Effects of Intravenous Hyoscine Butylbromide on Labour Outcome and Its Safety Among Parturients in Lautech Teaching Hospital Ogbomoso, Nigeria

DISSERTATION

TITLE:

EFFECTS OF INTRAVENOUS HYOSCINE BUTYLBROMIDE ON LABOUR OUTCOME AND ITS SAFETY AMONG PARTURIENTS IN LAUTECH TEACHING HOSPITAL OGBOMOSO, NIGERIA.

INSTITUTION

DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY, LADOKE AKINTOLA UNIVERSITY OF TECHNOLOGY TEACHING

HOSPITAL, OGBOMOSO.

INVESTIGATOR DR TAIWO OLUFIKOLA AKINBILE

DISSERTATION SUBMITTED IN PARTIAL FULFILLMENT OF THE PART II (FINAL) FELLOWSHIP EXAMINATION OF THE NATIONAL POSTGRADUATE MEDICAL COLLEGE OF NIGERIA

MAY, 2016.

DECLARATION

I, Dr Taiwo Olufikola AKINBILE, hereby declare that this dissertation is original and it has not been presented to any other College for a Fellowship nor has it been submitted elsewhere for publication.

Signature Date

TABLE OF CONTENTS

Pages

Title Page i

Declaration ii

Table of Contents iii

List of Tables iv

List of Figures v

List of Acronyms and Abbreviations vi

Certification viii

Abstract ix

1. Introduction 1

2. Literature Review 4

3. Justification of the Proposed Study 12

4. Objectives 14

5. Methodology 15

6. Result 23

7. Discussion 37

References 43

Appendix I (Information on the Study Procedure to Participants) 50

Appendix II (Consent Form) 51

Appendix III (Proforma) 52 3

LIST OF TABLES

Pages

Table 1: Socio-Demographic distribution among respondents 23

Table 2: Obstetric history among respondents in the study groups 25

Table 3: Pattern of First stage of labour among respondents in the study 26

groups

Table 4: Indication for Caesarean delivery among respondents that had 29

caesarean delivery in the study groups

Table 5: Pattern of Second and Third stages of labour among respondents in 30

the study groups

Table 6: Fetal Outcome in the study groups 32

Table 7: Maternal drug adverse effects 33

Table 8: Pain-Relief Assessment and Satisfaction scale among respondents 34

in the study groups

Table 9: Duration of first stage of labour and rate of cervical dilatation 39

among nulliparous and parous respondents

LIST OF FIGURES

Pages

Figure 1: Bar chart showing oxytocin augmentation of labour among 27

respondents in the study groups

Figure 2: Bar chart showing mode of delivery among respondents in 28

the study groups

LIST OF ACRONYMS AND ABBREVIATIONS

ANC : Antenatal clinic

CNS Central Nervous System

FDA Food and Drug Agency

LTH: LAUTECH Teaching Hospital

O & G Obstetrics and Gynaecology

SCBU Special Care Baby Unit

USA United States of America

WHO World Health Organization

SUPERVISOR’S ENDORSEMENT

This study dissertation was performed by Dr Taiwo Olufikola AKINBILE under our supervision and we supervised every stage of it from onset to completion, as well as the writing of the dissertation.

DR K. M. OWONIKOKO MB;BS (ILORIN), MSc (Reproductive Biol.) FWACS, FMCOG

SENIOR LECTURER/CONSULTANT

DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY,

LADOKE AKINTOLA UNIVERSITY OF TECHNOLOGY TEACHING HOSPITAL OGBOMOSO, OYO STATE.

DR A. O. ADENIJI, MBBS (Ib), FWACS, FMCOG(Nig), FICS

PROFESSOR/CONSULTANT

DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY,

LADOKE AKINTOLA UNIVERSITY OF TECHNOLOGY TEACHING HOSPITAL OGBOMOSO, OYO STATE.

CERTIFICATION

This is to certify that Dr. Taiwo Olufikola Akinbile is a Senior Registrar in the Department of Obstetrics and Gynaecology of Ladoke Akintola University of Technology Teaching and this study was conducted in the department.

DR A.S. ADEYEMI, MBBS (Ib), FWACS.

THE HEAD,

DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY,

LADOKE AKINTOLA UNIVERSITY OF TECHNOLOGY TEACHING HOSPITAL OGBOMOSO, OYO STATE.

ABSTRACT

Background

The search for methods that shorten and thus reduce the discomfort of labour processes without associated maternal or fetal adverse effects are still on-going.

Hyoscine butylbromide has been in use in contemporary obstetric practice but reports supporting its efficacy in reducing the duration of labour are still conflicting.

Objective

This study is aimed at determining the effect of intravenous hyoscine butylbromide in shortening the length of labour and its safety among the parturients.

Design

Randomized clinical trial.

Population

Consented pregnant women at term after spontaneous onset or induction of labour.

Methods

Either hyoscine butylbromide (Buscopan®) or placebo was given intravenously once the women entered active labour (at 3 - 5cm cervical dilatation) after randomization using computer generated numbers. Participants were evaluated using a proforma and data obtained were entered into computer. Analysis was done with Statistical Package of

Social Sciences (SPSS) version 17.

Results

Two hundred and sixty (260) parturients completed the study. Of these, 128 received hyoscine butylbromide and 132 women received the placebo. The mean age of patients in hyoscine group was 29.77 ± 6.49 years and 28.89 ±3.94 years for placebo group. The mean time for the first stage in the control group was 506.17±210.78 minutes, compared with 364.73±207.10 minutes in the hyoscine group (p<0.001). There was no statistically significant difference in the duration of the second (p = 0.757) and third stages of labour (p = 0.137) or in APGAR scores, as well as need for SCBU admission. No significant adverse effect was noted in the group of women receiving hyoscine compared with the control group. More women in the hyoscine group were significantly satisfied than placebo group following delivery (p<0.001), but no difference in pain assessment (p=0.060) or relief score (p=0.653) in both groups.

Conclusion

Intravenous hyoscine butylbromide was effective in shortening the duration of the first stage of labour, with no associated maternal or neonatal adverse outcomes.

Keywords: Hyoscine butylbromide; duration of labour; safety; outcome of labour.

1. INTRODUCTION

The subject of cervical dilatation and progress of labour has puzzled Obstetricians for a long time, with prolonged labour having implications for both the mother and the fetus.

Acceleration of labour is considered to be an important factor in reducing maternal morbidity as well as the neonatal complications. Several drugs like antispasmodics, tranquillizers, prostaglandins and psychotherapeutic methods have been tried in the past to facilitate cervical dilatation and hence augment labour, but majority of these were found to have ill effects on the mother and the fetus.1

The risks for complications of prolonged labour are much greater in poor resource settings. Therefore, it is common practice to intervene in labour process to avoid this by rupturing membranes (amniotomy), giving medications to speed up contractions and providing ongoing support2,6,8 – active management of labour. The principle of active management of labour was introduced to shorten the length of labour.3,6,13 Both the

Obstetrician and the labouring woman would like to accomplish the delivery in the shortest time without compromising the maternal and fetal safety.4

Labour is a multifactorial process which involves myometrial contraction, cervical effacement and dilatation and expulsion of fetus and placenta in an orderly manner.

Many times it is observed that despite good uterine contractions, cervix fails to dilate or dilates very slowly, that is cervical dystocia.5 This inadvertently results to prolonged labour with associated adverse fetal, neonatal and maternal outcomes. 11

Reducing the length of labour is a highly desirable goal of intrapartum care, both from a perspective of maternal and fetal well-being, and for the providers of the birth services.6

Avoiding a long, protracted labour entails shorter exposure to pain, anxiety and stress and would thus translate into a major improvement in maternal satisfaction with the childbirth experience.7

Based on the premise that shortening the length of labour is beneficial, interventions aimed at accelerating the progression of labour have been introduced routinely as part of standard labour management and care throughout the 20th century. Hence the advice for the use of antispasmodic agents like hyoscine butylbromide, to hasten the first stage of labour.

Potential benefits of a reduced first stage time include a reduced incidence of chorioamnionitis, neonatal sepsis, and puerperal sepsis; all of which are increased in women with prolonged labour.3,7,8 A need for reduced repeat doses of opioid analgesia, which is associated with neonatal respiratory depression, is also a major benefit of a shorter labour process. This is particularly true in regions where epidural analgesia is not widely available, so opioid medications are used with increased frequency. Additionally, it is certain that any intervention which can safely reduce the amount of time spent in the painful process of parturition would be greatly appreciated by our women.

The reduction in first-stage duration may also prove to be of particular importance in the context of women with borderline placental reserve, as may be encountered in 12 women with hypertension (both chronic and gestational), and in women with sickle cell anaemia, which is quite common in our population. Prolonged labour in these women may result in the feto-placental reserves being depleted, with consequent signs of fetal distress, and the increased possibility of a caesarean delivery. Shortening the labour duration could conceivably help prevent some of these surgical interventions.

This hospital based study is therefore to determine whether hyoscine butylbromide shortens the duration of labour, without an increase in maternal or neonatal complications in LAUTECH Teaching Hospital. The indigenous information thus obtained hopefully will be beneficial in formulating policies that will enhance better management of labour and prevent prolonged labour in this hospital.

2. LITERATURE REVIEW

Management of prolonged labour represents a challenging area in the daily obstetric practice. In 1993, Handa and Laros defined the arrest of active phase of labour, as failure of labour to progress for 2 hours or more,1 and in 1994, WHO proposed labour management partograph in which protraction is defined as less than 1cm/hour cervical dilatation for a minimum of 4 hours.6 The problems and hazards of prolonged labour, both for the mother and fetus have been recognized for many years. Prolonged labour increases the risk of maternal exhaustion, postpartum hemorrhage, sepsis, fetal distress and admission to the neonatal intensive care unit. Management of prolonged labour entails shorter exposure to pain, anxiety, and stress, and would thus translate into a major improvement in maternal satisfaction with child birth experience.8,11,13 Several methods have been used to prevent prolonged labour including amniotomy and oxytocin. Amniotomy has potential for infection, and can be combined with oxytocin for better results while oxytocin can cause uterine hyperstimulation, water intoxication, vomiting, diarrhea, fetal distress, and neonatal jaundice.4,7,8,11

Use of antispasmodics for reducing the duration of labour was first described in 1937 by

Hirsch, who reported a decrease in labour length by two to four hours following intrapartum administration of an antispasmodic-like drug (Syntropan®), mainly among older nulliparous12; this was followed by many studies that investigated the role of antispasmodics in prevention of prolonged labour. Antispasmodic agents like 14 drotaverine hydrochloride,15,35 hyoscine butylbromide,20-22,24-29,31,33,35-37,39-43 valethamate bromide,15,25 rociverine,14 phloroglucinol,41,42 have been used in shortening labour duration in various studies with good results. An ideal antispasmodic for accelerations of cervical dilations should have a prompt and long lasting action, no adverse effects on uterine contractility and be free from risk of uterine inertia. It should also have minimal side effects in the mother and foetus.42

For active management of labour along with good uterine contractions, simultaneous cervical dilatation and softening are required. Cervix plays essentially a passive role as an innocent obstruction and is acted upon by all the forces of labour. Cervical dilatation is the resultant of all the driving forces of uterine contractions acting against passive tissue resistance.27 But in spite of good uterine contractions, the cervical dilatation may be hampered due to inhibitory impulse in the form of spasm leading to prolonged labour.5,27 Recent biochemical evidence suggests that the cervix could obstruct labour by a sustained spasm due to insufficient connective tissue remodeling. Studies have also shown that besides a decrease in fibrous connective tissue in the cervix at term, there is an increase in the proportions of smooth muscle fibres, which also become dissociated and hypertrophic, and are aligned in a particular direction.43 These studies, relating to the presence of smooth muscle fibers in the cervix logically support the role of antispasmodics and smooth muscle relaxants in helping the cervix to dilate. Various drugs have been used so far to obtain effective dilatation of the internal os, majority of

15 them were found to have its effect on the fetus and mother. Modern Obstetricians are now in search of new drugs, which have got the sole beneficiary effect on the dilatation of the internal os with minimal side effects on fetus and the mother. 27

Hyoscine N-butylbromide (HBB) is a derivative of hyoscine, which is extracted from the leaves of the Dubosia tree found mainly in Australia. It is known for its antispasmodic action and has been around since 1951.16,23 HBB acts by inhibiting cholinergic transmission in the abdominal and pelvic parasympathetic ganglia, thus relieving spasm in the smooth muscles of gastrointestinal, biliary, urinary tract and female genital organs, especially the cervico-uterine plexus and thus aiding cervical dilatation.16,17,20

Uterine contractions are not affected,20 rather due to better co-ordination between uterine contractions and cervical dilatation, the latter is increased.20,21

Hyoscine-N-butylbromide is also referred to as Scopolamine-N-Butylbromide, N-

Butylscopolammonium Bromide, and butylscopolamine. It is a semisynthetic derivative of scopolamine and marketed under the trade name Buscopan.17-19,23 Its molecular formula is C21H30BrNO4 and has a molecular weight of 440.37. Hyoscine butylbromide contains a nitrogen molecule with four different bonds to varying chemical groups, making it a quaternary ammonium compound.18 Hyoscine butylbromide is highly polar, and in contrast to ammonium (NH4 +) and other related compounds, it retains its polar nature regardless of the surrounding pH. Hence it is only partially absorbed (8%) following oral administration and the systemic availability was found to be less than

1%18 Nevertheless, despite the briefly measurable low blood levels, hyoscine butylbromide and/or its metabolites have been observed at the sites of action.18 After intravenous administration, the substance is rapidly distributed into the tissues (t½ = 29 min). Its onset of action after intravenous dosing is 10 minutes, peak effect is seen at 20-

60 minutes, and action lasts for two to four hours.16,18

The attachment of the butyl-bromide moiety effectively prevents the movement of this drug across the blood–brain barrier minimizing undesirable CNS side-effects associated with hyoscine butylbromide, and plasma protein binding is low. Most of the drug is metabolized in the liver, with half-life of the terminal elimination phase being approximately 5 hours. Approximately half of the metabolites are excreted in urine.16,18,23,24,32

Hyoscine butylbromide is a peripherally acting antimuscarinic, anticholinergic agent.16

The mechanism of action of Buscopan® is that it blocks the action of acetylcholine on the muscarinic receptors found on the smooth muscle walls of the gastrointestinal, urinary and lower genital tracts and thus reduces the spasms and contractions. This relaxes the muscle and thus reduced the pain from the cramps and spasms.16,17,20-23

Recent studies have also shown that HBB potently blocks nicotinic receptors, in a non- competitive fashion, in vitro. If this action also occurs in vivo, then this would add an additional mechanism of action for the drugs spasmolytic activity.18 Since vagotonic states lead to increased tension at the lower uterine segment and cervix,

17 parasympatholytics(antispasmodics) are useful in arrested or delayed cervical dilatation.

In addition, the pain relieving effects of parasympatholytics made HBB the drug that was tried for labour acceleration and analgesia.21

Side effects of Buscopan® affect different people in different ways and some are more common than others. These include constipation, reduced ability to sweat, dry mouth, allergic skin reactions and rashes, flushing, light sensitivity, tachycardia, urinary retention, allergic reactions, confusion, nausea and vomiting and dizziness. Fortunately, the most common adverse effects are usually mild, and resolve spontaneously as the medication is cleared from the system.16,19,23 In addition, it should be noted that the type and severity of side effects are quite closely linked to the method of administration. Because the oral absorption and subsequent systemic bioavailability are so low (8%, and 1%, respectively), side effects from this method of administration are much less common at standard doses, than with the equivalent dose given parenterally.18 However, HBB has an excellent safety profile and as such has been approved by the Food and Drug Administration in the USA.17 In addition, the drug is considered compatible with breastfeeding.34 It is contra-indicated under the following circumstances: glaucoma, muscle weakness such as Myasthenia gravis; paralytic ileus, dilated colon (Megacolon), fructose intolerance, pyloric stenosis, and porphyria.16,18,19,23,32

Hyoscine butylbromide has been in usage for more than half a century in varying doses

(20, 30mg, 40mg) and various routes of administration (intramuscular, intravenous, rectal, oral).24 However, the advantages of intravenous route in a controlled manner

(slow IV over 1-2 minutes) are its rapid onset of action and bypass of hepatic metabolism. The rectal route is also popular for this reason.24,34 Corsen et al37 studied the various uses and mode of action of HBB in Obstetrics and Gynaecology, and found that most prompt action occurred with intravenous and suppository routes, optimal time of administration was at 2.5 - 3cm cervical dilatation and no side effects were observed with up to 30mg dose. Some authors have used a single 40mg dose of HBB24 while others used 40mg given in 2 doses at different intervals.25

Hyoscine butylbromide, in the form of Buscopan®, has been investigated by several authors as a labour accelerant, with HBB shown to cause a statistically and clinically significant reduction in the time from drug administration to delivery, with no significant adverse effects on either mother or neonate.20-22,24-29,31,33-37,39-43 Its value lies in the reduced time spent in the first stage, the reduced total duration of labour and consequently the reduced overall time spent in pain by the labouring mother. In contrast, Gupta et al26 conducted a study which compared HBB to drotaverine and to no drug (50 patients in each group), showed no difference between the three groups, resulting in the conclusion that neither drug has any place in the augmentation of labour. Many studies compared the drug to normal saline or no drug at all,22,24,34 and

19 some comparing it to another spasmolytic drug (drotaverine hydrochloride,26,27 valethemate bromide25,43), and the last comparing all three (HBB, drotaverine, and no drug).26

The drug was given intravenously in some studies, in doses between 20mg22,28 and

40mg24; intramuscularly20,21,29,33 and rectally27,34,38,43 in other studies. In a study by

Samal et al.33 and Samuels et al,22 IV administration of 20 mg HBB as a single dose led to shorter duration of labour. Tewari et al.25 demonstrated that administration of 40 mg IV hyoscine in two divided doses reduced the mean duration of labour by five hours and twelve minutes in the group receiving hyoscine compared with the control group.

Battacharya et al.21 studied the effect of 20 mg IM Hyoscine in the active phase of labour in 100 primigravid women and concluded that the mean duration of labour is reduced by 3 hours and 40 minutes. Prospective studies by Sirohiwal34 and Vellanki43 found that administration of HBB suppositories during labour significantly shortened the duration of the first stage of labour.

Some comparative studies have confirmed that Buscopan® is superior in shortening the duration of labour when compared with other antispasmodics. Sameena et al27 concluded that both Drotaverine and Hyoscine butylbromide are effective in shortening duration of labour without any significant detrimental effects to the mother and the new born. But Hyoscine butylbromide dilates the cervix more rapidly than Drotaverine and the duration of active phase was shorter in Hyoscine butylbromide group than

Drotaverine group. Similar result was demonstrated by Vellanki43 who compared the effects of buscopan® to epidosin® (Valathemate bromide) on cervical dilatation in labour. These authors recommended Hyoscine butylbromide, because of its convenience of administration (as rectal suppository), as a comparable alternative in rural setups where trained medical personnel may not be available most of the times.27,43

Above studies demonstrated that effective shortening of the duration of labour was achieved without any significant detrimental effects to the mother and the newborn.

However, Aldahhan et al44 reported that administration of buscopan® decelerate cervical dilatation in the first stage of labour and cause prolongation in its duration, with associated obvious fetal risk as well as increase in the rate of caesarean section.

Aggarwal et al24 looked at hyoscine butylbromide primarily as an analgesic for the pain associated with labour and showed that intravenous HBB provided pain relief of up to

36%, as compared to placebo. In this study, labour was shortened by 4 hours 30minutes in the test group compared to the controls.24 Moreover, other studies showed statistically significant associated pain relief or reduction in analgesic use in the HBB group.27,38

3. JUSTIFICATION OF THE PROPOSED STUDY

Active management of labour reduces the number of prolonged labours and labour duration, without having any adverse effects on the mother or the fetus1. A shorter duration of labour from admission to delivery has also been consistently reported in numerous studies that include women treated with the active management protocol2-5,7-

9. Intervention with drugs is among the options used through active management of labour; this includes use of analgesics,7 oxytocin,8,9 prostaglandin derivatives7 and smooth muscle relaxants.11 Smooth muscle relaxants (antispasmodics) are well accepted in progression of labour. Apart from uterine contraction, cervical dilatation is an important factor which determines the duration of labour. It is the resistant of all driving forces of uterine contraction against passive tissue resistance.4 Smooth muscle relaxants inhibit impulses in the form of spasm that impairs the effective cervical dilatation.11,12,14,15

The anticholinergic effect of antispasmodics, including hyoscine butylbromide, with consequent relief of spasm in the smooth muscles of gastrointestinal, biliary, urinary tract and female genital organs, especially the cervico-uterine plexus, aids cervical dilatation; thus they can be used for enhancing cervical ripening and shortening of the duration of labour.11-16,18

Administering antispasmodics during labour could also lead to faster and more effective dilatation of the cervix. Interventions to shorten labour, such as antispasmodics, can be 22 used as a preventative or a treatment strategy in order to decrease the incidence of prolonged labour.11

Many studies have been carried out to evaluate the effects of injectable forms of hyoscine butylbromibe on cervical dilatation; however, the results are conflicting. Some of these studies demonstrated the efficacy of hyoscine butylbromibe in accelerating labour, while others showed no effect on duration of labour.

The bewildering reports of previous studies on the subject warrant more convincing evidence for the use of hyoscine butylbromide during labour. Moreover, evidence for its efficacy in Sub-Saharan Africa, Nigeria inclusive, was previously largely anecdotal.

Therefore conducting this study could address the burden of maternal and perinatal morbidity and mortality associated with prolonged labour in our environment.

4. OBJECTIVES

4.1 General Objective

The aim of this study is to evaluate the effect of intravenous hyoscine butylbromide on duration of labour and its safety among parturients.

4.2 Specific Objectives

1. To determine the duration of labour in women who had intravenous hyoscine

butylbromide (20mg, 2ml) in labour.

2. To determine the duration of labour in women who had placebo (2mls of water-

for-injection) in labour.

3. To compare the duration of labour in women who had hyoscine butylbromide in

labour with those who had placebo.

4. To compare the fetal outcome among pregnant women who had intravenous

hyoscine butylbromide in labour with those who had placebo.

5. To evaluate maternal adverse effects associated with using intravenous hyoscine

butylbromide during labour.

5. METHODOLOGY

5.1 Study Area:

The study was carried out in LAUTECH Teaching Hospital (LTH), Ogbomoso. Ogbomoso is located in Oyo state and most inhabitants are Yoruba speaking. LTH Ogbomoso is in

Ogbomoso North Local Government and was officially commissioned in May, 2011. It has six hundred beds functioning presently though the hospital has a one thousand bed capacity. LTH Ogbomoso has various department including Surgery, Obstetrics and

Gynaecology, Paediatrics, Internal Medicine, Laboratory Medicine, Radiology,

Anaesthesia, Psychiatrics, Family Medicine, Community Medicine. LTH Ogbomoso is fully accredited by the Medical and Dental Council of Nigeria. The study was undertaken in the Obstetrics and Gynaecology Department of LTH that has about a hundred vaginal deliveries per month.

5.2 Study Population:

The population studied was all consented pregnant women with no contraindications to vaginal delivery in labour (at 3 - 5cm cervical dilatation).

5.3 Recruitment of Participants:

All consented booked patients were recruited from the ante-natal clinic. The unbooked patients recruited were enrolled after their admission into labour ward and informed about the study, fully assessed to be in labour (at 3 - 5cm cervical dilatation), met the

25 inclusion criteria and contraindications to use of hyoscine butylbromide as well as vaginal delivery had been ruled out.

5.4 Inclusion Criteria:

All consented women (booked and unbooked) in labour following spontaneous onset and induction of labour at term (gestational age between 37 – 42 weeks) with singleton pregnancy in cephalic presentation, cervical dilatation at 3 - 5cm, no evidence of maternal or fetal distress and no other contraindications for vaginal delivery.

5.5 Exclusion Criteria:

All patients with myasthenia gravis, hypertension (preeclampsia or essential hypertension), conditions characterized by tachycardia (including hyperthyroidism, cardiac insufficiency, cardiac surgery); untreated narrow angle glaucoma, tachycardia, angina, mechanical stenoses of the gastrointestinal tract and megacolon as well as obstetric contraindications to vaginal delivery were excluded from the study.

5.6 Study Design:

This was an Intervention study of the double blind randomized clinical trial type.

5.7 Sample Size Determination:

2(푍훼+푍훽)2 푃표(1−푃표) 푁 = (45) 푑2

Where;

N = Minimum Sample Size

Zα = Critical ratio at significance level of 5%

Zβ = Statistical power for one-sided test at 90%

Po = Means of the 2 prevalence in the 2 comparison groups

Zα = 1.96

Zβ = 1.28

Shorter duration of labour in test group = P1

Shorter duration of labour in control group = P2

푃1+푃2 Po = 2

Taking the Prevalence in the two groups (P1 and P2) to be 96% and 34% from a previous

27 similar study. P0 = 0.96 + 0.34/2 = 0.615 d = Difference between P1 and P2 = 0.62

2(1.96+1.28)2 0.62(0.38) 푁 = (0.62)2

20.99 푋 0.2337 푁 = 0.0384

4.91 푁 = 0.0384

푁 = 127

An additional 10% was added to the sample size for non-responders making the total sample size to be 140 for each group. These summed up to a total of 280 respondents for both groups.

5.8 Sampling Techniques:

Participants were duly educated about the study procedure at antenatal educational sessions. This information was re-emphasized on arrival in labour ward for booked patients while the referred/unbooked patients were duly educated and counseled about the study on arrival in labour ward.

The blocked randomisation technique was adopted for selection into each study arm, through the use of computer generated random numbers (sequenced into the hyoscine butylbromide and placebo groups) on sealed opaque envelopes containing either hyoscine butylbromide or water-for-injection in a syringe. The content of the syringes of either hyoscine or water-for-injection were prepared under sterile hygienic condition in the hospital pharmacy department by one of the hospital Pharmacists, who was the only person who knew which number was assigned to a particular drug. Each syringe contained either 2 mls of hyoscine butylbromide (20 mg) or 2 mls of water-for-injection.

Both liquids were colourless, so the syringes containing the active agent were

28 indistinguishable from those containing placebo. At presentation in labour, specifically after obstetric and vaginal examinations, each pregnant woman that met the inclusion criteria and that consented to be included in the study was allocated according to the sequence of the computer generated number. The correspondingly numbered envelope was opened to reveal the enclosed syringe and administered to the enrolled Participant as stated above. The conduct of labour for both the drug and placebo groups were in accordance with our labour ward protocol, which was based on the principles of active management. Thus, amniotomy was performed for all participants in established labour with cervical dilatation of 4 cm or more, who had no spontaneous rupture of membranes. Opioid analgesia was given for pain management. Fetal monitoring was done by intermittent auscultation every half hour. The labour progress, as well as feto- maternal parameters were closely monitored and documented on the partograph.

Oxytocin augmentation was initiated when the initial progress of labour (as assessed through partograph) was unsatisfactory. Caesarean delivery was performed for obstetric indications. The duration of labour during the first, second and third stages, birth weight and neonatal APGAR scores determined at 1 and 5 minutes after birth were recorded.

Any maternal side effects such as tachycardia, dryness of mouth, flushing, headache, hypotension, nausea, vomiting, and blurring of vision were noted and treated accordingly. Postpartum maternal observation for vital signs and vaginal bleeding was done. An hour after the delivery, evaluation of pain during labour and its relief following the administration of test drugs were done with Numeric pain rating scale46,47. 29

Respondents’ satisfaction was also assessed. The Investigator only had knowledge of which number was assigned to a particular drug at the end of study when the

Pharmacist independently in charge of drug preparation revealed it. Also, the data were disaggregated by the principal Investigator, using the record of randomization sequences to sort the participants and their data into the appropriate groups (hyoscine or placebo).

5.9 Instrument of Survey

The instrument of the survey was a proforma form. The proforma had different sections.

Section A: Sociodemographic data

Section B: Antenatal history

Section C: First stage of labour and Delivery

Section D: Second and third stages of labour

Section E: Fetal Outcome

Section F: Maternal Complications

Section G: Pain-relief Assessment and Satisfaction Scale

5.10 Data Collection

Data were collected using the proforma for a period of seven (7) months from

November 2014 – May 2015. Nurses in the department underwent a day training to intimate them of the ongoing research in the labour ward of the hospital. The randomization recruitment of the patients and administration of the study drug were done by the principal investigator, while this function was carried out by another trained

Senior Registrar during call hours when principal Investigator was not around. When a patient presented in labour, the time that patient was reviewed at presentation was documented as well as cervical dilatation. The patients that met the inclusion criteria were randomized. The allotted number was noted and corresponding envelope bearing the number opened and the contained drug was administered to patients in labour (at 3

- 5cm cervical dilatation). For other patients not in established labour randomization was done once cervical dilatation was equal to 3 - 5cm.

All entries into proforma were done by the principal Investigator or a trained Senior

Registrar during call hours.

5.11. Study Hypothesis

NULL HYPOTHESIS - There is no significant difference in the mean duration of labour when hyoscine butylbromide is used for parturients.

ALTERNATE HYPOTHESIS – There will be significant difference in the mean duration of labour when hyoscine butylbromide is used for parturients.

5.12. Data Management

Data were entered into the computer statistical package SPSS 17. Initial frequency tables and charts were generated for univariate analysis. At bivariate level, the Chi- square test was used to test significance for categorical variables. For continuous variable, the T-test for independent samples was used for test of significance. Any significant association was subjected to multivariate analysis. P-value < 0.05 was taken as significant.

5.13. Ethical Consideration

The respondents were informed that participation was voluntary and they did not suffer any consequence when they chose not to participate. All information gathered was kept confidential and participants were identified using only randomized numbers. Ethical clearance was obtained from the ethical committee of LTH Ogbomoso and permission was obtained from the O&G Head of department and Consultant staff to enroll their patients. Written informed consent was obtained from Participants.

6. RESULTS

Two hundred and eighty parturient women were recruited, of which only 260 participants completed the study (128 study group and 132 control group). Giving a response rate of 92.9%.

Table 1: Socio-Demographic distribution among respondents

Study group n(%) Chi Variables Hyoscine Placebo Total square Df p-value n= 128 n= 132 N=260 χ2 Age in years Mean Age 29.77±6.49 28.89±3.94 1.325** 258 0.186 Less than 20 7(5.5) 3(2.3) 10(3.8) 6.704 3 0.082 20 - 29 57(44.5) 76(57.6) 133(51.2) 30 - 39 58(45.3) 51(38.6) 109(41.9) 40 and above 6(4.7) 2(1.5) 8(3.1) Tribe Yorubas 110(85.9) 125(94.7) 235(90.4) 5.737 1 0.017* Others (Igbo, Hausa) 18(14.1) 7(5.3) 25(9.6) Occupation Unemployed 44(34.4) 58(43.9) 102(39.2) 4.511 3 0.211 Unskilled labour 18(14.1) 13(9.8) 31(11.9) Skilled Labour 41(32.0) 31(23.5) 72(27.7) Professionals 25(19.5) 30(22.7) 55(21.2) Level of Education Primary 4(3.1) 0(0.0) 4(1.5) 11.184*** 2 0.004* Secondary 53(41.4) 38(28.8) 91(35.0) Tertiary 71(55.5) 94(71.2) 165(63.5) * Significant ** T-test for two independent samples was used ***Likelihood ratio applied, df = degree of freedom 33

Table 1 shows socio-demographic profile distribution among respondents in the study groups. The mean age of patients in hyoscine group was 29.77 ± 6.49 years. Although this was marginally higher than the value for the placebo (28.89 ±3.94 years), this difference was not statistically significant (t = 1.366, df = 258; p = 0.186). The age range was between 18 and 44 years in each of the study groups. The largest proportion of subjects in each of the two groups (45.3% hyoscine and 57.6% placebo) belonged to the

30 - 39 years and 20 - 29 year age group. However, there were no statistically significant differences in the proportions of patients that used hyoscine and placebo in the different age groups (χ2 = 6.704, df = 3; p = 0.082). The distribution of respondents according to tribes and level of education were significantly different between the hyoscine and placebo study groups (p < 0.05) as shown above. The distribution of respondents according to occupation is statistically similar in the two study groups (p =

0.211)

Table 2: Obstetric history among respondents in the study groups

Study group n(%) Chi Variables Hyoscine Placebo Total square Df p-value n= 128 n= 132 N=260 χ2 Parity Nulliparous 51(39.8) 77(58.3) 128(49.2) 8.888 1 0.003* Parous 77(60.2) 55(41.7) 132(50.8) Gestational age at booking 1st Trimester 23(18.0) 23(17.4) 46(17.7) 0.122 2 0.941 2nd Trimester 72(56.2) 77(58.3) 149(57.3) 3rd Trimester 33(25.8) 32(24.2) 65(25.0) Admission during pregnancy Yes 21(16.4) 18(13.6) 39(15.0) 0.391 1 0.532 No 107(83.6) 114(86.4) 221(85.0) Reason for admission during pregnancy n= 21 n=18 n=39 Hyperemesis Gravidarum 6(28.6) 2(11.1) 8(20.5) 10.860** 4 0.028* Degenerating fibroid 2(9.5) 5(27.8) 7(17.9) coexisting with pregnancy Malaria in pregnancy 12(57.1) 5(27.8) 17(43.6) Threatened abortion 1(4.8) 4(22.2) 5(12.8) UTI 0(0.0) 2(11.1) 2(5.1) * Significant **Likelihood ratio applied, UTI = Urinary tract infection

Table 2 shows respondent’s antenatal history in the two study groups. There was statistically significant difference in distribution of parity and reason for admission during pregnancy in the two study groups (p = < 0.05) but gestational age at booking and admission during pregnancy show no statistically significant relationship.

Table 3: Pattern of First stage of labour among respondents in the study groups

Study group n(%) Variables Hyoscine Placebo T df p-value

Cervical dilatation on admission (in cm) Range 0 – 5 0 – 5 mean±SD 2.99±1.35 3.12±1.25 -0.799 258 0.425 Cervical dilatation at randomization (in cm) Range 3 – 5 3 – 5 mean±SD 3.98±0.76 3.87±0.83 1.066 258 0.287 Duration of first stage of labour (in minutes) Range 54 – 1050 80 - 1080 mean±SD 364.73±207.10 506.17±210.78 -5.176 232 <0.001* Rate of cervical dilatation (in cm/hour) Range 0.60 – 2.80 0.40 – 3.80 mean±SD 1.87±1.23 1.02±0.60 6.660 232 <0.001*

*Significant, cm = centimetres, t = T-test for two independent samples, df = degree of freedom

Table 3 shows the first stage of labour among respondents in the study groups. There was no statistically significant difference in the mean cervical dilatation on admission in centimetres in the two study groups (p=0.425). Similarly, cervical dilatation at

38 randomization shows no significant difference (p =0.287). The mean duration of first stage of labour (in minutes) in hyoscine group (364.73±207.10minutes) was shorter than that of the placebo group (506.17±210.78minutes), these difference in the mean was found to be statistically significant (p<0.001). The mean rate of cervical dilation in centimetres per hours was higher in hyoscine group (1.87cm/hour) than in placebo group (1.02cm/hour), these difference was also statistically significant (p<0.001)

60.00% 55.30% 53.90% χ2 = 0.051 df = 1 p = 0.821 50.00% 46.10% 44.70%

40.00%

30.00% Hyoscine Placebo

20.00%

10.00%

0.00% Yes No

Figure 1: Bar chart showing oxytocin augmentation of labour among respondents in the study groups

Figure 1 shows proportion of respondent that had oxytocin augmentation of labour within the two study groups. There was no statistically significant difference in the

39 proportion of respondents that had oxytocin augmentation of labour within the two study groups (hyoscine and placebo) p = 0.821.

χ2 = 2.496 df = 1 12.90% p = 0.116 Caesarean delivery 7%

Placebo Hyoscine

87.10% Vaginal delivery 93%

0% 20% 40% 60% 80% 100%

Figure 2: Bar chart showing mode of delivery among respondents in the study groups

Figure 2 shows respondent’s mode of delivery the two study groups. There was no statistically significant difference in the proportion of respondent that had caesarean and vaginal deliveries within the two study groups (hyoscine and placebo) p = 0.116.

Table 4: Indication for Caesarean delivery among respondents that had caesarean delivery in the study groups

Study group n(%) Chi Variables Hyoscine Placebo Total square df p-value n= 9 n= 17 N=26 χ2 Indication for Caesarean delivery Poor progress in labour 2(22.2) 5(29.4) 7(26.9) 3.320* 3 0.497 CPD 5(55.6) 7(41.2) 12(46.2) Prolonged 2nd stage 2(22.2) 2(11.8) 4(15.4) Fetal distress 0(0.0) 3(17.6) 3(11.5) *Likelihood ratio applied, df = degree of freedom, CPD = Cephalopelvic disproportion

Table 4 shows indication for caesarean delivery among respondents that had caesarean delivery in the study groups. There was no statistically significant difference in the proportion of patients across the various indication for caesarean delivery in those that had caesarean delivery within the two study groups (hyoscine and placebo) p = 0.497.

Table 5: Pattern of Second and Third stages of labour among respondents in the study groups

Study group n(%) Variables Hyoscine Placebo t Df p-value

Injection – Delivery Interval (in minutes) Range 51 – 705 100 - 1103 mean±SD 287.16±156.14 485.24±216.65 -7.990 232 <0.001* Duration of second stage of labour (in minutes) Range 3 – 60 3 – 65 mean±SD 15.90±11.04 16.41±13.58 -0.315 232 0.753 Duration of first and second stages of labour (in minutes) Range 57 – 1095 140 – 1103 -4.952 232 <0.001* mean±SD 382.27±208.80 519.77±215.97 Duration of third stage of labour (in minutes)

Range 2 – 15 1 – 19 1.570 mean±SD 4.55±1.97 4.10±2.48 232 0.178 Duration of whole length of labour (in minutes) Range 64 – 1098 145 – 1108 mean±SD 387.23±209.88 525.77±215.68 -4.980 232 <0.001*

* Significant, SD = Standard deviation, t = T-test for two independent samples, df = degree of freedom

Table 5 shows second and third stages of labour among respondents in the study groups. The mean injection to delivery interval in minutes was shorter in hyoscine group 42

(287.16±156.14) than in placebo group (485.24±216.65), these difference was statistically significance (p<0.001). There was no statistically significantly difference in the mean of duration of second stage of labour in minutes in the two study groups (p =

0.757). Similarly, the mean difference in the duration of third stage of labour in minutes of the two groups was statistically insignificant. However, duration of first and stages of labour in minutes was statistically significantly shorter in hyoscine group (382.27±

208.80) than placebo group (519.77 ±215.97) p<0.001. Likewise the mean duration of whole length of labour in minutes was significantly shorter in hyoscine group

(387.23±209.88) than in placebo (525.77±215.68) p< 0.001

Table 6: Fetal Outcomes in the study groups

Study group n(%) Chi Variables Hyoscine Placebo Total square Df p-value n= 128 n= 132 N=260 χ2 Birth weight Range 2.20 – 4.30 2.10 – 4.70 mean±SD 3.19±0.48 3.11±0.47 1.023* 258 0.307 APGAR score at 1minute Range 3 - 9 3 - 9 mean±SD 7.37±1.16 7.30±1.40 0.450* 258 0.653 APGAR score at 5minutes Range 6 – 10 5 – 10 mean±SD 9.36±0.90 9.17±0.96 1.641* 258 0.102 Need for NICU admission Yes 6(4.7) 9(6.8) 15(5.8) 0.543 1 0.461 No 122(95.3) 123(93.2) 245(94.2) Indication(s) for admission in NICU Hypoglycemia 1(16.7) 1(11.1) 2(13.3) 0.103** 2 0.950 Perinatal asphexia 3(50.0) 5(55.6) 8(53.3) Macrosomia 2(33.3) 3(33.3) 5(33.3) State of the baby Alive 128(100) 132(100) 260(100) Dead 0(0) 0(0) 0(0) * T-test for two independent samples was used, **Likelihood Ratio applied, df = degree of freedom, SD = Standard deviation, NICU = Neonatal intensive care unit

Table 6 shows fetal outcome in the study groups. There was no statistically significant difference in various foetal outcome (birth weight, APGAR score at 1 minute, APGAR score at 5minute, Need for NICU admission, indication for admission in NICU) in the two study groups (hyoscine and placebo). All babies in the two study groups are alive.

Table 7: Maternal drug adverse effects

Study group n(%) Variables Hyoscine Placebo Total n= 128 n= 132 N=260 Presence of drug adverse effects in mother Yes 30(23.4) 5(4.0) 35(27.4) No 98(76.6) 127(96.0) 225(86.6) Maternal drug adverse effects * Dry mouth 14(10.9) 1(0.8) 15(5.8) Headaches 4(3.1) 3(2.3) 7(2.7) Nausea & vomiting 14(10.9) 4(3.0) 18(6.9) Tachycarida 4(3.1) 3(2.3) 7(2.7) *Multiple responses applies

Table 7 shows maternal drug adverse effects. More of respondents in hyoscine group had drug adverse effects (23.4%) compare to those in placebo group (4.0%) with majority of these complications being dry mouth and nausea and vomiting (10.9%).

Table 8: Pain-Relief Assessment and Satisfaction scale among respondents in the study groups

Study group n(%) Chi Variables Hyoscine Placebo Total square Df p-value n= 128 n= 132 N=260 χ2 Pain assessment Mild pain 7(5.5) 2(1.5) 9(3.5) 7.388 3 0.060 Moderate 79(61.7) 68(51.5) 147(56.5) Severe pain 36(28.1) 53(40.2) 89(34.2) Worst possible pain 6(4.7) 9(6.8) 15(5.8) Relief Score mean±SD 7.37±1.16 7.30±1.40 0.450** 258 0.653 Satisfaction score mean±SD 5.97±1.82 4.87±1.17 5.808** 258 <0.001* * Significant ** T-test for two independent samples was used, df = degree of freedom, SD = Standard deviation

Table 8 shows pain-relief assessment and satisfaction scale among respondent in the study groups. There was no statistically significant difference (p value = 0.060) between the two study groups (hyoscine and placebo) in pain assessment. There is no significant difference in the mean relief score between hyoscine and placebo group (p = 0.653).

Respondents in hyoscine group are significantly well satisfied than in placebo group

(p<0.001).

Table 9: Duration of first stage of labour and rate of cervical dilatation among nulliparous and parous respondents

Study group n(%)

Variables Hyoscine Placebo t df p-value

mean±SD mean±SD

Nulliparous Duration of first stage

of labour (in minutes) 390.49±231.53 530.10±218.01 -3.261 113 0.001*

Rate of cervical

dilatation (in cm/hour) 1.83±1.27 0.95±0.56 5.077 113 <0.001*

Parous Duration of first stage

of labour (in minutes) 347.92±185.436 471.53±196.98 -3.468 117 0.001*

Rate of cervical

dilatation (in cm/hour) 1.89±1.22 1.12±0.64 3.987 117 <0.001*

*Significant, cm = centimetres, t = T-test for two independent samples, df = degree of freedom

Table 9 shows duration of first stage of labour and rate of cervical dilatation among nulliparous and also in parous respondents. This table checked the effect of parity on the mean difference noticed in the table 3 (in duration of first stage of labour in minutes and rate of cervical dilatation in cm/hour). The mean duration of first stage of labour in minutes was still statistically significantly shorter in hyoscine group than in placebo among nulliparous and parous respondents (p=0.001 in both). The mean rate of cervical

47 dilatation in centimetres per hour was still statistically significantly higher in hyoscine group than in placebo among nulliparous and parous respondents (p<0.001 in both).

7.0 DISCUSSION

Prolonged labour represents a challenging area in the daily obstetric practice because of its associated maternal morbidities as well as the fetal and neonatal complications.

Therefore, active management of labour was introduced to shorten the length of labour

2,3,6,8,13 without compromising the maternal and fetal wellbeing.4 Reducing the length of labour is a highly desirable goal of intrapartum care and entails shorter exposure to pain, anxiety and stress and would thus translate into a major improvement in maternal satisfaction with the childbirth experience.7

The mean ages in this study was 29.77 ± 6.49 years and 28.89 ±3.94 years for the hyoscine and placebo groups respectively. The mean age in this study is slightly higher than mean ages in the studies of Samuel et al22, Aggrawal et al24, Al Qahtani et al29 and

Sirohiwal et al34 possibly due to different geographical locations where these studies were carried out. This variation, however, has no direct implications on the outcome of the study. Majority of the respondents were of Yoruba ethnicity and this was expected due to the location of this study.

The parity distribution is similar to the study of Fouad Aldahan et al45; in some studies predetermined numbers of nulliparous and multiparous22,24,28,38 patients were used. In the study of Battacharya et al.21, Aggarawal et al.24 and Makvandi S38 use of hyoscine butylbromide shortened the duration of labour in nulliparous while results of Samuel et al.22 and Hussein et al.28 confirmed similar reports in both nulliparous and parous 49 women. However, Hussein et al28 concluded that such effect of HBB was pronounced in multigravida women only compared with control, and relatively greater than its effect in primigravid. It is, therefore, important to have a fairly equal distribution of nulliparous and parous respondents within the study groups.

Several studies, which included both primigravid and multigravid women, have shown that intravenous administration of HBB (20mg) during the active phase of labour increases cervical dilatation and decreases duration of labour.22,28,33 Tewari et al.25 showed that there was reduced mean duration of labour by five hours and twelve minutes in the group receiving hyoscine compared with the control. Sameena et al27 hyoscine butylbromide dilates the cervix more rapidly and the duration of active phase was shorter in hyoscine butylbromide group than control group. Samuels et al,22 Hussein et al28 and Sirohiwal et al34 concluded that hyoscine butylbromide is effective in significantly reducing the duration of the first stage of labour. In this study, the mean duration of first stage of labour in hyoscine group (364.73±207.10 minutes) was shorter than that of the placebo group (506.17±210.78 minutes). The mean rate of cervical dilation was higher in hyoscine group (1.87cm/hour) than in placebo group

(1.02cm/hour). Likewise the mean duration of whole length of labour was significantly shorter in hyoscine group (387.23±209.88 minutes) than in placebo (525.77±215.68 minutes) p< 0.001. In tune with many reported data, these results confirmed that HBB effect was limited to cervical dilatation and shortened the duration of labour by

50 increasing the rate of cervical dilatation during the active phase of labour. It was also demonstrated that there was no statistically significant difference in the durations of the second and third stages of labour similar to findings of Sirohiwal et al34, Samal et al33 and Qahtani et al29.

Fetal outcome in this study is similar in both hyoscine and placebo groups. All the babies were delivered alive with no statistically significant difference in mean birth weights,

APGAR at 1 and 5 minutes as well as need and indications for NICU admission. No significant adverse effects were noted in either mother or fetus and results are comparable with the study conducted by Samuels et al22 and Hussein et al28.

This study demonstrated no statistically significant difference (p value = 0.060) between the hyoscine and placebo groups in pain assessment and the relief score (p = 0.653). In the contrary, respondents in the study by Aggarawal et al24 reported pain relief between

25-75%, while control group patients reported no pain relief, or relief of <25% at two hours. Moreover, Sameena et al27 and Makvandi et al38 also reported significant associated pain relief and reduction in analgesic use in the HBB group. Whereas its analgesic properties are not well studied in the context of labour, authors have agreed that part of the pain relief afforded by HBB may be due to shortening the duration of labour in the first stage, and consequently the reduced overall time spent in pain by the laboring mother24,31

Evaluating for satisfaction within the two study groups showed that more respondents had maximum satisfaction in the hyoscine group when compared to the placebo group.

Though post-partum satisfaction is not commonly assessed in most studies, it could be accorded to the overall reduction in the duration of labour and short exposure to pain.

Another parameter assessed for is the influence of parity on the effectiveness of the intervention drugs used for this study on the duration of first stage of labour and rate of cervical dilatation among nulliparous and parous respondents. The mean duration of first stage of labour and mean rate of cervical dilatation were statistically significant in hyoscine group than placebo in both nulliparous and parous parturients. Study by

Samuels et al22 supported these findings, however, in the study by Hussein Al-Khishali et al28 such effect of HBB was pronounced in multigravida women only compared with control, and relatively greater than its effect in primigravidae. Such type of response seems reasonable as experience of multigravida women with normal labour may be of significant importance in this respect.

7.1 CONCLUSION

1. The findings of this study showed that HBB is effective in reducing the duration of labour than placebo.

2. There was no obvious neonatal adverse effect with intravenous HBB when used in pregnant women in labour.

3. There was no associated significant maternal side effect with intravenous HBB when used in pregnant women in labour.

4. Women in the hyoscine group expressed better satisfaction than those in the placebo group.

7.2 RECOMMENDATIONS

1. There was significant shortening of duration of labour with the use of hyoscine. Hence the drug can be prescribed for active management of labour.

2. In patients with no contraindication to its use; Hyoscine may be prescribed in labour, considering it better effects cervical dilatation and patients’ satisfaction.

3. It is recommended that a large multicenter study will be required for a more definite statement on safety profile in both the mothers and babies. 53

7.3 LIMITATIONS

1. There was no tonometric assessment of uterine contractility to verify the effects of hyoscine butylbromide on the uterus.

2. There was difficulty getting placebo similar to hyoscine butylbromide.

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Appendix I

INFORMATION ON THE STUDY PROCEDURE TO PARTICIPANTS (ENGLISH VERSION)

Greetings

I am Dr Akinbile T.O, from LAUTECH Teaching Hospital, Ogbomoso. I am here to conduct a research titled “The effects of hyoscine butylbromide on labour outcome and its safety among parturients”. It is a double-blind randomised clinical trial. The hope is that the findings from this research will improve current management of labour.

To achieve the objective, your informed consent is needed. Please note that the information obtained will be kept with utmost confidentiality.

You will be given a drug (an injection through the vein) during labour, that has been tested to be very safe to both the mother and unborn baby, which has the potential for shortening the duration of labour. Our expectation is that prolonged labour will be prevented when this drug is used during labour management. The drug shall be provided free of charge for every patient who consented to participate in the study.

You are free to refuse to participate in this study or to withdraw at any point in time and this will not affect your management in the hospital in any way. You may also raise any concern that you may have during the session of questioning. If you have any question(s) to ask concerning the study, please contact the principal investigator on phone 08038549282 or e-mail; [email protected].

Thank you for your participation.

Appendix II

CONSENT FORM (ENGLISH VERSION)

I have read/had someone read to me the entire explanation about this study and have been given the opportunity to discuss any question. I understand the nature, risk and benefits of this study and I may withdraw at any time without prejudice. Likewise I have received a copy of this informed consent document. I hereby consent to take part in this study.

SIGNATURE AND THUMBPRINT OF PARTICIPANT DATE SIGNED

SIGNATURE OF INVESTIGATOR DATE SIGNED

SIGNATURE OF WITNESS DATE SIGNED

Appendix III

PROFORMA

RANDOMISATION NUMBER…………..

SECTION A (SOCIO-DEMOGRAPHIC DATA)

1. Hospital No.______

2. Age:______

3. Parity:______

4. Gestational Age:______

5. Tribe:______

6. Occupation:______

7. Level of education: (a) Primary [ ] (b) Secondary [ ] (c) Tertiary [ ] (d)

No formal education [ ]

SECTION B: ANTENATAL HISTORY

8. Gestation age at booking:______

9. Any admission (a) Yes [ ] (b) No [ ]

10. If yes to (9), why: ______

SECTION C: FIRST STAGE OF LABOUR AND DELIVERY

11. Date & Time of admission: ………………………………………………………………………………

12. Cervical dilatation on admission: ……………………………………………………………………. 64

13. Time & Cervical dilatation of randomisation: …………………………………………………

14. Time of administration of study drug: ……………………………………………………………..

15. Time of diagnosing full cervical dilatation: ……………………………………………………….

16. Duration of first stage of labour (minutes):______

17. Rate of cervical dilatation(cm/hour): ……………………………………………......

18. Oxytocin augmentation of labour (a) Yes [ ] (b) No [ ]

19. Mode of delivery (a) Vaginal delivery [ ] (b) Caesarean delivery [ ]

20. Time when decision for Caesarean delivery is made: ………………………………………

21. Indication for Caesarean delivery: ……………………………………………………………………

SECTION D: SECOND AND THIRD STAGES OF LABOUR

22. Time of delivery of baby: …………………………………………………………………………………

23. Injection-Delivery Interval: ………………………………………………………………………………

24. Duration of second stage of labour(minutes): ……………………......

25. Duration of first and second stages of labour(minutes): ……………......

26. Time of delivery of the placenta: ……………………………………………………………………..

27. Duration of third stage of labour(minutes): …………………………………......

28. Duration of whole length of labour(minutes): ………………………………………………....

SECTION E: FETAL OUTCOME

29. Birth weight: ……………………………………………………………………………………………

30. APGAR score at 1 minute: ………………………………………………………………………..

31. APGAR score at 5 minutes: ………………………………………………………………………..

32. Need for NICU admission: (a) Yes [ ] (b) No [ ]

33. If yes to (32), Indication(s) for admission: ………………………………………………....

34. State of the baby: (a) Alive [ ] (b) Dead [ ]

SECTION F: MATERNAL COMPLICATIONS

35. Dry mouth (a) Yes [ ] (b) No [ ]

36. Headaches (a) Yes [ ] (b) No [ ]

37. Nausea & Vomiting (a) Yes [ ] (b) No [ ]

38. Tachycardia (a) Yes [ ] (b) No [ ]

39. Urinary urgency (a) Yes [ ] (b) No [ ]

40. Hypotension (a) Yes [ ] (b) No [ ]

41. Blurred vision (a) Yes [ ] (b) No [ ]

42. Skin rashes (a) Yes [ ] (b) No [ ]

SECTION G: PAIN-RELIEF ASSESSMENT AND SATISFACTION SCALE

43. Pain assessment(46,47)

0 – No pain, 1 – Mild, 2 – Moderate pain, 3 – Severe pain, 4 – Worst

possible pain

(46,47) 44. Relief Scale 10

No relief 66 Complete of pain relief of pain

45. Satisfaction scale(48) 10

No Maximum Satisfaction Satisfaction