“A COMPARITIVE STUDY OF PLAIN BUPIVACAINE AND COMBINATION

OF BUPIVACAINE WITH ONDENSETRON AS AN ADJUVANT IN

SUPRACLAVICULAR BRACHIALPLEXUS BLOCK”

Dissertation Submitted for

M.D. DEGREE (ANAESTHESIOLOGY)
Examination of
Dr KALOJI NARAYANA RAO UNIVERSITY OF HEALTH SCIENCES,
Warangal, Telangana
to be held in month of April 2019

By
Dr. M AJAY KUMAR MBBS
(Registration No. 16102001031D)

Under the guidance of

Dr. MSRC MURTHY DA, DNB.
Professor
Osmania Medical College

UPGRADED DEPARTMENT OF ANAESTHESIOLOGY& CRITICAL CARE

OSMANIA MEDICAL COLLEGE
HYDERABAD
 CERTIFICATE BY THE GUIDE

This is to certify that this dissertation entitled “A COMPARATIVE STUDY OF PLAIN

BUPIVACAINE AND COMBINATION OF BUPIVACAINE WITH ONDANSETRON

AS AN ADJUVANT IN SUPRACLAVICULAR BRANCHIAL PLEXUS BLOCK " is

a bonafide research work done by Dr. M AJAY KUMAR in partial fulfilment of the

requirement for the degree of M.D.(Anaesthesiology).

DATE : / / 2018

PLACE : HYDERABAD

Dr. MSRC MURTHY DA, DNB

Professor,
Upgraded Dept of Anaesthesiology & Critical
Care,
Osmania Medical College,
Hyderabad.
 ENDORSEMENT BY THE HEAD OF DEPARTMENT AND THE
PRINCIPAL OF THE INSTITUTION

This is to certify that this dissertation entitled “A COMPARATIVE

STUDY OF PLAIN BUPIVACAINE AND COMBINATION OF BUPIVACAINE

WITH ONDANSETRON AS AN ADJUVANT IN SUPRACLAVICULAR

BRANCHIAL PLEXUS BLOCK " is a bonafide research work done by Dr. M AJAY

KUMAR under the guidance of DR MSRC MURTHY DA DNB, Professor,

Department of Anaesthesiology & critical care, Osmania Medical College,

Hyderabad.

PROFESSOR AND HOD, PRINCIPAL,

Upgraded Department Of Anaesthesia, Osmania Medical College,
Osmania Medical College, Hyderabadhyderabad.
 DECLARATION BY THE CANDIDATE

I, hereby declare that this dissertation/thesis entitled “A COMPARATIVE STUDY

OF PLAIN BUPIVACAINE AND COMBINATION OF BUPIVACAINE WITH

ONDANSETRON AS AN ADJUVANT IN SUPRACLAVICULAR BRANCHIAL

PLEXUS BLOCK " is a bonafide and genuine research work carried out by me

under the guidance of Dr. MSRC MURTHY DA,DNB. Professor, Department of

Anaesthesiology & critical care, Osmania Medical College, Hyderabad.

DATE : / / 2018

PLACE : HYDERABAD (Dr. M AJAY KUMAR)

 COPYRIGHT

I hereby declare that the Dr Kaloji Narayana Rao University of Health sciences,

Hyderabad shall have the rights to preserve, use and disseminate this dissertation /

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

DATE : / / 2018

PLACE : HYDERABAD Dr. M AJAY KUMAR

 ACKNOWLEDGEMENTS

I wish to express my sincere thanks to Dr. MSRC MURTHY DA DNB, Professor,

Upgraded Department of Anaesthesiology and Critical Care, Osmania Medical

College / Modern government maternity hospital, petlaburz, Hyderabad under

whose guidance this study was undertaken. He has been very inspiring and

encouraging during the course of my study. I feel privileged to have worked under

him.

I thank all my Professors, Associate Professors, Assistant Professors and fellow

post-graduates of the department of Anaesthesiology for the cooperation extended

to me during the period of my study.

Last, but by no means least, I thank all the patients who participated in the present

study, without whose help and cooperation, the study would not have been

completed.

It is most appropriate that I begin by expressing my utmost gratitude to my FAMILY

without whose encouragement and support my dream to purse MD would have

remained only a dream. I am forever grateful and indebted to them.

Dr. M AJAY KUMAR

 LIST OF ABBREVIATIONS USED

ASA American Society of Anaesthesiologists

BP Blood pressure

BT Bleeding time

CNS Central nervous system

CT Clotting time

DBP Diastolic blood pressure

ECG Electrocardiogram

Hb Haemoglobin

PR Pulse rate

IV Intravenous

Kg Kilogram

µg Micro gram

Mg Milli gram

Min Minutes

Ml Milli litre

NS Statistically not significant

P value Probability

PKa Dissociation constant

PNS Peripheral nerve stimulator

RS Respiratory system

SBP Systolic blood pressure

SD Standard deviation

SPO2 Hemoglobin saturation

SS Statistically significant
ABSTRACT

Background and objectives: Adjuncts to local anaesthetics for brachial plexus

block may enhance the quality and duration of analgesia. Ondansetron, highly

selective and potent antagonist of 5-hydroxytryptamine subtype 3 (5-HT3)

receptors is known to produce antiemetic and in addition above effect it blocks

sodium channel and has antinociceptive property to enhance the effect of local

anaesthetic when given in peripheral nerve blocks. The purpose of this study was to

assess the effect of Ondansetron added to brachial plexus block by supraclavicular

approach.

Methods: A prospective, randomized, single blinded study was conducted on

60ASA Grade I or II adult patients undergoing upper limb surgeries under

supraclavicular brachial plexus block. Patients were randomly divided into two

groups. Patients in Group A (n = 30) were administered 30mL of 0.5% Bupivacaine

and Group B (n = 30) were given 30mL of 0.5% Bupivacaine with Ondansetron

8mg/kg. The onset time and duration of sensory and motor blockade were recorded.

Haemodynamic variables (i.e., heart rate, blood pressure and oxygen saturation),

sedation scores and rescue analgesic requirements were recorded for 24 hr

postoperatively.

Results: The onset of sensory and motor block was significantly faster in Group B

compared to Group A (p< 0.05). The duration of sensory and motor block was

significantly longer in Group B compared to Group A (p < 0.05). Rescue analgesic

requirements were significantly less in Group B compared to Group A (p< 0.05).

Haemodynamics and sedation scores did not differ between the two groups in the

post-operative period.

Conclusion: Ondansetron (8mg) in combination with 30mL of Bupivacaine (0.5%)

hastened onset of sensory and motor block, and improved postoperative analgesia

when used in brachial plexus block, without producing any adverse events.

Keywords: Bupivacaine, Ondansetron, Supraclavicular brachial plexus block

 TABLE OF CONTENTS

SL.NO. TOPIC PAGE NO.

1. INTRODUCTION 1

2. AIM AND OBJECTIVES 3

3. HISTORY OF BRACHIAL PLEXUS BLOCK 4

4. REVIEW OF LITERATURE 7

5 ANATOMY OF BRACHIAL PLEXUS 14

6. PHARMACOLOGY OF ONDANSETRON 22

7. PHARMACOLOGY OF BUPIVACAINE 27

8. PATIENTS AND METHODOLOGY 36

9. OBSERVATIONS AND RESULTS 43

10. DISCUSSION 55

11 CONCLUSIONS 66

12 SUMMARY 67

13. REFERENCES 69

14 ANNEXURES

1. PROFORMA 76

2. CONSENT FORM 79

3. ETHICAL CLEARANCE CERTIFICATE 83

4. KEY TO MASTER CHART 84

5. MASTER CHART
 LIST OF TABLES

Sl. No. Tables Page No.

A Dosage and concentration of Bupivacaine in various blocks 30

1 Age Distribution of Study groups 43

2. Weight Distribution of Study groups 44

3. Duration of Surgery of study groups 45

4 Time for onset of sensory block (min) 46

5 Time for onset of motor block (min) 47

6 Duration of sensory block (hours) 48

7 Duration of motor block (hours) 49

8 Number of rescue analgesics in post-op 24 hours 50

9 Pulse Rate (beats / min) 51

10 Systolic blood pressure (mm of Hg) 52

11 Diastolic blood pressure (mm of Hg) 53

12 Oxygen saturation (%) 54

 LIST OF GRAPHS

Sl. No. Graphs Pg. No.

1 Age Distribution of Study groups 43

2. Weight Distribution of Study groups 44

3. Duration of Surgery of Study groups 45

2 Onset of sensory block 46

3 Onset of motor block 47

4 Duration of sensory block 48

5 Duration of motor block 49

6 Number of rescue analgesics needed 50

7 Pulse rate 51

8 Systolic blood pressure 52

9 Diastolic blood pressure (mm of Hg) 53

10 Oxygen saturation (%) 54

 LIST OF FIGURES

Sl. No. Figures Pg. No.

1 Formation and the branches of the brachial plexus 15

2 Sheath around the brachial plexus 21

3 Chemical Structure of ondansetron 22

4 Sterile tray containing drugs and equipments 41

5 Drugs used for the study 41

6 Needle entry 1 cm cephalo-posterior to subclavian

artery Pulsation 42

7 Test drug injected after negative aspiration for blood 42

 INTRODUCTION

Brachial plexus block provides a useful alternative to general

anaesthesia for upper limb surgeries. They achieve near-ideal operating

conditions by producing complete muscular relaxation, maintaining stable

intra-operative haemodynamics and the associated sympathetic block. The

sympathetic block decreases postoperative pain, vasospasm and oedema.

Of various local anaesthetics, Bupivacaine is used most frequently, as it

has a long duration of action varying from 3 to 8 hours. However there are

many limiting factors like delayed onset, patchy or incomplete analgesia,

sometimes short duration etc.

Various drugs like Neostigmine, Opioids, Hyaluronidase, and Clonidine

etc. (1-4) have been added to local anaesthetics in order to modify the block in

terms of quick onset, good quality, prolonged duration and post-operative

analgesia. But these are not without adverse systemic effects or of doubtful

efficacy.

Ondansetron, a highly selective and potent antagonist of 5-

hydroxytryptamine subtype 3 (5-HT3) receptors is known to produce antiemetic

and in addition above effect it blocks sodium channel and has anti nociceptive

property to enhance the effect of local anaesthetic when given in peripheral

nerve blocks. Ondansetron produces this effect by its antagonistic action on

sodium channel. Peripheral (5-HT3) receptors are involved in pathway of

nociception. These receptors bind to opoids receptors and agonist activity.

1
 So the present study is being undertaken in a randomized single

blinded manner to evaluate the onset time and analgesic efficacy of

Ondansetron- Bupivacaine combination compared to plain Bupivacaine (0.5%)

for brachial plexus block by supraclavicular approach.

2
 AIMS AND OBJECTIVES

The present study is undertaken to compare the effectiveness of adding

Ondansetron (8mg) to Bupivacaine (0.5%) to supraclavicular technique of

brachial plexus block for upper limb surgeries with plain Bupivacaine (0.5%).

Following parameters are studied:

1) Onset of sensory and motor blockade.

2) Duration of sensory and motor blockade.

3) Haemodynamic variables (HR, BP, O2 saturation).

4) Number of rescue analgesics given in post-operative 24 hours.

3
 HISTORY OF BRACHIAL PLEXUS BLOCK

The first brachial plexus block was performed by William Stewart Halsted

in 1885, less than a year after Koller demonstrated the anaesthetic properties of

cocaine in Ophthalmologic surgeries.

Halsted exposed the roots surgically under local infiltration and injected

each of them with a small amount of dilute Cocaine (0.1%) interneurally under

direct vision. Only about 0.5 ml of local anaesthetic was required to produce

complete anaesthesia.

In 1897, Crile used a similar technique in which the plexus was exposed

under local anaesthesia. Just behind the sternocleidomastoid muscle, cocaine

was injected into the nerve trunks under direct vision which was done as a

therapeutic measure in a 12 year old boy who developed tetanic spasms

following a compound fracture of the forearm. Later this technique was used to

provide anaesthesia for upper arm surgeries.

EVOLUTION OF SUPRACLAVICULAR BRACHIALPLEXUS BLOCK:

In 1911-1912, Kulenkampff described the first percutaneous

supraclavicular approach. He pointed out that, above the clavicle the plexus lies

under the skin as it passes over the first rib and accessible to a percutaneous

technique. The midpoint of the clavicle and subclavian artery provided a

constant landmark, most frequently at the point where external jugular vein

intersects the clavicle. He performed his first attempt on himself and used 5 ml

of Novocaine, later he increased it to 10 ml and was able to obtain complete

anaesthesia. Direction of the needle was backwards, inwards and downwards

4
and the length of the needle was 4 cm. He emphasized that purpose of the

technique was not to hit the rib but to find the trunks by eliciting paraesthesia.

He said that the first rib just prevented pleural penetration.

In 1926, Livingston, carried out Kulenkampffs technique without the

production of paraesthesia as soon as the deep cervical fascia had been

penetrated. 30 ml of 2% procaine was injected. He wrote that the plexus and the

artery are separated from the surrounding structures by a fascial investment.

In 1940, Patrick chose to lay down a “wall of anaesthetic” through which

the plexus must pass in its course over the first rib, where 60-70 ml of solution

was being injected during 5-6 insertions. This technique became the “standard

technique” of supraclavicular block, subsequently referred to by many as the

“Classical Supraclavicular technique”.

In 1942 Knight modified Patrick‟s technique by making the three injections

through three separate needle insertion, parallel to one another. For the first

time he utilized a directly caudal direction of needle insertion.

In 1944, Murphy used a single injection technique and used lateral border

of anterior scalene muscle as the landmark and direction of needle insertion

caudal as with Knight‟s technique, not medial or dorsal, as with most other

techniques.

In 1949, Bonica and Moore utilized Kulenkampff‟s and Patrick‟s

techniques and developed a technique where it begins with utilizing the classical

landmarks and direction of needle insertion and demands a definite

paraesthesia prior to first injection. Then continue as Patrick‟s technique and lay

5
down a wall of anaesthetic solution by “walking the rib” and make multiple

injections during each withdrawal of the needle. This was used over subsequent

twenty years.

In 1958, Lookman fully realised the potential of the sheath, who like

Livingston realised on the fascial investment of the plexus. He carefully

dissected the plexus and said that plexus lies in a closed compartment. He said

this space lies between the anterior and middle scalene muscles and is

pyramidal in shape, with its apex pointing upwards and medially towards the exit

of the fourth cervical nerve. He did not verify the needle‟s proper placement

within the space before injection. He admitted the tendency for the point of the

needle to pass too posteriorly and hence to come to be within the substance of

(or even behind) the middle scalene muscle.

Fortin and Tremblay advocated the use of a short needle, which was long

enough to reach the plexus but short to reach the lung, in an attempt to

minimize the threat of pneumothorax.

In 1964, Winnie after numerous anatomical dissections showed that the

relation of the plexus and the subclavian artery to the midpoint of the first rib is

not constant. He showed that there is a constant relationship between the

anterior and middle scalene muscles, the plexus and the first rib. The plexus

between the two scalene muscles always lie on the first rib. He inserted needle

between the two muscles, in the direction of the space between them. Once a

paraesthesia is obtained, a single injection is made into the space.

6
 REVIEW OF LITERATURE

In a prospective double blind randomised study by Dr vasundha

jadhav, Dr Ranjeetsinha, Dr B.M. Diwanmal et al studies(5). Fifty adult

patients of either sex, aged 18-60yrs, ASA grade 1 & 2 scheduled for various

upper limb surgeries were divided into two groups to receive either Bupivacaine

+ Normal saline mixture (group A; n = 25) or Bupivacaine + Ondansetron (8mg)

mixture (group B; n = 25) in supraclavicular block . onset of sensory block,

onset of motor block, duration of sensory block, duration of motor block,

assessment of pain using numerically rating pain scale were recorded in both

groups at regular time intervals. A significantly higher numerically rating pain

scale reading (P < 0.05) was seen in group A. Mean duration of sensory block

in group A is 502.24± 52.6 minutes whereas mean duration of sensory block in

group B is 805.04±175.75 then after which required supplemented analgesia.

Time to regression of sensory analgesia was longer in group B (P< 0.05).

Duration of motor block & sensory block were prolonged with the addition of

Ondansetron to Bupivacaine. The authors concluded that addition of

Ondansetron to Bupivacaine in supraclavicular brachial plexus block reduced

intra operative and post operative analgesic use till 24 hrs, decreased onset of

motor block, and increased duration of sensory block without causing

significant adverse side effects.

A prospective randomised double blind study by Azim Honarmand et

al(6) was conducted to evaluate effect of adding 8mg ondansetron to lidocaine

for Biers block on post operative pain. Ninety patients ASA grade 1 & 2, aged

18-65 years old, scheduled for elective hand or fore arm surgeries were

7
randomly allocated to one of three groups. IVRA administered in three groups.

In the first group IVRA begins in hand injury with 3mg/kg 2% lidocaine diluted

with saline(group L n= 30) to a total dose of 40 ml and in other hand with 3ml

normal saline intravenously. In the second group IVRA begins in hand injury

with 8mg ondansetron plus 3mg/kg 2% lidocaine diluted with saline to a total

dose of 40 ml(group LO n=30) and in other hand with 3ml normal saline

intravenously. In third group, IVRA begins in hand injury with 3mg/kg 2%

lidocaine diluted with saline (group IO n=30) to a total dose of 40 ml and in the

other hand with 8mg ondansetron in volume of 3ml intravenously. The results

of this study showed that addition of ondansetron 8 mg to lidocaine for IVRA

significantly improved the onset time and duration of sensory and motor block,

decreased tourniquet pain, decreased intra-operative and post-operative

analgesic use till 24 h compared with Group L and Group IO without causing

important side effects. The quality of anesthesia was also significantly better in

Group LO compared with Group L and GroupIO. The authors concluded that

adding ondansetron 8 mg to lidocaine for IVRA reduced intraoperative and

post-operative analgesic use till 24 h, decreased onset of sensory and motor

block, increased duration of sensory and motor block, decreased tourniquet

induced pain, prolonged the rescue time for analgesic use, and finally improved

the patients' and surgeons' satisfaction without causing significant adverse

effects.

In a randomised double blinded study by Omid Azimaraghi,

Yasaman Aghajani, Maziar Molaghadimi, Malihe Khosravi, Kobra E slami,

Fatemeh Ghadimi Ali Movafeg(7) Etomidate causes pain when injected

intravenously if pre-treatment by ondansetron reduces the pain. 20 patients of

8
both sexes aged between 18 and 50 years of American Society of

Anaesthesiologists (ASA) physical status class I or II, who were candidates for

various elective surgical procedures requiring more than one intravenous

access lines were enrolled in the study. In the operating room, all patients were

monitored with an electrocardiogram (ECG), non-invasive blood pressure and

pulse oximetry. Two 22 gauge cannulas were inserted into the veins on the

dorsum of both hands. One hundred millimeters of saline was administered

over 10 min from each of the cannulas. Using an elastic band as a tourniquet,

venous drainage of both hands was occluded midarm. Eight milligrams (2 ml)

of ondansetron was administered from one hand and 2 ml of 0.9% saline from

the other hand at the same time. The elastic band was removed after 1 min and

2 mg (1 ml) of etomidate was administered at the same rate simultaneously at

both hands. The patients were asked to give a score from 0 to 10 (0 = no pain

and 10 = most severe pain) to each hand. Ondansetron has been shown to

bind to opioid µ-receptors in humans and possess agonist activity. Five

hydroxytryptamine receptors are involved in the nociceptive pathways. Five

hydroxytryptamine receptors play a pronociceptive role and mediate

descending excitatory controls that allow spinal neurons to fully code peripheral

stimuli. Ondansetron decreases chronic benign neuropathic pain, this effect

seems to be produced by an action on the neurons in the spinal cord that code

and transmit peripheral nociceptive stimuli. The authors concluded ondansetron

was equally effective in preventing pain of etomidate, propofol injection, holding

the analgesic properties of ondansetron, and was superior due to prevention of

post operative nausea and vomiting.

9
 A prospective randomised double blind study was conducted by Nahla

S. El Bahnasawy et al.(8) The effect of addition of different doses of

ondansetron to lidocaine as a component of intravenous regional anesthesia.

Ninety nine ASA physical status I or II patients, scheduled for short-procedure

surgery of the hand or the forearm. Patients were randomly assigned to one of

the three groups for administration of either lidocaine 0.5% (group C, n = 33),

lidocaine 0.5% plus 4 mg ondansetron (group O1, n = 33) or lidocaine 0.5%

plus 8 mg ondansetron (group O2, n = 33) for IVRA. Onset times of sensory as

well as motor block were significantly shorter in both O1 and O2 groups

compared with group C. Sensory and motor block recovery times were

significantly longer in both O1 and O2 groups compared with group C (P <

0.05), with an insignificant difference between O1 and O2 groups. The authors

concluded that Addition of ondansetron 4 or 8 mg to lidocaine provided

effective anaesthesia, prolonged postoperative analgesia, and decreased

postoperative analgesic consumption. Interdose comparison showed that 8 mg

ondansetron was significantly better than 4 mg without significant adverse

effects.

A Study was conducted by FARRUKH AYUB, INAM UL H AQ,

MUHAMMAD ASIM GHAURI(9) to compare the effects of intravenous

ondansetron and intravenous lidocaine on reduction of Propofol induced

vascular pain. Total 700 patients undergoing elective surgeries, having age

18–55 years of both sexes and having ASA Grade I & II were selected for this

study. Group A received Injection Lidocaine plain 2% (2ml) while group B

received Ondansetron 4 mg (2 ml) at the time of induction of anesthesia. In

group-A, 233 (66.6%) patients and in group-B 239 (68.3%) patients were males

10
while 117 patients (33.4%) in group-A and 111 patients (31.7%) in group-B

were females. Pain reduction was observed in 224 patients (64.0%) of group-A

while in group-B pain reduction was reported by 266 patients (76.0%). In

animal experiments, Ondansetron administered intrathecally reduces

nociceptive responses of dorsal horn neurons. In a experiment conducted in

rats it is found that Ondansetron is approximately 15 times more potent as local

anaesthetic than lignocaine. Ondansetron is found to have µ opioid agonist

action. So Ondansetron may be potentially used to decrease pain produced by

propofol.

A study was conducted by Dr. Jaafar Hameed Jaafar Mahboba#,

M.B.Ch.B, F.I.C.M & IC and Dr. Suadid Faris Saleh Aatallah^ M.B.CH.B(10) The

Analgesic Effect of Ondansetron when Added to Lidocaine for Intravenous

Regional Anesthesia Thirty patients were enrolled in this study and randomly

divided into two groups, Group A (n=15)received IVRA lidocaine 3 mg/kg 2%

diluted with isotonic saline to 0.5% concentration, Group B (n=15) received

lidocaine 3mg/kg 2% plus Ondansetron diluted with isotonic saline to 0.5%

concentration ,hemodynamic variables and VAS were recorded before and

after tourniquet inflation, tourniquet pain, post-operative pain and first analgesic

requirement time till 6 hours postoperatively were recordedThere was

significant decrease of tourniquet pain and postoperative pain in Group B and

relatively increase in mean time of first post-operative needing to analgesia by

1.6 hours in Group B relative to Group A. Conclusions: Adding 8 mg of

Ondansetron to lidocaine in IVRAdecrease the tourniquet pain, post-operative

pain, mean time for need of post-operative analgesia.

11
A study was conducted by Sushil P Ambesh et al(11). Ondansetron

Pretreatment to Alleviate Pain on Propofol Injection randomized, controlled,

double-blinded design to study the effect of ondansetron (OND) pretreatment

on the pain produced by the IV injection of propofol. Eighty patients were

randomly assigned to one of two groups: Group I received 2 mL of IV 0.9%

saline pretreatment, and Group II received OND (4 mg in 2 mg/mL solution)

pretreatment in the dorsum of the hand, followed by propofol 1 min later. Pain

was reduced significantly in the OND group (P<0.05). Approximately one third

of the patients in each group had myoclonic movements or skin rashes in the

limb that received propofol. We conclude that the OND pretreatment may be

used to reduce the incidence of pain on injection of propofol and to prevent

postoperative nausea and vomiting. Implications: In a double-blinded,

controlled study, IV ondansetron (4 mg) pretreatment was used to alleviate pain

on injection of propofol. Ondansetron was successful in relieving pain without

any adverse effect in a significant number of patients.

A study was conducted by Gangur basappa sumalatha et al(12) to

evaluate attenuation of propofol-induced pain by lignocaine, ondansetron, and

ramosetron. Pre-treatment with IV ramosetron and lignocaine significantly

reduced the propofol-induced pain when compared to ondansetron

A study conducted by Qixiong He, et al(13) to evaluate the Effect of 5-

Hydroxytryptamine Receptor Antagonist in Preventing Pain/Limb Shrinkage

Reaction Associated with Rocuronium Injection. In conclusion, 5-HT receptor

antagonist may be efective in preventing and reducing the occurrence of the

pain/limb shrinkage reaction associated with rocuronium injection. This study

shows that ondanseton has analgesic property

12
 A study was done by W. Hongzhu, et al.(14) Effect of ondansetron

compound lidocaine to prevent the pain of the rocuronium injection, showed

that ondansetron reduces some amount of pain produced by rocuronium.

13
 ANATOMY OF BRACHIAL PLEXUS

Knowledge of formation of brachial plexus and its ultimate cutaneous

and muscular distribution is absolutely essential to the intelligent and effective

use of brachial plexus anaesthesia for upper limb surgeries. A good familiarity

with the vascular, muscular and fascial relationships of the plexus is equally

essential to the mastery of various techniques, for it is these perineural

structures which serve as the landmark by which needle may accurately locate

the plexus percutaneously.

In its course from intervertebral foramina to the upper arm, the fibres

are composed consecutively of roots, trunks, divisions, cords and terminal

nerves.

FORMATION OF BRACHIAL PLEXUS

Brachial plexus is formed by the union of anterior primary rami of lower four

cervical nerves (C5, 6,7,8) and first thoracic nerve (T1) with frequent contributions

from C4 or T2.

When contribution from C4 is large, the plexus appears more cephalad

and is termed “prefixed”. When contribution from T2 is large and from C4 is

lacking, the plexus appears more caudad and is termed “postfixed”. Usually

prefixed or post fixed positions are associated with the presence either of a

cervical rib or of an anomalous first rib.

ROOTS

Represent the anterior primary divisions of lower four cervical and first

14
thoracic nerves. They emerge from the intervertebral foramina and fuse above

the first rib to form the trunks.

CORDS DIVISIONS TRUNK ROOTS

S

Fig. 1: Formation and the branches of the brachial plexus

TRUNKS

The roots combine above the first rib to form the three trunks of the plexus. C5

and C6 unite at the lateral border of the scalenus medius and form the “Upper

trunk”, C8 and T1 unite behind the scalenus anterior to form “lower trunk” and

C7 continues as a sole contributor to the “middle trunk”.

15
DIVISIONS

As the trunks pass over the first rib and under the clavicle, each one of

them divides into anterior and posterior divisions.

CORDS

The fibres, as they emerge from under the clavicle, recombine to form

three cords. The “lateral cord” is formed by anterior divisions of upper and

middle trunks, lateral to the axillary artery. The anterior division of lower trunk

descend medial to the axillary artery forming the “medial cord”. The posterior

divisions of all three trunks unite to form the “posterior cord”, at first above and

then behind the axillary artery.

The medial and lateral cords give rise to nerves that supply the flexor

surface of upper extremity, while nerves arising from the posterior cord supply

the extensor surface.

MAJOR TERMINAL NERVES

Each of these cords gives off a branch that contributes to or become one

of the major nerves to the upper extremity and then terminates as a major

nerve. The lateral and medial cords give off lateral and medial heads of the

medial nerve and continue as major terminal nerves, the lateral cord

terminating as musculocutaneous nerve and medial cord as ulnar nerve.

Posterior cord gives off, axillary nerve as its major branch and then continues

as the radial nerve.

16
DISTRIBUTION OF BRACHIAL PLEXUS

These are divided into those that arise above the clavicle – the supraclavicular

branches and those that arise below it, the infraclavicular branches.

Supraclavicular branches

From roots:

1. Nerves to scaleni and longus colli – C5,6,7,8

2. Branch to phrenic nerve – C5

3. Dorsal scapular nerve – C5

4. Long thoracic nerve – C5,6,(7)

From trunks

1. Nerve to subclavius – C5,6

2. Suprascapular nerve – C5,6

Infraclavicular branches

They branch from cords but their fibres may be tracked back to spinal nerves.

Lateral cord

1. Lateral pectoral nerve – C5,6,7

2. Musculocutaneous nerve – C5, 6,7

3. Lateral root of median nerve – C5,6,7

Medial cord

1. Medial pectoral nerve – C8, T1

2. Medial cutaneous nerve of forearm – C8, T1

3. Ulnar nerve – C7,8 T1

4. Medial root of median nerve – C8, T1

5. Medial cutaneous nerve of arm – C8, T1

17
Posterior cord

1. Upper subscapular nerve – C5, 6

2. Thoracodorsal nerve – C 6, 7, 8

3. Lower subscapular nerve – C5, 6

4. Axillary nerve – C5, 6

5. Radial nerve – C5, 6, 7, 8, T1

SYMPATHETIC CONTRIBUTION TO BRACHIAL PLEXUS

The segmental preganglionic sympathetic contributions are variable, but

generally extend more caudal. The highest contribution is usually T 2 with T1

contributing only rarely, while lowest may be as far as T 8, T9 or even T10. The

post ganglionic contributions are from gray rami communicans from the

sympathetic chain.

RELATIONS OF BRACHIAL PLEXUS

In its passage from the cervical transverse processes to the first rib, the plexus

is "sandwiched" between the anterior and middle scalene muscles and

invested in the fascia of those two muscles.

The subclavian artery crosses the first rib immediately in front of the

trunks in the interfascial compartment. Subclavian vein is separated from the

artery by the scalenus anterior. The fascia covering the muscles is derived

from the prevertebral fascia, which splits to invest these muscles and rejoins

again at their lateral margins to form an enclosed space, the interscalene

space. As the plexus cross the first rib, the three trunks are 'stacked' one on

top of the other vertically. Not infrequently, the inferior trunk gets trapped

18
behind and even beneath the subclavian artery above the rib, during

embryologic development.

This may be reason why local anaesthetics injected via the interscalene

technique sometimes fail to provide anaesthesia in the distribution of the ulnar

nerve, which may be buried deep within inferior trunk behind or beneath the

subclavian artery. After crossing the outer border of first rib, the trunks split to

form 2 divisions and subclavian artery becomes the axillary artery. In the axilla

the lateral and posterior cords are lateral to the first part of the axillary artery,

the medial cord being behind it. Around the second part of the artery, they are

related according to their names. In the lower axilla, cords divide into nerves

for the upper limb. In passing over the first rib under the clavicle, the

subclavian vein also becomes the axillary vein and its relationship with the

neurovascular bundle changes. Above the first rib the subclavian vein does

not lie within the neurovascular bundle, it is separated by the insertion of

scalenus anterior. As it passes over the first rib, becoming the axillary vein it

joins the neurovascular bundle so that parts of the plexus are sandwiched

between artery and vein. As all the three enter the axilla, they invaginate the

perivertebral fascia at the lateral margins of the anterior and medial scalene

muscles, carrying this fascial investment of the neurovascular bundle into the

axilla as the axillary fascia. In its course through the axilla and upper arm the

fascia of the surrounding muscles contribute to the axillary sheath, making it

thick and tough, providing the 'fascial click' to the anaesthetic while entering

the sheath. It is important to note that major terminal nerves leave the sheath

high in the axilla under pectoralis minor muscle.

19
 The musculocutaneous nerve enters the substance of coracobrachialis

and continues down within this muscle. The axillary nerve also leaves the

sheath immediately after arising from the posterior cord. The

interocostobrachial nerve travels parallel to but outside the axillary sheath and

medial cutaneous nerve of the arm runs similarly but occasionally it may

remain within the sheath.

THE BRACHIAL PLEXUS SHEATH

Volume of the sheath: 42ml.

Shape of the sheath: Cylindrical to conical – Wide proximally and narrow

distally.

Length: 8-10cms long.

- The connective tissue of the prevertebral fascia envelops the brachial

plexus as well as the subclavian and axillary artery in a neurovascular

“sheath”.

- The tissue is densely organized as it leaves the deep cervical fascia

proximally, but becomes more loosely arranged distally. The sheath blends

with the fascia of the biceps and brachialis muscle distally.

- Anatomic dissection, histologic examination and CT scanning after injection

of radio contrast into the sheath demonstrate the existence of connective

tissue septae which extend inward from the fascia surrounding the sheath.

The thin velamentous connective tissue septae frequently adhere to nerves

and vessels leaving no free space between layers and compartmentalizing

the components of the sheath.

20
Anaesthetic implications

Because of these connective tissue septae, anaesthesia might be complete

and rapid in onset in some nerves, but delayed and incomplete or completely

absent in others. The incidence of partial block is an exception rather than the

rule, as local anaesthetics can percolate through them.

Fig. 2: Sheath around the brachial plexus

21
 PHARMACOLOGY OF ONDANSETRON

ONDANSETRON (15, 16, 17,18,19)

Ondansetron is a highly selective and potent antagonist of 5-

hydroxytryptamine subtype 3(5-HT3) receptors in the brain. 5-HT3 receptors

occur in high density in the area postrema and the nucleus tractus solitarius,

equating with the chemoreceptor trigger zone. It also acts peripherally in the

gastrointestinal tract in addition to the site of action.

It is mainly used in the treatment of nausea and vomiting related to cancer

chemotherapy and radiotherapy, postoperative nausea and vomiting.

Structure

Pharmacokinetics

Ondansetron can be administered in oral, intramuscular and intravenous

routes. The tablets contain 4mg and 8mg of ondansetron base as the

hydrochloride dehydrate. Oral bioavailability is about 60% with effective blood

levels appearing 30-60 minutes after administration. Intravenous preparation is

22
an isotonic aqueous solution containing ondansetron hydrochloride dehydrates

2 mg/ml buffered to pH 3.5 with sodium citrate and citric acid monohydrate,

with a shelf life of 3 years. It is compatible with 0.9% sodium chloride, 5%

glucose and ringer‟s lactate solution. It can be administered either by slow i.v.

injection or by infusion.

A total daily dose of 32 mg administered by intravenous infusion or in

divided doses (0.1 – 0.15 mg/kg) provides control of acute emesis.

Intramuscular administration is not advisable as it is very painful.

It is bound to plasma proteins to a moderate extent (70-76%) with a

relatively large volume of distribution of approximately 3 hrs (3.5 + 1.2 hrs)

with only 5% being excreted unchanged by the kidneys. High performance

liquid chromatography after solid phase extraction is the method of choice for

determining the plasma concentration of ondansetron. The extent to which

ondansetron is excreted in breast milk or crosses the placenta is not known.

Metabolism and excretion

Oral absorption of ondansetron is rapid. The renal clearance of the drug

is low, indicating that the major route of systemic clearance is by metabolism.

The major route of metabolism is by hydroxylation followed by glucuronide or

sulfate conjugation in the liver. Most of these inactive metabolites appear in

the urine. The main metabolites are conjugates of 7-hydraoxy or 8-hydroxy

ondansetron which appears to have little or no pharmacological activity.

23
 Clearance is 5.9 + 2.6 ml/min/kg. Clearance is decreased in elderly,

cirrhotics and in females. This is due to reduced first pass hepatic metabolism

and a prolonged half life of 5.4 hrs in those more than 75 years of age.

Clearance is increased in children. Onset of action after I.V administration is

less than 30 minutes and duration of action is 12-24 hrs.

Pharmacodynamics of ondansetron

It does not affect respiratory or cardiac parameters like heart rate, blood

pressure or cardiac output. It does not interfere with CO2 regulation of the

respiratory drive, nor does it augment the respiratory depression produced by

alfentanil. It has no drug interactions with opioids, muscle relaxants, anxiolytics

or ethanol.

Formulations

It is available as oral, intramuscular and intravenous preparations.

Oral forms

Zofran tablets: Contain ondansetron hydrochloride equivalent to 4 mg or 8 mg

ondansetron.

Parenteral forms

Injection Zofran, Injection Nuset : An aqueous solution of approximately

pH 3.5 containing ondansetron hydrochloride equivalent to ondansetron 2

mg/ml. Infusions available in multidose vials of 20 ml.

The tablet and injection should be stored between 2 0C and 300C,

protected from light. Ampoules should not be autoclaved.

24
Dosage

Orally, a dose of 8-16 mg of ondansetron was found to be the most

effective dose in patients with or without a history of PONV given 1-2 hrs prior

to anaesthesia and repeated after 8-12 hrs. Parenterally, a dose of 4 mg by

i.m or slow i.v injection (over 2-5 min) immediately before induction of

anaesthesia is recommended.

Therapeutic uses

Chemotherapy

The chemotherapy drugs like cisplatin, 5-FU, doxarubicin used in the

treatment of certain malignancies cause nausea and vomiting. The incidence

of vomiting is high with cisplatin therapy. Ondansetron has been effectively

used as a single agent in doses of 8 mg or 20 mg i.v. in such cases as an

antiemetic. Addition of dexamethasone i.v. further enhances the effectiveness

of ondansetron.Radiotherapy

In radiotherapy, particularly in total body irradiation or when centred on

the upper abdomen, it acts as a potential cause of emesis.Ondansetron 8mg

dose has proved efficient in the control of early emesis.

Anaesthetic implications

Several studies have confirmed that ondansetron receiving patients suffered

less nausea and vomiting compared to group which received saline placebo.

The optimal dose was considered to be 4 mg, with 8mg perhaps offering

25
added benefits for those with a past history of nausea and vomiting after

general anaesthesia.

Studies have recommended that ondansetron 8mg should be

administered orally 1 hr before surgery followed by 2 further doses of 8 mg at

8 hourly intervals.

Alternatively a single dose of 4mg may be given as slow i.v. injection at

induction of Anaesthesia.

Adverse reactions

Headache(commonest)

Pruritus

Restlessness Constipation

Flushing or sensation of warmth

26
 PHARMACOLOGY OF BUPIVACAINE (20, 21, 22,23,24)

Local Anaesthetic Drugs

Local anaesthetics are drugs that produce reversible conduction

blockade of impulses along central and peripheral nerve pathways after

regional anaesthesia. With progressive increases in concentrations of local

anaesthetics the transmission of autonomic, somatic sensory and somatic

motor impulses are interrupted producing autonomic nervous system

blockade, sensory anaesthesia, and skeletal muscle paralysis in the area

innervated by the affected nerve. Removal of the local anaesthetic is followed

by spontaneous and complete return of nerve conductions, with no evidence

of structural damage to nerve fibres.

Local anaesthetics have similar configuration. They have one aromatic

lipophilic part (Benzene ring) and one hydrophilic part (quaternary ring)

connected by an intermediate ring either ester (-COO-) or an amide (-NHCO-).

Bupivacaine

Source

Bupivacaine, a synthetic drug, was prepared by A.F. Ekenstam in 1957.

Chemistry

The molecular weight of the chloride salt is 325 and that of the base form is
0
288. It has a melting point of 258 C. Solutions containing epinephrine have a

pH of about 3.5.

The chemical name is 1-n-butyl-DL-piperidine-2 carboxylic acid-2, 6

27
dimethylamilide hydrochloride. The molecular formula is C18N2OH28HCl.

CHEMICAL STRUCTURE

Physiochemical properties

1) Solubility: The base is sparingly soluble, but the hydrochloride is readily

soluble in water.

2) Stability and sterilization: Bupivacaine is highly stable and can withstand

repeated autoclaving.

3) pH of saturated solution : 5.2

0
4) Specific gravity : 1.021 at 37 C

0
5) Melting point : 247-258 C

Fig: Chemical Structure of Bupivacaine

28
Anaesthetic properties:

Potency:

Bupivacaine is approximately three to four times more potent than

Lidocaine. The duration of action for local anaesthesia is two to three times

longer than Lidocaine.

Anaesthetic index:

Bupivacaine‟s anesthetic index is 3.0 to 4.0.

Mechanism of action:

It is similar to that of any other local anaesthetics. The primary action of

local anaesthetics is on the cell membrane of the axon, on which it produces

electrical stabilization. The large transient increase in permeability to sodium

ions necessary for propagation of the impulse is prevented. Thus the resting

membrane potential is maintained and depolarization in response to

stimulation is inhibited.

The mechanism by which local anaesthetics block sodium conductance

is as follows:

a) Local anaesthetics in the cationic form act on the receptors within the

sodium channels on the cell membrane and block it. The local anaesthetic

can reach the sodium channel either via the lipophilic pathway directly

across the lipid membrane, or via the axoplasmic opening. This mechanism

accounts for 90% of the nerve blocking effects of amide local anaesthetics.

b) The second mechanism of action is by membrane expansion. This is a

nonspecific action in contrast to the more specific drug receptor interaction.

29
Dosage and preparations available

The dosage of Bupivacaine depends on area to be anaesthetized, the

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

blocked, individual tolerance and technique of local anaesthesia.

Available concentrations

0.25% (w/v), 0.5%, 0.75%; 0.25% and 0.5% soluble in isotonic saline and

0.5% solution in 8% dextrose.

These doses may be repeated in 3-4 hours but 400mg is the maximum dose

in 24 hours. The addition of vasoconstrictor produces a very slight increase in

the duration of action. However the peak blood level is significantly reduced,

thereby minimizing the systemic toxicity.

Table A: Dosage and concentration of Bupivacaine in various blocks

Dosage in
Type of block Concentration Dosage in ml mg

Upto
Local infiltration 0.25-0.5% 5-20ml 175mg

Brachial plexus block 0.25-0.5% 20-40ml 75-225mg

15-20mg
Intercostal nerve per each
block 0.25-0.5% 3-5ml
Nerve

Epidural block 0.25-0.5% 15-20ml 50-200mg

Caudal block 0.25-0.5% 15-30ml 75-15mg

Subarachnoid block 0.5-0.75% 2-4ml 10-20mg

30
ACTIONS:

Central nervous system:

Overdose of Bupivacaine produces light headedness and dizziness

followed by visual and auditory disturbances such as difficult to focus and

tinnitus. Disorientation and drowsiness can also occur. Shivering, muscular

tremors and tremors of muscles of face and distal part of extremities can

occur. Ultimately generalized convulsions of tonic clonic nature occurs. Further

increase in doses causes respiratory arrest.

Since Bupivacaine is a potent drug, smaller doses can cause rapid

onset of toxic symptoms when compared to other drugs.

Autonomic nervous system

Bupivacaine does not inhibit the Noradrenaline uptake and hence has

no sympathetic potentiating effect. Myelinated preganglionic beta fibres have a

faster conduction time and are more sensitive to the action of local

anaesthetics including Bupivacaine. Involvement of preganglionic sympathetic

fibres is the cause of widespread vasodilatation and consequent hypotension

that occurs is epidural and paravertebral block. When used for conduction

blockade, all local anaesthetics particularly Bupivacaine produce higher

incidence of sensory than motor fibres blockade.

Neuro-muscular junctions

Bupivacaine like other local anaesthetics can block motor nerves if

present in sufficient concentration but has no effect on the neuromuscular

junction as such.

31
Cardiovascular system

The primary cardiac electrophysiologic effect of local anesthetic is a

decrease in the maximum rate of depolarization in the purkinje fibres and

ventricular muscle. This is due to a decrease in the availability of sodium

channels. Action potential duration and the effective refractory period is also

decreased. The depression of rapid phase of depolarization (V-max) in

purkinje fibres and ventricular muscle by Bupivacaine is far greater compared

to Lignocaine. Also the rate of recovery of block is slower with Bupivacaine.

Therefore there is incomplete restoration of V-max between action potential

particularly at higher heart rates. Therefore, Bupivacaine is highly

arrhythmogenic. The cardiac contractility is reduced; this is by blocking the

calcium transport.

Low concentration of Bupivacaine produces vasoconstriction while

higher doses cause vasodilatation.

Respiratory system

Respiratory depression may be caused if excessive plasma level is

reached which in turn results in depression of medullary respiratory centre.

Respiratory depression may also be caused by paralysis of respiratory

muscles as may occur in high spinal or total spinal anaesthesia.

Pharmacodynamics

The onset of action of Bupivacaine is between 4 and 6 minutes and

maximum anaesthesia is obtained between 15 and 20 minutes. The duration

of anaesthesia varies according to the type of block; the average duration for

epidural block is about 3.5-5 hours, for nerve blocks, it is about 5 to 6 hours.

32
Toxicity

The toxic plasma concentration is set at 4-5μg/ml. Maximum plasma

concentration rarely approach toxic levels. Nonspecific local irritant effects on

nerve tissue have been noted in human subjects. No evidence of permanent

damage has been found in clinical dosage. There is no alteration is blood

picture or methaemoglobin formation due to this drug.

Bupivacaine can be detected in the blood within 5 minutes of infiltration

or following either epidural or intercostal nerve blocks. Plasma levels are

related to the total dose administered. Peak levels of 0.14 to1.18 μg/ml were

found within 5 minutes to 2 hours after the administration of anaesthesia and

they gradually declined to 0.1 to 0.34μg/ml by 4 hours.

Plasma binding

In plasma, drug binds avidly with protein (α1- acid glycoprotein) to the

extent of 70-95%. The order of protein binding for this and its homologues is

Bupivacaine followed by Mepivacaine and Lidocaine. Conversely, the unbound

active fraction is one seventh that of Lidocaine and one fifth that of

Mepivacaine.

Metabolism – elimination

Because Bupivacaine is an amide, the liver is the primary site of

metabolism. The drug is metabolized partly by N-dealkylation primarily to

pipecolyloxylidine. N-disbutyl-bupivacaine and 4-hydroxy-bupivacaine are also

formed. It crosses the placental barrier as any other local anaesthetic by

passive diffusion, but the lowest level of placental diffusion is reported for this

drug (umbilical vein/maternal ratio is 0.31 to 0.44). The high protein binding

33
capacity of the agent is probably the reason why less diffusion occurs across

the placenta. No effects on foetus have been noted.

About 10% of drug is excreted unchanged in urine within 24 hours; 5%

excreted as pipecolyloxylidine. Glucoronide conjugate is also excreted.

Toxic effects

Toxic effects occur with excessive plasma levels which may be due to

overdose, inadvertent IV injections or slow metabolic degradation. These

manifest by effects on CNS and CVS. The CNS effects are characterized by

excitation or depression. The first manifestation may be nervousness,

dizziness, blurring of vision or tremors followed by drowsiness, convulsions

unconsciousness and probably respiratory arrest.

Other effects may be nausea, vomiting, chills, constriction of pupils and

tinnitus. The CVS manifestations include myocardial depression, hypotension,

cardiac arrest and in obstetrics foetal bradycardia may occur. Allergic

reactions include urticaria, bronchospasm and hypotension.

Treatment of Bupivacaine toxicity

Treatment is mainly symptomatic. One should be prepared to maintain

circulation and to support ventilation with oxygen or controlled ventilation, if

required, supportive treatment with IV fluids and vasopressors restore the

cardiovascular stability, convulsions may be controlled with Diazepam (0.1- 0.2

mg/kg) or Thiopentone (2-3 mg/kg) or a muscle relaxant and controlled

ventilation with oxygen. Corticosteroids, if allergic reactions are suspected.

Treatment of ventricular fibrillation and tachycardia is by Amiodarone (5 mg/kg

IV) or defibrillation (2-6 Joule/kg).

34
20% Intralipid:

1. Administer 1.5 ml/kg as an initial bolus; the bolus can be repeated 1- 2

times for persistent asystole

2. Start an infusion at 0.25 ml/kg/min for 30-60 minutes; increase infusion rate

up to 0.50 ml/kg/min for refractory hypotension

Cardiovascular collapse / CNS ratio

The CC/CNS dose ratio for Bupivacaine is 3.7 ± 0.5 or findings

indicating that 3 times drug was required to induce irreversible cardiovascular

collapse as was

needed to produce convulsions. It has also been suggested that some of the

enhanced cardiac toxicity of Bupivacaine is due to greater myocardial uptake.

Role of additives

1) Adrenaline: Onset time reduced and duration prolonged.

2) Sodium bicarbonate: Onset time reduced and duration variable.

3) Clonidine: Onset time reduced and duration prolonged.

4) Opioids: Onset time reduced and duration prolonged. Reports controversial.

5) Midazolam: Onset time reduced and duration prolonged.

LEVOBUPIVACAINE

It is the S-enantiomer of Bupivacaine. Compared to Bupivacaine, it is

associated with less vasodilatation and has a longer duration of action. It is

approximately 13 % less potent (by molarity) than racemic bupivacaine.

35
 METHODOLOGY (23,24)

This study was conducted on 60 patients undergoing upper limb

surgeries aged between 18 to 65 years under supraclavicular block in

Osmania General Hospital, attached to Osmania Medical College, Hyderabad

between November 2016 and October 2018. Informed written consent was

taken. Results were recorded using a pre-set proforma.

Inclusion criteria

• ASA CLASS I & II

• Aged between 18 to 65 years

Exclusion criteria

• AGE <18years or >65years

• ASA grade >III

• Patient on drugs modifying pain perception

• Patient refusal

• Known case of hypersensitive reaction to Ondansetron or Bupivacaine

• Patients with abnormal coagulation profile, phrenic nerve or recurrent nerve

palsy.

• Local infection at the site of proposed puncture for supraclavicular block.

36
 Investigations Required

• Haemoglobin (Hb%), Total Leukocytes Count (TLC), Differential Leucocyte

Count(DLC), Bleeding Time (BT), Clotting Time(CT)

• Random Blood Sugar(RBS), Blood urea and Serum Creatinine

• ECG

• HIV, HBs Ag

Preliminaries

• Written informed consent

• Intravenous access with a 20 guage IV cannula on the contralateral upper

limb under aseptic techniques.

Equipment

a) For the procedure:

A portable tray covered with sterile towels containing

• Sterile syringes – Three 10ml

• Hypodermic needles of 5 cm length, 22 G

• Bowl containing Povidone iodine and spirit

• Sponge holding forceps

• Towels and towel clips

37
• Sterile gauze pieces

b) For emergency resuscitation

• The anaesthesia machine, emergency oxygen source (E type cylinders)

pipeline O2 supply, working laryngoscopes, appropriate size endotracheal

tubes with connectors and oropharyngeal airways.

• Working suction apparatus with suction catheter

• Intravenous fluids

• Drugs: Inj. Thiopentone, Succinylcholine, Hydrocortisone, Atropine,

Adrenaline, Aminophylline, Mephenteramine, Calcium gluconate and

Sodium bicarbonate

c) Monitors used

A multiparameter monitor with pulse oximeter, E.C.G and non Invasive Blood

pressure.

Procedure

A prospective, randomized, single blinded study was undertaken.60 patients

posted for upper limb surgeries under supraclavicular block were assigned to

2 groups, each containing 30 patients.

• Control group – Group-A: received 30 ml Bupivacaine (0.5%) and 4ml

normal saline

• Study group – Group B: received 30 ml of mixture of Bupivacaine (0.5%)

and Ondansetron (8 mg).

38
- Patients lay supine, arms by the side and head turned slightly to the other

side.

- The interscalene groove and mid-point of clavicle were identified.

- After aseptic preparation of the area, at a point 1.5 to 2.0 cm posterior and

cephalad to mid-point of clavicle, subclavian artery pulsations are felt. A

skin wheal was raised with local anaesthetic just cephalo-posterior to the

pulsations.

- Next, a 22 gauge, 5 cm needle, mounted on a 20 ml syringe, was passed

through the same point, parallel to the head and neck, in a caudad, slightly

medial and posterior direction, until either paraesthesia was elicited or first

rib was encountered.

- If the first rib was encountered, the needle would be moved over the first rib

until a paraesthesia was elicited either in the hand or arm.

- After eliciting paraesthesia the study medication was injected.

- All patients were monitored for anaesthesia and analgesia upto 24 hours

post-operatively.

- Sensory block was evaluated by pin prick testing using 22 guage on skin

dermatomes C4 to T2 whereas motor block was assessed by asking the

patient to adduct the shoulder and flex the fore-arm against gravity.

- Onset of sensory block was defined as the time elapsed between injection

of drug and complete loss of cold perception of the hand, while onset of

motor blockade was defined as the time elapsed from injection of drug to

inability to adduct arm and flex fore arm against gravity (inability to touch

one‟s nose).

39
- Pain was assessed by numerical rating pain scale where 0 represents no

pain n 10 means worst possible pain.

- Heart rate, non-invasive blood pressure and O2 saturation were also

monitored.

- Duration of sensory block (the time elapsed between injection of drug and

appearance of pain requiring analgesia) and duration of motor block (the

time elapsed between injection of drug and complete return of muscle

power) would also be recorded.

- IM injection of Diclofenac sodium was given as rescue analgesic when

patient complains of pain.

- Number of rescue analgesics needed in 24 hours of post-operative period

was also recorded.

- Quantitative data was analysed by student‟s „t‟ test.

- Qualitative data was analysed by Chi-square test.

- A p value of< 0.05 was considered statistically significant.

40
Fig. 4: Sterile tray containing drugs and equipment

Fig. 5: Drugs used for the study

41
Fig. 6: Needle entry 1 cm cephalo-posterior to subclavian artery pulsation

Fig. 7: Test drug injected after negative aspiration for blood

42
 OBSERVATION AND RESULTS
Sixty ASA Grade I and II of either sex aged between 18-65 years, posted for

upper limb surgeries under supraclavicular brachial plexus block were

selected for the study. The study was undertaken to evaluate the efficacy of

Ondansetron (8mg) as an adjuvant to Bupivacaine (0.5%) in comparison with

plain Bupivacaine (0.5%) for brachial plexus block by supraclavicular

approach.

Table 1: Age Distribution of Study groups

Mean ± SD
Study Groups (Age in years) p value Significance

Bupivacaine+
normal saline 34 ± 9.56
0.491 Not Sig
Bupivacaine+
Ondansetron 32.3 ± 9.45

Graph 1: Age Distribution of Study groups

34.5
34
34

33.5

33
Group A
32.5 32.3 Group B
32

31.5

31
AGE

The minimum age of the patient was 18 years and the maximum age was 65

years. The mean age of the patients in group B was 32.3 ± 9.56 and in group

A was 32.3 ± 9.45 years. Age distribution between two groups was

comparable.

43
 Table 2: Weight Distribution of Study groups

Mean ± SD
Study Groups (WT in KGs) p value Significance

Bupivacaine+
normal saline 81.7 ± 4.28
0.207 Not Sig
Bupivacaine+
Ondansetron 83.2 ± 4.82

Graph 2: weight Distribution of Study groups

83.5
83.2

83

82.5

82 Group A
81.7 Group B
81.5

81

80.5
WEIGHT

The mean weight of the patients in group B was 83.3 ± 4.28 and in group A

was 81.7 ± 4.82 kgs. Weight distribution between two groups were

comparable

44
 Table 3: Duration of surgery Distribution of Study groups

Mean ± SD
Study Groups (Duration in min) p value Significance

Bupivacaine+
normal saline 75.06 ± 6.30
0.120 Not Sig
Bupivacaine+
Ondansetron 72.7 ± 5.24

Graph 3: Duration of surgery Distribution of Study groups

75.5
75.06
75

74.5

74

73.5 Group A
Group B
73
72.7

72.5

72

71.5
Duration of surgery

The mean Duration of surgeries in group B was 72.06 ± 5.24(min) and in

group A was 72.7± 5.24(min). Duration of surgeries between two groups were

comparable

45
Time for onset of sensory block:

Table 4: Time for onset of sensory block (min)

Study Onset time

p value Significance
Group (min)

A 8.13 ±1.63
< 0.692 NS
B 8 ± 0.74

NS- Not Significant

Graph 4: Time for onset of sensory block (min)

8.15
8.13

8.1

8.05
Group A
8 Group B
8

7.95

7.9
Onset of action

The mean time for onset of sensory block in group B was 8 ± 0.74 minand in
group A was 8.13 ± 1.63 min. The statistical analysis by student‟s unpaired „t‟
test showed that, the time for onset of sensory block in group B was
comparable to group B (p>0.05).

46
Time for onset of motor block

Table 5: Time for onset of motor block

Study Onset time

p value Significance
Group (min)

A 9 ± 1.63
< 0.001 SS
B 7.76± 0.77

Graph 5: Time for onset of motor block

9.2
9
9
8.8
8.6
8.4
8.2 Group A
8
7.78 Group B
7.8
7.6
7.4
7.2
7
onset of motor

The mean time for onset of motor block in group B was 7.76 ± 0.77 min and in
group A was 9 ± 1.63 min. The statistical analysis by unpaired student‟s „t‟ test
showed that, the time for onset of motor block was significantly faster in group
Between compared to group A (p< 0.05).

47
Duration of sensory block:

Table 6: Duration of sensory block

Study Duration of
p value Significance
Group block (min)

A 504 ± 32.81
P < 0.001 SS
B 880 ± 59.91

SS- statistically significant

Graph 6: Duration of sensory block

1000
880
900

800

700

600
504
500 Group A
Group B
400

300

200

100

0
Duration of sensory block

Patients of both groups were observed for 24 hours. Time was noted when the
patient asked for rescue analgesics. The mean duration of sensory block in
group B was 880±59.91 min and in group A was 504±32.81. The statistical
analysis by students unpaired„t‟ test showed that the duration of sensory block
in group B was significantly longer when compared to group A (p< 0.05)

48
Duration of motor block:

Table 7: Duration of motor block

Study Duration of
p value Significance
Group block (min)

B 486 ± 32.40
p < 0.001 SS
A 754 ± 69.69

SS- statistically significant

Graph 7: Duration of motor block

800 754

700

600
486
500

400 Group A
Group B
300

200

100

0
Duration of motor block

The mean duration of motor block in group B was 754 ± 69.69 mins and in the
group A was 486 ± 32.40 mins. The statistical analysis by students‟t‟ test
shows significant difference, with p value less than 0.05 (p< 0.05).

49
Number of rescue analgesics in post-op 24 hours

Table 8: Number of rescue analgesics in post-op 24 hours

No. of Rescue BUPIVACAINE BUPIVACAINE

Analgesic doses in 24 + +
hours post-op NORMAL SALINE ONDANSETRON
3 15 (25) 0

2 45 (75) 15 (25)

1 0 45 (75)

Highly Significant
χ2 = 61.25 p< 0.0001

In group B, 75% patients required only 1 rescue analgesic dosage and

25% of patients required 2 rescue analgesic doses in post-op 24 hours. In
group A 75% of patients required 2 and 25% of patients required 3 rescue
analgesic doses in post-op 24 hours. This difference in number of rescue
analgesic doses required by patient of both groups is statistically significant by
2
chi-square test (χ = 61.25, P < 0.05).

Graph 8: Number of rescue Analgesics needed

45 45
50
40
1
30
15 15 2
20
3
10 0 0
0
Group A Group B

HAEMODYNAMIC VARIABLES

Pulse rate, systolic BP, diastolic BP, O2 saturation were recorded at 0 min,
5min, 15 min, 30 min, 60 min, 2 hours, 6 hours, 12 hours, 24 hours.

50
 Table 9: Pulse Rate (beats / min)

Time of Mean+/- SD p Signifi

Assessment Bupivacaine Bupivacaine Value Cance

+Normal saline +Ondansetron
0 min 83.5 ± 6.45 81.2 ± 6.58 >0.05 NS

5 min 80 ± 6.37 78.2 ± 6.27 >0.05 NS

15 min 78 ± 7.0 76.4 ± 6.58 >0.05 NS

30 min 77.7 ± 6.88 76.0 ± 7.15 >0.05 NS

60 min 77.8 ± 6.84 75.1 ± 7.05 >0.05 NS

2 hrs 78.03 ± 6.36 75.6 ± 6.23 >0.05 NS

6 hrs 78.5 ± 6.94 75.7 ± 6.24 >0.05 NS

12 hrs 78.6 ± 6.43 76.2 ± 6.19 >0.05 NS

24 hrs 79 ± 6.81 77.4 ± 6.20 >0.05 NS

Graph 9: Pulse Rate (beats / min)

86
83.5
84

82 81.2
80
80 78.6 79
78.2 78 78.03 78.5
77.7 77.8 77.4
78 Group A
76.4 76 76.2
75.6 75.7
76 75.1 Group B

74

72

70
0min 5min 15min 30min 60min 2hr 6hr 12hr 24hr

In group A, the mean pulse rate ranged from 77.7±6.88 to 83.5 ± 6.45beats/
min.In group B, the mean pulse rate ranged from 75.1± 7.05 to 81.2 ± 6.58
beats / min. The statistical analysis by student‟s unpaired „t‟ test showed that
there was no significant difference in pulse rate between the two groups (p>
0.05).

51
Systolic blood pressure
Table 10: Systolic blood pressure (mm of Hg)
Mean+/- SD
Time of
Bupivacaine
Bupivacaine+
+
Normal saline (in Significance
Ondansetron
Assessment mm of Hg) p-Value
0 min 119.2 ± 10.16 117.8 ± 9.64 >0.05 NS
5 min 121.5 ± 9.12 120.9 ± 7.45 >0.05 NS
15 min 119 ± 11.06 118 ± 10.31 >0.05 NS
30 min 118.9 ± 9.62 118.4 ± 9.49 >0.05 NS
60 min 117.7 ± 10.10 117.3 ± 10.02 >0.05 NS
2 hrs 118.6 ± 9.01 118.4 ± 9.18 >0.05 NS
6 hrs 116.8 ± 9.4 116.5 ± 9.74 >0.05 NS
12 hrs 117 ± 9.78 116.6 ± 9.85 >0.05 NS
24 hrs 117.7 ± 9.13 116.9 ± 9.07 >0.05 NS

Graph 10: Systolic blood pressure (mm of Hg)

124
Group A
121.5 Group B
122 120.9

120 119.2 119 118.9118.4 118.6118.4

117.8 117.7117.3 117.7
118 116.8 117 116.9
116.5 116.6
116

114

112

110
0 min 5 mi 15 min 30 min 60 min 2 hr 6 hr 12 r 24 hr

52
 Diastolic blood pressure

Table 11: Diastolic blood pressure (mm of Hg)

Mean+/- SD
Time of Bupivacaine Bupivacaine Signifi
Assessment p Value Cance
+ +
Normalsaline Ondansetron

0 min 76.8 ± 7.8 75.8 ± 7.13 > 0.05 NS

5 min 76.3 ±7.79 76.2± 8.34 > 0.05 NS

15 min 76.6 ± 7.19 76.4± 7.37 > 0.05 NS

30 min 75.8 ± 5.96 76.7 ± 7.40 > 0.05 NS

60 min 76.8 ± 6.65 76.5 ± 6.22 > 0.05 NS

2 hrs 76.8 ± 7.23 76.3 ± 6.91 > 0.05 NS

6 hrs 76.5 ± 7.32 76.3 ± 6.71 > 0.05 NS

12 hrs 76.3 ± 7.37 75.9 ± 6.61 > 0.05 NS

24 hrs 76.7 ± 6.65 76.5 ± 7.02 > 0.05 NS

Graph 11: Diastolic blood pressure (mm of Hg)

80
79
78
77
76
75 GroupA
74
Group B
73
72
71
70
0 min 5 min 15 30 60 2 hrs 6 hrs 12 hrs 24 hrs
min min min

In group A, the mean diastolic blood pressure ranged from 75.8 ± 5.96 to 76.8 ± 7.8
mm of Hg. In group B, DBP ranged from 75.9 ± 6.61 to 76.7 ± 7.40 mm of Hg. The
statistical analysis by unpaired student‟s„t‟ test showed that there was no significant
difference in systolic blood pressure between two groups (p > 0.05)

53
 Table 12: Oxygen saturation (%)

Time of Mean+/- SD p
Bupivacaine- Significance
Assessment Bupivacaine Value
Ondansetron
0 min 99.7 ± 0.57 99.7 ± 0.59 > 0.05 NS
5 min 99.8 ± 0.51 99.7 ± 0.54 > 0.05 NS
15 min 99.7 ± 0.63 99.7 ± 0.65 > 0.05 NS
30 min 99.7 ± 0.65 99.8 ± 0.53 > 0.05 NS
60 min 99.7 ± 0.58 99.8 ± 0.4 > 0.05 NS
2 hrs 99.7 ± 0.64 99.8 ± 0.48 > 0.05 NS
6 hrs 99.7 ± 0.56 99.8 ± 0.47 > 0.05 NS
12 hrs 99.7 ± 0.75 99.8 ± 0.55 > 0.05 NS
24 hrs 99.7 ± 0.53 99.8 ± 0.53 > 0.05 NS

Graph 12: Oxygen Saturation

104

102

100 99 99 99 99 99 99 99 99 99

98
Group A
96 Group B

94

92

90
0 min 5 min 15 30 60 2 hr 6 hr 12 hr 24 hr
min min min

In group A, the mean O2 saturation ranged from 99.7 ± 0.57% to 99.8 ±

0.51%. In group B, the mean O2 saturation ranged from 98 ± 0.5%. The

statistical analysis by students unpaired„t‟ test showed that there was no
significant difference in O2 saturation between the two groups (p> 0.05).

54
 DISCUSSION
Brachial plexus block provides postoperative analgesia of short duration, even

when a long-acting local anaesthetic like Bupivacaine is used alone. Various

adjuvant drugs like Opioids, Clonidine, Neostigmine and Hyaluronidase have

been evaluated in conjunction with local anaesthetics to prolong the period of

analgesia, but they were found to be either ineffective or to produce an

unacceptably high incidence of adverse effects. Intravenous Opiods and

nonsteroidal anti inflammatory drugs (NSAIDS) singly or incombination provide

good analgesia but cause various side effects. Most surgeries on fore arm and

hand are intermediate and minor surgeries and have relatively short duration

but have severe postoperative pain(25). Supraclavicular approach is simple and

cost effective and safe(26). As nerve trunks are more compact in that area so

homogeneous spread of the drug is there and fast onset of the block occurs
(27)
. Ondansetron, a highly selective and potent antagonist of 5-

hydroxytryptamine subtype 3 (5-HT3) receptors is known to produce antiemetic

and in addition above effect it blocks sodium channel and has antinociceptive

property to enhance the effect of local anaesthetic when given in peripheral

nerve blocks. Ondansetron produces this effect by its antagonistic action on

sodium channel. Peripheral (5-HT3) receptors are involved in pathway of

nociception. These receptors bind to opoids receptors and agonist activity.

A total of 60 patients within the age group of 18-65 were in included in

the study, 30 in each group. Out of which the mean age of group A (receiving

only Bupivacaine + Normal saline) was 34 ± 9.56 years and the mean age of

group B (receiving ondansetron with Bupivacaine) was 32.3 ± 9.45 years.

55
Hence both groups were comparable in regard to age. Male to female ratio

was almost same.

In our study we found that the onset of sensory block comparable in

both groups and motor blocks was significantly faster in patients who received

a combination of ondansetron and Bupivacaine. Onset of sensory block (group

A, 8.13 ± 1.63 min; group B, 8 ± 0.74 min). Onset of motor block (group A, 9 ±

1.63 min; group B, 7.76 ± 0.77 min). This could be due to a local anaesthetic

property of Ondansetron and its synergistic action with local anaesthetics.

The onset of motor block was found to be faster than the onset of

sensory block in our study groups. This is probably due to Pharmacokinetics of

local anaesthetics action on nerve bundles and their somatotrophic

arrangement of fibres. This has explained by Winnie et al(28). who also had

similar results in their study by observation that the motor fibres are located

more peripherally than sensory fibres and are easily blocked first as compared

to the centrally located sensory nerve fibres in the nerve bundles.

The sensory fibres are smaller as compared to motor fibres which are

larger. The minimal effective concentration of local anaesthetics to block large

fibres is greater than that of smaller sensory fibres. As a result motor function

returns back faster than pain perception during weaning period of the block as

concentration of drug decreases. This is what seen in our study as observed

by de Jong et al in their study “Physiological mechanism of peripheral

nerve block by local anaesthetics” (29).

The addition of ondansetron to local anaesthestic enchanced the onset

of motor block and increased duration of both sensory and motor block in our

56
study. This may be due to peripheral 5HT3 receptor & sodium channel

blocking action, mu opioid receptor agonist action which is similar to study with

ondansetron as an adjuvant in supra clavicular block observed by Dr

Vasundha Jadhav, Dr Ranjeetsinha, Dr B.M. Diwanmal et al(5).

In our study, the mean duration of sensory block (i.e. time elapsed from

time of injection to appearance of pain requiring analgesia) was significantly

higher (p< 0.05) in group B than in group A. (group B, 880 ± 59.91min; group

A, 504± 32.81min). Duration of sensory block, post operative analgesia is

more & requirement of rescue analgesic drugs is less in group B similar to a

study conducted by Dr Vasundha Jadhav et al studies(5).

A study of Ye et al(30) showed that the effect of subcutaneous injection

of ondansetron was 15 times than that of local anaesthesia with lidocaine. The

molecular structure of 5-HT3 receptor blockers was completely different from

that of local anesthetic, but it has a similar effect to that of local anesthetic.

However, the mechanism is not yet entirely clear; they found that 5-HT3

receptor antagonist could block the sodium channel of block the brain nerve

cells of rats. It activated opioid receptors while inhibiting the release and

uptake of norepinephrine to achieve analgesic effect. The molecular structure

of 5-HT3 receptor blockers is completely different from local anaesthetics, but

can produce similar local anaesthesia. The limitations of this study include

limited documentation of the inclusion criteria, relatively insufficient samples,

inadequate analysis .More high-quality studies with careful design are needed

to reduce and decrease the effect of bias on the study result

57
 Farber and et al(31) colleagues showed that 5-HT3 receptor antagonist

like tropesetron have analgesic effect in patients with fibromyalgic pain. Also

the analgesic effect of 5-HT3 receptor antagonist like alosterone in female

patients with diarrhea predominant irritable bowel syndrome was reported by

Camilleri et al(32). and Muller et al(33) showed that local administration of 5-HT3

antagonist had rapid analgesic effect in various rheumatic diseases. It was

reported that this local anesthetic effect lasts significantly longer compared

with local injection of local anesthetics combined with cortico steroids

Ondansetron potentiates the action of local anaesthestics due to its

peripheral action of blocking 5HT3 receptors & sodium channels, agonist

action on mu opioid receptors there by producing antinociceptive action. This

is seen not only seen in supraclavicular brachial plexus block but also

intravenous regional anaesthesia.

Stratz and colleagues(34) showed that 5-HT3 receptor antagonists had

anti-inflammatory effects and due to this property they could have a role in

decreasing pain following surgical incision pain. Also, they founded that 5-HT3

receptor antagonists could acted as supplement or replacement for local

administration of corticosteroids. Not only ondansetron but the other 5-HT3

antagonists such as tropisetron and alosetron have analgesic effect.

(35)
It was showed by the Zeitz et al that peripheral 5-HT3 receptors acts

as a novel complement for the primary afferent nociceptors. As tourniquet

inflation prevent whole body distribution of ondansetron. there study may be

useful model for investigating mechanism of peripheral action of ondansetron.

58
 Cui and colleagues(36) concluded that stimulation of periaqueductal gray

matter could increase release of 5-HT in dorsal horns of spinal cord that

consequently might inhibit the nociception of dorsal horn neurons.

Murphy RM et al(37) & Alhaider AA et al(38) showed that the 5-HT3

receptors, which are present on PAF (from the nociceptors up to the dorsal

horn) mediate pronociceptive action while those receptors located

postsynaptically in relation to PAF mediate the antinociceptive effect of

endogenous (5-HT) or administered agonist.

Gregory et al(39) showed that ondansetron may be effective in

preventing pain following injection of propofol by binding to the opioid

receptors.

Ondansetron has action on peripheral 5HT3 receptor mainly & minimal

action on central 5HT3 receptors. Ondansetron through above action

produces analgesic effect locally & increases pain threshold. A study was

conducted by Azim Honarmand et al(6) to evaluate effect of adding 8mg of

ondansetron to lidocaine for Biers block on post operative pain. Ninety

American Society of Anaesthesiologist (ASA) physical status I-II patients, aged

18-65 years old, scheduled for elective hand or forearm surgery were

randomly allocated to the three groups to receive 3 mg/kg 2% lidocaine diluted

with saline to a total dose of 40 mL (Group L, n = 30) or 8 mg ondansetron

plus 3 mg/kg 2% lidocaine diluted with saline to a total dose of 40 mL (group

LO, n = 30) or 3 mg/kg 2% lidocaine diluted with saline to a total dose of 40

mL plus 8 mg ondansetron intravenously (Group IO, n = 30). The sensory and

motor block onset times were significantly shorter in Group LO compared with

59
Group L and Group IO. The sensory and motor block recovery times were

significantly longer in Group LO compared with Group L and Group IO. Post-

operative VAS scores were significantly less in Group LO compared with

Group L and Group IO till 24 h after tourniquet deflation ( P < 0.05). The

addition of 8 mg ondansetron to lidocaine for IVRA reduced intraoperative and

post-operative analgesic use till 24 h. Results of above IVRA study shows that

analgesic action of ondansetron through peripheral 5HT3 receptor & sodium

channels in Group LO & central 5HT3 receptors in Group IO lead to faster

onset of sensory block, onset of motor block & duration of sensory block,

duration of motor block is more in GroupLO than Group L & Group IO. In our

study analgesic action of ondansetron may be through peripheral 5HT3

receptor and sodium channels in supra clavicular block which resulted in

faster onset of motor block, more duration of sensory block & motor block

except onset of sensory block.

Mc clean et al.,(40) showed that ondansetron as a 5 HT3 receptor

antagonist has potential benefit in neuropathic pain.

0ndansetron analgesic efffect by action on 5HT3 receptor increased by

increasing dosage of drug. A study was conducted by Nahla S. El Bahnasawy,

MD(8) to evaluate and compare the analgesic effect of adding two different

doses (4or 8 mg) of ondansetron to lidocaine for intravenous regional

anesthesia (IVRA). Signifi cantly shorter onset times and longer recovery

times of sensory and motor block were recorded in groups with ondansetron

4mg & ondansetron 8 mg compared with only lignocaine group. with no

significant difference between ondansetron groups. Delayed onset of

60
tourniquet pain occurred in ondansetron groups compared with only lignocaine

group . Addition of ondansetron to lidocaine enhanced the performance of

lidocaine when used in IVRA, prolonged postoperative analgesia and reduced

intraoperative and postoperative analgesic drugs. However, adding 8 mg

ondansetron to lidocaine provided better analgesia than 4 mg.

In our study ondansetron used as an adjuvant in supraclavicular block

they used ondansetron as an adjuvant in IVRA block & observed that there is

faster on set of sensory block & onset of motor block, longer duration of

sensory block & motor block, reduced post operative analgesic drugs

requirement similar resulted noted in our study except faster onset of sensory

block in ondansetron as an adjuvant group.

Ondansetron has been shown to bind to opioid µ-receptors in humans

and possess agonist activity. Five hydroxytryptamine receptors are involved in

the nociceptive pathways. Five hydroxytryptamine receptors play a

pronociceptive role and mediate descending excitatory controls that allow

spinal neurons to fully code peripheral stimuli. Ondansetron decreases chronic

benign neuropathic pain, this effect seems to be produced by an action on the

neurons in the spinal cord that code and transmit peripheral nociceptive

stimuli. Five hydroxytryptamine receptors are also a target for local

anesthetics. The ability of ondansetron to block sodium channels and 5-HT3

receptor has put forward the hypothesis that ondansetron possesses

antinociceptive properties probably in a similar way to local anesthetics. A

study conducted by Omid Azimaraghi, et al (7) to evaluate Ondansetron

reducing pain on injection of etomidate. The mean VAS for injection pain of

61
etomidate after pre-administration of intravenous ondansetron was 1.5 ± 1.2

which was lower compared to pre-administration of placebo.

A Study of Ye et al.(30) found that 5-HT3 receptor antagonist could block

the sodium channel of block the brain nerve cells of rats. It activated opioid

receptors while inhibiting the release and uptake of norepinephrine to achieve

analgesic effect.

Propofol is the drug of choice for induction of anaesthesia because of

its rapid onset and short duration of action, easy titration, and favourable

profile for side effects. Propofol injection associated with pain. Various drugs

pretreatment with propofol injection compared efficacy of this drugs. A Study

was conducted by FARRUKH AYUB, et al(9) to compare the effects of

intravenous ondansetron and intravenous lidocaine on reduction of Propofol

induced vascular pain. Pain reduction was observed in (64.0%) of group-A

while in group-B pain reduction was reported (76.0%) of patients. Ondansetron

is found to have µ opioid agonist action. So Ondansetron may be potentially

used to decrease pain produced by propofol. This Study shows that

ondansetron has less analgesic property & less side effects but more

analgesic & more side effects lignocaine.

A study done by Richardson BP et al(41) & Kidd EJ, et al(42). shown that

there is receptors similar to enteric neuron 5-HT3 on the nociceptive primary

afferent fibers (PAF) not only on the peripheral free terminal but also centrally

on their spinal terminal.(40,41) These receptors are present on the neurons of

the superficial lamina of the dorsal horn also(40,41).

62
Local anaesthetics contain hydrophilic and hydrophobic structures separated

by an intermediate amide or ester linkage. The hydrophilic group is a tertiary

or secondary amine, and the hydrophobic group an aromatic moiety. Although

ondansetron does not possess this aromatic moiety, it has been shown to

block sodium channels.Recently, ondansetron has been shown to bind to

opioid µ-receptors in humans and exhibit agonist activity. These properties,

together with the observation that 5-HT3 receptors are involved in the

nociceptive pathways, have been postulated to explain the anti-nociceptive

properties of ondansetron. A study was conducted by Gangur basappa

(12)
sumalatha, et al to evaluate attenuation of propofol-induced pain by

lignocaine, ondansetron, and ramosetron. Pre-treatment with IV ramosetron

and lignocaine significantly reduced the propofol-induced pain when compared

to ondansetron. But ramosetron is recent drug , not easily available , more

costlier ,over all side effects needs to be further evaluated. Ondansetron

which easily available drug, cheaper, over all less side effects also reduced

propofol induced pain to some extent but not more than ramosetron &

lignocaine. This study also shows that ondansetron analgesic property & anti

emetic property.

Ambesh et al(11). found that pain during injection of propofol can

successfully prevent by administration of 4 mg ondansetron. Also, in another

study performed by Reddy and colleagues(43), it was shown that ondansetron 4

mg could reduce significantly pain during injection of rocuronium and propofol.

Liu QM et al(44) showed Ondansetron in combination with small dose of

sufentanil prevention propofol injection pain.

63
 The mechanism of rocuronium induced injection remains unclear. There

are several mechanisms postulated. It may be due to stimulus of meta-acidic

liquor to endangium similar was noted in study of Lockey and Coleman.

Rocuronium molecules stimulated the mast c.ells and released a small amount

of histamines and trypsin and stimulated the terminal of the nerve fibers after

intravenously penetrating into the local injecting tissues similar mechanism

was noted in study of Blunk et al.It led to axon reflex, thus resulting in

vasodilatation and which was clinically represented as local erythema.The

excitatory signal as a result of stimulus was transmitted to the centre, and the

subject may feel local pains and itches. The dilution of rocuronium during

intravenous injection can effectively reduce the incidence of injection pain.

However, there are some disturbing factors in these studies, such as the fact

that the injection speed of rocuronium may be one of the influencing factors;

moreover, the effect of dilution of rocuronium has not been compared with that

of other drug interventions. Ondansetron is a commonly used drug for the

prevention and treatment of nausea and vomiting clinically as a specific 5-HT3

receptor antagonist. It was found that its local anaesthetic properties due to

main peripheral 5HT3 antagonist blocking started from the prevention of

propofol injection pain. Similar study conducted by Qixiong He, et al(13) to

evaluate the Effect of 5-Hydroxytryptamine Receptor Antagonist in Preventing

Pain/Limb Shrinkage Reaction Associated with Rocuronium Injection. In

conclusion, 5-HT receptor antagonist may be efective in preventing and

reducing the occurrence of the pain/limb shrinkage reaction associated with

rocuronium injection. This study shows that ondanseton has analgesic

property

64
 A similar study was done by W. Hongzhu, et al.(14) Effect of

ondansetron compound lidocaine to prevent the pain of the rocuronium

injection, showed that ondansetron reduces some amount of pain produced by

rocuronium.

D. Memi, et al,(45) study The prevention of pain from injection of

rocuronium by ondansetron, lidocaine, tramadol, and fentanyl showed that

ondansetron has analgesic properties.

65
 CONCLUSION

From our study, we conclude that, the addition of Ondansetron (8 mg)

as adjuvant to Bupivacaine (0.5%) has following effects :

i) Similar onset of sensory block

ii) Faster onset of motor block

iii) Longer duration of sensory and motor blocks

iv) Less number of rescue analgesics in post-op 24 hours

v) No significant difference in haemodynamic variables i.e., pulse rate,

Systolic Blood Pressure, Diastolic Blood Pressure and O2 saturation.

66
 SUMMARY

This study “A clinical comparison between Bupivacaine-Ondansetron

combination and Bupivacaine (plain) in brachial plexus block by

supraclavicular approach” was conducted in 60 patients of either sex,

belonging to 18-65 years of age, ASA grade I and II admitted to Osmania

General Hospital for upper limb surgeries from 2016-2018.

They were randomly divided into 2 group :

Group B – Received 30 ml of 0.5% Bupivacaine + 8 mg of Ondansetron

Group A – Received 30 ml of 0.5% Bupivacaine+ 4ml normal saline.

The following parameters were recorded and compared.

1) Onset of sensory and motor block

2) Duration of sensory and motor block

3) Number of rescue analgesics in post-op 24 hours.

4) Haemodynamic variables like pulse rate, systolic and diastolic blood

pressure and O2 saturation

Onset of sensory and motor block:

The mean time for onset of sensory block in group A was 8.13 ± 1.63 min and

in group BM was 8 ± 0.74 min.

The mean time for onset of motor block in group A was 9 ± 1.63 min and in

group BM was 7.76 ± 0.77 min.

67
Both differences were not statistically significant (p> 0.05).Duration of

sensory and motor block:

The mean duration of sensory block in group A was 504 ± 32.81min and in

group B was 880 ± 59.91 min.

The mean duration of motor block in group A was 486 ± 32.40min and in group

B was ± 69.69min. This difference was statistically significant (P < 0.05).

Both differences were statistically significant (p < 0.05)

Rescue analgesic requirements: In post op 24 hours

In group B 75% of patients required only 1 and 25% of patients required

2 rescue analgesic doses in post op 24 hours.

In group A, 75% of patients required 2 and 25% of patients required 3

rescue analgesic doses in post op 24 hours.

Rescue analgesia requirement in group A was significantly higher (p<

0.05)

Haemodynamic variables:

Both groups were comparable with regard to pulse rate, systolic blood

pressure and diastolic blood pressure and O2 saturation. There was no

statistically significant difference (p> 0.05).

68
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2. Bazin JE, Massoni C, Bruelle P, Fenies V, Groslier D, Schoeffler P. The

addition of local anaesthetics in brachial plexus block: The comparative

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3. Keeler JF, Simpson KH, Ellis FR, Kay SP. Effect of addition of

hyaluronidase to bupivacaine during axillary brachial plexus block. Br J

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4. Culebras X, Van Gessel E, Hoffmeyer P, Gamulin Z. Clonidine combined

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Ondesetron as an adjuvant in supraclavicular brachial plexus block IOSR

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2319-4219 Volume 6, Issue 6 (June 2016), PP. 20-22

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adding 8 milligrams ondansetron to lidocaine for Bier‟s block on post-

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7. Omid Azimaraghi Yasaman Aghajani Maziar Molaghadimi Malihe

Khosravi Kobra Eslami Fatemeh Ghadimi Ali Movafegh Ondansetron

reducing pain on injection of etomidate: a controlled randomized study

Rev. Bras. Anestesiol. vol.64 no.3 Campinas May/June 2014

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ondansetron to lidocaine as a component of intravenous regional

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9. FARRUKH AYUB , INAM UL H AQ , MUHAMMAD ASIM GHAURI

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75
 CASE PROFORMA

NAME: I.P.NO:
AGE: HOSPITAL:
SEX: DOA:
V/NV:
WEIGHT:
DIAGNOSIS:
SURGICAL PROCEDURE:

PRE-ANAESTHESTIC ASSESSMENT:
 CHIEF COMPLAINTS:
 PAST HISTORY:
 PERSONAL HISTORY:
 GENERAL EXAMINATION:
 AIRWAY ASSESSEMENT: Mallampati grading:
 ASA GRADE:
PRE-OPERATIVE INVESTIGATIONS:
 Complete blood picture:
 Random blood sugar:
 Serum Urea:
 Serum Creatinine:
 BT:
 CT:
 HIV I & II:
 HBsAg:
 Complete urine examination:
 ECG:
 Chest x ray:

76
PRE-PROCEDURE VITAL SIGNS:
 Pulse rate (BPM):
 Blood pressure (mmHg):
 SPO2:
ANAESTHETIC MANAGEMENT-

POSITION:

PRE-MEDICATION:

TIME OF DRUG INJECTION:

DOSE:

ONSET OF SENSORY BLOCK :

ONSET OF MOTOR BLOCK :

INTRA-OPERATIVE MONITORING:

Pulse SpO2 % mm
rate SPB mm of Hg of Hg SpO2 %

0 min

5 min

15 min

30 min

60 min

2 hrs

6 hrs

12 hrs

24 hrs

77
INTRA-OPERATIVE FLUIDS ADMINISTERED:

DURATION OF SURGERY

POST OPERATIVE VITALS :-

TIME 0 (MIN ) 2 (Hrs) 6(Hrs)

12(Hrs)

PR

BP

(SBP/DBP)

SPO2

DURATION OF MOTOR BLOCK :

DURATION OF PAIN RELIEF:

78
 CONSENT FORM

You are invited to be a part of study “COMPARATIVE STUDY OF PLAIN

BUPIVACAINE AND COMBINATION OF BUPIVACAINE & ONDENSETRON
AS AN ADJUVANT IN SUPRACLAVICULAR BRANCHIAL PLEXUS
BLOCK”

Your participation in this study is entirely voluntary. The study period for 2
Years. The identity of those participating in the study will not be shared with
anyone. It will be kept confidential. If you do not wish to continue, you are free
to withdraw from the study at any time. Your treatment at the hospital will not
be affected in any way.

Informed Consent Form :

I have read the above information. I consent voluntarily to participate as

participant in this research.
Name of the participant ________________________
Signature of the participant ________________________
Date ________________________

If illiterate

I have witnessed the accurate reading of the consent form to the potential
participant. I confirm that the individual has given consent freely.

Name of the witness ________________________

Signature of the witness ________________________

Date __________________

thumb print of participant

Statement by the researcher/person taking consent

I confirm that the participant was given an opportunity to ask questions about
the study, and all the questions have been answered correctly and to the best
of my ability. I confirm that the individual has not been forced into giving
consent and the consent has been given freely and voluntarily.

Name of the researcher/person taking the consent

_______________________________________________________________

Signature of the researcher/person taking the consent

______________________________________________________________

Date _________________ Contact number of researcher

79
80
-

81
82
83
 KEY TO MASTER CHART

Sl No - Serial Number

IP No - In-patient number

RA - Rescue analgesics

Yrs - Years

Min - Minutes

Postop - Post-operative

PR - Pulse rate

SBP - Systolic blood pressure

DBP - Diastolic blood pressure

Spo2 - Oxygen saturation

84
 MASTER CHART BUPIVACAINE + ONDANSETRON

DIASTOLIC BLOOD PRESSURE

SYSTOLIC BLOOD PRESSURE
DURATION OF SURGERY

ONSET OF BLOCK(MIN)

DURATION OF BLOCK
PATIENT NAME

SATURATION
PULSE RATE
SLNO.

IPNO.
AGE

SEX

WT
SEN MOTOR SEN MOTOR 0min 5min 15min 30min 60min 2hr 6hr 12hr 24hr 0min 5min 15min 30min 60min 2hr 6hr 12hr 24hr 0min 5min 15min 30min 60min 2hr 6hr 12hr 24hr 0min 5min 15min 30min 60min 2hr 6hr 12hr 24hr
1 Ravi 54 M 90 23031 65 8 8 815 650 79 77 72 72 73 74 74 75 75 110 112 114 110 116 112 114 116 112 70 72 71 70 72 71 71 72 71 100 100 100 100 100 100 100 100 100
2 Sabeer 28 M 78 88245 70 7 8 875 710 82 78 79 77 77 77 76 77 77 122 124 122 122 120 126 118 124 120 79 81 82 81 80 82 81 80 82 100 100 100 100 100 100 100 99 98
3 shivani 31 F 89 19303 72 8 10 795 655 88 86 86 87 85 80 81 82 81 104 116 102 110 106 108 100 102 106 69 68 69 70 69 70 69 70 70 100 99 99 99 98 99 100 100 100
4 Gaurishanker 53 M 80 23570 68 8 9 805 645 79 76 78 78 79 81 81 79 80 112 118 112 114 110 112 112 114 110 73 71 73 74 72 72 71 72 71 100 100 100 100 100 100 100 100 100
5 Santhoshi 34 F 84 16423 76 7 7 835 635 70 68 67 66 67 71 71 70 70 120 122 120 124 120 122 118 118 122 79 81 82 82 81 82 81 81 82 99 100 100 100 100 100 100 100 100
6 Naveen 37 M 87 25806 70 8 7 825 690 87 85 84 86 82 78 85 84 84 108 116 110 106 110 112 110 110 102 66 69 70 71 71 69 70 69 71 100 99 100 100 100 100 99 100 100
7 Naresh 24 M 78 18716 69 9 8 815 695 80 76 75 75 74 75 74 74 76 126 128 124 126 128 120 122 122 124 81 84 85 83 85 84 83 83 83 100 100 100 100 100 100 100 100 100
8 Mamatha 22 F 80 36936 75 7 8 850 715 80 78 74 75 76 77 74 75 76 134 134 136 130 132 138 132 130 130 87 87 87 88 85 90 91 83 84 100 100 100 100 100 100 100 100 100
9 Nareen 38 M 88 23474 72 7 7 905 785 88 84 80 79 80 79 81 80 82 102 110 100 106 98 98 102 100 110 70 70 71 73 72 69 70 69 70 100 100 100 100 100 100 100 100 100
10 Sunitha 42 F 92 19759 80 8 9 915 845 74 70 67 67 67 67 68 69 68 106 114 104 104 102 110 106 100 102 72 71 70 71 69 66 69 68 69 100 100 100 100 100 100 100 100 100
11 Yadagiri 34 M 78 22373 74 9 8 865 715 74 72 70 69 70 70 71 70 71 120 122 128 120 126 120 118 118 118 80 81 80 78 79 80 78 79 80 100 100 100 100 100 100 100 98 100
12 Samreen 45 F 89 25444 66 8 8 855 725 84 80 81 79 77 80 80 78 81 122 120 122 122 124 120 118 122 120 67 62 66 66 68 67 67 66 67 99 100 98 100 100 100 99 100 100
13 Ramulu 32 M 87 16421 78 7 7 885 705 82 78 74 76 77 73 75 79 80 108 112 104 106 108 110 104 106 110 69 70 71 69 70 70 71 69 70 100 100 100 100 100 100 100 100 100
14 Lateeq 36 M 83 37069 82 8 8 895 745 78 76 76 73 70 73 74 70 72 130 132 130 132 132 134 130 128 126 84 84 85 82 81 82 81 79 78 100 100 100 100 100 100 100 100 100
15 Akram 20 M 77 22330 74 7 9 945 810 94 88 85 81 80 82 82 82 80 128 124 126 128 126 128 120 126 126 83 84 73 83 82 81 80 81 80 100 100 100 100 100 100 100 100 100
16 Lavanya 45 F 81 14788 66 8 8 910 795 78 76 73 71 67 70 71 70 69 106 108 100 100 96 104 102 104 102 67 62 66 66 68 67 67 66 67 100 100 100 100 100 100 100 100 100
17 Abbas 28 M 89 20901 70 9 7 755 685 79 77 73 74 71 73 72 79 80 130 132 130 130 134 128 126 130 128 69 70 71 69 70 70 71 69 70 100 100 100 100 100 100 100 100 100
18 kishore 22 M 78 38143 67 8 7 865 775 88 84 84 83 83 81 81 84 86 102 112 102 106 110 112 100 98 102 84 84 85 82 81 82 81 79 78 100 100 100 100 100 100 100 100 100
19 Saraswathi 20 F 78 30991 69 7 8 925 815 74 72 70 70 67 71 68 69 72 116 124 114 116 114 116 118 114 116 83 84 73 83 82 81 80 81 80 100 99 99 98 99 99 100 100 100
20 Renuka 21 F 90 26208 78 8 7 855 750 78 76 74 72 70 72 72 72 74 122 124 120 118 118 124 126 118 120 67 60 66 66 68 67 66 65 66 100 100 100 100 100 100 100 100 100
21 Mohammad 24 M 88 22569 76 9 8 865 730 82 78 79 80 80 82 82 80 84 114 118 116 114 116 112 112 114 116 69 70 71 69 70 70 71 69 70 99 100 100 100 100 100 100 100 100
22 Hema 31 F 82 19352 74 8 7 965 845 78 76 78 79 72 81 80 79 79 126 124 122 122 122 118 120 118 118 84 84 85 82 81 82 81 79 78 99 99 100 100 100 100 100 100 100
23 Anitha 38 F 86 16214 78 8 7 1005 895 74 69 64 66 61 65 64 66 68 118 130 128 130 124 126 128 130 132 81 87 86 89 82 80 82 84 88 100 100 100 100 100 100 100 100 100
24 Yadamma 22 F 81 19352 70 9 8 835 750 72 68 66 62 67 63 64 65 67 128 128 126 130 118 128 130 124 124 88 85 86 85 84 81 80 86 88 100 100 100 100 100 100 100 100 100
25 Sayyad 37 M 87 24694 84 8 7 935 855 90 88 87 88 84 80 81 84 81 108 106 110 108 106 110 106 108 108 68 69 71 71 70 72 74 73 74 100 100 100 100 100 100 100 100 100
26 Srinivas 40 M 78 23570 64 9 8 955 785 94 90 88 90 91 90 86 88 89 134 130 132 130 132 130 132 132 130 82 86 85 85 82 86 88 84 88 100 100 100 100 100 100 100 100 100
27 Naik 25 M 83 266621 68 8 7 845 765 72 70 69 66 66 65 65 67 69 126 125 126 124 120 124 122 124 124 80 82 82 82 84 83 86 84 87 100 100 100 100 100 100 100 100 100
28 Divya 22 F 76 24249 72 9 8 885 775 90 86 79 80 81 79 79 80 86 114 122 124 124 116 112 110 110 110 72 74 73 73 76 74 76 78 74 100 100 100 100 100 100 100 100 100
29 Ramulu 32 M 79 16421 74 7 7 925 835 86 84 82 83 82 83 83 83 84 122 120 120 122 120 122 120 122 120 82 84 86 88 84 83 80 82 84 100 100 100 100 100 100 100 100 100
30 Venkatesh 34 M 81 21906 80 9 8 995 845 84 80 78 77 77 78 78 77 81 118 120 118 120 116 118 120 116 120 70 72 71 72 78 76 74 78 75 100 100 100 100 100 100 100 100 100

MASTER CHART BUPIVACAINE

SYSTOLIC BLOOD PRESSURE

DURATION OF SURGERY

ONSET OF BLOCK(min)

DURATION OF BLOCK

DIASTOLIC PRESSURE
PATIENTNAME

SATURATION
PULSE RATE
SLNO.

IPNO.
AGE

SEX

WT

SEN MOT SEN MOT 0min 5min 15min 30min 60min 2hr 6hr 12hr 24hr 0min 5min 15min 30min 60min 2hr 6hr 12hr 24hr 0min 5min 15min 30min 60min 2hr 6hr 12hr 24hr 0min 5min 15min 30min 60min 2hr 6hr 12hr 24hr
1 Bicha 28 M 78 28618 75 9 10 465 455 82 78 76 77 76 78 81 82 83 110 112 114 110 116 112 114 116 112 71 72 71 70 72 71 71 72 71 100 100 100 100 100 100 100 100 100
2 Hussain 48 M 82 30687 66 7 9 495 480 84 82 79 78 76 77 76 79 79 122 124 122 120 126 118 118 124 120 81 81 81 81 80 82 81 80 82 100 99 99 99 99 100 100 99 99
3 srinu 28 M 76 30654 82 8 8 450 445 93 88 86 87 86 87 86 88 88 104 108 102 110 106 108 100 102 106 68 68 69 70 69 70 69 70 70 100 100 100 100 100 100 100 100 100
4 Akshay 53 M 86 28526 78 8 10 485 470 92 84 82 80 79 81 81 82 84 132 136 134 132 129 130 126 114 128 72 71 73 74 72 72 71 72 71 99 100 99 100 100 99 99 100 100
5 Sushmitha 34 F 82 14978 70 9 9 525 515 77 75 69 68 70 71 71 72 70 120 122 120 124 120 122 118 118 122 83 81 82 82 81 82 81 81 82 100 100 100 100 100 100 100 100 100
6 Ravinder 37 M 80 32086 67 7 8 455 425 92 86 84 83 84 81 82 84 84 108 116 110 106 110 112 110 110 102 68 69 70 71 71 69 70 69 71 100 100 100 100 100 100 100 100 100
7 Toufiq 24 M 88 81070 74 8 9 525 500 82 76 75 75 76 79 85 86 85 126 126 124 126 128 120 122 122 124 84 84 85 83 85 84 83 83 83 98 99 99 99 98 99 99 98 99
8 Ambika 22 F 79 15327 66 7 10 515 495 84 78 74 75 75 75 74 78 79 134 136 144 130 132 138 124 130 130 88 87 87 83 85 90 91 83 84 99 99 99 99 99 99 99 99 99
9 Nagaraju 38 M 81 17426 80 9 8 505 485 87 82 80 79 80 79 81 80 82 102 104 100 106 98 98 102 100 110 69 70 71 73 72 69 70 69 70 100 100 100 100 100 100 100 100 100
10 Jhanavi 24 F 85 17496 69 8 8 485 465 76 69 67 67 66 67 68 69 68 106 108 104 104 102 110 106 100 102 81 80 80 80 79 78 80 81 82 100 100 100 100 100 100 100 100 100
11 Ramulu 38 M 82 25483 84 7 7 495 478 80 73 70 69 70 70 71 72 74 120 128 128 120 126 120 118 118 118 82 81 80 78 79 80 78 79 80 100 100 100 100 100 100 100 100 100
12 Savithri 35 F 78 24727 82 8 10 475 455 87 83 81 79 79 80 80 79 81 122 124 122 122 124 120 118 122 120 66 62 66 66 68 67 67 66 67 100 100 100 100 100 100 100 100 100
13 Anathaiah 29 M 89 17062 78 8 9 515 490 86 80 79 81 81 80 82 80 80 108 110 106 108 108 104 104 106 110 70 70 71 69 70 70 71 69 70 100 100 100 100 100 100 100 100 100
14 Ram 25 M 85 307086 76 9 10 475 467 80 79 72 73 71 73 74 72 72 130 132 130 132 132 120 130 128 126 85 84 85 82 81 82 81 79 78 100 100 100 100 100 100 100 100 100
15 Mahaboob 18 M 76 39731 68 9 9 545 522 89 88 82 81 83 82 82 81 83 128 126 126 128 126 110 120 126 126 85 84 73 83 82 81 80 81 80 100 100 100 100 100 100 100 100 100
16 Swapna 45 F 80 33009 80 8 9 505 488 79 74 69 71 69 70 71 70 71 106 108 100 100 96 134 102 104 102 66 60 66 66 68 67 66 65 66 100 100 100 100 100 100 100 100 100
17 Chennaiah 28 M 75 37823 78 9 10 525 504 82 75 73 74 75 73 72 78 71 130 132 130 130 134 128 126 130 128 76 74 74 74 75 72 72 73 75 100 100 100 100 100 100 100 100 100
18 Poojitha 56 F 84 25888 65 8 9 545 526 92 84 84 83 84 85 86 82 83 128 112 102 106 110 112 100 98 102 74 75 74 74 74 76 74 74 76 100 100 100 100 100 100 100 100 100
19 Sabha 26 F 82 30109 79 7 8 495 476 78 76 74 72 70 71 68 69 70 118 116 114 116 114 116 118 114 116 72 70 71 72 70 72 71 71 72 100 100 100 100 100 100 100 100 100
20 Saraswathi 28 F 78 30991 67 9 10 465 448 74 73 74 72 71 72 72 73 72 130 126 120 118 118 124 126 118 120 80 79 79 80 81 82 83 81 82 99 99 98 97 99 98 98 97 99
21 Veeramma 33 F 77 24674 69 8 8 495 472 82 80 79 80 81 82 82 81 80 102 117 116 114 112 116 116 118 120 64 66 65 64 66 65 64 65 68 99 99 98 99 99 98 99 98 99
22 Anitha 45 F 81 16214 78 7 9 485 464 79 77 78 79 80 81 80 78 79 116 123 122 122 120 118 120 118 122 86 84 85 84 85 84 87 88 86 98 98 98 98 98 98 98 98 98
23 Krishnaveni 34 F 79 19086 75 9 9 510 498 91 89 91 90 89 88 89 88 90 124 130 128 130 124 126 128 130 130 88 87 88 81 89 87 87 89 86 99 99 99 99 99 99 99 99 99
24 Safia 36 F 84 180944 70 9 10 575 554 78 79 78 79 80 78 80 76 80 128 130 126 130 118 128 130 124 124 88 85 85 79 85 86 87 88 85 100 100 100 100 100 100 100 100 100
25 Balram 27 M 83 30991 79 7 9 535 516 88 90 88 88 89 87 89 89 86 108 112 110 108 106 110 106 108 108 68 69 70 71 71 70 71 71 71 100 100 100 100 100 100 100 100 100
26 Srinivas 38 M 92 23570 84 9 10 585 568 92 90 91 90 89 88 89 88 90 134 133 132 130 128 130 132 132 130 86 86 85 80 86 87 84 86 85 100 100 100 100 100 100 100 100 100
27 Srinath 50 M 80 18705 86 7 9 535 528 92 90 91 90 89 88 89 88 90 126 127 126 124 120 124 122 124 124 80 82 82 80 81 83 82 80 81 100 100 100 100 99 100 100 100 100
28 Reshma 32 F 85 22028 80 9 8 495 481 68 66 66 65 67 66 65 67 67 114 123 122 120 116 112 110 120 110 72 74 73 71 74 73 72 69 70 100 100 100 100 100 99 100 100 100
29 Subhash 25 M 76 88245 79 8 9 485 463 84 83 75 74 75 76 75 74 76 122 124 120 122 118 122 120 122 120 82 84 86 82 84 83 81 85 86 100 100 100 100 100 100 100 100 100
30 Venkatesh 36 M 88 21906 68 9 9 475 460 76 75 75 74 75 76 75 74 75 118 120 118 120 116 118 120 116 120 70 72 71 73 71 72 70 71 72 100 100 100 100 100 100 100 100 100