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Antispasmodics for labour

  1. Anke C Rohwer1,*,
  2. Oswell Khondowe1,
  3. Taryn Young1,2

Editorial Group: Cochrane Pregnancy and Childbirth Group

Published Online: 5 JUN 2013

Assessed as up-to-date: 10 APR 2013

DOI: 10.1002/14651858.CD009243.pub3


How to Cite

Rohwer AC, Khondowe O, Young T. Antispasmodics for labour. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD009243. DOI: 10.1002/14651858.CD009243.pub3.

Author Information

  1. 1

    Stellenbosch University, Centre for Evidence-based Health Care, Faculty of Medicine and Health Sciences, Tygerberg, South Africa

  2. 2

    South African Medical Research Council, South African Cochrane Centre, Tygerberg, South Africa

*Anke C Rohwer, Centre for Evidence-based Health Care, Faculty of Medicine and Health Sciences, Stellenbosch University, Francie van Zijl Drive, Tygerberg, 7505, South Africa. arohwer@sun.ac.za.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 5 JUN 2013

SEARCH

 

Summary of findings    [Explanations]

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

 
Summary of findings for the main comparison. Antispasmodics versus control

Antispasmodics versus control

Patient or population: Women in labour
Settings: Hospital setting
Intervention: Antispasmodics
Comparison: Control

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlAntispasmodics

Duration of first stage of labour
minutes
173 to 346.31The mean duration of first stage of labour in the intervention groups was
74.34 lower
(98.76 to 49.93 lower)
1995
(13 studies)
⊕⊕⊝⊝
low1,2

Duration of second stage of labour
minutes
16.5 to 58The mean duration of second stage of labour in the intervention groups was
2.68 lower
(5.98 lower to 0.63 higher)
1297
(10 studies)
⊕⊕⊝⊝
low1,2

Duration of third stage of labour
minutes
5.52 to8.3The mean duration of third stage of labour in the intervention groups was
0.06 lower
(0.52 lower to 0.4 higher)
765
(5 studies)
⊕⊕⊝⊝
low1,2

Total duration of labour

minutes
192.2 to 413.9The mean total duration of labour (min) in the intervention groups was
85.51 lower
(121.81 to 49.2 lower)
797
(7 studies)
⊕⊝⊝⊝
very low1,2,3

Rate of cervical dilatation
cm/h
1.01 to 2.5The mean rate of cervical dilatation in the intervention groups was
0.61 higher
(0.34 to 0.88 higher)
820
(6 studies)
⊕⊕⊝⊝
low1,2

Rate of normal vertex deliveriesStudy populationRR 1.02
(1 to 1.05)
2319
(16 studies)
⊕⊕⊕⊝
moderate1

905 per 1000923 per 1000
(905 to 950)

Moderate

925 per 1000943 per 1000
(925 to 971)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 High risk for selection and incomplete reporting of outcomes in most studies
2 Significant, unexplained heterogeneity present
3 Wide 95% confidence interval

 

Background

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Description of the condition

Improving maternal health (the fifth Millennium Development Goal) and decreasing maternal mortality remains one of the main health concerns worldwide. Some progress has been made towards achieving the target of reducing maternal mortality by three-quarters between 1990 and 2015, as the global maternity mortality ratio (MMR) in 2008 was 260 maternal deaths per 100,000 live births, compared to 430/100,000 live births in 1990 (WHO 2010). However, in Sub-Saharan Africa, the burden is significant, with an MMR of 640/100,000 live births in 2008 (WHO 2010).

According to an analysis conducted by the World Health Organization (WHO) (Khan 2006), 4.1% of maternal deaths in Africa were due to obstructed labour. The percentage for Asia, and Latin America and the Caribbean, was 9.4% and 13.4% respectively. The leading cause of maternal mortality worldwide is haemorrhage (developed countries 13.4%; Africa 33.9%; Asia 30.8%; Latin America and the Caribbean 20.8%). This includes postpartum haemorrhage, although the proportion was not specified (Khan 2006).

Prolonged labour can lead to increased maternal and neonatal mortality and morbidity due to increased risks of maternal exhaustion, postpartum haemorrhage and sepsis, fetal distress and asphyxia and requires early detection and appropriate clinical response. The causes of prolonged labour relate to maternal age, induction of labour, prelabour rupture of membranes, early admission to the labour ward, epidural analgesia and high levels of maternal stress hormones, but are unknown in most cases (Dencker 2009). The risks for complications of prolonged labour are much greater in poor resource settings (Neilson 2003). It is difficult to give a clear definition for prolonged labour. In practice, as recommended by the WHO maternal health and safe motherhood programme (WHO 1994), a woman should be transferred to a higher level of care if her rate of cervical dilatation (according to the partogram) becomes less than 1 cm/hour, and requires prompt, appropriate management if it is less than 1 cm in four hours (Lavender 2009). In addition, a recent review to determine the “slowest-yet-normal” dilatation rate amongst primigravid women (Neal 2010), determined that this dilatation rate approximates 0.5 cm/hour and that expectations of a faster dilatation rate (1 cm/hour) can lead to unnecessary interventions aiming to accelerate labour.

The concept of “active management of labour” (O'Driscoll 1973) was developed to assure a woman that her labour would not exceed 12 hours. Anything beyond that constituted prolonged labour. This package of care includes accurate and early diagnosis of the first stage of labour, early artificial rupture of membranes, ongoing support of the woman in labour by a professional caregiver and augmentation of labour with oxytocin (O'Driscoll 1994). Active management of labour versus physiological, expectant management, has shown to decrease the occurrence of prolonged labour (more than 12 hours). A Cochrane review found that active management significantly shortened the duration of labour by 1.27 hours, while the first stage of labour was significantly reduced by 1.56 hours. It also showed a small reduction in the rate of caesarean sections. There was no significant difference in maternal and neonatal morbidity (Brown 2008). Wei 2009 showed that early intervention with amniotomy and oxytocin augmentation, as a preventative strategy with mild delays in progress, leads to a reduction of 1.16 hours in the duration of labour.

 

Description of the intervention

Administering antispasmodics during labour could lead to faster and more effective dilatation of the cervix (Samuels 2009).

Antispasmodics are drugs that relieve spasms of smooth muscle tissue and have either musculotropic or neurotropic effects. The cervix is composed of connective tissue and smooth muscle, innervated by parasympathetic nerve fibres. Smooth muscle constitutes about 15% of the cervix (Leppert 1995), which is mainly found just below the internal os (Buhimschi 2003).

Musculotropic antispasmodics directly relax smooth muscles. They are phosphodiesterase type IV inhibitors, structurally related to papaverine, have mild Calcium (Ca)-channel blocking effects, no anticholinergic effects and act directly on smooth muscle cells, inhibiting spasm (Sommers 2002).

Neurotropic antispasmodics break the connection between the parasympathetic nerve and the smooth muscle.They are parasympatholytics acting as antagonists of acetylcholine at muscarinic receptors, thus inhibiting muscle spasm (Samuels 2009; Sommers 2002).

Antispasmodics are commonly administered during labour in both developing and developed countries, although there is a paucity of scientific reports validating this. In India, drotaverine hydrochloride, an antispasmodic drug, forms part of their “Programmed Labour Protocol” to decrease the pain and the duration of labour (Yuel 2008). It is used in conjunction with amniotomy, oxytocin augmentation and administration of tramadol for pain relief. 

There are a number of case-reports, prospective studies and clinical trials describing the effects of antispasmodics during labour. A prospective study by Sirohiwal 2005 found that administration of hyoscine-butyl bromide suppositories during labour significantly shortened the duration of the first stage of labour.

Adverse effects of  these drugs are rare at therapeutic dosages and include dryness of the mouth, visual disturbances, tachycardia, drowsiness and fatigue. Some patients may experience paradoxical stimulation and excitation (Gibbon 2005).

 

How the intervention might work

As shown in studies conducted in India and elsewhere (Sirohiwal 2005; Yuel 2008), antispasmodics could be used as accelerators of labour. Although the exact mechanism of action of cervical dilatation and the influence of antispasmodics thereon is still somewhat unclear, more effective dilatation could lead to an accelerated labour.

Antispasmodics can be used in conjunction with the package of active management of labour, as has been done in India and across the world, or on its own. In the latter case, the general use of oxytocin would be reduced. Oxytocin, although widely used, has been described as the drug most commonly related to preventable adverse events during labour and has a very unpredictable therapeutic index (Clark 2009).

Furthermore, active management of labour as a whole package, or parts thereof, and other interventions to shorten labour, such as antispasmodics, can be used as a preventative strategy or a treatment strategy in order to decrease the incidence of prolonged labour. This depends on the setting, availability of resources and maternal preferences. 

 

Why it is important to do this review

The use of antispasmodics as accelerators of labour is largely anecdotal around the world. The results of the first version of the review showed that there was low quality evidence that antispasmodics reduced the duration of the first stage of labour and very low quality evidence that they reduced the total duration of labour. The WHO is updating their augmentation of labour guidelines in 2013 and as this review was identified as one of the reviews to feed into the guideline, it is important to include all recent studies in this updated version of the review. Considering all studies addressing this question and interpreting the results in light of the quality of the studies will help policy makers and clinicians to make well-informed decisions about the use of antispasmodics during labour.

 

Objectives

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

The aim of this review is to assess the effects of antispasmodics on labour in term pregnancies.

 

Methods

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Criteria for considering studies for this review

 

Types of studies

We considered randomised controlled trials for inclusion in this review and did not include quasi-randomised controlled trials, cluster-randomised trials or trials using a cross-over design. We included studies available only as an abstract, if they reported on all the necessary information.

 

Types of participants

Primi- and multigravid women with term pregnancies (equal to or greater than 37 weeks' gestation) at the time of delivery; with spontaneous onset and induction of labour; low- and high-risk pregnancies; active and expectant management of labour.

 

Types of interventions

We considered studies where any antispasmodic agent was administered during any stage of labour by means of oral, rectal, intramuscular or intravenous route compared with a control group (placebo or no medication) for inclusion in the review.

 

Types of outcome measures

 

Primary outcomes

Primary outcomes were the direct effect of antispasmodic drugs on labour.

  1. Duration of labour.
  2. Rate of cervical dilatation.
  3. Pain relief.
  4. Type of delivery (rate of normal vertex deliveries).

 

Secondary outcomes

  1. Maternal adverse events: these included any maternal adverse event, defined in the Cochrane Handbook for Systematic Interventions Reviews (Higgins 2011) as any "unfavourable outcome that occurs during or after the use of a drug or other intervention but not necessarily caused by it".
  2. Neonatal adverse events: this included any fetal or neonatal adverse event, defined in the Cochrane Handbook for Systematic Interventions Reviews (Higgins 2011), as any "unfavourable outcome that occurs during or after the use of a drug or other intervention but not necessarily caused by it".
  3. Maternal satisfaction.

 

Search methods for identification of studies

 

Electronic searches

We contacted the Trials Search Co-ordinator to search the Cochrane Pregnancy and Childbirth Group’s Trials Register (28 Febuary 2013).

The Cochrane Pregnancy and Childbirth Group’s Trials Register is maintained by the Trials Search Co-ordinator and contains trials identified from:

  1. monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL);
  2. weekly searches of MEDLINE;
  3. weekly searches of EMBASE;
  4. handsearches of 30 journals and the proceedings of major conferences;
  5. weekly current awareness alerts for a further 44 journals plus monthly BioMed Central email alerts.

Details of the search strategies for CENTRAL, MEDLINE and EMBASE, the list of handsearched journals and conference proceedings, and the list of journals reviewed via the current awareness service can be found in the ‘Specialized Register’ section within the editorial information about the Cochrane Pregnancy and Childbirth Group.

Trials identified through the searching activities described above are each assigned to a review topic (or topics). The Trials Search Co-ordinator searches the register for each review using the topic list rather than keywords. 

In addition, we searched the ProQuest dissertation and thesis database, the dissertation database of the University of Stellenbosch and Google Scholar (28 February 2013) (see Appendix 1 for search terms used).

 

Searching other resources

We contacted experts in the field and relevant pharmaceutical companies that manufacture antispasmodics, but did not receive any additional study reports.

We also scanned reference lists of included papers for additional studies.

We did not apply any language restrictions.

 

Data collection and analysis

 

Selection of studies

Two review authors (either Anke Rohwer (AR) and Taryn Young (TY) or AR and Oswell Khondowe (OK)) independently reviewed the search output. We screened titles and abstracts of search results to exclude irrelevant studies. We then retrieved full text articles of seemingly relevant studies and examined them to see whether they met the inclusion criteria. We resolved any disagreement through discussion.

 

Data extraction and management

We designed a data extraction form. For eligible studies, two review authors (either AR and TY or AR and OK) extracted the data using the agreed form. We resolved discrepancies through discussion. We entered data into Review Manager software (RevMan 2011) and checked it for accuracy.

When information regarding any of the above was unclear, we contacted authors of the original reports to provide further details.

 

Assessment of risk of bias in included studies

Two review authors (either AR and TY or AR and OK) independently assessed risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Interventions Reviews (Higgins 2011). We contacted authors for missing information and resolved any disagreement by discussion.

 

(1) Random sequence generation (checking for possible selection bias)

We described for each included study the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups.

We assessed the method as:

  • low risk of bias (any truly random process, e.g. random number table; computer random number generator);
  • high risk of bias (any non-random process, e.g. odd or even date of birth; hospital or clinic record number);
  • unclear risk of bias.   

 

 (2) Allocation concealment (checking for possible selection bias)

We described for each included study the method used to conceal allocation to interventions prior to assignment and assessed whether intervention allocation could have been foreseen in advance of, or during recruitment, or changed after assignment.

We assessed the methods as:

  • low risk of bias (e.g. telephone or central randomisation; consecutively numbered sealed opaque envelopes);
  • high risk of bias (open random allocation; unsealed or non-opaque envelopes, alternation; date of birth);
  • unclear risk of bias.   

 

(3.1) Blinding of participants and personnel (checking for possible performance bias)

We described for each included study the methods used, if any, to blind study participants and personnel from knowledge of which intervention a participant received. We considered that studies were at low risk of bias if they were blinded, or if we judged that the lack of blinding was unlikely to affect results. We assessed blinding separately for different outcomes or classes of outcomes.

We assessed the methods as:

  • low, high or unclear risk of bias for participants;
  • low, high or unclear risk of bias for personnel.

 

(3.2) Blinding of outcome assessment (checking for possible detection bias)

We described for each included study the methods used, if any, to blind outcome assessors from knowledge of which intervention a participant received. We assessed blinding separately for different outcomes or classes of outcomes.

We assessed methods used to blind outcome assessment as:

  • low, high or unclear risk of bias.

 

(4) Incomplete outcome data (checking for possible attrition bias due to the amount, nature and handling of incomplete outcome data)

We described for each included study, and for each outcome or class of outcomes, the completeness of data including attrition and exclusions from the analysis. We stated whether attrition and exclusions were reported and the numbers included in the analysis at each stage (compared with the total randomised participants), reasons for attrition or exclusion where reported, and whether missing data were balanced across groups or were related to outcomes. Where sufficient information was reported, or could be supplied by the trial authors, we re-included missing data in the analyses which we undertook.

We assessed methods as:

  • low risk of bias (e.g. no missing outcome data; missing outcome data balanced across groups);
  • high risk of bias (e.g. numbers or reasons for missing data imbalanced across groups; ‘as treated’ analysis done with substantial departure of intervention received from that assigned at randomisation);
  • unclear risk of bias.

 

(5) Selective reporting (checking for reporting bias)

We described for each included study how we investigated the possibility of selective outcome reporting bias and what we found.

We assessed the methods as:

  • low risk of bias (where it was clear that all of the study’s pre-specified outcomes and all expected outcomes of interest to the review had been reported);
  • high risk of bias (where not all the study’s pre-specified outcomes had been reported; one or more reported primary outcomes were not pre-specified; outcomes of interest were reported incompletely and so could not be used; study failed to include results of a key outcome that would have been expected to have been reported);
  • unclear risk of bias.

 

(6) Other bias (checking for bias due to problems not covered by (1) to (5) above)

We described any important concerns we had about other possible sources of bias.

 

(7) Overall risk of bias

We made explicit judgements about whether studies were at high risk of bias, according to the criteria given in the Cochrane Handbook for Systematic Interventions Reviews (Higgins 2011). With reference to (1) to (6) above, we assessed the likely magnitude and direction of the bias and whether we considered it as likely to impact on the findings. We explored the impact of the level of bias through undertaking sensitivity analyses - see Sensitivity analysis

 

Measures of treatment effect

For dichotomous data, we presented results as summary risk ratio with 95% confidence intervals, and for continuous data, we used the mean difference. All outcomes were measured in the same way between trials.

 

Unit of analysis issues

We dealt with studies with multiple treatment groups as recommended by the Cochrane Handbook for Systematic Interventions Reviews (Higgins 2011). If studies had two intervention groups with different antispasmodics and one control group, we included the two different intervention groups in the meta-analysis as separate intervention groups, but divided the control group in two (Ramsay 2003).

 

Dealing with missing data

For included studies, we noted levels of attrition. We explored the impact of including studies with high levels of missing data in the overall assessment of treatment effect by using sensitivity analysis.

For all outcomes, we carried out analyses, as far as possible, on an intention-to-treat basis, i.e. we attempted to include all participants randomised to each group in the analyses, and analysed all participants in the group to which they were allocated, regardless of whether or not they received the allocated intervention. The denominator for each outcome in each trial was the number randomised minus any participants whose outcomes were known to be missing.

 

Assessment of heterogeneity

We assessed statistical heterogeneity in each meta-analysis using the T², I² and Chi² statistics. We regarded heterogeneity as substantial if the I² was greater than 30% and either the T² was greater than zero, or there was a low P value (less than 0.10) in the Chi² test for heterogeneity. 

 

Assessment of reporting biases

We investigated reporting biases (such as publication bias) using funnel plots when outcomes included more than 10 studies. We assessed funnel plot asymmetry visually, and used formal tests for funnel plot asymmetry. For continuous outcomes we used the test proposed by Egger 1997, and for dichotomous outcomes we used the test proposed by Harbord 2006. If we detected asymmetry in any of these tests or by a visual assessment, we performed exploratory analyses to investigate it

 

Data synthesis

We carried out statistical analysis using the Review Manager software (RevMan 2011). We used fixed-effect meta-analysis for combining data where it was reasonable to assume that studies were estimating the same underlying treatment effect: i.e. where trials were examining the same intervention, and the trials’ populations and methods were judged sufficiently similar. Where there was clinical heterogeneity sufficient to expect that the underlying treatment effects differed between trials, or when we detected substantial statistical heterogeneity, we used random-effects meta-analysis to produce an overall summary if an average treatment effect across trials was considered clinically meaningful. We treated the random-effects summary as the average range of possible treatment effects and we discussed the clinical implications of treatment effects differing between trials.

When using random-effects analyses, we presented the results as the average treatment effect with its 95% confidence interval, and the estimates of  T² and I².

 

Subgroup analysis and investigation of heterogeneity

We investigated substantial heterogeneity using subgroup analyses. We considered whether an overall summary was meaningful, and if it was, we used random-effects analysis to produce it.

We carried out the following pre-specified subgroup analyses.

  1. Type of antispasmodic (musculotropic drugs versus neurotropic drugs).
  2. Route of administration (intravenous administration versus intramuscular administration).
  3. Gravidity of women (primigravidas versus multigravidas).
  4. Type of labour (spontaneous labour versus induced labour.

We also added three more non pre-specified subgroups:

  1. Type of management of labour (active management versus expectant management).
  2. Type of pregnancy (high risk versus low risk).
  3. Studies excluding versus studies including caesarean sections in their analysis.

We used the following outcomes in subgroup analysis.

  • Duration of labour.
  • Rate of cervical dilatation.
  • Pain relief.
  • Type of delivery.

For fixed-effect inverse variance meta-analyses, we assessed differences between subgroups by interaction tests. For random-effects and fixed-effect meta-analyses using methods other than inverse variance, we assessed differences between subgroups by inspection of the subgroups’ confidence intervals; non-overlapping confidence intervals indicated a statistically significant difference in treatment effect between the subgroups.

 

Sensitivity analysis

We performed sensitivity analysis on primary outcomes, to see what effect the exclusion of studies with high risk of bias (for allocation concealment, and incomplete outcome data) had on the overall result of the meta-analysis.

 

Results

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Description of studies

 

Results of the search

 

September 2011 search

The search of the Cochrane Pregnancy and Childbirth Group's Register retrieved 42 trial reports. The search of the dissertation databases did not retrieve additional studies and a search on Google Scholar retrieved two extra studies. Screening reference lists yielded four extra studies, while contact with experts yielded another, unpublished study. An additional study was identified through the peer-review process. After screening abstracts for eligibility, 23 studies were excluded (see Characteristics of excluded studies). Full text articles of seemingly relevant studies were obtained. Seven studies had insufficient information to be classified (Accinelli 1978; Ahmed 1982; Georges 2007; Rajani 2011; Ranka 2002; Recto 1997; Roy 2007), for more details, see Characteristics of studies awaiting classification. We contacted the study authors if a contact address was available to obtain additional information but none of the authors responded. One study was listed in the IRCT register and has not been published (Movahed 2010, see Characteristics of ongoing studies). We included one unpublished study (Mukaindo 2010) and 18 published studies (14 full texts, three conference abstracts and one letter to the editor), including 2798 participants, in the review (Table 1). Fifteen studies were included in the meta-analysis. For a summary of the search results, see Figure 1.

 FigureFigure 1. Study flow diagram - September 2011 search

 

February 2013 search

This updated search retrieved one report from the Cochrane Pregnancy and Childbirth Group's Register and four from Google Scholar. After removing one duplicate study, we assessed full text of four. We excluded Fouedjio 2012 and included Dahal 2013 and Sekhavat 2012. Zagami 2012 is awaiting translation (see Figure 2).

 FigureFigure 2. Study flow diagram - February 2013 search

 

Included studies

Twenty-one studies were included in this updated review of which 17 were included in the meta-analysis. See Characteristics of included studies.

 

Study location

Nine of the studies were conducted in India (Ajmera 2006; Gupta 2008; Khosla 2003; Kuruvila 1992; Madhu 2010; Raghavan 2008; Sharma 2001; Singh 2004; Warke 2003); three in Iran (Azari 2010; Sekhavat 2012, Makvandi 2010); two in Turkey (Batukan 2006; Yilmaz 2009); two in Saudi Arabia (Al Matari 2007; Al Qahtani 2011); and one each in Jamaica (Samuels 2007); the USA (Taskin 1993); Kenya (Mukaindo 2010), Italy (Cromi 2011) and Nepal (Dahal 2013). All the studies took place in a hospital setting, mostly a tertiary or teaching hospital.

 

Types of antispasmodics/interventions

The antispasmodics used in the intervention groups were valethamate bromide (Ajmera 2006; Batukan 2006; Dahal 2013; Khosla 2003; Kuruvila 1992; Madhu 2010; Raghavan 2008; Sharma 2001; Taskin 1993; Yilmaz 2009), drotaverine hydrochloride (Ajmera 2006; Dahal 2013; Gupta 2008; Khosla 2003; Madhu 2010; Sharma 2001; Singh 2004), hyoscine butyl bromide ( Al Matari 2007; Al Qahtani 2011; Gupta 2008; Makvandi 2010; Mukaindo 2010; Raghavan 2008; Samuels 2007; Sekhavat 2012; Taskin 1993), rociverine (Cromi 2011) and camylofin dihydrochloride (Warke 2003). One study used a combination of hyoscine and atropine (Azari 2010).

Drotaverine hydrochloride, rociverine and camylofin dihydrochloride are musculotropic agents - phosphodiesterase type IV inhibitors, structurally related to papaverine. They have mild Ca-channel blocking effects, no anticholinergic effects and act directly on smooth muscle cells, inhibiting spasm (Romics 2003; Sommers 2002). Valethamate bromide and hyoscine butyl bromide (Buscopan) are anticholinergic agents, which act as antagonists of acetylcholine at muscarinic receptors, inhibiting muscle spasm of smooth muscles innervated by the parasympathetic nerves (Samuels 2009; Sommers 2002).

NIne of the studies were multi-intervention studies (Ajmera 2006; Dahal 2013; Gupta 2008; Khosla 2003; Madhu 2010; Raghavan 2008; Sharma 2001; Taskin 1993; Yilmaz 2009), all with two or more intervention groups and one control group. Two multi-intervention studies (Taskin 1993; Yilmaz 2009) had one intervention arm of meperidine, which is not classified as an antispasmodic and was therefore not included in the meta-analysis. The other intervention arms of these two studies, valethamate bromide and hyoscine butyl bromide, were used for analysis. The other seven multi-intervention studies (Ajmera 2006; Dahal 2013; Gupta 2008; Khosla 2003; Madhu 2010; Raghavan 2008; Sharma 2001) included two different antispasmodic agents in the intervention groups and a control group. All three groups were included in the meta-analyses.

Antispasmodic drugs were administered intravenously (IV), intramuscularly (IM) or per rectum (PR). Hyoscine butyl bromide was administered IV or PR, while drotaverine hydrochloride was only administered IM. Valethamate bromide was administered either IV or IM. Rociverine as well as camylofin dihydrochloride were administered IM.

Fourteen studies (Al Qahtani 2011; Batukan 2006; Cromi 2011; Dahal 2013; Gupta 2008; Kuruvila 1992; Madhu 2010; Makvandi 2010; Mukaindo 2010; Samuels 2007; Sekhavat 2012; Singh 2004; Taskin 1993; Yilmaz 2009) followed a protocol for active management of labour, which included artificial rupture of membranes (aROM), augmentation with oxytocin, or both. Two studies ( Sharma 2001; Warke 2003) avoided aROM and did not augment labour with oxytocin. Five studies (Ajmera 2006; Al Matari 2007; Azari 2010; Khosla 2003; Raghavan 2008) did not mention aROM or oxytocin.

 

Participants

Ten studies included only primigravid women (Al Qahtani 2011; Azari 2010; Cromi 2011; Makvandi 2010; Mukaindo 2010; Raghavan 2008; Sharma 2001; Singh 2004; Warke 2003; Yilmaz 2009). Nine studies included both primi- and multigravid women (Ajmera 2006; Batukan 2006; Dahal 2013; Gupta 2008; Khosla 2003; Kuruvila 1992; Madhu 2010; Samuels 2007; Taskin 1993), the ratio of both not being statistically different in all the studies. Sekhavat 2012 only included multigravid women and Al Matari 2007 did not specify the gravidity of participants. Yilmaz 2009 included only women with induction of labour. Batukan 2006 and Dahal 2013 included women with induction of labour and women in spontaneous labour. Thirteen studies (Ajmera 2006; Al Qahtani 2011; Cromi 2011; Khosla 2003; Madhu 2010; Makvandi 2010; Mukaindo 2010; Raghavan 2008; Samuels 2007; Sekhavat 2012; Sharma 2001; Singh 2004; Warke 2003) only included participants in spontaneous labour. Five studies (Al Matari 2007; Azari 2010; Gupta 2008; Kuruvila 1992; Taskin 1993) did not specify whether participants were in spontaneous or induced labour.

Gupta 2008 included women with high-risk pregnancies as well as women with low-risk pregnancies. The rest of the studies only included women with low-risk pregnancies.

 

Outcomes

For 17 studies (Ajmera 2006; Al Matari 2007; Al Qahtani 2011; Batukan 2006; Dahal 2013; Gupta 2008; Khosla 2003; Madhu 2010; Makvandi 2010; Mukaindo 2010; Raghavan 2008; Samuels 2007; Sekhavat 2012; Sharma 2001; Singh 2004; Warke 2003; Yilmaz 2009), the primary outcome was the duration of labour. This included duration of first stage of labour (active stage of labour, from 3 cm to 4 cm to full cervical dilatation), second stage of labour (from full cervical dilatation to expulsion of baby), third stage of labour (from delivery of baby to delivery of placenta) and total duration of labour.

Ten studies (Ajmera 2006; Batukan 2006; Cromi 2011; Gupta 2008; Khosla 2003; Kuruvila 1992; Madhu 2010; Sharma 2001; Singh 2004; Yilmaz 2009), excluded participants delivering via caesarean section from their calculation of the mean duration of labour, while seven studies (Al Qahtani 2011; Dahal 2013; Makvandi 2010; Mukaindo 2010; Samuels 2007; Sekhavat 2012; Warke 2003) included participants undergoing caesarean section in the calculation of the mean duration of labour.

For three studies (Azari 2010; Cromi 2011; Kuruvila 1992), the primary outcome was rate of cervical dilatation. Singh 2004 reported on pain relief during labour. Taskin 1993 was only reported as an abstract and contains minimal information about methods, outcomes and results.

 

Excluded studies

Twenty-four studies (Aggarwal 2008; Akleh 2010; Baracho 1982; Bhattacharaya 1984; Chan 1963; De Nobrega-Correa 2010; Demory 1990; Fouedjio 2012; Guerresi 1981; Hamann 1972; Hao 2004; Kauppila 1970; Kaur 2003; Kaur 2006; Malensek 1985; Manpreet 2008; Maritati 1986; Mishra 2002; Mortazavi 2004; Rajkumar 2006; Sirohiwal 2005; Tabassum 2005; Tripti 2009; Von Hagen 1965) were excluded from the review. Reasons for exclusion were lack of randomisation, absence of a control group and inclusion of non-eligible participants. These are summarised in the Characteristics of excluded studies table.

 

Risk of bias in included studies

The risk of bias for each study is presented in the 'Risk of bias' tables in the Characteristics of included studies table. Figure 3 and Figure 4 illustrate the summary of risk of bias in all the studies.

 FigureFigure 3. 'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
 FigureFigure 4. 'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.

 

Allocation

Allocation sequence generation was assessed as adequate in 10 studies (Al Qahtani 2011; Cromi 2011; Dahal 2013; Kuruvila 1992; Mukaindo 2010; Samuels 2007; Sekhavat 2012; Sharma 2001; Singh 2004; Yilmaz 2009). Of these, seven (Cromi 2011; Dahal 2013; Mukaindo 2010; Samuels 2007; Sekhavat 2012; Sharma 2001; Yilmaz 2009), used computer-generated tables of random numbers; Kuruvila 1992 used a table of random numbers and two studies (Al Qahtani 2011; Singh 2004) drew paper slips from a box. Sequence generation was unclear in the remaining 11 studies (Ajmera 2006; Al Matari 2007; Azari 2010; Batukan 2006; Gupta 2008; Khosla 2003; Madhu 2010; Makvandi 2010; Raghavan 2008; Taskin 1993; Warke 2003).

Only six studies reported adequate allocation concealment (Al Qahtani 2011; Cromi 2011; Kuruvila 1992; Mukaindo 2010; Samuels 2007; Yilmaz 2009). Samuels 2007 and Mukaindo 2010 used sequentially numbered, pre-filled syringes, Kuruvila 1992 used identical, sequentially numbered ampoules and Yilmaz 2009 used sequentially numbered, opaque, sealed envelopes to conceal allocation. Cromi 2011 used an independent resident physician who managed the randomisation process and drew up the injectable in a separate pharmacy room in the labour ward, while Al Qahtani 2011 used the nurse in charge to draw an envelope from a box and prepare the injectable accordingly. In Batukan 2006, it was unclear whether sealed envelopes were opaque and sequentially numbered, in Makvandi 2010 it was unclear whether suppositories were in identical packages and sequentially numbered, while in Ajmera 2006 and Singh 2004, allocation concealment was evidently absent. Allocation concealment was not reported in the rest of the studies (Al Matari 2007; Azari 2010; Dahal 2013; Gupta 2008; Khosla 2003; Madhu 2010; Raghavan 2008; Sekhavat 2012; Sharma 2001; Taskin 1993; Warke 2003).

 

Blinding

Eight studies had low risk of performance bias and adequately reported on blinding of participants and personnel (Al Qahtani 2011; Batukan 2006; Cromi 2011; Kuruvila 1992; Makvandi 2010; Mukaindo 2010; Samuels 2007; Taskin 1993). In Yilmaz 2009, participants were blinded, but nurses were not blinded. In six studies (Ajmera 2006; Dahal 2013; Gupta 2008; Madhu 2010; Raghavan 2008; Sekhavat 2012), blinding of participants and personnel was absent. In the remaining seven studies (Al Matari 2007; Azari 2010; Khosla 2003; Sekhavat 2012; Sharma 2001; Singh 2004; Warke 2003), it was unclear whether blinding of participants and personnel occurred due to poor reporting.

Ten studies (Al Qahtani 2011; Batukan 2006; Cromi 2011; Kuruvila 1992; Makvandi 2010; Mukaindo 2010; Samuels 2007; Sekhavat 2012; Singh 2004; Yilmaz 2009) had low risk of detection bias and adequately reported on blinding of outcome assessors. Three studies (Ajmera 2006; Gupta 2008; Madhu 2010) did not blind outcome assessors and were considered to have a high risk of detection bias. The remaining studies ( Al Matari 2007; Azari 2010; Dahal 2013; Khosla 2003; Raghavan 2008; Sharma 2001; Taskin 1993; Warke 2003) were judged as unclear risk of detection bias, due to poor reporting of blinding of outcome assessors.

 

Incomplete outcome data

Four studies (Al Qahtani 2011; Singh 2004; Taskin 1993; Warke 2003) failed to adequately report on the outcomes of all the participants and were considered to have a high risk for attrition bias. Two studies (Singh 2004; Taskin 1993) did not report separate loss to follow-up figures for control and intervention groups, while Warke 2003 did not report on the details of participant outcomes and the percentages did not add up. Al Qahtani 2011 did not report outcomes for 13 participants who were randomised to intervention and control groups, had received the corresponding treatment but were excluded from the analysis due to various reasons. Four studies (Al Matari 2007; Azari 2010; Dahal 2013; Raghavan 2008) could not be classified as high or low risk of attrition bias. Azari 2010 and Raghavan 2008 only reported the number of participants enrolled in the study; while in Al Matari 2007 it was unclear whether or not women who did not deliver after four hours were included in the analysis. Dahal 2013 did not report the number of participants with the results. The remaining studies (Ajmera 2006; Batukan 2006; Cromi 2011; Gupta 2008; Khosla 2003; Kuruvila 1992; Madhu 2010; Makvandi 2010; Mukaindo 2010; Samuels 2007; Sekhavat 2012; Sharma 2001; Yilmaz 2009) reported adequately on all participants.

 

Selective reporting

Nine studies reported adequately on outcomes (Al Qahtani 2011; Batukan 2006; Cromi 2011; Gupta 2008; Mukaindo 2010; Samuels 2007; Sharma 2001; Warke 2003; Yilmaz 2009). Ten studies (Al Matari 2007; Azari 2010; Dahal 2013; Khosla 2003; Kuruvila 1992; Madhu 2010; Makvandi 2010; Raghavan 2008; Sekhavat 2012; Taskin 1993) were considered as having a high risk of reporting bias. Three of these studies (Azari 2010; Madhu 2010; Raghavan 2008), did not report on all the outcomes pre-specified in the study report, Makvandi 2010 did not report on the primary outcomes as specified in the study protocol; while the rest (Al Matari 2007; Khosla 2003; Kuruvila 1992; Taskin 1993), did not pre-specify which outcomes were being assessed in the methodology. In three studies (Ajmera 2006; Sekhavat 2012; Singh 2004), secondary outcomes were not clearly reported and Dahal 2013 omitted results of the control group for certain outcomes.

 

Other potential sources of bias

Six studies (Ajmera 2006; Al Qahtani 2011; Dahal 2013; Sharma 2001; Singh 2004; Warke 2003) had a high potential for other bias. Sharma 2001 reported a 100% rate of normal vertex deliveries (NVDs) although the hospital's normal rate of caesarean section is 12%, raising doubt about the validity of the study. Singh 2004 started the intervention at 3 cm to 6 cm cervical dilatation, but had more participants in the intervention group with 6 cm cervical dilatation than in the control group (18 versus three). In Al Qahtani 2011, there was a significant baseline imbalance between groups regarding rupture of membranes at enrolment and Dahal 2013 failed to report on baseline characteristics of participants and had different results for the outcomes "duration of active phase of labour" and "duration of labour until the end of first stage of labour", although these are essentially the same. In nine studies (Al Matari 2007; Azari 2010; Batukan 2006; Gupta 2008; Khosla 2003; Kuruvila 1992; Raghavan 2008; Sekhavat 2012; Taskin 1993) it was unclear if any other bias was introduced. Three studies (Al Matari 2007; Azari 2010; Taskin 1993) were only reported as conference abstracts and lack detail and contact information, while Raghavan 2008 was reported as a letter to the editor and also lacks details and contact information. Data extraction of Batukan 2006 was carried out by a translator and judgement about other biases was therefore difficult. Gupta 2008 did not have the same starting point for all participants, but reported that this was not significantly different between treatment and intervention groups and Sekhavat 2012 did not specify which outcome was used to calculate the sample size and included only multigravid women in their study. Six studies (Cromi 2011; Madhu 2010; Makvandi 2010; Mukaindo 2010; Samuels 2007; Yilmaz 2009) were assessed as being free of other bias.

Bias introduced by drug company sponsorship was evidently absent in eight studies ( Al Qahtani 2011; Cromi 2011; Madhu 2010; Makvandi 2010; Mukaindo 2010; Samuels 2007; Warke 2003; Yilmaz 2009). In the remaining 13 studies (Ajmera 2006; Al Matari 2007; Azari 2010; Batukan 2006; Dahal 2013; Gupta 2008; Khosla 2003; Kuruvila 1992; Raghavan 2008; Sekhavat 2012; Sharma 2001; Singh 2004; Taskin 1993), it was unclear whether drug company sponsorship was present, since conflict of interest was not explicitly mentioned.

 

Effects of interventions

See:  Summary of findings for the main comparison Antispasmodics versus control

A summary of the effects of the interventions is presented in  Table 1.

Although this review included 21 studies (3286 participants), only 17 studies (2617 participants) were included in the meta-analysis. Four studies (Al Matari 2007; Azari 2010; Raghavan 2008; Taskin 1993) were not included in the meta-analysis because they were only reported as abstracts and contained insufficient information on relevant data. In addition, they did not contain contact information of authors to obtain missing data.

 

Primary outcomes

 

1. Duration of labour

 
Duration of first stage of labour

Thirteen studies (Ajmera 2006; Al Qahtani 2011; Batukan 2006; Cromi 2011; Dahal 2013; Gupta 2008; Khosla 2003; Makvandi 2010; Samuels 2007; Sekhavat 2012; Singh 2004; Warke 2003; Yilmaz 2009) involving 1995 women were included in the random-effects meta-analysis ( Analysis 1.1). Antispasmodics reduced the duration of first stage of labour by an average of 74.34 minutes (mean difference (MD) -74.34 minutes; 95% confidence interval (CI) -98.76 to -49.93; T² = 2083.23; I² = 83%).

Subgroup analysis showed significant differences between subgroups for management of labour (active versus expectant management of labour) (Chi² = 4.44, P = 0.04, I² = 77.5%) ( Analysis 6.1) and type of pregnancy (low- versus high-risk pregnancy) (Chi² = 21.48, P < 0.00001, I² = 95.3%) ( Analysis 7.1). There were no significant differences between the other subgroups.

Sensitivity analysis, excluding studies with high risk of bias (inadequate allocation concealment and incomplete outcome data), included only three studies (Cromi 2011; Samuels 2007; Yilmaz 2009; n = 334) and showed a smaller, yet still significant reduction in duration of first stage of labour (MD -47.78 minutes; 95% CI -68.66 to -26.91, fixed-effect) with an absence of significant heterogeneity (Chi² = 2.48; P = 0.29; I² = 19%) ( Analysis 8.1).

The funnel plot for this outcome was asymmetrical (Figure 5).

 FigureFigure 5. Funnel plot of comparison: 1 Antispasmodics versus control, outcome: 1.1 Duration of first stage of labour (min).

 
Duration of second stage of labour

Ten studies (involving 1297 women) (Ajmera 2006; Al Qahtani 2011; Batukan 2006; Cromi 2011; Gupta 2008; Makvandi 2010; Samuels 2007; Sekhavat 2012; Singh 2004; Yilmaz 2009) were included in the random-effects meta-analysis ( Analysis 1.2). There was no significant reduction in the duration of the second stage of labour, with an average intervention effect of -2.68 minutes (95% CI -5.98 to 0.63, T² = 18.97; I² = 67%).

Subgroup analysis showed significant differences between subgroups for studies excluding versus studies including caesarean sections in the analysis (Chi² = 9.65, P = 0.002, I² = 89.6%) ( Analysis 2.2) and type of labour (spontaneous versus induced labour) (Chi² = 7.08, P = 0.008, I² = 85.9%) ( Analysis 5.2).

Sensitivity analysis included three studies (Cromi 2011; Samuels 2007; Yilmaz 2009) (involving 336 women) and did not show a significantly different effect (MD 2.64 minutes; 95% CI -6.34 to 11.61; I² = 78%) ( Analysis 8.2).

 
Duration of third stage of labour

Five studies (involving 765 women) (Ajmera 2006; Gupta 2008; Samuels 2007; Sekhavat 2012; Singh 2004) were included in the random-effects meta-analysis ( Analysis 1.3). Overall, there was no significant effect of antispasmodics on the third stage of labour (MD -0.06 minutes; 95% CI -0.52 to 0.40; T² = 0.17; I² = 52%). Subgroup analysis showed a significant difference between groups for gravidity of women (primigravidas versus primi-and multigravidas versus multigravidas) (Chi² = 7.93, P = 0.02, I² = 74.8%) ( Analysis 4.3).

Sensitivity analysis only included the Samuels 2007 study and did not show a significant effect on the duration of third stage of labour (MD 2.00 minutes; 95% CI -0.98 to 4.98; one study, 129 women) ( Analysis 8.3).

Total duration of labour

Seven studies (involving 797 women) (Al Qahtani 2011; Madhu 2010; Mukaindo 2010; Samuels 2007; Sharma 2001; Warke 2003; Yilmaz 2009) assessed this outcome. Random-effects meta-analysis ( Analysis 1.4) showed an average reduction of 85 minutes in the total duration of labour, but significant heterogeneity was also present (MD -85.51; 95% CI -121.81 to -49.20; T² = 2411.75; I² = 83%).

Subgroup analysis showed a significant difference between groups for route of administration (intravenous versus intramuscular administration) (Chi² = 4.01, P = 0.05, I² = 75.0%) ( Analysis 3.4), type of labour (spontaneous versus induced labour) (Chi² = 5.70, P = 0.02, I² = 82.5%) ( Analysis 5.4) and management of labour (active versus expectant management of labour) (Chi² = 12.76, P = 0.0004, I² = 92.2%) ( Analysis 6.4).

Sensitivity analysis included three studies (involving 304 women) (Mukaindo 2010; Samuels 2007; Yilmaz 2009) with adequate allocation concealment and without incomplete reporting of data. The results showed a smaller, but significant reduction in the total duration of labour (MD -44.79 minutes; 95% CI -80.19 to -9.39; random-effects, T² = 401.72, I² = 40%) ( Analysis 8.4). Heterogeneity was reduced considerably.

 

2. Rate of cervical dilatation

Seven studies (Cromi 2011; Gupta 2008; Kuruvila 1992; Madhu 2010; Mukaindo 2010; Sekhavat 2012; Sharma 2001) reported on the cervical dilatation rate and six of these (involving 820 women) were included in the meta-analysis ( Analysis 1.5). Kuruvila 1992 reported data in four different subgroups and was not included. Random-effects meta-analysis showed a significant average increase in the rate of cervical dilatation of 0.61 cm/hour. Significant heterogeneity was observed (MD 0.61cm/hour; 95% CI 0.34 to 0.88; random-effects, T² = 0.12; I² = 80%).

Subgroup analysis showed a significant difference for type of labour (spontaneous versus induced labour) (Chi² = 7.34, P = 0.007, I² = 86.4%) ( Analysis 5.5), management of labour (active versus expectant management of labour) (Chi² = 5.35, P = 0.02, I² = 81.3%) ( Analysis 6.5) and type of pregnancy (low- versus high-risk pregnancy) (Chi² = 7.34, P = 0.007, I² = 86.4%) ( Analysis 7.4).

Sensitivity analysis only included two studies (involving 190 women) (Cromi 2011; Mukaindo 2010) and showed a non-significant effect of antispasmodics on the rate of cervical dilatation (MD 0.22 cm/hour; 95% CI -0.39 to 0.83; I² = 66%) ( Analysis 8.5).

 

3. Pain relief

Only one study (Singh 2004) assessed the effect of antispasmodics on pain relief (n = 100), by using both a visual analogue scale (VAS) with a zero to 100 score, and a verbal rating scale from zero to four. Pain was assessed hourly. There was a similar trend in the experience of pain in both groups. During the second stage, the intervention group had more pain than the placebo group, but in the fourth stage, the intervention group had less pain. Three participants asked for pain relief in the intervention group, compared with two in the control group. The effect of the intervention was thus not significant.

 

4. Rate of normal vertex deliveries (NVDs)

Sixteen studies (Ajmera 2006; Al Qahtani 2011; Cromi 2011; Dahal 2013; Gupta 2008; Khosla 2003; Kuruvila 1992; Madhu 2010; Makvandi 2010; Mukaindo 2010; Samuels 2007; Sekhavat 2012; Sharma 2001; Singh 2004; Warke 2003; Yilmaz 2009) (involving 2319 women) were included in the fixed-effect meta-analysis on rate of normal vertex deliveries ( Analysis 1.6). Antispasmodics had no overall significant effect on the rate of normal vertex deliveries (risk ratio (RR) 1.02, 95% CI 1.00, 1.05). Subgroup analysis, however, showed a significant difference between groups for type of antispasmodic (neurotropic versus musculotropic) (Chi² = 4.97, P = 0.03, I² = 79.9%) ( Analysis 1.6).

Sensitivity analysis included four studies (involving 425 women) (Cromi 2011; Mukaindo 2010; Samuels 2007; Yilmaz 2009) with low risk of bias and did not show a difference in effect (RR 1.03; 95% CI 0.96 to 1.10; I² = 34%) ( Analysis 8.6).

The funnel plot for this outcome was symmetrical (Figure 6).

 FigureFigure 6. Funnel plot of comparison: 1 Antispasmodics versus control, outcome: 1.6 Rate of NVDs.

 

Secondary outcomes

 

1. Maternal adverse events

Maternal adverse events were reported using different approaches and are summarised in  Table 2. Adverse events that were reported across studies were tachycardia, mouth dryness, headache, nausea, vomiting, dizziness, giddiness, cervical laceration, flushing of face and postpartum haemorrhage. Meta-analysis was conducted for outcomes reported quantitatively.

Tachycardia ( Analysis 9.1)

Six studies (Ajmera 2006; Gupta 2008; Khosla 2003; Madhu 2010; Sharma 2001; Yilmaz 2009) involving 832 women were included in the fixed-effect meta-analysis. There was an increased risk for tachycardia for participants receiving antispasmodics (RR 4.54; 95% CI 2.53 to 8.16). Subgroup analysis showed a significant difference between groups for type of antispasmodic (neurotropic versus musculotropic agents), with a greater risk with neurotropic agents (Chi² = 12.90,(P = 0.0003), I² = 92.3%).

Mouth dryness ( Analysis 9.2)

Six studies (Ajmera 2006; Khosla 2003; Madhu 2010; Sharma 2001; Warke 2003; Yilmaz 2009) involving 738 women were included in the fixed-effect meta-analysis. There was an increased risk for mouth dryness for participants receiving antispasmodics (RR 6.81; 95% CI 2.71 to 17.12).

Headache ( Analysis 9.3)

Three studies (Ajmera 2006; Madhu 2010; Sharma 2001) involving 515 women were included in the fixed-effect meta-analysis.There was no significant difference in the risk for headaches between intervention and control groups (RR 1.51; 95% CI 0.56 to 4.10).

Nausea and vomiting ( Analysis 9.4;  Analysis 9.5)

Two studies (Warke 2003; Yilmaz 2009) involving 196 women had quantitative data on nausea and on vomiting and were included in the fixed-effect meta-analysis, showing no significant difference in risk between intervention and control groups for either nausea (RR 1.97; 95% CI 0.74, 5.28) or vomiting (RR 2.21; 95% CI 0.64 to 7.62).

Dizziness ( Analysis 9.6)

Only one study (Yilmaz 2009) involving 96 women reported quantitative data on dizziness, showing no significant difference in risk for dizziness between intervention and control groups (RR 3.13; 95% CI 0.66 to 14.73).

Giddiness ( Analysis 9.7)

Three studies (Ajmera 2006; Madhu 2010; Sharma 2001) involving 343 women were included in the fixed-effect meta-analysis, showing no significant difference in risk for giddiness between intervention and control groups (RR 0.25; 95% CI 0.05 to 1.16).

Cervical lacerations ( Analysis 9.8)

Three studies (Ajmera 2006; Warke 2003; Yilmaz 2009) including 342 women were included in the fixed-effect meta-analysis, showing no significant difference in risk for cervical lacerations between intervention and control groups (RR 0.79; 95% CI 0.20 to 3.12).

Flushing of face ( Analysis 9.9)

Four studies (Ajmera 2006; Khosla 2003; Madhu 2010; Sharma 2001) involving 542 women were included in the fixed-effect meta-analysis, showing a significant increased risk for flushing of the face in the intervention group (RR 8.48; 95% CI 1.98 to 36.35).

Postpartum haemorrhage ( Analysis 9.10)

Two studies (Mukaindo 2010; Singh 2004) involving 185 women, were included in the random-effects meta-analysis, showing no significant difference in risk for postpartum haemorrhage between intervention and control groups (RR 2.46; 95% CI 0.20 to 30.17;T² = 2.35; I² = 72%)

 

2. Neonatal adverse events

As with maternal adverse events, neonatal adverse events were reported using different approaches and are summarised in  Table 3. Adverse events reported admission to neonatal intensive care unit (NICU), fetal distress, fetal bradycardia, fetal tachycardia and presence of meconium-stained liquor. Apgar scores at one and five minutes after delivery were also reported. A low Apgar score (less than seven at both one and five minutes) was also seen as an adverse event. Meta-analysis was conducted for quantitatively reported outcomes.

Admission to NICU ( Analysis 10.1)

Five studies (Dahal 2013; Gupta 2008; Sekhavat 2012; Warke 2003; Yilmaz 2009) involving 845 babies, were included in the fixed-effect meta-analysis, showing no significant difference in the risk for admission to NICU between intervention and control groups (RR 0.84; 95% CI 0.34 to 2.05).

Fetal distress ( Analysis 10.2)

One study (Sharma 2001) involving 100 babies, reported quantitatively on this outcome and showed no difference in risk for fetal distress between intervention and control groups (RR 0.50; 95% CI 0.10 to 2.61).

Fetal bradycardia ( Analysis 10.3)

One study (Makvandi 2010) involving 130 babies, reported quantitatively on this outcome, showing no difference in risk for fetal bradycardia between intervention and control groups (RR 0.67; 95% CI 0.12 to 3.86).

Fetal tachycardia ( Analysis 10.4)

Two studies (Madhu 2010; Makvandi 2010) involving 230 babies were included in the fixed-effect meta-analysis, showing no significant difference in risk for fetal tachycardia between intervention and control groups (RR 3.40; 95% CI 0.85 to 13.67).

Meconium-stained liquor ( Analysis 10.5)

One study (Yilmaz 2009) involving 107 babies, reported quantitatively on this outcome, showing no significant difference in risk for meconium-stained liquor between intervention and control groups (RR 2.04; 95% CI 0.54, 7.73).

Low Apgar score

One- and five-minute Apgar scores reported quantitatively, were either reported as means with the range of scores, or as proportion of babies with a score of less than seven. Results were thus not combined in meta-analysis, but are presented in  Table 3.

 

3. Maternal satisfaction

Only Mukaindo 2010 reported on maternal satisfaction. The investigators developed a questionnaire using Likert rating scale questions. Women in the study were asked to rate their satisfaction based on their expectations on four items (overall labour experience, pain control during labour, duration of labour, whether they would consider receiving the study drug in their next labour). A composite score out of 20 points was calculated. The mean score for the treatment group was 13.7, compared with 14.4 in the placebo group, showing no significant difference in maternal satisfaction (MD 0.7; 95% CI -2.5 to 1.1; one study, 58 women).

 

Discussion

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Summary of main results

Twenty-one studies were included in this updated review,17 of which were included in the meta-analysis. Most studies were conducted in India. Valethamate bromide was the drug most commonly used in studies, followed by hyoscine-butyl-bromide. Both these drugs have anti-cholinergic actions.

Including the two new studies did not change the overall results of this review. On average, antispasmodics decreased the duration of the first stage of labour, as well as the total duration of labour. For both outcomes, significant heterogeneity was observed that remained mostly unexplained. Sensitivity analysis, considering only studies with low risk of selection and attrition bias, showed a significant reduction in the duration of first stage of labour, with the absence of heterogeneity. The total duration of labour was also reduced with significantly less heterogeneity when only studies with low risk of bias were considered.

Two Cochrane reviews (Brown 2008; Wei 2009) reporting on the outcome 'duration of labour' also reported significant, unexplained heterogeneity. Calculation of the duration of labour can be very difficult and subjective. Firstly, differences in measurement of cervical dilatation exist, possibly introducing detection bias. Secondly, the course of labour differs immensely between labouring women. While some present with strong, painful contractions at 2 cm cervical dilatation, others will experience the same amount of pain only at 4 cm cervical dilatation. This influences the individual perception of the beginning of labour, which in effect cannot be determined. Most studies thus defined their measurement of the first stage of labour as the point of administration of the intervention until full cervical dilatation. This timing of the administration of the intervention varied from 3 cm to 6 cm cervical dilatation ( Table 1), both within and between studies. Considering this, the rate of cervical dilatation would be a more accurate measurement. Random-effects meta-analysis of the results of the six studies that reported this outcome showed a significant increase in the rate of cervical dilatation. Significant, unexplained heterogeneity was also observed for this outcome and all results should thus be interpreted with caution.

Duration of second and third stage of labour was not affected by antispasmodics. Pain relief was only assessed by two studies and it remains unclear whether antispasmodics have an analgesic effect. The rate of normal vertex deliveries was not affected by antispasmodics. All but one study included only women with low-risk pregnancies, mostly already in active labour which in itself presents favourable conditions for normal vertex deliveries.

Results for seven of the studies included in the meta-analysis included patients who delivered via caesarean section in their calculation of the duration of labour. Subgroup analysis showed that there was no significant difference for the outcomes duration of first stage of labour and total duration of labour. There was a significant difference between subgroups for the outcome duration of second stage of labour. The rate of caesarean sections was similar in intervention and control groups in all these studies.

Maternal and neonatal adverse events were not reported consistently throughout studies. The most commonly reported maternal adverse events were tachycardia (six studies) and mouth dryness (six studies). For both, meta-analyses showed an increased risk for the intervention group. Both of these are documented side effects of antispasmodic drugs.

Neonatal adverse events were also reported inconsistently. The most commonly reported adverse event (five studies) was admission to NICU. None of the adverse events included in the meta-analyses showed a significant result. A low Apgar score was also seen as a neonatal adverse event. The one- and five-minute Apgar scores were reported inconsistently but were almost identical in the intervention and control groups for all studies reporting these.

 

Overall completeness and applicability of evidence

Most studies included in the meta-analysis were conducted in low- and middle-income countries, although it is known that the use of antispasmodics during labour is widespread in high-income countries as well. In most cases, labour is not a condition listed under the indications for the use of these drugs by their manufacturers, probably due to the lack of evidence regarding the safety for both mother and baby. Although there were no serious adverse events reported in any of the studies included in this review, less than half of the studies adequately reported on maternal and neonatal adverse events and there is thus insufficient information to make any conclusions about the safety of these drugs during labour.

Nine studies were conducted in India, where the administration of antispasmodics forms part of their protocol for programmed labour and is routinely administered (Daftary 2009; Yuel 2008). Yet, this still seems to be a widely debated topic. Valethamate bromide, a drug used quite commonly, is not even listed in the Indian Pharmacopoeia (Gitanjali 2010; Thirunavukkarasu 2010), again raising concerns about its safety when used during pregnancy.

Only one study (Mukaindo 2010) was carried out in an African country. Considering the selective availability of epidural analgesia in low- and middle-income countries such as India and Kenya, antispasmodics could provide an alternative and cost-effective method to shorten the duration and pain associated with labour. In high-income countries, women opting to deliver without epidural analgesia, could benefit from the same alternative. Maternal views on artificial shortening of labour in the absence of prolonged labour were only addressed in one study measuring maternal satisfaction with treatment (Mukaindo 2010). Maternal views should be taken into consideration when deciding on a treatment strategy.

Most studies included antispasmodics as part of their package of active management of labour, and the studies where labour was managed expectantly were all at high risk of bias. The results should be interpreted keeping this in mind and mostly apply within a context of active management of labour. This included either artificial rupture of membranes (aROM), oxytocin augmentation or both. Subgroup analysis showed a significant difference between groups for outcomes: duration of first stage of labour, total duration of labour and rate of cervical dilatation. The effect was greater in the expectantly managed groups for all outcomes.

 

Quality of the evidence

Most studies included in this review lacked methodological rigour. Only four studies (Cromi 2011; Mukaindo 2010; Samuels 2007; Yilmaz 2009) were considered as having a low risk of bias. Sequence generation and allocation concealment were poorly reported in most studies thus introducing risk of selection bias. There was low risk of performance bias and detection bias in only eight and 10 studies respectively. It can be argued that progression of labour cannot be influenced by the participants' as well as the personnel's knowledge of the received intervention, but maternal relaxation and reassurance in any form aids the natural progression of labour while measurement of cervical dilatation is subjective to the person examining the woman. There was high risk of selective outcome reporting for 10 studies. Four of these were only reported as abstracts and thus only selectively reported on results. These were not included in the meta-analysis. Judgement of risk of bias for this domain was mainly made by looking at the study report, since study protocols were available for three studies only.

We used GRADE Profiler software to assess the quality of the evidence by rating the quality of evidence for each outcome. Factors taken into consideration include study limitations, imprecision, inconsistency of results, indirectness of evidence and publication bias (Guyatt 2011). The quality of evidence ranged from "very low" for the outcome Total duration of labour; to "low" for the outcomes Duration of first stage of labour, Duration of second stage of labour, Duration of third stage of labour and Rate of cervical dilatation; and "moderate" for the outcome Rate of normal vertex deliveries (see  Summary of findings for the main comparison) .

When considering only studies with low risk of bias in the sensitivity analysis, the quality of evidence for the outcome Duration of first stage of labour was rated as "high" since heterogeneity was absent in this meta-analysis and no study limitations were present.

 

Potential biases in the review process

A comprehensive search strategy was established to include published and unpublished studies in all languages. Translators were involved to assist with studies in foreign languages.Two review authors independently selected studies for inclusion in the review, assessed the risk of bias and extracted the data in order to minimise bias. Funnel plots were used to assess reporting biases for the outcomes duration of first stage of labour (Figure 5) and rate of normal vertex deliveries (Figure 6). The funnel plot was symmetrical for the rate of normal vertex deliveries and asymmetrical for the duration of first stage of labour. The poor methodological design of the studies as well as the high level of unexplained heterogeneity between studies included in the meta-analysis of duration of first stage of labour could be a source of funnel plot asymmetry.

 

Agreements and disagreements with other studies or reviews

No other systematic review on the effect of antispasmodics for labour was found. The results of all but two studies showed a reduction in the duration of labour with the administration of antispasmodics. Gupta 2008 was the only study that included women with low- and high-risk pregnancies, while Mukaindo 2010 had a sample size of only 85 and did not show a significant effect.

 

Authors' conclusions

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

 

Implications for practice

There is low quality evidence that administration of antispasmodics during the active phase of labour leads to a reduction in the duration of the first stage of labour and that there is an increase in the rate of cervical dilatation. There is very low quality evidence that the total duration of labour is reduced. When considering only studies with low risk of selection and attrition bias, there is high quality evidence that the duration of labour is reduced. There is evidence of moderate quality that antispasmodics are not effective in lowering caesarean section rates. There is insufficient evidence to make conclusions regarding maternal and neonatal adverse events of antispasmodics administration during labour.

Antispasmodics were administered at the beginning of established labour in all studies. The results of this review therefore, only apply when using antispasmodics in the light of prevention of prolonged labour, and not as treatment. Although there is a statistically significant reduction of approximately an hour in the duration of the first stage of labour, it is questionable whether this has any clinical relevance. However, considering limited human resources, crowded labour rooms and limited availability of epidural analgesia in low- and middle-income countries, one hour per labouring woman could have a positive impact on both the birthing facilities and the labouring woman. In both low-and middle-income as well as high income countries, women should be allowed to make informed choices regarding management of labour.

 
Implications for research

Since none of the included studies assessed the value of antispasmodics for the treatment of prolonged labour, a rigorously designed, well-conducted randomised controlled trial (RCT) with a large sample size would be beneficial to answer this question. Only when the occurrence of prolonged labour is reduced, will there be a reduction in the associated complications such as postpartum haemorrhage.

Since most studies were conducted in a context of active management of labour and those that were conducted in the context of expectant management were all of poor quality, a methodologically sound RCT is needed to answer the question whether antispasmodics could be used as a replacement for active management of labour, including artificial rupture of membranes and oxytocin use.

The sample sizes of all studies were calculated relating to the effect of the duration of labour. It is unclear whether these samples are sufficient to conclude that there was no effect on the rate of caesarean sections as well as maternal and neonatal adverse events. Studies considering the mode of delivery and the safety of mother and baby as main outcomes with accordingly calculated sample sizes are required.

Conducting such studies in Sub-Saharan Africa would be useful, because their outcomes could address the high burden of maternal morbidity and mortality experienced in these countries.

 

Acknowledgements

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

The 2013 updated systematic review was financially supported by the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP) and the Department of Reproductive Health and Research (RHR), World Health Organization. The named authors alone are responsible for the views expressed in this publication.

The National Institute for Health Research (NIHR) is the largest single funder of the Cochrane Pregnancy and Childbirth Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NIHR, NHS or the Department of Health.

For translation of non-English language studies: Charles Okwundu (French studies), Baran Kalay (Turkish study), Ole Olsen (Danish study) and Marzia Lazzerini (Italian studies).

As part of the pre-publication editorial process, the first version of this review was commented on by four peer referees (an editor and three referees who are external to the editorial team), a member of the Pregnancy and Childbirth Group's international panel of consumers and the Group's Statistical Adviser.

 

Data and analyses

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
Download statistical data

 
Comparison 1. Antispasmodics versus control: neurotropic versus musculotropic agents

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Duration of first stage of labour (min)131995Mean Difference (IV, Random, 95% CI)-74.34 [-98.76, -49.93]

    1.1 Neurotropic agents
101216Mean Difference (IV, Random, 95% CI)-68.88 [-96.51, -41.25]

    1.2 Musculotropic agents
7779Mean Difference (IV, Random, 95% CI)-82.07 [-129.63, -34.51]

 2 Duration of second stage of labour (min)101297Mean Difference (IV, Random, 95% CI)-2.68 [-5.98, 0.63]

    2.1 Neurotropic agents
8919Mean Difference (IV, Random, 95% CI)-4.02 [-7.71, -0.33]

    2.2 Musculotropic agents
4378Mean Difference (IV, Random, 95% CI)0.55 [-6.61, 7.72]

 3 Duration of third stage of labour (min)5765Mean Difference (IV, Random, 95% CI)-0.06 [-0.52, 0.40]

    3.1 Neurotropic agents (min)
4497Mean Difference (IV, Random, 95% CI)-0.07 [-1.00, 0.87]

    3.2 Musculotropic agents
3268Mean Difference (IV, Random, 95% CI)0.08 [-0.31, 0.47]

 4 Total duration of labour (min)7797Mean Difference (IV, Random, 95% CI)-85.51 [-121.81, -49.20]

    4.1 Neurotropic agents
6549Mean Difference (IV, Random, 95% CI)-65.85 [-102.67, -29.03]

    4.2 Musculotropic agents
3248Mean Difference (IV, Random, 95% CI)-127.39 [-218.95, -35.83]

 5 Rate of cervical dilatation (cm/h)6820Mean Difference (IV, Random, 95% CI)0.61 [0.34, 0.88]

    5.1 Neurotropic agents
5487Mean Difference (IV, Random, 95% CI)0.47 [0.09, 0.85]

    5.2 Musculotropic agents
4333Mean Difference (IV, Random, 95% CI)0.85 [0.50, 1.19]

 6 Rate of normal vertex deliveries162319Risk Ratio (M-H, Fixed, 95% CI)1.02 [1.00, 1.05]

    6.1 Neurotropic agents
131536Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.97, 1.03]

    6.2 Musculotropic agents
8783Risk Ratio (M-H, Fixed, 95% CI)1.06 [1.02, 1.11]

 
Comparison 2. Antispasmodics versus control: studies including caesarean section versus studies excluding C/S in analysis

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Duration of first stage of labour (min)131995Mean Difference (IV, Random, 95% CI)-74.34 [-98.76, -49.93]

    1.1 Excluding C/S
71051Mean Difference (IV, Random, 95% CI)-59.10 [-95.81, -22.38]

    1.2 Including C/S
6944Mean Difference (IV, Random, 95% CI)-93.09 [-125.11, -61.08]

 2 Duration of second stage of labour (min)101297Mean Difference (IV, Random, 95% CI)-2.68 [-5.98, 0.63]

    2.1 Excluding C/S
6753Mean Difference (IV, Random, 95% CI)0.51 [-3.04, 4.06]

    2.2 Including C/S
4544Mean Difference (IV, Random, 95% CI)-6.82 [-9.78, -3.86]

 3 Duration of third stage of labour (min)5765Mean Difference (IV, Random, 95% CI)-0.06 [-0.52, 0.40]

    3.1 Excluding C/S
3448Mean Difference (IV, Random, 95% CI)0.12 [-0.23, 0.46]

    3.2 Including C/S
2317Mean Difference (IV, Random, 95% CI)0.23 [-2.28, 2.75]

 4 Total duration of labour (min)7797Mean Difference (IV, Random, 95% CI)-85.51 [-121.81, -49.20]

    4.1 Excluding C/S
3392Mean Difference (IV, Random, 95% CI)-102.60 [-164.12, -41.08]

    4.2 Including C/S
4405Mean Difference (IV, Random, 95% CI)-68.85 [-96.89, -40.81]

 5 Rate of cervical dilatation (cm/h)6820Mean Difference (IV, Random, 95% CI)0.61 [0.34, 0.88]

    5.1 Excluding C/S
4553Mean Difference (IV, Random, 95% CI)0.67 [0.39, 0.95]

    5.2 Including C/S
2267Mean Difference (IV, Random, 95% CI)0.44 [-0.49, 1.37]

 
Comparison 3. Antispasmodics versus control: intravenous versus intramuscular versus rectal administration

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Duration of first stage of labour (min)131995Mean Difference (IV, Random, 95% CI)-74.37 [-98.79, -49.95]

    1.1 Intravenous administration
5591Mean Difference (IV, Random, 95% CI)-47.58 [-74.09, -21.07]

    1.2 Intramuscular administration
91274Mean Difference (IV, Random, 95% CI)-86.34 [-119.03, -53.65]

    1.3 Rectal administration
1130Mean Difference (IV, Random, 95% CI)-89.1 [-134.86, -43.34]

 2 Duration of second stage of labour (min)101297Mean Difference (IV, Random, 95% CI)-2.68 [-5.98, 0.63]

    2.1 Intravenous administration
5594Mean Difference (IV, Random, 95% CI)-2.02 [-5.77, 1.72]

    2.2 Intramuscular administration
6573Mean Difference (IV, Random, 95% CI)-2.07 [-8.86, 4.72]

    2.3 Rectal administration
1130Mean Difference (IV, Random, 95% CI)-12.90 [-21.17, -4.63]

 3 Duration of thrid stage of labour (min)5765Mean Difference (IV, Random, 95% CI)-0.06 [-0.52, 0.40]

    3.1 Intravenous administration
3425Mean Difference (IV, Random, 95% CI)0.18 [-1.08, 1.44]

    3.2 Intramuscular administration
3340Mean Difference (IV, Random, 95% CI)0.03 [-0.35, 0.40]

 4 Total duration of labour (min)7797Mean Difference (IV, Random, 95% CI)-85.51 [-121.81, -49.20]

    4.1 Intravenous administration
3304Mean Difference (IV, Random, 95% CI)-44.79 [-80.19, -9.39]

    4.2 Intramuscular administration
4493Mean Difference (IV, Random, 95% CI)-107.88 [-158.53, -57.23]

 5 Rate of cervical dilatation (cm/h)6820Mean Difference (IV, Random, 95% CI)0.61 [0.34, 0.88]

    5.1 Intravenous administration
3339Mean Difference (IV, Random, 95% CI)0.27 [-0.49, 1.03]

    5.2 Intramuscular administration
4481Mean Difference (IV, Random, 95% CI)0.79 [0.56, 1.03]

 
Comparison 4. Antispasmodics versus control: primigravidas versus primi-and multigravidas

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Duration of first stage of labour (min)131995Mean Difference (IV, Random, 95% CI)-74.37 [-98.79, -49.95]

    1.1 Primigravidas
6616Mean Difference (IV, Random, 95% CI)-58.39 [-80.74, -36.04]

    1.2 Primi- and multigravidas
61191Mean Difference (IV, Random, 95% CI)-79.18 [-115.74, -42.62]

    1.3 Mulitgravidas
1188Mean Difference (IV, Random, 95% CI)-73.60 [-108.84, -38.36]

 2 Duration of second stage of labour (min)101297Mean Difference (IV, Random, 95% CI)-2.70 [-5.99, 0.59]

    2.1 Primigravidas
5518Mean Difference (IV, Random, 95% CI)-3.81 [-13.41, 5.79]

    2.2 Primi- and multigravidas
4591Mean Difference (IV, Random, 95% CI)-1.35 [-4.01, 1.32]

    2.3 Multigravidas
1188Mean Difference (IV, Random, 95% CI)-5.80 [-8.31, -3.29]

 3 Duration of third stage of labour (min)5765Mean Difference (IV, Random, 95% CI)-0.06 [-0.52, 0.40]

    3.1 Primigravidas
184Mean Difference (IV, Random, 95% CI)0.17 [-0.32, 0.66]

    3.2 Primi-and multigravidas
3493Mean Difference (IV, Random, 95% CI)0.12 [-0.40, 0.63]

    3.3 Multigravidas
1188Mean Difference (IV, Random, 95% CI)-0.70 [-1.17, -0.23]

 4 Total duration of labour (min)7797Mean Difference (IV, Random, 95% CI)-85.51 [-121.81, -49.20]

    4.1 Primigravidas
5522Mean Difference (IV, Random, 95% CI)-102.50 [-162.73, -42.26]

    4.2 Primi- and multigravidas
2275Mean Difference (IV, Random, 95% CI)-56.58 [-78.38, -34.78]

 5 Rate of cervical dilatation (cm/h)5632Mean Difference (IV, Random, 95% CI)0.55 [0.22, 0.87]

    5.1 Primigravidas
3340Mean Difference (IV, Random, 95% CI)0.63 [0.17, 1.08]

    5.2 Primi-and multigravidas
2292Mean Difference (IV, Random, 95% CI)0.44 [-0.08, 0.97]

 
Comparison 5. Antispasmodics versus control: spontaneous versus spontaneous and/or induced labour

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Duration of first stage of labour (min)131885Mean Difference (IV, Random, 95% CI)-72.76 [-98.57, -46.95]

    1.1 Spontaneous labour
91247Mean Difference (IV, Random, 95% CI)-84.09 [-109.60, -58.58]

    1.2 Spontaneous and induced/induced only
4638Mean Difference (IV, Random, 95% CI)-51.87 [-109.47, 5.74]

 2 Duration of second stage of labour (min)101297Mean Difference (IV, Random, 95% CI)-2.68 [-5.98, 0.63]

    2.1 Spontaneous labour
7957Mean Difference (IV, Random, 95% CI)-4.59 [-8.13, -1.05]

    2.2 Spontaneous and induced/induced only
3340Mean Difference (IV, Random, 95% CI)2.41 [-1.34, 6.16]

 3 Duration of third stage of labour (min)5765Mean Difference (IV, Random, 95% CI)-0.06 [-0.52, 0.40]

    3.1 Spontaneous labour
4619Mean Difference (IV, Random, 95% CI)0.00 [-0.57, 0.57]

    3.2 Spontaneous and induced/induced only
1146Mean Difference (IV, Random, 95% CI)-0.24 [-1.18, 0.71]

 4 Total duration of labour (min)7797Mean Difference (IV, Random, 95% CI)-85.51 [-121.81, -49.20]

    4.1 Spontaneous labour
6701Mean Difference (IV, Random, 95% CI)-93.77 [-134.30, -53.24]

    4.2 Spontaneous and induced/induced only
196Mean Difference (IV, Random, 95% CI)-31.60 [-62.58, -0.62]

 5 Rate of cervical dilatation (cm/h)6820Mean Difference (IV, Random, 95% CI)0.61 [0.34, 0.88]

    5.1 Spontaneous labour
5674Mean Difference (IV, Random, 95% CI)0.72 [0.46, 0.98]

    5.2 Spontaneous and induced/induced only
1146Mean Difference (IV, Random, 95% CI)-0.07 [-0.58, 0.44]

 
Comparison 6. Antispasmodics versus control: active versus expectant management of labour

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Duration of first stage of labour (min)131995Mean Difference (IV, Random, 95% CI)-74.38 [-98.80, -49.96]

    1.1 Active management
101377Mean Difference (IV, Random, 95% CI)-60.44 [-88.41, -32.47]

    1.2 Expectant management
3618Mean Difference (IV, Random, 95% CI)-108.81 [-144.05, -73.56]

 2 Duration of second stage of labour (min)101297Mean Difference (IV, Random, 95% CI)-2.68 [-5.98, 0.63]

    2.1 Active management
91079Mean Difference (IV, Random, 95% CI)-3.12 [-7.34, 1.10]

    2.2 Expectant management
1218Mean Difference (IV, Random, 95% CI)-1.30 [-4.79, 2.19]

 3 Duration of third stage of labour (min)5765Mean Difference (IV, Random, 95% CI)-0.06 [-0.52, 0.40]

    3.1 Active management
4547Mean Difference (IV, Random, 95% CI)-0.17 [-0.78, 0.44]

    3.2 Expectant management
1218Mean Difference (IV, Random, 95% CI)0.19 [-0.53, 0.92]

 4 Total duration of labour (min)7797Mean Difference (IV, Random, 95% CI)-85.51 [-121.81, -49.20]

    4.1 Active management
5547Mean Difference (IV, Random, 95% CI)-49.69 [-65.17, -34.21]

    4.2 Expectant management
2250Mean Difference (IV, Random, 95% CI)-172.91 [-238.73, -107.09]

 5 Rate of cervical dilatation (cm/h)6820Mean Difference (IV, Random, 95% CI)0.61 [0.34, 0.88]

    5.1 Active management
5670Mean Difference (IV, Random, 95% CI)0.47 [0.10, 0.83]

    5.2 Expectant management
1150Mean Difference (IV, Random, 95% CI)0.94 [0.77, 1.12]

 
Comparison 7. Antispasmodics versus control: low-risk versus high-risk pregnancies

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Duration of first stage of labour (min)131995Mean Difference (IV, Random, 95% CI)-74.37 [-98.79, -49.95]

    1.1 Low risk
121849Mean Difference (IV, Random, 95% CI)-86.31 [-108.94, -63.68]

    1.2 High risk
1146Mean Difference (IV, Random, 95% CI)34.84 [-11.13, 80.80]

 2 Duration of second stage of labour (min)101297Mean Difference (IV, Random, 95% CI)-2.68 [-5.98, 0.63]

    2.1 Low risk
91151Mean Difference (IV, Random, 95% CI)-3.67 [-7.30, -0.03]

    2.2 High risk
1146Mean Difference (IV, Random, 95% CI)1.65 [-3.52, 6.83]

 3 Duration of third stage of labour (min)5765Mean Difference (IV, Random, 95% CI)-0.06 [-0.52, 0.40]

    3.1 Low risk
4619Mean Difference (IV, Random, 95% CI)0.00 [-0.57, 0.57]

    3.2 High risk
1146Mean Difference (IV, Random, 95% CI)-0.24 [-1.18, 0.71]

 4 Rate of cervical dilatation (cm/h)6820Mean Difference (IV, Random, 95% CI)0.61 [0.34, 0.88]

    4.1 Low risk
5674Mean Difference (IV, Random, 95% CI)0.72 [0.46, 0.98]

    4.2 High risk
1146Mean Difference (IV, Random, 95% CI)-0.07 [-0.58, 0.44]

 
Comparison 8. Antispasmodics versus control: sensitivity analysis: studies with high risk of bias excluded

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Duration of first stage of labour (min)3334Mean Difference (IV, Fixed, 95% CI)-47.78 [-68.66, -26.91]

 2 Duration of second stage of labour (min)3336Mean Difference (IV, Random, 95% CI)2.64 [-6.34, 11.61]

 3 Duration of third stage of labour (min)1129Mean Difference (IV, Fixed, 95% CI)2.0 [-0.98, 4.98]

 4 Total duration of labour (min)3304Mean Difference (IV, Random, 95% CI)-44.79 [-80.19, -9.39]

 5 Rate of cervical dilatation (cm/h)2190Mean Difference (IV, Random, 95% CI)0.22 [-0.39, 0.83]

 6 Rate of normal vertex deliveries4425Risk Ratio (M-H, Fixed, 95% CI)1.03 [0.96, 1.10]

 
Comparison 9. Antispasmodics versus control: maternal adverse events

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Tachycardia6832Risk Ratio (M-H, Fixed, 95% CI)4.54 [2.53, 8.16]

    1.1 Neurotropic agents
6574Risk Ratio (M-H, Fixed, 95% CI)7.60 [3.54, 16.29]

    1.2 Musculotropic agents
3258Risk Ratio (M-H, Fixed, 95% CI)0.60 [0.19, 1.90]

 2 Mouth dryness6738Risk Ratio (M-H, Fixed, 95% CI)6.81 [2.71, 17.12]

    2.1 Neurotropic agents
5638Risk Ratio (M-H, Fixed, 95% CI)6.56 [2.48, 17.37]

    2.2 Musculotropic agents
1100Risk Ratio (M-H, Fixed, 95% CI)9.0 [0.50, 162.89]

 3 Headache3515Risk Ratio (M-H, Fixed, 95% CI)1.51 [0.56, 4.10]

    3.1 Neurotropic agents
3257Risk Ratio (M-H, Fixed, 95% CI)0.67 [0.15, 2.93]

    3.2 Musculotropic agents
3258Risk Ratio (M-H, Fixed, 95% CI)2.78 [0.63, 12.28]

 4 Nausea2196Risk Ratio (M-H, Fixed, 95% CI)1.97 [0.74, 5.28]

    4.1 Neurotropic agents
196Risk Ratio (M-H, Fixed, 95% CI)1.46 [0.50, 4.28]

    4.2 Musculotropic agents
1100Risk Ratio (M-H, Fixed, 95% CI)7.0 [0.37, 132.10]

 5 Vomiting2196Risk Ratio (M-H, Fixed, 95% CI)2.21 [0.64, 7.62]

    5.1 Neurotropic agents
196Risk Ratio (M-H, Fixed, 95% CI)1.39 [0.33, 5.88]

    5.2 Musculotropic agents
1100Risk Ratio (M-H, Fixed, 95% CI)7.0 [0.37, 132.10]

 6 Dizziness196Risk Ratio (M-H, Fixed, 95% CI)3.13 [0.66, 14.73]

 7 Giddiness3343Risk Ratio (M-H, Fixed, 95% CI)0.25 [0.05, 1.16]

    7.1 Neurotropic agents
2197Risk Ratio (M-H, Fixed, 95% CI)0.20 [0.02, 1.67]

    7.2 Musculotropic agents
1146Risk Ratio (M-H, Fixed, 95% CI)0.33 [0.04, 3.13]

 8 Cervical laceration3342Risk Ratio (M-H, Fixed, 95% CI)0.79 [0.20, 3.12]

    8.1 Neurotropic agents
196Risk Ratio (M-H, Fixed, 95% CI)3.13 [0.13, 74.85]

    8.2 Musculotropic agents
2246Risk Ratio (M-H, Fixed, 95% CI)0.5 [0.09, 2.68]

 9 Flushing of face4542Risk Ratio (M-H, Fixed, 95% CI)8.48 [1.98, 36.35]

    9.1 Neurotropic agents
4542Risk Ratio (M-H, Fixed, 95% CI)8.48 [1.98, 36.35]

 10 Postpartum haemorrhage2185Risk Ratio (M-H, Random, 95% CI)2.46 [0.20, 30.17]

    10.1 Neurotropic agents
185Risk Ratio (M-H, Random, 95% CI)0.75 [0.13, 4.26]

    10.2 Musculotropic agents
1100Risk Ratio (M-H, Random, 95% CI)9.00 [1.18, 68.42]

 
Comparison 10. Antispasmodics versus control: neonatal adverse events

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Admission to NICU5845Risk Ratio (M-H, Fixed, 95% CI)0.84 [0.34, 2.05]

    1.1 Neurotropic agents
4520Risk Ratio (M-H, Fixed, 95% CI)0.94 [0.27, 3.25]

    1.2 Musculotropic agents
3325Risk Ratio (M-H, Fixed, 95% CI)0.73 [0.20, 2.66]

 2 Fetal distress1100Risk Ratio (M-H, Fixed, 95% CI)0.5 [0.10, 2.61]

 3 Fetal bradycardia1130Risk Ratio (M-H, Fixed, 95% CI)0.67 [0.12, 3.86]

 4 Fetal tachycardia2230Risk Ratio (M-H, Fixed, 95% CI)3.4 [0.85, 13.67]

    4.1 Neurotropic agents
2230Risk Ratio (M-H, Fixed, 95% CI)3.4 [0.85, 13.67]

 5 Meconium-stained liquor1107Risk Ratio (M-H, Fixed, 95% CI)2.04 [0.54, 7.73]

 

Appendices

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Appendix 1. Search terms

We searched the Pro-quest dissertation database, the dissertation database of Stellenbosch University and Google Scholar using following keywords: (antispasmodic OR parasympatholytic OR spasmolytic) AND (labour OR labor OR childbirth OR delivery)

 

What's new

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

Last assessed as up-to-date: 10 April 2013.


DateEventDescription

8 April 2013New search has been performedSearch updated. Two additional studies have been included (Dahal 2013; Sekhavat 2012) and one excluded (Fouedjio 2012).

8 April 2013New citation required but conclusions have not changedReview updated.



 

Contributions of authors

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

Anke Rohwer (AR) developed the protocol and Taryn Young (TY) provided comments on the draft.

For the first version of the review, AR and TY; AR and Oswell Khondowe (OK) screened abstracts, selected studies for inclusion, assessed the risk of bias and extracted the data. OK adapted the methods section. AR performed the meta-analysis, interpreted results, wrote the discussion and conclusion. TY provided input into all sections.

For the 2013 update, AR and OK screened abstracts, selected studies for inclusion, assessed risk of bias and extracted the data. AR updated the backgournd, results, discussion and conclusion. TY provided input into all sections.

 

Declarations of interest

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

None known.

 

Sources of support

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Internal sources

  • University of Stellenbosch, South Africa.

 

External sources

  • Effective Health Care Research Consortium, UK.
  • UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP) and the Department of Reproductive Health and Research (RHR), World Health Organization, Switzerland.

 

Differences between protocol and review

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

Three additional subgroup analysis were added.

  • Type of management of labour (active management versus expectant management).
  • Type of pregnancy (high risk versus low risk).
  • Studies excluding versus studies including caesarean sections in their analysis.

References

References to studies included in this review

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. References to studies awaiting assessment
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
Ajmera 2006 {published data only}
  • Ajmera SK, Shah PK, Shinde GA. Comparative study of drotaverine vs. Valethamate in cervical phase of labour. Bombay Hospital Journal (http://www.bhj.org/journal/2006_4802_april/html/org_res_305-309.html) (accessed 16 December 2011).
Al Matari 2007 {published data only}
  • Al Matari F. Is buscopan (hyoscine-N-butylbromide) effective in shortening labor? [abstract]. 31st British International Congress of Obstetrics and Gynaecology; 2007 July 4-6; London, UK. 2007:114.
Al Qahtani 2011 {published data only}
  • Al Qahtani NH, Al Hajeri F. The effect of hyoscine butylbromide in shortening the first stage of labor: A double blind, randomized controlled trial. Therapeutics and Clinical Risk Management 2011;7:495-500.
Azari 2010 {published data only}
  • Azari M, Mardi A, Dargahi R. The effect of combination atropine and hyoscine progress of delivery in primiparous women in Ardabil - Alavi Hospital 2008. Journal of Maternal-Fetal and Neonatal Medicine 2010;23(S1):226.
Batukan 2006 {published data only}
  • Batukan AC, Ozgun MT, Turkyilmaz C, Dolanbay M, Muderris II. Effect of valethamate bromide in acceleration of labor: a double-blind, placebo-controlled trial [Valetamat bromurun dogum eylemini hizlandirmadaki etkisi: Plasebo kontrollu, cift kor bir calisma.]. Journal of the Turkish German Gynecology Association Artemis 2006;7(3):202-5.
Cromi 2011 {unpublished data only}
Dahal 2013 {published data only}
  • Dahal P, Banerjee B, Uprety DK, Das BP, Thakur A, Agrawal A. Comparative study of efficacy of drotaverine hydrochloride and valethamate bromide with control in first stage of labour. Health Renaissance 2013;11(1):38-42.
Gupta 2008 {published data only}
Khosla 2003 {published data only}
  • Khosla AH, Bala I, Dahiya K, Sangwan K. A comparative study of the efficacy of valethamate bromide with drotaverine in normal labor. Journal of Obstetrics and Gynecology of India 2003;53(6):568-70.
Kuruvila 1992 {published data only}
  • Kuruvila S, Jasper P, Peedicayil A, Mathai M. A randomized controlled trial of valethamate bromide in acceleration of labor. International Journal of Gynecology & Obstetrics 1992;38:93-6.
Madhu 2010 {published data only}
  • Madhu C, Mahavarkar S, Bhave S. A randomised controlled study comparing drotaverine hydrochloride and valethamate bromide in the augmentation of labour. Archives of Gynecology and Obstetrics 2010;282:11-5.
Makvandi 2010 {published data only}
  • Makvandi S. The effect of hyoscine - N - butyl bromide suppository on labor pain and process in nuliparous women. IRCT Iranian Registry of Clinical Trials (www.irct.ir) (accessed 6 December 2010) 2010.
Mukaindo 2010 {unpublished data only}
  • Mukaindo AM, Stones WR (Department of Obstetrics and Gynaecology, Aga Khan University Hospital Nairobi). Hyoscine-N-butylbromide for the acceleration of labor in first time parturients: a randomized, double-blind, placebo-controlled trial. Personal communication via email 24 October 2011.
Raghavan 2008 {published data only}
  • Raghavan R. The effect of hyoscine butyl bromide on the first stage of labour in term pregnancies. BJOG: an international journal of obstetrics and gynaecology 2008;115(8):1064-5.
Samuels 2007 {published data only}
Sekhavat 2012 {published data only}
  • Sekhavat L, Karbasi S, Fallah R, Mirowliai M. Effect of hyoscine butylbromide first stage of labour in multiparus women. African Health Sciences 2012;12(4):408-11.
Sharma 2001 {published data only}
Singh 2004 {published data only}
Taskin 1993 {published data only}
  • Taskin O, Saade G, Belfort M, Moise K. The effect of narcotics and spasmolytics on cervical dilatation in labor: a randomized placebo-controlled study. American Journal of Obstetrics and Gynecology 1993;168:362.
Warke 2003 {published data only}
  • Warke HS, Chauhan AR, Raut VS, Ingle KM. Efficacy of camylofin dihydrochloride in acceleration of labour: A randomised double blind trial. Bombay Hospital Journal 2003;45(3):420-3.
Yilmaz 2009 {published data only}
  • Yilmaz B, Kart C, Kelekci S, Gokturk U, Sut N, Tarlan N, et al. Meperidine versus valethamate bromide in shortening the duration of active labor. International Journal of Gynecology & Obstetrics 2009;107(2):126-9.

References to studies excluded from this review

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. References to studies awaiting assessment
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
Aggarwal 2008 {published data only}
  • Aggarwal P, Zutshi V, Batra S. Role of hyoscine N-butyl bromide (HBB, Buscopan) as labor analgesic. Indian Journal of Medical Science 2008;62(5):179-84.
Akleh 2010 {published data only}
  • Akleh HE, Al-Jufairi ZA. Effect of hyoscine-N-bulyl bromide (Buscopan) in accelerating first stage of labor. Journal of the Bahrain Medical Society 2010;22(3):103-7.
Baracho 1982 {published data only}
  • Baracho HM, Kamat JR, Kunkalekar K, Jacob L. Hyoscine-N-Butylbromide (Buscopan) in acceleration of labour. Journal of Obstetrics and Gynaecology of India 1982;34:509-12.
Bhattacharaya 1984 {published data only}
  • Bhattacharaya P, Joshi SG. Acceleration of labour intramuscular "Buscopan" injection. Journal of Obstetrics and Gynaecology of India 1984;35:1014-7.
Chan 1963 {published data only}
  • Chan DPC. The use of Buscopan during the first stage of labour. The Bulletin of the Hong Kong Chinese Medical 1963;15:69-71.
Demory 1990 {published data only}
  • Demory JE, Firmin JM, Parot P. The value of magnesium pyrrolidone carboxylate in true cervix dystocia. A double blind vs placebo study. Revue Francaise de Gynecologie et d Obstetrique 1990;85:413-6.
De Nobrega-Correa 2010 {published data only}
  • De Nobrega-Correa H, Guerra-Velasquez M, Reyna-Villasmil E, Mejia-Montilla J, Reyna-Villasmil N, Torres-Cepeda D, et al. Effects of intravenous hyoscine butylbromide-oxytocin or oxytocin on the duration of labor in term pregnancies [Spanish] [Efectos del butil bromuro de hioscina-oxitocina u oxitocina intravenosos en la duracion del parto de embarazos a termino]. Progresos de Obstetricia y Ginecologia 2010;53(12):502-6.
Fouedjio 2012 {published data only}
  • Fouedjio JH, Ymele Fouelifack F, Kenfack B, Wache Sime LC, Nana NP, Temkou S, et al. Efficacité du phloroglucinol sur le raccourcissement de la phase active du travail à la maternité de l'Hôpital Central de Yaoundé, Cameroun. Clinics in Mother and Child Health 2012;9:C12502.
Guerresi 1981 {published data only}
  • Guerresi E, Gori G, Beccari A, Farro M, Mazzanti C. Influence of spasmolytic treatment and amniotomy on delivery times: a factorial clinical trial. Clinical Therapeutics 1981;3(5):382-8.
Hamann 1972 {published data only}
  • Hamann GO. Avacan vs fortral. A controlled double blind investigation on parturient patients. Ugeskrift for Laeger 1972;134:2261-5.
Hao 2004 {published data only}
  • Hao Y, Zhai GR, Duan AH. Effects of spasfon on course of labor. Chung-Hua Fu Chan Ko Tsa Chih [Chinese Journal of Obstetrics and Gynecology] 2004;39(9):606-8.
Kauppila 1970 {published data only}
  • Kauppila O, Koistinen O, Vaalamo P. Drug-induced acceleration of labour. Trials of an Indan derivative in childbirth. Annales Chirurgiae et Gynaecologiae Fenniae 1970;59:85-9.
Kaur 2003 {published data only}
  • Kaur D, Kaur R. Comparison of drotaverine and epidosin in the first stage of labor. Journal of Obstetrics and Gynecology of India 2003;53(5):449-52.
Kaur 2006 {published data only}
  • Kaur D, Kaur A. "Anafortan" an old drug with its newer use in acceleration of labour [abstract]. 49th All India Congress of Obstetrics and Gynaecology; 2006 January 6-9; Cochin, Kerala State, India. 2006:59.
Malensek 1985 {published data only}
  • Malensek B. The influence of spasmoanalgetics on uterine activity. Jugoslavenska Ginekologija i Perinatologija 1985;25:75-9.
Manpreet 2008 {published data only}
  • Manpreet K, Gouramba R, Jyothi K, Venkatesh S, Biradar R. A comparative study of hyoscine butylbromide versus drotaverine hydrochloride in first stage of labor. Journal of Obstetrics and Gynecology of India 2008;58(3):230-4.
Maritati 1986 {published data only}
  • Maritati V, Tanganelli E, Boccardo E, Camandona F, Pietrasanta R, Maganza C, et al. The use of sintropium bromide, a new spasmolytic, in obstetrics and gynecology. Minerva Ginecologica 1986;38(11):965-9.
Mishra 2002 {published data only}
  • Mishra SL, Toshniwal A, Banerjee R. Effect of drotaverine on cervical dilatation: a comparative study with epidosin (valethamate bromide). Journal of Obstetrics and Gynecology of India 2002;52(3):76-9.
Mortazavi 2004 {published data only}
  • Mortazavi F, Rakhshani MH. The effect of atropine, hyoscine and promethazine on the duration of labor stages and rate of labor progress in multiparous women. Journal of the Gorgan University of Medical Sciences 2004;6(2):92.
Rajkumar 2006 {published data only}
  • Rajkumar K, Vedavalli R. Drotaverine hydrochloride vs valethamate bromide for cervical dilatation in active phase of labour [abstract]. 49th All India Congress of Obstetrics and Gynaecology; 2006 January 6-9; Cochin, Kerala State, India. 2006:96.
Sirohiwal 2005 {published data only}
Tabassum 2005 {published data only}
  • Tabassum S, Afridi B, Aman Z. Phloroglucinol for acceleration of labour: double blind, randomized controlled trial. JPMA - Journal of the Pakistan Medical Association 2005;55(7):270-3.
Tripti 2009 {published data only}
  • Tripti N, Jyoti J. To compare and evaluate the efficacy and safety of drotaverine and valethamate bromide. Journal of Obstetrics and Gynaecology of India 2009;59(4):324-31.
Von Hagen 1965 {published data only}
  • Von Hagen H. Clinical trials with the spasmo-analgesic Spasdolsin in obstetrics (with application of a new methodology). Zentralblatt fur Gynakologie 1965;36:1201-9.

References to studies awaiting assessment

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. References to studies awaiting assessment
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
Accinelli 1978 {published data only}
  • Accinelli G, Olivieri T, Vibelli C. The effectiveness of a new spasmolytic drug (DA 3177) during the active phase of labour. Acta Therapeutica 1978;4:19-27.
Ahmed 1982 {published data only}
  • Ahmed LT, Merouana A, Nait B, Souiah N, Chenntouf M, Larbi LO. Antispasmodics in obstetrics: myth or reality [Les antispasmodiques en obstetrique: mythe ou realite]. Journal de Gynecologie, Obstetrique et Biologie de la Reproduction 1982;11(2):281-4.
Georges 2007 {published data only}
  • Georges R, Aldahan F, Alwaeely F. The evaluation of the effect of buscopan (hyoscine-N-butyl bromide) on the duration of labour [abstract]. 31st British International Congress of Obstetrics and Gynaecology; 2007 July 4-6; London, UK. 2007:102.
Rajani 2011 {published data only}
  • Rajani M, Umadevi N, Jayasree S. Efficacy of valethamate bromide on cervical dilatation during the labour in comparison with placebo. 54th All India Congress of Obstetrics and Gynaecology; 2011 January 5-9; Hyderabad, Andhra Pradesh, India. 2011:141.
Ranka 2002 {published data only}
  • Ranka PR, Hishikar VA. Effect of drotaverine hydrochloride on normal labour - a randomised study. Journal of Obstetrics and Gynecology of India 2002;52(6):28-30.
Recto 1997 {published data only}
  • Recto CP, Co TV, Clemente V. The effect of hyoscine-n-butylbromide on the first stage of labor: a clinical trial. Acta Obstetricia et Gynecologica Scandinavica 1997;76 Suppl(167:1):45.
Roy 2007 {published data only}
  • Roy A, Patra KK, Mukhopadhyay S, Guha S. Study of drotaverine on first stage of labour and pregnancy outcome. Journal of the Indian Medical Association 2007;105(8):450.
Zagami 2012 {published data only}
  • Zagami SE, Golmakani N, Saadatjoo SAR, Dadgar S, Baghbani B. Comparison of effects of hyoscine N-butyl bromide and promethazine on length of active phase of first stage of labor. Iranian Journal of Obstetrics, Gynecology and Infertility 2012;15(6):16-21.

Additional references

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. References to studies awaiting assessment
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
Brown 2008
Buhimschi 2003
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Clark 2009
Daftary 2009
  • Daftary SN, Desai SV, Thanawala U, Bhide A, Levi J, Patki A, et al. Programmed labor - indegenous protocol to optimize labor outcome. South Asian Federation of Obstetrics and Gynecology 2009;1(1):61-4.
Dencker 2009
Egger 1997
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Gibbon 2005
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Gitanjali 2010
  • Gitanjali B. Valethamate bromide: Is there any proof of efficacy and safety for its use in labor?. Journal of Pharmacology and Pharmacotherapeutics 2010;1(1):2-3.
Guyatt 2011
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Harbord 2006
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Khan 2006
Lavender 2009
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Leppert 1995
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O'Driscoll 1973
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Ramsay 2003
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Romics 2003
Samuels 2009
  • Samuels L. Pharmacotherapy update: hyoscine butylbromide in the treatment of abdominal spasms. Clinical Medicine Insights: Therapeutics 2009;1:647-55.
Sommers 2002
  • Sommers De K. Sommers' Pharmacology. Pretoria: UP Drukkers, 2002.
Thirunavukkarasu 2010
  • Thirunavukkarasu AB, Vijayan S. Valethamate bromide: Conflicting evidence and continuing use. Journal of Pharmacology and Pharmacotherapeutics 2010.
Wei 2009
WHO 1994
  • World Health Organization maternal health and safe motherhood programme. World Health Organization partograph in management of labour. Lancet 4 June 1994;343(8910):1399-404.
WHO 2010
  • World Health Organization. Trends in maternal mortality: 1990-2008. Estimates developed by WHO, UNICEF, UNFPA and the World Bank. http://www.who.int/reproductivehealth/publications/monitoring/9789241500265/en/index.html (accessed 9 February 2010).
Yuel 2008
  • Yuel VI, Kaur V, Kaur D. Programmed labor for optimizing labor and delivery. JK Science 2008;10(2):62-4.