I

II

III

IV

V

ACKNOWLEDGEMENT

It is most appropriate that I begin by expressing my undying gratitude to the

ALMIGHTY GOD for giving me the strength both mentally and physically to

complete this task.

It gives me great pleasure in preparing this dissertation and I take this

opportunity to thank everyone who has made this possible.

First and foremost I would like to express my deep gratitude and sincere

thanks to my guide Dr. RAVISHANKAR R.B., M.D.,DA., Professor, Department of

Anaesthesiology, J.J.M. Medical College, Davangere for preparing me for this task,

guiding me with his superb talent and professional expertise, showing great care and

attention to details and without his supervision and guidance this dissertation would

have been impossible.

I am highly indebted to Dr. D. MALLIKARJUNA, M.D., DA., Professor &

H.O.D, Department of Anaesthesiology, J.J.M. Medical College, Davangere, for his

invaluable guidance, constant encouragement, immense patience, and great care and

attention to detail that he has so willingly shown in helping me prepare the

dissertation.

It gives me immense pleasure to extend my sincere thanks to Professors

Dr. MANJUNATH JAJOOR, M.D., D.A., Dr. M.J.MAHANTHESHA SHARMA,

M.D.,D.A., Dr. RAVI R., M.D., D.A, Dr. K.R. PALAKSHAPPA, M.D., D.A,

Dr. NALINAKSHAMMA SAJJAN, M.D.,D.A., Dr. ASHOK.R. M.D.,

Dr. RAJANNA SAHUKAR, M.D., DA., Dr. D.B. PRAKASH, M.D.,

Dr. RAVIKUMAR, M.D., for their interest and constant invaluable guidance and help

throughout the period of my study which is worth emulating and on whom I could

rely in my darkest moments.

I would like to thank Readers, Dr. RAMAPPA, M.D., D.A., Dr. B.G. PRABHU,

M.D., and Dr. UMA B.R., M.D., Dr. ANITHA HANJI, M.D., for their constant help and

guidance throughout the course of the present study.

I am thankful to Assistant Professors Dr. SHILPASHREE A.M., M.D.,

Dr. PRIYADARSHINI M.B., M.D., and Dr. GANGADHAR K.G. M.D., for greatly

contributing to my knowledge and for their valuable guidance in teaching me the day

to day facts.

VI

VII

LIST OF ABBREVIATIONS USED ASA American Society of Anaesthesiologists

bpm Beats per minute

cms Centimeters

CSF Cerebrospinal fluid

DBP Diastolic blood pressure

G Gauge

Group T Tramadol

Group B Bupivacaine

Group B+T Bupivacaine and Tramadol combination

HR Heart rate

I.P. No. In patient number

IM Intramuscular

IV Intravenous

kg Kilogram

L Lumbar

MAO Monoamino oxidase

MAP Mean arterial pressure

Mg Milligram

MRI Magnetic reasonance imaging

mmHg Millimeters of mercury

PR Pulse rate

RCT Randomized controlled trials

SBP Systolic blood pressure

Sl.No. Serial Number

S.D. Standard deviation

VIII

ABSTRACT

Background and objectives :

Epidural ana lgesia with various drugs is a popular method for post operative

pain relief. Epidural narcotics and epidural local anaesthetics have been tried in many

studies. The Aim of this study was to compare the onset, quality, duration,

cardiorespiratory parameters and side effects of epidural tramadol, epidural

bupivacaine and their combination for post - operative pain relief.

Methods :

90 patients of either sex, age group of 18-75 years, ASA grade I and II, posted

for abdominal and lower limb surgeries were selected. They were randomly divided

into 3 groups (n = 30). All surgeries were done under lumbar epidural anaesthesia.

Post operatively when the patient complied of pain either epidural tramadol 100 mg

diluted to 10 ml with normal saline, epidural bupivacaine 0.25% 10 ml or epidural

tramadol 50 mg with bupivacaine 0.125% diluted to 10 ml with normal saline was

given.

Results :

We found clinically and statistically insignificance difference in the mean

onset of analgesia between tramadol group (6.43 min), bupivacaine group (7.57 min)

and combination group (6.90min). Mean duration of action in tramadol group (2.37

hrs) was less than both bupivacaine group (3.67 hrs) or their combination (5.13 hrs)

which was statistically and clinically significant. Majority of patients in all the 3

groups labelled their analgesia as adequate and the differences between them were

clinically insignificant.

Statistically significant fall in SBP, DBP was seen with bupivacaine group

while a clinically significant rise in pulse rate was seen with tramadol group.

IX

Tramadol group had higher incidences of side effect like nausea and pruritus

compared to bupivacaine, while bupivacaine group has motor blockade as its only

side effect. The incidence of side effect in combination group were the least.

Conclusion :

All of the three regimens epidural tramadol 100mg, epidural bupivacaine

0.25% and bupivacaine 0.125% with tramadol 50 mg have almost similar efficacy and

similar time of onset of analgesia, except for duration of action whic h is longest for

combination group followed by bupivacaine and tramadol group respectively.

Keywords : Anaesthetic technique-epidural; analgesic tramadol; bupivacaine;

bupivacaine + tramadol; pain post operative.

X

TABLE OF CONTENTS

Page No.

1. Introduction 1-2

2. Objectives 3

3. Review of literature 4-62

4. Methodology 63-67

5. Results 68-78

6. Discussion 79-83

7. Conclusion 84

8. Summary 85-86

9. Bibliography 87-89

10. Annexures

I. Proforma 90

II. Consent form 91

III. Master chart 92-95

XI

LIST OF TABLES

Sl. No. Tables Page No.

1 Regional epidural space width and dural thickness 20

2 Adverse physiologic sequelae of pain 37

3 Classification of opioid receptors 44

4 Five point verbal response score (VRS) 66

5 Mean age 68

6 Sex incidence 69

7 Time of onset of analgesia 70

8 Duration of analgesia 71

9 Quality of analgesia 72

Cardiorespiratory side effects

10 a) Intra group comparison – Pulse rate 73

b) Intra group comparison – Systolic blood pressure 74

c) Intra group comparison – Diastolic blood pressure 75

d) Intra group comparison – Respiratory rate 76

11 Side effects 78

XII

LIST OF FIGURES

Sl. No. Figures Page No.

1. Vertebral column 12

2. Lateral view of lumbar vertebral column 13

3. Lumbar vertebra 13

4. Lateral view of lumbar vertebral ligaments 14

5. Epidural space 15

6. Cross section of epidural space 18

7. Loss of resistance technique 23

8. Modified pressure technique 24

9. Detection of epidural space – various techniques 25

10. The Macintosh Balloon Technique 26

11. Spread of drug in epidural space 28

12. Pain pathways 29

13. McGill Pain Questionnaire (MPQ) 40

14. Memorial pain assessment card 41

15. Structure of Tramadol 51

16. Structure of Bupivacine 60

XIII

LIST OF GRAPHS

Sl. No. Graphs Page No.

1 Mean age 68

2 Sex incidence 69

3 Time of onset of analgesia 70

4 Duration of analgesia 71

5 Quality of analgesia 72

6. Pulse rate 73

7 Systolic blood pressure 74

8 Diastolic blood pressure 75

9 Respiratory rate 77

10 Side effects 78

Introduction

1

INTRODUCTION

“Pain is perfect misery, the worst of evils, and excessive, overturns all patience”.

Milton, Paradise Lost

“We must all die. But that I can save him from days of torture, that is what I

feel as my great and ever new privilege. Pain is more terrible lord of mankind than

even death himself”.

Schwetzer a: on the edge of Primeval Forest

Pain has been a major concern of humankind since our beginning and it has

been the object of ubiquitous efforts to understand and control it. Today, as then,

proper management of pain remains one of the most important and most pressing

issues of society in general, the scientific community and the health care professionals

in particular.

Pain as a consistent and predominant complaint of most individuals following

most surgical interventions. Because of pain, these disadvantaged patients are often

unable to breathe adequately and cough effectively. They may not be able to move

enough even to carry out their own daily needs. Due to this, they may experience

feelings of help lessness, fear, anxiety, low mood and loss of self - control. We, the

anesthesiologists, the health care providers have, the first and foremost, a moral and

ethical obligation to help all patients manage their pain adequately, which may lead to

better outcomes for both the patient and the health care system.

Various modalities have been tried to relive the post-operative pain. Epidural

analgesia with various drugs have been tried. Epidural narcotics have been tried in

large number of studies in the treatment of post-operative pain. Epidural narcotics like

2

morphine have adverse effects like respiratory depression, drug dependence, pruritis

and cannot be used in the elderly.

Tramadol, an opioid agonist and monoamine reuptake blocker has been

shown to be a peri-operative analgesic without respiratory depression .It’s analgesic

potency is 1/5th -1/10th of morphine .But it also has side effects like nausea, vomiting,

urinary retention and hypotension.

Bupivacaine, a long acting amide local anaesthetic alone or in combination

with tramadol can also be tried for epidural post-operative analgesia. Bupivacaine has

a long duration of action of 180-300 minutes, it has also less incidence of nausea,

vomiting and pruritis when compared with opioids. However it can cause some

amount of motor blockade and hypotension.

Hence this clinical study is undertaken comparing epidural bupivacaine,

epidural tramadol and their combination in reduced doses to evaluate their efficacy for

post-operative analgesia and side effect profile.

Objectives

3

OBJECTIVES

1. To compare the efficacy of 3 drug formulations viz. epidurally administered

tramadol, bupivacaine and their combination for providing pain relief for

abdominal, pelvic and lower limb surgeries.

2. To compare the degree and duration of analgesia, cardiorespiratory effects and

side-effects between epidural tramadol, bupivacaine and their combination.

The 3 drugs used were bupivacaine 0.25 %, tramadol 100 mg and combination

of bupivacaine 0.125 with tramadol 50 mg.

3. The various parameters studied were

A. Onset of action

B. Degree (quality) of analgesia

C. Duration of analgesia

D. Motor blockade

E. Haemodynamic effects

F. Respiratory depression

G. Adverse effects like pruritis, vomiting, urinary retention and sedation.

Review of Literature

4

REVIEW OF LITERATURE

Painless surgery and painless post – operative period is probably the greatest

boon that has been granted to the patients and indirectly to the surgeons. There are

various methods used, each one carrying its merits and demerits. Opioids have been

administered for hundreds of years to allay and reduce pain associated with surgery.

In 1806, Serturner isolated morphine from crude opium and it was frequently

used for post – operative medication and post – operative analgesia.1

Opiate receptors were identified in the CNS in 1973 by Pert and Sunder, and

in 1977, large populations of these receptors were localized in the dorsal horn of the

spinal cord. These observations, coupled with the discovery of endogenous opioids

produces analgesia.

A report by Yoksh and Rudy concluded that, opioids applied to the

subarachnoid space of rats, induced significant analgesia with distribution that

paralleled the segments of the spinal cord exposed to the opioid.2

A study using epidural narcotics (methadone 1 mg, hydromorphone, 1 mg or

morphine sulfate 5 mg) for post – operative analgesia in 66 patients after surgery

under epidural and light general anaesthesia concluded that, the analgesia produced by

epidural narcotics is substantially of greater duration and is free of side effects

attributed to sympathetic and proprioceptive blockade (compared to LA) and

relatively free of central depression. The study also showed that, epidural narcotics

restored respiratory function (as measured by FEV1) more than twice as effective as

intravenously administered narcotics.3

5

The role of intrathecal and epidural administration of opioids for analgesia in

animals and humans was reviewed by Michael J Cousins and Laurence E. Mortin.

They concluded that, in patients with acute post – operative pain who are to have

opioids, the lipophilic drugs appear to have the best efficacy safety, ratio and also

seem to have a lower incidence of minor side effects compared to hydrophilic drugs.

Epidural route seems preferable because of the ability to titrate dose requirements and

ease of repeated doses or infusion techniques.4

In a study conducted 2 independent trials simultaneously in one Pethidine and

Tramadol was compared in 30 patients by Patient Controlled Analgesia (PCA) during

the first 24 hours of abdominal surgery. In the second trial they compared Tramadol

with Morphine sulfate approximately 1.5 times the equipotent dose as estimated from

the first trial Tramadol transiently depressed the rate of respiration but had no effect

on end tidal CO2 tension. Morphine causes apnea and considerable depression of

ventilation. The result suggested the mechanism other than opioid receptor activity

plays a significant role in analgesia produced by Tramadol.5

The incidence of post operative pain in general surgical ward are results of

different evaluation procedures. The pain treatment programme included intravenous

analgesia with tramadol after major surgery and concluded tramadol proves to be

particularly indicated in the treatment of post operative pain, given that it has

analgesic action combined with good local and general safety.

Three groups of patients, undergoing surgery receiving epidurally 50mg

tramadol, 100mg tramadol and 10ml of bupivacaine 0.25% for post operative pain

relief. They concluded that pain scores were significantly lower in patients receiving

100mg tramadol than those receiving 50mg tramadol or bupivacaine, while incidence

6

of nausea, vomiting and hypotension was more in the group receiving 100mg

tramadol.6

Yassen Majid, Khairat Mohammad. Comparison of caudal Bupivacaine/

Bupivacaine – Tramadol / Tramadol combination for postoperative analgesia. Caudal

Bupivacaine and Bupivacaine with Tramadol are equally effective in controlling

postoperative pain however pain score is lesser with combination of Bupivacaine with

Tramadol.7

A comparison of Tramadol with or without Bupivacaine Anis Aribogan,

Nurcan Dorerk. They suggested that a combination of Tramadol with Bupivacaine

can provide the most effective and safe postoperative analgesia with minimal risk of

side effect.8

The role of epidural tramadol for post – operative pain relief was also studied

by Rathie Pinky et al., on 50 patients undergoing elective surgery. Patients were

divided into two groups. Group I received 100 mg tramadol hydrochloride diluted in

10 ml normal saline. While the Group II patients received 10 ml normal saline. The

mean time of onset of pain relief after epidural tramadol 100 mg in 10 ml normal

saline in Group I was 12.08 ± 3.53 minutes and mean duration of pain relief was

615.75 ± 164.06 minutes, while in Group II, it was 8.33 ± 3.51 minutes and 10.60 ±

30.86 minutes respectively. Study concluded that epidural tramadol can be

recommended for adequate safe and prolonged post-operative analgesia.9

A study was done to compare lumbar eqidural tramadol and lumbar epidural

morphine for pain relief after thoracotomy, 40 patients, after elective muscle sparing

thoracotomy were randomized to receive doses of either 100 mg tramadol or 4 mg

7

morphine when they had pain scores of > 40 mm on VAS scale of 0 to 100. They

conclude that the quality of analgesia achieved with repeated doses of lumber epidural

tramadol is comparable to that achieved with repeated doses of lumber epidural

morphine.10

Caudal tramadol 2 mg kg–1, combined with bupivacaine 0.25% 0.75 ml kg–1,

provided longer duration of postoperative analgesia and reduced requirement for

rescue analgesic compared with tramadol 1 mg kg–1 or 1.5 mg kg–1 in children

undergoing inguinal herniotomy.

When tramadol 2 mg kg–1 is used to prolong the duration of caudal epidural

analgesia with bupivacaine in children, the duration of analgesia is longer and the

requirement for postoperative analgesia less than that seen with tramadol 1 or 1.5 mg

kg–1, without an increase in adverse effects. 11

A study compared the effect of single-dose caudal epidural bupivacaine,

bupivacaine plus ketamine and bupivacaine plus tramadol for postoperative pain

management in children having surgery for inguinal hernia. Following ethical

committee approval and informed parental consent, 75 children ASA PS I and II,

between three and nine years of age and scheduled for elective unilateral inguinal

hernia repair with general anaesthesia were recruited. The patients were randomly

divided into three groups to receive 0.5 ml/kg caudal bupivacaine 0.25% (group B),

bupivacaine 0.25% plus tramadol 1 mg/kg (group BT) or bupivacaine 0.25% plus

ketamine 0.5 mg/kg (group BK). The injections were performed under general

anaesthesia. Mean arterial pressure, heart rate, pulse oximetry, respiratory rate and

sedation and pain scores were recorded at defined intervals following recovery from

anaesthesia. The groups were similar in age, weight and duration of operation

8

(P >0.05). No patient experienced hypotension, bradycardia or respiratory depression.

Duration of analgesia was (mean+/-SD) 6.5+/-4.1 h in group B, 9.2+/-3.9 h in group

BK, and 8.5+/-3.1 h in group BT (P <0.05). More patients in group B required

supplementary analgesics in the first 24 h (P <0.05). Sedation scores were comparable

in all groups. Incidence of emesis and pruritus was similar in all the groups. Caudally

administered 0.5 ml/kg bupivacaine 0.25% plus ketamine or bupivacaine 0.25% plus

tramadol 1 mg/kg provided significantly longer duration of analgesia without an

increase in the adverse effects when compared to bupivacaine alone.12

In a prospective double-blind study, 40 children scheduled for hypospadias

repair were allocated randomly to receive either caudal tramadol (1 mg/kg) or 0.25%

plain bupivacaine (0.5 ml/kg). Postoperative pain score, side-effects and oxygen

saturation (SaO2) were recorded during 24-hour observation period. The results point

toward a significantly lower pain scores with caudal bupivacaine in the immediate

postoperative period, whereas caudal tramadol caused a significantly lower pain score

in the late postoperative period. Total consumption of rescue analgesics was

significantly higher in bupivacaine group as compared to tramadol group during the

study period (p < 0.001). The incidence of side-effects such as vomiting was more

frequent with caudal tramadol, but there was no detectable difference in SaO2. We

conclude that caudal tramadol can safely be used for postoperative analgesia with a

longer duration as compared to caudal bupivacaine.13

Sixty boys, aged 12–84 months, undergoing unilateral herniorrhaphy, were

allocated randomly to three groups. Children in group B received 0.25% plain

bupivacaine 1 ml kg- 1, group BT received an identical local anesthetic dose mixed

with tramadol 1.5 mg kg- 1 and group T received caudal tramadol 1.5 mg kg- 1 in 0.9%

9

sodium chloride in the same total volume (1 ml kg- 1). Pain and demeanour

assessments were made 1, 2, 3, 4, 6, 12 and 24 h after recovery from anesthesia with

reference to a three-point scale.

Analgesia time (time between caudal injection and first administration of

analgesic) in group BT (13.5±2.2 h) was significantly longer than in the other two

groups (P<0.05). In group T, more patients required additional analgesia after surgery

than in the other two groups (P<0.05). Pain scores in the three groups were similar up

to 4 hr after operation but the mean score in group T was higher than groups B and

BT 4 and 6 hr after operation (P<0.05). Significantly more patients who had received

caudal bupivacaine alone or with tramadol had lower pain and demeanour scores

during the first 24 h after operation compared with those in the tramadol group.

Caudal administration of bup ivacaine with the addition of tramadol resulted in

superior analgesia with a longer period without demand for additional analgesics

compared with caudal bupivacaine and tramadol alone without an increase of side

effects.14

Ruhiye R, Selmin Oksel. Comparison of Bupivacaine Tramadol combination

with Bupivacaine Fentanyl and plain Bupivacaine in epidural analgesia. Tramadol

Bupivacaine combination enhances postoperative analgesia when compared to

Bupivacaine – Fentanyl combination and plain Bupivacaine with better hemodynamic

stability and similar side effects.

Alon E and Atanassoff (1992). Conducted a study to examine the efficacy and

applicability of two analgesic drugs. Nalbuphrine and Tramadol administered by

continuous IV infusion combined with PCA device. General well being of the patients

10

on a 5 point scale improved significantly in Tramadol group than Nalbuphrine group

after 45, 60 and 90 minutes.

Subash PN, Zachariah They concluded that Tramadol is as efficient as

Pethidine when given as single dose in improving the quality of analgesia.

11

ANATOMY OF VERTEBRAL COLUMN AND EPIDURAL SPACE 15,16

Vertebral Column :

Composed of 33 vertebrae, 7 cervical, 12 thoracic, 5 lumbar, 5 fused sacral

and 4 coccygeal. It has 4 curves. The cervical and lumbar curves are convex anteriorly

while the thoracic and sacral curves are convex posteriorly. The curves are a

significant effect on the spread of local anaesthetic in the subarachnoid and epidural

space. The vertebral column is bounded together by several ligaments which give it

stability and elasticity.

a. Supraspinous ligament

b. Interspinous ligament

c. Ligamentum flavum

d. Longitudnal ligament

The cervical, thoracic and lumbar vertebrae have diffrenciating features. A

typical lumbar vertebra is made up of the following parts

1. The body

2. Vertebral arch

3. Transverse and spinous processes

4. Superior and inferior articular processes

12

Fig. 1 : Vertebral column

13

Fig. 2 : Lateral view of lumbar vertebral column

Fig. 3 : Lumbar vertebra

14

Fig. 4 : Lateral view of lumbar vertebral ligaments

15

Fig. 5 : Epidural space

16

EPIDURAL SPACE16,17 :

It is the potential space within the bony cavity of the spinal canal and

outside the dural sac. It is bounded anteriorly by the vertebrae, the intervertebral discs

and the posteriorl longitudinal ligament covering them.

Posteriorly it is bounded by the anterior surface of the vertebral laminae and

the ligamentum flavum. Superiorly it is closed by the fusion of the dura and

periosteum at the foramen magnum. Inferiorly by the sacrococcygeal ligament at the

sacral hiatus. Laterally by the pedicles of the vertebrae and the intervertebral

foramina.

The shape of the epidural space in cross section is nearly circular in the

cervical region and thoracic region, but becomes triangular in the lumbar region. The

depth of the epidural space is greatest in the midline in the lumbar region, where it is

said to be 5-6mm in adult males. For this region midline approach is advocated for

entering the lumbar epidural space.

Epidural space communicates with the paravertebral spaces via the

intervertebral foramina. The paravertebral spaces in the thoracic region lie between

the head of the ribs and are in direct contact with the pleura. The negative

intrathoracic pressure is thus conducted via the paravertebral spaces to the thoracic

epidural space.

To reach the epidural space in the midline saggital plane, the following

structures are penetrated:

• Skin and subcutaneous tissue

• Supraspinous ligament

17

• Interspinous ligament

• Ligamentum flavum

The ligamentum flavum is an important landmark for the technical

identification of epidural space during induction of epidural analgesia. The first three

structures offer little ressistance to the advancing needle, but when the ligamentum

flavum is reached, the ressistance increases .As the needle passes through this tissue,

there is sudden disappearance of resistance. In performing epidural anaesthesia, it is

essential that, this point to be recognized, little further advancement results in

subarachnoid penetration.

Contents of the epidural space

It is a potentially empty space with negative pressure with following contents

1. Spinal nerve roots- along with their dural cuffs they traverse the epidural space

on their way to their respective intervertebral foramina. They become more

inclined owing to the discrepancy between the length of the spinal cord and the

spinal canal, until the lower lumber and sacral roots are almost vertical. The roots

vary greatly in size and thickness. The thoracic roots are thin, while the cervical

and lumbosacral roots subserving the limbs are thick. The great differences in size

and neural populations within the roots are interrelated. The very large diameter

and high neural population of the dorsal and ventral roots of the first sacral

segment are associated with great resistance to epidural blockade. Prolonged

latency and poor analgesia of S1 segment are due to poor penetration of local

anaesthetic and it deserve a special mention as they have an important role in the

mechanism of the action of epidural anaesthesia . In the region of the dural cuff

the arachnoid villi and granulations invaginate the epidural veins and drain the

18

CSF from the subarachnoid space, into the blood stream. Those villi, which are

not in contact with the vessels, drain the CSF into the epidural fat, from where it is

drained by lymphatics.

Fig. 6 : Cross section of epidural space

19

2. Epidural vessels: The branches of subclavian, aortic and iliac arteries cross the

epidural space and enter the subarachnoid space in the region of dural cuffs. These

branches supply blood as far as spinal roots. Apart from the cervical region, the

entire blood supply to the spinal cord passes through the epidural space. The

epidural veins are arranged in the form of longitudinal plexuses on either side of

the midline they drain the spinal cord, vertebral canal and CSF from the

subarachnoid space. They do not posses valves. These although divided into

anatomical groups, all interconnect and form a series of horizontal segments

anastomosis. They connect with intervertebral foramina and communicate with

vertebral, ascending cervical, deep cervical intercostal, iliolumbar and lateral

sacral veins As the epidural veins have no valves they afford a connection

between the pelvic veins below and intracranial veins above. The epidural veins

become distended during coughing and straining and also when the inferior

venacava is obstructed by large abdominal tumors or late in pregnancy. This

distension of epidural veins diminishes the effective volume of the epidural space.

Under these circumstances the requirement of local anaesthetic is markedly

decreased, as a small volume of drug tends to spread over a wide area in the

epidural space.

3. Fat : The contents of the spinal canal lie cushioned in a packet of semifluid,

lobulated fat. Solutions injected into the epidural space, track up and down

between the fatty areolar tissue. The epidural fat constitutes an important

pharmacological space and depot for injected local anaesthetics and drugs and it is

one of the three competitors for the share of drug. The other two competitors

being, nervous tissue of spinal roots and cord and blood vessels within the spinal

canal. Drugs with high lipid solubility and lipoprotein binding characterstics will

20

tend to enter the fat phase and remain there for a period of time, depending on

their pharmacodynamics and on briskness of local blood flow competing for

uptake. The compliance of epidural fat varies from person to person and with age.

In children and young adults it offers very little ressistance.

4. Lymphatics: Surrounding and draining the dural sac, lymphatics run anteriorly

from each intervertebral foramen and empty into the longitudinal channels in front

of vertebral column.

Size of the Epidural Space :

Table 1 : Regional epidural space width and dural thickness

Epidural space (mm) Thickness of dura (mm)

Cervical 1 – 1.5 1.5 – 2.0

Upper thoracic 2.5 – 3.0 1

Lower thoracic 4.0 – 5.0 1

Lumbar 5.0 – 6.0 0.33 – 0.66

Applied aspects of anatomy of epidural blockade :

The epidural space is not as voluminous as the subarachnoid space.

Nevertheless it extends from the base of the skull to the sacrococcygeal membrane

and has direct communications with the paravertebral space and indirect

communications with the cerebrospinal veins, which connect with intracranial veins,

this is a potential direct route to the brain for drugs, air or other material when

inadvertently injected into an epidural vein. Within the cranium there is no epidural

space, as meningeal dura and endosteal dura are closely adherent, except where they

separate to form venous sinuses. Between the spinal dura and the spinal periosteum

21

lies the epidural space. The ligamentum flavum completes the posterior wall in direct

continuity with the periosteum of the spinal canal. Since the spinal canal is

approximately triangular in cross section, articular processes indent the triangle, the

epidural space narrows posteriorly and then widens again laterally towards the

intervertebral foramina. Thus the safest point of entry into the epidural space is in the

midline.

DETECTION OF EPIDURAL SPACE

I) Negative pressure techniques :

1) Hanging drop sign : After the needle has been introduced to the level of

resistance indicating the beginning of ligamentum flavum, a small drop of

sterile distilled water is placed on the hub of the needle. When needle is

advanced through the ligamentum flavum à drop will be “sucked into”

epidural space.

2) Capillary tube method – Odom devised a small capillary tube filled with

sterile saline in which 1 or 2 bubbles of air were placed. These acted as

meniscus. As needle enters epidural space, saline sucked in, and air bubbles

advanced into space.

3) Manometer technique – small ‘U’ shaped glass tube about 3 to 4 inch height

is used as a H2O manometer. As the needle advances into the intraspinous

ligament, the sterile glass manometer is attached. As it advances into the

epidural space is immediate movement of liquid signifies negative pressure.

1) Lower lumbar area à 0.5 cm H2O or less

2) Upper lumbar area à 2.0 cm H2O

3) Lower thoracic area à 2.0 cm H2O

22

II) Disappearance of resistance technique :

1) Syringe technique : Sicard and rorester in 1921. Sudden loss of resistance to a

pressure exerted on the plunger of a syringe filled with H2O.

2) Spring – loaded technique – (Visual technique) when epidural space is

entered, syringe automatically unloads itself by virtue of the diminished

resistance in the space.

3) Balloon technique of Macintosh – small light balloon mounted on a glass

adapter is attached to the needle when it reaches ligament flavum. Balloon

inflated with 2-3 ml of air. As needle advances and penetrates into epidural

space balloon collapses. (Pressure 50 mm Hg).

4) Brooks device – (Visual technique) Odom’s indicator / capillary tube sealed

at one end filled with water or saline and few bubbles are placed in tube part.

It is attached to epidural needle when it reaches ligament flavum – bulb is

heated to create a slight positive pressure. Needle penetrates epidural space –

meniscal bubble advances into epidural space.

5) Vertical tube of Dawkins – (Visual technique)

A slight positive pressure is created by a short vertical column of H2O in tube

less than 10cm high connected at right angles to needle a bubble of air also may be

placed in H2O. Force of gravity on the column of H2O produces pressure. When

epidural space is entered the level of column of H2O drops indicating disappearance

of resistance.

23

Fig 7 : Loss of resistance technique

24

Fig 8 : Modified pressure technique

25

Fig. 9 : Detection of epidural space – various techniques

26

Fig. 10 : The Macintosh Balloon Technique

27

Others :

• Ultrasonic localization

• Oxford epidural space indicator

Recent techniques :

• Use of Auditory Amplification of the sound made by the epidural needle as it

transverses the intraspinous ligament and ligamentum flavum.

• Doppler Guidance

• Pressure Transducer Guided Method.

Summary of spread of injected solution in epidural space :

Local anaesthetics or other agent injected into the spinal epidural space may

potentially spread as follows : Superior and inferior spread is mainly in posterior

portion of epidural space between dura and ligamentum flavum.

a) Superiorly the spread is to magnum. There is possibility of diffusion across dura at

base of brain to cerebral CSF with possibility of blockade of cranial nerves,

vasomotor and respiratory centers and other vital centers.

b) Inferiorly to sacral hiatus, caudal canal and through anterior sacral foramina.

c) Laterally through intervertebral foramina to paravertebral space, to produce

paravertebral neural blockade. There is rapid access to CSF at “dural cuff” region

to produce spinal nerve root blockade and also subsequent access to spinal cord.

d) Anteriorly is the thin epidural space between dura and posterior longitudinal

ligament. There is also access for injected solution to CSF by slow diffusion

across spinal dura, subdural space, and subarachnoid membrane into the

subarachnoid space. Vascular absorption by way of epidural veins may convey

drug directly to brain and epidural fat also takes up the drug.

28

Clinical factors in epidural spread :

1) Spread increases with age : Escape from the epidural space is less due to

intervertebral foramina being more fixed and epidural vessels less penetrable.

2) Spread is greater in pregnant women.

3) In arteriosclerosis and occlusive arterial disease the spread is also greater than

the normal.

4) Spread is decreased in dehydration, shock and cachexia.

5) Extent of anaesthesia is greater with more concentrated solutions.

6) A greater dose is required in taller persons.

Fig. 11 : Spread of drug in epidural space

29

ANATOMICAL AND PHYSIOLOGICAL ASPECTS OF PAIN

PERCEPTION18,19,20

Definition of Pain :

Pain is an extraordinary complex sensation which is difficult to define and

equally difficult to measure in an accurate objective manner. It has been variously

defined as:

1. Sensory appreciation of afferent nociceptive stimulation, which elicits an

affective (autonomic) component; both, are subjected to rational interpretation

by the patient.

2. An unpleasant sensory and emotional experience associated with actual

or potential tissue damage, or described in terms of such damages

[International Association for the Study of Pain (IASP), 1986].

3. Pain is a complex constellation of unpleasant sensory, perceptual, and

emotional experiences with associated autonomic psychological and

behavioural responses.

Pain can be represented as a Venn Diagram

This shows that the sensation of pain differs among individual patients.

Emotional Rational

Pain

Physical

30

Components of which are:

• Emotional - varies according to patient's psychological composition.

• Rational - varies with patient's previous experience, insight and motivation.

• Physical - varies with type and site of surgery.

Postoperative pain is usually transistory, which shows progressive

improvement over a relatively short time course.

All pain preception depends upon the transmission of impulses through

pathways within the nervous system from the site of the stimulus to the higher centers

of the brain, they may impinge upon our consciousness and be interpreted.

PAIN PATHWAYS20:

Pain is conducted along three-neuron pathways that transmit noxious stimuli

from the periphery to the cerebral cortex.

First-Order Neurons :

The majority of first-order neurons send the proximal end of their axons into

the spinal cord via the dorsal (sensory) spinal root at each cervical, thoracic and sacral

level.

Once in the dorsal horn, in addition to synapsing with second-order neurons,

the axons of first-order neurons may synapse with interneurons, sympathetic neurons

and ventral horn motor neurons.

Pain fibres originating from the head are carried by the trigeminal,

facial, glossopharyngeal and vagal nerves. The proximal axonal processes of the first-

order neurons in these ganglia reach the brain stem nuclei via their respective cranial

nerves, where they synapse with second-order neurons in brainstem nuclei.

31

Fig. 12 : Pain pathways

32

Second-Order Neurons :

As afferent fibres enter the spinal cord, they segregate according to size, with

large, myelinated fibres becoming medial, and small, unmyelinated fibres becoming

lateral. Pain fibres may ascend or descend one to three spinal cord segments in

Lissauers tract before synapsing with second-order neurons in the gray matter of the

ipsilateral dorsal horn. In many instances they communicate with second-order

neurons through interneurons. Spinal cord gray matter was divided by Rexed into 10

lamina. The first six lamina, which make up the dorsal horn, receive all afferent

neuronal activity, and represent principal site of modulation of pain by ascending and

descending neural pathways.

a. The Spinothalamic Tract: The axons of most second-order neurons cross the

midline close to their level of origin to the contralateral side of the spinal cord

before they form the spinothalamic tract and send their fibres to the thalamus, the

reticular formation, the nucleus raphe magnus and the penaqueductal gray. This

tract lies anterolaterally in the white matter of the spinal cord. The lateral

spinothalamic tract (neo-spinothalamic) projects mainly to the ventral

posterolateral nucleus of the thalamus and carries discriminative aspects of pain,

such as location, intensity and duration. The medial spinothalamic

(paleospinothalamic) tract projects to the medial thalamus and is responsible for

mediating the autonomic and unpleasant emotional perceptions of pain. Some

spinothalamic fibres also projects to the periaqueductal gray and thus may be an

important link between the ascending and descending pathways, collateral fibres

also project to the reticular activating system and the hypothalamus, these are

likely to be responsible for the arousal response of pain.

33

b. Alternate Pain Pathways: As with epicritic sensation, pain fibres ascend

differently, ipsilaterally and contralaterally; hence, some patients continue to

perceive pain following ablation of the contralateral spinothalamic tract. The

spinomesencephalic tract may be important in activating anti-nociceptive

descending pathways because it has some projections to periaqueductal gray. The

spinohypothalamic and spinotelencephalic tracts activate the hypothalamus and

evoke emotional behaviour. The spinocervical tract ascends uncrossed to the

lateral cervical nucleus, which relays the fibres to contralateral thalamus. This

tract is likely a major alternative pain pathway. Lastly, some fibres in the dorsal

columns (which mainly carry light, touch and proprioception) are responsive to

pain; they ascend medially and ipsilaterally.

c. Integration with the sympathetic and motor systems: Somatic and visceral

afferents are fully integrated with the skeletal motor and sympathetic systems in

the spinal cord, brainstem and higher centres. Afferent dorsal horn neurons

synapse both directly and indirectly with anterior horn motor neurons. These

synapses are responsible for reflex muscle activity-whether normal or abnormal

that is associated with pain. Synapses between afferent nociceptive neurons and

sympathetic neurons in the intermediolateral column result in reflex

sympathetically mediated vasoconstriction, smooth muscle spasm, and the release

of catecholamines both locally and from the adrenal medulla.

Third-Order Neurons :

Third-order neurons are located in the thalamus and send fibres to

somatosensory areas I and II in the postcentral gyrus of parietal cortex and superior

wall of sylvian fissure, respectively. Perception and discrete localization of pain take

34

place in these cortical areas. While most neurons from lateral thalamic nuclei project

to the primary somatosensory cortex, those from the intralaminar and medial nuclei

project to anterior cingulate gyrus and likely mediate the suffering and emotional

components of pain.

PHYSIOLOGY OF NOCICEPTION :

1. Nociceptors :

Receptors that transduce noxious stimuli are called nociceptors. Noxious

sensations can often be broken down into two components: a fast, sharp and well

localized sensation (first pain) which is conducted with a short latency (01s) by A5

fibres (tested by pin prick); and a duller, slower onset and often poorly localized

sensation (second pain) which is conducted by C fibres. Most nociceptors are free

nerve endings that sense heat, mechanical and chemical tissue damage.

a. Cutaneous nociceptors: Nociceptors which are present in skin.

b. Deep nociceptors: Less sensitive to noxious stimuli than cutaneous nociceptors,

but are easily, sensitized by inflammation. Pain arising from them is

characteristically dull and poorly localized. Specific nociceptors may exist in

muscles and joint capsules. They respond to mechanical, thermal and chemical

stimuli.

c. Visceral nociceptors: Visceral organs are generally insensitive tissues that mostly

contain silent nociceptors. Some organs appear to have specific nociceptors, such

as the heart, lung, testis and bile ducts. Organs such as intestines are innervated by

polymodal nociceptors that respond to smooth muscle spasm. Ischemia and

inflammation. A few organs such as brain lack nociceptors, however, the brain's

meningeal coverings do contain nociceptors.

35

2. Chemical mediators of pain :

Several neuropeptides and excitatory aminoacids function as neurotransmitters

for afferent neurons subserving pain.

Many if not most neurons contain more than one neurotransmitter which is

simultaneously co-released. The most important of these peptides are substance P (sP)

and calcitonin gene related peptide (CGRP). Glutamate is the most important

excitatory amino acid.

3. Modulation of pain :

Modulation of pain occurs peripherally at the nociceptors, in the spinal cord,

or in supraspinal structures. This modulation can either inhibit (suppress) or facilitate

pain.

Peripheral modulation :

a. Primary Hyperalgesia :

Sensitization of nociceptors results in a decrease in threshold, an increase in

the frequency response to the same stimulus intensity, a decrease in response latency,

and spontaneous firing even after cessation of the stimulus. Primary hyperalgesia is

mediated by the release of allogens from damaged tissues.

b. Secondary Hyperalgesia :

Neurogenic inflammation, also called secondary hyperalgesia, plays an

important role in peripheral sensitization following injury, it is manifested by the

triple response of a red flush around site of injury, (Flare), local tissue edema, and

sensitization to noxious stimuli. Secondary hyperalgesia is primarily due to

antidromic release of sP from collateral axons of the primary afferent neuron.

36

Central modulation :

a. Facilitation :

At least three mechanisms are responsible for central sensitization in the spinal cord.

• Wind-up and sensitization of second-order neurons - WDR (Wide dynamic

range) neurons increase their frequency of discharge with the same repetitive

stimuli and exhibit prolonged discharge, even after afferent C fibre input has

stopped.

• Receptor field expans ion - Dorsal horn neurons increase their receptive fields

such that adjacent neurons become responsive to stimuli to which they were

previously unresponsive

• Hyperexcitability of flexion reflexes - Enhancement of flexion reflexes is

observed both ipsilaterally and contralaterally.

b. Inhibition

Transmission of nociceptive input in the spinal cord can be inhibited by

segmental activity in the cord itself, as well as descending neural activity from

supraspinal centres.

1. Segmental Inhibition: Activation of large afferent fibres subserving epicritic

sensation inhibits WDR neuron and spinothalamic tract activity. Moreover,

activation of noxious stimuli in non-contiguous parts of the body inhibits WDR

neurons at other levels; that is, pain in one part of the body inhibits pain in other

parts. These two observations support a gate theory for pain processing in the

spinal cord.

2. Supraspinal Inhibition: Several supraspinal structures send fibres down the

spinal cord to inhibit pain in the dorsal horn. Important sites of origin for these

descending pathways include the periaqueductal gray, reticular formation and

37

Nucleus Raphe Magnus (NRM). Stimulation of the periaqueductal gray area in

midbrain produces widespread analgesia in humans

Table-2 : ADVERSE PHYSIOLOGIC SEQUELAE OF PAIN21

Organ System Clinical Effect RESPIRATORY Increased skeletal muscle tension Decreased total lung compliance

Hvpoxemia Hypercapnia Ventilation-perfusion abnormality Atelectasis Pneumonitis

ENDOCRINE Increased adrenocorticotropic hormone Increased cortisol Increased glucagon Increased epinephrine Decreased insulin Decreased testosterone Decreased insulin Increased aldosterone Increased antidiuretic hormone Increased cortisol Increased catecholamines Increased angiotension II

Protein catabolism Lipolysis Hyperglycemia Decreased protein anabolism Salt and water retention Congestive heart failure Vasoconstriction Increased myocardial contractility Increased heart rate

CARDIOVASCULAR Increased myocardia l work (mediated by catecholamines. angiotension II)

Dysarrythmias Angina Myocardial infarction Congestive heart failure

IMMUNOLOGIC Lymphopenia Depression of reticuloendothelial system Leukocytosis Reduced killer T-cell cytotoxicity

Decreased immune function

COAGULATION EFFECTS Increased platelet adhesiveness Diminished fibrinolysis Activation of coagulation cascade

Increased incidence of thromboembolic phenomena

GASTROINTESTINAL Increased sphincter tone Decreased smooth muscle tone

Ileus

GENITOURINARY Increased sphincter tone Decreased smooth muscle tone

Urinary retention

38

METHODS OF PAIN MEASUREMENT 1:

Merskey of International association for the study of pain (IASP) defined pain

‘as the sensory and emotional experience associated with actual or potential tissue

damage or described in terms of such damage’. One can not determine for the

individual patient how much nociception occurs in response to tissue damage for

which we have to rely on the expression of the patient to accurately measure the

subjective nature of pain. Loser, of multidisciplinary pain centre, University of

Washington put forward a multifaceted model. The core of the model is the

immeasurable nociception resulting from tissue damage. The next layer is the human

experience of emotional and sensory components integrated pain which is not

available for direct inspection. Pain leads to suffering and suffering leads to painful

behaviours which is available for observation in the form of -

• Withdrawing

• Grimacing

• Crying

• Asking for analgesics

Thus if one relies on the patient's report of pain it is possible to measure pain

intensity and the response to analgesic medications.

Introspective Method :

Patient or trained attender attempts to assess pain.

Behavioural Method :

Some, phys ical parameters which get altered in the presence of pain are

objectively measured and correlated with the severity of pain e.g. like tachycardia,

tachypnoea and increased blood pressure.

39

PAIN AS SELF-REPORT ON A SINGLE DIMENSION :

Verbal Descriptor Scales : Melzack and Torgerson introduced the following scale

for pain intensity; 'Mild, Discomforting, Distressing, Horrible, Excruciating'. This is

also called category scale.

Numeric Rating Scale (NRS) : Here patients are asked to indicate how strong the

pain is on a scale from 0 to 10 on which 0 represents ‘no pain at all’ and 10 ‘the worst

pain imaginate’.

No pain at all – 0 1 2 3 4 5 6 7 8 9 10 - The worst pain

imaginable.

Visual Analog Scale (VAS): Currently, the most commonly used method, first

described by Attken in 1966. The subject makes a mark on a 10 cms line - horizontal

or vertical, one end of which is marked as 'no pain' and the other as 'the worst pain

one can imagine'. The position of the mark on the line measures how much pain the

subject experiences.

No pain at all Worst pain imaginable,

Oral Analog Scale (OAS)

First put forward by Austin et al. It is a simple and clinically relevant rating

scheme. Absence of pain, presence of pain, and if the patient desired more analgesics

are rated 0, 1 and 2 respectively. This rating is simple, yet addresses the essence of

problem for the patient, whether pain present and if it is, does the patient desire more

pain relief, with more analgesic medications.

PAIN AS SELF-REPORTS ON MULTIPLE DIMENSIONS

Me Gill Pain Questionnaire - It scales pain in three dimensions: Sensory, Affective

and Evaluative.

40

Fig. 13. McGill Pain Questionnaire (MPQ)

41

West Haven-Yale Multidimensional Pain Inventory – This has been designed to be

briefer and more classical in its psychometric approach. It was designed to assess

dimensions relevant in chronic pain problems.

Brief Pain Inventory – Is a quick, multidimensional pain measurement that has

demonstrated reliability and validity in cancer and arthr itis patients.

Memorial Pain Assessment Card – It scales pain, pain relief and mood on VAS and

adds a set of adjectives reflecting pain intensity.

2

Moderate Strong

Just Noticeable

Mild Excruciating

No Pain

Severe Weak

RELIEF SCALE

No relief Complete relief

of pain of pain

3

4

MOOD SCALE

Worst Best

mood mood

PAIN SCALE

Least Worst

possible possible

pain pain

1

Fig. 14. Memorial pain assessment card

42

METHODS OF POST-OPERATIVE PAIN RELIEF

Preemptive Analgesia22 : The importance of peripheral and central modulation in

nociception has fostered the concept of ‘preemptive analgesia’ in patients undergoing

surgery. This type of management pharmacologically induces an effective analgesic

state prior to the surgical trauma. This may involve infiltration of the wound with

local anaesthetic, central neural blockade, or the administration of effective doses of

opioids, NSAJDS, or ketamine. Experimental evidence suggest that peemptive

analgesia can effectively attenuate peripheral and central sensitization to pain

Although some studies have failed to demonstrate preemptive analgesia in humans,

other studies have reported significant reduction in post-operative analgesic

requirements in patients receiving preemptive analgesia.

Multimodal Approach23 : Multimodal therapy is defined as two or more analgesic

agents or techniques used in combination. The ASA ‘Practice Guidelines for Acute

Pain Management in the Perioperative setting’ contains the following statement:

During the administration of anaesthetics for surgery, the needs of many patients may

best be met by taking advantage of the combined effects of a number of agents.

Similarly, there is growing conviction that a multimodality approach for providing

perioperative analgesia has advantages over the use of a single modality. The

literature supports the efficacy of two or more analgesic techniques (including non-

pharmacologic methods) used in combination for the control of perioperative pain,

especially when different sites and/or mechanisms of action are involved and/or when

surgery of effect is achieved. The literature also indicates that multimodality

approaches are associated with side effects no greater than those resulting from single

analgesic techniques for perioperative pain management.

43

TREATMENT METHODS20,21,22 :

Many options are available for treatment of postoperative pain. By considering

patients preferences and individualized assessment of the risks and benefits of each

treatment modality, the clinician can optimize the postoperative analgesic regimen for

each patient.

1. Systemic Analgesic Techniques

a. Opioids 24,25 : Opioid analgesics are cornerstone options for the treatment of

moderate to severe postoperative pain.

They can be Natural - Morphine, Codeine, Papaverine

Semisynthetic - Heroin, Dihydromorphone

Synthetic - Morphinan series - Levorphanol, Butorphanol

Diphenyl propylamine series - Methadone

Benzomorphan series - Pentazocine

Phenylpiperdine series -Meperidine, Fentanyl,

Sufentanil, Remifentanil

Mechanism of Action : Opioids are agonists at stereospecific opioid receptors at

presynaptic and postsynaptic sites in the central nervous system (principally the

brainstem and spinal cord) and outside the CNS in peripheral tissues.

The most likely mechanism of peripheral actions is activation of opioid

receptors located on primary afferent neurons. These opioid receptors are normally

activated by three endogenous opioid receptor ligands known as enkephalins,

endorphins and dynorphins. Opioids mimic their actions by binding to opioid

receptors resulting in activation of pain modulating systems.

Existence of opioids in ionized state is necessary for strong binding at the

anionic opioid receptor site. Only levorotatory forms of opioid exhibit agonist

44

activity, the affinity of most opioid agonist for receptors correlates well with their

analgesic potency.

Opioid receptor activation causes a decrease in neurotransmission. This occurs

largely by presynaptic inhibition of neurotransmitter (acetylcholine, dopamine,

norepinephrine, substance P) release. Postsynaptic inhibition of evoked activity may

also occur.

Depression of cholinergic transmission in the CNS due to opioid induced

inhibition of acetylcholine release from nerve endings play a prominent role in the

analgesic and other side effects of opioid agonists. Opioids neither alter

responsiveness of afferent nerve endings to noxious stimulation, nor do they impair

conduction of nerve impulses along peripheral nerves. It is assumed that increasing

opioid receptor occupancy parallels opioid effects.

Opioid Receptors

Opioid receptors are classified as µ, δ and κ receptors.

TabIe-3: CLASSIFICATION OF OPIOID RECEPTORS

µ1 µ2 κ δ

Effect Analgesia (Supraspinal, spinal) Euphoria Low base potential Miosis Bradycardia Hypothermia Urinary retention

Analgesia (spinal) Depression of ventilation Physical dependence Constipation (marked)

Analgesia (supraspinal spinal) Dysphonia. Sedation Miosis Diuresis

Analgesia (supraspinal. spinal) Depression of ventilation Physical dependence Constipation (minimal) Urinary retention

Agonists Endorphin Morphine Synthetic opioids

Endorphins Morphine Synthetic opioids

Dynorphins Enkephalins

Antagonists Naloxone Naltrexone Nalmefene

Naloxone Naltrexone Nalmefene

Naloxone Naltrexone Nalmefene

Naloxone Naltrexone Nalmefene

45

Omega (? ) receptor was one of the original triad of opioid receptors proposed

by W.R. Martin 1976, while it is not entirely understood, the results of many studies

now suggest that actually it did not mediate the psychomimmetic effects of agonist-

antagonist opioids, as originally proposed. Opioids may be administered by many

routes. They are:

1. Oral

Not useful for moderate to severe postoperative pain because of their lack of

titratability and prolonged time to peak effect. They also require a functional

gastrointestinal system.

2. Parenteral

Commonly used route for the treatment of moderate to severe pain.

a. Intravenous: This route has rapid onset of action compared to intramuscular route.

But limitations are that it requires close monitoring of patients for any respiratory

depression.

b. Patient Controlled Analgesia: Here patient can titrate his/her analgesic needs by

delivering a small bolus dose of an opioid when he/she activates a switch of a

PCA device. Limitations include, operator or mechanical error with PCA device

and selection of appropriate agents.

c. Intramuscular: It is simple to administer. Limitations for this route are pain at the

site of injection, patient's apprehensiveness of needle pricks, the potential for

delayed ventilatory depression and wide variability in drug serum

concentrations.

46

3. Transmucosal

4. Intrathecal

5. Epidural

b. Nonopioids Analgesics

Nonsteroidal Anti-inflammatory Agents (NSAIDS) : They are

1. COX-1 inhibitors: Aspirin, Acetaminophen, Ibuprofen, Diclofenac etc.

2. COX-2 inhibitors: Rofecoxib, Celecoxib.

Mechanism of action: They act by inhibiting the enzyme cyclooxygenase (COX) and

thus inhibiting the synthesis of prostaglandins which are important mediators for

peripheral sensitization and hyperalgesia.

They are used for treating minor or moderate postoperative pain They can also

be used as components of a multimodal analgesic regimen since they produce

analgesia through a different mechanism than that of opioids or local anaesthetics and

thus reduce the opioid related side effects and facilitating the recovery of patients. But

their perioperative use is associated with a number of side effects like decreased

haemostasis, renal dysfunction, gastrointestinal haemorrhage and effects on bone

healing and osteogenesis.

Ketamine: Perioperative administration of small dose of ketamine may be a valuable

addition to a multimodal analgesic regimen and adjunct to opioids and local

anaesthetics by enhancing analgesia and reducing opioid related side effects.

47

3. Regional Analgesic Techniques

Central Neuraxial Blockade:

Intrathecal: Intrathecal administration of opioids has the advantage of providing

longlasting analgesia after a single injection. Problem associated with this route are

lack of titratability and it requires extensive monitoring for ventilatory depression.

Epidural:

Agents used for epidural analgesia are:

Local Anaesthetics. Example: Lignocaine, Bupivacaine, Ropivacaine

Local anaesthetics reversibly block nerve impulse conduction in nociceptive

afferent and sympathetic efferent pathways, producing segmental analgesia and

sympathetic block.

Adverse effects include:

1. Cardiovascular and central nervous toxicity due to absolute local anaesthetic over

dose on intravascular injection.

2. Urinary retention.

3. Variable haemodynamic effects of sympathetic blockade, postural hypotension.

4. Motor block with higher concentration which along with sensory block may

contribute to the development of pressure areas.

Opioids:

Epidurally placed opioids gain access into the spinal cord by passive diffusion

across the duramater into CSF and by absorption into arachnoid villi and posterior

radicular arteries supplying the dorsal horn of the spinal cord resulting in a selective

spinal block of pain conduction. Numerically, there are plenty of opiate receptors in

the substant ia gelatinosa of dorsal horn.

48

The onset of action, analgesic potency and duration of analgesia are related to

CSF opioid concentration. The drug does not diffuse widely throughout the

subarchnoid space resulting in limited segmental block. It gets absorbed from these

spaces rapidly by vascular system. The low lipid solubility has opposite effects.

Advantages of Epidural Opioids

1. There is neither sympathetic blockade nor motor and sensory disturbances.

2. Success in alleviating pain is reasonably predictable.

3. Duration of pain relief is longer than that of other parenteral routes

Complications of Epidural Opioids

1. Pruritus

2. Nausea and vomiting

3. Urinary retention

4. Constipation

5. Sedation and drowsiness

6. Antitussive activity

7. Spasm of sphincter of oddi

8. Tolerance and addiction

9. Respiratory depression

10. Hypotension and bradycardia.

There are different techniques through which one can give epidural opioids. They are:

1. Intermittent bolus technique: It is simple to follow and does not require any

infusion devices, but the disadvantage is that it is difficult to titrate the dose of

opioid. It also has higher incidence of side effects compared to continuous

epidural infusion.

49

2. Continuous epidural infusion: Although it needs a sophisticated infusion

device, it provides continuous analgesia with minimum side effects.

3. PCEA (Patient Controlled Epidural Analgesia): It provides greater

patient satisfaction and is particularly used to manage dynamic changes in

pain related to patient activity (e.g. Coughing, chest physiotherapy), but it

needs a sophisticated infusion device.

Peripheral Regional Analgesia: This includes various nerve blocks like brachial

plexus, lumbar plexus, femoral, sciatic popliteal, intercostals and intrapleural blocks,

Nerve blocks can provide excellent postoperative analgesia. Drug can be administered

as single shot or continuous, through peripheral nerve catheters.

Other Techniques: Such as Transcutaneous Electrical Nerve Stimulation (TENS),

acupuncture and psychological approaches can be used in an attempt to alleviate

postoperative pain.

50

PHARMACOLOGY OF TRAMADOL23,24

(±) - Trans - 2 - (dimethylaminomethyl) - 1 - m.methoxyphenyl) Cylohexonal

hydrochloride.

Molecular formula: C16H25O2N.HCL

Tramadol (a synthetic codeine analogue) is a white, bitter, crystalline and

odorless powder. It is readily soluble in water and alcohol. The Pka value is 9.3 (at

293K), it is available as capsules, drops, suppositories and injections. Tramadol in

solution for injection contains only tramadol hydrochloride (50 mg/ml) in an aqueous

sodium acetate buffered solution; it is preservative free and the pH is 6 - 6.8.

Tramadol is supplied as a racemic mixture, which is more effective than either

enantiomers alone. The (+) enantiomers binds to the µ. receptor and inhibits serotonin

uptake. The (-) enantiomers inhibits nor-epinephrine uptake and stimulates alpha-

adrenergic receptors.

Mechanism of Analgesia :

The anti nociceptive action of tramadol is mediated by two components.

a. Opioid Component: Tramadol interacts with µ, delta and Kappa receptors where it

exhibits purely agonistic activity. It has moderate affinity for µ receptor (only 1/6000

that of morphine) and weak affinity for delta and kappa receptors. The onset of action

of analgesia is rapid after both oral and parenteral administration. The duration of

antinociception is relatively long, being comparable to morphine, and longer than that

of codeine and dextropropoxyphene. Tramadol is as effective as meperidine in the

treatment of labour pain and may cause less neonatal respiratory depression.

Tramadol induced analgesia is not entirely reversible by naloxone, but tramadol

51

induced respiratory depression can be reversed by naloxone, However, the use of

naloxone increases the risk of seizures.

b. Non-opioid Component: Tramadol inhibits the re-uptake of noradrenaline and

serotonin. These neurotransmitters elevate the pain threshold, thereby producing

spinal inhibition of pain. 50 to 100 mg of intravenous tramadol is equivalent in

analgesic potency to 5 to 15 mg morphine, as compared to1 epidural morphine is 30

time more potent than epidural tramadol.

Effects on Respiratory System :

Therapeutic dose of tramadol has no significant effect on respiratory rate,

tidal volume, minute volume, arterial CO2, ventilator/ CO2 response or mouth

occlusion pressure, over dosage may cause respiratory depression.

Effects on Cardiovascular System :

In therapeutic doses, tramadol has no significant effect on the cardiovascular

system, except for a transient reduction in pulmonary artery pressure. Hence it is

CHN

CH

O

CH3O

TRAMADOL Fig. 15 : Structure of Tramadol

52

suitable for pain relief in acute myocardial infarction and in diagnostic cardiac

catheterization. At a dose of 5-10 mg/kg given intravenously, it increases blood

pressure and heart rate; while at high doses, more than 10 mg/kg, have a direct

negative inotrophic effect.

Other Effects :

Tramadol has a minor direct action on smooth muscles hence it is unlikely to

cause cholestasis, urinary retention and constipation. It produces dose dependant

mydriasis and antitussive effect. In contrast to morphine, it does not produce

dependence, tolerance and addiction even after long term use.

Standard Dosage :

The average dose is 1 - 2 mg/kg body weight to be repeated every 4-6 hours.

The maximum recommended daily dose is 400 mg.

Indications :

Tramadol can be used for treating moderate to severe acute pain and chronic

pain resulting from cancer, surgical procedures, trauma, rheumatic disorders,

myocardial infarction, and painful diagnostic procedures.

Interaction with Other Drugs :

Tramadol should not be combined with MAO inhibitors because of its

inhibitory effect on serotonin uptake. It is contraindicated in acute intoxication with

alcohol, hypnotics, and analgesics. When combined with tranquillizers, it has a

favourable effect on pain sensation.

53

Side Effects :

• Dry mouth

• Nausea and vomiting

• Dizziness and fatigue

• Hot flushes, sweating and transient tachycardia may occur after rapid intravenous

injection

• Sedation

• Headache

• Seizures, and is exacerbated in patients with predisposing factors

• Respiratory depression and degree of constipation appears to be less with

equianalgesic dose of morphine

Over Dosage and Intoxication :

The features may be

Restlessness, Ataxia, Tremor, Salivation, Cramps, Vomiting, Prostration, Mydriasis.

Cyanosis, Dyspnoea

Miscellaneous :

Tramadol does not have organotoxic, carcinogenic, teratogenic, and

embryotoxic effects in therapeutic doses even after long term use. A small amount of

tramadol is excreted in milk of lactating mothers but the dose is 33-50 times below

the adult level hence no adverse effects.

Metabolism and Pharmacokinetics :

Tramadol is rapidly and completely absorbed after oral administration and the

peak serum concentration is reached within two hours, Tramadol is 68% bioavailable

after a single oral dose and 100% available when administered intramuscularly. When

54

administered parenterally, the onset of action is seen in 10-20 minutes and the

duration of analgesia lasts for about 4 to 6 hours.

Tramadol is metabolized in liver by n and o-demethylation and subsequent

conjungation. All the metabolites are pharmacologically inactive except for

O-demethyl tramadol. The metabolites and some inert tramadol is 2 to 4 times as

potent as parent drug and may account for part of the analgesic effect. Elimination

half life is 6 hours for tramadol and 7.5 hours for its active metabolites.

55

PHARMACOLOGY OF LOCAL ANAESTHETICS20,22,23

Local anaesthetics are the drugs that reversibly block nerve conduction when

applied locally to nerve tissue in appropriate concentrations. They act on any part of

nervous system and each type of nerve fibre.

The ideal local anaesthetic is not yet available. Such an anaesthetic should

possess the following pharmacologic and physiologic characteristics (Daniel C.M.,

Bridenbaugh L.D. et al).

1) Rapid onset of action.

2) Non-irrigating : It should not cause any permanent damage to the nerve

structure within the dose range required.

3) Wide and rapid spread.

4) Long duration of action.

5) Low systemic toxicity.

6) Rapid absorption from the site of injection.

7) Rapid detoxification without accumulation of the drug or its metabolic

products.

8) Stability permitting heat sterilisation.

Chemical structure of local anaesthetic agent :

Compounds which demonstrate clinical utility as local anaesthetic agents

share a following common structure.

Aromatic portion – intermediate chain – amine portion :

Amine portion is separated at a distance of 8 - 90 A from an unsaturated

(Aromatic) ring system usually a benzene ring, by an intermediate chain.

Aromatic portion – usually benzene – ring.

56

Intermediate chain – ester linkage / amide linkage.

Amine portion – secondary or tertiary amine.

Accordingly local anaesthetics are divided into two major groups

aminoamides and aminoesters. Lignocaine and bupivacaine are aminoamides and they

contain tertiary amine. The aromatic portion is lipophilic in nature while amine

portion is hydrophilic.

Mechanism of action of local anaesthetic drugs :

Local anaesthetic bases are poorly soluble in water but are soluble in relatively

hydrophobic organic solvents. Therefore as a matter of convenience these drugs are

marked as their hydrochloride salts, which are soluble in water but insoluble in

organic solvents.

The pKa of the drug and the tissue pH will determine the amount of drug that

exists as free base or as positively charged cation when injected into living tissue.

Early observations suggested that alkaline solutions of local anaesthetics more

effectively block nerve conduction (Shanes A.M. 1958) led to the belief that the

tertiary base is the so called “active form”. But studies on sheathed and desheathed

nerve led to the conclusion that the uncharged base traverses the lipophilic nerve

sheath more easily, but once this passage has occured, the positively charged cation

binds to the axonal membrane to block conduction. Thus both forms of local

anaesthetics must be present for the greatest effectiveness. Narahashi et al presented

further evidence of that cation is the active form of local anaesthetic.

57

Membrane site of action of local anaesthetics :

Local anaesthetics probably inhibit sodium flux by acting on specific receptors

that control gating mechanism responsible for conductance changes in sodium

channels. The exact site of conduction block in sodium channel has been subject of

investigation. Two receptor sites recognized are located on the external and internal

aspect of sodium channel. The external receptor site is blocked by positively charge

substances like tetrodotoxin and sekitoxin. The internal receptor site, on the other

hand is blocked by clinically useful local anaesthetics in their charged form when

placed on the internal surfaces of the nerve axons.

In actual clinical practice, the uncharged form (tertiary base) is placed in the

vicinity of the external surface of the neural membrane and must traverse it to reach

the interior aspect of sodium channel, where it acquires its positive charge and

interacts with the internal receptor site.

Hille suggested the alternative receptor theory which postulates a single local

anaesthetic receptor located on the inner aspect of sodium channel. This structure may

interact with neutral or charged local anaesthetics. But to reach this site there are two

ways, first via open sodium channel and second by traversing through the lipid

portion of the membrane. Clinically useful local anaesthetics such as lidocaine may

reach the internal receptor by either pathways via membrane lipid as the uncharged

base or via open sodium channels as the charged protonated form.

In summary, clinically used local anaesthetics exist in solution in both charged

and uncharged forms, the relative proportions depending on the pH of solution, pKa

of each drug. Uncharged lipophilic tertiary base form diffuses more readily across

neural sheaths and axonal membranes to reach the internal aspect of the sodium

58

channel. The base is protonated within the axoplasm and binds as the charged cation

to a specific receptor within the internal opening of sodium channel thereby inhibiting

sodium conductance.

Uncharged base penetrated the nerve sheath, then re equilibrium occurs

between the base and the cationic form on either side of the cell membrane. The

charged cation binds to the receptor site and causes block.

Pharmacological action of local anaesthetic agents :

1) Central nervous system :

Following absorption, all nitrogenous local anaesthetics stimulate the central

nervous system producing rest lessness tremors and toxic doses can cause even

convulsions. Central stimulation is followed by depression and death which is usually

due to respiratory failure.

2) Cardiovascular system :

These drugs have a stabilizing affect on the cell membranes of cardiac tissue

and they tend to depress automaticity in abnormal or demaged fibres and suppress

cardiac dysarrythmias.

Vascular smooth muscle – local anaesthetic drugs produce vasoconstriction of

varying degree in low doses and vasodilation in high doses.

The regional effect is simply vasodilation in the area supplied by blocked

sympathetic nerves. Systemic effect may be produced because of central nervous

system involvement. High doses cause circulatory collapse.

59

3) Neuromuscular junction :

Local anaesthetics can block neuromuscular transmission. Transmission of

autonomic ganglion is also blocked. Both, production of acetylcholine and response to

acetylcholine are diminished.

Fate of local anaesthetics :

These drugs are absorbed readily when injected into subarachnoid space. The

absorption can be delayed by addition of vasoconstric tor agent. In the plasma, local

anaesthetic drugs are bound to plasma proteins. A small portion related to free

concentration enters the red cells. The drug readily crosses lipid membranes, Blood

Brain Barrier and placenta. It is mainly metabolised in the liver by hepatic

microsomes. Only a small fraction of the drug is excreted unchanged through the

kidney. The metabolic fate of local anaesthetics is of great importance because their

toxicity depends largely on the balance between their rate of absorption and their rate

of destruction.

UNTOWARD EFFECTS AND TOXIC MANIFESTATIONS :

1) Hypersensitivity to local anaesthetics :

Rarely individuals exhibit hypersensitivity to local anaesthetic especially to

the ester type of anesthetics in the form of dermatitis, asthmatic attacks and

anaphylactic reactions.

2) Hypotension, bradyarrhythmias, bradycardia and cardiac arrest can occur.

3) Central nervous system toxicity :

Perioral tingling, muscle twitching, involuntary movements, restlessness,

convulsions, stupor and coma.

60

BUPIVACAINE22,23,25 :

HISTORY : Bupivacaine was synthesized by Ekenstam and associates in 1957.

CHEMICAL NAME : The chemical name is 1-n-butyl-DL-piperidine-2-carboxylic

acid-2, 6 dimethyl anilide hydroxychloride.

PHYSICOCHEMICAL PROPERTIES :

Molecular weight : 324.9

Specific gravity : 1.037 at 370C

Stability : Highly stable

Solubility : The base is sparingly soluble but the hydrochloride is

readily soluble in water.

pH : 5.4

pKa : 8.01

Potency : 3 to 4 times more potent than lignocaine and 8 times

than procaine.

It is a white crystalline power with a bitter taste. It can be autoclaved easily

without loss of potency. Bupivacaine is significantly longer acting than lignocaine

because it is highly bound to plasma proteins (86 – 96%) than either mepivacaine or

lignocaine, but the speed of onset is slower than lignocaine. It produces a low degree

NH CO

N

C4 H9 C H3

C H3

Fig. 16: Structure of Bupivacaine

61

of motor blockade (Bromage). It crosses placental barrier but in very minute

quantities owing to disparity between maternal and foetal protein binding. It is the

drug of choice in obstetric analgesia.

PHARMACOLOGICAL ACTIONS :

Central nervous system :

It readily crosses the blood brain barrier causing CNS stimulation, followed by

depression at higher doses. The earliest signs of toxicity are circumoral and tongue

numbness which may proceed to tinnitus, restlessness, tremors, convulsions, coma

and cardiorespiratory arrest at higher serum levels.

Cardiovascular system :

The local anaesthetic exerts effects on cardiac muscle and on peripheral

vascular smooth muscle causing arteriolar dilatation and myocardial depression. At

toxic concentration, the combined effect of peripheral vasodilation, decreased

myocardial contractility and depressant effect on cardiac rate and conduction leads to

circulatory collapse which may be difficult to reverse.

Dosage :

The maximum safe dose in man is 2 mg/kg. Tachyphylaxis is less common.

Metabolism :

It is metabolized in liver by N-dealkylation. The metabolite is pipe

colyl oxylidine (PPX) which is one eighth as toxic as bupivacaine.

62

SEQUENCE OF EVENTS OF LOCAL ANESTHETIC BLOCK :

Displacement of calcium ions from receptor siteà Binding of charged group

to receptor siteà blockade of sodium channelàDecrease in sodium conductanceà

Depression of rate of electrical depolarizationà Failure to achieve threshold potential

levelà Lack of development of propagated action potentialà Conduction blockade.

PRESENTATION :

Bupivacaine hydrochloride is available in solutions of 0.25 and 0.5%

concentration in 20 ml vials. For spinal anaesthesia it is available in strength of 0.5%

with 8% dextrose in 4 ml ampoules.

Methodology

63

METHODOLOGY26,27

The present clinical study was conduced to evaluate the efficacy and safety of

epidural tramadol 100 mg, bupivacane (0.25%) and their combination for comparison

of their post-operative pain relief. The study was undertaken in the Chigateri General

Hospital, Woman and Child Health Hospital and Bapuji Hospital attached to J.J.M.

Medical College, Davangere during the period of 2007-2009.

Ninety patients undergoing various abdominal, perineal and lower limb

surgeries were selected randomly. All the patients were ASA-1 and ASA-II and were

aged between 18-75 years. Patients were randomly divided into three groups of 30

each Group B received infection Bupivacaine 0.25% (6CC) epidurally, Group T

received injection tramadol 100 mg epidurally and Group C received epidural

Bupivacaine 0.125% with Tramadol 50 mg during their postoperative period when

they complained of pain for the first time.

Pre-Anaesthetic evaluation :

Patients were visited on the previous day of the surgery, a detailed medical

history was taken and systemic examination were carried out. The following patients

were excluded from the study :

1) All patients above ASA grade III.

2) Patients physically dependent on opioids.

3) Patients below 18 years and above 75 years of age.

4) All pregnant ladies.

5) All known contra- indications of epidural anaesthesia like,

a) Patients with raised intracranial tension.

b) Coagulation defects and patients on anticoagulants

64

c) Uncooperative or apprehensive patients

d) Severe haemorrhage or shock.

e) Local infection / inflammation.

Basic laboratory investigations like Hb%, FBS or RBS, blood urea and serum

creatinine, and urine analysis were carried out routinely on all patients. ECG was

done in patients more than 40 years of age and chest x-ray when indicated.

The entire procedure was explained to the patients and were asked to notify

after surgery when the patient experiences pain. Patients were also explained about

visual analogue scale (VAS) and were taught how to express the degree of pain in the

scale. Written consent was taken from the patient.

Premedication :

Tab. Diazepam 10 mg orally was given on the previous night. Patients were

kept nil orally for 8 hours before surgery. Injection ranitidine 50 mg IV was given

before insertion of epidural catheter.

Technique :

Drugs and equipments necessary for resuscitation and general anaesthesia

administration were kept ready. An autoclaved epidural tray was used.

Baseline blood pressure, heat rate and respiratory rate were noted. Then I.V.

line was secured with an 18 G cannula and infusion was started. Then the patient was

placed in left lateral position. With all aseptic precautions, a skin wheal was raised at

L2-L3 interspace with 2 cc of 1% lignocaine. The epidural space was identified using a

16G or 18G Touhy needle with loss of resistance to air technique. Then 18G catheter

65

was passed through the epidural needle till about 2-3 cm of the catheter is in the

space. Then the needle was withdrawn and the catheter was fixed to the back.

3 ml of 2% lignocaine with adrenaline 1:2,00,0000 was injected through the

catheter as a test dose and observed for any intravascular or intrathecal injection.

After confirming correct placement of catheter, 2% lignocaine or 0.5%

bupivacaine was injected. Dose of the drug was according to the patient, type of

surgery and duration of surgery. No narcotics were administered throughout the intra-

operative period.

The patients were sedated intra-operatively with injection diazepam I.V. (0.2

mg/kg) or midazolam (0.05 – 0.15 mg/kg).

The cases in which epidural blockade was inadequate with the need to

supplement general anaesthesia were excluded from the study.

Fluid management :

When the patients complained of pain, they were shown VAS and were asked

to express intensity of pain on the scale. When it reached > 5 mark on the scale, a

single dose of Bupivacaine (0.25%) 6cc, TRAMADOL 100 mg (6 cc) or tramadol 50

mg with 0.125%. bupivacaine made to 8 cc by adding normal saline was injected

through the epidural catheter. Assessment of pain relief was done at every five

minutes for first half an hour and later every ½ hour by using a 5 point verbal

response score.

66

Table 4 : Five point Verbal Response Score (VRS):

Score Subjective

0 No pain relief 0%

1 Little (poor) pain relief 25% pain relief

2 Some (fair) pain relief 50% pain relief

3 A lot of (good) pain relief 75% pain relief

4 Complete pain relief 100% pain relief

Observations made :

a) Onset of analgesia

b) Duration of analgesia

c) Degree/quality of analgesia

d) Cardio-respiratory effects

e) Side effects (if any) were studied

All the observations and particulars of each patients were recorded in a

proforma.

67

STATISTICAL ANALYSIS :

Note: The following list of formulae can be added in the analysis part

1. Arithmetic mean = Sum of all the values = SX No. of values n

2. Standard deviation, 1

)( 2

−−= ∑

nXX

SD

3. Oneway ANOVA

F= Between sample variance

Within sample variance

4. Tukey’s test

Tukey’s significant difference = (tuk)v[2S2 /n]

Tuk = table value, S2 = Mean error variance

5. Paired t test

t= Mean of paired differences S.E of paired differences 6. Chi square test

X2 = S ( O-E )2 E

O= Observed value, E= Expected value

Results

68

42.1

44.9

42.8

39.0

40.0

41.0

42.0

43.0

44.0

45.0

46.0

47.0

Mea

n (y

ears

)

Tramadol Bupvacaine B+T

RESULTS

Ninety adult patients in ASA I and II of either sex, aged between 21-60 years

posted for elective abdominal and lower limb surgeries were selected for the study.

The study was under taken to evaluate the efficacy and safety of epidural Tramadol

(100mg) diluted to 10 ml of normal saline in comparison with epidural Bupivacaine

0.25% diluted to 10cc and their combination as Bupivacaine (0.125%) with Tramadol

(50 mg) made to 10 cc with normal saline given for post operative pain relief.

TABLE 5 : MEAN AGE

Age (Years) Tramadol Bupvacaine B+T 25-34 3(10) 5(17) 6(20)

35-44 14(47) 11(37) 9(30)

45-54 10(33) 7(23) 10(33)

55-64 2(7) 3(10) 2(7)

65-74 1(3) 3(10) 3(10)

75 & above 0 1(3) 0

Mean 42.1 44.9 42.8 SD 9.4 13.0 11.1 P* Value, sig P>0.05 Not sig *Oneway ANOVA

The minimum age of the patients was 18 years and maximum age was 75 years.

Age incidences between the three groups were comparable.

GRAPH 1 : MEAN AGE (YEARS)

69

0

4047

100

60 63

0

10

20

30

40

50

60

70

80

90

100

Per

cen

tag

e

Male Female

Sex

Tramadol

Bupvacaine

B+T

TABLE 6 : SEX INCIDENCE

Sex Tramadol Bupivacaine B+T

Female 30(100) 18(60) 19(63)

Male 0 12(40) 11(47)

In Group T there were 30 (100%) females, in group B there were 60% females

and 40% males while group B + T had 63% females and 47% males.

GRAPH 2 : SEX DISTRIBUTION

70

6.43

7.57

6.90

5.70

5.90

6.10

6.30

6.50

6.70

6.90

7.10

7.30

7.50

7.70

Mea

n

Tramadol Bupvacaine B+T

TABLE 7 : TIME OF ONSET OF ANALGESIA

OOA (mins) Tramadol Bupivacaine B+T P* Value, sig

Mean 6.43 7.57 6.90

SD 2.39 2.18 1.84

Range 003-13 004-12 003-13

P>0.05 NS

*One way ANOVA test

The mean time of onset of analgesia in Group T was 6.43 minutes, in group B

was 7.57 minutes and group B + T was 6.90 minutes. The statistical analysis by

Student’s unpaired ‘t’ test showed that the difference between the time of onset of

analgesia in the 3 groups were statistically insignificant (p > 0.05).

GRAPH 3 : ONSET OF ANALGESIA (minutes)

71

2.37

3.67

5.13

0.00

1.00

2.00

3.00

4.00

5.00

6.00

Mea

n

Tramadol Bupvacaine B+T

TABLE 8 : DURATION OF ANALGESIA

Duration (mins) Tramadol Bupivacaine B+T P* Value, sig Significant pairs**

Mean 2.37 3.67 5.13

SD 0.68 0.83 1.63

Range 1.5-3.5 002-6 003-9

P<0.001 HS 1 & 2, 1 &

3, 2 & 3

*One way ANOVA test

** Tukey's post hoc test

Duration of analgesia was observed in these 3 groups till patient asked for next

dose of analgesic in post operative period, time was noted when patient asked for

rescue analgesia. The duration of analgesia in Group T was 2.37 hours in group B was

3.67 hours while in group B + T was 5.13 hours.

Statistical analysis by student’s ‘t’ test showed that time duration of analgesia

in Group B + T was significantly more when compared to the Group T and Group B

respectively.

GRAPH 4 : DURATION OF ANALGESIA (hours)

72

8790

100

13 100

0102030405060708090

100

Per

cent

age

Adequate Inadequate

Quality

Tramadol

Bupvacaine

B+T

TABLE 9 : QUALITY OF ANALGESIA

Quality Tramadol Bupivacaine B+T

Adequate 26(87) 27(90) 30(100)

Inadequate 4(13) 3(10) 0

χ2 =4.0 P>0.05 NS

In Group T 13% of the patient had quality of analgesia as inadequate, in group

B 10% deemed it as inadequate. While 0% (none ) of the patient group B + T had

reported inadequate analgesia.

GRAPH 5 : QUALITY OF ANALGESIA

73

74.2

77.3

79

76.3

78.478.8

71.072.073.074.075.076.077.078.079.080.0

Mea

n

Before After

Pulse Rate

Tramadol

Bupvacaine

B+T

CARDIORESPIRATORY SIDE EFFECTS

TABLE 10 A) : INTRA GROUP COMPARISON – PULSE RATE

Groups Pulse Rate Before After Mean difference P* Value, sig

Mean 74.2 76.3 Tramadol

SD 6.7 7.3 2.11 P<0.05 S

Mean 77.3 78.4 Bupivacaine

SD 10.3 9.4 1.11 P<0.05 S

Mean 79 78.8 B+T

SD 8 8.0 0.28 P>0.05 NS

* Student's paired t test

GRAPH 6 : PULSE RATE

74

110.8

116.8

113.8

116.6

111.0

115.4

107.0

108.0

109.0

110.0

111.0

112.0

113.0

114.0

115.0

116.0

117.0

Mea

n

Before After

SBP

Tramadol

Bupvacaine

B+T

TABLE 10 B) INTRA GROUP COMPARISON – SYSTOLIC BLOOD

PRESSURE

Groups SBP Before After Mean difference P* Value, sig

Mean 110.8 116.6 Tramadol

SD 9.3 11.2 5.22 P<0.05 S

Mean 116.8 111.0 Bupivacaine

SD 12.2 12.5 5.8 P<0.001 HS

Mean 113.8 115.4 B+T

SD 12.2 12.6 1.64 P<0.05 S

* Student's paired t test

GRAPH 7 : SYSTOLIC BLOOD PRESSURE

75

71.5

74.1

71.3

74.5

70.8

72.8

68.0

69.0

70.0

71.0

72.0

73.0

74.0

75.0

Mea

n

Before After

DBP

Tramadol

Bupvacaine

B+T

TABLE 10 C) INTRA GROUP COMPARISON – DIASTOLIC BLOOD

PRESSURE

Groups DBP Before After Mean difference P* Value, sig

Mean 71.5 74.5 Tramadol

SD 10.6 9.9 3.06 P>0.05 NS

Mean 74.1 70.8 Bupivacaine

SD 11.2 9.3 3.3 P<0.001 HS

Mean 71.3 72.8 B+T

SD 9.4 9.6 1.14 P<0.05 S

* Student's paired t test

GRAPH 8 : DISTOLIC BLOOD PRESSURE

76

TABLE 10 D) : INTRA GROUP COMPARISON – RESPIRATORY RATE

Groups RR Before After Mean difference P* Value, sig

Mean 17.5 18.3 Tramadol

SD 2.3 2.1 0.7 P<0.001 HS

Mean 18.9 18.3 Bupivacaine

SD 2.5 2.6 0.6 P<0.05 S

Mean 18.9 19.1 B+T

SD 2.2 2.2 0.2 P>0.05 NS

In Group T before giving tramadol average pulse rate was 74.2 bpm, systolic

blood pressure was 110.8 mmHg, diastolic blood pressure was 71.5mmHg and

respiratory rate 17.5 bpm. After giving tramadol average pulse rate was 76.3 bpm,

systolic BP was 116.6 mmHg, diastolic BP 74.5 mmHg and respiratory rate 18.3 bpm.

In Group B before giving Bupivacaine average pulse rate was 77.3 bpm,

systolic BP was 110.8 mmHg, diastolic BP was 74.1 mmHg and respiratory rate was

18.9 bpm.

In Group B + T before giving the drug average pulse rate was 79bpm, systolic

blood pressure was 113.8mmhg, diastolic blood pressure was 71.3 mmhg and

respiratory rate 18.9 bpm. After giving the drug average pulse rate was 78.8 bpm,

systolic blood pressure was 115.4 mmhg, diastolic blood pressure 72mmhg and

respiratory rate was 19.1 bpm.

77

17.5

18.9 18.9

18.3 18.3

19.1

16.5

17.0

17.5

18.0

18.5

19.0

19.5

Mea

n

Before After

Respiratory rate

Tramadol

Bupvacaine

B+T

GRAPH 9 : RESPIRATORY RATE

78

7773

83

13

010

0

27

310

0 30

102030405060708090

100

Per

cen

tag

e

None Nausea &vomiting

Motor blockade Pruritis

Side effects

Tramadol

Bupvacaine

B+T

TABLE 11 : SIDE EFFECTS

Side effects Tramadol Bupivacaine B+T

None 23(77) 22(73) 25(83)

Nausea & vomiting 4(13) 0 3(10)

Motor blockade 0 8(27) 1(3)

Pruritis 3(10) 0 1(3)

χ2 =20.0 P<0.05 S

In Group T 13% patients had nausea and 10% patient s had pruritis, in Group B

27% patient had motor blockade, while in group B + T 10% patients had nausea, 3%

patient had motor blockade and 3% had pruritis.

GRAPH 10 : SIDE EFFECTS

Discussion

79

DISCUSSION

Management of post-operative pain still poses lot of challenge to anaesthetists

paradoxically after all the efforts taken to make the intra-operative period pain free

and stress free, the patients are left to fend themselves in the post-operative period.

“Pain free at rest” is a reasonable aim. Pain relief is necessary for both

humanitarian and therapeutic reasons. Uncontrolled pain in the postoperative period

can have detrimental physiological effects.

1. Pain can greatly impede the return of normal pulmonary function, ability to cough,

bronchospasm (all leads to atelectasis and hypoxemia especially in upper

abdominal and thoracic surgeries).

2. Pain promotes immobility and hence the development of deep vein thrombosis.

3. Alteration in the stress response to surgery, increased catecholamine release,

increased oxygen demand and increased cardiac work.

4. Increased catabolic response to surgical trauma and impaired immune

mechanisms and delayed wound healing.

Hence, its relief undoubtedly decreases morbidity and mortality.

In recent times, the role of epidural and subarachnoid opioids for the relief of

post-operative pain promotes a new platform in this field. This is because of the direct

action of the opioids on specific opioid receptors that are richly distributed in the

posterior horn of the spinal cord and epidural opioids have a wider margin of safety as

against systemic opioids.

Tramadol hydrochloride an opioid agonist and monoamine reuptake blocker

has been used extensively in the peri-operative period as an analgesic. It’s analgesic

potency is 1/5th to 1/10th of morphine and it does not have respiratory depression. But

80

studies have shown that, in doses of 100 mg or more, it can have side effects like

nausea, vomiting, hypertension.

Bupivacaine is a long acting amide local anaesthetic. It is 3-4 times more

potent than lignocaine and 7-8 times more potent than procane. It was synthesized by

EKENSTAM et al in 1957. Bupivacine when used epidurally for post operative

analgesia causes good pain relief with mild hypotension and motor blockade as its

chief side effect. It is known to cause sedation and pruritis like tramadol. In few cases

nausea has been reported which was probably related to hypotension rather than the

side effect of drug itself. Inadvertent vascular injection may lead to cardiotoxicity in

form of arrythmias and neurotoxicity in the form of fasciculations and seizures.

Here an attempt is made to assess the efficacy of tramadol, bupivacaine and

their combination through epidural route in management of post operative pain.

A total number of 90 patients, belonging to age group 18-75 have been taken.

Out of which mean age of Group T (receiving epidural tramadol) was 42.1 years and

in Group B (receiving epidural bupivacaine) was 44.9 years, while those in group B +

T (receiving combination of epidural tramadol with bupivacaine) was 42.8 years.

Hence all of these groups were comparable as regards to age.

Patients undergoing abdominal and lower limb surgeries were selected,

patients were randomly divided in 3 groups of 30 each; group T( tramadol), Group B

(bupivacine) and group B + T (combination) groups. All surgeries were done under

epidural anaesthesia. In post operative period as soon as patients complained of pain,

patients in group T received epidural tramadol 100mg diluted in 10ml of normal

saline ,Group B received bupivacine 0.25% (10ml) and group B+T received

bupivacine 0.125% and tramadol 50mg diluted to 10ml with normal saline.

81

Onset of analgesia :

In our study, the mean time of onset of analgesia in group T (tramadol) was

6.43 ± 2.39 minutes, in group B (bupivacaine) was 7.57 ± 2.18 minutes and in group

B + T (combination) was 6.90 ± 1.84 minutes. The statistical analysis by Student’s

unpaired ‘t’ test showed that, the difference in time of onset of analgesia in these 3

groups were statistically insignificant (p > 0.05).

Duration of analgesia :

The duration of analgesia in group T ranged from 1.5 – 3.5 hours with a mean

± SD of 2.37 ± 0.68 hours, while in group B ranged from 2-6 hours with mean ± SD

of 3.67 ± 0.83 hours, while in group B + T ranged from 3-9 hours with mean ± SD of

5.13 ± 1.63 hours. The duration of onset when compared between them was

statistically significant (p < 0.001).

A study to compared epidural bupivacaine with epidural bupivacaine +

tramadol combination by Choudhary AH, Dharmani P, Kumar N and Prakash A had

shown duration of analgesia with bupivacaine as (mean ± SD) 6.5 ± 4.1 hours, while

(combination) group B + T it was found to be (mean ± SD) 8.5 ± 3.1 hours, which

was statistically significant (p < 0.05).

A study conducted by S Prakash, R Tyagi, A Gogia and S Praksh for

comparison of efficacy of caudally administered tramadol and combination of

tramadol with bupivacaine has shown that combination of bupivacaine with tramadol

provided a longer duration of post operative analgesia when compared to epidural

tramadol.

82

Quality of analgesia :

Quality of analgesia was assessed at the time when rescue analgesia was given

to the patient. Patient was asked to assess the analgesic effect as adequate or

inadequate. In group T (tramadol) 87% termed the analgesia as adequate, in group B

(bupivacaine) 90% of the patient graded analgesia as adequate while in group B + T

(combination) 100% of the patient found analgesia as adequate. The difference in the

group B + T and group T, group B was statistically significant. While difference was

statistically insignificant in group B and group T (p> 0.05).

Study by Yaddanapudi LN, Wig J, Singh B and Tewari MK found that

Summed Pain Intensity Difference (SPID) were comparable between tramadol group

(50mg of epidural tramadol) and morphine group (3mg of epidural morphine)

showing that, the overall pain relief was similar with both the groups.

Delilkan AE, Vijayan R in their study noted that quality of analgesia was

significantly better with 100mg tramadol at 3, 12, 24 hours when compared to

tramadol 50 mg as bupivacaine 0.25%. Hence our study is comparable to their study.

Cardiovascular effects :

In our study, the mean pulse rate (difference in pulse rate before and after the

drug) was higher in tramadol group than to bupivacaine or combination group but it

was statistically insignificant. While the difference in systolic blood pressure in group

T, mean difference 5.22, in group B -5.82 and group B +T was 1.64 all of which on

comparison were found to be statistically significant (p < 0.05).

Similarly diastolic blood pressure change was found to be significant on

comparison of group T and group B and comparison of group B with group B + T.

83

Changes in respiratory rate was found to be statistically insignificant when all

the 3 groups were compared. (p > 0.05).

Side effects :

In our study in group T 13% (4) patients were found to have nausea as a side

effect while 10% (3) were found to have pruritis as its side effect.

In group B, 27% (8) of patients had motor blockade as its only side effect.

While in group B +T 10% (3) of patients had nausea, 3% (1) had motor blockade and

3% (1) had pruritis. The difference of these was considered clinically significant (p <

0.05 and χ2 = 20.0).

None of these patients in any group has clinically significant hypotension and

respiratory depression.

The study of Delilkan AE, Vijayan MD noted more incidence of nausea and

vomiting in group receiving epidural tramadol 100mg compared to epidural tramadol

50mg. Overall frequencies of side effects were less in all the groups. Hence our study

is comparable to the above results.

Conclusion

84

CONCLUSION

It was concluded that epidural tramadol, epidural bupivacaine and their

combination all provide an adequate, rapid and excellent postoperative analgesia.

The duration and quality of analgesia was found to be longer and superior with

the (combination) epidural bupivacaine + tramadol than with either of these groups.

Our study found no statistically significant difference in onset of analgesia

among these groups.

The incidence of side effects was found to be higher with tramadol group

followed by bupivacaine group and was least when their combination was used.

Summary

85

SUMMARY

This study “A comparative study of pos- operative analgesia by epidural route

among three regimens – Bupivacine 0.25%, Tramadol 100mg and Bupivacine 0.125%

with Tramadol 50mg” was conducted in 90 patients of either sex, belonging to 18-75

years of age, ASA grade I and II admitted to Bapuji Hospital, Chigateri General

Hospital and Women and Child Hospital for abdominal and lower limb surgeries from

2007 to 2009.

In post operative period, when patient first complainEDf pain, they received

either epidural tramadol 100mg (group T), bupivacine (0.25%) 10ml (group B) or

bupivacine 0.125% with tramadol 50 mg diluted to 10 ml (group B + T).

The following parameters were monitored :

1) Onset of analgesia

2) Duration of analgesia

3) Quality of analgesia

4) Cardiorespiratory effects, pulse rate, blood pressure, respiratory rate.

5) Side effects like nausea, vomiting, pruritis, respiratory depression,

urinary retention etc.

Onset of analgesia :

The mean time of onset of analgesia in group T was 6.43 ± 2.39 min (mean ±

SD), in group B was 7.57 ± 2.19 min (mean ± SD) and in group B + T was 6.90 ±

1.84 min (mean ± SD). This was statistically insignificant (p > 0.05).

Duration of analgesia :

Duration of analgesia in group T was 2.37 ± 0.68 hours, in group B was 3.67 ±

0.83 hours and in group B + T was 5.13 ± 1.63 hours with ranges of 1.5 to 3.5 hours

86

(group T), 2-6 hours (group B) and 3-9 hours (group B + T). This difference was

clinically significant (p < 0.05).

Quality of analgesia :

87% patients in group T had adequate analgesia while in group B it was 90%

and it was 100% in group B + T. This difference was clinically not significant (p >

0.05).

Cardiorespiratory effects :

When compared to initial value group T has mean difference of pulse rate 2.11

which was clinically significant, group B has fall of pulse rate which was clinically

significant. While group B + T change in pulse rate was clinically not significant.

Changes (fall) in SBP and DBP was significant only in group B + T and was

insignificant in group B and group T.

The change in respiratory rate with group T had a mean rise of 0.7 which was

clinically significant, in group B mean difference was 0.6 which was also clinically

significant. But in group B + T change in respiratory rate was clinically insignificant.

On inter group comparisons changes in respiratory rate, SBP and DBP had

shown clinically significant difference among all the three groups.

Side effects :

In tramadol group 13% patients had nausea and 10% had pruritis, in

bupivacine group 27% patients had motor blockade as its only side effect. While in

combination group 10% had nausea and 3% had motor blockade and pruritis. So the

overall incidence of side effect in combination group was less when compared to

either of the two groups which was clinically significant (p < 0.05).

Bibliography

87

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Annexures

90

ANNEXURE – I

PROFORMA

Name : IP No. :

Age : Sex :

Weight : ASA grade :

Operation : Premedication :

Technique :

Pulse : BP : RR :

Drug and dosage :

Initial

15mt

1hr

5hr

8hr

10hr

Adverse effects : Analgesia score :

Nausea : Onset Duration

Vomiting : Sensory blockade :

Respiratory depression : Motor blockade :

Drowsiness :

Pruritis :

Urinary retention :

Others :

91

ANNEXURE - II

CONSENT FORM FOR

ANAESTHESIA/OPERATION

I ………………..with Hosp. No……………..in my full senses hereby give

my consent for ………………..or any other procedure deemed fit which is and / or

diagnostic procedure / biopsy / transfusion / operation to be performed on me / my

son / my daughter / my ward ………………age ………under any anaesthesia deemed

fit. The nature and risks involved in the procedures have been explained to me to in

my own language. The operation / procedure may be televised or photographed for

academic and scientific purposes.

Date:

Signature / Thumb Impression of

the Patient / Guardian

Name:

Place: Guardian

Relationship

Full Address

92

ANNEXURE - III MASTER CHART

TRAMADOL

Pulse rate Blood pressure Respiratory rate Sl.

No. Name Age Sex I.P. No. Surgery OOA (min)

Duration (hrs) Quality Side

effects Initial 15min 1 hr 2 hr 5 hr 8 hr 10 hr ini sys

ini dia 15min 1 hr 2 hr 5 hr 8 hr 10 hr Initial 15min 1 hr 2 hr 5 hr 8 hr 10 hr

1 Sheshamma 35 F 551396 Laprotomy 5 3.5 Adequate None 86 90 92 86 - - - 128 80 130 86 130 92 130 80 - - - - 17 17 19 16 - - - 2 Hanumakka 35 F 3070 TAH 4 2.5 Adequate None 70 72 76 76 - - - 120 80 120 80 132 88 124 82 - - - - 14 14 16 16 - - - 3 Lalitha 46 F 13513 Vaginal

Hysterectomy 4 2 Adequate None 78 80 84 82 - - - 110 70 110 70 116 76 112 72 - - - - 20 20 22 22 - - -

4 Somi bai 55 F 13820 Vaginal Hysterectomy

5 2.5 Adequate None 60 70 74 72 - - - 100 60 100 60 108 62 106 60 - - - - 18 18 19 20 - - -

5 Lalitha bai 35 F 13818 TAH 6 3 Adequate Nausea 78 68 76 70 - - - 100 60 100 60 110 70 108 70 - - - - 15 15 16 18 - - - 6 Shanthamma 50 F 142156 Laprotomy 4 2.5 Inadequte None 78 80 86 86 - - - 90 130 80 140 92 140 90 - - - - 20 20 22 24 - - - 7 Basamma 40 F 13749 TAH 5 1.5 Adequate None 70 70 76 82 - - - 124 80 100 60 108 62 104 60 - - - - 18 18 18 19 - - - 8 Thayaama 35 F 13715 TAH 7 3.5 Adequate None 62 60 60 60 70 - - 100 90 110 70 114 80 120 90 124 80 - - 15 15 15 15 17 - - 9 Lalithamma 51 F 13134 TAH 6 1.5 Adequate None 86 90 92 96 - - - 110 60 120 80 124 82 120 80 - - - - 15 15 15 18 - - -

10 Gangamma 45 F 12764 TAH 9 2 Adequate Nausea 80 78 74 78 - - - 110 80 114 68 120 60 110 60 - - - - 18 18 18 19 - - - 11 Ningamma 50 F 13677 Vaginal

Hysterectomy 13 1.5 Adequate None 80 80 80 86 - - - 110 70 110 70 110 40 112 90 - - - - 19 18 18 18 - - -

12 Revamma 45 F 12796 Laprotomy 9 2 Inadequte None 72 76 72 78 - - - 110 70 110 70 108 70 112 80 - - - - 19 17 21 - - - 13 Devamma 25 F 13677 TAH 9 1.5 Adequate None 68 68 64 66 - - - 110 60 110 60 100 60 110 60 - - - - 14 14 14 17 - - - 14 Kenchamma 45 F 12796 TAH 12 2 Adequate None 80 90 86 86 - - - 120 80 130 84 120 76 130 80 - - - - 20 20 18 21 - - - 15 Almabee 45 F 2653 Vaginal

Hysterectomy 5 2 Adequate None 82 82 80 80 - - - 120 80 120 80 120 80 124 82 - - - - 14 14 14 16 - - -

16 Bharamma 40 F 2736 Laprotomy 4 3 Adequate Nausea 70 72 70 76 - - - 100 70 110 70 116 76 120 76 - - - - 15 15 17 18 - - - 17 Fakerayya 47 F 10706 Vaginal

Hysterectomy 5 2 Adequate None 74 76 72 72 - - - 100 60 100 60 104 60 100 60 - - - - 16 16 15 17 - - -

18 Bharmayya 60 F 9325 TAH 7 1.5 Adequate None 78 80 80 80 - - - 100 60 100 60 100 60 100 60 - - - - 19 19 20 21 - - - 19 Chitramma 29 F 10019 Vaginal

Hysterectomy 7 2 Inadequte None 72 72 76 70 - - - 110 80 120 80 124 86 130 90 - - - - 16 16 18 18 - - -

20 Rukamma 39 F 10193 TAH 5 3.5 Adequate None 62 62 60 66 69 - - 100 60 100 60 110 70 108 70 110 90 - - 20 20 18 21 22 - - 21 Halamma 46 F 10585 TAH 7 2.5 Adequate Pruritis 70 72 70 70 - - - 100 70 110 70 110 70 120 80 - - - - 18 18 20 20 - - - 22 Amruthamma 30 F 10351 Vaginal

Hysterectomy 3 3 Adequate None 72 80 78 78 - - - 120 90 130 90 138 92 138 80 - - - - 18 18 20 21 - - -

23 Renukamma 40 F 10327 Vaginal Hysterectomy

7 2 Adequate Pruritis 78 78 76 74 - - - 110 70 110 70 120 80 112 80 - - - - 20 20 21 22 - - -

24 Halamma 40 F 10397 Vaginal Hysterectomy

5 3 Adequate None 70 70 70 72 - - - 120 70 100 60 104 70 110 70 - - - - 20 20 21 21 - - -

25 Kusuma 40 F 9782 TAH 5 3.5 Adequate Nausea 80 80 82 84 90 - - 110 60 110 70 110 70 120 80 124 82 - - 20 20 20 20 22 - - 26 Hanumakka 35 F 3070 TAH 5 2 Adequate Pruritis 70 72 74 73 - - - 110 60 120 80 120 86 130 80 - - - - 14 14 16 17 - - - 27 Sakamma 35 10758 Vaginal

Hysterectomy 9 3 Adequate None 68 70 72 73 - - - 110 60 120 80 120 80 130 86 - - - - 16 16 16 18 - - -

28 Girwa bai 35 F 11177 TAH 7 2 Adequate None 80 82 82 86 - - - 100 60 110 70 110 70 110 70 - - - - 19 19 19 20 - - - 29 Thimakka 40 F 11189 Vaginal

Hysterectomy 9 1.5 Inadequte None 76 78 74 76 - - - 120 80 120 80 120 80 130 86 - - - - 20 20 20 21 - - -

30 Mangala 70 F 10771 Vaginal Hysterectomy

5 3 Adequate None 76 76 76 76 - - - 130 84 140 90 146 96 150 100 - - - - 20 20 19 21 21 - -

93

BUPIVACAINE

Pulse rate Blood pressure Respiratory rate Sl. No.

Name Age Sex I.P. No. Surgery OOA (min)

Duration (hrs)

Quality Side effects Initial 15min 1 hr 2 hr 5 hr 8

hr 10 hr In sys In dia 15min 1 hr 2 hr 5 hr 8 hr 10

hr in rr 15min 1

hr 2 hr

5 hr

8 hr

10 hr

1 Gangamma 42 F 145015 TAH 5 3.5 Adequate None 70 70 68 68 66 - - 112 70 110 70 104 60 100 60 104 64 - - - 18 16 14 14 15 - - 2 Anusuya 35 F 1498/E TAH 7 3.5 Adequate None 60 64 62 62 62 - - 100 64 100 60 94 70 98 58 98 58 - - - 15 15 15 14 14 - - 3 Revakka 28 F 1528/E TAH 5 5.5 Adequate Motor

blockade 80 80 80 78 78 - - 120 70 110 70 108 70 110 70 110 70 - - - 20 20 19 20 20 - -

4 Thippeswamy 50 M 17412 Cystojejunostomy 9 4 Adequate None 70 70 74 72 72 - - 120 70 120 70 110 70 114 72 114 72 - - - 20 18 17 17 17 - - 5 Obanna 63 M 16737 Laparotomy 6 3 Inadequate None 100 100 106 104 104 - - 110 60 100 60 90 60 90 60 90 60 - - - 27 27 25 25 25 - - 6 Rajappa 45 M 15529 Cholecystectomy 9 3.5 Adequate None 70 74 72 79 72 - - 110 72 110 70 100 64 100 68 104 68 - - - 18 18 17 17 18 - - 7 Shanthamma 59 F 16725 BK amputation 5 5 Adequate Motor

blockade 90 96 86 96 96 - - 110 60 110 60 110 60 110 60 120 68 - - - 23 23 21 21 22 - -

8 Hanumanthamma 28 F 16527 Cholecystectomy 10 4 Adequate Motor blockade

90 90 86 94 94 - - 136 90 130 90 120 86 120 80 124 68 - - - 23 23 24 21 23 - -

9 Kenchamma 38 F 1473/S Vaginal Hysterectomy 8 4.5 Adequate None 60 64 63 63 63 - - 110 60 110 60 100 60 102 60 104 62 - - - 18 18 16 17 17 - - 10 Marasappa 40 M 14899 Laparotomy 8 3 Inadequate None 90 90 96 94 94 - - 100 60 100 60 90 60 90 60 90 60 - - - 19 19 23 20 19 - - 11 Haseena 35 F 14710 Mesh repair 4 6 Adequate Motor

blockade 70 70 70 70 70 70 - 120 76 120 70 120 70 120 70 120 70 120 80 - 20 20 20 20 20 20 -

12 Sahedati 35 F 15711 Cholecystectomy 6 4 Adequate None 80 80 76 76 76 - - 130 90 130 90 128 86 124 80 120 80 - - - 19 18 17 17 18 - - 13 Halamma 35 F 1596 Vaginal Hysterectomy 6 4 Adequate None 64 68 68 68 68 - - 114 70 110 70 104 62 100 60 104 60 - - - 20 20 20 20 20 - - 14 Haleshappa 25 M 14478 Trans vesical

urethrolethotomy 4 3.5 Adequate None 80 80 76 76 79 - - 136 82 136 82 130 80 132 80 130 80 - - - 16 16 16 15 17 - -

15 Kenelappa 65 M 15723 BK amputation 6 4 Adequate None 80 80 72 76 84 - - 110 70 110 70 100 60 100 60 100 60 - - - 19 19 17 18 19 - - 16 Halappa 75 M 17154 Transvesical prostectomy 7 3 Adequate None 90 90 86 66 88 - - 140 90 140 90 130 80 130 80 130 80 - - - 15 15 15 16 15 - - 17 Pakeeramma 50 F 1455/D TAH 4 4 Adequate None 80 80 78 78 78 - - 130 90 130 90 124 86 124 86 130 90 - - - 18 18 18 17 17 - - 18 Sheshamma 35 F 551396 Laparotomy 11 3 Adequate None 90 82 82 82 80 - - 120 78 120 78 116 70 116 70 120 76 - - - 20 20 21 20 20 - - 19 Rathnamma 45 F 13793 TAH 7 3.5 Adequate None 80 70 74 72 72 - - 120 74 110 70 104 66 106 68 106 68 - - - 18 18 17 17 17 - - 20 Vaganbee 34 F 13185 Laparotomy 11 2 Inadequate None 80 80 82 82 - - 130 90 130 90 124 82 124 80 - - - - - 22 20 20 22 - - - 21 Lakshmamma 50 F 13155 Ward Mayos repair 12 3.5 Adequate None 70 64 64 68 76 - - 110 70 110 70 100 60 104 80 120 80 - - - 17 17 15 17 19 - - 22 Puttamma 40 F 13579 Laparotomy 9 2.5 Adequate None 80 70 74 72 79 - - 100 60 100 60 90 60 94 62 110 70 - - - 18 18 19 18 22 - - 23 Hanumanthappa 50 M 17433 Cystogastrostomy 9 3 Adequate Motor

blockade 60 90 88 88 94 - - 100 60 100 60 94 56 94 56 98 56 - - - 20 20 20 21 20 - -

24 Mallamma 40 F 17489 Colostomy 7 3.5 Adequate Motor blockade

70 90 86 86 88 - - 120 86 120 80 114 72 112 60 120 76 - - - 16 16 16 16 17 - -

25 Kalappa 65 M 15818 Cholecystectomy 9 3 Adequate None 90 78 78 72 80 - - 100 70 100 70 90 64 98 68 104 72 - - - 19 19 20 19 19 - - 26 Lakshami 30 F 18549 Cholecystectomy 9 3 Adequate None 76 82 84 80 86 - - 100 60 90 60 86 60 88 60 90 60 - - - 17 17 18 17 17 - - 27 Ranganath 65 M 18529 Transvesical prostatectomy 9 3 Adequate None 80 70 74 72 76 - - 110 70 110 70 104 68 108 68 110 70 - - - 20 20 20 19 19 - - 28 Peersab 60 M 18536 Pylolithotomy 7 4 Adequate Motor

blockade 70 80 72 78 78 - - 130 90 130 90 120 82 124 80 124 80 - - - 16 15 15 15 15 - -

29 Alla Bhaksh 39 M 19256 Prostatectomy 9 4 Adequate None 80 80 86 82 82 - - 130 90 130 90 120 80 124 86 124 86 - - - 18 18 19 17 17 - - 30 Raziya Begum 45 F 12591 Vaginal Hysterectomy 9 4 Adequate Motor

blockade 70 70 76 74 78 - - 126 80 120 80 110 76 116 78 124 82 - - - 18 16 15 15 18 - -

94

BUPIVACAINE + TRAMADOL

Pulse rate Blood pressure Respiratory rate Sl. No.

Name Age Sex I.P. No. Surgery OOA (min)

Duration (hrs)

Quality Side effects Initial 15min 1 hr 2 hr 5 hr 8 hr 10 hr in

sys in dia

15min 1 hr 2 hr 5 hr 8 hr 10 hr in rr 15min 1 hr 2 hr 5 hr 8 hr 10 hr

1 Sujatha 30 F 20682 Cholecystectomy 6 4 Adequate None 78 78 82 76 80 - - 98 60 98 60 100 60 100 60 100 60 - - - - 19 19 19 20 21 - - 2 Manjunath 30 M 22027 Cholecystectomy 3 4.5 Adequate None 90 90 92 90 96 - - 110 70 110 70 116 80 120 82 120 80 - - - - 23 23 20 23 27 - - 3 Santhamma 65 F 11950 TAH 7 6 Adequate None 82 82 82 80 83 86 - 100 60 100 60 96 58 100 60 100 60 100 60 - - 19 19 17 17 19 19 - 4 Lokesh 40 M 21590 BK amputation 5 6 Adequate None 86 86 83 83 83 90 - 130 90 130 90 130 90 130 90 130 90 130 90 - - 20 20 20 20 21 20 - 5 Raziya Bee 45 F 12591 TAH 4 8 Adequate Nausea 76 76 72 72 72 72 76 110 70 110 70 108 70 110 70 110 70 110 70 - - 18 18 18 18 18 19 19 6 Geetha 38 F 12043 TAH 9 6.5 Adequate None 78 78 82 80 79 80 - 100 60 100 60 90 60 96 60 100 58 100 58 116 78 22 22 22 22 23 23 - 7 Pyari Jaan 40 F 12331 TAH 5 8 Adequate None 68 68 68 68 70 69 - 100 70 100 70 110 70 110 70 110 78 110 70 - - 16 16 16 16 16 16 - 8 Pushpa 40 F 12351 Vaginal

Hysterectomy 7 5 Adequate None 80 80 80 78 82 - - 110 70 110 70 110 70 116 72 116 70 - - - - 19 19 19 21 20 - -

9 Siddalingamma 35 F 12355 Laparotomy 10 4.5 Adequate None 66 66 68 68 69 - - 130 90 130 90 132 90 130 90 140 90 - - - - 21 21 21 20 21 - - 10 Basamma 45 F 1225/C TAH 5 7 Adequate None 70 70 70 72 74 - - 120 80 120 80 120 80 126 82 126 80 - - - - 19 19 21 21 21 - - 11 Gani Bi 65 M 10523 Laparotomy 6 4 Adequate None 80 80 82 82 86 - - 130 80 130 80 130 80 130 80 140 90 - - - - 16 16 16 17 17 - - 12 Lakkamma 41 F 12492 Vaginal

Hysterectomy 9 4.5 Adequate Nausea 67 67 69 69 67 - - 140 90 140 90 140 90 150 98 150 100 - - - - 23 23 23 27 22 - -

13 Vishalamma 55 F 11845 TAH 5 6 Adequate None 73 73 73 77 76 - - 110 70 110 70 120 80 120 80 124 80 - - - - 19 19 19 19 23 - - 14 Sharadamma 50 F 11121 Vaginal

Hysterectomy 7 4.5 Adequate None 70 70 70 70 70 - - 110 70 110 70 110 70 110 70 110 70 - - - - 18 18 17 18 18 - -

15 Santhamma 65 F 11950 Vaginal Hysterectomy

6 4 Adequate None 80 80 82 82 86 - - 130 70 130 70 130 76 130 70 138 80 - - - - 19 19 18 19 20 - -

16 Nirmala 45 F 11943 TAH 7 6.5 Adequate None 76 76 77 76 76 76 - 116 80 116 80 114 80 114 80 120 80 - - - - 21 21 20 20 19 19 - 17 Jamunamma 45 F 19346 Hemicolectomy 9 3 Adequate None 96 96 92 94 - - - 100 60 100 60 104 60 110 60 - - 110 96 - - 23 23 22 23 - - - 18 Kariyappa 45 M 19499 BK amputation 7 5 Adequate None 80 80 82 80 83 - - 100 70 100 70 110 70 110 70 120 70 - - - - 15 15 17 15 16 - - 19 Bhorappa 45 M 1081/E AK amputation 6 5 Adequate None 80 80 80 80 80 - - 130 70 130 70 130 70 130 70 140 80 - - - - 18 18 18 17 17 - - 20 Hanumakka 35 F 5123 Uretrolithotomy 10 3.5 Adequate None 78 78 76 76 76 - - 110 70 110 70 100 60 110 70 110 70 - - - - 20 20 21 21 21 - - 21 Ahmad Saab 39 M 5729 Laparotomy 9 3 Adequate None 96 96 92 96 - - - 100 50 100 50 90 50 96 60 - - - - - - 19 19 21 19 - - - 22 Gangamma 35 F 6393 Pylolithotomy 7 3.5 Adequate None 92 92 92 100 - - - 110 70 110 70 114 76 114 80 - - - - - - 18 18 18 22 - - - 23 Muriganna 50 M 4506 Cholecystectomy 7 5 Adequate Nausea 80 80 80 84 84 - - 130 70 130 70 130 70 140 76 140 80 - - - - 19 19 17 19 19 - - 24 Prakash 30 M 9382 Mesh repair 5 8 Adequate None 76 76 76 74 77 76 - 110 70 110 70 120 80 116 76 110 74 110 80 - - 17 17 17 17 18 18 - 25 Tahira 55 F 3924 Cholecystectomy 9 5 Adequate None 79 79 78 80 76 - - 100 60 100 60 100 60 100 60 110 70 - - - - 15 15 15 17 17 - - 26 Kamalamma 46 F 9284 Nephrectomy 9 4 Adequate None 72 72 72 74 76 - - 110 70 110 70 110 70 120 80 120 80 - - - - 16 16 16 17 17 - - 27 Krishna 28 M 9854 Pylolithotomy 7 3.5 Adequate None 90 90 92 92 - - - 120 80 120 80 124 84 130 90 - - - - - - 19 19 21 22 - - - 28 Mallamma 25 F 11012 Mesh repair 5 9 Adequate None 78 78 78 78 78 78 80 110 70 110 70 110 70 110 70 110 70 110 70 110 70 19 19 19 19 19 20 20 29 Durgappa 25 M 11337 Cholecystectomy 7 4 Adequate Motor

blockade 70 70 72 72 76 - - 130 80 130 80 130 80 130 80 140 90 - - - - 17 17 17 19 19 - -

30 Surappa 52 M 11753 Trans rectal prostectomy

9 3.5 Adequate Pruritis 68 68 68 70 - - - 110 70 110 70 110 70 130 80 - - - - - - 20 20 21 21 - - -

95

KEY TO MASTER CHART

Sl. No. - Serial Number

I.P. No. - Inpatient Number

O.O.A - Onset of Analgesia

Q.O.A - Quality of Analgesia

hrs - Hours

D.H.S. - Dynamic Hip Screw

DCP - Dynamic Compression Plate

SP nailing - Smith Patterson Nailing

ORIF - Open Reduction Internal fixation

K Nail - Kuntscher Nail

AMP - Austin Moor’s Prosthesis

TAH - Total Abdominal Hysterectomy

VH - Vaginal Hysterectomy

DCS - Dynamic Condylar Screw

BK Amputation - Below Knee amputation

Min - Minutes