Download RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA,
BANGALORE.
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1. NAME OF THE CANDIDATE AND
: DR. MALASHREE
ADDRESS
DEPT OF ANAESTHESIOLOGY
MYSORE MEDICAL COLLEGE
AND RESEARCH INSTITUTE,
MYSORE.
--------------------------------------------------------------------------------------------------------------------2. NAME OF THE INSTITUTION
: MYSORE MEDICAL COLLEGE
AND RESEARCH INSTITUTE,
MYSORE.
--------------------------------------------------------------------------------------------------------------------3. COURSE OF STUDY AND SUBJECT
: POST GRADUATE
MD. ANAESTHESIOLOGY
--------------------------------------------------------------------------------------------------------------------4. DATE OF ADMISSION TO THE
: 29/07/2013
COURSE
--------------------------------------------------------------------------------------------------------------------: “A COMPARATIVE CLINICAL
5. TITLE OF THE TOPIC
STUDY OF INTRATHECAL
DEXMEDETOMIDINE 5µg AND
INTRATHECAL FENTANYL 25µg
WITH 0.5% HYPERBARIC
BUPIVACAINE 12.5mg IN ELECTIVE
TOTAL ABDOMINAL
HYSTERECTOMY- A DOUBLE BLIND
CONTROLLED STUDY”
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6. BRIEF RESUME OF INTENDED WORK
6.1 NEED FOR THE STUDY:
Spinal anaesthesia is one of the most commonly used techniques for lower abdominal
surgeries as it is very economical and easy to administer with the advantage of providing surgical
anaesthesia. . However, postoperative pain control is a major problem because spinal anaesthesia
using local anaesthetics alone is associated with relatively short duration of action and thus early
analgesic intervention is needed in the postoperative period1. Various adjuvants have been used
along with local anaesthetic agents to avoid intraoperative visceral and somatic pain and to
prolong postoperative analgesia1. Fentanyl is a short acting mu receptor agonist. It exerts its
effect by combining with opioid receptor in the dorsal horn of spinal cord and may have a supraspinal spread and action. Addition of intrathecal Fentanyl as an adjuvant to spinal anaesthesia
produces faster onset time, decreases the visceral pain, somatic pain, improved intra-operative
analgesia and excellent quality of peri-operative analgesia1, 2. Fentanyl produces shorter duration
of post-operative analgesia and also known to produce side effects like pruritus, respiratory
depression and increased incidence of post-operative nausea and vomiting.
Recently α-2 adrenoreceptor agonists are being used as an adjuvant to local anaesthetic
agents because of their sedative, analgesic effect, good quality of intra-operative and prolonged
post-operative analgesia and haemodynamic stabilizing effects with minimal side effects1.
Dexmedetomidine can be used as an adjuvant to local anesthetics for intrathecal anaesthesia. Its
addition to local anesthetics has been found to prolong the duration of both motor and sensory
blockade without much side effects2, 3. Dexmedetomidine, acts by binding to pre-synaptic Cfibers and post synaptic dorsal horn neurons1, 3. Dexmedetomidine recently has been introduced
in India and not many studies have been done regarding its use as an intrathecal adjuvant to local
anaesthetics, a study is required to know its effectiveness as a spinal adjuvant.
Fentanyl is commonly used as an adjuvant to local anaesthetic for spinal anaesthesia in
our institution. A study is required to compare the traditionally used fentanyl with recently
introduced Dexmedetomidine as adjuvants to Bupivacaine intrathecal anaesthesia. Hence this
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study is to evaluate onset, duration of sensory and motor block, haemodynamic effects, postoperative analgesia, and adverse effects of Dexmedetomidine and Fentanyl given intrathecally
with 0.5% hyperbaric Bupivacaine for elective total abdominal hysterectomy.
.
6.2 REVIEW OF LITERATURE:
Al-Ghanem S M et al2. conducted a double blind controlled study in the year 2009 to evaluate
the onset and duration of sensory and motor block as well as operative analgesia and adverse
effects of Dexmedetomidine or Fentanyl given intrathecally with isobaric 0.5% Bupivacaine for
spinal anaesthesia.
76 patients of ASA status I/II scheduled for vaginal hysterectomy, vaginal wall repair, and
tension free vaginal tape were prospectively studied. Patients were randomly allocated to receive
intrathecal either 10mg plain Bupivacaine with 5 µg Dexmedetomidine- group D (n-38) or 10mg
plain Bupivacaine with 25 µg Fentanyl- group F (n-38). The sensory block level was assessed by
cold alcohol swab along the mid-clavicular line bilaterally. The motor block was assessed
according to the modified Bromage scale. The regression time for sensory and motor block
haemodynamic changes and side effects were recorded. Assessment of pain in intra-operative
and in post-operative anaesthesia care unit was done using VAS score 0-10. Statistical data were
analysed by using appropriate methods.
The onset time to reach T10 dermatome and time taken for peak sensory level, as well as
onset time to reach modified Bromage scale-3 motor block were statistically not significant
between the two groups. Patient in group-D had significant longer sensory and motor block time
than patient in G-F. The mean time of sensory regression to S1 was 274+73min in G-D and
179+47min G-F (p<0.001). The regression time of motor block to reach modified Bromage
scale-0 was 240+60min in G-D and 155+46min G-F(P<0.001).
Thus author study concluded that in patients undergoing vaginal reconstructive surgery
under spinal anaesthesia, 10mg plain Bupivacaine supplemented with 5 µg Dexmedetomidine
produces prolonged motor and sensory block with minimal side effects compared with 25 µg
Fentanyl.
Al-Mustafa MM5 et al. in 2009 conducted a study on effect of Dexmedetomidine added to
spinal isobaric Bupivacaine for urological procedures.
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66 patients of ASA grade 1-3 scheduled for TRUP, transurethral resection of bladder tumor or
placement of tension free vaginal tape for urinary incontinence control were studied, patient were
randomly allocated into of one of three groups (n=22). Group- N received isobaric Bupivacaine
12.5mg with normal saline, Group D5 received isobaric Bupivacaine 12.5mg with 5 µg
Dexmedetomidine and GroupD10 received isobaric Bupivacaine 12.5mg with 10 µg.
Dexmedetomidine. With patient in sitting position, lumbar puncture was performed at L3-4 inter
space with 25-gauge Quincke needle. All patients received a volume of 3ml intrathecal drug.
The level of sensory block (cold alcohol swab), grade of motor block (modified Bromage
scale), the time to reach T10 dermatome level, time to reach peak sensory level, two segment
regression, regression to the S1 dermatome, time to reach Bromage 3, regression to Bromage 0
and level of sedation(Ramsay sedation scale) were recorded.
The result of the study showed that the duration of onset of sensory blockade in Group D
10 was 4.7+2.0 mins, Group D5 was 6.3+2.7 mins and Group N was 9.5+3.0 mins and motor
blockade in Group D 10 was 10.4+3.4mins, Group D5 was 13.0+3.4 mins and Group N was
18.0+3.3 mins.
The results showed that time to reach T10 sensory level, Bromage 3 motor block and the
regression times to reach S1 sensory level (Group D10 was 338.9+44.8 mins, Group D5 was
277.1+23.2 mins and Group N was 165.5+32,9 mins) and the regression time to reach Bromage
0 motor scale (Group D10 was 302.9+36.7 mins, Group D5 was 246.4+25.7 mins and Group N
was 140.1+32.3 mins) were affected by the addition of Dexmedetomidine to the spinal
Bupivacaine in dose dependent manner.
There was no significant difference in MAP and HR between three groups
intraoperatively and postoperatively. Ramsay sedation scores were 2 in all patients in the three
groups.
Hence they concluded that the use of Dexemedetomidine improved the onset of sensory
and motor blockade and it prolonged the sensory and motor block when used with Bupivacaine
in spinal anaesthesia in a dose dependent manner.
Gupta R et al 1. In the year 2011 conducted a double blind study to evaluate the onset and
duration of sensory and motor block, haemodynamic effects, postoperative analgesia, and
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adverse effects of Dexmedetomidine or Fentanyl given intrathecally with hyperbaric 0.5%
Bupivacaine.
Sixty patients classified of ASA classes I and II scheduled for lower abdominal surgeries were
studied. The Patients with uncontrolled diabetes, hypertension & other co-morbid diseases were
excluded from the study. Patients were randomly allocated to receive either 12.5 mg hyperbaric
Bupivacaine plus 5 µg Dexmedetomidine (group D, n = 30) or 12.5 mg hyperbaric Bupivacaine
plus 25μg Fentanyl (group F, n = 30) intrathecally.
After intrathecal injection the time of onset and maximum level of sensory and motor
blockade, time to S1 level sensory regression and side effects were recorded. Sedation was
assessed by a modified Ramsay sedation scale. Postoperatively, the pain score was recorded by
VAS between 0-10, initially every 1 hour for 2hr, then every 2 hr for the next 8 hr & then after
every 4 hr till 24hr. Inj diclofenac was given IM as rescue analgesia when VAS >4. The data was
analysed by using the chi-square test. p<0.05 was considered statistically significant.
They found no significant difference between the groups with respect to onset of sensory
and motor block, time for maximum sensory and motor block. The mean time of sensory
regression to S1 was 476±23 min in group D and 187±12 min in group F (P<0.001). The
regression time of motor block to reach modified Bromage 0 was 421±21 min in group D and
149±18 min in group F (P<0.001). Time for rescue analgesia is 251.7+30 in group-D and
168.96+ 15.96 in group-F.
Thus the authors concluded that intrathecal Dexmedetomidine is associated with prolonged
motor and sensory block, haemodynamic stability, and reduced demand for rescue analgesics in
24 h as compared to Fentanyl.
Gupta R3 et al. conducted a study in 2011 to evaluate the efficacy and safety of
Dexmedetomidine added to ropivacaine. 60 patient’s of ASA physical status I or II, of either sex
(18-50 years) presenting for lower limb surgeries. Group R - 3 ml volume of 0.75% isobaric
ropivacaine and 0.5 ml normal saline and Group D- 3 ml volume of 0.75% isobaric ropivacaine
with 5 µg Dexmedetomidine in 0.5 ml of normal saline.
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After intrathecal injection, the time of onset and maximum level of sensory, motor blockade,
time to S1 level sensory regression and side effects like bradycardia, hypotension, nausea,
vomiting were recorded. Sedation was assessed by a four point verbal rating scale.
Postoperatively, pain scores were recorded by using VAS between 0 and 10 initially every 1 hour
for 2 hours, then every 2 hours for next 8 hours and then after every 4 hours till 24 hours.
Injection diclofenac 75 mg intramuscular was given as rescue analgesia when VAS ≥4.
Statistical data were analysed by using chi-squared test or the Fisher’s exact test. P<0.05 was
considered statistically significant. There was no difference between group D and R in the
highest level of block (T5 and T6, respectively) or in the time to reach peak level (11.65±1.73
and 12.05±1.64 minutes). Time to two segment regression and time to S2 regression were
significantly more in Group –D (468.3±36.8 min and 125.6 ±16.5 min) as compared to Group -R
(239.3±16.8 min and 62.7±8.3min) respectively. Time of rescue analgesia in group-D is
478.4±20.9 min and in group-R is 241.67±21.67 min.
There was no serious complication in 60 study patients, like nausea, vomiting, shivering, itching,
pruritus, sedation, respiratory depression and hypotension.
Thus author study concluded that, 5 µg Dexmedetomidine seems to be an attractive alternative as
an adjuvant to spinal ropivacaine in surgical procedures, especially those requiring long time. It
has excellent quality of postoperative analgesia with minimal side effects.
Mahendru V 4 et al. conducted a double blind study in 2013 to compare the onset, duration of
sensory and motor block, hemodynamic effects, postoperative analgesia, and adverse effects of
Dexmedetomidine, clonidine, and Fentanyl used intrathecally with hyperbaric 0.5% Bupivacaine
for spinal anaesthesia.
120 patients (ASA) class I and II were randomly allocated into four groups (30 patients each).
Group BS received 12.5 mg hyperbaric Bupivacaine with normal saline, group BF received 12.5
mg Bupivacaine with 25 µg Fentanyl, group BC received 12.5 mg of Bupivacaine supplemented
30 µg clonidine, and group BD received 12.5 mg Bupivacaine plus 5 μg Dexmedetomidine.
The onset time to reach peak sensory and motor level, the regression time of sensory and motor
block, hemodynamic changes and side effects were recorded.
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Patients in Group BD had significantly longer sensory and motor block times than
patients in Groups BC, BF, and BS with Groups BC and BF having comparable duration of
sensory and motor block. The mean time of two segment sensory block regression was 147 ± 21
min in Group BD, 117 ± 22 in Group BC, 119 ± 23 in Group BF, and 102 ± 17 in Group BS (P <
0.0001). The regression time of motor block to reach modified Bromage zero (0) was 275 ± 25,
199 ± 26, 196 ± 27, 161 ± 20 in Group BD, BC, BF, and BS, respectively (P < 0.0001). The
onset times to reach T8 dermatome and modified Bromage 3 motor block were not significantly
different between the groups. Dexmedetomidine group showed significantly less and delayed
requirement of rescue analgesic.
Thus their study concluded that intrathecal Dexmedetomidine is associated with prolonged motor
and sensory block, hemodynamic stability, and reduced demand of rescue analgesics in first 24
hrs as compared to clonidine, Fentanyl, or lone Bupivacaine.
6.3 OBJECTIVES OF STUDY:
To compare Dexmedetomidine 5µg and Fentanyl 25µg as an adjuvant to 12.5mg of hyperbaric
Bupivacaine for spinal anaesthesia in total abdominal hysterectomy surgeries regarding

Onset, maximum level and duration of sensory block.

Onset, quality and duration of motor block.

Duration of post-operative analgesia.

Side effects like hypotension, bradycardia, sedation, pruritus, post-operative nausea and
vomiting and respiratory depression.
7. MATERIALS AND METHODS:
1. SOURCE OF DATA:
After clinical approval of Institutional Ethical Clearance Committee and informed written
consent 90 female patients of ASA physical class I and II who are posted for elective total
abdominal hysterectomy(TAH) at Cheluvamba Hospital attached to Mysore Medical College and
Research Institute, Mysore, will be selected for the study. The study will be conducted from
November 2013 to July 2015. The study population will be randomly selected based on the
closed sealed opaque envelope technique.
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Group C- will receive 12.5mg (2.5ml) of 0.5% hyperbaric Bupivacaine with 0.5ml normal saline.
Group D - will receive 12.5mg (2.5ml) of 0.5% hyperbaric Bupivacaine with 5µg of
Dexmedetomidine in (0.5ml normal saline).
Group F -will receive 12.5mg (2.5ml) of 0.5% hyperbaric Bupivacaine with 25 µg Fentanyl in
(0.5ml normal saline).
INCLUSION CRITERIA:
Patients aged between 30 – 60 years belonging to ASA class I & II without any co-morbid
disease, admitted for elective TAH.
EXCLUSION CRITERIA:
1. Patients with co-morbid conditions like diabetes mellitus, asthma, hypertension, cardiac
disease, hematological disease ect
2. Allergy to local anaesthetics.
3. Patients belonging to ASA class III, IV and V.
4. Patients posted for emergency surgeries.
5. Patients with body mass index more than 28kg/m2.
6. Patients having absolute contraindication for spinal anaesthesia like raised intracranial
pressure, severe hypovolaemia, bleeding diathesis and local infection.
7. Patient’s refusal.
8. Surgeries with vertical incision.
7.2 Methods of collection of data:
Data is collected from 90 patients in the age group of 30-60 yrs of ASA class I & II, posted for
elective TAH without any co-morbid diseases are grouped randomly by using closed sealed
opaque envelope technique. The study drug will be prepared by an anaesthesiologist, who is not
involved with the study. All spinal block will be given by the same anaesthesiologist who also
will be the observer. Hence the patient and the observer will be blinded for the study drug.

Prescribed pro-forma meeting the objectives of the study.
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Group C (n=30) - will receive 12.5 mg (2.5ml) of 0.5% hyperbaric Bupivacaine with 0.5ml
normal saline
Group D (n=30) - will receive 12.5 mg (2.5ml) of 0.5% hyperbaric Bupivacaine with 5µg of
Dexmedetomidine in (0.5ml normal saline).
Group F (n=30) -will receive 12.5mg of 0.5% hyperbaric Bupivacaine with 25µg Fentanyl in
(0.5ml normal saline).

Preoperative assessment will be done for each patient and written informed consent is
taken.

Patients will be kept Nil per Oral for solids 6hrs and clear fluids 2 hrs before surgery.

Patients will be premedicated on the night before surgery with the tablet Ranitidine
150mg and tablet Alprazolam 0.5mg.

Intravenous line will be obtained with 18G cannula and will be preloaded with ringer
lactate 500ml(10ml/kg body weight) half an hour before anaesthesia.

Patients will be connected to multi channel monitor(Star plus Larsen Toubro ltd.India)
for monitoring pulse rate(PR), arterial oxygen saturation(SPO2), electrocardiograph(
ECG), non invasive blood pressure (NIBP) and mean arterial pressure(MAP).

Patient positioned in flexed lateral position.

Under aseptic precautions Subarachnoid block is performed at L2-L3/L3- L4 inter-space
through a midline approach using 25G Quincke’s spinal needle after confirming the clear
and free flow of CSF the study drug is injection into the subarachnoid space. Patients will
be turned to supine posture immediately with the table kept flat and supplemental oxygen
will be given.
The following parameters are noted

Onset of sensory and motor blockade.

Total duration of sensory and motor blockade.

Sensory blockade will be tested using pinprick method with a blunt tipped 27G
hypodermic needle at every 30 seconds for first 2 minutes, every minute for next 5
minutes and every 5 minutes for next 15 minutes and every 10 minutes for next 30
minutes and every 15 minutes till the end of surgery and there after every 30 minutes
until sensory block is resolved.
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
Maximum level of sensory blockade attained and the time taken for the same will be
noted.

Two segments sensory regression time will be noted.

Total duration of analgesia will be noted

The motor level is assessed according to Modified Bromage score.

Al the patients will be monitored during the period of block and peri-operative period
employing multi-channel monitor which displays heart rate, systolic and diastolic blood
pressure, mean arterial pressure, ECG, SPO2.

Sedation is assessed by a Modified Ramsay Sedation score.

In the post- operative period patients are monitored for post operative pain by VAS scale
initially every 1 hour for 2 hours, then every 2 hours for next 8 hours then every 4hr till
24hr which will have been explained to the patient’s pre operatively. When the VAS is
>5 patient is given rescue analgesia of 75mg of diclofenac intramuscularly.
DEFINITIONS:

Onset of sensory blockade: is defined as the time taken from the completion of the
injection of the drug till the patient does not feel the pin prick at T10 level.

Time taken for maximum sensory blockade: is defined as time from the completion of the
injection of the drug to the maximum sensory block attained.

Onset of motor blockade: Onset time of motor blockade is defined as the time required
from completion of injection of the drug till the patient develops Bromage -1.

Quality of motor blockade will be assessed by Modified Bromage scale6

0 = No motor paralysis

I = Unable to raise extended leg

2 = Unable to flex knee

3 = Unable to flex ankle

4 = Unable to move toes.
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
Time taken for maximum motor blockade: is defined as the time taken from the
completion of the injection of intrathecal bupivacaine to the maximum motor blockade
attained.

Duration of motor blockade: is defined as the time taken from the time of injection of the
drug till the patient attains complete motor recovery.

Duration of two segment sensory regression: is defined as the time taken from the
maximum level of sensory block attained till the sensation has regressed by 2 segments.

Duration of analgesia: is defined as the time taken from the completion of the injection of
the drug till the patient requests for rescue analgesic in the post operative period.

Duration of sensory blockade: is defined as the time taken from the time of injection of the
drug till the patient feels the sensation at S1 dermatome.

Postoperative Sedation scoring was done as per Ramsay sedation scale.
RAMSAY SEDATION SCORING7
Score
Description
Response
1
Awake
Anxious or restless or both
2
Awake
Cooperative, oriented and tranquil
3
Awake
Responding to commands only
4
Asleep
Brisk response to stimulus
5
Asleep
Sluggish response to stimulus
6
Asleep
No response to stimulus
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
Hypotension: is defined as reduction in systolic blood pressure(SBP) of more than 30%
below the base line or fall in SBP less than 90mm of Hg and it will be treated with increased
rate on intravenous(IV) fluids and if needed injection mephentermine 6mg IV in incremental
dose.

Bradycardia: is defined as heart rate of less than 60 beats per minute and will be treated with
injection Atropine 0.6mg IV.

Adverse effects: like nausea, vomiting, shivering, itching, pruritus, sedation, respiratory
depression and hypotension are recorded.
STATISTICAL METHODS
Sample size is calculated by purposive sampling method using the formula S= z2pq/d2 where z
is constant, p is prevalence, q is (1-p) and d is significance level.
In this study, considering hospital prevalence of 4% and confidence interval of 95%, z will be
1.96 and d will be 0.05.
The result of the study will be analyzed by following statistical methods, contingency coefficient analysis, ‘t’ test from independent samples, ‘t’ test from paired samples and repeated
measure ANOVA using SPSS for windows (version 16.0).
7.3 Does the study require any investigation / intervention to be conducted on Patients /
human / animals? If so, describe briefly.
- NO7.4 Has ethical clearance been obtained from your institution in case of 7.3?
-YES- Obtained (copy enclosed)
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8. LIST OF REFERENCES:
1. Gupta R, Verma R, Bogra .J, Kohli M, Raman R, and Kushwaha1 J. A Comparative Study of
Intrathecal Dexmedetomidine and Fentanyl as Adjuvant. Journal of Anesthesiol Clinical
Pharmacolol. 2011 jul-sep; 27930; 339-343.
2. Al-Ghanem S M, Massad I M, Al-Mustafa M M, Al-Zaben K, Qudaisat I Y, Qatawneh A M et
al. Effect of Adding Dexmedetomidine versus Fentanyl to Intrathecal Bupivacaine on Spinal
Block Characteristics in Gynecological Procedure: A Double Blind Controlled Study. American
Journal of Applied Science 6(5): 882-887, 2009.
3. Gupta R, Bogra J, Verma R, Kohli M, Kushwaha1 J K, Kumar S. Dexmedetomidine As An
Intrathecal Adjuvant For Postoperative Analgesia. Indian Journal of Anaesthesia | Vol. 55| Issue
4 | Jul-Aug 2011
4. Mahendru V, Tewari M, Katyal S, Grewal A, Singh M R, Katyal R. A Comparison of
Intrathecal Dexmedetomidine, Clonidine, and Fentanyl as Adjuvants to Hyperbaric Bupivacaine
for Lower Limb Surgery: A Double Blind Controlled Study. Journal of Anesthesiology Clinical
Pharmacology | October-December 2013 | Vol 29 | Issue 4
5. Al-Mustafa MM, Abu-Halaweb SA, Aloweidi AS, Mursbidi MM, Ammar BA, Awawad ZM,
et al. effect of Dexmedetomidine added to spinal bupivacaine for urological procedures. Saudi
Med J 2009; 30(3):365-70.
6. Finucane BT, Sandier AN, McKenna J, Reid D, Friedlander M, Muzyka D et al. A doubleblind comparison of ropivacaine 0.5%, 0.75%, 1.0% and bupivacaine 0.5%, injected epidurally,
in patients undergoing abdominal hysterectomy. CAN .I ANAESTH 1996 / 43:5 I pp442-9.
7. Akhavanakbari G, Entezariasl M, Isazadehfar K, Mirzarahimi T. The effects of oral pregabalin
on post-operative pain of lower limb orthopedic surgery: A double-blind, placebo-controlled
trial.
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