“COMPARISON OF 0.25% WITH 0.375% FOR FIELD BLOCK IN INGUINAL HERNIA REPAIR”

Dissertation submitted to The Tamil Nadu Dr.M.G.R. Medical University Chennai – 600032. In partial fulfilment of the regulations for the Degree of

M.D.ANAESTHESIOLOGY BRANCH – X

Under the guidance of Dr.R.SELVAKUMAR M.D., D.A., Professor and Head of the Department

DEPARTMENT OF ANAESTHESIOLOGY K.A.P.VISWANATHAM GOVT. MEDICAL COLLEGE, TRICHY.

APRIL - 2017 BONAFIDE CERTIFICATE

This is to certify that this dissertation titled “COMPARISON OF

0.25 % BUPIVACAINE WITH 0.375% ROPIVACAINE FOR

FIELD BLOCK IN INGUINAL HERNIA REPAIR” is a bonafide work of Dr.J.RAMYA, Post Graduate in M.D.Anaesthesiology,

Department of Anaesthesiology, K.A.P.V. Government Medical

College, Trichy and has been prepared by her under our guidance. This has been submitted in partial fulfilment of regulations of The Tamil Nadu

Dr. M.G.R. Medical University,Chennai-32 for the award of M.D. Degree in Anaesthesiology.

Prof. Dr.S.LILY MARY Dr. R.SELVAKUMAR. M.D, D.A Dean, Professor and Head of Department, K.A.P.V. Govt. Medical College, Department of Anaesthesiology Trichy. K.A.P.V. Govt. Medical College, Trichy

Place:Trichy Date:

DECLARATION

I Dr.J.RAMYA, solemnly declare that this dissertation titled

“COMPARISON OF 0.25% BUPIVACAINE WITH 0.375%

ROPIVACAINEFOR FIELD BLOCK IN INGUINAL HERNIA

REPAIR”, is a bonafide work done by me at K.A.P.V. Government

Medical College, during 2015-2016 under the guidance and supervision of Dr.R.SELVAKUMARM.D.,D.A., Professor and Head Of the department, Department of Anaesthesiology, K.A.P.V. Government

Medical College, Trichy.

The dissertation is submitted to The TamilnaduDr. M.G.R. Medical

University, towards the partial fulfillment of requirement for the award of

M.D. Degree in Anaesthesiology Branch X.

PLACE :TRICHY DATE : Dr. J.RAMYA,M.B.B.S., Post Graduate Student, Department of Anaesthesiology, K.A.P.V. GOVT. Medical College, Trichy.

COPYRIGHT DECLARATION BY THE CANDIDATE

I hereby declare that The Dr.M.G.R Medical University, Chennai, shall have the rights to preserve, use and disseminate this dissertation in print or electronic format for academic /research purpose.

Dr. J.RAMYA, M.B.B.S., Post Graduate Student, Department of Anaesthesiology, K.A.P.V. GOVT. Medical College, Trichy.

Place: Trichy Date:

ACKNOWLEDGEMENT

I thank our DEAN Prof.Dr.S.MARY LILLY, K.A.P.V. Govt. Medical College, Trichy for permitting me to conduct this study in the Department of Anaesthesiology, K.A.P.V. Government Medical College, Trichy.

My sincere thanks to Prof. Dr.R.SELVAKUMAR,M.D.,D.A., Head of Department of Anaesthesiology, for helping and guiding me during this study.

My heartfelt gratitude to Prof. Dr.G.SIVAKUMAR M.D.,D.A., Prof. Dr.M.SURESH,M.D.,D.A.,and Prof. Dr.P.ElANGO M.D for their esteemed guidance and valuable suggestions.

It is my privileged duty to thank Asst.Prof.DR.L.R.GANESSAN M.Dand DR.BALASUBRAMANIAGUHAN M.D., for their constant help and encouragement in preparing this dissertation.

My sincere thanks to all my Assistant Professors who have put in countless hours in guiding me in many aspects of this study and also in honing my anaesthetic skills.

I thank my fellow Post graduates who helped me in conducting the study.

I am greatly indebted to all my patients without whom this study would not have been a reality. I thank all the anaesthesia assistants and staff nurses who cooperated with me at all times.

My sincere thanks to Prof. Jesu raja for his help and advice on statistical methods.

I take this opportunity to thank my family and my friends for their unconditional love and support.

Dr.J.RAMYA, M.B.B.S., Post Graduate Student, Department of Anaesthesiology, K.A.P.V. GOVT. Medical College, Trichy.

Place: Trichy Date:

LIST OF ABBREVIATIONS USED

(In alphabetical order)

ASA - American Society of Anaesthesiologist

ASIS - Anterior superior iliac spine

BP - Blood pressure

CNS - central nervous system

CVS - cardiovascular system

ECG - electrocardiography

EOA - external oblique aponeurosis

GA - general anaesthesia

Gm - grams

HR - heart rate

I.M - Intramuscular

IOA - internal oblique aponeurosis

LA - local anaesthesia

Mcg - microgram

Min - Minute mmHg - Millimeter of mercury

MIL - midpoint of inguinal ligament

MPK - Mitogen activated protein kinase pathway

RS - respiratory system

SBP - Systolic blood pressure

Sec - Seconds

TF - transversalis fascia

VAS - visual analog scale

VRS - verbal rating score

% - Percentage

CONTENTS

S. No Title Page No. 1. INTRODUCTION 1 2. AIMS AND OBJECTIVES 3 3. REVIEW OF LITERATURE 4 4. HISTORICAL REVIEW 9 5. ANATOMY OF INGUINAL FIELD BLOCK 13 6. PHARMACOLOGY 19 7. MATERIALS AND METHODS 33 8. OBSERVATION AND RESULTS 42 9. DISCUSSION 71 10. CONCLUSION 77 11. SUMMARY 78 12. BIBLIOGRAPHY 80 ANNEXURES A. PROFORMA 86

B. CONSENT FORM 89 13. C. MASTER CHART 92

LIST OF FIGURES

Figure Page Title No. No.

1. LUMBAR PLEXUS 11

2. DERMATOMAL INNERVATION 12

3. TECHNIQUE OF FIELD BLOCK 15

4. CHEMICAL STRUCTURE OF 19 BUPIVACAINE

5. BUPIVACAINE HYDROCHLORIDE 19

6. CHEMICAL STRUCTURE OF 25 ROPIVACAINE

7. ROPIVACAINE HYDROCHLORIDE 25

8. VISUAL ANALOG SCALE 37

LIST OF GRAPHS

Graph Page Title No. No.

1. COMPARISON OF BMI 43

2. COMPARISON OF ASA 45

3. COMPARISON OF ONSET OF BLOCK 46

4. COMPARISON OF ADEQUACY OF 53 BLOCK

5. COMPARISON OF SIDE EFFECTS 55

6. COMPARISON OF SIDE EFFECTS 56 OBSERVED

7. COMPARISON OF SURGEON 58 SATISFACTION

8. COMPARISON OF TIME REQUIREMENT 60 FOR FIRST ANALGESIC

9. COMPARISON OF MEAN HEART RATE 66

10. COMPARISON OF MEAN SYSTOLIC 69 BLOOD PRESSURE

LIST OF TABLES

Table Page Title No. No.

1. PAIN SCORE WITH VISUAL ANALOG SCALE 37

2. ADEQUACY OF BLOCK 38

3. VERBAL RATING SCORE 40

4. SURGEON SATISFACTION SCALE 41

5. SURGEON SATISFACTION SCORE 41

6. COMPARISON OF BMI 43

7. COMPARISON OF ASA 45

8. COMPARISON OF ONSET OF BLOCK 46

9. AVERAGE TIME OF ONSET OF BLOCK 51

10. ONSET OF BLOCK IN ACTUAL NUMBER OF 52 PATIENTS

11. COMPARISON OF ADEQUACY OF BLOCK 53

12. COMPARISON OF SIDE EFFECTS 57

13. COMPARISON OF SURGEON SATISFACTION 59

14. COMPARISON OF TIME REQUIREMENT FOR 61 FIRST ANALGESIC

15. AVERAGE DURATION OF POST-OP PAIN 63 RELIEF

16. POST-OP ANALGESIC DURATION IN ACTUAL 64 NUMBER OF PATIENTS

17. COMPARISON OF MEAN HEART RATE 65

18. COMPARISON OF MEAN SYSTOLIC BLOOD 67 PRESSURE

INTRODUCTION

Hernia repair is one of the commonest surgery among worldwide operations. Herniorraphy and Hernioplasty are the techniques for Inguinal hernia repair. Newer technique of laparoscopic mesh repair is also in practice.

Hernia repair can be performed under spinal, epidural, general anaesthesia and inguinal field block. The preferred choice for all reducible Inguinal hernia is local since it inhibits the build up of local nociceptive receptors, hence a longer postoperative pain relief1. Also it is safe, simple and effective without post anaesthesia side effects.

Compared to other techniques spinal /General anaesthesia (GA), field block does not provide a satisfactory level. But it provides prolonged postoperative analgesia, reduced urinary retention and early ambulation.

Also it is a cost effective method2,3 in day care surgery warranting a speedy recovery and also the preferred anaesthesia in geriatric patients with underlying systemic pathology.

Postoperative analgesia is now regarded as an integral part of the surgical care. Insufficient analgesia can have significant pathophysiological and psychological effects in post-operative patients4.

Lack of pain relief may manifest as haemodynamic changes in the form

1 of tachycardia and hypertension, tachypnoea and hypoxemia, altered gastrointestinal motility, impaired urinary tract function5.

The introduction of Bupivacaine and Ropivacaine , other amide local anaesthetic agents with longer duration of action when compared with lignocaine which has a moderate duration of action6 has an added advantage of providing prolonged post op analgesia. Ropivacaine compared with bupivacaine has better cardiac stability with comparable analgesia7.

Hence this study of Field block is undertaken to objectively test the efficacy of block , side effects and degree of postoperative pain relief comparing the two drugs Bupivacaine and Ropivacaine.

2

AIMS AND OBJECTIVE

To study and compare the

The onset of analgesia

The adequacy of block

The duration of postoperative pain relief

Side effects if any, that occurs with the usage of the two drugs

Haemodynamic changes

3

REVIEW OF LITERATURE

A comparative study of 0.5% Bupivacaine and 0.5% Ropivacaine for day case inguinal herniorraphy in a Nigerian tertiary institution was done showing that Ropivacaine and Bupivacaine have comparable onset of actions and adequacy of anaesthesia8.

Randomized study of 160 patients conducted by F H Andersen K

Nielsen at surgical clinic Charlottenlund, Copenhagen, Denmark- combined ilioinguinal blockade and local infiltration anaesthesia for groin hernia repair, showed median intra-operative pain score reduced with additional ilioinguinal blockade. Study concluded that additional use of a preoperative ilioinguinal field block to well established local infiltration anaesthesia procedure for inguinal hernia repair improves intra-operative pain relief9.

Retrospective analysis conducted by P Sanjay, A Woodward, in department of surgery of Ninewells hospital and medical school, revealed tha patient satisfaction is more in local anaesthesia. Also it was seen that local complications like wound hematoma, wound infection, recurrence readmission, postoperative hydrocele is more with local anaesthesia, but there is significant reduction of postoperative urinary retention. Study concluded that use of Local Anaesthesia (LA) results in increased day

4 case-rates, lower postoperative analgesic requirements and fewer micturition problems10.

Prospective study of 454 patients of inguinal hernia repair with local anaesthesia in the outpatient by Flavio Antonio de Sa Ribeiro,

Fernanda Padron, et al showed that there were no adverse effect of local anaesthetics and concluded that procedure is feasible and causes no peri- operative pain, safe and has satisfactory patient acceptance11.

Study conducted by Khurram Niaz, Javed Iqbal et.al at Department of general surgery Bahawal Victoria hospital showed mean hospital stay was 3 days in patients operated under spinal anaesthesia as compared to

24 hours in patients operated under local anaesthesia. Patients operated under spinal anaesthesia had higher morbidity such as urinary retention, post spinal back ache, hypotension, pain and delayed mobilization in post-operative period. As compared patients operated under local anaesthesia had increased incidence of wound infection and hematoma.

They concluded that local anaesthesia is a better option for inguinal hernia repair as compared to spinal anaesthesia with respect to post- operative complications and patients comfort in young as well as old aged patients12.

Prospective study of 72 hernia patients operated under local anaesthesia by Jihad OdehMazenAlomari et al at Prince Ali hospital

5

Jordan, showed 83.3% of patients denied any discomforts during operation, 7% experienced mild discomfort, 5.5% experienced slight pain, and 4% required conversion to general anaesthesia due to patient‟s anxiety. The study concluded that preferred choice for all reducible, adult inguinal hernia repairs is local. It is safe simple, effective and economical without post anaesthesia side effects and produces longer post-operative analgesia13.

Comparative study of local versus spinal anaesthesia in 100 cases of inguinal hernia repair at Saraswati institute of medical sciences,

Srivastava Arati, Sharma Shailja et al. showed that operative analgesia was equally satisfactory in both groups and concluded that augmented LA results in increased day care surgery rates, lower post-operative analgesic requirements and fewer urinary problems14.

Development in local anaesthetic drugs were studied by J.B

Whiteside and J.A Wildsmith in 2001, they found similar onset and extent of both motor and sensory block but slightly longer duration of analgesia with a more concentrated solutions of Ropivacaine. However different concentrations were made in the both obstetric and non-obstetric population but no significant differences in onset and duration of sensory block was found. The motor block was less intense and of shorter duration with Ropivacaine15.

6

J.H.Mcclure in his study on Ropivacaine concluded that

Ropivacaine is an effective long acting local anaesthetic. The sensory block produced by Ropivacaine is similar to that produced by an equivalent dose of Bupivacaine for extradural block, but however the motor block is less intense slower in onset and duration when compared to Bupivacaine. This together with lower toxicity compared with

Bupivacaine, enables Ropivacaine to be used for surgical anaesthesia in concentrations up to 1%16.

M.s. Brockway , J.Bannister , J.H.McClure, D.Mckeown and

J.A.W.Wildsmith. Comparison of extradural ropivacaine and bupivacaine. Ropivacaine produced slower onset, shorter duration and less intense motor block as compared to same concentration of

Bupivacaine17.

Acute toxicity of Ropivacaine was compared with Bupivacaine by

D.Bruce scott Alistair lee et al. They concluded that Ropivacaine caused less neurological symptoms and 25% less toxic than Bupivacaine in regard to dose tolerated. There was no change in cardiac output. Although both drugs caused evidence of depression of conductivity and contractility of heart, these are found at a lesser plasma concentration with Bupivacaine than Ropivacaine18.

7

Pharmacology, toxicology and clinical use of new long acting local anaesthetics Ropivacaine and were studied by Stefania leone, Simone di et al on comparing racemic Bupivacaine with

Ropivacaine, they found that Ropivacaine showed the clinically relevant advantage of a stronger differentiation between sensory and motor blocks which is particularly useful for early mobilisation. They also found that

Ropivacaine is 40-50% less potent than Bupivacaine because of its lower lipid solubility. Equipotency ratio of 1.5:1 (ropivacaine:bupivacaine) gives a good preservation of motor function19.

Philipp Lirk, Ingridhaller, Hanspeter et al studied in vitro inhibition of mitogen activated protein kinase pathway (MAPK) protect against

Bupivacaine and Ropivacaine induced neurotoxicity. They showed that

Bupivacaine and Ropivacaine exert their neurotoxic effects by MAPKs, while specific pharmacologic inhibition of these kinases attenuates neurotoxicity in vitro20.

There were no significant differences between groups in pain, need for supplementary analgesic, motor block and ability to walk. Patients in the Ropivacaine group received significantly more ketorolac than patients with Bupivacaine. Time to discharge from hospital was similar with both group21.

8

HISTORICAL REVIEW

Hernia is the word derived from the Greek word “the herons” an offshoot or bulge. It is defined by Sir Astley Cooper (1840) as protrusion of viscus or any part of viscus through an abnormal opening in the walls of its containing cavity22.

August bier is the father of intrathecal anaesthesia. He theoritized that his technique , called cocainization of the spinal cord, might provide the pain relief necessary for major surgery.

The discovery of local analgesic effect of by Carl koller in

1884 made possible the vast array of peripheral local and regional analgesic therapy, whereas previously the only major site of pain control was thought to be brain23.

Cocaine is a naturally occurring compound. It was the first anaesthetic to be discovered and the only naturally occurring local anaesthetic. Introduced into Europe in 1800s, Sigmund freud the noted

Austrian psychoanalyst , used cocaine on his patients and became addicted through self experimentation.

In the latter half of 1800s, Koller introduced cocaine to the field of ophthalmology and Hall introduced into the dentistry. Halsted was the

9 first to use cocaine in nerve blocks in The United states in 1885 and also became addicted.

The use of cocaine for local and regional anaesthesia rapidly spread throughout Europe and America. The toxic effects of cocaine led to many deaths among both patients and medical staffs. The development of modern organic chemistry led to the synthesis of pure cocaine in 1891.

New amino esters were synthesized between 1891 and 1930 - tropocaine, eucaine, holocaine, orthoform, and . Amino amides were prepared between 1898 and 1972 nirvaquine, , choloroprocaine, , , , , efocaine, bupivacaine, and .

Procaine was the first synthetic derivative of cocaine introduced in

1904. Later Lofgren developed lignocaine, the most widely used LA during world war II in 1943. Bupivacaine is of special interest due to its long duration of action and wide clinical application. Synthesized in

1957, the introduction of bupivacaine also paralleled reports of neurotoxicity and cardiotoxicity which refined our study in understanding of local anaesthetics.

The study on optically active isomers of mepivacaine family led to the selection of ropivacine , a pure s-(-) enanatiomer, which was extensively studied for toxicity before introducing into market in 1996.

10

Figure-1 LUMBAR PLEXUS

11

Figure-2 DERMATOMAL INNERVATION

12

ANATOMY OF FIELD BLOCK (figure-1)

Nerves of interest for the inguinal field block are the ilio inguinal, ilio hypogastric, genitofemoral and lateral cutaneous nerves of thigh.

The ilio inguinal and ilio hypogastric nerves arise together from the first lumbar nerve L1. The ilio inguinal nerve emerges from the lateral border of the psoas major and passes obliquely across the quadratus lumborum. At a point just medial to the anterior superior iliac spine it pierces the transversus and the internal oblique muscle to enter the inguinal canal and exits through the superficial inguinal ring. It supplies the somatic sensation to the skin of the upper and medial thigh. In males it also innervates base of the penis and the upper scrotum. In females it innervates the mons pubis and the labium majus.

The ilio hypogastric nerve arises from T12 L1. After it pierces the deep abdominal wall it courses between the internal oblique and the transversus abdominis supplying both.

The genitofemoral nerve arises from L1 L2. Courses along the retro peritoneum and emerges on the anterior aspect of psoas. It then divides into genital and femoral branches. The genital branch enters the inguinal canal lateral to inferior epigastric vessels and it courses ventral to iliac vessels and ilio pubic tract. In males it travels through the

13 superficial inguinal ring and supplies the ipsilateral scrotum. In females it supplies the ipsilateral mons pubis and labium majus.

The femoral branch courses along the femoral sheath supplying the skin of the upper anterior thigh. The lateral femoral cutaneous nerves arises from L2 L3 emerges lateral to psoas muscle at the level of L4 and crosses the iliacus muscle obliquely towards the anterior superior iliac spine. It then passes inferior to the inguinal ligament where it supplies the lateral thigh.

14

Figure-3 FIELD BLOCK

3.a-2cm above and medial from Anterior superior iliac spine

3.b – pubic tubercle

3.c- 0.5cm below midpoint of inguinal ligament

15

3.d – midline for blocking crossing over fibres

3.e – skin incsion

16

PROCEDURE OF FIELD BLOCK FOR INGUINAL HERNIA

REPAIR

The block was done using the technique described by Pinnock et al24. (fig-3).

The dermatome involved in the block is shown in (fig-2)

1. Under strict aseptic precautions, 40 ml of solution for the block

(20ml of LA + 20ml distilled water) was prepared by the researcher

who is blinded further in the study.

2. The patient is placed in spine position

3. A skin wheal is made half inch medial and superior to anterior

superior iliac spine (ASIS). A 22 G hypodermic needle was fixed

to a syringe containing 10 ml of the local anaesthetic, was directed

perpendicular to the skin. The needle was placed above the Internal

oblique aponeurosis (IOA) piercing the External oblique (EOA)

and 2 ml of local anaesthetic was given and 4 ml was given in a fan

shaped manner at 45 degree. (Total = 2+2+2ml) (fig-3.a)

4. The Internal oblique aponeurosis pierced and local anaesthetic

injected in a fan shaped manner over the Transversalis fascia (TF).

(Total = 2+2+2ml) (fig-3.a)

5. A second wheal was made over the pubic tubercle (PT) and 5 ml of

local anaesthetic was injected (fig-3.b)

17

6. A third skin wheal was raised 0.5 cm above the midpoint of

inguinal ligament (MIL) and 5 ml of local anaesthetic deposited

(fig-3.c)

7. Then by using 23 G spinal (quincke) needle a subcutaneous

infiltration was done along the midline to block the crossing over

fibres. (8ML) (fig-3.d)

8. A 5 ml of local anaesthetic was infiltrated along the line of incision

(fig-3.e)

So a total of 35ml was given for the block and 5ml was reserved to be given at the neck of the sac , if needed during the traction.

18

PHARMACOLOGY

Figure -4 CHEMICAL STRUCTURE OF BUPIVACAINE

Figure-5 BUPIVACAINE HYDROCHLRIDE

19

BUPIVACAINE HYDROCHLORIDE25,26

It was synthesised in 1957 by BOAFEKEMSTAN and was clinically first used in 1963 in L.J.TELIVUO.

Structural formula: CH3CH2CH2CH2NC C18H28N2O, HCL

Physical and Chemical Properties :

a. It is a white, odourless, crystalline powder with a bitter

numbing taste.

b. It is chemically synthesized. The hydrochloride salt is available

in solution with and without epinephrine.

c. Intrathecal preparation specifically contains dextrose.

d. Chemically amide : 2-6 methyl amide.

e. Molecular weight : 325.

f. pH of saturated solution :5.2

g. pKa 8.1

h. Protein binding 96%

Mechanism of Action:

It prevents the generation and conduction of nerve impulses.it acts on the cell membrane, blocks the conduction by decreasing or preventing the increase in cell permeability of excitable membranes to Na + due to their direct interaction with voltage gated Na + channels.

20

PHARMACOKINETICS

Absorption:

It is rapidly absorbed from the site of injection, the rate of rise in plasma concentration and peak plasma levels depend on the particular anaesthetic technique employed.

Distribution:

It is explained by two compartment model.

a. The rapid distribution phase: It is by the uptake of rapid

equilibrating tissue (i.e tissues that have high vascular

perfusion).

b. The slow distribution phase: It is the distribution to slowly

equilibrating tissue, biotransformation and excretion of the

compound.

More highly perfused organs show higher concentrations of the drug. Though skeletal muscle does not show particular affinity for bupivacaine it is the largest reservoir of the drug.

21

Distribution Characteristics:

1. T1/2a - 2.7 min

2. T1/2b - 2.8 min

3. Volume of distribution at steady state – 72 litres

4. Clearance (lit/min) – 0.47

Biotransformation and Excretion

a. Bupivacaine undergoes enzymatic degradation primarily in the

liver.

b. It is excreted mainly through the kidneys. Renal perfusion and

urinary pH affect urinary excretion. Renal clearance of this drug

is related inversely to its protein binding capacity and pH of

urine.

c. Less than 5% of unchanged drug is excreted via the kidney

through urine. The major portion of injected agent appears in

urine in the form of 2,6 pipecoloxylidide which is a N de-

alkylated metabolite of Bupivacaine.

Dosage:

Maximal dose is 2mg/kg body weight (25-30ml 0.5% solution) and the strength used is 0.125%-0.75%.

22

Toxicity:

It is relatively free of side effects if administered in an appropriate dosage. It is more cardiotoxic than Ropivacaine and this is made worse by hypoxia, hypercapnia and by pregnancy.

1. Central Nervous System Toxicity (CNS)

CNS is more susceptible to Bupivacaine. The symptoms are light headedness and dizziness followed by visual and auditory disturbance.

Disorientation and occasional feeling of drowsiness may occur. Objective signs are excitatory in nature which are shivering, muscular twitching and tremors, involving muscles of face (perioral numbness) and part of extremities. Acidosis increases the risk by increased levels of PaCo2 which eventually increases the cerebral blood flow, hence more of anaesthetic is delivered rapidly to brain. Higher doses results in cardiovascular and respiratory arrest.

2. Cardiovascular System27

The primary cardiac effect of local anaesthetic is a decrease in the rate of depolarization in the fast conducting tissues of purkinje fibres and ventricular muscle. The reduction in rate is due to a decreased availability of fast sodium channels in cardiac membranes, action potential duration and refractory period. Bupivacaine depresses the rapid

23 phase of depolarization (vmax) in purkinje fibres and ventricular muscle to a greater extent than ropivacaine does. It decreasesthe rate of recovery which lead to incomplete restoration of Na+ channel availability between action potentials particularly at high heart rates.

The ratio of dosage required for irreversible cardiovascular collapse and the dosage that will produce CNS toxicity (convulsion) (i.e, the CC/CNS ratio) is lower for bupivacaine than ropivacaine.

Pregnancy enhances cardiotoxicity of bupivacaine.

3. Respiratory System Toxicity:

Depression of medullary respiratory centre may be caused if excessive plasma level is reached.

4. Autonomic Nervous System Toxicity

Myelinated preganglionic beta fibres have a faster conduction time and are more sensitive to the action of local anaesthetics. When used for conduction blockade all local anaesthetics particularly bupivacaine produces higher incidence of sensory blockade than motor fibres.

24

Figure-6 ROPIVACAINE CHEMICAL STRUCTURE

Figure -7 ROPIVACAINE HYDROCHLORIDE

25

ROPIVACAINE28,29,30,26

Ropivacaine is a new long acting local anaesthetic belonging to amino amide group. It was synthesised by EKENSTAM in 1957. It belongs to the same group as bupivacaine, the pipecoloxylidide local anaesthetics. It was introduced into clinical practice in 199231.

Historically Bupivacaine was used for its long duration of action, but it was found that propyl derivatives of pipecoloxylidide were less toxic than butyl derivatives. (i.e bupivacaine.)

It is the first local anaesthetic to be presented as an almost pure S-

Enantiomer (greater than 99% pure). It is used for infiltration, nerve blocks, epidural and of late for intrathecal anaesthesia.

Physical and Chemical Properties:

a. It is a white crystalline powder.

b. Molecular formula - C17H26N2O.HCL.H2O.

c. Molecular weight is 328

d. pKa 8.1 (approximately same as bupivacaine)

e. Ropivacaine has a lower lipid solubility (owing to substitution

of pipecoloxylidide with a 3 C side chain instead of 4 C side

chain.)

26

Dosage

Maximal dosage of Ropivacaine is 3mg/kg.

Ropivacaine is preservative free and is available as single dose containers in 2(0.2%), 5(0.5%), 7.5(0.75%) and 10(1%) mg concentrations.

Mechanism of Action

Ropivacaine reversibly interferes with the entry of sodium in nerve cell membranes leading to decrease permeability to sodium and thus

a. Block generation and conductance of nerve impulses

b. Slows propagation of nerve impulses

c. Reduce the rate of raise of action potential

Most local anaesthetics block the unmyelinated „C‟ fibres and myelinated delta fibres that transmit pain impulses at the same rate.

However the rate of blockade of A delta and A beta (that carry motor impulses) depends on the physiochemical properties of the local anaesthetic. As Ropivacaine is less lipid soluble compared to

Bupivacaine, the blockade of A delta and A beta is slow and hence produces less motor blockade than Bupivacaine.

27

Clinically the order of blockade of nerve fibres is autonomic, sensory and motor while the disappearance occurs in reverse order. The order of the loss of nerve function is

1. Pain

2. Temperature

3. Touch

4. Proprioception

5. Skeletal muscle tone

Pharmacokinetics

Absorbtion:

The systemic concentration of Ropivacaine is dependent on

1. Total dose and concentration of drug given

2. Route of administration

3. Patient‟s haemodynamic condition

4. Vascularity at the site of administration.

Distribution

After intravascular infusion Ropivacaine has a steady state of distribution of 417 litres. It is 94% protein bound mainly to alpha1 acid glycoprotein. Ropivacaine readily crosses the placenta.

28

Metabolism

1. Ropivacaine is metabolised by aromatic hydroxylation in the

liver, mediated by cytochrome p450 to 1alpha3 hydroxy

Ropivacaine.

2. Rest is excreted in the urine as free and conjugated 3 hydroxy

ropivacaine.

3. Low concentrations of 3hydroxy Ropivacaine is found in

plasma.

4. An additional metabolite, 2-hydroxy-methyl-ropivacaine has

been identified but not quantified.

Elimination:

Ropivacaine metabolites are excreted mainly through kidney.

After intravenous (iv) administration 86% of the dose is excreted in urine of which only 1% is in unchanged form.

Potency:

Lipid solubility determines the intrinsic anaesthetic potency.

Chemical compounds which are highly lipophilic tend to penetrate the nerve membrane more easily. So less number of molecules are required for conduction blockade. This results in increased potency of the drug.

29

Adverse Effects:

Excessive plasma levels are due to over dosage, unintentional or slow metabolic degradation. The mean doses at which CNS symptoms or toxicity begin to occur are 4.3 mcg/ml of total and 0.6 mcg/ml of free plasma concentrations respectively. Various possible side effects include

a. Cardiovascular System- vasovagal traction, syncope, postural

hypotension, nonspecific electrocardiographic abnormalities

b. Gastro Intestinal – nausea, vomiting, fecal incontinence,

tenesmus

c. CNS – tremor, neuropathy, vertigo, convulsion and coma.

Because of depressant effect of ropivacaine on medulla,

excitatory stage of CNS might not occur.

d. Liver and biliary- jaundice

e. Metabolic disorders- hypomagnesemia

Management of Complications:

1. Discontinuation of Ropivacaine should be done at the first sign

of toxicity.

2. No specific antidote is available.

3. Symptomatic and supportive management should be done

promptly.

30

4. Any change in mentation needs oxygenation. Secure airway and

provide assisted ventilation if any signs of respiratory

depression are observed.

5. Convulsions can be treated with barbiturates specific

anticonvulsants or neuromuscular blockers.

6. In case of cardiac arrest prolonged resuscitative efforts might

be required.

Advantages over other Local Anesthetics

1. Ropivacaine produces a more differential blockade allowing

better separation between sensory and motor block . Hence it is

a better choice for use in labour analgesia and postoperative

pain.

2. When compared to bupivacaine it produces less motor

blockade, shorter duration and hence permitting earlier

mobilization and discharge.

3. It has low systemic toxicity than Bupivacaine and has a better

cardio toxic profile

4. It is 40-50% less potent than Bupivacaine, Ropivacaine in an

equipotent ratio of 1.5 :1 results in a similar clinical profile with

good preservation of motor function.

31

Dosing of Local Anesthetics

Maximal dose of Bupivacaine is 2 mg/kg body weight and the strength used is 0.5%.

Maximus dose of Ropivacaine is 3 mg/kg and the strength used is

0.75%

The mean weight of the patients in the study is 60.0 kg and mean volume of LA used is 35 ml (20ml LA +20ml distilled water). The equipotent dosing of Ropivacaine and Bupivacaine is 1.5:1. It becomes clear that the total dose of local anaesthetic used lies within the recommended safe dosage.

32

Inclusion Criteria:

1. 18 - 60 years

2. ASA Physical status I & II

3. BMI 18-25

4. Co-operative patients

5. Unilateral hernia

6. Reducible hernia

7. Elective case

33

Exclusion Criteria:

1. Patients refusal

2. Hypersensitivity to local anaesthetics

3. BMI > 25

4. Chronic analgesic therapy

5. Giant inguinoscrotal hernias

6. Strangulated hernias

7. Hernia with hydrocele

8. Uncontrolled cardiovascular/respiratory/metabolic diseases

34

METHODOLOGY

Source of Data:

A clinical study of Prospective Double blinding was undertaken with 60 patients aged 18-60 years who are posted for elective unilateral inguinal hernia repair, agreeing and co-operative for inguinal field block.

Study was conducted at Mahatma Gandhi Memorial Government

Hospital, Trichy from period June 2015 – June 2016.

Sample Size:

Total of 60 cases.

30 cases of inguinal hernia repair under Field block with

Bupivacaine (Group B)

30 cases of inguinal hernia repair under Field block with

Ropivaciane (Group R)

Randomization:

Pre-anaesthetic evaluation was done a day prior to surgery and the procedure explained to the patients and consent obtained. The patients are randomised by coin toss method into two groups B-Bupivacaine and R-

Ropivacaine.

35

Blinding technique:

1. Double blinding is done by selecting a researcher who will

prepare the local solution and will not participate further in the

study.

2. Block is performed by myself and the patients is assessed

throughout in the due course of the surgery by me.

3. Observations were recorded by me throughout the study.

On the day of surgery, an intravenous line was secured with 18G iv cannula. Patients were given maintenance I.V fluid 20ml/kg 4hours before the procedure and they were asked to void prior to premedication.

Patients were pre-medicated with injection midazolam 1mg iv before performing the block. Patients were monitored continuously throughout the study every 5min during the procedure and then at an interval of

15min until the patient is shifted to the general ward. The pulse , heart rate ,oxygen saturation , blood pressure and a continuous ECG tracing were monitored.

Onset of block is assessed by pin prick test (22 gauge hypodermic needle) at the skin dermatomes involved in the surgical field from 30TH seconds.

36

Figure-8 VISUAL ANALOG SCALE

TABLE-1 PAIN SCORE WITH VISUAL ANALOG SCALE

VAS PAIN

0-1 NO PAIN

2-4 MILD PAIN

5-7 MODERATE PAIN

8-10 SEVERE PAIN

37

TABLE- 2 ADEQUACY OF THE BLOCK

0 Adequate block requiring no supplementation

1 Analgesia and relaxation adequate with minimal

discomfort and are comfortable with local anaesthetic at

the neck of sac

2 Patient complains of pain and inadequate relaxation which

needs a narcotic supplementation

3 Patient complains of severe pain and inadequate relaxation

which warrants general anaesthesia

38

Adequacy of the block is assessed by the subjective pain perception by VAS score (Fig-8, Table-1), relaxation level by the surgeon‟s verdict and mobility of the patient. Accordingly the adequacy of the block is judged as adequate, inadequate or failed ( Table-2). The patients are supplemented with local infiltration for mild pain, a narcotic supplementation (inj.fentanyl 2mcg/kg iv) for moderate pain and GA for the block failure patients.

The haemodynamics were recorded throughout the study.

At the end of surgery patients were observed in the recovery room for 60min and will be assessed by recovery room nurse every 15 min by verbal rating score (VRS) (Table-3) before discharging to ward.

The surgeon satisfaction were also assessed by taking into account the following criteria cited in (Table-4) and a satisfaction score (Table-5) for the surgeon is also computed.

Postoperative pain relief is defined as time lasting from completing block to the first requirement for analgesia and pain score assessed by

VRS (Table-3) by unit intern every 30min. Rescue analgesia was given with I.M. Diclofenac for severe pain and oral paracetamol 1gm for mild to moderate pain.

39

Table – 3 VERBAL RATING SCORE (VRS)

VRS VAS

0 0-1

1 2-4

2 5-7

3 8-10

40

TABLE-4 SURGEON SATISFACTION SCALE

0 1 2

COMFORTNESS GOOD ADEQUATE INADEQUATE

FIELD CLEAR MESSY BLOODY CLARITY

PATIENT’S GROSS NIL FIDGETY MOVEMENTS MOVEMENTS

Table -5 SURGEON SATISFACTION SCORE

SATISFACTION

VERY SATISFIED 0-2

SATISFIED 3-4

DISSATISFIED 5-6

41

Statistical Analysis

1. Chi square test

2. Independent student „t‟ test

The results are analyzed statistically using SPSS (Statistical presentation system software) for Windows, version16.0 (SPSS,

1999.SPSS Inc.: New York) or EPI info.

Descriptive data included mean, standard deviation and percentage which were determined for both the groups.

42

Graph -1 COMPARISON OF BMI

Table-6 COMPARISON OF BMI

Bupivacaine Ropivacaine Total Statistical

(n=30) (100%) (n=30) (100%) (n=60) (100%) inference BMI 18 to X2=1.111 16 53.3% 20 66.7% 36 60.0% 20 Df=1 .292>0.05 21 to 14 46.7% 10 33.3% 24 40.0% Not 25 Significant

43

RESULTS

1. Out of the 60 patients, 30 belong to the Bupivacaine group ( B

group) and 30 to Ropivacaine group (R group).

2. The mean duration of the surgery was 40 min.

3. All of them were males.

4. B group had 53.5% patients and R group had 66.7% patients within

the BMI range of 18-20 and within the BMI range 21-25, B group

had 46.7% patients and R group had 40% patients. (Graph-1)

5. 76.7% of the patients in B group and 73.3% in group R belong to

ASA I and 3.3% of the patients in B group and 26.7% in R group

belong to ASA II (Graph-2)

6. Above values shows no significance among the BMI & ASA

classification between the two groups. (Table-6 and 7).

44

Graph-2 COMPARISON OF ASA

Table-7 COMPARISON OF ASA

Bupivacaine % Ropivacaine % Total % SD ASA X2=.089

Yes 23 76.7% 22 73.3% 45 75.0% Df=1 .766>0.05 Not No 7 23.3% 8 26.7% 15 25.0% Significant

45

Graph-3 COMPARISON OF ONSET OF BLOCK

Table-8 COMPARISON OF ONSET OF BLOCK

Onset in Min Mean S.D T df Statistical inference

0.5 min

Bupivacaine (n=30) .00 .000(a) - - -

Ropivacaine (n=30) .00 .000(a) - - -

1min

Bupivacaine (n=30) .00 .000(a) - - -

Ropivacaine (n=30) .00 .000(a) - - -

1.5min

46

Bupivacaine (n=30) .00 .000(a) - - -

Ropivacaine (n=30) .00 .000(a) - - -

2min

Bupivacaine (n=30) .07 .254 1.439 58 .155>0.05

Ropivacaine (n=30) .00 .000 Not Significant

2.5min

Bupivacaine (n=30) .07 .254 1.439 58 .155>0.05

Ropivacaine (n=30) .00 .000 Not Significant

3min

Bupivacaine (n=30) .07 .254 1.439 58 .155>0.05

Ropivacaine (n=30) .00 .000 Not Significant

3.5min

Bupivacaine (n=30) .07 .254 1.439 58 .155>0.05

Ropivacaine (n=30) .00 .000 Not Significant

4min

Bupivacaine (n=30) .07 .254 1.439 58 .155>0.05

Ropivacaine (n=30) .00 .000 Not Significant

4.5min

Bupivacaine (n=30) .07 .254 1.439 58 .155>0.05

Ropivacaine (n=30) .00 .000 Not Significant

5min

47

Bupivacaine (n=30) .03 .183 1.000 58 .321>0.05

Ropivacaine (n=30) .00 .000 Not Significant

5.5min

Bupivacaine (n=30) .10 .305 1.027 58 .309>0.05

Ropivacaine (n=30) .03 .183 Not Significant

6min

Bupivacaine (n=30) .10 .305 1.027 58 .309>0.05

Ropivacaine (n=30) .03 .183 Not Significant

6.5min

Bupivacaine (n=30) .07 .254 1.439 58 .155>0.05

Ropivacaine (n=30) .00 .000 Not Significant

7min

Bupivacaine (n=30) .00 .000(a) - - -

Ropivacaine (n=30) .00 .000(a) - - -

7.5min

Bupivacaine (n=30) .10 .305 1.027 58 .309>0.05

Ropivacaine (n=30) .03 .183 Not Significant

8min

Bupivacaine (n=30) .07 .254 .584 58 .561>0.05

Ropivacaine (n=30) .03 .183 Not Significant

8.5min

48

Bupivacaine (n=30) .00 .000(a) - - -

Ropivacaine (n=30) .00 .000(a) - - -

9min

Bupivacaine (n=30) .07 .254 .000 58 1.000>0.05

Ropivacaine (n=30) .07 .254 Not Significant

9.5min

Bupivacaine (n=30) .03 .183 -.584 58 .561>0.05

Ropivacaine (n=30) .07 .254 Not Significant

10min

Bupivacaine (n=30) .00 .000 -1.439 58 .155>0.05

Ropivacaine (n=30) .07 .254 Not Significant

10.5min

Bupivacaine (n=30) .03 .183 1.000 58 .321>0.05

Ropivacaine (n=30) .00 .000 Not Significant

11min

Bupivacaine (n=30) .03 .183 -1.736 58 .088>0.05

Ropivacaine (n=30) .17 .379 Not Significant

11.5min

Bupivacaine (n=30) .00 .000 -1.000 58 .321>0.05

Ropivacaine (n=30) .03 .183 Not Significant

12min

49

Bupivacaine (n=30) .00 .000 -1.439 58 .155>0.05

Ropivacaine (n=30) .07 .254 Not Significant

12.5min

Bupivacaine (n=30) .00 .000 -1.439 58 .155>0.05

Ropivacaine (n=30) .07 .254 Not Significant

13min

Bupivacaine (n=30) .00 .000 -1.795 58 .078>0.05

Ropivacaine (n=30) .10 .305 Not Significant

13.5min

Bupivacaine (n=30) .00 .000 -1.000 58 .321>0.05

Ropivacaine (n=30) .03 .183 Not Significant

14min

Bupivacaine (n=30) .00 .000 -1.000 58 .321>0.05

Ropivacaine (n=30) .03 .183 Not Significant

14.5min

Bupivacaine (n=30) .00 .000 -1.439 58 .155>0.05

Ropivacaine (n=30) .07 .254 Not Significant

15min

Bupivacaine (n=30) .00 .000 -1.795 58 .078>0.05

Ropivacaine (n=30) .10 .305 Not Significant

50

Table-9 AVERAGE ONSET OF TIME

Statistical Onset in Min Mean S.D T df inference Bupivacaine - 5.6833 2.47220 58 .000<0.05 (n=30) 8.647 Ropivacaine 11.3333 2.58755 Significant (n=30)

As seen from the above graph-9,

The average time for onset of block in the Bupivacaine group is

5.7min whereas in the Ropivacaine group it is 11.3min.

(Graph 10) shows, none of the patients in R group had onset of block in the first 5min inferring that it has a late onset compared to B group. None of the patients in B group had onset after 11.5min, the onset starts from 2min in the B group and completes within 11.5min showing its quicker onset.

The statistical inference shows significance of <0.05 (Table-9)

51

TABLE-10 ONSET OF BLOCK IN ACTUAL NUMBERS OF PATIENTS

ONSET Bupivacaine Ropivacaine IN MIN N % N % 2min 2 6.70% 0 0.00% 2.5min 2 6.70% 0 0.00% 3min 2 6.70% 0 0.00% 3.5min 2 6.70% 0 0.00% 4min 2 6.70% 0 0.00% 4.5min 2 6.70% 0 0.00% 5min 1 3.30% 0 0.00% 5.5min 3 10.00% 1 3.30% 6min 3 10.00% 1 3.30% 6.5min 2 6.70% 0 0.00% 7.5min 3 10.00% 1 3.30% 8min 2 6.70% 1 3.30% 9min 2 6.70% 2 6.70% 9.5min 1 3.30% 2 6.70% 10min 0 0.00% 2 6.70% 10.5min 1 3.30% 0 0.00% 11min 1 3.30% 5 16.70% 11.5min 0 0.00% 1 3.30% 12min 0 0.00% 2 6.70% 12.5min 0 0.00% 2 6.70% 13min 0 0.00% 3 10.00% 13.5min 0 0.00% 1 3.30% 14min 0 0.00% 1 3.30% 14.5min 0 0.00% 2 6.70% 15min 0 0.00% 3 10.00%

52

Graph-4 COMPARISON OF ADEQUACY OF BLOCK

Table-11 COMPARISON OF ADEQUACY OF BLOCK

Rescue SD Bupivacaine % Ropivacaine % Total % Analgesia Nil 19 63.3% 17 56.7% 36 60.0% X2=.365 Local 4 13.3% 4 13.3% 8 13.3% Df=3 Opioids 4 13.3% 5 16.7% 9 15.0% .947>0.05 Not GA 3 10.0% 4 13.3% 7 11.7% Significant

53

Regarding the adequacy of block which is determined by the need for supplements (Graph-4)

In the Bupivacaine group,

1. 63.30% of the patients ( i.e.19 pts) had good analgesia without

the need for any analgesia.

2. 13.30% of the patients complained of discomfort and got relief

with local infiltration at the neck of the sac (4pts).

3. 13.30% of the patients had inadequate analgesia and relaxation

needing narcotic supplementation (4pts).

4. 10.0% of the patients (3 pts) had a failed field block and were

converted into GA.

In Ropivacaine group,

1. 56.7% of the patients had excellent analgesia (18pts) with no

supplementation.

2. 13.3% of the patients required LA infiltration at the neck of the

sac (4pts).

3. 16.7% of the patients needed narcotic supplementation (5pts) to

proceed with the procedure.

4. In 13.0% patients technique failed and were converted into GA

(4pts).

54

Graph-5 COMPARISON OF SIDE EFFECTS

55

Graph-6 SIDE EFFECTS OBSERVED

56

Table-12 COMPARISON OF SIDE EFFECTS

Side SD Bupivacaine % Ropivacaine % Total % effects 93.3 X2=1.456 No 25 83.3% 28 53 88.3% % Df=1 .228>0.05 6.7 Yes 5 16.7% 2 7 11.7% Not % Significant

1. No intraoperative complications were noted.

2. 83.3% of the patients in B group and 93.3% of the patients in R

group had no side effects.

3. 16.70% (5 pts ) in the B group and 6.7 % (2 pts) in the R group

had side effects.

57

Graph-7 COMPARISON OF SURGEON SATISFACTION

58

Table-13 COMPARISON OF SURGEON SATISFACTION

Satisfaction Bupivacaine % Ropivacaine % Total % SD level 21.7 X2=1.218 Dissatisfied 5 16.7% 8 26.7% 13 % Df=2 65.0 .544>0.05 Satisfied 20 66.7% 19 63.3% 39 % Not Very 13.3 Significan 5 16.7% 3 10.0% 8 Satisfied % t

1. The satisfaction level of surgeons fall mainly in the satisfied level,

66.7% in B group & 63.3% in R group.

2. Only 16.7% (5 surgeons) in B group and 10.0% ( 3 surgeons) in R

group expressed dissatisfaction.

3. The statistical inference gives no significance between the two

groups.

59

Graph- 8 COMPARISON OF TIME REQUIREMENT FOR THE

FIRST ANALGESIC

60

Table-14 – TIME PERIOD FOR THE FIRST REQUIREMENT FOR AN ANALGESIC

Time period for the first Statistical Mean S.D t Df analgesic req inference 0.5hr Bupivacaine (n=30) .00 .000 - - - Ropivacaine (n=30) .00 .000 - - - 1hr Bupivacaine (n=30) .00 .000 - - - Ropivacaine (n=30) .00 .000 - - - 1.5hr Bupivacaine (n=30) .00 .000 - - - Ropivacaine (n=30) .00 .000 - - - 2hr Bupivacaine (n=30) .00 .000 - - - Ropivacaine (n=30) .0 .000 - - - 2.5hr Bupivacaine (n=30) .00 .000(a) - - - Ropivacaine (n=30) .00 .000(a) - - - 3hr Bupivacaine (n=30) .03 .183 -.584 58 .561>0.05 Ropivacaine (n=30) .07 .254 Not Significant 3.5hr Bupivacaine (n=30) .07 .254 .000 58 1.000>0.05 Ropivacaine (n=30) .07 .254 Not Significant 4hr - Bupivacaine (n=30) .13 .346 58 .203>0.05 1.287

61

Ropivacaine (n=30) .27 .450 Not Significant 4.5hr Bupivacaine (n=30) .13 .346 .851 58 .398>0.05 Ropivacaine (n=30) .07 .254 Not Significant 5hr Bupivacaine (n=30) .13 .346 -.992 58 .325>0.05 Ropivacaine (n=30) .23 .430 Not Significant 5.5hr Bupivacaine (n=30) .10 .305 1.795 58 .008<0.05 Ropivacaine (n=30) .00 .000 Significant 6hr Bupivacaine (n=30) .10 .305 -.396 58 .694>0.05 Ropivacaine (n=30) .13 .346 Not Significant 6.5hr Bupivacaine (n=30) .17 .379 1.736 58 .006<0.05 Ropivacaine (n=30) .03 .183 Significant 7hr Bupivacaine (n=30) .03 .183 1.000 58 .321>0.05 Ropivacaine (n=30) .00 .000 Not Significant

62

Table-15 AVERAGE DURATION OF POST OP PAIN RELIEF

DURATION

Time period for the first Statistical Mean S.D t df analgesic req (hr) inference

Bupivacaine (n=30) 4.7167 1.61183 1.421 58 .161>0.05

Not Ropivacaine (n=30) 4.1500 1.47479 Significant

The postoperative analgesic need is the time period between the completion of the block and the first requirement of an analgesic. The block failure patients were excluded from the study (3in B group and 4 in

R group). The average duration of pain relief in Bupivacaine group is

4.71 and with Ropivacaine is 4.15 (Table-15).

(Table-16) shows in the Bupivacaine group, post op analgesia is longer as evident from the data showing significant number of patients

(12 patients) had analgesia even after 5 hours whereas in R group, only 5 patients had post op pain relief after 5 hrs.

A significance was noted between the two groups regarding the post-operative analgesic duration (Table-14) in the 5.5th hour and 6.5th hour. But the average duration does not show a significance.

63

Table16- POST OP ANALGESIA DURATION WITH

ACTUAL NUMBER OF PATIENTS

Time period for the Bupivacaine Ropivacaine

first Analgesic Req n % n %

3 hrs 1 3.3% 2 6.7%

3.5hrs 2 6.7% 2 6.7%

4hrs 4 13.3% 8 26.7%

4.5hrs 4 13.3% 2 6.7%

5hrs 4 13.3% 7 23.3%

5.5hrs 3 10.0% 0 0

6hrs 3 10.0% 4 13.3%

6.5hrs 5 16.7% 1 3.3%

7hrs 1 3.3% 0 0

64

Table- 17 COMPARISON OF HEART RATE

Mean S.D Statistical inference Age t=-.687 Df=58 Bupivacaine (n=30) 44.07 11.104 .495>0.05 Not Significant Ropivacaine (n=30) 45.83 8.667 HR PRE OP Bupivacaine (n=30) 74.07 9.951 t=-1.106 Df=58 .273>0.05 Ropivacaine (n=30) 77.10 11.254 Not Significant HR PRE 2min Bupivacaine (n=30) 80.93 14.458 t=-.221 Df=58 .826>0.05 Ropivacaine (n=30) 81.67 11.071 Not Significant HR PRE 5min Bupivacaine (n=30) 84.03 17.312 t=.043 Df=58 .966>0.05 Ropivacaine (n=30) 83.87 12.684 Not Significant HR PRE 10min

Bupivacaine (n=30) 84.80 16.369 t=-.696 Df=58 .489>0.05 Ropivacaine (n=30) 87.80 16.996 Not Significant HR PRE 15min Bupivacaine (n=30) 84.63 12.949 t=-.434 Df=58 .666>0.05 Ropivacaine (n=30) 86.10 13.231 Not Significant

65

Graph-9 COMPARISON OF HEART RATE

90

85

80

75

70

65 HR PRE OP HR PRE HR PRE HR PRE HR PRE HR PRE HR PRE HR PRE HR PRE HR PRE HR PRE 2min 5min 10min 15min 20min 25min 30min 40min 50min 60min

Bupivacaine Ropivacaine

66

Table-18 COMPARISON OF THE MEAN SYSTOLIC BLOOD

PRESSURE

BP PRE 2min Bupivacaine (n=30) 118.43 11.670 t=-1.129 Df=58 .264>0.05 Ropivacaine (n=30) 122.57 16.307 Not Significant BP PRE 5min Bupivacaine (n=30) 120.07 10.961 t=-1.624 Df=58 .110>0.05 Ropivacaine (n=30) 125.40 14.260 Not Significant BP PRE 10min Bupivacaine (n=30) 120.83 11.780 t=-1.371 Df=58 .176>0.05 Ropivacaine (n=30) 125.50 14.450 Not Significant BP PRE 15min Bupivacaine (n=30) 118.87 9.985 t=-1.306 Df=58 .197>0.05 Ropivacaine (n=30) 122.63 12.235 Not Significant BP PRE 20min Bupivacaine (n=30) 116.73 8.654 t=-1.223 Df=58 .226>0.05 Ropivacaine (n=30) 119.67 9.883 Not Significant BP PRE 25min Bupivacaine (n=30) 114.53 5.871 t=-1.275 Df=58 .207>0.05 Ropivacaine (n=30) 116.67 7.034 Not Significant

67

BP PRE 30min Bupivacaine (n=30) 113.37 4.398 t=-.799 Df=58 .428>0.05 Ropivacaine (n=30) 114.33 4.957 Not Significant BP PRE 40min Bupivacaine (n=30) 112.47 4.281 t=-.213 Df=58 .832>0.05 Ropivacaine (n=30) 112.73 5.369 Not Significant BP PRE 50min Bupivacaine (n=30) 112.40 4.882 t=.193 Df=58 .848>0.05 Ropivacaine (n=30) 112.13 5.800 Not Significant BP PRE 60min Bupivacaine (n=30) 113.07 4.660 t=-.050 Df=58 .960>0.05 Ropivacaine (n=30) 113.13 5.600 Not Significant

68

Graph-10 COMPARISON OF THE MEAN SYSTOLIC BLOOD

PRESSURE

130

125

120

115

110

105 BP PRE OP BP PRE BP PRE BP PRE BP PRE BP PRE BP PRE BP PRE BP PRE BP PRE 5min 10min 15min 20min 25min 30min 40min 50min 60min Bupivacaine Ropivacaine

69

The heart rate ( HR) and blood pressure (BP) in both groups were observed from the pre-operative period till the patient was discharged to the general ward (Table-17 & Table-18)

1. As seen from above (Graph-9), the mean value of the heart rate in

both groups are computed. It is seen that there is no significant

change in HR from the baseline in both the groups. Also there is no

significance between both the groups.

2. Graph-10 shows the mean systolic BP in both the groups. Only the

systolic BP is taken into account for convenience. It is found that

the BP is stable throughout the study with local anaesthesia. It is

also seen that there is no significance between the two groups of

study.

70

DISCUSSION

Inguinal hernia repair is one of the commonest surgeries in the world. In the advent of administering anaesthesia for the surgical correction, the technique employed should be cost effective, with adequate analgesia , minimal side effects and a speedy recovery32.

The advantage of field block is its safety, simplicity, cost effectiveness, easy technique, prolonged analgesia, early ambulation with no or minimal side effects 33. Hence it can be employed in the day care surgeries reducing the need for post-operative narcotic supplements34.

Since local anaesthetics do not hinder the respiratory and cardiovascular system in allowed dosage, good respiratory stability and haemodynamic stability were maintained.

Large series of studies are available in surgical and anaesthesia literature regarding the usage of local infiltration alone or combined with ilioinguinal nerve block for inguinal hernia repair. Most of these were compared with GA or neuraxial anesthesia or monitored anaesthesia care under deep sedation.

The advantage of field block over local anaesthesia is the almost complete coverage of the skin dermatomes involved in the surgical area; which is sometimes spared in local infiltration. The precise blocking of the nerves in field block provides adequate analgesia, avoiding multiple

71 pricks as in local infiltration thereby provides good co-operation from the patients. Hence field block proves as an excellent anaesthetic technique for hernia repair.

In the view of advantages, this study was undertaken to compare the safety and effectiveness of the two drugs namely Bupivacaine &

Ropivacaine. Since Bupivacaine has cardiotoxic properties even at a lower dosage35,36, Ropivacaine is studied and compared whether it can provide efficient analgesia at the cost of safety.

After performing the block, the onset is assessed from every 30 seconds by simple pin prick method with a 22G hypodermic needle in the dermatome involved in the surgical field.

The study shows that B group had onset from 2min and completes within 11.5min, none of the patients had onset after 11.5min. Hence it has quicker onset. None of the patients in R group had onset of block in the first 5min concluding it has a late onset compared to B group. The average time taken for onset for Bupivacaine is 5.8min compared with

Ropivacaine of 11.3min which is longer with statistical significance of

<0.05(table-8)

The perception of pain by the patients is assessed by the VAS scale

(fig-8).Pain is graded as mild, moderate and severe based on VAS scores

(Table-1). The adequacy of the block is assessed by requirement of

72 supplementary local anaesthetic ( at the neck of sac) / opioid / GA based on the patient‟s complaint. They were graded as adequate, inadequate or block failure (Table-2).

In our study, 4 patients in either group complained of discomfort and got relieved by local infiltration at the neck of the sac. This is similar to the Markhan A., Faulds D. study on Ropivacaine where traction pain can be obtunded with a LA infiltration at neck of the sac. 37.

Inadequate relaxation and pain during the surgery might need a narcotic supplementation. This is supported by the Zoilinger RM,

Konstantakos AK, Stellato TA, Hirgchfeld SS study of Local anaesthesia plus deep sedation for adult inguinal hernia repair 38. 13.30% of the patients in the B group and 16.7% of the patients in the R group fall into inadequate field block. They are supplemented with inj.fentanyl 1-2 mcg/kg and the surgery proceeded without interruption.

Few study states that some sedation during the operation may be required for anxious patients which has some of the benefits of avoiding

GA. Patients who are excessively nervous may be unsuitable and uncooperative for the surgery under LA. Similar to the study by Callesen

T, Beck K, Kehlet. H of inguinorraphy under LA 39,40,41. Those patients were taken as Block failure and proceeded with GA excluding from the

73 study. Thus 3 pts in B group and 4 pts in R group were excluded since they will give a false negative data.

Overall field block provided good adequacy of block with no need for any supplementation in 63.3% in B group and 56.7% in R group

(graph-4) There is no significant difference between the two drug groups inferring that Ropivacaine provides adequate analgesia and operating conditions compared with bupivacaine (Table-9).

The duration of post-op pain relief is taken from the time after completing the block till the patient demands for a pain relief medication.

The block failure patients were excluded from the study (3 in B group and 4 in R group). The average duration of pain relief in Bupivacaine group is 4.71hrs and with Ropivacaine is 4.15hrs (Table-15) which shows no significance. But in the Bupivacaine group, post op analgesia is longer as seen from the data showing significant number of patients(12 pts) having analgesia effect even after 5 hrs , whereas in R group, only 5 patients had post op pain relief after 5 hrs. (Table-16). A significance was noted between the two groups regarding the post-operative analgesic duration (Table-14) in the 5.5th hour and 6.5th hour. But the average duration did not show a significance. In our study Bupivacaine gives an average analgesic duration of 4.71hrs , Ropivacaine also gives a comparable average duration of 4.15 hrs. The present study correlates

74 with studies done by Covino et al42 . Both the drugs gives an average duration of 4 hrs post-op analgesia but Ropivacaine seems a better alternative with an added advantage of being cardio-friendly.

Both the groups had better haemodynamic stability and respiratory stability throughout the study(Table-13 & Table-14). This is more useful in geriatric patients and patients with cardio-respiratory instability.

Surgeon satisfaction was based on the criteria of field clarity, patients movement during the surgery and comfortness of the operating surgeon. (Table 4 and Table-5) .

The ease of surgery depends on the clarity of field, comfortness and immobility of the patient. The GA/ neuraxial block gives absolute relaxation and immobility , various studies show that the local infiltration gives adequate relaxation and almost nil patient movements during the surgery.

In this study with both groups surgeon satisfaction level was good.

Almost 66.7% of the surgeons in B group & 63.3% of surgeons in R group are satisfied. Only 16.7% (5 surgeons) in B group and 10.0% ( 3 surgeons) in R group gave dissatisfaction (Table-11). The surgeons made no comparable differences between the two drugs. As well the statistical inference gives no significance between the two groups.

75

Hence lesser motor blockade in Ropivacaine than Bupivacaine does not pose a significant constraint on the surgery.

The main advantage with the field block compared with the other anaesthetic techniques like GA/ neuraxial blockade are its safety with minimal or nil side effects.

No intraoperative complications were noted during the study.

83.3% of the patients in B group and 93.3% of the patients in R group had no side effects. Few of them 16.70% (5 pts ) in the B group and 6.7

% (2 pts) in the R group had side effects (Graph-5). 2 patients in either group complained of nausea and 2 had wound haematoma in group B.

One patient complained of headache in group B.

76

CONCLUSION

Inguinal field block is found to be safe compared with GA/ neuraxial blockade and fulfils the requirements of adequate analgesia and relaxation with better haemodynamic and respiratory stability, with minimal or no side effects and a longer postoperative pain relief. Thus field block can be the preferred choice for the day care inguinal hernia repair as it provides early ambulation and reduces the need for narcotic post operatively.

Ropivacaine drug compared to Bupivacaine provides comparable onset, efficient analgesia, adequate relaxation with good postoperative pain relief. Even though Ropivacaine and Bupivacaine have comparable qualities with Bupivacaine giving a quicker onset and good post-op analgesia, Ropivacaine can be preferred due to its lesser cardio toxic profile.

77

SUMMARY

Inguinal hernia surgery can be well undertaken in local infiltration technique. The field block technique meets all the requirements needed for the surgery, like adequate analgesia, enough relaxation, good haemodynamic stability, minimal side effects and in addition longer post operative pain relief. It is the well suited technique for day care surgery.

This study is undertaken to compare and study the two drugs Bupivacaine and Ropivacaine. The drug Bupivacaine provides excellent analgesia and adequate block but is cardiotoxic. Hence Ropivacaine is studied and compared to show that it will be a good alternative for bupivacaine.

The study was conducted in Mahatma Gandhi Memorial Hospital with 60 patients, divided into two groups of 30 each. They were randomized and the technique is double blinded. After performing the block, the onset is tested by a pink prick method from 30th sec. Adequacy of the block is assessed by the pain perception by VAS score, comfortness of surgeon and movement of the patient. Accordingly they were supplemented with local infiltration for mild pain, a narcotic supplementation for moderate and GA for the block failure patients. The haemodynamics were recorded throughout the study. The surgeon satisfaction and side effects were also studied. The post operative pain relief is calculated as the time period from completion of the block till the

78 next requirement for an analgesic . The results were computed. The onset of block is quicker in bupivacaine than ropivacaine. The quality of the block and a post operative pain relief duration showed no significance between the two drugs. The haemodynamics were stable throughout the study. There were minimal side effects in both the groups like nausea, headache and a wound haematoma but poses no significance. Thus from the study it is inferred that for the hernia field block, Ropivacaine can be a better alternative for Bupivacaine as it can give an adequate analgesia and a good longer post operative pain relief with a low threshold for cardiac toxicity.

79

BIBLIOGRAPHY

1. Amid PK, Shulman AG. Local anaesthesia for inguinal hernia repair

step by step procedure. Ann Surg 1994;220(6):735-737.

2. Song D, Greilich NB, White PF, Watcha MF, Tongier WK. Recovery

profiles and costs of anaesthesia for outpatient unilateral inguinal

herniorrhaphy. Anaesth Analg 2000;91:876-81.

3. Webb M., Prosser N. Public health evidence-based summary. Day

case elective surgery versus inpatient surgery. NPHS Health Social

Care Quality Document Database, Wales

2009.http://www.dh.gov.uk/en/ P u b l i c a t i o n s a n d s t a t i s t i c

s / P u b l i c a t i o n s / Publications Policy And Guidance/

DH_4005487 [Accessed 1st Sep 2009]

4. Cronin M, Redfern PA, Utting JE. Psychometry and post operative

complaints in surgical patients.Br J Anaesth 1973; 45 : 879-86.

5. Donovan BD.patients attitudes to postoperative pain relief. Anaesth

intens care 1983;11:125-28.

6. Covino B. G. Pharmacology of local anaesthetic agents. In: Nunn I. F.,

Uttig J. E., Brown BR Jr. (eds). General Anaesthesia 5th edn. London:

Butterworth-Heinemann 1989:1036–1048

7. Markhan A., Faulds D. Ropivacaine. A review of its pharmacology

and therapeutic use in regional anaesthesia. Drugs 1996; 52: 429–449.

80

8. *B. O. BOLAJI, **I. F. YUSUF, **G. A. AHMAN, **S. A.

KURANGA, *O. O. OYEDEPO *Departments of *Anaesthesia and

**Surgery, College of Health Sciences, University of Ilorin, Ilorin,

Nigeria

9. F.H. Andersen, K.Nielsen and H.kehlet. Combined ilioinguinal

blockade and local infiltration anaesthesia for groin hernia repair-a

double blind randomized study.BJA. 2005; 94(4):520-3

10. P Sanjay, A Woodward. Inguinal hernia repair: local or general

anaesthesia?. Ann R CollSurg Engl. 2007; 89:497-503

11. Flavio Antonio de Sa Riberio, TCBC-RJ, Fernando Padron, Tiago

Duarte Magalhaes Castro et al. Inguinal hernia repair with local

anaesthesia in the outpatient. Rev Col Bras Cir. 2010; 37(6)

12. KhurramNiaz, JavedIqbal, MuhammadIshaqKhan, Munzar Sarfraz.

Comparison of inguinal herniorrhaphy under local and spinal

anaesthesia. pjmhsonline.

13. JihadOdeh, MaazenAlomari, Abdullah Rababaah, AmjadMaslamani,

LaithKhasawneh. Inguinal Herniorraphy under Local Anaesthesia:

outcome and tolerance among patients in royal medicine services: A

prospective study. The Middle East Journal of Internal Medicine.

2010; 1(2)

81

14. SrivastavaArati, Sharma Shailja, GoyalRitu. Comparative study of

augmented local anaesthesia versus spinal anaesthesis in inguinal

hernia repair: a prospective randomized analysis. Indian journal of

public health research and development.2010; 1(2):3-6

15. J.B.Whiteside and J.A.W.Wildsmith. Developments in local

anaesthetic drugs. Br J Anaesth.2001; 87:27-35.

16. J.H.McClure. Ropivacaine .Br J Anaesth. 1996 ; 76 : 300-307.

17. M .s. Brockway , J.Bannister , J.H.McClure, D.Mckeown and

J.A.W.Wildsmith. Comparison of extradural ropivacaine and

bupivacaine. Br J Anaesth. 1991; 66:31-37.

18. D.Bruce Scott,Alister Lee , Denise Fagan , Geoffry M.r.Bowler et al.

Acute toxicity of ropivacaine compared with that of bupivacaine.

Anesth Analg.1989;69:563-569.

19. Stefania leonee, Simone Di Cianni, Andrea Casati , Guido Fanelli.

Pharmacology , toxicology and clinical use f new long acting local

anaesthetics, ropivacaine and levobupivacaine. Acta

Anaesthesiol.2008; 70:92-105.

20. Philipp Lirk, Ingrid Haller, Hans Peter Colvin , Leopold Lang et al. In

vitro, Inhibition of mitogen-activated protein kinase pathways protects

against bupivacaine and ropivacaine induced neurotoxicity. Anesth

Analg.2008;106:1456-1464.

82

21. H Jorgensen, J S Fomsgaard, J dirks, J Wetterslav, J B Dahl. Effect of

continuous epidural 0.2% vs 0.2%bupivacaine on postoperative pain,

motor block and gastrointestinal function after abdominal hysterectomy

. Br J Anaesth.2000; 84(2):141-8.

22. Kingsnorth, Bennett DH. Hernias, Umbillilus, Abdominal Wall Chapter

62. In : Short practice of surgery Bailey and Love. 23rd edn. 2000. p.

1143.

23. Brill S, gurman M, Fisher A. A history of administration of local

analgesics and opidos. EUR J Anaesthesiol.2003;20:682-689.

24. Pinnock C. A., Fischer H. B. J., Jones R. P. Peripheral nerve blockade

1st edn. Edinburgh: Churchill Livingstone 2002; pp 96–98.

25. Dollery C.Bupivacaine hydrochloride. In:Dollery C, ed. Therapeutic

Drugs, 2nd Edition; Edinburgh and Churchill Livingstone:1999.

26. Charles B.Berde , Gary R.Local Anaesthetics in Anaesthesia. In: Miller

Ronald d,ed.Miller‟s Anaesthesia 5th Edition,vol.1 Philadelphia;

Churchill Livingstone:2006.

27. Albright GA.Cardiac arrest following regional anaesthesia with

etidocaine or bupivacaine (Editorial). Anesthesiology.1979;51:285-87.

28. J.H.Mcclure.Ropivacaine.Br J Anaesth.1996;76:300-307.

29. The palce of ropivacaine in anaesthesia.Acta anaesthesiol

Belgica.2003;54(2):141-8.

83

30. Prys Roberts C, Brown BR. Local Anaesthetic Pharmacology. In: Prys

Roberts.ed. International Practice of Anaesthesia, 1st Edition,vol.2

Oxword Butterworth, 1996.

31. Ankit Agarwal, RK Verma, Shivika Srinivasta. Ropivacaine – The

latest Local Anaesthetic in the Indian market. J Clin Anesth.2010;26

:223-228.

32. Song D, Greilich NB, White PF, Watcha MF, Tongier WK. Recovery

profiles and costs of anaesthesia for outpatient unilateral inguinal

herniorrhaphy. Anaesth Analg 2000;91:876-81.

33. Kark AE, Kurzer M, Waters KJ. Tension free mesh hernia repair :

Review of 1098 cases using local anaesthesia in a day unit. Ann R Coll

Surg Engl 1995;77:299-304.

34. Prevoznik. Useful blocks in outpatient anaesthesia in international

anaesthesiology. Clinic Kurt F. Schmidt 4 edn, 1976;2:91-95.

35. Markhan A., Faulds D. Ropivacaine. A review of its pharmacology and

therapeutic use in regional anaesthesia. Drugs 1996; 52: 429–449.

36. Earle AS. Local anaesthesia for inguinal herniorrhaphy. Am J Surg

1960;100:782-786

37. Zoilinger RM, Konstantakos AK, Stellato TA, Hirgchfeld SS. Local

anaesthesia plus deep sedation for adult inguinal hernia repair in an

ambulatory surgery. Springlink-Journal article, Hernia 1998;2(2):77-80.

84

38. Dunn J, Day CJE. Local anaesthesia for inguinal and femoral hernia

repair update in anaesthesia for Inguinal and Femoral Hernia Repair.

1994;4Article 6:1-2.

39. Prado E, Herrera MF, Letay FV. Inguinal herniorrhaphy under local

anesthesia : a study of introperative tolerance. Am Surg

1994;60(8):617-619.

40. Covino, Benjamin G, Heleng, Vasalio. Clinical aspect of Local

anaesthesia. Chapter 4, Local anaesthetic mechanism of action and

clinical use. Published by Grane and Stralioninc New York 1976:58-59

41. Callesen T, Kehlet H. Post herniorrhaphy pain. Anaesthesiol

1997;87:1219-1230.

42. Callesen T, Beck K, Kehlet H. The feasibility, safety and cost of

infiltration anaesthesia for hernia repair. Anaesthesiology 1998;53:31-

85

ANNEXURES - A

PROFORMA

Date: Case No:

Name: Ht: IP NO:

Age: Wt: Address:

Sex: BMI:

ASA:

Diagnosis : PreMedication:

Procedure: Midazolam

Fortwin

OT shifting Time:

Time of administering Block:

Volume of LA:

Onset of Block:

Incision time:

INTRA OP

Time Adequacy Done Surgeon Side BP PR SPo2 IVF BY effects Of Block Satisfaction Pre Op Incision 5 10 15

86

20 25 30 40 50 60

POST OP – RECOVERY ROOM

Need For Time BP PR SPo2 VRS Analgesics

0

15

30

45

60

POST OP_ GENERAL WARD

VRS Time of Rescue Time Requirement on Analgesia On On First Analgesic lying Moving

0 30 1 1.30 2 2.30

87

3 3.30 4 4.30 5 5.30 6

88

ANNEXURES – B

89

PARENT/GUARDIAN CONSENT FORM

Title of the Study : A Prospective study of comparison of 0.5 % Bupivacaine vs 0.75 % Ropivacaine for Field block in inguinal hernia repair.

Study Centre: Mahatma Gandhi Memorial Government Hospital, Trichy.

Patient‟s Name : Age /Sex Parent/Guardian‟s Name : Address : The details of the study have been provided to me in writing and explained to me in my own language. I confirm that I have understood the above study and had the opportunity to ask questions about the anaesthetic techniques to be administered to the patient for surgery and postoperative pain relief.

I understand that the patient s participation in the study is voluntary and that I am free to withdraw at any time, without giving any reason, without affecting the medical care that will normally be provided by the hospital.

I understand that the doctor involved in the study does not require my permission, to monitor and assess the patient for various medical parameters.

I agree not to restrict the use of any data of results that arise from this study, provided such a use is only scientific purpose(s).

90

I fully consent for the patient to take part in the study and I have also been explained about the complications that may arise due to the anaesthesia techniques.

As the parent/ guardian of the patient, I give my consent for her to undergo the anaesthesia procedures involving local infiltration followed by injecting of anaesthetic drugs, 0.75 % Ropivacaine vs 0.5 % Bupivacaine for the study as mentioned in the patient information sheet.

I consent wholeheartedly after understanding that the study is taken up for the benefit of patient.

Signature/Thumb impression of the parent/guardian:

Date: Place:

Signature of the investigator:

91

ONSET IN NAME AGE SEX BMI GROUP ASA MIN 0.5 min 1min 1.5min 2min 2.5min 3min 3.5min 4min 4.5min 5min 5.5min 6min 6.5min 7min 7.5min 8min 8.5min 9min 9.5min 10min 10.5min 11min 11.5min 12min 12.5min 13min 13.5min 14min 14.5 MURUGAN 34 1 1 1 1 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 SARAVANAN 25 1 1 1 1 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 VARUN 45 1 1 1 1 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 CHETHAN 32 1 2 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 VEERAPPAN 56 1 2 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 ARUN 54 1 1 1 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 KANNAN 19 1 2 1 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 MOHAMMED 23 1 1 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 JESU RAJ 29 1 2 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 THANGAPPAN 36 1 2 1 1 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 RATHINAM 45 1 2 1 1 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 SEKAR 57 1 2 1 2 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 KUMAR SAMY 56 1 2 1 2 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 SHANMUGHAM 45 1 1 1 2 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 KRISHNAMOORTHY 43 1 1 1 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 JEEVA 46 1 1 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 PETER 42 1 1 1 1 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 SOUNDER RAJ 52 1 2 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 CHELLAIAH 38 1 2 1 1 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 MUSTAFA 58 1 2 1 1 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ANAND 37 1 2 1 1 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ARJUN 47 1 2 1 1 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 UMMER 53 1 2 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 RAJIV 43 1 1 1 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 HAMEED 56 1 1 1 2 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 PRAVEEN 47 1 1 1 1 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ANTONY 37 1 1 1 1 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 MARTHANDAM 56 1 1 1 1 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 RAJA 55 1 1 1 2 0 0 0 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 RAVISEKHAR 56 1 1 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

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