery are the same as those
used in healthy patients.

SUMMARY
Normal physiologic changes that occur during pregnancy may worsen many
respiratory diseases. In addition, these changes can make the diagnosis of a
respiratory disease challenging. Many pulmonary diseases seen during
pregnancy have adverse effects on maternal and neonatal outcomes, and
pregnancy sometimes alters the course of a given disease. Some of the
medications used to treat parturients with lung disease have not been fully
studied in terms of their negative impact. Early neuraxial analgesia during labor
is recommended for most parturients with respiratory disease. Larger studies are
needed to elucidate the pathophysiology and outcomes for most of the diseases
discussed in this chapter.

REFERENCES
1. Murphy VE, Clifton VL, Gibson PG. Asthma exacerbations during pregnancy: incidence and
association with adverse pregnancy outcomes. Thorax. 2006;61:169–176.
2. Maselli DJ, Adams SG, Peters JI, et al. Management of asthma during pregnancy. Ther Adv Respir
Dis. 2013;7:87–100.
3. Rocklin RE. Asthma, asthma medications and their effects on maternal/fetal outcomes during
pregnancy. Reprod Toxicol. 2011;32:189–197.
4. Murphy VE, Schatz M. Asthma in pregnancy: a hit for two. Eur Respir Rev. 2014;23:64–68.
5. Murphy VE, Powell H, Wark PA, et al. A prospective study of respiratory viral infection in pregnant
women with and without asthma. Chest. 2013;144:420–427.
6. Wang G, Murphy VE, Namazy J, et al. The risk of maternal and placental complications in pregnant
women with asthma: a systematic review and meta-analysis. J Matern Fetal Neonatal Med.
2014;27:934–942.
7. Murphy VE, Namazy JA, Powell H, et al. A meta-analysis of adverse perinatal outcomes in women
with asthma. BJOG. 2011;118:1314–1323.
8. Enriquez R, Griffin MR, Carroll KN, et al. Effect of maternal asthma and asthma control on pregnancy
and perinatal outcomes. J Allergy Clin Immunol. 2007;120:625–630.
9. Tegethoff M, Olsen J, Schaffner E, et al. Asthma during pregnancy and clinical outcomes in offspring:
a national cohort study. Pediatrics. 2013;132:483–491.
10. Schatz M, Dombrowski MP. Clinical practice. Asthma in pregnancy. N Engl J Med. 2009;360:1862–
1869.
11. National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): Guidelines for
the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol.
2007;120(suppl 5):S94–S138.
12. Tilley SL, Hartney JM, Erikson CJ, et al. Receptors and pathways mediating the effects of
prostaglandin E2 on airway tone. Am J Physiol Lung Cell Mol Physiol. 2003;284:L599–L606.
13. Woods BD, Sladen RN. Perioperative considerations for the patient with asthma and bronchospasm.
Br J Anaesth. 2009;103(suppl 1):i57–i65.
14. Groeben H. Epidural anesthesia and pulmonary function. J Anesth. 2006;20:290–299.
15. Kuczkowski KM. Labor analgesia for the parturient with respiratory disease: what does an obstetrician
need to know? Arch Gynecol Obstet. 2005;272:160–166.
16. Scavone BM, Ratliff J, Wong CA. Physiologic effects of neuraxial anesthesia. In: Wong C, ed. Spinal
and Epidural Anesthesia. New York, NY: McGraw-Hill; 2007:111–126.
17. Berg CJ, Callaghan WM, Syverson C, et al. Pregnancy-related mortality in the United States, 1998 to
2005. Obstet Gynecol. 2010;116:1302–1309.
18. Heit JA, Kobbervig CE, James AH, et al. Trends in the incidence of venous thromboembolism during
pregnancy or postpartum: a 30-year population-based study. Ann Intern Med. 2005;143:697–706.
19. Greer IA. Thrombosis in pregnancy: updates in diagnosis and management. Hematology Am Soc
Hematol Educ Program. 2012:203–207.
20. Donnelly JC, D’Alton ME. Pulmonary embolus in pregnancy. Semin Perinatol. 2013;37:225–233.
21. Cutts BA, Dasgupta D, Hunt BJ. New directions in the diagnosis and treatment of pulmonary
embolism in pregnancy. Am J Obstet Gynecol. 2013;208:102–108.
22. Saeed G, Möller M, Neuzner J, et al. Emergent surgical pulmonary embolectomy in a pregnant
woman: case report and literature review. Tex Heart Inst J. 2014;41:188–194.
23. Chau DF, Fragneto RY. Maternal embolism. Int Anesthesiol Clin. 2014;52:61–84.
24. Brennan MC, Moore LE. Pulmonary embolism and amniotic fluid embolism in pregnancy. Obstet
Gynecol Clin North Am. 2013;40:27–35.
25. Bourjeily G, Paidas M, Khalil H, et al. Pulmonary embolism in pregnancy. Lancet. 2010;375:500–512.
26. Gray G, Nelson-Piercy C. Thromboembolic disorders in obstetrics. Best Pract Res Clin Obstet
Gynaecol. 2012;26:53–64.
27. Costantine MM. Physiologic and pharmacokinetic changes in pregnancy. Front Pharmacol.
2014;5:65.
28. Tawfik MM, Taman ME, Motawea AA, et al. Thrombolysis for the management of massive
pulmonary embolism in pregnancy. Int J Obstet Anesth. 2013;22:149–152.
29. Mos IC, Klok FA, Kroft LJ, et al. Imaging tests in the diagnosis of pulmonary embolism. Semin Respir
Crit Care Med. 2012;33:138–143.
30. Horlocker TT, Wedel DJ, Rowlingson JC, et al. Regional anesthesia in the patient receiving
antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine
Evidence-Based Guidelines (Third Edition). Reg Anesth Pain Med. 2010;35:64–101.
31. Clark SL. Amniotic fluid embolism. Obstet Gynecol. 2014;123(2 pt 1):337–348.
32. Fong A, Chau CT, Pan D, et al. Amniotic fluid embolism: antepartum, intrapartum and demographic
factors. J Matern Fetal Neonatal Med. 2015;28:793–798.
33. Rath WH, Hoferr S, Sinicina I. Amniotic fluid embolism: an interdisciplinary challenge:
epidemiology, diagnosis and treatment. Dtsch Arztebl Int. 2014;111:126–132.
34. Kissko JM III, Gaiser R. Amniotic fluid embolism. Anesthesiology Clin. 2013;31:609–621.
35. McDonnell NJ, Percival V, Paech MJ. Amniotic fluid embolism: a leading cause of maternal death yet
still a medical conundrum. Int J Obstet Anesth. 2013;22:329–336.
36. Kim CS, Liu J, Kwon JY, et al. Venous air embolism during surgery, especially cesarean delivery. J
Korean Med Sci. 2008;23:753–761.
37. Philip J, Sharma SK. Respiratory disorders in pregnancy. In: Gambling D, Douglas MJ, McKay RS,
eds. Obstetric Anesthesia and Uncommon Disorders. 2nd ed. Philadelphia, PA: W.B. Saunders; 2008.
38. Mirski MA, Lele AV, Fitzsimmons L, et al. Diagnosis and treatment of vascular air embolism.
Anesthesiology. 2007;106:164–177.
39. Hadid V, Patenaude V, Oddy L, et al. Sarcoidosis and pregnancy: obstetric and neonatal outcomes in a
population-based cohort of 7 million births. J Perinat Med. 2015;43:201–207.
40. Einarson A, Riordan S. Smoking in pregnancy and lactation: a review of risks and cessation strategies.
Eur J Clin Pharmacol. 2009;65:325–330.
41. Hackshaw A, Rodeck C, Boniface S. Maternal smoking in pregnancy and birth defects: a systematic
review based on 173 687 malformed cases and 11.7 million controls. Hum Reprod Update.
2011;17:589–604.
42. Talbot L, Palmer J. Effects of smoking on health and anesthesia. Anaesth Intensive Care Med.
2013;14:107–109.
43. Morong S, Hermsen B, de Vries N. Sleep-disordered breathing in pregnancy: a review of the
physiology and potential role for positional therapy. Sleep Breath. 2014;18:31–37.
44. Ankichetty SP, Angle P, Joselyn AS, et al. Anesthetic considerations of parturients with obesity and
obstructive sleep apnea. J Anaesthesiol Clin Pharmacol. 2012;28:436–443.
45. Pamidi S, Pinto LM, Marc I, et al. Maternal sleep-disordered breathing and adverse pregnancy
outcomes: a systematic review and metaanalysis. Am J Obstet Gynecol. 2014;210:52.e1–52.e14.
46. Fung AM, Wilson DL, Barnes M, et al. Obstructive sleep apnea and pregnancy: the effect on perinatal
outcomes. J Perinatol. 2012;32:399–406.
47. Gerke AK. Morbidity and mortality in sarcoidosis. Curr Opin Pulm Med. 2014;20:472–478.
48. Stone S, Nelson-Piercy C. Respiratory disease in pregnancy. Obstet Gynaecol Reprod Med.
2010;20:14–21.
49. Freymond N, Cottin V, Cordier JF. Infiltrative lung diseases in pregnancy. Clin Chest Med.
2011;32:133–146.
50. Vahid B, Mushlin N, Weibel S. Sarcoidosis in pregnancy and postpartum period. Curr Resp Med Rev.
2007;3:79–83.
51. Paranjothy S, Griffiths JD, Broughton HK, et al. Interventions at caesarean section for reducing the
risk of aspiration pneumonitis. Cochrane Database Syst Rev. 2014;(2):CD004943.
52. Ng A, Smith G. Gastroesophageal reflux and aspiration of gastric contents in anesthetic practice.
Anesth Analg. 2001;93:494–513.
53. Kluger MT, Short TG. Aspiration during anaesthesia: a review of 133 cases from the Australian
Anaesthetic Incident Monitoring Study (AIMS). Anaesthesia. 1999;54:19–26.
54. Wong CA, McCarthy RJ, Fitzgerald PC, et al. Gastric emptying of water in obese pregnant women at
term. Anesth Analg. 2007;105:751–755.
55. Landay MJ, Christensen EE, Bynum LJ. Pulmonary manifestations of acute aspiration of gastric
contents. AJR Am J Roentgenol. 1978;131:587–592.
56. Kjaer K, Comerford M, Kondilis L, et al. Oral sodium citrate increases nausea amongst elective
cesarean delivery patients. Can J Anaesth. 2006;53:776–780.
57. de Souza DG, Doar LH, Mehta SH, et al. Aspiration prophylaxis and rapid sequence induction for
elective cesarean delivery: time to reassess old dogma? Anesth Analg. 2010;110:1503–1505.
58. Han TH, Brimacombe J, Lee EJ. The laryngeal mask airway is effective (and probably safe) in
selected healthy parturients for elective cesarean section: a prospective study of 1067 cases. Can J
Anaesth. 2001;48:1117–1121.
59. Whitty JE. Cystic fibrosis in pregnancy. Clin Obstet Gynecol. 2010;53:369–376.
60. Budev MM, Arroliga AC, Emery S. Exacerbation of underlying pulmonary disease in pregnancy. Crit
Care Med. 2005;33(suppl 10):S313–S318.
61. Deighan M, Ash S, McMorrow R. Anaesthesia for parturients with severe cystic fibrosis: a case series.
Int J Obstet Anesth. 2014;23:75–79.
62. Cohen R, Talwar A, Efferen LS. Exacerbation of underlying pulmonary disease in pregnancy. Crit
Care Clin. 2004;20:713–730.
63. Muammar M, Marshall P, Wyatt H, et al. Caesarean section in a patient with cystic fibrosis. Int J
Obstet Anesth. 2005;14:70–73.
64. Huffmyer JL, Littlewood KE, Nemergut EC. Perioperative management of the adult with cystic
fibrosis. Anesth Analg. 2009;109:1949–1961.
65. Vos R, Ruttens D, Verleden SE, et al. Pregnancy after heart and lung transplantation. Best Pract Res
Clin Obstet Gynaecol. 2014;28:1146–1162.
66. Gyi KM, Hodson ME, Yacoub MY. Pregnancy in cystic fibrosis lung transplant recipients: case series
and review. J Cyst Fibros. 2006;5:171–175.
67. Thakrar MV, Morley K, Lordan JL, et al. Pregnancy after lung and heart-lung transplantation. J Heart
Lung Transplant. 2014;33:593–598.
68. Cardonick E, Moritz M, Armenti V. Pregnancy in patients with organ transplantation: a review. Obstet
Gynecol Surv. 2004;59:214–222.
69. Halpern SH, Srebrnjak M. Anesthesia for the pregnant patient with immunologic disorders. In: Suresh
M, Roanne L, Preston MD, et al, eds. Shnider and Levinson’s Anesthesia for Obstetrics. 5th ed.
Philadelphia, PA: Lippincott Williams & Wilkins; 2013:626–646.
70. Baker ER, Cardenas DD. Pregnancy in spinal cord injured women. Arch Phys Med Rehabil.
1996;77:501–507.
71. Gupta S, Singariya G. Kyphoscoliosis and pregnancy—a case report. Indian J Anaesth. 2004;48:215–
220.
72. Lapinsky SE, Tram C, Mehta S, et al. Restrictive lung disease in pregnancy. Chest. 2014;145:394–398.
73. Baydur A, Adkins RH, Milic-Emili J. Lung mechanics in individuals with spinal cord injury: effects of
injury level and posture. J Appl Physiol. 2001;90:405–411.
74. Duarte AG. ARDS in pregnancy. Clin Obstet Gynecol. 2014;57:862–870.
75. Cole DE, Taylor TL, McCullough DM, et al. Acute respiratory distress syndrome in pregnancy. Crit
Care Med. 2005;33(suppl 10):S269–S278.
76. Bandi VD, Munnur U, Matthay MA. Acute lung injury and acute respiratory distress syndrome in
pregnancy. Crit Care Clin. 2004;20:577–607.
77. Graves CR. Acute pulmonary complications during pregnancy. Clin Obstet Gynecol. 2002;45:369–
376.
78. Kenn S, Weber-Carstens S, Weizsaecker K, et al. Prone position for ARDS following blunt chest
trauma in late pregnancy. Int J Obstet Anesth. 2009;18:268–271.
79. Nair P, Davies AR, Beca J, et al. Extracorporeal membrane oxygenation for severe ARDS in pregnant
and postpartum women during the 2009 H1N1 pandemic. Intensive Care Med. 2011;37:648–654.
 Obesity and Pregnancy
Brenda A. Bucklin and David R. Gambling

I. High-risk patient
A. Anesthetic challenges
B. Maternal comorbidities
C. Obstetric risk and outcomes
II. Obesity: definition and demographics
A. Consensus for definition of obesity
B. Body mass index
C. Increasing incidence of obesity
III. Physiologic changes of obesity and pregnancy
A. Pulmonary
B. Cardiovascular
C. Endocrine
D. Hypercoagulability
E. Gastrointestinal
IV. Anesthesia for the obese pregnant woman
A. Obesity and maternal mortality
B. Patient evaluation
C. General considerations
V. Implications for patients undergoing labor for vaginal delivery
A. Labor analgesia
B. Epidural analgesia/anesthesia in obese patients
C. Placement of neuraxial blocks
 D. Placement of epidural catheter
E. Cephalad spread of neuraxial block
VI. Implications for patients undergoing cesarean delivery
A. General considerations
B. Cesarean delivery: maternal morbidity and mortality
C. Anesthetic plan
D. Neuraxial anesthesia
E. General anesthesia
F. Considerations for the operating room
G. Surgical considerations
VII. Postoperative care
A. General considerations
B. Pulmonary considerations
C. Postoperative monitoring
D. Thromboprophylaxis
VIII. Newborn
A. Preterm delivery
B. Fetal anomalies
C. Fetal macrosomia
D. Stillbirth and neonatal deaths
E. Neonatal care
IX. Pregnancy after bariatric surgery
X. Cost
Summary

KEYPOINTS
1. Obesity increases risk of adverse outcomes, including morbidity and
mortality.
2. Anesthesiology consultation is recommended for obese women
 antepartum or “early in labor” to allow adequate time for development of
an anesthetic plan.
3. Neuraxial analgesia may precede the onset of labor or a patient’s request
for labor analgesia.
4. Preparation should include blood pressure monitoring and placement of
adequate intravenous access early in labor.
5. Blood products should be readily available.
6. Obese parturients are at risk for cesarean delivery (CD), especially
emergent CD.
7. Continuous catheter techniques are a better choice than single-injection
spinal anesthesia for CD.
8. Tracheal intubation, emergence, extubation, and recovery are critical
periods of anesthetic care in the obese parturient.
9. Multimodal analgesic techniques (e.g., nonsteroidal anti-inflammatory
agents) should be used to decrease total opioid requirements.
10. Communication with the obstetric team is essential for good care.

I. High-risk patient. The obese parturient is a high-risk patient with

increased rates of morbidity and mortality compared to nonobese
patients.
A. Anesthetic challenges. There are technical issues created by the
larger physical size, plus physiologic changes created by
pregnancy and concomitant medical conditions, which make the
care of an obese parturient a major challenge for all members of
the health care team (see Fig. 29.1).
B. Maternal comorbidities. Obesity is implicated as a direct cause
in the development of disease in many organ systems (see Table
29.1). As maternal body mass index (BMI) increases, the
probability of concomitant diseases also increases.1 Besides an
increased likelihood of chronic hypertension and type 2 diabetes
mellitus (DM), obese parturients are more likely to have
preeclampsia, fetal macrosomia, and a twofold increase in
cesarean delivery (CD).2–5 There has been increasing interest in
the relationship between “near-miss morbidity and mortality” and
comorbid conditions. Although obesity was not independently
associated with near-miss morbidity and mortality, a recent study
using the 2003 to 2006 Nationwide Inpatient Sample found that
hypertensive disorders of pregnancy, previous CD, DM,
preexisting hypertension, and multiple gestations were the most
common comorbidities associated with near-miss morbidity and
mortality.6
C. Obstetric risk and outcomes. There is an increased incidence of
various obstetric complications associated with obesity. They are
listed in Table 29.2. Besides an increased risk of CD,7,8 there are
more labor inductions for postdates pregnancy and there is an
increased incidence of failed induction in the obese parturient.8
The first and second stages of labor are prolonged, and oxytocin
augmentation is also more frequent. Excess adipose tissue may
make fetal heart rate (FHR) and uterine contractions difficult to
monitor, so fetal scalp electrodes and internal pressure monitors
are often necessary during labor. There is a positive correlation
between the use of oxytocin for labor augmentation and
increasing BMI.3,9 Dysfunctional labor is more common in obese
women compared to nonobese women,4 although it is not more
painful in obese women.10 Prolongation of the second stage of
labor is more common and correlates with increasing BMI. The
success of trial of labor after CD is also less likely.11 Fetal
macrosomia has been implicated in higher CD rates in obese
women. There is an increase in frequency of meconium-stained
amniotic fluid and intrapartum FHR abnormalities requiring CD,8
plus a higher incidence of instrumental deliveries and third-
degree or fourth-degree perineal lacerations.8 Several studies
 have found an increased risk of postpartum hemorrhage among
obese parturients.4,12 Sebire et al.4 also found a linear relationship
of postpartum hemorrhage with increasing BMI. Keep in mind
that hemorrhage remains a leading cause of maternal
mortality.13

CLINICAL PEARL As maternal BMI increases, the probability

of concomitant diseases also increases. Hypertensive disorders of
pregnancy, previous CD, DM, preexisting hypertension, and
multiple gestations are common comorbidities and can be
associated with near-miss morbidity and mortality.

II. Obesity: definition and demographics

A. Consensus for definition of obesity. In the past, there was no
consensus for the definition of obesity or morbid obesity. Some
used absolute weights (e.g., 100 kg and above), whereas others
used a percentage above ideal body weight or skin caliper fat
thickness measurements to define obesity. Insurance companies,
most notably the Metropolitan Life Insurance Company,
developed their own height/weight tables based on actuarial data.
As a result of these inconsistencies, it is difficult to compare older
studies with more recent studies that use the BMI.
B. Body mass index. BMI is a function of patient’s weight in
 kilograms divided by height in meters squared (kg per m2). The
World Health Organization (WHO) and the National Institutes of
Health (NIH) have both adopted the BMI to classify degree of
obesity. Although BMI can misclassify a very small subset of the
population, it has standardized the classification of weight ranges
from underweight to morbid obesity (see Table 29.3). The
Institute of Medicine14 has published a range for weight gain
during pregnancy that limits the gain to 11 to 25 lb when the BMI
is greater than 30 kg per m2 and 15 to 25 lb when the BMI is
between 25 and 29.9 kg per m2. The American College of
Obstetricians and Gynecologists recommends that height and
weight be recorded at the first prenatal visit and weight gain
monitored periodically.5

C. Increasing incidence of obesity. The prevalence of obesity

correlates with socioeconomic status. In developed countries,
poverty is associated with obesity; in developing countries,
affluence is associated with obesity.1 According to the WHO
criteria, the incidence of obese women in the United States has
reached epidemic proportions—more than doubling in a 10-year
period from 1994 to 2004. Recent estimates suggest that more
than one-third of all US women are obese, more than 50% of
pregnant women are overweight or obese, and nearly 10% of
women of reproductive age are extremely obese.15 Similar rates
of increase can be found in the United Kingdom and other
countries.
 CLINICAL PEARL Recent estimates suggest that more than
one-third of all US women are obese, more than 50% of pregnant
women are overweight or obese, and nearly 10% of women of
reproductive age are extremely obese.

III. Physiologic changes of obesity and pregnancy

A. Pulmonary
1. The pulmonary system adapts to meet the increased oxygen
and ventilation demands of pregnancy. Typically, minute
ventilation increases by 50% at term and PaCO2 is decreased
to approximately 34 mm Hg. Although functional residual
capacity (FRC), expiratory reserve volume (ERV), and
residual volume (RV) are all decreased due to the cephalad
displacement of the diaphragm by the gravid uterus, total lung
capacity is not changed because of an increase in chest
circumference. The smooth muscle relaxation effect of
progesterone in pregnancy may decrease airway resistance
and improve respiratory function.16 In the obese parturient,
oxygen consumption is increased in direct proportion to the
additional adipose tissue. The physiologic demands and added
weight of the excess adipose tissue frequently result in
respiratory compromise. Mechanically, the posture of the
obese parturient involves an accentuated thoracolumbar
lordosis (kyphosis) and a modified thoracic curvature. Rib
cage and sternal mechanics are diminished resulting in
increased work of breathing and possibly a deterioration of
ventilatory parameters. During quiet respiration, the
diaphragm is the principal muscle of inspiration and
expiration. Forced expiration is dependent on abdominal wall
muscles and intercostal muscles.
2. In obese parturients, chest wall adipose tissue exerts pressure
on the thorax and intraabdominal adipose tissue enhances the
cephalad shift of the diaphragm. This results in a further
 reduction in FRC, greater atelectasis formation, and an
increase in closing volume that often exceeds FRC. Supine,
lithotomy, and/or Trendelenburg position exacerbate this
respiratory impairment. A greater closing volume (the lung
volume during expiration at which airways begins to close)
produces abnormal distribution of ventilation. This, in turn,
results in a ventilation–perfusion mismatch (intrapulmonary
shunt) and impaired arterial oxygenation. In order to elucidate
the effects of airway closure, room air oxygen saturation can
be measured in the sitting and supine position to identify
those individuals who may require additional respiratory
assistance (e.g., supplemental oxygen, chest physiotherapy)
during labor or CD.

CLINICAL PEARL To determine if a patient is experiencing the

effects of airway closure and impaired arterial oxygenation, room
air oxygen saturation should be measured in the sitting and supine
position to identify those individuals who may require additional
respiratory assistance (e.g., supplemental oxygen, chest
physiotherapy) during labor or CD.

3. Spinal anesthesia in parturients is associated with a BMI-

dependent decrease in lung function. The baseline spirometric
measurements in nonobese and obese parturients at term are
similar. Spinal anesthesia causes minimal changes in
spirometric volumes in normal-weight, nonpregnant patients.
In the term parturient, however, spinal anesthesia to T5 level
results in significant decrease in vital capacity, forced vital
capacity, forced expiratory volumes in 1 second, and peak
expiratory flow rate (PEFR) and midexpiratory flow rates. In
the obese parturient receiving spinal anesthesia, a decrease in
vital capacity is significantly greater when compared to
parturients with normal BMI and correlates well with
 increasing BMI. This effect is seen for more than 3 hours after
initiation of spinal anesthesia for CD.17
4. Obstructive sleep apnea (OSA) is characterized by
intermittent pharyngeal obstruction resulting in episodic
apnea during sleep. Diagnosis can be made using the STOP-
BANG tool18 and for those at risk, the definitive test is a sleep
study. Because most parturients are undiagnosed during
pregnancy, these patients can present the greatest challenges
to anesthesia providers.19 Patients at risk should be screened
and treated if diagnosed. Signs and symptoms of sleep apnea
in the pregnant patient are listed in Table 29.4.

The main causes of obstruction are oropharyngeal soft

tissue enlargement (as a result of increased fat) and
pregnancy-related changes. Hormone-induced increases in
respiratory center sensitivity during early pregnancy may
decrease OSA symptoms.9,16 Later in pregnancy, women tend
to sleep in the lateral position and therefore the likelihood of
airway obstruction is mitigated. Recent data from the
Nationwide Inpatient Sample suggest that the rate of OSA has
increased from 0.3 per 10,000 to 7.3 per 10,000 from 1998 to
2009.20 In the cohort, sleep apnea increased the odds for the
following outcomes: (1) cardiomyopathy (odds ratio [OR],
9.0; 95% confidence interval [CI], 7.5 to 10.9), (2) eclampsia
(OR, 5.4; 95% CI, 3.3 to 8.9), (3) pulmonary embolus (OR,
4.5; 95% CI, 2.3 to 8.9), and (4) preeclampsia (OR, 2.5; 95%
CI, 2.2 to 2.9). In addition, there was a fivefold increased
odds of in-hospital mortality. These patients will require
 postpartum monitoring of respiratory function while in
hospital, especially if they receive any opioid analgesics.
They should sleep in a 45-to 60-degree head-up position and
may require supplemental oxygen therapy. A consult with the
respiratory service is recommended in order to offer
continuous positive airway pressure (CPAP) therapy and
follow their progress throughout the hospital stay.

CLINICAL PEARL Patients with OSA will require postpartum

monitoring of respiratory function while in hospital, especially if
they receive any opioid analgesics. CPAP therapy should be
considered to minimize airway collapse and desaturation
postoperatively.

5. Obesity hypoventilation syndrome (OHS), also known as

Pickwickian syndrome, is a combination of severe obesity
and OSA. Witnessed snoring, episodes of apnea, irregular
breathing patterns during sleep, restless sleep, and daytime
fatigue are often presenting symptoms. Identifying the patient
with OSA who has OHS is difficult in the nonpregnant
patient, but the physiologic changes of pregnancy will alter
such measures as low oxygen saturation, hypercapnia (while
breathing room air), and elevated serum bicarbonate that have
been suggested as screening tools.21 Chronic hypoxemia and
hypercapnia may lead to polycythemia, pulmonary
hypertension, and right ventricular dilation and failure (cor
pulmonale).22 Pickwickian syndrome in pregnancy may be
mitigated by increased progesterone during pregnancy.16
6. The prevalence of asthma is increased in the obese
population. Weight loss may improve and/or eliminate
asthma symptoms. Because there is a strong correlation
between gastroesophageal reflux disease (GERD) and BMI in
women,23 some have speculated that acid reflux may be the
 cause of asthma in obese women.
7. Obesity and pregnancy can both cause restrictive lung disease
by virtue of reducing chest wall compliance. In restrictive
lung disease, pulmonary function tests reveal hypoxemia,
decreased ERV, decreased maximum voluntary ventilation,
and decreased FRC.9 To maximize efficiency of breathing, the
obese parturient will alter her breathing pattern by decreasing
tidal volume and increasing respiratory rate. The effects of
progesterone may alleviate some of the restrictive
symptoms.16 Unfortunately, the symptoms are exacerbated in
the supine position necessary for surgery. Because the
parturient is usually awake for CD, she needs to be managed
in a ramped position and reassured that her respiratory
function is adequate. Supplemental oxygen is usually
necessary. If the patient receives general anesthesia, greater
positive pressure with larger tidal volumes may be required to
ventilate the obese parturient to mitigate the reduction of FRC
as it falls below closing capacity (CC). However, the
ventilation parameters must be balanced for optimal gas
exchange and prevention of barotrauma.
B. Cardiovascular
1. Hypertension is common in the obese population and is
positively correlated with BMI.22 Even when patients with
chronic hypertension are excluded, hypertension is more
common in the obese population.11 In a study of more than 56
million deliveries between 1995 and 2008, the prevalence of
primary and secondary hypertension increased from 0.9% in
1995–1996 to 1.52% in 2007–2008. 24 The following adverse
maternal outcomes were noted in 731,694 patients with
chronic hypertension: (1) acute renal failure (21%), (2)
pulmonary edema (14%), (3) preeclampsia (11%), and (4) in-
hospital mortality (10%). Because obesity is an independent
risk factor for developing preeclampsia,3,4,25 the incidence
of preeclampsia doubles with each 5 to 7 kg per m2 increase
 in prepregnancy BMI.25 Both hypertension and preeclampsia
in obese parturients independently increase risk of CD.
Hypertensive disease remains a leading cause of maternal
mortality.13
2. Blood pressure (BP) monitoring may be particularly
problematic in obese patients. The BP cuff must be of
appropriate size to obtain an accurate BP. If the BP cuff is too
small, the BP reading will be overestimated. The forearm of
the patient can be used if the upper arm is too large or of a
noncylindrical shape. An arterial line may be needed to
accurately determine BP. It also permits arterial blood gas
sampling in patients with suspected respiratory dysfunction.
3. In obese, term parturients without hypertension, left
ventricular wall thickness can be significantly greater when
compared to term parturients with normal BMI. Left
ventricular size and function, however, can be normal. The
change in left ventricular geometry decreases the radius-to-
wall thickness ratio and may be an adaptation to preserve
normal systolic function despite increased cardiac output.
Furthermore, the heart rate must increase to elevate cardiac
output, thereby decreasing the diastolic interval and time for
myocardial perfusion. Impaired myocardial diastolic
relaxation leads to diastolic dysfunction. The combination of
diastolic dysfunction and rapid heart rate may lead to
pulmonary edema.
4. Morbid obesity is associated with poor cardiac function
during pregnancy.9,22 Obesity is an independent risk factor for
the development of heart failure and the risk increases with
increasing BMI.26 Although obesity is associated with
hypertension, coronary artery disease, left ventricular
hypertrophy, and DM, all of which are important causes
of heart failure, multivariate analysis concludes that BMI
is a significant independent predictor of heart failure.
Whether obesity itself or some intermediary mechanism (e.g.,
 fat deposition in the myocardium or conduction pathways) is
responsible for the heart failure is unknown.
5. Obesity cardiomyopathy is a clinical syndrome generally
found in patients with BMI ≥40 for 10 years or greater.27 In
normal-weight parturients, circulating blood volume increases
by approximately 45% above prepregnancy levels as a result
of an increase in plasma volume and red blood cell mass. To
meet the metabolic demands of the increased tissue mass in
obese patients (every 100 g of fat increases cardiac output by
30 to 50 mL per minute), the blood volume, stroke volume,
and cardiac output in obese parturients are greater than that of
a patient with normal BMI. Interestingly, the magnitude of
blood volume increase in obese parturients is less than that
predicted by their weight. However, the increase in blood
volume may lead to left ventricular dilation, increased left
ventricular wall stress, compensatory left ventricular
hypertrophy, and diastolic dysfunction. Over time, the heart
may dilate and fail.9 Echocardiography is a useful test of
cardiac function in these patients.
6. A conglomerate of diseases known as metabolic syndrome, a
major risk factor for the developing cardiovascular disease, is
characterized by insulin resistance, dyslipidemia, elevated
C-reactive protein, increased propensity for thrombosis,
and activation of the sympathetic nervous system.
Metabolic syndrome plus hypertension may render the obese
patient at high risk for development of coronary artery
disease. A routine electrocardiogram is prudent, and one
should have a high index of suspicion for ischemic heart
disease.
7. Supine hypotension syndrome (SHS) is a well-known
phenomenon in parturients after mid second trimester. The
weight of the obese abdominal wall further enhances uterine
compression on the abdominal vasculature. Cardiovascular
collapse and death have been reported in obese patients in
 the supine position.28 Left uterine displacement is
therefore essential to prevent SHS.

CLINICAL PEARL Cardiovascular disease is associated with

adverse outcomes in morbidly obese parturients including acute
renal failure, pulmonary edema, preeclampsia, and in-hospital
mortality.

C. Endocrine
1. Type 2 DM is the paradigm of obesity-related disease. It is
often caused by obesity and will often resolve with weight
loss. Using a baseline BMI of 21, the Nurses’ Cohort Study
found that the risk of developing type 2 DM was increased
fivefold for BMI of 25, 35-fold for BMI of 30, and 93-fold for
BMI >35.2 Other groups have found similar trends of
increasing incidence and insulin use with increasing BMI.3
2. In pregnancy, the placenta secretes contrainsulin hormones
(e.g., human placental lactogen [hPL], human chronic
gonadotropin [hCG], steroids), and insulin resistance becomes
an increasing problem as pregnancy progresses. The
likelihood of developing gestational diabetes mellitus (GDM)
correlates well with prepregnancy BMI. Weiss et al.7 found
that 2.3% of normal-weight parturients developed GDM,
whereas 6.3% of obese and 9.5% of morbidly obese patients
developed GDM. The combination of preexisting insulin
resistance of obesity and the insulin resistance of pregnancy
likely leads to the large amounts of insulin required to achieve
glycemic control. The large insulin requirement, in turn, may
lead to excessive gestational weight gain. Therefore, a vicious
cycle of increasing insulin and weight gain ensues.
3. DM has significant adverse effects on the fetus (see
Chapter 23). Perinatal mortality in both type 1 and type 2 DM
is increased fourfold. The incidence of congenital anomalies
 in offspring of mothers with DM is twice that seen in
nondiabetic pregnancies. There is a fourfold increase in neural
tube defects and threefold increase in congenital heart disease.
It is well accepted that maternal obesity is a risk factor for
fetal macrosomia but the cause is unclear. Some believe that
maternal DM and hyperinsulinemia leads to fetal macrosomia,
whereas others have found that maternal obesity without DM
may cause fetal macrosomia.29 Good glycemic control
reduces the risk of adverse perinatal outcomes. HbA1c levels
should be <7%.
D. Hypercoagulability
1. Venous thromboembolism (VTE) is a leading cause of
maternal mortality. The risk of VTE is five times higher in a
pregnant woman than in a nonpregnant woman of similar
age.30 The incidence of VTE in obese parturients is more
than twice that of nonobese controls. Obesity is an
independent risk factor for deep vein thrombosis (DVT).9 In
women younger than 40 years, the relative risk for DVT is
increased sixfold in obese versus nonobese patients. Several
reasons may account for the increased incidence of venous
thrombus formation:
a. Immobility
b. Increased lower extremity venous stasis—secondary to
increased inferior vena cava pressure as a result of
increased intraabdominal pressure
c. Vascular damage occurs with both vaginal deliveries and
CD.
d. Pregnancy-induced hypercoagulable state—increase in
fibrin and factors II, VII, and X and decrease in protein S
and fibrinolytic system
e. Decreased fibrinolytic activity (decreased in individuals
with a combination of hyperlipidemia and insulin
resistance) and increased fibrinogen levels in obesity are
also contributory. Fibrinogen levels increase in proportion
 to increasing BMI.
f. Increased thromboxane production, secondary to
hyperlipidemia
g. Polycythemia leading to increased blood viscosity
2. Increased recognition and screening tools (i.e., Doppler
ultrasound) and increased use of thromboprophylaxis have
decreased the incidence of lower extremity venous thrombi.
Both unfractionated and low molecular weight heparin
(LMWH) are mainstays of thromboprophylaxis. An
anticoagulated patient provides a challenge for the
anesthesiologist. The major concern involves the increased
risk of epidural hematoma following placement of a neuraxial
blockade. Variations in the type of anticoagulant and dosing
regimen have led to different recommendations regarding the
appropriate timing for safely administering neuraxial
blockade.31

CLINICAL PEARL VTE is a leading cause of maternal

mortality. Obesity is an independent risk factor for DVT.

E. Gastrointestinal
1. The combination of obesity and pregnancy greatly increases
the risk for gastric content regurgitation and possibly
pulmonary aspiration. The frequency of GERD is strongly
correlated with increasing BMI in women.23 Physiologic
changes in normal pregnancy include a decrease in lower
esophageal sphincter tone. In laboring women, gastric
motility decreases and emptying may cease completely.
Parenteral and neuraxial opioid administration contribute to
decreased gastric motility. Obese patients may have larger
gastric volumes and lower gastric pH.32 Obese parturients are
less mobile, which also increases the risk of aspiration. The
increased risk of pulmonary aspiration necessitates strict
 nothing by mouth guidelines and the timely administration
of nonparticulate antacids, H2-receptor antagonists, and/or
metoclopramide before induction of anesthesia.33 Because
obese parturients have lower gastroesophageal junction tone
and an increased risk of airway difficulty, their risk for
aspiration is increased.
2. Fatty liver is commonly observed in obese individuals with an
estimated incidence of 60% to 90% among morbidly obese
patients.34 It is the most common cause for elevated
transaminases in the United States. The risk of steatosis
increases with type 2 DM, hyperlipidemia, and/or
hypertension. Unlike the clinically significant microvesicular
steatosis found in fatty liver of pregnancy, the
macrovesicular fatty liver associated with obesity is
usually a benign process. In rare cases, fatty liver associated
with obesity may progress to fibrosis, cirrhosis, and liver
failure. If liver function is compromised, evaluation for
possible coagulopathy must be considered. Decreased liver
function also results in altered drug metabolism and
clearance.
IV. Anesthesia for the obese pregnant woman
A. Obesity and maternal mortality. In the 2006 to 2008
Confidential Enquiries into Maternal Deaths and Child Health in
the United Kingdom, 49% (n = 227) of the women who died from
either direct (e.g., thromboembolic disease, preeclampsia,
hemorrhage) or indirect (e.g., cardiac disease) causes and for
whom the BMI was known were either overweight or obese.13
B. Patient evaluation. Both the physician and the obese parturient
benefit from antenatal anesthetic evaluation. The American
College of Obstetricians and Gynecologists (ACOG) recommends
anesthesiology consultation for obese women antepartum or
“early in labor” to allow adequate time for development of an
anesthetic plan.5 Unfortunately, the availability of antenatal
 anesthesia clinics is scarce—approximately 30% in a UK
survey.35 Manpower and financial constraints are factors that
limit availability of antenatal clinics. However, even without a
defined clinic, a sensitive discussion with the patient and her
support group as soon as she arrives on the labor and delivery unit
should include a dialogue about the potential difficulty of
initiating labor analgesia and risk of failure as well as the goals
for patient safety. Although surveys suggest that these discussions
are rare because of concerns of offending the patient,36,37 failure
to address these concerns can contribute to unrealistic patient
expectations or incomplete informed consent. Because obesity is
a social disability and is stigmatized by society, all members of
the health care team should be sensitive in their interactions with
obese parturients.
C. General considerations. Besides the technical challenges in
airway management and placement of neuraxial blocks, there
are associated medical problems and technical considerations.
Obese women should be screened for glucose intolerance early in
pregnancy. BP should be properly measured with correct cuff
size. If this is not possible, then an arterial line should be placed.
Accurate assessment of gestational age should be determined by
serial ultrasonographic examinations. Patients should be made
aware of the increased difficulty in establishing analgesia and
anesthesia, and early neuraxial analgesia should be encouraged.
Venous access may be difficult to obtain and extravasation of an
intravenous (IV) cannula can be easily overlooked. Ultrasound-
guided IV cannulation may facilitate venous access. Obese
parturients have a greater potential for blood loss during CD and
the postpartum period, so well-functioning, large-bore IV access
is essential. Patients need to be informed of the potential need for
central venous access, both for hemodynamic monitoring and
reliable IV access. Blood products also need to be readily
available because of the increased risk of uterine atony and
postpartum hemorrhage.
 CLINICAL PEARL Preparation should include BP monitoring
and placement of adequate IV access early in labor. Blood products
also need to be readily available.

V. Implications for patients undergoing labor for vaginal delivery

A. Labor analgesia. Labor analgesia is most effective with
neuraxial blockade.10 In addition to providing superior analgesia
compared to inhalational and parenteral medications, epidural
catheters also provide a safe and effective bridge to surgical
anesthesia, if required. Furthermore, neuraxial analgesia improves
respiratory function17 and decreases systemic catecholamine
levels. However, insertion of an epidural catheter can be a
technical challenge in morbidly obese women (see Fig. 29.2). The
obese laboring patient should be placed in a semisitting position
to minimize the reduction of FRC and the increase in CC
associated with the supine position.

B. Epidural analgesia/anesthesia in obese patients. Successful

placement of neuraxial anesthesia is technically more challenging
in obese patients. Multiple studies have demonstrated a higher
risk of failed epidural analgesia, more epidural catheter
 replacements, and more accidental dural punctures in obese
parturients.10,38,39 Furthermore, these women experience more
hypotension and prolonged FHR decelerations during labor
epidural analgesia.40 A systematic review of more than 37,000
women undergoing primary CD, identified the following risk
factors for failed neuraxial anesthesia: (1) increased maternal
size, (2) rapid decision-to-incision, and (3) placement later in
labor.41 Recently, a US registry captured more than 257,000
obstetric anesthetics over a 5 year period. There were 157 total
serious complications reported. High neuraxial block, respiratory
arrest in labor and delivery, and unrecognized spinal catheters
were the most frequent complications encountered. Of those
patients experiencing high neuraxial block, more than 30 percent
were obese.42 Critical evaluation of the quality and effectiveness
of epidural analgesia is essential to ensure that the epidural
catheter can be used emergently for abdominal deliveries. A
review and meta-analysis identified increasing number of boluses
required during labor analgesia, greater urgency for CD, and a
nonobstetric anesthesiologist as increasing the risk of failed
conversion of labor epidural analgesia to CD anesthesia.43 Any
epidural catheter that has questionable efficacy should be
replaced promptly.

CLINICAL PEARL Neuraxial analgesia may precede the onset

of labor or a patient’s request for labor analgesia in order to reduce
oxygen consumption and attenuate increases in cardiac output. Any
epidural catheter that has questionable efficacy should be replaced
promptly.

C. Placement of neuraxial blocks. The placement of neuraxial

blocks can be challenging. It is preferable to place the neuraxial
block in the sitting position. Anatomic landmarks, the vertebral
spinal processes and the iliac crests, guide placement of the
 neuraxial block; unfortunately, these landmarks are often
obscured in the obese patient. If the vertebral spinal processes,
used to define the midline, are difficult to palpate, one can draw a
line from the cervical vertebral spinal process to the uppermost
portion of the gluteal cleft. This line indicates the midline of the
patient over the vertebral column. If the iliac crests, used to
indicate the level of the fourth lumbar vertebrae, are difficult to
palpate, one can use the skin indentation from the FHR monitor
belt as a guide. This belt usually rests on the iliac crests over the
Tuffier line. By drawing a perpendicular line from the cervical
spinal processes down to this line, the intersection point acts as a
reasonable guide for the epidural or spinal needle insertion site at
L4. Predicting the depth of the epidural space is likewise difficult.
However, the distance between the skin and epidural space has
been shown to be greater as BMI increases.44 In differentiating
whether the needle is midline or lateral, the patient can often be
helpful.45 Ultrasonographic imaging makes identification of
midline, intervertebral space, and distance from the skin to the
epidural space accurate for determining the spinal/epidural needle
insertion point and the distance from the skin to epidural space.46
However, there is a steep learning curve when using ultrasound to
identify the epidural space. In obese patients, the distance to the
epidural space is often underestimated because of compression of
the subcutaneous tissue that can be required to compensate for
poor visibility. Standard needles (9 to 10 cm) are usually of
sufficient length to reach the epidural or intrathecal space. Longer
epidural (16 cm) or spinal needles are required occasionally in
extremely obese parturients.9 One study showed that epidural
venous cannulation in obese parturients is more likely in the
sitting position compared with the lateral, head-down position.47
To place a spinal anesthetic in an obese parturient, it is often
easier to use the stiffer epidural needle as a guide for the smaller
gauge, more flexible spinal needle.
D. Placement of epidural catheter. It is easier for an epidural
 catheter to become dislodged in an obese parturient. Before
securing the catheter to the skin, instruct the patient to assume an
upright sitting position and then ask the patient to lie down
laterally.48 Because the ligamentum flavum has a mild grip on the
epidural catheter, these movements will allow the epidural
catheter to be pulled into the subcutaneous fat, sometimes by
several centimeters. Once the patient is in the lateral position, the
epidural catheter should be secured with adhesive tape. In
addition, when the obese parturient moves in bed, the lateral
movement of the subcutaneous back fat can pull a catheter out of
the epidural space. The epidural catheter should be inserted at
least 5 cm into the epidural space to account for this potential
movement. Keep in mind that the further the epidural catheter is
inserted, the greater potential for IV cannulation and unilateral
sensory blockade.

CLINICAL PEARL Before securing the epidural catheter to the

skin, instruct the patient to assume an upright sitting position
(deflexed) and then ask the patient to lie down laterally.

E. Cephalad spread of neuraxial block. Although controversial,

the cephalad spread of anesthesia and analgesia has been
correlated with BMI.49,50 Many theories have been used to
explain this phenomenon. Increased abdominal pressure is
thought to be the mechanism that causes a smaller cerebrospinal
fluid (CSF) volume in obese patients. A decreased CSF volume
may account for more extensive spread of spinal and epidural
blockade. High epidural pressures have also been shown to cause
more extensive epidural blockade. Owing to the difficulty in
assessing anatomic landmarks, some have postulated that an
inadvertent higher needle insertion site in obese patients may
explain the greater cephalad blockade. The large buttocks of an
obese parturient can also elevate the lower vertebral column
 while in the supine position, and this process itself may result in
greater cephalad spread. Regardless of the etiology, care should
be given when dosing an epidural or spinal anesthetic in an obese
patient. Incremental epidural dosing is recommended and a lower
dose of drug for either a combined spinal-epidural (CSE) for
labor or an epidural is suggested and is prudent. A dose that is
80% of normal may be advisable. However, a CSE anesthetic
allows for an even smaller initial spinal dose because the
epidural catheter is available to supplement the anesthetic if
required.
VI. Implications for patients undergoing cesarean delivery
A. General considerations. A prospective multicenter study of
more than 16,000 patients suggested that rates of CD were 20.7%
when the BMI was ≤29.9, 33.8% when the BMI was between 30
and 34.9, and 47.7% when the BMI was between 35 and 39.9.7
Although the most common indication for CD is failure to
progress,9 reports suggest that 50% of CD are emergent in this
patient population.38 Elective CD is often scheduled for predicted
macrosomia, maternal, or obstetrician request. Complications
associated with obesity, namely, hypertension, preeclampsia, and
DM are indications for CD. Other indications for CD are
macrosomia,8 suboptimal uterine contractions,4 and/or increased
fat deposition in the pelvic soft tissues.51 Another possibility is
the difficulty in accurately and consistently monitoring FHR.52

CLINICAL PEARL Morbidly obese parturients are at risk for

CD. Up to 50% of these CDs may be emergent.

B. Cesarean delivery: maternal morbidity and mortality. Obesity

increases the risk of adverse outcomes associated with three or
more CD, including maternal death.53 The use of general
anesthesia has decreased in the last two decades and deaths
attributed to anesthesia have likewise decreased.54 Nevertheless,
 obesity and CD remain independent risk factors for maternal
morbidity and mortality.7

CLINICAL PEARL Obesity increases the risk of adverse

outcomes associated with three or more CD, including maternal
death.

C. Anesthetic plan. Spinal (single shot or continuous), epidural,

CSE, and general anesthesia are all acceptable techniques for CD
in obese parturients. The choice of anesthetic is dependent on the
clinical situation. A woman with severe asthma or
cardiomyopathy may not be able to tolerate a neuraxial block or a
potentially long surgical procedure. In urgent cases, a prudent
anesthetic plan with all available information is required to guide
the anesthesiologist’s approach. Fetal indications, although
important, are secondary to maternal safety. A maternal disaster
may result in fetal demise. As mentioned earlier, knowledge of
your surgical team’s skill level and time requirement is critical.
An honest evaluation of your own technical skill level is
paramount. Communication with the surgeon is important to
determine whether there are any unusual circumstances that
would make the surgery even more difficult.
D. Neuraxial anesthesia. A single-injection spinal anesthetic with
hyperbaric local anesthetic plus an opioid works well as long as
the surgery is of limited duration. Because the goal is to avoid a
general anesthetic (see subsequent text), the fixed duration of a
spinal anesthetic may not be prudent if the surgeon anticipates a
lengthy surgery. Although there is concern that higher levels of
spinal anesthesia may result from reduced CSF volume in obese
parturients, the dose requirements of intrathecal bupivacaine for
CD are similar in obese and normal-weight women.55 The median
dose for successful anesthesia in morbidly obese parturients
undergoing CD was 9.8 mg using a randomized dose response of
 spinal bupivacaine with fentanyl and morphine.56 An epidural or
continuous spinal anesthetic has the benefits of a neuraxial
anesthetic and allows the option of extending the anesthetic
duration. The incidence of postdural puncture headache is lower
in the obese population compared to normal-weight parturients
(see Chapter 19). A CSE anesthetic offers considerable
advantages in cases where surgical duration is unclear. It
allows rapid onset of surgical anesthesia, has minimal risk of
postdural puncture headache, and provides the option of
extending the anesthetic duration. CSE catheters fail at similar
rates compared with conventional epidural catheters,57,58 and
concerns about a so-called “untested” catheter are unwarranted.
Collectively, morbidly obese women undergoing scheduled CD
have greater overall anesthesia complications, more complicated
placement of neuraxial anesthesia, and more frequent
requirements for general anesthesia than lower weight women.59

CLINICAL PEARL A CSE anesthetic offers considerable

advantages in cases where surgical duration is unclear. CSE
catheters fail at similar rates compared to conventional epidural
catheters.

E. General anesthesia. One should avoid general anesthesia for CD

unless absolutely necessary.13,54 Maternal mortality related to
anesthesia is decreased when general anesthesia is avoided.
The most common anesthetic cause of maternal death is the
inability to oxygenate the patient and ventilate the lungs. Several
factors contribute to difficulties in visualizing pertinent airway
structures including fat deposition in the oropharynx, soft tissue
changes during pregnancy, and mucosal engorgement associated
with preeclampsia and labor. Because these anatomic changes are
known to make intubation difficult, a history of a prior successful
intubation does not guarantee similar results. Furthermore,
Mallampati classification worsens between the first and third
trimester as well as during labor.60 Key to successful endotracheal
intubation is proper patient positioning. A study investigating the
effects of position on laryngoscopic view in 60 morbidly obese
nonpregnant patients determined that the “ramped” position or
head elevated laryngoscopy position (HELP) clearly improved
the laryngeal view when compared with the standard “sniff”
position (see Fig. 29.3).61 Regardless of neuraxial or general
anesthesia administration, optimal patient positioning is
imperative prior to surgical incision.

1. The difficult airway and failed intubation. A recent study

of obstetric units in the United Kingdom from 2008 to 2010
determined that the rate of failed intubation was 1:224 and for
every 1kg per m2 increase in BMI, a 7% increase in risk of
failed intubation.62 It has been suggested that all morbidly
obese parturients be considered to have a problematic
airway. If time allows, awake laryngoscopy and endotracheal
intubation or awake fiberoptic intubation following topical
oropharyngeal local anesthesia may be prudent. Nasal
intubation should be avoided in term parturients because of
mucosal engorgement and the risk of hemorrhage. Rehearsed
emergency airway skills are essential for managing a failed
 neuraxial anesthetic. The laryngeal mask airway (LMA) and
new intubating devices, including the Airtraq and GlideScope,
may prove to be lifesaving tools in parturients with a difficult
airway.63 LMAs have been used for elective CD in healthy
fasted women with no evidence of aspiration.64 If an
endotracheal tube is not in place, one should ask the surgeon
to avoid applying abdominal pressure (use forceps or vacuum
delivery) to minimize aspiration of gastric contents. In
addition, the uterus should not be exteriorized for closure, if
possible. The American Society of Anesthesiologists’
algorithm for difficult airways should be available to serve as
a guide for the difficult intubation.65 A recent publication
from the UK addresses the difficult airway and failed
intubation in obstetrics which serves as a useful resource.66 In
addition to the difficulties in visualizing and identifying
airway structures for endotracheal intubation, confirmation of
proper placement of the endotracheal tube by auscultation of
breath sounds may be unreliable due to the thickness of the
adipose tissue. Verification of proper endotracheal intubation
can only be accomplished by capnography.

CLINICAL PEARL Risk of failed intubation increases with

increasing BMI. It has been suggested that all morbidly obese
parturients be considered to have a problematic airway.

2. Why avoid general anesthesia? There are other reasons to

avoid general anesthesia. The obese parturient is more likely
to have GERD, have greater gastric volume, and have lower
gastric pH placing her at risk for pulmonary aspiration and
Mendelson syndrome. Laryngoscopy and intubation of the
trachea are known to cause severe hypertension, especially in
women with preeclampsia. Hypertension remains a leading
cause of maternal morbidity and mortality.13 Fetal exposure to
 general anesthetic medications may be greater in the obese
parturient because of the possible additional time required for
delivery after induction of anesthesia. Infants delivered under
general anesthesia are more likely to have respiratory
depression and poor muscle tone requiring active resuscitation
than those delivered under neuraxial anesthesia.
3. The rapid sequence intubation. A rapid sequence induction
technique should be employed to minimize aspiration risk.
Adequate preoxygenation or denitrogenation is important to
minimize oxygen desaturation in the obese parturient. Cricoid
pressure (Sellick maneuver) has been shown to decrease
passive reflux of gastric contents. Recently, however, the use
of cricoid pressure has been questioned because of the
evidence that it decreases lower esophageal sphincter tone and
may make intubation more difficult. The ideal dose of the
induction medication has not been well studied in obese
parturients. As mentioned earlier, there is a positive
correlation between blood volume and BMI; therefore, logic
dictates a dose greater than that determined by ideal body
weight. Succinylcholine provides the most rapid intubating
conditions, but a high dose of rocuronium may be used if
succinylcholine is contraindicated. Isoflurane, desflurane, and
sevoflurane are safe in obese parturients. The latter two agents
have the advantage of more rapid recovery, faster patient
mobility, and reduced postoperative oxygen desaturation.
4. Extubation. Although the induction of anesthesia was
previously reported to be the most critical time during
anesthetic administration in parturients, more recent reports
suggest that emergence, extubation, and recovery are the most
critical periods of anesthetic care in the obese parturient.67
The morbidly obese parturient should only be extubated when
she is awake with adequate reversal of muscle relaxant. A
head-up position should also be used instead of supine
positioning. Taken together, risk for aspiration, airway, and
 respiratory difficulties are similar at extubation as at
intubation.

CLINICAL PEARL In addition to intubation, emergence,

extubation, and recovery are critical periods of anesthetic care in
obese parturients.

F. Considerations for the operating room. The weight limitation of

the standard operating room (OR) table is 130 to 160 kg. Newer
tables supporting up to 554 kg are available (STERIS 5085
General Surgical Table, STERIS Corp, Mentor, OH). Side
extensions are also available to support the additional patient
width (see Fig. 29.4). If side extensions are not available, one can
improvise with arm boards placed along the OR table. If the
maternal weight is in excess of the capacity of the available
OR table, it is prudent to perform the surgery on a hospital
bed. Similarly, a transport gurney must be of appropriate width
and weight capacity for the patient. The OR staff must use
sufficient padding and proper positioning of the obese patient to
prevent injuries while on the OR table or in transit. The patient
needs to be properly secured so that left lateral tilt for uterine
displacement can be safely accomplished. Additional personnel
are required to prevent lifting injuries. It is essential that the
anesthesiologist coordinate the team of people involved in
moving the patient. Use of patient-moving assistance devices
with HoverMatt or other lift devices help prevent lifting injuries
to the OR staff.
G. Surgical considerations
1. Panniculus. A large panniculus in a morbidly obese patient
may weigh 70 kg or more and cause unique problems. The
panniculus needs to be retracted to permit exposure of the
surgical field. This exposure can be accomplished either
caudally, allowing a vertical skin incision or cephalad, or
permitting a Pfannenstiel incision. Many techniques (e.g.,
retention sutures or towel clamps attached to IV poles,
securing the panniculus to the anesthesia screen, assistance to
retract the panniculus throughout the surgery, use of large op-
site plastic dressings, and suspender-type taping to the
shoulders) can be employed for cephalad retraction to achieve
exposure of the area immediately above the symphysis pubis,
but the end result may be deleterious. The force exerted on the
upper abdomen and chest can cause compression of the
inferior vena cava as well as decreased respiratory
compliance. The increased pressure on the inferior vena cava
can decrease venous return resulting in a dramatic decrease in
cardiac output and arterial BP. Increasing pressure on the
chest may exacerbate an already compromised ventilatory
state (further decrease in FRC and increase in CC) manifested
by hypoxemia, hypercarbia, and/or dyspnea. Verbal
 reassurance and supplemental oxygen are necessary but may
be insufficient to adequately resolve these problems during a
prolonged surgical procedure. Endotracheal intubation may be
necessary, and the risk of a lost airway is possible. Vertical
retraction of the panniculus obviates both the circulatory and
respiratory problems. Unfortunately, vertical retraction of a
large panniculus may be difficult to achieve. The use of extra
surgical assistance or an improvised vertical retraction device
must be employed. Surgical retraction may also result in
decreased uterine blood flow without decreasing maternal
arterial pressure. If the incision to delivery time is prolonged,
it may be prudent to monitor FHR during the surgery. Fetal
asphyxia can be an issue if there is undetected obstruction to
uterine artery blood flow. Intermittent retraction may be
employed to improve uterine arterial blood flow.

CLINICAL PEARL Regardless of the surgical approach, the

uterus must be displaced adequately, but carefully, to avoid
aortocaval compression.

2. Longer operative times and greater blood loss. Studies

conflict regarding whether obese parturients require longer
operative times and have increased blood loss for CD.68 In
one study, more than half the surgeons required more than 2
hours and had >1 L blood loss for CD in obese patients.3 Pathi
et al.12 found obese women required more blood transfusions
compared to nonobese parturients following CD. Others have
not found a significant difference in operative times or blood
loss. Knowledge of your surgical team’s operative skill will
dictate your course of action. The anesthesiologist needs to be
prepared and make provisions (e.g., generous IV access,
available cross-matched packed red blood cells, fluid
warmers, and rapid infusers) for longer operative times and
 greater blood loss. Communication between the surgeon,
anesthesiologist, and blood bank staff is important for a rapid
response to significant bleeding.
3. Postoperative wound infection. Because postoperative
wound infection is a major risk in obese patients (sevenfold
increase in one study),3 wound asepsis is essential.3,69
Although some have suggested preparing the skin with
povidone-iodine solution 30 to 40 minutes preoperatively and
then once again after the neuraxial anesthetic is completed, a
chlorhexidine/alcohol solution will provide immediate as well
as residual antiseptic activity. Although antimicrobial
prophylaxis is recommended for all patients undergoing CD
unless the patient is already receiving appropriate antibiotics
(e.g., for chorioamnionitis), “consideration should be given to
using a higher dose of preoperative antibiotics for surgical
prophylaxis” in obese women.5(p2) All women >120 kg
weight should receive 3 g cefazolin IV before skin incision
(not 2 g) unless they have an allergy to cephalosporins.
VII. Postoperative care
A. General considerations. Morbid obesity increases the risk of
postoperative complications, including hypoxemia, atelectasis,
deep venous thrombosis, pulmonary embolus, pneumonia,
pulmonary edema, postoperative endometritis, wound infection,
and dehiscence.
B. Pulmonary considerations
1. Avoid hypoxemia by preventing atelectasis. The absence of
a gravid uterus will improve pulmonary function. During the
initial postoperative period, the patient’s upper body should
be elevated to a nearly sitting position. This position will
improve respiratory mechanics and decrease the cephalad
pressure on the diaphragm. To decrease atelectasis, the patient
should be encouraged to take deep breaths and cough. An
incentive spirometer should be utilized. Supplemental oxygen
is often required.
 2. The sensory level of spinal anesthesia does not correlate with
post-CD respiratory impairment. In one report, there was no
difference in the pulmonary function measured immediately
after initiation of spinal anesthesia and 2 hours after CD,
despite resolution of sensory block from a T4 to a T12
dermatomal level during this period.17
3. Ambulation improves respiratory function for both obese and
normal-weight parturients after spinal anesthesia for CD. The
earlier mentioned study showed that spirometric values for
normal-weight parturients were close to baseline only after
patients ambulated. Although the pulmonary function of
obese parturients greatly improved after ambulation, they
remained significantly worse compared to nonobese women
and to their own baseline (prespinal) levels.17
4. The abdominal muscles are essential to generate a good
cough. Cough effectiveness, as measured by the PEFR, is
essential to decrease atelectasis as well as to prevent
aspiration. At 3 hours after CD, PEFR of obese parturients
remained significantly more impaired compared to normal-
weight parturients.17
5. Adequate pain control is essential for good respiratory effort
and ambulation. A midline vertical incision, as opposed to the
standard Pfannenstiel incision, may increase surgical
discomfort and postoperative pain. The increase in
postoperative pain can lead to poor respiratory effort and
decreased ambulation, which, in turn, can increase
postoperative complications (e.g., DVT formation). Midline
incisions are also associated with an increase in hernia
formation and wound dehiscence.68 Multimodal analgesic
techniques (e.g., nonsteroidal anti-inflammatory agents)
should be used to decrease total opioid requirements.70
C. Postoperative monitoring. Depression of ventilatory response to
hypoxia after administration of neuraxial morphine is similar to,
but longer lasting than, the administration of an equianalgesic
 dose of IV morphine. Obese patients may be more sensitive to the
respiratory depressant effects of opioids and sedative hypnotics.
The American Society of Anesthesiologists71 has published
recommendations for the postoperative care of patients with sleep
apnea although they are not pregnancy specific. Neuraxial
anesthesia, frequent respiratory rate measurements, pulse
oximetry, sedation scores, and/or apnea monitoring are all
important for the postoperative assessment of the obese
patient. In addition, monitoring in an intensive care unit or step-
down unit should be considered.72

CLINICAL PEARL Neuraxial anesthetic techniques should be

considered to reduce or eliminate the requirements for systemic
opioids in patients with OSA. Multimodal analgesic techniques
(e.g., nonsteroidal anti-inflammatory agents) should be used to
decrease total opioid requirements.

D. Thromboprophylaxis
1. Thromboprophylaxis is essential to prevent venous
thrombosis and pulmonary embolism.69 The obese patient is
at especially high risk for perioperative thrombotic events.3,52
They are less mobile due to a combination of obesity and
surgery, and fibrinolytic activity is markedly decreased in
individuals because of a combination of hyperlipidemia and
insulin resistance. Hyperlipidemia may also increase
thromboxane production leading to a greater coagulable state.
Thromboembolic deterrent stockings (TEDSs), LMWH,
adequate hydration, early ambulation, and physical
therapy have all been shown to decrease the incidence of
thromboembolic events. It is essential to communicate with
the surgeon regarding use of LMWH to prevent iatrogenic
mishaps. According to the Third Consensus Conference on
Neuraxial Anesthesia and Anticoagulation,31
 a. Patients with postoperative initiation of LMWH
thromboprophylaxis may safely undergo single-injection
and continuous catheter techniques. Management is based
on total daily dose, timing of the first postoperative dose,
and dosing schedule.
(1) Twice-daily dosing. This dosage regimen may be
associated with an increased risk of spinal hematoma.
The first dose of LMWH should be administered
no earlier than 24 hours postoperatively,
regardless of anesthetic technique, and only in the
presence of adequate (surgical) hemostasis.
Indwelling catheters should be removed before
initiation of LMWH thromboprophylaxis. If a
continuous technique is selected, the epidural catheter
may be left in overnight and removed the following
day, with the first dose of LMWH administered at
least 2 hours after catheter removal.
(2) Once-daily dosing. This dosing regimen
approximates the European application. The first
postoperative LMWH dose should be administered 6
to 8 hours postoperatively. The second postoperative
dose should occur no sooner than 24 hours after the
first dose. Indwelling neuraxial catheters may be
safely maintained. However, the catheter should be
removed a minimum of 10 to 12 hours after the last
dose of LMWH. Subsequent LMWH dosing should
occur a minimum of 2 hours after catheter removal.
VIII. Newborn
A. Preterm delivery. Some studies have indicated that premature
infants (deliveries <38 weeks’ gestation) are less likely in obese
parturients.4,12 However, a large population-based cohort study
determined that the risk of preterm, especially extreme preterm
delivery, was increased in overweight and obese women.73
B. Fetal anomalies. Maternal obesity increases the likelihood of
 macrosomia and other fetal and perinatal issues.1,51 Macrosomia
causes an increased risk of birth trauma. Most studies also
indicate an increase in incidence of congenital malformations,
including omphalocele, cardiac anomalies, and spina bifida or
other neural tube defects (independent of maternal age, education,
smoking status, alcohol use, and other known risk factors for
neural tube defect). Because the images on fetal ultrasonography
are often suboptimal in obese parturients, there is a higher risk of
failure to diagnose fetal anomalies.13
C. Fetal macrosomia. Macrosomia is defined as a term infant
weighing >4,000 g. An obese parturient has twice the likelihood
of a newborn being >90th percentile in weight versus nonobese
parturients.3,4 The Pedersen hypothesis, maternal hyperglycemia
causing hyperinsulinemia in the fetus resulting in enhanced fetal
growth, has been cited as the reason for fetal macrosomia.
However, studies have found that obese, mothers without diabetes
are more likely to have macrosomic babies compared to
nonobese, mothers with diabetes.29 Therefore, it appears that the
offspring of obese mothers develop fetal macrosomia through an
unknown mechanism. Macrosomic newborns are at increased
risk for birth trauma (e.g., shoulder dystocia and Erb palsy),
asphyxia, meconium aspiration, antepartum stillbirth,
hypoglycemia, hypocalcemia, and erythrocytosis. A term infant
weighing >4,500 g has a more than threefold increase in mortality
compared to an infant of average birth weight.
D. Stillbirth and neonatal deaths. Stillbirth is defined as delivery
of a dead fetus at 28 weeks’ gestation or later. Neonatal death is
defined as death of a live newborn on days 1 to 28 following
delivery.74 A recent meta-analysis and systematic review
evaluating maternal BMI and risk of perinatal mortality
determined that “modest” increases in maternal BMI increased
the risk of fetal death, stillbirth, neonatal, perinatal, and infant
deaths.75 Maternal prepregnancy obesity more than doubles the
risk of stillbirth and neonatal deaths.8,12,25,52 A study that
 separated nulliparous women from parous women found that in
parous obese parturients, there was no increase in early neonatal
deaths.25 Cnattingius et al.25 reported an increased risk of late
fetal death among obese women that correlated with
prepregnancy BMI and was independent of the presence or
absence of hypertensive disorders and diabetes. This finding is
contrary to others who found that uncomplicated obese
parturients have no additional risk of poor fetal outcome.12
However, these authors found that obese mothers with
preeclampsia, DM, hypertension, or advanced age had a higher
incidence of perinatal death.76
E. Neonatal care. A recent cohort study of women with BMI >40
determined that the risk of newborn injury to the peripheral
nervous system and skeleton was increased but there was also an
increased risk of respiratory distress syndrome, bacterial sepsis,
convulsions, hypoglycemia in newborns born to mothers with a
BMI >40. In neonates born to obese mothers, admission to a
neonatal intensive care unit was 4 to 10 times greater compared to
neonates born to mothers of normal weight.51 Most of the
admissions were for temperature regulation, glucose monitoring,
and assistance in feeding. Others have noted that neonates born to
obese diabetic parturients have the greatest risk of poor
outcomes.77 Difficulties in monitoring FHR during labor may
also lead to a delayed diagnosis of nonreassuring FHRs.
Furthermore, infants born to obese mothers are less likely to be
breastfed at hospital discharge. This may be related to the
decreased prolactin response to suckling leading to poor
lactogenesis and initiation of breastfeeding or social issues.4
IX. Pregnancy after bariatric surgery
A systematic review on bariatric surgery among women of
reproductive age determined that although rates of adverse maternal
and neonatal outcomes could be lower in women who become
pregnant after bariatric surgery compared with rates in obese pregnant
 women, more data are needed.78 In general, a history of bariatric
surgery is not associated with adverse perinatal outcome. However,
these patients should be assessed to rule out cardiomyopathy and
sleep apnea. Maternal anemia may be a result of nutritional
deficiencies following gastric bypass. Iron-deficiency anemia
(microcytic) may result from poor iron absorption. Folate and B12
deficiency may result from poor absorption resulting in macrocytic
anemia. Maternal nutritional deficiencies have resulted in intrauterine
growth restriction12 and neural tube defects. Gastrointestinal bleeding
during pregnancy has been reported following gastric band erosion
(vertical-banded gastroplasty).67
X. Cost
The cost of care for an obese parturient is significantly greater than
that of a normal-weight parturient69,79 and increases in direct
proportion with the BMI.1,12 Obesity predisposes parturients to
hypertension, preeclampsia, DM, insulin use, postpartum
complications, and increased hospitalization. In patients with BMI
>35, there is a 26-fold increase in outpatient visits and two-to fourfold
increase in hospitalizations.1 Other studies have found an increased
use of antepartum services and hospitalizations too. Pathi et al.12
determined that fetal monitoring, ultrasonography, and medical
management of diabetes and hypertension were all increased in this
population. The risk of complications during labor is higher and
includes an increased CD rate. The morbidly obese parturient has an
increased incidence of postoperative complications and antepartum
medical disease, and these factors contribute to longer
hospitalization.12 In one study, the cost of care for a morbidly obese
parturient was estimated at three times that of a normal-weight
parturient. Others have estimated a five-fold to ten-fold increase
depending on the degree of obesity.1 Although no studies evaluated
neonatal costs, the decrease in preterm delivery in the obese
population may offset some of the maternal health costs; however, the
increase in perinatal morbidity, mostly due to maternal DM will
 increase medical costs.12
SUMMARY
The anesthesiologist faces significant challenges when caring for the morbidly
obese parturient. Obesity is a significant risk factor for both maternal and
perinatal morbidity and mortality. Overall, the literature suggests that obese
parturients have a 14% to 25% incidence of preeclampsia, a 6% to 14%
incidence of GDM, and a 30% to 47% chance of requiring a CD.7,9 These
numbers are only estimates, and many studies correlate increasing complications
with increasing maternal BMI. The obese parturient may have concurrent
medical problems that need to be addressed. The anesthesiologist needs to
anticipate difficulties during labor and CD and must plan for them accordingly.
Communication with the obstetric team is essential for good care. Every effort
should be made to provide the best possible outcome for the obese parturient and
her fetus, but the life of the mother should never be endangered to save a
compromised fetus.

REFERENCES
1. Galtier-Dereure F, Montpeyroux F, Boulot P, et al. Weight excess before pregnancy: complications and
cost. Int J Obes Relat Metab Disord. 1995;19:443–448.
2. Aubert B, Boutigny D, De Bonis I, et al. Measurement of CP-violating asymmetries in B0 decays to
CP eigenstates. Phys Rev Lett. 2001;86:2515–2522.
3. Johnson SR, Kolberg BH, Varner MW, et al. Maternal obesity and pregnancy. Surg Gynecol Obstet.
1987;164:431–437.
4. Sebire NJ, Jolly M, Harris JP, et al. Maternal obesity and pregnancy outcome: a study of 287,213
pregnancies in London. Int J Obes Relat Metab Disord. 2001;25:1175–1182.
5. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 549: obesity in
pregnancy. Obstet Gynecol. 2013;121:213–217.
6. Mhyre JM, Bateman BT, Leffert LR. Influence of patient comorbidities on the risk of near-miss
maternal morbidity or mortality. Anesthesiology. 2011;115:963–972.
7. Weiss JL, Malone FD, Emig D, et al. Obesity, obstetric complications and cesarean delivery rate—a
population-based screening study. Am J Obstet Gynecol. 2004;190:1091–1097.
8. Cedergren MI. Maternal morbid obesity and the risk of adverse pregnancy outcome. Obstet Gynecol.
2004;103:219–224.
9. Saravanakumar K, Rao SG, Cooper GM. Obesity and obstetric anaesthesia. Anaesthesia. 2006;61:36–
48.
10. Ranta P, Jouppila P, Spalding M, et al. The effect of maternal obesity on labour and labour pain.
Anaesthesia. 1995;50: 322–326.
11. Durnwald CP, Ehrenberg HM, Mercer BM. The impact of maternal obesity and weight gain on vaginal
 birth after cesarean section success. Am J Obstet Gynecol. 2004;191:954–957.
12. Pathi A, Esen U, Hildreth A. A comparison of complications of pregnancy and delivery in morbidly
obese and non-obese women. J Obstet Gynaecol. 2006;26:527–530.
13. Cantwell R, Clutton-Brock T, Cooper G, et al. Saving mothers’ lives: reviewing maternal deaths to
make motherhood safer: 2006–2008. The Eighth Report of the Confidential Enquiries into Maternal
Deaths in the United Kingdom. BJOG. 2011;118(suppl 1):1–203.
14. Rassmusen KM, Yaktine AL, eds; for the Institute of Medicine. Weight Gain During Pregnancy:
Reexamining the Guidelines. Washington, DC: National Academies Press; 2009.
15. Flegal KM, Carroll MD, Kit BK, et al. Prevalence of obesity and trends in the distribution of body
mass index among US adults, 1999–2010. JAMA. 2012;307:491–497.
16. Unterborn J. Pulmonary function testing in obesity, pregnancy, and extremes of body habitus. Clin
Chest Med. 2001;22:759–767.
17. von Ungern-Sternberg BS, Regli A, Bucher E, et al. Impact of spinal anaesthesia and obesity on
maternal respiratory function during elective caesarean section. Anaesthesia. 2004;59:743–749.
18. Pataka A, Daskalopoulou E, Kalamaras G, et al. Evaluation of five different questionnaires for
assessing sleep apnea syndrome in a sleep clinic. Sleep Med. 2014;15:776–781.
19. Ankichetty SP, Angle P, Joselyn AS, et al. Anesthetic considerations of parturients with obesity and
obstructive sleep apnea. J Anaesthesiol Clin Pharmacol. 2012;28:436–443.
20. Louis JM, Mogos MF, Salemi JL, et al. Obstructive sleep apnea and severe maternal-infant
morbidity/mortality in the United States, 1998–2009. Sleep. 2014;37:843–849.
21. Macavei VM, Spurling KJ, Loft J, et al. Diagnostic predictors of obesity-hypoventilation syndrome in
patients suspected of having sleep disordered breathing. J Clin Sleep Med. 2013;9:879–884.
22. Tomoda S, Tamura T, Sudo Y, et al. Effects of obesity on pregnant women: maternal hemodynamic
change. Am J Perinatol. 1996;13:73–78.
23. Jacobson BC, Somers SC, Fuchs CS, et al. Body-mass index and symptoms of gastroesophageal reflux
in women. N Engl J Med. 2006;354:2340–2348.
24. Bateman BT, Bansil P, Hernandez-Diaz S, et al. Prevalence, trends, and outcomes of chronic
hypertension: a nationwide sample of delivery admissions. Am J Obstet Gynecol. 2012;206:134.e1–
134.e8.
25. Cnattingius S, Bergström R, Lipworth L, et al. Prepregnancy weight and the risk of adverse pregnancy
outcomes. N Engl J Med. 1998;338:147–152.
26. Kenchaiah S, Evans JC, Levy D, et al. Obesity and the risk of heart failure. N Engl J Med.
2002;347:305–313.
27. Alpert MA. Obesity cardiomyopathy: pathophysiology and evolution of the clinical syndrome. Amer J
Med Sci. 2001;321:225–236.
28. Tsueda K, Debrand M, Zeok SS, et al. Obesity supine death syndrome: reports of two morbidly obese
patients. Anesth Analg. 1979;58:345–347.
29. Green JR, Schumacher LB, Pawson IG, et al. Influence of maternal body habitus and glucose
tolerance on birth weight. Obstet Gynecol. 1991;78:235–240.
30. Toglia MR, Weg JG. Venous thromboembolism during pregnancy. N Engl J Med. 1996;335:108–114.
31. Horlocker TT, Wedel DJ, Rowlingson JC, et al. Executive summary: regional anesthesia in the patient
receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain
Medicine Evidence-Based Guidelines (Third Edition). Reg Anesth Pain Med. 2010;35:102–105.
32. Wong CA, McCarthy RJ, Fitzgerald PC, et al. Gastric emptying of water in obese pregnant women at
term. Anesth Analg. 2007;105:751–755.
33. American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Practice guidelines for
obstetric anesthesia: an updated report by the American Society of Anesthesiologists Task Force on
 Obstetric Anesthesia. Anesthesiology. 2007;106:843–863.
34. Fong DG, Nehra V, Lindor KD, et al. Metabolic and nutritional considerations in nonalcoholic fatty
liver. Hepatology. 2000;32:3–10.
35. Rai MR, Lua SH, Popat M, et al. Antenatal anaesthetic assessment of high-risk pregnancy: a survey of
UK practice. Int J Obstet Anesth. 2005;14:219–222.
36. Mhyre JM, Greenfield ML, Polley LS. Survey of obstetric providers’ views on the anesthetic risks of
maternal obesity. Int J Obstet Anesth. 2007;16:316–322.
37. Wen LM, Baur LA, Simpson JM, et al. Mothers’ awareness of their weight status and concern about
their children being overweight: findings from first-time mothers in south-west Sydney. Aust N Z J
Public Health. 2010;34:293–297.
38. Tonidandel A, Booth J, D’Angelo R, et al. Anesthetic and obstetric outcomes in morbidly obese
parturients: a 20-year follow-up retrospective cohort study. Int J Obstet Anesth. 2014;23:357–364.
39. Dresner M, Brocklesby J, Bamber J. Audit of the influence of body mass index on the performance of
epidural analgesia in labour and the subsequent mode of delivery. BJOG. 2006;113:1178–1181.
40. Vricella LK, Louis JM, Mercer BM, et al. Impact of morbid obesity on epidural anesthesia
complications in labor. Am J Obstet Gynecol. 2011;205:370.e1–370.e6.
41. Bloom SL, Spong CY, Weiner SJ, et al. Complications of anesthesia for cesarean delivery. Obstet
Gynecol. 2005;106:281–287.
42. D’Angelo R, Smiley RM, Riley ET, et al. Serious complications related to obstetric anesthesia: the
serious complication repository project of the Society for Obstetric Anesthesia and Perinatology.
Anesthesiology. 2014;120:1505–1512
43. Bauer ME, Kountanis JA, Tsen LC, et al. Risk factors for failed conversion of labor epidural analgesia
to cesarean delivery anesthesia: a systematic review and meta-analysis of observational trials. Int J
Obstet Anesth. 2012;21:294–309.
44. Clinkscales CP, Greenfield ML, Vanarase M, et al. An observational study of the relationship between
lumbar epidural space depth and body mass index in Michigan parturients. Int J Obstet Anesth.
2007;16:323–327.
45. Marroquin BM, Fecho K, Salo-Coombs V, et al. Can parturients identify the midline during neuraxial
block placement? J Clin Anesth. 2011;23:3–6.
46. Arzola C, Davies S, Rofaeel A, et al. Ultrasound using the transverse approach to the lumbar spine
provides reliable landmarks for labor epidurals. Anesth Analg. 2007;104:1188–1192.
47. Bahar M, Chanimov M, Cohen ML, et al. The lateral recumbent head-down position decreases the
incidence of epidural venous puncture during catheter insertion in obese parturients. Can J Anaesth.
2004;51:577–580.
48. Hamilton CL, Riley ET, Cohen SE. Changes in the position of epidural catheters associated with
patient movement. Anesthesiology. 1997;86:778–784.
49. Hodgkinson R, Husain FJ. Obesity and the cephalad spread of analgesia following epidural
administration of bupivacaine for cesarean section. Anesth Analg. 1980;59:89–92.
50. Taivainen T, Tuominen M, Rosenberg PH. Influence of obesity on the spread of spinal analgesia after
injection of plain 0.5% bupivacaine at the L3-4 or L4-5 interspace. Br J Anaesth. 1990;64:542–546.
51. Barau G, Robillard PY, Hulsey TC, et al. Linear association between maternal pre-pregnancy body
mass index and risk of caesarean section in term deliveries. BJOG. 2006;113:1173–1177.
52. Yu CK, Teoh TG, Robinson S. Obesity in pregnancy. BJOG. 2006;113:1117–1125.
53. Mourad M, Silverstein M, Bender S, et al. The effect of maternal obesity on outcomes in patients
undergoing tertiary or higher cesarean delivery. J Matern Fetal Neonatal Med. 2015;28:989–993.
54. Hawkins JL, Chang J, Palmer SK, et al. Anesthesia-related maternal mortality in the United States:
1979–2002. Obstet Gynecol. 2011;117:69–74.
55. Lee Y, Balki M, Parkes R, et al. Dose requirement of intrathecal bupivacaine for cesarean delivery is
similar in obese and normal weight women. Rev Bras Anestesiol. 2009;59:674–683.
56. Carvalho B, Collins J, Drover DR, et al. ED(50) and ED(95) of intrathecal bupivacaine in morbidly
obese patients undergoing cesarean delivery. Anesthesiology. 2011;114:529–535.
57. Pan PH, Bogard TD, Owen MD. Incidence and characteristics of failures in obstetric neuraxial
analgesia and anesthesia: a retrospective analysis of 19,259 deliveries. Int J Obstet Anesth.
2004;13:227–233.
58. Gambling D, Berkowitz J, Farrell TR, et al. A randomized controlled comparison of epidural analgesia
and combined spinal-epidural analgesia in a private practice setting: pain scores during first and
second stages of labor and at delivery. Anesth Analg. 2013;116:636–643.
59. Vricella LK, Louis JM, Mercer BM, et al. Anesthesia complications during scheduled cesarean
delivery for morbidly obese women. Am J Obstet Gynecol. 2010;203:276.e1–e5.
60. Kodali BS, Chandrasekhar S, Bulich LN, et al. Airway changes during labor and delivery.
Anesthesiology. 2008;108:357–362.
61. Collins JS, Lemmens HJ, Brodsky JB, et al. Laryngoscopy and morbid obesity: a comparison of the
“sniff” and “ramped” positions. Obes Surg. 2004;14:1171–1175.
62. Quinn AC, Milne D, Columb M, et al. Failed tracheal intubation in obstetric anaesthesia: 2 yr national
case-control study in the UK. Br J Anaesth. 2013;110:74–80.
63. Dhonneur G, Ndoko S, Amathieu R, et al. Tracheal intubation using the Airtraq in morbid obese
patients undergoing emergency cesarean delivery. Anesthesiology. 2007;106:629–630.
64. Han TH, Brimacombe J, Lee EJ, et al. The laryngeal mask airway is effective (and probably safe) in
selected healthy parturients for elective cesarean section: a prospective study of 1067 cases. Can J
Anaesth. 2001;48:1117–1121.
65. Apfelbaum JL, Hagberg CA, Caplan RA, et al. Practice guidelines for management of the difficult
airway: an updated report by the American Society of Anesthesiologists Task Force on Management
of the Difficult Airway. Anesthesiology. 2013;118:251–270.
66. Mushambi MC, Kinsella SM, Popat M, et al. Obstetric Anaesthetists’ Association and Difficult
Airway Society guidelines for the management of difficult and failed tracheal intubation in obstetrics.
Anaesthesia. 2015;70:1286–1306.
67. Mhyre JM, Riesner MN, Polley LS, et al. A series of anesthesia-related maternal deaths in Michigan,
1985–2003. Anesthesiology. 2007;106:1096–1104.
68. Thornton YS. Caesarean delivery and celiotomy using panniculus retraction in the morbidly obese
patient. J Am Coll Surg. 2001;193:458–461.
69. Alexander CI, Liston WA. Operating on the obese woman—a review. BJOG. 2006;113:1167–1172.
70. American Society of Anesthesiologists Task Force on Neuraxial Opioids, Horlocker TT, Burton AW,
et al. Practice guidelines for the prevention, detection, and management of respiratory depression
associated with neuraxial opioid administration. Anesthesiology. 2009;110:218–230.
71. American Society of Anesthesiologists Task Force on Perioperative Management of Patients with
Obstructive Sleep Apnea. Practice guidelines for the perioperative management of patients with
obstructive sleep apnea: an updated report by the American Society of Anesthesiologists Task Force
on Perioperative Management of Patients with Obstructive Sleep Apnea. Anesthesiology.
2014;120:268–286.
72. Loubert C, Fernando R. Cesarean delivery in the obese parturient: anesthetic considerations. Women’s
Health. 2011;7:163–179.
73. Cnattingius S, Villamor E, Johansson S, et al. Maternal obesity and risk of preterm delivery. JAMA.
2013;309:2362–2370.
74. Kristensen J, Vestergaard M, Wisborg K, et al. Pre-pregnancy weight and the risk of stillbirth and
 neonatal death. BJOG. 2005;112:403–408.
75. Aune D, Saugstad OD, Henriksen T, et al. Maternal body mass index and the risk of fetal death,
stillbirth, and infant death: a systematic review and meta-analysis. JAMA. 2014;311:1536–1546.
76. Rahaman J, Narayansingh GV, Roopnarinesingh S. Fetal outcome among obese parturients. Int J
Gynaecol Obstet. 1990;31:227–230.
77. Baron CM, Girling LG, Mathieson AL, et al. Obstetrical and neonatal outcomes in obese parturients. J
Matern Fetal Neonatal Med. 2010;23:906–913.
78. Maggard MA, Yermilov I, Li Z, et al. Pregnancy and fertility following bariatric surgery: a systematic
review. JAMA. 2008;300:2286–2296.
79. Chu SY, Bachman DJ, Callaghan WM, et al. Association between obesity during pregnancy and
increased use of health care. N Engl J Med. 2008;358:1444–1453.
 Trauma in the Obstetric Patient
Hen Y. Sela, Lior Drukker, and Sharon Einav

I. Introduction
II. Epidemiology of trauma
A. Epidemiology of obstetric complications during trauma
III. General treatment guidelines
A. Always prefer the mother
B. Adhere to standard care protocols
C. Perform trauma surveys, a pregnancy workup, and assess
fetal viability
IV. Limitations in assessing severity of maternal injury
A. Severity of injury
B. Advanced trauma life support training and use of vital signs
C. Implications of the physiologic changes of pregnancy
D. Clinical assessment of patient severity
V. Principles of radiologic assessment
A. Ultrasound imaging
B. Standard radiology and computed tomography scanning
C. Magnetic resonance imaging
VI. Clinical and test findings versuspregnancy outcome
A. Prenatal maternal injury
B. Minor injuries
C. Kleihauer-Betke testing
D. Flow cytometry
 VII. Anesthetic considerations
A. Airway management
B. Anesthetic induction and maintenance
VIII. Specific mechanisms of injury
A. Motor vehicle accidents
B. Falls
C. Domestic violence
D. Burns
E. Penetrating injury
IX. Salvage therapies
A. Extracorporeal membrane oxygenation
B. Perimortem cesarean delivery
Summary

KEYPOINTS
1. Prenatal maternal injury is associated with an increased risk of adverse
pregnancy outcome. Lack of maternal belting is consistently cited as a
risk for poor pregnancy outcome in motor vehicle accidents.
2. Because information regarding management of specific types of trauma
during pregnancy is limited, providers must extrapolate from other
clinical situations (e.g., peripartum hemorrhage) and remain open to the
likelihood that physiologic instability may result not only from
overlooked and/or untreated injuries, but also from baseline differences in
physiology stemming from the presence of pregnancy or from obstetric
complications.
3. Management of maternal trauma is driven primarily by maternal
condition.
4. Because fetal heart rate monitoring may provide early indication of
maternal distress, the fetus should be monitored both prior to and
immediately after surgery whenever possible. Routinely (twice daily if
 possible) monitoring is recommended for the duration of maternal
admission as well.
5. The principles guiding care of the pregnant patient with trauma are the
same as in the parturient without trauma: respect toward parental
opinions, which may differ from those of the treating staff, placement of
greater emphasis on fetal/neonatal condition than on gestational age after
24 weeks gestation.
6. Delivery should be considered in an initially unstable patient only if
maternal instability results from a complication of the pregnancy itself
(e.g., hemorrhage from placental abruption).
7. Standard advanced trauma life support (ATLS) shock categories may be
inadequate for classifying the severity of hemorrhage in the pregnant
population.
8. Ultrasound is the imaging mode of choice for all pregnant women.
9. The risk of fetal teratogenesis following exposure to radiation is greatest
during the first trimester of pregnancy.
10. Anesthetic management of the injured pregnant woman should be
directed toward optimization of maternal oxygenation and perfusion.
11. The respiratory reserves of pregnant women are limited. Decisions
regarding the timing of tracheal intubation must balance the increased
likelihood of airway management complications and the increased risk of
maternal/fetal compromise.
12. Regardless of the hospital location of the pregnant patient with trauma, a
birthing kit and heated incubator should always be on location.
13. Perimortem cesarean delivery (PMCD) may be instituted for maternal
salvage, provided aortocaval compression (secondary to the presence of
the gravid uterus) is considered a major contributor to maternal
cardiovascular collapse.
14. The American Heart Association recommends initiation of PMCD within
4 minutes of maternal nontraumatic resuscitation without return of
spontaneous circulation.

I. Introduction
Approximately 1 in 15 pregnant women are involved in some type of
 trauma, most commonly a motor vehicle accident (MVA) or a fall.
Health care providers must be able to perform a complete and
thorough trauma workup while evaluating mother and child for life-
threatening obstetric complications. Differences between maternal
physiology and the nonpregnant female physiology challenge
provider ability to distinguish between normal and abnormal clinical
and laboratory findings. Of particular concern is the complexity of
balancing the management of two endangered lives simultaneously.
The presence of the pregnancy itself diverts attention away from the
main trauma victim—the mother. When the fetus is considered viable,
additional challenges present in the form of questions regarding
treatment and salvage priorities.
Appropriate trauma care of the injured pregnant woman entails a
coordinated multidisciplinary effort, which should ideally include
providers with expertise in emergency medicine, trauma surgery,
maternal–fetal medicine, and/or obstetrics, and anesthesiology and
critical care. All providers should act in accordance with accepted
trauma guidelines, which prioritize maternal airway management and
support of breathing and circulation. All should also follow standard
protocols for assessment and management of trauma during
pregnancy.
The current chapter reviews the epidemiology of maternal trauma,
the unique challenges and ethical issues likely to occur during trauma
workup and management in this clinical situation, as well as
recommendations for treatment of the injured pregnant woman. It also
discusses the implications of specific trauma mechanisms and their
associated injuries during pregnancy.
II. Epidemiology of trauma
Trauma complicates approximately 3% to 12% of all pregnancies.1,2
It constitutes a major cause of both maternal2,3 and fetal4–6 mortality.
The incidence of maternal death from trauma is currently estimated to
be 1.4 per 100,000 pregnancies4 and fetal death after maternal trauma
is more than double (3.7 per 100,000 live births).4,5 A particularly
high incidence of fetal death (9.3 per 100,000 live births) has been
observed in trauma cases involving teen mothers (15 to 19 years old)5
possibly due to more severe injury.7 Maternal demise, placental
abruption, maternal shock, and uterine rupture are the most common
risk factors for fetal death.5
Pregnant women are more likely to seek help following trauma
than nonpregnant women,8 and pregnancy at a gestational age greater
than 20 weeks is an indication for transporting the mother to a trauma
center.9 Notwithstanding, the exact prevalence of trauma-related
morbidity and mortality remains unknown; most data are
retrospective, coding systems differ, trauma registries do not include
obstetric information, and some types of injuries are
underreported.2,5,10
Minor trauma is generally much more common than major trauma,
and trauma during pregnancy is no exception. Only 6% of injured
pregnant women are hospitalized, which suggests that most pregnant
women involved in trauma do not sustain severe injuries6; three-
quarters of those hospitalized (77.9%) remain in hospital for no more
than 1 day.8 Major maternal injury occurs in 23 per 100,000
pregnancies. Centers treating hospitalized pregnant women after
trauma report that 12.5% to 19% are severely injured.11–13 Among
these cases, maternal mortality approximates 5.6%.4 MVA, domestic
violence, and assaults are the leading causes of major maternal
trauma,2 whereas falls, burns, homicide, suicide, thermal injuries,
toxic exposure, and drowning account for the remainder.7 Thus,
unintentional injury accounts for most major trauma occurring during
pregnancy. A recent systemic review calculated the approximate
incidence of injuries during pregnancies resulting in live births
according to mechanism; other than domestic violence (incidence
8,307 per 100,000), most types of trauma seem to occur less
frequently among pregnant women than among nonpregnant women.
The incidence of MVAs was estimated at 207 per 100,000, that of
falls 49 per 100,000, toxic exposure 25.8 per 100,000, homicide 2.9
per 100,000, and suicide 2 per 100,000 live births.2
CLINICAL PEARL MVA, domestic violence, and assaults are
the leading causes of major maternal trauma, whereas falls, burns,
homicide, suicide, thermal injuries, toxic exposure, and drowning
account for the remainder.

A. Epidemiology of obstetric complications during trauma.

Maternal trauma carries an added risk for obstetric complications.
Women sustaining trauma prenatally may have a placental
abruption rate up to 56% higher than uninjured women.14
Although the proportion of maternal trauma cases suffering
placental abruption may be as low as 1% to 3% among minor
blunt trauma cases, placental abruption may occur in 5% to 8.5%
of the uninjured general maternal trauma population (injury
severity score [ISS] = 0),13–15 and minor abdominal injuries in
particular are associated with relatively high rates of placental
abruption.7,16,17
Premature rupture of membranes occurs in 0.7% to 2.4% of
cases7,14 and the proportion of maternal trauma cases with uterine
rupture is lower than 1%.4 This is a major threat to mother (10%
mortality) and to the fetus (near 100% mortality).14 Direct fetal
injuries are mostly described in case reports. In the United States,
approximately 4:1,000 delivery admissions are trauma related and
one in three women admitted to hospital as a consequence of
trauma during pregnancy will deliver during her hospitalization.18
However, even women who have not delivered during the index
trauma-related admission remain at increased risk for preterm
delivery, which occurs in overall 7% of cases of maternal
trauma.5

CLINICAL PEARL Women sustaining trauma prenatally may

have a placental abruption rate up to 56% higher than uninjured
women.
 III. General treatment guidelines
Treatment of maternal trauma is confounded by education and
training deficiencies, by lack of clarity regarding prioritization (i.e.,
treatment preference for the mother), by issues surrounding the
accepted limits of neonatal viability and their relevance after trauma,
and by acknowledged deviations from physiologic norms which
thwart recognition of signals indicating significant clinical
deterioration.
A. Always prefer the mother. Despite common concerns,
emergency trauma treatment of the pregnant woman rarely
presents an ethical conflict. When the mother is critically injured,
there is a general consensus that medical care should be targeted
toward maternal stabilization. The goal is a stable intrauterine
environment, which is optimal for development of all but the term
fetus. Thus, maternal and fetal interests generally remain aligned.
The one exception to this rule is the dilemma of somatic
support of the brain dead mother. Significant professional and
public debate has centered on this circumstance, whereupon the
treatment of the fetus may be approached independently of the
best interests or preference of the mother.19–22 In this rare and
extreme situation, decisions must be made on an individual basis
in accordance with local culture, ethical approaches, and social
norms.
More commonly, conflicts between the interests of the woman
and the fetus may arise when the mother is legally competent
(i.e., cognitively intact). Two situations in particular could be
associated with significant conflict: when the mother refuses
treatment recommended for the benefit of the fetus or is unwilling
to undergo treatment, which could benefit her yet potentially
harm the fetus.23 An example is a stable trauma patient who
refuses to undergo computed tomography (CT) imaging for fear
of teratogenesis. The latter situation is, in fact, an extension of the
dilemma facing any family doctor treating a mother who refuses
to change habits potentially damaging to the fetus (e.g., smoking,
 alcohol consumption). Regardless of the gestational age, treating
physicians tend to view the fetus as an independent medical
entity. However, this attitude remains generally unsupported by
law in most countries, which upholds the right of the pregnant
women to autonomy over her body and control of her medical
treatment.24–26

CLINICAL PEARL When the mother is critically injured, there

is a general consensus that medical care should be targeted toward
maternal stabilization. A stable intrauterine environment remains
optimal for development of all but the term fetus. Thus, maternal
and fetal interests generally remain aligned.

B. Adhere to standard care protocols. Prolonged systematic

exclusion of women from clinical trials have perpetuated existing
knowledge gaps regarding the physiologic indicators of severity
of blood loss and of impending cardiovascular collapse in this
patient population. The parameters for defining shock severity in
the general population have never been validated in the pregnant
population. This has led to a paucity of scientific data regarding
the risks and benefits of treatment protocols and medical
procedures in pregnant patients. Although a major policy shift
excluding pregnant women from clinical trials was reversed in
1990,27,28 major knowledge gaps in this field remain. Lacking
better data, current recommendations are to follow standard care
protocols that have proven lifesaving in the general population
with awareness of the limitations of these protocols in the
obstetric patient population.
C. Perform trauma surveys, a pregnancy workup, and assess
fetal viability (see Fig. 30.1). Management of maternal trauma is
driven primarily by maternal condition. A severely injured
unstable pregnant trauma patient should be treated similarly to
any other unstable trauma patient. The presence of a pregnancy
can be distracting to the trauma team29,30; thus, special attention
should be directed to completion of maternal primary (30- to 60-
second assessment of airway, breathing, circulation, and
neurologic status and Glasgow Coma Scale score) and secondary
surveys (total body inspection, palpation, and auscultation) prior
to initiation of pregnancy workup and assessment of fetal
viability. Obstetric consultation should be requested for all
pregnant patients with trauma and continuous electronic fetal
heart rate monitoring instituted. The ideal duration for fetal
monitoring has not been determined, but if maternal and fetal
abnormality has not been determined within 4 hours, then
monitoring can most likely be discontinued.11 Monitoring for 24
hours or greater is recommended for patients with mechanisms of
injury at high risk for morbidity11 (see Section VIII. Anesthetic
considerations).
CLINICAL PEARL A severely injured unstable pregnant trauma
patient should be treated similarly to any other unstable trauma
patient.

1. Pregnancy workup. Maternal pelvic examination should

 include abdominal palpation of the uterus for assessing
uterine tone, fundal height, fetal position, and sterile
speculum examination to determine if there is blood or
amniotic fluid leakage. Advanced trauma life support (ATLS)
guidelines advocate routine vaginal examination. Exclusion of
placenta previa by ultrasound should precede vaginal
examination because of the increased risk of inducing
hemorrhage. In cases of mild maternal injury, clinical
judgment has a role in determining the need to conduct
vaginal examination. Fetal condition should be monitored
only if the gestational age exceeds the limit of fetal viability.
Information regarding gestational age can be received from
the medical file or through physical examination; the uterine
fundus is palpable above the pubic crest from the second
trimester of gestation onward. Recurrent uterine contractions
suggest premature labor if accompanied by cervical change.
Excess uterine activity (>4 contractions per hour) without
cervical change suggests either placental abruption or
premature labor. A nonreassuring fetal heart rate should
always alert the clinician to the likelihood of undiagnosed
maternal injury; maternal hypotension causes uterine and fetal
hypoperfusion resulting in nonreassuring fetal heart rate
status.
2. Assessment and implications of fetal viability. Gestational
age and fetal condition should be considered when
determining the need for fetal monitoring, when considering
administration of steroids to promote fetal lung maturation,
and when deliberating delivery after initial maternal
stabilization. Ethical dilemmas surrounding the management
of neonates of borderline viability are more commonly
discussed in the delivery room than in the trauma unit.
However, the principles guiding care are the same: respect
toward parental opinions, which may differ from those of the
treating staff, placement of greater emphasis on fetal/neonatal
 condition than on gestational age after 24 weeks gestational
age, and understanding that impairment does not necessarily
equal poor quality of life.31 Premature delivery occurring at a
gestational age of less than 22 weeks will likely culminate in
fetal death. Should delivery occur at this stage, there may be a
strong preference for neonatal comfort care. When maternal
trauma occurs at a gestational age exceeding 24 weeks, there
may be a significantly greater inclination to maximize the
efforts invested in the neonate and to perform full neonatal
resuscitation.32 Regardless of gestational age, maternal
treatment should remain guided by maternal, rather than fetal,
condition. Optimizing maternal condition will also increase
the likelihood of ongoing pregnancy.

CLINICAL PEARL Regardless of gestational age, maternal

treatment should remain guided by maternal, rather than fetal,
condition. Optimizing maternal condition will also increase the
likelihood of ongoing pregnancy.

Delivery must be considered in an initially unstable

patient only if maternal instability results from a complication
of the pregnancy itself (e.g., hemorrhage from placental
abruption). Alternatively, delivery may be considered if a
potentially viable fetus (i.e., gestational age >24 weeks)
shows unresolving or intermittent signs of distress despite
maternal stability, provided that delivery will not compromise
the mother. Otherwise, the intrauterine environment is optimal
for the fetus. Antenatal steroids may be administered if there
is ongoing discussion regarding the option of early delivery. A
recent Cochrane database review concluded that “it remains
unclear whether one corticosteroid [or one particular regimen]
has advantages over another. Dexamethasone may have some
benefits compared with betamethasone such as less
 intraventricular hemorrhage . . . ”33 The evidence for
administration of vitamin D is experimental at best,34 and
there is insufficient evidence to support administration of
ambroxol.35
IV. Limitations in assessing severity of maternal injury
A. Severity of injury. Severity of injury in nonpregnant trauma
patients is commonly standardized by the use of trauma scores.
The ISS,36 new injury severity score (NISS),37 and the trauma
and injury severity score (TRISS)38 are the most commonly used
scoring methods.39 Although uterine rupture is rare in the
pregnant trauma victim, severe maternal injury may be associated
with a significantly increased risk of placental abruption. Both are
potentially life-endangering injuries. Placental abruption has been
associated with maternal mortality exceeding 50%,40 yet no
trauma score contains any reference to obstetric injury.
B. Advanced trauma life support training and use of vital signs.
ATLS training advocates use of vital signs (blood pressure, heart
rate, and respiratory rate) for clinical grading of shock severity.
The validity of this classification has been called to question in
the normal adult population41,42 and should be used even more
critically in the pregnant patient.
C. Implications of the physiologic changes of pregnancy. Cardiac
and pulmonary physiology undergo significant changes
throughout pregnancy; lowering of maternal peripheral vascular
resistance leads to a 5 to 10 mm Hg decrease in brachial systolic
blood pressure occurring from early pregnancy onward, as well as
a 5 to 25 beats per minute (bpm) increase in heart rate by the third
trimester.43 Pregnancy-induced effects on the chemoreflex
respiratory drive promote an increase in respiratory rate, creating
a physiologic state of hypocapnea.44 Although there is an overall
40% increase in total blood volume, cardiac output increases by
0.5 to 1.5 L per minute by the second trimester,43 rendering
tolerance to hemorrhage unpredictable.
 The increase in blood volume is not accompanied by an
increase in red blood cell production, resulting in a physiologic
decrease in hematocrit commonly observed in pregnant women.45
Furthermore, anemia is a common nutritional disorder in
pregnancy worldwide.46,47 Thus, baseline hemoglobin levels
below 11.0 mg per dL have been observed in up to 50% of
pregnant patients in some studies.48 Conversely, pregnancy is
accompanied by a hypercoagulable state49 and an increase in
plasma fibrinogen concentration,50 both of which may be
protective during acute hemorrhage.

CLINICAL PEARL Pregnancy is accompanied by a

hypercoagulable state and an increase in plasma fibrinogen
concentration, both of which may be protective during acute
hemorrhage.

D. Clinical assessment of patient severity. The first publications

noting inadequate tools for the clinical assessment of injury
severity in the pregnant population were the United Kingdom
Confidential Enquiries into Maternal and Child Health
(CEMACH)51,52 reports. In 2007, Swanton et al.53 surveyed 71%
of the lead obstetric UK anesthetists who responded on behalf of
their maternity units (158 out of 222). Although almost all of the
surveyed UK hospitals (96%) were using early warning scores at
this time, less than a quarter of the rezspondents (23%)
considered nonobstetric scores relevant to obstetric physiology.
Despite this, only 19% were using an obstetric early warning
score.53 In an attempt to address this issue, Carle et al.54
published a landmark paper in 2013, which described the use of
physiologic variables collected during the first 24 hours of critical
care obstetric admissions to derive a weighed obstetric early
warning score. Complex data regarding ventilation and level of
consciousness were simplified to adapt the score to the reduced
 monitoring capabilities of clinical settings in which pregnant
women were treated. The paper included a derivation cohort of
2,240 and a validation cohort of 2,200 obstetric admissions. The
authors achieved an area under the receiver operating
characteristic curve of 0.995 (95% confidence interval [CI], 0.992
to 0.998) for the statistical score and 0.957 (95% CI, 0.923 to
0.991) for the clinical score, demonstrating that clinical scores are
capable of discriminating obstetric survivors from nonsurvivors.54
Within 7 years, a repeat UK survey generating a response rate of
63% (130 per 205) demonstrated use of obstetric early warning
scores in all of the responding maternity units.55 Although
considerable data suggest that standard (in this case, ATLS) shock
categories may be inadequate for classifying the severity of
obstetric hemorrhage, similar analyses of obstetric trauma data
are still sorely missing.

CLINICAL PEARL The validity of the use of vital signs (blood

pressure, heart rate, and respiratory rate) for clinical grading of
shock severity as recommended by ATLS training has been called
into question in the normal adult population. Their use should be
viewed with an even more critical eye in the pregnant patient.

V. Principles of radiologic assessment

Radiologic imaging remains a mainstay of trauma care. Clinicians
often hesitate to order imaging studies for the pregnant patient
because of concern regarding the long-term effects of imaging on fetal
development and uncertainty regarding the impact of pregnancy on
test sensitivity. The fact that pregnant women are more likely to
sustain severe abdominal injuries than the general adult population56
creates a dilemma for the treating staff. One must always consider
whether potential maternal benefit outweighs the potential risk to the
fetus when choosing to perform imaging studies in maternal trauma.
However, there is no justification for refraining from testing when
clinically indicated.
A. Ultrasound imaging. Ultrasound imaging does not require the
use of ionizing radiation or contrast media. Thus, it is the imaging
mode of choice for pregnant women. Although laboratory studies
suggest that diagnostic levels of ultrasound can affect human
tissue,57,58 no adverse fetal effects have been associated with the
use of diagnostic ultrasound imaging in humans. B-mode, M-
mode, and 3D ultrasound imaging are not expected to result in
harmful fetal biologic effects. Conversely, Doppler imaging
requires high energy levels and focusing of the ultrasound beam
at a specific position for a prolonged period of time. The
International Society of Ultrasound in Obstetrics and Gynecology
has issued specific recommendations for the use of Doppler
imaging in pregnancy, including avoidance of pulsed Doppler
imaging in the first trimester whenever possible and use of
minimal exposure times with a displayed thermal index of 1.0 or
less.59
1. Focused assessment with sonography for trauma (FAST)
has not been studied adequately for diagnosing
nonpregnancy-related injuries in the pregnant trauma
patient.60 Although this test is often perceived to have
sensitivity and specificity similar to that observed in
nonpregnant trauma patients,61 particularly in severe injury,62
few clinicians are capable of detecting free intraperitoneal
fluid volumes smaller than 400 mL in this population. The
mean amount of detectable fluid usually exceeds 600 mL.63
The likelihood of a false negative study in the presence of an
intraabdominal amount of fluid exceeding a tenth of the total
adult blood volume should serve to caution that an initial
negative examination does not rule out the presence of
intraabdominal injury.61 Even when peritoneal fluid is
detected in this patient population, its clinical significance has
been questioned. Early studies noted that the presence of free
fluid may be physiologic in female patients of reproductive
 age who have undergone trauma, provided it is isolated to the
cul-de-sac.64 This determination has recently been refuted in a
study showing that <10% of pregnant patients without
antecedent trauma have free pelvic fluid.65 Despite this, many
authors recommend a FAST examination to evaluate for free
peritoneal fluid as a first-line diagnostic examination in
pregnant women who have sustained blunt
trauma.2,4,13,30,56,60 Regardless, ultrasound imaging in the
traumatized pregnant patient is no substitute for CT
examination; it is a significantly inferior imaging modality in
terms of injury detection.66,67
2. Fetal ultrasound can diagnose major fetal damage, such as
brain injury and decapitation in the setting of trauma.68,69
Regardless of time elapsing from the injury, fetal ultrasound is
indicated as a diagnostic adjunct when a nonreassuring fetal
status is observed during external fetal monitoring.
3. Placental abruption and uterine rupture, the two
pregnancy-related injuries that are of the greatest concern for
maternal well-being, are not easily diagnosed by ultrasound
imaging. The likelihood of a missed diagnosis of placental
abruption is very high (up to 80%), even in pregnant women
who have not sustained trauma,70,71 and there has been no
systematic study of the accuracy of ultrasonography for
diagnosing this specific injury in trauma. The diagnosis of
uterine rupture can be made in the presence of abnormal
findings, such as an empty uterus surrounded by echogenic
intraabdominal fluid (which is compatible with
hemoperitoneum).72

CLINICAL PEARL Ultrasound is the imaging mode of choice

for pregnant women because of its safety and the speed with which
it can be performed, despite limitations of its sensitivity.
B. Standard radiology and computed tomography scanning.
Standard radiology tests are considerably less informative than
CT imaging. CT imaging thus constitutes “the imaging study of
choice for narrowing the differential diagnosis and optimizing
management of the clinical condition.”73
1. Fetal risk
a. Imaging tests involving radiation may be divided into
three groups based on the degree of fetal exposure: low,
medium, and high. Cervical spine and extremity
radiography are considered low exposure tests because
they rarely require more than 0.001 mGy. Chest
radiography, which also belongs to this group, requires up
to 0.01 mGy. CT imaging of the chest belongs in the
lower range of the medium exposure group. This test
requires up to 0.66 mGy. Contrary to these less
controversial tests, lumbar spine imaging and CT imaging
of the head or neck may require up to 10 mGy, which
exceeds the recommended dose for non–life-threatening
situations. Abdominal and pelvic CT belong to the high
exposure group—these tests may require up to 35 and 50
mGy, respectively.73
b. The risk of fetal teratogenesis following exposure to
radiation is greatest during the first trimester of
pregnancy.74 Intrauterine exposure to radiation has also
been associated with an increased risk of childhood
cancer, but the precise level of risk at low doses of
exposure remains unknown.75 A typical radiologic
workup requires <50 mGy. Although this amount of
radiation may be associated with an increased risk of
childhood cancer, in absolute terms, the overall risk
remains low (1:250).73 In the past, concerns have also
been raised that in utero exposure to iodinated contrast
agents may be associated with an increased risk of fetal
hypothyroidism. However, recent studies have not
 confirmed this suspicion.76–79
2. Computed tomography imaging. CT imaging remains the
imaging of choice for diagnosis of traumatic maternal injury.
a. Diagnosis of head, spinal, and chest injuries is unaffected
by pregnancy. Abdominal and pelvic findings may be
detected despite pregnancy, but the radiologist must be
aware of the physiologic changes typically occurring from
the second semester of pregnancy onward. These may
include widening of the sacroiliac joints and pubic
symphysis, hydronephrosis, ovarian vein enlargement,
and inferior vena cava compression.80
b. CT imaging is also an excellent tool for diagnosing
placental abruption, impending abortion, and uterine
rupture. The accuracy of this imaging modality for
diagnosing placental abruption may be as high as 96%,
with a sensitivity of 86% to 100% and a specificity of
80% to 98%. Although CT imaging is not used routinely
for these indications, if performed for other maternal
reasons, evaluation should include surveillance for
placental abruption and uterine rupture81,82 because these
injuries can easily be overlooked.82 Decreased placental
enhancement on CT imaging is a strong indicator of
placental abruption.83,84 CT indicators of impending
abortion include the presence of low-lying products of
conception, products of conception in the cervix, and
blood in the cervix or vagina.85 Indicators of uterine
rupture include a through-and-through uterine wall defect,
extrauterine fetal location, and the presence of
hemoperitoneum.85–87

CLINICAL PEARL The radiologist must be aware of the

physiologic changes typically occurring from the second semester
of pregnancy onward including (1) widening of the sacroiliac joints
 and pubic symphysis, (2) hydronephrosis, (3) ovarian vein
enlargement, and (4) inferior vena cava compression.

C. Magnetic resonance imaging. The general recommendation

regarding magnetic resonance imaging (MRI) is to avoid use of
this imaging mode during the first trimester of pregnancy unless
the test result will determine maternal treatment. Although
exposure in the first trimester has not been associated with long-
term fetal sequelae, this may stem from an insufficient amount of
data concerning fetal exposure. During the second and third
trimesters, performance of an MRI does not increase the risk of
the fetus provided the dose remains <3.0 T. Experimental studies
suggest that gadolinium contrast agents do cross the placental
barrier, but this does not constitute a contraindication to use of
these agents.88 MRI is probably still underutilized in trauma for
three main reasons: the test is costly, time consuming, and
requires specialized monitoring techniques and equipment.89 This
imaging technique is well suited to detect placental trauma
because of the ability to improve tissue contrast by adapting the
pulse sequences and parameters and because it provides several
imaging planes in parallel.90 Excellent interobserver agreement
has been shown for MRI diagnosis of placental abruption.91 MRI
may also provide important information regarding the presence
and severity of fetal brain injury.92

CLINICAL PEARL The general recommendation regarding

MRI is to avoid use of this imaging mode during the first trimester
of pregnancy unless the test result will determine maternal
treatment.

VI. Clinical and test findings versus pregnancy outcome

A. Prenatal maternal injury. Prenatal maternal injury is associated
with an increased risk of adverse pregnancy outcome.14,15 Among
 the clinical predictors studied for their association with a poor
pregnancy outcome, lack of maternal belting in motor vehicles is
consistently cited.93,94 One study found that unbelted pregnant
women were almost three times more likely to experience fetal
death than belted pregnant women.1 Severe maternal injury has
also been associated with a significantly increased risk of
placental abruption, uterine rupture, and preterm labor,
particularly in the third trimester.7 A maternal ISS exceeding 25
has been associated with a 50% risk of fetal death,40 and maternal
shock also constitutes an important predictor of fetal
demise.40,95,96 Maternal pelvic fractures and loss of
consciousness, both of which contribute to a high ISS, have been
shown to be independent risk factors for adverse pregnancy
outcome.12,96
B. Minor injuries. Minor injuries considered less significant for the
general population may not be minor in the setting of pregnancy.
Fractures, dislocations, sprains, and strains are the most common
type of injury observed in pregnancy.14 Yet, minor injuries and
injuries away from the trunk may also lead to adverse pregnancy
outcomes.7 Although pregnancy outcomes worsen as the ISS
increases, the ISS remains nonpredictive for these outcomes
because they may occur with low as well as with high scores.14 In
fact, fetal demise may occur in the presence of an ISS as low as
zero.97 Although several studies have been performed in pregnant
patients after minor trauma in an attempt to identify risk factors at
admission (maternal obstetric variables, complaints, clinical
findings, lab test results, fetal heart rate monitoring, or tocometer
findings), which predict adverse pregnancy outcomes (e.g.,
placental abruption, preterm delivery, and neonatal low birth
weight), there has been little success in identifying them.15,98,99
Even in women who had sustained direct mild to moderate blunt
trauma specifically to the abdomen, no association has been
found between any of the potential predictors studied and poor
obstetric outcomes.100
CLINICAL PEARL Maternal pelvic fractures and loss of
consciousness, both of which contribute to a high ISS, have been
shown to be independent risk factors for adverse pregnancy
outcome.

C. Kleihauer-Betke testing. The Kleihauer-Betke (KB) blood test is

a qualitative assessment of the amount of fetal hemoglobin in the
maternal systemic circulation. A blood smear prepared from a
sample of maternal blood is exposed to an acid, which removes
adult hemoglobin from red blood cells. The smeared slide then
undergoes hemoglobin-staining, which results in those red blood
cells containing fetal hemoglobin appearing pink and those no
longer containing adult hemoglobin appearing as “ghosts.”
Stained cells are then counted microscopically in order to
calculate the proportion of fetal to maternal cells. The test is
generally used in Rh-negative mothers to determine the
requirement for immune prophylaxis to inhibit maternal
formation of Rh antibodies. Because the test is used to indicate
the presence of transplacental fetomaternal transfusion, it was
thought that the level of KB would indicate the presence of fetal
hemorrhage and predict an adverse pregnancy outcome in cases
of maternal trauma. Some studies suggest that KB testing may
indeed predict the risk of preterm labor after maternal trauma.99
Although elevated maternal serum α-fetoprotein exceeding 1,000
ng per mL is associated with adverse pregnancy outcomes after
MVAs,101 others have found a similar incidence of positive KB
tests in association with poor pregnancy outcomes in pregnant
women who had undergone maternal trauma. However, in women
with low-risk pregnancies, others have found no association
between positive KB results in trauma and the presence of
placental abruption or fetal distress102 or fetal or maternal
morbidity.100 The KB test may be inaccurate at least in part due to
minor variations in laboratory methodology (e.g., the pH of the
 citric acid–sodium phosphate buffer being used or incubation
time). The presence of a positive KB test alone thus does not
necessarily indicate pathologic fetal–maternal hemorrhage in
pregnant trauma patients,102 but it should prompt additional
evaluation and testing.

CLINICAL PEARL The presence of a positive KB test alone

thus does not necessarily indicate pathologic fetal–maternal
hemorrhage in pregnant trauma patients, but it should prompt
additional evaluation and testing.

D. Flow cytometry. Flow cytometry is an alternative diagnostic test

that circumvents some of the problems associated with the KB
screen.103 In this test method, red blood cells are permeabilized to
enable intracellular entrance of a specific antibody. Flow
cytometric methods that use a monoclonal anti-hemoglobin F
antibody for detecting fetal hemoglobin provide excellent
discrimination between fetal and adult red blood cells. The test
counts 50,000 cells, compared to the 2,000 counted in the KB test
and may be sensitive to as little as 0.02% of hemoglobin F cells.
However, this test requires validation in the maternal trauma
setting.
VII. Anesthetic considerations
Anesthetic management of the injured pregnant woman should be
directed toward optimizing maternal oxygenation and perfusion.
A. Airway management. The incidence of difficult/failed intubation
in obstetric anesthesia is four times higher than in the surgical
nonobstetric population.104 Difficult tracheal intubation may be
encountered in up to 5% of pregnant women.105,106 Precisely
because of the urgency of the situation during induction of
anesthesia in trauma cases, the anesthesiologist should always
approach airway management with an alternative plan in mind.
When preinduction preparation is possible, pulmonary damage
 caused by aspiration may be diminished through use of
nonparticulate antacids that neutralize acidic pH prior to
induction of anesthesia and drugs that increase the lower
esophageal sphincter tone.107 Although most trauma patients
should be considered to have a full stomach and will likely
undergo rapid sequence induction, this should not deter the
anesthesiologist from prescribing oral antacids in cases where the
patient is cooperative and there is no surgical contraindication
(e.g., obtundation due to severe traumatic brain injury, upper
gastrointestinal perforation). Tracheal intubation should be
performed using a tube with an internal diameter of 0.5 to 1 mm
smaller than that used for nonpregnant woman of similar size
(i.e., 6.5 to 7.0 mm).

CLINICAL PEARL Although most trauma patients should be

considered to have a full stomach and will likely undergo rapid
sequence induction, this should not deter the anesthesiologist from
prescribing oral antacids in cases where the patient is cooperative
and there is no surgical contraindication (e.g., obtundation due to
severe traumatic brain injury, upper gastrointestinal perforation).

One must keep in mind that hypoventilation and/or airway

obstruction may occur during maternal induction, emergence,
extubation, or recovery.108 Airway management should thus
optimally be performed by an experienced anesthesia provider.
Minute ventilation is increased by at least a third in pregnant
women compared to nonpregnant women, whereas both
functional residual capacity and expiratory reserve volume
decrease by about a third.109 The respiratory reserves of pregnant
women are thus low regardless of the presence of trauma.
Decisions regarding the timing of tracheal intubation must be
balanced between the increased likelihood of airway management
complications and the increased risk of maternal/fetal
 compromise stemming from mismatching of oxygen delivery and
consumption.
Anesthetic induction should be undertaken with efforts to avoid
vasodilation and hypotension regardless of maternal
hemodynamic status.
B. Anesthetic induction and maintenance. Rapid sequence
induction should be employed to minimize the risk of aspiration
and optimize airway visualization. Balanced anesthesia with
propofol and/or ketamine is recommended. Muscle relaxation is
best achieved with succinylcholine. If succinylcholine is
contraindicated (e.g., with burns), rocuronium may be used.
However, the clinician should be aware that the effect of this drug
is more prolonged in the pregnant population.110,111 Sugammadex
may be used to reverse rocuronium in cases of failed intubation,
but there is little to no data on the effect of sugammadex in
pregnancy. The pediatrician caring for the neonate should be
notified regarding any use of drugs which traverse the placenta
(e.g., propofol, ketamine, opiates) because these may cause
temporary neonatal respiratory depression and flaccidity.

CLINICAL PEARL Induction of anesthesia should be

undertaken with efforts to avoid vasodilation and hypotension
regardless of maternal hemodynamic status.

VIII. Specific mechanisms of injury

The anesthesiologist should be aware of the risks of specific trauma
mechanisms. Although the surgeon is often responsible for the initial
trauma workup, once the need for surgery (or lack thereof) has been
determined, surgical attention should focus on specific injuries rather
than on pregnant women as a whole. The anesthesiologist should
retain a wide perspective of the patient’s overall physiologic
condition. Because information regarding management of specific
types of trauma during pregnancy is limited, the anesthesia provider
 must be able to extrapolate from other clinical situations (e.g.,
peripartum hemorrhage) and remain open to the likelihood that
physiologic instability may result not only from overlooked and/or
untreated injuries, but also from baseline differences in physiology
stemming from the presence of pregnancy or from obstetric
complications.

CLINICAL PEARL Although the surgeon is often responsible

for the initial trauma workup, once the need for surgery (or lack
thereof) has been determined, surgical attention should focus on
specific injuries rather than on pregnant women as a whole.

A. Motor vehicle accidents. Approximately, a quarter of pregnant

trauma patients are injured in an MVA.18 Most of these injuries
(88.6%) are incurred by vehicle occupants.7 MVAs are
responsible for nearly a third of pregnancy-related maternal
deaths4 and for almost half of severe injuries during pregnancy.7
Because involvement in an MVA is the most common mode of
maternal injury, the rate of obstetric complications is relatively
well studied in this particular population. Placental abruption,
preterm delivery, and uterine rupture are potential obstetric
complications.
1. Placental abruption classically presents as painful vaginal
bleeding.
a. If a trauma patient is without neurologic deficits,
abdominal pain, severe contractions with pain
disproportionate to the degree of cervical dilation, and/or
vaginal bleeding are common symptoms. These
symptoms, and a tender and rigid uterus, are highly
suggestive of abruption. However, absence of the classic
symptoms and signs does not necessarily rule out this
complication, particularly in an obtunded patient. Of
major concern is that hemorrhage may be occult despite
 being clinically significant. In extreme cases and a
nonreassuring fetal heart rate may be an indicator of
impending maternal collapse. Fetal monitoring may
demonstrate bradycardia, prolonged decelerations, and
repetitive late decelerations.112 Because fetal heart rate
monitoring may provide early indication of maternal
distress, such monitoring should be conducted both prior
to and immediately after surgery whenever possible as
well as routinely (twice daily if possible) for the duration
of maternal admission.

CLINICAL PEARL In extreme cases of placental abruption, a

nonreassuring fetal heart rate may be an indicator of impending
maternal collapse.

b. As noted earlier, ultrasonography and the KB test are of

limited value; thus, diagnosis of abruption is made
clinically. The risk of placental abruption among women
who were involved in an MVA during pregnancy and then
delivered during the index hospitalization may be as high
as 25%. Even those who are only mildly injured and those
who are discharged from hospital and deliver at a later
date have a significantly increased risk of placental
abruption compared to the general population.8,13,113
Depending on hospital policy, the injured pregnant patient
may be admitted to one of several hospital departments.
Preoperative assessment and postoperative consults
should always include an assessment of current
hematocrit and hematocrit trends.

CLINICAL PEARL Preoperative assessment and postoperative

consults in women who are involved in an MVA during pregnancy
should always include an assessment of current hematocrit and
hematocrit trends.

c. The treatment of placental abruption should be tailored to

maternal and fetal condition. Severe abruption may cause
maternal hemodynamic instability, jeopardizing both the
mother and the fetus. In such cases, prompt delivery is
indicated. Expectant management is possible in selected
cases, provided maternal hemodynamic condition and
fetal well-being are closely monitored.114,115 Placental
abruption in the setting of MVA has been associated with
up to 40% fetal death.8

CLINICAL PEARL Severe abruption may cause maternal

hemodynamic instability, jeopardizing both the mother and the
fetus. Placental abruption in the setting of MVA has been associated
with up to 40% fetal death.

2. Preterm delivery (PTD) is defined as delivery occurring at a

gestational age of less than 37 weeks. The likelihood of PTD
is somewhat higher among women involved in an MVA
during pregnancy (adjusted relative risk 1.23; 95% CI, 1.19,
1.28).114 Immediate delivery at the time of trauma occurs in
3.5% of the cases with a gestational age greater than 20
weeks.8 PTD after maternal trauma is usually triggered by
placental abruption. Thus, it is not recommended to attempt to
arrest birth in this circumstance. Practicing clinicians should
be aware that according to the World Health Organization,
complications of PTD are the leading cause of death among
children younger than 5 years of age.116 Such deliveries
should be managed with an experienced neonatal intensive
care team at hand. Regardless of the location of the pregnant
patient with trauma, there should always be a birthing kit and
heated incubator on location. The relevant disciplines should
 be notified of the patient admission and be provided a priori
with access to the location of the mother lest unexpected early
delivery should occur.
3. Uterine rupture. Uterine rupture typically occurs with rapid
deceleration or direct compression injuries. Uterine adaptation
to pregnancy includes, among other things, a significant
increase in uterine blood flow. The fraction of cardiac output
distributed to the uterine vessels is 3.5% in early pregnancy
and 12% near term.117 Severe maternal hemodynamic
compromise may occur due to massive hemorrhage (external
and/or internal) from the ruptured uterus. One must also
consider the possibility of a mixed hemorrhage/amniotic fluid
embolism scenario. Severe fetal compromise may arise
indirectly from decreased uteroplacental perfusion (stemming
from maternal shock) and directly from total placental
abruption and loss of the protective uterine environment.
Fortunately, uterine rupture is an infrequent event, occurring
in approximately 0.3% of pregnant women involved in
MVAs4 and is mostly described in case reports.86,118,119
However, this rare complication has been implicated in 17.5%
of fetal and neonatal deaths resulting from MVAs, mostly in
association with fatal maternal injury.4

CLINICAL PEARL Uterine rupture typically occurs with rapid

deceleration or direct compression injuries. It has been implicated
in 17.5% of fetal and neonatal deaths resulting from MVAs, mostly
in association with fatal maternal injury.

B. Falls. Falls constitute the second leading cause for trauma

hospitalizations of pregnant women.18 Up to a fifth of the
pregnant women hospitalized due to trauma are injured due to a
fall,6,18,120 and more than a quarter of pregnant women (27%)
report falling at least once during their pregnancy.120 The high
 prevalence of falls during pregnancy is attributed to changes in
postural stability caused by the developing pregnancy,121,122
possibly caused by increased ankle stiffness123 and cruciate
ligament laxity.124 Anesthesia providers are thus highly likely to
encounter such cases during their career.
1. Falls rarely cause severe maternal injury or mortality14,125
but they are the most common cause of minor injuries.6 The
typical injuries resulting from a fall are fractures (47.4%),
especially of the lower extremities, contusions (18.0%), and
sprains (17.3%).126 Conversely, falls are associated with
significantly worse pregnancy outcomes. Almost a third of the
pregnant women hospitalized following a fall may deliver
during the same admission, and the proportion of women
undergoing CD is slightly higher among women with a fall
(25%) compared to those without (20%).126 Women
hospitalized after experiencing a fall had a 4.4-fold increase in
the risk of PTD, an 8.0-fold increase in the risk of placental
abruption, and a 2.1-fold increase in the risk of fetal distress
compared to pregnant women who had not undergone trauma
during pregnancy. The association with fetal death is more
controversial with some studies showing an increased risk14
and others showing no statistical difference.126

CLINICAL PEARL Falls rarely cause severe maternal injury or

mortality but they are the most common cause of minor injuries.

2. Anesthesia for minor trauma requiring surgery should be

managed similar to anesthesia for the pregnant woman for
nontrauma surgery. The degree of surgical urgency is
determined by maternal injury and condition. Pregnancy does
not make minor injury more urgent. If the mother is stable and
surgery can be postponed until the mother has undergone
appropriate preparation, this delay may be used to repeat fetal
 monitoring prior to surgery. Maintenance of maternal
hydration despite preoperative fasting is important for
prevention of early contractions.
C. Domestic violence. The proportion of pregnant women suffering
domestic violence during pregnancy is between 1% and
20%.127–130
1. Maternal consequences. There are 2.0 maternal suicides and
2.9 maternal homicides per every 100,000 live births, and
domestic violence contributes to approximately half of
these.131 More importantly, homicide constitutes the second
most common cause of trauma-related maternal deaths and
are responsible for 31% of these deaths. In comparison,
MVAs causes 44% of all maternal deaths.132 In order to avert
such outcomes, health care providers must remain alert to the
option of intentional injury and be aware of risk factors such
as minority status and teen pregnancy.132,133 Repeated injury
during pregnancy should also raise questions. Social services
should be involved in suspect cases.
2. Fetal/neonatal consequences of intentional injury during
pregnancy are not negligible either. Maternal injury from
domestic violence is associated with a 2.9- to 5.3-fold
increase in the risk of neonatal low birth weight (LBW),134,135
a 2.7-fold increase in the risk of PTD,135 and a 1.9-fold risk of
preterm premature rupture of membranes compared to women
who did not experience domestic violence.134 The offspring
of women who have undergone domestic violence during
pregnancy are also more likely to be admitted to a neonatal
intensive care unit (14.2% vs. 3.6%).136 If the mother is stable
and there is a significant risk to the neonate, appropriate
neonatal facilities and experienced neonatology staff should
be available for treating the potential newborn. If the
admitting trauma center does not have neonatal expertise,
arrangements should be made a priori for either maternal
transport (once the mother has received surgical clearance) or
 for neonatal transport.

CLINICAL PEARL Maternal injury from domestic violence is

associated with a 2.9- to 5.3-fold increase in the risk of neonatal
low birth weight (LBW), a 2.7-fold increase in the risk of PTD, and
a 1.9-fold risk of preterm premature rupture of membranes
compared to women who did not experience domestic violence.

D. Burns. All women of childbearing age admitted for treatment of

burns should undergo pregnancy testing. Case series describe an
incidence approaching 10% of positive pregnancy test
findings.137 Burns often reflect public health and social/cultural
issues; therefore, most literature regarding severe burns during
pregnancy originates from developing countries. Clinicians
treating a pregnant woman with burns must always consider the
possibility of assault and self-inflicted injury.138–142
1. Guidelines for management of burns have not been
reported for pregnant women; however, it is reasonable to
consider augmenting the fluid resuscitation to match
physiologic increases in blood volume observed during
pregnancy. A nonreassuring fetal heart rate may indicate
inadequate maternal volume repletion. Early intubation is
highly recommended in cases involving maternal inhalational
injury due to the greater likelihood of obstruction of an airway
that is already edematous secondary to the hormonal changes
of late pregnancy.143
2. Maternal mortality from burn injury increases with
increasing total body surface area (TBSA) involvement144–146
and in the presence of inhalational injury.146 Some suggest
that pregnancy is a risk factor for death,137 but this remains
controversial.147,148 Despite the presence of pregnancy,
maternal death rate may be as low as zero when TBSA is
<30%.146
CLINICAL PEARL All women of childbearing age admitted for
treatment of burns should undergo pregnancy testing. There are
series describing an incidence approaching 10% of positive
pregnancy test findings.

3. Fetal mortality also rises with increasing TBSA

involvement; when maternal TBSA exceeds 40% to 50%, the
fetal death rate approaches 100%.137,146 Some authors suggest
that if the gestational age is >24 weeks and the fetus is viable,
immediate delivery should be considered, given the near
certainty of a poor fetal outcome when maternal TBSA is
>50%.143,146 Fetal death more commonly occurs in the first
few days after injury. Decreased uterine blood flow, which
most likely represents volume under replacement, has been
associated with early fetal demise (i.e., within days of
injury).137 However, up to 20% of the women discharged
from hospital after the index admission will also lose the
pregnancy, albeit at a later stage.137

CLINICAL PEARL Decreased uterine blood flow, which most

likely represents volume under replacement, has been associated
with early fetal demise (i.e., within days of injury).

E. Penetrating injury. Approximately 10% of trauma during

pregnancy involves penetrating injury and most penetrating
injuries are inflicted by firearms.17 Penetrating injury in the first
trimester usually does not involve the fetus. At a gestational age
of approximately 12 weeks, the uterus rises above the pelvis, and
at this point, the fetus becomes vulnerable to direct injury. There
are multiple case reports of fetal injury caused by penetrating
maternal injury. Both firearms and knives may cause late, as well
as early, fetal morbidity and mortality.149–155 Maternal
 penetrating injury during the second and third trimesters carries a
higher risk of direct severe injury to the fetus than to the
mother.17 Lower abdominal penetrating injuries in particular are
more likely to lead to fetal injury than to maternal visceral injury.
This discrepancy has been attributed to the protective effect of the
enlarged uterus on the abdominal viscera.156 Fetal mortality in
maternal penetrating injury involving the abdomen has been
reported to be as high as 73%.17 Maternal mortality remains
largely unknown.

CLINICAL PEARL Maternal penetrating injury during the

second and third trimesters carries a higher risk of direct severe
injury to the fetus than to the mother.

IX. Salvage therapies

Maternal cardiovascular collapse may occur in the setting of trauma.
This circumstance may trigger one of two responses. Extracorporeal
membrane oxygenation (ECMO) may be considered in experienced
centers. This salvage therapy carries theoretical benefit to both mother
and fetus. Also, perimortem CD may be instituted for maternal
salvage if aortocaval compression (secondary to the presence of the
gravid uterus) is considered to be a major contributor to maternal
collapse. Alternatively, perimortem CD may be instituted for fetal
salvage in case of failure to resuscitate the mother.
A. Extracorporeal membrane oxygenation. According to the
Extracorporeal Life Support Organization (ELSO) practice
guidelines for the setting of adult respiratory failure, adult cardiac
failure, and adult resuscitation, pregnancy is not a
contraindication to ECMO therapy.157–159 Published cases on the
use of ECMO during pregnancy include treatment of respiratory
failure in the setting of H1N1-related pneumonia,160,161 treatment
of peripartum cardiomyopathy,162 and treatment of
thromboembolic phenomena.163–165 ECMO use for trauma is also
 increasing. This increase may be due to increased use of high-
flow techniques and heparin-coated tubing, thus averting the need
for heparinization and theoretically reducing the risk of
hemorrhage.166–169 To date, there is only one case report
describing ECMO in the setting of maternal trauma.170 ECMO
should therefore only be considered salvage therapy in the setting
of maternal trauma with refractory hypoxemia or collapse.

CLINICAL PEARL According to the ELSO practice guidelines

for the setting of adult respiratory failure, adult cardiac failure, and
adult resuscitation, pregnancy is not a contraindication to ECMO
therapy.

B. Perimortem cesarean delivery. The American Heart Association

recommends initiation of perimortem cesarean delivery (PMCD)
within 4 minutes of maternal nontraumatic resuscitation without
return of spontaneous circulation.171 A review of all published
cases of PMCD up to 2010 noted that only a minority of the
published cases had been performed following trauma (20%).172
A later case series described 91 cases of PMCD after maternal
trauma. Maternal gestational age in the latter series all exceeded
30 weeks. A third of the mothers (34%) survived to hospital
discharge, and most fetuses (81%) were liveborn.173

SUMMARY
Although 1:15 pregnant women are involved in trauma, data on maternal trauma
are lacking. Injury is usually unintentional (e.g., MVA or fall), but health care
providers must also remain alert to the option of intentional injury (i.e., domestic
violence). Appropriate trauma care of the injured pregnant woman requires a
coordinated multidisciplinary effort of professionals acting within accepted
trauma guidelines. Maternal care should be prioritized over treatment of the
fetus. A stable intrauterine environment remains optimal for all but the term
fetus. Thus, maternal and fetal interests generally remain aligned.
 Current treatment guidelines for injured pregnant women are generally in
keeping with standard trauma guidelines. The presence of a pregnancy can be
distracting to the trauma team. Therefore, attention should be directed to
completion of maternal primary and secondary surveys before initiating
pregnancy workup and assessing fetal viability. Standard ATLS shock categories
may be inadequate for classifying the severity of hemorrhage in the pregnant
population. Radiologic assessment should follow maternal indications despite
the risk of fetal teratogenesis.
Pregnancy workup includes maternal pelvic examination, and ultrasound and
vaginal examinations (except in mild trauma or placenta previa). Placental
abruption is the most common obstetric complication. Absence of typical
symptoms and signs of abruption does not necessarily rule out occult
hemorrhage from the placenta, particularly in an obtunded patient. CT imaging
and MRI can assist in diagnosing placental abruption. Premature rupture of
membranes, uterine rupture, and PTD are also possible complications. Thus,
regardless of maternal location, a birthing kit should always be kept at hand and
the relevant disciplines notified of patient location.
Fetal monitoring is indicated after maternal workup and stabilization if fetal
gestational age exceeds the limits of viability. Nonreassuring findings may
indicate either maternal instability or fetal distress. Flow cytometry may be used
to seek transplacental fetomaternal transfusion.
Delivery should be considered for maternal instability resulting from a
complication of the pregnancy itself (e.g., hemorrhage from placental abruption)
or for fetal signs of distress despite maternal stability. Antenatal steroids may be
administered if early delivery is being discussed. Anesthesia guidelines are
similar for all pregnant patients; maintenance of maternal oxygenation and
perfusion remain the primary anesthetic goals. Airway management should be
performed by an experienced operator; hypoventilation and/or airway
obstruction may occur during maternal induction, emergence, extubation, or
recovery. Surgical attention may be diverted by the presence of specific injuries.
It is therefore essential that the anesthesia provider consider the overall patient
physiology. In cases of maternal collapse, extracorporeal membrane oxygenation
using heparin-coated tubing and a high-flow technique is a viable salvage option.
PMCD should also be considered if aortocaval pressure secondary to the
presence of the gravid uterus is a major contributor to maternal hemodynamic
compromise. PMCD may also be performed for fetal salvage in cases of failure
to resuscitate the mother. Regardless of the indication, PMCD should ideally be
initiated within 4 minutes of arrest onset.

REFERENCES
1. Hyde LK, Cook LJ, Olson LM, et al. Effect of motor vehicle crashes on adverse fetal outcomes.
Obstet Gynecol. 2003;102: 279–286.
2. Mendez-Figueroa H, Dahlke JD, Vrees RA, et al. Trauma in pregnancy: an updated systematic review.
Am J Obstet Gynecol. 2013;209:1–10.
3. Fildes J, Reed L, Jones N, et al. Trauma: the leading cause of maternal death. J Trauma. 1992;32:643–
645.
4. Kvarnstrand L, Milsom I, Lekander T, et al. Maternal fatalities, fetal and neonatal deaths related to
motor vehicle crashes during pregnancy: a national population-based study. Acta Obstet Gynecol
Scand. 2008;87:946–952.
5. Weiss HB, Songer TJ, Fabio A. Fetal deaths related to maternal injury. JAMA. 2001;286:1863–1868.
6. Fischer PE, Zarzaur BL, Fabian TC, et al. Minor trauma is an unrecognized contributor to poor fetal
outcomes: a population-based study of 78,552 pregnancies. J Trauma. 2011;71:90–93.
7. Cheng HT, Wang YC, Lo HC, et al. Trauma during pregnancy: a population-based analysis of
maternal outcome. World J Surg. 2012;36:2767–2775.
8. Vivian-Taylor J, Roberts CL, Chen JS, et al. Motor vehicle accidents during pregnancy: a population-
based study. BJOG. 2012;119:499–503.
9. National Center for Injury Prevention and Control. 2011 guidelines for field triage of injured patients.
http://www.cdc.gov/fieldtriage/pdf/decisionscheme_poster_a.pdf. Accessed March 24, 2015.
10. Shah PS, Shah J. Maternal exposure to domestic violence and pregnancy and birth outcomes: a
systematic review and meta-analyses. J Womens Health (Larchmt). 2010;19:2017–2031.
11. Curet MJ, Schermer CR, Demarest GB, et al. Predictors of outcome in trauma during pregnancy:
identification of patients who can be monitored for less than 6 hours. J Trauma. 2000;49:18–24.
12. Aboutanos MB, Aboutanos SZ, Dompkowski D, et al. Significance of motor vehicle crashes and
pelvic injury on fetal mortality: a five-year institutional review. J Trauma. 2008;65:616–620.
13. Schiff MA, Holt VL. Pregnancy outcomes following hospitalization for motor vehicle crashes in
Washington State from 1989 to 2001. Am J Epidemiol. 2005;161:503–510.
14. El-Kady D, Gilbert WM, Anderson J, et al. Trauma during pregnancy: an analysis of maternal and
fetal outcomes in a large population. Am J Obstet Gynecol. 2004;190:1661–1668.
15. Weiss HB, Sauber-Schatz EK, Cook LJ. The epidemiology of pregnancy-associated emergency
department injury visits and their impact on birth outcomes. Accid Anal Prev. 2008;40:1088–1095.
16. Williams JK, McClain L, Rosemurgy AS, et al. Evaluation of blunt abdominal trauma in the third
trimester of pregnancy: maternal and fetal considerations. Obstet Gynecol. 1990;75:33–37.
17. Petrone P, Talving P, Browder T, et al. Abdominal injuries in pregnancy: a 155-month study at two
level 1 trauma centers. Injury. 2011;42:47–49.
18. Kuo C, Jamieson DJ, McPheeters ML, et al. Injury hospitalizations of pregnant women in the United
States, 2002. Am J Obstet Gynecol. 2007;196:161.e1–161.e6.
19. Farragher RA, Laffey JG. Maternal brain death and somatic support. Neurocrit Care. 2005;3:99–106.
20. Mallampalli A, Guy E. Cardiac arrest in pregnancy and somatic support after brain death. Crit Care
Med. 2005;33:S325–S331.
21. Esmaeilzadeh M, Dictus C, Kayvanpour E, et al. One life ends, another begins: management of a
brain-dead pregnant mother—a systematic review. BMC Med. 2010;8:74.
22. Mayo TW. Brain-dead and pregnant in Texas. Am J Bioeth. 2014;14:15–18.
23. Nelson LJ, Milliken N. Compelled medical treatment of pregnant women. Life, liberty, and law in
conflict. JAMA. 1988;259:1060–1066.
24. Uppal T, Pickering A, Erasmus K, et al. The legal status of the fetus in New South Wales. J Law Med.
2012;20:178–183.
25. Pinkerton JV, Finnerty JJ. Resolving the clinical and ethical dilemma involved in fetal-maternal
conflicts. Am J Obstet Gynecol. 1996;175:289–295.
26. Thampapillai D. Court-ordered obstetrical intervention and the rights of a pregnant woman. J Law
Med. 2005;12:455–461.
27. National Institutes of Health. NIH policy and guidelines on the inclusion of women and minorities as
subjects in clinical research—amended, October, 2001.
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. Accessed
February 23, 2015.
28. U.S. Food and Drug Administration. Women in clinical trials.
http://www.fda.gov/ScienceResearch/SpecialTopics/WomensHealthResearch/ucm131731.htm.
Accessed February 23, 2015.
29. Bowman M, Giles W, Deane S. Trauma during pregnancy—a review of management. Aust N Z J
Obstet Gynaecol. 1989; 29:389–393.
30. Sela HY, Weiniger CF, Hersch M, et al. The pregnant motor vehicle accident casualty: adherence to
basic workup and admission guidelines. Ann Surg. 2011;254:346–352.
31. Brunkhorst J, Weiner J, Lantos J. Infants of borderline viability: the ethics of delivery room care.
Semin Fetal Neonatal Med. 2014;19:290–295.
32. Fanaroff JM, Hascoët JM, Hansen TW, et al. The ethics and practice of neonatal resuscitation at the
limits of viability: an international perspective. Acta Paediatr. 2014;103:701–708.
33. Brownfoot FC, Gagliardi DI, Bain E, et al. Different corticosteroids and regimens for accelerating
fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2013;
(8):CD006764.
34. Lykkedegn S, Sorensen GL, Beck-Nielsen SS, et al. The impact of vitamin D on fetal and neonatal
lung maturation. A systematic review. Am J Physiol Lung Cell Mol Physiol. 2015;308:L587–L602.
35. Gonzalez Garay AG, Reveiz L, Velasco Hidalgo L, et al. Ambroxol for women at risk of preterm birth
for preventing neonatal respiratory distress syndrome. Cochrane Database Syst Rev. 2014;
(10):CD009708.
36. Baker SP, O’Neill B, Haddon W Jr, et al. The injury severity score: a method for describing patients
with multiple injuries and evaluating emergency care. J Trauma. 1974;14:187–196.
37. Osler T, Baker SP, Long W. A modification of the injury severity score that both improves accuracy
and simplifies scoring. J Trauma. 1997;43:922–925.
38. Champion HR, Sacco WJ, Hunt TK. Trauma severity scoring to predict mortality. World J Surg.
1983;7:4–11.
39. Tohira H, Jacobs I, Mountain D, et al. Systematic review of predictive performance of injury severity
scoring tools. Scand J Trauma Resusc Emerg Med. 2012;20:63.
40. Rogers FB, Rozycki GS, Osler TM, et al. A multi-institutional study of factors associated with fetal
death in injured pregnant patients. Arch Surg. 1999;134:1274–1277.
41. Guly HR, Bouamra O, Little R, et al. Testing the validity of the ATLS classification of hypovolaemic
 shock. Resuscitation. 2010;81:1142–1147.
42. Mutschler M, Nienaber U, Brockamp T, et al. A critical reappraisal of the ATLS classification of
hypovolaemic shock: does it really reflect clinical reality? Resuscitation. 2013;84:309–313.
43. Mahendru AA, Everett TR, Wilkinson IB, et al. A longitudinal study of maternal cardiovascular
function from preconception to the postpartum period. J Hypertens. 2014;32:849–856.
44. Jensen D, Duffin J, Lam YM, et al. Physiological mechanisms of hyperventilation during human
pregnancy. Respir Physiol Neurobiol. 2008;161:76–86.
45. Schoorl M, Schoorl M, van der Gaag D, et al. Effects of iron supplementation on red blood cell
hemoglobin content in pregnancy. Hematol Rep. 2012;4:e24.
46. DeMaeyer E, Adiels-Tegman M. The prevalence of anaemia in the world. World Health Stat Q.
1985;38:302–316.
47. McLean E, Cogswell M, Egli I, et al. Worldwide prevalence of anaemia, WHO vitamin and mineral
nutrition information system, 1993-2005. Public Health Nutr. 2009;12:444–454.
48. Peña-Rosas JP, De-Regil LM, Dowswell T, et al. Daily oral iron supplementation during pregnancy.
Cochrane Database Syst Rev. 2012;(12):CD004736.
49. Sharma SK, Philip J, Wiley J. Thromboelastographic changes in healthy parturients and postpartum
women. Anesth Analg. 1997;85:94–98.
50. Erez O, Novack L, Beer-Weisel R, et al. DIC score in pregnant women—a population based
modification of the International Society on Thrombosis and Hemostasis score. PLoS One.
2014;9:e93240.
51. Confidential Enquiry into Maternal and Child Health. Why Mothers Die 2000–2002. The Sixth Report
of the Confidential Enquiries into Maternal Deaths in the United Kingdom. London, United Kingdom:
RCOG Press; 2004.
52. Confidential Enquiry into Maternal and Child Health. Saving Mothers’ Lives: Reviewing Maternal
Deaths to Make Motherhood Safer 2003–2005. The Seventh Confidential Enquiry into Maternal
Deaths in the United Kingdom. London, United Kingdom: RCOG Press; 2007.
53. Swanton RD, Al-Rawi S, Wee MY. A national survey of obstetric early warning systems in the United
Kingdom. Int J Obstet Anesth. 2009;18:253–257.
54. Carle C, Alexander P, Columb M, et al. Design and internal validation of an obstetric early warning
score: secondary analysis of the Intensive Care National Audit and Research Centre Case Mix
Programme database. Anaesthesia. 2013;68:354–367.
55. Isaacs RA, Wee MY, Bick DE, et al. A national survey of obstetric early warning systems in the
United Kingdom: five years on. Anaesthesia. 2014;69:687–692.
56. Shah KH, Simons RK, Holbrook T, et al. Trauma in pregnancy: maternal and fetal outcomes. J
Trauma. 1998;45:83–86.
57. Abramowicz JS, Kossoff G, Maršál K, et al. Safety statement, 2000 (reconfirmed 2003): International
Society of Ultrasound in Obstetrics and Gynecology (ISUOG). Ultrasound Obstet Gynecol.
2003;21:100.
58. U.S. Food and Drug Administration. Ultrasound imaging: benefits/risks. http://www.fda.gov/radiation-
emittingproducts/radiationemittingproductsandprocedures/medicalimaging/ucm115357#benefitsrisks.
Accessed March 6, 2015.
59. Salvesen K, Lees C, Abramowicz J, et al. ISUOG statement on the safe use of Doppler in the 11 to 13
+ 6-week fetal ultrasound examination. Ultrasound Obstet Gynecol. 2011;37:628.
60. Svinos H. Best BETs from the Manchester Royal Infirmary. BET 1 using ultrasound to detect
peritoneal fluid in a pregnant patient with abdominal trauma. Emerg Med J. 2009;26:201–202.
61. Goodwin H, Holmes JF, Wisner DH. Abdominal ultrasound examination in pregnant blunt trauma
patients. J Trauma. 2001;50:689–693.
62. Brown MA, Sirlin CB, Farahmand N, et al. Screening sonography in pregnant patients with blunt
abdominal trauma. J Ultrasound Med. 2005;24:175–181.
63. Branney SW, Wolfe RE, Moore EE, et al. Quantitative sensitivity of ultrasound in detecting free
intraperitoneal fluid. J Trauma. 1995;39:375–380.
64. Sirlin CB, Casola G, Brown MA, et al. Use of blunt abdominal trauma: importance of free pelvic fluid
in women of reproductive age. Radiology. 2001;219:229–235.
65. Hussain ZJ, Figueroa R, Budorick NE. How much free fluid can a pregnant patient have? Assessment
of pelvic free fluid in pregnant patients without antecedent trauma. J Trauma. 2011;70:1420–1423.
66. Fleming S, Bird R, Ratnasingham K, et al. Accuracy of FAST scan in blunt abdominal trauma in a
major London trauma centre. Int J Surg. 2012;10:470–474.
67. Miller MT, Pasquale MD, Bromberg WJ, et al. Not so FAST. J Trauma. 2003;54:52–60.
68. Matsushita H, Harada A, Sato T, et al. Fetal intracranial injuries following motor vehicle accidents
with airbag deployment. J Obstet Gynaecol Res. 2014;40:599–602.
69. Aromatario M, Bottoni E, Cappelletti S, et al. Intrauterine fetal decapitation after a high-speed car
crash. Am J Forensic Med Pathol. 2015;36:6–9.
70. Glantz C, Purnell L. Clinical utility of sonography in the diagnosis and treatment of placental
abruption. J Ultrasound Med. 2002;21:837–840.
71. Elsasser DA, Ananth CV, Prasad V, et al. Diagnosis of placental abruption: relationship between
clinical and histopathological findings. Eur J Obstet Gynecol Reprod Biol. 2010;148:125–130.
72. Harrison SD, Nghiem HV, Shy K. Uterine rupture with fetal death following blunt trauma. AJR Am J
Roentgenol. 1995;165:1452.
73. Tremblay E, Thérasse E, Thomassin-Naggara I, et al. Quality initiatives: guidelines for use of medical
imaging during pregnancy and lactation. Radiographics. 2012;32:897–911.
74. Brent RL. What are the reproductive and developmental risks of ionizing radiation? In: Hales B,
Scialli A, Tassinari M, eds. Teratology Primer. 2nd ed. Philadelphia, PA: Thomas Jefferson
University; 2010:56–58.
75. Wakeford R, Little MP. Risk coefficients for childhood cancer after intrauterine irradiation: a review.
Int J Radiat Biol. 2003;79:293–309.
76. Atwell TD, Lteif AN, Brown DL, et al. Neonatal thyroid function after administration of IV iodinated
contrast agent to 21 pregnant patients. AJR Am J Roentgenol. 2008;191:268–271.
77. Kochi MH, Kaloudis EV, Ahmed W, et al. Effect of in utero exposure of iodinated intravenous contrast
on neonatal thyroid function. J Comput Assist Tomogr. 2012;36:165–169.
78. Bourjeily G, Chalhoub M, Phornphutkul C, et al. Neonatal thyroid function: effect of a single
exposure to iodinated contrast medium in utero. Radiology. 2010;256:744–750.
79. Rajaram S, Exley CE, Fairlie F, et al. Effect of antenatal iodinated contrast agent on neonatal thyroid
function. Br J Radiol. 2012;85:e238–e242.
80. Lowdermilk C, Gavant ML, Qaisi W, et al. Screening helical CT for evaluation of blunt traumatic
injury in the pregnant patient. Radiographics. 1999;19:S243–S255.
81. Manriquez M, Srinivas G, Bollepalli S, et al. Is computed tomography a reliable diagnostic modality
in detecting placental injuries in the setting of acute trauma? Am J Obstet Gynecol. 2010;202:611.e1–
611.e5.
82. Wei SH, Helmy M, Cohen AJ. CT evaluation of placental abruption in pregnant trauma patients.
Emerg Radiol. 2009;16: 365–373.
83. Kopelman TR, Berardoni NE, Manriquez M, et al. The ability of computed tomography to diagnose
placental abruption in the trauma patient. J Trauma Acute Care Surg. 2013;74:236–241.
84. Saphier NB, Kopelman TR. Traumatic Abruptio Placenta Scale (TAPS): a proposed grading system of
computed tomography evaluation of placental abruption in the trauma patient. Emerg Radiol.
 2014;21:17–22.
85. Raptis CA, Mellnick VM, Raptis DA, et al. Imaging of trauma in the pregnant patient. Radiographics.
2014;34:748–763.
86. Fusco A, Kelly K, Winslow J. Uterine rupture in a motor vehicle crash with airbag deployment. J
Trauma. 2001;51:1192–1194.
87. Dash N, Lupetin AR. Uterine rupture secondary to trauma: CT findings. J Comput Assist Tomogr.
1991;15:329–331.
88. Patenaude Y, Pugash D, Lim K, et al. The use of magnetic resonance imaging in the obstetric patient. J
Obstet Gynaecol Can. 2014;36:349–363.
89. Bergese SD, Puente EG. Anesthesia in the intraoperative MRI environment. Neurosurg Clin N Am.
2009;20:155–162.
90. Masselli G, Gualdi G. MR imaging of the placenta: what a radiologist should know. Abdom Imaging.
2013;38:573–587.
91. Masselli G, Brunelli R, Di Tola M, et al. MR imaging in the evaluation of placental abruption:
correlation with sonographic findings. Radiology. 2011;259:222–230.
92. Banović V, Škrablin S, Banović M, et al. Fetal brain magnetic resonance imaging and long-term
neurodevelopmental impairment. Int J Gynaecol Obstet. 2014;125:237–240.
93. Luley T, Fitzpatrick CB, Grotegut CA, et al. Perinatal implications of motor vehicle accident trauma
during pregnancy: identifying populations at risk. Am J Obstet Gynecol. 2013;208:466.e1–466.e5.
94. Klinich KD, Flannagan CA, Rupp JD, et al. Fetal outcome in motor-vehicle crashes: effects of crash
characteristics and maternal restraint. Am J Obstet Gynecol. 2008;198:450.e1–450.e9.
95. Baerga-Varela Y, Zietlow SP, Bannon MP, et al. Trauma in pregnancy. Mayo Clin Proc.
2000;75:1243–1248.
96. Kissinger DP, Rozycki GS, Morris JA Jr, et al. Trauma in pregnancy. Predicting pregnancy outcome.
Arch Surg. 1991;126: 1079–1086.
97. Poole GV, Martin JN Jr, Perry KG Jr, et al. Trauma in pregnancy: the role of interpersonal violence.
Am J Obstet Gynecol. 1996;174:1873–1877.
98. Garmi G, Marjieh M, Salim R. Does minor trauma in pregnancy affect perinatal outcome? Arch
Gynecol Obstet. 2014;290: 635–641.
99. Muench MV, Baschat AA, Reddy UM, et al. Kleihauer-betke testing is important in all cases of
maternal trauma. J Trauma. 2004;57:1094–1098.
100. Dahmus MA, Sibai BM. Blunt abdominal trauma: are there any predictive factors for abruptio
placentae or maternal-fetal distress? Am J Obstet Gynecol. 1993;169:1054–1059.
101. Tanizaki S, Maeda S, Matano H, et al. Elevated maternal serum α-fetoprotein after minor trauma
during pregnancy may predict adverse fetal outcomes. J Trauma Acute Care Surg. 2014;77:510–513.
102. Dhanraj D, Lambers D. The incidences of positive Kleihauer-Betke test in low-risk pregnancies and
maternal trauma patients. Am J Obstet Gynecol. 2004;190:1461–1463.
103. Wylie BJ, D’Alton ME. Fetomaternal hemorrhage. Obstet Gynecol. 2010;115:1039–1051.
104. Suresh M, Wali A. Failed intubation in obstetrics—airway management strategies. Anesthesiol Clin
North Am. 1998;16:477–498.
105. McKeen DM, George RB, O’Connell CM, et al. Difficult and failed intubation: incident rates and
maternal, obstetrical, and anesthetic predictors. Can J Anaesth. 2011;58:514–524.
106. McDonnell NJ, Paech MJ, Clavisi OM, et al. Difficult and failed intubation in obstetric anaesthesia: an
observational study of airway management and complications associated with general anaesthesia for
caesarean section. Int J Obstet Anesth. 2008;17:292–297.
107. Paranjothy S, Griffiths JD, Broughton HK, et al. Interventions at caesarean section for reducing the
risk of aspiration pneumonitis. Cochrane Database Syst Rev. 2014;(2):CD004943.
108. Peterson GN, Domino KB, Caplan RA, et al. Management of the difficult airway: a closed claims
analysis. Anesthesiology. 2005;103:33–39.
109. McAuliffe F, Kametas N, Costello J, et al. Respiratory function in singleton and twin pregnancy.
BJOG. 2002;109:765–769.
110. Pühringer FK, Sparr HJ, Mitterschiffthaler G, et al. Extended duration of action of rocuronium in
postpartum patients. Anesth Analg. 1997;84:352–354.
111. Gin T, Chan MT, Chan KL, et al. Prolonged neuromuscular block after rocuronium in postpartum
patients. Anesth Analg. 2002;94:686–689.
112. Usui R, Matsubara S, Ohkuchi A, et al. Fetal heart rate pattern reflecting the severity of placental
abruption. Arch Gynecol Obstet. 2008;277:249–253.
113. Vladutiu CJ, Marshall SW, Poole C, et al. Adverse pregnancy outcomes following motor vehicle
crashes. Am J Prev Med. 2013;45:629–636.
114. Bond AL, Edersheim TG, Curry L, et al. Expectant management of abruptio placentae before 35
weeks gestation. Am J Perinatol. 1989;6:121–123.
115. Combs CA, Nyberg DA, Mack LA, et al. Expectant management after sonographic diagnosis of
placental abruption. Am J Perinatol. 1992;9:170–174.
116. World Health Organization. Preterm birth. http://www.who.int/mediacentre/factsheets/fs363/en/.
Accessed March 10, 2015.
117. Thaler I, Manor D, Itskovitz J, et al. Changes in uterine blood flow during human pregnancy. Am J
Obstet Gynecol. 1990;162:121–125.
118. Enakpene CA, Ayinde OA, Omigbodun AO. Incomplete uterine rupture, following blunt trauma to the
abdomen: a case report. Niger J Clin Pract. 2005;8:60–62.
119. van Enk A, van Zwam W. Uterine rupture. A seat belt hazard. Acta Obstet Gynecol Scand.
1994;73:432–433.
120. Dunning K, Lemasters G, Bhattacharya A. A major public health issue: the high incidence of falls
during pregnancy. Matern Child Health J. 2010;14:720–725.
121. McCrory JL, Chambers AJ, Daftary A, et al. Dynamic postural stability in pregnant fallers and non-
fallers. BJOG. 2010; 117:954–962.
122. Inanir A, Cakmak B, Hisim Y, et al. Evaluation of postural equilibrium and fall risk during pregnancy.
Gait Posture. 2014; 39:1122–1125.
123. Ersal T, McCrory JL, Sienko KH. Theoretical and experimental indicators of falls during pregnancy as
assessed by postural perturbations. Gait Posture. 2014;39:218–223.
124. Charlton WP, Coslett-Charlton LM, Ciccotti MG. Correlation of estradiol in pregnancy and anterior
cruciate ligament laxity. Clin Orthop Relat Res. 2001;387:165–170.
125. Schiff MA, Holt VL, Daling JR. Maternal and infant outcomes after injury during pregnancy in
Washington State from 1989 to 1997. J Trauma. 2002;53:939–945.
126. Schiff M. Pregnancy outcomes following hospitalization for a fall in Washington State from 1987 to
2004. BJOG. 2008;115:1648–1654.
127. Bowen E, Heron J, Waylen A, et al. Domestic violence risk during and after pregnancy: findings from
a British longitudinal study. BJOG. 2005;112:1083–1089.
128. Stewart DE, Cecutti A. Physical abuse in pregnancy. CMAJ. 1993;149:1257–1263.
129. Devries KM, Kishor S, Johnson H, et al. Intimate partner violence during pregnancy: analysis of
prevalence data from 19 countries. Reprod Health Matters. 2010;18:158–170.
130. Johnson JK, Haider F, Ellis K, et al. The prevalence of domestic violence in pregnant women. BJOG.
2003;110:272–275.
131. Palladino CL, Singh V, Campbell J, et al. Homicide and suicide during the perinatal period: findings
from the National Violent Death Reporting System. Obstet Gynecol. 2011;118:1056–1063.
132. Chang J, Berg CJ, Saltzman LE, et al. Homicide: a leading cause of injury deaths among pregnant and
postpartum women in the United States, 1991–1999. Am J Public Health. 2005;95:471–477.
133. Krulewitch CJ, Pierre-Louis ML, de Leon-Gomez R, et al. Hidden from view: violent deaths among
pregnant women in the District of Columbia, 1988–1996. J Midwifery Womens Health. 2001;46:4–10.
134. Abdollahi F, Abhari FR, Delavar MA, et al. Physical violence against pregnant women by an intimate
partner, and adverse pregnancy outcomes in Mazandaran Province, Iran. J Family Community Med.
2015;22:13–18.
135. Wiencrot A, Nannini A, Manning SE, et al. Neonatal outcomes and mental illness, substance abuse,
and intentional injury during pregnancy. Matern Child Health J. 2012;16:979–988.
136. Jagoe J, Magann EF, Chauhan SP, et al. The effects of physical abuse on pregnancy outcomes in a
low-risk obstetric population. Am J Obstet Gynecol. 2000;182:1067–1069.
137. Masoodi Z, Ahmad I, Khurram F, et al. Pregnancy in burns: maternal and fetal outcome. Indian J
Burns. 2012;20:36–41.
138. Schubert W, Ahrenholz DH, Solem LD. Burns from hot oil and grease: a public health hazard. J Burn
Care Rehabil. 1990;11:558–562.
139. Lama BB, Duke JM, Sharma NP, et al. Intentional burns in Nepal: a comparative study. Burns.
2015;41:1306–1314. doi: 10.1016/j.burns.2015.01.006.
140. Peck MD. Epidemiology of burns throughout the World. Part II: intentional burns in adults. Burns.
2012;38:630–637.
141. Masoodi Z, Ahmad I, Yousuf S. Routine use of urinary hCG test in adult burn females to detect
“hidden” pregnancies: a review. Burns. 2013;39:803–807.
142. Maghsoudi H, Pourzand A, Azarmir G. Etiology and outcome of burns in Tabriz, Iran. An analysis of
2963 cases. Scand J Surg. 2005;94:77–81.
143. Pacheco LD, Gei AF, VanHook JW, et al. Burns in pregnancy. Obstet Gynecol. 2005;106:1210–1212.
144. Karimi H, Momeni M, Rahbar, H. Burn injuries during pregnancy in Iran. Int J Gynaecol Obstet.
2009;104:132–134.
145. Rezavand N, Seyedzadeh A, Soleymani A. Evaluation of maternal and foetal outcomes in pregnant
women hospitalized in Kermanshah Hospitals, Iran, owing to burn injury, 2003-2008. Ann Burns Fire
Disasters. 2012;25:196–199.
146. Maghsoudi H, Samnia R, Garadaghi A, et al. Burns in pregnancy. Burns. 2006;32:246–250.
147. Akhtar MA, Mulawkar PM, Kulkarni HR. Burns in pregnancy: effect on maternal and fetal outcomes.
Burns. 1994;20:351–355.
148. Jain ML, Garg AK. Burns with pregnancy—a review of 25 cases. Burns. 1993;19:166–167.
149. Gun F, Erginel B, Günendi T, et al. Gunshot wound of the fetus. Pediatr Surg Int. 2011;27:1367–1369.
150. Pasley JD, Demetriades D. Penetrating fetal trauma with late complications: a case report. J Pediatr
Surg. 2012;47:E9–E11.
151. Carugno JA, Rodriguez A, Brito J, et al. Gunshot wound to the gravid uterus with non-lethal fetal
injury. J Emerg Med. 2008;35:43–45.
152. Sakala EP, Kort DD. Management of stab wounds to the pregnant uterus: a case report and a review of
the literature. Obstet Gynecol Surv. 1988;43:319–324.
153. Shehu BB, Ismail NJ, Hassan I, et al. Fetal head injury from intentional penetrating abdominal trauma
in pregnancy. Ann Trop Paediatr. 2010;30:69–72.
154. Gallo P, Mazza C, Sala F. Intrauterine head stab wound injury resulting in a growing skull fracture: a
case report and literature review. Childs Nerv Syst. 2010;26:377–384.
155. Muzumdar D, Higgins MJ, Ventureyra EC. Intrauterine penetrating direct fetal head trauma following
gunshot injury: a case report and review of the literature. Childs Nerv Syst. 2006;22:398–402.
156. Awwad JT, Azar GB, Seoud MA, et al. High-velocity penetrating wounds of the gravid uterus: review
 of 16 years of civil war. Obstet Gynecol. 1994;83:259–264.
157. Extracorporeal Life Support Organization. Guidelines for adult respiratory failure.
https://www.elso.org/Portals/0/IGD/Archive/FileManager/989d4d4d14cusersshyerdocumentselsoguidelinesforadultresp
Accessed March 15, 2015.
158. Extracorporeal Life Support Organization. Guidelines for adult cardiac failure.
https://www.elso.org/Portals/0/IGD/Archive/FileManager/e76ef78eabcusersshyerdocumentselsoguidelinesforadultcardi
Accessed March 15, 2015.
159. Extracorporeal Life Support Organization. Guidelines for ECPR cases.
https://www.elso.org/Portals/0/IGD/Archive/FileManager/6713186745cusersshyerdocumentselsoguidelinesforecprcases
Accessed March 15, 2015.
160. Nair P, Davies AR, Beca J, et al. Extracorporeal membrane oxygenation for severe ARDS in pregnant
and postpartum women during the 2009 H1N1 pandemic. Intensive Care Med. 2011;37:648–654.
161. Robertson LC, Allen SH, Konamme SP, et al. The successful use of extra-corporeal membrane
oxygenation in the management of a pregnant woman with severe H1N1 2009 influenza complicated
by pneumonitis and adult respiratory distress syndrome. Int J Obstet Anesth. 2010;19:443–447.
162. Smith IJ, Gillham MJ. Fulminant peripartum cardiomyopathy rescue with extracorporeal membranous
oxygenation. Int J Obstet Anesth. 2009;18:186–188.
163. Weinberg L, Kay C, Liskaser F, et al. Successful treatment of peripartum massive pulmonary
embolism with extracorporeal membrane oxygenation and catheter-directed pulmonary thrombolytic
therapy. Anaesth Intensive Care. 2011;39:486–491.
164. Leeper WR, Valdis M, Arntfield R, et al. Extracorporeal membrane oxygenation in the acute treatment
of cardiovascular collapse immediately post-partum. Interact Cardiovasc Thorac Surg. 2013;17:898–
899.
165. Arlt M, Philipp A, Iesalnieks I, et al. Successful use of a new hand-held ECMO system in
cardiopulmonary failure and bleeding shock after thrombolysis in massive post-partal pulmonary
embolism. Perfusion. 2009;24:49–50.
166. Biderman P, Einav S, Fainblut M, et al. Extracorporeal life support in patients with multiple injuries
and severe respiratory failure: a single-center experience? J Trauma Acute Care Surg. 2013;75:907–
912.
167. Wen PH, Chan WH, Chen YC, et al. Non-heparinized ECMO serves a rescue method in a multitrauma
patient combining pulmonary contusion and nonoperative internal bleeding: a case report and
literature review. World J Emerg Surg. 2015;10:15.
168. Zhou R, Liu B, Lin K, et al. ECMO support for right main bronchial disruption in multiple trauma
patient with brain injury—a case report and literature review. Perfusion. 2015;30:403–406.
169. Muellenbach RM, Redel A, Küstermann J, et al. Extracorporeal membrane oxygenation and severe
traumatic brain injury. Is the ECMO-therapy in traumatic lung failure and severe traumatic brain
injury really contraindicated? Anaesthesist. 2011;60:647–652.
170. Plotkin JS, Shah JB, Lofland GK, et al. Extracorporeal membrane oxygenation in the successful
treatment of traumatic adult respiratory distress syndrome: case report and review. J Trauma.
1994;37:127–130.
171. Vanden Hoek TL, Morrison LJ, Shuster M, et al. Part 12: cardiac arrest in special situations: 2010
American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency
Cardiovascular Care. Circulation. 2010;122:S829–S861.
172. Einav S, Kaufman N, Sela HY. Maternal cardiac arrest and perimortem caesarean delivery: evidence
or expert-based? Resuscitation. 2012;83:1191–1200.
173. Chibber R, Al-Harmi J, Fouda M, et al. Motor-vehicle injury in pregnancy and subsequent feto-
maternal outcomes: of grave concern. J Matern Fetal Neonatal Med. 2015;28:399–402.
 Management of the Opioid Dependent Parturient
Jessica L. Young, Ellen M. Lockhart, and Curtis L. Baysinger

I. Introduction
II. Obstetric management
A. Risks of opioid dependence in pregnancy
B. Identification
C. Treatment
D. Chronic pain in pregnancy
E. Peripartum obstetric management
III. Neonatal abstinence syndrome
A. Definition and incidence
B. Symptoms
C. Diagnosis
D. Risk factors
E. Treatment of neonatal abstinence syndrome
IV. Pain management during the peripartum period
A. Opioid tolerance
B. Baseline long-acting opioid maintenance
C. Pain management for labor and delivery
D. Anesthetic management of cesarean delivery
E. Postcesarean delivery analgesia
Summary


KEYPOINTS
1. Opioid dependent (OD) parturients should have long-acting opioid
therapy either instituted or maintained during pregnancy because it
improves obstetric outcomes. Acute detoxification is not recommended.
2. Postdelivery breastfeeding is safe and should be encouraged.
3. Pain management is complicated by opioid tolerance, hyperalgesia to
sensory stimuli, psychosocial issues, and possible use of other illicit
substances.
4. Neuraxial analgesia for labor and vaginal delivery is safe and effective
when similar doses of local anesthetics are used in OD women compared
to non-OD women.
5. The therapeutic window between analgesia and respiratory depression of
acutely administered opioids may be narrowed in OD women. Tolerance
to other side effects of opioid therapy does not imply a decrease in risk of
respiratory depression.
6. Treatment of pain after cesarean delivery should employ a multimodal
approach to pain control including division of daily maintenance opioid
into several doses and non-opioid analgesics.

I. Introduction
Opioid use has increased dramatically among women of childbearing
age over the past 15 years, with a concomitant rise in OD parturients
who present for labor and delivery. Nonmedical use of prescription
opioids and opioid-related deaths tripled between 1999 and 2010 (see
Fig. 31.1). Recent reports cite that more than 12% of parturients with
commercial insurance were prescribed opioids during their pregnancy
in 2011 (see Fig. 31.2) with an increase of 5% between 2000 and
2007; among parturients on Medicaid, this increase was nearly 20%.
Neonatal abstinence syndrome (NAS) has increased proportionately
as well. Parturients who take opioids chronically pose obstetric and
social challenges to all obstetric care providers.
 II. Obstetric management (see Fig. 31.3)
A. Risks of opioid dependence in pregnancy
1. Opioid dependence in pregnancy is associated with poor
maternal and fetal outcomes including miscarriage, preterm
labor, preterm delivery, premature rupture of membranes,
intrauterine growth restriction, and NAS.
2. Withdrawal symptoms during pregnancy can be dangerous for
 the fetus because it causes maternal tachycardia,
hypertension, decreased placental perfusion, and uterine
contractions.1
3. Women in the cycle of intoxication and withdrawal are at
higher risk for intrauterine growth restriction, insufficient
nutrition, or exposure to illicit opioids such as heroin.
4. Rates of infectious disease, such as hepatitis C, are higher in
this population.2,3
5. Due to a combination of psychosocial risk factors, this patient
population is at risk for delayed or inadequate prenatal care.
6. Poor fetal outcomes and increased risk of neonatal abstinence
can be attributed to the concurrent use of other substances
including tobacco, alcohol, benzodiazepines, and other illicit
drugs.4–6
7. Concurrent psychiatric disorders are also common in this
population, with one 2010 study reporting up to 65% of these
patients have symptoms of mental illness.7
8. Opioids are not thought to be teratogenic, particularly with
short-term use.
a. Most large retrospective studies have shown no
association between opioid exposure and congenital
anomalies8; however, one retrospective study suggests an
association between codeine exposure in the first trimester
and cleft palate, cardiac defects, and pyloric stenosis.9
b. More recently, the 2011 National Birth Defects
Prevention Study showed an association between cardiac,
spinal, and abdominal wall defects with opioid exposure
in the first trimester, but these results have not been
replicated.10

CLINICAL PEARL Opioid dependency during pregnancy is

associated with poorer obstetric and neonatal outcomes due to
increased rates of viral and nonviral infectious disease, opioid
withdrawal, use of illicit substances, and less prenatal care. Opioid
dependency is aggravated in many cases by concomitant maternal
psychiatric illness.

B. Identification. Identification of the OD woman early in

pregnancy is important for early treatment, education, and
intervention.
1. The American College of Obstetricians and Gynecologists
(ACOG) suggests that all pregnant women be screened for
substance abuse with a validated screening tool such as 4P’s
Plus or the Car, Relax, Alone, Forget, Friends, Trouble
(CRAFFT) screening questionnaires.11–14
2. Universal urine drug testing is not recommended during
pregnancy because of informed consent issues and testing
limitations.
3. Urine drug testing can be a valuable tool to measure
adherence to a treatment plan, if done with transparency and
consent.15
4. Prior to ordering toxicology screening, the provider should be
familiar with the scope and limitations of the available tests,
including the metabolites of commonly abused drugs and
medications that cause false-positive results.
5. Once identified as OD, a patient should be educated about the
risks of opioid dependence in pregnancy and referred to an
addiction treatment program.

CLINICAL PEARL All pregnant women should be screened for

opioid use using validated screening tools; the use of screening
urinalysis is not recommended.

C. Treatment. Maintenance therapy with methadone or

buprenorphine is the standard of care for treatment of opioid
addiction in pregnancy.
1. Methadone maintenance has been the standard of care for the
treatment of opioid addiction in pregnancy for decades.
a. Women on methadone maintenance are more likely to
attend prenatal visits, have improved obstetrical
outcomes, and are less likely to have children placed in
foster care.15
b. There is evidence that methadone maintenance reduces
the risk of NAS 50% to 75%.16
c. Disadvantages of methadone maintenance therapy include
cost, requirements of daily visits to a licensed treatment
facility, and social stigma.
2. Buprenorphine is a μ-opioid receptor agonist which is also
being used for treatment of opioid dependence during
pregnancy.
a. In the Maternal Opioid Treatment: Human Experimental
Research (MOTHER) trial, women treated with
buprenorphine were shown to have comparable outcomes
in the treatment of opioid dependence to those women
receiving methadone.17
b. The advantages to buprenorphine are that it is an office-
based treatment and is often covered by insurance.
c. The symptoms of NAS in babies exposed to
buprenorphine may be less severe.17
d. Due to its high affinity for the μ-opioid receptor,
buprenorphine cannot be administered to someone who
has recently used other opioids because it might
precipitate withdrawal symptoms.18
3. Detoxification is generally not recommended during
pregnancy.
a. The risk of relapse during pregnancy is high following
detoxification. One retrospective study showed that
inpatient detoxification was initially successful in 53 of
95 addicted women, but 45% of those women relapsed.15
b. If not done carefully, detoxification can trigger
 withdrawal symptoms leading to preterm labor or
premature delivery.18,19
c. The average length of inpatient stay for the women who
are successfully detoxified is about 25 days.20

CLINICAL PEARL Opioid-addicted women should receive

long-acting opioid maintenance therapy because it is associated
with better obstetric and neonatal outcomes; detoxification from
opioid use should be discouraged.

D. Chronic pain in pregnancy. Chronic pain in pregnancy

requiring opioid therapy may be managed using a patient’s
current regimen as long as there is no sign of abuse or addiction.
1. There is limited data but a few studies suggest that NAS is
less common in this population with an incidence of 11% to
38%.17,21
2. Treatment plans must be individualized with consideration of
maternal quality of life, fetal risks, and patient goals.
3. Opioid therapy in these instances should not be stopped
abruptly but instead tapered if detoxification is appropriate.
E. Peripartum obstetric management. Peripartum obstetric
management itself in OD women does not differ appreciably
from that of non-OD women.
1. Serial ultrasounds are recommended after 24 weeks of
gestation to monitor fetal growth.22
2. There is no evidence to support additional antenatal testing
without other pregnancy-related risk factors.
3. The frequency of routine visits may be increased in order to
monitor adherence to addiction treatment.
4. Delivery plans do not need to be altered if the patient is stable
in treatment.

CLINICAL PEARL Obstetric management of OD women

 should be the same as in non-OD women.

III. Neonatal abstinence syndrome

A. Definition and incidence
1. NAS appears after the sudden discontinuation of
transplacental opioids at birth and represents neonatal
dependence.
2. Symptoms are noted in approximately 50% to 80% of opioid-
exposed neonates after birth.23–25
3. If left untreated, NAS can result in seizures and death.25,26
B. Symptoms
1. Symptoms reflect central nervous system, gastrointestinal,
and autonomic nervous system dysfunction and can indicate
the severity of withdrawal and need for treatment.
2. Symptoms include high-pitched cry, feeding difficulties,
tremors and hypertonia, sweating, fever, and tachypnea.
C. Diagnosis
1. The American Academy of Pediatrics (AAP) recommends the
use of an assessment tool such as the Finnegan Neonatal
Abstinence Scoring Tool (FNAST).27
2. Maternal history and drug testing and fetal urine and
meconium testing can also be useful.
3. Decisions regarding treatment are based on a cumulative
threshold score.27 For example, two or more consecutive
FNAST scores of 8 or 9 is a common indicator for
intervention.28
4. Breastfeeding lowers the incidence of NAS and leads to
shorter duration of treatment in infants with NAS.29

CLINICAL PEARL Breastfeeding is encouraged in women who

are opioid dependent because it reduces the incidence of NAS.

D. Risk factors
 1. The dose of methadone does not influence the rate of NAS
diagnosis but does affect its severity and the need for
treatment.30–32
2. Preterm birth does not influence the odds of the infant
receiving treatment.
3. Timing and mode of delivery as well as timing of the last
maternal methadone dose are significant risk factors for the
development of NAS requiring treatment.24
4. The need for pharmacologic therapy is affected by genetics,
other drug exposures, gestational age, breastfeeding, and
maternal rooming-in.28
5. Maternal buprenorphine use may reduce the incidence and
severity of NAS when compared to other opioids.17
E. Treatment of neonatal abstinence syndrome
1. Pharmacologic intervention is required for 50% to 70% of
infants with NAS who demonstrate escalating symptoms.
2. Once symptoms resolve, treatment can be weaned over a
period of days to weeks.33
3. Methadone and morphine are most commonly used to treat
NAS.
4. The efficacy of clonidine has not been proven, but can be
used as an adjuvant to other therapies.27
5. Barbiturates and benzodiazepines have been used but are not
currently recommended as primary agents.27
6. The use of naloxone is contraindicated because it may induce
neonatal seizures.27

CLINICAL PEARL NAS probably affects nearly all of the

newborn offspring of OD mothers. Increasing severity of symptoms
on repeat assessment tests (e.g., FNAST) necessitates treatment
with a long-acting opioid.

IV. Pain management during the peripartum period (see Fig. 31.3)
A. Opioid tolerance. Opioid tolerance, opioid hyperalgesia,
physical dependence with risk of withdrawal, and concomitant
use of illegal drugs create challenges to effective pain
management.
1. Women with opioid dependence exhibit hypersensitivity to
pain stimuli such as cold pressor tests and electrical
stimulation.34
2. Opioid tolerance is thought to be due to opioid receptor
downregulation and decreases in central glutamate receptor
activity (i.e., decreased antinociception). Opioid-induced
hypersensitization is due to increased N-methyl-D-aspartate
receptor activity. In addition, there are increases in spinal cord
dynorphin concentrations (i.e., increased pronocioception).
Both mechanisms result in an increase in the amount of opioid
required to achieve a given level of pain control.34
3. Studies of peripartum pain management are limited. Hence,
any recommendations for pain management in OD pregnant
women are based on reports from nonpregnant women with
opioid dependence who have undergone anesthesia and
surgery. Although these reports commonly measure changes
in opioid use, the results may not be applicable in the OD
patient (see Table 31.1).
CLINICAL PEARL Clinical studies to guide pain control during
the peripartum period are virtually nonexistent in OD patients.
Guidelines for management can be extrapolated from studies in
nonpregnant surgical patients and non-OD parturients.
 B. Baseline long-acting opioid maintenance. The baseline opioid
consumed by the OD parturient should be continued through the
peripartum period. Use of mixed agonist/antagonist opioids
may precipitate withdrawal and are to be avoided.35
1. Once daily dosing of long-acting opioids prevents withdrawal,
but dividing daily doses of methadone and buprenorphine into
6 to 8 hour intervals will improve the quality of analgesia.36
2. Small doses of methadone and buprenorphine are often
effective in opioid-naive surgical patients, but even the large
doses commonly seen in OD patients may be inadequate after
cesarean delivery in a woman with opioid dependence.
C. Pain management for labor and delivery37,38
1. Studies of pain management and neuraxial analgesia in
laboring women with opioid dependence are lacking.
2. Neuraxial techniques commonly used in women without
opioid dependence are likely to be effective in most women
with opioid dependence because local anesthetic efficacy is
not affected.34
3. Opioid requirements for analgesia after vaginal delivery have
not been shown to be significantly increased in OD
women.37,38
4. Use of non-opioid analgesics following vaginal delivery
should be similar to that used in parturients without opioid
dependence.37,38

CLINICAL PEARL The baseline dose of long-acting opioid

should be continued during labor and delivery. Women with opioid
dependence who undergo vaginal delivery will require similar doses
of opioid after delivery as women without opioid dependence, if
non-opioid analgesics are administered.

D. Anesthetic management of cesarean delivery

1. Studies that have compared general versus neuraxial
 anesthesia in OD parturients have not been reported.
2. Neuraxial anesthesia is the technique of choice in OD women,
for the same reasons in women without opioid dependence.
3. Combined spinal-epidural and epidural alone catheter
techniques may be considered for neuraxial analgesia. Either
technique may be helpful if other methods of pain control are
ineffective.
E. Postcesarean delivery analgesia
1. Use of opioids
a. Studies by Meyer et al.37,38 suggest that oxycodone
consumption is 70% higher in parturients on chronic
methadone and 50% higher in women taking
buprenorphine. This is similar to data reported in surgical
nonpregnant patients with opioid dependence.39
b. The risk of respiratory depression may be increased in
nonpregnant women with opioid dependence. Tolerance
to respiratory depression cannot be inferred from
tolerance to other opioid side effects (pruritus, nausea,
vomiting). The doses required for analgesia may approach
that associated with apnea. Moderate to severe
postoperative sedation approaches 50% in patients with
opioid dependence compared with 19% in opioid-naive
patients, despite having higher pain scores.39
c. Titration of opioids to pain scores after cesarean delivery
should not be relied on because the increased respiratory
drive associated with pregnancy may not protect against
respiratory depression.40

CLINICAL PEARL Opioid requirements after cesarean delivery

are approximately 50% to 70% greater in OD women compared to
women without opioid dependence, when using a multimodal
approach for pain relief. The risk of respiratory depression may be
greater in OD women if titration to pain score is used to determine
optimum therapy.

2. Transversus abdominis plane (TAP) block and other

peripheral nerve blocks have not been studied for
postcesarean delivery pain relief in women with opioid
dependence.
a. Ultrasound-guided TAP block reduces opioid
consumption and improves analgesia when used in
conjunction with other non-opioid analgesics for
postcesarean delivery pain relief in patients without
opioid dependence. It fails to improve analgesia when
neuraxial morphine has been used. The effectiveness of
TAP block in patients with opioid dependence is
unknown, but its use has minimal morbidity and there are
reports of its effectiveness after other pain relief
modalities have failed.41
b. Iliohypogastric and ilioinguinal nerve blocks may
reduce pain scores in non-OD women after cesarean
delivery, whether or not they have received neuraxial
morphine. Variations in reported results may reflect
differences in where the local anesthetic is placed because
blocks performed below the transversalis fascia may be
more effective.42
3. Patient-controlled epidural analgesia
a. Patient-controlled epidural analgesia significantly reduces
opioid consumption in OD women following cesarean
delivery. Rescue from intractable pain has been reported
in a few patients when other techniques failed.37,38
b. It may not offer better pain relief than that associated with
wound infiltration.42
c. Significant motor block may accompany its use in non-
OD patients, thus limiting its usefulness. It is best used for
rescue in women only if an epidural catheter is retained
following delivery.43
4. Neuraxial opioids and other adjuncts
a. Opioid withdrawal is not prevented by neuraxial opioid
use, and estimation of an effective neuraxial dose is
difficult due to opioid receptor downregulation. Work in
postoperative nonpregnant OD patients suggests that a
dose of two or three times that used in opioid-naive
patients is effective.44
b. Neuraxial opioid administration may not offer any benefit
for postcesarean pain relief in women with opioid
dependence. Postcesarean delivery of supplemental opioid
administration was similar in a study in OD women
regardless of whether a neuraxial opioid was used.38
c. Intrathecal clonidine, 30 to 150 µg, and epidural
clonidine, 75 to 150 µg, provide analgesia for 4 hours, but
a significant incidence of maternal sedation. A U.S. Food
and Drug Administration warning against its use in
pregnant patients has discouraged its use.45 However, in
OD patients in whom the optimum dose of neuraxial
opioid is unknown, addition of 2 to 7.5 µg to an epidural
solution used for pain relief may offer benefit.
5. Multimodal analgesia
a. Most reviews recommend the use of adjunct non-opioid
analgesics for postoperative pain relief in nonpregnant
patients with opioid dependence, but no studies examine
their use after cesarean delivery in women with opioid
dependence.46
b. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be
used with safety in breastfeeding women, and potential
complications of bleeding, uterine atony, and
gastrointestinal side effects have not been demonstrated
after delivery.47
c. Oral acetaminophen is a drug with a good safety profile,
although its effectiveness when added to an NSAID is
reported as variable. The effectiveness of the intravenous
 (IV) preparation for labor analgesia was recently
reported.48
d. Gabapentin in doses of 300 to 1,200 mg orally may cause
sedation in non-OD women, but it significantly reduces
pain on patient movement and may be useful in women
with opioid dependence where maternal sedation may be
desirable.49
e. Oral clonidine in doses of 0.4 µg per kg was associated
with significant reductions in morphine use after cesarean
delivery in non-OD women, but conclusions about
neonatal safety cannot be made.50
f. Intravenous ketamine reduces postoperative opioid use in
surgical patients with opioid dependence when used in
bolus doses of 0.25 to 0.5 mg per kg or by continuous
infusion (1 to 2 µg/kg/minute). Ketamine has a long
safety record when used in obstetrics; however, one report
showed no opioid sparing effect when 10 mg doses were
used for control of pain following spinal anesthesia for
cesarean delivery.51

CLINICAL PEARL The use of peripheral nerve blocks may

offer a benefit to women with opioid dependence following
cesarean delivery. Use of non-opioid adjuncts such as NSAIDs,
gabapentinoids, acetaminophen, and clonidine are safe and are
recommended.

SUMMARY
The OD parturient requires a multidisciplinary approach to
management. Screening for opioid dependence early in pregnancy
should occur in women not already identified as OD, and appropriate
long-term therapy should be prescribed. Patient fears of opioid
withdrawal and pain during the peripartum period require reassurance
 and counseling. Neuraxial techniques for pain relief during vaginal
delivery are similar to those used in non-OD women. Postcesarean
delivery analgesia requires a multimodal approach utilizing
appropriate neuraxial analgesic techniques, additional opioid
administration, and non-opioid supplements. Prospective trials
evaluating optimal pain management in these patients do not exist; all
recommendations are based on retrospective studies with small
numbers of patients and reports from nonpregnant surgical patients.

REFERENCES
1. Bolnick JM, Rayburn WF. Substance use disorders in women: special considerations during
pregnancy. Obstet Gynecol Clin North Am. 2003;30:545–558, vii.
2. Wu L-T, Ling W, Burchett B, et al. Gender and racial/ethnic differences in addiction severity, HIV
risk, and quality of life among adults in opioid detoxification: results from the National Drug Abuse
Treatment Clinical Trials Network. Subst Abuse Rehabil. 2010;2010:13–22.
3. Rondinelli AJ, Ouellet LJ, Strathdee SA, et al. Young adult injection drug users in the United States
continue to practice HIV risk behaviors. Drug Alcohol Depend. 2009;104:167–174.
4. Jones HE, Heil SH, O’Grady KE, et al. Smoking in pregnant women screened for an opioid agonist
medication study compared to related pregnant and non-pregnant patient samples. Am J Drug Alcohol
Abuse. 2009;35:375–380.
5. Green TC, Grimes Serrano JM, Licari A, et al. Women who abuse prescription opioids: findings from
the Addiction Severity Index-Multimedia Version Connect prescription opioid database. Drug Alcohol
Depend. 2009;103:65–73.
6. Stine SM, Heil SH, Kaltenbach K, et al. Characteristics of opioid-using pregnant women who accept
or refuse participation in a clinical trial: screening results from the MOTHER study. Am J Drug
Alcohol Abuse. 2009;35:429–433.
7. Benningfield MM, Arria AM, Kaltenbach K, et al. Co-occurring psychiatric symptoms are associated
with increased psychological, social, and medical impairment in opioid dependent pregnant women.
Am J Addict. 2010;19:416–421.
8. Chen CH, Lin HC. Prenatal care and adverse pregnancy outcomes among women with depression: a
nationwide population-based study. Can J Psychiatry. 2011;56:273–280.
9. Brennan MC, Rayburn WF. Counseling about risks of congenital anomalies from prescription opioids.
Birth Defects Res A Clin Mol Teratol. 2012;94:620–625.
10. Broussard CS, Rasmussen SA, Reefhuis J, et al. Maternal treatment with opioid analgesics and risk for
birth defects. Am J Obstet Gynecol. 2011;204:314.e1–314.e11.
11. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 524: opioid
abuse, dependence, and addiction in pregnancy. Obstet Gynecol. 2012;119:1070–1076.
12. Chang G, Orav EJ, Jones JA, et al. Self-reported alcohol and drug use in pregnant young women: a
pilot study of associated factors and identification. J Addict Med. 2011;5:221–226.
13. Sarkar M, Burnett M, Carrière S, et al. Screening and recording of alcohol use among women of child-
bearing age and pregnant women. Can J Clin Pharmacol. 2009;16:e242–e263.
14. Roberts SC, Nuru-Jeter A. Women’s perspectives on screening for alcohol and drug use in prenatal
 care. Women’s Health Issues. 2010;20:193–200.
15. Kaltenbach K, Berghella V, Finnegan L. Opioid dependence during pregnancy: effects and
management. Obset Gynecol Clin North Am. 1998;25:139–151.
16. Winklbaur B, Kopf N, Ebner N, et al. Treating pregnant women dependent on opioids is not the same
as treating pregnancy and opioid dependence: a knowledge synthesis for better treatment for women
and neonates. Addiction. 2008; 103:1429–1440.
17. Jones HE, Kaltenbach K, Heil SH, et al. Neonatal abstinence syndrome after methadone or
buprenorphine exposure. N Engl J Med. 2010;363:2320–2331.
18. McNicholas L. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid
Addiction. Rockville, MD: U.S. Department of Health and Human Services; 2004.
19. Cleary BJ, Donnelly JM, Strawbridge JD, et al. Methadone and perinatal outcomes: a retrospective
cohort study. Am J Obstet Gynecol. 2011;204:139.e1–139.e9.
20. Stewart RD, Nelson DB, Adhikari EH, et al. The obstetrical and neonatal impact of maternal opioid
detoxification in pregnancy. Am J Obstet Gynecol. 2013;209:267.e1–267.e5.
21. Sharpe C, Kuschel C. Outcomes of infants born to mothers receiving methadone for pain management
in pregnancy. Arch Dis Child Fetal Neonatal Ed. 2004;89:F33–F36.
22. Young JL, Martin PR. Treatment of opioid dependence in the setting of pregnancy. Psychiatr Clin
North Am. 2012; 34:441–460.
23. Raith W, Kutschera J, Müller W, et al. Active ear acupuncture points in neonates with neonatal
abstinence syndrome (NAS). Am J Chin Med. 2011;39:29–37.
24. Liu AJ, Jones MP, Murray H, et al. Perinatal risk factors for the neonatal abstinence syndrome in
infants born to women on methadone maintenance therapy. Aust N Z J Obstet Gynaecol. 2010;50:253–
258.
25. Jansson LM, Velez M. Neonatal abstinence syndrome. Curr Opin Pediatr. 2012;24:252–258.
26. Patrick SW, Schumacher RE, Benneyworth BD, et al. Neonatal abstinence syndrome and associated
health care expenditures: United States, 2000-2009. JAMA. 2012;307:1934–1940.
27. Hudak ML, Tan RC; and the Committee on Drugs; Committee on Fetus and Newborn. Neonatal drug
withdrawal. Pediatrics. 2012;129:e540–e560.
28. Logan BA, Brown MS, Hayes MJ. Neonatal abstinence syndrome: treatment and pediatric outcomes.
Clin Obstet Gynecol. 2013;56:186–192.
29. Welle-Strand GK, Skurtveit S, Jansson LM, et al. Breastfeeding reduces the need for withdrawal
treatment in opioid-exposed infants. Acta Paediatr. 2013;102:1060–1066.
30. Cleary BJ, Donnelly J, Strawbridge J, et al. Methadone dose and neonatal abstinence syndrome-
systematic review and meta-analysis. Addiction. 2008;105:2071–2084.
31. Seligman NS, Almario CV, Hayes EJ, et al. Relationship between maternal methadone dose at delivery
and neonatal abstinence syndrome. J Pediatr. 2010;157:428–433.
32. Dryden C, Young D, Hepburn M, et al. Maternal methadone use in pregnancy: factors associated with
the development of neonatal abstinence syndrome and implications for healthcare resources. BJOG.
2009;116:665–671.
33. McCarthy JJ. Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone
tapers: can we assure the safety of the fetus? J Matern Fetal Neonatal Med. 2012;25:109–112.
34. Mitra S, Sinatra RS. Perioperative management of acute pain in the opioid-dependent patient.
Anesthesiology. 2004;101:212–227.
35. Stromer W, Michaeli K, Sandner-Kiesling A. Perioperative pain therapy in opioid abuse. Eur J
Anaesthesiol. 2013;30:55–64.
36. Alford DP, Compton P, Samet JH. Acute pain management for patients receiving maintenance
methadone or buprenorphine therapy. Ann Intern Med. 2006;144:127–134.
37. Meyer M, Paranya G, Keefer Norris A, et al. Intrapartum and postpartum analgesia for women
maintained on buprenorphine during pregnancy. Eur J Pain. 2010;14:939–943.
38. Meyer M, Wagner K, Benvenuto A, et al. Intrapartum and postpartum analgesia for women
maintained on methadone during pregnancy. Obstet Gynecol. 2007;110(suppl 1):261–266.
39. Rapp SE, Ready LB, Nessly ML. Acute pain management in patients with prior opioid consumption: a
case-controlled retrospective review. Pain. 1995;61:195–201.
40. Walker JM, Farney RJ, Rhondeau SM, et al. Chronic opioid use is a risk factor for the development of
central sleep apnea and ataxic breathing. J Clin Sleep Med. 2007;3:455–461.
41. Mishriky BM, George RB, Habib AS. Transversus abdominis plane block for analgesia after cesarean
delivery: a systematic review and meta-analysis. Can J Anaesth. 2012;59:766–778.
42. Rackelboom T, Le Strat S, Silvera S, et al. Improving continuous wound infusion effectiveness for
postoperative analgesia after cesarean delivery: a randomized controlled trial. Obstet Gynecol.
2010;116:893–900.
43. Vercauteren M, Vereecken K, La Malfa M, et al. Cost-effectiveness of analgesia after caesarean
section: a comparison of intrathecal morphine and epidural PCA. Acta Anaesthesiol Scand.
2002;46:85–89.
44. de Leon-Casasola OA, Myers DP, Donaparthi S, et al. A comparison of postoperative epidural
analgesia between patients with chronic cancer taking high doses of oral opioids versus opioid-naive
patients. Anesth Analg. 1993;76:302–307.
45. Pan PH. Post cesarean delivery pain management: multimodal approach. Int J Obstet Anesth.
2006;15:185–188.
46. Young JL, Lockhart EM, Baysinger, CL. Anesthetic and obstetric management of the opioid-
dependent parturient. Int Anesthesiol Clin. 2014;52:67–85.
47. American Academy of Pediatrics Committee on Drugs. Neonatal drug withdrawal. Pediatrics.
1998;101:1079–1088.
48. Jahr JS, Lee VK. Intravenous acetaminophen. Anesthesiol Clin. 2010;28:619–645.
49. Moore A, Costello J, Wieczorek P, et al. Gabapentin improves postcesarean delivery pain
management: a randomized, placebo-controlled trial. Anesth Analg. 2011;112:167–173.
50. Yanagidate F, Hamaya Y, Dohi S. Clonidine premedication reduces maternal requirement for
intravenous morphine after cesarean delivery without affecting newborn’s outcome. Reg Anesth Pain
Med. 2001;26:461–467.
51. Bauchat JR, Higgins N, Wojciechowski KG, et al. Low-dose ketamine with multimodal postcesarean
delivery analgesia: a randomized controlled trial. Int J Obstet Anesth. 2011;20:3–9.
 Maternal Morbidity and Mortality
Jill M. Mhyre

I. Maternal mortality
A. Definitions
B. Epidemiology
C. Etiologies
D. Risk factors
II. Severe maternal morbidity
A. Definitions
B. Epidemiology
III. Prevention and lessons learned
A. Confidential enquiries into maternal death
B. Preventable factors
C. Morbidity surveillance systems
IV. Anesthesia-related maternal mortality
A. Definitions
B. Epidemiology
C. Etiologies

KEYPOINTS
1. Anesthesia is rarely the direct cause of maternal death; nevertheless,
anesthesia providers have the potential to improve overall patient safety
 through multidisciplinary collaboration to deliver high-quality peripartum
care.
2. Cardiovascular disease is the most common cause of maternal death, but
hemorrhage, hypertensive disorders of pregnancy, venous
thromboembolism, and sepsis appear to be the most preventable.
3. Preexisting medical conditions increase maternal risk, but deaths occur in
previously healthy women.
4. Failed airway management is the most common cause of maternal death
with general anesthesia. Airway management drills can help maintain
optimal skills, equipment, and preparation for actual airway management
emergencies.
5. High neuraxial block is the leading cause of maternal death from
neuraxial anesthesia. The potential need for airway rescue and
resuscitation should be anticipated with every neuraxial block placement.

OVER THE PAST 50 YEARS, anesthesia has become remarkably safe; however,
pregnancy continues to lead to unacceptable rates of maternal harm. The primary
reason to analyze maternal mortality and morbidity is to identify opportunities to
improve safety for future patients. Patterns of preventable maternal morbidity
and mortality point to priorities for individual clinical care as well as health
system improvements. Anesthesiologists, with expertise in physiology,
resuscitation, critical care, and high reliability systems, are well-positioned to
lead multidisciplinary teams to implement solutions that will ensure future
maternal and perinatal patient safety.
I. Maternal mortality
A. Definitions
1. A maternal death is defined by the World Health
Organization (WHO) as a death of women while pregnant or
within 42 days of termination of pregnancy, irrespective of the
duration and site of the pregnancy, from any cause related to
or aggravated by the pregnancy or its management, but not
from accidental or incidental causes.1
2. Late maternal death transpires more than 42 days, but less
 than 1 year after termination of pregnancy. Late maternal
deaths are excluded from official maternal mortality ratio
(MMR) statistics for the purpose of international comparison.
3. A direct maternal death results from obstetric complications
of the pregnant state or from interventions, omissions,
incorrect treatment, or a chain of events resulting from any of
the above.
4. An indirect maternal death results from previous existing
disease or disease that developed during pregnancy and which
is not due to direct obstetric causes, but was aggravated by the
physiologic effects of pregnancy.
5. A pregnancy-related death, classified by the United States
Centers for Disease Control and Prevention, refers to the
death of a woman while pregnant or within 1 year of the end
of her pregnancy, from any cause related to or aggravated by
her pregnancy, its management, but not from accidental or
incidental causes.
B. Epidemiology
1. The WHO defines the MMR as the number of direct and
indirect maternal deaths per 100,000 live births. The MMR
declined to 210 maternal deaths per 100,000 live births in
2013, from 380 in 1990.1
2. A total of 289,000 women died while pregnant or within 42
days of the end of pregnancy in 2013.1 The majority of global
maternal deaths take place in Sub-Saharan Africa (62%) or
South Asia (24%).1
3. The 2013 MMR was 16 per 100,000 live births in the
developed world and 230 per 100,000 in developing regions,
a 14-fold difference.1
4. The U.S. MMR was 13.8 between 2006 and 2010, whereas
the pregnancy-related mortality ratio was 16.2
5. Contemporaneous MMRs in other developed countries were
5.6 in the United Kingdom (2009 to 2011),3 10.3 in France
(2007 to 2009),4 6.8 in Australia (2006 to 2010), and 6.1 in
 Canada (2009 to 2011).
C. Etiologies
Although direct causes of maternal death claim the most lives
globally (e.g., hemorrhage, hypertensive disorders, and infection),
an increasing proportion deaths in the developed world are
attributed to indirect causes (e.g., cardiovascular disease and
other medical conditions exacerbated by pregnancy). Figure 32.1
illustrates cause-specific proportional pregnancy-related mortality
for the United States between 1987 and 2010.

1. Cardiac disease is the leading cause of maternal death in

both the United States and the United Kingdom.2,5
a. The combination of cardiovascular disease and
cardiomyopathy caused 26% of maternal deaths in the
United States between 2006 and 2010.2
b. A large number of deaths from peripartum
cardiomyopathy transpire more than 42 days after the end
of pregnancy.
c. Chronic hypertension is the most important factor
associated with increasing population prevalence of
cardiomyopathy in the United States.6
2. Infection led to 13.6% of maternal deaths in the United States
between 2006 and 2010.2
a. Influenza was the leading cause of death due to infection
in both the United States and the United Kingdom3;
prevention strategies include universal influenza
vaccination and rapid testing and antiviral therapy for
pregnant women exhibiting flu-like symptoms.
b. Genital tract infection caused by group A Streptococcus
can lead to septic shock within 2 hours of initial
presentation.3,7
3. Noncardiovascular medical conditions contribute to another
12.8% of maternal deaths in the United States.
a. Altogether, indirect causes lead to more than half of
maternal deaths in the United Kingdom3 and close to half
in the United States.2
b. Poorly controlled preexisting medical and psychiatric
conditions are among the most important risk factors for
maternal mortality.8
4. Hemorrhage (11.4%) was the leading cause of maternal
death in the United States between 1987 and 1990 and
continues to be a common cause of maternal morbidity and
mortality during the hospitalization for delivery.9
a. The majority of deaths due to hemorrhage are judged to
be preventable in multiple confidential mortality
reviews.3,10
b. The most common preventable factors involve delays in
diagnosis and treatment.9,11
5. Hypertensive disorders of pregnancy (9.4%) may
precipitate lethal intracranial hemorrhage; less common
mechanisms of death include pulmonary edema and hepatic
rupture.
a. In one large health system review, the most common
preventable causes of death from hypertensive disorders
were failure to adequately control blood pressure and
 failure to diagnose and treat pulmonary edema.9
b. Protocols for rapid antihypertensive therapy for defined
blood pressure thresholds can reduce preeclampsia-related
deaths.12
6. Venous thromboembolism (9.3%) includes both cerebral
venous thrombosis and pulmonary embolism.
a. Universal thromboembolism prophylaxis with
intraoperative sequential compression devices during
cesarean delivery (CD) and targeted postpartum
pharmacologic anticoagulation is the most important
strategy to reduce maternal mortality from venous
thromboembolism.12
b. Cerebral venous thrombosis and other serious intracranial
pathology should be considered in the differential
diagnosis for postpartum headache.3
7. Amniotic fluid embolism (5.3%) is often considered not
preventable. Aggressive supportive therapy improves the
likelihood of survival.
8. Injury-related deaths are relatively common, but are
considered pregnancy-associated and are not included in the
statistics for pregnancy-related death.

CLINICAL PEARL Indirect causes are the main reasons for

maternal death in the developed world; cardiac disease is the
leading cause of maternal death in the United States and United
Kingdom.

D. Risk factors
The most potent risk factors for maternal mortality and
severe morbidity are clinically significant medical conditions
that predate the pregnancy.3,8,13,14
1. Three-quarters of women who died in the United Kingdom
between 2009 and 2012 had a preexisting medical condition.3
2. Preconception counseling and intensive multidisciplinary
antepartum and intrapartum care may improve outcomes for
women with serious medical or mental health conditions that
may be aggravated by pregnancy.3,15
3. Insufficient prenatal care may result in suboptimal
management of existing medical conditions or delay the
diagnosis of pregnancy complications.2,8
4. Advanced maternal age increases maternal risk,16 with a
linear trend evident for each 5-year increase in maternal age
beyond 34 years.15
5. Racial and ethnic minority groups experience increased
risk.8,15
a. In the United States, non-Hispanic black race confers a
threefold increase in the risk of maternal death compared
with non-Hispanic white women.2,17 The disparity is
exacerbated by increasing maternal age. Non-Hispanic
black women older than 25 years have a fourfold
increased risk of death, as illustrated in Figure 32.2.2
 b. Immigrants and nonnative speakers experience high
rates of both maternal death and substandard care.15,18,19
6. Obesity (body mass index [BMI] ≥30 kg per m2) increases
risk of death when severe pregnancy complications develop.18
Conversely, very low body weight (<60 kg) may increase risk
of hemorrhage-related mortality due to extremely small
circulating blood volume.3,8
7. Multifetal pregnancies increase risk of serious complications
of pregnancy and maternal death.15,20
8. Cesarean delivery is associated with maternal death.21,22
a. Most maternal deaths following CD are caused by the
underlying medical or obstetric disease that indicated the
CD; rarely, cesarean surgery causes fatal infection,
hemorrhage, or venous thromboembolism.9
b. Cesarean deliveries increase the risk of placenta accreta in
subsequent pregnancies and thus contribute to the overall
population level risk of maternal death.23
II. Severe maternal morbidity
A. Definitions
1. Severe morbidity refers to serious complications in
pregnancy with the potential to cause end-organ injury or
maternal death. A practical definition of severe morbidity is
either intensive care unit (ICU) admission or the
administration of ≥4 units of erythrocytes or whole blood, or
both.3
2. Near-miss morbidity includes life-threatening complications
that result in severe end-organ dysfunction or failure.14,24
B. Epidemiology
1. Severe morbidity complicates 1.6% of pregnancies in the
United States, corresponding to more than 60,000 pregnancies
per year.25
2. Near-miss morbidity develops in approximately 0.13% to
0.2% of US hospitalizations for delivery.14,26
 CLINICAL PEARL For each maternal death, approximately 50
to 100 women experience a severe morbidity.

III. Prevention and lessons learned

A. Confidential enquiries into maternal death review case records to
identify lessons to improve health systems and clinical care.
1. The United Kingdom Confidential Enquiry into Maternal
Death (UK CEMD) is the longest running and largest
confidential enquiry, and has been conducted in the United
Kingdom since 1952.5,15,27
2. In the United States, the certification of death is the legal
responsibility of individual states, and the federal government
has limited authority to review maternal deaths. Most, but not
all, state death certificates include a question about pregnancy
status at the time of death.28 Under the U.S. Pregnancy
Mortality Surveillance System, states identify maternal deaths
by an obstetric ICD-10 code, by the pregnancy question on
the death certificate, or by another means (e.g., matching
maternal death certificates with neonatal birth certificates or
fetal death records) and forward only the corresponding death
certificates to epidemiologists at the United States Centers for
Disease Control and Prevention.2
3. Increasingly, individual states in the United States are
following the lead of the United Kingdom by completing
comprehensive confidential reviews of all maternal deaths
within the state and using the findings to prioritize
improvements in systems of maternity care.29 The most
notable is California (www.cmqcc.org).11
B. Preventable factors are modifiable features in health systems and
clinical care believed to have a reasonable chance to prevent the
maternal death; their identification has become a major focus
during mortality and near-miss morbidity reviews.5,30,31
1. Between 20% and 40% of maternal deaths are preventable.32
 2. Preventable factors are most often noted among deaths caused
by hemorrhage, hypertensive disorders of pregnancy, venous
thromboembolism, and sepsis.5,11,30
3. Regional maternal care networks have been proposed to
improve maternal care and neonatal outcomes by directing
individual patients to facilities that provide the most
appropriate level of service.33,34 Birth centers and Level I
facilities offer basic services for lowest risk women and
promise to “de-medicalize” birth, whereas facility Levels II to
IV offer increasingly comprehensive health care services for
women with progressively complex medical and obstetric
conditions. Regional Perinatal Health Care Centers (Level IV)
coordinate health care services across the network, provide
consultative services (e.g., by telemedicine), accept transfers,
optimize policies and protocols for dissemination across the
network, and facilitate quality reviews and improvement
within the network.
4. The National Partnership for Maternal Safety is an
interdisciplinary multistakeholder organization that is
developing safety bundles for the most common causes of
preventable maternal death, including hemorrhage, venous
thromboembolism, and hypertensive disorders of pregnancy
(www.safehealthcareforeverywoman.org).35,36
5. Systems to ensure prompt evaluation, diagnosis, and
treatment for women with abnormal vital signs have the
potential to avoid preventable maternal harm.37
C. Morbidity surveillance systems
1. The UK Obstetric Surveillance System (UKOSS) collects
data on severe maternal morbidities alongside maternal
deaths.5
2. Analyzing maternal mortality and morbidity together
improves the statistical power of quantitative analysis and
allows for comparisons to identify key factors that increase
likelihood of survival.5,7
 3. Facility-based review of severe maternal morbidity cases to
identify preventability factors and opportunities for
improvement may improve outcomes for future patients.3,38

CLINICAL PEARL The most recent reviews of morbidity and

mortality have focused on identifying modifiable features in health
systems and clinical care believed to have a reasonable chance to
prevent maternal death.

IV. Anesthesia-related maternal mortality

A. Definitions
1. An anesthesia-related maternal death can be directly
attributed to a complication of anesthesia.
2. Anesthesia-contributing deaths are those in which anesthetic
care contributed, but did not directly cause maternal death.
a. Deaths involving anesthesia are almost always
multifactorial and complex.3
b. Optimal anesthetic care is often most complex in women
with life-threatening illness, so review of “nonanesthetic
deaths” offers important lessons for anesthetic
management.
c. Early involvement of anesthesiologists in the care of
women developing critical illness may be lifesaving.
B. Epidemiology
1. Anesthesia causes approximately 1% of all maternal deaths,2,5
with a cause-specific mortality ratio between 1 and 3 deaths
per million pregnancies (see Table 32.1).3,39
2. The majority of anesthesia-related deaths (>80%) occur
around the time of CD, so risk is concentrated among those
women who deliver by cesarean.39
a. Before 1990, general anesthesia was significantly more
hazardous than neuraxial anesthesia for CD (see Table
32.2). Neuraxial anesthesia safety improved in the mid-
1980s, when awareness of local anesthetic toxicity led to
several changes that improved the safety of epidural
anesthesia (e.g., routine epidural catheter testing,
incremental dosing, withdrawal of 0.75% bupivacaine for
epidural use).

b. After 1990, the safety of general anesthesia for CD

 improved (see Table 32.2). Reasons for improvement may
include better awareness of the increased risk of difficult
intubation and rapid desaturation in pregnant women,
improved technologies for airway rescue (e.g., laryngeal
mask airway [LMA], video laryngoscopy), better
monitoring standards (e.g., pulse oximetry, capnography),
and established protocols and training for difficult airway
management.
c. In contemporary practice, both general and neuraxial
anesthesia are very safe, but either technique can lead to
maternal death. In the United States between 1998 and
2002:
(1) General anesthesia for CD caused 6.5 deaths per
million anesthetics (approximately 1:150,000).39
(2) Neuraxial anesthesia for CD caused 3.8 deaths per
million anesthetics (approximately 1:250,000).39
(3) These events are sufficiently rare that available data
are insufficient to statistically distinguish the two
rates.
d. General anesthesia is widely believed to remain more
hazardous than neuraxial anesthesia for the following
reasons.
(1) General anesthesia requires that the airway be
secured, and airway management is more difficult in
pregnant women compared with nonpregnant surgical
patients.
(2) General anesthesia is often selected in emergencies
when the time for optimal preparation and
preoperative evaluation of the patient is limited.
(3) General anesthesia is often administered in the
highest risk patients for whom neuraxial anesthesia is
contraindicated (e.g., hemolysis, elevated liver
enzymes, low platelets [HELLP] syndrome, cardiac
disease, hemorrhage).
 (4) General anesthesia is usually selected when neuraxial
fails or produces a high block that compromises
oxygenation and ventilation.

CLINICAL PEARL Although the safety of general anesthesia

for CD has markedly improved in recent decades, neuraxial
anesthesia remains associated with a lower risk of anesthetic-related
death and morbidity.

C. Etiologies
1. Potential etiologies of anesthesia-related maternal death are
listed in Table 32.3.

2. Failed intubation appears to be the most frequently reported

life-threatening complications of general anesthesia.39–41
a. Simulation drills to practice perioperative airway crises
are important to ensure optimal airway management when
general anesthesia is used infrequently in the obstetric
 surgical suite.
b. Episodes of postoperative hypoventilation have been
associated with general anesthesia, obesity, sleep apnea,
asthma, opioid and other sedatives by neuraxial or
intravenous routes, and inadequate postoperative
respiratory monitoring.5,15,27,42
3. Postoperative hypoventilation is also possible following
neuraxial analgesia.
a. Supplemental oxygen can delay recognition of inadequate
ventilation, particularly if pulse oximetry is the only
monitor used to evaluate the respiratory system.
b. Postoperative monitoring and documentation for obstetric
patients should be comparable as for nonobstetric
patients.
4. High block is the most frequently reported life-threatening
complication of neuraxial anesthesia,39–41 with an event rate
of approximately 1:4,300 neuraxial anesthetics for labor or
CD.41
a. High blocks are most common when spinal anesthesia is
induced after large volumes of local anesthetics (>10 mL)
have been administered in the epidural space, often in the
context of an attempt to manage failed conversion of
epidural analgesia to anesthesia for CD.41
b. High blocks are most often fatal when they develop after
the anesthesia provider has left the bedside or when
resuscitation equipment (i.e., equipment to deliver
positive pressure ventilation, suction, and hemodynamic
support) is not immediately available.43 Unrecognized
intrathecal catheters intended for the epidural space
typically produce a high block within 30 minutes of the
initial loading dose,40,43,44 with an event frequency of
1:12,300 attempted epidural catheter insertions for
labor.41
CLINICAL PEARL High neuraxial blockade is the most life-
threatening complication associated with neuraxial anesthesia in
obstetrics.

REFERENCES
1. World Health Organization. Trends in Maternal Mortality: 1990 to 2013: Estimates by WHO,
UNICEF, UNFPA, The World Bank and the United Nations Population Division. Geneva, Switzerland:
Department of Reproductive Health and Research; 2014.
2. Creanga AA, Berg CJ, Syverson C, et al. Pregnancy-related mortality in the United States, 2006–2010.
Obstet Gynecol. 2015;125:5–12.
3. Callaghan WM, Grobman WA, Kilpatrick SJ, et al. Facility-based identification of women with severe
maternal morbidity: it is time to start. Obstet Gynecol. 2014;123:978–981.
4. Saucedo M, Deneux-Tharaux C, Bouvier-Colle MH; for French National Experts Committee on
Maternal Mortality. Ten years of confidential inquiries into maternal deaths in France, 1998-2007.
Obstet Gynecol. 2013;122:752–760.
5. Knight M, Kenyon S, Brocklehurst P, et al, eds. Saving Lives, Improving Mothers’ Care: Lessons
Learned to Inform Future Maternity Care from the UK and Ireland Confidential Enquiries into
Maternal Deaths and Morbidity 2009-2012. Oxford, United Kingdom: National Perinatal
Epidemiology Unit, University of Oxford; 2014.
6. Grotegut CA, Kuklina EV, Anstrom KJ, et al. Factors associated with the change in prevalence of
cardiomyopathy at delivery in the period 2000-2009: a population-based prevalence study. BJOG.
2014;121:1386–1394.
7. Acosta CD, Kurinczuk JJ, Lucas DN, et al. Severe maternal sepsis in the UK, 2011–2012: a national
case-control study. PLoS Med. 2014;11:e1001672.
8. Nair M, Kurinczuk JJ, Brocklehurst P, et al. Factors associated with maternal death from direct
pregnancy complications: a UK national case-control study. BJOG. 2015;122:653–662.
9. Clark SL, Belfort MA, Dildy GA, et al. Maternal death in the 21st century: causes, prevention, and
relationship to cesarean delivery. Am J Obstet Gynecol. 2008;199:36.e1–36.e5.
10. Berg CJ, Harper MA, Atkinson SM, et al. Preventability of pregnancy-related deaths: results of a
state-wide review. Obstet Gynecol. 2005;106:1228–1234.
11. California Department of Public Health. The California Pregnancy-Associated Mortality Review:
report from 2002 and 2003 Maternal Death Reviews. Stanford, CA: California Maternal Quality Care
Collaborative; 2011.
12. Clark SL, Christmas JT, Frye DR, et al. Maternal mortality in the United States: predictability and the
impact of protocols on fatal postcesarean pulmonary embolism and hypertension-related intracranial
hemorrhage. Am J Obstet Gynecol. 2014;211:32.e1–32.e9.
13. Bateman BT, Mhyre JM, Hernandez-Diaz S, et al. Development of a comorbidity index for use in
obstetric patients. Obstet Gynecol. 2013;122:957–965.
14. Mhyre JM, Bateman BT, Leffert LR. Influence of patient comorbidities on the risk of near-miss
maternal morbidity or mortality. Anesthesiology. 2011;115:963–972.
15. Cantwell R, Clutton-Brock T, Cooper G, et al. Saving mothers’ lives: reviewing maternal deaths to
make motherhood safer: 2006-2008: The Eight Report of the Confidential Enquiries into Maternal
Deaths in the United Kingdom. BJOG. 2011;118(suppl 1):1–203.
16. Callaghan WM, Berg CJ. Pregnancy-related mortality among women aged 35 years and older, United
States, 1991-1997. Obstet Gynecol. 2003;102:1015–1021.
17. Creanga AA, Bateman BT, Kuklina EV, et al. Racial and ethnic disparities in severe maternal
morbidity: a multistate analysis, 2008-2010. Am J Obstet Gynecol. 2014;210:435.e1–435.e8.
18. Kayem G, Kurinczuk J, Lewis G, et al. Risk factors for progression from severe maternal morbidity to
death: a national cohort study. PLoS One. 2011;6:e29077.
19. Creanga AA, Berg CJ, Syverson C, et al. Race, ethnicity, and nativity differentials in pregnancy-
related mortality in the United States: 1993-2006. Obstet Gynecol. 2012;120:261–268.
20. Walker MC, Murphy KE, Pan S, et al. Adverse maternal outcomes in multifetal pregnancies. BJOG.
2004;111:1294–1296.
21. Deneux-Tharaux C, Carmona E, Bouvier-Colle MH, et al. Postpartum maternal mortality and cesarean
delivery. Obstet Gynecol. 2006;108:541–548.
22. Liu S, Liston RM, Joseph KS, et al; for the Maternal Health Study Group of the Canadian Perinatal
Surveillance System. Maternal mortality and severe morbidity associated with low-risk planned
cesarean delivery versus planned vaginal delivery at term. CMAJ. 2007;176:455–460.
23. Solheim KN, Esakoff TF, Little SE, et al. The effect of cesarean delivery rates on the future incidence
of placenta previa, placenta accreta, and maternal mortality. J Matern Fetal Neonatal Med.
2011;24:1341–1346.
24. Say L, Pattinson RC, Gülmezoglu AM. WHO systematic review of maternal morbidity and mortality:
the prevalence of severe acute maternal morbidity (near miss). Reprod Health. 2004;1:3.
25. Callaghan WM, Creanga AA, Kuklina EV. Severe maternal morbidity among delivery and postpartum
hospitalizations in the United States. Obstet Gynecol. 2012;120:1029–1036.
26. Geller SE, Rosenberg D, Cox S, et al. A scoring system identified near-miss maternal morbidity during
pregnancy. J Clin Epidemiol. 2004;57:716–720.
27. Lewis G, ed. Saving Mothers’ Lives: Reviewing Maternal Deaths to Make Motherhood Safer — 2003-
2005. The Seventh Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom.
London, United Kingdom: Confidential Enquiry into Maternal and Child Health; 2007.
28. MacKay AP, Berg CJ, Liu X, et al. Changes in pregnancy mortality ascertainment: United States,
1999-2005. Obstet Gynecol. 2011;118:104–110.
29. Callaghan WM. State-based maternal death reviews: assessing opportunities to alter outcomes. Am J
Obstet Gynecol. 2014;211:581–582.
30. Geller SE, Koch AR, Martin NJ, et al. Assessing preventability of maternal mortality in Illinois: 2002-
2012. Am J Obstet Gynecol. 2014;211:698.e1–698.e11.
31. Farquhar C, Sadler L, Masson V, et al. Beyond the numbers: classifying contributory factors and
potentially avoidable maternal deaths in New Zealand, 2006-2009. Am J Obstet Gynecol.
2011;205:331.e1–331.e8.
32. Mhyre JM. Maternal mortality. Curr Opin Anaesthesiol. 2012;25:277–285.
33. American College of Obstetricians and Gynecologists. Obstetric Care Consensus No. 2: levels of
maternal care. Obstet Gynecol. 2015;125:502–515.
34. Hankins GD, Clark SL, Pacheco LD, et al. Maternal mortality, near misses, and severe morbidity:
lowering rates through designated levels of maternity care. Obstet Gynecol. 2012;120:929–934.
35. D’Alton ME, Main EK, Menard MK, et al. The national partnership for maternal safety. Obstet
Gynecol. 2014;123:973–977.
36. Main EK, Menard MK. Maternal mortality: time for national action. Obstet Gynecol. 2013;122:735–
736.
37. Mhyre JM, D’Oria R, Hameed AB, et al. The maternal early warning criteria: a proposal from the
national partnership for maternal safety. Obstet Gynecol. 2014;124:782–786.
38. Kilpatrick SJ, Berg C, Bernstein P, et al. Standardized severe maternal morbidity review: rationale and
process. J Obstet Gynecol Neonatal Nurs. 2014;43:403–408.
39. Hawkins JL, Chang J, Palmer SK, et al. Anesthesia-related maternal mortality in the United States:
1979-2002. Obstet Gynecol. 2011;117:69–74.
40. Davies JM, Posner KL, Lee LA, et al. Liability associated with obstetric anesthesia: a closed claims
analysis. Anesthesiology. 2009;110:131–139.
41. D’Angelo R, Smiley RM, Riley ET, et al. Serious complications related to obstetric anesthesia: the
serious complication repository project of the Society for Obstetric Anesthesia and Perinatology.
Anesthesiology. 2014;120:1505-1512.
42. Mhyre JM, Riesner MN, Polley LS, et al. A series of anesthesia-related maternal deaths in Michigan,
1985-2003. Anesthesiology. 2007;106:1096–1104.
43. Lofsky A. Doctors company reviews maternal arrest cases. Anesth Patient Saf Found Newsl.
2007;22:28–30.
44. Mhyre JM. Why do pharmacologic test doses fail to identify the unintended intrathecal catheter in
obstetrics? Anesth Analg. 2013;116:4–5.
Guidelines
from National
Organizations
 Guidelines from National Organizations
Kathryn J. Zuspan

I. Terms used to label guidance documents
II. American Society of Anesthesiologists as a leader in developing
guidance documents
III. “Practice Parameter” is the American Society of Anesthesiologists
term for guidance documents
A. Evidence-based practice parameters
B. Consensus-based American Society of Anesthesiologist
Practice Parameters
C. Other—statements, positions, and protocols
IV. How should Practice Parameters be used?
V. Limitations of guidance documents
VI. How to judge/compare documents
VII. National organizations with guidance relevant to obstetric
anesthesia
VIII. American Society of Anesthesiologists website access and relevant
documents
A. American Society of Anesthesiologist documents specific to
obstetric anesthesia practice
IX. American College of Obstetricians and Gynecologists
X. American Academy of Pediatrics and American College of
Obstetricians and Gynecologists Collaboration: Guidelines for
Perinatal Care
XI. Relevant documents from the American Society of Regional
 Anesthesia and Pain Medicine
XII. Relevant document from the American Heart Association
XIII. Relevant document from the Society for Obstetric Anesthesia and
Perinatology

KEYPOINTS
1. Guidelines from organizations provide valuable information but cannot
guarantee a specific outcome. Interpretation and application of guidelines
takes place at the local level. A departure from recommendations may be
appropriate if the facts and circumstances show a physician’s care met his
or her duty to the patient.
2. All guidelines are not created equal. They can be based on evidence,
consensus, expert opinion, or any combination of these. They can provide
minimum requirements, recommendations for a range of strategies, and
statements to help in decision-making.
3. In evidence-based documents, every researched topic is discussed
followed by a grade referring to the amount of science supporting the
relationship (linkage) between the clinical intervention and clinical
outcome. Level 1 (supportive) has sufficient scientific evidence; level 2
(suggestive) has some evidence; level 3 (equivocal) has little or unclear
evidence; inconclusive, insufficient, or silent grades mean a linkage lacks
supporting evidence.
4. Knowledge of relevant guidelines is an important part of medical
practice.
5. Not all documents agree. The reader is encouraged to compare
documents to discover the reasons for discrepancies; to examine the dates
of acceptance, revision, and its references; and to check the source of
information.

I. Terms used to label guidance documents

 Over the past 35 years, guidelines have been developed by national
medical organizations to assist in clinical decision-making and patient
safety. These documents are called by a variety of terms such as
standards, guidelines, and practice parameters, which describe their
makeup and function. The meaning of these terms is crucial to
understanding the information in each document. The American
Society of Anesthesiologists’ (ASA) documents will be used to
illustrate this concept. Organizations have similar, although not
identical, terms for their guidance documents. Terms used by the
American College of Obstetricians and Gynecologists (ACOG) will
be discussed later.
II. American Society of Anesthesiologists as a leader in developing
guidance documents
The ASA was the first professional medical society to develop and
disseminate standards of care for its members.1 The ASA was also an
early leader in developing an evidence-based, expert-based, and
consensus-based model for practice guidelines and advisories.
III. “Practice Parameter” is the American Society of
Anesthesiologists term for guidance documents
The term “Practice Parameter” is used to describe the majority of
ASA guidance type documents. These documents offer requirements,
recommendations, or statements to improve anesthesia practice and
promote, although not guarantee, favorable outcomes.2
The ASA states that practice parameters may be revised and/or
updated when appropriate. The document states that “reasonable”
anesthesiologists may depart from specific practice parameters based
on clinician judgement.
The ASA divides their Practice Parameter documents into two
classes: evidence-based and consensus-based.
A. Evidence-based practice parameters
These are divided into ASA standards, guidelines, and
practice advisories.
1. Standards give rules or minimum requirements that are
 accepted by nearly all experts and surveyed ASA
members. These documents are based on evidence and may
be modified only under special circumstances such as extreme
emergencies. Example: Basic Standards for Preanesthesia
Care, approved 1987, reaffirmed 2010.
2. Practice guidelines give recommendations for a basic
management strategy or a range of basic management
strategies for patient care. These are accepted by a majority
of experts and surveyed ASA members. Areas of differing
opinion are also included. The ASA’s model for practice
guidelines and advisories is evidence-based, expert-based, and
consensus-based and includes information from five sources:
an evidence-based search of the scientific literature, expert
opinion from a task force, surveys of ASA members,
feasibility data, and input from ASA members collected at
open forums.
3. Development begins at the ASA House of Delegates, which is
composed of around 300 members including representatives
from each state society and from seven subspecialty societies,
as well as ASA officers, past ASA presidents, and chairs of
appropriate sections. This group chooses the practice
parameter topics and timing of updates.
4. The ASA Committee on Standards and Practice Parameters
guides new evidence-based documents through production
and existing documents through the revision process.
a. This committee selects a task force of experts from a
representative variety of anesthesia practices
(academic/private, large/small, urban/rural, and different
regions of the country).
b. The task force meets with the ASA’s two methodologists
and decides the issues or questions that should be
addressed in the parameter. They word these questions as
“linkages” between a “clinical intervention” and a
“clinical outcome.”
c. The methodologists do an extensive literature search for
all qualified articles (randomized clinical trials or meta-
analyses) either for or against support of each linkage. An
article must have sound science and statistics to qualify
for inclusion in the literature used for a parameter.
d. The evidence for each linkage receives a grade that refers
to the amount of science supporting the relationship
between that particular clinical intervention and a
clinical outcome.
(1) Supportive—category A or level 1. This grade
means sufficient numbers of adequately designed
studies exist for a meta-analysis to determine a
statistically significant relationship between a clinical
intervention and a clinical outcome.
(2) Suggestive—category B or level 2. This grade is
given when there are several adequately designed
studies but not enough to attain statistical
significance about the outcome.
(3) Equivocal—category C or level 3. This grade is
given when the studies on a clinical intervention do
not provide a clear direction for a clinical outcome or
when there are too few studies available.
(4) Inconclusive, insufficient, or silent—category D.
This grade is given when scientific evidence is
lacking.
e. Using evidence-based findings, the task force writes an
initial document, as well as a related survey, that is sent to
a wide range of ASA members.
f. The task force then includes input from the survey results,
the feasibility data, and comments from open forums in
the final version of the document.
g. This version is submitted to the House of Delegates at the
ASA annual meeting for possible acceptance. If rejected
even on one small area, the entire document is rejected. It
 can be revised and resubmitted the following year.
h. New practice guidelines may take several years from
development to acceptance. Revisions of older practice
guidelines typically take a few years. Example: Practice
Guidelines for Obstetric Anesthesia, approved 1999,
amended 2006, revision in progress.
5. Practice advisories are evidence-based statements that
assist decision-making in areas of patient care where there
are not enough clinical trials to perform a meta-analysis.
These reports provide a synthesis of expert opinion, open
forum commentary, clinical feasibility data, and consensus
surveys. The majority of experts and ASA members agree
with these as well.
Example: Practice Advisory for Intraoperative Awareness and
Brain Function Monitoring, 2006.
B. Consensus-based American Society of Anesthesiologist
Practice Parameters
Unlike the evidence-based documents, these provide consensus-
based opinions formulated by ASA appointed experts through
scientific information that may be used if available.
Consensus-based parameters are divided into policy parameters
and clinical practice parameters.
1. Policy parameters are consensus-based and discuss
policies and protocols around professional conduct. Topics
include ethical practice, credentialing, clinical privileges,
expert witnesses, and continuing medical education.
Example: Policy Statement on Practice Parameters, approved
2007, amended 2013.
2. Clinical practice parameters discuss consensus-based
clinical management, patient safety, and recommendations
for patient care.
Example: Is Postoperative Cognitive Decline Clinically
Relevant?, 2010.
C. Other—statements, positions, and protocols
 These are ASA documents that do not fit these evidence or
consensus models: They have been approved by the ASA
House of Delegates and represent opinions of the House of
Delegates on a variety of topics.
1. These documents may not have undergone the same level of
scientific review as practice parameters. Variances from the
opinions expressed in the documents should be based on the
judgment of a responsible anesthesiologist.
2. Example of a position document. Recommended Scope of
Practice of Nurse Anesthetists and Anesthesiologist
Assistants, 2009.
3. Example of a protocol. Massive Transfusion Protocol (MTP)
for Hemorrhagic Shock—ASA Committee on Blood
Management, 2011.
IV. How should Practice Parameters be used?
The ASA developed practice parameters to improve patient care and
safety. They can be used as clinical and/or educational tools to
improve decision-making and promote favorable outcomes.
Knowledge of relevant guidelines is an important part of medical
practice.

CLINICAL PEARL The ASA is aware of the wide variety of

anesthesia practices and varying resources. It does not intend for
practice parameters to dictate appropriate care and notes that
modifications may be appropriate to provide the best patient care in
specific locations and/or situations.

V. Limitations of guidance documents

A. Confusing language. Documents with complex or confusing
wording are more likely to confuse the reader, which limits their
effectiveness.
B. Subtle bias. Subtle biases from the most even-minded authors
may affect the direction of a document. This is more likely when
 a document is not evidence-based or when written by a single
author. Before the popularity of evidence-based medicine, most
organizations would convene a committee of experts who came to
a joint consensus on a topic and found literature to support their
views. Unlike the evidence-based approach, both sides of the
issue may not have been represented in the document.
C. Conflict of interest. Authors with conflicts of interest limit the
transparency and trust in documents. The ASA has a conflict of
interest policy that eliminates individuals with conflicts of interest
from working on ASA projects.3 Funding for development of all
practice parameters, guidelines, and advisories comes from the
ASA, which spends approximately $500,000 per year on this
endeavor. No outside or industry payments are allowed.4
D. Unrealistic expectations. Documents that are too restrictive or
too difficult to use in real world situations (e.g., rural or smaller
practices) have limited value.
E. Failure to consider the grade of the supporting evidence. In
evidence-based documents, all of the linkages are presented
regardless of the amount of science supporting or rejecting a
relationship between intervention and outcome. This may mislead
some readers who interpret a document assuming equal weight
behind each statement (R. T. Connis, oral communication,
October 2014).
F. Failure to ask the right questions or limited studies available.
Evidence-based documents are not perfect. They can be limited
by the use of intervention–outcome questions. What if the wrong
questions are asked or they are asked but never studied? What if
the studies were completed but were implemented poorly? What
if the studies were done well but had inconsistent results or
publication bias? They would be disqualified even if the clinical
intervention question was pertinent. What if the outcome occurs
so rarely that it cannot be studied? For example, spinal
hematomas are rare, so little evidence is available and certainly
not enough for a clinical trial. Evidence-based medicine has
 strengths and limitations.5
G. Production time and cost. It takes several years, large numbers
of man hours and thousands of dollars to develop an evidence-
based practice parameter. Typically, a revised edition is needed
every 5 to 10 years. Revision requires a similar process as an
initial document, but often requires fewer years to complete, often
at the same expense (R. T. Connis, oral communication, October
2014). This limits the number of documents and revisions an
organization may produce.
VI. How to judge/compare documents
Do not assume agreement between all documents.
A. Look at the date the document was accepted by the national
organization. Is it recent? Have any major changes in the
literature occurred since the acceptance/revision date?
B. Look at the articles in the reference list. Are they recent and
from reputable sources (e.g., peer-reviewed journals, Cochrane
Review)?
C. Look at the date of last revision. Was it an actual revision—was
anything changed or updated? Was it a revision or a
reaffirmation? Was there a change or updating in the list of
references?
D. Look at the basis of the document (i.e., evidence-
based/consensus-based, standard/guidelines). Is the basis
appropriate to the topic being addressed?
E. When there are discrepancies, go to the sources which the
document cites. Does the document suggest outcomes that are
consistent with similar documents on this topic from related
organizations? If not, determine the discrepancy between the
documents. Check the reference lists to locate the source of the
information. Follow the source of the information back to the
original document. Check to see if the problem was a misprint,
misinterpretation of the source material, or a misinterpretation of
the source material by another document that is then duplicated in
this document.
1. Example: The American Society of Regional Anesthesia and
Pain Medicine (ASRA)6 practice advisories and guidelines are
considered the gold standard on regional anesthesia topics.
ASRA’s practice guideline on Regional Anesthesia in the
Patient Receiving Antithrombotic or Thrombolytic Therapy:
American Society of Regional Anesthesia and Pain Medicine
Evidence-Based Guidelines (Third Edition)7 is used and
quoted by a majority of national organizations. ASRA
recommends delaying placement of an epidural needle or
catheter for 10 to 12 hours after a smaller, once-daily
prophylactic dose of low molecular weight heparin (LMWH)
and at least 24 hours after a larger often twice-daily
therapeutic or treatment dose of LMWH.
The Seventh American College of Chest Physicians
(ACCP) Conference on Antithrombotic and Thrombolytic
Therapy: Evidence-Based Guidelines, 2004,8 claims to follow
the ASRA recommendations on this topic, but their document
mistakenly suggests delaying the epidural until at least 8 to 12
hours after a twice-daily prophylactic dose of LMWH, or at
least 18 hours after a once-daily LMWH injection.
Prophylactic doses are not given twice daily. Did they mean
to say twice-daily therapeutic dose? Was this a misprint?
2. In another example, the ACOG’s9 Practice Bulletin on the
Prevention of Deep Vein Thrombosis and Pulmonary
Embolism, No. 84, 2007, reaffirmed 2013, uses the incorrect
information from the Chest Physicians document and thus
makes an incorrect recommendation. Fortunately, the ACOG
has three documents that correctly agree with the ASRA time
delay between LMWH dose and epidural placement. These
include the Practice Bulletin on Obstetric Analgesia and
Anesthesia, No. 36, 2002, reaffirmed 2013; the Practice
Bulletin on Thromboembolism in Pregnancy, No. 123, 2011,
reaffirmed 2014; and the Practice Bulletin on Inherited
Thrombophilias in Pregnancy, No. 138, 2013.9
F. Is the information outdated? Check the acceptance date, dates
of any revisions, and age of the references. Not all documents
require rapid revisions; however, revisions are needed when the
literature provides changes in practice.
1. For example, the ACOG’s Practice Bulletin on Obstetric
Analgesia and Anesthesia, No. 36, accepted 2002 and
reaffirmed without changes in 2013, has references all of
which predate 2003.9 It states that early epidural analgesia
increases the risk of cesarean delivery (CD) and sources this
from an ACOG 2000 Task Force Document on Cesarean
Delivery Rates with references that predate 2000.10 Therefore,
ACOG’s evidence-based Practice Bulletin on Obstetric
Analgesia and Anesthesia (reaffirmed in 2013) has 10-year-
old references and relies on an outdated 13-year-old, level III
reference (no longer available on their website) for this
particular recommendation.
2. This is surprising because the ACOG’s 2006 Committee
Opinion on Analgesia and Cesarean Delivery, No. 339,
reaffirmed in 2013, has references as recent as 2005 and
presents literature that disqualifies that prior finding. It states
early epidural analgesia use does not increase the risk of CD.
G. Is the interpretation influenced by specialty? At times, the
needs of one specialty differ from that of another. The ACOG’s9
Practice Bulletin on Inherited Thrombophilias in Pregnancy, No.
138, 2013, states, “Patients receiving unfractionated heparin or
LMWH who require rapid reversal of the anticoagulant effect for
delivery can be treated with protamine sulfate.” It is correct that
protamine sulfate reverses some of the anticoagulant effects of
LMWH. This may be enough to reduce some surgical bleeding if
an urgent CD is needed. So obstetricians might agree with the
suggestion that protamine sulfate can reverse the anticoagulant
effect of LMWH because it works well enough to meet their
needs. However, protamine sulfate does not completely reverse
the anticoagulant effect of LMWH, so it is impossible to ensure
 completely safe epidural placement (C. Lockwood, MD, oral
communication, September 2012). Many anesthesiologists might
then disagree with the ACOG’s statement and instead agree with
the ASRA Practice Advisory (mentioned earlier) stating that the
anticoagulation of LMWHs is not reversed by protamine sulfate.
H. Are discrepancies between documents due to international
differences in clinical practice? For example, the time delay
recommended before proceeding with regional
analgesia/anesthesia following the use of LMWH is shorter in
Europe than that recommended in the United States. The
explanation is that the typical prophylactic LMWH dose in
Europe is smaller than that used for the same purpose in the
United States. As a result, the shorter European time interval is
not valid in the United States.

CLINICAL PEARL Guidance documents may conflict with one

another, even if published by the same national organization.
Author and specialty bias, failure on the part of the authors to
consider all of the available information, and outdated
recommendations may limit their usefulness.

VII. National organizations with guidance relevant to obstetric

anesthesia
A. Specific documents are presented below from the following:
1. American Society of Anesthesiologists (ASA)
2. American College of Obstetrics and Gynecology (ACOG)
3. American Academy of Pediatrics (AAP)
4. American Society of Regional Anesthesia and Pain Medicine
(ASRA)
5. Society for Obstetric Anesthesia and Perinatology (SOAP)
6. American Heart Association (AHA)
B. Best access to up-to-date versions of documents from national
organizations.
 Documents are frequently updated, making hard copies subject to
outdating. The best source for documents is each organization’s
official website. Some organizations require membership for
access, some give documents as attachments, and some provide
web addresses for documents that change with time and provide
updates. This makes web addresses for specific documents
transient or difficult to attain. Therefore, directions will be given
for the most reliable web sources for access to the documents
discussed.
VIII. American Society of Anesthesiologists website access and
relevant documents
The official ASA website (www.ASAhq.org) offers free online access
to documents. Look at the top of the ASA home page for the heading
“For Health Professionals”, click to see the drop-down panel list, and
then click on “Standards, Guidelines, and Statements”11 or on
“Evidence-Based Practice Parameters”12 for access to needed
documents. The former section provides the new and updated
documents, followed by an alphabetical access list for the rest of the
standards, guidelines, and statements. Locate the document by date of
recent update or by title. Continue down that page to a group of “other
documents” providing comments the ASA solicited from ASA
committees. The ASA Committee on Obstetric Anesthesia has
submitted two documents: one on the effectiveness of interventions to
decrease cesarean births and the other on use of nitrous oxide for
labor analgesia. Access the section called “Practice Parameters”
where the documents are in no obvious order and provided in pdf
versions.

CLINICAL PEARL Access to the most recent documents is

typically provided through an organization’s website. Access to
some documents may be limited only to the organization’s
members.
A. American Society of Anesthesiologist documents specific to
obstetric anesthesia practice
The names of the documents, dates of approval, or last update
are provided, followed by a brief summary or listing of the
issues relevant to obstetric anesthesia (see Table 33.1).

1. Relevant American Society of Anesthesiologists standards

a. Basic Standards for Preanesthesia Care
Approved 1987, last amended 2010.11
In summary, these standards apply to all patients who
receive anesthesia care. These standards require the
following: review of the patient record, patient interview
and focused exam, preoperative testing and consultation
when needed, and a check of the surgical consent. Under
exceptional circumstances, these standards may be
 modified. In that case, the circumstances requiring the
modification should be documented in the chart.
b. Standards for Basic Anesthetic Monitoring
Approved 1986, last amended 2011.11
In summary, the basics include the monitoring of
oxygenation, ventilation, circulation, and temperature, and
require the presence of qualified anesthesia personnel to
perform these tasks. These standards apply to all
anesthesia care, although, in emergency circumstances,
appropriate life support measures take precedence. These
standards are not intended for application in the care
of the obstetric patient in labor. However, they do
apply for procedures occurring in labor and delivery
operating rooms.
c. Standards for Postanesthesia Care
Approved 2004, last amended 2009.11
In summary, these standards apply to postanesthesia
care in all locations. All patients who have received
general anesthesia (GA), regional anesthesia, or
monitored anesthesia care for operative procedures shall
receive appropriate postanesthetic management.
Furthermore, a member of the anesthesia team will
manage patient care during transport to the postanesthesia
care unit (PACU) and, after arrival, reevaluate the patient
and give a verbal report to the PACU nurse.
2. Relevant American Society of Anesthesiologists Practice
Guidelines
a. Practice Guidelines for Obstetric Anesthesia
Approved 1999, last amended 2006, revisions in progress,
2014.12
These guidelines have been systematically developed to
assist the practitioner and patient in making decisions
about anesthetic care. Their purpose is to enhance the
quality of anesthetic care for obstetric patients, improve
patient safety by reducing the incidence of anesthesia-
related complications, and increase patient satisfaction.
The guidelines focus on the anesthetic management of
pregnant patients during labor, nonoperative delivery,
operative delivery, and selected aspects of postpartum
care and analgesia (i.e., neuraxial opioids for postpartum
analgesia after neuraxial anesthesia for CD). The intended
patient population includes, but is not limited to,
intrapartum and postpartum patients with uncomplicated
pregnancies or with common obstetric problems. The
guidelines do not apply to patients undergoing surgery
during pregnancy, gynecologic patients, or parturients
with chronic medical disease (e.g., severe cardiac, renal,
or neurologic disease). These guidelines do not address
postpartum analgesia for vaginal delivery, analgesia
after tubal ligation, or postoperative analgesia after
GA for CD.
The current recommendations include:
(1) Perianesthetic evaluation
(a) “Examination of the airway, heart and lungs,
consistent with the ASA Practice Advisory on
Preanesthesia Evaluation.”
(b) “Recognition of significant anesthetic or
obstetric risk factors should encourage
consultation between the obstetrician and the
anesthesiologist. A communication system
should be in place to encourage early and
ongoing contact between obstetric providers,
anesthesiologists, and other members of the
multidisciplinary team.”
(c) “The fetal heart rate (FHR) should be monitored
by a qualified individual before and after
administration of neuraxial analgesia for labor.
Continuous electronic recording of the FHR
 may not be necessary in every clinical setting
and may not be possible during initiation of
neuraxial analgesia.”
(d) “A routine platelet count is unnecessary in the
healthy parturient before neuraxial anesthesia.”
(e) “A type and screen or cross-match should be
ordered on an individual basis, depending on
risk factors and ‘local institutional policies.’”
(2) Aspiration prophylaxis
(a) “The oral intake of modest amounts of clear
liquids may be allowed for uncomplicated
laboring patients. The uncomplicated patient
undergoing delivery may have modest amounts
of clear liquids up to 2 h before the induction of
anesthesia. However, patients with additional
risk factors for aspiration (e.g., morbid obesity,
diabetes) or patients at increased risk for CD
(e.g., nonreassuring FHR) may have further
restrictions of oral intake, determined on a case-
by-case basis.”
(b) “Solid foods should be avoided in laboring
patients.” Recommendations are consistent with
the ASA Practice Guidelines for Preoperative
Fasting stating, “the patient undergoing elective
surgery (e.g., scheduled CD or PPTL) should
undergo a fasting period for solids of 6–8 h
depending on the type of food ingested (e.g., fat
content).”12
(c) “Before surgical procedures, practitioners should
consider the timely administration of
nonparticulate antacids, H2-receptor antagonists,
and/or metoclopramide for aspiration
prophylaxis.”
(3) Anesthetic care for labor and vaginal delivery
 (a) “Patients in early labor (i.e., < 5 cm dilation)
should be given the option of neuraxial analgesia
when this service is available. Neuraxial
analgesia should not be withheld on the basis of
achieving an arbitrary cervical dilation, and
should be offered on an individualized basis.
Patients should be reassured that the use of
neuraxial analgesia does not increase the
incidence of CD.”
(b) “Patient-controlled epidural analgesia (PCEA)
may be used to provide an effective and flexible
approach for the maintenance of labor
analgesia.” The Task Force notes that the use of
“PCEA may be preferable to continuous infusion
techniques for providing fewer anesthetic
interventions, reduced dosages of local
anesthetics, and less motor blockade than fixed-
rate continuous epidural infusions. PCEA may
be used with or without a background infusion.”
(c) “Combined spinal-epidural techniques may be
used to provide effective and rapid onset of
analgesia for labor.”
(4) Anesthetic choices for cesarean delivery
(a) “Equipment, facilities, and support personnel
available in the labor and delivery operating
suite should be comparable to those available in
the main operating suite.”
(b) “The decision to use a particular anesthetic
technique for CD should be individualized,
based on several factors. These include
anesthetic, obstetric, or fetal risk factors (e.g.,
elective vs. emergency), the preferences of the
patient, and the judgment of the
anesthesiologist.”
 (c) “Neuraxial techniques are preferred to GA for
most CD. An indwelling epidural catheter may
provide equivalent onset of anesthesia compared
with initiation of spinal anesthesia for urgent
CD. If spinal anesthesia is chosen, pencil-point
spinal needles should be used instead of cutting-
bevel spinal needles.”
(d) “However, GA may be the most appropriate
choice in some circumstances (e.g., profound
fetal bradycardia, ruptured uterus, severe
hemorrhage, severe placental abruption). Uterine
displacement (usually left displacement) should
be maintained until delivery regardless of the
anesthetic technique used.”
(e) “Intravenous [IV] fluid preloading may be used
to reduce the frequency of maternal hypotension
after spinal anesthesia for CD. Although fluid
preloading reduces the frequency of maternal
hypotension, initiation of spinal anesthesia
should not be delayed in order to administer a
fixed volume of IV fluid.”
(f) “IV ephedrine and phenylephrine are both
acceptable drugs for treating hypotension during
neuraxial anesthesia. In the absence of maternal
bradycardia, phenylephrine may be preferable
because of improved fetal acid–base status in
uncomplicated pregnancies.”
(g) “Pencil-point spinal needles should be used
instead of cutting-bevel spinal needles to
minimize the risk of postdural puncture
headache.”
(5) Postpartum tubal ligation
(a) “For postpartum tubal ligation [PPTL], the
patient should have no oral intake of solid foods
 within 6–8 h of the surgery, depending on the
type of food ingested (e.g., fat content).
Aspiration prophylaxis should be considered.”
(b) “Both the timing of the procedure and the
decision to use a particular anesthetic technique
(i.e., neuraxial vs. general) should be
individualized, based on anesthetic risk factors,
obstetric risk factors (e.g., blood loss), and
patient preferences. However, neuraxial
techniques are preferred to GA for most PPTLs.”
(c) “The anesthesiologist should be aware that
gastric emptying will be delayed in patients who
have received opioids during labor, and that an
epidural catheter placed for labor may be more
likely to fail with longer postdelivery time
intervals.”
(d) “If a PPTL is to be performed before the patient
is discharged from the hospital, the procedure
should not be attempted at a time when it might
compromise other aspects of patient care on the
labor and delivery unit.”
(6) Management of obstetric and anesthetic emergencies
(a) “Institutions providing obstetric care should
have resources available to manage hemorrhagic
emergencies [see Table 33.2]. In an emergency,
the use of type-specific or O negative blood is
acceptable.”
(b) “In cases of intractable hemorrhage when
banked blood is not available or the patient
refuses banked blood, intraoperative cell-salvage
should be considered if available.”
(c) “Labor and delivery units should have personnel
and equipment readily available to manage
airway emergencies, to include a pulse oximeter
and qualitative carbon dioxide detector,
consistent with the ASA Practice Guidelines for
Management of the Difficult Airway. Basic
airway management equipment should be
immediately available during the provision of
neuraxial analgesia [see Table 33.3]. In addition,
portable equipment for difficult airway
management should be readily available in the
operative area of labor and delivery units [see
Table 33.4]. The anesthesiologist should have a
preformulated strategy for intubation of the
difficult airway. When tracheal intubation has
failed, ventilation with mask and cricoid
pressure or with a laryngeal mask airway [LMA]
or supraglottic airway device (e.g., Combitube,
Intubating LMA [Fastrach]) should be
considered for maintaining an airway and
ventilating the lungs. If it is not possible to
ventilate or awaken the patient, an airway should
be created surgically.”
 (d) “Basic and advanced life-support equipment
should be immediately available in the operative
area of labor and delivery units. If cardiac arrest
occurs during labor and delivery, standard
resuscitative measures should be initiated. In
addition, uterine displacement (usually left
displacement) should be maintained. If maternal
circulation is not restored within 4 min, CD
should be performed by the obstetric team.”
b. Practice Guidelines for Preoperative Fasting
Approved in 1999, last amended in 2010.12
The ASA Practice Guidelines for Obstetric Anesthesia
reference the older (1999) version of this document when
 addressing the topic of fasting in the obstetric patient (see
preceding text); however, there have been no changes in
the recommendations between the original and revised
version.
c. Practice Guidelines for Postanesthetic Care
Approved 2001, last amended 2012.12
(1) These guidelines update the literature, but provide no
change to the 2001 recommendations for care of all
patients following anesthesia care.
(2) Patient assessment and monitoring; prophylaxis and
treatment of nausea and vomiting; treatment for
emergence and recovery; antagonism of the effects of
sedatives, analgesics, and neuromuscular blocking
agents; and the protocol for discharge are addressed.
d. Practice Guidelines for the Prevention, Detection, and
Management of Respiratory Depression Associated
with Neuraxial Opioid Administration
Approved 2008.12
Respiratory depression following neuraxial opioid
administration is an important cause of perioperative
morbidity and mortality. These guidelines apply to
management of patients on labor and delivery. These
guidelines incorporate (but are not limited to) the
following recommendations.
(1) Prevention
(a) The anesthesiologist should “conduct a focused
history and physical examination before
administering neuraxial opioids.” Particular
attention should be directed “toward signs,
symptoms, or a history of sleep apnea, co-
existing diseases or conditions (e.g., diabetes,
obesity), current medications (including
preoperative opioids), and adverse effects
following opioid administration.”
 (b) “The lowest effective dose of neuraxial opioids
should be administered to minimize the risk of
respiratory depression.”
(c) “Parenteral opioids or hypnotics should be
cautiously administered in the presence of
neuraxial opioids.”
(d) “The concomitant administration of neuraxial
opioids and parenteral opioids, sedatives,
hypnotics, or magnesium requires increased
monitoring (e.g., intensity, duration, or
additional methods of monitoring).”
(2) Detection
(a) “All patients receiving neuraxial opioids should
be monitored for adequacy of ventilation (e.g.,
respiratory rate, depth of respiration [assessed
without disturbing a sleeping patient]),
oxygenation (e.g., pulse oximetry when
appropriate), and level of consciousness.”
(i) “For single-injection neuraxial lipophilic
opioids (e.g., fentanyl), monitoring should
be performed for a minimum of 2 h after
administration. Continual monitoring (i.e.,
repeated regularly and frequently in steady
rapid succession) monitoring should be
performed for the first 20 min after
administration, followed by monitoring at
least once per hour until 2 h has passed.
After 2 h, frequency of monitoring should
be dictated by the patient’s overall clinical
condition and concurrent medications.”
(ii) “For continuous infusion or PCEA with
neuraxial lipophilic opioids, monitoring
should be performed during the entire time
the infusion is in use. Monitoring should be
 continual for the first 20 min after
initiation, followed by monitoring at least
once per hour until 12 h has passed. From
12 to 24 h, monitoring should be performed
at least once every 2 h. After 24 h,
monitoring should be performed at least
once every 4 h. After discontinuation of
continuous infusion or PCEA with
neuraxial lipophilic opioids, frequency of
monitoring should be dictated by the
patient’s overall clinical condition and
concurrent medications.”
(iii) “For single-injection neuraxial
hydrophilic opioids (e.g., morphine, not
including sustained-or extended-release
epidural morphine), monitoring should be
performed for a minimum of 24 h after
administration. Monitoring should be
performed at least once per hour for the
first 12 h after administration, followed by
monitoring at least once every 2 h for the
next 12 h (i.e., from 12 to 24 h). After 24 h,
frequency of monitoring should be dictated
by the patient’s overall clinical condition
and concurrent medications.”
(iv) “For continuous infusion or PCEA with
neuraxial hydrophilic opioids, monitoring
should be performed during the entire time
the infusion is in use. Monitoring at least
once every hour should be performed for
the first 12 h after initiation, followed by
monitoring at least once every 2 h for the
next 12 h. After 24 h, monitoring should be
performed at least once every 4 h. After
 discontinuation of continuous infusion or
PCEA, frequency of monitoring should be
dictated by the patient’s overall clinical
condition and concurrent medications.”
(v) “For sustained-or extended-release
epidural morphine, monitoring at least once
every hour should be performed during the
first 12 h after administration, and at least
once every 2 h for the next 12 h (i.e., from
12 to 24 h). After 24 h, monitoring should
be performed at least once every 4 h for a
minimum of 48 h.”
(vi) “Increased monitoring (e.g., intensity,
duration, or additional methods of
monitoring) may be warranted in patients at
increased risk of respiratory depression
(e.g., unstable medical condition, obesity,
obstructive sleep apnea, concomitant
administration of opioid analgesics or
hypnotics by other routes, extremes of
age).”
(3) Management/treatment
(a) “For patients receiving neuraxial opioids,
supplemental oxygen should be available.”
(b) “Supplemental oxygen should be administered
to patients with altered level of consciousness,
respiratory depression, or hypoxemia and
continued until the patient is alert and no
respiratory depression or hypoxemia is present.”
(c) “Routine use of supplemental oxygen may
increase the duration of apneic episodes and may
hinder detection of atelectasis, transient apnea,
and hypoventilation.”
(d) Reversal agents should be available.
 Noninvasive positive-pressure ventilation is an
option to improve ventilation status.
e. Practice Guidelines for Management of the Difficult
Airway
Approved 2002, last amended 2012.12
This updated document presents updated evidence and
literature, but the recommendations remain unchanged
from the 2002 document.
(1) The recommendations state: “the preoperative airway
evaluation should include an airway history and
physical exam and appropriate additional evaluation
when appropriate.”
(2) “Basic preparation for a potential difficult airway
case includes informing the patient, presence of a
readily available portable cart containing necessary
equipment, and the availability of additional staff for
assistance.”
(3) “Facemask oxygenation is imperative prior to airway
management and supplemental oxygen is needed
throughout the intubation process.”
(4) Strategies for intubation and extubation of the
difficult airway are given as well as suggestions for
follow-up with the patient.
3. Relevant American Society of Anesthesiologists Practice
Advisories
a. Practice Advisory for Preanesthesia Evaluation
Approved 2001, last amended 2010.12
This Advisory is an update of the original document,
providing new scientific information, but no changes in
the recommendations. It discusses the timing of the
preanesthetic evaluation and content of that exam.
Although routine preop tests are not necessary, selective
tests may help in patient assessment and management.
Specific tests and timing of tests should be individualized.
 (1) On preanesthesia pregnancy testing, it states,
“Patients may present for anesthesia with early
undetected pregnancy.” The Task Force believes that
the literature is inadequate to inform patients or
physicians on whether anesthesia causes harmful
effects on early pregnancy.
(2) “Pregnancy testing may be offered to female patients
of childbearing age and for whom the result would
alter the patient’s management.”
b. Practice Advisory for Intraoperative Awareness and
Brain Function Monitoring
Approved 2006.12
This document defines consciousness, GA, depth of
anesthesia or depth of hypnosis, recall, amnesia, and
intraoperative awareness.
(1) Its stated purpose is to identify risk factors that may
be associated with intraoperative awareness. The risk
factors pertinent to obstetrics include CD, emergency
surgery, reduced anesthetic doses in the presence of
paralysis, planned use of muscle relaxants during the
maintenance phase of GA, total IV anesthesia, and
the planned use of nitrous oxide-opioid anesthesia.
(2) To reduce the frequency of unintended intraoperative
awareness, the advisory suggests avoiding equipment
malfunction or misuse by using a checklist.
(3) The document states, “Intraoperative monitoring of
depth of anesthesia, for the purpose of minimizing
the occurrence of awareness, should rely on multiple
modalities, including clinical techniques (e.g.,
checking for clinical signs such as purposeful or
reflex movement) and conventional monitoring
systems (e.g., electrocardiogram, blood pressure, HR,
end-tidal anesthetic analyzer, capnography). The use
of neuromuscular blocking drugs may mask
 purposeful or reflex movements and adds additional
importance to the use of monitoring methods that
assure the adequate delivery of anesthesia.”
(4) “It is the consensus of the Task Force that the
decision to use a brain function monitor should be
made on a case-by-case basis by the individual
practitioner for selected patients (e.g., light
anesthesia).”
c. Practice Advisory for the Prevention, Diagnosis, and
Management of Infectious Complications Associated
with Neuraxial Techniques
Approved 2009.12
This document identifies patients who are at increased
risk for infectious complications with neuraxial
techniques, looks at ways to reduce their risk, and how to
intervene should infectious complications arise.
(1) To reduce the risks associated with neuraxial
techniques, consider alternative options for patients at
high risk, administer preprocedure antibiotic therapy
for patients with known or suspected bacteremia,
consider the evolving medical status of the patient,
and avoid a lumbar puncture in a patient with a
known epidural abscess.
(2) Use aseptic techniques when preparing equipment
(e.g., ultrasound) and performing the procedure.
Aseptic technique includes removing jewelry (e.g.,
rings and watches), hand washing, wearing sterile
gloves, wearing a cap, wearing a mask that covers
the nose and mouth, and consideration for
changing the mask between cases.
(3) For skin preparation, use individual packets of
antiseptics, use chlorhexidine (preferably with
alcohol), and allow adequate drying time before the
procedure. Use sterile drapes and sterile occlusive
 dressings at the catheter insertion site. Consider using
bacterial filters for extended continuous epidural
infusions, limit the disconnection and reconnection of
neuraxial delivery systems, and consider removing
unwitnessed accidentally disconnected catheters.
Remove catheters as soon as no longer clinically
necessary.
(4) To diagnose infection, the ASA advisory states,
“Daily evaluation of patients with indwelling
catheters for early signs and symptoms (e.g., fever,
backache, headache, erythema, and tenderness at the
insertion site) of infectious complications should be
performed throughout their stay in the facility. To
minimize the impact of an infectious complication,
promptly attend to signs or symptoms.”
(5) If an infection is suspected, (a) remove an in situ
catheter and consider culturing the catheter tip, (b)
order appropriate blood tests, (c) obtain appropriate
cultures, and (d) if an abscess is suspected or
neurologic dysfunction is present, imaging studies
should be performed, and consultation with other
appropriate specialties should be promptly obtained.
(6) Treatment includes appropriate antibiotic therapy,
appropriate consultation, and possible laminectomy.
4. Relevant American Society of Anesthesiologist Statements,
Positions, and Protocols
a. Statement on Nonoperating Room Anesthetizing
Locations
Approved 1994, last amended 2013.11
The updated title now calls this a statement (not a
guideline, which is appropriate because it does not meet
the definition of an evidence-based document).
(1) In summary, these guidelines apply to all anesthesia
care involving anesthesiology personnel for
 procedures in locations outside an operating room,
such as in birthing rooms in labor and delivery.
(2) These are minimal guidelines for equipment and
staffing for nonoperating room settings, except where
they are not applicable to an individual patient or care
setting.
b. Optimal Goals for Anesthesia Care in Obstetrics
Approved 2007, amended 2010, ASA/ACOG review in
progress in 2014.11
This is a joint statement from ASA and ACOG that
discusses the optimal goals for availability of equipment,
qualified physicians, other personnel (e.g., obstetric,
anesthesia, and neonatal resuscitation providers) for
elective and emergent obstetric cases involving GA and
neuraxial anesthesia, as well as the timing of these cases.
It emphasizes the importance but is not limited to:
(1) “Availability of anesthesia and surgical personnel to
permit the start of a cesarean delivery within 30
minutes of the decision to perform the procedure.”
(2) “Because the risks associated with trial of labor after
cesarean delivery (TOLAC) and uterine rupture may
be unpredictable, the immediate availability of
appropriate facilities and personnel (including
obstetric anesthesia, nursing personnel, and a
physician capable of monitoring labor and
performing CD, including an emergency CD) is
optimal.” When resources are not available, the
patient should be informed of the potential increased
risk and management options. “The definition of
immediately available personnel and facilities
remains a local decision based on each
institution’s available resources and geographic
location.”
(3) “Persons administering or supervising obstetric
 anesthesia should be qualified to manage the
infrequent but occasionally life-threatening
complications of major neuraxial anesthesia such as
respiratory and cardiovascular failure, toxic local
anesthetic convulsions, or vomiting and aspiration.
Mastering and retaining the skills and knowledge
necessary to manage these complications require
adequate training and frequent application.”
(4) “A qualified physician with obstetric privileges to
perform operative vaginal or cesarean delivery should
be readily available during administration of
anesthesia. Readily available should be defined by
each institution within the context of its resources and
geographic location.”
(5) “Availability of equipment, facilities, and support
personnel equal to that provided in the surgical
suite.”
(6) “Personnel other than the surgical team should be
immediately available to assume responsibility for
resuscitation of the depressed newborn. The surgeon
and anesthesiologist are responsible for the mother
and may not be able to leave her care for the newborn
even when a regional anesthetic is functioning
adequately.”
(7) “In larger maternity units and those functioning as
high-risk centers, 24-hour in-house anesthesia,
obstetric and neonatal specialists are usually
necessary.”
c. Statement on Pain Relief during Labor
Approved 1999, last amended 2010, ASA/ACOG joint
review in progress 2014.11
(1) This joint ASA/ACOG statement says that “labor
results in severe pain for many women. There is no
circumstance where it is considered acceptable for an
 individual to experience untreated severe pain,
amenable to safe intervention, while under a
physician’s care. In the absence of a medical
contraindication, maternal request is a sufficient
medical indication for pain relief during labor.”
(2) “Pain management should be provided whenever
medically indicated.” Women should not be denied
anesthesia services based on “their insurance or
inadequate nursing participation.”
d. Guidelines for Neuraxial Anesthesia in Obstetrics
(previously titled: Guidelines for Regional Anesthesia
in Obstetrics)
Approved 1988, last amended 2013.11
Neuraxial anesthesia is an updated term for regional
anesthesia, thus the name change. This document (and its
recommendations) is called “Guidelines for Neuraxial
Anesthesia in Obstetrics,” but it functions like an ASA
statement. The document also references four other ASA
documents: The Standards for Basic Anesthetic
Monitoring, Standards for Postanesthesia Care, the
Guidelines for Perinatal Care, and an ASA House of
Delegates opinion document on the Anesthesia Care
Team. These “guidelines” are nevertheless important
because they apply to the use of neuraxial anesthesia or
analgesia for the parturient during labor and delivery.
(1) In summary, “They are intended to encourage quality
patient care, but cannot guarantee any specific patient
outcome. Because the availability of anesthesia
resources may vary, members are responsible for
interpreting and establishing the guidelines for their
own institutions and practices.”
(2) There are 10 “guidelines” that review location
requirements, physician privileging, monitoring, and
IV requirements. Also, physicians with obstetric
 privileges “should remain readily available” who are
capable of performing an emergent operative
delivery. Other personnel for emergencies and
resuscitation equipment should also be available.
(3) It states, “Qualified personnel, other than the
anesthesiologist attending the mother, should be
immediately available to assume responsibility for
resuscitation of the newborn.”
e. Statement on Regional Anesthesia
Approved 1983, last amended 2012.11
This document states in part that “regional anesthesia
involves diagnostic assessment, the consideration of
indications and contraindications, the prescription of
drugs, and the institution of corrective measures and
treatment in response to complications.” Medical and
technical expertise involved in performing regional
anesthesia is part of the practice of medicine and are best
performed by a skilled anesthesiologist.
f. Definition of “Immediately Available” when Medically
Directing
Approved 2012.11
(1) “A medically directing anesthesiologist is
immediately available if s/he is in physical proximity
that allows the anesthesiologist to return to re-
establish direct contact with the patient to meet
medical needs and address any urgent or emergent
clinical problems. These responsibilities may also be
met through coordination among anesthesiologists of
the same group or department.”
(2) “Differences in the design and size of various
facilities and demands of the particular surgical
procedures make it impossible to define a specific
time or distance for physical proximity.”
g. Statement on Nonobstetric Surgery during Pregnancy
 Approved by ASA-2009, Review by ASA/ACOG in
progress in 2014.11
This is a joint ASA/ACOG statement.
(1) “Due to the difficulty of conducting large-scale
randomized clinical trial in this population, there are
no data to allow for specific recommendations.”
(2) In general, “no currently used anesthetic agents have
been shown to have any teratogenic effects in humans
when using standard concentrations at any gestational
age.”
(3) Fetal heart rate monitoring may assist in maternal
positioning and cardiorespiratory management, and
may influence a decision to deliver the fetus.
(4) Consensus recommendations state that pregnant
woman, regardless of gestational age, should never
be denied surgery. Delay elective surgical cases until
after delivery. If possible, delay urgent cases until the
second trimester.
(5) General guidelines for fetal monitoring for previable
and viable fetuses are given, although the decision to
use fetal monitoring should be individualized.
h. Statement on the Role of Registered Nurses in the
Management of Continuous Regional Analgesia
Approved 2002, last amended 2013.11
(1) This document states that experienced registered
nurses, under medical supervision, can participate in
managing patients with regional anesthesia catheter
techniques in all settings, including labor and
delivery.
(2) This includes beginning, adjusting, and discontinuing
catheter infusions, administering physician prescribed
analgesic boluses through the catheter, using aseptic
technique while replacing empty medication syringes
and bags with new prefilled syringes and bags,
 monitoring the patient for analgesic efficacy, side
effects and treating related side effects, monitoring
the catheter insertion site, and removing the catheter.
5. Relevant American Society of Anesthesiologist Committee
Opinions
Proposed by the Agency for Healthcare Research and Quality
(AHRQ).
a. Comparative Effectiveness of Interventions to
Decrease Cesarean Births11
(1) The House of Delegates requested that the ASA
Committee on Obstetric Anesthesia explore the
interventions used for decreasing the CD rate.
(2) Neuraxial anesthesia does not increase the risk of
CD.
(3) Dysfunctional labor and macrosomia are more likely
risk factors for operative delivery. These factors also
increase labor pain, patient request for analgesia, and
epidural use.
(4) Epidural analgesia does not mask the symptoms of
uterine rupture during a TOLAC. Adequate pain
relief from an epidural may encourage patients to
choose and then complete a TOLAC, therefore
helping decrease the repeat CD rate.
b. Nitrous oxide for labor analgesia11
(1) The use of nitrous oxide for labor analgesia is
common in other countries, but rare in the United
States.
(2) Further studies are needed to study the efficacy of
nitrous oxide for labor analgesia and the reasons for
maternal satisfaction with use. Reductions in pain
scores appear to be similar to those seen with
systemic opioids.
(3) Adverse effects include mild maternal hypoxemia,
maternal drowsiness, possible neurotoxic effects, and
 environmental pollution.
(4) Nitrous oxide has no effect on uterine activity.
(5) If nitrous oxide analgesia is planned, then patient
consent and use of appropriate protocols is warranted.
IX. American College of Obstetricians and Gynecologists
Official website: www.acog.org
A. As ACOG documents are revised and replaced, their identifying
numbers and web addresses change. Some documents are deleted,
such as the Practice Bulletin No. 49, 2003 on Dystocia and
Augmentation of Labor and the Committee Opinion No. 276,
2002, “Safety of Enoxaparin (Lovenox) in Pregnancy.” The best
way to find up-to-date ACOG documents is through the lists of
Practice Bulletins and Committee Opinions on the official
website. This also gives access to the latest documents from this
organization. Members have free online access to all ACOG
documents via the ACOG official website. Categories for the
documents are listed on the left side of the home page under the
heading “For Physicians.”
B. Nonmembers have free online access only to the Committee
Opinions and Patient Safety checklists in that location.
Nonmembers can purchase ACOG Practice Bulletins (labeled
Compendium of Selected Publications) in hard copy or CD or
ROM9, and the Guidelines for Perinatal Care13 in hard copy or e-
book via the ACOG Bookstore (see ACOG home page store site
on left side of the home page).
Specific ACOG documents are listed by the approval year or
the year of last revision (not reaffirmation) based on the more
recent document.
C. The ACOG Committee on Obstetric Practice is responsible for
obstetric-related ACOG Committee Opinions, Practice Bulletins,
and the Guidelines for Perinatal Care.
1. This committee is made up of obstetricians and includes an
obstetric anesthesiologist whose input is solicited in those
areas that impact obstetric anesthesia. This liaison
 anesthesiologist is appointed by the ASA and serves as
Chairman of the ASA Committee on Obstetric Anesthesia.
2. The relevant ACOG documents include Practice Bulletins,
Committee Opinions, and portions of the Guidelines for
Perinatal Care that concern the practice of obstetric anesthesia
(see Table 33.5). Revised documents are altered to fit updates.
Reaffirmed documents are unchanged.

D. ACOG American College of Obstetricians and Gynecologists

Practice Bulletins
ACOG Practice Bulletins are evidence-based guidelines that
summarize a preferred method of diagnosis and management of a
condition. The evidence is graded and peer-reviewed research
dictates the recommendations. Graded evidence categories are as
follows:
Level A: good, consistent scientific evidence
Level B: limited or inconsistent evidence
Level C: evidence mostly consensus and expert opinion
These are not standards. Variations in practice should be based
on individual patient needs available resources, and limitations
unique to the institution or type of practice.
1. Obstetric Analgesia and Anesthesia, No. 36, July 2002,
reaffirmed 2013.9
 This is the primary ACOG document that concerns the
practice of anesthesiology. Recommendations for
administration of regional analgesia include availability and
options for pain relief, need for platelet counts, appropriate
platelet counts, and recommendations concerning neuraxail
anesthesia in patients with preeclampsia. It also discusses
factors that determine when to initiate analgesia, including
concerns about cervical dilation. Other recommendations
include administration of parenteral pain medications, effects
of analgesia on breastfeeding, clear liquid intake, preoperative
sodium citrate administration, identification of potential
anesthetic risk factors, anesthesia consultation, and
monitoring to avoid respiratory depression. Although the
document was reaffirmed in 2013, it contains outdated
material as discussed earlier in this chapter.
2. Vaginal Birth after Previous Cesarean Delivery, No. 115,
2010, reaffirmed 2013.9
Recommendations stated in this document are based primarily
on consensus and expert opinion (Level C) and include:
a. Evidence supports epidural analgesia as part of a TOLAC.
b. “A trial of labor after previous CD should be undertaken
at facilities capable of emergency deliveries. Because of
the risks associated with TOLAC and that uterine rupture
and other complications may be unpredictable, the
College recommends that TOLAC be undertaken in
facilities with staff immediately available to provide
emergency care.”
c. When resources for immediate CD are not available, the
College recommends that health care providers and
patients consider TOLAC and discuss the hospital’s
resources and availability of obstetric, pediatric,
anesthetic, and operating room staffs.
d. “Respect for patient autonomy supports that patients
should be allowed to accept increased levels of risk;
 however, patients should be clearly informed of such
potential increase in risk and management alternatives.”
3. Thrombocytopenia in Pregnancy, No. 6, September 1999,
reaffirmed 2014.9
This document discusses whether parturients with
thrombocytopenia and platelet counts between 50,000 and
100,000 per µL can receive neuraxial anesthesia. It concludes
by saying that such a decision requires a consensus between
the obstetrician, anesthesiologist, and patient. The
recommendation states that “epidural anesthesia is safe in
patients with platelet counts of more than 100,000 per µL.”
4. Thromboembolism in Pregnancy, No. 123, 2011, reaffirmed
2014.9
This document discusses whether parturients receiving
anticoagulants can receive neuraxial anesthesia. There are two
Level C recommendations:
a. “Women receiving either therapeutic or prophylactic
anticoagulation may be converted from LMWH to the
shorter half-life unfractionated heparin in the last month
of pregnancy, or sooner, if delivery appears imminent.”
b. “It is recommended to withhold neuraxial blockade for
10–12 h after the last prophylactic dose of LMWH or 24 h
after the last therapeutic dose of LMWH.”
5. Inherited Thrombophilias in Pregnancy, No. 138, 2013.9
a. This document states that “patients receiving prophylactic
anticoagulation therapy should be instructed to withhold
their injections at the onset of labor. If vaginal or CD
occurs more than 4 h after a prophylactic dose of
unfractionated heparin, the patient is not at significant risk
of hemorrhagic complications. Beyond 12 h after a
prophylactic dose or 24 h after a therapeutic dose of
LMWH, spinal anesthesia should not be withheld because
the risk of procedure-related bleeding is limited.”
b. It also states: “Patients receiving unfractionated heparin
 or LMWH who require rapid reversal of the anticoagulant
effect for delivery, can be treated with protamine sulfate.”
Clarification: In a personal communication, Charles
Lockwood, MD, an expert ACOG consultant on this
document, stated that rapid reversal is about 80%
effective, which is adequate for proceeding with an
emergency CD, but not adequate for neuraxial anesthesia
(C. Lockwood, MD, oral communication, September
2012).
6. Prevention of Deep-Vein Thrombosis and Pulmonary
Embolism, No. 84, 2007, reaffirmed 2013.9
The anesthesia related issue concerns the following statement,
called a Clinical Consideration and Recommendation:
“Patients receiving twice-daily low molecular weight heparin
should not receive regional anesthesia for 8–12 h after the last
dose, and for 18 h after a once-daily low molecular weight
heparin dose. Administration of low molecular weight heparin
should be held for 2 h after removal of a spinal or epidural
catheter.”
a. These time intervals are incorrect and based on
information from the American College of Chest
Physicians (ACCP). The ACCP recommendation is
confusing, possibly a misprint and claims to agree with
the ASRA recommendation.
b. The correct ASRA time intervals are to delay of 10 to 12
hours after a prophylactic, usually once-daily dose of
LMWH. For the larger often twice-daily dose of LMWH,
the recommended delay is 24 hours. A post procedure
dose of LMWH may be given no sooner than 4 hours
after removal of the neuraxial catheter.
c. ASRA previously recommended a 2-hour delay, but
revised their timing due to a recent FDA Drug Safety
Communication (11/6/13) recommending a 4-hour delay
before restarting LMWH.
E. Relevant American College of Obstetrician and Gynecologists
Committee Opinions
The ACOG Committee Opinions discuss emerging issues in the
practice of obstetrics and gynecology and, thus, are reviewed and
updated regularly. They are consensus-based and include
scientific evidence when available. They do not dictate an
exclusive course of action.
Access to all Committee Opinions is free via the ACOG
website (www.ACOG.org).
1. Optimal Goals for Anesthesia Care in Obstetrics, No. 433,
2009.9
This is ACOG’s version of the ASA/ACOG joint statement
and states goals for optimal anesthesia care for the parturient.
It mirrors the recommendations in the ASA statement with the
same name (discussed earlier).
2. Nonobstetric Surgery in Pregnancy, No. 474, 2011,
reaffirmed 2013.9
Although it is not stated in the ACOG document, this was a
joint statement by ASA/ACOG. It mirrors the statements in
the ASA document by the same name (discussed earlier).
3. Pain Relief during Labor, No. 295, 2004, reaffirmed 2008.9
This is a joint statement by ASA and ACOG, and mirrors the
information in the ASA statement (earlier) by the same name.
4. Nalbuphine Hydrochloride Use for Intrapartum
Analgesia, No. 376, 2007, reaffirmed 2012.9
Written in response to fetal safety concerns, ACOG states,
“To date there are insufficient data to support fetal safety
concerns or to recommend any change in the administration
of nalbuphine hydrochloride for analgesia in labor.”
5. Analgesia and Cesarean Delivery Rates, No. 339, June
2006, reaffirmed 2013.9
This document discusses newer studies demonstrating no
difference in the incidence of CD between patients receiving
early epidural analgesia versus later epidural placement and
 patients receiving IV pain relief. It concludes that none of the
current labor pain relief techniques appear to increase the
patient’s risk of CD.
X. American Academy of Pediatrics and American College of
Obstetricians and Gynecologists Collaboration: Guidelines for
Perinatal Care, Seventh Edition, 201213
In the title page, the statement reads, “Guidelines for Perinatal Care
was developed through the cooperative efforts of the American
Academy of Pediatrics’ (AAP) Committee on Fetus and Newborn and
the American College of Obstetricians and Gynecologists’ (the
College) Committee on Obstetric Practice.”
A. The guidelines should not be viewed as a body of rigid rules.
They are general recommendations and are intended to be
adapted to many different situations, taking into account the
needs and resources particular to the locality, the institution, or
type of practice. Variations and innovations that improve the
quality of patient care are to be encouraged rather than restricted.
“The purpose of these guidelines will be well served if they
provide a firm basis on which local norms may be built.”
B. This handbook is updated every 5 years. It contains guidelines for
managing parturients and neonates during their inpatient care.
The following topics are relevant to obstetric anesthesia:
anesthesia personnel availability and credentials, gastric
aspiration prevention in the parturient, labor analgesia and
delivery anesthesia options, availability of personnel for patients
attempting VBAC, timing of elective and emergency procedures
in labor and delivery (including CD and PPTL), support persons
in the delivery room, postoperative pain management, and
neonatal resuscitation.
C. There is a section stressing patient safety that suggests creating a
culture of safety using a number of measures, including
improving communication, creating safety protocols, and training
with drills and simulations.
 XI. Relevant documents from the American Society of Regional
Anesthesia and Pain Medicine
ASRA official website: www.ASRA.com (see Table 33.6)

The ASRA is a well-respected national organization with interests, as

the name implies, in issues related to both neuraxial anesthesia and
pain management. Their most recent and important guidelines and
advisories are available free to the public on the ASRA website. Go to
the home page (www.ASRA.com) and then click on the box at the top
labeled “Advisories and Guidelines.” This includes the guideline on
Regional Anesthesia in the Patient Receiving Antithrombotic or
Thrombolytic Therapy and the checklist for emergency management
of local anesthetic systemic toxicity (LAST). Websites are provided
for the other documents.
A. Regional Anesthesia in the Patient Receiving Antithrombotic
or Thrombolytic Therapy: American Society of Regional
Anesthesia and Pain Medicine Evidence-Based Guidelines
(Third Edition), 2010, with fourth edition in progress.7
ASRA convenes conferences on this topic to discuss and gather
consensus information from multispecialty and international
experts to produce this practice guideline. The adverse outcome
for these patients, spinal hematoma, is rare so there are no meta-
analyses or randomized clinical trials available.
1. Evidence comes from epidemiologic and observational
studies, case reports, and expert opinion. The document
discusses all forms of antithrombotic and thrombolytic
 therapy.
2. The management guidelines for LMWH are particularly
helpful for obstetric patients. These include, but are not
limited to, the following:
a. The anti-Xa level is not predictive of bleeding risk, so
monitoring is not helpful.
b. Antiplatelet or oral anticoagulant medications should not
be given with LMWH due to a potentiation effect.
c. Blood return in the neuraxial needle during placement
should not be a cause to postpone surgery, but LMWH
therapy should be delayed 24 hours postoperatively.
d. The time delay between last dose of LMWH, and
placement of the neuraxial needle in a patient on the
smaller thromboprophylactic dose of LMWH, is 10 to 12
hours.
e. The delay for a patient on the higher treatment dose is at
least 24 hours. For patients on single-daily LMWH doses,
thromboprophylactic doses may resume 6 to 8 hours
postoperative. For patients on twice-daily treatment doses,
the delay is 24 hours.
B. American Society of Regional Anesthesia and Pain Medicine
Practice Advisory on Local Anesthetic Systemic Toxicity,
201014
This practice advisory summarizes current knowledge on the
prevention, diagnosis, and treatment of LAST. The results are
summarized in an appendix, which was designed to be a hard
copy reference document for the operating room.
C. American Society of Regional Anesthesia and Pain Medicine
Practice Advisory on Neurologic Complications in Regional
Anesthesia and Pain Medicine, 200815
Due to the rarity of neurologic complications with neuraxial
anesthesia, there are no evidence-based studies in the literature.
This advisory comes from the opinions of a small group of expert
panelists and a review of the limited literature. The panel looked
 at etiology, differential diagnosis, prevention, and treatment.
Complications due to infection or hemorrhage are discussed in
other advisories.
XII. Relevant document from the American Heart Association (see
Table 33.6)
2010 American Heart Association Guidelines for Cardiopulmonary
Resuscitation and Emergency Cardiovascular Care Part 12:
Cardiac Arrest in Special Situations16
This 2010 document by the AHA includes a section on management
of the pregnant patient in cardiac arrest. An updated and expanded list
of recommendations is provided with the document.
XIII. Relevant document from the Society of Obstetric Anesthesia and
Perinatology (see Table 33.6)
Society of Obstetric Anesthesia and Perinatology (SOAP) is the ASA
subspecialty society for obstetric anesthesia.
Access the SOAP official website, www.SOAP.org, to read the
document
A. The Society of Obstetric Anesthesia and Perinatology
Consensus Statement on the Management of Cardiac Arrest
in Pregnancy, May 2014.17
This 2014 document is a consensus statement based on
guidelines, expert opinion, literature reviews, simulation data, and
case reports. It provides updates, highlights areas of weak
knowledge, and expands on the 2010 AHA cardiopulmonary
resuscitation (CPR) guidelines specific to pregnancy (referenced
earlier).
1. The document discusses that advanced cardiovascular life
support (ACLS) trained providers lose appropriate maternal
CPR knowledge and skills with rare use.
2. A maternal CPR checklist is provided in the document to
improve team performance, especially after specific
modifications for institution and location (ER [emergency
room], L&D [labor & delivery], radiology, ICU [intensive
 care unit]) are made.
3. The document recommends periodic performance drills or
simulations along with development of local protocols that
address deficiencies, improved communication, teamwork,
and leadership.
4. The document points out several areas of weakness in
maternal CPR performance.
a. For example, left lateral uterine displacement is
frequently neglected. Unlike the AHA, SOAP
recommends no delay in chest compressions or CD while
waiting for capnography.
b. This differs from the AHA which recommends continuous
capnography to confirm endotracheal tube placement and
efficacy of chest compressions.
c. SOAP states fetal monitors should be removed as CPR
commences because they are irrelevant to management of
the mother.
5. The AHA recommends fetal delivery within 5 minutes of the
arrest, but this is seldom achieved.
6. SOAP recommends calling for surgical equipment, delivery
preparations, and the neonatal team as soon as cardiac arrest
occurs. This expedites the delivery process in which optimal
skin incision is at 4 minutes, with delivery at 5 minutes.6 The
delivery should occur at the site of the arrest because the
timing is more important than the location of delivery.

REFERENCES
1. Williams MS, Davies JM. Medicolegal issues in obstetric anesthesia. In: Chestnut DH, ed. Chestnut’s
Obstetric Anesthesia: Principles and Practice. 5th ed. Philadelphia, PA: Elsevier Saunders; 2014:780–
781.
2. American Society of Anesthesiologists. Standards, guidelines, and statements: policy statement on
practice parameters. https://www.asahq.org/For-Members/Standards-Guidelines-and-Statements.aspx.
Accessed November 13, 2014.
3. American Society of Anesthesiologists. Potential conflict of interest policy.
https://www.asahq.org/For-Members/Publications-and-Research/Newsletter-
 Articles/2010/May2010/competing-allegiances-equals-a-conflict-of-interest.aspxm. Accessed
November 18, 2014.
4. Weiskopf RB. Conflicts of interest in expert-authored practice parameters, standards, guidelines,
recommendations. Anesthesiology. 2010;113:751–752.
5. Djulbegovic B, Guyatt GH. Evidence-based practice is not synonymous with delivery of uniform
health care. JAMA. 2014;312:1293–1294.
6. American Society of Regional Anesthesia and Pain Medicine. Advisories and guidelines.
http://www.asra.com/advisory-guidelines. Accessed November 20, 2014.
7. Horlocker TT, Wedel DJ, Rowlingson JC, et al. Regional anesthesia in the patient receiving anti-
thrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine
Evidence-Based Guidelines (Third Edition). Reg Anesth Pain Med. 2010;35:64–101.
8. Geerts WH, Berggvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College
of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(suppl
6):381S–453S.
9. American College of Obstetricians and Gynecologists. 2014 Compendium of selected publications.
http://www.sales.acog.org/2014-compendium-of-selected-publications-cd-rom-P498.aspx. Accessed
November 20, 2014.
10. Freeman RK, Cohen AW, Depp R III, et al. American College of Obstetrics and Gynecology Task
Force on Cesarean Delivery: evaluation of cesarean delivery.
http://archive.poughkeepsiejournal.com/assets/pdf/BK15725757.PDF. Accessed November 23, 2014.
11. American Society of Anesthesiologists. Standards, guidelines, and statements. Guidelines for
Neuraxial Anesthesia in Obstetrics. www.asahq.org/quality-and-practice-management/standards-and-
guidelines.aspx. Accessed November 9, 2015.
12. American Society of Anesthesiologists. Practice parameters (practice guidelines).
http://www.asahq.org/for-members/practice-management/practice-parameters.aspx. Accessed
November 20, 2014.
13. American Academy of Pediatrics, American College of Obstetricians and Gynecologists. Guidelines
for Perinatal Care. 7th ed. Washington, DC: American Academy of Pediatrics; 2012.
http://shop.aap.org/Guidelines-for-Perinatal-Care-7th-Edition-eBook. Accessed October 30, 2015.
14. Neal JM, Bernards CM, Butterworth JF IV, et al. ASRA practice advisory on local anesthetic systemic
toxicity. Reg Anesth Pain Med. 2010;35:152–161.
15. Neal JM, Bernards CM, Hadzic A, et al. ASRA practice advisory on neurologic complications in
regional anesthesia and pain medicine. Reg Anesth Pain Med. 2008;33:404–415.
16. Vanden Hoek TL, Morrison LJ, Shuster M, et al. Part 12: cardiac arrest in special situations: 2010
American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency
Cardiovascular Care. Circulation. 2010;122(18 suppl 3):S829–S861.
17. Lipman S, Cohen S, Einav S, et al. The Society of Obstetric Anesthesia and Perinatology consensus
statement on the management of cardiac arrest in pregnancy. Anesth Analg. 2014;118:1003–1016.
Index
Page numbers followed by f and t indicate figures and tables, respectively.

Abdominal binder, 383

Abruptio placentae
anesthetic management, 325–326
classification, 325
definition, 324
diagnosis, 325
epidemiology, 324
obstetric considerations, 324–325
obstetric management, 325
signs and symptoms, 324–325
ACE inhibitors, 85t
Acetaminophen, 372
Acetaminophen (IV), 429
Acidosis, 344–346
ACLS. See American Heart Association Advanced Cardiovascular Life Support
Acromegaly, 466–467
Activated recombinant factor VII, 321
Acupuncture, 383
acupressure and, 140–141
Acute fatty liver of pregnancy (AFLP), 571, 575–577, 576t
Acute kidney injury, 568–569, 568t, 569t
Acute normovolemic hemodilution, 318
Acute respiratory distress syndrome (ARDS), 604–605, 604t
Addisonian crisis, 470
Adrenal disorders
Cushing disease and syndrome, 471–472
anesthetic considerations, 472
antepartum considerations, 471–472
antepartum management, 472
clinical presentation, 471
 laboratory studies and imaging, 471
maternal and fetal considerations, 472
pathophysiology, 471
pheochromocytoma, 178, 473–475
anesthetic considerations, 474–475
diagnosis, 473
fetal considerations, 475
intrapartum and surgical considerations, 474
laryngoscopy and tracheal intubation, 474–475
maternal and fetal risks, 473
medical therapy, 474
medications, 475
regional anesthesia, 475
signs and symptoms, 473
timing of surgery for, 474
primary adrenal insufficiency, 470–471
Addisonian crisis, 470
antepartum considerations, 470
emergency situations, 471
fetal considerations, 470
intrapartum and anesthetic considerations, 470–471
maternal complications, 470
pathophysiology, 470
primary adrenocortical insufficiency, 470
unexplained hypotension, 471
β-Adrenergic receptor effects, 58t
Adrenocorticotropic hormone, 383
Advanced pulmonary artery hypertension therapies, 519
AFE. See Amniotic fluid embolism
AFLP. See Acute fatty liver of pregnancy
AI. See Aortic insufficiency
Air embolus, 508–509, 520
Airtraq VL, 279
Airway examination, 216
Alcohol, 31t, 85t
Alfentanil, 153
Ambulation in labor
advantages, 183
disadvantages, 183
during labor, 183, 183t, 232
neuraxial analgesia and, 183, 232
postdural puncture headache and, 384
suggested guidelines for, 183t
American Academy of Pediatrics, 698
American College of Obstetricians and Gynecologists
American Academy of Pediatrics collaboration with, 698
on breech presentation, 296
on multiple gestation pregnancy, 290
on umbilical cord gas sampling, 311
website and relevant documents, 695–698
American Heart Association, 699
American Heart Association Advanced Cardiovascular Life Support (ACLS), 48
American Society of Anesthesiologists (ASA), 79
Basic Standards for Preanesthesia Care, 684
Definition of “Immediately Available” when Medically Directing, 694
Guidelines for Neuraxial Anesthesia in Obstetrics, 693–694
guidelines from national organizations and, 680–681
Optimal Goals for Anesthesia Care in Obstetrics, 692–693
postpartum sterilization practice guidelines, 418
Practice Advisory for Intraoperative Awareness and Brain Function
Monitoring, 691
Practice Advisory for Preanesthesia Evaluation, 691
Practice Advisory for Prevention, Diagnosis, and Management of Infectious
Complications Associated with Neuraxial Techniques, 692
Practice Guidelines for Anesthetic Management in Obstetric Patients with
Predicted Difficult Airway, 273
Practice Guidelines for Management of Difficult Airway, 691
Practice Guidelines for Obstetric Anesthesia, 685–688
 practice guidelines for obstetric anesthesia, in multiple gestation pregnancy,
289–290
Practice Guidelines for Postanesthetic Care, 689
Practice Guidelines for Preoperative Fasting, 688–689
Practice Guidelines for Prevention, Detection, and Management of
Respiratory Depression Associated with Neuraxial Opioid
Administration, 689–691
practice parameters, 680–681
relevant committee opinions, 694–695
Standards for Basic Anesthetic Monitoring, 685
Standards for Postanesthesia Care, 685
Statement on Nonobstetric Surgery during Pregnancy, 694
Statement on Nonoperating Room Anesthetizing Locations, 692
Statement on Pain Relief during Labor, 693
Statement on Regional Anesthesia, 694
Statement on the Role of Registered Nurses in the Management of
Continuous Regional Analgesia, 694
website and relevant documents, 684–695
American Society of Regional Anesthesia and Pain Medicine, 698–699
Amino-amides, 36, 49
Amino-esters, 36, 49
Aminoglycosides, 31t
Amiodarone, 45
Amnioinfusion, 110
Amniotic fluid embolism (AFE), 317–318
background, 593
clinical presentation, 337
diagnosis, 594
differential diagnosis, 337t
management, 337–338
maternal death from, 669
outcome, 338
pathophysiology, 337, 594
risk factors, 336, 594
 symptoms and presentation, 593–594, 593t
timing, 593
treatment, 594–595
Androgens, 85t
Angiotensin-converting enzyme inhibitors, 31t
Antenatal health education, 138
Antepartum blood donation, 317
Antepartum hemorrhage
abruptio placentae, 324–326
incidence, 321
placenta previa, 321–323
uterine rupture, 326–327
vasa previa, 323–324
Anthrax, 129
Anticonvulsants, 31t
Antithrombin deficiency, 485
Antithyroid drugs, 85t
Aortic defects
coarctation of aorta, 521–522
Marfan syndrome (MFS), 522–523
Aortic insufficiency (AI), 506–507
Aortic stenosis (AS), 502–504
Aortocaval compression, 6, 14
Aortopulmonary collaterals, 510
Apgar score, 348–349, 348t
ARDS. See Acute respiratory distress syndrome
Aromatherapy, 140
Arterial blood gases, 6, 7t
Arterial embolization, 329, 332t
Artery of Adamkiewicz, 398–399
AS. See Aortic stenosis
ASA. See American Society of Anesthesiologists
ASDs. See Atrial septal defects
Aspiration, 272
Aspiration pneumonitis, 599–600
Aspiration prophylaxis, 168, 244, 424
Aspirin, 31t, 490t
Asthma
acute exacerbation of, 587f
cesarean delivery and anesthesia, 586–589
classification and control, 584–585, 585t
effect of, on pregnancy, 584
effect of pregnancy on, 584
introduction, 583–584
labor and delivery and, 584, 585–586
medical management, 585
obesity and, 614
Atlanto-occipital joint extension, 268, 269f
Atosiban. See Oxytocin antagonist
Atracurium, 475
Atrial septal defects (ASDs), 520–521
Atrial switch, 512, 514
Autoimmune hepatitis, 578
Autologous epidural blood patch, 405
Autologous transfusion, 317
Autonomic hyperreflexia, 541–542, 542t, 544
Awake intubation
indications, 275
oral fiberoptic intubation technique, 276–277
preparation for fiberoptic intubation, 275–276

Back pain, 49, 186

Bacterial meningitis, 408–409
Barbiturates, 45, 110
Bariatric surgery, 627
Bed rest, 382
Benign intracranial hypertension (pseudotumor cerebri), 382
Benzodiazepines, 45, 84–85, 110, 330, 473
Beta blocker, 111, 462t, 463
Betamethasone, 110–111
Bicarbonate, 39
Biophysical profile (BPP), 100–101, 100t
Bioterrorism, 128–129
Birth partners, 138
Birth plans, 78
Blood pressure control, 443–444, 444t, 446, 448
Blood volume, 4, 4t
BMI. See Body mass index
Body mass index (BMI), 611, 612t
BPP. See Biophysical profile
Breastfeeding, 233, 425
lactation headache, 382
lactation requirements for labeling of prescription drugs and biological
products, 30t
medications, in breast milk, 373
Breathing exercises, 138
Breech presentation
American College of Obstetricians and Gynecologists on, 296
anesthesia for, 295–303
cesarean delivery for, 300
anesthesia, for planned cesarean delivery, 300
anesthesia, for urgent cesarean delivery, 300
emergent cesarean delivery (Zavanelli maneuver), 300
overview of, 300
risks, 300
complete breech, 296–297, 296f
demographics for, 296–297
external cephalic version (ECV), 300–303, 301t
anesthesia for, 302–303
costs for, 303
emergency preparations, 303
factors associated with external cephalic version failure, 301t
 labor following, 302
maternal and fetal indications, 300–301
overview, 300
risks, 301
success of, 301
utilization of, 301
frank breech, 296–297, 296f
historical perspective on, 296
incomplete breech, 296–297, 296f
introduction to, 295–296
neonatal resuscitation in, 303
obstetric management, 297–298
historical perspective, 297
uterine relaxation, for vaginal delivery, 298
vaginal breech delivery, 297–298
risk factors, 297, 297t
vaginal breech delivery, 297–300
complications, 299–300, 299t
fetal head entrapment, 299–300
obstetric management, 297–298
preterm breech delivery, 299
umbilical cord prolapse, 299
Bupivacaine, 37t, 41, 43, 44t, 45, 48
advantages, 177
concentration and dose, 178
disadvantages, 177–178
for PPTL, 429
for spinal anesthesia, in cesarean delivery, 253
Buprenorphine, 659
Burns, 646
Butorphanol, 110, 157, 366

Caffeine, 381, 383

Calcium channel blockers, 58–59
Carbamazepine, 85t
Carbetocin, 65–66
Carboprost (Hemabate), 67–68
Cardiac arrest, 197–198
Cardiac dysrhythmias, 508, 529, 530f
Cardiac disease
cardiac dysrhythmias and pregnancy, 508, 529, 530f
cardiac transplant, obstetric care after, 527–528
cardiomyopathy, 524–527, 615
cardiopulmonary resuscitation, in obstetric patient, 530–531
congenital heart disease, 507–523
general anesthetic considerations, 498–499
ischemic heart disease, in pregnancy, 529
maternal death from, 668–669
neonatal risk, 499
NYHA classification, 498, 498t
obstetric delivery considerations, 499–500
overview, 498–500
physiology, 498
primary pulmonary hypertension, 523–524
pulmonary vascular resistance (PVR), 507
valvular heart disease, 500–507
WHO classification, 499t
Cardiac surgery, 89
Cardiac transplant
anesthetic management, 528
general anesthesia, 528
obstetric care after, 527–528
pathophysiology, 528
peripartum considerations, 528
Cardiomyopathy
dilated cardiomyopathy (DCM), 526
hypertrophic obstructive cardiomyopathy (HOCM), 526–527
idiopathic dilated cardiomyopathy (IDC), 526
 obesity and, 615
peripartum cardiomyopathy (PPCM), 524–526
anesthetic management, 526
cesarean delivery and, 526
invasive monitors, 526
overview, 524–525
pathophysiology, 525
peripartum considerations, 525–526
Cardiopulmonary resuscitation, 530–531
Cardiovascular disease, 124–125
Cardiovascular drugs, 111
Cardiovascular system
fetal physiology, 344, 345f
in hypertensive disorders, 441
in multiple gestation pregnancy, 290–291
obesity, pregnancy, and, 615–616
postpartum changes to, 418
in pregnancy, 4–6
Central nervous system
in hypertensive disorders, 440, 441
in multiple gestation pregnancy, 291
in pregnancy, 13–14
shunts, maternal, 547
Central venous pressure, 504
Cephalic-cephalic presenting twins, 294
Cephalic-noncephalic presenting twins, 294
Cephalosporins, 31t
Cerebral venous thrombosis, 381
Cervidil. See Dinoprostone
Cesarean delivery
anesthesia, in multiple gestation pregnancy, 295
anesthetic management in obstetric patients with predicted difficult airway,
274
anesthetic techniques, 246–255
 basic considerations, 246–247
combined spinal-epidural anesthesia for cesarean delivery, 253–254
epidural anesthesia for cesarean delivery, 247–250
general anesthesia for cesarean delivery, 254–255
spinal anesthesia for cesarean delivery, 250–253
aortic insufficiency (AI) and, 507
asthma and anesthesia during, 586–589
background, 238
for breech presentation, 300–301
complications, 240–243
anesthetic complications, 240–241
hemorrhage, 241, 241t
subsequent pregnancy risk, 242–243
surgical complications, 241–242
conclusion, 255
diabetes mellitus (DM) and, 457–458
Eisenmenger syndrome and, 518
hypertensive disorders and, 447
hyperthyroidism and, 463–464
hypothyroidism and, 466
indications, 239, 239t
myasthenia gravis and, 552
neuraxial analgesia impacting, 230–231
obesity and, 620–624
opioid dependency
anesthetic management of, 661
postcesarean delivery analgesia, 661, 664
perimortem, 647
peripartum cardiomyopathy (PPCM) and, 526
placenta previa and, 322–323, 322t
postoperative management, 255
preoperative considerations, 243–246
aspiration prophylaxis, 244
blood products, 244
 consent, 244
intraoperative medications, 245–246
other preparations, 245
preoperative assessment, 243
supplemental oxygen, 245
scoliosis and, 540
surgical considerations, 239–240
Maylard incision, 239
Pfannenstiel incision, 239
technical aspects, 239–240
vertical incision, 240
Chemical injury, 399
Chemotherapeutic agents, 85t
Chest pain, 197
Chickenpox, 128
Chloroprocaine, 45
2-Chloroprocaine, 37t, 44t, 178, 335
Cholestasis of pregnancy, 574–575
Chorioamnionitis, 117–119
Chronic hypertension, 436, 437
Clonidine, 180, 368, 369, 444t
Clopidogrel, 489t
C-MAC VL, 279
CMV. See Cytomegalovirus
Coagulation. See also Thrombophilia
amplification, 480f
anticoagulants, comparison of, 490t
classical clotting cascade, 483f
disorders of, 490–495
acquired disorders, 492–493
anesthetic management, 491t
disseminated intravascular coagulation, 494–495
inherited disorders, 490–491, 491t
precipitants of disseminated intravascular coagulation in pregnancy,
 494t
factors, 9–10
hemostatic changes, at term pregnancy, 482t
in hypertensive disorders, 441, 446
initiation, 480f
measurements of, in pregnancy, 483–484
bleeding time, 484
near patient testing, 484
routine tests, 483
overview of normal hemostatic coagulation, 479–480
physiologic changes, in pregnancy, 480–483
coagulation factors, 481–482
fibrinolysis, 483
platelets, 9, 481, 493
thrombotic control, 481f, 482–483
propagation, 481f
summary of, 490–495
Cocaine, 31t, 85t
Codeine phosphate, 156
Collagen vascular diseases, 564
Combined spinal-epidural anesthesia, 253–254
Combined spinal-epidural technique, 501–502
catheter placement, 174
complications, 174
different interspaces technique, 173–174
intrathecal medication, 174
needle-through-needle technique, 173, 174f
securing catheter, 174
Combitube, 281
Complementary therapies, 139–141
Complete breech, 296–297, 296f
Computed tomography pulmonary angiogram (CTPA), 590, 591f
Computed tomography (CT) scanning, 639–640
Congenital heart disease
 aortic defects, 521–523
cyanotic lesions, 508–519
general peripartum considerations, 508
left-to-right shunting, 520–521
overview, 507–508
tachyarrhythmias and, 509t
Continuous epidural infusion, 180–181
Continuous spinal technique, 175, 182
Contraction stress test (CST), 99
Cortical vein thrombosis (CVT), 548
Corticosteroids, 31t, 110–111
in multiple gestation pregnancy, 293, 295
for postdural puncture headache, 383
Coumadin, 85t
Cryoprecipitate, 494
CST. See Contraction stress test
CTPA. See Computed tomography pulmonary angiogram
CT scan. See Computed tomography scanning
Cushing disease and syndrome, 471–472
CVT. See Cortical vein thrombosis
Cyanosis, 508
Cyanotic lesions
Eisenmenger syndrome (ES), 517–519
advanced pulmonary artery hypertension therapies, 519
anesthetic management, 518
general anesthesia, 518–519
labor and delivery, 518
monitoring, 519
pathophysiology, 518
peripartum considerations, 518
general considerations, 508–510
aortopulmonary collaterals, 510
invasive monitoring, 509
prolonged second stage labor, 510
 risk of air embolus, 508–509
systemic vascular resistance, 509
Tetralogy of Fallot (ToF), 510–512
anesthetic management, 512
normal heart compared to, 510f
pathophysiology, 511
peripartum considerations, 511–512
transposition of great vessels (TGV), 512–514, 513f
tricuspid atresia and hypoplastic left heart syndrome, 514–517
Cyclooxygenase (prostaglandin synthase) inhibitors, 61–62
Cystic fibrosis, 601–602
Cytomegalovirus (CMV), 122
Cytotec. See Misoprostol

Dalteparin, 487t
DCM. See Dilated cardiomyopathy
D-dimer, 592
Decreased placental perfusion, 438–439
Deep venous thrombosis, 216, 697
Desflurane, 475, 573
Dexamethasone, 462t
Diabetes insipidus (DI), 469
Diabetes mellitus (DM)
effect of, on pregnancy, 453–454
hyperglycemia, 453–454
effect of pregnancy on, 452–453
complications of, 452–453
diabetic nephropathy, 453
glycemic control, 452
GDM, 452
introduction, 451–452
management, during labor and delivery, 456–458
anesthetic management, 457–458
cesarean delivery, 457–458
 glucose management, 457
labor analgesia, 457–458
timing of delivery, 456–457
management, during pregnancy, 454–456
diabetic ketoacidosis, 455–456
insulin, 454, 455t
with oral hypoglycemic agents, 454–455
renal disease and, 456
retinopathy and, 456
postpartum care, 458
insulin, 458
neonatal hypoglycemia, 458
renal disease and, 564
Type 1, 452
Type 2, 452
Diabetic ketoacidosis (DKA), 455–456
Diamorphine (heroin), 147–148, 366
DIC. See Disseminated intravascular coagulation
Diethylstilbestrol, 85t
Difficult airway management
airway assessment, 266–271
atlanto-occipital joint extension, 268, 269f
history, 266
jaw protrusion or mandibular protrusion test, 268, 268f
Mallampati classification, 266–267, 267f
mentohyoid distance, 268, 269f, 270f
mouth opening, 268
physical examination, 266
specific individual tests, 266
thyromental distance, 268
anatomic and physiologic changes contributing to, 265–266
airway changes, 265
cardiovascular changes, 266
gastrointestinal changes, 266
 recommendations for airway management and, 266
respiratory changes, 266
anesthesia-related morbidity and mortality, 263–264
experience in United Kingdom, 264
experience in United States, 263–264
anesthetic management in obstetric patients with predicted difficult airway,
273–277
ASA practice guidelines, 273
with emphasis on awake intubation, 275–277
undergoing labor or operative delivery, 273–275
aspiration of gastric contents, 272
conclusion, 283
definitions, 261
difficult and failed intubation, 262
difficult laryngoscopy, 261
extubation and postanesthesia care unit airway issues, 283
failed intubation, 261
goals for airway management during pregnancy, 261–262
introduction, 260
management of pregnant patient with unanticipated difficult airway, 277–
283
failed intubation, 279–281
GlideScope, C-MAC VL and Airtraq VL, 279
maintenance of oxygenation/ventilation, 279–281
management of “cannot intubate, cannot ventilate” situation, 281–282
management with patient with critical airway and hypoxemia, 282–
283
tracheal intubation, step one, 277–279, 278f
tracheal intubation, step two, 277–279, 278f
maternal deaths and airway-related issues, 265
United Kingdom data, 265
United States data, 265
morbid obesity in pregnancy and airway, 271–272
supraglottic airway, 261
Digoxin, 31t
Dilated cardiomyopathy (DCM), 526
Dilutional anemia, 9
Dilutional coagulopathy, 319–320
Dinoprostol, 67
Dinoprostone (Cervidil), 68
Diphenhydramine, 370
Direct maternal death, 667
Disseminated intravascular coagulation (DIC), 320, 321t, 494–495
DKA. See Diabetic ketoacidosis
DM. See Diabetes mellitus
Domestic violence, 645
Doppler ultrasound, 312
Doppler velocimetry, 101–102
Doulas, 138
Droperidol, 475
Dührssen incisions, 299
Dyspnea, 197
Dysrhythmias. See Cardiac dysrhythmias

ECG. See Electrocardiogram

Echocardiography, 591–592. See also Ultrasound and echocardiographic
techniques
ECV. See External cephalic version
Eisenmenger syndrome (ES), 517–519
Electrocardiogram (ECG), 5
Electrolyte balance, 319
Electromyography (EMG), 400–401, 401f, 401t
Electronic fetal monitoring, 96
intrapartum, 102–107
characterization of fetal heart rate, 103–107
classification of, 107–109
management of abnormal electronic fetal monitoring patterns and in
utero resuscitation, 109–110
 uterine activity, 102
Electrophysiologic (EP) studies, 402
Embolectomy, 592
Emergency percutaneous cricothyroidotomy, 282
Emergent cesarean delivery (Zavanelli maneuver), 300
Emerging infectious diseases, 128–129
EMG. See Electromyography
Endocrine disorders
adrenal disorders, 470–475
conclusion, 475
diabetes mellitus, 451–458
HIV and, 124–125
pituitary disorders, 466–469
thyroid disorders, 458–466
Endocrine system
obesity, pregnancy, and, 616
in pregnancy, 12–13
Endometritis, 121–122
Endothelin receptor antagonists, 519
Endotracheal intubation, 14
in newborn resuscitation, 351–353, 352f, 353t
Enoxaparin, 487t
Epidural, lumbar, 390
Epidural abscess, 409–410
Epidural anesthesia
anesthetic management in obstetric patients with predicted difficult airway,
274
for cesarean delivery, 247–250
adjuvants to local anesthetics for, 250
contraindications, 248t
epinephrine and, 250
local anesthetics for, 249–250
opioids, 250
potential complications, 248–249
 frequency of complications, 390t
for postcesarean analgesia, 367–368, 370–371
Epidural blood patch, 384, 385
autologous, 405
prophylactic, 407
Epidural colloid administration, 384
Epidural doses, 15
Epidural hematoma, 187, 410–411
Epidural morphine, 383, 429
Epidural opioids, 367–368, 368t
Epidural reactivation, 425–427
Epidural saline, 383
Epidural technique
combined spinal-epidural technique, 173–174, 174f, 501–502
continuous spinal technique, 175, 182
epidural catheter, 172–173
depth of catheter insertion, 173
material, 172
multihole versus single hole, 172–173
obesity and placement of, 619–620
epidural tray, 169
identification of lumbar interspace, 170
important components, of aseptic technique before neuraxial anesthetic
placement, 170t
sterile precautions, 170
suggested epidural technique, 169t
techniques, 170–172
bevel orientation, 172
loss of resistance, 170–172
Epidural test dose, 175–177
Epilepsy, 553–554, 553t
Epinephrine, 39, 45, 48, 49
disadvantages of, 179
for epidural anesthesia, in cesarean delivery, 250
 for newborn resuscitation, 355–356
in postcesarean analgesia, 368, 369
for spinal anesthesia, in cesarean delivery, 253
EP studies. See Electrophysiologic studies
Ergot alkaloids, 66–67
Erythromycin, 31t
ES. See Eisenmenger syndrome
Esmolol, 502
Ethanol, 473
Ethical and legal considerations
assessment of facts, 74
disclosure and apology, 80
informed consent, 74–79
introduction to ethics, 73–74
litigation, specific to obstetric anesthesia, 79–80
maternal autonomy and fetal beneficence, 80–81
other consent issues, 77–79
birth plans and Ulysses directive, 78
professional negligence, 79
written consent, 78
Etomidate, 502, 519
Extended-release epidural morphine, 368
External cephalic version (ECV), 300–303, 301t
Extracorporeal membrane oxygenation, 592, 647
Extubation, 283, 623

Factor V Leiden, 485

Failure to transition, 344–346
Falls, 644
FAST. See Focused assessment with sonography
Femoral nerve, 395
Fentanyl, 149, 179, 366, 367–368, 367t
dose ranges, 179t
recommended single doses, for postcesarean analgesia, 368t, 369t
Fetal acid–base balance, 309–310
Fetal asphyxia
antepartum fetal monitoring and, 98t
causes, 309
fetal acid–base balance and, 309–310
fetal response to, 310
Fetal assessment and monitoring, 95–96
antepartum fetal monitoring, 97–102
biophysical profile, 100–101, 100t
CST or oxytocin challenge test, 99
Doppler velocimetry, 101–102
fetal asphyxia and, 98t
maternal monitoring of fetal movement, 98–99
NST, 99
purpose and principals, 97
screening ultrasound survey, 97–98
electronic fetal monitoring, 96
interpretation, 97
intrapartum fetal surveillance, 102–110
intermittent auscultation, 110
intrapartum electronic fetal monitoring, 102–107
management of abnormal electronic fetal monitoring patterns and in
utero resuscitation, 109–110
physiology, 102
medication and anesthetic effects on fetal surveillance, 110–112
general anesthesia, 112
maternally administered medications, 110–111
regional anesthesia, 111–112
special circumstances, 111t
physiologic basis of, 96
Fetal beneficence, 80–81
Fetal bradycardia, 326–327
Fetal circulation, 21–22
Fetal distress, 307–308. See also Nonreassuring fetal status
Fetal goiter, 461, 464
Fetal head
entrapment, in breech presentation, 299–300
trauma caused by, 394
Fetal heart rate (FHR)
abnormalities, from neuraxial analgesia, 186
characterization of, 103–107
accelerations, 104
baseline variability, 103, 103f, 104f
decelerations, 105–107
early decelerations, 105, 106f
late decelerations, 105, 106f
prolonged decelerations, 106–107, 107f, 108f
sinusoidal pattern, 107
variability, 103–104
variable decelerations, 105–106, 107f
classifications of, 247t
interpretation of, 310
interventional maneuvers for nonreassuring fetal heart rate patterns, 109t
monitoring, 310–311
nonreassuring fetal status and fetal distress, 307–315
pattern, 310
three-tier interpretation of fetal heart rate patterns, 108t
tracing, 348t
Fetal interventions, 89–91, 90t
Fetal macrosomia, 626
Fetal malposition, 229
Fetal surgery, 292
Fetal ultrasound, 369
Fever
infectious causes of, 117–129
neuraxial analgesia and maternal fever rates, 232–233
noninfectious fever in parturients, 116–117
in pregnancy, 116–129
FHR. See Fetal heart rate
Fiberoptic intubation, 275–276
Fiberoptic technique, 276–277
Fibrinogen concentrate, 494
Fibrinolysis, 483
5-HT3 receptor antagonists, 370
FIX deficiency, 490–491
Flow cytometry, 641–642
Fluoroquinolones, 31t
Focused assessment with sonography (FAST), 638–639
Focused cardiac ultrasound
clinical applications, 196–198
cardiac arrest, 197–198
chest pain, 197
dyspnea, 197
hypotension, 196–197
preeclampsia and FoCUS, 198
FoCUS training, certification, and program maintenance, 198
introduction, 192–193
techniques, 193–196
basic FoCUS examination views, 193
contractility, 194–195
FoCUS protocols, 195–196
intravascular volume, 193–194
Fontan procedure, 515
Frank breech, 296–297, 296f
FRC. See Functional residual capacity
Functional residual capacity (FRC), 8
FVIII deficiency, 490–491

Gabapentin, 373, 383

Gastric volume measurement
applications, 212–213
introduction, 211–212
 technique, 212
Gastrointestinal system
obesity, pregnancy, and, 617
postpartum changes to, 418–419
in pregnancy, 10–11
GBS. See Group B streptococcus
GDM. See Diabetes mellitus
General endotracheal anesthesia (GETA), 588–589, 598–599, 600
Genitourinary/renal system, 441–442
Gestational diabetes (GDM). See Diabetes mellitus
Gestational hypertension, 436
GETA. See General endotracheal anesthesia
GFR. See Glomerular filtration rate
GlideScope, 279
Glomerular diseases, 563
Glomerular filtration rate (GFR), 11–12
Glucocorticoids, 463
Glucose metabolism, 12–13
Graves disease, 460, 461, 465
Group B streptococcus (GBS), 122
Guidelines from national organizations
American Academy of Pediatrics and American College of Obstetricians
and Gynecologists collaboration, 698
American College of Obstetricians and Gynecologists and, 695–698
American Heart Association relevant documents, 699
American Society of Anesthesiologists and, 680–681, 684–695
American Society of Regional Anesthesia and Pain Medicine relevant
documents, 698–699
documents from other relevant organizations, 698t
judging and comparing documents, 682–683
limitations of guidance documents, 682
organizations with guidance relevant to obstetric anesthesia, 684
Society of Obstetric Anesthesia and Perinatology relevant documents, 699–
700
 terms used, 680

Halothane, 475
HELLP syndrome. See Hemolysis, elevated liver enzymes, low platelets
syndrome
Hemabate. See Carboprost
Hematologic disorders, 124–125
Hematologic system
in multiple gestation pregnancy, 291
in pregnancy, 9–10
Hemolysis, elevated liver enzymes, low platelets syndrome (HELLP syndrome),
577–578, 578t
Hemolytic uremic syndrome (HUS), 571
Hemophilia A, 490–491, 491t
Hemophilia B, 490–491, 491t
Hemorrhage. See Maternal hemorrhage; specific types of hemorrhage
Heparin, 31t, 411t, 488, 489t, 590, 592–593
Hepatic disease
anesthetics and, 573
characteristics, 572, 572t
diagnosis of liver disease, in pregnancy, 573
diseases exacerbated by pregnancy, 578–579
autoimmune hepatitis, 578
organ transplantation and, 578–579
viral hepatitis, 578
diseases unique to pregnancy, 574–578
acute fatty liver of pregnancy (AFLP), 571, 575–577, 576t
cholestasis of pregnancy, 574–575
hemolysis, elevated liver enzymes, low platelets syndrome (HELLP
syndrome), 577–578, 578t
hyperemesis gravidarum, 574
hepatic anatomy and physiology, in pregnancy, 573
hepatic function assessment, 573
introduction, 558–559
 multidisciplinary team, 559
Hepatic function, 11, 12t, 573
Hepatitis
acute hepatitis, 122
anesthetic considerations, 123–124
autoimmune and viral, 578
chronic hepatitis, 123
neuraxial anesthesia for, 123
Hepatobiliary system, 442
Heroin. See Diamorphine
Herpes simplex virus (HSV-1 and HSV-2), 126
Herpes zoster (shingles), 128
HIV. See Human immunodeficiency virus
HOCM. See Hypertrophic obstructive cardiomyopathy
HSV-1. See Herpes simplex virus
HSV-2. See Herpes simplex virus
Human immunodeficiency virus (HIV)
anesthetic considerations, 125–126
cardiovascular disease, 124–125
endocrine disorders, 124–125
gastrointestinal involvement, 124–125
general anesthesia, 126
general considerations, 124
hematologic disorders, 124–125
neuraxial anesthesia, 125
neurologic disease, 124–125
pulmonary complications, 124
renal disease, 124–125
systemic manifestations, 124–125
transmission, from mother to fetus, 124
HUS. See Hemolytic uremic syndrome
Hydralazine, 31t, 444, 444t, 472
Hydromorphone, 366, 367–368, 367t
recommended single doses, for postcesarean analgesia, 368t, 369t
Hydrotherapy, 141–142
Hypercoagulability, 616–617
Hyperemesis gravidarum, 574
Hyperfibrinogenemia, 10
Hyperglycemia, 453–454. See also Diabetes mellitus
Hypertensive disorders
anesthetic considerations, 445–446
assessment of volume status, 445–446
blood pressure control, 446
coagulation in, 441, 446
delivery mode and anesthetic technique, 446–447
cesarean delivery, 447
vaginal delivery, 446–447
differential diagnosis and definitions, 436–437
chronic hypertension, 436
chronic hypertension with superimposed preeclampsia, 437
gestational hypertension, 436
preeclampsia, 436–437
epidemiology, 438
incidence, 438
maternal mortality, 438
neonatal mortality, 438
etiology, 438–439
antioxidants, 439
decreased placental perfusion, 438–439
genetic influences, 439
inflammatory mediators, 439
lifestyle modifications, 439
oxidative stress, 439
placental ischemia outcome, 439
prostaglandin imbalance, 439
vasoactive substances, 439
maternal death from, 669
obesity and, 615
 obstetric management, 442–445
antihypertensive agents, 444t
blood pressure control, 443, 444t
prediction and prevention of preeclampsia, 442
seizure prophylaxis, 443
timing and route of delivery, 442–443
pathophysiology, 439–442
placenta and, 442
postpartum care, 448
analgesia, 448
blood pressure control, 448
fluid balance, 448
long-term sequelae, 448
seizure prophylaxis, 448
pregnancy-induced hypertension, 492–493
risk factors, 438, 438t
Hyperthermia, 186
Hyperthyroidism
antepartum considerations, 461–462
fetal goiter and Graves disease, 461, 464, 465
medications, 461
thyroid storm, 461–463
causes of, 460, 460t
clinical presentation, 460
definition and pathophysiology, 459–460
drugs, 462t
fetal outcome, 461
intrapartum and anesthetic considerations
cesarean delivery, 463–464
labor analgesia, 463
major concerns, 463
management, 461
physiology of, 460
Hypertrophic obstructive cardiomyopathy (HOCM), 526–527
Hypnosis, 140
Hypoglycemia, neonatal, 458
Hypopituitarism, 468, 468t
Hypoplastic left heart syndrome, 514–517
anesthetic management, 517
invasive monitoring, 517
pathophysiology, 515
peripartum considerations, 517
surgical correction, 515, 517
Hypotension, 184
focused cardiac ultrasound, 196–197
obesity and, 615–616
spontaneous intracranial, 382, 408
unexplained, 471
Hypothyroidism
antenatal care, 465
clinical presentation, 464
intrapartum and anesthetic considerations, 465–466
obstetric risk and complications, 465
pathophysiology, 464
treatment, 464
Hypoxemia, 7–8, 14
fetal compensatory measures to, 25
management of patients with critical airway, 282–283
transient, 344–346
Hysterectomy, 329

Ibuprofen, 429
Idiopathic dilated cardiomyopathy (IDC), 526
Idiopathic intracranial hypertension (pseudotumor cerebri), 546–547
Iliohypogastric and ilioinguinal peripheral nerve blocks, 371, 663
Immune function, 10
Implied consent, 75
Incomplete breech, 296–297, 296f
Indirect maternal death, 667
Indomethacin, 61
Influenza, 120
Informed consent
background on, 74–75
delegation of, 77
exceptions to, 78–79
failure to obtain, 79
implied consent, 75
laboring women and, 75
law and, 79
from minors, 77
presentation of information and risk, 76
purpose of informed consent discussion, 76
refusal to be informed, 76–77
refusal/withdrawal of consent, 77
withholding information, 76
written consent, 78
Inhalation agents, 428
Inhalation techniques, 143–145
Inherited thrombophilias, 485–486, 487t
Instrumental vaginal delivery, 182–183
neuraxial analgesia and, 227–229
Insulin
diabetes mellitus (DM) management with, 454, 455t
glucose management, in labor and delivery, 457
postpartum care, 458
Intermittent auscultation, 110
Intermittent bolus injection, 180
Intra-arterial monitoring, 519
Intracerebral hemorrhage, 381
Intracranial hemorrhage, 380–381
anesthetic management, 548
clinical issues, 547–548
 obstetric management, 548
overview, 547
Intracranial neoplasms
anesthetic management, 545–546
clinical issues, 544–545
obstetric management, 545
signs and symptoms, 544–545, 545t
Intracranial pressure measurement, 209–211
Intraoperative cell salvage, 317–318
Intrapartum emergencies
amniotic fluid embolism (AFE), 336–338, 337t
preterm labor and delivery, 333–334
shoulder dystocia, 334–336
umbilical cord compression/prolapse, 336
Intrapartum evaluation, 347–348
Intrathecal catheter, 383
Intrathecal opioids, 368–369, 369t
Intrathecal saline, 383
Ischemic heart disease, in pregnancy, 529
Isoflurane, 573

Joint mobility, 13

Ketamine, 369, 372, 519, 642, 664

Ketorolac, 61, 429
King LTS, 281–282
Kleihauer-Betke testing, 641

Labetalol, 444–445, 444t, 472, 473

Labor and delivery. See also Cesarean delivery; Vaginal delivery
ambulation during, 183, 183t, 232
anesthetic management in obstetric patients with predicted difficult airway,
273–275
asthma and, 584, 585–586
cardiac disease and considerations for, 499–500
 cyanotic lesions and, 510, 518
diabetes mellitus (DM), management of, 456–458
Eisenmenger syndrome, 518
external cephalic version and, 302
hypertensive disorders and timing of, 442–443
hyperthyroidism and, 463–464
hypothyroidism and, 465–466
informed consent and, 75
multiple gestation labor patterns, 294
myasthenia gravis and, 550–551, 552
neuraxial analgesia
fetal malposition and, 229
first stage of labor and impact of, 223–224
immediate versus delayed pushing and, 226
maternal perineal injury and, 229
progress of labor and, 222–223
second stage of labor and impact of, 225–226
neurologic deficits following, 390–412
non-neuraxial pharmacologic methods of pain relief during, 143–158
nonpharmacologic methods of pain relief during, 138–143
obesity and, 618–624
opioid dependent parturient, pain management in, 661
pain pathways during, 162
support for, 138
Lactation
headache, 382
requirements for labeling of prescription drugs and biological products, 30t
Landry-Guillain-Barré, 552–553
Laparoscopic surgeries, 89
Laryngeal mask airway (LMA), 280
Fastrach, 281
ProSeal, 281
Supreme, 281
Laryngoscopy, 261, 474–475
Late maternal death, 667
Lateral femoral cutaneous nerve of thigh, 394–395
Lead, 85t
Left-to-right shunting, 520–521
Leukocytes, 10
Levobupivacaine, 44, 179
Lidocaine, 37t, 41, 43, 44t, 45, 48, 49
advantages of, 178
for pheochromocytoma, 178
for PPTL, 429
for shoulder dystocia, 336
for spinal anesthesia, in cesarean delivery, 253
Lipid emulsions, 45
Listeria, 127
Lithium, 31t, 85t
Lithium carbonate, 462t
Litigation, 79–80. See also Ethical and legal considerations
Liver function tests, 12t
Liver disease. See Hepatic disease
LMA. See Laryngeal mask airway
Local anesthetics, 13
accidental IV of, 186–187
additives, 39
bicarbonate, 39
epinephrine, 39
opioids, 39
phenylephrine, 39
cesarean delivery
epidural anesthesia for, 249–250
spinal anesthesia for, 253
chemical structure, 36
amino-amides, 36
amino-esters, 36
choice of, 177–180
commonly used local anesthetics and attendant physiochemical properties,
37t
differential blockade, 37–39
anesthetic implications, 39
physiologic basis, 37–38
effect of pregnancy on, 39
maximum single doses, 44
mechanism of action, 36–37
local anesthetic binding to sodium channel, 37
local anesthetic dissociation from binding site, 37
local anesthetic effects, on other membrane-bound proteins, 37
local anesthetic entry into cell, 36–37, 36f
other reactions, 48–49
allergic reactions, 49
back pain, 49
myotoxicity, 49
neurotoxicity, 48
transient neurologic symptoms (TNS), 48–49
pharmacokinetics, 40–41
amide protein binding, 41
chronobiology, 41
clearance, 41
distribution, 41
effect of pregnancy on, 41
elimination, 41
local anesthetic continuous infusions, 41
systemic absorption, 40–41
placenta and, 41
in postcesarean analgesia
epidural, 370–371
iliohypogastric and ilioinguinal peripheral nerve blocks, 371
surgical wound infiltration, 371
transversus abdominis plane blocks, 371
for PPTL, 428–429
 systemic toxicity, 42–48
comorbidities, 44
early and late signs, 42t
effects of pregnancy on, 44
incidence of, 42
prevention, 44–45
signs and symptoms, 42–44
treatment, 45–48
Lower extremity vein ultrasound, 216–218
Lumbar arteries, 399
Lumbar epidural, 390
Lumbar lordosis, 13
Lumbar plexus, 393–394, 393f
Lung transplantation, 602–603
Lung volumes, 7
Lyme disease, 126–127
Lymphocytic hypophysitis, 469

Macroadenoma expansion, 466

Macrosomia, 626
Magnesium, 369, 372
Magnesium sulfate, 111, 381
anesthetic considerations, 61
effects of increasing plasma magnesium levels, 61t
for hypertensive disorders and seizure prophylaxis, 443, 444t
mechanism of action, 60
in multiple gestation pregnancy, 294, 295
myasthenia gravis and, 550
for pheochromocytoma, 474–475
route of administration/dose, 60
toxicity/side effects, 60–61
uses, 59–60
Magnesium toxicity, 360
Magnetic resonance imaging (MRI), 640
Mallampati classification, 266–267, 267f
Mandibular protrusion test, 268, 268f
Mandibulohyoid distance, 268, 269f, 270f
Marfan syndrome (MFS), 522–523
MAS. See Meconium aspiration syndrome
Massage, 139
Maternal autonomy, 80–81
Maternal central nervous system shunts, 547
Maternal death, 667–669. See also Maternal morbidity and mortality
Maternal hemorrhage
antepartum hemorrhage, 321–327
from cesarean delivery, 241, 241t
clinical signs of hemorrhagic shock, 315t
intracranial hemorrhage, 380–381
management of obstetric hemorrhage, 315–321
maternal death from, 669
in multiple gestation pregnancy, 292
postpartum hemorrhage, 327–333
Maternal hyperthermia, 186
Maternal infection and fever
fever in pregnancy, 116–129
infectious causes of fever in parturients, 117–129
chorioamnionitis, 117–119
cytomegalovirus, 122
group B streptococcus, 122
hepatitis, 122–124
herpes simplex virus, 126
HIV, 124–126
miscellaneous infections, 126–129
postpartum infection (endometritis), 121–122
respiratory tract infection and influenza, 120
respiratory tract infection and pneumonia, 119–120
urinary tract infection (UTI), 120–121
neuraxial analgesia and maternal fever rates, 232–233
 neuraxial anesthesia for febrile parturient, 131
noninfectious fever in parturients, 116–117
mechanisms, 117
noninfectious fever and epidural analgesia for labor, 116–117
sepsis and septic shock, 129–131
anesthetic management, 130–131
general considerations, 129
treatment, 130, 130t
Maternal monitoring, of fetal movement, 98–99
Maternal morbidity and mortality, 15
anesthesia-related maternal mortality, 672–675, 672t, 673t, 674t
definitions, 667–668
difficult airway management, anesthesia-related morbidity and mortality,
263–265
epidemiology, 668
etiologies, 668–669
hypertensive disorders and, 438
in multiple gestation pregnancy, 293
obesity and maternal mortality, 617, 620
preventability and lessons learned, 671–672
risk factors, 669–670
severe maternal morbidity, 670–671
in United States, 668f
Maternal perineal injury, 229
McRoberts maneuver, 335
Meconium, 311
Meconium aspiration syndrome (MAS), 357–358
Meconium-stained amniotic fluid, 357–358
Meningitis, 187, 382
bacterial, 408–409
postdural puncture, 408–409
diagnosis, 408–409
prevention of, 409
signs and symptoms, 409
Meperidine, 110, 147–148, 366
Mepivacaine, 37t, 44t
Mercury, 85t
Metabolic syndrome, 615
Methimazole, 462
Methyldopa, 31t, 444t, 473
Methylergonovine, 328
15-Methyl prostaglandin F2a, 328
Metoclopramide, 424, 475
Metronidazole, 31t
MFS. See Marfan syndrome
MG. See Myasthenia gravis
Migraine, 380
β-Mimetic therapy
anesthetic considerations, 57–58
drugs, 56
mechanism of action, 56, 57f
route of administration/dose, 56–57
toxicity/side effects, 57
uses, 56
Minimum alveolar concentration, 13
Minors, 77
Misoprostol (Cytotec), 67–68, 328
Mitral regurgitation (MR), 504–506
Mitral stenosis (MS), 500–502
Mitral valve prolapse (MVP), 506
Mivacurium, 428
Monkeypox, 128–129
Morphine, 149, 179, 366, 367t, 475
dose ranges, 179t
epidural, 383, 429
extended-release epidural morphine, 368
recommended single doses, for postcesarean analgesia, 368t, 369t
Motor block, 186
Motor vehicle accidents, 643–644
MR. See Mitral regurgitation
MRI. See Magnetic resonance imaging
MS. See Mitral stenosis; Multiple sclerosis
Multimodal therapy, 366
Multiple gestation pregnancy
anesthesia for, 289–295
in cesarean delivery, 295
in vaginal delivery, 294–295
cephalic-cephalic presenting twins, 294
cephalic-noncephalic presenting twins, 294
costs of, 295
delivery route, 294
introduction, 289
labor patterns, 294
maternal adaptation to, 290–291, 290t
cardiovascular system, 290–291
central nervous system, 291
hematologic changes, 291
respiratory system, 291
national guidelines, 289–290
obstetric conditions and concerns, 291–293
fetal surgery, 292
maternal hemorrhage in, 292
maternal morbidity in, 293
other concerns, 293
preeclampsia, 291
pharmacologic therapies, 293–294, 295
preterm birth in, 293–294
anesthesia for, 294
pharmacologic therapies to prevent, 293–294
predicting, 293
preventing, 293
timing of delivery, 293
 triplet/+ birth rates, 289f
Multiple sclerosis (MS), 549–550
Muscle relaxants, 15, 428, 552
Musculoskeletal changes, 13
Music, 138
MVP. See Mitral valve prolapse
Myasthenia gravis (MG)
anesthetic management, 551–552
cesarean delivery, 551–552
labor and delivery, 551
muscle relaxants, 552
postoperative care, 552
preanesthetic evaluation, 551–552
clinical issues, 550
labor and delivery and, 550–551
medications known to exacerbate symptoms of, 551t
obstetric management, 550–551
Myocardial contractility, 5

Nalbuphine, 158
Neonatal abstinence syndrome (NAS), 659–660
Neonatal hypoglycemia, 458
Neonatal resuscitation. See Newborn resuscitation
Neonatal shock, 356
Neonate evaluation
Apgar score, 348–349, 348t
umbilical cord blood gas measurements, 349
Neoplasm, 381
intracranial, 544–546
Neostigmine, 112, 180, 369
Nerve conduction studies, 401–402
Neuraxial analgesia
ambulation during labor, 183
advantages, 183
 disadvantages, 183
suggested guidelines for, 183t
analgesia for vaginal delivery, 182–183
instrumental vaginal delivery, 182–183
spontaneous vaginal delivery, 182
in cesarean delivery, with obesity, 621
contraindications, 165, 165t
description of technique, 169–175
combined spinal-epidural technique, 173–174, 501–502
continuous spinal technique, 175
epidural technique, 169–173
fetal malposition, labor, and, 229
impact on obstetric outcomes, 221–234
ambulation, 232
benefits, 222t
breastfeeding success rates, 233
cesarean delivery, 230–231
conclusion, 234
effects of neuraxial analgesia on progress of labor, 222–223
first stage of labor, 223–224
instrumental vaginal delivery, 227–229
introduction, 221–222
maternal fever rates, 232–233
oxytocin augmentation, 231–232
second stage of labor, 225–226
indications, 164–165
local anesthetics, choice of, 177–180
concentration and dose considerations, 177–179
use of adjuvants in labor analgesia, 179–180
maintenance of analgesia, 180–182
continuous epidural infusion, 180–181
continuous spinal analgesia, 182
intermittent bolus injection, 180
patient-controlled epidural analgesia, 181, 181t
 maternal perineal injury and, 229
maternal request, 164–165
preparation, 167–169
aspiration prophylaxis, 167t
evaluation and consent, 167–168
intrapartum platelet counts and blood type and screen, 168
intravenous access, 168
monitoring, 168–169
procedure checklist, 167t
rationale for choice of technique, 166–167
anesthetic considerations, 167
maternal coexisting disease, 166
obstetric considerations, 166
side effects and complications, 184–187
accidental IV local anesthetic, 186–187
back pain, 186
epidural hematoma and abscess, 187
failed analgesia, 184–185
fetal heart rate abnormalities, 186
hypotension, 184
maternal hyperthermia, 186
meningitis, 187
motor block, subdural, and high/total spinal block, 186
neurologic deficits, 187
treatment for pruritus, 184
unintended dural puncture, 185
urinary retention, 186
Neuraxial anatomy
difficult identification of ligamentum flavum, 164
engorgement of epidural veins, 164
higher level of apex of thoracic kyphosis, 164
reduction in intervertebral gap, 162–163
widening and rotation of pelvis, 163
Neuraxial anesthesia, 13
 anesthetic management in obstetric patients with predicted difficult airway,
274
ASA on, 693–694
for chorioamnionitis, 119
for febrile parturient, 131
for hepatitis, 123
HIV, 125
obesity and cesarean delivery, 621
pain pathways, during labor, 162
thoracic, 587–588, 588f
thrombophilia and anticoagulated patient, 488, 489t
tubal sterilizations and, 423
ultrasound-guided neuraxial anesthesia, 202–208
Neuraxial blocks
guidelines for administering, 411–412, 411t
infectious complications of, 408–410
in vaginal delivery, with obesity, 619, 620
Neurologic and neuromuscular diseases
anatomic disease
idiopathic intracranial hypertension (pseudotumor cerebri), 546–547
intracranial neoplasms, 544–546
maternal central nervous system shunts, 547
scoliosis, 535–540
spina bifida, 543–544
spinal cord injury, 540–543
spinal surgery, 540
conclusion, 554
epilepsy
anesthetic management, 554
classification of seizure disorders, 553t
obstetric management, 553–554
immunologic disease
Landry-Guillain-Barré, 552–553
multiple sclerosis (MS), 549–550
 myasthenia gravis (MG), 550–552
vascular disease
cortical vein thrombosis, 548
intracranial hemorrhage, 547–548
Neurologic deficits, following labor and delivery
basic anatomy, 393–394
common obstetric neuropathies, 394–397
femoral nerve, 395
lateral femoral cutaneous nerve of thigh, 394–395
obstetric nerve injury and implications, 395t
obturator nerve, 395
peripheral nerve injuries, 394t
sciatic nerve, 395–397
sensory innervation of lower extremities, 396f
diagnosis and treatment of neuropathies, 400–402
electromyography, 400–401, 401f, 401t
electrophysiologic studies, 402
nerve conduction studies, 401–402
epidural hematoma, 410–411
history and initial evaluation, 392–393
causes of postpartum neurologic injury, 393
extent of injury, 393
relevant questions during evaluation, 392–393
infectious complications of neuraxial blocks, 408–410
epidural abscess, 409–410
postdural puncture meningitis, 408–409
ischemic injury to spinal cord, 398–399
artery of Adamkiewicz, 398–399
blood supply to spinal cord, 398, 398t
diagnosis of spinal cord ischemia, 399
lumbar arteries, 399
lesion types, 399–400
chemical injury, 399
direct nerve trauma, 399–400
 neurologic injury, 390–392
frequency of transient and permanent neurologic deficits, 391t
incidence, 390–392
peripheral nerve injuries, 402–403
differential diagnosis, 403t
neurologist consultation and imaging studies, 402–403
preexisting causes, 402
recommendations, 412
spinal fluid leakage, 404–408
autologous epidural blood patch, 405
complications related to, 404–408
imaging studies, 405
intracranial hematomas, 407–408
postdural puncture headache, 404, 405f, 406–408
prophylactic epidural blood patch, 407
seizures, 408
spontaneous intracranial hypotension, 408
Neurosurgical procedures, 88–89
Newborn resuscitation
anticipating depressed newborn, 346–348
antepartum evaluation, 346–347
antepartum factors associated with resuscitation, 347t
intrapartum evaluation, 347–348
intrapartum factors associated with resuscitation, 347t
discontinuation of resuscitative efforts, 357
evaluating neonate, 348–349
medications, 355–357, 355t
epinephrine, 355–356
sodium bicarbonate, 356–357
volume expanders, 356
neonatal adaptations to extrauterine life, 344–346
fetal cardiovascular and pulmonary physiology, 344, 345f
normal peripartum transition to extrauterine life, 344
prolonged hypoxemia/acidosis and failure to transition, 344–346
 neonatal resuscitation
assisted ventilation, 350–353
in breech presentation, 303
chest compression, 354, 355f
considerations for establishing ventilation, 353
endotracheal intubation, 351–353, 352f, 353t
initial resuscitation, 350
maintainance of normothermia, 350
oxygen administration, 353–354
preparation, 349, 350t
protocol, 351f
resuscitation algorithm, 350
special resuscitation circumstances, 357–360
magnesium toxicity, 360
meconium-stained amniotic fluid, 357–358
opioid-induced respiratory depression, 359
premature infants, 358–359
umbilical vein catheterization, 354–355
New York Heart Association (NYHA), 498, 498t
Nifedipine, 59, 444t, 445
Nitric oxide, 519
Nitrofurantoin, 31t
Nitroglycerin, 444t, 445, 475
anesthetic considerations, 63
in breech presentation, 298
mechanism of action, 62
route of administration/dose, 62
toxicity/side effects, 63
uses, 62
Nitroprusside, 474
Nitrous oxide, 85, 519, 695
Non-neuraxial analgesic techniques, 137
non-neuraxial pharmacologic methods of pain relief, 143–158
inhalation techniques, 143–145
 non-opioid analgesia and sedatives, 145–147
opioid analgesia, 147–158, 179
nonpharmacologic methods of pain relief, 138–143
antenatal health education, 138
complementary therapies, 139–141
hydrotherapy, 141–142
relaxation techniques, 138
sterile water injection, 142–143, 143f
support, during labor, 138
transcutaneous electrical nerve stimulation (TENS), 142
Non-neuraxial pharmacologic methods of pain relief, 143–158
Nonobstetric surgery, during pregnancy
alterations in maternal physiology, 84
incidence and anesthetic concerns, 83–84
intraoperative anesthetic management, 87–88
maintenance of fetal oxygenation, 84
postoperative care, 88
preoperative plan and counseling, 86–87
prevention and treatment of preterm labor, 84
principles for anesthetic management, 86t
special situations, 88–91
cardiac surgery requiring cardiopulmonary bypass, 89
fetal interventions, 89–91, 90t
laparoscopic surgeries, 89
neurosurgical procedures, 88–89
trauma, 88
teratogenicity of anesthetic agents, 84–85, 86t
Non-opioid analgesia and sedatives, 145–147
Nonpharmacologic methods of pain relief, 138–143
Nonreassuring fetal status
diagnosis, 310–313
Doppler ultrasound, 312
fetal heart rate interpretation, 310
fetal heart rate monitoring, 310–311
 fetal heart rate pattern, 310
presence of meconium, 311
umbilical cord gases, 311
fetal distress, 307–308
pathophysiology, 308–310
basic causes of fetal compromise, 309t
fetal acid–base balance and asphyxia, 309–310
fetal asphyxia causes, 309
fetal response to asphyxia, 310
treatment, 312–315
anesthetic management, 313–315
maternal safety, 314–315
obstetric management, 312–313
Nonsteroidal anti-inflammatory drugs (NSAIDs), 372, 490t, 664
Nonstress test (NST), 99
NSAIDs. See Nonsteroidal anti-inflammatory drugs
NST. See Nonstress test
NYHA. See New York Heart Association

Obesity, in pregnancy
anesthesia for obese pregnant women, 617–618
general considerations, 618
obesity and maternal mortality, 617
patient evaluation, 617
asthma and, 614
cardiomyopathy and, 615
cesarean delivery and, 620–624
anesthetic plan, 620–621
general anesthesia, 621–623
general considerations, 620
maternal morbidity and mortality, 620
neuraxial anesthesia, 621
operating room considerations, 623–624
surgical considerations, 624
cost and, 627
definition and demographics, 611–612
high-risk patient, 610–612
anesthetic challenges, 610
maternal comorbidities, 610, 611t
obstetric risk and outcomes, 610–611, 612t
hypertensive disorders and, 615
hypotension and, 615–616
morbid obesity and airway, 271–272
newborns and, 626–627
fetal anomalies, 626
fetal macrosomia, 626
neonatal care, 627
preterm delivery, 626
stillbirth and neonatal deaths, 626–627
physiologic changes, 612–617
cardiovascular system, 615–616
endocrine system, 616
gastrointestinal system, 617
hypercoagulability, 616–617
pulmonary system, 612–614
postoperative care, 625–626
general considerations, 625
postoperative monitoring, 625
pulmonary considerations, 625
thromboprophylaxis, 625–626
postoperative wound infection, 624
pregnancy, after bariatric surgery, 627
projected prevalence of, by 2025, 271f
summary of, 627–628
vaginal labor and delivery, 618–620
epidural analgesia, 618–619
epidural catheter placement, 619–620
labor analgesia, 618
 neuraxial blocks, cephalad spread of, 620
neuraxial blocks, placement, 619
venous thromboembolism and, 616–617
Obesity hypoventilation syndrome (OHS), 614
Obstetric emergencies
categories of, 307
intrapartum emergencies, 333–338
nonreassuring fetal status, 307–315
peripartum bleeding, 315–333
Obstetric medications. See Tocolytic medications; Uterotonic medications;
specific medications
Obstetric nerve injury and implications, 395t
Obstructive sleep apnea (OSA), 598–599, 614f
Obturator nerve, 395
OCT. See Oxytocin challenge test
OHS. See Obesity hypoventilation syndrome
Ondansetron, 31t
ONSD. See Optic nerve sheath diameter
Opioid analgesia, 147–158, 179
dose ranges, 179t
Opioid dependent parturient, management of
introduction, 655
neonatal abstinence syndrome (NAS), 659–660
obstetric management, 655–659
algorithm for, 657f
chronic pain, in pregnancy, 659
identification, 658
peripartum, 659
rates of dependency, 656f
risk of dependency, in pregnancy, 655, 658
treatment, 658–659
pain management during peripartum period, 660–664
anesthetic management of cesarean delivery, 661
baseline long-acting opioid management, 661
 opioid tolerance, 660–661
pain management for labor and delivery, 661
postcesarean delivery analgesia, 661, 664
summary of studies reporting peripartum pain management, 662t
summary, 664
Opioid-induced respiratory depression, 359
Opioid partial agonists, 157–158
Opioids, 39, 110
adjuncts, 368, 369
epidural, 367–368, 368t
for epidural anesthesia, in cesarean delivery, 250
intrathecal, 368–369, 369t
in postcesarean analgesia, 366–370
side effects, 369–370
for spinal anesthesia, in cesarean delivery, 253
systemic, 366–367
Optic nerve sheath diameter (ONSD). See Intracranial pressure measurement
Oral fiberoptic intubation technique, 276–277
Oral hypoglycemic agents, 454–455
OSA. See Obstructive sleep apnea
Ovarian arteries, 21
Oxycodone, 157
Oxymorphone, 366, 367t
Oxytocin, 13
anesthetic considerations, 65
mechanism of action, 64
neuraxial analgesia and augmentation of, 231–232
route of administration/dose, 64
toxicity/side effects, 65
uses, 64
for uterine atony, 328
Oxytocin antagonist (atosiban), 63
Oxytocin challenge test (OCT), 99
Pain, 137
ASA Statement on Pain Relief during Labor, 693
back pain, 49, 186
gate control theory, 139f
non-neuraxial pharmacologic methods of pain relief, 143–158
nonpharmacologic methods of pain relief, 138–143
opioid dependency and management of, 659–664
pathways, during labor, 162
uncontrolled maternal pain, 8
Pancreatic function, 12–13
Pancuronium, 475
Panniculus, 624
Paracervical block, 112
Paresthesia, 399–400
Parvovirus B19, 127
Patent ductus arteriosus (PDA), 521
Patient-controlled epidural analgesia, 181, 181t
PDA. See Patent ductus arteriosus
Pelvic/abdominal ultrasound, 213–215
Penetrating injury, 646–647
Penicillin, 31t
Pentazocine, 475
Perimortem cesarean delivery, 647
Peripartum bleeding
antepartum hemorrhage, 321–327
management of obstetric hemorrhage, 315–321
acute normovolemic hemodilution, 318
antepartum donation and autologous transfusion, 317
clinical signs of hemorrhagic shock, 315t
complications, 318
fundamentals of obstetric hemorrhage, 315–316
intraoperative cell salvage, 317–318
key management considerations, 316
massive blood loss and transfusion, 318–321, 318t
 transfusion, 316–317
postpartum hemorrhage, 327–333
Peripartum cardiomyopathy (PPCM), 524–526
Peripheral nerve fiber classification, 38
Peripheral nerve injuries, 394t, 402–403, 403t
Peroneal nerve, 397f
Pharmacokinetics, 40–41
Phenobarbital, 462t
Phenothiazines, 31t, 110
Phenoxybenzamine, 474
Phentolamine, 475
Phenylephrine, 39
Phenytoin, 85t
Pheochromocytoma, 178, 473–475
Phosphodiesterase inhibitors, 519
PI. See Pulsatility index
Pickwickian syndrome. See Obesity hypoventilation syndrome
Pituitary disorders
introduction, 466
pituitary adenomas, 466–468
acromegaly, 466–467
antepartum maternal risk, 467
classification, 466
clinical considerations, 466–467
intrapartum considerations, 467–468
macroadenoma expansion, 466
management, 467
prolactinomas, 466
pituitary insufficiency, during pregnancy, 467, 468–469
antepartum risks, 469
diabetes insipidus, 469
hypopituitarism, 468, 468t
intrapartum considerations, 469
lymphocytic hypophysitis, 469
 Sheehan syndrome, 469
Pituitary function, 13
Placenta, 19–20. See also Uteroplacental anatomy
abnormal placentation types, 331f
abruptio placentae, 324–326
hypertensive disorders and, 442
local anesthetics and, 41
macroscopically, 21
microscopically, 21
retained, 329–330
Placenta accreta
anesthetic management, 331–332
definition, 330
diagnosis, 330–331
epidemiology, 330
interventional radiology techniques, 332
obstetric management, 331
Placental abruption, 643
Placental ischemia, 439
Placenta previa
anesthetic management, 323
cesarean delivery and, 322–323, 322t
definition, 321
diagnosis, 322
epidemiology, 322
obstetric management, 322–323
Plasma progesterone concentrations, 418
Platelet count and function, 9, 168, 481, 493
Pneumonia, 119–120
Postcesarean analgesia
epidural anesthesia for, 367–368, 370–371
introduction, 365–366
medications, 366–373
acetaminophen, 372
 in breast milk, 373
gabapentin, 373
ketamine, 369, 372
local anesthetics, 370–371
magnesium, 369, 372
nonsteroidal anti-inflammatory drugs, 372
opioids, 366–370
multimodal therapy, 366
summary, 373–374
Postdural puncture headache
characteristics of, 404
diagnosis, 379–380
clinical characteristics, 379–380
occurrence of, 379
differential diagnosis, 380–382, 380t
benign intracranial hypertension (pseudotumor cerebri), 382
cerebral venous and sinus thrombosis, 381
intracranial hemorrhage, 380–381
lactation headache, 382
medications/substance withdrawal, 381
meningitis, 382
migraine, 380
neoplasm, 381
posterior reversible leukoencephalopathy syndrome, 382
preeclampsia, 381
spontaneous intracranial hypotension, 382
tension headache, 380
incidence of, 404f
intracranial hematomas and, 407–408
location of, 405f
managing, 406–407
pathophysiology, 378
prevention and treatment, 382–384
recommendations, 384–385
 ambulation, 384
analgesics, 384
epidural blood patch, 385
hydration, 384
pharmacologic therapy, 384–385
prevention, after known accidental dural puncture, 385
risk factors, 378–379
scope of problem, 378
spinal fluid leakage and, 404, 405f, 406–408
Postdural puncture meningitis, 408–409
Posterior reversible leukoencephalopathy syndrome, 382
Postpartum hemorrhage
definition, 327
placenta accreta, 330–332
retained placenta, 329–330
uterine atony, 327–329
uterine inversion, 332–333
Postpartum infection (endometritis), 121–122
Postpartum tubal ligation (PPTL), 417
anesthetic considerations, 422–429
anesthesia provider and operating room times, 426f
anesthetic risk, 422–423
aspiration risk and prophylaxis, 424
breastfeeding and anesthesia, 425
general anesthetics, 428
local anesthetics, 428–429
neuraxial anesthesia and tubal sterilizations, 423
preoperative assessment, 424
regional anesthetics, 425–428
ASA Practice Guidelines for Postpartum Sterilization, 418
Pomeroy method, 422f
postpartum anatomic and physiologic changes, 418–419
cardiovascular changes, 418
gastrointestinal changes, 418–419
 summary of, 429
surgical clip method, 423f
surgical considerations relevant to anesthesiologist, 421–422
overweight or obese patients, 421–422
tubal sterilization, 421
timing of tubal sterilization, 419–421
factors affecting, 419t
for high risk patients, 421
interval versus delayed postpartum sterilization, 419–420
from obstetrician’s perspective, 420–421
Potassium iodide, 462t
PPCM. See Peripartum cardiomyopathy
PPTL. See Postpartum tubal ligation
Preeclampsia, 381
chronic hypertension with superimposed preeclampsia, 437
differential diagnosis and definition, 436
epidemiology, 438
etiology, 438–439
FoCUS and, 198
in multiple gestation pregnancy, 291
obstetric management, 442–445
optic nerve sheath diameter in preeclamptic patients, 210–211, 211f
pathophysiology, 439–442
prediction and prevention, 442
renal failure and, 569–570
risk factors, 438, 438t
signs and symptoms, 437t, 440t
Pregabalin, 383
Pregnancy. See also specific topics
after bariatric surgery, 627
fever in, 116–129
requirements for labeling of prescription drugs and biological products, 30t
Pregnancy, physiological changes of
cardiovascular system in, 4–6
 aortocaval compression, 6
blood volume, 4, 4t
cardiac output, 4
ECG changes, 5
myocardial contractility, 5
SVR, 5
central nervous system in, 13–14
biochemical changes, 12
inhalation anesthetics and minimum alveolar concentration, 13
neuraxial anesthesia/local anesthetics, 13
endocrine system in, 12–13
pancreatic function and glucose metabolism, 12–13
pituitary function, 13
thyroid function, 12
gastrointestinal system in, 10–11
gastric emptying, 11
gastric position and pressure, 10
gastric secretion, 10–11
lower esophageal sphincter tone, 10
hematologic system in, 9–10
coagulation factors, 9–10
dilutional anemia, 9
leukocytes and immune function, 10
platelet count and function, 9
hepatic function in, 11, 12t
hepatic blood flow, 11
liver function tests, 12t
serum albumin concentration, 11
serum estrogen in, 11
serum progesterone in, 11
splanchnic, portal, and esophageal venous pressure, 11
maternal physiologic changes, anesthetic implications, 14–15
aortocaval compression, 14
blood loss replacement, 15
 endotracheal intubation, 14
epidural doses, 15
hypoxemia, 14
morbidity, 15
mortality, 15
muscle relaxants, 15
subarachnoid doses, 15
upper airway changes, 14
ventilation, 14
musculoskeletal changes, 13
joint mobility, 13
lumbar lordosis, 13
renal system in, 11–12
anatomic changes, in renal blood flow, 11, 12
GFR, 11–12
respiratory system in, 6–9
arterial blood gases, 6, 7t
FRC, 8
lung volumes, 7
mechanisms of hypoxemia, 7–8
oxygen delivery, 8–9
respiratory consequences of uncontrolled maternal pain, 8
Pregnancy-induced hypertension, 492–493
Pregnancy-related death, 668
Premature infants, resuscitation for, 358–359
Preterm birth
anesthetic management, 333–334
in breech presentation, 299
in multiple gestation pregnancy, 293–294
obesity and, 626
prevention and treatment, of preterm labor, 84
risk factors, 333
trauma and, 644
Prilocaine, 48
Primary apnea, 346
Primary pulmonary hypertension, 523–524
Procaine, 37t, 44t, 48
Professional negligence, 79
Progesterone, 11, 14
Prolactin, 13
Prolactinomas, 466
Prone position, 382
Prophylactic antibiotics, 245
Prophylactic epidural blood patch, 384, 407
Propofol, 504, 519, 642
Propranolol, 475
Propylthiouracil (PTU), 462t, 463
Prostacyclin analogues, 519
Prostaglandin imbalance, 439
Prostaglandins
anesthetic considerations, 68
drugs, 67
mechanism of action, 67
route of administration/dose, 67–68
toxicity/side effects, 68
uses, 67
Prostaglandin synthase. See Cyclooxygenase inhibitors
Protein C deficiency, 485
Protein S deficiency, 485–486
Prothrombin gene mutation, 485
Pruritus, 184, 370
Pseudoephedrine, 31t
Pseudotumor cerebri. See Benign intracranial hypertension; Idiopathic
intracranial hypertension
PTU. See Propylthiouracil
Pulmonary artery catheter, 504
Pulmonary embolism, during pregnancy
guidelines on, 697
 imaging studies, 590–592, 591f
introduction, 589
treatment, 592
venous thromboembolism
maternal death from, 669
obesity and, 616–617
pregnancy effects on, 589
risk factors for, 590
treatment and anesthetic implications, 592–593
Pulmonary function tests, 583f, 584–585
Pulmonary hypertension, 508, 523–524
Pulmonary physiology, fetal, 344, 345f
Pulmonary system, 612–614
Pulmonary ultrasound
applications, 200–201
introduction, 199
sensitivity and specificity of auscultation, chest radiography, and lung
ultrasonography, 201t
technique, 199–200
Pulmonary vascular resistance (PVR), 507
Pulsatility index (PI), 101
Pulse oximetry, 519
PVR. See Pulmonary vascular resistance
Pyelonephritis, 570–571
Pyridostigmine, 550

Radiation, 85t
Radioactive iodine 131, 461, 462t
Rapid sequence intubation, 622–623
Recombinant factor VII, 321, 494
Reflexology, 139
Relaxation techniques, 138
Remifentanil, 148, 149–150, 150f–152f, 153, 502
maternal and neonatal effects, 155t
 for pheochromocytoma, 178
studies for labor analgesia, 154t
Renal disease
anesthetic implications
altered responses to drugs, 566
potential nephrotoxins, 566
preoperative preparation and laboratory studies, 566–567
anesthetic management, 467
categories of renal dysfunction and influence on pregnancy, 561–562, 561t
DM and, 456
etiology
collagen vascular diseases, 564
diabetes mellitus and hypertension, 564
primary renal diseases, 563–564
renal transplant patients, 564–565
general management strategies, 565
HIV and, 124–125
introduction, 558–559
loop diuretics and, 565
monitoring, during pregnancy, 563t
multidisciplinary team, 559
renal anatomy, 559
renal changes, in pregnancy, 560t
renal disease, dialysis, and pregnancy outcomes, 571–572
renal failure associated with pregnancy
acute fatty liver of pregnancy (AFLP), 571, 575–577, 576t
acute kidney injury, 568–569, 568t, 569t
hemolytic uremic syndrome (HUS), 571
preeclampsia and, 569–570
pyelonephritis, 570–571
renal colic, 571
renal function assessment, in pregnancy, 560–561
renal physiology, 559–560
signs and symptoms of acute renal decompensation, 565t
 systemic effects, 562, 563t
of chronic renal disease, 567t
Renal system, 11–12, 441–442
Resistance index (RI), 101
Respiratory diseases, obstetric anesthesia for parturients with
acute respiratory distress syndrome (ARDS) and respiratory failure, 604–
605, 604t
amniotic fluid embolism (AFE), 593–595
aspiration pneumonitis, 599–600
asthma, 583–589, 614
cystic fibrosis, 601–602
introduction, 582
lung transplantation, 602–603
obstructive sleep apnea (OSA), 598–599, 614f
pulmonary embolism, during pregnancy, 589–593
restrictive lung disease, 603–604
sarcoidosis, 599
smoking, 597
summary, 605
venous air embolism (VAE), 595–597
Respiratory gas exchange, 24–26
Respiratory system
in hypertensive disorders, 441
in multiple gestation pregnancy, 291
in pregnancy, 6–9
Respiratory tract infection, 119–120
Restrictive lung disease, 603–604
Resuscitation, 169, 530–531. See also Newborn resuscitation
Retained placenta, 329–330
Retinopathy, 456
RI. See Resistance index
Risk disclosure, 80
Ritodrine, 56, 57
Rocuronium, 428
Ropivacaine, 37t, 41, 43, 44t, 179
for spinal anesthesia, in cesarean delivery, 253

Sacral plexus, 394

Salbutamol, 56, 57
Salvage therapies, 647
Sarcoidosis, 599
SARS. See Severe acute respiratory syndrome
Sciatic nerve, 395–397
Scoliosis
anesthetic considerations, 536–538
cesarean delivery and, 540
clinical issues, 535–536
intrapartum management, 538–540
obstetric management, 536
other neuromuscular disorders and, 538
pathophysiology, 536–537
preanesthetic consultation, 538
respiratory function, 537–538
restrictive lung disease and, 603
Screening ultrasound survey, 97–98
S/D. See Systolic-to-diastolic ratio
Secondary apnea, 346
Seizure prophylaxis, 443, 444t, 448
Seizures, 408
epilepsy, 553–554, 553t
Sepsis and septic shock, 129–131
neonatal shock, 356
Serum albumin concentration, 11
Serum estrogen, 11
Serum progesterone, 11
Severe acute respiratory syndrome (SARS), 128
Severe maternal morbidity, 670–671
Severe thyrotoxicosis, 459–460
Severe ventricular dysrhythmias, 45
Sheehan syndrome, 469
Shingles. See Herpes zoster
Shock. See Sepsis and septic shock
Shoulder dystocia
anesthetic management, 335–336
diagnosis and recognition, 334
obstetric management, 334–335
delivery of posterior arm, 335
intravaginal pressure on posterior shoulder, 335
McRoberts maneuver, 335
suprapubic pressure, 335
Zavanelli maneuver, 335
risk factors, 334
SHS. See Supine hypotension syndrome
Sinus thrombosis, 381
Sleep apnea, 598, 599, 614f
Smoking, 597
Society for Obstetric Anesthesia and Perinatology (SOAP), 699–700
Sodium bicarbonate, 356–357
Sodium iodide, 462t
Sodium nitroprusside, 444t, 445
Spina bifida, 543–544
Spinal anesthesia
anesthetic management in obstetric patients with predicted difficult airway,
274–275
for cesarean delivery, 250–253
additives to local anesthetics, 253
examples of spinal needles, 251f
after failed epidural, 253
local anesthetics for, 253
potential complications, 252–253
for PPTL, 427–428
single-shot, 520, in left-to-right shunting
Spinal cord injury
anesthetic management, 542–543
clinical issues
acute phase, 540–541
autonomic hyperreflexia, 541–542, 542t, 544
chronic phase, 541
level of injuries, 541
other complications, 541
obstetric management, 542
restrictive lung disease and, 603
with spinal needles, 400
Spinal cord ischemia, 398–399
Spinal fluid leakage, 404–408
Spinal surgery, 540
Spontaneous intracranial hypotension, 382, 408
Spontaneous vaginal delivery, 182
Sterile water injection, 142–143, 143f
Stillbirth and neonatal deaths, 626–627
Streptomycin/kanamycin, 85t
Stress-dose steroids, 470–471
Subarachnoid block, 390
Subarachnoid doses, 15
Subarachnoid hemorrhage, 380
Subdural hematoma, 381
Succinylcholine, 428, 475, 502, 543, 552, 642
Sufentanil, 153, 156, 179, 366, 367–368
dose ranges, 179t
for PPTL, 429
recommended single doses, for postcesarean analgesia, 368t, 369t
Sugammadex, 642
Sulfonamides/trimethoprim, 31t
Sulindac, 61
Supine hypotension syndrome (SHS), 615–616
Supraglottic airway, 261
Suprapubic pressure, 335
Surgical cricothyroidotomy, 282
Surgical wound infiltration, 371
SVR. See Systemic vascular resistance
Sympathomimetics, 48
Syphilis, 127
Systemic vascular resistance (SVR), 5, 509, 520
Systolic-to-diastolic ratio (S/D), 101

T4 sensory level, 425

TA. See Tricuspid atresia
Tachyarrhythmias, 509t
TENS. See Transcutaneous electrical nerve stimulation
Tension headache, 380
Teratogenicity
agent effects, 30
of anesthetic agents, in nonobstetric surgery, during pregnancy, 84–85, 86t
classification of birth defects, 29
dose effect, 30
drug teratogenicity, 30–31, 30t, 31t
etiology of congenital malformations, 29
genetic susceptibility, 29
manifestations, 29
mechanisms of, 29
principles of, 29–30
timing of exposure, 29
Terbutaline, 56, 111
Terminal apnea, 346
Tetracaine, 37t
Tetracycline, 31t, 85t
Tetralogy of Fallot (ToF), 510–512
TGV. See Transposition of great vessels
Thalidomide, 85t
The Joint Commission 2015 National Patient Safety Goals, 169
Thoracic neuraxial anesthesia, 587–588, 588f
Thrombocytopenia, 492–493
Thrombolysis, 592
Thrombophilia
acquired, 488
anesthetic implications, 488–489
guidelines for timing neuraxial anesthesia, in anticoagulated patient,
488, 489t
guidelines on, 696–697
inherited, 485–486, 487t
management of parturients with suspected thrombophilia, 486–488
recommended anticoagulation regimes, 487t
recommended thromboprophylaxis, with inherited thrombophilia, 487t
screening, 486
treatment, 486–488
risk factors, 484–485, 486t
risk of venous thromboembolism, 486t
Virchow’s triad, 484
Thromboprophylaxis, 487t, 625–626
Thrombotic control, 481f, 482–483
Thyroid disorders
changes in thyroid function test results, 459t
hyperthyroidism, 459–464
hypothyroidism, 464–466
introduction, 458
thyroid physiology, 458–459
Thyroid function, 12
Thyroid storm, 461–463
Thyromental distance, 268
Tinzaparin, 487t
TNS. See Transient neurologic symptoms
Tocolytic medications. See also specific medications
calcium channel blockers, 58–59
cyclooxygenase (prostaglandin synthase) inhibitors, 61–62
 magnesium sulfate, 59–61
β-mimetic therapy, 56–58
in multiple gestation pregnancy, 293–294
nitroglycerin, 62–63
oxytocin antagonist (atosiban), 63
ToF. See Tetralogy of Fallot
Tracheal intubation, 261, 277–279, 447, 448f
pheochromocytoma, 474–475
Tramadol, 156–157
Transcutaneous electrical nerve stimulation (TENS), 142
Transfusion
activated recombinant factor VII, 321
autologous, 317
dilutional coagulopathy, 319–320
disseminated intravascular coagulation, 320, 321t
electrolyte balance, 319
massive blood loss and, 318–321, 318t
monitoring, 319
in obstetric hemorrhage, 316–317, 318–319, 318t
risks, 318t
Transient neurologic symptoms (TNS), 48–49
Transposition of great vessels (TGV), 512–514, 513f
Transtracheal jet ventilation, 283
Transversus abdominis plane blocks, 371, 663
Trauma, 88
anesthetic considerations, 642
airway management, 642
anesthetic induction and maintenance, 642
assessing severity of maternal injury, limitations, 637–638
advanced trauma life support training and use of vital signs, 637
clinical assessment of patient severity, 637–638
implications of physiologic changes of pregnancy, 637
severity of injury, 637
clinical test findings versus pregnancy outcome, 640–642
 flow cytometry, 641–642
Kleihauer-Betke testing, 641
minor injuries, 641
prenatal maternal injury, 640–641
direct nerve, 399–400
epidemiology, 632–633
by fetal head, 394
general treatment guidelines, 634–637
always prefer mother, 634
assessment and implications of fetal viability, 636–637
perform trauma surveys, 634–636, 635f
pregnancy workup, 636
standard care protocols, 634
introduction, 632
preterm birth and, 644
radiologic assessment, principles of, 638–640
magnetic resonance imaging (MRI), 640
standard radiology and computed tomography scanning, 639–640
ultrasound imaging, 638–639
salvage therapies, 647
specific mechanisms of injury, 643–647
burns, 646
domestic violence, 645
falls, 644
motor vehicle accidents, 643–644
penetrating injury, 646–647
summary, 647–648
uterine rupture, 644
Tricuspid atresia (TA), 514–517
Tricyclic antidepressants, 473
Trimethadione, 85t
Trimethaphan, 475
Tuberculosis, 127–128
Tubulointerstitial diseases, 563–564
Ultrasound
fetal, 369
screening ultrasound survey, 97–98
for trauma, 638–639
Ultrasound and echocardiographic techniques
airway examination, 216
focused cardiac ultrasound, 192–198
gastric volume measurement, 211–213
intracranial pressure measurement, 209–211
introduction to, 191–192
lower extremity vein ultrasound, 216–218
pelvic/abdominal ultrasound, 213–215
pulmonary ultrasound, 199–201
scanning and equipment requirements, 192t
ultrasound-guided neuraxial anesthesia, 202–208
applications, 206–208
introduction, 202
operator outcomes ultrasound-versus non-ultrasound-guided epidural
analgesia, 207t
technique, 202–206
ultrasound-guided regional anesthesia, 208–209
application, 208–209
introduction, 208
technique, 208
Ulysses directive, 78
Umbilical blood flow, 24
Umbilical cord blood gas measurements, 349
Umbilical cord compression/prolapse, 336
in breech presentation, 299
Umbilical cord gases, 311
Uncontrolled maternal pain, 8
Unfractionated heparin, 590, 592–593
Unintended dural puncture, 185
Urinary retention, 186
Urinary tract infection (UTI), 120–121
Uterine arteries, 20
Uterine atony, 246
epidemiology, 327–328
invasive therapy, 329
medical management, 328
Uterine blood flow, 22–24, 23f, 26f
Uterine hypertonus, 56
Uterine inversion, 332–333
Uterine rupture, 644
anesthetic considerations, 327
conditions associated with, 326
definition, 326
diagnosis, 326–327
epidemiology, 326
obstetric management, 327
Uteroplacental anatomy
anatomic and physiologic changes,20–21
fetal circulation, 21–22
human placenta, 21
nutrient drug/transfer, 27–29
drugs, easily crossing placenta, 28t
drug transfer, 27–28
mechanisms of exchange, 27
nutrient transfer, 28–29
respiratory gas exchange, 24–26
carbon dioxide transfer, 26
oxygen transfer, 24–26
teratogenicity, 29–31
uteroplacental circulation, 22–24
placental circulatory development, 22
umbilical blood flow, 24
uterine blood flow, 22–24, 23f, 26f
Uterotonic medications. See also specific medications
 carbetocin, 65–66
ergot alkaloids, 66–67
mechanism of action, 65f
oxytocin, 64–65
prostaglandins, 67–68
Uterus, 55
UTI. See Urinary tract infection

VAE. See Venous air embolism

Vaginal delivery
analgesia for, 182–183
anesthesia, in multiple gestation pregnancy, 294–295
for breech presentation, 297–300, 299t
hypertensive disorders and, 446–447
instrumental vaginal delivery, 182–183, 227–229
obesity and, 618–620
spontaneous vaginal delivery, 182
Valproic acid, 85t
Valvular heart disease
aortic insufficiency (AI), 506–507
anesthetic management, 507
cesarean delivery and, 507
general anesthesia, 507
pathophysiology, 506
peripartum considerations, 506
aortic stenosis (AS), 502–504
anesthetic management, 503–504
general anesthesia, 504
invasive monitors, 504
overview, 502–503
pathophysiology, 503
peripartum considerations, 503
mitral regurgitation (MR), 504–506
pathophysiology, 504–505
 peripartum considerations, 506
mitral stenosis (MS), 500–502
anesthetic management, 501–502
general anesthesia, 502
invasive monitoring, 502
pathophysiology, 500–501
peripartum considerations, 501
mitral valve prolapse (MVP), 506
Vancomycin, 475
Varicella zoster immune globulin (VZIG), 128
Varicella zoster virus (VZV), 128
Vasa previa, 323–324
Vasopressin, 48
Vasopressor administration, 245–246
Vecuronium, 428
Vena cava filter, 592
Venous air embolism (VAE), 595–597
Venous thromboembolism. See Pulmonary embolism, during pregnancy
Ventilation/perfusion scans, 590
Ventilation/perfusion single photon emission computed tomography, 590–591
Viral hepatitis, 578
Vitamin A derivatives, 85t
Volume expanders, 356
von Willebrand disease, 490, 491t
VZIG. See Varicella zoster immune globulin
VZV. See Varicella zoster virus

Warfarin, 31t, 490t, 592

Written consent, 78

Zavanelli maneuver, 300, 335