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CERTIFICATE

This is to certify that this dissertation entitled “A

comparative study on the effects of intravenous tramadol and

pethidine for post operative shivering of patients under spinal

anaesthesia” is abonafide record of the work done by Dr. Jisha

Roy Babu under my guidance and supervision in the Department

of Anaesthesiology during the period of her postgraduate study

for M.D Anaesthesiology [Branch−X] from 2013−2016.

Dr.Thavamani, DA,MD

[Guide] HOD & Professor Department of Anaesthesiology Sree Mookambika Institute of Medical Science Kulasekharam Kanyakumari (Dist) – 629161

Dr.Rema. V. Nair, M.D, D.G.O. Director Sree Mookambika Institute of Medical Sciences Kulasekharam Kanyakumari District Tamil Nadu -629161

Dr.Rommy Geever.T, MD [Co-Guide] Assistant Professor Department of Anaesthesiology SreeMookambika Institute of Medical Science Kulasekharam Kanyakumari (Dist) – 629161

DECLARATION

In the following pages is presented a consolidated report of

the study “A comparative study on the effects of intravenous

tramadol and pethidine for post operative shivering of patients

under spinal anaesthesia” a randomized controlled trial, on cases

studied and followed up by me at Sree Mookambika Institute of

Medical Sciences, Kulasekharam from 2014−2015. This thesis is

submitted to the Dr.M.G.R. Medical University, Chennai in partial

fulfilment of the rules and regulations for the award of MD

Degree examination in Anaesthesiology.

Dr.Jisha Roy Babu,

Junior Resident in Anaesthesiology,

Department of Anaesthesiology,

Sree Mookambika Institute of Medical Sciences,

Kulasekharam,

Kanyakumari District.

ACKNOWLEDGEMENT

I thank God almighty, for all his blessings, without which this work

would not have been possible.

I express my heartfelt gratitude to our Director Dr.Rema V. Nair and our

Chairman Dr.Velayudhan Nair who provided me the infrastructure and for

permitting me to carry out this study. They are the foundation pillars of the

various activities that have been initiated in our institution.

I thank my HOD and guide Dr.Thavamani whose suggestions, help and

critical views which was present throughout the study. It has been a

tremendous and wonderful experience to work under his guidance. He gave me

constant support, without which this dissertation would not have been

completed on time.

I thank my co-guide Dr.Rommy Geever for his valuable help,

suggestions and supervision throughout the study. His encouragement from the

inception of this research to its culmination has been profound.

I humbly thank Dr.Jayaprakash whose support, guidance, help, critical

views throughout my study period. His suggestions were very valuable at each

stage of my dissertation work. I am indebted to him for his guidance and

support throughout my post graduate days.

I express my sincere gratitude to Dr Parvathy for her constant

motivation which was present throughout the study period. She lent her full

support in times of difficulties that I encountered during this study period.

I sincerely thank Dr.Anand for his valuable help and guidance

throughout the study. He is a source of inspiration for us post graduates. His

humbleness and sincerity in teaching both undergraduates and postgraduate

students has made him our role model.

I also thank Dr.Gopalakrishnan for his guidance during my initial study

period.

I am also grateful to Dr.Subramaniam for his valuable support and

constant encouragement.

I also thank Dr.Prashanthan, Dr.Mahilamani, Dr Beula, Dr.Saji, Dr.Ravi

Shankar and all the staff members of Anaesthesiology for their valuable

support.

I thank Dr.Suzannae Prasad, my co-pg, for her valuable and timely help

which made me complete my study on time.

I am really thankfull to my seniors Dr.Rakhi and Dr.Mohsina for their

guidance, help and support all throughout my study.

I am grateful to my junior post graduates Dr.Archana, Dr.Sahil,

Dr.Anitha and Dr.Sathish for the various technical aspects of my study.

I would also like to thank Mr.Sarath for his help in statistical work.

I thank our anaesthesia technician, nursing staffs for their help and

support.

I express my thanks to Dharsan printers for timely completion of

printing work.

I am grateful to my husband and family members for their full support,

unfaltering love and help.

Without the whole hearted cooperation of my patients, this thesis would

not have reached a conclusion. I express my sincere gratitude to all my patients

at Sree Mookambika Institute of Medical Sciences, Kulasekharam.

Dr.Jisha Roy Babu.

LIST OF CONTENTS

Sl.No. Contents Page No

1. Introduction 1

2. Aims and Objectives 3

3. Review of Literature 4-53

4. Methodology 54-58

5. Results 59-72

6. Discussion 73-76

7. Conclusion 77

8. Summary 78

9. Bibliography 79-92

10. Annexures I-V

LIST OF TABLES

Sl. No Tables Page No

1 Comparison of demographic data between the groups

59

2 Comparison of time of onset, duration and grade of shivering between two groups

60

3 Distribution of patients according to grade of shivering

62

4 Distribution of patients according to time of onset 62

5 Distribution of patients according to duration of shivering

63

6 Comparison of heart rate between the groups at different time intervals

64

7 Comparison of systolic blood pressure between the groups at different time intervals

66

8 Comparison of diastolic blood pressure between the groups at different time intervals

67

9 Comparison of oxygen saturation between the groups at different time intervals

68

10 Comparison of temperature between the groups at different time intervals

69

11

12

Comparison of number, percentage of recurrence and grade of shivering during recurrence

Comparison of number and percentage of adverse drug reactions between the two groups.

70

72

LIST OF FIGURES

Sl. No Figures Page No

1 Spinal curvatures; cervical, thoracic and lumbar

vertebra

14

2 Structure of vertebra 15

3 Spinal cord 17

4 Blood supply of spinal cord 19

5 Structure of Pethidine 29

6 Metabolism of Pethidine 31

7 Structure of Tramadol 35

8 Comparison of time of onset and duration of

shivering between two groups

61

9 Comparison of heart rate between the groups at

different time intervals

65

10 Comparison of systolic blood pressure between the

groups at different time intervals

66

11 Comparison of diastolic blood pressure between

the groups at different time intervals

67

12 Comparison of oxygen saturation between the

groups at different time intervals

68

13 Comparison of temperature between the groups at

different time intervals

69

14 Comparison of percentage of recurrence of

shivering between the groups

71

ABSTRACT

Background and Objectives:

Shivering is very unpleasant and stressful for the patient after

undergoing a comfortable analgesic surgery. It may induce arterial hypoxemia,

lactic acidosis, increased intracranial pressure and intraocular pressure,

interferes with haemodynamics and increase wound pain. Various

pharmacological and non-pharmacological methods are available for control of

shivering. Drugs like Clonidine, Doxapram, Pethidine, Tramadol etc have been

tried but debate on an ideal antishivering drug still continues. Thus in a patient

with limited myocardial oxygen reserve or known coronary artery disease,

shivering may further compromise myocardial function. Here we are

comparing a synthetic opioid, IV Tramadol at 1mg/kg with IV Pethidine

0.5mg/kg, standard drug for treatment of shivering in quest for a more safe and

efficacious drug.

Materials and Methods:

Seventy four patients who developed shivering after elective surgery

under spinal anaesthesia were randomized into two groups each having thirty

seven patients-tramadol group (Group 1) and pethidine group (Group 2).

Patients were treated with 1mg/kg tramadol (Group 1) and 0.5mg/kg pethidine

(Group 2). Haemodynamic stability, onset of action of each drug and side

effects were closely monitored at different time intervals before shivering,

during shivering and at 5 minute interval for 15 minutes. All patients were

given spinal anaesthesia with 0.5% heavy bupivacaine. All the patients with

shivering were administered oxygen at 6 L/min via venti mask.

Statistical Analysis:

Based on the ratio between recurrence of shivering with reference from

study of Aditi.A Dhimer, with α error-5%, power-95%, sample size on each

arm found to be 37 each, using EZR version 1.1 on R commander version 1.8-

4.

Results: After intravenous administration of tramadol 1 mg/kg,cesation of

shivering occured immediately. Shivering lasted for more time after

administration of pethidine 0.5 mg/kg. Recurrence rate in tramadol group was

found to be less than pethidine group. Nausea and vomiting was more in

tramadol group.

Conclusions: Intravenous tramadol is more effective than pethidine in

controlling post spinal anaesthesia shivering.Tramadol has less response rate

and recurrence.It is cheap as compared to pethidine and freely available

without drug licence.

Keywords: Tramadol, Pethidine, postoperative shivering, spinal anaesthesia

Introduction

1

INTRODUCTION

Spinal anaesthesia is a popular and safe anaesthetic technique for

various surgeries. Around 40-60% of the patients under spinal anaesthesia

develop shivering. The incidence varies depending on the type of anaesthesia,

gender, age, and the duration of the anaesthesia or the operation.

Neutral temperature is defined as ambient temperature that results in

least oxygen consumption. It varies according to age. It is 34◦C in preterm

neonate, 32◦C in term neonate, 28◦C in adults. Critical temperature is that

ambient temperature below which an unclothed, unanaesthetised person cannot

maintain normal core body temperature.

Shivering is described as an involuntary, oscillatory muscular activity. It

is a physiological response of body to raise core temperature by increasing the

metabolic heat production. It may be normal thermoregulatory shivering in

response to body’s core hypothermia or may be a result of release of cytokines

in response to surgical intervention. In a patient with shivering, oxygen

consumption may increase by 200-500% along with rise in CO₂ production. In

a patient with known coronary artery disease or limited myocardial oxygen

reserve, shivering may affect the myocardial function. Shivering elevates

intraocular pressure, intracerebral pressure and may increase wound pain. Even

though shivering is not a life-threatening process, it can be a discomfort for the

patient, and may interfere with pulse oxygen saturation, electrocardiogram and

blood pressure monitoring.

Introduction

2

Tramadol is a synthetic opioid with moderate affinity for mu receptors

and weak delta and kappa receptor affinity. It inhibit neuronal reuptake of

norepinephrine and 5-HT. It has analgesic action with less chance of depression

of ventilation. Studies1 have proved that intravenous tramadol in a dose of 1-2

mg/kg is effective in post operative shivering. Tramadol2 has high safety

profile and weak sedative properties.

Pethidine is a synthetic opioid agonist at mu and kappa opioid receptors.

It is a potent alpha₂ agonist, it might contribute to antishivering effects. It may

produce analgesia postoperatively and during labour and delivery. Studies3

have shown that role of k opioid receptors are more significant than μ opioid

receptors in the treatment of post anaesthetic shivering.

In our study we are analysing the effect of tramadol (1 mg/kg) and

pethidine (0.5 mg/kg) intravenously for post spinal anaesthesia shivering.

Aims and Objectives

3

AIMS AND OBJECTIVES:

1. To study the effect of Tramadol and Pethidine on post operative

shivering.

2. To compare the efficacy and safety of Tramadol and Pethidine.

Review of Literature

4

REVIEW OF LITERATURE

HISTORY

James Leonard Corning(1855–1923), a neurologist in New York in the

year 1885 administered first spinal analgesia. He was interested on work on

cocaine on spinal nerves of a dog. Accidentally, he injured the duramater. On

October 12, 1885, he injected 120 mg of cocaine at T11 and T12 interspace in

a 45-year-old male patient and observed loss of sensation of the legs and

perineum. He concluded that cocaine has action on spinal cord and proposed its

spinal spasticity cases and for genitourinary surgeries. In 1891, Heinrich I

Quincke(1842-1922) realised that the dural sac which was described by

Domenico Cotugno (1736-1822) in 1787, could be punctured by a needle

insertion between lumbar spinous processes. Quincke tried to treat

hydrocephalus by draining cerebrospinal fluid from dural sac but was

unsuccessful.

On August 15, 1898, August Bier and his assistant August Hildebrandt

(1868-1854) used the Quincke method and injected 5-15 mg of cocaine to

produce spinal anesthesia in 6 cases for surgeries on lower part of the body.

They also reported results of spinal anesthesia given to each other. It later

became one of the classic clinical papers in medical literature. Arthur E. Barker

(1850-1916) conducted studies to determine factors involved in spread of the

local anesthetic within the subarachnoid space. He advised meticulous sterile


5

technique and introduced the use of dextrose to produce hyperbaric solutions.

His conclusion on gravity as an essential determinant of spread of local

anesthetic remains an important fact of the spinal technique today.

The word opium is derived from opos, which means juice in Greek, as

the drug is derived from juice of opium poppy Papaver Somniferum. Opiates

are drugs derived from opium and morphine, codeine, and thebaine are natural

products. There are many semisynthetic congeners derived from them.

In 3rd century BC, Theophrastus has mentioned about opium in his

writings . Many of the opium uses were appreciated from middle ages. In 1806,

Serturner reported the isolation of a pure substance in opium which he named

as morphine after Morpheus, the Greek god of dreams. By the middle of the

nineteenth century, the use of pure alkaloids spread throughout the medical

world.

SHIVERING

Shivering is commonly presented as an irregular tremor which on

graphical evaluation seen as overlapping spikes of myofibril depolarization. It

consist of 4 to 10 cycles per min, waxing-and-waning activity. This slow

amplitude change occured simultaneously and synchronously in all muscle

groups.4 Shivering is not usually seen in pediatric age group . This is because,

in paediatric patients, shivering threshold is low as compared to the

vasoconstriction threshold,5shivering occurs as a last resort response to extreme


6

cold. In adults, sustained shivering increase metabolic heat production 50-100

percent . This increase during shivering is small compared to that produced by

exercise, which can increase metabolism 5 times, is ineffective.

THERMOREGULATION DURING NEURAXIAL ANAESTHESIA

Epidural anaesthesia6,7 and spinal anaesthesia7,8each reduce the

thresholds of shivering and vasoconstriction above the level of the block by

about 0.6°C . This decrease cannot be explained by recirculation of neuraxially

administered local anaesthetic because the effect is similar during both epidural

and spinal anaesthesia6,7,8 even though the location and amount of local

anaesthetic administered differ. It is found that dose of intravenous lignocaine

producing plasma concentrations has no thermoregulatory effect.9 2-

chloroprocaine, a local anaesthetic with a plasma half-life of 20 seconds, also

impairs thermoregulatory control when injected intrathecally.10,11

The shivering thresholds and vasoconstriction are decreased during

regional anaesthesia,8 suggesting a change in central control. Intravenously or

intramuscularly given local anesthesics may affect centrally mediated

thermoregulation by modulating afferent thermal input from lower limbs. The

basis behind this is that tonic cold signals dominate thermal signals in a

operating room environment.12 Regional anesthesia blocks all thermal input

from the blocked areas, which is primarily cold information. The brain may

then interpret reduced cold information as relative leg warming. This is


7

considered as an unconscious process in which perceived temperature does not

increase.13As skin temperature is an important input to thermoregulatory

control system, leg warming proportionately reduce the possibility of

vasoconstriction and decrease shivering thresholds. Consistent with this

theory, a skin temperature of leg near 38°C is required to produce the same

reduction in cold-response thresholds in an unanesthetized patient as produced

by regional anesthesia.14 In addition to this, decrease in thresholds vary

depending on the number of spinal segments blocked.15 Thus major conduction

anesthesia may decrease the shivering and vasoconstriction thresholds by

producing an abnormal increase in apparent leg temperature. However, this

explanation remains speculative.

As neuraxial anesthesia prevents shivering and vasoconstriction in

blocked regions, epidural anesthesia reduce the maximum shivering intensity.

Epidural anesthesia also decrease the gain of shivering, which imply that the

regulatory system is not able to compensate for paralysis of lower body.16

Usually neuraxial anesthesia is supplemented with analgesic and

sedative medications which can impair thermoregulatory control17,18,19 The

impairment become severe with combination of patient comorbidities, old age,

analgesics and sedatives and neuraxial blockade.

Core hypothermia during regional anesthesia may not trigger cold

perception .6,20 It is because, thermal perception is mainly determined by skin


8

than core temperature. Core hypothermia is followed by a real elevation in skin

temperature during regional anesthesia. The end result is, continued or more

warmth perception with activation of autonomic thermoregulatory responses

including shivering . 6,20

Altogether, these data imply that various aspects of thermoregulatory

control are inhibited by neuraxial anaesthesia. The shivering and

vasoconstriction thresholds are decreased by regional techniques6,7,8,14,15 and

which is further reduced by advanced age22 and adjuvant drugs.18,21 Even if

once triggered, the maximum response and gain intensity of shivering are about

half the normal. Thus behavioral thermoregulation is impaired.20 During

regional anesthesia cold defenses are triggered at a lower temperature and once

stimulated defenses are less effective, and patients often do not recognize

hypothermia. As core temperature are not monitored during regional

anesthesia, substantial hypothermia remains undetected in most of the

patients.23

Opioid-based anesthesia probably reduces thermoregulatory thresholds

to a similar extent as that of potent inhaled agents .18 However, pethidine

stands unique among opioids in its ability to effectively attenuate or terminate

shivering. The antishivering effect of pethidine is primarily related to reduction

in the shivering threshold 24 and seems to be mediated by its activity on the κ-

receptor.25But, more specific κ-receptor agonist nalbuphine do not exhibit

significant antishivering activity.26 Pethidine exerts agonist activity at the α2B-


9

adrenoreceptor subtype, this may be the possible reason for its antishivering

action .27 Alfentanil, morphine, and fentanyl are not as effective as pethidine in

the treatment of postoperative shivering. Tramadol (0.5 mg/kg) suppressed

post–epidural anesthetic shivering in parturients as effectively as pethidine

(0.5 mg/kg),28 but the incidence of somnolence was less with tramadol

compared to pethidine.11

Shivering during neuraxial anaesthesia

Shivering is common response during neuraxial anesthesia.Four causes

have been postulated for shivering:

1) shivering can occur as a response reaction to low body temperature,

2) shivering can occur in patients with normal temperature and those having

fever ;

3) intrathecal or epidural administration of local anaesthetics can stimulate cold

receptors; and,

4) non-thermoregulatory shivering .

There can be other causes for shivering. For example, a cause for the

intense shivering in caesarean patients occuring immediately after spinal or

epidural anesthesia, i.e even before core temperature had time to reduce, is still

unknown.


10

Most shivering associated with neuraxial anaesthesia appears to be

normal shivering occuring as a response to hypothermia. Shivering is preceded

by vasoconstriction and core hypothermia atleast in volunteers receiving

neuraxial anaesthesia.6 Electromyographic evaluation can confirm diagnosis of

shivering by their typical pattern.29 Fever during surgery considered as a rare

etiology of shivering.

All birds and mammals have spinal thermoreceptors. There is a chance

for development of shivering in patients receiving cold drugs neuraxially . This

was proved by a study on pregnant patients.Those patients who received cold

solutions intrathecally had more shivering rate compared to those who received

warm solutions.30 In contrast, study on normal patients32 did not show

increased incidence of shivering even after large amount of cold saline

injection epidurally.31 This summarize that temperature of local anaesthetic

injected rarely stimulates shivering.

All shivering-like tremor are not thermoregulatory. Mild shivering is

noted in patients during surgery33 or during labor34 . This may be due to

sympathetic nervous system activation35 or due to pain. Exact cause is

unknown.

It is a serious complication that 100 % increase in oxygen consumption

in proportion to intraoperative heat loss.36 As oxygen demand is increased,

myocardial ischaemia can occur in patients with compromised myocardial


11

function. In addition to increasing intracranial pressure and intraocular

pressure, postoperative shivering possibly elevate wound pain by stretching

sutures. Most important determinants of shivering risk found are young age and

low core temperature.37

Treatment of postanaesthetic shivering

Skin surface warming, warming room can reduce shivering as skin

temperature has a role in temperature regulation .38 Skin surface has 20% 39,40

and the lower part of body has 10% contribution in temperature regulation14. In

short, skin warming is beneficial for only a small fraction of patients.

Heat loss by conduction is reduced by warming the room and heat lost

by convention is minimised by warm blankets. In infants, use of double shelled

isolette during transport decrease heat lost by radiation and use of plastic

wrap,humidification of inspired air lessen heat lost by evaporation.

Postanesthetic shivering can also be treated with many drugs, including

physostigmine (0.04 mg/kg IV),43 clonidine (75 µg IV),41 tramadol,42

ketanserin (10 mg IV), 41 magnesium sulfate (30 mg/kg IV)45 ,

dexmedetomidine, and nefopam (0.15 mg/kg)44 . The specific mechanisms by

which ketanserin, tramadol, physostigmine, and magnesium sulfate stop

shivering remain unknown. Clonidine46 and dexmedetomidine47 reduce the

shivering and vasoconstriction thresholds, thus suggesting that they act on the

central thermoregulatory system and not preventing shivering peripherally.


12

Alfentanil, a pure µ-receptor agonist, significantly alters

thermoregulatory control.18 Pethidine is more effective in treating shivering

than other µ-agonists.48 It is found that it reduces shivering threshold two times

as much as the vasoconstriction threshold19 without reducing gain or maximum

intensity of shivering.24 The efficacy of pethidine is partially preserved during

naloxone administration at a dose of 0.5 µg/kg/min but virtually obliterated by

large doses (5.0 µg/kg/min).25 These data imply about the action of this drug on

non–µ-opioid receptors. Pethidine possesses considerable κ activity49 and has

central anticholinergic activity. Neither of these mechanism mediate pethidine's

special antishivering activity.

SPINAL ANAESTHESIA

Spinal anaesthesia is also called spinal analgesic or spinal block or

subarachnoid block(SAB). It is a form of regional anaesthesia in which local

anaesthetic is injected into subarachnoid space through a fine needle, usually

9 cm long (3.5 inches). Longer needles of 12.7 cm / 5 inches are available for

extremely obese patients. Spinal needle has a point or small bevel at the tip.

Pencil point needles are also available.

Spinal, epidural, and caudal neuraxial blocks result in sympathetic

block, sensory analgesia or anaesthesia and motor blockade, depending on the

dose, concentration, or volume of local anesthetic injected after insertion of a

needle in the plane of the neuraxis.


13

ANATOMY

The spine consist of vertebral bones and fibrocartilaginous

intervertebral disc. There are seven cervical, twelve thoracic, and five lumbar

vertebra. 5 sacral vertebrae fused to form sacrum, and small rudimentary

coccygeal vertebra are also present. The spine provides protection for the spinal

cord and nerves, structural support for the body, and allows a degree of

mobility. Paired spinal nerves exit at each vertebral level.

Size and shape of vertebra at various level differs. The atlas, the first

cervical vertebra, lacks a body and has unique articulations with the base of the

skull and the second vertebra. The axis, second vertebra, has atypical

articulating surfaces. All thoracic vertebrae articulate with their corresponding

rib.

Figure 1:F

thoracic an

Lum

hollow rin

processes

Figure sho

nd sacral v

mbar verteb

ng anterio

laterally, a

owing spin

vertebra in d

brae have

orly by the

and the lam

14

ne with cu

detail.

large anter

e vertebra

mina and sp

R

urvatures (

rior cylindr

al body, th

pinous proc

Review

(lateral vie

rical verteb

he pedicle

cesses post

of Liter

ew) and c

bral body.

es and tra

teriorly.

rature

cervical,

It has a

ansverse


15

Figure 2 :Figure of vertebra

The part between the spinous processes and the transverse processes is

called lamina and the part between the transverse processes and the vertebral

body is called pedicle. The hollow rings become the spinal canal in which the

spinal cord and its coverings pass. The individual vertebral bodies are

connected by the intervertebral disc.Each vertebra has 4 small synovial joints, 2

joints articulate with above vertebra and 2 joints articulate with the vertebra

below it. These are the facet joints near the transverse processes. The pedicles

are notched superiorly and inferiorly, these notches form the intervertebral

foramina, through which the spinal nerves exit.5 Sacral vertebrae fuse to one

large bone, the sacrum, but each one has discrete anterior and posterior

intervertebral foramina. The laminae of fifth sacral vertebra and fourth sacral

vertebra do not fuse completely, leaving a caudal opening to the spinal canal,

called the sacral hiatus .


16

The spinal column forms a double C, being convex anteriorly in the

cervical and lumbar regions. Ligaments provide structural support and together

with supporting muscles, maintain the unique shape of spine. Anteriorly, the

vertebral bodies and intervertebral disc are connected and supported by the

anterior and posterior longitudinal ligaments. Posteriorly, the ligamentum

flavum, interspinous ligament, and supraspinous ligament provide additional

stability. Using the midline approach, a needle passes through these 3 posterior

ligaments and through an oval space between the bony lamina and spinous

processes of adjacent vertebra.

The Spinal Cord

The spinal canal contains, spinal cord with its coverings called

meninges, fatty tissue, and a venous plexus. Meninges have three layers: the

pia mater, the arachnoid mater, and the dura mater; all are continuous with their

cranial counterparts. The pia mater is closely adherent to spinal cord, whereas

the arachnoid mater is usually closely adherent to thicker and denser dura

mater. Cerebrospinal fluid (CSF) is contained between the pia and arachnoid

mater in the subarachnoid space. The spinal subdural space is poorly

demarcated. It exists between the dura and arachnoid membranes. The epidural

space is a better defined potential space within the spinal canal that is bounded

by the dura and the ligamentum flavum.


17

Figure 3:Spinal cord

In adults,spinal cord extends from foramen magnum to the lower border

of L1. In infants, the spinal cord ends at L3 and moves up as they grow old.

The anterior and posterior nerve roots at each spinal level join together and exit

through intervertebral foramina as spinal nerves from C1 to S5. At the cervical

level, the nerves pass above their respective vertebrae, but from T1 they exit

below respective vertebrae. There are 8 cervical nerve roots but only 7 cervical

vertebrae. The cervical and upper thoracic nerve roots join together from the

spinal cord and exit through vertebral foramina nearly at the same level. As the

spinal cord normally ends at L1, lower nerve roots course some distance before

exiting intervertebral foramina. These lower spinal nerves form the cauda

equina ( horse's tail ). Therefore, lumbar or subarachnoid puncture done below


18

L1 in an adult and L3 in a child avoids potential needle injury to the cord.

Cauda equina injury, rarely occurs. As these nerve fibres are floating in CSF,

there will just slip off during spinal needle insertion rather than getting injured.

The dural sac and the subarachnoid and subdural spaces usually extend

to S2 in adults and often to S3 in case of children. Because of this fact and the

smaller body size, caudal anesthesia carries a greater risk of subarachnoid

injection in children than in adults. Filum terminale is an extension of piamater.

It penetrates the duramater and attaches conus medullaris to the periostium of

the coccyx .

The blood supply to the spinal cord and nerve roots is provided by a

single anterior spinal artery and paired posterior spinal arteries. The anterior

spinal artery originate from the vertebral artery at the base of the skull and

course down along the anteriorly. The anterior spinal artery supplies the

anterior ⅔ of the cord, whereas the 2 posterior spinal arteries supply the

posterior ⅓. The posterior spinal arteries origin from the posterior inferior

cerebellar arteries and course down along the posterior surface of the cord

medial to the dorsal nerve roots. The anterior and posterior spinal arteries

receive additional blood flow from the intercostal arteries in the thorax and the

lumbar arteries in the abdomen. One of these radicular arteries is typically

large, the artery of Adamkiewicz, or arteria radicularis magna, arise from the

aorta . It is unilateral and always arises on the left side, providing the major


19

blood supply to the anterior, lower two-thirds of the spinal cord. Injury to this

artery can result in anterior spinal artery syndrome.50

Figure 4:Blood supply to spinal cord

Cerebrospinal Fluid

CSF is found in the cerebral ventricles and cisterns and in the

subarachnoid space surrounding the brain and spinal cord. Its predominant

function is to protect the CNS against injury.

CSF is mostly formed by the choroid plexuses of the cerebral (mainly

lateral) ventricles. Some amounts are formed directly by the ventricle’s

ependymal cell linings and some amount from fluid leaking into the

perivascular spaces surrounding cerebral vessels (blood–brain barrier leakage).

In elderly, normal total CSF production is about 21 ml/h (500 ml/d), total CSF

volume is only about 150 ml. CSF flows from the lateral ventricles through the

intraventricular foramina (foramen of Monro) and then into the third ventricle

through the cerebral aqueduct or aqueduct of Sylvius into the fourth ventricle,

and through the median aperture of the fourth ventricle (foramen of Magendie)


20

and the lateral aperture of the fourth ventricle (foramina of Luschka) drain into

the cerebellomedullary cistern (cisterna magna). CSF from the

cerebellomedullary cistern, enters the subarachnoid space, circulating around

the brain and spinal cord before being absorbed in arachnoid granulations over

the cerebral hemispheres.

Formation of CSF involves secretion of sodium in the choroid plexuses.

The resulting fluid is isotonic with plasma despite reduced potassium,

bicarbonate, and glucose concentrations. Its protein content is very less.

Carbonic anhydrase antagonist like acetazolamide, corticosteroids,

spironolactone, isoflurane, furosemide, and vasoconstrictors reduce CSF

production.

Translocation of fluid from the arachnoid granulation into cerebral

venous sinuses involves absorption of CSF. Some amounts are absorbed at

nerve root sleeves and by meningeal lymphatics. Although the mechanism

remains unclear, absorption is inversely proportionate to cerebral venous

pressure and directly proportionate to intracranial pressure. As the spinal cord

and brain lack lymphatics, absorption of CSF is the important source by which

perivascular and interstitial protein is returned to blood.50


21

Physiological effects of neuraxial blockade

Somatic blockade

When there is sensory blockade, it interrupts both visceral and somatic

painful stimuli, motor blockade produce relaxation of skeletal muscle. The

effect of local anaesthetics on nerve fibers differs and depend on the size of

nerve fiber, whether it is myelinated, and the concentration obtained and the

extent of contact . Spinal nerve roots contain different types of fiber. Smaller

and myelinated fibers are mostly more easily blocked than larger and

unmyelinated ones. The differential blockade typically it results in sympathetic

blockade which can be evaluated by temperature sensitivity; sensory block

(pain, light touch) at two segment lower level; and the motor blockade, two

segments lower than sensory blockade.

Autonomic Blockade

Neuraxial blockade produce both sympathetic and some

parasympathetic blockade . Sympathetic transmission from the spinal cord may

be explained as thoracolumbar, whereas parasympathetic outflow is

craniosacral. Sympathetic preganglionic nerve fibers are small, myelinated B

fibers.They leave out of spinal cord with the spinal nerves from T1 -L2 level

and may course many levels above or down the sympathetic chain before they

join with a postganglionic cell in a sympathetic ganglia. Parasympathetic

preganglionic fibers comes out of the spinal cord along with the cranial and


22

sacral nerves. Vagus nerve not blocked in neuraxial blockade. The

physiological responses brought about by neuraxial blockade is due to reduced

sympathetic tone and unopposed parasympathetic tone.

Cardiovascular Manifestations

Neuraxial blocks produce reduction in blood pressure and that may be

followed by a reduction in heart rate and cardiac contractility. It depend on the

level of sympathetic blockade. Sympathetic fibers arising from T5 - L1,

innervating venous and arterial smooth muscle, regulate the vascular tone. So

sympathetic blockade cause vasodilation of the venous system, pooling of

blood, and thus reduced venous return to the heart. Arterial vasodilation may

also reduce systemic vascular resistance but it will be compensated by

vasoconstriction above the blockade level. A high block can affect cardiac

accelerator fibers arising from T1–T4 inaddition to inhibition of

vasoconstriction. As a result, hypotension, decreased contractility and

bradycardia occurs. These effects worsen in pregnancy or head up posture due

to reduction in venous return. The sudden cardiac arrest seen with spinal

anesthesia may be explained by unopposed vagal tone.

Anticipate deleterious cardiovascular effects and prepare with necessary

steps to reduce the degree of hypotension.In a healthy adult, hypotension can

be prevented to an extent by fluid loading with 10–20 ml/kg of intravenous

fluid. Hypotension if occurs, can be managed with changing position to head


23

low , increasing rate of fluid infusion and vassopressor. Atropine can be used

for treatment of symptomatic reduction in heart rate. Phenylephrine, which is

an alpha agonist, can be used to treat hypotension. Ephedrine, alpha agonist,

enhance contractility and rise heart rate directly and produce vasoconstriction

indirectly. If severe bradycardia, hypotension persist despite these measures,

epinephrine (5–10 mcg intravenously) should be administered immediately.

Pulmonary Manifestations

Clinically changes in pulmonary physiology are usually minimal with

neuraxial blocks because innervation of diaphragm is by the phrenic nerve with

fibers originating from C3–C5. Even with high thoracic levels, tidal volume

remain unchanged; there is only a small decrease in vital capacity, which

results from loss of the abdominal muscle’s contribution to forced expiration.

Phrenic nerve function may remain even in cases of total spinal anesthesia.

Apnea often resolves with hemodynamic resuscitation, suggesting that brain

stem hypoperfusion is responsible for apnea.

Severe chronic lung disease patients may rely upon accessory muscles

of respiration like intercostal and abdominal muscles to actively inspire or

exhale. High block affect these muscles. For these reasons, neuraxial blocks

should be used cautiously in patients with limited respiratory reserve. Thoracic

or upper abdominal surgery is associated with reduced diaphragmatic function

postoperatively (from decreased phrenic nerve activity) and reduced functional


24

residual capacity (FRC), which can ultimately lead to atelectasis and hypoxia

via ventilation/perfusion mismatch.

Gastrointestinal Manifestations

Sympathetic supply for gastrointestinal system is from T5 to L1 level.

Blockade at this level result in small, contracted gut and increase peristalsis.

Hepatic blood flow will reduce with decrease in mean arterial pressure

from any anesthetic technique. For intraabdominal surgery, the decrease in

hepatic blood flow is related more to surgical manipulation than to anesthetic

technique .

Urinary Tract Manifestations

Autoregulation maintain renal blood flow, and there is little clinical

effect upon renal function from neuraxial blockade. Neuraxial blockade at

lumbar and sacral level, affect parasympathetic and sympathetic bladder

function. Loss of autonomic bladder control results in urinary retention. If no

urinary catheter is anticipated perioperatively, it is wise to use the shortest

acting and smallest amount of drug required for the surgical procedure and if

possible, limit the amount of intravenous fluid administration. The patient

should be monitored for urinary retention to avoid bladder distention following

neuraxial anesthesia.


25

Metabolic & Endocrine Manifestations

Surgical trauma produces a neuroendocrine response through a localized

inflammatory response and activation of visceral and somatic afferent nerve

fibers. This result in elevation in levels of norepinephrine, adrenocorticotropic

hormone, epinephrine, vasopressin and cortisol. It stimulate renin angiotensin

aldosterone axis. Clinical manifestations include tachycardia, intraoperative

and postoperative hypertension, protein catabolism, hyperglycemia, altered

renal function and suppressed immune responses. Blockade can partially block

(during major invasive surgery) or totally suppress (during lower extremity

surgery) this stress response. By decreasing catecholamine release, neuraxial

blocks may reduce perioperative arrhythmias and reduce the incidence of

ischemia. Neuraxial block should precede incision and extend into the

postoperative period to achieve maximum blunting of neuroendocrine stress

response.

Indications of spinal anaesthesia

Lower extremity surgery

Lower abdominal surgery,

Urogenital surgery


26

Inguinal surgery and

Rectal surgery.

Contraindications of spinal anaesthesia

Patient refusal,

Infection at the site of injection,

Severe hypovolemia,

Bleeding diathesis,

Elevated intracranial pressure,

Anatomical disorders of the spine and

Severe stenotic valvular heart disease or ventricular outflow obstruction

Spinal Anesthetic Agents

Many local anesthetics were used for spinal anesthesia in the past, but

now only a few are in use. Only preservative-free local anaesthetic solutions

are used now. Adding vasoconstrictors (α-adrenergic agonists) and opioids may

enhance the quality and prolong the duration of spinal anaesthesia .

Vasoconstrictors include phenylephrine (1–2 mg) and epinephrine (0.1–0.2

mg). Both these drugs decrease the uptake and clearance of local anesthetics

from CSF and may have weak spinal analgesic properties.

Heavy bupivacaine and tetracaine are the most commonly used drugs for

spinal anesthesia. Both these drugs are slow in onset of action (5 to10 min) and


27

have long duration of action (90 to120 min). Tetracaine has more motor

blockade than bupivacaine in same dose. Addition of adrenaline to spinal

bupivacaine do not have much change in duration of action. But adrenaline

used in combination with tetracaine has prolonged duration of action.

Phenylephrine prolongs tetracaine anaesthesia but has no effect on bupivacaine

spinal blocks. Lignocaine and procaine have a fast onset of action (3–5 min)

and short duration of action (60–90 min).Although lignocaine for spinal

anesthesia has been used worldwide, there are reports of phenomenon of cauda

equina syndrome and transient neurological symptoms (TNS).

Hyperbaric spinal anesthesia is more commonly used than the isobaric

or hypobaric techniques. The level of anesthesia is dependent on the patient's

position during and immediately after injection. In the sitting position, saddle

block can be achieved by making the patient sit for 3 to 5 min after injection. If

the patient is changed from sitting position to supine immediately after

injection, the agent will move more cephalad to the dependent region defined

by the thoracolumbar curve,as drug not fully fixed. Hyperbaric anesthetics

injected intrathecally with the patient in a lateral decubitus position are used for

unilateral lower extremity procedures. The patient is placed laterally with the

extremity to be operated on in dependent position. If the patient is kept in this

position for about 5 min following drug administration, the block will be

denser and achieve a higher level on the operative dependent side.

If hypobaric spinal anaesthesia is chosen for surgical procedures


28

involving hip or lower extremity fracture, patient need not lie on the fractured

extremity.

Regardless of the anaesthetic agent used, the expected effect is to

block the transmission of afferent nerve signals from peripheral nociceptors.

Produce analgesia as sensory signals from the site are blocked. The extent of

blockade produced depends on concentration and amount of local anaesthetic

used and the properties of the axon. Thin unmyelinated C-fibres which are

associated with pain and heavily myelinated, small preganglionic sympathetic

are blocked first, and thick, heavily myelinated A-alpha motor neurons are

moderately blocked. Pressure sensation may still persist after neuraxial

blockade due to incomplete blockade of the thicker A-beta mechanoreceptors.

COMPLICATIONS OF SPINAL ANAESTHESIA

• Post dural puncture headache (PDPH) –related with the type and size of

spinal needle used.

• Hypotension

• Cauda equina injury - due to high insertion site.

• Cardiac arrest - very rare. It is due to the underlying comorbidities of the

patient.

• Spinal canal haematoma with or without any neurological symptoms can

occur due to compression over spinal nerves. CT/MRI confirms the diagnosis.

It should be treated immediately by surgical decompression.

• Epi

meningitis

and bladd

treat by su

PETHID

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30

elimination half-life noted in elderly patients; but in neonates and infants, the

median elimination half-life prolonged; i.e 8 to 10 hours, with greater

individual variability which is more compared to adults.

80 to 100 mg intramuscular dose of pethidine is equivalent to about 10 mg of

intramuscular morphine. Pethidine produces sedation, euphoria, nausea,

vomiting, and depression of ventilation as morphine in same analgesic dose of

morphine. Pethidine is well absorbed from the gastrointestinal tract.

Metabolism

First-pass uptake of meperidine by lungs is about 65%. It has high

clearance rate (10 ml/kg/min) which reflects high hepatic extraction ratio; its

N-demethylation in liver form normeperidine which is the principal metabolite,

and it is then hydrolyzed to meperidinic acid. Both metabolites are conjugated53

and excreted through kidneys. Normeperidine is pharmacologically active

metabolite and is potentially toxic.

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32

produces analgesia.54 This has led to its popularity for epidural and

subarachnoid administration, especially in obstetric anesthesia. Neuraxial

pethidine have found to produce motor, sensory blockade and sympatholytic

effects that are not exhibited by other opioids. These effects are due to local

anaesthetic effects. Pethidine is found to be effective in treating postoperative

shivering that can result in increases in oxygen demand.

Pethidine in treatment of shivering

Pethidine is effective in reducing shivering due to different causes,

including fever, general and epidural anesthesia, administration of

amphotericin B, hypothermia and transfusion reactions. It eliminates visible

shivering and thus side effects of shivering55 following epidural and general

anesthesia. Antishivering effect of pethidine is not due to their action on µ-

opioid receptors as other opioids like morphine or fentanyl do not exhibit this

effect. So this effect is considered to be mediated by κ-opioid receptors. Low

doses of naloxone (which block µ receptors), did not reverse the antishivering

effect of pethidine, but high-dose of naloxone, which block both κ and µ

receptors reverse the antishivering effect.25 The observation that other types of

drugs, such as serotonin antagonists,41 α1-adrenergic agonists (clonidine 1.5

µg/kg), and propofol,17 can reduce postoperative shivering suggests that a

nonopioid mechanism is also involved. Physostigmine 0.04 mg/kg can also

prevent postoperative shivering, suggesting a role for the cholinergic system.43


33

Side Effects

Pethidine has similar side effects as that of morphine. It causes rise in

heart rate due to atropine-like action. Orthostatic hypotension may be due to its

interference with compensatory sympathetic nervous system reflexes. It

decreases myocardial contractility in large doses and this effect cannot be

reversed with naloxone.56 1 mg/kg in patients with cardiac disease decrease

cardiac index, heart rate, and rate–pressure product.57 In high doses, pethidine

causes significantly more hemodynamic instability than fentanyl or morphine

and its derivatives,58 this effect at least partially contributed by histamine

release. In a comparison study of opioids used for balanced anesthesia, Flacke

et al.58 found that 25% patients in pethidine group had abnormally elevated

plasma histamine concentrations and experienced severe hypotension.

Interestingly, only 1 patient in morphine group had similar histamine plasma

concentration(morphine dose used was 0.6mg/kg) . So in short, pethidine is not

recommended in high doses for safe clinical anaesthesia.

Norpethidine, an active metabolite, stimulate central nervous system and

cause seizures and delirium. It cross the placenta and impairs ventilation. It

cause mydriasis due to modest atropine-like actions.

Active Metabolites

Normeperidine is an active metabolite with action on central nervous

system. Mood alterations such as restlessness and apprehension, as well as


34

neurotoxic effects such as myoclonus, tremors and seizures, have been

reported. The elimination half-life of norpethidine is 14 - 21 hours, this is

longer than the parent compound, and therefore it gets accumulated with

prolonged or repeated administration, especially in patients with renal

impairment.58 Seizures and myoclonus are reported in those receiving pethidine

for a longer period. Patients who developed seizures had mean plasma

normeperidine concentration of 0.81 µg/mL.59 Pethidine dose of 1000mg/day is

associated with an increased risk of seizures, even in patients without renal

dysfunction.

Dosage and Administration of Pethidine

Single dose of pethidine has shorter duration of action compared to

morphine. Intravenous analgesic doses of meperidine for adults is 0.1 to 1

mg/kg. Intravenous doses for shivering is 12.5 to 50 mg IV. High dose of this

drug are not recommended because of hemodynamic instability. Repeated

dose or high single dose or prolonged administration may produce seizures

because of its active metabolite norpethidine and the total daily dose should not

exceed 1,000 mg in 24 hours.60

TRAMAD

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36

Synthesis and stereoisomerism

Tramadol 2-(dimethylaminomethyl)-1-(3-methoxyphenyl)cyclohexanol]

has two stereogenic centers at cyclohexane ring. 2-(dimethylaminomethyl)-1-

(3-methoxyphenyl)cyclohexanol may exist in 4 different forms:

• (1R,2R)-isomer

• (1R,2S)-isomer

• (1S,2S)-isomer

• (1S,2R)-isomer

The synthetic pathway leads to 1:1 mixture of (1S,2S)-isomer and

(1R,2R)-isomer as main products. Racemic mixture of (1S,2R)-isomer and

(1R,2S)-isomer are also formed in small amounts. Hydrochloride

recrystallization isolates (1S,2S)-isomer and (1R,2R)-isomer from the

diastereomeric minor racemate [(1R,2S)-isomer and (1S,2R)-isomer] . The

resolution of the racemate [(1R,2R)-(+)-isomer / (1S,2S)-(–)-isomer] was

explained by (R)-(–)- or (S)-(+)-mandelic acid66.

Pharmacodynamics

Tramadol is available as a racemic mixture ( R- and S-stereoisomers). Its

volume of distribution is 203 L after parenteral administration and 306 L after

oral administration approximately. After oral administration,it takes 1 hour to

analgesic effect to come and peak action in 2-4 hours . Naloxone, opioid

antagonist can only partially reverse its analgesic effect. It is available as


37

tablets, capsules, including extended release formulations and injections for im

or iv.70

Pharmacokinetics

Tramadol is metabolised in liver via the cytochrome P450 isozyme

CYP2B6, CYP2D6 and CYP3A4, being O- and N-demethylated to 5 different

metabolites. O-desmethyltramadol is the more important among five

metabolites. It is because of its properties like elimination half-life of 9 hours,

whereas tramadol’s elimination half life is 6 hours and it has two hundred times

more μ affinity than tramadol . There are studies suggesting requirement of

30% increase in dose in those with decreased CYP2D6 activity to attain the

same degree of analgesia as those with normal level of CYP2D6 activity.67,68

Phase II hepatic metabolism makes the metabolites water-soluble. Water

soluble metabolites are excreted through kidneys. As tramadol is metabolised

in liver and excreted by kidney, it is good to reduce its dose in those with

hepatic and renal impairment.69

USES

Tramadol is used mainly for treatment of mild to severe acute and

pain.69,68 European League Against Rheumatism has recommended tramadol

for the treatment of fibromyalgia.71 Studies have shown effectiveness of

tramadol 0.5 mg/kg in suppressing post epidural anesthetic shivering in


38

parturients and concluded that it is as effective as meperidine 0.5 mg/kg28 with

less sedation.

Side effects

Serious side effects may include decreased alertness, increased risk of

serotonin syndrome, seizures and drug addiction. It should be used with caution

when combined with drugs that can lower seizure threshold eg: neuroleptic

agents, mono amino oxidase inhibitors. Common side effects are nausea and

vomiting. Dose need to be adjusted in liver and renal diseases. It should be

avoided in patients with suicidal tendency and breast feeding women.72

Drug interactions

Tramadol interacts with certain herbs (e.g. passiflora, St. John's wort

etc.), tricyclic antidepressants, serotonergics, noradrenergic and specific

serotonergic antidepressants, monoamine oxidase inhibitors, serotonin-

norepinephrine reuptake inhibitors, certain analgesics (fentanyl, oxycodone,

dextromethorphan and pethidine ), selective serotonin reuptake inhibitors,

serotonin antagonist and reuptake inhibitors, certain anxiolytics (such as the

buspirone and SSRIs), certain antibiotics (isoniazid and linezolid), methylene

blue, lithium, phenethylamines, amphetamines, phentermine and others.73,70

Any enzyme inducer or inhibitor will interact with tramadol as it is metabolised

by cytochrome P450 enzyme. Administration of combinations of amphetamine


39

and tramadol cause epinephrine or norepinephrine receptors toxicity or

dysfunction.70,74

Trekona NA75, et al in 2004, conducted a study in hundred patients on

therapeutic effect of opioid tramadol hydrochloride in treatment of

postoperative shivering. They concluded that tramadol 1-2 mg/kg arrested post

operative shivering in about 98% of patients.

De Witte J76, et al in 1997 studied on effects of normal saline and

tramadol in 3 doses (0.5mg/kg, 1mg/kg and 2mg/kg) in suppression of post

operative shivering in 40 patients after general anaesthesia. They found that

tramadol have weak sedative properties and high safety profile. So it is

considered as a better option in patients with decreased cardiorespiratory

reserve.

Najafi Anaraki A77, et al in 2012 studied effects of combination of

pethidine with heavy lignocaine intrathecally on blood loss and haemodynamic

changes on 77 patients posted for open prostatectomy. They concluded that it

has minimal effect on hemodynamics intraoperatively but prevent blood loss in

post operative room.

Mohta M78, et al in 2009 studied on comparison of intravenous

pethidine 0.5 mg/kg with tramadol 1, 2 and 3 mg/kg for prevention of

postanaesthetic shivering and to find a dose of tramadol that could provide

analgesic effect and antishivering effect in the postoperative room. The study


40

included 165 patients, randomly allocated to 5 groups of thirty three each.

Pethidine 0.5 mg/kg, tramadol in doses of 1, 2 and 3 mg/kg, or normal saline

were administered at the time of suturing. All 3 doses of tramadol were found

to be effective and comparable to pethidine in preventing postanaesthetic

shivering. Among all doses, tramadol at 2 mg/kg had the best combination of

analgesic and antishivering efficacy without excessive sedation and so seemed

to be a good option to be given at the time of suturing to provide antishivering

effect and analgesia without any major adverse effects in the postoperative

room.

Khooshideh M79 et al. in 2009 conducted a study on comparison of

tramadol and pethidine on duration of analgesia during labour in 160 patients.

They found that tramadol to have less incidence of maternal side effects short

duration of labour analgesia when compared to pethidine,mainly in 2nd stage of

labour.

Tarkkila P3 et al. in 1998 studied on comparison of effects of tramadol

and pethidine on respiration system on 36 patients. They concluded that

tramadol 0.6mg/kg does not produce ventilatory depression.

Bhatnagar S1 et al. in 2001 conducted a double blind study on

comparison of effects of tramadol on postoperative shivering with pethidine.

They did this study on 30 ASA I and II patients. Patients received either

intravenous pethidine 0.5 mg/kg or tramadol 1 mg/kg. Tramadol ceased

shivering in 12 patients ,whereas pethidine stopped shivering in only 4 patients.


41

This result was statistically significant also. Recurrence rate in tramadol group

was zero. So they arrived at a conclusion that iv tramadol 1 mg/kg is more

effective than pethidine 0.5 mg/kg for treatment of postoperative shivering .

Anne Miu Han Chan2 et al. in 1999 studied on control of shivering

under regional anaesthesia in obstetric patients with tramadol and concluded

that tramadol is effective in control of intraoperative shivering and no

demonstrable difference in response rate or side effects between two doses of

0.5mg/kg and 0.25mg/kg.

Van den Berg AA80 et al. in 1999 did a comparative study on

analgesic property of nalbuphine(0.3mg/kg) ,tramadol(3 mg/kg) and

pethidine(1.5 mg/kg) with placebo (saline 0.02ml/kg). This study conducted on

152 ASA 1 children and young adults posted for adenotonsillectomy. Tramadol

group required esmolol intra operatively but had analgesia postoperatively

(P<0.05). Nalbuphine(0.005) and pethidine(P<0.025) group did not require

esmolol intraoperatively or opioids postoperatively(P<0.005 each). They

concluded that pethidine 1.5 mg/kg and nalbuphine 0.3 mg/kg is better than

tramadol 3 mg/kg. Patients in pethidine group had prolonged recovery as

compared to other two groups.

Reda S. Abdelrahman81 did a comparative study on midazolam,

midazolam plus ketamine, tramadol and tramadol plus ketamine for prevention

of shivering in 2012. 100 ASA status I and II patients undergoing elective

orthopedic surgery under lumbar spinal anaesthesia were included in the study.


42

Patients were randomly assigned into 5 groups; group M (n=20) received

Midazolam 75μg /kg, group C(n=20) received saline as a control, group

MK(n=20) received Midazolam 37.5μg/kg plus Ketamine 0.25 mg/kg , group

T(n=20) received Tramadol 0.5mg/kg and group TK(n=20) received Tramadol

0.25mg/kg plus Ketamine 0.25mg/kg. They found that ketamine when

combined to any other drug showed more anti-shivering action.So they derived

at a conclusion that intravenous midazolam plus ketamine or tramadol plus

ketamine is better than tramadol or midazolam for post spinal shivering.

Aditi.A Dhimer82 et al. studied on tramadol for control of shivering

(comparison with pethidine). Sixty patients from either gender, 20-60 years of

age, of ASA I, II or III undergoing various surgeries under regional anaesthesia

were taken for the study. All the patients who experienced shivering were

randomly divided into Group T and Group P. Group T received Tramadol in a

dose of 1 mg/kg and Group P received Pethidine in a dose of 1 mg/kg. Result

of study was: onset of disappearance of shivering was found at around 1 min

and 3 mins for tramadol, pethidine respectively. Recurrence of shivering after

50 minutes was found to be 50% in pethidine and 10% in tramadol.

Complications were more for pethidine compared to tramadol.

Serdar Ekemen83 et al. performed a comparison study on efficacy of

pethidine and tramadol for postoperative analgesia in children. They concluded

that pethidine could provide better postop analgesia than tramadol in paediatric

age group.


43

I.J Wrench84 et al. did a comparison on pethidine, alfentanil, and

placebo in the treatment of postoperative shivering. They found alfentanil 250

mcg had almost same effects as placebo in the treatment of postop shivering.

Thus they arrived at a conclusion that pethidine with action on kappa receptors

are more effective for shivering than alfentanil which is a mu receptor agonist .

Mahesh T85 et al. did a comparative study on onset, efficacy and

duration of action of pethidine and tramadol in ceasation of shivering

intraoperatively. They did this trial on 40 patients of ASA 1 and 2 posted for

elective surgical procedures under neuraxial block. Group P (n=20) received

Pethidine 0.5mg/kg IV and group T (n=20) received tramadol 1.0 mg/kg IV.

Both the drugs were found to be effective in ceasation of shivering. Nineteen

patients in the Group T stopped shivering by 5 minutes but no patients had

shivering control in Group P (p < 0.0001). This result was found to be

statistically significant. Both drugs had similar haemodynamic effects.

Tramadol reduced postanaesthetic shivering at a higher rate than pethidine.

This study showed that tramadol is more effective for early control of shivering

and its effect on recurrence of shivering is greater than pethidine. Also,

Tramadol has less side effects like nausea and vomiting, respiratory depression.

Tramadol is easily available and cheap drug. Hence concluded tramadol is

better than pethidine.

A Seifi86 et al.did a double blind study on 60 ASA1 or 2 patients who

developed postop shivering. 30 of them were given with pethidine 0.5mg/kg


44

and remaining 30 were given tramadol 1mg/kg. In this study 16 from thirty

patients had complete ceasation of shivering with pethidine ( 53.3% ) and 20

from thirty, improved completely with tramadol (66.66% ). 6.66% of tramadol

group and 20% of pethidine group had no effect.They concluded that both

drugs have same effects. This discrepancy could be due to difference in various

factors like age, duration, temperature which was not considered in this study.

R Talakoub87 et al. carried out a double-blind clinical trial on 73 ASA-

I pregnant patients posted for cesarean section under lumbar spinal anesthesia.

Patients with postop shivering were identified and divided into 2 groups

receiving tramadol or pethidine to control postop shivering. Group T(tramadol)

were given 0.5 mg/kg tramadol and group M (meperidine) were given 0.5

mg/kg meperidine. Both drugs were given as slow iv injection. The response

rate(cesation of shivering within 15 minutes) was 97.2% and 91.9% for groups

Tramadol and Meperidine respectively. In conclusion, both pethidine (0.5

mg/kg) and tramadol (0.5 mg/kg) effectively stopped post-spinal shivering, but

tramadol had more adverse effects like nausea, vomiting and somnolence.So

they recommended further studies on tramadol before considering it as a drug

of choice for shivering.

Sayed Morteza Heidari88et al. conducted a prospective randomized

double-blind clinical trial.In this study, 80 patients of ASA I and II between

age group of 15 to 70 years posted for elective surgery under general anesthesia

were randomly divided to receive oral tramadol 50 mg and placebo. Patients


45

were randomly allocated according to random number table to receive oral

tramadol 50 mg capsule in the intervention group and placebo with a 50 mg

capsule with 50 ml water in the placebo group, 1 hour before surgery by a

physician who was blinded to the name of drugs. Post anaesthetic shivering

was seen in 5 patients (12.5%) in the oral tramadol premedication group and 10

patients (25%) in the placebo group . In this study overall incidence of post

anaesthetic shivering was not significantly different in the two groups, grades

of post anaesthetic shivering were significantly lower in the tramadol group. It

may be due to small sample size and low dose of tramadol.

Tahereh P89et al did a double-blind prospective randomized clinical

trial to study the efficacy of pethidine and buprenorphine for prevention and

treatment of postanaesthetic shivering. A total of 60 ASA class I-II female

patients of 18-40 years of age who underwent elective ceasarian section under

general anesthesia were selected for the study.They are divided randomly to

two groups of 30 each.One group treated with 0.5 mg/kg pethidine and other

group treated with 3 μg/kg buprenorphine. They derive at a conclusion that

buprenorphine is an effective analgesic drug with no hemodynamic

complication, its antishivering effect even in higher doses is less than

pethidine.

N Manouchehrian90 et al conducted a double blind study on

comparison of therapeutic effect of pethidine and tramadol for treatment of

shivering after spinal anaesthesia in elective caesarian section. They studied 70


46

obstetric patients with ASA class I or II who had shivering following spinal

anesthesia (SA) . All patients were randomly allocated to one of the two groups

receiving tramadol 0.5 mg/kg (group T, n = 35), or pethidine 0.5 mg/kg (group

M, n = 35). Shivering stopped after 2.57±2.26 and 6.24±4.76 mins in group T

and group M respectively. In pethidine group, hemodynamic changes before

and after was found to be statistically significant (p<0.001). Nausea and

vomiting occurred more frequently in the meperidine group compared to the

tramadol group (p<0.001). They concluded that tramadol is more effective than

pethidine in the treatment of postoperative shivering, with less side effects in

obstetric patients.

Javaherforoosh F91 et al. studied effects of tramadol for postoperative

shivering in elective caesarian section. Ninety patients who underwent cesarean

section of American Society of Anesthesiologist (ASA) I or II, were randomly

allocated to one of two groups. Towards the end of operation, 1mg/kg tramadol

in 20ml normal saline administered to study group and 20ml of normal saline

to control group was slowly injected intravenously. 39 patients(86.6%)in

control group developed shivering, while only four patients (8.8%)in study

group developed shivering. They found tramadol to be safe and effective in

prevention and treatment of post spinal anaesthesia shivering. This drug had no

hemodynamic side effect and did not affect arterial oxygen saturation

percentage and body temperature.

Zahedi H92 conducted study on comparison of tramadol and pethidine

for post anaesthetic shivering in elective cataract surgery.This study was


47

conducted on 300 patients. Intravenous tramadol 1 mg/kg or pethidine 0.5

mg/kg was given for alternate subjects who developed postanesthetic shivering.

In the tramadol group, shivering terminated within eight minutes after injection

and had no recurrence of shivering, respiratory depression, reduction in SpO2

and nausea or vomiting during post operative period. In the pethidine group,

shivering ceased within 13 minutes after injection, but had recurrence in 10

patients after 30 minutes. In pethidine group 28 patients had desaturation,

respiratory depression, nausea and vomiting but none of them needed any

medication. They concluded that tramadol is superior to pethidine as it induced

a faster ceasation of postanesthetic shivering and did not have any adverse

effects on the respiratory system and, recurrence of shivering or nausea and

vomiting. Easy availability and minimum monitoring requirements are other

advantages of tramadol.

Lim F93 et al. did a study on comparison of tramadol, pethidine and

dexmedetomidine for the treatment of post neuraxial anaesthesia shivering. 20

patients were selected for each group. They were divided and treated with

either iv dexmedetomidine 0.5 μg/kg, pethidine 0.5 mg/kg or tramadol 0.5

mg/kg. The dexmedetomidine group had highest response rate, and it was

statistically significant when compared to the tramadol group (p = 0.0012).

Response rate of pethidine group was better than tramadol group but was not

statistically significant (p = 0.082). There was no statistically significant

difference in time from the start of treatment to the cessation of shivering and

efficiency between the three groups. In conclusion, dexmedetomidine 0.5 μg/kg


48

was found to be more effective than tramadol 0.5 mg/kg and pethidine 0.5

mg/kg, and both tramadol and pethidine have similar efficacy, in the treatment

of post neuraxial anaesthesia shivering. Significant side effects of

dexmedetomidine was hypotension and bradycardia.

Singh SN94 et al.conducted a randomized clinical trial for comparing

pethidine and tramadol for prophylaxis of post anaesthetic shivering in patients

posted for elective abdominal surgery.They conducted study on 120 patients. Iv

pethidine (0.5mg/kg) or tramadol (1mg/kg) was given to alternate subjects who

developed post anaestheic shivering. Tramadol stopped shivering within 5

minutes after administration and had no recurrence of shivering, SPO2

reduction, respiratory depression, nausea and vomiting during postop period.

Pethidine stopped shivering within 8 minutes after administration, but 7

patients had recurrence after 30 minutes and 6 patients had SPO2 reduction,

respiratory depression, and 10 patients had nausea and vomiting but none of

them required any intervention. So they concluded that tramadol is better

option than pethidine to control postop shivering with less side effects.

Ezike95 et al,did a randomised control study in 80 children between 5

to 18 years of age to find efficacy of tramadol and pethidine in controlling post

anaesthetic shivering. The children were randomized to receive 0.4 mg/kg of

either drug. The mean time for cessation of post anaesthetic shivering

following treatment with tramadol was 5.57 min , while with pethidine was

7.42 min (P = 0.04). This difference was significant. 4 (10%) patients in the

tramadol group and 17 (42.5%) patients in the pethidine group developed


49

significant side effects(P = 0.03) . There was a 10% recurrence of post

anaesthetic shivering after 45 min in the tramadol-treated group and a 50%

recurrence with the pethidine-treated group. Rescue treatment with 0.25mg/kg

of the medication was given in all cases. They came to a conclusion that

tramadol is recommended for the treatment of post anaesthetic shivering in

children as it has a faster onset of action, less recurrence rate, and less side

effects when compared with pethidine at same dose.

Hoseinkhan Z96 et al conducted a prospective, randomized, placebo-

controlled, double-blinded, clinical trial on a study population of 72 adults

scheduled for elective surgery under general anaesthesia in 2003. After

transferring the patients to the recovery room, shivering was noted and, in

patients with a shivering score of 1 or more was randomly administered

intravenous morphine (2.5 mg), pethidine (25 mg), fentanyl (25 μg) or normal

saline with a volume of 10 ml by a 2 minute injection. A second shivering

score was recorded 10 minutes later.They conclusion was pethidine and

fentanyl were significantly more effective than normal saline, but no

significant difference between normal saline and morphine groups. Pethidine

was more effective than other two drugs in shivering control. So they

interpreted that pethidine was more effective than two other drugs. Fentanyl

was found to be less effective than pethidine in controlling shivering, whereas

morphine had no effect on postoperative shivering similar to normal saline.

Nasir A97 et al did a study on 90 patients of American Society of

Anesthesiologist (ASA) grades I and II of either sex, 18-60 years of age posted


50

for elective orthopedic surgery of lower limbs under spinal anaesthesia. They

were randomly divided into 3 groups. Just after intrathecal bupivacaine

injection, all patients received prophylactically intravenous drug as either

normal saline (Group S, n=30) or ketamine 0.5mg/kg (Group K, n =30) or

tramadol 0.5mg/kg (Group T, no=30) for shivering. The intraoperative

shivering was found to be significantly less in ketamine group than in the

normal saline group (p <0.05). 18 patients in normal saline group had grade 2

shivering and were treated with tramadol. 3 patients in ketamine group had

grade 2 shivering. 2 patients in tramadol group had grade 2 shivering. After 30

min, there were no difference in the grade of shivering between groups

(p>0.05). No patients required a second dose of tramadol for grade 2 shivering

within 30 minutes. They concluded that prophylactic use of ketamine had a

similar efficacy as that of tramadol in preventing post spinal shivering in

elective lower limb surgery.

Tariq MA98 carried out randomized clinical trial in 2012. 200 patients

of ASA I-II, posted for urologic surgery were selected by card method into 2

groups of 100 each. All patients were given spinal anaesthesia with 15 mg

bupivacaine. The patients were allocated to receive ketamine 0.25 mg/kg plus

midazolam 37.5 μg/kg (Group A) or ketamine 0.5 mg/kg alone (Group B). A

shivering score at 5 min intervals was recorded during surgery. After 15

minutes after spinal anaesthesia, if a grade 3 or 4 shivering developed, then

prophylaxis considered ineffective and pethidine 25 mg iv given. The


51

incidences of shivering in groups A and B were 4% and 25% after 15 minutes.

Group B had significant number of patients with grade 3 or more shivering(

P=0.0434). So they arrived at a conclusion that prophylactic use of ketamine

(0.25 mg/kg) plus midazolam (37.5 μg/kg) iv was more effective than iv

ketamine (0.5 mg/kg) alone in preventing shivering developed during spinal

anaesthesia.

Porwal Sanjay K et al99 did a study on 60 ASA I and II patients.

Neuraxial anaesthesia was performed with 3.0 ml of 0.5% of Bupivacaine

heavy in all patients The patients were divided into 2 groups of 30 each to

receive tramadol 0.5 mg/kg (group T) and ketamine 0.5 mg/kg (group K)

intravenous after appearance of shivering. Disappearance and recurrence of

shivering noted. If recurrence of shivering if occurred then additional dose of

either ketamine or tramadol 0.5 mg/kg was given in respective group.In their

study they found that disappearance of shivering was found at 1 minute in

tramadol group P<0.05 and 3 minutes in ketamine group <0.05. The complete

disappearance of shivering took 5 minutes for tramadol group and 8 minutes

for ketamine group. Recurrence rate of shivering was 10% in T and 20% in K

group of patients respectively. No complications other than nausea and

vomiting were noted in the study.In conclusion, tramadol and ketamine were

found equally efficacious, but tramadol was more potent in controlling

shivering and its recurrence.


52

S Atashkhoy100 et al conducted a randomised double blind clinical trial

in 70 healthy obstetric patients. 35 patients were randomly given intravenous

tramadol 1mg/kg and 35 patients were given normal saline. They found lower

incidence of shivering in patients received tramadol(26.57%) compared to

patients who received normal saline(65.71%)(p<0.0001). 26 patients who

received normal saline had postoperative pain whereas only 4 patients of

tramadol had pain. Thus they concluded that 1 mg/kg tramadol is effective for

prevention of shivering after spinal anaesthesia in caesarian section.

Philip et al101, did a randomized, double-blind study in 116 ASA I and

II physical status patients undergoing hip, lower abdominal, lower limb and

urogenital surgeries. Sixty patients who developed shivering after

administering epidural anesthesia were divided into 2 groups and received

either intravenous 25 mg pethidine or 50 mg tramadol. The disappearance,

recurrence of shivering, hemodynamic and respiratory parameters were

monitored at regular intervals. Complete disappearance of shivering in majority

of patients took less than 5 min in tramadol group and 10 min in pethidine

group that was statistically significant (P < 0.05). Recurrence of shivering was

more in pethidine group (33%) than tramadol group (14%). Hemodynamic and

respiratory parameters were comparable in two groups. Adverse effects like

nausea and vomiting was more in tramadol group (20%) compared to

pethidine(16%), which was not statistically significant (P > 0.05). They

concluded that both tramadol and pethidine are equally effective in abolishing


53

shivering during epidural anesthesia, tramadol is faster acting and low

recurrence rate compared with pethidine.

Methodology

54

METHODOLOGY

The present study was conducted in the department of anaesthesiology

of Sree Mookambika Institute of Medical Sciences, Kulasekharam,

Kanyakumari. The study was started after getting clearance from ethical

committee of Sree Mookambika Institute of Medical Sciences, Kulasekharam,

Kanyakumari. The data was collected from 74 patients of both genders of ASA

1 and 2 between 20-65 years of age.The study was conducted over a period of

one year (2014-2015).

Design of study:Randomised controlled trial

Sample size:The sample size of this study was 74. Scientific basis of

sample size used in the study was based on the ratio between recurrence of

shivering with reference from study of Aditi.A Dhimer, with α error-5%,

power-95%, sample size on each arm found to be 37 each, using EZR version

1.1 on R commander version 1.8-4.

The study group (n=74) was divided into two groups consisting of

equal number.

Group I:This group (n=37) received intravenous tramadol 1mg/kg when they

developed shivering post operatively.

Group II:This group (n=37) received intravenous pethidine 0.5mg/kg when

they developed shivering post operatively.

Methodology

55

Inclusion criteria:

1. Patients giving valid consent.

2. Patients under ASA (American Society Of Anaesthesiologist) physical

status I and II.

ASA I-Normal healthy patients, ASA II-Patients with mild systemic

disease without any functional limitation.

3. Patients undergoing surgery under spinal anaesthesia.

4. Patients of both genders aged between 20 to 65 years.

Exclusion criteria:

1. Patients who are not giving consent.

2. Patients with ASA physical status III or more.

3. Patients who are allergic to any of these drugs.

4. Patients with thyroid disease, obesity, fever and compromised

cardiovascular status, seizure disorder.

5. Contraindication to spinal anaesthesia like raised intracranial pressure,

coagulopathy, patient’s refusal etc.

Methodology

56

Methods

The study was conducted on patients of both genders of age group 20-

65 years with American Society of Anaesthesiology physical status I or II

undergoing surgery under spinal anaesthesia who develop shivering in the post

operative period upto 2 hours. They were divided into two equal groups. Group

I- received 1 mg/kg Tramadol and Group II- received 0.5 mg/kg Pethidine.

All the patients were visited preoperatively on the night before surgery

and a detailed history and detailed evaluation was done. All routine

investigations according to hospital protocol were done. A written informed

consent obtained if inclusion criteria was met. Standard routine monitors were

connected to all patients in recovery room and recorded all parameters. Special

care was taken to infuse intravenous fluids at room temperature and maintain

operating room and recovery room temperature at 26 to 30 degree Celsius.

Spinal anaesthesia was performed with 23 , 25 or 26 G Quincke spinal needle

in lateral/sitting position at L₂-₃/L₃‐₄ interspace with 0.5% heavy(due to

addiction of dextrose) bupivacaine in a dose of 1.8 ml-4 ml to get adequate

block level at T8-10 dermatome in accordance with surgical procedures.

Patients were closely monitored for occurrence of shivering in post operative

period.

Methodology

57

Shivering intensity was graded on a scale of 0-3;

0- in cases with no shivering,

1- Shivering localised in face and head (mild),

2- visible tremors with involvement of more than one group of muscle

(moderate),

3 gross muscular activity which involves entire body,bed shaking(severe).

Patients with shivering of grade 2 or 3 during postoperative period

were given treatment. From the start of shivering (grade 2 or 3), O₂

administered with face mask at 6L/min and drug as per group allocation were

administered. Shivering control was said to be achieved when shivering score

declined to 0 after drug administration, said to be incomplete when scores

reduced but did not stop the shivering completely and said to be failed if no

change in shivering scores post treatment.

Sedation was assessed on a 4-point scale in which grade

0-alert,

1-arouse to voice,

2-arouse to tactile stimulation and

4-no awareness.

The time taken for cessation of rigors and haemodynamic changes

were recorded at regular 5 minutes interval up to 15 minutes. Recurrence of

shivering noted and additional dose of tramadol and pethidine given in

respective groups.

Methodology

58

Statistical analysis

Statistical Package for Social Sciences (SPSS 16.0) used for statistical

analysis. Unpaired sample t test applied to find the statistical significant

between the groups. P value less than 0.05 (P<0.05) considered statistically

significant at 95% confidence interval. The data expressed in number,

percentage, mean and standard deviation. Data entered in microsoft excel sheet.

Results

59

RESULTS

Table-1: Comparison of demographic data between the groups

Demographic data Group-I (Tramadol) Group-II (Pethidine)

Age (years) (MEAN±SD)

44.45±1.21 42.18±1.39

Gender

Male 16 (43.24 %) 19 (51.35 %)

Female 21 (56.76 %) 18 (48.65 %)

Body weight (Kg) (MEAN±SD)

56.81±8.69 57.21±8.61

The demographic data of age, gender and weight are expressed as

numbers and percentages.

In both study groups the age distribution is more or less the same.In group I,16

males (43.24%) and 21 females (56.76%) were included whereas in group II,19

males (51.35%) and 18 (48.65%) were included.

Most of the patients in the study had weight between 40-60 kg.

Results

60

Table-2: Comparison of time of onset, duration and grade of shivering

between two groups

Shivering parameters

Group-I (Tramadol) (MEAN±SD)

Group-II (Pethidine) (MEAN±SD)

P value

Time of onset 17.70±11.40 13.37±8.66 0.07

Duration of shivering

5.08±4.81 7.11±4.78* 0.03

Grade of shivering

2.24±0.43 2.21±0.41 0.48

(*P<0.05 significant compared group-I with group-II)

Time of onset of shivering post operatively was noted .It cannot be compared

as this study includes different types of surgeries.

Duration of shivering signifies the onset of drug action .Group I has lesser

duration of shivering as compared to group II.That means tramadol ceases

shivering faster than pethidine.

Only patients with 2 or 3 grade of shivering are included in the study.

Figure 8:

two group

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61

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Results

62

Table-3: Distribution of patients according to grade of shivering

Grade of

shivering

Group-I Group-II

Number Percentage (%)


0 grade 0 00.00 0 00.00

1st grade 0 00.00 0 00.00

2nd grade 28 75.66 29 78.38

3rd grade 9 24.34 8 21.62

In group I, 28 patients had grade 2 shivering and 9 patients had grade 3

shivering. In group II, 29 patients had grade 2 shivering and 8 patients had

grade 3 shivering.

Table-4: Distribution of patients according to time of onset

Time of onset of

shivering

Group-I Group-II



1-10 min 19 51.36 23 62.16

11-20 min 7 18.92 8 21.63

21-30 min 7 18.92 5 13.51

31-40 min 3 08.10 1 02.70

41-50 min 1 02.70 0

In group I and II , greater number of patients developed shivering within first

10 minutes in recovery room.

Results

63

Table-5: Distribution of patients according to duration of shivering

Duration

of

shivering

Group-I Group-II

Number Percentage

(%)

Number Percentage

(%)

1-10 min 36 97.30 34 91.89

11-20 min 0 00.00 2 05.41

21-30 min 1 02.70 1 02.70

Most of the patients in group I stopped shivering in first 10 minutes compared

to patients in group II.

Results

64

Table-6: Comparison of heart rate between the groups at different time

intervals

Group Heart rate

before

shivering

Mean±SD

Heart rate

(0 min)

Mean±SD

Heart rate

(5 min)

Mean±SD

Heart rate

(10 min)

Mean±SD

Heart rate

(15 min)

Mean±SD

Group-I 75.48±1.39 76.51±1.39 76.78±1.35 76.67±1.24 76.51±1.19

Group-II 70.83±7.28 73.54±8.63 75.35±8.45 74.97±8.28 75.16±8.13

P value 0.07 0.49 0.57 0.27 0.58

(P>0.05 not significant compared group-I with group-II)

There is not much variation in heart rate before shivering, during shivering and

15 minutes of monitoring in group I. In group II, there is mild increase in heart

rate after shivering or after administration of drug.

Figure 9:

intervals

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variations

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20

30

40

50

60

70

80

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p-II 110.5

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27±14.53

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76±1.21

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Group-II

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Mean±SD

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Results

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an±SD

57±1.23

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Group-I

Group-II

P value

Table-8:

different t

DBPbefshiveriMean±70.83±

74.72±9

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(*P<0.05 s

Figure 11

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G

67

astolic bloo

) DBP (Mean

73.43

77.00

0.

ed group-I

iastolic blo

ent variatio

essure of g

oted during

in 5 m

Tim

Group-I G

od pressu

(5 min) n±SD

D

3±9.4

0±9.9

12

with grou

ood pressu

ons in dias

roup II wa

g different

min 10

me

Group-II

re betwee

DBP (10 mMean±S

73.18±9.

78.59±10.

0.02

up-II)

ure betwe

stolic bloo

as found to

stages.

min 15

R

en the gro

min) SD

D

M.99 72

.65* 76.

een the gro

d pressure

be slightly

5 min

Results

oups at

DBP (15 min)

Mean±SD2.16±9.54

.78±10.58*

0.05

oups at

e during

y higher

*

Groups

Group-I

Group-I

P value

Table-9: C

time inter

s Oxsatu

beshivMea

I 99.91±

II 99.64±

0.03

(*P<0.05 s

Figure 12

different t

This table

after shive

1

21

41

61

81

101

121

Satu

ratio

n

Compariso

rvals

xygen uration efore vering an±SD

±0.36

±0.63*

significant

2: Compa

time interv

and graph

ering.

Before

on of oxyg

Oxygesaturat

(0 minMean±

99.81±0.

99.64±0.

0.21

t compare

arison of

vals

h show no v

e 0 min

Group

68

gen satura

en tion n)

±SD

Osat

(5M

51 99.8

58 99.6

0.13

ed group-I

oxygen s

variations

n 5 mi

Tim

p-I Gro

ation betwe

Oxygen turation 5 min) ean±SD

86±0.48

67±0.57

3

with grou

saturation

in oxygen

in 10 m

e

oup-II

een the gr

Oxygesaturati(10 min

Mean±S

99.86±0.4

99.64±0.5

0.08

up-II)

n between

saturation

min 15 m

R

roups at di

en ion n) SD

Osat(1

Me

48 99.9

58 99.6

0.03

n the gro

n before, du

min

Results

ifferent

Oxygen turation 5 min) ean±SD

91±0.36

64±0.63*

3

oups at

uring or

Grou

Group

Group

P valu

Table-10:

time inter

up Tes

p-I 98

p-II 98

ue

(P>0.05 n

Figure 13

time inter

There was

study.Valu

2

4

6

8

10

Tem

pera

ture

Compari

rvals

mp beforehivering

Mean±S

8.55±0.16

8.53±0.18

0.69

o significa

3: Compar

rvals

s no drast

ues obtaine

0

20

40

60

80

00

Befor

ison of te

e

SD

Temm

Mea

98.55

98.53

0.

ant differe

rison of t

ic tempera

ed were ins

re 0 min

Grou

69

emperatur

mp (0 min) an±SD M

5±0.16 9

3±0.18 9

.69

nce compa

temperatu

ature chan

significant

n 5 min

Time

up-I Gro

re between

Temp (5 min)

Mean±SD

98.51±0.20

98.55±0.16

0.46

ared group

re betwee

nges noted

statisticall

n 10 min

oup-II

n the gro

Temp min)

Mean±

98.56±0

98.55±0

0.64

p-I with gr

en the gro

at differe

y.

n 15 min

R

oups at di

(10 )

±SD

Temm

Me

0.13 98.5

0.17 98.5

4 1

roup-II)

oups at di

ent phases

Results

ifferent

mp (15 min) an±SD

56±0.13

56±0.14

1.00

ifferent

of this

Results

70

Table-11: Comparison of number, percentage of recurrence and grade of

shivering during recurrence

Shivering Group-I Group-II P value



Recurrence 7 18.92 13 35.14* 0.01

Recurrence grade

1st grade 4 10.81 2 05.43* 0.03

2nd grade 3 08.11 11 29.72* 0.01

(*P<0.05 significant compared group-I with group-II)

Recurrence rate in group II is more compared to group I. 13 patients in a

study group II of 37 got recurrence of shivering. Of that 11 patients had grade 2

shivering and 2 patients had grade 1 shivering.In group 1, only 7 patients had

recurrence and of which 4 patients had only grade 1 shivering. All these data

are statistically insignificant.

Figure 14

the group

The differ

chart.

4: Compar

ps

rence in re

Gr35

rison of pe

ecurrence r

roup-II 5.14 %

71

ercentage

rate betwe

of recurr

een two gr

Group-I 18.92 %

rence of sh

roups are s

R

hivering b

shown in t

Results

between

this pie

Results

72

Table-12: Comparison of number and percentage of adverse drug

reactions between the two groups

Adverse drug

reaction

Group-I Group-II



No ADR 28 75.68 29 78.38

Vomiting 6 16.22 3 08.10

Sedation 3 08.10 5 13.52

6 patients in group I had vomiting and 3 patients had sedation. In group II, 5

patients had sedation and 3 patients vomited after giving the drug.

Discussion

73

DISCUSSION

Shivering is an unpleasant condition especially after a surgery. It

increases intra ocular pressure, intracranial pressure, increase oxygen

consumption, result in wound pain. The cause of shivering after regional

anesthesia is not well known, but the probable causes could be decrease in core

body temperature after sympathetic block; enhanced cutaneous blood flow,

peripheral vasodilatation; which leads to increased heat loss through skin; rapid

infusion of cold intravenous fluids; cold temperature of operation room; and

cold anesthetic drugs stimulating thermosensitive receptors in the spinal cord.

So shivering should be effectively controlled as fast as possible.

Many methods have been tried for control of shivering like body

warmers, using warm iv fluids, blankets etc.Many drugs have been studied for

their effectiveness for control of shivering like pethidine, nalbuphine, tramadol

or butorphanol , ketanserin, ondansetron propofol, granisetron, doxapram,

clonidine, physostigmine, and nefopam etc. But still an effective drug for

control of shivering not yet found.

In our study we could not find any relationship of shivering to age,

gender, type of surgery, duration of surgery. Most of the patients were

normothermic , so shivering related to hypothermia is ruled out.

In this study, we have compared two drugs : pethidine - which was

considered standard drug for shivering and tramadol – a new synthetic opioid.

Many causes of shivering has been postulated but still exact cause is unclear.

Discussion

74

Pethidine is a phenylpiperidine derivative. It has agonist action at κ and

µ opioid receptors.This should not be used in higher dosage as it can cause

hemodynamic instability, myocardial depression, seizures due to accumulation

of its metabolite, nausea , vomiting, sedation and respiratory depression. Total

daily dose should not exceed 1000mg.

In this study, group II patients with grade 2 or 3 shivering received 0.5

mg/kg and we did not observe any serious complications in our patients other

than nausea and vomiting for 3 patients and sedation for 5 patients. Nausea,

vomiting of patients could be managed with promethazine or ondansetron.The

main disadvantage of pethidine noted in this study was their recurrence rate and

on comparing to tramadol, it took more time to cease shivering. Availability of

this drug is a problem as it need drug registration. Singh94 et al found that

patients had respiratory depression, nausea and vomiting and reduction in

oxygen saturation associated with pethidine 0.5 mg/kg. Zahedi92 et al also had

same complications with pethidine used in control of shivering in patients

under general anaesthesia.

Tramadol hydrochloride, a μ-opioid receptor agonist , act on central

mono-aminergic pathways, and cause inhibition of the neuronal uptake of

serotonin or noradrenaline and encourage hydroxytryptamine secretion which

has a major role in regulating the body temperature regulation center.

Group I patients in our study received tramadol 1 mg/kg when they

developed grade 2 or 3 shivering. In most of the cases, it could cease shivering

Discussion

75

within 3 minutes and recurrence rate was also less compared to group II.

Disadvantage of this drug noted was nausea and vomiting, but it could be

managed with ondansetron. Tramadol is freely available without drug licence

and it is cheaper than pethidine.

Many studies have been conducted to find the ideal drug for shivering.

But such a drug is under debate. Javaherforoosh F91 et al.studied prophylactic

effect of 1mg/kg tramadol for caesarian section. Only 8.8 % patients developed

shivering after receiving tramadol. Heidari88 et al studied effectiveness of oral

tramadol as premedication. They concluded that it reduced incidence of

shivering. Dar 97 et al compared tramadol and ketamine for prevention of

shivering. Bhatnagar1 et al concluded in his study that tramadol 1 mg/kg is

effective in controlling shivering with less side effects. That is the reason why

we chose the same dose in our study.

Manouchehrian N90 et al conducted a double blind study for

comparison of therapeutic effect of pethidine and tramadol for treatment of

post spinal anaesthesia shivering in elective caesarian section. As in our study,

they also found response time of tramadol is less comparatively. In our study,

there was variation in heart rate in pethidine group before, during and after

shivering. But they found variation in heart rate, oxygen saturation and

respiratory rate in pethidine group. As contradiction to our study, they found

nausea and vomiting more in pethidine group.

Discussion

76

Mathew103 et al. studied different doses of tramadol and found 96%

success with 1 mg/kg tramadol and 98 % success with 2 mg/kg. Philip101 et al

conducted study on tramadol and pethidine for shivering control for patients

under epidural anaesthesia. They had simlar findings as in our study with 50

mg tramadol and 25 mg pethidine for all patients irrespective of their weight.

Joshi SS102 et al compared tramadol with ondansetron and

butorphanaol and found patients who received tramadol and butorphanal had

good postoperative analgesia.But there are many other studies with

contradictory results. Abdelrahman RS81 compared tramadol plus

ketamine,midazolam plus ketamine,tramadol and ketamine for prevention of

shivering and found drugs given in combination were more effective than drugs

used alone. Fern L93 et al. compared tramadol, pethidine and dexmedetomidine

for post operative shivering and found dexmedetomidine associated

bradycardia and hypotension.

In this study ,there were no significant variation in heart rate, blood

pressure, oxygen saturation and axillary temperature. The response rate of

tramadol and pethidine was 5 minutes and 7 minutes respectively. Recurrence

in shivering noted in both groups.35 % recurrence with pethidine and 18%

recurrence with tramadol were observed.

Conclusion

77

CONCLUSION

Intravenous tramadol is more effective than pethidine in controlling post

spinal anaesthesia shivering. Tramadol has less response rate and recurrence. It

is cheap as compared to pethidine and freely available without drug licence.

Summary

78

SUMMARY

This study was done to compare efficacy of intravenous tramadol and

pethidine in controlling post operative shivering after spinal anaesthesia. The

study was done on 74 ASA1 or 2 patients in age group of 20 to 65 years.

Patients developing grade 2 or 3 shivering in recovery room were randomly

divided into two groups of 37 each. Group I medicated with tramadol 1mg/kg

and group II with pethidine 0.5 mg/kg intravenously. Patients monitored for 15

minutes for response, haemodynamic stability and adverse effects . Recurrence

of shivering also observed in recovery room. If recurrence of shivering with

grade 2 or 3 occured, a repeat dose of same drug administered. In most of the

cases, repeat administration were not required and shivering subsided its own.

In our study, intravenous tramadol has less response rate compared to

pethidine. 35% of patients in group II had recurrence whereas only 18% in

tramadol group.6 patients of group I and 3 patients of group II experienced

nausea and vomiting.It was treated with ondansetron. Sedation was more seen

in pethidine group.

In conclusion, intravenous tramadol is more effective in controlling

shivering in view of fast onset of action, less recurrence rate, cheap and free

availability without drug licence.

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78

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ANNEXURE-I

ANNEXURE - II

CONSENT FORM

PART 1 OF 2

INFORMATION FOR PARTICIPANTS OF THE STUDY

Dear Participants,

We welcome you and thank you for your keen interest in participation in this research project. Before you participate in this study, it is important for you to understand why this research is being carried out. This form will provide you all the relevant details of this research. It will explain the nature, the purpose, the benefits, the risks, the discomforts, the precautions and the information about how this project will be carried out. It is important that you read and understand the contents of the form carefully. This form may contain certain scientific terms and hence, if you have any doubts or if you want more information, you are free to ask the study personnel or the contact person mentioned below before you give your consent and also at any time during the entire course of the project.

1.Name of the Principal Investigator: Dr. Jisha Roy Babu

PG student-MD Anaesthesia

Sree Mookambika Institute Of Medical Sciences

2. Name of the guide: Dr.A.Thavamani

3. Name of the Co-Guide: Dr.Rommy Geever .T

4.Institute: Sree Mookambika Institute of Medical Sciences

Kulasekharam

Kanyakumari district-629161

Tamil Nadu

5. Title of the study:

A comparative study on effects of Tramadol and Pethidine for post operative shivering of patients under spinal anaesthesia.

6.Background information:

After surgery under spinal anaesthesia, shivering is seen in some patients. Various drugs have been tried for to prevent shivering. In this study,we are comparing the effects of intravenous Tramadol and Pethidine for postoperative shivering.

7.Aims and Objectives:

1.To study the effect of tramadol and pethidine on postoperative shivering.

2. To compare the efficacy and safety of tramadol and pethidine.

8.Scientific justification of the study:

Shivering is very unpleasant and stressful for the patient after undergoing a intracranial pressure and intraocular pressure,interferes with haemodynamics and increase wound pain. Various pharmacological and non-pharmacological methods are available for control of shivering. Drugs like Clonidine, Doxapram, Pethidine,Tramadol etc have been tried but debate on an ideal antishivering drug still continues. Thus in a patient with limited myocardial Oxygen reserve or known coronary artery disease, shivering may further compromise myocardial function. Here we are comparing a synthetic opioid,Tramadol with Pethidine, standard drug for treatment of shivering in quest for more safer and efficacious drug.

9.Procedure for the study:

Patients developing postoperative shivering are divided into two groups. For one group 50 mg Tramadol i.v is given and for another group 0.5 mg/kg Pethidine i.v is given. Time taken for the drug effect, recurrence of shivering, haemodynamic changes are studied for 2 hours postoperatively.

10.Expected risks for the participants:

Allergy to drug, respiratory depression, nausea and vomiting may occur.

11. Expected benefits of research for the participants:

There may not be any personal benefits, but this study will be beneficial for the betterment of the health sector.

12. Maintenance of Confidentiality:

All data collected for the study will be kept confidentially and would reflect on general statistical evaluation only and would not reveal any personal details.

13.Why have I been chosen to be in this study?

You developed post operative shivering after spinal anaesthesia and fulfil the criteria of selection.

14. How many people will be in the study? 74

15.Agreement of Compensation to the participants(In case of a study related injury):

Yes

16. Anticipated prorated payment,if any, to the Participant (s) of the study:

Nil

17. Can I withdraw from the study at any time during the study period?

Yes

18. If there is any new findings/information, would I be informed?

Yes

19. Expected duration of the Participant’s participation in the study

2 hours postoperatively.

20. Any other pertinent information:

No

21. Whom do I contact for further information?

Dr. Jisha Roy Babu

Place:

Signature of Principal Investigator

Date:

Signature of the Participant

For any study related queries,you are free to contact Dr. Jisha Roy Babu Postgraduate-MD Anaesthesiology Department of Anaesthesiology Sree Mookambika Institute of Medical Sciences, Kulasekharam Mobile no: 9751842875 Email ID:[email protected]

CONSENT FORM

PART 2 0F 2

PARTICIPANTS CONSENT FORM

The details of the study have been explained to me in writing and the details have been fully explained to me. I am aware that the results of the study may not directly beneficial to me but will help in the advancement of medical sciences. I confirm that I have understood the study and had the opportunity to ask questions. I understand that my participation in the study is voluntary and that I am free to withdraw at any time, without giving any reason, without the medical care that will normally be provided by the hospital being affected. I agree not to restrict the use of any data or results that arise from this study provided such a use is only for scientific purpose(s). I have been given an information sheet giving details of the study. I fully consent to participate in the study titled “A comparative study on the effects of intravenous tramadol and pethidine for post operative shivering under spinal anaesthesia”.

Serial no/Reference no:

Name of the Participant: Address of the Participant:

Contact number of the Participant:

Signature /thumb impression of the participant/Legal guardian

Witnesses:

1.

2.

ANNEXURE- III

CASE RECORD FORM

Name:

Age :

Sex :

Weight :

IP no :

Surgical diagnosis:

Proposed surgery:

American society of Anaesthesiologists class:

Premedication

Inj.Ranitidine

Inj.Metoclopramide

IV fluids-DNS/RL/NS/D5

Spinal anaesthesia

Position:

Site :

Needle type and size:

Drug:

Total dose:

Vasopressors:

Complications if any:

Time Pulse Rate

BP Temperature SpO2 Grades of

shivering

Grades of

sedation

Recurrence of

shivering

ANNEXURE - IV

LIST OF ABBREVIATIONS

5-HT : 5 hydroxytrptamine

ASA : American Society of Anaesthesiologists

CBF : Cerebral Blood Flow

CMRO2 : Cerebral Metabolic Rate of Oxygen

CNS : Central nervous system

CSF : Cerebro Spinal Fluid

CT : Computed tomography

CVS : Cardiovascular system

DBP : Diastolic blood pressure

ECG : Electrocardiogram

GABA : Gamma amino butyric acid

GIT : Gastrointestinal system

ICP : Intra Cranial Pressure

ICU : Intensive Care Unit

IM : Intramuscular

IOP : Intra Ocular Pressure

IV : Intravenouus

kg : Kilogram

MAC : Monitored Anaesthesia Care

MAP : Mean Arterial Pressure

mg : Milligram

min : Minute

ml : Millilitre

MRI : Magnetic resonance imaging

NS : Normal Saline

PACU : Post Anaesthesia Care Unit

PAS : Post anaesthetic shivering

PDPH : Post dural puncture headache

Postop : Postoperative

RS : Respiratory system

SBP : Systolic blood pressure

SD : Standard deviation

Temp : Temperature

TNS : Transient neurological symptom

α : Alpha

β : Beta

γ : Gamma

δ : Delta

κ : Kappa

μ : Mu

ANNEXURE -V

KEYS TO MASTER CHART

Sl no- Serial number

IP no- IN patient number

Wt- Weight

TOO- Time of onset of shivering

G - Grading of shivering

DS- Duration of shivering

A1- Heart rate before shivering

A2- Heart rate at 0 minutes




B1- Systolic blood pressure before shivering

B2- Systolic blood pressure at 0 minutes




C1- Diastolic blood pressure before shivering

C2- Diastolic blood pressure at 0 minutes



C5 - Diastolic blood pressure at 15 minutes

D1- Oxygen saturation before shivering

D2- Oxygen saturation at 0 minute

D3- Oxygen saturation at 5 minutes



E1- Temperature before shivering

E2- Temperature at 0 minute

E3- Temperature at 5 minutes



R- Recurrence of shivering

R1- Recurrence shivering grading

ADR- Adverse drug reaction

SI IP no Name Age Sex Wt TOO G DS A1 A2 A3 A4 A5 B1 B2 B3 B4 B5 C1 C2 C3 C4 C5 D1 D2 D3 D4 D5 E1 E2 E3 E4 E5 R R1 ADR Surgery

1 223604 Princy 23 F 50 30 3 30 70 72 72 71 80 120 120 107 125 110 70 70 84 80 80 100 98 98 98 99 98 98 98.6 99 98.6 No 0 NIL LSCS

2 224553 Thankam 51 F 52 10 3 5 60 64 64 68 68 100 108 108 110 110 65 65 65 70 70 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 vomiting Hysterectomy

3 224310 Prema 53 F 55 30 2 2 70 70 74 74 78 110 110 115 118 110 70 70 76 76 70 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 NIL Vault repair

4 210384 Radhamani 52 F 53 45 3 3 64 64 64 73 80 130 136 136 109 138 76 76 70 90 78 98 98 98 98 98 98.6 98.6 98.6 99 98.6 No 0 NIL Hysterectomy

5 197017 Seiba Nisha 38 F 65 5 2 1 112 112 114 106 106 130 130 118 120 120 80 80 90 80 80 100 100 100 100 100 98 98 98 98 98.6 Yes 1 NIL URSL

6 191612 Sreeja 34 F 60 10 2 2 99 99 90 82 80 90 90 90 100 100 60 60 60 66 66 100 100 100 100 100 98.6 98.6 98 99 98.6 No 0 NIL Laparotomy

7 186419 Gopinath Nair 60 M 70 35 2 3 62 62 60 55 55 120 120 120 118 118 70 70 70 70 70 100 99 100 99 100 98.6 98.6 98.6 99 98.6 No 0 NIL TURP

8 203691 Athira 18 F 35 5 3 3 60 60 60 58 58 100 100 110 110 110 70 70 70 70 70 100 100 100 100 100 98 98 98 98 98.6 Yes 2 vomiting Appendicectomy

9 204273 Kumaraswamy 60 M 50 10 3 5 72 72 72 70 70 100 100 100 98 100 60 60 66 60 60 100 99 100 100 100 98.6 98.6 98.6 99 98 No 0 NIL Rt hemiarthoplasty

10 205080 Faizal Beegum 52 F 60 5 2 5 80 80 73 77 75 120 120 130 130 130 80 80 70 77 70 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 NIL Rt bimalleolar orif

11 197337 Ramesh 41 M 50 10 2 3 69 69 80 77 81 135 135 136 136 139 72 72 82 82 76 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 NIL L Hernioplasty

12 197822 Yesudhas 56 M 62 30 2 10 70 70 72 70 74 130 130 130 130 134 80 80 80 80 76 100 100 100 100 100 98.6 98.6 98.6 99 98.6 Yes 2 NIL Lt tendon repair

13 183421 Bindhu 33 F 56 10 2 10 74 74 76 76 75 90 90 100 95 100 56 56 70 57 66 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 NIL LSCS

14 194416 Priya 23 F 73 10 2 5 75 75 86 86 80 120 120 130 130 120 80 80 80 80 80 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 vomiting LSCS

15 186417 Jalaja 56 F 50 25 2 2 62 62 55 55 55 120 120 118 118 118 70 70 70 70 70 99 99 99 100 100 98.6 98.6 98 99 98.6 No 0 Sedation Hysterectomy

16 197019 Sumathi 48 F 65 10 2 5 110 112 116 116 110 130 130 117 118 117 80 80 90 90 90 100 100 100 100 100 98.6 98.6 98.6 99 98.6 Yes 1 NIL URSL

17 203556 Elta 52 F 48 15 2 5 100 100 82 82 80 86 86 100 100 102 40 40 66 66 66 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 NIL Hysterectomy

18 203960 Mallika 42 F 41 20 2 5 74 74 74 80 80 100 100 100 100 100 60 60 60 60 60 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 NIL Hysterectomy

19 237893 Haripriya 22 F 58 10 2 5 68 69 70 70 70 120 120 130 120 120 80 80 80 80 80 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 NIL LSCS

20 206949 Rasi 55 F 48 20 2 5 90 94 88 89 86 100 108 108 108 106 72 72 72 72 72 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 NIL Hysterectomy

21 206986 William 53 M 60 40 2 5 90 94 82 80 80 90 90 102 102 102 60 60 56 56 56 100 100 100 100 100 98.6 98.6 98.6 99 98.6 Yes 2 NIL Rt DHS

22 205872 Kavitha 32 F 45 20 2 10 74 74 89 82 80 100 108 97 100 90 70 70 60 57 60 100 100 100 100 100 98.6 98.6 98.6 99 98.6 Yes 1 NIL Fistula in ano

23 206572 Samraj 38 M 60 10 2 2 68 68 70 73 70 140 146 120 112 115 80 80 70 65 72 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 NIL Varicocele

24 209374 Manuel 55 M 45 10 2 10 50 53 52 55 53 110 117 122 122 122 60 60 66 60 60 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 Sedation TURP

25 209740 Freeda 32 F 65 15 2 5 80 80 80 80 79 120 120 120 120 124 80 80 80 80 84 100 100 100 100 100 98.6 98.6 98.6 99 98.6 Yes 1 NIL LSCS

26 218918 Sundaran 60 M 56 20 2 2 88 88 88 86 80 110 116 110 110 110 70 70 70 70 70 100 100 100 100 100 98.6 98.6 98 99 98.6 No 0 Sedation TURBT

27 202038 Rajalekshmi 48 F 64 30 3 3 80 80 80 84 80 130 130 120 120 130 70 70 78 78 70 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 NIL Haemorrhoidectomy

28 205833 Vilasini 58 F 60 10 2 5 70 74 74 74 78 120 120 120 120 120 80 80 80 80 80 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 NIL Haemorrhoidectomy

29 209351 Radha 53 F 60 15 2 3 80 80 84 86 86 130 130 130 130 130 90 90 90 90 90 100 100 100 100 100 98.6 98.6 98.6 99 98 No 0 vomiting Haemorrhoidectomy

30 209478 Ajikumar 30 M 73 10 3 5 74 76 76 78 78 120 120 120 120 120 80 80 80 80 80 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 NIL Lt hernioplasty

31 209999 Vinu 37 M 60 30 2 5 70 74 74 74 78 120 124 124 124 124 80 80 90 86 84 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 NIL Fissurectomy

32 213317 Palas 56 M 56 5 3 3 90 90 94 94 96 130 130 130 130 130 90 90 90 90 94 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 Vomiting Rt hernioplasty

33 213508 Harikumar 39 M 58 10 3 2 60 60 60 68 60 110 110 110 112 110 60 60 66 70 60 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 NIL Rt hernioplasty

34 214220 Rajasekhar 36 M 60 30 2 3 70 74 77 74 77 100 100 100 100 100 60 60 66 66 60 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 NIL Appendicectomy

35 214528 Poomani 48 M 70 40 2 3 70 74 75 70 70 100 100 100 100 100 60 60 64 60 60 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 NIL Lt Hernioplasty

36 214822 Joseph Raj 44 M 48 10 2 3 60 60 66 68 69 100 108 108 108 100 70 70 70 70 70 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 NIL Rt hernioplasty

37 215376 Rajayyan 57 M 61 5 2 5 78 78 78 76 76 110 110 110 110 110 70 70 70 74 70 100 100 100 100 100 98.6 98.6 98.6 99 98.6 No 0 Vomiting Appendicectomy

Si. No IP no Name Age Sex Wt TOO G DS A1 A2 A3 A4 A5 B1 B2 B3 B4 B5 C1 C2 C3 C4 C5 D1 D2 D3 D4 D5 E1 E2 E3 E4 E5 R R1 ADR Surgery1 183181 Yanose 65 M 54 10 2 5 80 80 80 80 82 110 118 120 114 140 76 70 74 80 80 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 NO 0 NIL orrhoidectomy2 206123 hwanath 60 M 60 10 2 5 70 76 76 73 76 100 106 100 90 90 70 70 70 50 50 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 NO 0 Sedation TURP3 204430 Victor 46 M 70 25 2 5 77 80 82 87 82 100 104 118 110 110 80 84 75 74 71 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 YES 1 NIL e amputation4 223603 Bindhu 38 F 62 25 2 6 60 61 60 66 60 100 99 100 110 100 60 57 60 70 70 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 NO 0 NIL sterectomy5 217341 lappan N 48 M 50 10 3 6 74 76 77 76 68 100 110 96 100 106 70 65 60 70 70 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 YES 2 NIL TURP6 225831 Maheen 56 M 56 15 2 8 70 72 75 65 70 140 150 150 170 150 80 80 90 94 90 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 NO 0 NIL ithotripsy7 14064251 Sunija 23 F 63 25 2 5 80 87 66 78 74 120 130 100 120 120 90 90 60 80 70 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 YES 2 NIL LSCS8 185484 Wilson 55 M 64 10 2 5 82 80 82 80 80 130 140 140 140 140 90 90 90 90 90 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 NO 0 NIL ernioplasty9 185291 Vijayan 53 M 60 20 2 10 70 70 74 75 70 110 120 120 120 120 80 80 80 80 80 100 100 100 100 100 98 98 98 98 98 NO 0 NIL orrhoidectomy10 186348 opakum 42 M 64 5 2 15 60 60 66 66 64 100 110 110 114 110 70 70 70 74 70 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 NO 0 NIL ernioplasty11 187648 Nisar 29 M 68 5 2 10 70 72 70 70 70 120 130 120 120 120 90 90 80 80 80 99 99 100 99 100 98.6 98.6 98.6 98.6 98.6 YES 2 NIL ernioplasty12 188102 Mini 20 F 50 5 2 5 66 60 64 68 68 100 110 110 130 110 60 70 70 90 74 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 NO 0 Vomitingendicectomy13 188946 Chandrik 46 F 61 5 3 5 70 70 74 76 78 110 120 120 124 124 74 80 80 80 80 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 YES 2 NIL orrhoidectomy14 190954 Nagaraj 53 M 68 10 2 15 58 60 68 70 74 120 130 130 130 130 86 90 90 90 90 98 99 99 99 98 98.6 98.6 98.6 98.6 98.6 NO 0 NIL ernioplasty15 191711 kumaran 56 M 56 10 2 30 70 80 82 82 83 130 134 134 134 134 78 90 90 90 90 99 99 99 99 99 98 98 98.6 98 98.6 YES 2 NIL orrhoidectomy16 195868 Kamaliya 54 M 70 5 3 10 70 72 74 74 76 120 130 130 130 130 80 90 90 90 90 98 98 98 98 98 98.6 98.6 98.6 98.6 98.6 NO 0 NIL ernioplasty17 198044 Greesan 35 M 65 5 3 5 80 80 84 80 89 100 110 110 110 114 70 70 70 74 74 99 99 99 99 99 98.6 98.6 98.6 98.6 98.6 YES 1 Vomitingendicectomy18 197710 Rani 33 F 60 5 2 5 60 66 68 68 70 110 100 100 100 108 66 70 77 70 70 99 99 99 99 99 98 98 98 98.6 98.6 NO 0 NIL enburg stripping19 200741 hul Ham 49 M 48 10 2 6 66 70 72 74 80 130 140 140 140 140 88 90 90 90 90 99 99 99 99 99 98.6 98.6 98.6 98.6 98.6 NO 0 NIL ernioplasty20 205080 izal Bega 52 F 50 20 2 10 70 80 82 82 84 120 130 130 130 130 80 80 82 82 82 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 NO 0 NIL F ankle joint21 203992 ishnamm 63 F 48 10 2 5 80 86 88 80 80 100 120 120 120 120 80 80 80 80 82 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 YES 2 Sedation DHS22 204693 Nelson 50 M 66 10 2 6 70 70 72 72 70 110 110 110 110 110 70 70 70 72 72 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 NO 0 NIL on band wiring23 207320 Ammini 60 F 50 15 2 5 66 60 64 64 64 100 100 100 100 100 60 60 60 60 60 98 98 98 98 98 98.6 98.6 98.6 98.6 98.6 NO 0 Sedation DHS24 212010 Paul Raj 47 M 68 20 3 5 70 80 80 80 84 100 110 110 112 112 77 70 74 70 70 100 99 99 99 99 98 98 98 98 98 NO 0 NIL both bone LL25 213829 Perinbam 35 F 40 30 2 10 70 78 78 80 80 110 120 120 126 130 68 80 86 86 80 99 99 99 99 99 98.6 98.6 98.6 98.6 98.6 YES 2 NIL t removal ankle26 216573 har Mee 26 M 58 10 2 5 80 90 92 92 94 110 118 118 128 116 80 78 78 88 80 99 99 99 99 99 98.6 98.6 98.6 98.6 98.6 NO 0 NIL t removal ankle27 223605 Sheela 45 F 48 15 2 6 70 74 80 76 70 100 108 110 112 110 70 70 70 70 70 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 NO 0 Vomitingsterectomy28 223973 Rekha 29 F 48 30 2 7 78 80 80 80 82 110 118 120 114 140 70 70 74 80 80 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 YES 2 NIL LSCS29 224655 Saroja 25 F 43 5 2 8 74 75 76 70 76 100 120 120 120 120 88 80 80 88 88 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 NO 0 NIL LSCS30 225182 elen Pap 26 F 50 10 3 5 80 80 80 80 80 110 100 100 100 100 58 60 66 60 60 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 NO 0 Sedationparotomy31 225194 anikand 61 M 52 10 3 4 88 90 100 100 90 130 140 140 140 140 88 90 98 98 98 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 YES 2 Sedation URSL32 219113 Sudha 23 F 45 5 2 5 60 66 67 62 70 100 100 106 110 110 70 70 70 70 80 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 YES 2 NIL TVT33 223445 Omana 55 F 50 15 3 5 70 78 77 76 77 110 120 120 120 120 78 88 89 90 90 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 NO 0 NIL al fistulectomy34 224198 Nishamil 21 F 60 20 2 3 60 64 66 68 68 100 100 100 100 100 60 60 70 70 70 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 NO 0 NIL LSCS35 225741 Sudakai 30 M 68 10 2 6 70 70 78 78 70 110 120 128 128 120 80 80 86 86 60 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 YES 2 NIL URSL36 225929 Arya 25 F 53 5 2 4 66 60 64 60 60 100 110 120 110 110 70 70 80 70 70 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 NO 0 NIL LSCS37 231885 Asha 27 F 71 40 2 3 66 68 70 66 68 120 126 120 118 122 60 67 70 72 70 100 100 100 100 100 98.6 98.6 98.6 98.6 98.6 NO 0 NIL LSCS

a comparative study o n the effec ts of intravenous tramadol...

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