1

COMPARISION OF USE OF LEVOBUPIVACAINE WITH

DEXAMETHASONE VERSUS PLAIN LEVOBUPIVACAINE

IN PATIENTS UNDERGOING FOREARM SURGERIES

UNDER AN INFRACLAVICULAR BLOCK - A DOUBLE

BLINDED RANDOMIZED CONTROLLED TRIAL

Dissertation submitted to the Tamil Nadu Dr M.G.R. Medical University

in partial fulfilment of the requirement for the award of M.D.

(Anaesthesiology) degree April, 2017

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DECLARATION

I hereby declare that this dissertation titled “COMPARISION OF USE OF

LEVOBUPIVACAINE WITH DEXAMETHASONE VERSUS PLAIN

LEVOBUPIVACAINE IN PATIENTS UNDERGOING FOREARM

SURGERIES UNDER AN INFRACLAVICULAR BLOCK: A DOUBLE

BLINDED RANDOMIZED CONTROLLED TRIAL ” is carried out by me

under the guidance and supervision of Dr.Serina Ruth Salins, Associate

Professor in the department of Anaesthesiology, Christian Medical College,

Vellore.

This dissertation is submitted in partial fulfilment of the requirements for the

degree of MD Anaesthesiology examination of the Tamil Nadu

Dr.M.G.R.Medical University to be held in April 2017.

Vellore Dr.M.Anand Babu

Date: Reg No: 201520351

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CERTIFICATE

This is to certify that this dissertation, “COMPARISION OF USE OF

LEVOBUPIVACAINE WITH DEXAMETHASONE VERSUS PLAIN

LEVOBUPIVACAINE IN PATIENTS UNDERGOING FOREARM

SURGERIES UNDER AN INFRACLAVICULAR BLOCK: A DOUBLE

BLINDED RANDOMIZED CONTROLLED TRIAL”, is an original work of

research done by Dr.M.Anand Babu, Reg no. 201520351 that was carried out

under the guidance and supervision of Dr.Serina Ruth Salins, Associate

Professor in Anaesthesiology, Christian Medical College, Vellore towards

partial fulfilment of the requirements for the award of MD Anaesthesiology

examination to be held in April 2017.

Dr. Anna B Pulimood

Principal

Christian Medical College

Vellore

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CERTIFICATE

This is to certify that “COMPARISION OF USE OF LEVOBUPIVACAINE

WITH DEXAMETHASONE VERSUS PLAIN LEVOBUPIVACAINE IN

PATIENTS UNDERGOING FOREARM SURGERIES UNDER AN

INFRACLAVICULAR BLOCK – A DOUBLE BLINDED

RANDOMISED CONTROLLED TRIAL” is the bona fide work of Dr

Anand Babu M, reg No. 201520351 under my supervision in the Department

of Anaesthesia, Christian Medical College, Vellore in partial fulfilment of the

requirements for the M.D. Anaesthesiology Examination of the Tamil Nadu Dr.

M.G.R Medical University to be held in April 2017 and no part thereof has

been submitted for any other degree.

Signature of the Guide:

Dr.Serina Ruth Salins

Associate Professor

Dept of Anaesthesiology

Christian Medical College Hospital

Vellore 632004.

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CERTIFICATE

This is to certify that this dissertation, “COMPARISION OF USE OF

LEVOBUPIVACAINE WITH DEXAMETHASONE VERSUS PLAIN

LEVOBUPIVACAINE IN PATIENTS UNDERGOING FOREARM

SURGERIES UNDER AN INFRACLAVICULAR BLOCK: A DOUBLE

BLINDED RANDOMIZED CONTROLLED TRIAL”, is an original work of

research done by Dr.M.Anand Babu, Reg No. 201520351, that was carried out

under the guidance and supervision of Dr.Serina Ruth Salins, Associate

Professor in Anaesthesiology, Christian Medical College, Vellore towards

partial fulfilment of the requirements for the award of MD Anaesthesiology

examination to be held in April 2017.

Signature of the Head of the Department:

Dr. Sajan Philip George,

Professor and Head of the Department,

Dept of Anaesthesiology,

Christian Medical College Hospital

Vellore 632004

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PLAGIARISM CHECK

7

Clinical Trial Registry of India

REF/2016/02/010691

From:

<http://ctri.nic.in/Clinicaltrials/submittrialmain.php?EncHid=66553.94830&mod

id=1&compid=12&tid=13692>

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ACKNOWLEDGEMENT

I would like to thank the Lord Almighty for enabling me accomplish this dissertation

and helping me out in each and every step.

I express my sincere and heartfelt gratitude to Dr.Serena Ruth Salins, Associate

Professor, Department of Anaesthesiology, Christian Medical College, Vellore for her

encouragement, support and guidance during the study.

I express my sincere and heartfelt gratitude to Dr. Rahul Pillai, Assistant Professor

Department of Anaesthesiology, Christian Medical College, Vellore for his support

and assistance throughout the study.

I thank Dr.Kalyana Chakravarthy, Associate Professor Department of

Anesthesiology, Christian Medical College, Vellore for his support.

I acknowledge my sincere gratitude to Dr.Samuel C Raj, Professor and Dr. Kiran,

Assistant Professor, Department of Hand and Reconstructive surgery, Christian

Medical College, Vellore for being a great support as a Orthopaedic surgeon and

giving us generous encouragement for the conduct of this study.

My sincere thanks to Dr Vinoo Matthew Cherian and Dr Tilak, from Orthopaedics

department, for their co operation throughout the study.

I express my sincere thanks to Mrs Gowri, Senior demonstrator, Department of

Biostatistics, Christian medical college, Vellore for helping me through the study

design and statistical analysis of this study.

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I am extremely grateful to Dr. S. Anna Durai, Professor & In charge, Manufacturing

division, Department of Pharmacy who did meticulous work in ensuring blinding and

randomisation of the study drugs.

I express my sincere thanks to Dr. Sajan Philip George, Professor and Head,

Department of Anaesthesiology, Christian medical college, Vellore for his support and

encouragement throughout the study.

I thank all my colleagues and anaesthesia technicians for their sincere and

overwhelming support at all stages of this study.

I thank all the patients who consented to be part of this study without whom it would

be impossible to do this study.

I would like to thank my friends Dr. Samuel and Dr. Khushboo for going an extra mile

in helping me to complete the thesis.

I would like to thank my wife Dr Annie Prasanthi without whom it would be

impossible for me to accomplish this task of dissertation and with whom it was made

an easy task.

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TABLE OF CONTENTS

DECLARATION ............................................................................................................ 2

CERTIFICATE ............................................................................................................... 3

PLAGIARISM CHECK ................................................................................................. 6

Clinical Trial Registry of India ....................................................................................... 7

LIST OF ABBREVIATIONS ...................................................................................... 14

List of figures ................................................................................................................ 15

LIST OF TABLES........................................................................................................ 16

ABSTRACT ................................................................................................................. 19

1. INTRODUCTION ................................................................................................ 21

2. AIMS AND OBJECTIVES .................................................................................. 24

3. REVIEW OF LITERATURE ............................................................................... 25

ANATOMY .............................................................................................................. 26

SENSORY AND MOTOR INNERVATION OF THE ARM ................................. 29

ASSESSING THE EXTENT OF BRACHIAL PLEXUS BLOCKADE ................. 30

ADJACENT STRUCTURES ................................................................................... 32

HISTORY ................................................................................................................. 32

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APPROACH TO BRACHIAL PLEXUS ................................................................. 34

INTERSCALENE BLOCK ...................................................................................... 35

CERVICAL PARAVERTEBRAL BLOCK ............................................................ 36

INTERSTERNOCLEIDOMASTOID BLOCK ....................................................... 36

SUPRACLAVICULAR BLOCK ............................................................................. 37

INFRACLAVICULAR BLOCK .............................................................................. 38

AXILLARY BLOCK ............................................................................................... 41

COMPLICATIONS .................................................................................................. 41

a. Peripheral Nerve Injury ............................................................................... 41

b. Mechanical Trauma ..................................................................................... 42

c. Ischemic Trauma ......................................................................................... 42

d. Chemical injury ........................................................................................... 43

LOCAL ANAESTHETICS ...................................................................................... 45

LEVOBUPIVACAINE ............................................................................................ 46

ADDITIVES OR ADJUVANTS .............................................................................. 50

DEXAMETHASONE .............................................................................................. 51

4. MATERIAL AND METHODS ........................................................................... 54

RANDOMISATION, ALLOCATION CONCEALMENT AND BLINDING: ...... 55

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INCLUSION CRITERIA: ........................................................................................ 56

EXCLUSION CRITERIA: ....................................................................................... 56

CONSENT: ............................................................................................................... 56

IMPLEMENTATION: ............................................................................................. 57

PRIMARY OUTCOME: .......................................................................................... 62

SECONDARY OUTCOME: .................................................................................... 62

SUMMARY OF METHODOLOGY ....................................................................... 63

SAMPLE SIZE CALCULATION: .......................................................................... 64

STATISTICAL ANALYSIS .................................................................................... 65

5. RESULTS ............................................................................................................. 66

DESCRIPTION OF BASELINE CHARACTERISTICS ........................................ 66

DATA OBTAINED DURING THE INTRA OPERATIVE PERIOD .................... 74

DATA OBTAINED IN THE POST-OPERATIVE PERIOD .................................. 88

6. DISCUSSION ....................................................................................................... 92

7. CONCLUSION .................................................................................................... 97

8. LIMITATIONS .................................................................................................... 98

9. Scope For Future Research: .................................................................................. 99

10. BIBLIOGRAPHY ............................................................................................ 100

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11. ANNEXURES .................................................... Error! Bookmark not defined.

Annexure 1: Institutional review board acceptance and fluid grant letter ............. 111

Annexure 2: Information sheet ............................................................................... 114

Annexure 3:Informed consent form ....................................................................... 115

Annexure 4: Informed consent in Hindi ................................................................. 116

Annexure 5: Patient information sheet in Hindi ..................................................... 117

Annexure 6: Patient information sheet in Tamil .................................................... 118

Annexure 6: Patient information sheet in Tamil .................................................... 118

Annexure 7: Informed consent form in Tamil ........................................................ 119

Annexure 8: PROFORMA of the study ................................................................. 120

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LIST OF ABBREVIATIONS

VAS VISUAL ANALOGUE SCALE

LA LOCAL ANAESTHETIC

GA GENERAL ANAESTHESIA

ASA AMERICAN SOCIETY OF ANESTHESIOLOGISTS GRADING OF

PHYSICAL STATUS

BMI BODY MASS INDEX

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List of figures

Figure 3.1: Anatomy of brachial plexus

Figure 3.2: Cutaneous sensory distribution of upper extremity (anterior view)

Figure 3.3: Cutaneous sensory distribution of upper extremity (posterior view)

Figure 3.4: mechanism of peripheral nerve injury

Figure 4.1: Ultrasound machine S-nerve

Figure 4.2:High frequency linear probe 13-6 MHz

Figure 4.3: sonoplex needle

Figure 4.4: ultrasound image - posterior cord

Figure 4.5: ultrasound image – lateral cord

Figure 4.6: ultrasound image – medial cord

Figure 4.7: flow chart of the study

Figure 5.1: range of age in both groups

Figure 5.2: ASA grading

Figure 5.3: distribution of study population

Figure 5.4: comparison of duration of surgery

Figure 5.5: frequency distribution of midazolam

Figure 5.6: frequency distribution of fentanyl

Figure 5.7: adequacy of surgical anaesthesia

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LIST OF TABLES

Table 5.1 General Demographic Characteristics Of Study Participants In Relation To

Drug

Table 5.2: Association Of Variables With Drug

Table 5.3: American Society Of Anaesthesiologists Grading Of Physical Status

Classification In Study Population

Table 5.4: Association Of ASA Grading And Drug:

Table 5.5: Frequency Distribution Of The Drug

Table 5.6 Comparison Of Duration Of Surgery In Both Groups

Table 5.7 Comparison Of Means And Standard Deviations (SD) Of Baseline

Characteristics

Table 5.8 Frequency Distribution Of The Midazolam

Table 5.9 Frequency Distribution Of The Fentanyl Administered

Table 5.10 Sensory Grading Of Radial Nerve

Table 5.11: Improvement Of Radial Nerve And Drug Association

Table 5.12 Association For Onset Of Anaesthesia And Drug In Radial Nerve

Table 5.13 Association For Onset Of Anaesthesia And Drug In Median Nerve

Table 5.14: Improvement Of Median Nerve And Drug Association

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Table 5.15 Association Between Onset Of Sensory Blockade And The Drug For

Median Nerve

Table 5.16 Association Between Onset Of Sensory Blockade And The Drug For Ulnar

Nerve

Table 5.17: Improvement Of Ulnar Nerve And Drug Association

Table 5.18: Association Between Onset Of Sensory Blockade And The Drug For

Ulnar Nerve

Table 5.19: Duration And Motor Grading Using Modified Bromage Scale

Table 5.20: Motor Grade Improvement And Drug Association At 5 Min

Table 5.21: Motor Grade Improvement And Drug Association At 20 Min

Table 5.22: Modified Bromge Scale Grading In Association With Drug

Table 5.23: Adequacy Of Surgical Anesthesia

Table 5.24: Association between Adequacy Of Surgical Anaesthesia And Drug Used

Table 5.25: VAS Score

Table 5.26: VAS Score In Relation To Levobupivacaine and Dexamethasone

Table 5.27: VAS Score In Relation To Levobupivacaine

Table 5.28: Supplementation of Aceclofenac In Study Population

Table 5.29: Aceclofenac Administration In Relation To Drug

Table 5.30: Supplementation Of Morphine In Study Population.

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Table 5.31: Association Of Morphine And Drug.

Table 5.32: Supplementation Of Paracetmol In Study Population

Table 5.33: Association of Paracetamol And Drug

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ABSTRACT

BACKGROUND: Regional neural blockade with local anaesthetic can reduce pain

following orthopaedic surgery and result in greater patient satisfaction. Injecting local

anaesthetic around the brachial plexus is useful in providing anaesthesia to patients

undergoing upper limb surgeries. Infraclavicular block has been proven to be safe to

perform and in efficacy compared to other approaches. Levobupivacaine is a long

acting local anesthetic which is an S( -) enantiomer of bupivacaine with less

cardiovascular and central nervous system toxic effects. Dexamethasone prolongs the

action of local anesthetics.

METHODS: This was a randomized controlled double blinded study approved by the

Institutional review board and ethics committee of Christian Medical College, Vellore.

This study was registered under clinical trial registry of India. Block randomization

was used. Study was done among the patients who underwent forearm orthopaedic

surgeries in Christian Medical College, Vellore between May 2016 to August 2016.

Inclusion criteria: Age between 18-70yrs posted for forearm surgery, ASA I-III,

weight greater than or equal to 50 kg. Exclusion criteria: Patients who are not willing

for the block, patient’s with coagulopathy, local infection over the block area,

pregnant women, patients requiring general anaesthesia, patient’s weighing less than

50kg, allergy to local anesthetic. A total of 40 patients of ASA (American Society of

Anaesthesiologist) preoperative risk classification I, II and III aged between18 years to

70 years were recruited in the study.

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STATISTICAL ANALYSIS: Data was summarized using mean (SD)/ median (IQR) for

continuous variables and frequency (percentage) for categorical variables. Independent

test/ranksum test (continuous) and chi-square (categorical) tests were used to compare the

baseline characteristics among the drugs. The outcome was defined as grade improvement

from 3min to 20min. A chi-square test was performed to compare the improvement among

drugs. A fisher exact test was used to compare the 3 min and 20 min grading among the drug

groups. All the significance levels were kept for p<0.05. All the statistical analysis was done

using stataic 13.1.

RESULT: In this study we assessed 45 patients for eligibility to be included in the study. 5

patients were excluded as some of them did not fulfill the inclusion criteria and for some

others there was a change in the operative plan on the day of surgery. Hence a total of 40

patients were recruited. Data collected from 40 patients was analyzed with 20 patients in one

arm and 20 patients in another arm.

CONCLUSION: There was no statistical difference in the onset of sensory and motor

blockade and in the duration of post-operative analgesia in the two groups: 0.5%

Levobupivacaine with Dexamethasone and 0.5% Levobupivacaine with normal saline added

in infraclavicular block in patients undergoing forearm orthopaedic surgeries. However there

was a significant improvement in sensory grading of median nerve and ulnar nerve between a

duration of 3 min and 20 min.(P value was 0.028 and 0.013 respectively) in the group with

0.5% Levobupivacaine with 4mg of dexamethasone in comparison with the group with 0.5%

Levobupivacaine with 1 ml of normal saline.

KEYWORDS: Levobupivacaine, Dexamethasone, Infraclavicular Block, Visual

Analog Score, Forearm Surgery

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1. INTRODUCTION

Severe post operative pain in orthopaedic upper limb surgeries remains a major

problem. It occurs in 20-40% of patients(1). Anesthesia for orthopaedic surgeries

involving upper limb can be provided by general anesthesia. Regional nerve blocks or

nerve blocks can supplement general anesthesia to provide intra operative and

postoperative analgesia and minimise the problems associated with general anesthesia.

Brachial plexus nerve block with local anesthetic provide an alternate for general

anesthesia for surgeries involving upper limb (2). Regional neural blockade with local

anesthetic can reduce chronic pain following orthopaedic surgery and result in greater

patient satisfaction (4). It provides longer duration of pain free period in the post

operative period (3).

The upper limbs of the body are supplied by a group of nerves. These nerves provide

sensation and movement to hand, forearm and arm. All these nerves arise from

brachial plexus. Injecting local anaesthetic around this brachial plexus is useful in

providing anaesthesia to patients undergoing upper limb surgeries. There are many

techniques of injecting local anaesthetic around the brachial plexus to provide

anaesthesia for surgery of the forearm. The brachial plexus can be approached with a

needle at various positions along its course. Some of the names of the techniques of

brachial plexus block are interscalene block (injection is given between a pair of

muscles called scalenus), supraclavicular block (injection above the collar bone),

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infraclavicular (injection below the collar bone) and axillary block ( injection at the

armpit ) and mid humeral technique ( injection at the mid arm region).

Infraclavicular block has been proven to be safe to perform and in efficacy compared

to other approaches(2). In experienced hands it reduces the complications and results

in better block (4). Ultrasound machine is used to identify the nerves and inject the

local anaesthetics. Alternately a machine called nerve stimulator is also in practice to

perform this procedure. Performing block under ultrasound guidance showed

superior results of successful sensory and motor blockade(5).

Local anaesthetics are a class of drugs that block the nerve action and prevent pain

and sensation when injected close to the nerves. There are many types of local

anaesthetic drugs with varied duration of action. Levobupivacaine a long acting local

anesthetic is an S( -) enantiomer of bupivacaine with less cardiovascular and central

nervous system toxic effects has been in clinical use for regional blocks since 20 yrs

(6).It provides equal efficacy to bupivacaine with lesser side effects(7). Increasing

dosage of local anesthetic is associated with increased incidence of systemic

toxicity(6). There are some ways to increase the duration of the action of the local

anaesthetics and prolong the time of pain relief. Pharmacological agents used as

adjuvants that increase the duration of local anesthetic action prolong the

postoperative analgesia of the patient during post operative period. Effective analgesia

is maintained during the postoperative period with the decreased use of opioid agents

(8,9). This also allows a continuous extended release of local anesthetic (10). One of

the drugs that prolong the action of local anesthetics is dexamethasone.

Dexamethasone improves the postoperative pain relief (3).

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Perineural dexamethasone prolonged the durations of analgesia and motor blockade

when used with local anaesthetics (8). Decreased nociceptive C-fibre activity via a

direct effect on glucocorticoid receptors and inhibitory potassium channels is probably

the mechanism of action of dexamethasone. Some authors suggest a local

vasoconstrictive effect which results in reduced local anesthetic absorption(11)

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2. AIMS AND OBJECTIVES

AIM:

The aim of this study is to compare the efficacy of Levobupivacaine with

dexamethasone versus plain Levobupivacaine in patients undergoing forearm

surgeries under an infraclavicular block of anaesthesia.

OBJECTIVES:

To compare the onset of sensory and motor blockade of 0.5% Levobupivacaine

with 4 mg dexamethasone and 0.5% Levobupivacaine with 1 ml of normal

saline added in infraclavicular block in patients undergoing forearm

orthopaedic surgeries.

To compare the duration of post-operative analgesia of 0.5% Levobupivacaine

with 4 mg dexamethasone and 0.5% Levobupivacaine with 1 ml of normal

saline added in infraclavicular block in patients undergoing forearm

orthopaedic surgeries.

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3. REVIEW OF LITERATURE

For surgeries involving extremity, regional anaesthesia is an excellent alternative to

general anaesthesia(12). Lower arm anaesthesia, from the elbow to the hand, may be

achieved promptly by injection of local anaesthetic around the brachial plexus(13). It

provides better analgesia in the post operative period and quicker recovery from the

anaesthesia. During the early postoperative phase of healing, sometimes post operative

analgesic duration is not adequate to compensate acute nociception associated with

surgery. In an effort to enhance post operative analgesia, many adjuvants like

clonidine, neostigmine, epinephrine, tramadol, buprenorphine and dexamethasone

have been added to local anesthetics (LA)(12,14). Several clinical studies have

evaluated the effectiveness of dexamethasone applied perineurally with local

anaesthetics in regional nerve blocks including epidural(15,16) brachial plexus (17),

femoral and sciatic(18) and facial and dental blocks (19). Alternatives used for

measuring postoperative pain (e.g., duration of analgesia, pain scores, opioid

consumption) appear to be improved by the addition of dexamethasone to LA agents

injected perineurally (20). Pain scores were lowered at 24 hours and 48 hours

postoperatively by adding dexamethasone to local anaesthetic, corresponding to less

opioid consumption over those 24– 48 hours. This opioid-sparing effect could result in

decreasing opioid-related noxious effects like nausea, vomiting, urinary retention,

constipation, pruritis and respiratory depression(12). Perineurally administered

dexamethasone added to local anaesthetic during the brachial plexus block delayed the

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latency and prolonged the recovery of motor block. This is similar to the analysis done

by Choi et al (21). The technique of brachial plexus block may result in

neurological complications including respiratory distress, Horner’s syndrome and

recurrent laryngeal nerve injury(22).

ANATOMY

The brachial plexus are a group of nerves that begin as spinal nerve roots and continue

as nerves to the end branches and supply the upper limb. The main purpose of the

brachial plexuses is to provide nerves supply to the upper limb but it also provides

sensory and motor branches to cervical and upper thoracic wall. The brachial plexus

origins as the accord of the ventral primary rami of cervical nerves 5 to 8 (C5–C8) and

a most of the first thoracic nerve (T1). Sometimes fourth cervical C4 vertebrae and

second thoracic nerve T2 contribute in the plexuses. (23). The roots of brachial

plexuses are the ventral rami. The brachial plexuses originate in neck and then

descend into the root of the neck, between the scalene muscles the nerve roots

coalesce and form trunks.

These trunks divides at clavicle into divisions i.e., anterior and posterior which again

coalesce and form cords and runs under the clavicle (collarbone) and in position to

the 2nd part of the axillary artery are classified as medial, lateral and posterior cords.

27

The cords run through the axilla (armpit) and give rise to the nerves and down the

arm. The cervical rami C5 and C6 typically coalesce near the medial margin of the

middle scalene muscle and become the superior trunk of the brachial plexus; the C7

ramus gives rise to the middle trunk; and the lower cervical rami C8 and upper

thoracic rami T1 unite and form the inferior trunk. The absence of anterior tubercle

C7 transverse process, helps in ultrasonographic location of the C7 nerve root(24)

Through the interscalene groove the roots and trunks traverse. Interscalene groove is a

palpable surface and identification landmark between the anterior and middle scalene

muscles. At the lateral border of the first rib, each trunk divides individually and gives

anterior and posterior divisions.

Divisions reorganize into cords. Cords are defined by their relationship to the second

part of the axillary artery. The lateral cord is the result of the fusion of anterior part of

superior and middle trunks of the plexus, the posterior divisions of all trunks unite and

form the posterior cord; and the anterior division of the inferior trunk gives rise to the

medial cord. The three cords divide and give rise to the terminal branches of the

plexus. From each cord two main terminal branches and many small and

intermediary branches originate (23). Lateral cord gives rise to musculocutaneous

nerve and the lateral component of the median nerve. The dorsum of the upper limb is

supplied by the radial and axillary nerves which are the terminal braches from the

posterior cord. The ulnar nerve and the medial component of the median nerve arise

from the median cord.

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Figure 3.1: Anatomy of Brachial Plexus

29

SENSORY AND MOTOR INNERVATION OF THE ARM

The knowledge regarding the cutaneous dermatomal distribution of nerves and the

nerve supply to the end branches is important in identifying the incomplete blockade

during surgeries and to identify whether the patient had preoperative neurological

deficit or postsurgical deficit. Understanding the sensory and motor supply is

important to elicit adequacy of anesthesia during block performance involving the

upper limb. The cutaneous supply of the upper limb arises from different spinal

segments. Motor supply can be elicited by using a peripheral nerve stimulator and

stimulation response to the nerve.

Figure 3.2 Cutaneous Sensory Distribution of the Upper Extremity (Anterior view)

30

Figure 3.3 Cutaneous Sensory Distribution of the Upper Extremity (Posterior view)

ASSESSING THE EXTENT OF BRACHIAL PLEXUS BLOCKADE

Innervation of the arm comes from different nerves. Hence the extent of blockade is

best assessed by assessing the functions unique to each terminal nerve. A method of

31

performing such an assessment is the 4 P’s(25). The patient is asked to push the arm

by extending the forearm at the elbow against resistance (radial nerve), this is

followed by resisting the pull of the forearm at the elbow (musculocutaneous nerve).

The ability to distinguish a pinch at the palmar base of the index finger assesses the

median nerve, whereas another pinch at the palmar base of the little finger evaluates

the ulnar nerve. Movement of the little finger during infraclavicular block (ICB) helps

in identifying which cord is being stimulated. With the arm adducted, movement of

the little finger medially toward the body indicates the stimulation of the medial cord,

whereas stimulation of lateral cord is by the lateral movement away from the body.

The posterior cord stimulation is identified by the posterior movement of the little

finger (26).

Peripheral nerves are made of a varying number of fascicles that consist of individual

nerve fibers (axons). These individual nerve fibres are contained within endoneurium.

Fascicles are enclosed within perineurium, while groups of fascicles are enclosed

within epineurium. As the nerve travels away from the spinal cord, the density of the

epineurium (stroma and connective tissue) decreases, but its total volume increases.

The amount of neural tissue remains stable.

Thus, the ratio of non neural to neural tissue contained within the epineurium

increases from 1:1 in the proximal plexus to 2:1 in the distal plexus. The cross-

sectional area of a peripheral nerve may consist of up to 70% loose connective

tissue(27). The clinical significance of this observation is that when a needle enters a

peripheral nerve by mistake, it does not always come to rest within a fascicle but may

instead lie within connective tissue.

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ADJACENT STRUCTURES

Vascular structures are very important anatomic landmarks and the structures to be

avoided while performing the block. The vertebral artery course forwards from its

origin in the subclavian artery. The cervical roots of the brachial plexus travel directly

posterior to the vertebral artery as they exit the intervertebral foramina(28). This

places the vessel at a potentially vulnerable site for intravascular injection, especially

if the needle courses anterior and medial to the anterior scalene muscle. The external

jugular vein usually overlies the interscalene groove at the level of C6. The subclavian

artery lies close to the brachial plexus as they travel over the first rib. Here, the

trunks/divisions of the brachial plexus lie posterior, cephalad, and ultimately lateral to

the subclavian artery(28). They form a reliable anatomic landmark during placement

of supraclavicular block(29). Nerve-vascular relationships change with the changes in

the arm position and during application of external pressure while performing the

block.

HISTORY

Halstead first performed brachial plexuses block using cocaine under direct

visualisation. Later on, Herschell described the percutaneous brachial plexus

block(54). Labat was the first to describe in his book of regional anaesthesia about

33

infraclavicular block in 1922(55). The first description of a neurostimulation-guided

infraclavicular block was by Raj and colleagues in 1973(56). Whiffler (57) followed

in 1981 with his description of the technique using the coracoid process as the main

surface landmark, but it was not until Kilka and colleagues described their vertical

infraclavicular plexus block in 1995 that significance in the infraclavicular approach

really blossomed(54). Lateral sagittal infraclavicular block using MRI has shown to

be effective in measuring the depth and angle and success of block (58).

Since then several alternatives of the nerve stimulation guided infraclavicular block,

using slightly different surface landmarks, have been described and adopted into

clinical practice. Most recently, ultrasound-guided techniques of infraclavicular block

(49,59) in which the axillary artery and surrounding brachial plexus are directly seen

using ultrasound and have gain more importance . By allowing direct visualization of

the needle tip, target nerves and the spread of local anaesthetic as it is injected

ultrasound can improve the success of the block(60). Study conducted by Wu TJ et al

has shown the advantage of ultrasound guidance they were able to identify the nerves

segments and with ease performed the infraclavicular block (61). Sandhu et al

suggested deposition of the drug is accurate using ultrasound, the brachial plexuses are

seen in real time imaging where they observed the deposition of the drug around the

targeted nerves (62). Posterior parasagittal in plane approach using ultrasound by Zhi

Yuen et al suggested better success rate(63) .

34

APPROACH TO BRACHIAL PLEXUS

There are many techniques of brachial plexus blockade that can be used to provide

anaesthesia for surgery of the lower arm. The brachial plexus may be approached with

a needle at various sites along its course. The ability to accurately localize a nerve or

plexus and successfully place local anesthetic around the structure is both an art and

science. The use of ultrasound for brachial plexus block helps the practitioner

visualize anatomy, needle placement and local anesthetic spread. The use of

ultrasound and the basic rules of safe regional anesthesia practice help in successful

and safe performance of brachial plexus block. The basic rules of safe regional

anesthesia include good training, knowledge of anatomy and careful technique

including slow injection of local anesthetic with regular syringe aspiration and

maintenance of verbal contact with the patient. These approaches include interscalene

block where the trunks are blocked (where the needle passes between the scalene

muscles after piercing the skin in the front of the neck); supraclavicular block, the

brachial plexus are blocked at the level of cords (where the skin is pierced in the root

of the neck above the clavicle lower and more laterally); infraclavicular block

functionally blocks the cords (where the skin is pierced in the area below the clavicle)

; axillary block (where the skin is pierced in the axilla) where the nerves are

anaesthetised and mid-humeral block (where the skin is pierced in the upper

arm)individual nerves are blocked.

35

The choice of which technique to use depends upon the practitioner’s preference, site

of the surgery, expected efficacy and safety of each technique(13).

INTERSCALENE BLOCK

Winne demonstrated land mark technique of interscalene block by identifying scalene

muscles at the level of cricoid and suggested the interscalene space is in contact with

subclavian perivascular space(30). Rochh et al proposed identification of paraesthesia

in the shoulder alone sufficient for drug administration and will result in successful

interscalene block (31). Some radiological studies have shown a higher volume of

drug can cause complete cervical and brachial plexuses block (32) .The perineural

space surrounding the brachial plexuses aids in the spread of local anaesthetic but

might not be spread evenly resulting in incomplete blockade(33) . The placement of

catheter straighter or angulated around the trunks for continuous interscalene block is

achieved better using modified lateral technique as demonstrated by Borgeat A (34)

As reported by Urmey et al, high occurrence of ipsilateral phrenic nerve blockade

with interscalene block is almost 100% under ultrasound guidance and also decrease

in the pulmonary function even with lesser volumes of local anesthetics (35). Incidents

of severe hypotension and bradycardia in patients undergoing awake shoulder surgery

occur due to stimulus from intracardiac mechanoreceptors in sitting position and this

36

response can be reduced by prior administration of beta blockers (36). Spread of the

drug into the epidural space and intrathecal administration is prevented with the

correct placement of the needle around a depth of 2.5 cm and an angulations at 50

degrees in caudal plane (37) .

This block should be avoided in deeply sedated patients and after administering

general anesthesia as intramedullary needle placement and cervical spinal cord injury

damage are reported to occur(38) .

CERVICAL PARAVERTEBRAL BLOCK

Cervical paravertebral block is mainly used for surgeries involving shoulder. Posterior

approach to the brachial plexus were popularised by Pippa et al and recently redefined

by Boezaart et al. There is less motor blockade (39) and a greater ease of perineural

catheter placement(40) with cervical paravertebral block as compared with traditional

interscalene approaches.

INTERSTERNOCLEIDOMASTOID BLOCK

The inter-sternocleidomastoid block (ISCMB) is used in the surgery of hand and arm.

In this technique the needle is directed laterally between the heads of the

sternocleidomastoid muscle(41). This technique is popularised for its ease of catheter

insertion and supposedly reduces the risk of pneumothorax.

37

SUPRACLAVICULAR BLOCK

Supraclavicular block, the brachial plexus at the level of cords is blocked (where the

skin is pierced lower and more laterally in the root of the neck above the clavicle).

Many approaches like classic approach of Kulenkampff , Winne’s subclavian

perivascular technique, modified lateral paravascular approach by Moorthy (42,43) are

published and in use .

Plumb-bob technique by Brown and Bridenbaugh’s is commonly used as it is

associated with less chance of pneumothorax(44) . To reduce the chance on

complications of vascular puncture and lung injury Klasttad et al proposed that initial

needle advancement should be directed cephalad with an 45 degree angulation and

then gradually move caudally. Identifying hand contraction while stimulating middle

trunk results in efficient block. Ultrasound enables faster implementation of

supraclavicular block and avoids sparing of ulnar nerve in comparison to nerve

stimulator and landmark technique(45). Identification of subclavian artery and bunch

of grapes is needed in an ultrasound approach. The volume of drug administered by

conventional landmark, using nerve stimulation or ultrasound should be same(46).

Pneumothorax is the most common complication associated with supraclavicular

block. Hemi diaphragmatic paresis is common. Its incidence in supraclavicular block

is 50% - 60% using nerve stimulator technique(47) while its occurrence is low using

ultrasound. Other complication is vascular injury to subclavian artery and transverse

cervical artery.

38

INFRACLAVICULAR BLOCK

The infraclavicular space is a pyramidal shaped and contains the brachial plexus,

subclavian-axillary artery and vein, and lymph nodes and loose fatty tissue .The apex

is a triangular surface. It is formed by the confluence of the clavicle, scapula and first

rib. The base of the triangle is formed by the skin and subcutaneous tissue of the

armpit. The posterior wall is formed by the scapula and its associated muscles and

their investing fasciae and the anterior wall by the pectoralis major and minor. The

lateral wall is constituted by humerus, and the converging muscles and tendons of the

anterior and posterior walls that insert into it.

The bony thoracic cage with its overlying layer of serratus anterior muscle and fascia

forms the medial wall. At the level of the infraclavicular space the brachial plexus is

organized as three cords (lateral, medial and posterior) surrounding the axillary artery.

The infraclavicular block targets the brachial plexus in the infraclavicular space.

Infraclavicular block functionally blocks the cords (where the skin is pierced in the

area below the clavicle).

None of the major terminal branches arise at this level(13). The purported advantages

of infraclavicular block are as follows. First, it provides complete anaesthesia of the

upper limb because it blocks the brachial plexus at the place where the three cords run

close together in a neurovascular bundle with the axillary artery. The axillary block

often fails to block the axillary nerve and musculocutaneous nerves, while the

39

interscalene and supraclavicular approaches may often fail to grant anaesthesia in the

distribution of the ulnar nerve. There also appears to be a lower incidence of

tourniquet pain with the infraclavicular block. This is attributed to spread to the

intercostobrachial nerve that runs close to the brachial plexus in the infraclavicular

space(48,49). Secondly, the risk of unintended lung or pleural puncture is lower than

with the interscalene and supraclavicular approaches as the lung does not lie in the

path of the needle. Thirdly, by piercing the skin below the clavicle, injury to the other

neurovascular structures in the neck are avoided (unlike with the interscalene or

supraclavicular approaches). Fourthly, infraclavicular block does not require

abduction of the arm at the shoulder can be performed in any arm position and neck

position need not be changed. Finally, it is an ideal site for inserting a catheter for

continuous infusion of local anaesthetic.

The bulk of the pectoralis muscle firmly anchors the catheter, arm movement is not

impaired and hygiene is easily maintained(50).

Tourniquets are frequently used in orthopaedic surgeries to give relatively a clear field

for operation and to reduce overall blood loss. Tourniquet pain is a common

complication associated. Tourniquet pain may occur in around 66 percent of the

patients following approximately one hour after cuff inflation. The probable

underlying pathophysiology for tourniquet pain is both mechanical compression and

ischaemia of the nerve. During local anaesthetic induced conduction blockade, small

unmyelinated C fibres are more resistant in comparison to large myelinated A fibres.

40

Hence as the concentration of local anaesthetic comes down, the C fibres begin to

conduct impulses earlier. As a result dull tourniquet pain occurs (61).

The decrease in tourniquet pain has been attributed to local anaesthetic spread to the

intercostobrachial nerve. This arises from the second thoracic nerve root and runs

through the axilla in close proximity to the axillary vein and infraclavicular space to

supply part of the medial surface of the upper arm (49). The infraclavicular block was

also faster to perform than the multiple-injection techniques of axillary block and

midhumeral block, by an average time difference of three and five minutes

respectively. This advantage is slightly offset by the increased sensory block onset

time observed with infraclavicular block. The overall complication rate of the

infraclavicular block was low and no different from that observed with the other

blocks. Exclusively there were no case reports of pneumothorax.

The risk of Horner’s syndrome was also significantly reduced with the infraclavicular

block approach. Vascular puncture was the most commonly observed complication of

infraclavicular block due to the proximity of the axillary artery and vein to the brachial

plexus. This is in view of high risk patients with coagulation abnormalities as the

axillary vessels are deeply placed in the infraclavicular region may make it harder to

achieve haemostasis by compression(13). But with the advent of ultrasound guidance

the risk of vascular penetration is significantly reduced.

41

AXILLARY BLOCK

Axillary block is commonly indicated for hand, elbow and forearm surgeries. Axillary

artery is the landmark for axillary block. The neurovascular bundle is oriented around

the axillary artery. Median nerve is above axillary artery, ulnar nerve is below and

radial nerve is posterior or lateral to axillary artery. Axillary block effectively blocks

median nerve, ulnar nerve and radial nerve. It fails to block musculocutaneous and

intercosto brachial nerves as they course away from the axillary artery and leave the

brachial plexus at the level of coracoid process. Musculo cutaneous nerve can be

blocked by injecting into the coracobrachialis muscle. Radial nerve identification is

very crucial in the success of the block as it is deepest and difficult to access.

Deposition of local anaesthetic around the axillary artery results in successful block

(62).

COMPLICATIONS

Brachial plexus blockade is associated with complications like seizures, cardiac arrest,

death and radiculopathy.

a. Peripheral Nerve Injury

Peripheral nerve injury is an uncommon problem during regional anesthesia. It can

present as numbness, reduced sensation or rarely as paresis (64). Timing of

presentation of nerve injury is variable. Considerable part of injuries is evident during

the early postoperative period. Reason for immediate presentation of the neurological

deficits within the first 24 hours is mostly due to haematoma, edema of the nerve or a

42

lesion involving a significant number of axons. Delayed symptoms may present weeks

after surgery. Cause for delayed neuropathy is probably due to tissue reaction or scar

formation resulting in degeneration of nerve fibre or due to pain or immobility in the

perioperative period. Many factors contribute for nerve injury in the peri operative

period.

Unrelated risk factors to anesthesia include patient and surgical issues. Mechanical

trauma, ischemic injury, or chemical injury contribute to anaesthesia related nerve

injury and are directly related to regional anesthetic factors.

b. Mechanical Trauma

Rice and McMahon (68) reported that long-bevelled needles in the parallel

configuration caused less neuronal damage in comparison with transverse long- or

short-bevelled needles. This finding was seen instantly after injury and at 7 days later

also. Injuries caused due to long-bevelled needles were slowly resolving whereas

those caused by short-bevelled needles showed signs of severe injury. Neural repair

may be accelerated and more structured with long-bevelled injuries. Hence long term

consequences are less concerning(68).

c. Ischemic Trauma

Failure of blood flow to primary afferent nerve causes metabolic stress.

Microcirculation of peripheral nerve consists of blood vessels within the endoneurium

and an extrinsic supply of larger, non nutritive vessels(69).The function of a peripheral

nerve is very much reliable on its microcirculation. Extrinsic blood supply is

responsive to epinephrine. Epinephrine may aggravate nerve injury if there is a barrier

43

disruption. Barrier disruption of the nerve may occur due to intraneural injection(70)

or due to chemotherapy-induced neurotoxicity, atherosclerosis or diabetic

neuropathies(71). Intrafascicular injection of local anesthetic may also cause ischemic

nerve injury(70). This may cause degeneration and dystrophy of axon. Later fibroblast

proliferation occurs at the injury site. These changes may cause delayed tissue reaction

or scar formation. As a result symptoms of neurological injury may manifest days to

weeks after the peripheral nerve blockade.

d. Chemical injury

Local anesthetic can cause severe degenerative changes leading to neurological

sequelae when inappropriately high concentrations are used, when nerves are exposed

for a prolonged time or when intraneuronal injections are encountered(70). The

neurotoxic effects of local anesthetics are concentration-dependent(72). Acute-phase

(48 hrs) effects usually resolve completely within 10 to 14 days (73).

According to Cochrane review(13), infraclavicular block (ICB) is as effective as other

techniques of brachial plexus blockade for providing surgical anaesthesia of the lower

arm. The average success rate of this technique was found to be 88%. Subgroup

analysis by method of nerve localization (ultrasound or neurostimulation) and by the

different comparator block techniques shows that infraclavicular block maybe a

superior technique compared to the single-injection axillary block; as there was

significantly lower risk of requiring general anaesthesia and of failing to achieve

sensory block of the musculo cutaneous nerve with infraclavicular block. Increased

accuracy of local anaesthetic injection encompassing the brachial plexus by

ultrasound resulted to both the outcomes which were; no difference in the risk of

44

requiring supplementation and the mean difference in onset time between an

infraclavicular block and all other blocks, while still statistically significant, has also

decreased from 3.9 to 1.9 minutes.

Figure 3.4 Mechanisms of Peripheral Nerve Injury.

45

Direct Needle Trauma can rarely tear and Injure a Nerve (A) Or, More Commonly,

Injure the Perineurium (B) And Thereby Expose the Axons to Potential Local

Anesthetic Neurotoxicity (Shaded Area)

LOCAL ANAESTHETICS

Local anaesthetics are the drugs that block the conduction of action potential by

reversible action on voltage gated sodium channels on nerves. Local anaesthetics

exert their analgesic and anaesthetic properties by reversible blockade of neuronal

Sodium channels. Myelinated fibres are more readily blocked by action of local

anaesthetic at the nodes of Ranvier than unmyelinated fibres. Small nerves are more

easily blocked than large nerves(74). The prolonged duration of action is due to

delayed absorption into axonal cytoplasm(75). Local anaesthetics are tertiary amine

with aromatic ring in between connected by an ester or an amide. Local anaesthetics

are basically classified as amide or esters. Few examples of esters are cocaine,

procaine etc and amides are lignocaine, bupivacaine etc . The properties of the local

anaesthetics depends mainly on liphophilic hydrophobic nature and dissociation

constant i.e hydrogen ion concentration. The more the hydrophobicity the more

effective and acts for longer duration. Local anaesthetics can be used as topical,

46

infiltration, intravenous ,in peripheral nerve blocks and in central neuraxial

anesthesia. Lidocaine was the most commonly used and has been the first amide

local anaesthetic. It has fast to intermediate onset of action and intermediate duration

of action . Because it can cause transient neurological symptoms its use is reduced.

Bupivacaine is an amide local anaesthetic. It has a structure similar to Mepivacaine

with butyl group. Its pKa is 8.1 and more lipid soluble and highly protein bound. It

has slow onset of action and prolonged duration, requirement of repeated

administration of local anaesthetic and top doses are avoided. In low concentrations,

it predominantly causes sensory blockade and minimal motor blockade and provides

effective analgesia. There were many reported cases where accidental intravenous

injection of bupivacaine resulted in cardio toxicity and deaths . Bupivicaine has 2

stereoisomer S- and R+ ,the R isomer is proven to be associated with the cardio toxic

effects of bupivacaine(76) . Ropivacaine and Levobupivacaine are the S- isomers of

bupivacaine Levobupivacaine is a pure S(-)- enantiomer of racemic bupivacaine .

It is developed as an alternative anesthetic drug to bupivacaine. It was developed

with a purpose of achieving lower risk of cardio toxicity than bupivacaine.

LEVOBUPIVACAINE

Levobupivacaine (Chirocaine) is a long-acting amide local anaesthetic belongs to the

47

Family of n-alkyl substitute pipecoloxylidide with chemical formula C18H28N2O.

It has a dissociation constant of 8.1 which determines the physiology and mechanism

of action of block. Mechanism of action of Levobupivacaine and its pharmacologic

properties are similar to bupivacaine it acts mainly by reversible inhibition of Sodium

channel. It attaches intracellularly and blocks the influx of sodium and there by

prevents nerve condition. Its pharmacokinetic properties like protein binding and

plasma clearance are greater where as volume of distribution and t1/2 beta are less

compared to its racemic Bupivacaine(77). Levobupivacaine is mainly protein bound

97% it attaches mainly to alpha1 glycoprotein .The route of administration and the

amount of drug determines plasma concentration absorption mainly depends upon the

blood supply of the tissue . Absorption of the drug into epidural space is biphasic

smaller amounts reaches the blood earlier while the other portion reaches little slower

the peak concentration is reached after 30 min of administration. Epidural absorption

of the drug is influenced by age absorption is much slower in older as compared to

adults. Levobupivacaine is eliminated unchanged mainly through kidney and

gastrointestinal system. Levobupivacaine have been used as intrathecal in comparison

with bupivicaine and was proven to be statistically significant in providing surgical

anaesthesia in caesarean section(78) .

Alley and et al found that sensory and motor block were similar between the same

doses of bupivacaine and hyperbaric Levobupivacaine(79). Intrathecal administration

of Levobupivacaine and racemic Bupivacaine didn’t show any variation in

hemodynamic variables and in their potency also any difference in the time of onset of

sensory block and duration of motor block. Waning of motor block is earlier in

48

Levobupivacaine(80). Adequate surgical anaesthesia was achieved with

Levobupivacaine administered as intrathecal in children between age groups of 1-14

yrs. Post operative pain score and rescue analgesic requirements are similar in major

orthopaedic surgeries when Levobupivacaine in spinal anaesthesia (81) .

Levobupivacaine used for epidural anaesthesia has similar onset time, spread of drug

, and motor block its efficacy was similar when equal doses of drug is used in

comparison to bupivacaine .(82) Its efficacy for caesarean anaesthesia is shown to be

adequate when 25 ml either of the drug is administered both were satisfactory in

terms of sensory and motor blockade, cephalad spread even though motor block to the

limbs is for longer duration in Levobupivacaine group (83). Fetal and maternal plasma

concentrations of the drug was assessed using umbilical vein to maternal vein after

drug was administer for caesarean anaesthesia and found out no difference in

maximum concentration of the drug between two drugs (84). Increase in the

concentration of the drug is associated with more hypotension and increase in the

duration of sensory blockade and also time of regression of the block(82) .Both

Levobupivacaine and bupivacaine exhibits hypotension when similar doses are

administered for caesarean epidural anaesthesia. Levobupivacaine when used in

Thoracic epidural for intraoperative and postoperative analgesia was found to

effective as bupivacaine (85) .

Levobupivacaine has been safely used in vascular surgery in high risk elderly patients

in lumbar epidural anaesthesia ,addition of adjuvants prolonged the duration of

sensory and motor blockade and regression of block was also prolonged(86) . Its

effectiveness is supported in epidural and peripheral nerve blocks as prolonged

49

infusions providing suitable anaesthesia and pain relief in knee arthroplasty (87) .

Levobupivacaine is used in retro bulbar anaesthesia associated with appropriate

anaesthesia(88) . It can be used as bolus or continuous infiltration. It is generally well

tolerated and useful alternative to bupivacaine(89). Different additives have been used

to prolong regional blockade. Bupivacaine binds with Na channels in both activated

state and inactivated state and shows greater selectivity and faster towards the open

Na channels which is responsible for its cardiac inhibitory activity and toxicity where

as Levobupivacaine doesn’t show any selectivity explains the less cardio toxicity(90) .

Levobupivacaine ‘s three dimensional structure is the reason for less cardiac and

CNS toxicity(91) it’s an left isomer of bupivacaine with smaller difference in their

potency .Widening of QRS complex and severe arrhythmias are less in

Levobupivacaine compared to bupivacaine as published by Mazoit et al in a rat study

(92).

Graf et al studied the electrophysiology in isolated heart using bupivicaine and its

optical isomers and identified bupivacaine produces prolonged AV conduction delay

and secondary AV block in comparison to Levobupivacaine(93) .Huang YF et al

studied the toxicity of Levobupivacaine and bupivicaine in sheep .

The drug was injected intravenously at a graded doses 75mg and more incremental

doses and concluded that Levobupivacaine exhibits less toxicity than

bupivacaine(94). Many studies reported that Levobupivacaine provided longer

duration of analgesia than Ropivacaine in surgeries involving upper limb.

50

ADDITIVES OR ADJUVANTS

Pain involves complex pathway systems and is mediated by the neurotransmitters and

is transmitted to the central and peripheral nervous systems .It is blocked to an extent

by one drug like local anaesthetics or block technique. Search for combination of

drugs has started in the early 1900’s to provide a better blockade. Matas tried

combining morphine to cocaine during spinal anesthesia to prolong the action of

cocaine and for sedation. Later on, after the identification of opioid receptors on the

spinal cord in 1970, the use of opioids have become very popular and became a part

of routine practise. The purpose of adjuvants is mainly to increase the speed of onset,

prolong the duration of action of local anaesthetics and reduce the total amount of

drug. Adjuvants augment the postoperative analgesia with fewer side effects and also

should act mainly on the peripheral sites with less of central side effects like cardiac,

nervous and respiratory systems. Mechanism of action of adjuvant is by modulation of

A delta and C fibres in the spinal cord and thereby provides spinal analgesia(95).

Epidural administration of opioids resulted in delayed onset of anesthesia and did not

decrease the requirement of volatile anaesthetics. Perineural administration of opioids

may not reach the effect site by axonal transport there by its effects are minimal in the

peripheral nerves (96).

Only Tramadol and combination of Buprenorphine with tramadol have shown to be

effective in peripheral nerves and are in use. Vasoconstrictors are most commonly

used as adjuvants in spinal anaesthesia. It reduces the peak blood levels and provides

more consistent block with better analgesia and anaesthesia (97).Use of epinephrine

resulted in decrease in amount of local anaesthetics and there by local anaesthetic

51

toxicity. Epinephrine causes dose related effects at lower doses. Its effects are mainly

due to beta action at higher doses. It causes vasoconstriction mainly by alpha receptors

resulting in a decrease in blood supply and reduced uptake of local anaesthetics into

the circulation. At higher doses it can cause arrhythmias(98).

Clonide, an alpha 2 agonist has been used as an adjuvant. It has local anaesthetic

properties and its action is mediated by inhibition of C fibres. Clonidine when used in

peripheral nerves doses up to of 1.5mcg/ml and prolongs sensory block and duration

of analgesia(99). However recent studies recently has shown that the addition of

clonidine to long acting local anaesthetics like bupivacaine and Ropivacaine did not

benefit overall effect(100).

DEXAMETHASONE

Dexamethasone is a high-potency, long-acting glucocorticoid with little

mineralocorticoid effect. It has been shown to prolong peripheral nerve blockade in

animals and, when added to bupivacaine microspheres, to extend the duration of

analgesia in humans(8). The analgesic potency of corticosteroids is not fully

understood The analgesic effects of spinal and systemic corticosteroids in addition

with local anaesthetics in human studies have been recognised, whereas

dexamethasone microspheres have increased blockade duration in both human and

animal studies (101,102).

Furthermore, dexamethasone has been shown to possess an anti-inflamatory

action(103). Steroids produce vasoconstriction, so they reduce local anaesthetic

absorption. They adhere to the intracellular receptor to alter nuclear transcription. Stan

52

et al. (104)argued that the steroid suppresses the production and secretion of various

inflammatory mediators, which prolongs the period of analgesia up to 48 hours, and

Attardi et al.(105) showed that dexamethasone act on glucocorticoid receptors, which

increase the activity of inhibitory potassium channels on nociceptive C-fibers,

decreasing their activity. Other postulated mechanism of action of dexamethasone

include suppression of ectopic neural discharge and suppression of neuropeptide

immune response to injury(106).

The addition of dexamethasone to local anaesthetic administration in order to prolong

analgesia duration has recently been explored. Tandoc et al., has investigated low-

dose dexamethasone, but this was added to large dosages of bupivacaine for

interscalene blockade(107). This study concluded that addition of dexamethasone to

bupivacaine appreciably prolonged the duration of the motor block and improved the

quality of analgesia following interscalene block. There was no variation in the length

of analgesia and motor block between low-dose and high-dose dexamethasone. Persec

did a randomized controlled study in which he concluded that, using single-shot low-

dose dexamethasone in a mixture with Levobupivacaine causes long lasting analgesia

duration and less analgesic use compared with Levobupivacaine(108). Dexamethasone

was shown to extend the analgesia time when added as an adjuvant to local

anaesthetics for different blocks and administration routes.

In a prospective, randomized, double-blind study by Naghipour et al performed on 72

patients(16), 8 mg dexamethasone administrated via the epidural method prolonged

the analgesia time by two hours. Parrington etal(109) observed the same effect of

dexamethasone in a block of the supra clavicular brachial plexus as 104 minutes.

53

According to a meta-analysis, adding perineural dexamethasone for brachial plexus

blocks similarly did not alleviate against the development of these complications as

the incidence of dyspnoea, hoarseness and Horner’s syndrome were shown to be alike

in both control an dexamethasone treated groups(12). In a study of Holte et al(110) on

volunteer patients, dexamethasone was added to bupivacaine microcapsules by

subcutaneous infiltration to obtain 50 μg in 10 ml, and a significant increase in

analgesia time was observed. The randomized controlled, double blinded study done

by Akkaya etal (111)showed that: the time before the administration of the first

additional analgesic dose was prolonged significantly (p=0.004), the pain scores were

lower for superficial pain and deep pain and reduction of total additional analgesic

substances required in the dexamethasone group compared to the Levobupivacaine

group .

54

4. MATERIAL AND METHODS

The proposal for the study titled “A randomized, controlled, double blind, prospective

study comparing Levobupivacaine with dexamethasone versus plain Levobupivacaine

in patients undergoing forearm surgeries under an infraclavicular block” was reviewed

and approved by the Institutional review board and ethics committee of Christian

Medical college, Vellore. After the approval of the institutional review board, the

study was registered under clinical trial registry of India. The aim of the study was to

compare the onset of sensory and motor blockade and the duration of post operative

analgesic efficacy with plain 0.5% Levobupivacaine against 0.5% Levobupivacaine

with 4mg dexamethasone added in infraclavicular block in patients undergoing

forearm orthopaedic surgeries.

INTERVENTION AGENT: 0.5% Levobupivacaine with dexamethasone 4mg (1 ml)

COMPARATOR AGENT: 0.5% Levobupivacaine with 1 ml normal saline

55

RANDOMISATION, ALLOCATION CONCEALMENT AND BLINDING:

The patients who were recruited for the study were randomised into two arms. One

group got 30ml 0.5% Levobupivacaine plus four milligrams of dexamethasone 1ml

and the other group 30ml 0.5% Levobupivacaine with 1 ml normal saline. The

randomisation sequence was generated by a biostatistician not directly involved in the

study using a computer programme. The randomization sequence was handed over to

the pharmacist who packaged and labelled the drugs.

The drugs manufactured by the Neon Labs, were packaged in amber colored bottles

by the department of Pharmacy, Christian Medical College, Vellore. These bottles

were then carefully organized as per the randomization sequence and were labelled

from 1 to 60. The drugs were then handed over to the principal investigator to be used

in patients in a sequential order. Block randomization method was used. The patient

and the principal investigator remained blinded about the drug being administered

throughout the period of study. The randomization code was confidentially preserved

in the department of pharmacy till it was unblinded at the end of the study.

Study was done among the patients who underwent forearm orthopaedic surgeries in

Christian Medical College, Vellore, May to August 2016. A total of 40 patients ASA

(American Society of Anaesthesiologist) preoperative risk classification I, II and III

aged between18 to 70 were included in the study.

56

INCLUSION CRITERIA:

1. Age between 18-70yrs posted for forearm surgery

2. ASA I-III

3. Patients who are willing to undergo the block.

4. Weight greater than or equal to 50kg

EXCLUSION CRITERIA:

Patients who are not willing for the block

Patient’s with coagulopathy

Local infection over the block area

Pregnant women

Patients requiring general anaesthesia

Patient’s weighing less than 50kg.

Allergy to local anesthetic

CONSENT:

The information sheet containing all relevant information in lay language translated

into the language patient or patient’s relative can understand was provided sufficiently

prior to the surgery for them to deliberate and clarify. The principal investigator

discussed about the study with the patient and clarified their queries on the night

before the surgery. Then the patient was invited to be a part of the study and the

57

consent signature was obtained in the consent form. Patients were recruited and given

a study number after informed written consent.

IMPLEMENTATION:

The consenting patients who fulfilled the inclusion criteria were recruited into the

study.

The patients were premedicated with Tab. Diazepam 5mg and Cap. Omeprazole 20

mg on the day of the surgery and standard preoperative fasting orders were followed.

In the operating room an intravenous access was obtained in the opposite side of the

limb undergoing surgery and block performed with standard monitoring such as ECG,

pulse oxymetry and blood pressure. This is as per ASA (American Society of

Anaesthesiologists) guidelines. In each group under aseptic precautions brachial

plexus block was performed via the infraclavicular approach using SonoSite S nerve

ultrasound system using a 13-6 MHZ linear frequency probe and an 22g Sonoplex

nano Lins stim canula. We identified the 2nd part of the axillary artery and vein using

ultrasound and given 1-2ml of local infiltration to the skin and using the sonoplex

nanolins stim canula confirmed the cords by using the nerve stimulator once the

twitches are identified till 0.5 m Amp current then 30 ml of the drug is administered

along the 3 regions surrounding the 2 nd part of axillary artery to cover posterior

medial and lateral cords.

58

.

Figure 4.1: Ultrasound machine S Nerve used in our study

59

Figure 4.2: High frequency linear probe 13-6 MHZ used in the study

Figure 4.3: Sonoplex needle used in the study

60

Figure 4.4: Ultrasound image showing needle advancement around the posterior cord

Figure 4.5: Ultrasound image showing needle advancement around the lateral cord

61

Figure 4.6: Ultrasound image showing needle advancement around the medial cord

Initial assessment was immediately after administration of the drug till 20 minutes.

Patients were assessed for sensory blockade by pin prick using a 26G needle or Ice

cube in the dermatomal distribution of ulnar, median and radial nerves. Sensation over

the thenar eminence is median, dorsum of hand is radial and hypothenar corresponds

to ulnar and graded accordingly as Grade 0- pain/normal sensation ,Grade 1-analgesia

/ decreased sensation, Grade 2-anesthesia / no sensation. A modified Bromage scale

for the upper extremity was used to assess motor power and was assessed by the

primary investigator. This scale consists of the following 4 scores: 0, able to raise the

extended arm to 90° for a full 2 seconds; 1, able to flex the elbow and move the

fingers but unable to raise the extended arm;2, unable to flex the elbow but able to

move the fingers; and 3, unable to move the arm, elbow, or fingers. End of the

injection of the drug was taken as time 0. Patients were evaluated for the onset of

62

sensory every 1,2,3,4,5,10,15,20 minutes and motor blockade every 5, 10, 15, 20

minutes and duration of analgesia postoperatively at 3 hours, 6 hours and 12 hours for

24 hours. Patients were assessed for sensory blockade by pin prick using a 26G needle

in the dermatomal distribution of ulnar, median and radial nerves.

A modified Bromage scale for the upper extremity was used to assess motor power

and was assessed by the primary investigator. Postoperatively, perception of pain was

assessed using the visual analog scale (VAS). The staff nurse assigned to the patient

documented the visual analog scale under the supervision of the primary investigator.

Rescue analgesia was administered when VAS score was equal to or more than 4.

Rescue analgesia was Tab. Aceclofenac. This was followed by 0.1 mg/kg morphine if

pain score remains more than 4 despite administration of Aceclofenac. Number of

rescue medications between the two groups was noted.

PRIMARY OUTCOME:

To compare the onset of sensory and motor blockade of 0.5% Levobupivacaine with

dexamethasone versus 0.5% Levobupivacaine with 1 ml normal saline.

SECONDARY OUTCOME:

To compare the duration of postoperative analgesia and requirement for rescue

analgesia between the two groups (0.5% Levobupivacaine with dexamethasone versus

0.5% Levobupivacaine with 1 ml normal saline).

63

SUMMARY OF METHODOLOGY

Figure: 4.7: Flow chart of the study

64

SAMPLE SIZE CALCULATION:

Target sample size and rationale:

To estimate the mean difference of 3 minutes in onset of sensory block between two

groups with standard deviation of 4 and 80% power at 5% level of significance, the

required sample size was estimated to be 60 (30 in each group).

Formula:

N= 2σ2 [Z1-α/2+Z1-β]2 /[μ1-μ2]2

Mean difference, μ1-μ2 = 3 mins

Standard deviation, σ = 4 mins

Normal value of Z1-α/2 for 5% level of significance= 1.96

Normal value of Z1-β for 80% power = 0.84

N= 2*42[1.96+0.84]2/[3]2 = 28 ∼ 30

Descriptive statistics for all continuous variables was given using Mean (SD) or

Median (IQR). Categorical factors were presented using frequency and percentage

and their association with the two groups were assessed using chi-square test. The

primary outcome and all other continuous covariates were assessed for normality

assumption and independent t-test was used.

To assess the association between two groups else Mann-Whitney U test was used.

The correlation of primary outcome with all other continuous covariates was assessed

65

using Pearson correlation coefficient or Spearman’s rank correlation. P-value of <0.05

was considered for statistical significance.

STATISTICAL ANALYSIS

Data was summarized using mean (SD)/ median (IQR) for continuous variables and

frequency (percentage) for categorical variables. Independent test/rank sum test

(continuous) and chi-square (categorical) tests were used to compare the baseline

characteristics among the drugs. The outcome was defined as grade improvement

from 3min to 20min. A chi-square test was performed to compare the improvement

among drugs. A fisher exact test was used to compare the 3 min and 20 min grading

among the drug groups. All the significance levels were kept for p<0.05. All the

statistical analysis was done using stataic 13.1.

66

5. RESULTS

The data collected have been analysed under the following categories

I. Description of baseline characteristics

II. Data obtained during the intra operative period

III. Data obtained in the post-operative period

DESCRIPTION OF BASELINE CHARACTERISTICS

Baseline characteristics of the patients have been enumerated in Table no 1. On the

whole there were no significant differences in the baseline characteristics of both

treatment arms. In this study we assessed 45 patients for eligibility to be included in

the study. 5 patients were excluded as some of them did not fulfil the inclusion criteria

and for some others there was a change in the operative plan on the day of surgery.

Hence a total of 40 patients were recruited with ASA (American Society of

Anaesthesiologist) preoperative risk classification I, II and III. The patients were aged

between 18 to 70 years. Data collected from 40 patients was analysed with 20 patients

in one arm and 20 patients in another arm.

67

Table 5.2 General demographic characteristics of study participants in relation to

drug

Variable Levobupivacaine

with

dexamethasone

Levobupivacaine Total

(n=40)

P value

Age

group

18-35

years

12 12 24

0.81 36-55

years

06 06 12

56-75

years

02 02 04

Figure 5.1 Range of age in both groups

68

Table 5.2: Association of variables with drug

Variables

Levobupivacaine

with

dexamethasone

(n=20)

Levobupivacaine

(n=20)

P value

Age Mean, (SD) 34.90 (14.48) 35.90 (12.85) 0.77

Height Mean, (SD) 167.35 (7.01) 163.55 ( 8.73) 0.54

Weight Mean, (SD) 68.85 (14.77) 65.60 (8.98) 0.37

BMI Mean, (SD) 24.58(4.98) 24.54(2.91) 0.98

AGE AND GENDER:

The mean age of the participants in the study was around 36 years, the youngest being

18 years and the oldest 65 years. Of the 40 patients analysed, 37 were male and 3 were

female.

The mean BMI of the participants in the study was around 25 kg/m2, minimum is 17

kg/m2 and maximum being 35 kg/m2.

ASA PHYSICAL STATUS CLASSIFICATION:

Majority of the patients (28 out of the 40) recruited in the study were of ASA

Physical status grade 1.(Table 2)

69

Table 5.3: American Society of anaesthesiologists grading of physical status

classification in study population

ASA grading Total (n=40)

Grade 1 28 (70.00%)

Grade 2 10 (25.00%)

Grade 3 2 (5.00%)

Table 5.4: Association of ASA grading and drug:

ASA

physical

Status

Levobupivacaine

with

dexamethasone

n(%)

Levobupivacaine

n(%)

Total

n(%)

P value(chi2)

Grade 1 12(60.00%) 16(80.00%) 28(70.00%) 0.226(2.9714)

Grade 2 6 (30.00%) 4 (20.00%) 10(25.0%)

Grade 3 2 (10%) 0(0.00%) 2(5.00%)

Figure 5.2 American Society of Anaesthesiologists Grading Of Physical Status

Classification In Study Population

70

Table 5.5: Frequency Distribution of the Drug

Drug Total (n=40)

LEVOBUPIVACAINE AND

DEXAMETHASONE

20( 50.00%)

LEVOBUPIVACAINE 20 (50.00%%)

There was equal distrubution of patients in both arms (50%)

Figure 5.3 Distribution of the study population between both the groups

DURATION OF SURGERY:

Duration of surgery in both the Levobupivacaine with dexamethasone and

Levobupivacaine arms was comparable around 1 hour 20 minutes to 1 hr 40 min.

71

Table 5.6 Comparison of Duration of Surgery in Both Groups

LEVOBUPIVACAINE WITH

DEXAMETHASONE

LEVOBUPIVACAINE P VALUE

DURATION

OF

SURGERY

MEAN SD MEAN SD 0.145

80.25 38.51 104.45 61.73

Figure 5.4 Comparison of duration of surgery in both groups

72

Table 5.7 Comparison of Means and standard deviations (SD) of baseline

characteristics

Variables

Levobupivacaine

with

dexamethasone

(n=20)

Levobupivacaine

(n=20)

P value

Age Mean, (SD) 34.90 (14.48) 35.90 (12.85) 0.818

Height Mean, (SD) 167.35 (7.01) 163.55 ( 8.73) 0.14

Weight Mean, (SD) 68.85 (14.77) 65.60 (8.98) 0.41

BMI Mean, (SD) 24.58(4.98) 24.54(2.91) 0.98

Dur.ofsurgery Mean,

(SD)

80.25(38.51) 99.50 (65.93) 0.15

Systolic BP Mean, (SD) 133.35(15.48) 125.40 (11.93) 0.07

Diastolic BP Mean, (SD) 73.75 (7.97) 76.50 (7.74) 0.27

Sp02 Mean, (SD) 99.70 (0.80) 99.75 (0.91) 0.85

Heart rate Mean, (SD) 77.70 (13.16) 112.35 (150.51) 0.86

PPT systolic BP Mean,

(SD)

125.45 (14.36) 120.65 (14.08) 0.29

PPT diastolic BP Mean,

(SD)

71.90(7.53) 71.95 (8.17) 0.98

PPT Spo2 Mean, (SD) 99.55 (1.10) 99.90 (0.45) 0.19

PPT heart rate Mean,

(SD)

77.45(11.48) 75.35 (10.38) 0.55

73

Table 5.8 Frequency Distribution Of The Midazolam

Midazolam Total (n=40)

Given 28 (70.00%)

Not given 12 (30.00%)

Among the 40 study participants, midazolam was given to 70% of patients .

Figure 5.5 Frequency Distribution Of The Midazolam

Table 5.9 Frequency Distribution Of The Fentanyl Administered

Fentanyl Total (n=40)

Given 28 (70.00%)

Not given 12 (30.00%)

Among the study population fentanyl was given to 70% of patients.

74

Figure 5.6 Frequency Distribution Of The Fentanyl

DATA OBTAINED DURING THE INTRA OPERATIVE PERIOD

Table 5.10 SENSORY GRADING OF RADIAL NERVE

Grade 0

(pain/

normal

sensation)

Grade 1

(analgesia /

decreased

sensation)

Grade 2

(anesthesia/

no sensation)

Radial nerve 1 min 20 (52.63%) 15 (39.47%) 3 (7.89%)

2 min 16 (42.11%) 19 (50.00%) 3 (7.89%)

3 min 14 (36.84%) 21 (55.26%) 3 (7.89%)

4 min 10 (25.64%) 24 (61.54%) 5 (12.82%)

5 min 4 (10.00%) 27 (67.50%) 9 (22.50%)

10 min 2 (5.00%) 22 (55.00%) 16 (40.00%)

15 min 2 (5.00%) 14 (35.00%) 24 (60.00%)

20 min 2 (2.56%) 6 (15.00%) 32 (80.00%)

75

Table 5.11: Improvement Of Radial Nerve And Drug Association

Improvement of Radial

nerve sensory grading

Levobupivacaine

with dexamethasone

Levobupivacaine P value(chi2)

0 3(5.00%) 7(35.00%) 0.144(2.133)

1 17(85.00%) 13(65.00%)

Total 20(100%) 20(100%)

There was considerable improvement of sensory grading from 5 to 85 % in

Levobupivacaine with dexamethasone group and also the difference between two

groups was 20% for grade 1 sensory grading of radial nerve. Over all P value was

0.144 which shows no significant improvement in radial nerve sensory grading

between the time duration of 3 min to 20 min.

76

Table 5.12 Association For Onset Of Anaesthesia And Drug In Radial Nerve

LEVOBUPIVACAINE WITH

DEXAMETHASONE

LEVOBUPIVACAINE

Grade 0

(pain/

normal

sensation)

Grade 1

(analgesia

/

decreased

sensation)

Grade 2

(anesthesia

/ no

sensation)

Grade 0

(pain/

normal

sensation)

Grade 1

(analgesia /

decreased

sensation)

Grade 2

(anesthesia/

no

sensation)

Radial

Nerve

1

min

12

(63.16%)

6 (31.58%) 1 (5.26%) 8 (42.11%) 9 (47.37%) 2 (10.53%)

2

min

11

(57.89%)

7 (36.84%) 1 (5.26%) 5 (26.32%) 12 (63.16%) 2 (10.53%)

3

min

10

(52.63%)

8 (42.11%) 1 (5.26%) 4 (21.05%) 13 (68.42%) 2 (10.53%)

4

min

7

(35.00%)

12

(60.00%)

1 (5.00%) 3 (15.79%) 12 (63.16%) 4 (21.05%)

5

min

2

(10.00%)

15

(75.00%)

3 (15.00%) 2 (10.00%) 12 (60.00%) 6 (30.00%)

10

min

1 (5.00%) 13

(65.00%)

6 (30.00%) 1(5.00%) 9 (45.00%) 10 (50.00%)

77

15

min

1 (5.00%) 7 (35.00%) 12

(60.00%)

1 (5.00%) 7 (35.00%) 12 (60.00%)

20

min

1 (5.00%) 2 (10.00%) 17

(85.00%)

1 (5.00%) 4 (20.00%) 15 (75.00%)

In Levobupivacaine with dexamethasone group, 60-75% of the patients had onset of

sensory blockade for radial nerve around 4-5 min and 85% at the end of 20 min where

as 75% achieved sensory blockade of radial nerve after 20 min in Levobupivacaine

group. However this was not statistically significant.

Table 5.13 Association For Onset Of Anaesthesia And Drug In Median Nerve

Grade 0 (pain/

normal

sensation)

Grade 1

(analgesia /

decreased

sensation)

Grade 2

(anesthesia/ no

sensation)

Median nerve 1 min 21 (52.50%) 16 (40.00%) 3 (7.50%)

2 min 17 (42.50%) 20 (50.00%) 3 (7.50%)

3 min 13 (32.50%) 23 (57.50%) 4 (10.00%)

4 min 10 (25.00%) 23 (60.00%) 6 (15.00%)

5 min 3 (7.50%) 28 (72.50%) 8 (20.00%)

10 min 2 (5.00%) 24(60.00%) 14 (35.00%)

15 min 2 (5.00%) 17 (42.50%) 21 (52.50%)

20 min 1 (2.50%) 11(27.50%) 28 (70.00%)

Around 60-70% of the patients had onset of anaesthesia by around 4-5 minutes and

70% had anaesthesia by 20 minutes in median nerve

78

Table 5.14: Improvement Of Median Nerve And Drug Association

Improvement of

sensory blockade

in medial nerve

Levobupivacaine

with

deamethasone

Levobupivaciane P(chi2)

Grade 0 2(10%) 8(40%) 0.028

Grade 1 18(90%) 12(60%)

20(100%) 20(100%)

There was a considerable improvement in sensory grading from 10 to 90 % in

levobupivacaine with dexamethasone group and also the difference between the two

groups was 30% for grade 1. P value was 0.028.This shows statistically significant

improvement in median nerve sensory grading between a duration of 3 min and 20

min.

79

Table 5.15 Association Between Onset Of Sensory Blockade And The Drug For

Median Nerve

Levobupivacaine with

dexamethasone

Levobupivacaine

Grade 0

(pain/

normal

sensation)

Grade 1

(analgesia

/ decreased

sensation)

Grade 2

(anesthesia

/ no

sensation)

Grade 0

(pain/

normal

sensation)

Grade 1

(analgesia /

decreased

sensation)

Grade 2

(anesthesia/

no

sensation)

Median

Nerve

1

min

11

(55.00%)

8(40.00%) 1 (5.00%) 10

(50.00%)

8 (40.00%) 2 (10.00%)

2

min

10

(50.00%)

9 (45.00%) 1 (5.00%) 7(35.00%) 11 (55.00%) 2 (10.00%)

3

min

8

(40.00%)

11

(55.00%)

1 (5.00%) 5 (25.00%) 12 (60.00%) 3 (15.00%)

4

min

5

(25.00%)

14

(70.00%)

1 (5.00%) 5 (25.00%) 10 (50.00%) 5 (25.00%)

5

min

2

(10.00%)

15

(75.00%)

3 (15.00%) 1 (5.00%) 14 (70.00%) 5 (25.00%)

10

min

1

(05.26%)

13

(65.00%)

6 (30.00%) 1(5.00%) 11 (55.00%) 08 (40.00%)

80

15

min

1 (5.00%) 7 (35.00%) 10

(60.00%)

1 (5.00%) 10 (50.00%) 09 (45.00%)

20

min

0 (0.0%) 4 (20.00%) 16

(80.00%)

1 (5.00%) 7 (35.00%) 12 (60.00%)

In levobupivacaine with dexamethasone group, 70-75% of the patients had onset of

sensory blockade for median nerve around 4-5 min and 85% at the end of 20 min

where as 60% achieved complete sensory blockade for median nerve after 20 min in

levobupivacaine group.

Table 5.16 Association Between Onset Of Sensory Blockade And The Drug For Ulnar

Nerve

Grade 0

(pain/

normal

sensation)

Grade 1

(analgesia /

decreased

sensation)

Grade 2

(anesthesia/

no sensation)

Ulnar nerve 1 min 21 (52.50%) 18 (45.00%) 1 (2.50%)

2 min 17(42.50%) 20 (52.50%) 2 (5.00%)

3 min 10 (25.00%) 25 (65.00%) 4 (10.00%)

4 min 6 (15.00%) 27 (67.50%) 7 (17.50%)

5 min 2 (5.00%) 29 (72.50%) 9 (22.50%)

10 min 1 (2.50%) 22 (57.50%) 16 (40.00%)

15 min 2 (5.00%) 14 (35.00%) 24 (60.00%)

20 min 2 (5.00%) 9 (22.50%) 29 (72.50%)

81

Around 65-70% of the patients had onset of anaesthesia by around 4-5 minutes .

Almost 70% had complete sensory anaesthesia by 20 minutes in ulnar nerve.

Table 5.17: Improvement Of Ulnar Nerve And Drug Association

Improvement of

sensory blockade

in ulnar nerve

Levobupivacaine

with

dexamethasone

Levobupivacaine P value(chi2)

0 2(10.00%) 9(45.00%) 0.013(6.1442)

1 18(90.00%) 11(55.00%)

20(100.00%) 20(100.00%)

There was a significant improvement of sensory grading from 10 to 90% in

levobupivacaine with dexamethasone group and also the difference between the two

groups was 45% for grade 1. P value was 0.013 which shows a significant

improvement in ulnar nerve between duration of 3 min and 20 min.

82

Table 5.18: Association Between Onset Of Sensory Blockade And The Drug For

Ulnar Nerve

LEVOBUPIVACAINE WITH

DEXAMETHASONE

LEVOBUPIVACAINE

Grade 0

(pain/

normal

sensation)

Grade 1

(analgesia

/

decreased

sensation)

Grade 1

(analgesia

/

decreased

sensation)

Grade 0

(pain/

normal

sensation)

Grade 1

(analgesia /

decreased

sensation)

Grade 1

(analgesia /

decreased

sensation)

Ulnar

Nerve

1

min

12

(60.00%)

8( 40.00%) 0(0.00 %) 9(45.00 %) 10(50.00 %) 1(05.00%)

2

min

10(50.00

%)

10(50.00

%)

0(0.00 %) 7(35.00 %) 11(55.00%) 2(10.00%)

3

min

06(30.00

%)

13(65.00%

)

1(5.00%) 4(20.00 %) 13(65.00 %) 3(15.00%)

4

min

03(15.00

%)

14(70.00

%)

3( 15.00%) 3(15.00 %) 13(65.00 %) 4(20.00%)

5

min

01(5.00%) 15(75.00%

)

4( 20.00%) 1( 5.00 %) 14(70.00 %) 5(25.00%)

83

10

min

0(0.00 %) 11(55.00%

)

9(45.00%) 1(5.00 %) 12(60.00%) 7(35.00%)

15

min

1(5.00 %) 6(30.00%) 13(65.00%

)

1(5.00%) 8(40.00%) 11(55.00 %)

20

min

0(5.00 %) 2(10.00%) 17(85.00%

)

1( 5.00%) 7(35.00%) 12(60.00%)

In levobupivacaine with dexamethasone group, 70-75% of the patients had onset of

anaesthesia around 4-5 min and 85% at the end of 20 min where as 60% achieved

complete sensory blockade after 20 min in levobupivacaine group for ulnar nerve.

Table 5.19: Duration And Motor Grading Using Modified Bromage Scale

Motor

grading

Grade

0

Grade 1 Grade 2 Grade 3

0 0 1 0 2 0 3

T

i

m

e

5

min

9 2

(13.33%)

13

(86.67%)

2

(25.00%)

6

(75.00%)

1 (50.00%) 1 (50.0%)

10

min

4 1 (5.26%) 18

(94.74%)

2

(12.50%)

13

(87.50%)

1 (50.00%) 1 (50.0%)

15

min

2 1 (7.14%) 13

(92.86%)

2 (8.33%) 21

(91.67%)

1 (33.33%) 1 (66.67%)

20

min

2 1

(33.33%)

2

(66.67%)

1 (3.57%) 25

(96.43%)

1

(16.67%)

5 (83.33%)

Almost 80% of patients had onset of motor blockade at 10 min

62.5% of the population had grade 2 motor blockade.

84

Table 5.20: Motor Grade Improvement And Drug Association At 5 Min

Grade of motor

improvement at

5 min

Levobupivacaine

with

dexamethasone

Levobupivacaine Fischer exact

0 5(33.33%) 4(28.57%) 0.262

1 5(33.33%) 8(57.14%)

2 5(33.33%) 1(7.14%)

3 0(0.00%) 1(7.14%)

There is no statistical significant improvement in motor grading at the end of 5 min

85

Table 5.21: Motor grade improvement and drug association at 20 min

Grade of motor

improvement at

20 min

Levobupivacaine

with dexamethasone

levobupivacaine Fischer exact

0 1(5.88%) 1(5.56%) 0.025

1 0(0.00%) 2(11.11%)

2 11(64.71%) 15(83.35%)

3 5(29.41%) 0(0.00%)

Motor improvement at end of 20 min is statistically significant. There is an 65 %

improvement of grade 1 to grade 2 in Levobupivaicane with dexamethasone group

and 85% improvement with Levobupivaciane group.

86

Table 5.22: Modified Bromge Scale Grading In Association With Drug

Levobupivacaine with dexamethasone

Motor grading

Levobupivacaine

Motor grading

Time Grade 0 Grade

1

Grade

2

Grade

3

Grade

0

Grade

1

Grade

2

Grade

3

5min 5

6 5 0 4 9 2 2

10min 2 9 8 0 2 10 7 2

15min 1 6 12 3 2 8 11 1

20min 1 0 11 6 1 3 16 1

87

Table 5.23: Adequacy Of Surgical Anesthesia

Adequacy of surgical anasthesia Total (n=40)

Yes 35 (87.50%)

No 5 (12.50%)

Figure 5. 7: Adequacy Of Surgical Anaesthesia

88

Table 5.24: Association Between Adequacy Of Surgical Anaesthesia And Drug Used

Drug Total Chi

square

P value

1 2

Yes 18

(90.00%)

17

(85.00%)

35 (87.50%) 0.2286 0.633

No 2(10.00%) 3

(15.00%)

5 (12.50%)

The adequacy of surgical anaesthesia was assumed to be satisfactory when the

surgeon was able to perform the surgery with complete sensory and motor blockade of

the patient’s forearm and when the patient was completely painless during the surgery.

Among the 40 patients who underwent forearm orthopaedic surgeries infraclavicular

block was able to provide adequate surgical anaesthesia for 87.5% of patients. In both

the groups the success of the block is negligible as p value is 0.633.

DATA OBTAINED IN THE POST-OPERATIVE PERIOD

Post operative analgesia requirement was measured using an visual analog scale

(VAS) . In this study the highest score was 7.

Table 5.25 VAS SCORE

VAS score 0 1 2 3 7

Time in

hours

3 hours 28

(70.00%)

8

(20.00%)

4

(10.00%)

6 hours 24

(60.00%)

11

(27.50%)

4

(10.00%)

1

(2.50%)

12 hours 22(55.00%) 11

(27.50%)

4

(10.00%)

2

(5.00%)

1

(2.50%)

24 hours 21

(52.50%)

7

(17.50%)

11

(27.50%)

1

(2.50%)

89

Table 5.26: VAS score in relation to Levobupivacaine and Dexamethasone

Levobupivacaine with dexamethasone

VAS

score

0 1 2 3 7

Time in

hours

3hrs 13(65.00%) 5(25.00%) 2(10.00%)

6hrs 11(55.00%) 8(40.00%) 1(5.00%)

12hrs 11(55.00%) 6(30.00%) 2(10.00%) 1(5.00%)

24hrs 10(50.00%) 5(25.00%) 5(25.00%)

Table 5.27: VAS score in relation to Levobupivacaine

Levobupivacaine

VAS

score

0 1 2 3 7

Time

in

hours

3hrs 15(75.00%) 3(15.00%) 10

6hrs 13(65.00%) 3(15.00%) 3(15.00%) 1(5.00%)

12hrs 11(55.00%) 5(25.00%) 2(10.00%) 1(5.00%) 1(5.00%)

24hrs 11(55.00%) 2(10.00%) 6(30.00%) 1(5.00%)

Post-operative pain was measured using an visual analog scale ranging from 0-10 and

was recorded at various time intervals. There were no differences in post-operative

pain scores in both arms.

In Levobupivacaine with dexamethasone group the maximum documented pain score

was 3 where as in the Levobupivacaine group it is 3 and 7. However it was

statistically insignificant.

90

Table 5.28: Supplementation of Aceclofenac in study population

12 hrs 24 hrs

T.Aceclofenac Given 4 (10.00%) 3 (7.50%)

Not

given

36(90.00%) 35

(92.50%)

In the entire study population only 4 needed tab. Aceclofenac after 12 hrs where as the

rest never needed.

Table 5.29: Aceclofenac administration in relation to drug

Time of

administration

of Aceclofenac

Levobupivacaine

with dexamethasone

Levobupivacaine

12 hrs 1(5.26%) 3(15.79%)

24 hrs 1(5.26%) 2(10.53%)

In both groups Aceclofenac administration was minimal.

Table 5.30: Supplementation of Morphine in study population.

6 hrs 12 hrs 18 hrs 24 hrs

Inj.

Morphine

0.1 mg/kg

Given 0 1 (2.50%) 0 0

Not

given

39 38

(97.50%)

39 39

Table 5.31 Association of Morphine and drug.

6hrs 12hrs 18hrs 24hrs P value

Levobupivacaine

with

dexamethasone

given 0 0 0 0

Not

given

20 20 20 20

Levobupivacaine given 0 1(5.00%) 0 0

Not

given

19 19 19 19

91

In the post operative period only 1 participant in the Levobupivacaine arm had 1 dose

of morphine and there is no statistical significance between two arms in relation to

administration of morphine.

Table 5.32: Supplementation of Paracetamol in study population

6 hrs 12 hrs 18 hrs 24 hrs

Inj.

Paracetamol

Given 1 (2.56%) 5

(12.50%)

3(7.89%) 3(7.69%)

Not

given

39

(94.44%)

35

(87.50%)

37(92.11%) 37(92.31%)

Table 5.33: Association Of Paracetamol And Drug

6hrs 12hrs 18hrs 24hrs

Levobupivacaine

with

dexamethasone

Given 0 2 1 1

Not

given

20 18 19 19

Levobupivacaine Given 1 3 2 1

Not

given

19 17 18 20

92

6. DISCUSSION

In orthopedic surgeries involving the forearm, surgical anesthesia can be achieved by

regional anesthesia techniques which frequently involve a brachial plexus block.

Regional anaesthesia is an excellent alternative to general anaesthesia specially for

surgeries involving extremity (12). This technique provides longer duration of pain

relief, minimizes intra and post operative requirements of opiods while at the same

time avoiding the complications of general anesthesia which include airway trauma,

postoperative nausea and vomiting. Lower arm anesthesia, from the elbow to the

hand, may be promptly achieved by injection of local anaesthetic around the brachial

plexus(13). It provides better analgesia in the post operative period and quicker

recovery from the anaesthesia. During the early postoperative phase of healing,

sometimes post operative analgesic duration is not adequate to compensate acute

nociception associated with surgery. In an effort to enhance post operative analgesia,

many adjuvants like clonidine, buprenorphine, neostigmine, tramadol,epinephrine and

dexamethasone have been added to local anesthetics (LA)(12,14). Several clinical

studies have assessed the efficacy of dexamethasone applied perineurally with local

anaesthetics in regional nerve blocks including epidural(15,16) brachial plexus (17),

femoral and sciatic(18) and facial and dental blocks (19). Alternatives used for

checking postoperative pain (e.g., duration of analgesia, pain scores, opioid

consumption) appear to be enhanced by the addition of dexamethasone to LA agents

injected perineurally (20).

93

Innervation of the arm comes from different nerves. Hence the extent of blockade is

best assessed by evaluating functions unique to each terminal nerve. Pain scores were

lowered at 24 hours and 48 hours postoperatively by adding dexamethasone to local

anaesthetic, corresponding to less opioid consumption over those 24– 48 hours. This

opioid-sparing effect could potentially translate into a reduction in opioid-related

adverse events, including nausea, vomiting, pruritis, and urinary retention,

constipation, and respiratory depression(12). Perineurally administered

dexamethasone added to local anaesthetic delayed the latency and prolonged the

recovery of motor block after brachial plexus block, similar to the analysis from Choi

et al (21). According to a study done by Jasminka, single-shot dexamethasone in a

mixture with Levobupivacaine for Supraclavicular block results in prolonged

analgesia duration and less analgesic use in comparison with Levobupivacaine(106).

Dexamethasone is a highly potent, long-acting glucocorticoid with little

mineralocorticoid effect. It has shown to prolong peripheral nerve blockade in

animals. When dexamethasone is added to bupivacaine microspheres, it extends the

duration of analgesia in humans(8,10).

In our study we found that there was considerable improvement of sensory grading

from 5 to 85 % in levobupivacaine with dexamethasone group and also the difference

between two groups was 20% for grade 1 sensory grading of radial nerve. Over all P

value was 0.144 which shows no significant improvement in radial nerve sensory

grading between the time duration of 3 min to 20 min.(Table 7)

In Levobupivacaine with dexamethasone group, 60-75% of the patients had onset of

sensory blockade for radial nerve around 4-5 min and 85% at the end of 20 min where

94

as 75% achieved sensory blockade of radial nerve after 20 min in Levobupivacaine

group. However this was not statistically significant.(Table 8)

There was a considerable improvement in sensory grading from 10 to 90 % in

Levobupivacaine with dexamethasone group and also the difference between the two

groups was 30% for grade 1. P value was 0.028.This shows statistically significant

improvement in median nerve sensory grading between a duration of 3 min and 20

min.(Table 9)

There was a significant improvement of sensory grading from 10 to 90% in

Levobupivacaine with dexamethasone group and also the difference between the two

groups was 45% for grade 1. P value was 0.013 which shows a significant

improvement in ulnar nerve between duration of 3 min and 20 min.(Table 11)

In our study almost 80% of the patients had onset of motor blockade at the end of 10

min. The difference between the two groups is although not significant.

In our study we identified 65% improvement in motor grading to grade 2 in

Levobupivacane with dexamthasone and 85% improvement to grade 2 in

levobupivacaine at the end of 20 min overall there is significant improvement of

motor blockade at the end of 20 min p value is 0.025 .

Infraclavicular block in particular has its advantages over supraclavicular block. It has

fewer complications, provides complete surgical anesthesia of the operative part, and

immobilization of the upper limb during surgery. The purported advantages of

infraclavicular block are as follows. First, it provides complete anaesthesia of the

upper limb as it blocks the brachial plexus where the three cords run close together in

95

a neurovascular bundle with the axillary artery. There also appears to be a lower

incidence of tourniquet pain with the infraclavicular block, which is attributed to

spread to the intercostobrachial nerve that runs close to the brachial plexus in the

infraclavicular space(48,49). Secondly, the risk of inadvertent lung or pleural puncture

is lower than with the interscalene and supraclavicular approaches as the lung does not

lie in the path of the needle. Thirdly, by piercing the skin below the clavicle, injury to

the other neurovascular structures in the neck are avoided (unlike with the interscalene

or supraclavicular approaches). Fourthly, infraclavicular block does not require

abduction of the arm at the shoulder and can be performed in any arm position and the

neck position need not be changed(50). In our study, patients were assessed for

sensory blockade by pin prick using a 26G needle or ice cube in the dermatomal

distribution of ulnar, median and radial nerves. A modified Bromage scale for the

upper extremity was used to assess motor power.

In our study, among the 40 patients who underwent forearm orthopaedic surgeries,

infraclavicular block was able to provide adequate surgical anesthesia for 87.5% of

patients. But the success of the block was not statistically significant. P value was

0.33.(Table 14)

In our study, post-operative pain was measured using an visual analog scale ranging

from 0-10 and was recorded at various time intervals. There were no differences in

post-operative pain scores in both arms.(Table 15). Only 5% of patients in

Levobupivacaine with dexamethasone group required aceclofenac at the end of 2

hours compared to 15% of patients in Levobupivacaine.

96

The technique of brachial plexus block may result in neurological complications

including respiratory distress, Horner’s syndrome and recurrent laryngeal nerve

injury(22). However, none of the patients developed any complication directly

attributable to the intervention. There was no incidence of post-operative nausea and

vomiting in any of the patients.

97

7. CONCLUSION

1. There was no statistical difference in the onset of sensory and motor blockade of

0.5% Levobupivacaine with 4mg of dexamethasone and 0.5% Levobupivacaine with

1 ml of normal saline added in infraclavicular block in patients undergoing forearm

orthopaedic surgeries . However there was a significant improvement in sensory

grading of median nerve and ulnar nerve between a duration of 3 min and 20 min.(P

value was 0.028 and 0.013 respectively) and also in motor grading improvement at 20

min duration (P value 0.025) in the group with 0.5% Levobupivacaine with 4mg of

dexamethasone in comparison with the group with 0.5% Levobupivacaine with 1 ml

of normal saline.

2. There was no difference in the duration of post-operative analgesia in the group

with 0.5% Levobupivacaine with dexamethasone when compared with the group with

0.5% Levobupivacaine with 1 ml of normal saline added in infraclavicular block in

patients undergoing forearm orthopaedic surgeries.

98

8. LIMITATIONS

Although a larger sample size might have brought out some difference in the post-

operative pain scores in favour of addition of dexamethasone, its clinical implication

is doubtful.

99

9. Scope For Future Research:

A study with larger population size with higher frequency probes can be used to apply

the results in a larger population.

100

10. BIBLIOGRAPHY

1. Gerbershagen HJ, Aduckathil S, van Wijck AJM, Peelen LM, Kalkman CJ,

Meissner W. Pain intensity on the first day after surgery: a prospective cohort

study comparing 179 surgical procedures. Anesthesiology. 2013

Apr;118(4):934–44.

2. Chin KJ, Singh M, Velayutham V, Chee V. Infraclavicular brachial plexus

block for regional anaesthesia of the lower arm. Anesth Analg. 2010

Oct;111(4):1072.

3. Knezevic NN, Anantamongkol U, Candido KD. Perineural dexamethasone

added to local anesthesia for brachial plexus block improves pain but delays

block onset and motor blockade recovery. Pain Physician. 2015 Feb;18(1):1–14.

4. Walker KJ, McGrattan K, Aas-Eng K, Smith AF. Ultrasound guidance for

peripheral nerve blockade. Cochrane Database Syst Rev. 2009;(4):CD006459.

5. Lewis SR, Price A, Walker KJ, McGrattan K, Smith AF. Ultrasound guidance

for upper and lower limb blocks. Cochrane Database Syst Rev.

2015;9:CD006459.

6. Foster RH, Markham A. Levobupivacaine: a review of its pharmacology and

use as a local anaesthetic. Drugs. 2000 Mar;59(3):551–79.

7. Gristwood RW, Greaves JL. Levobupivacaine: a new safer long acting local

anaesthetic agent. Expert Opin Investig Drugs. 1999 Jun;8(6):861–76.

8. Albrecht E, Kern C, Kirkham KR. A systematic review and meta-analysis of

perineural dexamethasone for peripheral nerve blocks. Anaesthesia. 2015

Jan;70(1):71–83.

9. Neal JM, Gerancher JC, Hebl JR, Ilfeld BM, McCartney CJL, Franco CD, et al.

Upper Extremity Regional Anesthesia. Reg Anesth Pain Med. 2009;34(2):134–

70.

10. Holte K, Werner MU, Lacouture PG, Kehlet H. Dexamethasone prolongs local

analgesia after subcutaneous infiltration of bupivacaine microcapsules in human

volunteers. Anesthesiology. 2002 Jun;96(6):1331–5.

11. Johansson A, Hao J, Sjölund B. Local corticosteroid application blocks

transmission in normal nociceptive C-fibres. Acta Anaesthesiol Scand. 1990

Jul;34(5):335–8.

12. De Oliveira GS, Castro Alves LJ, Nader A, Kendall MC, Rahangdale R,

McCarthy RJ. Perineural dexamethasone to improve postoperative analgesia

with peripheral nerve blocks: a meta-analysis of randomized controlled trials.

101

Pain Res Treat [Internet]. 2014 [cited 2016 Jul 1];2014. Available from:

http://www.hindawi.com/journals/prt/2014/179029/abs/

13. Chin KJ, Alakkad H, Adhikary SD, Singh M. Infraclavicular brachial plexus

block for regional anaesthesia of the lower arm. Cochrane Database Syst Rev.

2013;(8):CD005487.

14. Bailard NS, Ortiz J, Flores RA. Additives to local anesthetics for peripheral

nerve blocks: Evidence, limitations, and recommendations. Am J Health Syst

Pharm [Internet]. 2014 [cited 2016 Jul 1];71(5). Available from:

http://search.ebscohost.com/login.aspx?direct=true&profile=ehost&scope=site&

authtype=crawler&jrnl=10792082&AN=94514272&h=MVAC9ww%2FAIJUz

CtBx88tzCkjMpbFltbiqiw4Ri0%2BaS8teuRZD4dRto3rG%2FMnRklJqsBlb0ad

wm6WrzOUZb72LA%3D%3D&crl=c

15. Lauretti GR, Rizzo CC, Mattos AL, Rodrigues SW. Epidural methadone results

in dose-dependent analgesia in cancer pain, further enhanced by epidural

dexamethasone. Br J Cancer. 2013 Feb 5;108(2):259–64.

16. Naghipour B, Aghamohamadi D, Azarfarin R, Mirinazhad M, Bilehjani E,

Abbasali D, et al. Dexamethasone added to bupivacaine prolongs duration of

epidural analgesia. Middle East J Anaesthesiol. 2013 Feb;22(1):53–7.

17. Persec J, Persec Z, Kopljar M, Zupcic M, Sakic L, Zrinjscak IK, et al. Low-dose

dexamethasone with levobupivacaine improves analgesia after supraclavicular

brachial plexus blockade. Int Orthop. 2014 Jan;38(1):101–5.

18. Fredrickson Fanzca MJ, Danesh-Clough TK, White R. Adjuvant dexamethasone

for bupivacaine sciatic and ankle blocks: results from 2 randomized placebo-

controlled trials. Reg Anesth Pain Med. 2013 Aug;38(4):300–7.

19. Jürgens TP, Müller P, Seedorf H, Regelsberger J, May A. Occipital nerve block

is effective in craniofacial neuralgias but not in idiopathic persistent facial pain.

J Headache Pain. 2012 Apr;13(3):199–213.

20. Waldron NH, Jones CA, Gan TJ, Allen TK, Habib AS. Impact of perioperative

dexamethasone on postoperative analgesia and side-effects: systematic review

and meta-analysis. Br J Anaesth. 2013 Feb;110(2):191–200.

21. Choi S, Rodseth R, McCartney CJL. Effects of dexamethasone as a local

anaesthetic adjuvant for brachial plexus block: a systematic review and meta-

analysis of randomized trials. Br J Anaesth. 2014 Mar;112(3):427–39.

22. Conroy PH, Awad IT. Ultrasound-guided blocks for shoulder surgery. Curr

Opin Anaesthesiol. 2011 Dec;24(6):638–43.

23. Standring S. Gray’ Anatomy. The Anatomical Basis of Clinical Practice. 39th

ed. Edinburgh: Elsevier Churchill Livingstone;

102

24. Martinoli C, Bianchi S, Santacroce E, Pugliese F, Graif M, Derchi LE. Brachial

plexus sonography: a technique for assessing the root level. AJR Am J

Roentgenol. 2002 Sep;179(3):699–702.

25. Thompson GE,Brown DL. The commom nerve blocks. 5th edition. London:

Butterworths; 1989. 1068-1069 p.

26. Borene SC, Edwards JN, Boezaart AP. At the cords, the pinkie towards:

Interpreting infraclavicular motor responses to neurostimulation. Reg Anesth

Pain Med. 2004 Apr;29(2):125–9.

27. Moayeri N, Bigeleisen PE, Groen GJ. Quantitative architecture of the brachial

plexus and surrounding compartments, and their possible significance for plexus

blocks. Anesthesiology. 2008 Feb;108(2):299–304.

28. Brown DL. Atlas of Regional Anesthesia. 3rd ed. Philadelphia: Elsevier

Saunders; 2006.

29. Sauter AR, Smith H-J, Stubhaug A, Dodgson MS, Klaastad Ø. Use of magnetic

resonance imaging to define the anatomical location closest to all three cords of

the infraclavicular brachial plexus. Anesth Analg. 2006 Dec;103(6):1574–6.

30. Kilka HG, Geiger P, Mehrkens HH. [Infraclavicular vertical brachial plexus

blockade. A new method for anesthesia of the upper extremity. An anatomical

and clinical study]. Anaesthesist. 1995 May;44(5):339–44.

31. Raj PP, Montgomery SJ, Nettles D, Jenkins MT. Infraclavicular brachial plexus

block--a new approach. Anesth Analg. 1973 Dec;52(6):897–904.

32. Raj PP, Montgomery SJ, Nettles D, Jenkins MT. Infraclavicular brachial plexus

block--a new approach. Anesth Analg. 1973 Dec;52(6):897–904.

33. Whiffler K. Coracoid block--a safe and easy technique. Br J Anaesth. 1981

Aug;53(8):845–8.

34. Koscielniak-Nielsen ZJ, Rasmussen H, Hesselbjerg L, Gũrkan Y, Belhage B.

Clinical evaluation of the lateral sagittal infraclavicular block developed by

MRI studies. Reg Anesth Pain Med. 2005 Aug;30(4):329–34.

35. Dingemans E, Williams SR, Arcand G, Chouinard P, Harris P, Ruel M, et al.

Neurostimulation in ultrasound-guided infraclavicular block: a prospective

randomized trial. Anesth Analg. 2007 May;104(5):1275–1280, tables of

contents.

36. Sandhu NS, Manne JS, Medabalmi PK, Capan LM. Sonographically guided

infraclavicular brachial plexus block in adults: a retrospective analysis of 1146

cases. J Ultrasound Med Off J Am Inst Ultrasound Med. 2006

Dec;25(12):1555–61.

103

37. McCartney CJL, Lin L, Shastri U. Evidence basis for the use of ultrasound for

upper-extremity blocks. Reg Anesth Pain Med. 2010 Apr;35(2 Suppl):S10-15.

38. Wu TJ, Lin SY, Liu CC, Chang HC, Lin CC. Ultrasound imaging aids

infraclavicular brachial plexus block. Ma Zui Xue Za Zhi Anaesthesiol Sin.

1993 Jun;31(2):83–6.

39. Sandhu NS, Capan LM. Ultrasound-guided infraclavicular brachial plexus

block. Br J Anaesth. 2002 Aug;89(2):254–9.

40. Beh ZY, Hasan MS, Lai HY, Kassim NM, Md Zin SR, Chin KF. Posterior

parasagittal in-plane ultrasound-guided infraclavicular brachial plexus block-a

case series. BMC Anesthesiol. 2015;15:105.

41. Winnie AP. Interscalene brachial plexus block. Anesth Analg. 1970

Jun;49(3):455–66.

42. Roch JJ, Sharrock NE, Neudachin L. Interscalene brachial plexus block for

shoulder surgery: a proximal paresthesia is effective. Anesth Analg. 1992

Sep;75(3):386–8.

43. Winnie AP. Interscalene brachial plexus block. Anesth Analg. 1970

Jun;49(3):455–66.

44. Lanz E, Theiss D, Jankovic D. The extent of blockade following various

techniques of brachial plexus block. Anesth Analg. 1983 Jan;62(1):55–8.

45. Borgeat A, Dullenkopf A, Ekatodramis G, Nagy L. Evaluation of the lateral

modified approach for continuous interscalene block after shoulder surgery.

Anesthesiology. 2003 Aug;99(2):436–42.

46. Urmey WF, Gloeggler PJ. Pulmonary function changes during interscalene

brachial plexus block: effects of decreasing local anesthetic injection volume.

Reg Anesth. 1993 Aug;18(4):244–9.

47. Liguori GA, Kahn RL, Gordon J, Gordon MA, Urban MK. The use of

metoprolol and glycopyrrolate to prevent hypotensive/bradycardic events during

shoulder arthroscopy in the sitting position under interscalene block. Anesth

Analg. 1998 Dec;87(6):1320–5.

48. Sardesai AM, Patel R, Denny NM, Menon DK, Dixon AK, Herrick MJ, et al.

Interscalene brachial plexus block: can the risk of entering the spinal canal be

reduced? A study of needle angles in volunteers undergoing magnetic resonance

imaging. Anesthesiology. 2006 Jul;105(1):9–13.

49. Benumof JL. Permanent loss of cervical spinal cord function associated with

interscalene block performed under general anesthesia. Anesthesiology. 2000

Dec;93(6):1541–4.

104

50. Boezaart AP, Koorn R, Rosenquist RW. Paravertebral approach to the brachial

plexus: an anatomic improvement in technique. Reg Anesth Pain Med. 2003

Jun;28(3):241–4.

51. Boezaart AP, De Beer JF, Nell ML. Early experience with continuous cervical

paravertebral block using a stimulating catheter. Reg Anesth Pain Med. 2003

Oct;28(5):406–13.

52. Pham-Dang C, Gunst JP, Gouin F, Poirier P, Touchais S, Meunier JF, et al. A

novel supraclavicular approach to brachial plexus block. Anesth Analg. 1997

Jul;85(1):111–6.

53. Kulenkampff D. BRACHIAL PLEXUS ANAESTHESIA: ITS INDICATIONS,

TECHNIQUE, AND DANGERS. Ann Surg. 1928 Jun;87(6):883–91.

54. Moorthy SS, Schmidt SI, Dierdorf SF, Rosenfeld SH, Anagnostou JM. A

supraclavicular lateral paravascular approach for brachial plexus regional

anesthesia. Anesth Analg. 1991 Feb;72(2):241–4.

55. Brown DL, Cahill DR, Bridenbaugh LD. Supraclavicular nerve block: anatomic

analysis of a method to prevent pneumothorax. Anesth Analg. 1993

Mar;76(3):530–4.

56. Williams SR, Chouinard P, Arcand G, Harris P, Ruel M, Boudreault D, et al.

Ultrasound guidance speeds execution and improves the quality of

supraclavicular block. Anesth Analg. 2003 Nov;97(5):1518–23.

57. Duggan E, El Beheiry H, Perlas A, Lupu M, Nuica A, Chan VWS, et al.

Minimum effective volume of local anesthetic for ultrasound-guided

supraclavicular brachial plexus block. Reg Anesth Pain Med. 2009

Jun;34(3):215–8.

58. Renes SH, Spoormans HH, Gielen MJ, Rettig HC, van Geffen GJ.

Hemidiaphragmatic paresis can be avoided in ultrasound-guided supraclavicular

brachial plexus block. Reg Anesth Pain Med. 2009 Dec;34(6):595–9.

59. Desroches J. The infraclavicular brachial plexus block by the coracoid approach

is clinically effective: an observational study of 150 patients. Can J Anaesth J

Can Anesth. 2003 Mar;50(3):253–7.

60. Brown DL. Brachial plexus anesthesia: an analysis of options. Yale J Biol Med.

1993 Oct;66(5):415–31.

61. Sharma JP, Salhotra R. Tourniquets in orthopedic surgery. Indian J Orthop.

2012;46(4):377–83.

62. Guntz E, Herman P, Delbos A, Sosnowski M. The radial nerve should be

blocked before the ulnar nerve during a brachial plexus block at the humeral

canal. Can J Anaesth J Can Anesth. 2004 Apr;51(4):354–7.

105

63. Spence BC, Sites BD, Beach ML. Ultrasound-guided musculocutaneous nerve

block: a description of a novel technique. Reg Anesth Pain Med. 2005

Apr;30(2):198–201.

64. Neal JM, Bernards CM, Hadzic A, Hebl JR, Hogan QH, Horlocker TT, et al.

ASRA Practice Advisory on Neurologic Complications in Regional Anesthesia

and Pain Medicine. Reg Anesth Pain Med. 2008 Oct;33(5):404–15.

65. Auroy Y, Narchi P, Messiah A, Litt L, Rouvier B, Samii K. Serious

complications related to regional anesthesia: results of a prospective survey in

France. Anesthesiology. 1997 Sep;87(3):479–86.

66. Lee LA, Posner KL, Domino KB, Caplan RA, Cheney FW. Injuries associated

with regional anesthesia in the 1980s and 1990s: a closed claims analysis.

Anesthesiology. 2004 Jul;101(1):143–52.

67. Horlocker TT, Kufner RP, Bishop AT, Maxson PM, Schroeder DR. The risk of

persistent paresthesia is not increased with repeated axillary block. Anesth

Analg. 1999 Feb;88(2):382–7.

68. Rice AS, McMahon SB. Peripheral nerve injury caused by injection needles

used in regional anaesthesia: influence of bevel configuration, studied in a rat

model. Br J Anaesth. 1992 Nov;69(5):433–8.

69. Myers RR, Heckman HM. Effects of local anesthesia on nerve blood flow:

studies using lidocaine with and without epinephrine. Anesthesiology. 1989

Nov;71(5):757–62.

70. Selander D, Brattsand R, Lundborg G, Nordborg C, Olsson Y. Local

anesthetics: importance of mode of application, concentration and adrenaline for

the appearance of nerve lesions. An experimental study of axonal degeneration

and barrier damage after intrafascicular injection or topical application of

bupivacaine (Marcain). Acta Anaesthesiol Scand. 1979 Apr;23(2):127–36.

71. Schneider U, Jund R, Nees S, Grafe P. Differences in sensitivity to

hyperglycemic hypoxia of isolated rat sensory and motor nerve fibers. Ann

Neurol. 1992 Jun;31(6):605–10.

72. Kalichman MW, Moorhouse DF, Powell HC, Myers RR. Relative neural

toxicity of local anesthetics. J Neuropathol Exp Neurol. 1993 May;52(3):234–

40.

73. Myers RR, Kalichman MW, Reisner LS, Powell HC. Neurotoxicity of local

anesthetics: altered perineurial permeability, edema, and nerve fiber injury.

Anesthesiology. 1986 Jan;64(1):29–35.

74. Sanford M, Keating GM. Levobupivacaine: a review of its use in regional

anaesthesia and pain management. Drugs. 2010 Apr 16;70(6):761–91.

106

75. Bajwa SJS, Kaur J. Clinical profile of levobupivacaine in regional anesthesia: A

systematic review. J Anaesthesiol Clin Pharmacol. 2013 Oct;29(4):530–9.

76. Aberg G. Toxicological and local anaesthetic effects of optically active isomers

of two local anaesthetic compounds. Acta Pharmacol Toxicol (Copenh).

1972;31(4):273–86.

77. Thomas JM, Schug SA. Recent advances in the pharmacokinetics of local

anaesthetics. Long-acting amide enantiomers and continuous infusions. Clin

Pharmacokinet. 1999 Jan;36(1):67–83.

78. Sundarathiti P, Sangdee N, Sangasilpa I, Prayoonhong W, Papoun S.

Comparison of intrathecal bupivacaine, levobupivacaine for cesarean section. J

Med Assoc Thail Chotmaihet Thangphaet. 2014 Jul;97(7):710–6.

79. Alley EA, Kopacz DJ, McDonald SB, Liu SS. Hyperbaric spinal

levobupivacaine: a comparison to racemic bupivacaine in volunteers. Anesth

Analg. 2002 Jan;94(1):188–193, table of contents.

80. Glaser C, Marhofer P, Zimpfer G, Heinz MT, Sitzwohl C, Kapral S, et al.

Levobupivacaine versus racemic bupivacaine for spinal anesthesia. Anesth

Analg. 2002 Jan;94(1):194–198, table of contents.

81. Fattorini F, Ricci Z, Rocco A, Romano R, Pascarella MA, Pinto G.

Levobupivacaine versus racemic bupivacaine for spinal anaesthesia in

orthopaedic major surgery. Minerva Anestesiol. 2006 Aug;72(7–8):637–44.

82. Cox CR, Faccenda KA, Gilhooly C, Bannister J, Scott NB, Morrison LM.

Extradural S(-)-bupivacaine: comparison with racemic RS-bupivacaine. Br J

Anaesth. 1998 Mar;80(3):289–93.

83. Faccenda KA, Simpson AM, Henderson DJ, Smith D, McGrady EM, Morrison

LMM. A comparison of levobupivacaine 0.5% and racemic bupivacaine 0.5%

for extradural anesthesia for caesarean section. Reg Anesth Pain Med. 2003

Oct;28(5):394–400.

84. Bader AM, Tsen LC, Camann WR, Nephew E, Datta S. Clinical effects and

maternal and fetal plasma concentrations of 0.5% epidural levobupivacaine

versus bupivacaine for cesarean delivery. Anesthesiology. 1999

Jun;90(6):1596–601.

85. Cok OY, Eker HE, Turkoz A, Findikcioglu A, Akin S, Aribogan A, et al.

Thoracic epidural anesthesia and analgesia during the perioperative period of

thoracic surgery: levobupivacaine versus bupivacaine. J Cardiothorac Vasc

Anesth. 2011 Jun;25(3):449–54.

86. Sathyanarayana LA, Heggeri VM, Simha PP, Narasimaiah S, Narasimaiah M,

Subbarao BK. Comparison of Epidural Bupivacaine, Levobupivacaine and

107

Dexmedetomidine in Patients Undergoing Vascular Surgery. J Clin Diagn Res

JCDR. 2016 Jan;10(1):UC13-17.

87. Fedriani de Matos JJ, Atienza Carrasco FJ, Díaz Crespo J, Moreno Martín A,

Tatsidis Tatsidis P, Torres Morera LM. Effectiveness and safety of continuous

ultrasound-guided femoral nerve block versus epidural analgesia after total knee

arthroplasty. Rev Esp Anestesiol Reanim. 2016 Jul 8;

88. Aksu R, Bicer C, Ozkiris A, Akin A, Bayram A, Boyaci A. Comparison of 0.5%

levobupivacaine, 0.5% bupivacaine, and 2% lidocaine for retrobulbar anesthesia

in vitreoretinal surgery. Eur J Ophthalmol. 2009 Apr;19(2):280–4.

89. McClellan KJ, Spencer CM. Levobupivacaine. Drugs. 1998 Sep;56(3):355-362-

364.

90. Valenzuela C, Snyders DJ, Bennett PB, Tamargo J, Hondeghem LM.

Stereoselective block of cardiac sodium channels by bupivacaine in guinea pig

ventricular myocytes. Circulation. 1995 Nov 15;92(10):3014–24.

91. Leone S, Di Cianni S, Casati A, Fanelli G. Pharmacology, toxicology, and

clinical use of new long acting local anesthetics, ropivacaine and

levobupivacaine. Acta Bio-Medica Atenei Parm. 2008 Aug;79(2):92–105.

92. Mazoit JX, Boïco O, Samii K. Myocardial uptake of bupivacaine: II.

Pharmacokinetics and pharmacodynamics of bupivacaine enantiomers in the

isolated perfused rabbit heart. Anesth Analg. 1993 Sep;77(3):477–82.

93. Graf BM, Martin E, Bosnjak ZJ, Stowe DF. Stereospecific effect of bupivacaine

isomers on atrioventricular conduction in the isolated perfused guinea pig heart.

Anesthesiology. 1997 Feb;86(2):410–9.

94. Huang YF, Pryor ME, Mather LE, Veering BT. Cardiovascular and central

nervous system effects of intravenous levobupivacaine and bupivacaine in

sheep. Anesth Analg. 1998 Apr;86(4):797–804.

95. Hamber EA, Viscomi CM. Intrathecal lipophilic opioids as adjuncts to surgical

spinal anesthesia. Reg Anesth Pain Med. 1999 Jun;24(3):255–63.

96. Picard PR, Tramèr MR, McQuay HJ, Moore RA. Analgesic efficacy of

peripheral opioids (all except intra-articular): a qualitative systematic review of

randomised controlled trials. Pain. 1997 Sep;72(3):309–18.

97. Burm AG, van Kleef JW, Gladines MP, van Duinen M, Spierdijk J. Spinal

anesthesia with hyperbaric lidocaine and bupivacaine: effects of epinephrine on

the plasma concentration profiles. Anesth Analg. 1987 Nov;66(11):1104–8.

98. Katz RL, Bigger JT. Cardiac arrhythmias during anesthesia and operation.

Anesthesiology. 1970 Aug;33(2):193–213.

108

99. Murphy DB, McCartney CJ, Chan VW. Novel analgesic adjuncts for brachial

plexus block: a systematic review. Anesth Analg. 2000 May;90(5):1122–8.

100. Hutschala D, Mascher H, Schmetterer L, Klimscha W, Fleck T, Eichler HG, et

al. Clonidine added to bupivacaine enhances and prolongs analgesia after

brachial plexus block via a local mechanism in healthy volunteers. Eur J

Anaesthesiol. 2004 Mar;21(3):198–204.

101. Kopacz DJ, Lacouture PG, Wu D, Nandy P, Swanton R, Landau C. The dose

response and effects of dexamethasone on bupivacaine microcapsules for

intercostal blockade (T9 to T11) in healthy volunteers. Anesth Analg. 2003

Feb;96(2):576–582, table of contents.

102. Movafegh A, Razazian M, Hajimaohamadi F, Meysamie A. Dexamethasone

added to lidocaine prolongs axillary brachial plexus blockade. Anesth Analg.

2006 Jan;102(1):263–7.

103. Kim YJ, Lee GY, Kim DY, Kim CH, Baik H-J, Heo S. Dexamathasone added

to levobupivacaine improves postoperative analgesia in ultrasound guided

interscalene brachial plexus blockade for arthroscopic shoulder surgery. Korean

J Anesthesiol. 2012 Feb;62(2):130–4.

104. The effect of dexamethasone on postoperative pain and emesis after intrathecal

neostigmine. - PubMed - NCBI [Internet]. [cited 2016 Aug 8]. Available from:

http://www.ncbi.nlm.nih.gov/pubmed/11133633

105. Attardi B, Takimoto K, Gealy R, Severns C, Levitan ES. Glucocorticoid

induced up-regulation of a pituitary K+ channel mRNA in vitro and in vivo.

Receptors Channels. 1993;1(4):287–93.

106. Abdallah FW, Johnson J, Chan V, Murgatroyd H, Ghafari M, Ami N, et al.

Intravenous dexamethasone and perineural dexamethasone similarly prolong the

duration of analgesia after supraclavicular brachial plexus block: a randomized,

triple-arm, double-blind, placebo-controlled trial. Reg Anesth Pain Med. 2015

Apr;40(2):125–32.

107. Tandoc MN, Fan L, Kolesnikov S, Kruglov A, Nader ND. Adjuvant

dexamethasone with bupivacaine prolongs the duration of interscalene block: a

prospective randomized trial. J Anesth. 2011 Oct;25(5):704–9.

108. Persec J, Persec Z, Kopljar M, Zupcic M, Sakic L, Zrinjscak IK, et al. Low-dose

dexamethasone with levobupivacaine improves analgesia after supraclavicular

brachial plexus blockade. Int Orthop. 2014 Jan;38(1):101–5.

109. Parrington SJ, O’Donnell D, Chan VWS, Brown-Shreves D, Subramanyam R,

Qu M, et al. Dexamethasone added to mepivacaine prolongs the duration of

analgesia after supraclavicular brachial plexus blockade. Reg Anesth Pain Med.

2010 Oct;35(5):422–6.

109

110. Holte K, Werner MU, Lacouture PG, Kehlet H. Dexamethasone prolongs local

analgesia after subcutaneous infiltration of bupivacaine microcapsules in human

volunteers. Anesthesiology. 2002 Jun;96(6):1331–5.

111. Akkaya A, Yildiz I, Tekelioglu UY, Demirhan A, Bayir H, Ozlu T, et al.

Dexamethasone added to levobupivacaine in ultrasound-guided tranversus

abdominis plain block increased the duration of postoperative analgesia after

caesarean section: a randomized, double blind, controlled trial. Eur Rev Med

Pharmacol Sci. 2014;18(5):717–22.

112. Persec J, Persec Z, Kopljar M, Zupcic M, Sakic L, Zrinjscak IK, et al. Low-dose

dexamethasone with levobupivacaine improves analgesia after supraclavicular

brachial plexus blockade. Int Orthop. 2014 Jan;38(1):101–5.

110

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Annexure 1: Institutional review board acceptance and fluid grant

letter

112

113

114

Annexure 2: Information sheet

115

Annexure 3:Informed consent form

116

Annexure 4: Informed consent in Hindi

117

Annexure 5: Patient information sheet in Hindi

118

119

Annexure 7: Informed consent form in Tamil

120

Annexure 8: PROFORMA of the study

Levobupivacaine with dexamethasone versus levobupivicaine in patients undergoing

forearm and hand surgeries under an infraclavicular block

1.Study no:

2.Name:

3.Hospital number :

4.Mobile number :

5.Age ( in years)

6.Height : Weight:

7.Name of surgery:

8.Date of surgery:

9.DRUG: A /B

10.Duration of surgery:

ASA grade:

Preoperative:

Baseline vitals : BP, SPO2,HR-

Midazolam:

Fentanyl:

11.Time of Onset of sensory blockade:

121

Nerves

Grading

1min 2min 3min 4min 5min 10

min

15

min

20min

Radial

nerve

Median

nerve

Ulnar

nerve

Grading of sensory blockade pin prick/ice. Thenar eminence- median , dorsum of

hand –radial

Hypothenar –ulnar .

Grade 0- pain / normal sensation .

Grade 1-analgesia / decreased sensation

Grade 2-anesthesia / no sensation

12. Onset of Motor blockade:

Grading 5 min 10 min 15min 20 min

0

1

2

3

This scale ( modified bromage )consists of the following 4 scores:

122

0- able to raise the extended arm to 90°for a full 2 seconds;

1 -able to flex the elbow and move the fingers but unableto raise the extended arm;

2 -unable to flex the elbow but able to move the fingers; and

3 -unable to move the arm, elbow, or fingers

Intraop analgesia:

POST PROCEDURE VITALS:BP,SPO2,HR-

Intraoperative: ADEQUECY OF SURGICAL ANESTHESIA

YES

NO

If no, please mention if additional analgesics were given or if conversion to general

anaesthesia was

needed

Post operative:

12.Duration of analgesia

Time 3hrs 6hrs 12hrs 24hrs

VAS

Tab

aceclofenac

Inj morphine

123

13. VAS score: 0/1/2/3/4/5/6/7/8/9/10

14. Tab Aceclofenac: Yes/No

15. inj .Morphine 0.1mg/kg: yes/no

16.inj .paracetmol 1gm :yes /no.