i

POST OPERATIVE ANALGESIC EFFECT OF INTRATHECAL

DEXMEDETOMIDINE ON BUPIVACAINE SUBARACHNOID BLOCK FOR OPEN

REDUCTION AND INTERNAL FIXATION OF FEMORAL FRACTURES

BY

DR NWACHUKWU CYRIL EMEKA

THIS DISSERTATION IS SUBMITTED TO THE NATIONAL POSTGRADUATE

MEDICAL COLLEGE OF NIGERIA IN PART FULFILLMENT OF THE

REQUIREMENTS FOR THE AWARD OF THE FELLOWSHIP OF THE COLLEGE

IN ANAESTHESIA

MAY, 2017.

ii

iii

iv

v

DEDICATION

This work is dedicated to God Almighty and my family.

vi

ACKNOWLEDGEMENTS

My eternal gratitude goes to God Almighty for the abundant grace, wisdom and guidance

throughout this programme.

I would like to sincerely appreciate my supervisors, Prof. B.U.O Umeh, Prof. N.P

Edomwonyi, and Dr. Idehen Hanson for their constant guidance, valuable suggestions and

unparalleled encouragement throughout the course of my training and this study.

I express my special thanks to my colleagues in the Department of Anaesthesia, Nnamdi

Azikiwe University Teaching Hospital, NAUTH, Nnewi for their kind assistance during this

study.

With deep sense of gratitude and affection, I thank my wife Chiugo for all her support.

I would like to sincerely thank my parents and siblings for these years of unconditional love

and support.

Finally, I thank all the staff of Trauma Centre, Nnamdi Azikiwe University Teaching

Hospital for their assistance.

vii

TABLE OF CONTENTS

Title page i

Declaration ii

Certification iii

HOD’s Certification iv

Dedication v

Acknowledgements vi

Table of Contents vii

List of abbreviations viii

List of Tables ix

List of figures x

Summary 1

Chapter One:

Introduction 3

Aim and Objectives 7

Chapter Two:

Literature Review 8

Chapter Three:

Methodology 23

Chapter Four:

Results 32

Chapter Five:

Discussion 47

Conclusion 56

Limitation 57

Recommendation 58

References 59

Appendices:

Appendix I: Proforma 64

Appendix II: Institutional Ethical clearance 69

Appendix III: Informed Consent 70

Appendix IV: NAFDAC Approval 72

Appendix V: Alternative Measurement 74

viii

LIST OF ABBREVIATIONS

α - Alpha

0C - Degree Centigrade

µg - Microgram

ANOVA - Analysis of Variance

ASA - American Society of Anesthesiologists

b/min - Beat per Minutes

BMI - Body Mass Index

cm - Centimetre

DBP - Diastolic Blood Pressure

ECG - electrocardiography

Hr - Hour

Kg - Kilogram

L - Lumbar

M - meter

MABP - Mean arterial blood pressure

mg - Milligram

ml - Millitlitre

mmHg - Millimetre mercury

NRS - Numeric Rating Scale

ORIF - Open Reduction and Internal Fixation

PR - Pulse Rate

S - Sacral

SBP - Systolic Blood Pressure

SD - Standard Deviation

SPO2 - Peripheral Oxygen Saturation

T - Thoracic

VAS - Visual Analogue Scale

VRS - Verbal Rating Scale

ix

LIST OF TABLES

Table I: Demographic characteristics of the study groups 35

Table II: Sensory and motor block characteristics of the study groups (Mean ±SD) 36

Table III: Time to first analgesic request and total analgesic consumed (Mean ±SD) 37

TABLE IV: Proportion of patients with NRS < 4 and corresponding mean pain scores at

various time intervals in both groups 38

Table V: Sedation Scores of the study groups (Mean ±SD) 39

Table VI: Incidence of side effect on both groups 40

Table VII: Patients’ satisfaction using the Likert scale 41

x

LIST OF FIGURES

Figure 1: Trends of the mean pulse rate 42

Figure 2: Trends of the mean systolic blood pressure 43

Figure 3: Trends of the mean diastolic blood pressure 44

Figure 4: Trends of the mean arterial blood pressure 45

Figure 5: Trends of the mean Oxygen saturation 46

1

SUMMARY

Background

Regional anaesthesia especially spinal anaesthesia is mostly used in lower limb orthopaedic

surgeries for intra and post operative analgesia. It has a drawback of short duration of

analgesia with local anaesthetics alone. Various adjuvants have been used to prolong the

duration of analgesia with varying side effects. Dexmedetomidine, an α2 adrenergic agent has

been found to posses analgesic effect. This study was conducted to determine the

postoperative analgesic effect of intrathecal dexmedetomidine on open reduction and internal

fixation of femoral fractures.

Aim

To determine the analgesic efficacy of intrathecal 7.5 µg of dexmedetomidine and its

complication in open reduction and internal fixation of femoral fractures.

Method

Seventy ASA I or II patients scheduled for open reduction and internal fixation of femoral

fracture were randomised into two groups of 35 each to receive 3 ml of 0.5% hyperbaric

bupivacaine combined with either 7.5µg of dexmedetomidine in 0.3 ml of normal saline

(group D) or 0.3 ml of normal saline alone (group S) in a double blinded study. Patients were

assessed for time to first analgesic request for which 30mg of intravenous pentazocine was

given when NRS is > 3, proportion of patient with pain score < 4 in the postoperative period

using NRS, total analgesic consumed in 24 hours, incidence of side effects and patient

satisfaction.

2

Results

The groups were comparable demographically. The time to first request of analgesia in group

D (407.83±36.04 minutes) was significantly longer than group S (233.09±23.79 minutes),

P<0.0001. The proportion of patients with pain score < 4 in the postoperative period in both

groups using NRS were 100% in group D versus 86% in group S (P=0.34) in 1st hour, 100%

in group D versus 17% in group S (P=0.001) in the 2nd hour. No patient in group S was pain

free beyond the 2nd hour while 9% of the patients in group D reached the 5th hour. Total

analgesic consumed in 24hrs was significantly lower in group D (90.00 ± 7.27 mg)

compared to group S (125.14 ± 11.47 mg) with a P value of 0.0001. Incidences of side

effects such as hypotension, bradycardia, shivering and nausea were not statistically

significant between the groups (P>0.05). Patient satisfaction was better in group D compared

to group S (P < 0.001).

Conclusion

This study demonstrated that the addition of 7.5µg of dexmedetomidine to bupivacaine

subarachnoid block for patient undergoing open reduction and internal fixation of femoral

fractures significantly prolonged the duration of postoperative analgesia without significant

side effects.

3

CHAPTER ONE

INTRODUCTION

Lower limb surgeries may be performed under local, regional or general anaesthesia, but

central neuraxial blockade is the preferred mode of anaesthesia. This is because it provides

good motor block for the surgery, good intraoperative and immediate post operative

analgesia, enhances early ambulation, avoids airway manipulation and is adequate for the

surgical procedure. Lower limb orthopaedic surgeries like arthroplasty for hip and knee, open

reduction and internal fixation, closed reduction and external fixation, amputation, tendon

repair are mainly done using subarachnoid block.1

The use of subarachnoid block is an established and reliable method of providing anaesthesia

for lower abdominal and lower limb surgeries. It is very economical and easy to administer. It

has a rapid onset, superior sensory blockade and less failure rate compared to epidural.2

Local anaesthetic alone without adjuvant for subarachnoid block may not provide adequate

pain relief especially in the immediate post operative period when pain is most excruciating,

due to its duration of action, necessitating early analgesic intervention.

Adjuvants are administered by various routes such as epidural, intrathecal and intravenous.2

A number of adjuvants to local anaesthetics have been used intrathecally to prolong the intra

operative as well as immediate post operative analgesia.3 Adjuvants like clonidine,

magnesium sulphate, midazolam, opioids and neostigmine have been used with varying side

effects.3 When used for spinal anaesthesia, they prolong and also give better analgesic profile.

Opioids are the most commonly used intrathecal adjuvants. Being lipophilic, addition of a

small dose to spinal anaesthesia can produce rapid onset and good quality of surgical block.

Its rapid recovery of motor function allows for early discharge after surgery. However, side

4

effects such as pruritis, nausea, vomiting, urinary retention and delayed respiratory

depression have prompted further research toward non opioid analgesics with less serious

side effects.4

Alpha-2 adrenergic receptor agonists such as clonidine and dexmedetomidine have been the

focus of interest for their sedative, analgesic, perioperative sympatholytic and haemodynamic

stabilising properties.5 Clonidine has been used successfully intrathecally and epidurally over

the last decade as an adjuvant to prolong the analgesic effect of local anaesthesia. However,

its effect in reduction of blood pressure led to the search for other α2 -adrenergic agonists.5

The introduction of dexmedetomidine has further widened the scope of alpha-2 agonists in

regional anaesthesia as it provides stable haemodynamic condition, good quality of

intraoperative and prolonged post operative analgesia with minimal side effects.5 It is 8 to 10

times more selective towards α2 -adrenergic receptor than clonidine.6

Dexmedetomidine is a highly selective α2 –adrenergic receptor agonist that was initially

approved in 1999 by the food and drug administration (FDA) of United States of America for

short term sedation for mechanically ventilated patients in the intensive care units.7 Given its

well documented beneficial effects of anxiolysis, sedation, analgesia and sympatholysis with

minimal respiratory depression, it has been used in clinical scenarios as an adjuvant to local

anaesthetics in epidural and intrathecal anaesthesia.8

The highly lipophilic nature of dexmedetomidine allows rapid absorption into the

cerebrospinal fluid and binding to α2-adrenergic receptor of spinal cord for its analgesic

action. It prolongs the duration of both sensory and motor blockade induced by local

anaesthetics thereby prolonging the duration of analgesia. The use of dexmedetomidine as an

adjuvant has been variously carried out with prolongation of post operative analgesia and

varying side effects.2, 9

5

Post operative pain following lower limb orthopaedic surgeries in our centre is presently

managed by the surgeons with parenteral doses of 30mg pentazocine 6 hourly. This post

operative pain regimen is grossly inadequate especially during the immediate post operative

period when pain is most excruciating leaving the patient to suffer a great deal of avoidable

pain.

Nnamdi Azikiwe University Teaching Hospital (NAUTH) Nnewi, is one of the very few

teaching hospitals in Nigeria with a relatively young Department of Anaesthesia with limited

number of skilled anaesthetists. There is inadequate number of anaesthetists to provide the

enormous responsibilities that includes anaesthesia and postoperative pain management of the

patients. It is therefore imperative to utilise a potent adjuvant that will extend the analgesic

property to the immediate post operative period.

Currently, the standard technique of anaesthesia for open reduction and internal fixation of

femoral fractures includes the use of local anaesthetics only for subarachnoid block. This

study aims to achieve extension of intraoperative analgesia into the immediate post operative

period when pain is most excruciating. It will also help in the reduction of the total opioid

consumed in post operative pain management with its associated side effects.

The block characteristics of dexmedetomidine such as prolonged motor and sensory block if

demonstrated in our patients will be of benefit in open reduction and internal fixation of

femoral fractures where immediate ambulation and weight bearing are not required while

providing prolonged analgesia post operatively.

The comparison of the effect of intrathecal bupivacaine plus dexmedetomidine with

intrathecal bupivacaine plus saline for post operative analgesia for this surgical procedure is

justified. The outcome of this study if found to be favourable, will be of relevance in low

6

resource generating environment like ours where the availability of equipment and expertise

for instituting epidural anaesthesia are scarce.

This study is therefore undertaken to determine the post operative analgesic effect produced

by intrathecal administration of 7.5µg of dexmedetomidine with 3ml of hyperbaric

bupivacaine for open reduction and internal fixation of femoral fractures.

7

AIM

To evaluate the effect of intrathecal dexmedetomidine in bupivacaine spinal anaesthesia for

post operative analgesia in open reduction and internal fixation of fractures of the femur

Objectives

1. To determine the time to first analgesic request in dexmedetomidine group and

control groups.

2. To determine and compare the proportion of patients with numeric rating scale (NRS)

for pain score less than 4 points in both groups at 4 hours and thereafter 8hrs, 12hrs,

18hrs and 24hrs post operatively.

3. To determine the incidence of side effects such as bradycardia, hypotension, sedation,

shivering, pruritus, nausea, and vomiting, post operative headache and paraesthesia of

the buttock, thigh and lower limb.

4. To determine total analgesic requirement within twenty four hours post operatively in

the two groups.

5. To assess patients’ satisfaction using the Likert’s scale.

8

CHAPTER TWO

LITERATURE REVIEW

Pain is one of the sequelae of acute injury and it may initiate a whole host of physiological,

psychological and behavioural responses which if left unchecked, may adversely affect the

cardiopulmonary, autonomic and social functions of the patient. Effective analgesia enhances

early postoperative recovery and reduces morbidity.

Open reduction and internal fixation of lower limb fractures are procedures which have

relatively intermediate duration. If done under subarachnoid block, it requires adjuvants

which help provide adequate sensory block for the surgery and pain in the immediate post

operative period. Various adjuvants like clonidine, magnesium sulphate and

dexmedetomidine have been used with local anaesthetics in spinal anaesthesia to prevent

intraoperative visceral and somatic pain and provide prolonged post operative analgesia.2,10

Dexmedetomidine is a highly selective α2 adrenoceptor agonist recently introduced to

anaesthesia. It produces dose dependent sedation, anxiolysis and analgesia which involve

the spinal and supraspinal sites without respiratory depression. The presynaptic activation of

the α2 adrenoceptor inhibits the release of norepinephrine terminating the propagation of pain

signals. Postsynaptic activation of α2 adrenoceptors in the central nervous system inhibits the

sympathetic activity and thus can decrease blood pressure and heart rate.11 Administration of

an α2 agonist through an intrathecal or epidural route provides an analgesic effect in

postoperative pain without severe sedation.12 It produces clinical effect after binding to G-

protein coupled α2-adrenergic receptors which are of three subtypes (α2Α, α2B and α2C) with

each having different physiological functions and pharmacological activities. These receptor

subtypes are found ubiquitously in the central, peripheral and autonomic nervous systems as

9

well as in vital organs and blood vessels.13 Dexmedetomidine also has a higher α2A-

adrenergic receptor and α2C-adrenergic receptor affinity than clonidine.14

The Locus ceruleus of the brain stem is the principal site for the sedative action and spinal

cord is the principal site for the analgesic action both acting through α2A-adrenergic receptor.

The central mechanism for the analgesic action of dexmedetomidine is due to the presence of

α2-adrenergic receptor in the dorsal horn of the spinal cord. The agonist acts on both pre and

post synaptic mechanisms leading to the depression of the release of C-fibre transmitters and

hyperpolarisation of post synaptic dorsal horn neurons.15 It also causes a decrease in heart

rate by blocking cardio accelerator nerve and bradycardia via α2A-adrenergic receptor

through a vagomimetic action. In peripheral vasculature, there is sympatholysis mediated

vasodilatation and smooth muscle cell receptor-mediated vasoconstriction.16

The superior analgesic profile of dexmedetomidine has been demonstrated by some authors.

Shukla and colleagues,2 demonstrated that alpha-2 agonist such as dexmedetomidine

potentiates bupivacaine induced sensory spinal block, increasing the duration of post

operative analgesia without significant haemodynamic alteration. In this comparative study,

ninety patients scheduled for lower abdominal and lower limb procedures were prospectively

studied. Patients were randomly allocated to 3 different groups receiving intrathecally 15mg

of 0.5% hyperbaric bupivacaine plus either 0.1ml (10µg) dexmedetomidine or 0.1ml (50mg)

magnesium sulphate or 0.1ml saline. It was found that the onset of sensory block was rapid in

the dexmedetomidine group with a time of 2.27±1.09 minutes compared to 6.46 +/- 1.33

minutes in magnesium sulphate group and 4.14 +/- 1.06 minutes in saline group with P values

of < 0.001 in dexmedetomidine group versus saline group and magnesium sulphate group

versus saline group (ANOVA summary: P < 0.0001). There was a prolonged mean regression

time of sensory block of 352 +/- 45 minutes in the dexmedetomidine group compared with

265 +/- 65 minutes in magnesium sulphate group and 194+/-55 minutes in saline group with

10

P values of < 0.001 in dexmedetomidine versus saline group and magnesium sulphate versus

saline group (ANOVA summary: P < 0.0001). The mean regression time of motor block to

Bromage 0 was 331+/-35 minutes in the dexmedetomidine group, 251+/-51 minutes in the

magnesium sulphate group and 140+/-34 minutes in the saline group with P values of < 0.001

in dexmedetomidine group versus saline group and magnesium sulphate group versus saline

group (ANOVA summary: P < 0.0001). The groups were similar with respect to

haemodynamic variables, though there were higher incidences of bradycardia and

hypotension in the dexmedetomidine group which were not statistically significant (P>0.05).

They concluded that intrathecal dexmedetomidine supplementation of spinal bupivacaine is a

good alternative to magnesium sulphate as it produces earlier onset and prolonged duration of

sensory and motor block without associated significant haemodynamic changes. The major

drawback of this study included the use of different surgical procedures which have variable

duration and pain intensity. The prolonged duration of motor block probably attributed to the

dose of dexmedetomidine may be undesirable for short duration surgical procedures or

ambulatory surgeries.

This superior analgesic quality of dexmedetomidine was also observed by Ramila et al.17

They conducted a study to compare the effect of adding dexmedetomidine to intrathecal

bupivacaine versus intrathecal bupivacaine alone on spinal block characteristics for lower

limb orthopaedic procedures. They randomized sixty patients into two groups of thirty

patients each. The patients received intrathecal injection of 3ml of 0.5% hyperbaric

bupivacaine plus either 0.5ml of normal saline or 5µg dexmedetomidine in 0.5ml of normal

saline. Patients in the dexmedetomidine group had significant longer sensory block with

mean duration of 306 +/- 21.8 minutes compared to 192 +/- 9.9 minutes in the saline group

(P<0.05) and motor block with mean duration of 236 +/- 16.6 minutes compared to 162.5+/-

7.5 minutes in the saline group (P<0.05). Although, there were slower onsets of sensory and

11

motor block in the dexmedetomidine group, these were not statistically significant

(P>0.05).These slower onset time may be due to the lower dose of dexmedetomidine used

(5µg) compared to that of Shukla et al2 (10µg). They reported that patients in both groups

were pain free in the 1st 2 hours till the 3rd hour postoperatively when 40% of the patients in

saline group had pain score >4 while 10% of the patients in dexmedetomidine group had

score >4 to receive rescue analgesic (P <0.05). In the 4th hour, the remaining 60% in the

saline group had score >4 while 36.7% in dexmedetomidine group exceeded score of 4

(P>0.05). Forty percent and 13.3% of patients in dexmedetomidine group had score >4 at the

5th and 6th hour. The incidence of hypotension was found to be 30% in dexmedetomidine

group compared to 16.6% in the saline group (P>0.05) while the incidence of bradycardia

was 12.4% in dexmedetomidine group compared to 9.1% in the saline group (P>0.05).

Higher sedation score was also found among the dexmedetomidine group with mean sedation

score at the 60th minutes of 1.7 compared to 1.0 in the saline group (P<0.05). They submitted

that 5µg of dexmedetomidine is an attractive adjuvant to spinal bupivacaine as it provides

good quality of intraoperative analgesia, stable haemodynamic condition and excellent post

operative analgesia. The findings in the study were similar to that of Shukla et al, 2 except

that they had slower onset time of sensory and motor block in the dexmedetomidine group

compared to the saline group, though not significant but unlike in Shukla et al,2 where

dexmedetomidine group had a significant faster onset. This finding may be due to the lower

dose of dexmedetomidine (5µg) they used. The shorter duration of sensory and motor block

in the dexmedetomidine group according to Ramila and colleagues17 when compared to the

dexmedetomidine group in Shukla et al2 may also be due to the lower dose of

dexmedetomidine (5µg) they used. Ramila et al17 has shown that adjuvant dexmedetomidine

improved analgesic condition with no statistical significant difference in the haemodynamic

12

changes, although there was no standardisation of the surgical procedures because different

lower limb orthopaedic procedures have variable duration and pain intensity.

Dexmedetomidine as an adjuvant was studied by Fahmy and group18 to determine its

analgesic qualities. They randomised 60 ASA I or II patients undergoing orthopaedic

surgeries into 2 groups. The patients received 3ml of 0.5% hyperbaric bupivacaine with 0.4

ml of saline (group S) or 10µg of dexmedetomidine (group D). It was found that the time of

onset of sensory block to T10 was significantly shorter in group D with a mean time of

1.7±0.81 minutes compared to 2.92±0.93 minutes in group S (P<0.01). This finding is

similar to the result from Shukla et al2 but contrary to the finding from Ramila and

colleagues.17 The different result may be due to the lower dose of dexmedetomidine (5µg)

used by Ramila et al17. The duration of sensory block was prolonged in group D

(228±27 minutes) compared to group S (179±19 minutes) with a P value of <0.01. Motor

block was also prolonged in group D (197±18 minutes) compared to S (175±18 minutes)

(P<0.01). The incidence of shivering was higher in group S than group D (P<0.05).

A group of researchers studied the effect of intrathecal dexmedetomidine on bupivacaine

spinal block in patients undergoing lower limb surgery.19 Sixty patients aged 20 to 60 years

were randomly allocated into two groups of 30 patients each. They received 2.5ml of 0.5%

hyperbaric bupivacaine plus either 0.5ml of normal saline or 10µg of dexmedetomidine and

noted a non significant faster onset of sensory block with a mean time of 3.53±1.1 minutes in

dexmedetomidine group and 3.6±1.2 minutes in saline group (P >0.05). The mean time of

sensory regression to the S1 segment was 336.17+/-40.81 minutes in the dexmedetomidine

group compared to 202+/- 30.11 minutes in the saline group (P < 0.001). The time to rescue

analgesia was prolonged in dexmedetomidine group (376.37±20.6 minutes) compared to

saline group (210.8±16.83 minutes) (P<0.001). There was no significant difference in the

13

incidence of hypotension, nausea and vomiting between the 2 groups (P>0.05). The

prolonged duration of sensory block in the dexmedetomidine group when compared to saline

group observed in this study is similar to the finding from Fahmy et al,18 but the longer time

of the sensory block observed here despite using 2.5ml of hyperbaric bupivacaine when

compared to the 3ml of hyperbaric bupivacaine used by Fahmy and colleagues18 with the

same dose of dexmedetomidine can be explained. This may be due to the different surgical

procedures of the lower limb involving different dermatomal innervations with varying

degree of tissue manipulation and pain levels recruited by the 2 researchers. Fahmy et al18

studied orthopaedic surgeries while Rakesh19 studied lower limb procedures which may be

non orthopaedic surgeries with lower pain intensities.

Dexmedetomidine was used as an adjuvant in combination with 0.75% isobaric Ropivacaine

for spinal anaesthesia in lower limb surgeries. In a study by Gupta et al,12 60 ASA I or II

patients 18 to 50 years were randomly grouped into 2. They received 3 ml of 0.75% isobaric

ropivacaine plus 5µg of dexmedetomidine (group D) or 0.5 ml of normal saline (group S).

The onset time of sensory block to T10 was not significant between the 2 groups (P=0.455).

This was different to the finding of Fahmy et al18 which was significant (P<0.01). The

difference may be due to the higher dose of dexmedetomidine (10µg) used by Fahmy et al.18

The duration of analgesia was significantly longer in group D (478.4±20.9 mins) compared

to group S (241.7±21.7mins) (P<0.001). The dose of analgesia requested in 24 hours was

smaller in group D compared to group S (P<0.001). This is due to the longer duration of

analgesia achieved in group D. Two patients (6.6%) had hypotension in group D while a

patient (3.3%) had it in group S. Two patients had bradycardia in group D while none

experienced it in group S. Shivering occurred in group S without an incidence in group D.

These incidences of side effects were not significant.(P>0.05) .

14

Dexmedetomidine was found to confer superior analgesic quality when used as an adjuvant

in epidural anaesthesia. In a comparative study conducted by Bajuwa and group,20

dexmedetomidine and fentanyl were evaluated for epidural analgesia in lower limb

orthopaedic surgeries. They compared the haemodynamic, sedative and analgesic effects of

these drugs when combined with ropivacaine. They randomized 100 patients going for lower

limb orthopaedic surgery into two groups of 50 each receiving 15ml of 0.75% ropivacaine

with either 1µg/kg of dexmedetomidine or 1µg/kg of fentanyl epidurally. Epidural top ups

were continued post operatively as rescue analgesic. It was found that there were faster onset

time of sensory block to reach T10 in dexmedetomidine group (7.12 +/- 2.14 minutes)

compared to the fentanyl group (9.14 +/- 2.94 minutes) (P=0.016) and time of motor block to

reach Bromage 3 in dexmedetomidine group (18.16+/-4.52 minutes) compared to fentanyl

group (22.98+/- 4.78 minutes) (P=0.033). The duration of sensory regression to S1 was found

to be longer in dexmedetomidine group compared to fentanyl group (P=0.0082) while the

time for motor regression to Bromage 0 was also found to be longer in dexmedetomidine

group compared to fentanyl group (P<0.05).

The duration of analgesia was significantly longer in dexmedetomidine group (366.62 +/-

24.42 minutes) compared to fentanyl group (242.16 +/- 23.81 minutes) (P=0.012). It was also

reported that the analgesic dose consumption in 24 hours was significantly reduced in

dexmedetomidine group when compared to fentanyl group (P=0.026). The median sedation

grade was 2 in dexmedetomidine group and 1 in fentanyl group (P<0.05). The incidence of

nausea was 14% in dexmedetomidine group compared to 26% in fentanyl group (P<0.05)

while that of vomiting was 4% in dexmedetomidine group compared to 12% in fentanyl

group (P<0.05). There was no significant difference on the incidences of headache, shivering,

dizziness, urinary retention and haemodynamic changes between the 2 groups.(P>0.05). They

submitted that dexmedetomidine is a better alternative to fentanyl as an epidural adjuvant as

15

it provided comparable stable haemodynamic, early onset and establishment of sensory

anaesthesia, prolonged post operative analgesia, lower consumption of post operative local

anaesthetic for epidural top ups but, with higher sedation levels. The major drawback of this

study is the lack of specificity of surgical procedures as various lower limb orthopaedic

surgeries affect various dermatones with different pain intensity and surgical duration.

Adjuvants such as dexmedetomidine, clonidine and fentanyl have been compared when used

intrathecally with hyperbaric bupivacaine. In a study by Mahendru et al10 in which they

compared the time of onset and duration of sensory and motor block, haemodynamic effects,

post operative analgesia and adverse effects, one hundred and twenty ASA I and II patients

scheduled for lower limb surgery were enrolled in a prospective randomised and double

blinded study. The patients received 2.5ml of 0.5% hyperbaric bupivacaine plus either 25µg

of fentanyl, 30µg of clonidine, 5µg of dexmedetomidine or 0.5ml of normal saline. They

noted that there was no statistical significant difference on the time of onset of sensory block

(P=0.113) and motor block (P=0.086) in all the four groups. Their findings were similar to

the finding by Gupta et al.12 They also observed statistically significant prolonged duration of

sensory block (P=0.0001) and motor block (P=0.0001) in the dexmedetomidine group

compared to other groups. This was similar to the findings of Bajuwa and group.20

The saline group had statistically significant shorter duration of both sensory and motor block

when compared to the fentanyl, clonidine and dexmedetomidine groups (P<0.0001).

However, clonidine and fentanyl groups were comparable on the duration of sensory and

motor block without any statistically significant difference (P>0.05). They also observed that

the total analgesic requirement in 24 hours were minimal in dexmedetomidine group

compared to fentanyl group (P=0.009) and clonidine group (P=0.05). Saline group had a

statistically significant more requirement of rescue analgesic when compared to fentanyl

group, clonidine group, and dexmedetomidine group with P values of 0.04, 0.008 and 0.005

16

respectively. The mean value of mean arterial pressure, heart rate and sedation were

comparable between the four groups with no significant difference (P>0.05). One patient had

nausea in saline group, 2 patients in clonidine group compared to none in dexmedetomidine

group (P>0.05). There was no statistically significant difference on the incidence of

hypotension and respiratory depression among the groups (P>0.05).

Mahendru et al,10 submitted that the use of dexmedetomidine as an adjuvant is an attractive

alternative to fentanyl and clonidine for long duration surgical procedures due to its profound

intrathecal anaesthetic and analgesic properties combined with minimal side effects although

the prolonged duration of motor block may be undesirable for short duration procedures.

A comparative study by Sarma and colleagues21 to determine the characteristics of intrathecal

clonidine, dexmedetomidine and saline as adjuvants for bupivacaine subarachnoid block for

lower limb surgeries was conducted in which they randomly allocated 150 patients into 3

groups. Each received 3 ml of 0.5% hyperbaric bupivacaine with either 5µg of

dexmedetomidine or 50µg of clonidine or 0.5 ml of saline. They observed a faster onset of

sensory block in dexmedetomidine group compared to saline group. (P<0.05).This was

similar to what Fahmy et al18 observed. There was no significant difference in the onset time

of the sensory block in dexmedetomidine group when compared to the clonidine

group.(P>0.05). This was also noted by Mahendru and colleagues.10The duration of sensory

regression to S1 was found to be longest in the dexmedetomidine group compared to

clonidine group and saline group.(P<0.001). They reported that dexmedetomidine as an

adjuvant had a longer duration of analgesia than clonidine and saline with a mean time of

336.80±55.38 minutes, 309.60±50.99 minutes and 204.80±16.81 minutes respectively

(P<0.001).

Dexmedetomidine was also compared with clonidine and saline by Solanki et al22 as

adjuvants in bupivacaine subarachnoid block to determine their analgesic effect in trauma

17

patients undergoing lower limb surgeries. They reported that there was no significant

difference in the onset time of sensory block between dexmedetomidine group and clonidine

group.(P>0.05). This is similar to the findings of other reporters10,21 They also noted that the

time to first analgesic request prolonged significantly in dexmedetomidine group compared to

clonidine group (P=0.01) and saline group (P=0.0001). Post operative pain scores were lower

in clonidine group and dexmedetomidine group compared with saline group. The request for

analgesia during the first 24 hours post operative was significantly less in clonidine and

dexmedetomidine groups compared to the saline group (P=0.0001) and comparable between

clonididne and dexmedetomidine groups (P =0.2O3). They concluded that 5µg of

dexmedetomidine added to 15mg of intrathecal bupivacaine produces longer postoperative

analgesia than 50µg of clonidine and placebo among trauma patients undergoing lower limb

surgery. This study considered various lower limb surgical procedures with different duration

and pain intensity.

It has been shown that the duration and efficacy of the analgesia produced following the use

of different doses of dexmedetomidine as adjuvant increases with the increasing dose.

Hala Eid and Colleagues,23 conducted a study to determine the dose related prolongation of

hyperbaric bupivacaine spinal anaesthesia by dexmedetomidine. They randomized forty eight

adult patients scheduled for anterior cruciate ligament reconstruction to one of three groups.

Each was given 3.5ml of spinal injectate containing 3ml of 0.5% hyperbaric bupivacaine and

0.5ml containing 10µg dexmedetomidine, 15µg dexmedetomidine or normal saline.

It was found that time to reach T10 was not statistically significant among the groups with a

time of 8.7 +/- 3.3 minutes in saline group,7.7 +/- 3.6 minutes in D1(10µg

dexmedetomidine) group and 8 +/- 2.5 minutes in D2(15µg dexmedetomidine)

group(P>0.05). The median and range of the peak sensory level reached were T6(T3-T10) in

saline group,T5(T3-T9) in D1 and T7(T4-T9) in D2. The time for sensory regression to S1 and

18

motor regression to Bromage 0 was found to be statistically significant in the

dexmedetomidine groups when compared to the saline group. The time was 238+/-57

minutes in saline group, 320+/-65.8 minutes in D1group and 408.7 +/-68 minutes in D2

group with P values of <0.001 in D1 compared to saline group, <0.001 in D2 compared to

saline group and < 0.05 in D1 compared to D2. Time for regression of motor block to

modified Bromage 0 was found to be 202+/-41.8 minutes in saline group with a P value of

<0.001 when compared to 280 +/- 46 in D1 group and 336 +/- 58 minutes in D2 group.

Dexmedetomidine as an adjuvant, significantly extended the duration of analgesia by 240

minutes in D1 and 520 minutes in D2 (P<0.001). Total doses of intramuscular diclofenac as

rescue analgesics in 24hrs were significantly more in the saline group with average of 1.9

compared to 1.4 in D1 group (P<0.05) and 0.6 in D2 group (P<0.001).There was associated

higher sedation scores in D2 with a median score of 4 compared to median score of 2 in D1.

The increase in the sedation score may be due to the higher dose of dexmedetomidine used in

D2. There was no significant difference in the incidence of hypotension among the groups

which was treated with ephedrine in 2 patients in saline group,3 patients in D1 and 2 patients

in D2.

The increased duration of analgesia following increase in dose of dexmedetomidine was also

reported by Aditi and co-workers.24 In their study to determine the block characteristics and

post operative analgesic effect of dexmedetomidine in lower limb orthopaedic surgeries, they

randomised 90 patients into 3 groups of 30 each. The patients received 2.5 ml of 0.5%

hyperbaric bupivacaine with 0.5 ml of saline (group S) or 5µg of dexmedetomidine (group

D1) or 10µg of dexmedetomidine (group D2). They reported a statistically significant faster

onset of sensory block to T10 with increase in dose of dexmedetomidine compared to saline in

a mean time of 2.17±0.68 minutes,1.59±0.58 minutes and 1.21±0.40 minutes for group

S,D1 and D2 respectively (P<0.001). This was different from what Hala Eid and colleagues23

19

observed. It may be due to the lower dose of bupivacaine (2.5ml) used by Aditi et al24

compared to 3ml used by Hala Eid and colleagues.23 Faster onset of motor block was also

reported with increase in dose of dexmedetomidine (P<0.001). They also reported longer

sensory and motor block with increased dose of dexmedetomidine (P<0.001). Duration of

analgesia was significantly longer with higher dose of dexmedetomidine with a mean time of

272.13±49.37 minutes in group S, 356.5±43.98 minutes in D1 and 422.5±57.29 minutes in

D2 with P value of <0.001 when the dexmedetomidine groups were compared to the saline

group and <0.001 when D1 was compared to D2. This dose dependent increase in duration of

analgesia was similar to what Hala Eid and colleagues23 observed. The average number of

analgesic doses received in 24 hours was noted to be significantly more in the saline group

(2.16+/-0.79) compared to the dexmedetomidine groups (P<0.001) but found to be more in

D1 (1.4+/-0.49) compared to D2 (1.13+/-0.34) (P<0.05). This was also observed by Hala Eid

and colleagues.23 The median sedation score was 2 in saline group and 3 in dexmedetomidine

groups. They submitted that increase in the dose of dexmedetomidine increases the duration

of analgesia with a reduction in the number of rescue analgesia doses received in 24 hours

while slightly increasing the level of sedation.

Contrary to the finding by Aditi and co-workers24 on the dose dependent effect of

dexmedetomidine on the onset of sensory block when used as an adjuvant in subarachnoid

block, Baghel et al25 and Chaudhry et al26 submitted that increase in dose of

dexmedetomidine does not have a significant effect on the onset of sensory block to T10

(P>0.05) but increases the duration of analgesia with a P value of <0.001 and 0.029

respectively. Chaudhry et al26 observed that the number of doses of analgesics received in the

1st 24 hours was found to be lower in patients that received higher dose of dexmedetomidine

with a P value of 0.037.

20

A reduction in the incidence of shivering observed with the use of dexmedetomidine was

studied by Bajwa and colleagues.27 They randomised 80 ASA I or II patients scheduled for

laparascopic surgeries under general anaesthesia into 2 groups. Group D received

intravenously 1µg/kg of dexmedetomidine while group N received normal saline 30 mins to

the end of surgery. It was observed that 42.5% of patients in group N shivered while 5% of

the patients in group D had shivering (P=0.014). They submitted that dexmedetomidine

reduces shivering by lowering vasoconstriction and increasing shivering thresholds. The anti

shivering property of dexmedetomidine is mediated by its central α2 activity. Alpha 2

adrenergic agonists decrease the central thermo sensitivity by suppressing the neuronal

conductance mediated by increasing potassium ion conductance through Gi coupled proteins

which causes hyperpolarisation of neurons.

The versatility of analgesic property of dexmedetomidine has been demonstrated in the

intravenous route. Aloweidi et al28compared the effect of intravenous dexmedetomidine with

intravenous propofol as adjuvant to spinal intrathecal anaesthesia on the duration of spinal

anaesthesia and haemodynamic parameter during total knee replacement. They reported a

statistically significant increase in the duration of sensory block in dexmedetomidine group

when compared with propofol (P<0.05) without any significant clinical haemodynamic

changes in the dexmedetomidine and propofol groups (P>0.05).

Other adjuvants have been used in orthopaedic surgical procedures. In a study by Tan and

colleagues,29 they compared the post operative analgesic effect of intrathecal bupivacaine

with morphine or neostigmine after total knee replacement surgery. In this prospective double

blinded study, 60 patients were randomly distributed into 3 equal groups each received 15mg

of hyperbaric bupivacaine with either 0.5 ml of normal saline or 50 µg of neostigmine or

300µg of morphine. It was found that there was no significant difference in the maximal

height of sensory block amongst the three groups of patients. The mean time for first request

21

of analgesia was significantly higher in morphine group (750+/-156 minutes) compared to the

neostigmine (558+/-132 minutes) and saline (366+/-72 minutes) groups (P <0.05).Duration of

motor block was prolonged in neostigmine group (342+/-24 minutes) compared to the saline

(282+/-18 minutes) and morphine (270+/- 12 minutes) groups (P<0.05).

There was no difference between the groups in the number of intramuscular diclofenac

injection requested in the 24hrs following surgery as rescue analgesics with an average of 2

doses per patient in all the groups although, the 24hrs Visual Analogue Score (VAS)

assessment was found to be highest in the saline group (P<0.05).However, the frequency of

nausea and vomiting was found to be higher in the neostigmine group (35%) compared to the

saline group (5%) and morphine group (20%). There was a 70% incidence of pruritus in the

morphine group and none in the neostigmine and saline groups. The high incidence of

adverse effects reported may be due to the adjuvants used.

Post operative pain control is very important after lower limb surgeries, as poorly controlled

pain is an impediment to post operative recovery due to the physiological, psychological and

behavioural responses associated with pain. Lower limb orthopaedic surgeries are associated

with intense pain especially at the early post operative period; it is pertinent that it is well

monitored and managed. Pain monitoring scale is used for the assessment of the severity of

pain and patients response to analgesics.

Pain can be monitored with the practice of self reporting of pain intensity using Verbal

Rating Scale (VRS) (pain categorised into 0-None, 1-Mild, 2-Moderate, 3-Severe),Visual

Analogue Scale (VAS) (using a linear scale of 0 to 10cm where 0 is no pain and 10 is worst

imaginable pain while the other points on the scale correspond to various pain intensity) and

Numeric Rating Scale (NRS) (patient describes the intensity of pain on a scale of 0-10

22

depending on severity where 0 is no pain, 10 is worst imaginable pain,1-3 is mild pain, 4-6 is

moderate pain while 7-10 is severe pain).

These methods of self reporting allow continuous measurements while analgesics or placebo

are administered and produces data that allow analgesics to be compared with each other

across separate trials. VRS, VAS and NRS are usually administered using pen and paper but

NRS may also be administered verbally. The simple technology of NRS is congruent with

clinical practice to the extent that it has been adapted by health professionals as a guide to the

treatment of individual patients.30

Although all three strands of pain measurements have found a place in modern clinical

practice or drug development, it is the reporting of pain by patients undergoing treatment

using simple scales of intensity such as NRS that provides the crucial information by which

analgesic therapies can be evaluated and compared.30

23

CHAPTER THREE

METHODOLOGY

Study Design

This was a prospective randomized double blind placebo controlled study.

Setting

The study was conducted at the Nnamdi Azikiwe University Teaching Hospital, Nnewi

Anambra state. This is a tertiary health care facility providing specialized care for a large

proportion of patients living in some of the South East and South South geopolitical zones of

Nigeria. The study was commenced in April 2014 while data collection was from May 2015

to July 2016.

Study Population

The study population was drawn from patients scheduled for elective open reduction and

internal fixation (ORIF) of femoral fractures.

Ethical Consideration

Approval was sought from the ethical committee of the institution and eligibility for

participation in the study was defined using some inclusion and exclusion criteria. Informed

consent was obtained from only the eligible patients.

Inclusion criteria:

- Consenting patients scheduled for elective open reduction and internal fixation of

femoral fractures.

- American Society of Anesthesiologists (ASA) Physical status class I or II patients.

24

- Age 18 to 50 years.

- Height 155cm to 175cm which was determined using alternative measurement.31

Exclusion criteria

- Patients’ refusal.

- Known allergy to the study medication.

- Body mass index (BMI) > 30kg/m2 determined using alternative measurement.31

- Patient with contra-indication to spinal anaesthesia.

Alternative Measurement

This is a means of estimating height from other measurable parts of the body such as length

of forearm (ulna), knee height and demispan. It can also be used to estimate body mass index

category using mid upper arm circumference. Height is estimated by measuring the point of

the elbow (olecranom process) and the midpoint of the prominent bone of the wrist (styloid

process). The height is estimated from a table provided using the value obtained. See

appendix V.

Informed Consent

The patients scheduled for elective open reduction and internal fixation of femoral fracture

were visited during the preoperative evaluation and those found to be eligible for the study

were given information about the study. The eligible patients who gave consent to be

included were allocated to 2 groups using simple random sampling. Patients were informed

of their rights to withdraw at any time from the study and still receive standard care for

surgeries. The cost of the study was borne by the researcher.

25

Sample size Estimation

Sample size was determined prospectively using data from a previous study by Tan et al29

where it was found that the mean time to first request of rescue analgesia was 366 mins

(SD 72) in the placebo group.

This study sought to extend the mean time to first request for analgesia by 60 minutes with

addition of 7.5µg of dexmedetomidine to 15mg of 0.5% hyperbaric bupivacaine. The sample

size was determined by the formula below.32

M (sample size per group) = 2c + 1

δ 2

Where δ = µ2 - µ1 is the standardized effect size

σ

µ2 and µ1 are the means of the two treatment groups.

σ is the common standard deviation.

µ2 = 426 minutes

µ1 = 366 minutes

µ2 - µ1 = 60 minutes

σ = 72 minutes

C = 7.9 for 80% power and 10.5 for 90% power.

Therefore,

26

δ = 60 = 0.833

72

Taking 90% power,

M = 2 x 10.5 + 1

(0.83)2

= 21 + 1

0.6889

= 30.48 + 1

= 31.48

Approximately 32

Thus 32 patients per group

Adding 10% attrition, the sample size obtained was 35 patients per group totalling 70

patients.

Hypothesis

Null hypothesis: This assumes that there will be no difference in the time to first request of

analgesia between the patients that will receive intrathecally 7.5µg of dexmedetomidine

added to 3ml of hyperbaric bupivacaine and those that will receive 3ml of hyperbaric

bupivacaine and saline.

Alternative hypothesis: This assumes that there will be difference in the time to first request

of analgesia between the patients that will receive intrathecally 7.5µg of dexmedetomidine

added to 3ml of hyperbaric bupivacaine and those that will receive 3ml of hyperbaric

bupivacaine and saline.

27

Study Procedure

A preoperative evaluation was done for each patient to improve perioperative outcome and to

identify patients who met the inclusion criteria in the study. This involved taking a detailed

history, measurement of the physical attributes such as BMI and height using alternative

measurements31 and carrying out a general physical examination. Systemic examination of

the cardio-respiratory systems and Mallampati assessment for ease of tracheal intubation

were also carried out. Routine investigations including full blood count, and electrolyte/urea

and creatinine were done and reviewed to evaluate organ system functions. Blood was

grouped and crossmatched. Any specific investigation, indicated was requested for. The

physical health status of the patients was evaluated using the American Society of

Anesthesiologists’ (ASA) classification.

Patients were advised to fast overnight prior to the surgery. No sedative premedication was

administered. A detailed explanation of perioperative expectations and implications of

inclusion in the study was given to the patients and a written informed consent obtained. The

patients were educated about the pain assessment tool used which was numeric rating scale

(NRS). Numeric rating scale uses a scale of 0-10 depending on the degree of pain intensity

from which a patient chooses a value corresponding to the severity of pain where 0 means no

pain and 10 worst pain imaginable.

In the theatre, the patients were randomized into 2 groups – D and S. They picked from an

envelope containing sequential randomized alphabets D and S representing group D and

group S for dexmedetomidine and saline respectively. Group D received 3ml of 0.5%

hyperbaric bupivacaine plus 7.5µg dexmedetomidine ( 100µg/ml of dexmedetomidine added

to 3ml of normal saline gave 4ml of 100µg dexmedetomidine solution. 0.3ml of the solution

gave 7.5µg dexmedetomidine) while group S received 3ml of 0.5% hyperbaric bupivacaine

28

plus 0.3ml of normal saline. The syringe and the containing drug were prepared by a junior

resident anaesthetist while the researcher who was blinded to the contents of the syringes

performed the spinal anaesthesia, assessed, cared for the patients and recorded the study data.

The patients and the researcher were blinded to the drugs.

DASH 4000 multiparameter monitor (Manufactured by GE medical system Information

technology incorporation, 8200W, Tower avenue Milwaukee, Wisconsin USA) was attached

to the patients. Baseline blood pressure, heart rate, ECG and peripheral oxygen saturation

were obtained and recorded. The monitoring continued intraoperatively at 5 minutes interval

and in the post anaesthesia care unit. Intravenous access was secured using size 18 gauge

Cannula and each patient ̓s circulation was preloaded with 750ml of normal saline over 20

minutes prior to establishment of subarachnoid block.

In the sitting position, the skin overlying the lumbar region was cleaned using a solution of

chlorhexidine with cetrimide, methylated spirit and draped. The L3/L4 intervertebral space

was identified and the skin and subcutaneous tissue infiltrated with 2ml of 2% plain

Lidocaine. Using aseptic technique, a 25 gauge Whitacre spinal needle was inserted into the

subarachnoid space through the interspace using a midline approach. The efflux of clear free

flowing cerebrospinal fluid led to the injection of 3ml of 0.5% hyperbaric bupivacaine and

7.5µg of dexmedetomidine in 0.3ml normal saline or 3ml of 0.5% hyperbaric bupivacaine

plus 0.3ml of normal saline based on the group randomization over 10-15 seconds into the

subarachnoid space, the needle withdrawn and dressing placed over the puncture site. The

patients were gently returned to the supine position with 30o head up tilt. There was

continuous monitoring of the haemodynamic parameters like blood pressure, pulse rate,

oxygen saturation, electrocardiography and blood loss.

29

Blood pressure was monitored every 2 minutes for the first 10 minutes then, 5 minutes

interval till the end of surgery. Intraoperative complications like hypotension, bradycardia,

respiratory depression, pruritus, sedation, shivering, nausea and vomiting were managed and

recorded appropriately.

Hypotension for this study was defined as a systolic blood pressure of <90mmHg or 30%

drop from the base line value33 and treated with intravenous fluid bolus (750ml of normal

saline) and 5mg aliquots of intravenous ephedrine if the hypotension persists. Bradycardia

(heart rate<60bpm)34 was treated with intravenous atropine 0.6mg. Shivering was treated

using warmed intravenous fluid, warm blanket and adequate covering of patients. The

proportion with complaint of nausea was determined and documented. The proportion of

patients in whom vomiting or retching was observed was documented. Nausea and vomiting

was treated with intravenous metoclopromide 10mg. Oxygen was administered through a

face mask whenever the oxygen saturation dropped to ≤ 93%. Normal saline was used for

fluid maintenance at 10 ml/kg for the first hour and 5 ml/kg subsequently while blood loss

was replaced with blood transfusion when the calculated maximum allowable blood loss was

exceeded. The patients’ sensory and motor block characteristics like onset and duration of

blocks and intraoperative events were documented.

After the establishment of the subarachnoid block, the block height was assessed with the

loss of temperature sensation using methylated spirit soaked cotton wool along the

midclavicular line bilaterally every 2 minutes until the maximum block height reached for

two consecutive tests. The desired sensory block height of T10 was achieved before

commencement of surgery, the time noted while the time to reach the maximum sensory

block height was also noted.

30

The motor block was assessed using the modified Bromage score35 (Bromage 0- Free

movement of legs and feet with ability to raise extended leg, Bromage 1- Inability to raise

extended leg and knee flexion is decreased, but full flexion of feet and ankle is present,

Bromage 2- Inability to raise leg or flex knees but flexion of ankle and feet is present,

Bromage 3- Inability to raise leg, flex knee or ankle or move toes). This was assessed every 2

minutes after intrathecal injection of the drugs and time taken to reach modified Bromage

score 3 noted. Sedation was monitored every 15minutes using modified Ramsay Sedation

Scale36 (1- Anxious, agitated and restless, 2- cooperative, oriented and tranquil, 3- Respond

to command only, 4- Brisk response to light glabellar tap, 5- sluggish response to light

glabellar tap, 6- no response). Urine output was noted.

At the end of surgery, the patient was transferred to the post anaesthesia care unit where close

monitoring of physiologic parameters (heart rate, blood pressure, oxygen saturation, sedation

score, temperature) continued. Assessment and treatment of pain and other post operative

complications were done. Pain was assessed using numeric rating scale (NRS)30 between 0

and 10 (0-No pain, 10-worst pain imaginable). This was assessed postoperatively every hour

for 4 hours, then at 8hr, 12hr, 18hr and 24hr. The sensory and motor block level were

determined at the end of surgery and monitored every 20 minutes to detect the time for block

regression to S1 and modified Bromage 0 respectively (Calculated from the time of

subarachnoid drug administration). The patient was transferred to the ward for continued care

when stable.

Time to first analgesic request which was the time from intrathecal administration of the

study drugs to the time for first request of analgesics when NRS ≥ 4 was documented and

30mg of pentazocine was administered intravenously. After this, post operative pain

management continued with intravenous administration of 30mg pentazocine on demand and

not less than 4 hourly when NRS is ≥ 4.

31

A week follow up was done post operatively by the blinded researcher. Presence of headache

and other complications such as paraesthesia of the buttock, thighs or lower limbs were

sought for.

Measurement of Outcomes

1. Primary Outcomes: -

a. Duration of analgesia defined as the time from intrathecal administration to

time of first analgesic request.

b. Proportion of patients scoring less than 4 points at 4hrs and thereafter 8hrs,

12hrs, 18hrs and 24hrs post operatively using numeric rating scale (NRS).

2. Secondary Outcomes:

a. Haemodynamic profile of study medication.

b. Sedative profile of study medication.

c. Total analgesic requirement within 24hrs post operatively.

d. Patient satisfaction using 5 points Likertʼs scale37 which was assessed as

excellent, very good, good, poor, very poor.

Statistical Analysis

Data were analyzed using SPSS (Statistical Package for the Social Sciences) version 20

developed by International Business Machines (IBM) Corporation of United States of

America. The parametric data were summarized as means and standard deviation (SD) and

dichotomous data presented as counts and frequencies. The comparison of time to the request

of first analgesia was done using the unpaired t-test. Categorical data were analyzed using the

Chi-square test. The level of significance was set at probability of ≤ 0.05.

32

CHAPTER FOUR

RESULTS

A total of 70 adults aged 18-50 years in ASA class I and II were enrolled into this study, with

35 patients in each group. Group S received 3ml of 0.5% hyperbaric bupivacaine with 0.3ml

of normal saline while group D received 3ml of 0.5% hyperbaric bupivacaine with 7.5µg of

dexmedetomidine. No patient was lost to protocol violation.

There was no significant difference in the demographic characteristics between the study

groups as shown in Table 1.The mean duration of surgery was similar in both groups with a

time of 128.63±13.80 minutes in group D and 119.29±17.01 minutes in group S. (P =

0.122)

The sensory and motor block characteristics are shown in Table II. There was a faster time of

onset of sensory block to T10 in group D (4.57±1.0 minutes) compared to group S (5.54±1.69

minutes) with a P value of <0.001. There was no significant difference in the time to

maximum sensory block height in both groups with a time of 11.14±2.39 minutes in group D

and 9.94±1.57 minutes in group S. (P =0.11). The sensory block regression time to S1 was

significantly longer in group D (358.74±30.97 minutes) compared to group S (210.54±21.48)

with a P value of 0.02. There was a significant shorter time for the motor block to reach

Bromage 3 in group D (7.28±2.49 minutes) compared to group S (8.41±2.34 minutes) (P =

0.020) and a longer time of motor regression to Bromage 0 in group D (330.11±31.86

minutes) compared to group S (195.97±19.69 minutes) (P value = 0.004).

The time to first analgesic request was significantly prolonged in group D compared to group

S (Table III). The time was 407.83±35.55 minutes in group D compared to 233.09 ±23.79

minutes in group S. (P <0.0001).

33

The proportion of patients with numeric rating scale (NRS) for pain less than 4 at various

intervals is shown in table IV. At the end of surgery which corresponds to the 0 hour, all the

patients in both groups had pain score of less than 4. (Mean pain score of 0.00 versus 0.00).

At the 1st hour, 86% of the patients in group S had NRS< 4 with mean pain score of

1.79±1.48 compared to 100% of those in group D and mean score of 0.00 (P=0.34).

Seventeen percent of patients in group S had NRS <4 with mean pain score of 2.67±0.52 at

the 2nd hour compared to 100% of patients in group D with mean score of 0.40±0.60

(P=0.001). At the 3rd hour, all patients in group S had NRS > 4 necessitating rescue

analgesics and excluded from the study (from further pain assessment) compared to group D

where 100% had NRS < 4 at the 3rd hour, 29% at the 4th hour and 9% at the 5th hour.

Furthermore, all patients in group D required rescue analgesics at the 6th hour because NRS

was > 4. All patients from both groups had NRS greater than 4 after the 5th hour therefore, no

further pain assessment was done at the 8th hour, 12th hour, 18th hour and 24th hour.

There was a significant difference in the mean total analgesic consumption in the first 24

hours between the two groups. The mean total analgesic consumption in group D was

90.00±7.27 mg pentazocine compared to 125.14±11.47 mg in group S (P=0.0001) see table

III.

The haemodynamic variables between the 2 groups showed no significant difference with

time. The mean pulse rates were not statistical significant between the 2 groups (P>0.05). See

figure 1. There was a gradual decrease in the pulse rate except in the 2nd minute following the

intrathecal injection of the study drugs in both groups. The decrease in pulse rate was slightly

more in group D compared to group S. (P>0.05).

The mean systolic blood pressures were not significantly different in both groups at all time

intervals (P>0.05). See figure 2. The pattern observed in the mean diastolic blood pressure

34

between the 2 groups was comparable with no significant difference (P>0.05). See figure 3.

Finally, the mean arterial blood pressure and oxygen saturation were comparable and not

significantly different in both groups (P>0.05). See figure 4 and 5.

The sedation scores of the patients in both groups were comparable as shown in table V with

no level of significance in their mean scores at various time intervals (P>0.05). The median

sedation scores of the patients in both groups were comparable and found to be 2.

There was no statistical difference in the incidence of complications between the two groups.

Group D had 20% incidence of hypotension compared to 17% in group S (P=0.910). There

were 14% incidence of bradycardia in group D compared to 9% of the patients in group S

(P=0.750). Shivering occurred in 3% of patients in group D and 11% in group S. (P=0.477).

There were 3% incidence of nausea in both groups D and S (P=1.000). There were no

incidence of vomiting, pruritus, postoperative headache and pareasthesia of buttock, thigh

and lower limbs. These can be seen in table VI.

The level of satisfaction of patient pain management using Likert scale showed that 5% of

patients in group D reported that the pain relief was excellent while there was none in group

S. Ninety percent of the patients in group D reported very good pain relief while none in

group S reported such. Furthermore, Five percent of the patients in group D rated the pain

relief as good compared to 66% in group S (P=0.032). There was no patient in group D who

reported their level of satisfaction as poor unlike 34% of patients in group S. No patient

reported very poor pain relief in the 2 groups. These can be seen in table VII.

35

Table I: Demographic characteristics of the study groups

Parameter Group S Group D Pvalue Level of Significance

N=35 N=35

Age(years) 36.30±8.95 36.35±8.85 0.52 NS

(Mean ± SD)

Height(m) 1.64±0.54 1.65±0.50 0.54 NS

(Mean ± SD)

ASA 1 28(80%) 29 (82.9%) - -

ASA11 7(20%) 6 (17.1%) 0.5 NS

NS - Not Significant.

36

Table II: Sensory and motor block characteristics of the study groups (Mean±SD)

Time(minutes) Group S Group D Pvalue Level of significance

N=35 N=35

Time of onset of

block to T10 5.54±1.69 4.57±1.50 <0.001 S

Time to maximum Sensory

block height 9.94±1.57 11.14±2.39 0.11 NS

Time of Regression

To S1 210.54±21.48 358.74±30.97 0.02 S

Time to reach

Modified Bromage 3 8.41±2.34 7.28±2.49 0.02 S

Time of motor regression

To Bromage 0 195.97±19.69 330.11±31.86 0.004 S

S- Significant

NS- Not Significant

37

Table III: Time to first analgesic request and total analgesic consumed. ( Mean ± SD )

Time Group S Group D Pvalue Level of Significance

N=35 N=35

Time to first 233.09±23.79 407.83 ±35.55 <0.0001 S

analgesic request (min).

Total analgesic 125.14±11.47 90.00± 7.27 0.0001 S

consumed (mg)

S - Significant.

38

TABLE IV: Proportion of patients with NRS < 4 and corresponding mean pain scores

at various time intervals in both groups.

Time(min) Group S

N=35

Group D

N=35

P value Level of

significance

N % Mean Pain

Score

N % Mean Pain

Score

0 hour 35 100 0.0 35 100 0.0 1 NS

1 hour 30 86 1.79±1.48 35 100 0.0 0.34 NS

2 hour 6 17 2.67±0.52 35 100 0.40±0.60 0.001 S

3 hour 0 0 - 35 100 1.77±0.87 - -

4 hour 0 0 - 10 29 2.80±0.42 - -

5 hour 0 0 - 3 9 3.00±0.0 - -

6 hour 0 0 - 0 0 - - -

NS: Not significant

S: significant

39

Table V: Sedation Scores of the study groups ( Mean ± SD )

Time interval (Group S) (Group D) (Pvalue) Level of Significance

(Minutes) N=35 N=35

Baseline 1.77±0.43 1.71±0.46 0.06 NS

15 1.91±0.28 2.00±0.00 1 NS

30 2.03±0.17 2.00±0.23 0.12 N.S

45 2.11±0.32 2.23±0.43 0.19 N.S

60 2.31±0.47 2.43±0.50 0.30 N.S

75 2.11±0.32 2.37±0.49 0.09 NS

90 2.06±0.24 2.11±0.32 0.08 NS

105 2.06±0.24 2.11±0.32 0.08 NS

120 2.10±0.11 2.12±0.13 0.32 NS

N.S - Not Significant

40

Table VI: Incidence of side effect in both groups.

GROUP S GROUP D Pvalue Level of significance

N=35 % N=35 %

Hypotension 6 17 7 20 0.910 NS

Bradycardia 3 9 5 14 0.750 NS

Shivering 4 11 1 3 0.477 NS

Nausea 1 3 1 3 1.000 NS

NS – Not Significant

41

Table VII: Patients’ satisfaction using the Likert scale

Parameters GROUP S GROUP D Pvalue Level of Significance

N=35 N=35

Excellent 0(0%) 2(5%) -

Very Good 0(0%) 31(90%) -

Good 23(66%) 2(5%) 0.032 S

Poor 12(34%) 0(0%) -

Very Poor. 0(0%) 0(0%) -

S - Significant

42

Figure 1:Trends of the mean pulse rate

0

20

40

60

80

100

120

PU

LSE

(b/m

in)

Time (Minutes)

GROUP S

GROUP D

43

Figure 2: Trends of the mean systolic blood pressure

0

20

40

60

80

100

120

140

160

SBP

(m

mH

g)

Time (Minutes)

GROUP S

GROUP D

44

Figure 3:Trends of the mean diastolic blood pressure

0

10

20

30

40

50

60

70

80

90

DB

P (

mm

Hg)

Time (Minutes)

GROUP S

GROUP D

45

Figure 4: Trends of the mean arterial blood pressure

0

20

40

60

80

100

120

MA

BP

(m

mH

g)

Time (Minutes)

GROUP S

GROUP D

46

Figure 5:Trends of the mean Oxygen saturation.

97

97.2

97.4

97.6

97.8

98

98.2

98.4

98.6

98.8

99

Baseline 2 10 20 40 60 80 100 120

SPO

2(%

)

Time (Minutes)

Group (S)

Group (D)

47

CHAPTER FIVE

DISCUSSION

This study showed that intrathecal addition of dexmedetomidine to bupivacaine for

subarachnoid block resulted in prolonged post-operative analgesic period without significant

side effects. This assertion was made because of prolonged time to first analgesic request,

lower pain scores in the postoperative period and reduced total analgesic consumed in the

first 24 hours in the dexmedetomidine compared to the control group.

Ramila et al17 reported that the time to first analgesic request was significantly longer in the

group that had dexmedetomidine as an adjuvant in a time of 274 minutes compared to the

placebo group with 216 minutes.(P<0.05). The time extension reported by Ramila17 was

shorter than the time found in this study. This may be due to lower dose of dexmedetomidine

(5µg) that was used in their study. This prolongation of time to first analgesic request was

also observed by Rakesh19 with a P value of < 0.001. It was noticed that the time extension in

dexmedetomidine group was shorter than the time noted in this index study despite using a

larger dose of dexmedetomidine (10µg). This could be as a result of lower dose of hyperbaric

bupivacaine (2.5ml) used in their study compared to 3ml used in this study. The prolongation

of analgesia may result from the synergism between the analgesic effects of the local

anaesthetic and dexmedetomidine. Sarma et al21 also noted a prolonged time to first analgesic

request but the time was shorter than what was obtained in this study. This could be as a

result of a lower dose of dexmedetomidine (5µg) used. The study by Gupta et al12 who

evaluated patients going for lower limb surgery showed a longer mean time to first request of

analgesia in the group that had dexmedetomidine compared to the placebo group.(P<0.001) .

They reported longer time than what was reported in this study despite using a smaller dose

of dexmedetomidine (5µg). This cannot be explained because it was reported that the time to

48

first analgesic request increases with increase in dose of dexmedetomidine.24 The local

anaesthetic (Isobaric Ropivacaine) they used was also reported to provide shorter time to first

analgesic request when compared to bupivacaine used in our study as confirmed by Chari et

al38 who compared the efficacy of 0.75% isobaric ropivacaine with 0.5% hyperbaric

bupivacaine for lower limb and lower abdominal surgeries and found that the mean time to

first analgesic request was shorter in the ropivacaine group than bupivacaine group (P>0.05).

Mahendru et al10 also corroborated the finding that dexmedetomidine increased time to first

analgesic request in their study. The time was longer in dexmedetomidine group (295.5±44.3

minutes) when compared to fentanyl (235.5±38.3 minutes), clonidine (242.3±54.2 minutes)

and placebo (183.0±31.0 minutes) groups (P<0.0001). However, the time observed in

dexmedetomidine group from their study was still shorter than the time noted in our study.

This noted difference may be due to the lower dose of local anaesthetic (2.5 ml of hyperbaric

bupivacaine) and dexmedetomidine (5µg) used which have a synergistic effect in determining

the duration of analgesia.

It was noted by Aditi and colleagues24 that the time to first request for analgesia increases

with increase in doses of dexmedetomidine used. In their study, intrathecal dexmedetomidine

significantly increased the time of request for analgesic compared to placebo (P<0.001). The

time was further significantly enhanced with increased dose of dexmedetomidine from 5µg to

10µg (P<0.001). The time (356.50 ±43.98 minutes) they reported by addition of 5µg was

shorter than the time reported in the index study and as expected, was due to the lower dose

of dexmedetomidine they used but longer when 10µg was added.

Chaudhry et al26 corroborated the findings that increased dose of dexmedetomidine results in

increased post operative analgesic period. They found that the time to first analgesic request

was significantly lower in 5µg of dexmedetomidine compared to 10µg (P=0.029). The time

49

of first analgesic request (210.3±45.2 minutes) they reported was shorter when 5µg of

dexmedetomidine was added than the time reported in this index study. However, the time

observed when 10µg of dexmedetomidine was added (254.18±40.55 minutes) was shorter

when compared to 7.5µg used in this study. This may be as a result of the lower dose of local

anaesthetic (2.5ml of hyperbaric bupivacaine) used in their study.

In summary, from the above; there are different variables that can affect time to first

analgesic request. These are, the type and dose of local anaesthetic agent and adjuvant used.

It is therefore imperative to look at these variables when comparing outcomes from different

studies as these can affect conclusion.

The proportion of patients with NRS score of < 4 was observed to be more among group D

patients compared to group S in this study. This outcome shows that the addition of

dexmedetomidine resulted in superior analgesic profile compared to placebo. The use of

adjuvant dexmedetomidine extended the duration of pain relief in the post operative period

by at least 3 hours in all the patients in the group. This is in contrast to the outcome when no

adjuvant was used, as some of the patients without dexmedetomidine experienced pains in the

first hour. It is clear from the forgoing that the use of dexmedetomidine prolongs the duration

of post-operative analgesia. Using multimodal approach in post operative pain management,

this period could be extended for a longer duration for example, with the use of local

anaesthetic infiltration and non steroidal anti inflammatory drugs.39

In a study by Ramila et al17 they observed that intrathecal addition of dexmedetomidine to

bupivacaine spinal anaesthesia resulted in an increase in the proportion of patients that were

pain free in the postoperative period. They found that the patients that received placebo were

pain free postoperatively up to the 3rd hour contrary to the finding in our study in which no

patient was pain free among the placebo group at the 3rd hour postoperatively. This difference

50

in results may be due to the type of procedures they carried out, surgeries carried out included

those of the foot, ankle and tibio fibula which were of lower dermatomes compared to ours.

Incision for open reduction and internal fixation of femoral fracture surgeries involve a

higher dermatone L1/L2 compared to those of tibiofibular, ankle or foot as in Ramila ̓s

study.17 Sensory block regression takes a longer time to get to the lower dermatone involving

the tibiofibular , ankle or foot and results in longer postoperative pain period compared to

ours with a higher dermatone. It was noted by Curatolo et al40 in their multifactorial analysis

to explain inadequate surgical analgesia after a regional block that the type of surgery affects

the risk of feeling pain. They submitted that femur and hip surgeries were associated with

greater risk of inadequate analgesia compared to the ankle surgery because of their dermatone

levels. There was no patient with NRS score <4 at the 8th hour, 12th hour, 18th hour and 24th

hour postoperatively. This was similar to the finding by Ramila et al.17 This is because all the

patients had received rescue analgesics at the 6th hour and no further pain assessment was

made afterwards.

It was observed from our study that prolonged duration of analgesia due to the longer time

to first request for analgesia reduced the analgesic requirement in the dexmedetomidine group

(90. 00 ± 7.27 mg) compared to the saline group (125.14±11.47 mg) (P<0.0001) over a

period. This reduction in analgesic requirement was similar to that reported by Mahendru et

al.10 They noted a significant reduction in total analgesic (tramadol) consumption in the

dexmedetomidine group when compared to the saline group (P<0.05). Gupta et al12 stated

that the total analgesic requirement (diclofenac) in the first 24 hours in the postoperative

period was significantly less in the dexmedetomidine group (0.97±0.19 dose) compared to

placebo group (2.70±0.47 doses) (P<0.001). The reduction in analgesic requirement

observed was due to the prolonged time for first analgesic request reported in the

dexmedetomidine group.

51

The total analgesic consumption in the first 24 hours has been found to decrease with

increased dose of dexmedetomidine. Hala Eid and colleagues23 observed that the mean

analgesic dose in the first 24 hours using 75mg intramuscular diclofenac decreased when the

dose of dexmedetomidine was increased from 10µg (1.4 doses) to 15µg (0.4 dose) compared

to the placebo (1.9 doses). This was corroborated by Aditi and co workers.24They reported

that the mean dose of analgesic consumption in the first 24 hours decreased as the dose of

dexmedetomidine was increased from 5µg to 10µg when compared to the placebo (P<0.001).

Furthermore, when the 2 different doses were compared with each other, there was

significant difference (P<0.05). Chaudhry and group26 also noted that increased dose of

dexmedetomidine significantly decreased the number of doses of analgesic in the first 24

hours (P=0.037).

The addition of dexmedetomidine did not have any profound haemodynamic changes as

observed in this study. This is as a result of the negligible effect low dose intrathecal

dexmedetomidine has on sympathectomy. Sympathectomy is almost maximal with the use of

local anaesthetic agents alone. The addition of low dose dexmedetomidine to the local

anaesthetic does not significantly affect the near maximal sympathectomy.41 This can explain

the negligible effect of the drug on blood pressure and pulse rate.

Our findings are in keeping with the result of Ramila and co-workers17 who observed that

addition of 5µg of dexmedetomidine to bupivacaine spinal anaesthesia did not significantly

decrease the blood pressure and pulse rate. The haemodynamic changes were not

significantly different between the 2 groups (P>0.05). Gupta et al12 also noted that there was

no statistical significant difference in the haemodynamic changes observed in their study

(P>0.05). The findings by these studies suggest that intrathecal dexmedetomidine does not

cause significant haemodynamic effect when used as an adjuvant in spinal anaesthesia.

52

The incidence of shivering in the dexmedetomidine group in our study was clinically lower

with an incidence of 3% compared to 11% in the placebo group although, the difference was

not statistically significant (P=0.477). Shivering following spinal anaesthesia is due to a fall

in core body temperature. This occurs in response to the core to peripheral redistribution of

body heat due to peripheral vasodilatation that occurs in regional anaesthesia which leads to

heat loss. Spinal anaesthesia has been found to decrease shivering threshold.42 In the study by

Gupta et al,12 shivering was not observed in dexmedetomidine group compared to 3.3%

incidence in saline group. Sarma and colleagues21 also reported a non statistical significant

difference in the incidence of shivering in their study. They noted 16% incidence in saline

group compared to 8% in dexmedetomidine group (P>0.05). This is similar to what was

documented in the index study. Observation from Fahmy et al18 were surprising as addition of

10µg dexmedetomidine to bupivacaine subarachnoid block resulted in 23.3% incidence of

shivering in dexmedetomidine group compared to 56.7% in saline group, which was of

significance difference statistically (P<0.05). The reason for the high incidence observed in

their study compared to this index study may be that they used cold Ringer̓s lactate solution

for preloading and cold normal saline for fluid maintenance. Bajwa et al27 in their study

observed 5% incidence of shivering in the dexmedetomidine group compared to 42.5% in

saline group (P=0.014). This reduction on the incidence of shivering in the dexmedetomidine

group compared to the saline group could be explained by the fact that dexmedetomidine

reduces vasoconstriction and increasing shivering thresholds mediated by its central α2

activity.27

There was no statistical difference in the incidence of nausea between the 2 groups (3%

each).This could be explained by the non significant difference in the incidence of

hypotension which was 17% in saline group and 20% in dexmedetomidine group (P>0.05).

Hypotension causes cerebral hypo perfusion which causes nausea and vomiting. This

53

outcome was also supported by the study conducted by Gupta and colleagues12 who reported

a non significant incidence of 3.3% nausea in dexmedetomidine group and 6.6% in saline

group (P>0.05) with 6.6% incidence of hypotension in dexmedetomidine group and 3.3%

incidence in saline group (P>0.05) . Rakesh et al19 noted a non significant incidence of

nausea as observed in this study when dexmedetomidine was compared to the placebo group.

The non significant difference on the incidence of nausea noted by Sarma et al21corroborated

the report of this study. They observed 12% incidence in saline group and 8% in

dexmedetomidine group (P>0.05) with 8% incidence of hypotension in each of the groups.

Sedation score observed in this study had no statistical significance difference at different

time intervals between the two groups. The median sedation score observed in this study was

2 in both groups. Although dexmedetomidine has sedative properties, there was no significant

effect on the study. This may be due to the low dose used in this study. However, the level of

sedation observed here was beneficial (patients were cooperative, oriented and tranquil)

because the sedation score was at the desirable level of sedation required for the surgery. The

sedation score obtained in this study is closely related to what other authors reported. Ramila

and group17observed a mean sedation score of 1 in the saline group and 1.73 in

dexmedetomidine group at the 60th minute (P<0.05). The mean sedation score in their study

was lower compared to the score in the index study. This may be due to the lower dose of

dexmedetomidine (5µg) used in their study. Aditi et al24 reported an increase in the

proportion of patients with a higher level of sedation following an increase in the dose of

dexmedetomidine in their study. Hala Eid and colleagues 23 also concluded that increasing

dose of dexmedetomidine also increases the sedation Score. It is believed that

dexmedetomidine produces sedation centrally by activating the α2 adrenoceptors in the Locus

Ceruleus.43

54

The quality of block associated with the intrathecal administration of dexmedetonidine was

demonstrated in our study. The motor block characteristics showed that the time for motor

regression to Bromage 0 was longer in the dexmedetomidine group compared to the saline

group. This was also observed by Ramila and colleagues17 who reported a longer time of

236±16.6 minutes in the dexmedetomidine group and 162.5±7.5 minutes in saline group

(P<0.05). The shorter time observed in their study compared to the index study may be due to

the lower dose of dexmedetomidine (5µg) they used. This was also observed by other

researchers.2, 21 This motor block prolongation was also found to significantly increase with

increased dose of dexmedetomidine as documented by Baghel et al.25 The prolongation of

motor block following spinal anaesthetic with addition of dexmedetomidine may result from

binding of the α2 adrenergic agonist to motor neurons in the dorsal horn.44 This prolongation

of the duration of motor block is not beneficial especially in the ambulatory surgeries or short

and intermediate duration orthopaedic surgical procedures where early ambulation is

desirable. It is accepted that early mobilisation is vital to avoiding post operative medical

condition such as deep venous thrombosis, urinary tract infection, pressure ulcer and early

hospital discharge.45 However, there is hesistancy among some surgeons to allow early

ambulation after femoral and hip fracture surgeries using sliding screw plate fixation because

of concern of mechanical failure thus, favouring prolonged motor block. Wolfgang and

colleagues46 in their study on treatment of intertrochanteric fracture of the femur found 9%

mechanical fracture complication due to early ambulation.

Patients’ level of satisfaction with the quality of analgesia achieved was assessed with five

level Likert scale. This study revealed that 66% of patients in group S rated as good the

quality of analgesia they received while 34% rated it as poor. This is contrary to the

observation in group D where 5% of the patients rated the quality of analgesia as excellent,

90% as very good and the remaining 5% as good. Thus, the level of satisfaction of the

55

patients that received dexmedetomidine showed that there was good quality of analgesia

associated with the intrathecal administration of dexmedetomidine as an adjuvant in

bupivacaine subarachnoid block. There is no information on the level of satisfaction from the

available literatures. It is assumed that the studies that reported the same quality of analgesia

as in this index study may probably report the same level of satisfaction because it is a

measure of adequacy of post operative pain management.

56

CONCLUSION

This study has demonstrated that intrathecal administration of 7.5µg of dexmedetomidine

combined with 3ml of 0.5% hyperbaric bupivacaine provided stable haemodynamic

condition, minimal side effects, excellent quality of postoperative analgesia and reduced the

requirement of post operative rescue analgesia when compared with 3ml of 0.5% hyperbaric

bupivacaine alone.

57

LIMITATION

Difficulty to standardise the pain variables as it is a subjective phenomenon with a wide

variability of responses among individuals. Although numeric rating scale is an acceptable

tool for pain assessment, individual pain threshold varies.

58

RECOMMENDATION

Dexmedetomidine should be considered as the adjuvant of choice in spinal anaesthesia for

lower limb surgeries due to the quality of analgesia and prolonged pain relief in the post

operative period.

Its cost effectiveness can be explored since an ampoule of 100µg that was used for 13

patients costs three thousand naira which translates to approximately two hundred and thirty

one naira per patient.

It is not a controlled drug unlike opioids and do not have major side effects, thus, should be

recommended.

59

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APPENDIX I

PROFORMA

Post operative analgesic effect of Intrathecal Dexmedetomidine on Bupivacaine

Subarachnoid Block for Open reduction and Internal Fixation of Femoral Fractures.

PERSONAL INFORMATION

1. Serial Number:………………………. Date:………………

2. Group Number:………………………

3. Hospital Number:……………………

4. Age (yrs):…………… Height(m):……BMI:……

5. Tribe:…………………………………………………………………….

6. ASA Status:……………………………………………………………..

7. Any Intercurrent medical condition:……………………….

INTRAOPERATIVE CARE

8. Time of subarachnoid drug administration:…………….

9. Interspace for administration of local anaesthesia:…………

10. Vital Signs

Parameter Pulse SBP(mmHg) DBP(mmHg) MABP(mmHg) SPO2(%)

Baseline

2 Minutes

4 Minutes

6 Minutes

8 Minutes

10 Minutes

65

15 Minutes

20 Minutes

25 Minutes

30 Minutes

35 Minutes

40 Minutes

45 Minutes

50 Minutes

55 Minutes

60 Minutes

65 Minutes

70 Minutes

75 Minutes

80 Minutes

85 Minutes

90 Minutes

95 Minutes

100 Minutes

105 Minutes

110 Minutes

115 Minutes

120 Minutes

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16 . Maximum Block height

Time Sensory (dermatone) Motor (modified Bromage Score)

2 Minutes

4 Minutes

6 Minutes

8Minutes

10 Minutes

12Minutes

14Minutes

16Minutes

18minutes

20minutes

17.Time of onset of analgesia at T10:…………………………….

18.Time to reach modified Bromage 3 (complete block):………..

19. Sensory block level at the end of surgery ..............................

20. Bromage score at the end of surgery.......................................

21. Block regression post operatively

Time Sensory (dermatone) Motor (modified Bromage Score)

20 Minutes

40 Minutes

60 Minutes

80Minutes

100 Minutes

120Minutes

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22. Time (from subarachnoid block drug administration) of sensory regression to

S1:…………………………….

23. Time (from subarachnoid block drug administration) of motor regression to Bromage 0

(no block):…………..

24. Sedation score if present using modified Ramsay sedation scale

Score Interpretation Base

line

15mins 30mins 45mins 60mins 75mins 90mins 105mins 120mins

1 Anxious, agitated

and restless

2 Cooperative,

oriented and

tranquil

3 Respond to

command only

4 Brisk response to

light glabellar tap

5 Sluggish response

to light glabellar

tap

6 No response

25.

Other complications Intra op Post op Treatment Outcome

Hypotension

Bradycardia

Respiratory depression

Nausea

Retching

Vomiting

Pruritus

Shivering

Headache

Paraesthesia of the buttock, thigh and

lower limb

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26. Duration of surgery in minutes (from skin incision to last stitch):………………………

47. Estimated blood loss:………………….

48. Urine output:…………………

49. Pain score post operatively using numeric rating scale (NRS).

Time 0hr 1hr 2hr 3hr 4hr

NRS

Time 8hr 12hr 18hr 24hr

NRS

50. Time (from subarachnoid block drug administration) to first request for analgesia

(minutes):………………………………..

51. Total analgesic consumption in the 1st 24hours:…………

52. Patients’ satisfaction with pain relief (5 point Likert Scale)

Excellent Very good Good Poor Very poor

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APPENDIX II

INSTITUTIONAL ETHICAL CLEARANCE

70

APPENDIX III

INFORMED CONSENT FORM

Dear Patient,

This is to request for your permission to be included as a subject in a research titled: Post

Operative Analgesic Effect of Intrathecal Dexmedetomidine on Bupivacaine Subarachnoid

block for Open reduction and Internal Fixation of Femoral Fractures.

Investigator: DR. NWACHUKWU CYRIL EMEKA Department of Anaesthesia, Nnamdi

Azikiwe University Teaching Hospital, Nnewi.

Purpose and description of the Study: This study is to determine the duration of analgesia

produced by the addition of dexmedetomidine to hyperbaric bupivacaine for patients

undergoing surgery for open reduction and internal fixation of femoral fracture and its

associated side effects.

You will undergo this surgical procedure which may cause some degree of pain requiring

pain relief. This can be provided through a technique known as spinal anaesthesia, w hereby

an injection of a drug which could be 3ml of 0.5% hyperbaric Bupivacaine plus 7.5µg of

dexmedetomidine or 0.5% hyperbaric bupivacaine plus saline will be given through the lower

part of the back.

During and after the surgical procedure, presence of pain will be assessed using a pain

scoring system known as numeric rating scale (NRS) and if present, injection pentazocine

will be used for treatment.

71

Potential Risk: The study drug is relatively safe. Some risks may be associated such as low

pulse rate, low blood pressure, failure to achieve adequate analgesia which if occur, will be

treated.

Compensation: You will not be paid for participation.

Participation: Please understand that your participation in this study is entirely voluntary

and you can terminate or withdraw participation from the study without affecting the quality

of care you will get.

Confidentiality: All information obtained in the course of this study will be treated

confidentially. You will not be identified by name during data analysis.

Benefits: The results will enable doctors to help their patients undergoing open reduction and

internal fixation of femoral fractures with using a combination of the study drugs to achieve

adequate pain relief in the immediate postoperative period.

I …………………………………………of……………………………….. accept to freely

participate in this research.

Patient signature/Date:…………………………………….

Witnessed (Name/Signature/Date):……………………..

Investigator Signature/Date:………………………………

Contact:

Dr. Nwachukwu Cyril Emeka

Department of Anaesthesia,

Nnamdi Azikiwe University Teaching Hospital,

Nnewi, Anambra State.

Phone Number: 08037599536

Email: chezzb2000@yahoo.co.uk.

72

APPENDIX IV

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