Dengue GCP Guidelines For Pregnancy 2021

Download as pdf or txt
Download as pdf or txt
You are on page 1of 90

DENGUE GCP GUIDELINES FOR PREGNANCY 2021

Adapted and modified from Guidelines for Clinical Management of Dengue Infection in
Pregnancy - Ministry of Health – Sri Lanka

DENGUE 2021
GCP GUIDELINES
1st Edi on

Edited By:
Somia Iqtadar, MBBS, FCPS, FRCP (London)
Associate Professor of Medicine
King Edward Medical University, Lahore Pakistan
Chairperson Dengue Expert Advisory Group, Punjab
Muhammad Ali Khan, MBBS, DCH, MRCP (UK)
Professor of Pediatrics, Rahbar Medical & Dental College
Secretary Dengue Expert Advisory Group, Punjab

DEAG Secretariat
Services Institute of Medical Sciences, Jail Road,
Lahore, Tel: +92 (042) 99205404, Website: www.deag.punjab.gov.pk
Email: [email protected]
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

This book is dedicated to

Prof. Faisal Masud(Late)


Founder and Former Chairman Dengue Expert Advisory Group

an ins tu on in himself and inspiri on to medical professionals.


He has been the real soul behind controlling the epidemic of
Dengue in Pakistan and developing guidelines and protocols for
management of dengue disease. He has le behind a rich legacy
for the future genera on of the doctors to emulate and prac ce
ethics in medicine.
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

Foreword
Dengue epidemics have become a serious concern with devasta ng health, social and economic
consequences in most tropical and sub-tropical regions globally. Many countries are repor ng
dengue outbreaks among adolescents and adults, and Pakistan is no excep on. In 2011, Lahore the
Capital City of the Punjab Province reported its first major outbreak of dengue which mostly
affected adults. Early diagnosis and clinical management of dengue in adults is more challenging
and requires standardized approaches to prevent disease complica ons and unwarranted
consequences.

World Health Organiza on (WHO) is aiming to reduce preventable dengue deaths to 'zero' in their
Global Strategy for Dengue Preven on and Control, 2021 - 2030. Increasing number of pregnant
women infected with dengue virus can have poor outcome without early iden fica on of clinical
disease and proper medical care. In fact, dengue haemorrhagic fever (DHF), the more severe form
of dengue illness, will become a leading cause of maternal deaths in endemic countries and
regions. The out-pa ent and in-ward departments of the hospitals in Punjab are seeing pregnant
women with dengue. As such, the recent trends on morbidity and mortality of dengue has caught
the a en on of the Health Services of the Punjab Province. This new guidelines on management of
clinical dengue in pregnant women developed by the Dengue Expert Advisory Group (DEAG),
Punjab Province is expected to further improve the exis ng knowledge and bridge any gaps on this
evolving subject. With the latest concepts highlighted this new guideline will help in strengthening
case management and ul mately reduce the number of severe cases and prevent any deaths due
to dengue associated with pregnancy.

We are extremely happy and humbled to provide guidance to the development of this document
based on the Na onal Guidelines on Clinical Management of Dengue Infec on in Pregnancy,
Ministry of Health Sri Lanka, 2019. Wish to congratulate all those who have ac vely contributed to
this important task. Special men on is necessary for Dr. Somia Iqtadar, Chairperson DEAG for her
un ring dedica on in improving case management of dengue. We sincerely hope that these
guidelines will be prac ced by all clinicians and will help in ensuring safety of mothers affected with
dengue and the safe delivery of healthy babies.

Dr. Hasitha Tissera, MD


Consultant Epidemiologist and Na onal Focal Point on Dengue
Ministry of Health Sri Lanka
Member, WHO-STAG-NTD Working Group on MER, WHO-SEA-RTAG for Dengue

i
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

From Chairperson DEAG


Dengue virus infec on has become a major public health problem in many parts of
the tropical and sub troplical regions of the world. World Health Orginaza on has
labelled it among top ten threats to the world. In 2011, Lahore, the capital of Punjab,
Pakistan experienced its first Dengue outbreak which was probably one of the largest
the world has ever witnessed. In last decade Dengue has emerged in several other
provinces of Pakistan with increasing frequency and magnitude of these epidemics.
Dengue Expert Advisory Group published its first set of guidelines for clinical
management of Dengue fever in 2012 which were then updated in 2019 keeping in
view updated knowledge and best prac ces of the world. Dengue effects mostly
adults in Pakistan, and there is increasing numbers of pregnant females infected
with dengue virus. Dengue virus can have poor outcome and more severe form of
dengue illness in pregnant popula on. This document is an effort to provide
guidence to clinicians on diagnosis and management of dengue in pregnant females
which can be challenging.
I am grateful to all people who taught me and par cularly pa ents who allowed me
to examine them and learn from them in this process. I am also thankful to my
colleagues who collaborated with me in academic ac vi es. It is humbling to note
that knowledge is never complete and that a persistent effort is always needed to
improve upon the exis ng. This new book is part of that effort. I am grateful to the
faculty of gynae & obstetrics, pediatrics and anesthesiology for their valuable
contribu on.

Somia Iqtadar(MBBS, FCPS, FRCP)


Associate Professor of Medicine
King Edward Medical University, Lahore Pakistan
Chairperson Dengue Expert Advisory Group, Punjab
Member Degue Advisory Group ISNTD.

ii
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

Objec ves
To provide evidence based guidance in the management of pregnant pa ents with dengue
infec on.
SPECIFIC OBJECTIVES
Ÿ To improve recogni on and diagnosis of dengue fever in pregnancy and provide appropriate
advice for the care to these pa ents.
Ÿ To iden fy severe dengue infec on where it becomes mandatory to provide focused close
monitoring and prompt appropriate management.
Ÿ To provide guidance on appropriate and mely fluid management and the use of blood and
blood products.

Scope of this Document


This document is intended for clinicians taking care of hospitalized pregnant pa ents with dengue
infec on. It is not meant to replace clinical judgment or specialist consulta on but rather to
strengthen clinical management of these pa ents and provide up-to-date guidance. These
guidelines are developed based on clinical experience, publica ons and opinions of prac cing
clinicians based on best available evidence at the me of wri ng.

Review of the Guidelines


The authors have issued these GCP guidelines for pregnancy in 2021. It would be reviewed in 2024
or sooner if new evidence becomes available.

Development and Review Committee


In addi on to the primary authors, we wish to thank our contributors for par cipa ng in the first
edi on of Dengue GCP guidelines for pregnancy 2021. We are especially grateful to Interna onal
Dengue Experts Dr. Hasitha Tissera Consultant Epidemiologist and Na onal Focal Point on Dengue,
Ministry of Health Sri Lanka and Prof. Lucy Lum Chai See (Faculty of Medicine, University of Malaya,
Malaysia) for their valuable input in development and review of this document.

Acknowledgement
We have all benefited from clinical wisdom and commitment of our associate authors. Many
students and physicians also have contributed useful sugges on to this manuscript. We con nue
to welcome comments and recommenda ons for future edi on in wri ng or via electronic mail.
We are also thankful to Dr. Muhammad Shahzad Hafeez, (Assistant Secretary DEAG) for his support
and Mr. Sheharyar Khalid (Senior Program Manager, PITB) for contribu ng in designing of this
document.

Secretarial Staff
The authors are indebted to the Mr. Muhammad Adil Bin Ali for providing secretarial assistance in
prepara on of this manuscript.

iii
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

PREFACE

Dengue GCP Guidelines for Pregnancy – 2021


This is the first edi on of Good Clinical Prac ce Guidelines published by Dengue Expert Advisory
Group (DEAG) for the management of dengue infec on in pregnant female, hence forth going to be
referred to as Dengue GCP guidelines for pregnancy 2021.
It must be emphasized that these guidelines are only meant to provide broad recommenda ons for
good clinical prac ce, based on the best evidence available at the me of development of these
recommenda ons. As each pa ent is unique hence adherence to these guidelines will, by no
means, guarantee the best outcome in every case.
A endinghealthcare provider is best suited to make appropriate decisions for his/her pa ents,
taking ground reali es into considera on, regarding implementa on / modifica ons of these
“generic” protocols. A er all, he/she is primarily responsible, for the management of his/her
“unique pa ent” based on the clinical picture and the locally available management op ons.

Disclosure Statement
None of the primary authors holds shares in pharmaceu cal firms or acts as consultants to such firms.

Sources of Funding
The development of the Dengue GCP guidelines for pregnancy 2021 was supported financially in its
en rety by the Government of the Punjab Pakistan and was developed without any involvement of
the pharmaceu cal industry.

iv
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

Guidelines Development
Primary Authors
Dr. Somia Iqtadar
Associate Professor, King Edward Medical Univrsity, Lahore
Prof. Mohammad Ali Khan
Professor of Pediatrics Medicine, Rahbar Medical and Dental College

Contribu ng Authors
Prof. Rubina Sohail
Professor of Gyneocology/Obstetrics. Services Ins tute of Medical Sciences (SIMS), Lahore.
Prof. Tayyaba Wasim
Professor of Gyneocology/Obstetrics. Services Ins tute of Medical Sciences (SIMS), Lahore.
Prof. Zohra Khanum
Professor of Gyneocology/Obstetrics. Fa ma Jinnah Medical University, Lahore.
Prof. Farhat Naz
Professor of Gyneocology/Obstetrics. Allama Iqbal Medical College, Lahore.
Prof. Shamila Ijaz Munir
Professor of Gyneocology/Obstetrics. Fa ma Jinnah Medical University, Lahore.

Associate Authors:
Dr. Muhammad Faheem Afzal
Associate Prof. of Pediatrics Medicine, King Edward Medical University, Lahore.
Prof. Jodat Saleem
Prof. of Anesthesia, Post Graduate Medical Ins tute/LGH, Lahore.
Dr. Kiren Khurshid Malik
Associate Professor Gyneocology/Obstetrics. Services Ins tute of Medical Sciences (SIMS), Lahore.
Dr. Natasha Bushra
Assistant Professor of Gyneocology/Obstetrics. Services Ins tute of Medical Sciences (SIMS), Lahore.
Dr. Sofia Iqbal
Associate Professor of Gyneocology/Obstetrics. Fa ma Jinnah Medical University, Lahore.
Dr. Amna Wasif
Assistant Professor of Gyneocology/Obstetrics. Fa ma Jinnah Medical University, Lahore.

v
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

Preface iv
Guidelines Development v
1. Introduc on 1
1.1 Clinical Manifesta on 1
1.2 Gesta on and Dengue 2
2. Natural Course Of Dengue Illness
3
2.1 Clinical Diagnosis of Dengue Illness 4
2.2 Dengue Fever 5
2.2.1 Clinical and Laboratory Findings
2.3 Dengue Haemorrhagic Fever (DHF) 6
2.3.1 Natural Course of DHF 7
2.3.2 Cri cal Phase in DHF 7
2.3.3 Warning Signs of Plasma Leakage in DHF 7
2.3.4 Features of Fluid Leakage 8
2.3.5 Ultrasound Features of Plasma Leakage in DHF 9
2.4 Dengue Shock Syndrome (DSS) 9
2.5 Convalescent Phase 9
3. Physiological Changes in Pregnancy 10
3.1 Cradiovascular Changes 10
3.1.1 Heart Rate 10
3.1.2 Blood Pressure 10
3.1.3 Systemic Vascular Resistance 11
3.1.4 Pulmonary Vascular Resistance 11
3.1.5 Plasma And Blood Volume 12
3.2 Haematological Changes In Pregnancy 12
3.3 Biochemical Changes In Pregnancy 14
3.4 Respiratory Changes In Pregrancy 14
3.5 Renal Changes In Pregnancy 15
4. Dengue heamarrrhagic Fever and Dengue Shock Syndrome (DSS) in pregnancy 16
4.1 Features of Dengue shock syndrome (DSS) with pregnancy 16
4.1.1 Cri cal Phase 16
4.1.2 Warning Signs 16
4.1.3 Diagnos c signs of Dengue Shock Syndrome 17
4.1.4 Differen al Diagnosis 20
4.1.5 Special Cau ons in Dengue Shock Syndrome with pregnancy 21
4.1.6 Complica ons of Fetomaternal Unit 22
4.2 Haemodynamic Changes in Dengue Shock Syndrome 23

vi
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

4.2.1 Compensated shock 23


4.2.2 Decompensated Shock 23
4.2.3 Prolonged Shock 23
5. Management of Dengue in Pregnancy 25
5.1 Early Management and Admission 25
5.1.1 First Contact Care 25
5.1.2 Admission Criteria 25
5.2 Assessment of Admi ed Pa ents 26
5.2.1 Febrile Phase 26
5.2.2 Cri cal Phase 26
5.2.3 Dengue Shock Syndrome 27
5.3 General Principles of Fluid Management in DHF 27
5.4 Management According to Trimester 28
5.5 Management Delays and Steps to Minimize them 29
6. Labour In Dengue Pa ents 31
6.1.1 Timing and mode of delivery 31
6.1.2 Prepara on for delivery 31
6.1.3 Monitoring during delivery 31
6.1.4 Post delivery care 32
6.2: Risk of Complica ons in Women with Dengue by Opera ve Interven ons 33
6.2.1 Febrile Phase 33
6.2.2 Cri cal Phase 33
6.2.3 Convalescent Pahse 34
6.2.4 Post Recovery 34
6.3: Dengue Fever with PIH 35
6.4: Dengue Fever with Diabetes 35
6.5: Dengue with Morbid Adherent Placenta 35
7. Bleeding During Pregnancy in Degue Infec on 36
7.1 Haemosta c Changes in Dengue Fever 36
7.2 Causes of Hemorrhage 36
7.3 Types of Bleeding 36
7.4 Pa ents at Risk of Major Bleeding 37
7.5 Bleeding as a Complica on of DHF 37
7.6 Warning Signs Indica ng Haemorrhage 37
7.7 Management of Bleeding 38
7.7.1 Indica ons of Blood Transfusion 39
7.7.2 Role of Platelet Transfusion 40
7.7.3 Transfusion of other Blood Products 40
7.8 Role of Adjunc ve Therapy in Dengue 41

vii
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

8. Nursing Care During Pregnancy and Counseling 42


8.1 Nursing Interven ons 42
8.2 General In Ward Care 42
8.2.1 Febrile Phase 42
8.2.2 Cri cal Phase 43
8.2.3 Convalescent Phase 44
8.3 Discharge and Home Care Guidelines 43
8.3.1 For Undelivered Pa ents 43
8.3.2 For Delivered pa ents 44
8.3.3 Home Care Advice 44
8.4 Counseling of pa ent and rela ves with Dengue Fever 45
8.5 Discharge Criteria 46
9. Dengue In Puerperium 47
9.1 Physiological Changes during Puerperium 47
9.1.1 Hematological changes 47
9.1.2 Cardiovascular changes 47
9.1.3 Vitals signs 47
9.1.4 Urinary system 48
9.1.5 Gestrointes nal changes 48
9.1.6 Respiratory func on 48
9.2 Fever in Puerperium 48
9.3 Differen al Diagnosis of Puerperal Fever 48
9.4 Clinical Presenta on of Dengue in Puerperium 49
9.4.1 Differen al Diagnosis of Dengue In Puerperium 49
9.4.2 How to Diagnose Dengue in Puerperium 50
10. Maternal, Fetal and Neonatal Outcome in Pregnant Dengue Pa ents 50
10.1 Dengue fever in pregnancy and miscarriage 51
10.2 Dengue fever and Intrauterine demise 51
10.3 Dengue fever and Preterm birth 51
10.4 Dengue fever and Low Birth Weight 51
10.5 Ver cal transmission of Dengue virus 51
10.6 Fetal complica ons 52
10.7 Clinical Features of Dengue Fever in Neonates 52
10.8 Laboratory diagnosis 52
10.9 Management 52
10.10 Breast feeding in Maternal Dengue fever 53
10.11 Monitoring of asymptoma c newborn 53
Appendices 53

viii
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

1. Introduc on
Dr. Somia Iqtadar
There has been a lot of concern related to dengue infec on in pregnant women in recent years due
to an increase in number of infec ons world wide .Pregnant women with dengue need early
iden fica on and their clinical management requires a mul -disciplinary approach. Timely and
precise interven ons in dengue infected pregnant women are needed for op mal outcome. Early
detec on and access to proper medical care in this specific group can reduce complica ons and
mortality.

1.1 Clinical Manifesta ons


Spectrum of Dengue virus infec on ranges from asymptoma c to symptoma c forms. Clinically it
can manifest as undifferen ated febrile illness, dengue fever (DF), or dengue hemorrhagic fever
(DHF) including dengue shock syndrome (DSS).Symptoma c dengue infec on can present as
either of two clinical en es DF and DHF or are collec vely considered as Dengue Illness. Dengue
fever (DF) and DHF are dis nct from each other as DHF is characterized by plasma leakage due to
increased capillary permeability. This plasma leakage is mostly seen in secondary infec on due to
cytokine storm and is specifically noted in the pleural and peritoneal cavi es. When this plasma
leakage is massive and not compensated it leads to decreased intravascular volume and may lead
to a state of circulatory failure and shock known as Dengue Shock Syndrome (DSS). The dura on of
leak, known as the 'cri cal phase' ranges from 24-48 hours. Majority of the dengue illness presents
as DF, but the risk of developing DHF is higher in individuals who have secondary infec on with a
different serotype. Hemorrhage, though more likely in DHF, is common to both DF and DHF.

Dengue fever (DF) is generally an acute febrile illness with severe headache, retro orbital pain,
myalgia, arthralgia and rashes. It is characterized by leucopenia and thrombocytopenia. Although
DF is usually benign, it could be incapacita ng with severe headache, retro orbital pain, muscle,
joint and bone pain, par cularly in adults. Occasionally DF pa ents have unusual hemorrhage such
as epistaxis, gastrointes nal bleeding and menorrhagia or occult bleeding.

Dengue hemorrhagic fever (DHF) is associated with repeated dengue infec on (secondary
infec on) with a different virus serotype.Unlike in DF where usually pa ents will have a brief febrile
phase followed by convalescent phase, in DHF, pa ents will have intermediate cri cal phase where
plasma leaks out of vessels into inters al and serosal spaces. This leads to decreased intravascular
volume and has a tendency to develop hypovolemic shock (dengue shock syndrome). Preceding
warning signs such as persistent vomi ng, severe abdominal pain, lethargy or restlessness, or
irritability and oliguria are important for early detec on of impending shock and warrant
interven on to prevent shock. Bleeding is more frequently seen in DHF than DF.

More recently, there have been reports of DF and DHF with unusual or atypical manifesta ons.

1
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

These include isolated organ involvement such as neurological, severe hepa c, renal and other
organs. These could be explained as complica ons of profound and prolonged shock or associated
with underlying co-infec ons or co-morbidi es. Although a rare clinical en ty, such manifesta ons
are now categorized as Expanded Dengue Syndrome (EDS).

1.2 Gesta on and Dengue


Dengue illness has been increasingly reported in pregnant women in the last few years. A higher
percentage of more severe form of dengue known as Dengue Hemorrhagic Fever (DHF) has been
seen among pregnant women compared to non-pregnant women suffering from dengue illness.
The overall severity of DHF is also higher in pregnant women as compared to non-pregnant
women.

Dengue has many implica ons during pregnancy;


Ÿ Acute dengue illness during third trimester can increase the risk of fetal compromise. This is
largely a ributed to maternal hemodynamic decompensa on which may lead to increased
need of surgical interven on for delivery.

Ÿ In pregnancy with Dengue there is more likelihood of early overt or occult bleeding specially in
DHF. Trauma c procedures during delivery, such as instrumenta on or surgery will further
increase the risk of bleeding. Labour during dengue illness can be associated with worse
maternal outcomes as a result of massive bleeding due to surgical interven ons such as
caesarean sec on and opera ve vaginal delivery. Both mother and the newborn with dengue
infec on, if progress to DSS undetected, may be at an increased risk of severe hemorrhage due
to coagulopathy.

Ÿ Delayed or misdiagnosed DHF/DSS in the early stage can lead to complica on and may even
cause death. Common causes of death in pregnant women with dengue can be prolonged shock
with mul -organ failure, massive bleeding, fluid overload or due to a combina on of the above
condi ons.

Ÿ Ver cal transmission among women with dengue during the late pregnancy period is a well
established fact. All babies born to such mothers should be closely observed during perinatal
period.

2
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

2. Natural Course Of Dengue Illness


Dr. Somia Iqtadar
Dengue infec on remains asymptoma c in large number of cases and spectrum of symptoma c
clinical disease ranges from mild illness in the form of undifferen ated fever or DF to more serious
illness of DHF and DSS and some mes EDS

Asypmtomatic Mild Fever Undifferentiated febrile disease DF DHF DSS EDS

1. Undifferen ated Fever


2. Dengue Fever (DF)
3. Dengue Haemorrhagic Fever (DHF)
4. Dengue Shock Syndrome (DSS)
5. Expanded Dengue Syndrome (EDS)

During the ini al few days termed as febrile phase both DF and DHF are clinically similar. While DF
pa ents progress to convalescent phase as temperature se les, DHF pa ents develop the Cri cal
Phase due to increase vascular permeability leading to plasma leakage. Hence, the hallmark of DHF
is plasma leakage which differen ates it from DF.

Fig: Clinical Course and Labortory Parameters of Dengue Infec on.


3
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

2.1 Clinical Diagnosis of Dengue Illness


Early diagnosis of Dengue illness on first contact point relies on high index of suspicion based on
presence of fever along with any two clinical signs and symptoms sugges ve of dengue fever.
Clinical features used to suspect dengue in pregnant women are same as in non pregnant women
and include headache, abdominal pain, retro orbital pain, rash, bleeding, arthralgia, and decreased
urinary output.
Dengue should be considered high up in the differen al diagnosis in any pregnant woman
presen ng with acute fever specially in dengue season.
Form O designed by DEAG can be used for early detec on and repor ng of these cases

4
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

2.2 Dengue Fever


Dengue Fever (DF) is generally an acute febrile illness, with non-specific clinical signs and
symptoms. Although DF is a benign condi on, rarely can be associated with unusual bleeding
which can be serious, if not recognized and treated early.

2.2.1 Clinical and laboratory findings;

2.2.1.a Signs and Symptoms of Dengue Fever (DF)

• Acute onset of high grade fever (las ng 2-10 days) with headache ,retro orbital pain,
myalgia, arthralgia, rash, abdominal pain or bleeding manifesta on. Some pa ents may
have anorexia,diarrhea, flu like illness and conjunc val infec on.

• Rash looks like flushed skin on day 1 to 2, which may mimic as pregnancy rash.

• Minor bleeding can manifest as petechial haemorrhages, mucosal bleeding or epistaxis.


However,bleeding may be heavy in some pa ents if they are on medica ons such as
Aspirin, NSAIDS, steroids or long-term an -platelet drugs.

• Occasionally, unusual haemorrhage such as gastrointes nal bleeding, menorrhagia and


epistaxis may occur, especially GI bleeding is seen in those having an underlying pep c
ulcer disease.

• Physical examina on may reveal no focus of infec on except facial and skin flushing and
posi ve tourniquet test.

• All suspected pa ents should be subjected to Complete blood count(CBC) which in dengue
infec on typically shows leucopenia and thrombocytopenia.

• While NS1 An gen/IgM An body tests will provide an ae ological diagnosis, a nega ve
result should not exclude dengue if high clinical suspicion is there.

Dengue viraemia in a pa ent is short, typically occurring a day or two before the onset of fever and
lasts for up to four to seven days of illness. During this period the dengue virus, its nucleic acid and
circula ng viral an gen can be detected. Viral an gen detec on (NS1) has become the most
common early diagnos c tool to confirm dengue infec on.

2.2.1.b. NS1 An gen and IgM/IgG An bodies – results depend on the tested day of fever; NS1
an gen is usually diagnos c on first 3-4 days. An -dengue IgM an body is usually detectable by
day 5 of the illness or later. In most pa ents IgM may persist up to 60 days. In primary infec on IgG is
usually detectable few days a er IgM an bodies and in secondary infec on IgG will become
posi ve early. Therefore, IgG might be useful to differen ate primary and secondary dengue
infec ons. If IgG is posi ve by day 3 it would indicate a secondary infec on and may have some use
in predic ng DHF.If pa ent is clinically sugges ve of dengue, even if NS1 an gen is nega ve,
consider dengue as a possibility and manage accordingly.

5
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

RT-PCR remains the gold standard for confirma on. The advantage of this test is its high sensi vity
and specificity in acute sample and iden fica on of serotypes. It is, however, an expensive
technology that requires sophis cated instruments and skilled professionals.
Complete Blood Count (CBC) -
Fever/history of fever and other clinical features with leukopenia (WBC <4,000 cells/μl), is strongly
sugges ve of dengue in endemic areas.
However, in pregnancy, leukopenia may not be a feature (o en WBC could be normal or high)
and serial CBC may only show a drop in the total WBC count with a significant reversal of
lymphocyte to neutrophil ra o with atypical cells in the blood picture.
• Progressive decrease in WBC count is an early indica on of dengue.
• Thrombocytopenia (<100x10⁹/L) or decreasing trend
• Hematocrit (HCT) could be normal or high

Presence of fever with at least 2 signs and symptoms men oned above are sufficient to suspect
dengue illness in pregnancy. Presence of leucopenia and thrombocytopenia in suspected cases
make the diagnosis of probable infec on.All probable dengue cases must be admi ed to
hospital and inves gated via confirmatory tests NS1 an gen ,PCR or An bodies depending upon
the day of illness.

2.3 Dengue Haemorrhagic Fever (DHF)


Features of DHF Includes:
1. Fever: acute onset high fever(2-10 days) or recent history of acute fever
2. Haemorrhagic manifesta ons (at least in the form of a posi ve tourniquet test or epistaxis, gurm
bleed, haemoptysis, GI bleeding, menorrhagia, hematuria)
3. Thrombocytopenia of <100x10⁹/L with a rising HCT (towards 20% from baseline)
4. Objec ve evidence of selec ve capillary plasma leaking into chest or abdomen
(visualiza on of fluid in the peritoneal cavity and pleural space by real- me ultra sound scan of
the abdomen and chest).
Onset of leaking is usually heralded by:

Ÿ Se ling of fever (defervescence)


Ÿ CBC changes:
Ÿ WBC tends to rise following a progressive fall to a nadir (lowest value)
Ÿ Thrombocytopenia (<100x10⁹/L)
Ÿ Hematocrit (HCT) rising above the baseline ( towards 20%)

6
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

2.3.1 Natural Course of DHF


The febrile phase of illness is iden cal for both DF and DHF. Phenomenon of plasma leakage usually
manifests a er the first 72 hours of the fever, at a me when the fever is coming down to normal
(defervescence). If DF, pa ent improves when fever subsides, but in DHF pa ent develops warning
signs (Ref Chapter 2.33).
Unlike DF, which has a febrile phase followed by a convalescent phase, DHF pa ents have 3 phases
which include a cri cal (leaking) phase between the febrile and convalescent phases. Therefore,
DHF pa ents are different from DF pa ents in that they have plasma leakage during the cri cal
phase.
1) Febrile Phase (similar to that of DF - Refer Sec on 2.2.1)
2) Cri cal Phase (Sec on 2.3.2)
3) Convalescent Phase (Sec on 2.5)
DHF has two clinical en es:
1) DHF (grade 1 and grade 2)withouth shock
2) DHF (grade 3 and grade 4)with shock
Therefore, in any pregnant woman who prsents with shock (par cularly afebrile at presenta on)
consider DSS as a likely diagnosis.

2.3.2 Cri cal Phase in DHF


Cri cal phase occurs towards the late febrile phase, o en a er the end of 3 day of fever, usually
with defervescence (se ling of fever). However, in pregnancy this may occur outside the usual
dura on, earlier or later. Therefore, daily Complete Blood Count (CBC) assessments together with
regular and frequent HCT and ultrasound scans of abdomen and pelvis of pregnant dengue
pa ents are important to iden fy plasma leakage as early as possible.

Dengue fever with haemorrhagic manifesta ons must be differen ated from dengue
haemorrhagic fever heralded by plasma leakage.
In DF –no plasma leakage
In DHF –plasma leakage is seen
Se ling of fever is not a sign of recovery, as the pa ent may leak when fever se les.
Plasma leakage in DHF is selec ve, transient and self-limi ng, usually las ng 24-48 hours.

2.3.3 Warning Signs of Plasma Leakage in DHF


Pa ents should be closely observed for warning signs predic ng significant plasma leak. If not
detected and treated mely and adequately it can lead to serious consequences due to
hypovolemic shock and complica ons. However, some DHF pa ents may develop shock due to
significant plasma leakage without any warning signs.

7
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

Warning sings include.


• Clinical deteriora on or no improvement with se ling of fever
• Severe abdominal pain
• Excessive vomi ng
• Bleeding (epistaxis, gum bleeding, malena, vaginal bleeding)
• Irritability or restlessness
• Cold-clammy peripheries
• Prolonged Capillary Refill Time (CRFT >2 seconds)
• No urine output for 4-6 hours

2.3.4 Features of Fluid Leakage


Features sugges ve of fluid leakage:
• Narrowing of pulse pressure with increasing diastolic pressure ( pulse pressure <30)
• Tachycardia with low-volume pulse (HR >100/bpm)
• Postural hypotension
• Tender hepatomegaly
• Reduced urine output (Uop < 0.5ml/kg/hr).
• Prolonged capillary refill me ( CRFT>2 sec)
• Haematocrit (HCT) rise (increase of 15% –20% above baseline is an early indirect evidence
of plasma leakage). If no baseline HCT is available consider HCT 30 - 35% as the baseline.
• Platelet counts less than 100x10⁹/L or a rapid drop in platelet count ( drop of >40,000 in 24
hours).
Biochemical inves ga ons such as serum albumin and non-fas ng cholesterol are not useful
during pregnancy.
Features confirming plasma leakage:
• Ultrasonography (USG) of chest and abdomen gives evidence of plasma leakage into the
third space. There can be a me gap from ini al point of leaking to USG detec on of fluid in
pleural and peritoneal cavi es. During this period the hematocrit and heart rate may go up
or else, the UOP may drop, sugges ng leaking. In such pa ents, repeat interval USG to see
whether there is objec ve evidence of leaking is recommended.
• If repeated USG does not show fluid and if the pa ent is haemodynamically unstable,
reduced UOP and low HCT,alterna ve diagnosis (bleeding) should be considered.
Chemical accumula on of fluid in peritoneal and pleural spaces is a late finding of cri cal phase.

In cri cal phase of DHF it is not recommended to rely exclusively on USG for diagnosis of leakage.
Other parameters such as se ling of fever, vital signs, platelet count, gradual rise in HCT and
reduced urine output are important to diagnose the onset of leaking . However, demonstra on of
fluid in the peritoneal cavity and pleural space on repeated ultrasound scan confirms that the
pa ent has developed plasma leakage and is in cri cal phase.

8
DENGUE GCP GUIDELINES FOR PREGNANCY 2021
2.3.5 Ultrasound Features of Plasma Leakage in DHF
• Bed side ultrasound scan of the abdomen and the chest in supine posi on, with no
prepara on, can iden fy free fluid in pleural space or abdomen.
• Gall bladder wall oedema with a thin rim of fluid around it, is the earliest sonographic
finding in plasma leakage.
• Thin rim of fluid in hepato renal recess, indicates approximately six hours has elapsed since
beginning of plasma leakage.
• Fluid in the peritoneal cavity, among bowel loops and in the pelvis, indicates more than six
hours have elapsed since beginning of plasma leakage.
• Fluid in the pleural space, is commonly seen on the right side and indicates more than six
hours have elapsed since beginning of plasma leakage.
• Fluid in the perirenal space, is commonly seen on the right side. This indicates more than six
hours have elapsed since beginning of plasma leakage.
• In a pa ent where bilateral pleaural effusions and ascites is seen; implies that the pa ent is
in the later part of the cri cal phase when major por on of leaking (probably >50% of
leaking) is over.
Fluid therapy for such pa ents should be carefully guided (vital sings and HCT) as increased rates of
fluid can lead to fluid overload.

2.4 Dengue Shock Syndrome (DSS)


DHF alongwith evidence of circulatory failure (hypovolemic shock) in pregnant women should be
labeled as DSS.It is manifested by;
Ÿ Clinical signs of shock: rapid and weak pulse with delayed CRFT and cold-clammy skin
Ÿ Narrowing of pulse pressure 25-30 mmHg (compensated shock due to plasma leakage)
Ÿ Rising HCT ≥20% from baseline
Ÿ Thrombocytopenia (<100,000/mm³)
Ÿ Hypotension (SBP<90mmHg) with postural giddiness - if present consider possibility of
bleeding in addi on to leaking .(decompensated shock probably due to leaking and bleeding).
Pathophysiology of shock in DSS is usually due to plasma leakage and subsequent bleeding when
leaking is not corrected. But, presence of hypoglycemia, excessive vomi ng leading to dehydra on
and sepsis due to co-infec on may also contribute towards a state of shock.

2.5 Convalescent Phase


A er 48 hours of cr cal phase pa ent goes into recovery phase or convalescence. Clinical
condi on of pa ent starts to improve and WBC and platelet count start rising. Pa ent regain their
appe te. There can be appearance of recovery rash, itchy and more prominent on palms and soles.

9
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

3. Physiological Changes in Pregnancy


Prof. Farhat Naz, Prof. M. Ali Khan

Pregnancy results in significant anatomical physiological and bio chemical changes in all organ
systems during antepartum,intrapartum and postpartum period. Understanding these changes
and resul ng clinical implica ons is crucial in the management of dengue fever in a pregnant
pa ent.

3.1 Cradiovascular Changes


Soon a er concep on, the maternal cardiovascular system undergo major adapta ons that
progresses throughout pregnancy.
3.1.1 Heart Rate
A progressive increase in the heart rate con nues un l the third trimester of pregnancy. Heart rate
increases from 80bpm in non pregnant state to 90-95bpm in pregnancy i.e.10-20% above non
pregnant state but typically not greater than 95bpm.

Clinical Implica on during Dengue


Res ng heart rate in pregnant woman more than 100 bpm (without fever) is taken as tachycardia
which warrants further evalua on.

3.1.2 Blood Pressure


• The greater part of normal pregnancy is characterized by a reduc on in arterial blood
pressure (BP). The extent to which BP decreases is variable, but in most pregnant women
systolic blood pressure (SBP) drops by 5-10mmHg and diastolic blood pressure (DBP) can
drop upto 15mmHg in normal pregnancy.
• BP falls gradually at first trimester reaching a nadir around 22-24 weeks rising again from 28
weeks and reaching preconcep on levels by 36 weeks of gesta on.
• As DBP and Mean arterial pressure (MAP) decreases more than SBP this eventually leads to
an increase in pulse pressure in normal pregnancy.
• In pregnancy, pulse pressure normally ranges from 30-50mmHg.

Clinical Implica on during Dengue


Narrowed pulse pressure of ≤25mmHg indicates compensatory shock in dengue with
pregnancy, requiring immediate a en on.
In pregnant woman, always measure BP in complete le lateral or 15-30 degree le laterally
lted posi on. It will avoid the compression of inferior vena cava by gravid uterus which can
lead to substan al decrease in cardiac output and hence blood pressure.

10
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

3.1.3 Systemic Vascular Resistance


• Early pregnancy is characterized by intense peripheral vasodilata on and 35-40% fall in
systemic vascular resistance from 700-1500 dynes/sec/cm to 400-800 dynes/sec/cm by the
mid-second trimester.
• This single pregnancy adapta on is important for maintaining normal BP in pregnancy.
• In normal pregnancy, marked increase in cardiac output results from increase in both heart
rate and stroke volume. Despite the increase in cardiac output, BP decreases for most of
pregnancy. This implies a very substan al reduc on in total peripheral vascular resistance
(TPVR)

3.1.4 Pulmonary Vascular Resistance


• There is reduc on in pulmonary vascular resistance, increased pulmonary blood flow with
normal mean pulmonary artery pressure.
• Reduced serum colloid osmo c pressure by 10-20% due to decrease albumin level and
predisposing to pulmonary edema in pregnancy

Clinical Implica on in Dengue


A sudden increase in cardiac preload (rapid use of IV fluid) or increased pulmonary capillary
permeability as in Pre eclampsia can precipitate pulmonary edema in pregnancy.
As DHF is also leaky capillary condi on so a pre-eclamp c woman with dengue may have a
high risk of developing severe pulmonary edema.

11
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

3.1.5 Plasma And Blood Volume


• Plasma volume increases un l 30-34 weeks with a total gain of 30-50% above that in non-
pregnant women. Normally, at an average, a woman contains 2600ml of plasma volume
and experiences an increase of 1250ml in pregnancy.
• Blood volume increases by 50% at 30 weeks of gesta on with similar increase in cardiac
output from 5L/min to 7.5L/min.
• Soon a er delivery, apart from release of aortocaval compression complete uterine
contrac on and retrac on lead to auto transfusion that is diversion of 400-500ml blood
into maternal circula on.

Clinical Implica on in Dengue


A pregnant woman with Dengue may not show features of hypovolemia even with
significant blood loss un l late stages.
Blood transfusion is recommended in DHF even with minimal blood loss (<500ml)

Key Points: Cardiovascular Changes in Pregnancy


Heart rate : ↑ 10-15 bpm Blood volume: ↑30%
Systolic BP : ↓5mm Hg Plasma Volume : ↑ 45%
Diastolic BP: ↓ 15mm Hg Cardiac output : ↑ 30-50%
Mean arterial pressure: ↓ 10% Stroke volume : ↑ 25%
Pulse pressure : ↑ Peripheral resistance: ↓ 35%
Pulmonary vascular resistance: ↓20-30%

3.2 Haematological Changes In Pregnancy


• Red blood cell mass increases by 30% in pregnancy. As this increase is less than in plasma
volume, so it results in physiological anemia in pregnancy and fall in haematocrit (32-34%).
Range of haematocrit (HCT) in normal pregnancy is depicted below.

Non Pregnant Adult First Trimester Second Trimester Third trimester


34-44% 31-41% 30-39% 28-40%
• Eleva on of haematocrit in dengue is masked by haemodilu on due to increase in plasma
volume especially in the 2nd& 3rd trimester.
• Serial HCT measurement is crucial for DHF monitoring in pregnancy.

12
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

Clinical Implica on in Dengue


• Rise in haematocrit warrants further evalua on for DHF. HCT of 38-40% may indicate
leaking in DHF.
• The detec on of third space fluid accumula on is difficult due to the presence of
gravid uterus.

• There is a rise in WBC count during normal pregnancy ranging from 9000-15,000 cell/10¹²

• The platelet count tends to fall progressively during normal pregnancy although it usually
remains within normal limits.

• In a propor on of women (5-10%) the platelet count will reach levels of 100 to 150 x10⁹ /L
by term in the absence of any pathological process however <100x10⁹/L are rarely
encountered.

Non Pregnant Adult First Trimester Second Trimester Third trimester

165-415 x10⁹ /L 174-391x10⁹ /L 155-409 x10⁹ /L 146-429 x10⁹ /L

• Even in gesta onal thrombocytopenia, whose incidence is 6-10%, platelet count seldom fall
below 80x10⁹/L.

• In a normal pregnancy there is a marked increase in some coagula on factors like thrombin,
fibrinogen, factor VII,VIII,IX,X,XII resul ng in increased risk for thromboembolic
complica ons.

Clinical Implica on in Dengue


• WBC<4000 cell/10¹²may not be seen in febrile phase of dengue in pregnancy. A
downward trend of WBC is important in the absence of leucopenia.

• In pregnant pa ent with fever and low platelets count it is important to rule out
dengue.

13
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

3.3 Biochemical Changes In Pregnancy


• Serum albumin(3.5 to 5.5g/dL) falls in pregnancy to 2.5-2.8g/dL

• Non-fas ng cholesterol rises by 40% from 200mg /dL to 250-300mg/dL in pregnancy.

Clinical Implica on in Dengue


With plasma leakage in DHF, serum albumin also leaks into poten al spaces only to return
with reabsorp on. Indirect feature of reabsorp on is an eleva on in serum albumin level
above 2.8g/dL in a pa ent who has completed cri cal phase.
Non-fas ngcholesterol is not a good indicator to iden fy leaking of plasma in pregnancy
with dengue fever.

3.4 Respiratory Changes In Pregrancy


• There is an increase in dal volume and decreases in vital capacity and func onal residual
capacity, with higher PO₂ and lower PCO₂.

• Thus pregnant woman becomes hypoxic easily compared to non-pregnant.

• In normal pregnancy there is compensatory respiratory alkalosis with pH between 7.40 to


7.45. It may lead to delay in detec on of acidosis requiring correc on in dengue.

14
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

3.5 Renal Changes In Pregnancy


Renal changes are marked by:
• Increase in renal blood flow by 60-75%
• Increase in glomerular filtra on rate by 50%-85%
• Enhanced clearance of most substances.
• Although frequent urina on is o en reported in pregnant women, rarely there could be
true polyuria(>3L/day).

Clinical Implica on in Dengue


In DSS (DHF with shock) with pregnancy, intense thirst may not appear and despite
intravascular volume deple on a normal urine output may persist. Therefore, urine output
may not be a good marker of degree of shock in pregnancy.

15
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

4. Features of Dengue Heamarrrhagic Fever and Dengue


Shock Syndrome (DSS) in pregnancy
Prof. Rubina Sohail, Dr. Kiren Khursheed Malik
4.1 Features of Dengue shock syndrome (DSS) with pregnancy
Dengue shock syndrome (DSS) is suspected when warning signs of circulatory failure or pre shock
appear in a pa ent suffering from dengue haemorrhagic fever .Diagnosis of DSS is made on some
specific features but challenge in pregnancy is that most of symptoms and signs appear late or are
masked by physiological systemic changes in pregnancy. This poses a major diagnos c challenge in
pregnant woman presen ng with dengue shock syndrome.

4.1.1 Cri cal Phase


• Onset of the cri cal phase of dengue fever is similar in both pregnant and non pregnant
woman i.e around the me when fever is se ling and is usually between 3rd to 5 day of
illness and may be up to 7th day. However this is unlike other viral illnesses, which have a
tendency to improve when the fever se les down.
• Typically this phase lasts for 24-48 hours in which circulatory changes and plasma leakage
happens. However, in some pa ents these changes progress to severe disease and end up
in dengue shock syndrome.
• This may be more severe in pregnant women due to reduced onco c pressure and increase
in vascular permeability. This results in higher maternal mortality (around 40%) as
compared to non pregnant popula on (20-30%) with dengue shock syndrome.

4.1.2 Warning Signs


4.1.2. a. Vomi ng and Abdominal pain
• Onset of DHF may be accompanied with acute abdominal pain and persistent vomi ng. This
is one of the warning sign and o en precedes the onset of cri cal phase in non pregnant
women.
• In pregnant women there are a number of other causes which mimic these and hence these
warning signs can be missed and result in late detec on of onset. Acute abdominal pain in
pregnancy can be due to preterm labour, labour, abrup on, uterine rupture, urinary tract
infec on and degenera on of fibroid.
• For detec ng the actual cause, history, abdominal and vaginal examina on for bishop
score, complete blood count (CBC), urine analysis, obstetrical ultrasound and serological
evidence for dengue infec on are required.
4.1.2. b. Restlessness and Lethargy
• Restlessness and lethargy are features of DHF and DSS

16
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

• In pregnancy these symptoms can be very confusing as pregnant women especially in third
trimester can be uncomfortable due to gravid uterus pressure on pelvic bones, joints and
major vessels specially in supine posi on.
• Pregnant women can be lethargic due to anaemia which has a high prevalence in Pakistan
(36-52%).
4.1.2 c. Altered Conscious Level
• Altered conscious level may be observed in pa ents with Dengue shock syndrome.
• Altered conscious level in pregnancy can be seen with some pregnancy specific condi ons
as severe pre eclampsia, eclampsia, cerebral thrombosis. Raised Blood Pressure,
protenuria and CT scan brain can help in the diagnosis.
4.1.2. d.Vaginal bleeding
• This is one of the warning signs in DHF and adds to morbidity due to addi onal hypovolemia
leading to DSS.
• In pregnant women bleeding can be due to other causes as placenta previa, placental
abrup on, local causes and systemic causes as gesta onal thrombocytopenia &
hepa s E in pregnancy. A er delivery bleeding can be due to post partum hemorrhage
(PPH) as a result of uterine atony, genital tract injury and retained products of
concep on.
• All these require proper obstetrics history and examina on along with laboratory
inves ga ons.Complete Blood Count including Platelet count, Liver Func on Tests,
Hepa s serology and obstetrical scan is mandatory in such cases.
4.1.2. e.Tender Hepatomegaly
• In non pregnant women presence of enlarged tender liver > 2 cm below costal margin is
considered a warning sign.
• However, It is very difficult to palpate liver in pregnant women especially in third trimester
due to gravid uterus and can easily be missed as an early warning sign.

4.1.3 Diagnos c Signs of Dengue Shock Syndrome


4.1.3 a Circulatory System

• As a result of plasma leakage and vasoconstric on, cardiovascular system is affected the
most both in pregnant and non pregnant pa ents. However due to physiological changes in
pregnancy most of the signs described below are difficult to iden fy or appear late in
pregnant pa ents with Dengue Shock Syndrome and ul mately lead to delay in diagnosis
and high morbidity.

• Tachycardia, prolonged capillary refill me, narrow pulse pressure, and low volume of
pulses may be present.

17
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

Table No 1: Features of Circulatory Changes in pregnant and non pregnant


pa ents with Dengue Shock Syndrome
Non pregnant pa ent with DSS
Normal Pregnancy with DSS
Parameters Compensated Decompensated/ specific features
circula on
shock hypotensive shock
Normal for Baseline rise 10-15% in
Severe rise/
age adults pregnancy. This can mask
Heart rate Tachycardia bradycardia In late
60-90 early detec on, >100bpm
shock
beats/min must alert
Capillary Prolonged >2 Mo led skin, very Same as in non pregnant
< 2 sec
refill me sec prolonged refill me women
Warmer and palmar
Warm and Cold Cold clammy erythema due to
Extremi es
pink extremi es extremi es vasodilata on in pregnancy
can mask this sign
30% rise in blood volume,
10% rise in stroke volume
Peripheral Good Weak & & Cardiac output lead to
Feeble or absent good volume pulses
pulses volume thready
Appearance of weak pulses
is late feature of DSS

Normal for Normal


Blood Diastolic BP already low-
age max systolic BP
pressure Hypotension/ 30% fall in vascular
upto 120/80 & raised
diastolic BP, Un recordable BP resistance so mask early
mm of Hg
rise
Postural drop
Lower diastolic BP in
pregnancy leads to wider
Normal for Narrowing of PP
Pulse Narrowing PP Pulse pressure,
age >30 <20 mmHg or not
pressure <30 mmHg
mm of Hg recordable It leads to late detec on of
narrowing of PP

4.1.3.b Respiratory System

• In DSS without pregnancy, acidosis mediated respiratory center s mula on causes


hyperven la on so tachypnea, (respiratory rate >20) is observed.

18
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

• In pregnancy physiological changes in thoracic anatomy, decrease in func onal residual


capacity with higher PO₂ and lower PCO₂ is observed. This predisposes pregnant woman to
earlier hypoxia than non pregnant women with DSS.

• Moreover gravid uterus and upward pushing of diaphragm already causes dyspnoea in
pregnant woman and this may mask tachypnea in early stages. Compensatory alkalosis in
pregnancy (PH 7.40-7.45) can lead to delay in detec on of acidosis in pregnant woman with
HDF/DSS. These pose a diagnos c challenge in pregnancy for DSS.

4.1.3.c.Renal System

• Reduc on in renal circula on (GFR) due to vasoconstric on in DSS manifests itself in the
form of reduced urine produc on.

• In normal pregnancy GFR rises by 50%. In pregnancy with dengue shock syndrome
appearance of reduced GFR is delayed making detec on of renal compromise difficult.

• In decompensated shock ul mately severe oliguria (less than 15 ml/hr) or anuria ensues.

• Late features are similar in pregnant women. Though oliguria in pregnancy can be seen in
other condi ons specific to pregnancy as renal failure due to abrup on, severe
hypertension and massive hemorrhage.

4.1.3.d.Plasma Leakage Indicators

Plasma leakage is typical in pleural and peritoneal cavi es both in pregnant and non
pregnant pa ents in DHF. It is severe in pregnancy due to pre exis ng reduced onco c
pressure and increased vascular permeability.

In pregnancy gravid uterus makes it difficult to assess leakage in peritoneal cavity so early
diagnosis of third space fluid loss may be missed. Pregnant women are predisposed to
pulmonary odema due to increased respiratory blood flow and reduced onco c pressure
confounded with lesser space in thoracic cavity, leading to severe respiratory distress.
Hence lesser volume of plasma leakage in pleural cavity can cause more respiratory distress
and ARDS in pregnant woman with DSS.

Ÿ In pregnancy Ultrasound chest and abdomen is used for detec on of fluid and instead of
relying on clinical examina on only, physician must resort to USG early in the disease
course.

Ÿ Chest X ray to detect plasma leakage in pleural cavity is a good inves ga on in


pa ents with DSS but it is difficult to perform in pregnant women especially in third
trimester and can lead to supine hypotension during posi oning and exposes to radia on
hazards.

• Haematocrit (HCT): Rising HCT 20% or more is taken as an important indicator for detec on
and monitoring of DHF.

19
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

In pregnant woman HCT is already low due to plasma volume expansion by 30-50% (75-82
ml/kg body weight - normal range) and physiological anaemia.HCT is taken as 32-34%
normal in pregnancy as compared to 35-36% in other pa ents. Rise of HCT can be a late sign
in pregnancy with DHF and leads to late detec on and difficulty in monitoring of the
disease.

So logically in second and third trimester of pregnancy with DHF, HCT rise less than 20%
may be considered significant and serial monitoring from baseline is more helpful in a
pregnant women with DHF.

• Serum Albumin: One of the plasma leakage indicator In non pregnant women is serum
albumin measurement and cut off value is <3.5 gm%,

In pregnant women during third trimester there is a fall in serum albumin upto 1gm/dl in
and normal range falls upto 2.5gm%. In pregnancy albumin values has to be interpreted
with cau on and fall of 0.5g/dl from baseline can be taken as an indicator.

• Serum Cholesterol: In DHF serum cholesterol cut off value less than 100 mg/dL is taken as
an indicator. In Pregnancy, there is a natural rise in serum cholesterol in second trimester
and rise reaches its peak around 40% in third trimester and levels return to normal four
weeks postpartum. Hence cut off value must be interpreted with cau on in pregnant
woman with DHF. If normal value of pregnant woman is already known then drop of 20mg
/dl can be taken as significant otherwise this is not good indicator of plasma leakage in
pregnancy.

4.1.3.e.Thrombocytopenia

• Rapid decrease in platelet count is taken as a warning sign of Dengue and progression to
DHF requiring strict observa on and treatment.

• In pregnancy there is a mild fall in platelet count physiologically but less than 100,000/mm³
is rarely encountered. Even in gesta onal thrombocytopenia –a condi on specific to
pregnancy seldom count falls below 80,000/mm3. There can be marked lowering of
platelet count in pregnant woman with DHF as compared to non pregnant.

4.1.4 Differen al Diagnosis


It is difficult to diagnose DHF and DSS in pregnancy as the clinical features are non specific and
mimic many other condi ons in pregnancy. Physician should have high index of suspicion to make
an accurate diagnosis.

20
DENGUE GCP GUIDELINES FOR PREGNANCY 2021
Table no.2 Differen al Diagnosis in of DHF and DSS with pregnancy
Differen al
Clinical features Differen al diagnosis diagnosis specific Differen a ng points
to pregnancy

Abdominal pain Acute appendici s, Labour, Placental Obstetrical abdominal &


Cholecys s, Viral abrup on, Uterine vaginal examina on,
hepa s, Perforated rupture, Fibroid obstetrical USG and
viscera, Ketoacidosis degenera on urinalysis can help in
Urinary Tract establishing diagnosis
Infec on

Shock Sep c shock, Hemorrhage, Uterine contour and


Cardiogenic shock Embolism consistency, V/T scan,
Postpartum sepsis USG for RPOCS

Respiratory Diabe c Ketoacidosis, Pulmonary embolism Clinical correla on


distress Renal failure, Lac c Amnio c fluid + VT scan
acidosis embolism

Bleeding Aplas c anaemia, Coagula on Obstetrical examina on,


Acute leukemia, disorders, APH USG, In PPH rule out
(Placenta previa, atony & injuries.
Abrup on), DIC due Coagula on profile
to fetal demise,
Abrup on, PPH

Thrombocytopenia ITP, TTP, Malaria, Gesta onal HELLP syndrome is usually


& Leucopenia Typhoid, SLE thrombocytopenia, associated with
HELLP syndrome Hypertension.
Elevated liver enzymes
and evidence of hemolysis.
Confirma on by viral
serology

4.1.5 Special Cau ons in Dengue Shock Syndrome with pregnancy


• PIH
Pa ents with hypertension may be on an -hypertensive therapy that masks the
cardiovascular response in shock. The pa ent's own baseline blood pressure should be
considered. A blood pressure that is perceived to be normal may in fact be low for these
pa ents.
Ÿ Pa ents on An coagula on
An -coagulant therapy may have to be stopped temporarily during the cri cal period.

21
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

• Haemoglobinopathies: These pa ents are at risk of bleeding and will require blood
transfusion. Cau on should accompany overhydra on and alkaliniza on therapy, which
can cause fluid overload and hypocalcemia.

• Fetal anomalies are not associated with dengue infec on, however some complica ons of
fetomateual unit may be encountered in pragnant pa ents with dengue.

4.1.6 Complica ons of Fetomaternal Unit

Maternal Fetal
Complica ons Preterm birth (10-55%)
Preterm birth (41%) Ver cal transmission (5.6%-12%)
Hypertension (12%) Fetal demise (14%)
Haemorrhage (10%) Meconium aspira on
Abrup on (2%) Oligohydroamnios
Post Partum Hemorrhage

Key points
• Features of dengue shock syndrome in pregnancy can mimic other causes of shock in
pregnancy as HELLP syndrome & embolism
• Clinical and laboratory parameters need special interpreta on according to
pregnancy changes
• Bleeding at the me of child birth can further aggravate the shock so prompt
management is necessary
• Physicians should have clear concept of physiological changes of pregnancy to
understand the pathophysiology of Dengue Shock Syndrome (DSS).

22
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

4.2 Haemodynamic Change in Dengue Shock Syndrome


The vital signs and urine output in different phases are as below:

4.2.1 Compensated shock


• In le lateral posi on narrow pulse pressure <30 mm of Hg (though wider pulse pressure in
pregnancy may mask rising of diastolic BP)
Associated features include:
(all may not be present at the same me)

• Prolonged capillary refill me >2 seconds, cold extreme es


• Low volume pulse, Tachycardia >100 bpm without fever
• Normal systolic BP with Raised diastolic BP in le lateral or seated BP, may be masked by
lower diastolic BP in pregnancy
• Reduced urine output and intense thirst or may be without reduced output in pregnancy
• Even in the presence of shock pa ent can be fully ra onale and conscious.

4.2.2 Decompensated Shock


Warning Signs: Refer to Page Section 4.1.2

Main features
• Systolic BP <80mmHg and/or reduc on in SystolicBP by >20mmHg
• Mean arterial BP <70 mmHg or un recordable BP at le lateral posi on
Associated features
(All these may not be present at a given me)
• Change of mental state e.g.: restless, comba ve or lethargy
• Prolonged CRFT (capillary refill me) with mo led skin, cold-clammy extremi es
• Severe tachycardia with weak or absent peripheral pulses
• Oliguria or anuria
• Tachypnea with metabolic acidosis.

4.2.3 Prolonged shock


shock las ng more than 4 hours. No passage of urine for 4-6 hours is a predictor to be
confirmed by urinary catheteriza on. The pa ent presents with no peripheral pulses and
BP is unrecordable. This condi on is complicated with - Acidosis, Bleeding, Hypocalcaemia
and Hypoglycaemia.

23
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

Key points
• Vital signs and urine output varies in different phases of DSS and in pregnant women
many features are masked by physiological changes.
• In pregnant females with hypertension or on an hypertensive medica on may cause
difficulty in assessment of Blood Pressure.
• Pulse pressure is one of the important parameters and in pregnancy is masked by
lower diastolic BP due to decreased vascular resistance

Changes in Vital signs and urine output in compensated and


decompensated shock

24
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

5. Management of Dengue in Pregnancy


Prof. Tayyaba Waseem, Dr. Natasha Bushra
The clinical manifestations, treatment and outcome of dengue in pregnant women are
different from those of nonpregnant women.Misdiagnosis or delayed diagnosis are due to
some of the overlapping clinical and/or laboratory features with the better recognized
conditions of pregnancy like HELLP syndrome, pulmonary embolism, various obstetric causes
of per-vaginal bleeding and other infectious diseases .

5.1 Early Management and Admission


5.1.1 First Contact Care
Suspect Dengue in every pregnant lady coming with high grade fever
Symptoms of dengue in pregnancy are similar to that in non pregnant popula on and include:
• High grade fever
• Headache
• Retro orbital pain
• Bone, Muscle and Joint pains
• Bleeding ( epistaxis,gum bleed,haemetemesis ,hematuria etc)
• Rash (flushed skin or petechiae)
• Nausea, Vomi ng and Abdominal pain
If a pa ent comes with these symptoms, she is labeled a SUSPECTED case of Dengue infec on
• Do baseline CBC on Day 1 and day 2 of fever
• If WBC count <4000/mm3 along with thrombocytopenia (<100,000/ùl) it becomes a
PROBABLE dengue case
• If first CBC is normal but there is clinical suspicion of Dengue,repeat CBC a er 24 hours.
• Label Probable if there is falling trend in WBC or platelet count.
• Refer to form O of DEAG for case defini ons of Suspected and Probable (Page 4)

5.1.2 Admission Criteria


All pregnant pa ents with probable dengue fever are advised admission for close
monitoring.

25
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

5.2 Assessment of Admi ed Pa ents


5.2.1 Febrile Phase
Monitor
o Temperature char ng , Pulse, BP and Pulse pressure 4-6 hourly .
o Ensure urine output at least 4-6 hours. ( minimum 100 cc every 4 hours)
o Intake Output record.
o Labs : Daily CBC , USG abdomen and for fetal well being and other inves ga ons if
necessary.

Treatment of febrile phase


o Paracetamol 500-1000mg 6 hourly. Warn the pa ent that fever may not se le with
this dose but NOT to exceed 4 grams paracetamol in24 hours. Nor to take other
NSAID like ibuprofen and diclofenac Sodium.
o Tepid sponging for fever.
o With hold Aspirin if she is taking it.
o Oral Intake encouraged.
o ORS, fluids, juice all are encouraged apart from rou ne food.
o If nausea/vomi ng of pregnancy, restrict oral intake, give IV fluid(NS) 100 cc/ hour.
o Keep on maintenance fluid around 2 litre/day.
o Platelet count should be kept >75000/mm³.
• If the pa ent is in first or second trimester and <37 weeks of gesta on, con nue the
pregnancy with close monitoring
• If the pa ent is 37 weeks of gesta on, pa ent can be delivered by vaginal delivery or
caesarean sec on depending on the obstetrical indica ons.
• Arrange platelet concentrate if platelet count is < 75000/mm³.

5.2.2 Cri cal Phase


• It is characterized by warning signs of :
o Abdominal pain and tenderness
o Persistent vomi ng
o Lethargy

26
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

o Restlessness
o Tender hepatomegaly (Liver >2 cm enlarged)
o Capillary Refill Time>2sec.
o Decreased urine output.
o Mucosal Bleed : epistaxis, gum bleed pe chae.
o Rise in HCT (20% of baseline)( If baseline is not known consider 36 as baseline).
If any of these signs develop, label the pa ent in cri cal phase and shi to High Dependency Unit
(HDU).
• Monitor
o Vitals( BP /Pulse/Pulse pressure, Capillary Refill) hourly
o Ultrasound abdomen for any fluid leak and obstetric ultrasound to document fetal
well being. Ultrasound can also be used to measure size of IVC and its collapsibility,
sign of hypovolemic shock or fluid overload.
o Catheterize to know precise UOP hourly ( Aim 0.5ml/kg/hour).
• Treatment
o Start fluid therapy according to algorithm (Page 30).
o Bolus of 5-10ml/kg/hour X 2 hours given followed by 3-5ml/kg/hr as a
maintenance.
o This is monitored by UOP and Pulse pressure
o Avoid induc on of labour/ planned surgery in this phase.

5.2.3 Dengue Shock Syndrome


These pa ents should be managed in ICU se ng.
Timely fluid management can save life.

5.3 General Principles of Fluid Management in DHF


o It should follow the DEAG algorithm. of DHF (Page 30)

o Monitoring of clinical findings (at least twice a day), vital signs (at least every 1-2
hours) HCT (at least every 4-6 hours), and urine output (at least every 8 hours)
should be done and documented on chart.

27
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

5.4 Management According to Trimester


• Management of pa ents with dengue fever remain the same regardless of the trimester.

• In majority of cases, mothers have uncomplicated antenatal period but there is risk of post
partum hemorrhage with dengue fever over general popula on.

• If the pa ent is in first or second trimester and <37 weeks of gesta on, con nue the
pregnancy with close monitoring in febrile phase.

• Delivery is indicated in febrile phase by induc on of labour or caesarean sec on


(obstretrical indica on) if pa ent is at term.

• In severe cases perinatal mortality is being reported due to severe thrombocytopenia in


new borns.

• Delivery should be avoided in cri cal phase due to risk of hemorrhage.

Important Points:
• Avoid NSAIDs for fever. Paracetamol upto 4 gm /day can be given

• Prophylac c platelet transfusion is not recommended if platelet count is >50,000/cmm.


Platelet transfusion should be given to pa ents with overt bleeding and when delivery is
imminent.

• There is no role of steroids, IV immunoglobulin and an bio cs.

• Tocoly cs may be considered to postpone labour during cri cal phase of dengue illness.

• Delivery should be spontaneous labour.


Ÿ Opera ve delivery should be considered for obstetric indica ons. Delivery during cri cal
Phase with marked thrombocytopenia can lead to severe hemorrhage. Appropriate
arrangements should be made in this regard.

• Delivery should be in a hospital properly equipped with trained obstetricians,


physicians,ICU team, neonatologist and blood bank facility.

• Timely interven on can reduce mortality to less than 1%.

28
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

5.5 Management Delays and Steps to Minimize them

• A high index of suspicion, early admission, close monitoring, mely interven on and
cri cal considera on of physiological changes of pregnancy when interpre ng clinical
situa on, can help us to achieve the successful outcome in pregnancy.
• Pregnant women with dengue fever should be considered for admission early
because of its unpredictable course.
• Maintaining normothermia and adequate hydra on should be the goal.
• Sharp decline in platelet counts should be taken as a marker of severity of the disease.
• Oligohydramnios is an ominous sign when seen concomitantly with dengue infec on
because the high fetal mortality of associated with it. The exact cause of
oligohydramnios is not known but dehydra on associated with dengue fever may be
contributory.
• Hydra on should be maintained by encouraging oral intake of oral rehydra on
solu on (ORS), fruit juice, and other fluids containing electrolytes and glucose for
replacing losses from fever and associated vomi ng.
• The lack of understanding of the exact pathophysiology of dengue has led to a paucity
of sufficient evidence-based management protocols aimed at specific
pathophysiological phenomena of the illness in pregnancy. Many pa ents, due to lack
of awareness, present late to hospital, some mes in shock; their management is
difficult, with a poor outcome.

29
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

30
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

6. Labour In Dengue Pa ents


Prof. Shamila Ijaz Munir, Dr. Sofia Iqbal

6.1.1 Timing and Mode of Delivery


• Pregnant women with symptoma c dengue infec on have a slightly higher risk of
maternal death as compared to pregnant women without dengue, and this risk is
considerably higher with DHF.

• If possible elec ve delivery should be postponed ll pa ent is out of cri cal phase of
disease.

• If delivery is inevitable, bleeding should be an cipated and closely monitored.

• Mode of delivery must be decided according to obstetrical indica ons.

• Normal vaginal delivery is preferred method over opera ve delivery.

• Tocoly c agents and measures to postpone labor to a suitable me may be considered


during the cri cal phase of dengue illness.

6.1.2 Prepara on for Delivery


• Blood and blood products should be cross-matched and saved in prepara on for delivery.

• Transfusion of platelet concentrates should be ini ated during or at delivery but not too far
aheadof delivery, as the platelet count is sustained by platelet transfusion for only a few
hours during the cri cal phase.

• Fresh whole blood/fresh packed red cells transfusion should be administered as soon as
possible if significant bleeding occurs.

• Do not wait for blood loss to exceed 500ml before replacement, as in postpartum
hemorrhage. Do not wait for the hematocrit to decrease to low levels.

6.1.3 Monitoring during delivery


• Vitals(BP /Pulse/Pulse pressure/Capillary Refill) hourly.

• Catheterize to know precise hourly urinary output (aim 0.5ml/kg/hour).

• Carefully trated fluid resuscita on (normal saline). Bolus of 5-10ml/kg/hour x 2 hourly

31
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

given followed by 3-5ml/kg/hour as maintenance. This is monitored by urinary output and


Pulsepressure.

• Foetal monitoring must be done by con nuous electronic FHR monitoring.

• Progress of labour must be evaluated by partogram.

• Opera ve delivery should be avoided during cri cal phase.

• If delivery is unavailable platelet count must be above 50,000 x 10³/mm³.

• Consultant obstetrician must conduct opera ve or instrumental delivery to keep the


trauma or injury to the minimum.

• It is essen al to check for complete removal of the placenta a er delivery.

• Oxytocin infusion should be commenced to contract the uterus a er delivery to prevent


postpartum hemorrhage. Misoprostol may be given for PPH prophylaxis/treatment.

• Intramuscular injec ons are to be avoided.

• No steroids should be given.

6.1.4 Post Delivery Care


• Keep under strict observa on.

• Strict monitoring for BP, Pulse, pulse pressure and urine output.

• Observa on regarding Post Partum Hemorrhage.

• Prophylac c use of uterotonic drugs like Oxytocin and Misoprostol is indicated.

• If delivery occur in less than seven days from appearance of symptoms of dengue fever,
then risk of ver cal transmission is high.

• Baby should be evaluated for congenital Dengue.

• Breast feeding is not contraindicated in Dengue fever.

32
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

6.2: Risk of complica ons in women with dengue by opera ve


interven ons:
6.2.1 Febrile Phase (Moderate to High Risk)
Febrile Phase (1-3 days): Fever, headache, myalgia and no evidence of fluid leak
Specific precau ons before opera ve interven on:
• Mul disciplinary Team (MDT) discussion: Fresh blood (<5 days old) or blood components to
be arranged a er crossmatching.
• Place of management : Pre-opera ve in ward and post- opera ve in HDU\ICU
• Possible indica on of Caesarean sec on :
a) Fetal:
1. Late fetal heart rate decelera ons during labour
2. Evidence of fetal hypoxia
b) Maternal:
i. First 2 days of fever with PLT >130 ×10⁹ and no ultrasound evidence of fluid leak
Ÿ Previous cesarean in labour
Ÿ Bleeding placenta previa even without hypovolemia and failed instrumental
delivery
ii. 3rd day of fever when PLT<130×109 , but no ultrasound evidence of fluid leak
Only to save the mother's life –e.g.
Ÿ Significant placental abrup on
Ÿ Maternal cardiorespiratory distress due to a cause other than dengue
Specific inves ga ons before delivery and opera ve interven ons:
• NS1 Ag
• PLT
• CBC, HCT
• USG-abdomen and chest

6.2.2 Cri cal Phase (Very High Risk)


Cri cal leaky phase occures 48 hours following febrile phase: Rising WBC>4000. PLT
dropping <100×103\µL. Rising HCT and USS evidence of fluid leak and evalua on of IVC and
its collapsibility
Place of management. Preopera ve management in ward post-opera ve in HDU\ICU
Specific inves ga ons before delivery and opera ve interven on:
• NS1 Ag and IgM

33
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

• PLT, CBC and HCT


• Coagula on,ROTEM
• Cross match fresh blood (<5 days old) and components
• USG-abdomen chest and IVC
• SGPT\SGOT
Specific precau ons before opera ve interven on:
• Correct PLT>50× 10⁹\L
• Correct deranged coagula on
• Correct Hb>10g/dl
• Op mize organ func on
• Be ready to manage major post –partum haemorrhage, DIC
• Possible indica on for Caesarean sec on is only to save the mother's life(Placental
abrup on or maternal cardiorespiratory distress )

6.2.3 Convalescent Phase (Moderate Risk)


Ÿ Appe te improved, bradycardia, convalescent rash\itching, diuresis
Ÿ Lab WBC Normal, PLT rising >50×10⁹\l ,PCV Normal
Place of management: HDU\ICU
Specific inves ga ons before delivery and opera ve interven on:
• IgG\IgM
• PLT,Hb, HCT
• Coagula on,ROTEM
• SGPT\SGOT
Specific precau ons before opera ve interven on:
• Correct PLT>100×10⁹\L
• Correct deranged coagula on
• Correct Hb.10g/dL
• Be ready to manage PPH
• Beware of sepsis in presence of IUD
• Indica on For Caesarean sec on are fetal comprise, maternal compromise,
postponed CS during febrile or cri cal phase

6.2.4 -Post Recovery (Low Risk)


Indica on for caesarean sec on is opera on at short no ce but no clinical urgency and elec ve CS

34
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

6.3: Dengue Fever with PIH


• Dengue fever with PIH should be managed by MDT.
• An -hypertensive medica on should be con nued accordingly with careful monitoring of
BP and pulse pressure.
• Warning feature of impending shock must be evaluated like abdominal pain, vomi ng and
reduce urine out put.
• Send CBC, RFTs, LFTs, Urine albumin (if required 24 hour urinary protein and protein:
crea nine ra o )
• Fetal surveillance tests like USG, DOPPLER, CTG, Biophysical profile.
• Delivery must be postponed ll the pa ent is out of the acute phase of the disease.
• If delivery is inevitable, pre delivery prepara on must be done by arranging blood and
blood products and PLT.
• Injury must be kept at minimal level, and opera ve delivery must be avoided un l and
unless very necessary.
• Increase Risk of PPH must be kept in mind.

6.4: Dengue Fever with Diabetes


• Dengue fever with diabetes in pregnancy should be managed by MDT
• Pa ent with diabetes with subop mal glycemic control with or without co morbidi es are
significantly at high risk for the development of DHF and DSS
• The blood sugar level must be op mized. Best to use con nuous insulin infusion and trate
according to blood sugar level. Avoid sub cutaneaus insulin.
• The rest of management of dengue with diabetes is same as without dengue

6.5:Dengue with Morbid Adherent Placenta


• Delivery should be postponed ll the cri cal phase of disease is resolved.
• High risk consent must be taken in regard of caesarean hysterectomy as well.
• PLT level must be >100×10⁹ \L.
• Blood and blood products must be at hand.
• Surgery must be done by consultant obstetrician.

35
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

7. Bleeding During Pregnancy in Degue Infec on


Prof Rubina Sohail, Dr Somia Iqtadar, Prof Jodat Saleem

7.1 Haemosta c Changes in Dengue Fever


Ÿ Dengue infec on is characterized by endothelial and coagula on pathways ac va on and
thrombocytopenia. There is a rise in thrombomudolin, ssue factor and Won Willebrand factor
levels in severe Dengue infec on.
Ÿ Pregnancy can affect these changes, as in pregnancy there can be a decrease in platelet count
by gesta onal thrombocytopenia and pregnancy itself is a pro thrombo c stage and increases
the risk of deep venous thrombosis and pulmonary embolism.
Ÿ These physiological changes predispose a pregnant pa ent with Dengue to a higher risk of
developing disseminated intravascular coagula on (DIC), bleeding and end organ damage.

7.2 Causes of Hemorrhage


Bleeding is common in dengue illness. This can range from petechial haemorrhages to life
threatening bleeding. In adults, clinically significant bleeding can occur in DF, DHF with shock and in
DHF without shock. As such, bleeding is an important complica on in pregnant dengue pa ents.
Furthermore, if the pa ent delivers during the illness, bleeding is likely to be more due to oozing
from raw uterine surface. Surgical maneuvers, including Lower Segment Caesarean Sec on, can
result in severe, life threatening bleeding and should be avoided in Cri cal phase of DHF unless to
save mother's life.

7.3 Types of Bleeding


Ÿ Overt bleeding which can manifest as bleeding from any site.

Ÿ Concealed or Occult, which can occur into gsatrointes nal tract, muscles, abdominal cavity,
thoracic cavity and brain.
Ÿ In pregnancy Antepartum hemorrhage and Postpartum hemorrhage can be a cuase of maternal
mortality. Bleeding can be occult or revealed vaginally (especially in placental abrup on).
Ÿ If the pregnant pa ent is suffering from bleeding due to a pregnancy complica on dengue
illness can add to morbidity and vice versa.
Ÿ Delivery whether vaginal or abdominal can result in life threatening hemorrhage and should be
avoided in cri cal phase.

36
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

7.4 Pa ents at Risk of Major Bleeding:


Ÿ In prolonged/refractory shock

Ÿ Hypotensive shock and renal or liver failure and/or severe and persistent metabolic acidosis

Ÿ Given non-steroidal an -inflammatory agents

Ÿ Pre-exis ng pep c ulcer disease

Ÿ On An coagulant therapy (in pregnancy with an phospholipid syndrome, cardiac valve


replacement)
Ÿ Any form of trauma: vaginal delivery or caesarean sec on

7.5 Bleeding as a Complica on of DHF


DSS is hypovolemic shock caused by plasma leakage and main characteris cs are increased
systemic vascular resistance, manifested by narrowed pulse pressure (systolic pressure is
maintained with increased diastolic pressure, e.g. 100/90 mmHg).
When hypotension is present, one should suspect either decompensated shock or that severe
bleeding, and o en concealed gastrointes nal bleeding, may have occurred in addi on to the
plasma leakage.

7.6 Warning Signs Indica ng Haemorrhage


Following warning signs in a pregnant woman with dengue fever must alert the physician to look
for haemorrhage and do prompt management:
Ÿ Any of the hemodynamic parameters become abnormal (e.g. tachycardia dispropor onate to
fever, prolonged CRFT, reduc on of urine output (UOP) with reduc on of HCT).
Ÿ When pa ents present with shock, especially hypotension, postural hypotension, dizziness,
fain ng but no adequate rise in HCT. Further, in these pa ents AST/ALT will be elevated >200
IU/L.
Ÿ Significant increase in WBC count (neutrophil leucocytosis) with reappearance of fever can be
due to Bleeding, Bacterial infec on and Hepa s.
Ÿ Tachycardia (>110/min) without fever

Ÿ Sudden fall of HCT below baseline (following fluid resuscita on in shock)

Ÿ Drop of HCT >10 points following a bolus of Dextran-40 (administered 10 ml/kg/ hr)

37
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

Guidelines for visual es ma on of blood loss

Ÿ 60ml: small 10×10cm swab (maximum saturated capacity)

Ÿ 140ml: medium 30×30 cm swab (maximum saturated capacity)

Ÿ 350ml: large 45×45cm swab (maximum saturated capacity)

Ÿ 500ml: 50cm diameter floor spill Excessive vaginal bleeding—soaking a pad in an hour.

7.7 Management of Bleeding


A er detec on of haemorrhage in pa ents with DHF/ DSS in pregnancy following measures must
be taken:
Ÿ If the source of bleeding is iden fied, a empts should be made to stop the bleeding if possible.
Severe epistaxis, for example, may be controlled by nasal packing. Urgent blood transfusion is
life-saving and should not be delayed ll the HCT drops to low levels.
Ÿ If blood loss can be quan fied, this should be replaced. However, if this cannot be quan fied,
5ml/kg of fresh whole blood or 10 ml/kg of freshly packed red cells should betransfused and
response evaluated.
Ÿ In gastrointes nal bleeding, H-2 antagonists and proton pump inhibitors have been used, but
there has been no proper study to show its efficacy.
Ÿ There is no evidence to support the use of blood components such as fresh frozen plasma or
cryoprecipitate. Its use could contribute to fluid overload.
Ÿ Recombinant Factor 7 might be helpful in some pa ents without organ failure, but it is very
expensive and generally not available.
Ÿ Management of bleeding is volume replacement with blood. Un l blood is available, fluid
should be transfused: crystalloids in early or middle of the cri cal phase and Dextran-40 in the
la er part of the cri cal phase. If the pa ent is unstable, blood should be given rapidly. A er the
transfusion, haematocrit (HCT) should be repeated.
Ÿ Even if bleeding is likely and haematocrit is >45% do not give blood without bringing down the
HCT first by giving a colloid (Dextran-40, 10ml/kg/hr).
Ÿ Threshold for blood transfusion is low in dengue with pregnancy. Packed Red Cells (PRC) 5ml/kg
can be given at a me. HCT is expected to rise by 5 points (e.g. from 30% to 35%) with this
amount of blood.
Ÿ Ac ve management of third stage of labour must be done

Ÿ Immediately a er the baby's delivery (end of the second stage of labour), the cervix and vagina
should be thoroughly inspected for lacera ons and surgical repair should be performed early.

38
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

Ÿ If the pa ent had delivery either Normal Vaginal Delivery or Lower Segment Caesarean
Sec on( LSCS) it is advisable to replace the es mated lost blood volume immediately.
Ÿ It is essen al to monitor haematocrit and haemodynamic parameters frequently in such
pa ents as they are likely to have con nuous bleeding and may need further blood
transfusions.

7.7.1 Indica ons of Blood Transfusion


Ÿ Mild bleeding does not require blood transfusion but in a pregnant pa ent with dengue
fever and bleeding special considera on and cau on must be taken in this regard.
Ÿ If the source of bleeding is iden fied, a empts should be made to stop the bleeding if
possible for example repair of genital tract injury.
Ÿ Blood transfusion is life-saving and should be given as soon as significant or severe bleeding
is suspected or recognized.
Ÿ Do not wait for the haematocrit to drop too low before deciding on blood transfusion
Ÿ At the me of delivery if blood loss is more than normal limit (500ml at vaginal and 1000ml
at abdominal delivery).
Ÿ

7.7.1.a Absolute Indica ons For Blood Transfusions


Ÿ Overt blood loss of 250-300 ml

Ÿ Drop in haematocrit without clinical improvement despite adequate fluid replacement.

Ÿ A drop in haematocrit of >10 points a er Dextran- 40 10 ml/kg (or 500 ml) bolus

Ÿ Dengue shock not responding to adequate fluid therapy i.e. 40-60 ml/kg (Refractory shock)

Ÿ Hypotensive shock with low or normal haematocrit

Ÿ Persistent or worsening metabolic acidosis despite adequate fluid replacement

7.7.1.b Rela ve Indica ons for Blood Transfusions


Ÿ If the pa ent is in shock but haematocrit (HCT/PCV) rise is not high enough as expected for the
degree of leak leading to shock
Ÿ Low or normal PCV with unstable haemodynamic parameters such as; cold clammy extremi es,
prolonged CRFT, tachycardia, narrow pulse pressure (25-35 mmHg), and reduced Urine Output.
Ÿ Increased INR (liver failure) with low PCV

Ÿ Anaemia in pregnancy – Pregnant women with low haemoglobin (Hb ≤8g/dl) e.g. Iron
Deficiency, Thalassemia Minor, with dengue illness, blood transfusion should be considered
early.

39
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

7.7.1.c Method
Ÿ Transfuse 5 ml/kg of fresh-packed red cells or 10 ml/kg of fresh whole blood at an appropriate
rate and observe the clinical response.
Ÿ Repeat blood transfusion if there is further blood loss or HCT fails to rise appropriately a er
blood transfusion.
Ÿ P transfusions.

7.7.2 Role of Platelet Transfusion


Ÿ Low platelet count is not an indica on for prophylac c platelet transfusions as there is no
rela onship with bleeding and low platelet count (without trauma).
Ÿ If delivery is evident or labour progressing in spite of tocoly cs or if LSCS is essen al (to save
mother's life) platelet transfusions would be necessary to keep the platelet count >30x10⁹/L-
50x10⁹/L respec vely.
Ÿ If the pa ent con nues to bleed in spite of several blood transfusions, there is a place for
therapeu c platelet transfusions.
Ÿ Platelet transfusion may be indicated in the presence of heavy overt bleeding with low platelet
counts.
Ÿ Inser on of central venous catheter/ vas cath for CRRT – aim >30x10⁹ /L

7.7.3 Transfusion of other Blood Products


Ÿ If pa ent develops liver failure, platelet, FFP and cryoprecipitate would be indicated. However,
clinicians have to be conscious of the possible fluid overload with platelet and FFP transfusions.
Ÿ Factor VII may have a place only if the bleeding is from a single point (e.g. Gastric ulcer)

Ÿ Prothrombin concentrate complex (containing factors II, VII, IX, X) may have a place in bleeding
with liver failure.

Ÿ Key points
Ÿ High index of suspicion of bleeding should be there if vitals deteriorate inspite of
resuscitative measures in DSS
Ÿ Physician must be aware of indications of blood transfusion
Ÿ In pregnant women delivery can worsen the dengue shock due to hemorrhage so
preventive measures must be taken
Ÿ Clear guidelines of platelet and other product transfusion must be followed to avoid fluid
overload

40
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

7.8 The Role of Adjunc ve Therapy in Dengue


There is insufficient evidence to support the use of recombinant ac vated factor VII in dengue
pa ents with significant bleeding The coagula on system seems to be over-ac vated in dengue
and infusion of ac vated factor concentrates may increase the risk of thrombosis. Pregnancy is a
pro thrombo c state and predisposes the pa ent with dengue fever to further risk.

There is insufficient evidence to support the use of intravenous immunoglobulin and Steroids.
Likewise, there appears to be no role for the use of Vitamin K and tranexamic acid in dengue fever.
In pregnancy there is definite role of tranexamic acid in postpartum hemorrhage, hence a pregnant
pa ent with dengue illness suffers from PPH, along with other measures tranexamic acid can be
used.

41
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

8. Nursing Care During Pregnancy and Counseling


Prof. Shamila Ijaz Munir, Dr. Amna Wasif
8.1 Nursing Interven ons
Nursing interven ons appropriate for a pa ent with DHF include:
Ÿ Blood pressure monitoring. Measure blood pressure as indicated.

Ÿ Monitoring pain. Note pa ent's complaint of pain in specific areas, whether pain is increasing,
diffused, or localized.
Ÿ Vascular access. Maintain patency of vascular access for fluid administra on or blood
replacement as indicated.
Ÿ Medica on regimen. There must be a periodic review of the medica on regimen to iden fy
medica ons that might exacerbate bleeding problems.
Ÿ Fluid replacement. Establish 24-hour fluid replacement needs.

Ÿ Managing nose bleeds. Elevate posi on of the pa ent and apply ice bag to the bridge of the
nose and to the forehead.
Ÿ Trendelenburg Posi on. Place the pa ent in Trendelenburg posi on to restore blood volume to
the head.

8.2 General In Ward Care


8.2.1 Febrile Phase
Ÿ Do baseline CBC on D1/D2 of fever

If WBC count is normal/Lower side suspect DF and repeat CBC a er 24 hours and compare further
fall in platelets/ rise in PCV (>10% rise is considered as significant).
Monitor:
Ÿ 4 hourly Temperature char ng, pulse, BP.

Ÿ Intake Output record…Ensure urine output at least 4 hourly. (minimum 100 cc every 4 hours)

Ÿ Capillary refill me (CRFT)

Ÿ Labs: Daily CBC, other inves ga ons if necessary.

Ÿ Oral Intake encouraged. ORS, juice all are encouraged apart from rou ne food
Ÿ Aim of at least 2.5 liters of fluid intake in 24hrs.

Ÿ If nausea/vomi ng of pregnancy restrict oral intake give IV fluid (NS) 100 ml/ hour
Ÿ Paracetamol 500-1000mg 6 hourly. Warn the pa ent that fever may not se le with this dose but

42
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

NOT to exceed 4 grams paracetamol in 24 hours


Ÿ Don't take other NSAID like Ibuprofen and Diclofenac Sodium.

Ÿ Tepid sponging for fever

Ÿ Withhold Aspirin if she is taking it

Ÿ No fy to duty doctor if:

ü Urine output is less than 30 ml\hour


ü Vomi ng, lethargy, narrowing of pulse pressure (<20). delayed capillary refill >2 seconds.

8.2.2 Cri cal Phase


Ÿ These pa ents need ins tu onal management in HDU setup.

Ÿ Timely fluid management with appearance of any warning symptom prac cally prevents
further complica on.
Ÿ Monitor Vitals (BP /Temp/Pulse pressure, Capillary Refill) hourly

Ÿ Catheterize to know precise urine output hourly (0.5ml/kg/hour).

Ÿ Carrfully trate fluid resuscita on (Normal saline) Bolus of 5-10ml/kg/hour x 2 hours given
followed by 3-5ml/kg/hour as a maintenance. This is monitored by urinary output and pulse
pressure.(DEAG, DHF Algorithms Page 30)
Ÿ Avoid induc on of labour/ planned surgery in this phase.

Ÿ Draw blood for CBC, HCT, grouping cross match, LFTs, Electrolytes, Blood sugar levels.

8.2.3 Convalescent Phase


Ÿ Rise of WBC count followed by rise of platelet count.
Ÿ Stabiliza on of HCT marks convalescent phase.
Ÿ Watch for signs of fluid overload – cough, wheeze, and tachypnea, Rise of both SBP and DBP.
Ÿ Recovery rash might appear.

8.3 Discharge and Home Care Guidelines


8.3.1 For Undelivered Pa ents
Ÿ Regular antenatal visits for antenatal pa ents.
Ÿ Immediately report the hospital in case of fever and any warning signs like abdominal pain
tenderness, vomi ng, fa gue and lethargy.
Ÿ There are chances of increased risk of ver cal transmission so surveillance of foetal movements
is very important and foetal surveillance tests must be reassuring.

43
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

Ÿ Delivery should take place in a hospital where blood/blood components with a team of skilled
obstetricians and a neonatologist available.
Ÿ There are increased chances of preterm labour and birth so tocoly c agents and measures to
postpone labor to a suitable me may be considered during the cri cal phase of dengue illness.
However there is currently a lack of evidence on this prac ce.
Ÿ Most cases of dengue fever during pregnancy had favorable outcomes for the mother and
neonates; therefore pregnancy can be con nued un l late term or full term with adequate fluid
therapy.

8.3.2 For Delivered Pa ents


Ÿ Rou ne care of perpeurium.
Ÿ Rou ne use of an bio cs in case of opera ve delivery.
Ÿ Newborns with mothers who had dengue just before or at delivery, should be closely monitored
a er birth in view of the risk of ver cal transmission at or near term delivery. Severe fetal or
neonatal dengue illness and death may occur when there is insufficient me for the produc on
of protec ve maternal an bodies.
Breast Feeding
Ÿ Breas eeding is safe if the mother is infected with dengue. The risk of transmission of dengue
virus from mother to the baby through breast milk is next to negligible. Evidence shows that the
colostrum (the first breast milk) and breast milk have an -dengue an bodies which make the
baby immune from the infec on.
Ÿ According to the guidelines by WHO, it is important to breas eed the newborn during maternal
dengue infec on as breast milk has lot of nutrients and an bodies which helps protect the baby,
prevent dehydra on and maintain emo onal well-being in the baby. If a mother is moderate to
severely ill, then the doctor can put the newborn on formula or top feed.

8.3.3 Home Care Advice


Ÿ Oral care. Recommend use of so toothbrush to reduce risk of injury to the oral mucosa.
Ÿ Diet. Foods rich in vitamin K should be recommended to promote blood clo ng.
Ÿ Avoid diure cs. caffeine and alcohol to reduce effects of diuresis.
Ÿ Educa on. Educate pa ent on the
Ÿ Use of mosquito nets and insec cides.
Ÿ Elimina ng mosquito breeding sites.
Ÿ Make sure window and door screens are secure and free of holes.
Ÿ Regularly change the water in outdoor and indoor containers.

44
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

Ÿ When outdoors, wear long-sleeved shirts and long pants tucked into socks. When indoors, use
air condi oning if available. Stay away from heavily populated residen al areas.
Ÿ Maintain good hygiene at home and environment.

8.4 Counseling of pa ent and rela ve with Dengue Fever


Arrange for Adequate Time
Review relevant clinical informa on and prepare in advance.
Ÿ Dengue is the most common cause of fever during pregnancy. It is reported to be (46%)
Ÿ The mortality rate for severe dengue fever is 0.8–2.5%, and pregnancy should be recognized as a
coexis ng risk factor for serious infec on.
Ÿ The rates of preterm birth, low birth weight, and s llbirth are 20%, 5.0%, and 5.0%, respec vely
Ÿ There is no increased risk of miscarriages or congenital anomalies.
Ÿ Most cases of dengue fever during pregnancy have favorable outcomes for the mothers and
neonates; therefore pregnancy should be con nued un l late term or full term period with
adequate fluid replacement therapy.
Ÿ Dengue is classified using three disease categories: Dengue Fever (DF), Dengue Hemorrhagic
Fever (DHF), and Dengue Shock Syndrome (DSS).
Ÿ Simple dengue fever does not pose any serious threat to mother or foetus.
Ÿ DHF needs hospitaliza on and close monitoring.
Ÿ Dengue shock syndrome is a serious life threatening condi on and may result in
serious consequences and complica ons if not diagnosed and treated in me.
Ÿ Warning signs are defined as abdominal pain, persistent vomi ng, fluid accumula on, mucosal
bleeding, lethargy, liver enlargement, and increasing haematocrit with decreasing platelets.
Ÿ The risk of ver cal transmission is well established among women with dengue during the
perinatal period.
Ÿ Severe bleeding may complicate delivery and/or surgical procedures performed on pregnant
pa ents with dengue during the cri cal phase.
Ÿ Early diagnosis and hospitaliza on may result in decrease in maternal and perinatal
mortality.

45
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

Build a Therapeu c Environment/Rela onship


Ÿ Introduce yourself.
Ÿ Only give that informa on which a pa ent wants to know.
Ÿ Involve the partner and family as well.
Ÿ Schedule follow up appointment.
Communicate Well
Ÿ Give all detailed informa on about the disease.
Ÿ Inform the future outcome.
Ÿ Discuss treatment or solu on.
Deal with Pa ents Reac ons
Ÿ Be empathe c.
Ÿ Don't argue or cri cize.
Encourage and Validate Emo ons
Ÿ Offer realis c hope according to the pa ent's status.
Ÿ Encourage her about her future pregnancies and inform about precau onary measures.
8.5 Discharge Criteria

46
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

9. Dengue In Puerperium
Prof. Zohra Khanum, Prof. Muhammad Ali Khan, Dr. Somia Iqtadar

Introduc on:
Dengue has emerged one of the most important mosquito borne viral diseases of the humans.If
not managed mely and properly it can carry significant morbidity and mortality.Concern
regarding women who are pregnant or in postpartum period ge ng infected with Dengue virus
has been heightened in recent years due to an increase in adolescents and adult infec on.Pregnant
women with Dengue need early iden fica on. Clinical management requires a mul -disciplinary
approach and precise me related interven ons for op mal outcome.Early detec on and access to
medical care will reduce complica ons and mortality in puerperium.

Puerperium:
It is the period of adjustment a er pregnancy and delivery when anatomical and physiological
changes of pregnancy are reversed and the body returns to the normal non pregnant state.It is a
period of 6 weeks which commences following comple on of third stage of labour.
9.1 Physiological Changes during Puerperium

9.1.1 Hematological Changes


Ÿ Hemoglobin concentra on increases in first few postpartum days.

Ÿ Several clo ng factors (fibrinogen)increases on the first few days.


Ÿ Marked leukocytosis and thrombocytosis is seen in labor and postpartum period.

Ÿ Normally hemoglobin and hematocrit fluctuate moderately during the first few postpartum
days.

9.1.2 Cardiovascular Changes


Ÿ Blood volume which increases during pregnancy is eliminated by the tenth day of puerperium
and returns to non pregnant values by 6 weeks postpartum.
Ÿ Cardiac output increases immediate a er delivery ,slowly declines, reach late pregnancy levels
2 days postpartum and returns to normal in 2 to 6 weeks.
Ÿ Hematocrit increases and increased red blood cell produc on stops.

9.1.3 Vitals signs


Blood Pressure: No change is encountered but if hypotension is present postpartum hemorrhage

47
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

may be suspected.
Ÿ Pulse: A er the ini al tachycardia associated with labour and delivery, a bradycardia o en
develops in the early puerperium.By the end of the first week the pulse rate will have returned
to normal.
Ÿ Temperature: A woman may show slight increase in temperature during the first 24 hours a er
birth.

9.1.4 Urinary system


Within 12 hours of birth women begin to lose the excess ssue fluid that has accumulated during
the pregnancy.The fluid lose through increased urinary output accounts for weight loss of
approximately2.2kg during the puerperium.

9.1.5 Gastrointes nal changes


A spontaneous bowel evacua on may be delayed un l 2 to 3 daysa er childbirth. This can be
explainedby decreased musle tone of the intes nes during labour and the immediate puerperium,
prelabor diarrhea, lack of food or dehydra on.

9.1.6 Respiratory func on


Returns to normal by approximately 6 to 8 weeks postpartum.Basal metabolic rate increases for
7 to 14 days postpartum , secondary to mild anemia,lacta on and psychological changes.

9.2 Fever in Puerperium


Fever that lasts for more than 24 hours within the first 10 days a er a woman has had a baby must
be inves gated. Puerperal fever is usually due to an infec on.If infec on involves the bloodstream
it cons tutes puerperal sepsis.

9.3 Differen al Diagnosis of Puerperal Fever


1. Endometri s
2. Wound Infec on
3. Mas s
4. UTI
5. Thrombophlebi s

48
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

9.4 Clinical Presenta on of Dengue in Puerperium


Clinically significant dengue Infec on may be
Ÿ Simple Dengue Fever(DF)

Ÿ Dengue Hemorrhagic Fever(DF)

Ÿ Dengue Shock Syndrome(DSS)

Symptoms:
Ÿ Sudden,high grade fever

Ÿ Fever >2 And <10 days

Ÿ Severe headache

Ÿ Pain behind the eyes

Ÿ Severe joint and muscle pain

Ÿ Fa gue

Ÿ Abdominal Pain

Ÿ Bleeding Menifesta ons(epistaxis, hematemesis, bloody stools, menorrhagia, hemoptysis)

Ÿ Decreased urine output despite adequate intake

Ÿ Skin rash which appears 2 To 5 days a er the onset of fever

9.4.1 Differen al Diagnosis of Dengue in Puerperium


Ÿ HELLP syndrome

Ÿ Toxemia of pregnancy

Ÿ Pre eclamsia

Ÿ Gesta onal thrombocytopenia

Following physiological changes in pregnancy may make the diagnosis and assessment of plasma
leakage challenging.
Ÿ Eleva on of HCT in dengue is masked by hemodilu on due to increase in plasma volume
rd
especially in 3 trimester and immediate postpartum period.Serial HCT measurements is crucial
for disease monitoring in pregnancy and puerperium.
Ÿ The detec on of third space fluid accumula on is difficult due to the presence of gravid uterus.

Ÿ Baseline blood pressure is o en lower and pulse pressure wider.

Ÿ Baseline heart rate may be higher.

49
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

9.4.2 How to Diagnose Dengue in Puerperium


CBC and platelet count
FIRST 5 DAYS
1: NS1
2: PCR
AFTER 5 DAYS
IgM & IgG
Analysis of hematological parameters.
Special Risks
Ÿ Postpartum Hemmorhage
Ÿ Pleural Effusion Myocardial Involvment
Ÿ Pulmonary Edema
Ÿ Hepa c Involvment
Ÿ Seizures,encephalopathy
Ÿ Dengue Hemmorrhagic Fever
Ÿ Dengue Shock Syndrome

Management:
Ÿ Reduc on of high grade fever by Paracetamol only.Avoid NSAIDS such as aspirin as they can
increase the risk of bleeding
Ÿ Promote oral feeding:So drink,milk,fruit juice,oral rehydra on solu on(ORS).
Ÿ Avoid IV fluid if there is no vomi ng and moderate/severe dehydra on.
Ÿ Empiric an bio c therapy
Ÿ Transfuse blood,preferably fresh packed red cells as indicated.
Ÿ H2-blockers or proton pump inhibitor may be given to alleviate gastro intes nal bleeding.
Ÿ Watch for warning signs. In case of any warning sign ask pa ent to come immediately in
emergency.

Breast Feeding in Dengue


Some studies suggest that the dengue virus can be found in breast milk and there may be
possibility of breastmilk being a poten al transmission method of virus but the risk of a mother
passing the dengue virus to her baby through milk is thought to be very low. The health benefits of
breas eeding are much greater than the likelihood of passing the infec on.

50
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

10. Maternal, Fetal and Neonatal Outcome in Pregnant


Dengue Pa ents
Prof. Farhat Naaz, Prof. Rubina Suhail, Dr. M. Faheem Afzal
The evidence is present worldwide and especially in endemic areas that dengue infec on during
pregnancy increases the risk of adverse outcomes in pregnancy. The effects of this infec on during
pregnancy on fetal or neonatal outcomes may be due to inflammatory response,
thrombocytopenia, plasma leakage or hemorrhagic tendency. These complica ons could result in
compromised placental circula on leading to complica ons.

10.1 Dengue Fever in Pregnancy and Miscarriage


Various studies conducted have shown an increased rate of miscarriage or loss of product of
concep on less than 22 weeks of gesta on ranging from 3.8-16%.

10.2 Dengue Fever and Intrauterine Demise


Dengue fever in pregnancy increases incidence of s ll birth ranging from 4.7- 13%. It has been
seen that it is 6 mes higher in symptoma c dengue than women without dengue infec on.

10.3 Dengue Fever and Preterm Birth


Preterm birth (less than 37 weeks) incidence ranges from 3.1-26.6% in pregnant women with
dengue infec on as compared to 2-8% risk in general popula on. The associa on between
preterm labor and dengue can be due to pathological changes such, as increased in interleukin-6,
interleukin 8 and tumor necrosis factor.

10.4 Dengue Fever and Low Birth Weight


Low birth weight is taken as less than 2500grams at 37 weeks of gesta on. Like preterm birth it is
also considered as the most common adverse outcome of pregnancy with dengue. Its incidence
ranges from 1-58%.

10.5 Ver cal Transmission of Dengue Virus


Ver cal transmission is not considered a common mode of transmission of dengue infec on. It has
been reported upto 6%. Neonate must be monitored for platelet count if there is suspicion of
congenital dengue fever. A possible explana on for ver cal transmission can be maternal infec on
acquired near the me of delivery would not have had enough me for protec ve an bodies to be

51
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

produced and transferred to the neonate, conferring a passive immunity. The maternal viremia
would therefore be transferred to the unprotected fetus resul ng in neonatal infec on ranging
from asymptoma c infec on to death.

10.6 Fetal Complica ons


Meconium aspira on and oligohydroamnios are associated with the disease in different studies.
One of study quoted that Dengue during pregnancy increased the odds of a neurologic congenital
anomaly by 50% but this result was not sta s cally significant.

10.7 Clinical Features of Dengue Fever in Neonates


Neonates can pose differences. They never shiver. Fever or hypothermia may be the ini al
manifesta ons. Neonates are unable to complaint of any symptoms so par cularly, cons tu onal
symptoms may be missed.
Early recogni on of dengue illness in neonates due to perinatal transmission deserves special
a en on. Onset of fever in the newborn varies from 1 to 11 days a er birth. Fever is the ini al
presenta on in most babies, commonly on 4-5 days a er birth or even on day 01 of birth or later
than 6 days. Therefore, suspected neonate should be observed at least for 1 week for evidence of
ver cal transmission. Clinical manifesta ons of ver cally infected neonates vary from mild illness
such as fever with petechial rash, thrombocytopenia and hepatomegaly, to rarely severe illness
with pleural effusion, gastric bleeding, circulatory failure, massive intracerebral haemorrhage.

10.8 Laboratory Diagnosis


In early febrile phase leucopenia may not be found as leukocytosis is common in early infancy.
Neonates are more suscep ble to organ impairment and electrolyte imbalance. If they develop
DHF, dura on of plasma leakage is shorter (usually 12 – 24 hrs). As leucopenia is not common,
increased haematocrit (possibly with ultrasound evidence) and thrombocytopenia will help clinical
diagnosis of DHF. Non-structural an gen (NS1) can become posi ve even up to 7 days a er birth
peaking at the 5th day. IgM and IgG an bodies can take 2-3 weeks to be posi ve.

10.9 Management
Difference in the management of dengue infec on in neonates and children is type of fluid. In
neonates, N/2 + 5% Dextrose is recommended. For rest of management, it is referred to algorithm.
(Page 30)

52
DENGUE GCP GUIDELINES FOR PREGNANCY 2021

10.10 Breast Feeding in Maternal Dengue Fever


Dengue fever in mother or neonate is NOT contraindica on for breast feeding. A pregnant woman
already infected with dengue can pass the virus to her fetus during pregnancy or around the me of
birth. To date, there has been one documented report of dengue spread through breast milk.
Because of the benefits of breas eeding, mothers are encouraged to breas eed even in areas with
risk of dengue.

10.11 Monitoring of Asymptoma c Newborn


One should carefully observe the baby born to a mother with dengue infec on for a minimum
period of two weeks a er birth with periodic checks, and screen again for Dengue serology at 2
weeks of age.

53
APPENDICES
APPENDIX 1a Dengue Fever Proforma after Admission

54
APPENDIX 1b Radiology Request Form

55
APPENDIX 2 Dengue Monitoring Charts
2a. DEAG DF Form -1 (4 days) Monitoring

56
2b. DEAG DF Form – 2 (To be lled 48 hours data)

57
58
APPENDIX 3a OPD Form

DEAG FORM - O
Revised, June 2019
Dengue Expert
Advisory Group
Filling of all fields is compulsory

Hospital MR # Unit: Date:


Name s/o d/o w/o Age & Sex:
NIC # Profession
Home Address Contact #
Workplace Address Contact #

Essential Criterion Fever > 2 and < 10 days

Associated symptoms
Headache Rash
Retro orbital pain Bleeding manifestations (epistaxis, gum bleed,
Myalgia bloody stools, hematemesis, hemoptysis,
menorrhagia, hematuria)
Arthralgia/ severe backache/ bone pains Severe abdominal pain
Irritability in infants Decreased urinary output despite adequate fluid intake

Presence of any 2 associated symptoms in addition to fever

Declared Suspected Case

Record vitals; Temperature:_______HR:________ BP:__________ PP:________

Request CBC, HCT & Look for presence of any Warning Signs

DoF HCT WBC Platelet Any 2 or more Warning Signs (one or more)
No clinical improvement / worsening clinical parameters
Persistent vomiting
D3 1. WBC < 4000
Severe abdominal pain
Lethargy and or restlessness
+ OR Giddiness
D4 Pale cold clammy extremities
2. Platelet <100000
Bleeding: epistaxis, gum bleed, bloody stools,
or hematemesis, hemoptysis, menorrhagia, hematuria
D5 Pulse Pressure < 25mmHg
HCT < 30% or
3. > 55% Less / no urine output for 4 - 6 hours

Declared Probable Case

Admit Patient & fill Reporting Form R


* If Admission is not indicated, explain warning signs and advise treatment and followup.

__________________
Name, Signature and Date
PTO

59
60
APPENDIX 4a Reporting for Dengue Patients (Suspected & Probable)

61
APPENDIX 5

62
APPENDIX 6

63
APPENDIX 7

Data Entry Counter

64
APPENDIX 8
Home Care Advice Leaflet for Dengue Pa ents
Front View

HOME CARE ADVICE FOR DENGUE PATIENTS


What should be done?
— Adequate bed rest
— Adequate fluid intake (more than 5 glasses for an average person)
- Milk, fruit juice (cau on with diabetes pa ents) and isotonic electrolyte
solu on (ORS) and barley water
- Plain water alone is not sufficient and may cause electrolyte imbalance.
(Nicaragua 2003, Level 8)
— Take Paracetamol (not more than 4 gram per day)
— Tepid sponging
— If possible, use mosquito repellent or rest under a mosquito net even during day me
to prevent mosquito bites
— Look for mosquito breeding places in and around the home and eliminate them
What should be avoided?
— Do not take non-steroidal an -inflammatory (NSAIDs) e.g. aspirin / Mefenamic acid
(Ponstan) or steroids. If you are already taking these medica ons please consult your
doctor.
An bio cs are not required.

THE DANGER SIGNS OF DENGUE INFECTION


(IF ANY OF THESE ARE OBSERVED, PLEASE GO IMMEDIATELY TO THE NEAREST HOSPITAL)

1. Bleeding
for example:
— Extensive red spots or patches on the skin
— Excessive bleeding from nose or gums
— Black tarry stools
— Heavy menstrua on / vaginal bleeding
2. Frequent vomi ng
3. Severe abdominal pain
4. Drowsiness or irritability
5. Pale, cold and clammy skin
6. Difficulty in breathing

65
APPENDIX 9
Patient Information Brochure in Urdu

66
APPENDIX 10 Diagnostic Criteria – Non Epidemic Setting

67
68
APPENDIX 11 Diagnostic Criteria – Epidemic Setting

69
70
APPENDIX 12 Inpatient Form

71
72
APPENDIX 13 Reporting Form for Dengue Patients (Con rmed)

73
74
75
76
77
List of Abbrevia ons (GCP Guidelines for Pregnancy)
APH Antepartum Haemorrhage
ALT Alanine Transaminase
AST Aspartate Aminotransferase
BP Blood Pressure
BU Blood Urea
CRT Capillary Refill Time
CTG Cardiotocography
CVC Central Venous Catheter
CBC Complete Blood Count
CRRT Continuous Renal Replacement Therapy
CS Caesarean Section
DBP Diastolic Blood Pressure
DF Dengue Fever
DIC Disseminated Intravascular Coagulation
DHF Dengue Hemorrhagic Fever
DSS Dengue Shock Syndrome
EDS Expanded Dengue Syndrome
FBC Full Blood Count
FFP Fresh Frozen Plasma
FRC Functional Residual Capacity
GCS Glasgow Coma Scale
GFR Glomerular Filtration Rate
CRFT Capillary Refill Time
GXM Group Cross Match
Hb Hemoglobin
HbA1C Hemoglobin A1c
HCT Hematocrit
HCO3 Bicarbonate
HELLP Hemolysis, Elevated Liver Enzymes, Low Platelets
HI Hemagglutination inhibition
HR Heart Rate
ICU Intensive Care Unit
IgG Immunoglobulin G
IgM I mmunoglobulin M
ITP Immune Thrombocytopenic Purpura
LFT Liver function Test
LSCS Lower Segment Caesarean Section
IUD Intrauterine Devices
MAP Mean arterial pressure
MDT Multi Disciplinary Team
NG Tube Naso - Gastric Tube

78
List of Abbrevia ons (GCP Guidelines for Pregnancy)
NSAID Nonsteroidal Anti - inflammatory D rugs
NS1 Ag Non- structural Protein – 1A ntigen
ORS Oral Rehydration Solutions
PCR Polymerase chain reaction
PCO₂ Partial Pressure of Carbon Dioxide
PCV Packed- Cell Volume
PO ₂ Partial Pressure of Oxygen
ROTEM Rotational Thromboelastometry
PLT Platelet
PP Pulse pressure
PPH Post - Partum Hemorrhage
PR Pulse rate
RBS Random blood sugar
RR Respiratory rate
RPOC Retained Products of Conception
RT - PCR Reverse transcriptase Polymerase chain reaction
SBP Systolic blood pressure
SE Serum Electrolytes
SGOT Serum Glutamic - Oxaloacetic Transaminase
SGPT Serum Glutamic - Pyruvic Transaminase
SLE Systemic Lupus Erythematosus
TCO 2 Total CO 2
TTP Thrombotic Thrombocytopenic Purpura
UOP Urinary Output
USG Ultrasonography
UTI Urinary Tract Infection
WBC White Blood cell count
WHO World Health Organization

79

You might also like