i

EFFICACY OF 1.2GRAM PARACETAMOL IN THE

MULTIMODAL MANAGEMENT OF POSTCAESAREAN

SECTION PAIN

BY

DR. AUDU ALEXANDER MBBS(BENIN) 2000, PGDA(BENIN) 2004

DEPARTMENT OF ANAESTHESIOLOGY

UNIVERSITY OF BENIN TEACHING HOSPITAL

BENIN-CITY

MAY 2015

ii

EFFICACY OF 1.2 GRAM PARACETAMOL IN THE

MULTIMODAL MANAGEMENT OF POSTCAESAREAN

SECTION PAIN

A DISSERTATION SUBMITTED TO THE NATIONAL

POSTGRADUATEMEDICAL COLLEGE OF NIGERIA IN

PART FULFILLMENT OF THE

REQUIREMENTS FOR FELLOWSHIP AWARD OF THE

FACULTY OFANAESTHESIA

BY

DR. AUDU ALEXANDER MBBS(BENIN) 2000, PGDA(BENIN) 2004

DEPARTMENT OF ANAESTHESIOLOGY

UNIVERSITY OF BENIN TEACHING HOSPITAL

BENIN-CITY

MAY 2015

iii

iv

v

DEDICATION

This work is dedicated to God Almighty who in his divine mercy and providence had

kept me alive till today, to my parents, Sir and Lady A. A. Audu, who laid the foundation

of hard work for me and to my wife, Joyce.

vi

ACKNOWLEDGEMENT

I am most grateful to the Almighty God for His favour that has enabled me to

survive the difficult terrain during my training in Anaesthesiology. I want to

acknowledge the pioneer Anaesthesiologists of the Department especially Prof. M. O.

Obiaya. The seed he sowed had continued to grow and bear fruits from which I had

benefitted.

My profound thanks and appreciation to my supervisors Prof. CO Imarengiaye

and Prof. (Mrs) NP Edomwonyi for their unrelenting encouragement, support and

invaluable guidance from the proposal writing up to the presentation of this research

work. I am grateful to all the consultant anaesthesiologists in the University of Benin

Teaching Hospital who provided direction, leadership and training: Prof Imarengiaye CO,

Prof. Edomwonyi NP, Dr. FE Amadasun, Dr OP Adudu, Dr. IT Ekwere, Dr. IJ Isa, Dr. S.

Tudjegbe and Dr. DD Akpoduado.

I also thank all my teachers in the Department of Anaesthesia, Lagos University Teaching

Hospital where I had my posting in Neuroanaesthesia.

I appreciate and thank my contemporaries in the residency training Dr. T Isesele,

now a consultant in the Department of Anaesthesia and Dr. FE Edobor. I also want to

express my sincere gratitude to my friends and colleagues in the Department of

Anaesthesia, University of Benin Teaching Hospital, Benin city, particularly those

registrars who assisted in my data collection. Many thanks to some House officers and

ward nurses for their support and cooperation during my data collection.

I am grateful to my immediate family for their support and encouragement. I want

to express my gratitude to my Uncle, Bar. PU Aliu for his guidance in the Medical

school. He also assisted me with some textbooks in the early part of my training before

the world became a global village through the computers and internet.

vii

TABLE OF CONTENTS

Cover Page..........................................................................................................................i

Title Page ………………………………………………..................................................ii

Certification……………………………………………..................................................iii

Declaration ……………………………………………..................................................iv

Dedication ……………………………………………….................................................v

Acknowledgements ………………………………………..............................................vi

Table of contents …………………………………........................................................vii

List of tables …………………………………………...................................................viii

List of figures ……………………………………………...............................................ix

List of Abbreviations.........................................................................................................x

Summary …………………………………………….....................................................xii

CHAPTER ONE

Introduction ……………………………………………..................................................1

CHAPTER TWO

Aim and Objectives ……………………………………..................................................4

Justification for the Study..................................................................................................5

CHAPTER THREE

Literature review …………………………………….......................................................6

CHAPTER FOUR

Methodology................……………………………………............................................15

CHAPTER FIVE

Results …………………………………………………….............................................23

CHAPTER SIX

Discussion ……………………………………………………………….......................40

Conclusion........................................................................................................................52

Study limitations ……………………………..................................................................53

Recommendations ……………………………...............................................................54

References ………………………………………………………..................................55

Appendices ………………………………......................................................................65

viii

List of Tables.

Table I: Table I: Demographic and other patients characteristics

Table II: Indications for Caesarean section

Table III. Preoperative Vital Signs

Table IVa: Block height

Table IVb: Interspace for injection

Table V: Intraoperative clinical variables

Table VI: Intraoperative complications

Table VII: Duration of analgesia and pain score at 6th hour.

Table VIII: Proportion of women with pain score ≤ 4 on NRS at 6th hour

Table IX: Postoperative complications

Table Xa: Mother’s satisfaction with pain relief.

Table Xb: Mother’s satisfaction with injection at the back

Table Xc: Mother’s satisfaction with manipulation at delivery.

ix

List of Figures

Figure Ia: Intraoperative Systolic and Diastolic BP

Figure Ib: Introperative Mean Arterial Pressure and Pulse Rate

Figure 2: Pattern of pain score at rest before request for analgesic

Figure 3: Pattern of pain score with activity before request for analgesic

Figure 4a: Systolic and Diastolic BP in Post Anaesthetic Care Unit

Figure 4b: Mean Arterial Pressure and Pulse Rate in PACU

x

List of Abbreviations

IASP International Association for the Study of Pain

NSAIDs Non-steroidal Antiiflamatory Drugs

VRS Verbal Rating Scale

NRS Numerical Rating Scale

VAS Visual Analogue Scale

COX-2 Cyclooxygenase 2

COX-3 Cyclooxygenase 3

PCA Patient Controlled Analgesia

CI Confidence Interval

SD Standard Deviation

ASA America Society for Anaesthesiologist

NaCl Sodium Chloride

ECG Electrocardiograph

IU International Unit

SPSS Statistical Package for Social Science

g gram

mg milligram

vs versus

% per cent

n number

CS Caesarean Section

PACU Post Anaesthetic Care Unit

Fig Figure

SBP Systolic Blood Pressure

xi

List of Abbreviations

DBP Diastolic Blood Pressure

MAP Mean Arterial Pressure

PR Pulse Rate

xii

SUMMARY

Adequate analgesia is important after Caesarean section because it is desirable for

mothers to be energetic, ambulate, interact and care for the newborn. It also reduces the

risk of thromboembolic event post operatively. Despite improvements in analgesic

delivery, several studies showed that up to 80% of patients report moderate to severe pain

after surgery. The approach to adequate post-caesarean pain treatment has been a trend

away from monotherapy towards multimodal strategy. Multimodal strategy was

evaluated in a randomized controlled trial to determine the efficacy and safety of

bupivacaine/pethidine/paracetamol combination for pain treatment after caesarean section

in our hospital.

Approval was received from the Research and Ethics Committee of the hospital.

Women scheduled for elective caesarean section consented to participate in the study.

These patients were randomized to receive subarachnoid block with

bupivacaine/pethidine and paracatamol or bupivacaine/pethidine and saline.

The blood pressure, pulse rate, oxygen saturation, ECG and body temperature of

all patients were monitored using the Multi-parameter monitor. The pain scores of the

patients were also monitored from time of administration of study medication up to 24

hours postoperatively. Time to first request for analgesia, pain score at 6 hour and at

request for first analgesia, analgesic consumption, adverse effects, maternal satisfaction

were documented.

Data analysis was done using SPSS version 16.0. Continuous variables were

analyzed using unpaired student t-test and categorical data analyzed with Chi-square test,

where appropriate. The level of significance was set at a probability of 5%.

A total of 112 women were randomized to receive bupivacaine/

pethidine/paracetamol or bupivacaine/pethidine/saline. There was no difference in the

sociodemographic characteristics between the two groups. There was a significant

difference in time to first request for analgesia between the paracetamol group (322.80 ±

66.00mins) compared to the control group( 242.40 ± 43.80mins; p = 0.002). The

paracetmol group consumed less pentazocine than the saline group (109.82 ± 28.03mg vs

xiii

124 ± 32.30mg; p = 0.002). Hypotension was the most common intraoperative

complication in the population studied 51(40.8%). Adverse effects in the postoperative

period were few. Patients satisfaction was rated higher in the paracetamol group.

This study shows that paracetamol in combination with bupivacaine/pethidine

spinal anaesthesia as a multimodal strategy is effective in the treatment of pain following

Caesarean delivery with minimal side effects. It is recommended therefore, that this

combination should be offered to women who delivered their newborn by Caesarean

section.

1

CHAPTER ONE

INTRODUCTION

Caesarean section is one of the commonest operations worldwide. In Western

countries, 15 – 25% of women give birth by Caesarean section1. The rate of 22.2% in our

centre2 is similar to the global rate. This procedure is often associated with acute pain of

moderate to severe intensity in the post operative period. Several authors have reported

the incidence of post operative pain to be as high as 80%.3-7

Effective pain management is an important component of post surgical care8.

Since postsurgical pain treatment relies on the subjective nature of patient pain

perception, new methods of pain treatment has been developed such as continuous

epidural analgesia or patient controlled analgesia.1 However these new technologies are

not readily available in many hospitals especially in the developing countries like

Nigeria. They are expensive and require expertise and special equipment. Post Caesarean

delivery women are expected to recover expeditiously and care for their newborn within

a few hours after the operation. Therefore they are reluctant to become sleepy, drowsy, or

to be restricted by equipment which might prevent their ability to care for their babies1.

These effects are frequently encountered with modern methods of analgesia which

employ the use of opioids.

The ideal postoperative analgesic treatment should provide rapid and effective

pain relief, have low incidence of adverse effects, minimal impact on major organ

systems or no significant interaction with other pharmacological agents.8 Systemic

opioids remain the agent of choice for severe pain. However, the analgesic effect of

2

opioids is associated with dose dependent adverse effects ranging from pruritus, nausea,

and vomiting to sedation and respiratory depression8.

A multimodal approach has been recommended for the treatment of pain after

surgery. Multimodal analgesia involves the use of drugs that have different mechanisms

of action and the combination allows for addictive and even synergistic effects in

reducing pain and decreases the side effects produced by either class of drugs9. The

addition of non-steroidal anti-inflammatory drugs (NSAIDs) to a post-caesarean

analgesic regimen has been shown to improve post-caesarean pain and reduce opioid

requirements10-12. Potential maternal side effects (e.g, antiplatelet and gastrointestinal)

and effects on the breast-feeding infant have raised concerns about their use in the post-

caesarean delivery setting13. Paracetamol may be used when NSAIDs is contraindicated

or primarily as a component of multimodal or balanced analgesia to decrease opioid dose

requirement and may reduce associated adverse effects while reducing post-surgical pain

intensity.

Paracetamol in therapeutic doses is safe, inexpensive and well tolerated. It has a

well established safety, antipyretic and analgesic profile. Over a century, it has been used

in oral doses of 500mg to 1000mg to achieve these effects14. The recent development of

a parenteral form of paracetamol has widened the possibilities of a well tolerated drug

being used in the postoperative period, when the intravenous route is most often

required15. This route ensures 100% bioavailability and is more effective in terms of

onset of analgesia than the oral paracetamol.

3

It may be necessary therefore, to evaluate the place of intravenous paracetamol in

the management of post caesarean section pain. This will improve the armamentarium of

the Anaesthetists in the multimodal management of post caesarean section pain.

4

CHAPTER TWO

AIM AND OBJECTIVES

AIM:

To evaluate the analgesic efficacy and safety of 1.2g intravenous Paracetamol for

the management of pain after Caesarean section using Pethidine/Bupivacaine for

Subarachnoid Block.

OBJECTIVES:

1. To determine and compare the time to first analgesic requirement following

the administration of Paracetamol and Placebo in the immediate postoperative

period.

2. To determine the proportion of patients with favourable pain scores (NRS ≤ 4)

on the numerical rating scale following the use of Paracetamol analgesia at 6

hours postoperatively.

3. To determine the analgesic consumption 24 hours after caesearean section.

4. To determine the incidence of adverse effects related to the study medications.

5. To determine the maternal satisfaction with the technique of post caesarean

section pain management.

5

JUSTIFICATION FOR THE STUDY

Currently, the common practice for cesarean delivery includes the use of

bupivacaine only for spinal block with intravenous pentazocine 30mg 4-6hourly for post

operative analgesia. This is grossly inadequate as the sole analgesic thus leaving the

parturient to suffer a great deal of avoidable pain. In the absence of patient controlled

analgesia device in our institution and the West Africa sub-region, it may be justifiable to

evaluate the effectiveness and safety of available analgesics such as paracetamol. Also

the addition of pethidine to bupivacaine, will result in the use of lower doses of the local

anaesthetic agent , thus reducing the complications associated with bupivacaine such as

hypotension.

This study aims to achieve prolongation of intraoperative analgesia into the early

post operative period when pain is most excruciating by exploiting the use of

bupivacaine, pethidine and paracetamol. If consistency of efficacy and safety can be

achieved with this combination, it could improve the standard of care available for

parturients in the early post cesarean delivery period in our centre and the West Africa

sub-region.

6

CHAPTER THREE

LITERATURE REVIEW

Pain is defined by the International Association for the study of Pain (IASP) as an

unpleasant sensory and emotional experience associated with actual or potential tissue

damage or described in terms of such damage.16 It is a subjective experience and is

difficult for an observer to accurately assess. The provision of a reliable and a valid

means of assessing pain is important because it allows some degree of improvement after

analgesic intervention. Pain assessment can be done in various ways. Verbal rating scale

(VRS): no pain is scored 0, slight pain = 1, moderate pain = 2, severe pain = 3, worst pain

imaginable = 4. Numerical rating scale (NRS): This is a linear scale, scoring between 0

and 10, where 0 = no pain, and 10 = worst pain imaginable. Visual analogue scale (VAS):

the patient is asked to score on a 10cm or 100mm line with “no pain” at one end and

“worst pain ever” at the other end; this is then measured by the observer to give a score of

0 – 10cm or 0 – 100mm.17

Since paracetamol was first synthesized in 18783 it has become one of the most

popular and widely used drugs for the first line treatment of fever and pain. Mechanism

of action remains unclear. There is increasing evidence of a central antinociceptive

effect, and the potential mechanisms for this include inhibition of a central nervous

system COX-2, inhibition of a putative central cyclooxygenase-3 ‘COX-3’ that is

selectively susceptible to paracetamol and modulation of inhibitory descending

serotonergic pathway.18-20 It has been shown to prevent prostaglandin production at the

cellular transcriptional level, independent of cyclooxygenase activity.21 It is therefore an

7

effective postoperative analgesic with potency slightly less than a standard dose of

morphine or the NSAIDs.22,23

The availability of intravenous paracetamol will enhance and extend the use of

this drug as a fundamental component of multimodal analgesia after surgery.23-25 The

injectable prodrug, propacetamol has been available in various countries for some time,

but has the disadvantage that it must be reconstituted before use (2g propacetamol is

equivalent to 1g paracetamol). Now a more convenient ready for use aqueous solution

(Perfalgan, Britolmyers Squibb) is available, and 1g Perfalgan is equivalent in

pharmacokinetics to 2g of propacetamol with better injection site tolerance.26 The

intravenous formulation produces a more predictable plasma concentration in the

immediate postoperative period than the oral preparation.27 The efficacy of intravenous

paracetamol appears to be convincing. In volunteers, intravenous paracetamol has been

shown to reduce central hyperalgesia, further evidence of a central action.21 However,

adverse effects such as rash and other allergic reactions may occasionally occur. The rash

is usually erythematous or urticarial and may be accompanied with drug fever and

mucosal lesions. Hepatotoxicity is rare and is associated with overdose.28

There are compelling reasons to provide adequate pain relief for mothers

undergoing cesarean delivery. The risk of thromboembolic disease which is increased

during pregnancy may be further exacerbated by immobility related to pain during the

puerperium. Immobility due to pain increases venous stasis, one of the Virchow’s triad in

the pathogenesis of pulmonary embolism.29 Pain may also impair the mother’s ability to

optimally care for the new born baby in the immediate postpartum period and may

adversely affect early interactions between mother and the baby.30 Inadequate pain relief

8

in the early post cesarean delivery may put the mother at risk of developing chronic pain.

Nikolajsen et al31 found that 12% of women were still complaining of pain after 10

months following caesarean section and 6% had pain that interfered with their quality of

life. Kainu and colleagues32 reported persistent pain after caesarean section to be 12.3%

at 10 months and 18% after 12 months, this was correlated to pain on the day of surgery.

Therefore, it is pertinent to adequately treat pain in the immediate postoperative period.

To achieve adequate analgesia after Caesarean section, different methods of pain

treatment has been evaluated. In a prospective randomized controlled single-blind study,

Salmah et al33 determined the effect of intrathecal morphine 0.1mg as compared with

intrathecal fentanyl 25µg in terms of analgesia and duration of pain relief after caesarean

section. Sixty patients were randomly allocated to two groups. Group 1 received 1.8ml of

0.5% hyperbaric bupivacaine combined with 0.1mg morphine, group 2 received 1.8ml of

0.5% hyperbaric bupivacaine combined with 25µg fentanyl for spinal anaesthesia.

Postoperatively all patients were provided with PCA morphine. The Visual Analogue

Score for pain, cumulative PCA morphine requirement were both significantly lower in

group 1 (p < 0.05) during the 24hour study period. The time to first analgesic demand

was also significantly longer in group 1 (p < 0.05). There were no significant difference

between the 2 groups in side effects, except for high incidence of nausea and vomiting

requiring treatment in group 2. However, the authors did not exclude nausea and

vomiting that may result from hypotension due to subarachnoid block. The authors

concluded that addition of 0.1mg morphine for spinal anaesthesia provided superior and

longer postoperative analgesia after Caesarean section.

9

In a prospective, randomized, double-blind placebo controlled trial, Yu and

colleagues34 investigated the effect of adding meperidine 10mg to intrathecal bupivacaine on

the duration of early post operative analgesia. Forty patients scheduled for elective Caesarean

section under spinal anaesthesia were randomly assigned to receive intrathecal injection of

10mg of 0.5% hyperbaric bupivacaine, plus either normal saline 0.2ml (S group) or

10mg(0.2ml) of 5% meperidine (M group). After surgery all patients were given intravenous

patient controlled analgesia using morphine. The mean duration of effective analgesia defined

as the time from intrathecal injection to first patient-controlled analgesia demand was greater in

the meperidine group (mean 234min, 95% CI 200 – 269min) compared with the saline group

(mean 125min, 95% CI 111 -- 138min; P< 0.001). The 24hours morphine requirement was

similar in the two groups with greater incidence of intraoperative nausea and vomiting in the

meperidine group compared with saline group (11 vs 3; P=0.02). There was no mention of the

desired block height and the maximum block height achieved before commencement of

surgery. Inadequate block may contribute to nausea and vomiting due to peritoneal

manipulation. The investigators concluded that 10mg of meperidine added to intrathecal

bupivacaine for caesarean section is associated with prolonged postoperative analgesia but with

greater incidence of intraoperative nausea and vomiting.

It is salutary that pethidine which is available in Nigeria has been used in the treatment

of postoperative pain. Imarengiaye et al35 in a randomized, double blind, placebo-controlled

trial, determined the quality of perioperative analgesia and side effect profile of hyperbaric

bupivacaine 10mg plus pethidine 7.5mg for spinal anaesthesia for Caesarean section. Their

results showed that the addition of pethidine 7.5mg resulted in block height higher than T6 and

longer duration of analgesia (256.9 ± 112.2min.) compared with the saline group (160.5 ±

10

65.0min; p = 0.0005). Maternal hypotension occurred more in the pethidine group (10/25 vs

2/25; p =0.01). Peritoneal irritation and inadequate anaesthesia were more frequent in the saline

group with nausea, vomiting and drowsiness occurring only in the pethidine group. It was

concluded that a combination of bupivacaine and pethidine resulted in better quality of

anaesthesia, longer postoperative analgesia with acceptable side effects profile.

Clearly, the effectiveness of the intrathecal opioids, as used in these studies,33-35 was

limited to about 4 hours. The pain of postcaesarean section persists beyond 4 hours. This has

provoked critical reassessment of post caesarean section analgesia and resulting in the concept

of multimodal analgesia.

Multimodal pain therapy has gained popularity in the management of postoperative

pain relief in different types of surgery. Siddik and coworkers36 evaluated the postoperative

analgesic effects of paracetamol and or diclofenac in parturients undergoing elective caesarean

section under spinal anaesthesia. They found a lower VAS score at 2 hours, in group MDP and

MD compared with group M (P< 0.05) with still a tendency towards lower pain scores at 24

hours. This difference was only statistically significant at rest between the MDP group, the MP

and M groups. The morphine consumption was lower in the MDP and MD groups compared

with MP and M groups (P < 0.05). The morphine-sparing effect was higher in group MDP and

MD group compared with group MP (57% and 46%, respectively vs 8.2%, P < 0.05). They

concluded that diclofenac improves analgesia and has a highly significant morphine-sparing

effect. They were unable to demonstrate significant morphine-sparing of propacetamol or

additive effect of propacetamol and diclofenac in this group of patients.

In a similar study, Munishankar and colleagues14 in a double-blind randomized

control trial investigated the efficacy and side effects of diclofenac and paracetamol used

11

for pain relief after caesarean section. Seventy-eight patients were recruited to receive

one of three analgesic modalities: paracetamol, diclofenac, or diclofenac and

paracetamol. Study medications were given as suppository at the end of surgery, then

orally for 24 hours. They concluded that the patients given a combination of diclofenac

and paracetamol used 38% less morphine compared to patients given paracetamol alone.

This study strongly supported the superiority of analgesia using a combination of agents

as compared with use of single agent.

Contrary to the findings of Munishankar and colleagues, Peduto et al15 reported

significant morphine-sparing effect of propacetamol when they evaluated the analgesic

efficacy of propacetamol, in combination with morphine. Propacetamol 2 gram or

placebo were administered after hip arthroplasty (n = 97). Morphine was administered by

a patient controlled analgesia device. At the end of the 24 hour study period, their results

confirmed a significant morphine-sparing effect and significantly better pain scores. The

values in this study compares favourably to those reported for propacetamol by Delbos et

al.37

Varrassi and colleagues38, in a double-blind, randomized, parallel-group study in

a multi-center trial, assessed the relative morphine consumption in a combined analgesic

regimen (on-demand morphine plus propacetamol or ketorolac) after abdominal

hysterectomy. They concluded, that propacetamol and ketorolac, combined with patient

controlled analgesia morphine, show similar analgesic efficacy following abdominal

hysterectomy. Even at the similar analgesic profile, the side effects of NSAIDs were

notable and could be disturbing unlike paracetamol.

12

Recently, Sinatra et al⁸ in a repeated-dose, randomized, double-blind, placebo-

controlled, evaluated the analgesic efficacy and safety of intravenous paracetamol as

compared with its prodrug (propacetamol) after total hip replacement. Patients reporting

moderate to severe pain received either1g intravenous paracetamol, 2g propacetamol or

placebo at 6hour interval over 24 hours. Patients were allowed “rescue” intravenous

patient-controlled analgesia using morphine. They found that intravenous paracetamol,

1g administered over 24–h period in patients with moderate to severe pain after total hip

replacement provided rapid and effective analgesia and was well tolerated. This was

similar to the finding of Moller et al39 who demonstrated that the stable and ready to use

intravenous paracetamol 1g has a better tolerability profile than propacetamol 2g with

comparable efficacy after third molar surgery. Although the analgesic effects were

comparable in the above studies35,38 the nature and severity of postcaesarean section pain

having somatic and visceral components is different from that after orthopaedic pain

which has only somatic component.

Piguet et al40 have demonstrated in healthy volunteer that the analgesic effect and

plasma concentration of paracetamol were closely correlated and were dose dependent.

The authors concluded that intravenous paracetamol has a dose dependent central

antinociceptive effect. Recently Juhl et al41 confirmed this result in a single-center,

randomized double-blind study. The authors demonstrated that the analgesic efficacy of

2g starting dose of intravenous paracetamol was superior to the recommended dose of 1g

in terms of magnitude and duration of analgesic effect, for postoperative pain following

third molar extraction with no significant difference between groups regarding safety.

Pain of molar extraction and orthorpaedic surgery are both somatic unlike post caesarean

13

section pain which have somatic and visceral components. It is therefore difficult to

extrapolate this finding to caesarean section but the safety profile of 2g paracetamol

demonstrated in this study (Juhl et al) is commendable.

This may have formed the platform for evaluation of the pharmacokinetics of a

loading dose of intravenous paracetamol post caesarean delivery.42 These authors studied

2g intravenous paracetamol as loading dose following Caesarean section and reported

that the paracetamol plasma concentration after 1, 2, 4, and 6h, were 22.5, 15.25, 7.9 and

3.9mg/L respectively. Median[range] paracetamol clearance was 20.3[11.8-62.8]L/hr,

distribution volume 58.3[42.9-156]L. The peak and trough concentrations in women

following caesarean delivery were lower than in non-pregnant patients due to a larger

distribution volume and higher clearance, suggesting that reducing the interval between

consecutive doses(typically 6 hourly at present) or increasing the regular dose (typically

1g at present) may be considered in the postpartum period.

Kolawole et al⁶ in a prospective descriptive study to assess the common methods

of analgesia for post caesarean delivery recruited eighty-eight patients. Pentazocine was

prescribed intramuscularly in 86.4% of the patients while the remaining 13.6% had

intramuscular tramadol. They reported that most of the patients (95%) experience some

degree of pain in the immediate postoperative period. The first 24 hour postoperatvely

was particularly painful for the patients with 79.6% and 54.6% reporting moderate to

severe pain in the recovery room and on day 1 respectively. However despite this high

incidence of postcaesarean section pain most of the patient (85.2%) still expressed

satisfaction with the level of pain relief.

14

Pain remains an enormous problem after caesarean delivery in our environment.

Edomwonyi et al⁷ found moderate to severe pain post operatively in 24% of women who

had caesarean delivery, making it the commonest complication of caesarean delivery in

the post operative period. Hence there is need to seek means and methods of treating pain

adequately following caesarean section particularly in our environment.

This study therefore evaluated the efficacy of 1.2g intravenous paracetamol in the

multimodal management of pain in the immediate postoperative period after caesarean

section.

15

CHAPTER FOUR

METHODOLOGY

STUDY DESIGN: A prospective randomized double blind placebo-controlled study.

SETTING: The study population was drawn from the Obstetric patients scheduled for

elective Caesarean section at the University of Benin Teaching Hospital. The patients

participating in the study were reviewed prior to surgery, received intraoperative care and

followed up from the recovery room up to 24 hours postoperatively.

ETHICAL CONSIDERATIONS: Following approval by the institution’s Research and

Ethics Committee, the study was carefully explained to the understanding of the patients.

The patients were asked to sign a consent form if they had no objection to the study.

Data and safety monitoring board was set up to monitor the progress of the study as part

of Institutional Ethics Committee requirements. Serious complications resulting from the

study medications were reported to the Board who may take critical decisions regarding

the continuation or otherwise of the use of study medications.

SAMPLE SIZE ESTIMATION

Sample size was determined prospectively using data from previous study by

Imarengiaye et al35 where it was found that with addition of 7.5mg pethidine to

bupivacaine for subarachnoid block a mean duration of effective analgesia was

256.9mins(SD 112.2) compared with 160.5mins (SD 65.0) in the placebo group. This

study evaluated the extension (by 60mins) in the mean duration of effective analgesia

(257mins) obtained by Imarengiaye et al35 in the early post operative period. If we

consider 60minutes (23%) extension of the mean duration of effective analgesia as

clinically significant, the required sample size was determined by

16

{m (sample per group) = 2𝑐

𝛿² + 1}43

where δ = µ2−µ1

𝜎 is the standardized effect size

µ1 and µ2 are the means of the two treatment groups

σ is the standard deviation of the treatments and

c = 7.9 for 80% power and 10.5 for 90% power

μ1 (treatment 1) = mean duration of effective analgesia from the above study = 257mins

μ2 (treatment 2) = assumed mean duration of effective analgesia in this study = 317mins

σ = standard deviation of the treatment from the above study =112

Therefore:

δ = 60

112 = 0.54

thus

m (sample size per group) = 2 × 7.9

0.54²

m = 15.8

0.29+ 1

m (sample size per group) = 55

total sample size = 55 2 = 110

assuming a 10% drop out rate, an adjustment factor, y = 100/100–10 = 1.1

thus adjusted sample size = 121

17

ELIGIBLITY

Inclusion Criteria; All women with 37 weeks and above gestation with singleton

pregnancy, ASA I or II booked for elective caesarean section and expected to be

delivered of a live neonate were recruited for the study.

Exclusion criteria;

-Height less than 150cm or greater than 180cm.

-Weight greater than 110kg.

-Significant history of medical or obstetric illness such as uncontrolled diabetes mellitus,

pregnancy induced hypertension, renal disorder.

-Use of narcotic analgesic, anticonvulsant, non-steroidal anti-inflammatory drug less

than 24 hours before surgery.

-History of alcohol, analgesic or narcotic abuse.

-Inadequate intraoperative neuroaxial block requiring supplemental analgesia or

conversion to general anaesthesia.

-Absolute contraindication to subarachnoid block such as patient's refusal, skin infection

at the lumbar region for the block and coagulopathy.

RANDOMIZATION AND INTERVENTION

After approval by the Research and Ethics Committee, eligible patients were

recruited into the study. Following informed consent patients were randomized into one

of two groups. An assistant created a randomization schedule by picking an opaque

sealed envelope containing sequential random numbers that identified and placed patient

in one of two groups A or B. Group A received 1.2gram of paracetamol infusion and

Group B received 100ml of normal saline at skin closure in addition to the

18

pethidine/bupivacaine subarachnoid block. The paracetamol infusion was constituted by

adding 4 ampoules of paracetamol (Drugamol, Drugfield Pharmaceutical) into 92ml of

5% Dextrose water. The patients and assessor of outcome measures were blinded to the

study medication.

PROCEDURE:

All patients were assessed preoperatively a day before surgery by the investigator.

This includes detailed history, physical examination of all the systems, routine

investigations such as full blood count and urine analysis were requested for. Patient

blood was grouped and two units of donor's blood cross matched. The anaesthetic

procedure and pain assessment (numerical rating scale for pain) were explained to the

patient and informed written consent for the study obtained. All patients observed

overnight fasting guidelines and intravenous Ranitidine 50mg and Metochlorpramide

10mg were administered 30mins prior to commencement of anaesthesia. Equipments and

drugs for general anaesthesia and resuscitation were prepared.

On arrival in the operating theatre, the patients were randomly assigned to a group

as described above using concealed opaque envelope. Preoperative pulse rate, arterial

blood pressure (non-invasive), peripheral body temperature and oxygen saturation were

recorded using the Multiparameter monitor (HCE Marathon Z). Electrocardiography was

monitored continuously. A venous access was secured using an 18 gauge cannula in a

large forearm vein and intravenous infusion of 0.9% saline commenced.

During the 15minutes preceding the spinal block, subjects received 15ml/kg of

0.9% NaCl infusion for preloading. Spinal anaesthesia was performed by the investigator

under aseptic conditions in all patients at L2/L3 or L3/L4 interspace with the patient in

19

sitting position. After routine cleaning of lumbar half of the back with 0.5%

chlorhexidene solution and methylated spirit, a drape with an opening was applied. L2/L3

or L3/L4 interspace was identified by palpation and a 25 gauge Whitacre needle was

passed through the interspace into the subarachnoid space. Correct needle placement was

confirmed by the reflux of clear cerebrospinal fluid. On exclusion of parasthesiae, 0.5%

hyperbaric bupivacaine 10mg with pethidine 7.5mg was injected into the space. After

injection of the intrathecal medications, the parturient was returned to the supine position

with left uterine displacement. The sensory block height to cold sensation with spirit

soaked gauze was determined. Surgery was allowed to commence on attainment of

sensory block height of T6 or above. Verbal contact was maintained with the patient at all

times. The arterial blood pressure, pulse rate, mean arterial pressure, ECG and oxygen

saturation were monitored every 2minutes after deposition of the spinal medication for

the first 10minutes and subsequently every 5minutes interval till the end of the surgery.

The blood loss and urine output were also monitored during the surgery.

Complications were recorded and treated appropriately. Hypotension, (reduction

of systolic blood pressure > 25% from the preoperative value or < 90mmHg at any

time)34 was treated with fluid bolus and or aliquots of intravenous ephedrine 3mg.

Bradycardia (heart rate < 50beats/min) was treated with 0.2-0.6mg of intravenous

atropine. Fluid maintenance was achieved with normal saline at 1.6ml/kg/hr and blood

loss replaced with same at three units of fluid for each unit of blood loss and transfusion

commenced when necessary. Fluids administered were warmed to minimize the risk of

hypothermia and shivering (treated with active warming and supplemental oxygen if it

occurred). Intraoperative pain or discomfort was treated with intravenous pentazocine

20

0.5mg/kg and ketorolac 0.5mg/kg. Such patient was excluded from data analysis. Pruritus

was treated with chlorpheniramine 10mg intravenously. Respiratory depression (breath

rate < 12/min or oxygen saturation of <90%) was managed with supplemental oxygen by

a facemask and ventilatory support if necessary. At delivery of the baby 5IU oxytocin

was administered slowly intravenously with 30 IU added into 5% dextrose infusion to run

at 25drops per min.

Time of injection of local anaesthetic T₀, and skin incision was recorded. The

vital signs (systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse

rate, respiratory rate) and ECG were monitored continuously during the surgery. At skin

closure, a second Anaesthetist administered the constituted paracetamol infusion or saline

as determined by the random number picked from the envelope intravenously over

15minutes.

Time of administration of the study medication was defined as time T₁, the pain

score at this time was recorded by the investigator and then at 15mins interval into the

recovery room where the pulse rate, arterial blood pressure, respiratory rate and oxygen

saturation were monitored at the same interval for the first 1 hour, subsequently 30mins

interval till discharge to the ward. Pain score measurement was continued till patient

requests for analgesia, thereafter pain was assessed at every 2 hours for 6 hours, 4hourly

till 24 hours postoperatively. The postoperative pain score assessment was done by the

investigator and or a different assistant who was properly briefed about the study. Time

of first request for analgesia T₂ was recorded. Pain intensity was measured using

numerical rating scale from 0 to 10 with 0 representing no pain and 10 representing worst

pain imaginable at rest and at movement (defined as sitting up 90⁰ or straight leg

21

bending). Duration of effective analgesia was defined as time from deposition of local

anaesthetic to time of first request for analgesia (T₀ to T₂). Intravenous pentazocine

0.5mg/kg was administered at first analgesic request and then given 4hrly for

postoperative analgesia.

Data form was used to document patient characteristics, perioperative events,

complications and management

Measurement of outcomes:

1. Primary outcome: Time to first request for analgesia defined as time interval from

deposition of local anaesthetic agent to time of first analgesic request.

2. Secondary outcome:

a. Maternal pain scores at the time of first request for analgesic using the

numerical rating scale (NRS). This linear scale ranges ranges from 0 – 10,

where 0 represent no pain and 10 represents worst pain imaginable. The

patient was asked to score her pain after adequate explanation of the

scales.

b. Proportion of women with low pain score (NRS ≤ 4) at 6 hours

postoperatively was determined.

c. Side effects were documented.

i. Proportion of women who reported pruritus within the study

period. This was graded on a three point scale18 (0 = no symptom,

1 = symptom present but not requiring treatment, 2 = symptom

present and treatment given on request)

22

ii. Nausea/retching/vomiting – was assessed as yes or no. the

proportion of parturient in whom vomiting or retching was

observed was noted. Nausea as reported by the patients was noted

also.

iii. Sedation – assessed and graded according to a sedation scoring43

between 0 and 3 (0 = awake and alert, 1 = drowsy but respond to

verbal stimuli, 2 = drowsy but respond to physical stimuli, 3 =

unresponsive). Sedation was reported as present when the scores

was equal to or more than 1.

iv. Respiratory depression - this was documented when the respiratory

rate decreases < 10breaths/min

d. Patient satisfaction – this was assessed looking at specific aspects

(positioning/injection at the back, manipulation at delivery, post operative

pain relief) of the patient care. The 4 point Likert scale was used where

satisfaction was assessed as 0 = poor, 1 = fair, 2 = good, 3 = excellent.

DATA ANALYSIS:

Continuous data measured over time such as numerical rating scale, pulse rate and

blood pressure was assessed using unpaired student t-test to determine differences

between groups (over time). Categorical data was assessed by the X² and Fisher’s Exact

test as appropriate. Other data were analysed using statistical package for social science

(SPSS). A P-value< 0.05 was considered significant. All tests were two tailed.

23

CHAPTER FIVE

RESULTS.

A total of 121 women were recruited into the study. 112 paturients completed

the study, 3 withdrew from the study after randomization, 6 paturients were excluded

from analysis. In 2 paturients the surgery was prolonged and necessitated conversion to

general anaesthesia, 3 were excluded due to protocol violation (had analgesic

administered before they requested) and 1 received intraoperative analgesia. 57 were

randomized into paracetamol group and 55 into saline group.

Demographic characteristics were similar between the groups (Table 1). The age

of the paturients ranged from 30 – 37 yr in the paracetamol group and 29 – 37 yr in the

saline group. Most of the women in both groups were multiparous. Majority of the

women in both groups were class ASA I (n=96) with Mallampatti score of II (n=72).

There were various indications for Caesarean Section in the hospital. Repeat

Caesarean section (33.3% vs 18.2%) and abnormal lie (30.9% vs 22.8%) were the

leading indications for surgery in paracetamol and saline groups respectively. Foetal

concerns, bad obstetric history, maternal request, were other indications for elective

Caesarean section (Table II).

The baseline haemodynamic parameters were similar (Table III). The heart rate,

systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, respiratory

rate, oxygen saturation, temperature values did not exhibit statistical difference when

subjected to independent two sample t-test. The systolic blood pressure ranged between

114 – 140mmHg and diastolic blood pressure varied between 65 – 87mmHg. This

indicates that there was no haemodynamic difference within the population studied.

24

The majority of women 43.9% (n = 25/57) in the paracetamol group achieved

maximum block height of T4 compared to 32% (n = 18/55) in the saline group. This did

not achieve statistical difference, p = 0.553 (Table IV). The L3/L4 intervertebral space

was most commonly used for subarachnoid block in both groups.(Table IVb)

Table V shows that the mean volume of crystalloid for preloading was

1267.11±192.26 in the paracetamol group compared to the saline group 1230.68±182.22.

The mean skin incision to delivery time was 11.14 ± 7.57mins in the paracetamol group

compared to saline group(10.87±7.20mins) did not achieve statistical significance (p =

0.848, t-test) likewise the duration of surgery between the two groups. (p=0.288, t-test).

There was no statistical difference between the estimated blood loss and the urine output

in both groups (Table V).

Hypotension was the commonest intraoperative complication. The incidence was

51(40.8%). Thirty-three patients (26.4%) were drowsy but easily arousable. Shivering,

nausea, vomiting, bradycardia were other intraoperative complications. (Table VI).

Table VII shows that the duration of effective analgesia was longer in the

paracetamol group (322.80 ± 66.00mins) compared to the control group (242.40 ±

43.80mins; p = 0.002). The total pentazocine consumed in 24hours was higher in the

control group (124 ± 32.30mg) compared to the paracetamol group(109.82 ± 28.03mg; p

= 0.002). There was significant difference between the paracetamol group and control

group in pain score at 6 hours after deposition of local anaesthetic (2.95 ± 1.14 vs 3.65 ±

1.36 p = 0.002).

25

More women in the paracetamol group 48/57 (84.2%) had pain score less than 4

compared to control group 38/55(69.1%) at 6th hour, however, this was not statistically

significant (p = 0.058; X²-test) (Table VIII).

Majority of women in the two groups did not have postoperative complications,

41/57 (71.9%) and 41/55 (74.5%) in the paracetamol and saline groups respectively. Five

patients (8.8%) in the paracetamol group were drowsy but easily arousable as against

seven (12.7%) in the saline group. Seven patients (12.3% ) in the paracetamol group had

pruritus compared to four (7.3%) in the saline group in the post anaesthetic care unit.

These did not achieve statistical difference (p = 0.546; X²-test). Shivering, vomiting,

headache and backache were other complications in the postoperative period. There was

no event of respiratory depression. (Table IX).

Table Xa shows that 56.1% of mothers in the paracetamol group, rated their

satisfaction with pain relief after caesarean section as good compared to 36.4% in the

control group. The difference was statistically significant (P = 0.0396) Six women

(10.5%) rated satisfaction with pain relief as fair in the paracetamol group compared to

nine (16.4%) in the saline group. With regards to patient's satisfaction with injection at

the back, there was no difference between the two groups. Similarly no difference was

observed between groups in mother’s satisfaction with abdominal manipulation at

delivery (Tables Xb and Xc).

Figure 1a and 1b shows the intraoperative haemodynamic variables. The mean

systolic blood pressure was within normal values in both groups, though there was initial

decrease within the first few minutes and a later surge. The mean diastolic blood was

26

within normal in both groups. The mean Heart rate in both groups were within normal

values though higher values were observed in the early part of the surgery. This

observation may be related to maternal anxiety prior to the procedure.

The trend in pain score at rest from administration of study medication to first

request for analgesic against time is shown figure 2. The increasing trend of pain

intensity assessed on numerical rating scale showed a similar pattern in both groups prior

to analgesic request. The pain severity increased steadily from T1 onwards in both

groups, however, the paracetamol group showed a tendency towards lower pain scores in

the first few hours after surgery. Similar pattern was observed with activity in the two

groups as shown in figure 3.

Figures 4a and 4b shows haemodynamic parameters in the Post Anaesthetic Care

Unit. The haemodynamic variables appear to increase slowly over time in a similar

pattern with a lower trend observed in the paracetamol group.

27

Table I: Demographic and Other Patients Characteristics.

Parameter Paracetamol

group, N = 57

(mean ± SD)

Saline group

N = 55

(mean ± SD)

P value Level of

Significa

nce

Age (years) 33.56 ± 3.19 32.85 ± 4.10 0.310 NS

Weight (kg) 84.46 ± 12.78 82.10 ± 12.13 0.320 NS

Height (m) 1.63 ± 0.04 1.62 ± 0.06 0.320 NS

Parity

Nulliparity (0)

Multiparity (1-4)

Grand multipara( >4)

9(15.8)

46(80.7)

2(3.5)

12(21.8)

43(78.2)

0(0.0)

0.347

NS

ASA Status

ASA I

ASA II

47(82.5)

10(17.5)

49(89.1)

8(10.9)

0.420

NS

Mallampatti score

I

II

III

18(3.16)

31(54.4)

8(14.0)

10(18.2)

41(74.5)

4(7.3)

0.088

NS

NS = Not statistically significant

28

Table II: Indications for Caesarean section

Indication Paracetamol group

N = 57

n(%)

Saline group

N = 55

n(%)

Abnormal lie I3(22.8) 17(30.9)

Previous CS 19(33.3 10(18.2)

Cephalopelvic

disproportion

0(0.0) 2(3.6)

Bad obstetric history 4(7.0) 4(7.3)

Foetal concerns 10(17.5) 14(25.5)

Maternal request 2(3.5) 2(3.6)

Prevention of HIV

transmission

3(5.3) 1(1.8)

Advanced maternal age 1(1.8) 2(3.6)

Elderly primigravida 2(3.5) 1(1.8)

Placenta Previa 3(5.3) 2(3.6)

TOTAL 57(100.0) 55(100.0)

P Value = 0.594 X² = 7.827

29

Table III. Preoperative Vital Signs

Parameter Paracetamol

group, N = 57

(mean ± SD)

Saline group

N = 55

(mean ± SD)

P Value Level of

Significance

Pulse rate (bpm) 92.36 ± 12.34 95.25 ± 15.21 0.475 NS

Systolic BP (mmHg) 128.12 ± 13.80 123.22 ± 13.01 0.056 NS

Diastolic BP (mmHg) 75.91 ± 11.09 76.51 ± 11.18 0.777 NS

Mean Arterial Pressure(mmHg) 90.38 ± 11.41 91.01 ± 11.75 0.774 NS

Respiratory rate (bpm) 21.66 ± 2.06 21.70 ± 2.82 0.930 NS

Saturation (SpO2%) 97.88 ± 1.15 98.11 ± 0.88 0.234 NS

Body temperature (ºC) 36.04 ± 0.62 36.07 ± 0.36 0.723 NS

Packed cell volume (%) 33.98 ± 3.02 34.31 ± 2.89 0.560 NS

NS = Not Statistically Significant

30

Table IVa: Block height

Block height Paracetamol group

N = 57

Saline group

N = 55

T3 1(1.8) 2(3.6)

T4 25(43.9) 18(32.7)

T5 15(26.3) 20(36.4)

T6 16(28.1) 15(27.3)

Total 57(100.0) 55(100.0)

P = 0.553; X2 = 2.184

Interspace

for injection

Paracetamol

group

N = 57

Saline group

N = 55

P value Level of

Significance

L2/L3

L3/L4

2(3.5)

55(96.5)

6(19.9)

49(89.1)

0.158 NS

Table IVb: Interspace for Injection

31

Table V: Intraoperative clinical variables

Parameter Paracetamol

Group, N = 57

(mean ±SD)

Saline Group

N = 55

(mean ±SD)

P Value Level of

Significance

Fluid volume for preloading(ml)

1267.11±192.26

1230.68±182.22

0.306 NS

Incision to delivery time

11.14 ± 7.57

10.87±7.20

0.848 NS

Estimated blood loss (ml)

Urinary output (ml)

494.74 ±166.82

275.44 ±123.61

547.27±281.43

333.63±192.70

0.230 NS

0.059 NS

Duration of Surgery (min)

67.49±24.36

63.27±16.52

0.288 NS

NS = Not Statistically Significant

32

Table VI: Intraoperative complications

Complications Frequency Percentage (%)

Hypotension 51 40.8

Shivering 7 5.6

Pruritus 1 0.8

Sedation 33 26.4

Bradycardia

Rectching

Nausea

Vomiting

7

8

12

6

5.6

6.4

9.6

4.8

TOTAL 125 100.0

33

Table VII: Duration of analgesia and pain score at 6th hour.

Parameter Paracetamol

group, N =57

(mean ± SD)

Saline group

N = 55

(mean ± SD)

P value Level of

significa

nce

Time to first

analgesic request

(mins)

322.80 ± 66.00 242.40 ± 43.80 0.002 SS

Total pentazocine

consumed in 24hrs

(mg)

109.82 ± 28.03 124.45 ± 32.30 0.012 SS

Pain score at 6hour

At rest

With activity

2.95 ± 1.14

4.00 ± 1.10

3.65 ± 1.36

4.80 ± 1.24

0.003

0.003

SS

SS

SS = Statistically Significant

34

Table VIII: Proportion of women with pain score ≤ 4 on NRS at 6th

hour

parameter Paracetamol

group, N = 57

n (%)

Saline group

N = 55 n(%)

P Value Level of

significance

Favorable pain score

NRS 0 – 4 at rest

48(84.2) 38(69.1) 0.058 NS

Unfavorable pain score

NRS 5 – 10 at rest

9(15.8) 17(30.9)

Total 57(100.0) 55(100.0)

35

Table IX: Postoperative complications

Complications Paracetamol Group, N = 57 (%)

Saline Group N = 55 (%)

No complication Shivering Vomiting Sedation Pruritus Backache Headache

41(71.9) 1(1.8) 0(0.0) 5(8.8) 7(12.3) 2(3.5) 1(1.8)

41(74.5) 2(3.6) 1(1.8) 7(12.7) 4(7.3) 0(0.0) 0(0.0)

Total 57(100.0) 55(100.0)

P = 0.546; X2 = 5.451

36

Table Xa: Mother’s satisfaction with pain relief.

Level of

satisfaction

Paracetamol

group,

N = 57

n(%)

Saline P-Value Level of

Group Significance

N = 55

n(%)

Poor 0(0.0) 1(1.8) 0.4911 NS

Fair 6(10.5) 9(16.4) 0.7833 NS

*Good *32(56.1) 20(36.4) 0.0396 SS

Excellent 19(33.3) 25(45.5) 0.2459 NS

Total 57(100.0) 55(100.0)

*P = 0.0396 RR =1.477; 95%CI = 1.022-2.135

Table Xb: Mother’s satisfaction with injection at the back

Level of

satisfaction

Paracetamol

group

N = 57

n(%)

Saline P-Value Level of

group Significance

N = 55

n(%)

Poor 0(0.0) 0(0.0) -- ---

Fair 5(8.8) 10(18.2) 0.1725 NS

Good 29(50.9) 30(54.5) 0.7097 NS

Excellent 23(40.4) 15(27.3) 0.1658 NS

Total 57(100.0) 55(100.0)

Table Xc: Mother’s satisfaction with manipulation at delivery.

Level of

satisfaction

Paracetamol

group

N = 57

n(%)

Saline P-Value Level of

group Significance

N = 55

n(%)

Poor 0(0.0) 0(0.0) -- ---

Fair 2(3.5) 3(5.5) 0.6761 NS

Good 27(47.4) 23(41.8) 0.5742 NS

Excellent 28(49.1) 29(52.7) 0.7103 NS

Total 57(100.0) 55(100.0)

37

Fig 1a: Intraoperative Systolic and Diastolic BP

Fig.1b:Introperative MAP and PR

38

Fig. 2 Pattern of pain score at rest before request for analgesic

Fig. 3 Pattern of pain score with activity before request for analgesic

0

1

2

3

4

5

6

7

8

9

10

0 15 30 45 60 90 120150180210240270300330360390420

Paracetamol Group

Saline group

Time (minutes)

0

1

2

3

4

5

6

7

8

9

10

0 30 60 120 180 240 300 360 420

Paracetamol group

Saline group

Numerical

Rating

Scale

Time (minutes)

39

Figure 4a: Systolic and Diastolic BP in PACU

Figure 4b: MAP and PR in PACU

40

CHAPTER SIX

DISCUSSION

This study shows that 1.2gram paracetamol infusion in addition to

pethidine/bupivacaine subarachnoid block for Caesarean section is an effective modality

for the management of post caesarean pain with an acceptable side effect profile. The

administration of intravenous1.2grammes paracetamol prolonged the duration of

effective analgesia, reduced the total pentazocine consumption in twenty four hours with

low pain score at sixth hour of deposition of intrathecal bupivacaine 10mg plus pethidine

7.5mg. There was no observable difference between the groups with regards to the

preoperative and intraoperative variables, therefore the results of this study was not due

to chance but rather to the intervention carried out. However, disparity between groups in

number of participants may reduce the power to detect statistically significant difference

between the groups.

This combination is rather not a common strategy in the multimodal approach to

post caesarean section pain control. However, studies evaluating the efficacy of

paracetamol in obstetric population are few and have reported conflicting results.14,36,46,

Alhashemi et al44 compared IV paracetamol with oral ibuprofen in the post cesarean

section patients and found no difference in 48-hour morphine consumption. Munushankar

et al14 and Cliff et al45 demonstrated that combination of paracetamol and diclofenac

resulted in significantly less morphine requirement than paracetamol alone. Similar

effectiveness was demonstrated by Abu omar et al46 in a double-blind randomized study.

These studies agree with the results of our study in which paracetamol was found to

reduce the requirement of opioids for pain control after cesarean section. In contrast,

41

Siddik and colleagues36 did not find a significant morphine-sparing effect with IV

paracetamol even when combined with rectal diclofenac.

In these studies, opioid sparing effect was the primary outcome unlike our study

where time to first rescue analgesia was used as primary outcome measure. Measurement

of opioid consumption and the deduction of opioid sparing effect is largely dependent on

technology. A PCA device is needed to record and keep a memory of opioid requests and

uses in the immediate postoperative period. This is not a ready tool in our centre.

Secondly, time to request for analgesic represents a true measure of pain control at the

time of request. Furthermore, the activation of the PCA device in anticipation of pain

cannot be ruled out in such experiment designs. This may explain the conflicting

outcomes particularly in studies with opioid consumption as a measure of outcome.14,36

Time to first analgesic request (duration of analgesic effect) is one of the clinical

endpoints for analgesia trials. A prolonged time to first analgesic request is suggestive of

an effective postoperative pain treatment. This was evaluated in the pioneering effort of

Kafle and colleagues47 when they studied the relevance of intrathecal pethidine in

postoperative pain control. These authors, with a robust study design, evaluated spinal

pethidine alone for caesarean section. They reported a longer duration of postoperative

analgesia in the pethidine group (6hr) than the lidocaine only group (1hr). In addition, the

reported complications were mainly pruritus and drowsiness with insignificant incidence

of nausea and vomiting as the pethidine group received intravenous metochlorpramide

preoperatively. The dual properties of pethidine being an opioid agonist and local

anaesthetic may account for these observations.48

42

In a similar study, Yu et al34 demonstrated prolonged postoperative analgesia and

increased side effects particularly intra-operative nausea and vomiting. Unlike the

previous study,47 these authors used pethidine in combination with bupivacaine and

bupivacaine alone. The time from intrathecal injection to first patient-controlled analgesia

was 234mins in the pethidine group compared with 125mins in the saline group. The

pethidine group had greater incidence of intraoperative nausea and vomiting compared

with the saline group. These findings may be due to higher levels of sensory block (T2-

T4) with increased incidence of hypotension which could be related to height of patients

studied rather than body mass index. The addition of opioids make the spinal medication

to be slightly hypobaric49. Recently, Imarengiaye et al35 reported better quality of

anesthesia, longer postoperative analgesia (256.9±112.2mins vs 160.5±65.0mins;

p=0.0005) with acceptable side effect profile using reduced dose of intrathecal pethidine.

These authors show the importance of intrathecal pethidine in the prolongation of

postoperative pain free period.

However, the results of the current study show a further prolongation of

postoperative analgesia with the addition of paracetamol. This observation underscores

the role of intravenous paracetamol in multimodal strategy in the control of post

caesarean section pain. The improved postoperative analgesia, as seen in this study, may

be attributed to the action of paracetamol at both the central and peripheral component of

the pain pathway21 in synergy with pethidine action at the opioid receptors in the spinal

nerve roots.

The results of our study show superiority over some previous studies50,51

evaluating different treatment modality of postoperative pain after Caesarean section in

43

this sub-region. Idowu et al50 reported the mean duration of effective analgesia as

240±29mins as against 322.80±66.00 in our study after evaluation of the effect of

intrathecal fentanyl on duration of analgesia following Caesarean section. Menkiti et al51

reported mean time to first request for analgesia as 209±14.7min; when they evaluated

low-dose intravenous ketamine for postoperative analgesia after Caesarean section as

against our findings of 322.8±66.0mins. Our study demonstrated that the combination of

a single dose paracetamol 1.2g in addition to spinal bupivacaine/pethidine, in a

multimodal analgesic fashion, offers superior analgesia and could add value to current

practices in the sub-region.

Pain intensity may be defined as the magnitude of pain felt by a subject. It is the

single most widely assessed outcome domain in therapeutic trials. It is usually measured

using NRS, VAS, VRS, and other measures sometimes used in special population. It is

generally accepted that evaluation of a pain treatment should involve at least 2, or

possibly 3 pain measurement time points including pretreatment pain (eg, ‘‘baseline’’),

posttreatment pain (eg, at time points across the relevant pharmacokinetic profile of a

study medication).52 Thus, the current study evaluated pain intensity at first request for

analgesia and at 6 hour of administration of study medication. Evaluation of pain

intensity at first analgesic request has limited evidence. One study35 reported a higher

pain score of 7.1±2.2 in Pethidine group vs 7.5±1.6 in the control group at time of first

request for analgesia, however, this difference was not statistically significant (p =0.46).

The lower pain score (2.95±1.14 Vs 3.65±1.36, p = 0.33) at request observed in the

current study must have been as a result of better understanding of pain assessment tool

by the patients and closer monitoring prior to request.

44

The 6th hour pain score is a timeline in postoperative period where the possible

effect of the analgesics combination on pain intensity is assessed to determine if this

combination would provide adequate analgesia for this period. In our study, there was a

significant difference in terms of pain intensity at 6 hour of administration of study

medication between the control (placebo) and intervention groups. This observation was

similar to the results of some previous studies.36,46,53-55 Kilicasian et al55 studied the

effects of intravenous paracetamol on postoperative analgesia and tramadol consumption

after Caesaerean section. The authors assessed pain score at 1, 3, 6, 12, and 24 hour

postoperatively. They found that the pain score at 6 hour and the cummulative tramadol

consumption were significantly lower in the paracetamol group than the control

group(p<0.05), which agree with our findings. Although the cummulative tramadol

consumption was lower in the treatment group it is not clear how much rescue analgesic

that was given in both groups before the 6th hour. This may explain the lower pain score

observed in their study. Joshi and colleagues53 investigated the analgesic efficacy of

rectal tramadol and diclofenac in suppressing post Caesarean section pain. They found

that the mean VAS score at 6 hours was 2.63 in the diclofenac group compared with

tramadol group(2.93) with statistically significant difference. However, rectal tramadol

was associated with lower incidence of vomiting unlike the oral or parenteral route. The

favorable pain scores( ≤ 4 on NRS scale) at 6 hours in our study may be as a result of the

peak effects of rescue analgesia administered approximately an hour before the pain

assessment.

In contrast, there is a plethora of evidence suggesting that pain scores at the 6th

hour of administration of study medication may be higher.56-58. Shahraki et al58 reported

45

higher pain score at 6hour after cesaerean section under spinal anaesthesia. They

compared oral methadone and intramuscular pethidine administered in the recovery room

for pain relief after Caesarean section in primiparous pregnant women under spinal

anaesthesia. This observation may be due to the pharmacokinetics variation associated

with the route of administration of the medications. In addition multiparous women tend

to tolerate pain better than primiparous women.59 It may also be that the pain threshold in

our population is higher than that of the caucasians. However, this confounding variable

does not affect the interpretation of our result as there was no observable difference in the

distribution of primiparous women in both groups.

Pain perception by mothers after Caesarean section is an individual experience

and influenced by multifactorial attributes including beliefs, mental preparation,

adequacy of perioperative analgesia, mood and ability to cope. It has also been shown

that ethnicity affect post caesarean pain perception.60 The parturients' personality affect

pain perception and response to pain relieving medications. A higher pain score at 6th

hour was also reported by Laloola and colleagues57 when they evaluated the effect of

diclofenac suppository on post-caesarean section pain. These authors randomized 80

patients into two groups of 40 each, one group was treated with diclofenac suppository

and the other group with intramuscular morphine. The pain score at 6 hour was 8.48±0.51

in the morphine group and 8.65± 0.48 in suppository diclofenac group (p= 0.118) which

is at variant with our findings. The methodology of this study was not clear on the

technique of anaesthesia and intraoperative analgesia received by these women, these

factors may influence the mean of the pain score at the 6th hour after caesarean section.

46

Multimodal analgesia, as seen in this study, is the preferred management option

for the control of post Caesarean section pain. Interestingly, our study shows

improvements in the pattern of pain score in the intrathecal

bupivacaine/pethidine/paracetamol group. This finding seem to suggest that the

combination of paracetamol and intrathecal pethidine provides a better quality of pain

relief, as confirmed by the lower pain scores expressed by the patient in the intervention

group in postoperative period before request for analgesic. Our results agree with some

previous studies on multimodal strategy in pain treatment.14,61-63 Mitra et al62 investigated

the efficacy of diclofenac-acetaminophen combination with diclofenac-tramadol

combination in a randomized double-blind controlled trial. They reported that pain scores

were low in both groups across various time intervals while rescue analgesic

consumption was comparable between the groups(13% vs. 12%, P = 0.872). Overall, the

diclofenac-tramadol combination was more efficacious but associated with higher

incidence of post-operative nausea.

Similarly, in a resource poor setting as Nigeria, Adeniji and colleagues61

demonstrated effectiveness of multimodal analgesia in post-Caesaerean section pain

management. These authors compared the efficacy of intramuscular pentazocine or

tramadol as a single analgesic agent and in combination with daily intramuscular

piroxicam for the management of postcesaerean pain. They concluded that a multimodal

approach combining pentazocine or tramadol with an NSAID such as piroxicam would

achieve a better pain relief and maternal satisfaction. Their study indicates that

combination of pentazocine and piroxicam was significantly better than tramadol with

piroxicam though with greater level of sedation. Timelines in this study may have played

47

a role in the interpretation of results, because by 30minutes after surgery, the effect of

spinal bupivacaine may still be on board when study medication was administered.

The cummulative analgesic consumption at the end of a study is a common

measure in pain trials.64-66 The amount of analgesics consumed in the postoperative

period is a function of the intensity of postoperative pain. The amount of analgesia the

patient needs over the ensuing hours or days is measured in a number of simple ways

like amount of tablets or number of injectables or using hitech methods like PCA. The

methods based on high technology are not available in most centres in Nigeria including

our institution. Hence, the reliance on simple methods like counting of frequency of

injectable or tablets consumed.

An effective intervention should result in lower analgesic consumption than an

ineffective intervention to achieve the same pain intensity. Our study shows less

analgesic consumption in the treatment group than the control group. The literature

abound with similar observations of reduced analgesic consumption as seen in our

study.,34,50,67 Kilicasian et al55 reported that paracetamol produces effective analgesia and

reduces tramadol consumption after Caesaerean Section. These authors administered the

paracetamol 6 hourly for 24hours unlike our study where the effect of a single dose after

intrathecal pethidine was evaluated. In a multimodal fashion paracetamol has been shown

to reduce total analgesic consumption significantly14, and that the morphine-sparing

efficacy of IV paracetamol after orthopedic surgery was comparable with NSAIDs at

approximately 35%.14,15,37 In contrast, some studies36,67 could not demonstrate significant

opioid sparing effect of paracetamol as a component of multimodal analgesia. These

48

opposing observation may suggest that visceral pain could be less sensitive to

paracetamol.

The intraoperative haemodynamic changes in mean systolic blood pressure, mean

diastolic blood pressure and mean arterial blood pressure appear to be within normal

values despite the increased incidence of hypotension observed in our study. The initial

reduction in these variable is most probably due to sympathectomy attributable to spinal

anaesthesia. The transient surge or increase in these variable may reflect autotransfusion

from the placenta bed after delivery of the baby. Prevention of hypotension by

preloading, treatment with vasopressor and adequate volume replacement with

crystalloids and or blood transfusion may contribute to the stable intraoperative

haemodynamic variables observed in our study. Recently, Langesaeter et al68 evaluated

maternal haemodynamic changes during spinal anaesthesia for Caesarean section. They

used continuous invasive blood pressure and cardiac output monitoring unlike our study

which employed the traditional discontinuous noninvasive blood pressure and heart rate.

This has lead to better understanding of the maternal haemodynamic effects of spinal

anaesthesia and effect of vasopressors. They suggest that heart rate changes to

vasopressors is a good surrogate marker for cardiac output.

The postoperative haemodynamic parameters after Caesarean section increased

over time in a similar pattern but these variables were consistently lower in the

paracetamol group. This observation may be related to sympathetic response as the pain

intensity increases with the elimination of the analgesics received by the patient. A more

favourable evolution of heart rate, a good index of pain control together with lower

postoperative pain score were also observed in the current study. Nevertheless, these

49

findings seem to suggest that the combination of paracetamol and intrathecal pethidine

gives a better qaulity of pain relief, as confirmed by the higher satisfaction scores

expressed by patient on pain relief at the end of the study.

It is often perceived that multimodal treatment of pain would result in reduced

side effects of the component drugs used. The findings of our study further confirm this.

The most common side effect of spinal anaesthesia is maternal hypotension. The

incidence varies, some studies reported 70 - 80%,69 others reported 15% - 57%.70-74

although the incidence is dependent on the definition of hypotension used in such a study.

Several factors including dose of local anaesthetic agent, positioning, fluid preloading

and co-loading, and the use of prophylactic or therapeutic vasopressors affect the

incidence of spinal induced maternal hypotension. In our study the incidence was 40.8%,

which was lower than the report of some authors69 but comparable to 46.8% reported by

Hartmann and colleagues.72 The observation in the current investigation despite the use

of reduced dose of bupivacaine may be due to the speculations that addition of opioid

reduces the baricity of bupivacaine and altered its spread in an in vitro model.49 The

reduced density of the intrathecal bupivacaine makes the mixture hypobaric in

cerebrospinal fluid. Hence the block is higher than predicted with consequent increased

pharmacologic sympathectomy and a decrease in blood pressure. Vasodilatation caused

by pethidine may also contribute to the increased incidence of hypotension.

One of the goals of anaesthetist-managed post caesarean pain is low incidence of

side effects,75 therefore it is worthwhile to determine the occurence of complications or

side effects in the postoperative period. It is interesting to note that the observed few

complications were most probably due to intrathecal opioid rather than paracetamol in

50

this multimodal analgesia. Such side effects as seen in our study includes pruritus,

sedation, nausea and vomiting but none of these necessitated treatment. Amongst these,

sedation(drowsy but easily arousable ) was the most common. This effect has been

speculated to be of benefit as it obviates the need for any probable sedation during spinal

anaesthesia47 as may be necessary in other regional techniques. This observation is in

agreement with the report of a previous study35 where small dose of intrathecal pethidine

was evaluated. However, significant nausea, vomiting and pruritus have been reported in

a study which employed two to three times the dose (15mg and 25mg) of pethidine used

in the current study, particularly where pethidine was used as a sole agent for

subarachnoid block.34 Pruritus which is quite common after intrathecal morpine76 was

seen in our study unlike in some previous studies34,35 in which pruritus was not observed

with intrathecal pethidine. The mechanism for this not clear. The larger sample size in

our study may account for this observation.

Satisfaction is one of the most frequently reported measures for quality of care

and enhanced satisfaction has been identified as a goal for improvement in health

care.77,78 However, the concept of satisfaction is complex and poorly defined.79 A

definition suggested by Ware et al80 is that an individual's satisfaction with health care is

a "personal evaluation of healthcare services and providers". These evaluations reflect the

personal preferences of the individual, the individual's expectations, and realities of the

care received. Linder-Pelz and Struening81 provide a similar definition noting that

satisfaction comprises of a "multiple evaluations of distinct aspects of healthcare which

are determined (in some way) by the individual perceptions, attitudes and comparison

51

processes". This definition highlights the multidimensional nature of satisfaction which

the current study attempted to evaluate.

Our study evaluated patient satisfaction with specific aspect of care; pain relief,

injection at the back and uterine manipulation at delivery of the baby. Our study shows

that majority of women were more satisfied with postoperative pain relief than injection

at back and uterine manipulation at delivery of the baby. The differential satisfaction rate

among women with these aspects of care may be due to the relative importance or value

individual women place on the different aspects of care. This is unlike previous

studies,1,8,13,15,82 where satisfaction was measured as a 'secondary outcome' by simply

assessing the overall or global satisfaction. Most of these measurements may have been

data driven and not based on the main theoretical models of satisfaction. For example,

none of the measurements incorporated fulfillment of expectation into their assessment,

which has been shown to be particularly important for women during childbirth.75,83

Indeed, the measurement of a multidimensional entity like satisfaction with care, using a

unidimensional tool (VAS, Likert scale) as shown in several studies, often fail to evoke

the appropriate opinion about care. The assessment of the different component of care

should be emphasized

52

CONCLUSION

This prospective randomized controlled trial of bupivacaine/pethidine/

paracetamol and bupivacaine/pethidine/placebo, demonstrated that bupivacaine,

pethidine, and paracetamol combination provided superior pain relief post Caesarean

section. The improved efficacy and quality of post-operative analgesia with this

combination was also evidenced by higher satisfaction with pain relief expressed by

mothers at the end of the study. The associated side effects were minimal. This

combination may therefore be recommended as a management protocol for pain

treatment after caesarean section in our institution and West Africa sub-region at large

where other opioids and high technology PCA are not readily available.

53

LIMITATION OF THE STUDY

1. Non-availability of patient controlled analgesia device. It has the advantage of

being accurate, objective assessment of the timing and titration of analgesic

requirement with minimum external interference. However, cost and increased

nursing surveillance of patient and pump's function are some limitations of this

device.

2. It may have been clinically prudent to estimate the drug level of paracetamol in

the blood and estimate the liver enzymes involved in the metabolism of

paracetamol. Evidence in the literature indicate lack of untoward effects at the

dose used in this study

54

RECOMMENDATIONS

1. In the absence of ready preparation of intravenous paracetamol infusion

1.2gram paracetamol should be constituted and used to treat postcaesarean

pain.

2. Multimodal Analgesia should be encouraged with available medications for the

management of postcaesarean section pain. This provides high quality

postoperative analgesia with minimal side effects.

3. Paturients should be educated in the antenatal clinics/classes on postoperative

pain management. This has been shown to increase the efficacy of systemic

opioids analgesic technique after Caesarean Section.

55

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APPENDIX I

INFORMED CONSENT

TITLE OF STUDY: EFFICACY OF 1.2 GRAM PARACETAMOL IN THE

MULTIMODAL MANAGEMENT OF POST CAESAREAN SECTION PAIN.

INVESTIGATOR:

DR AUDU ALEXANDER, Department of Anaesthesiology, University of Benin

Teaching Hospital.

FINANCIAL SPONSORSHIP:

This research project is self-sponsored. The study medication will be provided by the

hospital. There is no conflict of interest. I do not have any financial relationship with the

company that produce the drug neither does any member of my family work in the

company.

PURPOSE OF THE STUDY:

Pain is a common experience after operation to deliver a baby. It is not desirable yet it

cannot be completely prevented. It is more severe immediately after the operation and

this may prevent you to care for your baby very well after the operation. The injection

given to you at your back to make you not feel pain will last 2 to 3hours. The purpose of

the research is to know whether this period will be prolonged if another drug called

pethidine is added to the injection, and another injection called Paracetamol is given to

you through a drip after the operation.

PROCEDURE INVOLVED IN THE STUDY:

You are being requested to participate in this study because you are undergoing an

operation to deliver your baby. You will be asked some questions related to your general

state of health. You will be randomly assigned to one of two groups: Group 1 will receive

the normal care for the management of pain after the operation while Group 2 will

receive an injection called Paracetamol in addition to the normal care. If you are assigned

to Group 2, after delivery of your baby, you will be given an injection called Paracetamol

through a drip to help reduce pains after the operation.

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VOLUNTARY PARTICIPATION:

You have a choice to participate in this study or not to participate in it. You are free to

withdraw from the study at any time if you so desire. Your refusal or withdrawal from

participation will not in any way affect your management or care in the University of

Benin Teaching Hospital.

COMPENSATION:

There shall be no financial compensation for participation in this study.

CONFIDENTIALITY:

The information provided in this study shall be treated with utmost confidentiality. Every

information obtained with the questionnaire will be encoded in a file in my personal

computer and pass worded. The questionnaire/data will be stored under lock and key in

my file cupboard.

BENEFITS:

The study when completed will help determine if paracetamol (1.2gram) can be added as

a routine analgesic to treat pain after the operation to deliver a baby. Benefits may

include closer monitoring and a longer pain free period after the operation.

RISKS:

There are minimal complications from the use of paracetamol when used at safe doses

(as in this study), the occurence of complications such as nausea and vomiting will be

minimal. Liver damage is rare and associated with overdose.

CONTACT INFORMATION:

Dr Audu Alexander

Department of Anaesthesiology

University of Benin Teaching Hospital,

Benin City

Phone Number:08056282665

Email: docalexaudu@yahoo.com

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Ethics and Research Committee,

University of Benin Teaching Hospital,

Benin City.

Phone Number: 0818194045

Consent: I have read the above statement and was able to ask questions and express my

concerns which have been satisfactorily responded to by the investigator. I hereby accept

to participate freely in the study

Name……………………………………………………………..

Signature………………………………………………………....

Date……………………………………………………………….

Witness’s Name……………………………………………..........

Signature……………………………………………………….....

Date……………………………………………………………….

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APPENDIX II

EFFICACY OF 1.2 GRAM PARACETAMOL IN THE MULTIMODAL

MANAGEMENT OF POSTCAESAREAN SECTION PAIN

DATA COLLECTION FORM

Preoperative

Date……………………………………………………………………………...

Name: …………………………………… Hospital No: ……………………….

1. Age (years): ………………………………………………………………….

2. Parity: ………………………………………………………………………..

3. Height (m): ...………………………………………………………………

4. Weight (kg): …………………………………………:……………………...

5. Indication for surgery: ……………………………………………………….

6. Intercurrent Medical Illness: ………………………………………………...

7. Drug therapy if 6 is yes……………………………………………................

8. Mallampatti score……………………………………………………………

9. ASA Status: ……………………………………………….............................

10. Results of Investigations;

a. FBC

b. Serum electrolyte and Urea

c. Urine analysis

d. Others

11. Premedication: ……………………………………………………………….

12. Baseline vital signs;

a. Pulse rate (bpm): …………………………………………………..

b. Systolic blood pressure (mmHg)…………………………………..

c. Diastolic blood pressure (mmHg)………………………………….

d. Mean Arterial pressure (mmHg)…………………………………...

e. Oxygen saturation (%): ……………………………………………

f. Body temperature (⁰C): ……………………………………………

g. Respiratory rate……………………………………………………

Intraoperative care:

13. Volume of fluid for preloading (ml)…………………………………………

14. Medications used/dosage

Bupivacaine (mg)…………………………………………………………

Pethidine (mg)…………………………………………………………….

15. Time of LA deposition T₀: …………………………………………………

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16. Vital signs;

Time/min 2 4 6 8 10 15 20 25 30 35 40 45 50 55 60

BP(syst/dia)

mmHg

P.R (bpm)

SPO₂ (%)

Temp(⁰C)

Resp.

rate/min

17. Interspace used for block: ……………………………………………..

18. Maximum Block height: ……………………………………………….

19. Immediate complications:

Hypotension…………………………………………………………

Vomiting…………………………………………………………….

Others……………………………………………………………….

20. Treatment

Fluid……………………………. ………………………………….

Ephedrine use (mg)…………………………………………………

Others…………………………………............................................

21. Time of Skin Incision: …………………………………………………

22. Time of delivery: ………………………………………………………

23. Intraoperative Analgesic supplement……………………………….......

24. Time of commencement of Skin Closure/Time of Administration study

Medication T₀: ……………………………………………………………

25. Study Medication Administered: A……………. B…………………….

26. Time surgery ended (last stitch) …………………………………………….

27. Duration of surgery (skin incision to last stitch): ……………………………

28. Cadre of Surgeon: ……………………………………………………………

29. Vital signs in the Recovery Room; Time/min 15 30 45 60 90 120 150 180

BP, syst/dist(mmHg)

P.R(bpm)

SpO₂(%)

Temp.(⁰C)

Resp. rate// min

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Pain scores

Time/hours

NRS

30. Time of first Analgesic request T₁: ………………………………………

31. Time to first Analgesic request T₀ - T₁: ………………………………………

32. Total analgesia administered in 24 hours (mg): ……………………………

33. Complications:

Complications Intraoperative Postoperative

Hypotension Yes/No Yes/No

Resp depression Yes/No Yes/No

Shivering Yes/No Yes/No

Bradycardia Yes/No Yes/No

Retching Yes/No Yes/No

Nausea Yes/No Yes/No

Vomiting Yes/No Yes/No

Sedation Yes/No Yes/No

Backache Yes/No Yes/No

Pruritus Yes/No Yes/No

Others…………….

34. Pruritus score: ……………………………………………………………

35. Sedation score: …………………………………………………

36. Management of complications.

………………………………………………………………………………………

……………………………………………………………………………

Time 0min 15 30 45 60 90 120 160 190 220 250 280 310 340 370 300 330 360

NRS

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37. Estimated blood loss…………………………………………………

38. Urine output………………………………………………………

39. APGAR score……………………………………………………………

40. Patient satisfaction with pain relief;

Poor [ ], Fair [ ], Good [ ], Excellent [ ]

41. Patient satisfaction with positioning/injection at the back

Poor [ ], Fair [ ], Good [ ], Excellent [ ]

42. Patient satisfaction with manipulation at delivery;

Poor [ ], Fair [ ], Good [ ], Excellent [ ]