Intervention Review

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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

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Characteristics of included studies [ordered by study ID]
Ajmera 2006

MethodsStudy design: randomised controlled trial.

Allocation generation: random allocation.

Allocation concealment: not done.

Blinding: open trial.

Loss to follow-up: intervention: 3.3% control: 2.6%.


ParticipantsTotal number of participants randomised: 225.

Inclusion criteria: primi- and multigravidas. Gestational age 37-41 weeks, singleton pregnancy, cephalic presentation, spontaneous labour, no obstetric or medical complications.

Exclusion criteria: none specified.


InterventionsIntervention:

1. Drotaverine hydrochloride 40 mg IMI, administered in active phase at 3 cm dilatation and repeated every 2 h for max 3 doses.

n = 75.

2. Valethamate bromide 8 mg IVI, administered in active phase, at 3 cm dilatation, repeated every half an hour for a max of 3 doses.

n = 75.

Control:

No medication.

n = 75.


OutcomesPrimary outcomes:

1. Duration of first stage of labour (from 3 cm to full dilatation of cervix)

2. Duration of second and third stage of labour.

3. Mode of delivery.

Secondary outcomes:

Neonatal and maternal adverse events.


NotesEthics: ethical approval not mentioned, informed consent not mentioned.

Location: India, Mumbai.

No contact details.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandom allocation - not clearly described.

Allocation concealment (selection bias)High riskThis is an open trial.

Blinding of participants and personnel (performance bias)
All outcomes
High riskThis is an open trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskThis is an open trial.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data, all participants accounted for.

Selective reporting (reporting bias)Unclear riskPrimary outcomes:

1. Duration of labour: adequately reported.

2. Mode of delivery: adequately reported.

Secondary outcomes:

1. Maternal adverse events: adequately reported.

2. Neonatal adverse events: Apgar scores not reported.

Other biasHigh riskAuthors did not mention spontaneous or artificial rupture of membranes, the use of other drugs to augment labour or analgesia. All these are known to influence the duration of labour and could have biased results.

No contact details are present.

Drug company sponsorship: not mentioned.

Al Matari 2007

MethodsStudy design: randomised controlled trial.

Allocation generation: randomised (no details present).

Allocation concealment:not described.

Blinding: double-blind (no details present).

Loss to follow-up: intervention: 3%.

Control: 3%.


ParticipantsTotal number of participants randomised:199.

Inclusion criteria:patients at term with singleton pregnancy, cephalic presentation.

Exclusion criteria: contraindication for vaginal delivery, previous caesarean section.


InterventionsIntervention: Buscopan Hyoscine-N-Butylbromide (no details about dosage).

n = 99.

Control: placebo (no details present).

n = 100.


OutcomesPrimary outcomes:

1. Duration of first stage of labour (from intervention to full dilatation).

2. Duration of first and second stage of labour (from intervention to delivery of baby).

Secondary outcomes:

1. Apgar scores at 1 and 5 minutes.


NotesEthics: not mentioned.

Location: Saudi Arabia.

This study was only published as an abstract at the British International Congress of Obstetrics and Gynaecology.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described in detail, only mentioned the word "randomised".

Allocation concealment (selection bias)Unclear riskNot described.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described in detail, only mentioned "double-blind".

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described in detail, only mentioned "double-blind".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskUnclear whether 3 participants who did not deliver after 4 hours were excluded from the analysis or not. not known how many participants were in each group.

Selective reporting (reporting bias)High riskNo prespecified outcomes in the methods section.

Other biasUnclear riskThis is only a conference abstract and lacks a lot of information. it is therefore difficult to judge whether any other biases are present.

Drug company sponsorship: not mentioned.

Al Qahtani 2011

MethodsStudy design: randomised controlled trial.

Allocation generation: cards with either "HBB" or "placebo" written on them placed in sealed envelopes. Envelopes were placed in a box, mixed and drawn by the nurse in charge.

Allocation concealment: opaque sealed envelopes containing cards with either "HBB" or "placebo" written on them mixed in a box and drawn by the nurse in charge when the patient consented for participation in the study.

Blinding: patients, nurses and physicians unaware of contents of syringe. Nurse in charge prepared syringe according to card in envelope. HBB and saline are both colourless and the contents of the syringes could thus not be established.

Loss to follow-up: intervention: 10%.

Control: 13%.


ParticipantsTotal number of participants randomised: 110.

Inclusion criteria: singleton pregnancy, vertex presentation at term, no chronic or pregnancy-induced illnesses, no contraindications to vaginal delivery, all in established, spontaneous labour with either intact or spontaneous rupture of membranes for less than 12 hours.

Exclusion criteria: previous uterine scarring, malpresentation, antepartum haemorrhage, multiparity, twin pregnancy, induced delivery, any medical disease, oxytocin induction, prolonged premature rupture of membranes (more than 12 hours), epidural analgesia.


InterventionsIntervention: Buscopan Hyoscine Butylbromide 40 mg (2 mL) IMI; administered at 3-4 cm cervical dilatation (once-off dose) n = 58 (randomised) n = 52 (analysed).

Control: Placebo (normal saline) 2 mL IMI; administered at 3-4 cm cervical dilatation (once-off dose) n = 52 (randomised) n = 45 (analysed).


OutcomesPrimary outcomes:

1. Duration of first stage of labour (from 4 cm cervical dilatation to full dilatation).

2. Duration of first and second stage of labour (from 4 cm cervical dilatation to delivery of baby).

3. Duration of second and third stage of labour.

Secondary outcomes:

1. Postpartum haemorrhage.

2. Rate of caesarean sections.

3. Apgar score.


NotesEthics: informed consent signed by participants before randomisation, study approved by Ethical committee of the University of Dammam.

Location: Saudi Arabia.

Authors contacted to clarify number of participants randomised to each group and to clarify the measurement of duration of labour in case of a caesarean section. Authors responded.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskDrawing envelopes containing cards either placebo or HBB written on them from a box

Allocation concealment (selection bias)Low riskSequentially numbered, opaque, sealed envelopes – mixed in box and drawn by nurse in charge once patient had signed consent.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskNurse in charge prepared syringes containing either placebo or HBB, which are both colourless fluids. She then attached the card from the envelope to the participants file after delivery. Participants, physicians and attending nurses were thus blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskPrincipal investigator collected the raw data sheets from the labour rooms and was also blinded.

Incomplete outcome data (attrition bias)
All outcomes
High riskUnclear in study report whether 13 participants not included in the analysis were randomised to a group before being excluded. Author confirmed that seven of these received placebo and six received HBB and were excluded from analysis due to augmentation with oxytocin which indicates that there was attrition of 10% in the intervention group and 13% in the placebo group.

Selective reporting (reporting bias)Low riskNo protocol of the study found, but all outcomes prespecified in methods section addressed.

Other biasHigh riskYes – 44% (23/52) participants in HBB group had spontaneous ROM at baseline, compared with 22% (10/42) in the placebo group – this is a statistically significant difference (P = 0.0039) which can influence the duration of labour

Azari 2010

MethodsStudy design: randomised controlled trial.

Allocation generation: random division of patients. No details about method of sequence generation.

Allocation concealment:not described.

Blinding:double-blind - no details present.

Loss to follow-up: not mentioned.


ParticipantsTotal number of participants randomised: 200.

Inclusion criteria: primiparous women in labour.

Exclusion criteria: not specified.


InterventionsIntervention:

20 mg Hyoscine and Atropine infusion.

n = not mentioned.

Control:

2 mL Dextrose water infusion.

n = not mentioned.


OutcomesPrimary outcomes:

1. Cervical dilatation rate and effacement of cervix.

2. Duration of active phase of labour.

3. Duration of second stage of labour.

4. Duration of third stage of labour.

Secondary outcomes:

1. Fetal heart rate.

2. Apgar scores at 1 and 5 minutes.


NotesEthics: not mentioned.

Location: Iran.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskParticipants were "randomly divided".

Allocation concealment (selection bias)Unclear riskNot described.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described in detail, only mentioned that the trial was "double-blind".

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described in detail, only mentioned that the trial was "double-blind".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskUnclear, only total number of participants at beginning of study is present.

Selective reporting (reporting bias)High riskOutcomes prespecified in the methods section were not addressed in the results section (3rd stage of labour, Apgar scores).

Other biasUnclear riskThis study is only published as a congress abstract and it is thus very difficult to judge whether it is free of other bias.

Drug company sponsorship: not mentioned.

Batukan 2006

MethodsStudy design: randomised controlled trial.

Allocation generation: not specified.

Allocation concealment: done by sealed envelope technique.

Blinding: doctors and observers were blinded.

Loss to follow-up: 2% had caesarean sections.


ParticipantsTotal number of participants randomised: 100.

Inclusion criteria: women with gestational age 38-41 weeks in spontaneous labour or with induction of labour, vertex presentation, intact membranes.

Exclusion criteria: cervical dilatation of more than 5 cm, placenta previa, spontaneous rupture of membranes at randomisation, intrauterine growth restriction, women with oligohydramnios, antepartum haemorrhage, pre-eclampsia, hypertension, diabetes mellitus, fetal macrosomia (> 4000 g), cephalo-pelvic disproportion, previous caesarean section, grande multipara.


InterventionsIntervention:

Valethamate bromide 8 mg/mL IMI at the beginning of active phase of labour (4-5cm cervical dilatation) at hourly intervals for a total of 3 doses.

n = 49.

Control:

NaCl 0.9% 1 mL IMI at the beginning of active phase of labour (4-5 cm cervical dilatation) at hourly intervals for a total of 3 doses.

n = 51.


OutcomesPrimary outcomes:

1. Time elapsed to second stage of labour (from intervention to full cervical dilatation).

2. Duration of second stage of labour.

3. Need for augmentation with oxytocin.

Secondary outcomes:

Subjective impression of physician about efficacy of intervention and the associated adverse effects.


NotesEthics: ethical approval from institutional ethics committee, informed consent obtained from all patients.

Location: Turkey.

Study published in Turkish, with English abstract. Translator consulted.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskSealed envelope technique.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDoctors blinded, not clear if participants were blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessors were blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data, all participants accounted for.

Selective reporting (reporting bias)Low riskPrimary outcomes:

1. Time elapsed to second stage of labour: adequately reported.

2. Duration of second stage of labour: adequately reported.

3. Need for augmentation with oxytocin: adequately reported.

Secondary outcomes:

Subjective impression of physician about efficacy of intervention and the associated adverse effects: adequately reported.

Other biasUnclear riskDifficult to judge due to foreign language.

Drug company sponsorship: unclear.

Cromi 2011

MethodsStudy design: randomised controlled trial.

Allocation generation: computer-generated randomisation sequence.

Allocation concealment: independent resident was responsible for records of group allocation and drawing up of injectable, Rociverine and saline have similar appearances. Randomisation list was kept in a secure box in the labour ward. Injectable was drawn up by resident in a separate pharmacy room in the labour ward.

Blinding: midwives, clinicians and patients were blinded.

Loss to follow-up: 8.3% in intervention group, 6.7% in placebo group.


ParticipantsTotal number of participants randomised:120.

Inclusion criteria: primiparous women with gestational age of more than 37 weeks, in spontaneous labour, with cervical dilatation between 3 and 5 cm, live fetus, singleton pregnancy with cephalic presentation.

Exclusion criteria: contraindications to vaginal delivery, induced labour, twin pregnancies, gestational age < 37 weeks, non-Italian speaking, labour diagnosed > 5 cm cervical dilatation.


InterventionsIntervention:

Rociverine 20 mg (2 mL) IMI; administered between 3-5 cm cervical dilatation.

n = 60.

Control:

NaCl 0.9% 2 mL IMI; administered between 3-5 cm cervical dilatation.

n = 60.


OutcomesPrimary outcomes:

1. Cervical dilatation rate.

Secondary outcomes:

1. Injection-full dilatation time.

2. Oxytocin augmentation.

3. Length of second stage.

4. Operative delivery.

5. Epidural rate.

6. Blood loss.

7. Arterial cord blood pH.

8. 5-minute Apgar scores.

9. Maternal side effects.


NotesEthics: written informed consent obtained from all participants, study approved by Institutional Review Board.

Location: Italy.

Authors contacted regarding outcomes and allocation procedure, responded to clarify.

Authors declared no conflict of interest.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomisation sequence.

Allocation concealment (selection bias)Low riskRecords of group allocation were maintained by an independent resident physician responsible for randomisation and drawing up of injectable and kept in a secure box in the labour war. Rociverine and saline have identical appearances. The resident drew up the injectable in a separate pharmacy room in the labour ward.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskParticipants, midwives and clinicians were blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskLabour and delivery clinicians were blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll participants accounted for.

Selective reporting (reporting bias)Low riskAll pre-specified outcomes were reported on.

Other biasLow riskNo other sources of bias identified.

Dahal 2013

MethodsStudy design: randomised controlled trial.

Allocation generation: computer-generated randomisation.

Allocation concealment: not described.

Blinding: not described whether participants, physicians or outcome assessors were blinded. The authors only state that this was a "single-blind" RCT.

Loss to follow-up: not clearly described.


ParticipantsTotal number of participants randomised: 300.

Inclusion criteria: Women with term pregnancies in early active stage of labour (2-3 contractions per 10 minutes lasting for 30 seconds), induced and spontaneous labour, vertex presentation.

Exclusion criteria: Previous uterine scar, malpresentation, multiple pregnancies, antepartum haemorrhage, cephalopelvic disproportion, pre-eclampsia and other hypertensive disorders, glaucoma, heart disease.


InterventionsIntervention:

1. Valethamate bromide 8mg, IMI every half hour for three doses.

n = 100.

2. Drotaverine hydrochloride 40mg, IMI every two hours for a maximum of three injections.

n =100.

Control:

No treatment.

n = 100.


OutcomesPrimary outcomes:

1. Duration of active phase of labour.

2. Duration of second stage of labour.

3. Duration of third stage of labour.

4. Total duration of labour (injection to delivery time).

Secondary outcomes:

1. Blood loss.

2. Adverse events.


NotesEthics: Informed consent obtained from all participants, study approved by BPKIHS ethical committee.

Location: Nepal.

Authors contacted to clarify who was blinded; and to request missing data of control group.

Authors did not report whether any conflict of interest was present.

Table 2: Missing in PDF (cervical dilatation at the start of the study).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomisation.

Allocation concealment (selection bias)Unclear riskNo method of concealing allocation described.

Blinding of participants and personnel (performance bias)
All outcomes
High riskNot described, but both participants and personnel were aware which group they were allocated to.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described. Authors describe study as being "single-blind". Not clear who was blinded.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot clear because the number of participants analysed was not reported with the results.

Selective reporting (reporting bias)High riskControl group results not always reported. Primary and secondary outcomes not clearly pre-specified. All results of pre-specified outcomes not reported.

Other biasHigh riskData for the "duration of active phase of labour" and "duration of labour until end of first stage" are not the same. It is not clear how authors distinguish between these two outcomes. No sample size calculation present. Characteristics of participants in all groups only partly described.

Gupta 2008

MethodsStudy design: randomised controlled trial.

Allocation generation: participants randomised by simple randomisation.

Allocation concealment: not described.

Blinding: no blinding.

Loss to follow-up:
Intervention: 4%.

Control: 0%.


ParticipantsTotal number of participants randomised: 150.

Inclusion criteria:primi- and multigravidas at term, singleton pregnancy, cephalic presentation. High-risk pregnancies were included. Hypertensive disorders, gestational diabetes, portal hypertension, tuberculosis, idiopathic thrombocytopenia, intra-hepatic cholestasis, anaemia, IUGR and oligohydramnios.

Exclusion criteria: preterm gestation, multiple pregnancy, CPD, non-vertex presentation.


InterventionsIntervention:

1. Drotaverine hydrochloride 40 mg (2 mL) IMI in active labour at 3 cm dilatation, repeated every 2 h

n = 50.

2. Hyoscine Butyl bromide 20 mg, (1 mL) IVI in active labour at 3 cm dilatation, repeated every 20 min

n = 50.

Control:

No medication.

n = 50.


OutcomesPrimary outcomes:

1. Duration of active phase of labour (3 cm to full cervical dilatation).

2. Rate of cervical dilatation (cm/h).

3. Duration of second stage of labour.

Secondary outcomes:

1. Duration of third stage.

2. Mode of delivery.

3. Complications.


NotesLocation: India.

Ethics: informed consent obtained, ethical approval not mentioned.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSimple randomisation, method not explicitly described.

Allocation concealment (selection bias)Unclear riskNo allocation concealment described.

Blinding of participants and personnel (performance bias)
All outcomes
High riskNo blinding of participants and personnel.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo blinding of outcome assessors.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll participants accounted for, no missing data.

Selective reporting (reporting bias)Low riskPrimary outcomes:

1. Duration of active phase of labour - adequately reported.

2. Rate of cervical dilatation - adequately reported.

3. Duration of second stage - adequately reported.

Secondary outcomes:

1. Mode of delivery - adequately reported.

2. Complications - adequately reported.

3. Duration of 3rd stage - adequately reported.

Other biasUnclear riskMedications were given via different routes and no placebo was used, the control group did not receive any medication Cervical dilatation was not the same at starting point in all the groups - although it was shown not to be statistically significant (P value: 0.5).

Drug company sponsorship: not mentioned.

Khosla 2003

MethodsStudy design: randomised controlled trial.

Allocation generation: participants were randomly assigned (no details present).

Allocation concealment: not mentioned.

Blinding: not mentioned.

Loss to follow-up: not mentioned.


ParticipantsTotal number of participants randomised: 300.

Inclusion criteria: women with normal, singleton pregnancy at 38-41 gestational age with vertex presentation, intact membranes and spontaneous onset of labour.

Exclusion criteria: women with previous uterine scar, cephalopelvic disproportion, grand multiparity, antepartum haemorrhage, twin pregnancy.


InterventionsIntervention:

1. Valethamate bromide (Epidosin): 8 mg every half hour for 3 doses, intramuscular administration at 4 cm dilatation.

n = 100.

2. Drotaverine hydrochloride (Drotin): 40 mg every 2 hours for a maximum of 3 doses, intramuscular administration at 4 cm dilatation.

n = 100.

Control:

no medication.

n = 100.


OutcomesPrimary outcomes:

1. Duration of first stage of labour (not defined).

2. Rate of cervical dilatation.

3. Duration of second stage of labour.

4. Duration of third stage of labour.

Secondary outcomes:

1. Maternal complications.

2. Neonatal condition at birth.


NotesEthics: not mentioned.

Location: India.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomly assigned.

Allocation concealment (selection bias)Unclear riskNot described.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll participants accounted for.

Selective reporting (reporting bias)High riskOutcomes not prespecified in methods section.

Other biasUnclear riskStudy was poorly reported. It is therefore difficult to judge whether it is free of other bias.

Drug company sponsorship: not mentioned.

Kuruvila 1992

MethodsStudy design: randomised controlled trial.

Allocation generation: random number tables used to number the batches of ampoules.

Allocation concealment: identical ampoules containing either 1 mL of Valethamate bromide or 1 mL saline were prepared in batches of 3 and packed in 2 sets of 60X3. Each batch was sequentially numbered.

Blinding: coding was only broken on completion of the study.

Loss to follow-up:

Intervention: 8%.

Control: 9%.


ParticipantsTotal number of participants randomised: 120.

Inclusion criteria: low-risk pregnancy at term, vertex presentation, cervical dilatation 2-4 cm on initial examination, no clinical suspicion of cephalopelvic disproportion.

Exclusion criteria: not specified.


InterventionsIntervention:

Valethamate bromide 8 mg (1 mL) IM at amniotomy, after 30 min and after 60 min.

n = 62.

Control:

1 mL normal saline IM at amniotomy, after 30 min and after 60 min.

n = 58.


OutcomesNo primary outcomes specified, objective is to assess the usefulness of valethamate bromide in acceleration of labour. Mean rate of cervical dilatation was reported as an outcome regarding this objective.


NotesEthics: Informed consent was signed by participants. Authors did not mention approval by ethics committee.

Location: India.

Contact authors regarding outcomes.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom table of numbers.

Allocation concealment (selection bias)Low riskIdentical ampoules, sequentially numbered.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskNot explicitly stated, but the coding of the active ingredient was only broken after completion of the analyses.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskNot explicitly stated, but the coding of the active ingredient was only broken after completion of the analyses.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll participants accounted for.

Selective reporting (reporting bias)High riskNo outcomes prespecified in the methods section and no outcomes were explicitly reported on.

Other biasUnclear riskAll primigravidae received pethidine, which could affect the outcomes. They did not mention that any multigravidas received analgesia, which is questionable. The outcomes are very poorly reported and it is difficult to judge whether there are any other biases.

Drug company sponsorship: TKK Pharma limited sponsored drug and placebo, unclear whether there is conflict of interest.

Madhu 2010

MethodsStudy design: randomised controlled trial.

Allocation generation: randomisation.

Allocation concealment: sealed envelope technique Blinding: not described.

Loss to follow-up:

Intervention: 2%.

Control: 4%.


ParticipantsTotal number of participants randomised: 150.

Inclusion criteria: primi- and multigravidas, gestational age 37-40 weeks, with low risk pregnancy, in spontaneous labour, cephalic presentation.

Exclusion criteria: malpresentation, multiple pregnancy, intrauterine growth restriction, medical problems, previous caesarean section, antepartum haemorrhage, induction of labour, cervical dilatation of > 5 cm.


InterventionsIntervention:

1. Drotaverine hydrochloride 40 mg (2 mL) IMI at 4 cm dilation and every hour for a max of 3 doses

n = 50.

2. Valethamate bromide 8 mg (1 mL) IMI at 4 cm dilation and every hour for a max of 3 doses.

n = 50

Control:

NaCl 0.9% 2 mL IMI at 4 cm dilation and every hour for a max of 3 doses.

n = 50.


OutcomesPrimary outcomes:

1. Injection to delivery time.

2. Mean cervical dilatation rate (cm/h).

3. Duration of second stage.

Secondary outcomes:

Adverse maternal and neonatal events.


NotesEthics: ethics approval from medical research committee of the college.

Location: India.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation by sealed envelope technique.Not described how random numbers were generated.

Allocation concealment (selection bias)Unclear riskSealed envelope technique. Not clear how this was done and if allocation was concealed.

Blinding of participants and personnel (performance bias)
All outcomes
High riskNo blinding due to lack of resources.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo blinding due to lack of resources.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll participants accounted for.

Selective reporting (reporting bias)High riskPre-specified outcomes not reported: Duration of 2nd and 3rd stage of labour Apgar scores of newborns not reported No follow-up report (mothers and babies were followed for 3 days and at day 10 postnatal).

Other biasLow riskThe study appears to be free of other sources of bias. Confounding factors are not statistically significantly different between groups.

Drug company sponsorship: no.

Makvandi 2010

MethodsStudy design: randomised controlled trial.

Allocation generation: block randomisation.

Allocation concealment: suppositories were prepared by a pharmaceutical technician who was not included in the trial. No details about packaging of suppositories.

Blinding: patients and medical investigator were blinded.

Loss to follow-up:

Intervention: 7.6% had caesarean sections.

Control: 9.23% had caesarean sections.


ParticipantsTotal number of participants randomised: 130.

Inclusion criteria: primigravid women between 18 and 34 years of age with normal, singleton pregnancy, 37-42 weeks gestational age, cephalic presentation and spontaneous onset of labour.

Exclusion criteria: body mass index > 25, maternal tachycardia, antepartum haemorrhage, prolonged rupture of membranes, previous uterine scar, cephalopelvic disproportion, augmentation of labour with oxytocin, pre-eclampsia, heart disease, any other serious medical conditions.


InterventionsIntervention:

Hyoscine 20 mg suppository at beginning of active phase of labour (3-4 cm cervical dilatation).

n = 65.

Control:

Placebo suppository consisting of a suppocire AM-15 (semi-synthetic fatty acid glyceride) at beginning of active phase of labour.

n = 65.


OutcomesPrimary outcomes:

1. Duration of active phase of labour (not defined).

2. Rate of cervical dilatation.

3. Duration of second stage of labour.

Secondary outcomes:

1. Neonatal Apgar scores at 1 and 5 minutes after birth.

2. Fetal heart rate.

3. Maternal pulse rate.

4. Maternal blood pressure.


NotesEthics: study approved by Ethics Committee of Ahvaz Jundishapur University of Medical Sciences. Written consent obtained at antenatal visits.

Location: Iran.

Author contacted regarding randomisation and allocation concealment.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskBlock randomisation (blocks of 4) unclear what method of sequence generation was used.

Allocation concealment (selection bias)Unclear riskRandom numbers were assigned to each package. They do not mention whether the packages were identical.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskPatients were unaware of the contents of the package, unclear whether personnel were blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskMedical investigator was unaware of the contents of the packages.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll participants accounted for.

Selective reporting (reporting bias)High riskThe primary outcome (pain relief), as specified in the protocol,was not at all addressed in the study report.

Other biasLow riskUnlikely that other biases are present.

Drug company sponsorship: absent. No conflict of interest.

Mukaindo 2010

MethodsStudy design: randomised controlled trial.

Allocation generation: computer-generated random sequence of numbers.

Allocation concealment: randomisation sequence was sequentially coded. The pharmacist, who was the only one with access to the code, prepared the syringes, which were only labelled with the randomisation number, accordingly and handed them over to the labour ward staff.

Blinding: participants, labour ward staff and investigator were blinded.

Loss to follow-up: intervention: 8% were excluded from the analysis.

Control: 7% were excluded from the analysis.


ParticipantsTotal number of participants randomised: 85.

Inclusion criteria: nulliparas above 18 years of age, at term, with singleton pregnancy, cephalic presentation in spontaneous labour and without contraindications to hyoscine butyl bromide.

Exclusion criteria: multiparas, induced labour, preterm labour, contraindications to vaginal delivery or hyoscine butyl bromide, high-risk pregnancies.


InterventionsIntervention:

Hyoscine butyl bromide 40 mg (2 mL) IVI, administered between 3 and 6 cm cervical dilatation.

n = 40.

Placebo:

Sterile water, 2 mL IVI, administered between 3 and 6 cm cervical dilatation.

n = 45.


OutcomesPrimary outcomes:

1. Duration of labour (from diagnosis of active phase of labour to delivery).

Secondary outcomes:

1. Rate of cervical dilatation (cm/h).

2. Maternal postpartum satisfaction scores.


NotesEthics: all participants required to sign informed consent. Study was approved by the ethics committee of the Aga Khan University Hospital.

Location: Kenia.

Author contacted regarding standard deviations of continuous measures, inclusion and exclusion criteria and flow diagram of study participants.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random sequence of numbers.

Allocation concealment (selection bias)Low riskRandomisation sequence was sequentially coded. The pharmacist, who was the only one with access to the code, prepared the syringes, which were only labelled with the randomisation number, accordingly and handed them over to the labour ward staff.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskParticipants and labour ward staff were blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskInvestigator was blinded until conclusion of the study.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll participants accounted.

Selective reporting (reporting bias)Low riskAll outcomes pre-specified in the methods section reported on.

Other biasLow riskUnlikely that other bias is present.

Funding: research grant, no funding received from any pharmaceutical company.

Raghavan 2008

MethodsStudy design: randomised controlled trial.

Allocation generation: random allocation (not specified).

Allocation concealment: not described.

Blinding: "double blinded" but blinding not described.

Loss to follow-up: not mentioned.


ParticipantsTotal number of participants randomised: 150.

Inclusion criteria: primigravid women in spontaneous labour, at term, with singleton fetus.

Exclusion criteria: cephalopelvic disproportion.


InterventionsIntervention:

1. Hyoscine butyl bromide suppository (dosage not specified).

n = 50.

2. Valethamate bromide intravenous infusion (dosage not specified).

n = 50.

Control:

No medication.

n = 50.


OutcomesPrimary outcomes:

1. Duration of first stage of labour.

2. Duration of Total duration of labour.

3. Mode of delivery.

Secondary outcomes:

1. Maternal adverse effects.

2. Complications of labour.

3. Neonatal adverse effects.


NotesEthics: study approved by Hospital ethics committee (Vani Villas Hospital, Bangalore).

Location: India.

This study was reported in a letter to the editor in response to the study by Samuels 2007.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described how randomisation was achieved.

Allocation concealment (selection bias)Unclear riskNot described.

Blinding of participants and personnel (performance bias)
All outcomes
High riskNot specifically mentioned, but 1 group received intravenous medication, the other 1 suppositories, while the control group did not receive any medication. The patients and personnel could thus not have been blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot mentioned.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThey only mention how many participants were enrolled at the beginning of the study.

Selective reporting (reporting bias)High riskNot all prespecified outcomes were reported in the results.

Other biasUnclear riskThis study was only reported in a letter to the editor and it is thus difficult to judge if other bias is present.

Drug company sponsorship: unclear, not mentioned.

Samuels 2007

MethodsStudy design: randomised controlled trial.

Allocation generation: computer-generated random sequence of numbers.

Allocation concealment: sequentially numbered syringes only PI knew correlation, which was only shown after analysis

Blinding: participants, midwives and obstetricians were blinded.

Loss to follow-up: Intervention: 0% Control: 0%.


ParticipantsTotal number of participants randomised: 129.

Inclusion criteria: primi- and multigravidas, > 18 years old, at term, in established, spontaneous labour, with no pregnancy induced or chronic illness.

Exclusion criteria: complicated pregnancies (not further specified).


InterventionsIntervention:

Hyoscine butyl bromide 20 mg (1 mL) IVI, between 4-5 cm dilatation.

n = 60.

Control:

Placebo: NaCl 1 mL IVI, between 4-5 cm dilatation.

n = 69.


OutcomesPrimary outcomes:

1. Duration of first stage of labour (time from intervention to full dilatation).

Secondary outcomes:

1. Duration of second and third stages of labour.

2. Blood loss.

3. Rate of caesarean section.

4. Apgar scores.


NotesLocation: Jamaica.

Other: standard deviations not reported. Author contacted. Could not provide standard deviations, hence they were imputed.

Ethics: ethical approval obtained, informed consent obtained.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random sequence of numbers.

Allocation concealment (selection bias)Low riskSequentially numbered syringes.

Content of syringes was only known to PI during the study and was revealed after completion of the study.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskParticipants and personnel were blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessors were blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll participants accounted for, no missing data.

Selective reporting (reporting bias)Low riskPrimary outcome:

duration of first stage of labour: adequately reported.

Secondary outcomes:

duration of 2nd and 3rd stages of labour, blood loss at delivery, rate of caesarean section, Apgar scores: all adequately reported 95% confidence intervals present.

No standard deviations reported with the means.

Other biasLow riskNo other sources of potential bias detected.

Drug company sponsorship: no.

Sekhavat 2012

MethodsStudy design: randomised controlled trial.

Allocation generation: computer-generated random number list.

Allocation concealment: not described.

Blinding: Participants and caregivers/physicians not blind. Outcome assessors blind.

Loss to follow-up: Intervention: 0% Control: 0%.


ParticipantsTotal number of participants randomised: 188.

Inclusion criteria: Multigravidas only with normal, singleton pregnancy, gestational age 37-42 weeks, vertex presentation, normal labour (spontaneous, presence of regular uterine contractions), active phase of labour (3-4 cm cervical dilatation), intact membranes.

Exclusion criteria: Chronic or pregnancy-induced illnesses, contra-indication to vaginal delivery, antepartum haemorrhage, multiple pregnancy, previous caesarean section, parity > 4.


InterventionsIntervention:

Hyoscine butyl bromide 20 mg (1 mL) IVI, after admission to labour ward (at 3-4 cm cervical dilatation).

n = 94.

Control:

Placebo: NaCl 1 mL IVI, after admission to labour ward (at 3-4 cm cervical dilatation).

n = 94.


OutcomesPrimary outcomes:

1. Duration of first stage of labour.

2. Duration of second stage of labour.

3. Duration of third stage of labour.

4. Cervical dilatation rate.

Secondary outcomes:

1. Delivery route.

2. Clinical side effects.

3. Neonatal Apgar score ar one and five minutes.


NotesLocation: Iran.

Other: Authors did not address conflict of interest.

Ethics: Ethical approval obtained by the ethics committee of Shadid Sadoughi University of Medical Sciences, Yazd, Iran, informed consent obtained from participants.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random number list.

Allocation concealment (selection bias)Unclear riskNot described.

Blinding of participants and personnel (performance bias)
All outcomes
High riskBoth participants and physicians were unblinded.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessors were blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll participants accounted for.

Selective reporting (reporting bias)High riskAuthors did not report on maternal adverse effects (prespecified in methods section).

Other biasUnclear riskNot clear what outcome authors used to calculate sample size. Study only included multiparous women.

Sharma 2001

MethodsStudy design: randomised controlled trial.

Allocation generation: computer-generated random numbers.

Allocation concealment: not described.

Blinding: not described.

Loss to follow-up:

Intervention: 0%.

Control: 0%.


ParticipantsTotal number of participants randomised: 150.

Inclusion criteria: primigravidae between 18-30 years old, at term with healthy, singleton fetus, vertex presentation, intact membranes, in active phase of labour.

Exclusion criteria: any medical, surgical or obstetric complications, like pre-eclampsia, antepartum haemorrhage, induced labour, cervical dilatation of > 5 cm.


InterventionsIntervention:

1. Drotaverine hydrochloride 40 mg IMI at 4 cm dilatation and every 2 h for a max of 3 doses.

n = 50.

2. Valethamate bromide 8 mg IMI at 4 cm dilatation and every hour for a max of 3 doses.

n = 50

Control: No medication.

n = 50.


OutcomesPrimary outcomes:

1. Duration of labour (injection to delivery time).

Secondary outcomes:

1. Mode of delivery.

2. Side effects.

3. Neonatal outcome.


NotesEthics: study approved by institutional review board, written informed consent obtained.

Location: India.

Authors contacted:


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random numbers.

Allocation concealment (selection bias)Unclear riskNot described.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo blinding described. Placebo group did not receive any medication. It is thus assumed that no blinding was done.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo blinding described. Placebo group did not receive any medication. It is thus assumed that no blinding was done.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll participants accounted for, no missing data.

Selective reporting (reporting bias)Low riskPrimary outcomes:

1. Injection-to-delivery time: adequately reported.

Secondary outcomes:

1. Mode of delivery: adequately reported.

2. Duration and complications of 3rd stage: adequately reported.

3. Apgar scoring: not adequately reported: "there was no statistically significant difference...although 2 newborns in group II and 4 in group III had fetal distress".

Other biasHigh riskAll 150 patients in the study delivered vaginally. The study reports, that the hospital has a caesarean section rate of 12%. They claim that it was purely coincidental, but this raises questions about the selection of participants and introduction of selection bias.

Drug company sponsorship: not mentioned.

Singh 2004

MethodsStudy design: randomised controlled trial.

Allocation generation: identical paper slips with either drug or placebo written, on drawn from box, patient's serial number written on slip and kept in separate box.

Allocation concealment: not clearly described.

Blinding: patients and observers were blinded.

Loss to follow-up: 16% - it is not specified to which group these participants were allocated to.


ParticipantsTotal number of participants randomised:100.

Inclusion criteria: primigravidae at term with singleton pregnancy, vertex presentation, established spontaneous labour, cervical dilatation of at least 3 cm.

Exclusion criteria: any medical, surgical or obstetric complications.


InterventionsIntervention:

Drotaverine hydrochloride 40 mg (2 mL) IMI in active labour, cervix at least 3 cm dilated.

n = 50.

Control:

Distilled water 2 mL IMI in active labour, cervix at least 3 cm dilated..

n = 50.


OutcomesPrimary outcomes:

1. Duration of first stage of labour (time of intervention to full cervical dilatation).

2. Pain.

3. Cervical dilatation rate.

Secondary outcomes:

1. Maternal and neonatal outcome.

2. Side effects.


NotesEthics: approved by institutional ethical committee, informed consent obtained.

Location: Delhi, India.

Authors contacted:


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskIdentical paper slips 50 with "drug" and 50 with "placebo" written on. A slip was drawn from the box and patient's serial no written on it, kept in separate box.

Allocation concealment (selection bias)High riskNo allocation concealment took place. The nurse administering the intervention knew whether placebo or active ingredient was administered. The paper slips were not sequentially numbered, but explicitly stated "drug" or "placebo".

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskParticipant was blinded, nurse administering intervention was not blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessor was blinded.

Incomplete outcome data (attrition bias)
All outcomes
High risk100 patients were enrolled, 16 were excluded before intervention was administered. 4 patients had caesarean section due to fetal distress, 5 patients opted out of the study and 7 had incomplete data. It is not mentioned to which group all these participants belonged to, which is inadequate.

Selective reporting (reporting bias)Unclear riskDuration of different stages of labour: adequately reported cervical dilatation rate: only reported in bar-chart. The mean cervical dilatation rate of the intervention group is mentioned, but not of the control group. Pain assessment results are adequately reported It is not stated how many instrumental deliveries or caesarean section were done after the intervention.

Other biasHigh riskThe starting point of the intervention was not the same in every participant. It varied from 3-6 cm cervical dilatation. The number of participants in each group was not the same. In the group that received the intervention at 6 cm, there were 18 in the treatment group compared to 3 in the control group. The results presented are not statistically significant, but imbalances like that introduce bias. Drug company sponsorship: not mentioned.

Taskin 1993

MethodsStudy design: randomised controlled trial.

Allocation generation: randomisation (not specified) Allocation concealment: not described.

Blinding: patients and physicians were blinded. Not clear whether observers were blinded.

Loss to follow-up: 13% were excluded from the analysis.
because they underwent caesarean section. Not specified to which group they belonged to.


ParticipantsTotal number of participants randomised: 120.

Inclusion criteria: term patients in labour with cervical dilatation of 5cm or less, with uncomplicated pregnancies.

Exclusion criteria: patients with abnormal presentation, previous caesarean section, ruptured membranes, evidence of fetal or maternal compromise.


InterventionsIntervention:

1. Meperidine 50 mg intravenously at 4-5 cm.

n = 30.

2. Hyoscine bromide 20 mg intravenously at 4-5 cm.

n = 30.

3. Valethamate bromide 8 mg intravenously at 4-5 cm.

n = 30.

Control:

Placebo (not specified) intravenously at 4-5 cm.

n = 30.


OutcomesOutcomes not specified.

Outcome data on administration to delivery time is present.


NotesLocation: USA.

Study was only published as an abstract and therefore minimal information is present.

No contact details of authors are present.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation - not specified.

Allocation concealment (selection bias)Unclear riskNot mentioned.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskPhysicians and participants were blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot clear whether outcome assessors were blinded.

Incomplete outcome data (attrition bias)
All outcomes
High riskNo outcomes specified.

Selective reporting (reporting bias)High riskNo details about participants.

Other biasUnclear riskStudy only published as an abstract and therefore minimal information is present. Drug company sponsorship: not mentioned.

Warke 2003

MethodsStudy design: randomised controlled trial.

Allocation generation: random sequence generation.

Allocation concealment: not described.

Blinding: not described.

Loss to follow-up:

Intervention: 0%.

Control: 0%.


ParticipantsTotal number of participants randomised: 100.

Inclusion criteria: primigravidas, gestational age 37-40 weeks, between 18-35 years old, in active phase of labour, singleton fetus, vertex presentation.

Exclusion criteria: antenatal pregnancy complications like pre-eclampsia, other medical disorders of pregnancy, CPD, premature rupture of membranes, induction or augmentation of labour.


InterventionsIntervention:

Camylofin dihydrochloride 50 mg IMI in active phase of labour, at 3 cm dilatation.

n = 50.

Control:

Placebo - type of placebo and dose not specified. Given IMI in active phase of labour, at 3 cm dilatation.

n = 50.


OutcomesPrimary outcomes:

1. Duration of active labour (time from onset of active labour (3 cm) to full cervical dilatation).

2. Rate of cervical dilatation (cm/h).

3. Effects on second and third stage of labour.

Secondary outcomes:

Side effects on mother and fetus.


NotesEthics: institutional ethics approval obtained, written, informed consent obtained.

Location: India.

Other: no contact details.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandom allocation - not adequately described.

Allocation concealment (selection bias)Unclear riskNot described.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear risk"Double-blind trial."

Not known who was blinded and if this was adequate.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk"Double-blind trial."

Not known who was blinded and if this was adequate.

Incomplete outcome data (attrition bias)
All outcomes
High riskNo numbers showing flow of participants. Percentages of modes of delivery do not add up, this could be a mistake or due to missing information.

Selective reporting (reporting bias)Low riskTime from onset of active labour to full cervical dilatation - no SD reported with means.

Rate of cervical dilatation - no SD reported with means.

Effects of treatment on second and third stage of labour - no SD reported with means.

Maternal side effects adequately reported.

Neonatal side effects not specified.

Other biasHigh riskTables are unclear and confusing. No contact details of the authors are present. Drug company sponsorship: no.

Yilmaz 2009

MethodsStudy design: randomised controlled trial.

Allocation generation: computer-generated random number.

Allocation concealment: opaque, sealed envelopes that were consecutively numbered.

Blinding: patients and physicians blinded.

Loss to follow-up:

Intervention: 10%.

Control: 9%.


ParticipantsTotal number of participants randomised: 160.

Inclusion criteria: primigravidae, 18-30 years old, with gestational age 40+, healthy, with single fetus in vertex presentation, needing induction due to oligohydramnios, rupture of membranes or post-term.

Exclusion criteria: spontaneous labour, fetal weight > 4000 g, CPD, non-reassuring CTG, allergy to meperidine or valethamate bromide, previous uterine surgery, active PV bleeding, placenta previa, use of analgesia prior to randomisation.


InterventionsIntervention:

1. Meperidine 50 mg (1 mL) in 9 mL NaCl IVI between 4 and 6 cm dilatation.

n = 53.

2. Valethamate bromide 16 mg (2 mL) IVI in 8 mL of NaCl between 4 and 6 cm dilatation.

n = 53.

Control:

NaCl 10 mL IVI between 4 and 6 cm dilatation.

n = 54.


OutcomesPrimary outcomes:

1. Duration of first stage or labour (time from intervention to complete dilatation).

2. Duration of second stage.

3. Total duration of labour.

Secondary outcomes:

1. Mode of delivery.

2. Cervical lacerations.

3. Adverse maternal and fetal events.


NotesEthics: approval by Human Research Review Committee Location: Turkey.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random numbers.

Allocation concealment (selection bias)Low riskOpaque, sealed and consecutively numbered envelopes.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskParticipants blinded, nurses not blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessor blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll participants are accounted for, flow-chart present.

Selective reporting (reporting bias)Low riskAll pre-specified outcomes have been reported.

Primary outcomes: time to complete dilation, duration of second stage of labour, labour duration - no missing outcome data.

Secondary outcomes: mode of delivery, presence of cervical lacerations and adverse maternal and neonatal events - no missing outcome data.

Other biasLow riskNo other potential bias detected. Drug company sponsorship: no.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Aggarwal 2008Study used consecutive randomisation and is thus not considered a truly randomised controlled trial.

Akleh 2010Study is not randomised.

Baracho 1982Study does not indicate that randomisation took place.

Bhattacharaya 1984Study is not randomised.

Chan 1963Study includes preterm labour.

De Nobrega-Correa 2010Study compares hyoscine butyl-bromide-oxytocin and oxytocin. No control group.

Demory 1990All participants had cervical dystocia at randomisation.

Fouedjio 2012Authors used alternative randomisation and is thus not considered a truly randomised controlled trial.

Guerresi 1981No control group.

Hamann 1972No indication that randomisation took place.

Hao 2004Study compares Spasfon and Atropine - no control group.

Kauppila 1970Study does not have control group.

Kaur 2003Study compares Drotaverine and Epidosin, no control group and no randomisation.

Kaur 2006Study comparing Anafortan and Epidosin, no control group and no randomisation.

Malensek 1985No randomisation.

Manpreet 2008No control group.

Maritati 1986Included women with post-operative spasms.

Mishra 2002Study compares drotaverine and Epidosin, no control group and no randomisation present.

Mortazavi 2004Study is "semi-experimental".

Rajkumar 2006Non-randomised study.

Sirohiwal 2005Non-randomised study.

Tabassum 2005Study included women with preterm deliveries (> 34 weeks' gestational age).

Tripti 2009Study compares drotaverine and valethamate bromide, no control group and no randomisation.

Von Hagen 1965Non-randomised study.

 
Characteristics of studies awaiting assessment [ordered by study ID]
Accinelli 1978

MethodsParticipants were grouped according to a "randomized double-blind scheme". The physician broke the code when he thought treatment was inadequate to decide on the next course of action.

ParticipantsPrimiparae and multiparae, aged 17-42, for whom normal labour was expected.

InterventionsIntervention:

1. DA 3177 (scopalamine-N-(cyclopropylmethyl) bromide).

2. Hyoscine-N-butyl bromide.

3. Placebo (not specified).

OutcomesDuration of the period of dilatation.

Duration of expulsive period.

NotesGestational age of participants not clear.

Ahmed 1982

MethodsDouble-blind study. Sequence generation and allocation concealment not clear.

ParticipantsPrimiparous women between 20 and 25 years old at term; no pregnancy related disease, 3 cm cervical dilatation, cephalic presentation.

InterventionsIntervention: 6 different types of antispasmodics.

Control: placebo (NaCl).

OutcomesThe effect of antispasmodics on labour.

NotesNot clear whether study is a RCT. Author contacted, awaiting reply.

Georges 2007

MethodsAllocation generation: not known ("divided in two groups").

Allocation concealment: not described.

Blinding: "double-blind".

Loss to follow-up: not described.

ParticipantsInclusion criteria: women in the labour ward.

Exclusion criteria: not described.

InterventionsIntervention: Buscopan 20 mg IVI at 3 cm cervical dilatation.

Controls: placebo (unknown) IVI.

OutcomesPrimary outcomes:

1. Duration of stages of labour.

Secondary outcomes:

1. Maternal outcome.

2. Neonatal outcome.

NotesEthics: not mentioned.

Location: Iraq.

Notes: not clear whether this is a randomised study. Author contact details needed.

Rajani 2011

MethodsAllocation generation: not known ("divided in.to 2 groups").

Allocation concealment: not described

Blinding: not described.

Loss to follow-up: not described.

ParticipantsInclusion criteria: women in labour with an unscarred uterus.

Exclusion criteria: not described.

InterventionsIntervention: Valethamate bromide 1 mL IVI half hourly for a maximum of 3 doses starting at 3 cm cervical dilatation.

Control: normal saline 1 mL, maximum of 3 doses half hourly.

OutcomesPrimary outcomes:

1. Duration of first stage of labour.

2. Duration of second stage of labour.

3. Duration of third stage of labour.

Secondary outcomes:

1. Maternal side effects.

2. Fetal side effects.

3. Caesarean section rate.

4. Third stage bleeding.

NotesEthics: not mentioned.

Location: India.

Notes: not reported that participants were randomised. Trying to obtain author's contact details.

Ranka 2002

MethodsAllocation generation: not described.

Allocation concealment: not described.

Blinding: not described.

Loss to follow-up: not described.

ParticipantsInclusion criteria: primigravidae in labour.

Exclusion criteria: not described.

InterventionsIntervention: Drotaverine hydrochloride.

Control: no medication.

OutcomesProgress and outcome of labour.

NotesEthics: not described.

Location: India.

Only reported as an abstract. Not clear whether this is a RCT. Trying to get author's contact details.

Recto 1997

MethodsAllocation generation: "randomised" - not clearly described.

Allocation concealment: not described.

Blinding: not described, but states "double-blind".

Loss to follow-up: not described.

ParticipantsPrimi- and multigravidas. No other information.

InterventionsIntervention: 10 mg of hyoscine-N-Butylbromide on admission and in 4-hourly intervals until full cervical dilatation. Admission route not specified.

Control: placebo - not specified.

OutcomesPrimary outcomes:

1. Duration of first stage of labour.

2. Duration of second stage of labour.

Secondary outcomes:

1. Maternal adverse effects.

2. Neonatal adverse effects.

NotesEthics: not mentioned.

Location: Philipines.

Not clear whether participants were really randomised: In both the treatment and control group there were 38 primi- and 38 multigravid women. The process of randomisation is not clearly described. Author contact details missing.

Roy 2007

MethodsProspective randomised study – not clear whether study was really randomised.

ParticipantsWomen with spontaneous onset of labour.

InterventionsIntervention:

Drotaverine hydrochloride 40 mg IVI.

Control:

No medication.

Outcomes1. Effects of drug on progress of labour.

2. Outcome of labour.

NotesMethods not explicitly stated, not clear whether participants were randomised. Authors contacted, awaiting reply.

Zagami 2012

Methods

Participants

Interventions

Outcomes

NotesPersian study - no suitable translator found to date.

 
Characteristics of ongoing studies [ordered by study ID]
Movahed 2010

Trial name or titleThe effect of hyoscine on duration on the first stage of labour in term pregnancies.

MethodsAllocation generation: randomised.

Allocation concealment: not described.

Blinding: double-blind.

ParticipantsInclusion criteria: term pregnancy, cephalic presentation, singleton pregnancy.

Exclusion criteria: contraindications for vaginal delivery.

InterventionsIntervention: hyoscine 20 mg (1 mL) intravenous injection, during the active phase of labour.

Control: distilled water, 1 mL intravenous injection during active phase of labour.

OutcomesPrimary outcomes:

1. Duration of first stage of labour.

Secondary outcomes:

1. Duration of second stage of labour.

2. Duration of third stage of labour.

Starting dateDate registered: 29 May 2010.

Contact informationFarideh Movahed: fmovahed@qums.ac.ir

NotesAuthor contacted to request interim results. Not able to share these at this stage.

 
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]

 
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
 
Table 1. Summary of included studies

StudyCountryNumber of participantsLow-/high-risk pregnancyGravidity of participantsTime of interventionIntervention (dose and route of administration)ControlNon-study interventionsInduced/spontaneous labour

Ajmera 2006India225Low riskPrimi-and multigravidasActive phase, 3 cm dilatationDrotaverine hydrochloride (40 mg IMI¹)

Valethamate bromide (8 mg IVI²)
No medicationNone specifiedSpontaneous

Al Matari 2007Saudi Arabia199Not mentionedNot mentionedNot mentionedHyoscine-N-butyl bromide (not mentioned)Placebo (not specified)None specifiedNot mentioned

Al Qahtani 2011Saudi Arabia110Low riskPrimigravidasEstablished labour, 3-4 cm dilatationHyoscine butyl bromide (40 mg IMI)NaCl³ 0.9% (2 mL IMI)Amniotomy, opioid analgesiaSpontaneous

Azari 2010Iran200Not mentionedPrimigravidas4 cm dilatation and ruptured membranesHyoscine and atropine (20 mg IVI)Dextrose water (2 cc IVI)Not specifiedNot mentioned

Batukan 2006Turkey100Low riskPrimi-and multigravida4-5 cm dilatationValethamate bromide (8 mg IMI)NaCl 0.9% (1 mL IVI)Oxytocin if necessary, amniotomy if no spontaneous ROM⁴ at 8-10 cmSpontaneous and induced

Cromi 2011Italy120Low riskPrimigravida3-5 cm dilatationRociverine (20 mg IMI)NaCl 0.9% (2 mL IMI)Amniotomy, augmentation with oxytocin, epidural analgesiaSpontaneous

Dahal 2013Nepal300Low riskPrimi- and multigravidasUnclearValethamate bromide (8mg IMI)

Drotaverine hydrochloride (40mg IMI)
No medicationAmniotomy once cervical dilatation > 4cm, or if Bishop's score was favourable, oxytocin augmentationSpontaneous and induced

Gupta 2008India150Low and high riskPrimi-and multigravidas3 cm dilatationDrotaverine hydrochloride (40 mg IMI)

Hyoscine butyl bromide (20 mg IVI)
No medicationOxytocin if necessary, amniotomyNot specified

Khosla 2003India300Low riskPrimi-and multigravidas4 cm dilatationValethamate bromide (8 mg IMI)

Drotaverine hydrochloride (40 mg IMI)
No medicationNot specifiedSpontaneous

Kuruvila 1992India120Low riskPrimi- and multigravidas2-4 cmValethamate bromide (8 mg IMI)NaCl 0.9% (1 mL IMI)Oxytocin if necessary, amniotomy, pethidine 75 mg for primigravidas)Not specified

Madhu 2010India150Low riskPrimi-and multigravida4 cm dilatationDrotaverine hydrochloride (40 mg IMI)

Valethamate bromide (8 mg IMI)
NaCl 0.9% (2 mL IMI)Amniotomy, oxytocin if required, paracetamol and pethidine for labour analgesiaSpontaneous

Makvandi 2010Iran130Low riskPrimigravidas3-4 cm dilatationHyoscine butyl bromide (20 mg PR⁵)Placebo suppositoryAmniotomy when presenting part was fixedSpontaneous

Mukaindo 2010Kenia85Low riskPrimigravidas3-6 cm dilatationHyoscine butyl bromide (40 mg IVI)Sterile water (2 mL IVI)Amniotomy and augmentation with oxytocin as per protocolSpontaneous

Raghavan 2008India150Not mentionedPrimigravidasNot mentionedHyoscine butyl bromide (PR)

Valethamate bromide (IVI)
No medicationNot specifiedSpontaneous

Samuels 2007Jamaica129Low riskPrimi- and multigravidas4-5 cm dilatationHyoscine butyl bromide (20 mg IVI)NaCl 0.9% (1 mL IVI)Routine amniotomy, opioid analgesia, oxytocinSpontaneous

Sekhavat 2012Iran188Low riskMultigravidas3-4 cm dilatationHyoscine butyl bromide (20 mg IVI)NaCl 0.9% (1 mL IVI)Amniotomy, oxytocinSpontaneous

Sharma 2001India150Low riskPrimigravidas4 cm dilatationDrotaverine hydrochloride (40 mg IMI)

Valethamate bromide (8 mg IMI)
No medicationNoneSpontaneous

Singh 2004India100Low riskPrimigravidas3-6 cm dilatationDrotaverine hydrochloride (40 mg IMI)Distilled water 2 mL (IMI)Amniotomy, oxytocin, pentazocine and promethazine, episiotomySpontaneous

Taskin 1993USA120Low riskPrimi-and multigravidas4-5 cm dilatationValethamate bromide (8 mg IVI)

Hyoscine bromide (20 mg IVI)

Meperidine (50 mg IVI)
Placebo (not specified, IVI)Not specifiedNot mentioned

Warke 2003India100Low riskPrimigravidas3 cm dilatationCamylofin dihydrochloride (50 mg IMI)Placebo (not specified (IMI)NoneSpontaneous

Yilmaz 2009Turkey160Low riskPrimigravidas4-6 cm dilatationValethamate bromide (16 mg IVI)

Meperidine (50 mg IVI)
NaCl 0.9% (10 mL)Amniotomy, oxytocin, episiotomyInduced only

 ¹IVI: intravenous injection
²IMI: intramuscular injection
³NaCl: sodium chloride/saline
⁴ROM: rupture of membranes
⁵PR: per rectum
 
Table 2. Maternal adverse events

StudyTachycardiaMouth drynessNauseaVomitingDizzinessCervical lacerationGiddinessBlood lossFlushing of faceHeadache

Ajmera 2006

(Drotaverine hydrochloride)
2.7%00001.3%1.3%Not reported04%

Ajmera 2006

(Valethamtate bromide)
14.6%2.7%00000Not reported5.3%2.7%

Ajmera 2006

(Placebo)
5.3%1.3%0004%4%Not reported02.7%

Al Matari 2007Did not report on maternal adverse events


Al Qahtani 2011

(Hyoscine butyl bromide)
PPH¹: 0/52; Tear: 2/50


Al Qahtani 2011

(Placebo)
PPH: 0/45; Tear: 0/45


Azari 2010Did not report on maternal adverse events


Batukan 2006Women receiving Valethamate bromide experienced more dizziness and mouth dryness than women receiving placebo


Cromi 2011

(Rociverine)
No maternal side effects reported300 mL (100-1400)




Cromi 2011

(Placebo)
No maternal side effects reported350 mL (50-2000)




Dahal 2013Dryness of mouth, vomiting, tachycardia and retention of urine were more pronounced in the valethamate bromide group than in the drotaverine hydrochloride and control groups


Gupta 2008

(Drotaverine hydrochloride)
20% of participants experienced adverse events, the main ones being nausea and vomiting


Gupta 2008

(Hyoscine butyl bromide)
10%0Main complaintMain complaint24% of participants experienced adverse effects






Gupta 2008

(Placebo)
No reported maternal adverse events


Khosla 2003

(Valethamate bromide)
16%4%Not reported4%Not reported






Khosla 2003

(Drotaverine hydrochloride)
No maternal adverse events reported


Khosla 2003

(Control)
No maternal adverse events reported


Kuruvila 1992Maternal pulse rate > 110/min observed in significantly more women receiving Valethamate bromide. Flushing of face and dryness of mouth not statistically significant between groups.


Madhu 2010

(Drotaverine hydrochloride)
4%0000000010%

Madhu 2010

(Valethamate bromide)
81.6%20%00000010%2%

Madhu 2010

(Control)
6.30%4.2%00002.1%000

Makvandi 2010

(Hyoscine butyl bromide)
Mean heart rate:83.34 beats/min, SD:10.56

Mean systolic BP: 108.78 mmHg, SD: 12.34


Makvandi 2010

(Placebo)
Mean heart rate:86.65 beats/min, SD:12.87

Mean systolic BP: 110.09 mmHg, SD:13.67


Mukaindo 2010

(Hyoscine butyl bromide)
1 patient reported transient palpitations

PPH in 5.7% participants


Mukaindo 2010

(Placebo)
No adverse events reported

PPH in 7.3% of participants


Raghavan 2008

(Hyoscine butyl bromide)
Mild tachycardia, dryness of mouth and vomiting


Raghavan 2008

(Valethamate bromide)
Mild tachycardia, dryness of mouth and vomiting


Raghavan 2008

(No medication)
No adverse events reported


Samuels 2007

(Hyoscine butyl bromide)
0000000150 mL (50-1800 mL)00

Samuels 2007

(Placebo)
0000000150 mL (50-550 mL)00

Sekhavat 2012No adverse events reported


Sharma 2001

(Drotaverine hydrochloride)
4%000000004%

Sharma 2001

(Valethamate bromide)
20%10%0000004%0

Sharma 2001

(Control)
4%000006%004%

Singh 2004

(Drotaverine hydrochloride)
18% had atonic PPH


Singh 2004

(Control)
2.5% had atonic PPH


Warke 2003

(Camylofin dihydrochloride)
1%5%5%6%02%0000

Warke 2003

(Control)
000002%0000

Yilmaz 2009

(Valethamte bromide)
21.3%14.9%14.9%8.5%12.8%2.1%0000

Yilmaz 2009

(Control)
4.1%010.2%6.1%4.1%00000

 ¹PPH: postpartum haemorrhage
 
Table 3. Neonatal adverse events

StudyApgar 1 minApgar 5 minMeconium-stained liquorFetal tachycardiaFetal distressAdmission to NICU¹Need for resuscitation

Ajmera 2006

(Drotaverine hydrochloride)
No report on neonatal adverse events or Apgar scores


Ajmera 2006

(Valethamate bromide)
No report on neonatal adverse events or Apgar scores


Ajmera 2006

(Control)
No report on neonatal adverse events or Apgar scores


Al Matari 2007

(Hyoscine butyl bromide)
Mean score: 8.7Mean score: 9.4No other adverse events reported




Al Matari 2007

(Control)
Mean score: 8.7Mean score: 9.3No other adverse events reported




Al Qahtani 2011

(Hyoscine butyl bromide)
5/52 babies:

score of 7-8
Score: 8-10 for all babiesNo adverse events noted




Al Qahtani 2011

(Placebo)
8/45 babies:

score of 7-8
Score: 8-10 for all babiesNo adverse events noted




Azari 2010No reports of any neonatal adverse events


Batukan 2006No reported neonatal adverse events


Cromi 2011

(Rociverine)
Not reportedScore < 7: 0%Arterial cord blood pH: 7.28 SD 0.11not reported





Cromi 2011

(Placebo)
Not reportedScore < 7: 1.8%Arterial cord blood pH: 7.27 SD 0.08not reported





Dahal 2013

(Valethamate bromide)
Not reported4not reported




Dahal 2013

(Drotaverine hydrochloride)
Not reported2not reported




Dahal 2013

(Control)
Not reported2not reported




Gupta 2008

(Drotaverine hydrochloride)
Mean score: 8 (7-9)Mean score: 9 (8-9)0002not reported

Gupta 2008

(Hyoscine butyl bromide)
Mean score: 8 (1-9)Mean score: 9 (3-9)0001not reported

Gupta 2008

(Control)
Mean score: 8 (4-9)Mean score: 9 (8-9)0003not reported

Khosla 2003"All babies had good Apgar scores and were discharged in good condition"


Kuruvila 1992No neonatal adverse events reported


Madhu 2010

(Drotaverine hydrochloride)
No report on neonatal adverse effects or Apgar scores


Madhu 2010

(Valethamte bromide)
Not reported10%00not reported






Madhu 2010

(Control)
No report on neonatal adverse effects or Apgar scores


Makvandi 2010

(Hyoscine butyl bromide)
Score < 7: 2Score < 7: 0Bradycardia: 3.10%; Tachycardia: 4.60%not reported





Makvandi 2010

(Control)
Score < 7: 0Score < 7: 0Bradycardia: 4.60%; Tachycardia: 3.10%not reported





Mukaindo 2010

(Hyoscine butyl bromide)
Not reported10 (8-10)No adverse events reported




Mukaindo 2010

(Placebo)
Not reported10 (7-10)No adverse events reported




Raghavan 2008No significant adverse events reported in any of the groups


Samuels 2007

(Hyoscine butyl bromide)
Mean score: 9 (2-9)Mean score: 9 (2-10)not reported




Samuels 2007

(Control)
Mean score: 9 (3-9)Mean score: 9 (8-10)not reported




Sekhavat 2012

(Hyoscine butyl bromide)
Mean score: 8.4 (SD 1.6)Mean score: 7.8 (SD 1.2)not reported12






Sekhavat 2012

(Placebo)
Mean score: 8.1 (SD 1.8)Mean score: 8.1 (SD 0.9)not reported11






Sharma 2001

(Drotaverine hydrochloride)
Not statistically different from other groupsnot reported







Sharma 2001

(Valethamate bromide)
Not statistically different from other groups004%0not reported







Sharma 2001

(Control)
Not statistically different from other groups008%0not reported







Singh 2004

(Drotaverine hydrochloride)
Mean score: 9.84Mean score: 9.960000not reported

Singh 2004

(Control)
Mean score: 9.59Mean score: 9.930000not reported

Taskin 1993not reported


Warke 2003

(Camylofin dihydrochloride)
Not reported0002%not reported







Warke 2003

(Control)
Not reported0002%not reported







Yilmaz 2009

(Valethamate bromide)
Score < 7: 8.5%Score < 7: 2.1%10.6%000not reported

Yilmaz 2009

(Control)
Score < 7: 6.1%Score < 7: 4.1%6.1%002%not reported

 ¹NICU: neonatal intensive care unit