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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: [email protected].
72
APPENDIX IV
73
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