“COMPARATIVE STUDY OF EPIDURAL 0.

75% ROPIVACAINE
WITH DEXMEDETOMIDINE AND 0.75% ROPIVACAINE
ALONE IN LOWER ABDOMINAL AND LOWER LIMB
SURGERIES”

By

Dr.SWARNA GOWRI S.,MBBS

Dissertation Submitted to the
Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore

In partial fulfillment
of the requirements for the degree of
DOCTOR OF MEDICINE
in
ANAESTHESIOLOGY

Under the guidance of

Dr. VIJAYANAND S., MD
Associate Professor

DEPARTMENT OF ANAESTHESIOLOGY
KEMPEGOWDA INSTITUTE OF MEDICAL SCIENCES,
BANGALORE - KARNATAKA

2014

i
 RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA, BANGALORE

DECLARATION BY THE CANDIDATE

I hereby declare that this dissertation entitled “COMPARATIVE STUDY OF

EPIDURAL 0.75% ROPIVACAINE WITH DEXMEDETOMIDINE AND

0.75% ROPIVACAINE ALONE IN LOWER ABDOMINAL AND LOWER

LIMB SURGERIES” is a bonafide and genuine research work carried out by me

under the guidance of Dr. VIJAYANAND S., MD Associate Professor, Department

of Anaesthesiology, Kempegowda Institute of Medical Sciences Bangalore.

Date: Dr. SWARNA GOWRI S.

Postgraduate in Anaesthesiology

Place: Bangalore Kempegowda Institute of Medical Sciences

Bangalore

ii
 RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES,

KARNATAKA, BANGALORE

CERTIFICATE BY THE GUIDE

This is to certify that the dissertation entitled “COMPARATIVE STUDY OF

EPIDURAL 0.75% ROPIVACAINE WITH DEXMEDETOMIDINE AND

0.75% ROPIVACAINE ALONE IN LOWER ABDOMINAL AND LOWER

LIMB SURGERIES” is a bonafide research work done by Dr. SWARNA GOWRI

S., in partial fulfillment of the requirement for the degree of Doctor of Medicine in

Anaesthesiology.

Date: Dr. VIJAYANAND S., MD

Associate Professor

Place: Bangalore Department of Anaesthesiology,

Kempegowda Institute of Medical Sciences

Bangalore

iii
 ENDORSEMENT BY

THE HEAD OF THE DEPARTMENT

This is to certify that the dissertation entitled “COMPARATIVE STUDY OF

EPIDURAL 0.75% ROPIVACAINE WITH DEXMEDETOMIDINE AND

0.75% ROPIVACAINE ALONE IN LOWER ABDOMINAL AND LOWER

LIMB SURGERIES”is a bonafide research work done by Dr. SWARNA GOWRI

S., under the guidance of Dr. VIJAYANAND S., MD Associate Professor,

Department of Anaesthesiology, Kempegowda Institute of Medical Sciences

Bangalore.

Date: Dr.CHAYA S., M.D.,DA

Professor and Head
Department of Anaesthesiology,
Place: Bangalore Kempegowda Institute of Medical Sciences
Bangalore.

iv
 ENDORSEMENT BY

THE PRINCIPAL

This is to certify that the dissertation entitled “COMPARATIVE STUDY OF

EPIDURAL 0.75% ROPIVACAINE WITH DEXMEDETOMIDINE AND

0.75% ROPIVACAINE ALONE IN LOWER ABDOMINAL AND LOWER

LIMB SURGERIES”is a bonafide research work done by Dr. SWARNA GOWRI

S., under the guidance of Dr. VIJAYANAND S., MD Associate Professor,

Department of Anaesthesiology, Kempegowda Institute of Medical Sciences

Bangalore.

Date: Dr.M.K.SUDARSHAN., M.D

Dean and Principal
Place:bangalore Kempegowda Institute of Medical Sciences
Bangalore

v
 COPYRIGHT

DECLARATION BY THE CANDIDATE

I hereby declare that the Rajiv Gandhi University of Health Sciences,

Karnataka, Bangalore shall have the rights to preserve, use and disseminate this

dissertation in print or electronic format for academic/research purpose.

Date: Dr. SWARNA GOWRI S.

Postgraduate in Anaesthesiology
Place: Bangalore Kempegowda Institute of Medical Sciences
Bangalore

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES

vi
 ACKNOWLEDGEMENTS

It is most appropriate that I begin by expressing my undying gratitude to my guide

Dr. VIJAYANAND.S, Associate Professor, Department of Anaesthesiology,

Kempegowda Institute of Medical Sciences, Bangalore, for his invaluable guidance,

supervision and constant encouragement in preparing this dissertation.

I am extremely grateful and wish my sincere thanks to

Dr. CHAYA S, Professor and Head, Department of Anaesthesiology, Kempegowda

Institute of Medical Sciences, Bangalore, for her concern and support in preparing this

dissertation.

I am extremely grateful to Dr. NARENDRA BABU M.C..,

Professor,Department of Anaesthesiology, Kempegowda Institute of Medical

Sciences, Bangalore, for his concern and constant encouragement in preparing this

dissertation.

I wish to express my sincere gratitude to Dr. MADHAVA REDDY.R

Professor, Department of Anaesthesiology, Department of Anaesthesiology,

Kempegowda Institute of Medical Sciences, Bangalore for his concern in preparing

this dissertation.

I also wish to express my sincere gratitude to Dr. SRI RAGHU Associate

Professor, Department of Anaesthesiology, Department of Anaesthesiology,

Kempegowda Institute of Medical Sciences, Bangalore his concern in preparing this

dissertation.

vii
 I wish to express my sincere gratitude to DR. SREESHA, Dr. NAGARAJA,

Dr. ASHWINI, Dr. VINOD, Dr. ASHOK, Dr. SURAJ , Dr. MITHUN,

Dr. CHANDRAKANTH, Dr. SHWETHA K.M, Dr. HEMANTH, Dr. TULSI,

Dr. JYOTHSNA SINGH, Dr. SALEEM IQBAL Assistant professors,

Dr. SHASHIKIRAN, Dr. VIJAYKUMAR, Dr. R P HARSHA, Dr. KIRAN,

DR.KANAKARAJ, Dr. ASHA, tutors for their constant help and encouragement in

preparing this dissertation.

I also express my gratitude to the Dean and Principal, Superintendent of

Kempegowda Institute of Medical Sciences, Bangalore and Ethical Committee of

Kempegowda Institute of Medical Sciences, Bangalore, for granting me permission to

conduct this study.

I would like to thank my colleagues and friends for their whole hearted help

to carry out the study.

I would like to express my thanks to staff members of Kempegowda

Institute of Medical Sciences, Bangalore, for their kind cooperation during my

study.

I am grateful to my father Sri. SRINIVAS. P and my mother

Smt. RATHNA.S.R, for their everlasting blessing and encouragement.

I am grateful to my husband Dr. HARSHAVARDHANA H S. and my

sister KAVYA S, father in law SHADAKSHARAPPA H V, my mother in law

GIRIJA L C and brother in law Dr. ASHOK KUMAR H S for their everlasting

wishes, constant support and encouragement.

viii
I thank Dr. LANCY D’SOUZA for his efficient work on statistics.

I thank RR CANON SERVICE CENTER for efficient and excellent computer

work.

Last, but not the least, I am extremely grateful to all my patients who have willingly

cooperated for the course of the study.

Date: Dr. SWARNA GOWRI.S.

Place: Bangalore Postgraduate in Anaesthesiology

Kempegowda Institute of Medical Sciences,

Bangalore

ix
 LIST OF ABBREVIATIONS

ASA → American Society of Anaesthesiologists

DBP → Diastolic Blood Pressure

ECG → Electrocardiogram

HR → Heart rate

Hrs → Hours

IV → Intravenous

Kg → Kilograms

MAP → Mean Arterial Pressure

mcg(μ) → microgram

ml → millilitre

mg → Milligrams

min → Minutes

mmHg → Millimeter of Mercury

SBP → Systolic Blood pressure

% → Percentage

x
 ABSTRACT

INTRODUCTION

Intrathecal anaesthesia and epidural anaesthesia are the most popular

regional anaesthesia techniques used for lower abdominal and lower limb surgeries.

The advantages of epidural anaesthesia being ,it provides effective surgical

anaesthesia and can meet the extended duration of surgical needs, provides prolonged

post operative analgesia, reduces the incidence of hemodynamic changes.

Ropivacaine is a relatively new amide local anesthetic. It has less

cardiovascular toxic effects compared with bupivacaine. The drawback being less

intense motor blockade.

The fear of surgery, strange surroundings of the operation theatre, the sight

and sound of sophisticated equipments and the masked faces of many strange

personale makes the patient panic to any extent.

Sedation, stable haemodynamics and an ability to provide smooth and

prolonged post-operative analgesia are the main desirable qualities of an adjuvant in

neuraxial anaesthesia

α-2 adrenergic agonists have both analgesic and sedative properties when

used as an adjuvant in regional anaesthesia. Dexmedetomidine is a highly selective α2

adrenergic agonist with an affinity of eight times greater than clonidine.

Dexmedetomidine prolongs the duration of analgesia, motor block and post

operative analgesia makes it a very useful pharmacologic agent. Hence we compared

0.75% ropivacaine with dexmedetomidine and 0.75% ropivacaine alone.

xi
 OBJECTIVES OF THE STUDY

To study the synergistic effect of adding dexmedetomidine to ropivacaine 0.75%

in epidural anaesthesia for lower abdominal and lower limb surgeries, regarding

1. Onset and duration of sensory blockade

2. Onset and duration of motor blockade

3. Haemodynamic changes

4. Maximum dermatomal level of analgesia

5. Intensity of motor blockade

6. Sedation

7. Any adverse effects

MATERIAL AND METHODS

A study entitled “Comparative study of Epidural 0.75% Ropivacaine with

Dexmedetomidine and 0.75% Ropivacainealone in lower abdominal and lower limb

surgeries” was undertaken in Kempegowda Institute of Medical Sciences (K.I.M.S)

hospital,Bangalore during the period October 2011 to July 2013. The study was

undertaken after instituitionalethical committee clearance as well as informed consent

from all patients.

One hundred patients, scheduled for various elective lower abdominal and

lower limb surgical procedures belonging to ASA class I and II were included in the

study. The patients were normotensive with age varying from 18 to 65 years. Patients

xii
with hypertension, cardiac, coronary, renal, hepatic, cerebral diseases and peripheral

vascular diseases were excluded from the study

The study population was randomly divided into two groups with 50 patients in each

group.

1. Group R - 15ml of 0.75% ropivacaine

2. Group RD - 15ml of 0.75% ropivacaine + 0.6µg/kg of

dexmedetomidine.

Epidural space identified with loss of resistance to air technique at L2-L3/L3-

L4 level in sitting position using 18G tuohy’s needle. After confirming the correct

position of the catheter, patient will be turned to supine position. Five minutes

after the test dose, in the absence of any adverse sequalae, 15ml of study drug

will be given at a rate of 1ml/3sec through the catheter.

Assessment ofsensory and motor blockade were done at the end of each

minute with the patient in supine position after completion of the injection of 15 ml of

the study drug, which is taken as the starting time. The onset time and the maximum

level of sensory and motor block were recorded.

Sedation scoring as per five point sedation scale

RESULTS

Dexmedetomidine group had rapid onset of action (p<0.05), prolonged duration of

sensory and motor block (p<0.05),better sedation score and postoperative analgesia

(p<0.05), and determine more intense motor block (p<0.05).There was no difference

in the maximal dermatomal level of analgesia, incidence of hypotension and

bradycardia (p>0.05). The occurrence of side effects (tremor, nausea and SpO2<90%)

was low and similar between groups (p>0.05).

xiii
INTERPRETATION AND CONCLUSION

There is a clear synergism between dexmedetomidine and ropivacaine compared with

plain ropivacaine in epidural anesthesia without increased morbidity.

KEY WORDS:Ropivacaine, Dexmedetomidine, Epidural

xiv
 TABLE OF CONTENTS

Sl. TITLE Page No.

No

1 INTRODUCTION 1

2 OBJECTIVES 5

3 APPLIED ANATOMY 6

4 PHYSIOLOGICAL EFFECTS OF EPIDURAL BLOCKADE 20

5 PHARMACOLOGY OF ROPIVACAINE 27

6 PHARMACOLOGY OF DEXMEDETOMIDINE 35

7 REVIEW OF LITERATURE 47

8 METHODOLOGY 68

9 RESULTS 74

6. DISCUSSION 94

7. CONCLUSION 102

8. SUMMARY 103

9. BIBLIOGRAPHY 105

10. ANNEXURES

i. PROFORMA 116

ii. KEY TO MASTER CHART 121

iii. MASTER CHART

122

xv
 LIST OF FIGURES

Figure Title Page

No. No.

Vertebral column, in lateral view (left) and posterior view (right),

1 6
illustrating curvatures, lumbar interlaminar spaces and sacral hiatus

2 Components of a lumbar vertebra 7

Ligaments of the lumbar vertebral column, shown in lateral

3 9
view (A)and sagittal section (B)

4 Boundaries of the epidural space 10, 11

5 Responses that can be mediated by α-2 adrenergic receptors 36

6 Graph showing age distribution 75

7 Graph showing sex distribution 76

8 Graph showing body weight distribution 77

9 Graph showing body height distribution 78

10 Mean duration of surgery 80

xvi
 LIST OF FIGURES

Figure Title Page

No. No.

11 Graph showing mean time for onset of sensory block (minutes) 81

12 Graph showing maximum level of sensory blockade attained 82

13 Graph showing grade of motor blockade 83

14 Graph showing sedation score 84

15 Graph showing Duration of sensory and motor blockade (minutes) 85

16 Graph showing mean heart rate (bpm) at various time intervals 87

Graph showing systolic blood pressure (mmHg) at various time

17 89
intervals

Graph showing diastolic blood pressure (mmHg)at various time

18 91
intervals

Graph showing mean arterial pressure (mmHg) at various time

19 93
intervals

xvii
 LIST OF TABLES

Table Title Page

No. No.

1 Sedation scoring as per (Five point scale) 71

2 Age distribution 74

3 Sex Distribution between Group R and Group RD 76

4 Body Weight Distribution 77

5 Height distribution 78

6 Type of surgical procedure 79

7 Mean time for onset of sensory and motor block (minutes) 81

8 Maximum level of sensory blockade attained 82

9 Grade of motor blockade 83

10 Sedation score 84

11 Duration of sensory and motor blockade (minutes) 85

xviii
 LIST OF TABLES

Table Title Page

No.
No.

12 Mean heart rate (bpm) at various time intervals 86

13 Mean systolic blood pressure (mmHg) at various intervals 88

14 Mean diastolic blood pressure (mmHg) at various time intervals 90

15 Mean mean arterial pressure (mmHg) at various time intervals 92

Chemical and physical properties of ropivacaine and

16 95
dexmedetomidine

17 Results obtained in the present study 104

xix
 INTRODUCTION

Regional anaesthesia has lot of advantages compared to general anaesthesia

for lower abdominal and lower limb surgeries. The advantages are1

1. Awake patient

2. Polypharmacy avoided

3. No airway manipulation

4. Good motor and sensory blockade

5. Early food intake by the patient

6. Less incidence of post operative nausea and vomiting

7. Prolonged postoperative analgesia

8. Ideal operating conditions can be met

Intrathecal anaesthesia and epidural anaesthesia are the most popular regional

anaesthesia techniques used for lower abdominal and lower limb surgeries. Intrathecal

anaesthesia also called as sub arachnoid block has few limitations1 like, short duration

of anaesthesia, extension of anaesthesia cannot be made for prolonged surgeries, rapid

onset of sympathetic blockade, shorter duration of post operative analgesia and

troublesome complication of postdural puncture headache (PDPH). Hence epidural

anaesthesia is the most preferred anaesthetic technique for lower abdominal and lower

limb surgeries these days.

1
 The advantages of epidural anaesthesia being it2,

1. Provides effective surgical anaesthesia and can meet the extended duration of

surgical needs.

2. Provides prolonged post operative analgesia.

3. Reduces the incidence of hemodynamic changes as a result of sympathetic

blockade as it produces segmental anaesthesia unlike subarachnoid block

anaesthesia.

4. There is no incidence of PDPH as the dura is not pierced.

Different local anaesthetics are used for epidural anaesthesia3, most popular in

India being Lidocaine and Bupivacaine. The drawback of lidocaine is its intermediate

duration of action and the drawback of bupivacaine though long acting, is increased

incidence of fatal cardiac toxicity after accidental intravascular injection, because of

narrow cardiovascular collapse/central nervous system toxicity (cc/cns)4. For this

reason there has been a search for alternative drugs with desirable blocking properties

of bupivacaine but with a greater margin of safety. Ropivacaine and levobupivacaine

are the newer long acting amide local anaesthetics which have a wide margin of safety

compared to bupivacaine, with all its advantages4.

Recently Ropivacaine has been introduced and since Ropivacaine has all the

advantages of bupivacaine with less cardiac toxicity5, it appears that it may be an

ideal local anaesthetic for epidural anaesthesia. Various studies have found,

Ropivacaine to be an effective local anaesthetic for epidural anaesthesia6,7,8,9, Richard

Aurthur et al10.in their comparative pharmacokinetics of bupivacaine and ropivacaine

have found that when applied directly to an isolated vagus nerve preparation,

ropivacaine was less potent than bupivacaine in terms of conduction blocks of Aβ

fibers, but ropivacaine blocked Aδ and C fibers to a greater extent than did

2
bupivacaine. It is also been found that, lipid solubility of Ropivacaine is 2.9 compared

with 3.9 of bupivacaine11. Hence in our study ropivacaine was selected as the study

drug.

The fear of surgery, the strange surroundings of the operation theatre, the sight

and sound of sophisticated equipment, dynamicity of an operation during regional

anaesthesia and the masked faces of so many strange personale makes the patient

panic to any extent. The intense sensory and motor block, continuous supine position

for a prolonged duration and the inability to move the body during regional

anaesthesia brings a feeling of discomfort and phobia in many of the patients12.

The high cephalic spread of analgesia with local anaesthetics may be

significant but still its quality sometimes may not correlate with the level of sensory

analgesia. At this stage, the impulsive use of large doses of sedation or even general

anaesthesia with mask, defeats the novel purpose of regional anaesthesia ,whereby a

continuous verbal contact with the patient is lost12.

Sedation, stable haemodynamics and an ability to provide smooth and

prolonged post-operative analgesia are the main desirable qualities of an adjuvant in

neuraxial anaesthesia.

α-2 adrenergic agonists have both analgesic and sedative properties when used

as an adjuvant in regional anaesthesia. Dexmedetomidine is a highly selective α2

adrenergic agonist with an affinity of eight times greater than clonidine. Various

studies have shown that the dose of clonidine is 1.5 – 2 times higher than

dexmedetomidine when used in epidural route. The anaesthetic and the analgesic

requirement get reduced to a huge extent by the use of dexmedetomidine because of

its analgesic properties and augmentation of local anaesthetic effects as they cause

hyperpolarisation of nerve tissues by altering transmembrane potential and ion

3
conductance at locus coeruleus in the brainstem12. The stable haemodynamics and the

decreased oxygen demand due to enhanced sympathoadrenal stability make it a very

useful pharmacologic agent.

Hence it would be ideal to compare 0.75% ropivacaine with dexmedetomidine

and 0.75% ropivacaine alone in lower abdominal and lower limb surgeries.

Hence a study was undertaken to compare 0.75% ropivacaine with

dexmedetomidine and 0.75% ropivacaine alone in lower abdominal and lower limb

surgeries.

4
 OBJECTIVES

To study the synergistic effect of adding dexmedetomidine to ropivacaine 0.75%

in epidural anaesthesia for lower abdominal and lower limb surgeries, regarding

1. Onset and duration of sensory blockade

2.Onset and duration of motor blockade

3.Haemodynamic changes

4.Maximum dermatomal level of analgesia

5.Intensity of motor blockade

6.Sedation

7.Any adverse effects

5
 APPLIED ANATOMY

Epidural blockade is becoming one of the most useful and versatile procedures

in modern anaesthesiology. It is unique in that, it can be placed at virtually any level

of the spine, allowing more flexibility in its application to clinical practice.13

Anatomy

The key to safe and effective administration of an epidural blockade begins

with a thorough understanding of the anatomy of the vertebral column, ligaments and

blood supply, the epidural space, spinal canal and associated structures.13

The vertebral column consists of 7 cervical, 12 thoracic and 5 lumbar

vertebrae. At the caudal end, the 5 sacral vertebrae are fused to form the sacrum, and

the 4 coccygeal vertebrae are fused to form the coccyx.13

The normal spinal column is straight when viewed dorsally or ventrally. When

viewed from the side, there are two ventrally convex curvatures in the cervical and

lumbar regions, giving the spinal column the appearance of double C.13

Figure 1: Vertebral column, in lateral view (left) and posterior view (right),
illustrating curvatures, lumbar interlaminar spaces and sacral hiatus

6
Structure of the vertebrae14

Each vertebra is composed of a vertebral body and a bony arch.

Body:It is the mass of the bone through which the weight of the subject is transmitted.

Figure 2: Components of a lumbar vertebra

Vertebral arch: surrounds and protects the spinal cord lying in the vertebral foramen.

The arch comprises of pedicles, lamina and spinous process.

Pedicles are notched. The notches of the adjacent vertebrae pair together to

form an intervertebral foramen through which the spinal nerves emerge on each side.

Lamina carries a transverse process, superior and inferior articular processes which

bear the artificial facets on each side.

Spinous process project backwards from the centre of the neural arch and

forms an important palpable land mark for the anaesthesiologist.

Spinous process of the cervical vertebrae14

The spinous process of the cervical vertebrae is short and bifid [with exception

of C1 and C7] and is directed almost horizontally to the body of the vertebra.

7
Spinous process of the thoracic vertebra

The spinous process of the thoracic vertebra is long and is inclined at an angle

of 45 to 60 degree to the body of the vertebra and the skin. So the needle should be

directed at an angle of 45-60°cranially, to follow the upper border of the spine to enter

the ligamentum flavum.

Spinous process of lumbar vertebra

The spinous process of the lumbar vertebra is directed horizontally backwards

virtually 90o to the body of the vertebra and the skin. So the needle is to be directed

perpendicular to the skin.

Intervertebral disc

These are the connecting links between the vertebral bodies and they account

25% of the length of spine. Each disc adheres above and below to the hyaline

cartilage which covers the facet of adjacent vertebral body in front and behind and

also attached to the anterior and posterior longitudinal ligaments.

Joints of the vertebral column13

The vertebrae articulate at the intervertebral and facet joints. The

intervertebral joints are located between adjacent vertebral bodies. They maintain the

strength of attachment between vertebrae. The facet joints are formed betweenthe

articular processes.

Ligaments1

The vertebrae are joined together by a series of ligaments and discs. Slight

movement, flexion, extension and rotation are duly possible between the adjacent

vertebrae but the individual joint movements summate and produce the marked

flexibility of vertebral column. The vertebral column is bound together by several

ligaments which give it stability and elasticity.

8
Figure 3: Ligaments of the lumbar vertebral column, shown in lateral view (A)
and sagittal section (B)

Supraspinous ligament

It is a strong fibrous cord that connects the apices of the spinous processes

from the sacrum to C7, where it is continued as ligamentum nuche. It is thickest and

broadest in the lumbar region and varies with patient age, sex and body built.

Interspinous ligament

It is a thin membranous ligament that connects the spinous processes blending

anteriorly with the ligamentum flavum and posteriorly with the supraspinous

ligaments. Like supraspinous ligaments, the interspinous ligaments are thickest and

broadest in the lumbar region.

Ligamentum flavum1

It comprises of yellow elastic fibers and connects adjacent laminae that run

from the caudal edge of vertebra above to the cephalad edge of the lamina below.

Laterally, this ligament begins at the roots of the articular processes and extends

posteriorly and medially to the point where the laminae join to form the spinous

process. Hence the two components of the ligament are limited, thus covering the

interlaminar space. Because of its elasticity and its thickness of several millimeters in

9
the lumbar region, the ligaments impart a characteristic ‘springy’ resistance,

particularly to large bore needle with an upturned end [tuohy needle].

The ligament thickness, distance to dura and skin to dura distance vary with

the area of vertebral canal.

Characteristics of ligamentum flavum at different vertebral level3

Site Thickness of ligament (mm)
Cervical 1.5 – 3.0
Thoracic 3.0 – 5.0
Lumbar 5.0 – 6.0
Caudal 2.0 – 6.0

Longitudinal ligament

Anterior and posterior longitudinal ligaments bind vertebral bodies together.

Epidural space1

Figure 4: Boundaries of the epidural space

10
Figure 4: Boundaries of the epidural space

11
 It is the space that lies between the spinal meninges and the sides of the

vertebral canal. It extends from the foramen magnum where the dura is fused to the

base of the skull, to the sacral hiatus, which is covered by sacrococcegeal ligament. It

is bounded anteriorly by the posterior longitudinal ligament, laterally the pedicles and

the intervertebral foramina and posteriorly by the ligamentum flavum and anterior

surface of lamina. The anterior epidural space is very narrow because of the proximity

of the dura and the anterior surface of the vertebral canal. The epidural space is widest

posteriorly and varies with the vertebral level ranging from 1 to 1.5 mm at C5 to 2.5

to 3 mm at T6 to its widest point 5 to 6 mm at the level of L2.

It is a space filled with fat, areolar tissue, lymphatics, veins and nerve roots

that traverse it but no free fluid. Thus it is a potential space.The epidural space is rich

in blood vessels, including Batsons venous plexus. Batsons plexus is continuous with

the iliac vessels in the pelvis and the azygous system in the abdominal and thoracic

body walls. Because this plexus has no valves, blood from any of the connected

system can flow into the epidural vessels and connect with intracranial veins. This is a

potential direct route to brain for drugs, air or other material inadvertently injected

into an epidural vein. Within the cranium, there is no epidural space as the meningeal

dura and the endosteal dura are closely adherent, except where they separate to form

the venous sinuses.

Epidural fat1

Is semifluid lobulated areolar tissue extends throughout the spinal and caudal

epidural space. It is most abundant posteriorly, diminishes adjacent to the articular

processes, and increase laterally around spinal nerve roots, where it is continuous with

the fat surrounding the spinal nerves in the intervertebral foramina and hence with the

fat in the paraveretebral space. Overall the amount of fat in the epidural space tends to

12
vary in direct relation to that present else where in the body, so that obese patients

may have epidural spaces that are occupied by generous amount of fat. The fat itself

has a great affinity for drugs with high lipid solubility, which may remain in epidural

fat for longer periods. Uptake of local anaesthetics in to epidural fat competes with

vascular and neural uptake.

Epidural veins1

The large valveless epidural veins are part of the internal vertebral venous

plexus, which drains the neural tissue of the cord, the CSF and the bony spinal canal.

The major portion of this plexus lies in the anterolateral part of the epidural space, out

of reach of a correctly placed epidural needle.

The plexus has rich segmental connections at all levels with in the

intervertebral foramina and the epidural space and within the body of the vertebrae.

Superiorly, the plexus communicates with the occipital, sigmoid and basilar venous

sinuses within the cranium. Inferiorly, anastomosis by way of the sacral venous

plexus links the vertebral plexus to uterine and iliac veins.

By way of intervertebral foramina at each level, the vertebral plexus

communicates with the thoracic and abdominal veins, so that pressure changes in

these cavities are transmitted to epidural veins but not to the supporting bony

elements of the neural arch and vertebral bodies.

Thus, marked increase in intra abdominal pressure may compress the inferior

vena cava while distending the epidural veins, increasing flow upto the

vertebrobasilar plexus. This increased flow is accommodated mostly by means of the

azygous vein, which ascends in the right chest over the root of right lung into the

superior vena cava.

13
 Distension of epidural veins, owing to direct inferior vena cava obstruction [eg

by the gravid uterus] or owing to increased thoracic and abdominal pressure, will also

diminish the effective volume of the epidural space, with the result that injected local

anaesthetic spread more widely up and down the epidural space.

Three important aspects of safety include:

1. The epidural needle should pierce the ligamentum flavum in the midline to avoid

the laterally placed epidural veins.

2. Insertion of epidural needles or catheters or injections of local anaesthetics should

be avoided during episodes of marked increase in size of epidural veins, such as

that which occur with increased thoraco abdominal pressure during straining.

3. The presence of venacaval obstruction calls for a reduction in dose, a decrease rate

of injection and increased care in aspirating of blood before epidural injection.

Spinal arteries1

It is of significance to epidural block that the spinal branches of the

subclavian, aortic and iliac arteries cross the epidural space and enters the epidural

space in the region of the dural cuffs. The anterior spinal artery territory supplying the

anterior horn or motor area of the spinal cord is most vulnerable.

Epidural lymphatics1

The dural cuff region is supplied with rich lymphatic network that rapidly

conveys debris from arachnoid villi out through intervertebral foramina to reach

lymph channels in front of the vertebral bodies.

Duralsac

Containing dura, arachnoid, spinal fluid, pia, spinal nerves and spinal cord is

contained with in the annular epidural space.

14
Dura15

Dura mater is the outermost and the thickest meningeal tissue. The spinal dura

mater begins at the foramen magnum where it fuses with the periosteum of the skull

forming the cephalad border of the epidural space. Caudally dura mater ends at

approximately S2, where it fuses with the filumterminale. The dura mater extends

laterally along the spinal nerve roots and becomes, continuous with the connective

tissue of the epineurium at approximately the level of the intervertebral foramina. The

dura mater is largely acellular except for a layer of cells that form the border between

the dura and arachnoid mater. The inner edge of the dura mater is highly vascular

which likely results in the dura mater being an important route of drug clearance from

both the epidural space and the sub arachnoid space.

The inner surface of the dura mater abuts the arachnoid mater. There is a

potential space between these two membranes called subdural space. Occasionally it

is possible to inadvertently insert an epidural catheter into the subdural space.

Arachnoid mater15

The arachnoid mater is a delicate, avascular membrane. In the region where

the spinal nerve roots traverse the dura and arachnoid membranes, the arachnoid

mater herniates through the dura mater into the epidural space to form arachnoid

granulations. The granulations serve as sites for material in the subarachnoid space to

exit the central nervous system.

Epidural pressure

In the lumbar region, the major cause of generation of a negative pressure lies

in coning of the dura by the advancing needle point. Negative pressure increases as

the needle advances across the epidural space towards the dura. Blunt needles with

side openings produce the greatest negative pressure; they produce a good coining

15
effect on the dura without puncturing it and transmit the negative pressure well

because of their side opening.

Slow introduction of the needle produces the greatest negative pressure.

Greatest negative pressure can be obtained if the dura is not distended [eg. By gravity

in sitting position or by high abdominal or thoracic pressure]. In pregnancy, the

epidural space may well have a positive pressure. Hence hanging drop technique may

not be reliable in pregnant women to identify the epidural space.

Detection of epidural space2

The methods for identification of the epidural space take the advantage of

either the potential negative pressure or the sudden loss of resistance when the needle

tip penetrates the tough ligamentum flavum.

Negative pressure techniques

1. Hanging drop technique of Gutierrez

2. Odom capillary tube method

3. Manometer method

Loss of resistance technique [described by Sicard, Forester and Dogliotti]

1. Syringe technique [using either normal saline or air]

2. Spring loaded syringe

3. Macintosh balloon technique

4. Brookes device

5. Vertical tube of dawkins

16
Factors affecting epidural blockade1

Many factors affect the efficacy, spread of blockade, fiber types blocked and

other aspects of epidural blockade.

Site of injection and nerve root size

Blockade tends to be most intense and has the most rapid onset close to the

site of injection. After lumbar epidural injection, there is a somewhat greater cranial

than caudal spread and there may be a delay in the L5 and S1 segments. The delay in

onset at these segments appears to be due to the large size of these nerve roots.1

Age

With advancing age, anatomic changes occur in the epidural space. In young

individual, the areolar tissue around the intervertebral foramina is soft and loose. In

elderly areolar tissue becomes dense and firm, partially sealing the intervertebral

foramina. With aging, the dura becomes more permeable to local anaesthetics because

of significant increase in the size of the arachnoid villi.

The onset time to maximal caudal spread decrease with advancing age

following epidural administration of bupivacaine. Bromage demonstrated that with

age the epidural segmental dose requirement decreases in a linear way. The technique

is technically difficult and hence there is always a chance of failure.1

Height and weight

The correlation between patient height or weight and spread of epidural block

is weak and of little clinical significance.

17
Position

Comparison of sitting and lateral positions for epidural block reveals no

significant difference in cephalad spread. Caudal spread of block in seated patients is

slightly favoured by the sitting position.1

Speed of injection

Increasing the speed of injection has no effect on bulk flow of solutions in the

epidural space. Also, spread of analgesia is only minimally influenced. However,

rapid injection of large volumes of solution may increase CSF pressure, decrease

spinal cord blood flow, increase intracranial pressure and pose a risk of spinal or

cerebral complications. Local anaesthetics should be injected into the epidural space

slowly and preferably in incremental doses.

Volume, concentration and doses of local anaesthetics15

Within the range typically used for surgical anaesthesia, drug concentration is

relatively unimportant in determining block spread. However, drug dose and volume

are important variables determining both spread and quality of epidural block.

Increasing the volume of local anaesthetics will result in significantly greater average

spread and greater block density, with regard to motor blockade, dosage becomes less

important when dilute solutions are used. Increasing the dosages results in a linear

increase in degree of sensory block and duration of epidural block, where as

increasing concentration results in a reduction in onset time and intensity of motor

blockade.

Local anaesthetics15

Choice of local anaesthetics is the most important determinant of the duration

of epidural block. Chloroprocaine is the shortest duration drug, Lidocaine and

Mepivacaine provides intermediate duration, and Bupivacaine, Ropivacaine and

18
Etidocaine provide the longest lasting epidural block. The differential capabilities of

local anaesthetics to block sensory and motor fibers have been referred to as ‘sensory

motor dissociation’.

Epinephrine16

Epinephrine in a concentration of 5µg/ml [1:200000] is the most common

adrenergic agonist added to epidural local anaesthetics. It has been shown to prolong

the duration of lidocaine and mepivacaine epidural block by as much as 80%.

Vasoconstrictors have been assumed to prolong block by producing local

vasoconstriction and thus decreased local anesthetic clearance from the epidural

space. Prolongation of motor and sensory block may be due in part to direct inhibitory

effects of epinephrine on sensory and motor neurons. Epinephrine does not

significantly prolong the duration of anaesthesia when added to concentrated solutions

of bupivacaine or ropivacaine.

Number and frequency of local anaesthetics injections1

Whether augmentation or diminution of neural blockade occurs after repeated

epidural injection of local anaesthetics depends on the local anaesthetic agent, the

number of injection and timing between injections.

Tachyphylaxis has been most clearly demonstrated in association with

continuous epidural block in patients in whom repeated injections of the short acting

amides – lidocaine, prilocaine or mepivacaine are used. The mechanism of

tachyphylaxis is not known. It may be partly explained by pH changes in spinal fluid

with repeated injections.

19
 PHYSIOLOGICAL EFFECTS OF EPIDURAL BLOCKADE1

With currently available local anaesthetic agents, spinal epidural neural

blockade implies sympathetic blockade accompanied by somatic blockade, which

may involve sensory and motor blockade alone or in combination. Some of the most

important (but not all) of physiological effects of epidural blockade can be discussed

in relation to either sympathetic blockade only of vasoconstrictor fibers (below T4)

and or of cardiac sympathetic fibers.

Zone of differential blockade15

Sensory

In intradural block sympathetic fibers are blockade two or three segments

higher than sensory fibers. In extradural block, the relationship is complex. Level of

sympathetic block is the same as (or lower than) sensory with epidural blockade.

Sympathetic block will be greater when more concentrated solutions are used or when

adrenaline added, as this has similar effect.

Motor

In intradural block, the difference between sensory and motor block is slight

(two segments). In extradural block, the difference in levels is greater, depending very

much on nature of local analgesic solution.

All types of nerve fibers are affected by local anaesthetics, but with in any one

fiber type, there is tendency for small, slower conducting fibers to be more readily

blocked than large, fast conducting fibers. Between fiber types however, these rules

do not hold good. Myelinated preganglionic B fibers which have a faster conduction

time are about three times more sensitive to local anaesthetics than the slower non-

myelinated post ganglionic C fibers.

20
 Sensory Aα fibers appear to be more sensitive to blockade than motor Aβ

fibers, although of the same conduction velocity, This may be because sensory fibers

conduct at a higher frequency. It has been suggested that this selectivity for sensory

fibers exhibited by Bupivacaine and Ropivacaine is a function of frequency dependent

block, a property not shared by Etidocaine and Amethocaine.

Cardiovascular System15

There are different ways in which intra and extradural spinal block can

influence the cardiovascular system.

1. Vasodilatation of resistance and capacitance vessels. Block of cardiac efferent

sympathetic fibers from T1 and T4 resulting in loss of chronotropic and Inotropic

drive and fall in cardiac output.

2. The arterial or Bainbridge reflex causing-bradycardia.

3. The operation of Marey’s law causing tachycardia.

4. Depression of vascular smooth muscle and β adrenergic blockade of myocardium

with fall in cardiac output.

5. Adrenaline effect (if used) following absorption, resulting in β stimulation and

associated rise in cardiac output and reduction in peripheral resistance.

The overall effect is likely to be greater fall in mean arterial pressure than if

adrenaline had not been used. Block not extending above T4 is not always associated

with fall of blood pressure in fit young adults although the elderly many suffer

significant hypotension when moderate volumes are injected into the epidural space.

Corrective measures may be considered if arterial pressure falls more than 1/3 below

its pre-operative level.

Slowing of heart rate is caused if any of the anterior roots carrying

sympathetic cardiac accelerator fibers are blocked, as may happen in higher spinal

21
blockade above T4, T5. A further cause of slow pulse rate is the lowering of blood

pressure in the right atrium consequent on diminished venous return [Bainbridge

(1874-1921) effect]. On the other hand, Tachycardia during spinal analgesia may

result from the operation of Marey’s Law (a pulse of low tension is fast). Bradycardia

is the more frequent effect.

Theories of causation of fall in blood pressure

1. Diminished cardiac output consequent on reduction of venous return to heart, and

lack of muscular propulsive force on veins.

2. Dilatation of post arteriolar capillaries and small venules due to paralysis of

vasoconstrictors, compensatory vasoconstriction takes place in areas not

anaesthetized via carotid sinus reflexes. In high spinal blocks, majority of

vasoconstrictor fibers including those to arm [T2-T10], are paralyzed, hence low

blood pressure. Total peripheral resistance decreases by only 18% following

complete sympathetic block in healthy young adults.

3. Paralysis of sympathetic nerve supply to heart T1-T4. Bradycardia may give rise

to fall in cardiac output.

4. Paralysis of sympathetic nerve supply to adrenal glands splanchnic nerves, with

consequent catecholamine depletion

5. Absorption of drug into circulation. This is more likely to be a cause of

hypotension after extradural than after intradural analgesia because of the large

amount of analgesic drug injected.

6. Ischemia and hypoxia of vital centers

7. Hypovolemia, if present, may give rise to fall in blood pressure if central neural

blockade is employed.

22
8. Compression of great vessels within abdomen, by the pregnant uterus, abdominal

tumours or abdominal packs may cause severe hypotension in presence of central

neural blockade.

Respiratory system15

The phrenic nerve supplying diaphragm arises from the anterior roots of C3,

C4, C5 and should not be encroached on in spinal anaesthesia, but phrenic nerve

paralysis can occur.

Apnoea may be due to medullary ischemia or to a toxic effect of the drug- in

extradural blocks. During spinal analgesia breathing becomes quite and tranquil. This

is not only due to motor blockade, but also to differentiation with reduction of sensory

input to respiratory centre.

Lowered arterial and venous tone also lessens the work of heart and tends to

relieve any pre existing pulmonary congestion. The ventilation perfusion during

extradural block is not greatly altered and effects on respiratory functions are

relatively small with no evidence on FRC or V/Q ratio. The pulmonary gas exchange

is preserved.

The effect of block is largely on cardiovascular system. Vital capacity and

force expiratory volume may be reduced, especially in cigarette smokers. Intercostals

muscle paralysis is compensated for by descent of diaphragm, which is made easier

the by the lax abdominal walls. This not accompanied by hypoxia and hypercapnia

although the ability to cough forcibly to expel secretion is impaired.

The patient may stop breathing so that respiratory support by IPPV and, if

necessary the tracheal intubation required. Causes may be:

• Inadequate medullary blood flow due to inadequate cardiac output-a serious

situation demanding immediate cardiorespiratory support.

23
• Total spinal analgesia with denervation of all respiratory muscles. True phrenic

nerve paralysis is uncommon because all motor roots are large and analgesic

solution is likely to be weak when it reaches the cervical region.

• Massive epidural spread.

• Accidental subdural injection

• Toxic effects of local anaesthetic drug.

• Injecting narcotic analgesic drugs

Gastrointestinal system15

Preganglionic sympathetic fibers from T5 to L1 are inhibitory to gut, there is

no effect on oesophagus, the innervations of which is vagus. The small gut is

contracted as the sympathetic inhibitory impulses are removed, the vagus being all

powerful, Sphincters are relaxed and peristalsis is active although not more frequent.

Pressure within the bowel lumen is increased.

Nausea and vomiting due to the hypotension may occur and usually come on

in waves-lasting a minute or so and then passing away spontaneously.

Stimuli arising in the upper abdomen may ascend along the unblocked vagi

and perhaps the phrenic nerve, and cause discomfort, if the patient is conscious.

Infiltration of local anesthetic solutions may prevent this by blocking vagal afferents.

Colonic blood supply and oxygen availability are increased, perhaps an important

factor in the prevention of anastomotic breakdown following gut resection.

Theories of causation of nausea and vomiting:

1. Hypotension, correction using a pressor drug may relieve nausea

2. Increased peristalsis

3. Traction on nerve endings and plexuses, especially via vagus

4. Presence of bile in stomach due to relaxation of pyloric and bile-duct sphincters

24
5. Narcotic analgesics (premedication)

6. Psychological factors

7. Hypoxia

Gastric emptying time is quicker when extradural block is employed for

postoperative pain relief than when narcotic analgesics are used.

Liver15

There are no specific effects of significance. The degree of hypotension that

compromises liver function is not known. Liver disease may interfere with the

metabolism of local anaesthetic drugs.

Endocrine system

The usual increase of ADH during surgery is suppressed. Spinal block delays

adrenal response to trauma, whereas operations under general anaesthesia cause a rise

in steroids.

In any case, either regional or general, there is no difference in the

postoperative period once the effects of the block are discontinued. Spinal block

suppresses the hyperglycemic response to surgery and stress and so is useful in

diabetic patients but this does not extend into postoperative period. The response to

insulin is augmented and anaesthetist should be aware of possibility of hypoglycemia.

Extradural block prevents lymphopenia and granulocytosis after operation,

thus inhibiting the metabolic endocrine response to surgery and preventing immune

depression.

Genitor urinary system

Sympathetic supply of kidney is from T11 to L1 via the lowest splanchnic

nerves. Any effects on renal function are due to hypotension. Auto regulation of renal

blood flow is impaired if mean arterial pressure falls below 50 mmHg. These changes

25
are transient and disappear when blood pressure rises again. Sphincters of bladder are

not relaxed, so soiling of table by urine is not seen and tone of ureters is not greatly

altered. The penis is often engorged and flaccid due to paralysis of the Nervi erigentes

[S2 and S3]. This is a useful positive sign of successful block. Post spinal retention of

urine may be moderately prolonged as L2 and L3 contain small autonomic fibers and

their paralysis lasts longer than of the larger sensory and motor fibers.

Body temperature

Vasodilatation favors heat loss. Absence of sweating favors hyperpyrexia in

hot environments. Catecholamine secretion is depressed, hence less heat is produced

by metabolism.

Extradural space is a temperature sensitive zone, whereas intradural space is

not.

Cold solutions injected into extradural space may induce shivering

1. Because the large veins act as exchangers.

2. As a result of sensory input.

3. Possibly because of the existence of thermal sensors.

26
 PHARMACOLOGY OF ROPIVACAINE16, 17, 18

Ropivacaine is a long acting local anaesthetic that is structurally related to

bupivacaine, unlike bupivacaine which is racemate, Ropivacaine is a pure S (-)

enantiomer developed for the purpose of reducing the potential toxicity and

improving the relative sensory and motor block profiles.

Chemical structure

It is a monohydrate of hydrochloride salt of 1-propyl-2’, 6’-pipecoloxylidide.17

Ropivacaine is a long acting amide local anaesthetic agent belonging to the

pipecoloxylidine group.

Physiochemical properties4

Molecular weight – 328.89

274 (base)

Pka – 8.1

Plasma protein binding – 94%

Lipid solubility – 2.9

Structural formula17

27
Mechanism of action

Like other local anaesthetics, ropivacaine elicits nerve block via reversible

inhibition of sodium ion influx in nerve fibers. This action is potentiated by dose

dependent inhibition of potassium channels.18 Ropivacaine is less lipophilic than

bupivacaine and is less likely to penetrate large myelinated motor fibers, therefore it

has selective action on the pain transmitting Aδ and C nerves rather than Aβ fibers,

which are involved in motor function.16

Pharmacodynamics

CNS and cardiovascular effects18

As with other local anaesthetics, Ropivacaine has the potential to induce CNS

and cardiovascular toxicity at high plasma concentrations such as those occurring

after large doses or inadvertent intravascular administration.

Ropivacaine is less lipophilic than bupivacaine and that, together with its

stereo selective properties, contributes to ropivacaine having a significantly higher

threshold for cardiovascular and CNS toxicity than bupivacaine in animals and

healthy volunteers. The lower lipophilicity of ropivacaine versus bupivacaine

correlated with the lesser cardio depressant effects of both ropivacaine isomers than of

the bupivacaine isomer in animal studies.

The CNS effects occurred earlier than cardiotoxic symptoms during an

intravenous infusion of local anaesthetic (10 mg of Ropivacaine and bupivacaine) in

human volunteers and the infusion was stopped at this point. Significant changes in

cardiac function involving the contractility, conduction time and QRS width was

found to be significantly smaller with Ropivacaine than with bupivacaine.

28
Other effects18

Ropivacaine has been shown to inhibit platelet aggregation at concentrations

of 3.75 and 1.88 mg/ml, which corresponds to those which could occur in the epidural

space during infusion. Like other anaesthetics, Ropivacaine has antibacterial activity

in vitro, inhibiting the growth of Staphylococcus aureus, Escherichia coli and

Pseudomonas aerugenosa.

Pharmacokinetic properties

Absorption and distribution18

The plasma concentration of Ropivacaine depends on the total dose

administered and the route of administration, as well as the hemodynamic/circulatory

condition of the patient and the vascularity of the administration site.

When Ropivacaine is administered intravenously, its pharmacokinetics were

linear and dose proportional upto 80 mg. Ropivacaine from epidural space shows

complete and biphasic absorption. The half life of the initial phase is approximately

14 min followed by a slower phase with a mean absorption t1/2 of approximately 4.2

hrs.

Ropivacaine is bound to plasma proteins to an extent of 94%, mainly to α1–

acid glycoprotein. [The total plasma concentration increase during continuous

epidural infusion of Ropivacaine is caused by an increase in the degree of protein

binding and subsequent decrease in the clearance of Ropivacaine.] Ropivacaine

readily crosses the placenta during epidural administration for cesarean section.

After intravascular administration, volume of distribution of Ropivacaine at

steady state was 41L. The administration of epinephrine with Ropivacaine may

29
improve analgesia by reducing vascular uptake of local anaesthetics and by a direct

agonist effect on spinal α2 receptors.

Metabolism and elimination16

Ropivacaine is metabolized extensively in the liver, predominantly by

aromatic hydroxylation to 3’-hydroxy Ropivacaine by cytochrome P450 (CYP) 1A2

and N-dealkylation to 2’6’-pipecoloxylidide by CYP3A4. The kidney is the main

excretory organ for Ropivacaine, accounting for 86% of the excretion of the drug in

the urine after a single intravenous dose administration. It has a mean ± SD terminal

half life of 1.8 ± 0.7 hrs and 4.2 ± 1.0 hrs after intravenous and epidural

administration respectively.

Relative potency16

A strict correlation exists between the lipid solubility of the local anaesthetic

and its potency and toxicity. According to minimum local anaesthetic concentration

studies, Ropivacaine has similar potency to bupivacaine at higher doses, Ropivacaine

is less potent than bupivacaine at lower doses such as those used for epidural or

Intrathecal analgesia.

Tolerability16

In adults

Ropivacaine is generally well tolerated regardless of the route of

administration. In a pooled analysis of data from controlled clinical trials, adverse

events that occurred in ≥ 5% of patients who received Ropivacaine 0.125%-1% via

various routes of administration for surgery, labour, cesarean section, post operative

pain management, peripheral nerve block or infiltration were hypotension (32%),

30
nausea (17%), vomiting (7%), bradycardia (6%) and headache (5%). Epidural

administration of ropivacaine for surgery generally produced dose dependent adverse

events similar to those observed with equal doses of bupivacaine.

The incidence of Ropivacaine induced cardiovascular symptoms may be age

related; patient’s aged ≥ 61 years who received epidural ropivacaine 1% had a

significantly higher incidence of bradycardia and hypotension.

In children

Ropivacaine is generally well tolerated in pediatric patients aged from 1

month to 15 years regardless of the route of administration. The overall incidence of

adverse events associated with Ropivacaine appeared to be low, with nausea and

vomiting occurring more frequently.

In exposed fetuses and neonates

Ropivacaine is generally well tolerated in the foetus and neonate following the

use of regional anaesthesia in women undergoing caesarean section or during labour.

The most common fetal and neonatal adverse event with Ropivacaine were fetal

bradycardia, neonatal jaundice and unspecified neonatal complications.

Drug interaction16
Ropivacaine should be used with caution in patients receiving other local

anaesthetics or agents structurally related to amide type local anaesthetics, since the

toxic effect of these drugs are additive.

Cytochrome P4501A2 metabolizes ropivacaine to 3-hydroxy Ropivacaine, the

major metabolite. Thus strong inhibitors of cytochrome P4501A2, such as

fluvoxamine given concomitantly during administration of ropivacaine can interact

with ropivacaine and thus lead to increased Ropivacaine plasma levels. Possible

31
interactions with drugs known to be metabolized by CYP1A2 via competitive

inhibition such as theophylline and imipramine may also occur.

Dosage16

The dose of Ropivacaine varies with the anaesthetic procedure, the area to be

anaesthetized, the vascularity of the tissue, the number of neuronal segments to be

blocked, the depth of anaesthesia and degree of muscle relaxation, individual

tolerance and physical condition of the patient.

Clinical applications

Numerous clinical trials have evaluated the efficacy of Ropivacaine for

surgical anaesthesia, for labour pain and post operative pain in adults and children

Surgical anaesthesia

Clinical trials indicate that Ropivacaine is an effective regional anaesthetic

when administered via several routes.

Epidural administration

Epidural Ropivacaine, administered primarily in the lumbar region, has an

effect of anaesthetic for a number of surgical procedures.

a. Cesarean section

Clinical trials indicate that Ropivacaine (0.5%-0.75%) provides a clinically

similar onset of sensory and motor block to that of bupivacaine 0.5%.

b. Hip or lower limb surgery

In patients undergoing lumbar epidural anaesthesia for lower limb surgeries,

Ropivacaine provided a similar anaesthetic profile with regard to onset of analgesia or

anaesthesia and onset of motor block to those of bupivacaine or levobupivacaine.

32
Intrathecal administration
Single doses of 2-4 ml of 0.5% -2% solutions of Ropivacaine have been

shown to be less potent than bupivacaine when administered intrathecally.

Peripheral nerve blocks

Peripheral nerve blocks are employed for anaesthesia for orthopaedic surgery,

and the onset and spread of local anaesthetic is influenced by the site of injection. The

long acting sensory and motor block provided by Ropivacaine 0.5% or 0.75% for

axillary, interscalene and subclavian perivascular brachial plexus block for hand or

arm surgery compared favourably with bupivacaine 0.5% with similar quality of

regional anaesthesia. In lower limb surgeries where sciatic or combined femoral and

sciatic block was given, Ropivacaine 0.75% had significantly faster onset of sensory

and motor block than 0.5% bupivacaine. Although Ropivacaine had a significantly

shorter duration of sensory block, the duration of motor block remained similar with

both agents.

Management of postoperative pain

Lower doses of local anaesthetics are generally required for postoperative

pain relief than for anaesthesia. Post operative pain relief can be provided by

Epidural administration

Peripheral nerve blocks

Local infiltration, instillation and intra articular administration

Management of labour pain

Epidurally administered Ropivacaine is effective in providing relief from

labour pain. Analgesic efficacy of Ropivacaine is similar or slightly less than

bupivacaine.

33
 Intrathecally administered Ropivacaine as a part of combined spinal epidural

technique produces rapid and effective labour pain relief with less incidence of motor

block.

Thus Ropivacaine with its efficacy, lower propensity for motor block, and

reduced potential for CNS toxicity and cardiotoxicity, appears to be an important

option for regional anaesthesia and postoperative and labour pain.

34
 PHARMACOLOGY OF DEXMEDETOMIDINE

Dexmedetomidine hydrochloride, an imidazole compound is the pharmacologically

active s-enantiomer of medetomidine, a veterinary anaesthetic agent. It is described

chemically as (+)-4-(s)[2 3–(dimethylphenyl) ethyl]-11 H-imidazole

monohyrochloride. Its empirical formula is C13H16N2HCl and its molecular weight is

236.7.19

Structural formula

Chemical structure of dexmedetomidine20

PHYSIOCHEMICAL PROPERTIES

A white or almost white powder that is freely soluble in water with Pka of 7.1.

Partition coefficient in octanol: water at pH 7.4 is 2.89.

Preservative free dexmedetomidine is available in o.5ml,1ml and 2 ml

ampoule as Dexmedetomidine Hydrochloride for intravenous use (Dexem,

Themis Medicare Ltd., 200 µg/ml).

It can also be used for intrathecal and epidural anaesthesia.

MECHANISM OF ACTION OF DEXMEDETOMIDINE

Dexmedetomidine is the dextro enantiomer of medetomidine, the methylated

derivative of etomidine, its specificity for the alpha-2 receptor is 8 times that of

clonidine, with an alpha-2:alpha-1 binding affinity ratio of 1620:1 and its effects are

35
dose dependently reversed by administration of a selective alpha-2 antagonist such as

atipamezole.21

Specific alpha-2 receptor subtypes mediate the varied pharmacodynamic

effects of Dexmedetomidine. Agonism at alpha 2A receptor appears to promote

sedation, hypnosis, analgesia, sympatholysis, neuroprotection22 and inhibition of

insulin secretion.23 Agonism at the alpha -2B receptor suppresses shivering centrally,

promotes analgesia at spinal cord sites and induces vasoconstriction in peripheral

arteries.The alpha 2C receptors are associated with modulation of cognition, sensory

processing, mood and stimulant-induced locomotor activity and regulation of

epinephrine outflow from the adrenal medulla. Inhibition of nor epinephrine release

appears to be equally affected by all three alpha-2 receptor subtypes.24

Figure 5: Responses that can be mediated by α-2 adrenergic receptors25

36
 The mechanism of action of Dexmedetomidine is unique and differs from

currently used sedative drugs. Alpha-2 adrenoceptors are found in CNS in highest

densities in the locus ceruleus, the predominant noradrenergic nuclei of the brainstem

and an important modulator of vigilance. Presynaptic activation of alpha-2A

adrenoceptor in the locus ceruleus inhibits the release of nor-epinephrine and results

in the sedative and hypnotic effects.26 In addition, the locus ceruleus is the site of

origin for the descending medullospinal nor adrenergic pathway, known to be an

important modulator of nociceptive neurotransmission. Stimulation of alpha-2

adrenoceptors in this area terminates the propagation of pain signals leading to

analgesia. Postsynaptic activation of alpha-2 receptors in the CNS results in decrease

in sympathetic activity leading to hypotension and bradycardia.27

At the spinal cord, stimulation of alpha-2 receptors at the substantia gelatinosa

of the dorsal horn leads to inhibition of the firing of nociceptive neurons and

inhibition of release of substance P. Also the alpha-2 adrenoceptors located at the

nerve endings have a possible role in the analgesic mechanism by preventing nor

epinephrine release. The spinal mechanism is the principal mechanism for the

analgesic action of Dexmedetomidine even though there is a clear evidence for both a

supraspinal and peripheral sites of action.28

PERIPHERAL ACTION: Alpha-2 receptors are located on blood vessels where

they mediate vasoconstriction and on sympathetic terminals, where they inhibit

norepinephrine release. The responses of activation of alpha-2 receptors in other areas

include contraction of vascular and other smooth muscles; decreased salivation and

decreased bowel motility in the gastrointestinal tract, inhibition of rennin release,

increased glomerular filtration and increased secretion of sodium and water in the

37
kidney, decreased release of insulin from the pancreas, decreased intraocular pressure,

decreased platelet aggregation and decreased shivering threshold by 2˚C.25

Pharmacodynamics of dexmedetomidine

Dexmedetomidine is considered as the full agonist at alpha-2 receptors

compared to clonidine which is considered as a partial agonist at alpha-2

adrenoceptors. The selectivity of Dexmedetomidine to alpha-2 receptors compared to

alpha-1 receptors is 1620:1, where as with clonidine it is 200:1. The selectivity is dose

dependant, at low to medium doses and on slow infusion, high levels of alpha-2

selectivity is observed, while high doses or rapid infusions of low doses are associated

with both alpha-1 and alpha-2 activities.25

Central nervous system

1. Sedation, anxiolysis, hypnosis and amnesia

Dexmedetomidine provides dose dependant increase in anxiolysis and

sedation. However, the quality of sedation appears to be unique in comparison with

gamma-aminobutyric acid (GABAnergic) agents such as midazolam or propofol.

Arousability is maintained at deep levels of sedation, with good correlation between

the level of sedation and the bispectral EEG (BIS). Once aroused subjects performed

well on tests of vigilance, such as the critical flicker-fusion frequency.

Dexmedetomidine induced sedation qualitatively resembles normal sleep.

Dexmedetomidine induces sleep by activating endogenous non-rapid eye movement

pathways. Stimulation of alpha-2A receptors in the nucleus ceruleus inhibits nor

adrenergic neurons and disinhibits GABAnergic neurons in the ventrolateral preoptic

nucleus (VLPO). In contrast, GABAnergic agents such as propofol or

benzodiazepines, directly enhance the inhibitory effects of the GABAnergic system at

38
the VLPO. As such norepinephrine release remains unaffected, thus leading to less

restful sleep.29

The participation of non-rapid eye movement sleep pathways seems to explain

why patients who appear to be deeply asleep from Dexmedetomidine are relatively

easily aroused in much the same way as occurs with natural sleep. This type of

sedation is branded “cooperative or arousable”, to distinguish it from sedation induced

by drugs acting on the GABA system, such as midazolam or propofol which produce

a clouding of consciousness.30 Sedation with Dexmedetomidine is dose dependant,

however even low doses might be sufficient to produce sedation.31 Dexmedetomidine

may lack amnestic properties but amnesia is achieved with dexmedetomidine only at

high plasma levels (>1.9 ng/ml) without retrograde amnesia.32

2. Analgesia

Dexmedetomidine appears to exert analgesic effects at the spinal cord level

and at supraspinal sites. However there has been a considerable debate as to whether

its analgesic effects are primary or simply opioid sparing. In comparison with

hypnotic agents such as propofol or postoperative opioids used alone,

Dexmedetomidine significantly decreases opioid requirement.33,34

Dexmedetomidine may also provide antinociception through nonspinal

mechanisms. Intra-articular administration during knee surgery improves

postoperative analgesia, with less sedation than IV route.35 Suggested mechanisms are

activation of alpha-2A receptors, inhibition of the conduction of nerve signals through

C and Aδ fibres and the local release of encephalin.36

Respiratory effects

Dexmedetomidine is able to achieve its sedative, hypnotic and analgesic

effects without causing any clinically relevant respiratory depression unlike opioids.

39
The changes in ventilation appeared similar to those observed during natural sleep.

Dexmedetomidine do not cause any changes in arterial oxygenation, pH and

respiratory rate.32It also exhibited a hypercarbic arousal phenomenon, which has been

described during normal sleep and is a safety feature. The obstructive respiratory

pattern and irregular breathing seen with high doses of 1-2µg/kg given over 2 minutes

and are probably related more to deep sedation and anatomical features of the patient

and this could be easily overcome by insertion of an oral airway.37 Co-administration

of dexmedetomidine with anaesthetic agents, sedatives, hypnotics or opioids is likely

to cause additive effects.34

Intravenous or inhaled Dexmedetomidine has been implicated in blocking

histamine induced bronchoconstriction in dogs.38

Dexmedetomidine is effective in achieving excellent sedation without

respiratory depression during fibreoptic intubation or other difficult airway

procedures.39,40 Intubating conditions are further enhanced because Dexmedetomidine

decreases saliva production and airway secretions.41

Cardiovascular effects

Dexmedetomidine does not appear to have any direct effects on the heart. A

biphasic cardiovascular response has been described after the application of

dexmedetomidine.42,43 The administration of a bolus of 1 μg/kg body weight, initially

results in a transient increase of the blood pressure and a reflex decrease in heart rate,

especially in young healthy patients. The initial reaction can be explained by the

peripheral alpha 2B adrenoceptors stimulation of vascular smooth muscles and can be

attenuated by a slow infusion over 10 or more minutes. Even at slower infusion rates

however the increase in mean arterial pressure over the first 10 minutes was shown to

be in the range of 7% with a decrease in heart rate between 16% and 18%.43 The

40
initial response lasts for 5-10 minutes and is followed by a decrease in blood pressure

of approximately 10%-20% below baseline values; both these effects are caused by

the inhibition of the central sympathetic outflow overriding the direct stimulant

effects. Another possible explanation for the subsequent heart rate decrease is the

stimulation of presynaptic alpha-2 adrenoceptors, leading to a decrease in

norepinephrine release.44

The application of a single high dose of Dexmedetomidine reduced

norepinephrine release by as much as 92% in young healthy volunteers. The release of

epinephrine is also reduced by the same amount. The baroreceptor reflex is well

preserved in patients who received dexmedetomidine, and the reflex heart rate

response to a pressor stimulus is augmented. These results illustrate that

cardiovascular response is evoked mainly by decrease in central sympathetic

outflow.45

Dexmedetomidine could result in cardiovascular depression i.e. bradycardia

and hypotension. The incidence of postoperative bradycardia has been reported as

high as 40% in healthy surgical patients who received Dexmedetomidine, especially

high doses. Usually these temporary effects were successfully treated with atropine or

ephedrine and volume infusions.46

Effect on adrenocorticotrophic hormone (ACTH) secretion

Although Dexmedetomidine has no significant effect on ACTH secretion at

therapeutic doses, cortisol’s response to ACTH may be reduced after prolonged use or

high doses. The ratio of levels of inhibition caused by etomidate and

Dexmedetomidine was shown to be in the order of 100:1, suggesting that the biologic

effects of the inhibitory activities of Dexmedetomidine are not clinically important.47

41
Effect on renin release

Renin release is stimulated by β-adrenoceptor mechanisms, whereas alpha-2

adrenoceptor agonists directly inhibit renin release.48

Effect on insulin release

Stimulation of alpha-2 adrenoceptors on islet cells directly inhibits the release

of insulin; this effect has unproven clinical importance, because hyperglycemia has

never been reported to be significant in patients receiving clonidine.48

Effect on thermoregulation

Like clonidine, Dexmedetomidine is associated with lower rates of shivering.

Intravenous infusion of Dexmedetomidine reduced the vasoconstriction and shivering

threshold but do not change the sweating threshold. Therefore with

Dexmedetomidine, thermoregulatory response were inhibited within a wider range of

temperature.49 Dexmedetomidine and other alpha-2 agonists suppress shivering,

possibly by their activity at alpha-2B receptors in the hypothalamic thermoregulatory

centre of the brain. Low dose Dexmedetomidine has an additive effect with

meperidine on lowering the shivering threshold, and Dexmedetomidine may be

beneficial in decreasing patient discomfort from postanaesthetic shivering.29

Effects on renal function

Alpha-2 agonists exert a diuretic effect by inhibiting the antidiuretic action of

arginine vasopressin at the collecting duct, resulting in decreased expression of

aquaporin-2 receptors and decreased salt and water absorption.48

Organ protective effects

The ability of alpha-2 agonists to decrease tachycardia and hypertension

suggests that they may play a role in cardioprotection by enhancing myocardial

oxygen balance. There is considerably more experimental evidence that

42
dexmedetomidine has neuroprotective effects by several mechanisms. These include

sympatholysis, preconditioning and attenuation of ischemic reperfusion injury.50There

is also evidence that dexmedetomidine decreases cerebral blood flow. But its ratio

with cerebral metabolic rate i.e. flow metabolism coupling appears to be preserved.51

Pharmacokinetics

After intravenous injection, Dexmedetomidine has an onset of action after

approximately 15 minutes. Peak concentrations are usually achieved within 1 hr after

continuous infusion. It has a rapid distribution half life (t1/2α) of 6 minutes and a

terminal elimination half life (t1/2β) of between 2 and 2.5 hrs. The drug is highly

protein bound (94%) with a 6% free fraction. It has a steady state volume of

distribution (Vdss, 1.33 l/kg). Dexmedetomidine is rapidly distributed and extensively

metabolized in the liver. It undergoes conjugation (41%), n-methylation (21%) or

hydroxylation followed by conjugation. Dexmedetomidine is 94% protein bound and

its concentration ratio between blood and plasma is 0.66. The elimination half life is

2 to 3 hrs with a context sensitive half time ranging from 4 minutes after a 10 minute

infusion to 250 minutes after an 8 hr infusion.52 Total plasma clearance is age

independent, thus similar rates of infusion can be used in children and adults to effect

a steady state plasma concentration. Plasma protein binding is similar to adults.53

Dexmedetomidine is also absorbed systematically through transdermal, buccal

or intramuscular routes, with a mean bioavailability from the latter 2 routes of 82%

and 104% respectively. After intramuscular administration, the time to maximum

concentration (Tmax) in the blood is 1.6 to 1.7 hrs, with an absolute bioavailability of

73%. After transdermal administration, the Tmax is six hours with an absolute

bioavailability of 88%.54

43
Perioperative uses of Dexmedetomidine

1. Premedication

Dexmedetomidine has anxiolytic, sedative, analgesic, antisialogogue and

sympatholytic properties which render it suitable as a premedication agent. As a

premedicant, Dexmedetomidine, at IV doses 0.33 to 0.67μg/kg given 15 minutes

before surgery, seems efficacious, while minimizing the cardiovascular side effects of

hypotension and bradycardia.

a. It reduces thiopental requirements.55,56,33

b. Reduces the requirements of volatile anaesthetics.57,58,59

c. More effectively attenuates the haemodynamic responses to endotracheal

intubation.55,56,57,60,61,62,63,64

d. Decreases plasma catecholamine concentrations.45

e. Improves perioperative haemodynamic and sympathoadrenal stability.

2. Use of dexmedetomidine for regional anaesthesia

a. Epidural dexmedetomidine at a dose of 100µg decreased the incidence of

postoperative shivering.65

b. Intrathecal dexmedetomidine at a dose of 3µg causes significant prolongation of

sensory and motor blockade.66

c. Addition of 0.5µg/kg body weight of dexmedetomidine to lidocaine for intravenous

regional anaesthesia improves the quality of anaesthesia and perioperative

analgesia.67

3. Use in monitored anaesthesia care (MAC): Dexmedetomidine confers arousable

sedation with ease of orientation, anxiolysis, mild analgesia without respiratory

depression.68

44
4. Dexmedetomidine has also been used as sole anaesthetic agent upto doses of

10µg/kg/hr.40

5. Use of dexmedetomidine in postoperative period: infusion can be continued in

extubated and spontaneously breathing patients. The ongoing sedation and

sympatholytic effects is beneficial in reducing postoperative myocardial ischemic

events in high risk patients undergoing non-cardiac surgery.68

6. Useofdexmedetomidineinpaediatricagegroup69 – addition of dexmedetomidine

2µg/kg body weight to bupivacaine for caudal analgesia promotes analagesia after

anaesthetic recovery without increasing the incidence of side effects.

7. Use of dexmedetomidine in intensive care unit (ICU): it provides adequate

sedation with minimal respiratory depression and can be used for weaning patients

from ventilator.70

Adverse effects

Other side effects of dexmedetomidine other than hypotension and

bradycardia are hypertension after loading dose, dystonic movements, atelectasis,

nausea and vomiting, dry mouth, tachycardia, atrial fibrillation, haemorrhage,

acidosis, confusion, agitation and rigors which are rare.

Withdrawal phenomenon is reported after abrupt discontinuation with

prolonged administration of dexmedetomidine, leading to development of

hypertension, tachycardia, emesis, agitation, dilated pupils, diarrhea, increased muscle

tone and tonic clonic seizures.71,72

Dosage and administration

The recommended Dexmedetomidine dose is an IV infusion bolus of 1 μg/kg

body weight over a 10 minute period, followed by a continuous IV infusion of 0.2-0.7

μg/kg/hr. The maintenance dose is titrated until the sedation goal is reached.

45
 It is not necessary to discontinue Dexmedetomidine before, during or after

extubation. Dose up to 2.5µg/kg/hr for up to seven days, with no rebound effect on

withdrawal and no compromise in haemodynamics stability have been used in clinical

trials.73

Drug interactions

Dexmedetomidine has shown to inhibit CYP2 D6 in vitro, but the clinical

significance of this inhibition is not well established. Dexmedetomidine appears to

have little potential for interactions with drugs metabolized by the cytochrome p450

system.

Co-administration of Dexmedetomidine with sevoflurane, isoflurane,

propofol, alfentanil and midazolam may result in enhancement of sedative, hypnotic

or anaesthetic effects.74

46
 REVIEW OF LITERATURE

Sigmund Freud (1856-1939), noticed cocaine’s ability to produce numbness of

the tongue and provided a small sample to his junior colleague, Carl Koller (1858-

1944), an intern who was interested in producing local anaesthesia for operations on

the eye. In 1884 Koller reported that the topical application of cocaine to the eye

produced anaesthesia of the cornea and conjuctiva.1

Within months of publication of Koller’s paper, cocaine started being injected

to produce regional anaesthesia and not just topical anaesthesia. In 1885, Halsted used

cocaine to block the brachial plexus, and J Leonard Corning, a neurologist in New

York, injected cocaine intervertebrally in dogs and in patients to relieve chronic pain

and not to provide operative anaesthesia.1 Spinal anaesthesia with cocaine was

initially produced inadvertently by J Leonard Corning, in 1885 and first used

deliberately by August Bier in 1898. On August 15 1898, August Bier and his

assistant August Hildebrandt used the Quinckes method of entering the Intrathecal

space and injected between 5 and 15 mg of cocaine to produce spinal anaesthesia in

six cases for operations on the lower part of the body. They also reported the result of

spinal anaesthesia given to each other.1

Jean Enthuse Sicard and Fernand Cathelin independently introduced cocaine

through the sacral hiatus in 1901, becoming the first practitioners of caudal epidural

anaesthesia. 19 years later, a Spanish military surgeon Archile Mario Dogliotti

performed abdominal surgery using single shot lumbar epidural anaesthesia. He

correctly identified the epidural space describing the sudden loss of resistance noted

after the needle had crossed the ligamentum flavum. Aburel, Higson and Edwards all

devised methods for continuous but cumbersome epidural blockade. However Cuba

anaesthesiologist, Manual Martinez Curbelo, is credited with making the technique

47
more practical. On his visit to Mayo Clinic in 1947, he watched Tuohy perform

continuous spinal block. Curbelo used the Tuohy needle with a silk ureteral catheter

to provide continuous segmental lumbar peridural anaesthesia. Several modifications

of the Tuohy-Huber epidural needle have been developed in the more recent past and

are being utilized in modern anaesthesia practice.13

History of local anaesthetics

The toxicity of cocaine, coupled with its vast potential for usefulness in

surgery, led to an intensive search for less toxic substitutes. Procaine was synthesized

by Einhorn in 1904, but the limitation was its short duration of action. Mcisches

synthesized Dibucaine in 1925, Uhlmann introduced it clinically. In 1928, Eisleb

synthesized Tetracaine and introduced into clinical practice.1

Most of the chemical compounds synthesized during this first pharmaceutical

period were amino ester derivatives. Most of these amino ester agents were relatively

unstable and could not be subjected to repeated autoclaving for sterilization. In

addition, the hydrolysis of aminoesters by enzyme psuedocholinesterase resulted in

the formation of para amino benzoic acid which was responsible for reported allergic

reactions.

Lidocaine, synthesized in 1943 by Lofgren and Lundquist was a stable

compound that was not influenced by repeated exposures to high temperature and thus

could be resterilised often. In addition, the metabolites of lidocaine did not include p-

amino benzoic acid. Thus allergic reactions were avoided.1

Subsequent to lidocaine release, a number of amino amide compounds were

synthesized and four eventually found their way into clinical practice. In 1956,

48
Ekenstam in Sweden synthesized Mepivacaine, whose anesthetic properties were

similar to lidocaine. In 1959,

Lofgren and co workers synthesized prilocaine. Lidocaine and mepivacaine were

tertiary amides compounds while prilocaine was secondary amide.1

Bupivacaine was synthesized by Ekenstam in 1956 and introduced into

clinical practice in 1963 by Telivuo. In 1971 Takman synthesized Etidocaine and it

was found that etidocaine produced more intense and prolonged motor blockade than

sensory blockade, hence not producing ideal perioperative anaesthesia.1

Since then bupivacaine is extensively used and became very popular for

epidural anaesthesia as well as analgesia, because of its long duration of action and

preferential sensory block in lower concentrations. Only drawback of bupivacaine

was cardiotoxicity, which when accidentally injected intravascularly. Hence there was

a need for introduction of drugs with all the advantages of bupivacaine without the

cardiotoxicity.

Although identified as a local anaesthetic in 1957, Ropivacaine testing did not

begin until 1988.11 Ropivacaine was introduced into clinical practice in 1990.15

Vieira AM, Schnaider TB et al74in 2004 conducted a randomized double-blind study

on forty patients belonging to ASA1 and 2 posted for subcostal cholecystectomy

under combined lumbar epidural and general anesthesia to evaluate the effects of

epidural clonidine and dexmedetomidine for analgesia and sedation in the post

operative period.

Forty patients of both gender participated in the study, aged between 18 to 50 years,

weighing 50 to 100kg, submitted to subcostal cholecystectomy.

49
The patients were distributed into two groups; Clonidine(CG), receiving clonidine

(1ml=150microg) associated with 0.75% epidural ropivacaine (20ml).

Dexmedetomidine(DG), receiving dexmedetomidine (2microg/kg) associated with

0.75% epidural ropivacaine (20ml). Analgesia and sedation were evaluated 2, 6 and

24 hours following anesthetic recovery.

Anesthesia was induced with etomidate (0.2mg/kg), alfentanil (30microg/kg) and

rocuronium (0.6mg/kg) and maintained with isoflurane (1% to 3%). In the presence of

clinical signs or hemodynamic responses suggesting inadequate anesthesia (sweating,

tearing, arterial hypertension and tachycardia), intravenous alfentanil(500 to 1000

microg) was administered to both the groups.

There have been no statistically significant differences in sedation for the clonidine

group at 2 and 6 hours. There have been statistically significant differences in the

dexmedetomidine group at 2 and 6 hours. There have been no statistically significant

differences when comparing both groups at 2 and 6 hours.

There have been statistically significant differences in analgesia for the clonidine

group when 2 and 6 hours observations were compared to 24 hours. There have been

statistically significant differences in the dexmedetomidine group when 2 hours

observations were compared to 6 and 24 hours, as well as when 6 hours observations

were compared to 24 hours. There have been statistically significant differences

between groups at 24 hours.

50
Authors concluded that the association of clonidine and dexmedetomidine to 0.75%

ropivacine induces analgesia and sedation in 2 and 6 hours after anesthetic recovery in

patients submitted to subcostal cholecystectomy and that clonidine promotes more

prolonged analgesia.

Schnaider TB, Vieira AM, et al.75in 2005 conducted a randomized double-blind

study on 70 patients aged between 18 to 50 years belonging to ASA 1 and 2 posted

for subcostal cholecystectomy under general anesthesia associated with lumbar

epidural anesthesia to compare the intraoperative analgesic effect of epidural

ketamine, clonidine and dexmedetomidine.

All patients were premedicated with oral diazepam (10mg) the day before and with

oral midazolam (15mg) 40 minutes before surgery. In the operating room after venous

puncture patients were given solutions with midazolam (5mg), fentanyl (50μg) and

metoclopramide (10mg).

Lumbar epidural anesthesia was induced with patients in the sitting position in L1-L2

interspace and the following solutions were administered.

Control group: 20ml of 0.75% ropivacaine associated to 1 ml of 0.9% saline solution

(n=10)

Ketamine group: 20ml of 0.75% ropivacaine associated to 0.5 mg/kg ketamine (n=20)

Clonidine group: 20ml of 0.75% ropivacaine associated to 1ml clonidine with 150μg

(n=20)

51
Dexmedetomidine group: 20ml of 0.75% ropivacaine associated to 2μg/kg

dexmedetomidine (n=20)

All patients received the same volume of drug combinations.Anesthesia was induced

with etomidate (0.2mg/kg), alfentanil (30μg/kg), and rocuronium (0.6 mg/kg) and was

maintained with isoflurane (0.5 vol% to 3 vol%). When clinical signs or

hemodynamic responses suggested inadequate anesthesia (sweating, tearing,

hypertension and tachycardia),intermittent intravenous alfentanil (500μg) was

administered.Analgesia was evaluated by clinical signs and inhalational agent inspired

concentration was evaluated by inspired and expired gas analysis.

All patients receiving ketamine, clonidine or dexmedetomidine had decreased heart

rate and systemic blood pressure as a consequence of NMDA receptors block by

ketamine, or of pre-synaptic self-inhibitory feedback mechanism of alpha 2-

adrenergic receptors by clonidine and dexmedetomidine, and of epidural block by

ropivacaine and had no need for intraoperative analgesic complementation in any

patient. For the same patients, isoflurane inspired concentration varied from 0.5vol%

to 1vol% and there were no clinical signs or responses suggesting inadequate

anesthetic levels.

Authors concluded that epidural ketamine,clonidine or dexmedetomidine decreases

alfentanil consumption and isoflurane inspired concentration in the intraoperative

period

52
Wahlander S, Frumento RJ et al76 in 2005 conducted a study to test the hypothesis

that after thoracic surgery, the supplementation of a low-dose thoracic epidural (ED)

bupivacaine (0.125%) infusion followed by intravenous (IV) dexmedetomidine

decreases the analgesic requirement without causing respiratory depression. The

primary endpoint was the need for additional ED bupivacaine administered through

patient-controlled epidural analgesia (PCEA). Secondary endpoints included the

requirement for supplemental opioids and the impact of dexmedetomidine on CO2

retention.

Twenty-eight patients scheduled to undergo elective thoracotomy for wedge resection,

lobectomy, or pneumonectomy were included in the study. On intensive care unit

arrival, the thoracic ED catheter was loaded with 0.125% bupivacaine to a T4 sensory

level and a continuous infusion of 0.125% bupivacaine without opioid was

commenced at 4 mL/h. Patients were then randomized into 1 of 2 groups. The

dexmedetomidine group received an IV loading dose of dexmedetomidine of 0.5

μg/kg over 20 minutes, followed by continuous IV infusion at 0.4 μg/kg/h. The

placebo group received IV saline at the same calculated loading and infusion rates by

volume. If necessary, supplemental analgesia (increased ED rate, ED fentanyl,

ketorolac [IV]) was provided to ensure a visual analog scale (VAS) score of ≤3.

The analgesic effect was monitored by the VAS, and the requirement for PCEA

dosing and additional analgesics was recorded. Heart rate, blood pressure, and blood

gases were also monitored.

53
Results showed there was no significant difference in PCEA use and VAS score

between the 2 groups, but requirement for supplemental ED fentanyl analgesia was

significantly greater in the placebo group (66.1 ± 95.6 v 5.3 ± 17.1 μg, p = 0.039).

Mean PaCO2 was also significantly greater in the placebo group (40.3 ± 4.1 v 43.9 ±

4.3 mmHg, p = 0.04). Patients in the dexmedetomidine group exhibited significantly

decreased heart rate (1 patient required and responded to atropine) and blood pressure

(4 patients required and readily responded to IV fluid) compared with the placebo

group.

The authors concluded that in postthoracotomy patients, IV dexmedetomidine is a

potentially effective analgesic adjunct to thoracic ED bupivacaine infusion and may

decrease the requirement for opioids and potential for respiratory depression.

Coskuner I, Tekin M et al77 in 2007 conducted a study on 60 ASA 1 and 2 patients

to evaluate the effects of intravenous dexmedetomidine on the duration of anaesthesia,

level of wakefulness and respective side effects in bupivacaine-induced epidural

anaesthesia.

Sixty ASA 1 and 2 patients were included in the study. Consecutive patients were

allocated to groups according to the last digit(odd/even) of their admission numbers.

Patients were divided into two groups. Group 1 (bupivacaine + dexmedetomidine)

and Group 2 (bupivacaine + normal saline). All patients had epidural anaesthesia with

bupivacaine 0.5% performed by the same experienced anaesthesiologist. In first

group, the patients were administered intravenous dexmedetomidine infusion just

54
after the administration of epidural anaesthesia and continued during the operation,

while those in the second group were administered physiologic saline in fusion at the

same amount and duration.

The recovery time of sensory block was significantly longer in the first group. The

bispectral index values were lower in the first group than in the second. Also, heart

rate was significantly lower in group 1 than in group 2. Side effects like shivering was

significantly less frequent in the first group, whereas there was significant increase in

the requirement of atropine in the first group as dexmedetomidine caused bradycardia.

Authors conclude that intravenous administration of dexmedetomidine prolonged the

duration of epidural anaesthesia, provided sedation and had few side-effects.

Saravia P.S.F, Sabbag AT et al78 in 2008conducted a double blind, controlled study

on 40 patients belonging to ASA 1 and 2undergoing surgery ona hernia or abdominal

wall, varicose vein of the lower limbs to evaluate the clinical characterestics of

epidural anaesthesia performed with ropivacaine associated with dexmedetomidine.

Patients were randomly assigned into one of the two groups,

Control group (n=20): 1ml of sodium chloride 0.9% (placebo)

Dexmedetomidine group (n=20): 1μg/kg dexmedetomidine + solution of sodium

chloride 0.9% in order to complete the volume of 1ml syringe.

After the injection of study drug were administered 20ml of ropivacaine 0.75%

(150mg),at the rate of 1ml every 3 seconds.The variables studied were: Onset of

55
sensory block, maximum dermatome anaesthesia, duration of analgesia and motor

block, motor block intensity, level of sedation, haemodynamic variables, post-

operative analgesia and the occurrence of side effects.

Results of the study showed dexmedetomidine did not affect the latency of

anaesthesia nor the maximum level of sensory block (p>0.05), but prolonged the

duration of analgesia and motor block (p<0.05) and postoperative analgesia (p<0.05)

and determine more intense motor block(p<0.05). The bispectral index values were

lower in the dexmedetomidine group (p<0.05). There was no difference in the

incidence of hypotension, bradycardia(p>0.05). The occurrence of side

effects(tremors, nausea and SPo2) was low and similar between groups(p>0.05).

Author concluded that dexmedetomidine at a dose of 1μg/kg, acts synergistically with

0.75% ropivacaine in epidural anaesthesia. It increases the duration of analgesia,

motor block intensifies and prolongs the duration of post-operative analgesia,without

increased morbidity.

Lopez SAO, Sanchez KAM et al 79in 2008 conducted a descriptive, prospective

study on 40 ASA1 and 2 patients posted for surgery on abdomen and lower limbs to

evaluate the effects of epidural dexmedetomidine in regional anesthesia to reduce

anxiety.

Monitoring included ECG, NIBP, and oxygen saturation(SPO2). A load volume of

10ml/kg physiological saline was administered to prevent hypotension by sympathetic

effect of epidural block.

56
After placement of epidural catheter, local anesthetic (lidocaine plus 2% epinephrine

at 3-4mg/kg doses) was administered along with dexmedetomidine solution at 1μg/kg

dose via epidural. While the patient was in dorsal decubitus, sedation level was

evaluated using the Ramsay’s scale during the transoperative period.

Ramsay’s sedation scale

Patient Grade

Awake, excited or agitated 1

Awake, quiet, responds 2

Obnubilado, quiet, responds 3

Asleep, respons strongly to verbal or tactile 4

stimulation

Asleep, respons lazily to verbal or tactile 5

stimulation

Asleep, no responds to stimulation 6

Hemodynamic changes, the diffusion and degree of analgesia produced by

dexmedetomidine during transoperative period were recorded at 5,10,15,30 minutes,

subsequently every half hour until the end of the anesthetic and surgical events.

The degree of sedation obtained according to Ramsay, at five minutes was 3, and it

was 3-4 from 15-90 minutes, in 90% of the population. These frequencies were

analyzed through the 2 being p<0.05. The patients kept their hemodynamic

parameters stable, without respiratory depression.

57
Authors concluded that the use of dexmedetomidine by peridural route at 1μg/kg dose

plus local anesthetics is an alternative to achieve an anesthetic quality that enables to

keep the patient in a state of active sedation, which reduces the likelihood of

respiratory depression, which can arise when adjuvant drugs are administered

intravenously. It also reduces the doses of local anesthetics, as it potentiates the

effects of both drugs, with consequent reduction of their adverse effects.

Hennawy AME, Elwahab AMAet al80 in 2009 conducted a double-blind

randomized study on sixty patients (6 months to 6year) posted for lower abdominal

surgeries to evaluate the analgesic effects and side effects of dexmedetomidine and

clonidine added to bupivacaine.

After sevoflurane in oxygen anaesthesia, each patient received a single caudal dose of

bupivacaine 0.25%(1ml/kg) combined with either dexmedetomidine 2μg/kg in

normal saline 1ml, clonidine 2μg/kg in normal saline 1ml or corresponding volume of

normal saline according to group assignment. Haemodynamic variables, end-tidal

sevoflurane, and emergence time were monitored. Postoperative analgesia, use of

analgesics, and side effects were assessed during the first 24 hour.

Results showed addition of dexmedtomidine or clonidine to caudal bupivacaine

significantly promoted analgesia time [median (95% confidence interval, CI): 16 (14-

18) and 12 (3-21) hour, respectively] than use of bupivacaine alone [median (95%

CI):5(4-6)hour] with p < 0.001.

58
However, there was no statistically significant difference between dexmedetomidine

and clonidine as regards the analgesia time (p = 0.796). No significant difference was

observed in incidence of haemodynamic changes or side effects.

Authors concluded that addition of dexmedtomidine or clonidine to caudal

bupivacaine significantly promoted analgesia in children undergoing lower abdominal

surgeries with no significant advantage of dexmedetomidine over clonidine and

without an increase in incidence of side effects.

Elhakim M, Abdelhamid D et al81 in 2010 conducted a randomized controlled study

on 50 adult male patients to evaluate the effect of epidural dexmedetomidine on

intraoperative awareness and post-operative pain after one-lung ventilation.

Fifty male patients were randomly divided into two groups; Group D and Group B.

Group D received epidural dexmedetomidine 1 microg/kg with bupivacaine 0.5% and

Group B received bupivacaine 0.5% alone after induction of general anaesthesia.

Gasometric, haemodynamic and bispectral index values were recorded. Post-operative

verbal rating score for pain and observer’s assessment of alertness/sedation scale were

determined by a blinded observer.

Results showed dexmedetomidine reduced the use of supplementary fentanyl during

surgery. Patients in group B consumed more analgesics and had higher pain scores

after operation than patients of group D. The level of sedation was similar between

59
the two groups in the ICU. Two patients(8%) in group B reported possible

intraoperative awareness. There was a limited decrease in PaO2 at one lung

ventilation in group D compared with group B (p<0.05).

Authors concluded that in thoracic surgery with one lung ventilation, the use of

epidural dexmedetomidine decreases the anaesthetic requirements significantly,

prevents awareness during anaesthesia and improves intraoperative oxygenation and

post-operative analgesia.

Bajwa SJ, Bajwa SK, Kaur J et al82in 2011 conducted a prospective randomized

double blind study on 50 adult female patients aged between 44 and 65years of ASA

1and 2 patients who underwent vaginal hysterectomies to compare the effect of

dexmedetomidine and clonidine in epidural anaesthesia. Patients with haematological

disease,bleeding or coagulation test abnormalities, psychiatric diseases, diabetes,

history of drug abuse and allergy to local anaesthetics of the amide type were

excluded from the study.

Patients were allocated into one of the two groups,

Ropivacaine + clonidine (RC) group (n=25)

Ropivacaine + Dexmedetomidine (RD) (n=25)

Group RC was administered 17ml of 0.75% epidural ropivacaine and 2μg/kg of

clonidine.

Group RD were administered 17ml of 0.75% epidural ropivacaine and 1.5μg/kg of

dexmedetomidine.

60
The parameters studied were, initial period of onset of analgesia; the highest

dermatomal level of sensory analgesia; the complete establishment of motor blockade,

the time to two segment regression of analgesic level, regression of analgesic level to

S1 dermatome and time to complete recovery and side effects(hypotension, nausea,

vomiting, pruritis).

Addition of dexmedetomidine to ropivacaine resulted in earlier onset of sensory

analgesia at T10 as compared to addition of clonidine. Dexmedetomidine not only

provided a higher dermatomal spread but also helped in achieving the maximum

sensory anaesthetic level in a shorter period compared to clonidine. Modified

Bromage scale 3 was achieved earlier in patients who were administered

dexmedetomidine as adjuvant. All these initial block characterestics turned out to be

statistically significant values on comparison(p<0.05).

Grading of sedation was evaluated by a five point scale.

Alert and wide awake 1

Arousable to verbal command 2

Arousable with gentle tactile stimulation 3

Arousable with vigorous shaking 4

Unarousable 5

61
Mean sedation scores were significantly higher in RD group compared to RC

group(p<0.0001).

Dexmedetomidine provided a smooth and prolonged post-operative analgesia as

compared to clonidine. The evidence was shown in the prolonged time to two

segmental dermatomal regression as well as return of motor power to Bromage 1

(p<0.05). Side effects in both the groups were observed intra-op and post-op period.

The incidence of side effects dry mouth, nausea, vomiting, headache, shivering and

dizziness were comparable in both groups and statistically non-significant(p>0.05).

Author concluded that dexmedetomidine is a better adjuvant than clonidine in

epidural anaesthesia as far as patient comfort, stable cardio-respiratory parameters,

intra-operative and post-operative analgesia is concerned and provides superior

sedative and anxiolytic properties during the surgical procedure under regional

anaesthesia.

Bajwa SJ, Arora V, Kaur J et al 83 2011conducteda randomized controlled study on

100 patients to evaluate the effect of epidural dexmedetomidine and fentanylepidural

analgesia in lower limb orthopaedic surgeries.

A total 100 patients of both gender aged 21-56 years belonging to ASA 1 and 2who

underwent lower limb orthopaedic surgery were enrolled into the study.Patients were

randomly divided ino two groups: Ropivacaine + Dexmedetomidine (RD) and

Ropivacaine + Fentanyl(RF), comprising 50 patients each.Inj.Ropivacaine 15ml of

0.75% was administered epidurally in both the groups with addition of 1μg/kg of

62
dexmedetomidine in RD group and 1μg/kg of fentanyl in RF group at the rate of

1ml/second.

The following parameters were observed immediately after the administration of

epidural block.

1.Time to onset of analgesia at T10

2.Maximum sensory level achieved

3.Time to achieve the maximum sensory level

4.Time to complete motor blockade

5.Time to two segmental dermatomal regression

6.Regression toS2

7.First feeling of pain/rescue analgesia

8.Total dose consumption or local anesthetic used over 24hours.

Cardio-respiratory and sedation scores were observed.

At the end of the study, data was compiled systematically and analyzed using

ANOVA with post-hoc significance, Chi-square test and Fisher’s exact test.Value of

p<0.05 is considered significant and p<0.001 as highly significant.

Results showed onset of sensory analgesia at T10 (7.12± 2.44 VS 9.14 ± 2.94) and

establishment of complete motor blockade (18.16 ± 4.52 vs 22.98 ± 4.78) was

significantly earlier in the RD group. Postoperative analgesia was prolonged

significantly in the RD group (366.62 ± 24.42) and consequently low dose

consumption of local anesthetic LA (76.82 ± 14.28 VS 104.35 ± 18.96) during

epidural top-ups postoperatively. Sedation scores were much better in the RD group

and highly significant (p<0.001). Incidence of nausea and vomiting was significantly

63
higher in the RF group, while incidence of dry mouth was higher in the RD group

(14%) (p<0.05).

Authors concluded that dexmedetomidine is a better alternative to fentanyl as an

epidural adjuvant as it provides comparable stable hemodynamics, early onset and

establishment of sensory anesthesia, prolonged post operative analgesia, lower

consumption of post-op LA for epidural analgesia; and much better sedation levels.

Sinha S, Mukherjee M et al 84 in2012 studied the analgesic efficacy of ropivacaine

with ropivacaine plus dexmedetomidine for paravertebral block in unilateral renal

surgery.

Sixty adult patients of ASA I & II, undergoing unilateral renal surgery, were included

in the prospective, randomized study. After infiltration with local anaesthetic, 2.5 cm

lateral to the tip of spinous process of L1 vertebra, Tuohy needle was advanced

perpendicular to the skin in all planes to contact the transverse process of the vertebra,

typically at a depth of 2 to 4 cm. After the transverse process was identified, the

needle was redirected cephalad and gradually advanced until loss of resistance was

felt 1 to 1.5 cm distal to its superior edge. Through the needle a multiorifice 18G

epidural catheter was placed 3 cm inside T12–L1 paravertebral space. After negative

aspiration for blood, CSF and air, test dose of 2% lignocaine (3 ml) with 1:2,00,000

adrenaline was administered through the epidural catheterAfter placing the catheter in

T12–L1 paravertebral space, block was randomly activated either by 18 ml of

ropivacaine 0.25% (Group I) or by 18 ml of ropivacaine 0.25% plus 1µg/kg

dexmedetomedine (Group II).

64
General anaesthesia was instituted with injection propofol and endotracheal

intubation was facilitated by injection rocuronium bromide, 90 µg/Kg body weight.

Anaesthesia was maintained with O₂, N₂O and 1 MAC of Isoflurane. At the end of

surgery residual neuromuscular blockade was reversed with 50 µg/Kgneostigmine

with 10 µg/Kg glycopyrrolate. After recovery from general anaesthesia, pain was

assessed by VAS. When VAS score exceeded 3, the time was noted and top up doses

of 0.25% ropivacaine (6ml) ( Group I ) or ropivacaine (6ml) and dexmedetomidine

(0.25 µg/Kg) (Group II) were administered. Total requirement of ropivacaine in the

first 24 hrs was noted in both the groups.

Results showed mean duration of analgesia was longer in Group II (324.4±56.35 min)

as compared to Group I (149.2 ±30.64 min) (p<0.05). Mean total consumption of

ropivacaine was 84±14.12 mg in Group II and 120±15.26 mg in Group I (p<

0.05).VAS were comparable in the immediate post operative period but after that it

became significantly higher VAS in Group I on all the post operative recordings. The

baseline systolic and diastolic blood pressures and the pulse rates were comparable

(p>0.05) between Group I and II and showed no significant differences.

Authors concluded that addition of dexmedetomidine to local anaesthetic agent

ropivacaine significantly prolongs the duration of analgesia in paravertebral blocks

without causing significant haemodynamic instability. Also co administration of

dexmedetomidine leads to decreased total consumption of ropivacaine which is very

beneficial for renal compromised patients.

65
Brummett CM, Norat MA et al85 in 2013 conducted a study to test the hypothesis

that high-dosedexmedetomidine added to local anesthetic would increase the duration

of sensory and motor blockade in a rat model of sciatic nerve blockade without

causing nerve damage.

An investigator (CMB) blinded to the drug condition carried out both the injections

and subsequent neurobehavioral testing. Thirty-one adult Sprague Dawley rats

without any signs of preprocedural neurobehavioral impairment were anesthetized

and maintained with 1.5% isoflurane. The sciatic nerve of both hind extremities was

exposed using a lateral incision over the thigh. Sixteen rats in the bupivacaine-

dexmedetomidine (Bupiv-DMET) group received either 0.5% bupivacaine (0.2 ml) or

0.5% bupivacaine plus 0.005% dexmedetomidine (0.2 ml) assigned at random, with

the other drug injected on the contralateral side. Fifteen rats in the saline-

dexmedetomidine (Saline-DMET) group received either 0.005% dexmedetomidine

(0.2 ml) or normal saline (0.2 ml) assigned at random, with the other drug injected on

the contralateral side.

Sensory and motor function were assessed by a blinded investigator every 30 minutes

until the return of normal sensory and motor function. Sciatic nerves were harvested

at either 24 hours or 14 days after injection and analyzed for perineural inflammation

and nerve damage.

Results showed high-dose dexmedetomidine added to bupivacaine significantly

enhanced the duration of sensory and motor blockade. Dexmedetomidine alone did

not cause significant motor or sensory block. All of the nerves analyzed had normal

66
axons and myelin at 24 hours and 14 days. Bupivacaine plus dexmedetomidine

showed less perineural inflammation at 24 hours than the bupivacaine group when

compared with the saline control.

Authors concluded that high-dose dexmedetomidine can safely improve the duration

of bupivacaine-induced antinociception following sciatic nerve blockade in rats is an

essential first step encouraging future studies in humans. The dose of

dexmedetomidine used in this study may exceed the sedative safety threshold in

humans and could cause prolonged motor blockade, therefore future work with

clinically relevant doses is necessary.

67
 METHODOLOGY

A study entitled“Comparative study of Epidural 0.75% Ropivacaine with

Dexmedetomidine and 0.75% Ropivacaine alone in lower abdominal and lower limb

surgeries” was undertaken in Kempegowda Institute of Medical Sciences (K.I.M.S)

hospital, Bangalore during the period October 2011 to July 2013. The study was

undertaken after obtaining ethical committee clearance as well as informed consent

from all patients.

One hundred patients, scheduled for various elective lower abdominal and

lower limb surgical procedures belonging to ASA class I and II were included in the

study.

The study population was randomly divided using computer generated

randomization numbers into two groups with 50 patients in each group.

1. Group R (n=50) - 15ml of 0.75% ropivacaine (Ropivacaine 0.75% preservative

free – ROPIN 0.75% 20 ml ampoules – Neon laboratories India limited).

2. Group RD (n=50) -15ml of 0.75% ropivacaine + 0.6µg/kg of dexmedetomidine

(inj.DEXTOMID-1ml=100mcg,1ml ampoule)

Inclusion criteria for the study

• Adult patients aged between 18 to 65 years of both sex.

• Patients belonging to ASA class I and II posted for elective lower abdominal

and lower limb surgical procedures.

• Weight > 50 kgs

• Height 150-180cms

68
Exclusion criteria for the study

• Patient refusal for regional anaesthesia.

• Pregnancy and lactation.

• Patients posted for Emergency surgeries.

• Obese patient with BMI > 30.

• Patients having:

§ raised intracranial pressure

§ severe hypovolemia

§ bleeding coagulopathy

§ local infection

§ uncontrolled hypertension/ diabetis mellitus

§ neurological disorderand deformities of spine

§ cardiac disease

§ hepatic disease

§ allergy to local anaesthetics and dexmedetomidine

A routine pre-anaesthetic examination was conducted on the evening before

surgery, assessing

• History and general condition of the patient

• Airway assessment by Mallampatti grading.

• Nutritional status, height and weight of the patient

• A detailed examination of the Cardiovascular system, Respiratory system and

Central nervous system

• Examination of the spine

69
The following investigations were done in all patients

• Hemoglobin estimation

• Bleeding time and clotting time

• Random blood sugar

• Blood urea and Serum creatinine.

• Standard 12-lead electrocardiogram

The patients were premedicated with tablet alprazolam 0.5 mg and tablet

ranitidine 150 mg orally at bed time on the previous night before surgery. They were

kept nil orally 10 pm onwards on the previous night.

On the day of surgery, patient’s basal pulse rate and blood pressure were

recorded. A peripheral intravenous line with 18 gauge cannula after local anaesthesia

was secured in one of the upper limbs. All the patients were preloaded with 500 ml of

Ringer lactate 30 minutes prior to the epidural procedure . Multiparameter monitor

was connected which records heart rate, non-invasive measurement of systolic blood

pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure(MAP),

continuous electrocardiogram (ECG) monitoring and oxygen saturation (SPO2)

With the patients in sitting position under aseptic precautions, epidural space

was identified by loss of resistance technique to air using 18G Tuohy needle via the

midline approach at either L2-3 or L3-4 inter spinous space. An epidural catheter was

threaded and fixed at 3 cms inside the epidural space. A test dose of 3 ml of 2%

lignocaine with 1:200000 adrenaline was injected through the catheter after

aspiration. After ruling out intrathecal and intravascular placement of the tip of the

catheter, study drug was injected in increments of 5 ml . The patients were turned to

supine position after 1 min.

70
 Assessment of sensory and motor blockade were done at the end of each

minute with the patient in supine position after completion of the injection of 15 ml of

the study drug, which is taken as the starting time. The onset time for sensory and

motor block, the maximum level of sensory block,intensity of motor block and

sedation score were recorded.

Sensory blockade was assessed using a short bevel 22 gauge needle and was

tested in the mid clavicular line on the chest, trunk and lower limbs on either side.

Motor blockade in the lower limbs was assessed using modified Bromage

scale.

0 – able to perform a full straight leg raise over the bed for 5 sec

1– unable to perform the leg raise but can flex the leg on the knee articulation

2 – unable to flex the knee but can flex the ankle

3 – unable to flex ankle but can move the toes

4 – unable to move toes (total paralysis).

Table 1: Sedation scoring as per (Five point scale):

Alert and wide awake 1

Arousable to verbal command 2

Arousable with gentle tactile stimulation 3

Arousable with vigorous shaking 4

Unarousable 5

71
Measurements of blood pressure, heart rate, and oxygen saturation will be recorded

every 5 minutes till the end of 1hour and then every 15 minutes till the end of

surgery

Intraoperatively and postoperatively complications like fall in blood pressure,

variation in heart rate were noted, treated and tabulated.

Hypotension is defined as reduction of systolic blood pressure more than 30%

from basal systolic blood pressure or SBP less than 90 mmHg and is treated with

increased rate of intravenous fluids and if needed injection mephentermine 3 mg (I.V)

given in increments. Bradycardia (<60 beats/min) was treated with injection Atropine

0.6 mg (I.V).

After the surgery, patients referred to the recovery room (PACU)

post anaesthesia care unit where they remained until there was complete

recovery of sensory and motor blockade. Epidural top up was given with 8ml of

0.2% inj.ropivacaine once the patient complains of pain. Postoperatively vital

parameters will be recorded every 15minutes ,and also duration of sensory

and motor blockade, any adverse events like nausea, vomiting, pruritis,

shivering etc will be noted.

Onset of sensory blockade: is taken as the time from the completion of the injection

of the study drug till loss of sensation at T10 level.

Onset of motor blockade: is taken from the completion of the injection of study drug

till the patient develops modified Bromage scale grade 1 motor blockade.

Duration of motor block: is taken from the time of injection till the patient attains

complete motor recovery (Bromage 0).

72
Duration of sensory block: is taken from the time of injection till the patient

complains of pain at the T10 dermatome.

The results of the study were statistically analysed between the two groups.

STATISTICAL METHOD APPLIED

Statistical analysis was done using SPSS version 13.0. Descriptive statistics

was done by calculating mean, standard deviation, range and proportion

appropriately. The inferential statistics (test of significance) was done using unpaired

t- test two way repeated measure ANOVA and chisquare test.

73
 RESULTS

Table 2: Showing the age distribution

Age in yrs Group R Group RD

15-25 10 8

26-35 8 11

36-45 10 11

46-55 11 12

56-65 11 8

Total 50 50

Minimum Age in Yrs 20 18

Maximum Age in Yrs 60 56

74
Figure 6: Graph showing age distribution

12

10

8
No. of patients

0
15-25 26-35 36-45 46-55 56-65
Age groups
Ropivacaine

Ropi+Dexme

Table 2 and figure 6 showing age distribution of the patients in both the groups. The

minimum age in groups R and RD were 18 and 20 years respectively. The maximum

age in both groups R and RD was 65 years respectively. There was no significant

difference in the age of patients between the Group R and Group RD. Both groups

were similar with respect to age distribution (p>0.05).

75
Table 3: Sex Distribution between Group R and Group RD

GROUP R GROUP RD

SEX No of patients Percent No of patients Percent

MALE 36 72.0 31 62.0

FEMALE 14 28.0 19 38.0

TOTAL 50 100.0 50 100.0

Figure 7: Graph showing sex distribution

Female
40
Male
35
30
No. of patients

25
20
15
10
5
0
Ropivacaine Ropi+Dexme
Groups

Table 3 and figure 7 showing the sex distribution of the patients in both the

groups. There is no significant difference in the sex distribution of the patients

between the groups. In both the groups there is a predominance of male patients.

76
Table 4: Showing the Body Weight distribution

Group R Group RD p-value

Weight (in kgs) 58.64±5.17 56.10±6.11 0.27

Figure 8: Graph showing body weight distribution

Ropi+Dexme
Groups

Ropivacaine

0 15 30 45 60
Mean weight (in Kgs.)

Table 4 and figure 8 showing the body weight distribution of patients. The

mean body weight in group R is 58.64 ± 5.17 kg and group B is 56.10± 6.11 kg.

There is no significant difference in the body weight of patients between the groups

(p=0.27).

77
Table 5: Height distribution

Height (cms) Group R Group RD

Mean height in cm 170 169.03
Minimum height in cm 150 152
Maximum height in cm 180 180

Figure 9: Graph showing body height distribution

Ropi+Dexme
Groups

Ropivacaine

Mean height (in cms.)

Table 5 and figure9 showing height distribution of patients. The mean height in

group R is 170 cm and group RD is 169.03 cm. There is no significant difference

in the height between the groups.

78
Table 6: Type of surgical procedure

Group R Group RD ( ropivacaine and

(Ropivacaine group) dexmedetomidine group)

Type of surgery
Number of Number of
Percent Percent
patients patients

# Both bones leg 13 26 12 24

# Femur 25 50 23 46

Inguinal
12 24 15 30
hernioplasty

There is no difference in the type of surgical procedures in both the groups

79
Figure 10: Mean duration of surgery

Mean duration (min)

Group RD

Group R Group RD

The mean duration of surgery is 96.83 ± 27.49 mins in group R and 90.83

± 23.12 mins in group RD. There is no statistically significant difference between

the groups.

80
Table 7: Mean time for onset of sensory and motor block (minutes)

Mean time for Mean time for

sensory onset p-value motor onset

(mins) SD (mins) SD p value

Group 10.04 2.55 15.36 3.28

Group 5.26 1.49 0.000 11.22 2.61 0.000

RD

Figure 11: Graph showing mean time for onset of sensory block (minutes)

Ropivacaine
16 Ropi+Dexme
14
12
Mean values

10
8
6
4
2
0
Sensory onset Motor onset
Onset

The mean time of onset of sensory blockade in group R is 10.04±2.5 mins and in

group RD is 5.26±1.49mins. There is highly statistical significant difference between

the groups (p=0.000). The mean time taken for the onset of motor blockade

is15.36±3.28 mins in group R and 11.22±2.61 mins in group RD. There is statistical

significant difference between the groups (p=0.000).

81
Table 8: Maximum level of sensory blockade attained

Max Sensory level Group R Group RD p-value

(No.of patients) (No.of patients)

T5 0 5

T6 31 38

T8 17 6 0.10

T10 2 1

Figure 12: Graph showing maximum level of sensory blockade attained

40 Ropivacaine

35 Ropi+Dexme

30
No. of patients

25
20
15
10
5
0

T5 T6 T8 T10

Table 8 and figure 12 showing maximum level of sensory blockade attained by the

two groups. Group RD had the highest level of T5 and highest level in R group was

T6. There is no significant difference between the two groups(p>0.05)

82
Table 9: Grade of motor blockade

Group R Group RD p-value

Bromage 2 15 0 <0.001

Bromage 3 35 34 0.35

Bromage 4 0 16 <0.001

Figure 13: Graph showing grade of motor blockade

Ropivacaine
35 Ropi+Dexme
30
25
No. of patients

20
15
10
5
0
M2 M3 M4
Motor block

Table 9 and figure 13 showing grade of motor blockade in both the groups. Number

of patients with Bromage 2 were 15 in group R and 0 in group RD, whereas patients

with Bromage 4 were 0 in group R and 16 in group RD. More intense motor blockade

of Bromage 4 was found in patients in group RD compared to patients in group R,

the p value being 0.001 is highly significant.

83
Table 10:Sedation score

Sedation score Group R Group RD p-value

S1 17 0

S2 33 15

S3 0 29 0.001

S4 0 6

Figure 14: Graph showing sedation score

35 Ropivacaine
Ropi+Dexme
30
25
No, of patients

20
15
10
5
0
S1 S2 S3 S4
Sedation

Table 10 and figure 14showing sedation score in both groups. Group R had the

highest score of 2 and highest score in group RD was 4.Dexmedetomidine had

greater scores compared to ropivacaine alone. There is statistically highly significant

difference between the groups (p=0.001).

84
Table 11:Duration of sensory and motor blockade (minutes)

Mean SD p-value

Duration of Sensory Block

Group R 198.00 24.05

Group RD 359.30 61.94 0.001

Duration of Motor Block

Group R 149.00 14.21

Group RD 233.70 15.36 0.001

Figure 15: Graph showing Duration of sensory and motor blockade (minutes)

Ropivacaine
400 Ropi+Dexme
350
300
Mean values

250
200
150
100
50
0
Sensory block Motor block
Duration

The mean duration of sensory block is 198.0±24.05 mins in group R and

359.30±61.94 mins in group RD. There is statistically highly significant difference

between the groups (p=0.001).The mean duration of motor blockade is 149.00±14.21

mins in group R and 233.70±15.26 mins in group RD. There is statistically highly

significant difference between the group (p=0.001)

85
Table 12:Mean heart rate (bpm) at various time intervals

Group R Group RD p-value

HR-0min 83.72 87.06

HR-5min 81.68 84.04

HR-10min 80.72 81.26

HR-15min 77.54 77.92

HR-20min 76.42 75.88

HR-25min 73.78 73.46

HR-30min 73.86 72.84

HR-35min 73.14 71.54

HR-40min 72.6 70.32

0.62
HR-45min 72.7 69.6

HR-50min 71.56 68.72

HR-55min 71.38 69.08

HR-60min 71.56 68.76

HR-75min 70.86 68.76

HR-90min 70.48 68.34

HR-105min 70.9 69.02

HR-120min 71.6 69.84

86
Figure 16:Graph showing mean heart rate (bpm) at various time intervals

90

Ropivacaine
85
Ropi+Dexme
80
Mean HR

75

70

65
Min Min Min Min Min Min Min Min Min Min Min Min Min Min Min Min Min
0 5 10 15 20 25 30 35 40 45 50 55 60 75 90 105 120
Duration

There is no statistically significant difference in the mean heart rate between

groups at various intervals.4 patients in RD group developed bradycardia which was

treated with inj.atropine 0.6mg.

87
Table 13: Mean systolic blood pressure (mmHg) at various intervals

Group R Group RD p-value

SBP-0min 123.42 130.74

SBP-5min 119.56 126.44

SBP-10min 115.48 120.78

SBP-15min 111.82 116.28

SBP-20min 108.72 114.72

SBP-25min 108.02 112.3

SBP-30min 107 110.44

SBP-35min 107.46 108.38

SBP-40min 107.14 108.38

0.8
SBP-45min 107.56 106.72

SBP-50min 107.84 107.68

SBP-55min 107.86 108.34

SBP-60min 108.64 107.78

SBP-75min 109.48 108.76

SBP-90min 109.82 108.68

SBP-105min 110.8 109.46

SBP-120min 111.14 110.38

88
Figure 17:Graph showing mean systolic blood pressure (mmHg) at various time

intervals

140

Ropivacaine
130
Ropi+Dexme
Mean SBP

120

110

100
Min Min Min Min Min Min Min Min Min Min Min Min Min Min Min Min Min
0 5 10 15 20 25 30 35 40 45 50 55 60 75 90 105 120
Duration

There is no statistically significant difference in systolic blood pressure

between both the groups. 7 patients in group RD and 4 patients in group R developed

hypotension which was treated with intravenous fluids and inj mephentermine.

89
Table 14: Mean diastolic blood pressure(mmHg) at various time intervals

Group R Group RD p-value

DBP –0min
76.9400 83.76
DBP –5min
74.26 79
DBP –10min
71.02 75.12
DBP –15min
68.06 71.64
DBP –20min
66.08 70.84
DBP –25min
65.28 69.56
DBP –30min
63.92 67.52
DBP –35min
64.06 67.4
DBP –40min
63.62 66.28 0.4
DBP –45min
62.46 64.88
DBP –50min
63.32 65.1
DBP –55min
62.94 64.86
DBP –60min
62.58 64.72
DBP –75min
63.32 64.96
DBP –90min
63.46 65.46
DBP –105min
64.4 64.56
DBP –120min
64.64 65.14

90
Figure 18:Graph showing mean diastolic blood pressure (mmHg)at various time

intervals

85
Ropivacaine
80
Ropi+Dexme
Mean DBP

75

70

65

60
Min Min Min Min Min Min Min Min Min Min Min Min Min Min Min Min Min
0 5 10 15 20 25 30 35 40 45 50 55 60 75 90 105 120
Duration

There is no statistically significant difference in diastolic blood pressure between both

the groups.

91
Table 15: Mean arterial pressure(mmHg) at various time intervals

Group R Group RD p-value

MAP- 0min 92.12 98.58

MAP-5min 88.82 94.36

MAP-10min 85.5 89.7

MAP-15min 82.3 86.02

MAP-20min 80.08 85.32

MAP-25min 79.24 83.3

MAP-30min 78.36 81.68

MAP-35min 78.36 81.1

MAP-40min 77.76 80.04

0.5
MAP-45min 77.34 78.7

MAP-50min 77.8 79.26

MAP-55min 77.86 78.72

MAP-60min 77.9 78.14

MAP-75min 78.06 78.46

MAP-90min 78.22 78.56

MAP-105min 78.82 78.88

MAP-120min 79.42 76.14

92
Figure 19:Graph showing mean arterial pressure (mmHg) at various time

intervals

100

Ropivacaine
95
Ropi+Dexme

90
Mean MAP

85

80

75
Min Min Min Min Min Min Min Min Min Min Min Min Min Min Min Min Min
0 5 10 15 20 25 30 35 40 45 50 55 60 75 90 105 120
Duration

There is no statistically significant difference in mean arterial pressure between both

the groups.

93
 DISCUSSION

A study entitled “Comparative study of Epidural 0.75% Ropivacaine with

Dexmedetomidine and 0.75% Ropivacaine alone in lower abdominal and lower limb

surgeries” was undertaken in KIMS hospital, Bangalore to evaluate the sensory and

motor blocking properties of Ropivacaine 0.75% compared with 0.75% Ropivacaine

with Dexmedetomidine.

After informed consent 100 patients of ASA class I and II, posted for various

elective lower abdominal and lower limb surgeries were grouped randomly into either

Group R or Group (RD). After identification of epidural space with loss of

resistance technique and introduction of epidural catheter, 3 ml of lignocaine 2% with

adrenaline test dose, 15 ml of the study drug was injected and various parameters

were studied.

Hypothesis made before starting the study

The hypothesis that was made before the study was that Ropivacaine will produce

lesser duration of sensory and motor blockade than Ropivacaine +

dexmedetomidine, as dexmedetomidine causes significant prolongation of sensory

and motor blockade78 and improves the quality of anaesthesia and perioperative

analgesia.79

Drugs selected for the study

In our study, the drugs selected for epidural anaesthesia were Ropivacaine and

dexmedetomidine. Ropivacaine is being regularly used for epidural anaesthesia for

lower limb orthopaedic surgeries in our hospital. Ropivacaine,has structural similarity

to bupivacaine. Without cardiotoxic effects of bupivacaine, has been introduced to

94
Indian market recently. Dexmedetomidine has been studied by various authors as an

adjuvant to epidural local anaesthetic74,75,76,77,78,79,80,81,81.Few studies have compared

ropivacaine and dexmedetomidine for epidural anaesthesia in India. Hence

ropivacaine and dexmedetomidine combination was selected for our study to compare

with ropivacaine alone.

Concentrations of the drugs selected

The potency of the local anaesthetics is correlated to the lipid solubility of the

drug. The lower lipid solubility of Ropivacaine would predict that it is likely to

produce a greater differential block of sensory and motor function than bupivacaine.28

Ropivacaine is less lipophilic than bupivacaine due to substitution of the

pipecoloxylidine with a 3 – carbon side chain instead of a 4-carbon side chain.4

Table no 16: Chemical and physical properties

Ropivacaine Dexmedetomidine

Molecular weight 274 248

Pka 8.1 7.1

Partition coefficient 9 2.89

Protein binding [%] 94 94

Casati et al.86 in their study reported that patients receiving 0.5% Ropivacaine

more frequently had an inadequate motor blockade during surgery than those

receiving bupivacaine.

We also conducted a pilot study in ten patients using Ropivacaine 0.5% for

epidural anaesthesia. Many of the patients had inadequate sensory and motor

95
blockade. Hence in our study 0.75% Ropivacaine was selected instead of 0.5%

Ropivacaine

Dexmedetomidine dose employed in our study is 0.6mcg/kg. we conducted a

pilot study in ten patients using dexmedetomidine 1mcg/kg. Many patients had

significant hypotension. Hence we selected a dose of 0.6mcg/kg

Dose of the drugs selected

The volume of 0.5% bupivacaine used in our hospital routinely for inguinal

hernia repair and lower limb orthopaedic surgeries under epidural anaesthesia is 15

ml after using 3 ml of 2 % lidocaine with adrenaline, the total dose being 18 ml. this is

calculated as 1ml/segment upto 150 cms of height, and adding 0.1ml/segment for

every 5 cms of increasing height2,the mean height in our study also being 170 cms in

both the groups and block upto T10 [13 segments] is required for inguinal

hernioplasty and lower limb surgeries, total volume required would be 18 ml. Hence

in both the groups 15 ml was selected as the volume of the study drug other than the

test dose.

Casati et al26 in their study of epidural anaesthesia for total hip replacement

compared bupivacaine and Ropivacaine and used graded epidural and found 15 ml of

Ropivacaine and 14 ml of bupivacaine is the volume required to achieve T10

anaesthesia, as in our study.

In our study all the patients were given epidural block in sitting position, because the

patients with lower limb fractures, found sitting position more comfortable. In our

study, the study drug was given in the sitting position, before bringing the patient to

96
supine posture. Because lower lumbar and sacral nerves are the thickest nerve roots,

and they will have a dense block when the drug is given in the sitting position.1

Demographic data

Demographic data comparing age, sex, weight, height shows no statistically

significant difference among both the groups.

Sensory blockade

Onset of sensory blockade

In our study the mean time for onset of sensory analgesia at T10 is 10.04 ±

2.55 mins in group R and 5.26±1.49 mins in group RD. This is statistically highly

significant (p<0.001).

Saravia P.S.F, Sabbag AT et al78 found no significant change in the onset time for

sensory block between control and dexmedetomidine groups.

82
The studies conducted by Bajwa SJ, Bajwa SK, Kaur J et al showed onset of

sensory analgesia at T10 in ropivacaine + dexmedetomidine group was 8.52 ± 2.36

min Vs 9.72 ± 3.44 min in ropivacaine + clonidine group and this is statistically

significant similar to our study.

83
Bajwa SJ, Arora V, Kaur J et al showed onset of sensory analgesia at T10 in

ropivacaine + dexmedetomidine group was 7.12± 2.44 mins VS 9.14 ± 2.94 mins in

ropivacaine + fentanyl group and this is also statistically significant similar to our

study.

These studies have added clonidine and fentanyl to ropivacaine while comparing with

ropivacaine + dexmedetomidine. That’s why we got statistically highly significance

compared to above studies.

97
Maximum sensory level

In our study the maximum level of sensory block in group RD was T5 (n=5)

and in group R was T6. The range of block was very wide in both the groups (T12-

T4).

Saravia P.S.F, Sabbag AT et al78 found maximum level of sensory block at T6

between control and dexmedetomidine groups.

The studies conducted by Bajwa SJ, Bajwa SK, Kaur J et al 82 showed maximum level

of sensory block at T5-6 level in group RD compared to T6-T7 in group RC which

compares with our study

Bajwa SJ, Arora V, Kaur J et al 83 showed maximum level of sensory block at T4-6

level in group RD compared to T5-T7 in group RF which again compares with our

study.

Duration of sensory block

In our study the duration of sensory block is longer with Ropivacaine +

Dexmedetomidine group compared with Ropivacaine group. It is 359.30±61.94 mins

with ropivacaine + Dexmedetomidine group compared to 198.0 ± 24.05 mins with

ropivacaine group. This is statistically highly significant(p<0.001).

83
Our study concurs with the study conducted by J Bajwa SJ, Arora V, Kaur J et al

who observed the mean duration of analgesia to be 366.62±24.42 mins in group RD

compared to 242.16±23.86 mins with in group RF which is highly significant.

Requirement of additional analgesics

Three patients in Ropivacaine group required supplemental analgesics intra-

operatively as they had inadequate block where as1 patient in Ropivacaine +

98
Dexmedetomidine group required supplemental analgesics. There was no statistical

significant difference in the requirement of supplemental analgesics.

Motor blockade

Onset of motor blockade

The onset of motor blockade was 15.36 ± 3.28 min in group R and 11.22 ± 2.61 mins

in group RD. This is statistically significant.

In our study motor blockade is assessed using modified Bromage scale and onset was

taken as soon as the patient developed grade I motor blockade.

Saravia P.S.F, Sabbag AT et al78 found no significant change in the onset time for

motor block between control and dexmedetomidine groups.

Degree of motor block

In our study it was found that group RD produced more intense motor block than

group R. 16 patients in RD group had grade 4 motor blockcompared with 0 patients

in group R. Also 15patients in R group had grade 2 motor block compared with 0

patients in group RD group. This is statistically highly significant( p<0.001).

In a study conducted by Saravia P.S.F, Sabbag AT et al78 found maximum motor

block at level 4 in 68% and 32% had grade 2 and 3 block with no patient remained in

grade 1 motor block in dexmedetomidine group patients. Whereas in control group,

29% of patients remained with grade 1 motor block, 47% and 24% grade 2 and 3. Our

study compares with this study as more number of patients had grade 4 motor

blockade in both the studies.

99
Duration of motor block

The duration of motor block in group RD is 233.70±15.36 mins compared to

149.00 ± 14.21 in group R. The duration of motor block with RD group is more

prolonged than with group R, which is statistically highly significant (p<0.001).

In a study conducted by Saravia P.S.F, Sabbag AT et al78 found the duration of

motor blockade was significantly higher in the dexmedetomidine group, averaging

30% higher than that observed in the control group similar to our study.
82
The studies conducted by Bajwa SJ, Bajwa SK, Kaur J et al showed the

mean duration of motor blockade was 246.72 ± 30.46 mins in ropivacaine +

dexmedetomidine group and 228.44 ± 27.18 mins in ropivacaine + clonidine group.

This was not statistically significant.

Heart rate

There is no statistically significant difference in the heart rate between the two

groups at various time intervals. 4 patients in RD group developed bradycardia which

was treated with inj.atropine 0.6mg. No patients in group R developed significant

bradycardia. The above result is consistent with the study conducted by Saravia P.S.F,

Sabbag AT et al78 wherein there was no statistically significant difference in the heart

rate intra and post-operatively.

Blood pressure

There was no statistically significant difference in SBP, DBP, MAP monitored

at various intervals between the two groups.However seven patients in group RD and

4 patients in group R developed hypotension which was treated with intravenous

fluids and inj mephentermine.

100
 In the studies conducted by Saravia P.S.F, Sabbag AT et al78, no statistical

significant difference was found in SBP, DBP, MAP in both the groups which

compares with our study.

Sedation score

Group R had the highest sedation score of 2 and in group RD was 4.

Dexmedetomidine had greater scores compared to ropivacaine alone. This is

statistically highly significant (p=0.001).

Similar results were observed by Saravia P.S.F, Sabbag AT et al78 who studied

bispectral index 30 mins after the execution of anaesthesia and before sedation or

additional analgesia. They noted that bispectral values were lower and patients were

more sedated in dexmedetomidine group than in the control group (p<0.05).

Similar results were also observed by Bajwa SJ, Bajwa SK, Kaur J et al 82 who

studied five point sedation. Mean sedation scores were significantly higher in

dexmedetomidine group compared to clonidine group (p<0.0001)

Side effects

In dexmedetomidine group, 4 patients developed bradycardia which was

treated with inj.atropine 0.6mg and significant hypotension seen in 7 patients in group

RD and 4 patients in group R which was treated with intravenous fluids and inj

mephentermine.

101
 CONCLUSION

From the present study it can be concluded that

1. There was statistically significant difference in the onset of sensory and motor

blockade between Ropivacaine and Ropivacaine and dexmedetomidine group.

2. Ropivacaine and dexmedetomidine group produced more intense motor blockade

than Ropivacaine group.

3. Duration of sensory block is prolonged with ropivacaine and dexmedetomidine

group compared to Ropivacaine group.

4. Duration of motor block is also prolonged with ropivacaine and

dexmedetomidine group compared to Ropivacaine group.

5. Ropivacaine and Dexmedetomidine group had greater sedation scores compared

to ropivacaine group.

6. Side effects like hypotension and bradycardia were not observed in any of the

group.

Hence it can be concluded that dexmedetomidine given epidurally with

ropivacaine produces synergistic effect of profound and prolonged motor

blockade and also a prolonged duration of sensory blockade. Ropivacaine and

dexmedetomidine can be a safe and effective agent for epidural blockade in lower

abdominal and lower limb surgeries.

102
 SUMMARY

A prospective randomized controlled study was undertaken to evaluate the

sensory and motor blocking properties of epidurally administered 15 ml of

Ropivacaine 0.75% and dexmedetomidine compared with Ropivacaine 0.75% in

lower abdominal and lower limb surgeries.

One hundred patients between the age group of 18-65 years belonging to

ASA I and II posted for elective lower abdominal and lower limb surgeries were

randomly divided into two groups. Each group consisting of 50 patients to receive

epidurally 15 ml of roipvacaine 0.75% (group R) and 15 ml roipvacaine 0.75%

and dexmedetomidine 0.6μg/kg (group RD).

Patients who had contraindications for epidural anaesthesia, patients posted

for emergency surgery, patients whose height is less than 150 cms and more than

180 cms, pregnant patients and patients with BMI > 30 were excluded from the

study.

In both the groups epidural space was identified in sitting position using

loss of resistance technique and epidural catheter was introduced for 3 cms inside.

After negative aspiration for blood and CSF ,test dose with 3 ml of lignocaine 2%

with adrenaline, 15 ml of the study drug was given in sitting position and the

patient was put in supine position.

The onset, maximum level and duration of sensory and motor blockade and

hemodynamic parameters were studied.

103
Table no 17: The following table shows the results obtained in the present study.

Max Intensit Duration Duration

Sensory Motor
Grou senso y of of sensory of motor
onset onset Sedation
p ry motor block[min block
[mins] [mins]
level block s] [mins]

10.04±2. 15.36±3.
R T6 Br3 198±24 149±14.2 2
5 2

RD 5.26±1.4 11.2±2.6 T5 Br4 359.5±61 233±54.2 4

Dexmedetomidine group had rapid onset of action (p<0.001), prolonged duration of

sensory and motor block (p<0.001), better sedation score (p=0.001), and determine

more intense motor block (p<0.001).There was no difference in the maximal

dermatomal level of analgesia, incidence of hypotension and bradycardia

(p>0.05). The occurrence of side effects (tremor, nausea and SpO2<90%) was low and

similar between groups (p>0.05).

104
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63. Yildiz M, Tavlan A, Tuncer S, Reisli R, Yosunkaya A, Otelcioglu. Effect of

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64. Maarouf M. Evaluation of effect of dexmedetomidine in reducing shivering

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65. Kanazi GE, Aonad MT, Jabbour Khonry SI, AJ-Jazzar MD, Alameddine MM,

AL-Yaman R, et al. Effect of small dose dexmedetomidine or clonidine on the

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50:222-7.

66. Memis D, Turan A, Karamanlioglu B, Pamukai Z, Kurt I. Adding

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Analg; 2004; 98(3);835-40.

67. Vanda G Yazbek Karam, Marie M Auad. Perioperative uses of

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bupivacaine prolongs caudal analgesia in children. Br J Anaesth 2009;

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69. Siobal SM, Kullet HR, Kivett AV, Tang FJ. Use of dexmedetomidine to

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from dexmedetomidine after protracted use in pediatric patient. Pediatric

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71. Darnell C, Steiner J, Seff, Szmuk, Peter, Sheerun, et al. Withdrawal from

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72. Shebabi Y, Ruettimann V, Adamson H, Inner R, Ickeringill M.

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115
 PROFORMA

DEPT. OF ANAESTHESIOLOGY AND CRITICAL CARE, KIMS,

BANGALORE

Patient name: I.P.No:

Age: Ward:

Sex: Unit:

Address: Date of admission:

Date of sugery:

Diagnosis: Operation:

Pre-anaesthetic evaluation

H/O:

Clinical examination: Investigations

Hb%-

Pulse rate :

BP: BT-

CT-

Cardiovascular system: Hiv/HbSAg/VDRL

Respiratory system : FBS/PBS

116
 Blood urea

Spine : Serum creatinine

ASA GRADING : Blood group and Rh-

Airway assessment: : ECG

Weight:

Height: CXR

BMI:

Pre-Operative Instructions:

Anaesthetic management

Date: Time:

Anaesthesia procedure:

117
Drugs used:

Onset of sensory block:

Onset of motor blockade :

Maximum dermatomal level of analgesia:

Intensity of motor blockade(Modified Bromage scale):

118
Sedation score (Five point scale):

Alert and wide awake 1

Arousable to verbal command 2

Arousable with gentle tactile stimulation 3

Arousable with vigorous shaking 4

Unarousable 5

Duration of sensory blockade:

Duration of motor blockade:

119
Vitals→ time PULSE SBP DBP MAP SPO2
in min ↓ RATE

10

15

20

25

30

35

40

45

50

55

60

75

90

105

120

120
 KEY TO MASTER CHART

cm - Centimeters
D - Dexmedetomidine
DBP - Diastolic blood pressure
F - Female
HR - Heart rate
I.P. No. - Inpatient number
Kg - Kilograms
ligno 2% - Inj Lignocaine 2% with adrenaline [1:200000]
m - Inj Mephentermine
M - Male
MAP - Mean arterial pressure
Mins - Minutes
mmHg - Millimeters of mercury
R - Ropivacaine
SBP - Systolic blood pressure
Sl.No. - Serial number
Wt. - Weight
# - Fracture

121
 0.75% ROPIVACAINE ALONE

Max dermatomal level of analgesia

Duration of sensory block (min)

Duration of motor block (min)

Intensity of motor block
Sensory onset(min)

Motor onset(min)
Type of surgery
weight (in kgs)
Age in yrs

Sedation
SL NO

IP NO

Sex
1 19248 52 F 58 # BB LEG 8 13 T6 2 2 180 150
2 264623 50 F 60 IH 10 15 T6 3 2 180 150
3 20835 45 M 62 IH 12 18 T8 3 2 210 135
4 20839 60 F 52 IH 8 15 T8 2 2 210 150
5 20264 65 M 58 IH 16 21 T6 2 1 210 170
6 20420 32 M 58 IH 8 10 T8 2 2 270 210
7 20994 39 M 60 IH 8 13 T6 3 2 210 150
8 20995 60 F 51 IH 12 18 T8 3 2 180 165
9 21002 40 M 63 # IT femur 12 15 T6 3 2 210 150
10 23438 55 F 52 # IT femur 10 18 T6 2 2 210 150
11 22578 32 M 60 # IT femur 8 12 T6 3 1 240 170
12 24051 38 M 70 IH 8 10 T10 3 1 210 150
13 24845 18 M 61 # BB LEG 10 15 T6 3 2 180 135
14 26043 51 M 74 # IT femur 8 12 T6 3 2 180 150
15 25321 65 F 58 # IT femur 12 18 T8 3 2 210 150
16 25890 50 M 59 # IT femur 15 18 T8 3 2 210 150
17 27788 60 M 58 # IT femur 8 15 T6 3 2 180 135
18 26128 60 F 52 # IT femur 8 10 T6 2 2 180 150
19 28540 60 M 60 # IT femur 8 12 T6 2 1 180 150
20 28949 24 M 62 # BB LEG 8 15 T6 2 1 210 150
21 1552 48 M 64 # BB LEG 10 18 T8 3 2 180 150
22 1285 30 M 58 # IT femur 12 18 T8 2 2 250 150
23 2246 58 M 60 # BB LEG 8 15 T6 3 2 180 135
24 2501 46 M 59 # IT femur 8 12 T10 2 1 180 150
25 2360 40 M 58 # BB LEG 8 12 T6 3 2 210 150
26 2472 25 M 60 # IT femur 10 18 T8 3 2 210 165
27 4223 40 M 62 # IT femur 8 15 T6 3 2 180 150
28 26047 60 M 60 # IT femur 12 15 T6 3 2 190 135
29 27459 62 F 50 # IT femur 12 15 T6 3 2 210 150
30 22096 25 F 52 IH 10 12 T6 2 2 180 150
31 16288 21 F 51 # BB LEG 8 12 T6 3 2 180 135
32 16634 23 M 54 # BB LEG 13 15 T8 3 1 210 150
33 21983 65 M 58 # IT femur 15 18 T6 3 2 220 150
34 23693 43 M 61 # IT femur 20 25 T6 3 2 190 160
35 23141 24 M 64 # BB LEG 8 15 T8 3 2 135 105
36 25643 23 M 52 IH 8 12 T6 3 1 210 150
37 22944 48 M 60 # IT femur 10 18 T6 3 1 180 135
38 54095 29 M 61 # BB LEG 11 18 T6 2 1 210 150
39 11103 48 M 50 # IT femur 12 18 T8 3 1 180 150
40 14141 43 M 62 # IT femur 12 15 T6 3 2 210 160
41 13611 28 M 70 # IT femur 10 18 T8 2 2 180 150
42 69907 36 F 58 IH 9 24 T6 3 1 220 150
43 50382 32 F 60 # BB LEG 8 15 T8 3 1 180 130
44 63821 24 M 65 IH 9 15 T8 3 2 210 135
45 64328 42 F 55 # IT femur 8 12 T8 3 1 190 150
46 949 25 F 50 # IT femur 10 12 T6 2 2 220 150
47 33484 32 M 56 # BB LEG 8 12 T6 2 2 210 165
48 721 29 M 59 # BB LEG 10 15 T6 3 1 220 150
49 33267 50 M 60 # IT femur 9 18 T6 3 1 180 135
50 589 55 M 55 # IT femur 9 18 T8 3 1 190 135
 0.75% ROPIVACAINE ALONE

SBP105

SBP120
HR105

HR120

SBP10

SBP15

SBP20

SBP25

SBP30

SBP35

SBP40

SBP45

SBP50

SBP55

SBP60

SBP75

SBP90
IP NO

HR10

HR15

HR20

HR25

HR30

HR35

HR40

HR45

HR50

HR55

HR60

HR75

HR90

SBP0

SBP5
HR-0

HR5
19248 92 94 90 86 94 80 70 77 70 73 67 64 65 64 68 70 80 130 127 124 118 125 117 109 108 106 98 92 101 98 98 102 109 110
264623 90 86 84 82 80 81 82 78 76 78 79 78 76 74 74 74 72 124 118 112 108 110 104 104 105 106 102 102 106 102 108 110 104 104
20835 64 64 62 61 61 60 58 57 56 58 58 55 56 56 56 56 58 108 106 108 100 98 95 92 90 94 94 96 92 92 94 92 94 94
20839 81 78 80 77 76 76 72 69 70 70 71 70 69 69 68 69 69 140 132 124 124 118 112 116 112 112 118 116 118 112 114 112 110 112
20264 97 86 98 90 87 91 85 85 82 78 76 78 74 70 70 68 68 137 113 79 79 85 102 99 97 97 85 91 93 79 109 103 109 110
20420 65 65 63 62 65 69 72 68 67 65 64 64 64 65 66 65 65 123 124 115 105 100 94 94 100 98 102 104 104 104 102 106 102 104
20994 90 94 94 92 95 85 84 83 86 81 80 84 86 86 82 85 82 126 115 129 117 117 118 115 114 109 112 114 111 120 116 114 118 118
20995 85 82 82 80 79 76 76 78 75 74 76 80 76 74 74 75 76 118 110 110 108 102 95 98 102 96 96 98 100 102 102 104 103 104
21002 88 86 80 74 74 72 76 70 72 76 74 70 72 74 73 70 70 130 126 124 116 118 118 110 108 102 108 106 106 104 108 110 106 108
23438 94 83 88 80 84 87 88 82 78 76 78 76 75 72 69 69 68 118 116 114 116 110 113 112 110 110 108 112 110 108 108 108 110 110
22578 82 82 80 76 78 77 74 70 69 69 70 67 65 68 64 65 65 126 120 116 112 110 106 104 108 110 110 112 108 110 112 108 108 106
24051 90 94 92 91 89 88 85 86 89 82 80 81 80 82 80 76 78 130 122 120 112 110 104 104 102 106 102 102 104 106 102 106 104 106
24845 74 77 75 72 70 74 69 66 68 69 67 67 68 68 70 71 75 136 124 124 120 118 116 120 118 112 116 116 114 112 113 114 112 112
26043 92 91 90 88 87 84 82 80 81 78 76 77 78 75 77 75 76 120 118 112 110 106 110 106 108 102 106 108 108 110 106 106 110 110
25321 70 71 68 66 65 66 64 64 67 68 69 64 65 65 66 67 62 104 104 95 92 90 88 85 86 90 92 92 95 96 94 96 97 98
25890 80 80 79 74 72 71 70 68 65 68 69 68 67 66 65 65 66 148 148 142 136 134 134 130 130 132 130 126 130 128 126 124 126 126
27788 84 80 82 79 79 82 76 75 76 73 72 70 69 64 65 64 66 122 120 104 108 104 110 108 110 112 112 110 108 110 106 106 110 108
26128 70 69 69 67 66 67 66 64 68 62 62 64 65 65 65 64 64 110 102 102 98 96 100 96 98 98 103 102 100 104 104 106 102 104
28540 94 92 86 80 78 76 72 74 73 74 74 76 76 75 76 76 76 130 126 126 120 120 122 122 121 120 118 120 116 118 118 122 118 118
28949 88 89 85 80 82 76 78 78 76 76 75 76 78 74 74 76 76 106 102 102 100 98 92 86 94 90 88 94 96 98 96 96 98 98
1552 70 68 68 66 65 58 56 58 60 60 62 60 60 62 62 63 64 116 118 106 108 106 104 104 102 104 108 108 106 104 106 110 106 106
1285 92 90 89 90 84 85 80 79 77 78 74 76 78 72 70 76 74 112 109 110 102 98 95 96 98 100 98 98 96 102 106 104 102 102
2246 84 80 82 78 78 80 82 78 75 72 74 70 69 68 69 70 68 128 121 118 114 112 112 114 110 114 115 116 112 112 114 110 110 110
2501 90 84 88 86 85 78 78 79 74 76 77 78 75 77 74 78 79 136 132 129 132 124 125 128 130 128 128 126 130 126 126 124 128 126
2360 70 67 66 66 60 58 59 55 54 56 60 64 64 66 62 65 65 118 120 118 116 112 114 110 112 112 116 112 112 112 114 115 116 114
2472 94 93 82 74 68 66 65 69 69 79 79 77 81 80 76 75 75 124 120 116 110 104 104 102 104 104 106 108 108 104 104 106 112 110
4223 84 80 83 84 80 78 79 76 79 77 72 73 74 73 75 76 74 112 110 102 102 100 98 100 102 104 105 110 106 108 110 108 110 116
26047 95 92 94 85 84 88 86 84 82 78 78 80 78 79 76 78 78 134 132 130 129 126 128 126 128 130 128 130 132 130 138 134 134 134
27459 80 76 78 80 76 72 68 68 70 70 68 69 70 72 70 74 74 120 120 116 116 110 110 114 110 112 114 114 116 118 112 114 114 118
22096 86 80 84 77 79 84 79 78 74 80 74 81 77 75 72 73 79 122 120 120 118 116 118 114 112 114 116 116 115 114 116 116 118 116
16288 96 90 94 87 89 97 89 88 83 90 84 91 87 85 82 83 89 110 104 111 108 109 113 104 111 121 113 107 114 120 115 110 120 116
16634 97 90 90 71 81 73 73 71 78 78 74 71 71 72 75 72 69 102 102 95 104 105 105 107 101 102 102 104 103 103 107 100 110 106
21983 92 88 82 74 71 73 85 85 85 84 78 76 76 75 75 80 85 138 132 90 81 80 92 90 108 107 105 110 113 113 113 111 115 122
23693 82 78 80 78 75 75 75 74 70 72 68 69 68 67 67 66 65 133 126 124 127 120 123 123 129 125 124 120 120 124 124 120 126 124
23141 84 79 82 83 79 77 78 75 78 76 71 72 72 71 70 73 74 135 133 133 129 133 124 126 129 134 134 129 121 131 125 129 128 126
25643 89 86 90 93 83 81 79 82 80 83 81 75 68 69 72 74 75 119 119 116 122 111 107 103 103 95 95 99 107 108 110 106 106 110
22944 95 94 83 74 67 65 64 68 68 77 79 76 80 79 75 74 74 160 158 152 108 95 92 90 95 82 101 101 98 108 99 116 119 121
54095 76 71 71 64 64 55 54 56 53 55 55 58 59 56 58 60 58 122 134 130 129 125 124 130 125 124 128 124 120 120 121 122 120 124
11103 70 68 67 69 69 65 65 67 68 62 61 61 59 58 58 59 58 132 130 122 120 116 118 114 112 116 116 118 111 112 116 112 112 110
14141 81 82 85 78 79 76 74 75 76 78 77 79 74 72 70 71 72 112 110 106 100 95 92 94 98 98 98 100 102 102 100 104 104 102
13611 80 82 72 72 69 69 65 67 67 69 67 66 70 67 68 68 66 124 118 120 113 110 112 110 104 108 110 106 105 102 102 104 108 110
69907 87 90 81 79 74 88 91 84 83 75 70 70 92 96 95 75 85 115 112 117 116 105 93 104 107 97 92 81 94 109 112 129 132 130
50382 83 84 80 81 80 78 77 79 76 75 76 78 78 75 75 76 76 123 120 112 110 108 104 106 102 102 104 118 110 111 108 110 108 108
63821 74 79 71 70 72 69 66 67 68 68 62 61 65 65 64 62 62 116 108 106 110 106 104 102 108 106 110 108 110 108 110 106 106 104
64328 89 89 82 85 80 79 77 75 73 70 70 70 69 69 70 71 72 122 120 121 118 112 110 108 102 104 104 106 106 106 108 110 112 112
949 80 75 79 81 77 73 69 69 71 71 69 70 71 73 71 75 75 110 102 102 100 95 94 90 89 90 90 94 94 94 96 94 94 98
33484 96 89 90 85 84 85 82 82 83 82 85 81 80 78 79 84 85 130 120 122 118 116 112 112 110 114 108 106 108 110 112 110 106 108
721 81 80 86 78 77 79 72 72 71 74 75 70 71 70 71 74 73 120 120 118 114 105 110 106 104 102 100 102 102 104 104 102 106 104
34597 65 65 60 61 64 60 59 55 56 57 54 55 56 56 59 56 60 128 130 126 118 115 118 116 112 110 112 110 108 110 114 112 110 112
589 74 72 70 71 67 67 68 70 65 65 67 63 62 60 62 64 65 112 105 104 100 98 96 97 95 96 98 98 94 94 96 98 98 98
 0.75 % ROPIVACAINE ALONE

MAP105

MAP120
DBP105

DBP120

MAP10

MAP15

MAP20

MAP25

MAP30

MAP35

MAP40

MAP45

MAP50

MAP55

MAP60

MAP75

MAP90
DBP10

DBP15

DBP20

DBP25

DBP30

DBP35

DBP40

DBP45

DBP50

DBP55

DBP60

DBP75

DBP90

MAP0

MAP5
IP NO

DBP0

DBP5
19248 74 74 65 73 69 61 62 74 60 52 47 45 56 58 60 69 76 90 87 79 83 83 76 75 81 70 64 59 56 66 67 68 69 76
264623 80 72 69 68 69 65 62 64 64 60 60 58 58 60 60 61 60 94 87 83 83 84 80 79 80 76 74 74 75 73 76 78 75 75
20835 80 78 78 76 76 75 76 72 72 70 72 70 68 65 69 69 66 89 87 88 88 84 83 81 81 78 79 78 81 77 74 74 75 75
20839 88 81 76 78 76 75 71 70 70 69 70 69 66 68 68 67 68 105 96 92 93 90 89 86 83 83 84 84 86 85 87 86 85 84
20264 78 63 51 51 53 60 56 52 51 49 52 52 52 60 61 60 62 92 75 57 57 60 70 65 62 62 58 68 67 68 69 69 68 68
20420 67 73 71 63 61 55 54 58 61 63 64 62 60 61 64 65 64 83 93 88 79 78 70 69 65 69 72 68 67 65 67 68 69 70
20994 75 68 73 63 52 58 50 62 77 63 66 69 71 71 66 78 68 89 79 88 74 69 72 76 76 83 75 78 78 82 80 81 80 82
20995 72 74 70 69 66 61 62 60 58 60 62 61 60 62 60 58 60 87 85 83 81 78 72 73 74 72 72 74 74 74 75 74 73 75
21002 70 66 67 65 62 60 57 58 56 58 60 60 58 55 56 58 55 90 86 85 82 80 80 76 77 78 80 80 79 78 75 75 76 76
23438 83 80 80 80 77 74 77 75 76 72 70 68 66 65 67 66 65 94 90 91 91 88 82 80 86 86 84 84 82 82 80 81 82 80
22578 74 75 67 67 65 64 62 65 65 63 65 61 61 62 60 62 62 91 90 83 80 80 80 78 80 80 79 80 80 76 78 75 76 74
24051 91 86 85 82 79 78 78 70 72 72 71 69 72 72 70 72 70 104 98 97 92 89 86 86 80 80 79 79 78 78 82 82 81 80
24845 82 80 78 70 69 68 67 68 69 66 65 64 64 67 66 64 64 100 94 92 87 85 85 86 86 83 84 80 80 81 81 83 80 80
26043 76 71 70 65 66 68 65 63 66 65 67 68 64 66 60 65 66 90 86 83 80 78 82 80 81 78 80 81 81 80 79 75 79 80
25321 70 72 65 64 65 60 61 56 55 56 57 54 51 56 55 52 54 81 81 75 73 73 70 69 66 67 68 67 67 65 67 68 67 68
25890 94 95 89 82 80 80 78 75 75 73 74 74 70 71 70 72 70 112 112 106 100 96 96 95 93 93 92 91 92 90 90 88 89 89
27788 80 80 69 68 65 67 67 66 67 68 62 70 72 68 68 65 66 94 93 80 81 80 81 81 82 82 83 80 83 83 82 82 80 80
26128 76 70 69 65 66 65 62 64 65 66 65 62 62 60 62 62 63 89 80 80 78 77 78 73 74 74 76 76 76 78 77 78 75 75
28540 88 85 85 76 75 75 72 72 70 69 69 70 71 70 68 68 69 102 98 98 90 90 91 87 87 87 86 86 85 86 85 83 83 84
28949 68 65 66 62 60 61 58 59 58 55 56 58 55 57 59 56 56 80 77 77 75 74 72 71 70 68 66 68 68 67 69 69 71 71
1552 78 80 76 70 71 68 65 62 62 60 61 64 62 65 65 62 62 90 92 82 81 79 75 76 75 75 76 76 74 72 74 80 81 81
1285 70 64 65 50 56 57 55 58 59 56 56 58 55 58 58 59 60 84 79 80 67 70 70 69 70 72 70 70 71 73 74 73 73 73
2246 82 78 76 75 70 69 70 66 68 67 69 65 65 67 64 64 64 97 90 92 88 85 85 87 82 85 85 84 80 80 82 79 79 79
2501 84 80 79 78 75 74 75 72 70 70 68 68 69 70 70 72 69 101 97 95 96 91 91 92 92 90 90 88 89 89 88 87 88 90
2360 80 78 75 72 68 65 65 67 67 65 67 65 63 65 61 64 64 92 92 89 87 82 81 80 82 82 80 81 80 81 80 80 81 81
2472 72 72 70 62 56 55 54 55 57 57 58 56 56 55 58 58 60 89 87 86 78 72 72 71 72 73 72 74 74 72 72 74 75 75
4223 78 70 62 62 59 60 60 62 62 60 65 65 62 65 65 68 66 89 83 75 75 72 70 72 72 71 76 80 78 78 80 78 82 84
26047 81 80 79 74 71 70 68 65 65 67 68 68 69 70 71 70 72 97 95 93 90 91 89 85 87 85 86 84 85 85 82 80 81 80
27459 86 85 80 79 73 72 74 70 72 71 74 74 72 70 69 69 70 97 92 91 91 86 84 85 83 84 84 85 87 87 85 85 86 86
22096 80 82 82 76 75 76 72 70 72 70 70 72 70 68 65 68 68 94 94 93 90 89 90 88 84 88 89 89 88 88 87 86 89 88
16288 66 65 58 71 71 68 62 67 70 55 60 64 64 70 60 70 68 83 81 84 87 85 87 79 85 88 75 80 87 84 85 82 88 88
16634 62 58 51 49 59 57 57 48 49 50 50 50 50 51 52 50 51 77 77 70 73 76 76 76 72 72 73 75 73 73 74 72 68 64
21983 84 73 53 50 45 57 57 68 61 65 74 69 66 63 69 68 79 106 95 68 63 56 71 70 87 80 82 86 87 85 84 86 89 96
23693 74 71 79 75 76 78 77 77 74 76 75 72 70 72 71 72 74 89 84 90 87 86 88 89 89 88 87 88 86 84 88 89 87 89
23141 80 79 76 75 78 78 76 77 79 77 75 74 76 75 72 74 75 95 92 93 90 92 91 94 94 96 98 95 90 92 90 89 89 90
25643 75 75 71 68 65 63 61 62 59 62 65 62 64 65 62 65 65 83 86 82 81 77 74 71 71 68 70 69 70 74 75 76 75 74
22944 98 94 89 63 54 58 57 64 53 65 64 67 65 65 71 76 76 128 127 115 79 72 73 70 75 63 79 79 78 84 79 84 91 97
54095 71 75 71 71 69 65 66 74 64 65 67 65 66 64 64 65 65 93 97 93 93 93 90 88 92 93 87 87 90 87 86 85 85 85
11103 80 76 70 68 68 65 62 60 62 60 64 60 62 64 60 60 58 97 94 87 85 84 82 79 77 78 78 80 79 79 80 79 79 75
14141 60 58 55 53 52 50 50 48 49 50 52 50 51 50 54 52 52 77 75 72 68 67 64 65 64 65 67 68 69 68 67 61 70 70
13611 68 62 64 60 59 58 55 56 55 56 57 55 50 54 55 53 57 87 80 82 77 75 76 74 72 70 74 74 73 67 68 69 70 74
69907 72 69 67 63 61 57 54 57 56 42 42 50 45 50 69 73 73 90 85 84 81 78 69 76 75 73 56 57 68 71 72 90 94 98
50382 80 80 78 70 70 69 70 68 65 64 66 67 68 64 68 68 68 94 92 89 83 83 81 82 79 78 78 83 81 81 80 82 80 80
63821 70 66 65 67 67 62 61 62 59 58 58 60 61 60 62 60 59 85 80 78 80 79 76 75 76 75 72 75 77 76 77 78 76 75
64328 68 68 62 69 58 59 56 55 56 57 57 58 60 60 58 58 60 86 85 81 85 76 75 73 70 71 71 72 72 73 73 75 75 76
949 70 64 64 59 56 56 55 50 50 49 52 52 54 53 54 54 56 80 76 76 72 69 69 67 63 63 63 66 66 67 68 66 66 68
33484 72 68 68 69 66 65 65 62 64 60 59 60 62 62 60 62 62 91 85 86 85 83 81 81 79 81 76 75 76 79 80 77 76 77
721 80 80 76 75 75 71 70 70 69 73 72 70 74 74 75 71 72 93 93 90 89 85 81 82 82 81 84 82 81 84 84 83 83 84
34597 92 90 82 84 78 78 75 72 72 70 69 65 65 67 67 68 67 104 104 96 95 88 89 88 86 84 84 82 80 80 80 79 81 82
589 68 65 65 59 52 54 55 56 54 57 58 58 56 56 55 58 56 82 78 78 72 67 67 68 67 67 70 71 69 68 69 70 71 70
 Ropivacaine with Dexmedetomidine

Max dermatomal level of analgrsia

Duration of sensory block(min)

Duration of motor block(min)

Intensity of motor block
Sensory onset(min)

Motor onset(min)
Type of surgery
Weight (in kgs)

Sedation score
Age in yrs
SL NO

IP NO

Sex
1 16266 38 M 54 # IT femur 8 12 T6 4 3 255 240
2 19079 45 M 50 # IT femur 4 6 T6 3 3 320 280
3 19246 48 F 50 # IT femur 9 15 T6 3 3 300 210
4 19578 45 F 55 # BB LEG 4 5 T6 4 2 300 220
5 19967 21 F 61 # IT femur 4 5 T6 3 2 435 280
6 20405 50 F 50 IH 4 8 T6 3 3 400 270
7 21571 50 F 50 # BB LEG 4 6 T6 3 3 330 240
8 21700 60 M 55 IH 4 9 T6 4 3 330 210
9 23084 65 M 65 IH 5 10 T6 3 3 390 300
10 23102 61 M 50 IH 6 12 T6 3 2 450 330
11 23870 50 F 50 IH 5 9 T6 3 2 360 210
12 24035 38 M 65 IH 6 15 T6 3 2 260 210
13 24220 40 F 70 IH 4 11 T6 4 2 320 180
14 24842 60 M 65 IH 4 11 T8 3 3 350 210
15 25375 58 M 62 # IT femur 5 11 T6 3 3 400 270
16 25958 52 F 50 # BB LEG 4 12 T6 3 4 350 210
17 25410 52 F 54 # IT femur 4 6 T6 3 3 390 330
18 26955 58 F 50 # BB LEG 6 11 T8 4 3 400 270
19 372540 35 F 53 # IT femur 5 11 T6 3 3 310 190
20 29010 27 M 58 # BB LEG 4 10 T6 3 3 360 180
21 462 52 M 50 # IT femur 4 12 T6 4 4 310 190
22 822 45 M 50 # BB LEG 5 12 T6 4 4 390 210
23 1413 28 M 64 # IT femur 3 11 T5 3 3 390 210
24 2107 36 M 60 # BB LEG 6 10 T6 3 4 390 230
25 1853 28 F 52 # IT femur 5 15 T8 3 3 400 280
26 1913 20 M 50 # IT femur 7 15 T6 4 3 360 180
27 1031` 28 M 55 # BB LEG 7 15 T6 4 2 310 190
28 2874 21 M 61 # IT femur 6 12 T6 3 3 310 210
29 3429 26 M 50 # IT femur 4 10 T6 3 3 390 210
30 24517 55 M 62 IH 3 10 T6 3 3 540 405
31 25645 54 F 50 IH 6 13 T6 3 2 400 270
32 23432 43 M 60 # IT femur 4 12 T5 4 2 480 330
33 11098 48 F 50 IH 5 12 T6 3 3 340 210
34 11209 23 F 70 # BB LEG 7 15 T6 3 4 480 320
35 12334 24 M 50 # IT femur 8 12 T10 3 2 510 380
36 1207 22 M 50 # BB LEG 4 15 T6 3 2 280 170
37 1230 30 M 54 # IT femur 5 12 T6 3 2 310 190
38 1412 42 F 52 # IT femur 7 14 T8 4 3 375 210
39 1902 50 M 60 # BB LEG 6 11 T6 3 2 360 210
40 2314 28 M 58 # IT femur 7 12 T6 4 2 390 210
41 2436 20 M 59 IH 7 12 T6 4 2 310 240
42 2891 48 M 64 # IT femur 9 11 T6 4 3 300 210
43 3217 34 M 54 # IT femur 4 10 T5 3 3 310 180
44 3462 56 M 54 # IT femur 4 12 T5 3 3 360 210
45 5769 62 F 50 # BB LEG 4 10 T8 4 3 390 240
46 4721 40 F 53 # IT femur 6 10 T6 3 4 310 190
47 4734 42 M 62 # IT femur 4 10 T6 3 3 280 180
48 5102 28 F 56 IH 5 12 T6 3 3 360 180
49 7906 25 M 68 IH 7 15 T8 4 3 310 190
50 7388 22 M 60 IH 5 14 T5 3 3 310 210
 ropivacaine with dexmedetomidine

SBP105

SBP120
HR105

HR120

SBP10

SBP15

SBP20

SBP25

SBP30

SBP35

SBP40

SBP45

SBP50

SBP55

SBP60

SBP75

SBP90
HR10

HR15

HR20

HR25

HR30

HR35

HR40

HR45

HR50

HR55

HR60

HR75

HR90
IP N0

SBP0

SBP5
HR-0

HR5
16266 116 110 110 103 103 89 93 95 89 86 85 84 89 89 92 95 95 138 132 128 124 127 109 114 113 110 97 102 102 100 104 108 108 108
19079 109 116 120 113 96 88 90 90 86 87 89 96 94 93 90 86 81 143 141 134 122 108 106 110 108 108 104 101 100 89 110 111 103 99
19246 92 94 90 86 94 80 70 77 70 73 67 64 65 64 68 70 80 130 127 124 118 125 117 120 109 108 106 98 92 101 98 98 102 109
19578 87 78 76 67 66 67 70 69 70 66 71 76 76 75 66 65 68 114 80 102 100 95 95 98 90 93 90 109 117 113 107 105 107 110
19967 75 67 59 57 55 58 57 57 56 62 58 57 59 56 56 60 62 117 114 116 100 111 107 103 100 107 104 94 102 108 116 114 117 118
20405 84 79 74 76 71 68 70 73 72 66 68 65 66 65 65 64 67 146 148 142 138 138 130 128 132 128 120 122 120 118 124 120 120 124
21571 74 70 65 61 60 61 61 60 60 61 60 60 59 60 73 75 75 110 118 107 109 97 94 98 95 98 96 94 98 115 110 108 110 110
21700 78 70 71 66 62 59 72 71 73 74 74 72 71 70 72 70 72 145 129 113 93 111 107 96 118 113 115 97 103 105 108 108 105 106
23084 65 60 54 56 50 53 53 50 50 51 50 50 51 51 56 54 56 140 146 136 113 116 117 112 112 114 114 115 117 117 126 131 134 134
23102 68 65 68 72 70 65 64 61 58 56 55 55 55 54 54 65 65 148 140 156 161 139 131 128 120 115 110 115 122 118 120 127 119 120
23870 80 76 77 78 72 71 70 72 70 69 68 69 66 65 65 67 65 124 118 112 116 112 110 102 102 100 98 102 102 100 106 105 106 106
24035 82 80 76 76 72 68 68 70 78 76 77 78 74 76 82 82 83 153 146 134 138 144 148 140 133 133 133 133 135 139 140 136 137 136
24220 86 84 84 80 80 79 74 70 68 70 76 78 91 92 88 86 88 129 117 104 99 103 94 104 99 100 103 103 103 103 104 102 98 102
24842 90 80 69 58 56 57 57 56 55 56 55 55 55 63 63 64 64 133 108 96 90 92 92 94 94 89 89 109 106 103 106 108 108 108
25375 84 84 82 80 78 79 80 76 74 70 71 69 68 68 67 65 66 150 144 126 118 120 108 102 98 114 112 108 104 107 108 110 108 110
25958 78 70 72 72 71 70 68 69 68 67 66 67 65 64 65 62 62 114 98 90 102 106 104 110 108 106 102 98 110 108 108 106 110 112
25410 76 75 78 72 70 68 65 62 60 57 58 54 55 56 56 55 57 122 110 112 110 98 96 96 90 92 92 108 106 106 102 108 110 108
26955 98 95 90 86 82 80 74 75 70 68 65 64 66 65 67 67 68 146 146 140 132 118 120 118 116 112 116 118 120 118 122 120 126 126
372540 80 80 76 77 73 72 74 71 69 68 68 69 70 72 71 70 71 110 104 97 94 90 89 89 90 89 104 102 104 104 106 106 102 102
29010 102 100 98 94 95 93 90 91 90 88 85 86 82 78 76 75 72 138 140 145 140 130 130 128 120 122 120 124 120 118 120 121 124 120
462 98 99 89 96 86 89 88 88 84 83 81 82 75 73 68 74 72 158 144 110 102 90 130 112 128 105 103 104 96 86 88 90 102 99
822 99 96 95 93 97 91 93 93 91 88 88 88 88 87 88 87 86 110 101 104 103 103 98 99 96 92 89 94 89 91 93 97 97 98
1413 125 126 113 111 104 98 101 102 98 98 97 105 103 110 96 98 94 107 104 89 96 108 108 105 99 97 96 94 106 103 110 96 102 108
2107 86 80 76 75 76 70 71 75 74 77 76 75 74 75 70 72 73 124 126 122 120 118 116 115 110 112 110 114 112 116 115 112 114 116
1853 96 92 90 76 82 82 76 74 77 76 74 68 68 65 64 64 66 159 151 129 120 128 133 130 130 118 120 118 120 120 110 97 110 110
1913 103 106 90 73 69 64 62 54 53 52 53 64 60 55 50 60 76 130 131 128 120 123 121 114 117 111 108 128 131 120 108 104 112 128
1031 101 95 90 92 85 82 80 76 72 70 68 69 70 68 66 67 68 122 120 112 108 106 110 108 105 104 102 105 108 110 106 108 110 112
2874 70 69 70 66 65 61 60 56 59 59 56 55 54 54 55 54 54 136 138 130 126 126 121 120 112 110 110 112 110 108 109 108 110 109
3429 79 75 76 75 72 71 71 70 69 65 64 67 67 65 65 64 64 128 110 102 100 96 103 104 98 95 95 98 98 96 95 98 102 98
24517 85 83 71 79 69 70 69 65 65 63 59 59 61 58 60 61 64 144 136 127 136 122 120 121 118 114 115 107 101 110 112 108 106 106
25645 121 124 118 80 85 81 79 79 81 82 81 80 80 80 84 77 76 126 112 100 98 103 106 95 98 114 94 104 102 96 95 101 94 110
23432 94 90 82 80 84 80 79 76 79 76 75 75 74 74 71 70 72 118 109 108 107 100 92 85 82 102 98 92 95 97 92 92 94 94
11098 91 89 89 87 85 82 82 83 80 80 76 78 75 72 71 73 72 126 135 136 131 128 121 114 109 110 116 112 110 108 109 108 110 110
11209 88 85 88 86 85 85 84 84 85 82 78 75 75 76 75 80 82 130 128 130 134 130 128 128 128 130 128 126 120 118 118 118 120 120
12334 70 68 68 65 64 64 64 65 64 62 64 60 59 63 64 59 58 130 134 130 128 126 126 124 120 120 120 118 124 118 120 118 112 112
1207 68 65 65 69 63 65 63 63 60 59 58 56 60 62 60 62 60 138 140 146 135 129 124 125 121 121 114 104 100 112 112 114 110 108
1230 82 83 80 81 82 80 79 77 77 75 74 75 75 76 74 74 75 120 128 130 124 116 114 107 108 110 108 112 112 109 109 110 108 109
1412 95 96 95 92 92 90 90 89 85 87 85 82 81 84 82 82 82 134 140 136 126 132 130 128 125 128 126 126 124 118 120 118 119 116
1902 71 70 72 70 69 69 67 68 69 68 68 67 65 65 63 65 65 118 116 116 112 112 104 106 98 100 99 102 102 103 102 104 104 102
2314 87 86 85 83 83 80 79 78 79 76 76 75 77 74 73 74 74 122 135 134 126 120 108 108 106 104 108 108 110 110 108 112 110 109
2436 104 100 102 101 99 96 95 90 89 88 86 89 88 90 89 88 89 154 165 132 130 132 118 118 120 124 122 120 124 120 118 119 118 118
2891 84 86 82 81 78 77 79 76 76 75 77 78 77 76 78 78 78 142 146 140 138 140 136 132 130 132 128 130 129 128 128 126 132 130
3217 80 79 80 78 77 75 76 70 66 65 60 59 58 58 59 58 60 140 144 138 130 128 122 120 122 120 116 118 122 122 125 124 120 120
3462 68 67 62 62 60 59 56 52 51 52 52 51 50 50 52 51 52 144 134 132 130 122 112 110 116 118 114 110 108 104 102 104 110 108
5769 78 75 72 70 70 66 64 62 55 51 52 55 52 56 54 58 56 130 122 118 114 110 106 98 96 90 94 88 98 96 100 102 98 98
4721 88 80 77 70 66 60 60 55 56 60 54 55 57 58 60 62 60 122 115 110 108 100 98 100 92 90 88 90 92 96 98 94 96 100
4734 92 80 78 77 70 68 65 62 55 56 52 58 60 55 54 59 58 118 114 112 104 100 98 96 92 98 92 98 90 88 98 100 98 99
5102 88 75 72 70 68 66 64 60 58 60 62 60 60 62 58 59 60 116 116 112 110 100 102 104 98 100 98 106 105 100 98 102 102 100
7906 80 78 77 75 66 62 60 58 62 66 64 66 60 62 62 64 68 122 112 110 108 110 102 110 100 104 106 106 104 102 100 104 104 108
7388 78 72 70 72 67 65 66 62 61 58 60 60 58 59 60 60 61 119 110 102 100 98 104 96 98 95 94 88 92 94 95 94 95 96
 Ropivacaine with Dexmedetomidine

MAP105

MAP120
DBP105

DBP120

MAP10

MAP15

MAP20

MAP25

MAP30

MAP35

MAP40

MAP45

MAP50

MAP55

MAP60

MAP75

MAP90
DBP10

DBP15

DBP20

DBP25

DBP30

DBP35

DBP40

DBP45

DBP50

DBP55

DBP60

DBP75

DBP90

MAP0

MAP5
IP NO

DBP0

DBP5
16266 90 80 90 80 80 79 73 76 73 70 70 72 67 70 72 72 70 102 100 98 97 95 86 88 90 88 72 77 78 82 80 81 79 80
19079 104 85 56 66 54 62 45 45 49 45 45 45 47 54 50 53 56 101 95 80 80 75 64 72 62 60 61 55 54 54 65 58 70 66
19246 70 68 66 65 68 69 68 65 62 60 58 55 56 56 56 57 58 90 87 85 82 84 82 84 81 82 82 78 76 74 76 75 76 74
19578 78 62 68 65 65 64 63 60 62 60 64 67 67 65 65 66 65 90 68 81 76 75 74 74 70 72 70 79 82 81 80 80 79 79
19967 75 76 72 64 63 63 63 69 67 61 64 64 61 70 65 65 67 93 91 91 78 77 87 82 84 79 84 83 77 84 85 88 85 88
20405 90 92 90 87 85 81 80 80 79 76 77 75 75 76 72 71 72 108 110 107 104 103 100 99 99 96 90 91 89 85 88 88 88 88
21571 80 76 72 52 68 62 56 61 50 61 61 61 52 57 83 65 65 89 86 84 67 83 74 71 77 64 77 74 74 72 70 90 73 75
21700 92 76 65 57 66 62 51 69 64 63 54 50 62 60 62 60 60 103 86 76 66 75 72 60 85 76 74 65 64 71 71 69 72 72
23084 79 81 79 66 65 63 65 66 71 68 71 68 68 76 78 76 78 93 96 93 78 77 76 76 77 82 79 82 81 79 89 92 89 92
23102 88 87 87 82 75 72 72 68 69 65 66 68 68 68 70 71 69 108 104 110 108 96 91 90 85 83 80 81 86 85 85 87 85 85
23870 76 69 68 70 65 64 60 60 62 60 64 64 60 62 64 64 64 92 85 82 85 80 79 76 77 75 73 74 75 73 75 75 76 76
24035 92 85 81 82 90 95 92 82 79 76 82 80 84 82 80 76 84 106 99 92 95 104 108 104 95 93 90 94 92 96 94 92 90 92
24220 89 67 61 55 60 55 56 59 58 58 57 58 54 59 59 58 58 98 79 71 65 70 65 66 67 68 68 69 68 65 71 68 70 68
24842 75 65 56 59 60 61 61 60 61 60 59 71 71 71 68 68 70 97 81 69 70 70 71 72 73 72 69 69 85 83 82 80 80 82
25375 96 92 84 81 80 78 78 72 70 70 69 70 68 68 69 70 70 114 109 96 93 93 88 86 80 84 84 82 81 82 81 84 84 83
25958 70 64 60 60 58 60 61 62 62 60 58 60 60 62 62 60 65 84 75 70 74 74 74 74 74 75 72 72 75 76 76 74 76 76
25410 80 72 75 67 61 60 55 56 55 55 58 58 58 54 56 58 58 93 85 82 74 72 68 67 67 74 74 72 72 74 72 72 74 74
26955 96 102 100 90 82 84 84 80 78 75 76 76 78 74 74 75 75 112 116 112 104 94 96 94 92 90 90 91 92 90 90 92 94 92
372540 70 66 60 54 56 52 50 49 49 50 52 52 50 50 56 54 54 83 78 72 67 67 64 63 68 69 68 72 70 68 68 70 72 70
29010 90 92 92 88 87 85 80 81 80 76 78 75 72 71 71 70 70 106 108 108 101 99 96 96 97 94 93 94 90 89 89 88 89 84
462 105 95 70 71 70 87 78 77 67 66 71 66 57 56 49 69 65 127 110 87 83 78 105 90 91 83 81 83 78 69 68 61 83 80
822 75 51 58 60 57 64 60 59 58 56 58 55 53 57 59 61 60 87 75 77 75 74 76 77 72 72 70 74 71 63 71 74 77 77
1413 71 62 45 63 68 65 62 61 56 45 50 57 52 53 57 57 56 80 77 61 76 84 80 79 76 71 62 73 70 69 66 73 73 71
2107 82 80 79 76 70 69 70 65 65 65 67 66 67 62 60 61 60 96 95 93 90 87 84 85 82 82 80 82 80 80 82 82 80 80
1853 108 104 85 85 90 90 86 86 78 80 80 80 76 80 76 58 58 122 120 99 97 101 102 100 100 92 92 91 92 84 86 81 83 83
1913 82 82 79 76 76 72 70 70 68 72 70 72 68 65 65 64 65 98 98 92 90 90 88 85 85 82 85 92 90 89 80 78 60 84
1031 78 75 70 69 70 65 66 67 67 64 64 65 67 67 66 67 67 92 90 84 82 82 78 78 76 79 76 76 77 79 79 75 77 76
2874 102 102 98 95 88 85 86 88 85 82 82 80 80 78 78 80 80 113 114 108 105 100 97 95 95 95 92 92 90 88 86 85 90 89
3429 70 65 61 56 56 57 56 58 55 56 58 58 60 56 57 56 58 89 80 74 70 69 72 72 70 67 67 68 68 70 68 68 71 72
24517 84 82 75 82 73 71 74 72 68 67 57 58 59 57 59 57 59 106 100 92 100 92 90 90 89 87 86 85 78 75 75 75 78 75
25645 80 68 60 54 65 63 58 58 68 57 65 62 63 63 67 58 70 89 79 70 61 75 74 67 65 77 66 75 71 71 71 75 67 80
23432 68 65 66 60 57 55 48 48 52 50 52 52 54 54 55 54 54 84 79 79 75 71 67 60 59 68 66 65 66 67 65 65 67 67
11098 82 80 84 72 75 76 72 70 65 68 68 65 67 66 67 67 67 96 98 101 91 91 90 86 82 80 82 81 80 80 80 81 81 81
11209 70 70 76 76 70 68 68 70 68 68 66 66 70 65 64 66 66 90 89 94 96 90 88 88 89 89 88 86 84 84 82 82 83 83
12334 80 80 80 68 68 68 60 64 64 66 64 68 66 60 60 60 60 102 102 102 94 94 94 89 89 88 82 82 80 79 79 79 80 80
1207 93 90 88 77 88 82 89 81 80 74 60 58 71 68 64 64 60 111 111 108 104 105 97 99 96 95 88 77 75 87 80 78 78 80
1230 90 90 92 84 80 78 78 80 82 80 81 78 76 76 76 76 78 100 102 102 93 92 90 87 89 90 89 92 90 87 87 87 88 88
1412 86 86 82 84 80 80 76 79 78 76 77 76 75 77 72 70 70 102 104 102 98 97 96 94 94 95 95 95 95 92 92 87 86 86
1902 68 65 68 62 64 60 59 55 55 54 56 56 59 58 58 59 57 86 87 87 83 84 79 76 75 74 74 72 74 72 73 71 72 72
2314 74 78 70 72 67 62 62 60 60 58 60 56 58 58 60 58 58 90 97 91 90 88 77 77 75 74 74 75 73 74 74 76 75 75
2436 92 96 85 85 84 78 78 79 80 80 79 74 75 72 70 68 69 112 119 100 99 99 91 91 92 94 92 92 93 90 89 88 84 84
2891 88 86 85 80 80 76 76 75 76 72 73 72 70 68 70 71 72 106 106 103 99 100 96 94 93 94 90 92 91 89 88 88 91 91
3217 96 96 98 92 90 85 85 86 82 82 78 78 80 82 82 75 78 110 112 111 104 101 97 97 98 96 93 94 93 94 95 94 90 91
3462 102 100 98 98 90 84 84 87 86 87 82 82 80 80 78 80 80 116 111 109 108 100 93 93 96 96 96 91 90 87 86 84 91 90
5769 94 88 86 82 82 80 76 76 70 70 72 70 71 72 74 70 70 106 99 96 92 93 91 83 83 77 78 77 79 79 81 82 80 80
4721 80 78 72 68 64 64 60 60 62 60 58 58 60 62 62 60 60 94 90 84 81 76 75 73 70 70 69 69 70 72 74 73 73 73
4734 78 74 67 60 58 55 56 57 56 56 58 58 54 60 60 60 58 91 87 82 73 72 69 68 68 70 68 69 68 65 72 73 72 70
5102 74 70 65 65 60 60 58 50 52 52 56 56 54 54 60 60 60 88 86 80 80 73 74 73 66 68 66 72 71 70 68 70 73 73
7906 80 68 67 58 58 50 58 56 56 56 58 58 60 60 60 58 58 94 82 81 74 75 67 75 70 71 71 72 72 74 73 73 72 75
7388 76 67 65 62 56 58 54 56 55 56 52 54 56 57 56 55 56 90 81 77 74 70 73 69 70 68 67 65 66 65 66 67 68 68