Interventions for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

James D Griffiths; Gillian ML Gyte; Shantini Paranjothy; Heather C Brown; Hannah K Broughton; Jane Thomas

doi:10.1002/14651858.CD007579.pub2

. 2012 Sep 12;2012(9):CD007579. doi: 10.1002/14651858.CD007579.pub2

Interventions for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

James D Griffiths ^1,^✉, Gillian ML Gyte ², Shantini Paranjothy ³, Heather C Brown ⁴, Hannah K Broughton ³, Jane Thomas ⁵

Editor: Cochrane Pregnancy and Childbirth Group

PMCID: PMC4204618 EMSID: EMS58086 PMID: 22972112

Abstract

Background

Nausea and vomiting are distressing symptoms which are experienced commonly during caesarean section under regional anaesthesia and can also occur in the period following the procedure.

Objectives

To assess the efficacy of pharmacological and non‐pharmacological interventions given prophylactically to prevent nausea and vomiting in women undergoing regional anaesthesia for caesarean section.

Search methods

We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (27 February 2012) and reference lists of identified studies.

Selection criteria

We included randomised controlled trials (RCTs) and excluded quasi‐RCTs and cross‐over studies.

Data collection and analysis

Review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. Data entry was checked.

Main results

Fifty‐two studies met the inclusion criteria but only 41 studies, involving 5046 women, provided useable data for the review involving women having caesareans under regional anaesthesia. The majority of the studies involved women undergoing elective caesarean section. Only two studies included emergency surgery, however, they did not stratify data according to type of surgery. The studies covered numerous comparisons, but the majority of studies involved 5‐HT₃ receptor antagonists, dopamine receptor antagonists, corticosteroids or acupressure. Studies were mainly small and of unclear quality.

Three classes of intervention were found to be effective in at least three out of four of our primary outcomes (intraoperative nausea, intraoperative vomiting, postoperative nausea and postoperative vomiting). These interventions were 5‐HT₃ antagonists, dopamine antagonists and sedatives. Other classes of intervention were effective for fewer than three of our primary outcomes.

With 5‐HT antagonists, we found a reduction in intraoperative nausea (average risk ratio (RR) 0.64, 95% confidence interval (CI) 0.46 to 0.88, eight studies, 720 women). There were also reductions in postoperative nausea (average RR 0.40, 95% CI 0.25 to 0.64, four studies, 405 women) and vomiting (average RR 0.50, 95% CI 0.32 to 0.77, five studies, 565 women). We did not detect a significant reduction in intraoperative vomiting (average RR 0.56, 95% CI 0.31 to 1.00, seven studies, 668 women).

Dopamine antagonists demonstrated a reduction in intraoperative nausea (average RR 0.38, 95% CI 0.25 to 0.57, nine studies, 636 women) and intraoperative vomiting (average 0.39, 95% CI 0.24 to 0.64, eight studies, 536 women), with similar reductions in postoperative nausea (average RR 0.60, 95% CI 0.40 to 0.91, five studies, 412 women) and vomiting (average RR 0.57, 95% CI 0.36 to 0.91, six studies, 472 women). These differences were observed with both metoclopramide and droperidol.

Sedatives (most commonly propofol) demonstrated a reduction in intraoperative nausea (average RR 0.71, 95% CI 0.52 to 0.96, four studies, 285 women) and intraoperative vomiting (average RR 0.42, 95% CI 0.26 to 0.68, four studies, 285 women), also with a reduction in postoperative nausea (average RR 0.25, 95% CI 0.09 to 0.71, two studies 145 women) and vomiting (average RR 0.09, 95% CI 0.03 to 0.28, two studies, 145 women).

Acupressure was found to be effective for intraoperative nausea (average RR 0.59, 95% CI 0.38 to 0.90, six studies, 649 women) but not postoperative nausea (average RR 0.83, 95% CI 0.68 to 1.00, three studies, 429 women). Acupressure was not effective at reducing vomiting either intraoperatively (average RR 0.74, 95% CI 0.46 to 1.18, six studies, 649 women) or postoperatively (average RR 0.69, 95% CI 0.45 to 1.06, three studies, 429 women).

Other effective intervention classes included corticosteroids, antihistamines, and anticholinergics.

There were insufficient data to demonstrate any class of intervention was superior to another. There were no significant differences observed in the comparison of combined versus single interventions.

Few studies assessed our secondary outcomes or the incidence of adverse effects. However, one study showed an increase in respiratory depression with sedation (midazolam) compared with dopamine antagonists.

Authors' conclusions

This review indicates that many different interventions have efficacy in preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section. There is little evidence that combinations of treatment are better than single agents.

Plain language summary

Reducing nausea and vomiting in women receiving regional anaesthesia for caesarean section

Caesarean section is a commonly performed operation for the birth of a baby when difficulties arise either for the mother or for the baby. Women may be either awake for the procedure (regional anaesthesia) or asleep (general anaesthesia). Nausea and vomiting are common and distressing symptoms, which can occur during the procedure if the woman is awake or they can also occur after the procedure. Low blood pressure and some of the medications administered during the procedure may contribute to the nausea and vomiting.

A wide range of medications are commonly used either to reduce the chance of symptoms occurring, or are given as a treatment if symptoms do occur. In addition, a number of non‐drug approaches have been tried such as using acupuncture or acupressure; giving extra oxygen; or giving extra intravenous fluids. We aimed to study the effectiveness of the various treatments to reduce the occurrence of nausea and vomiting during elective or emergency caesarean section using regional anaesthesia. We found 41 studies (involving 5046 women) that met our inclusion criteria and provided data which we could analyse. These were mainly small studies of unclear or poor quality.

Nevertheless, we found that many drugs, such as 5‐HT₃ antagonists (e.g. ondansetron), dopamine antagonists (e.g. metoclopramide, droperidol) and sedatives (mainly propofol) were effective in reducing the occurrence of nausea and vomiting either during surgery under regional anaesthesia or afterwards. Other effective interventions for some nausea and vomiting included corticosteroids (e.g. dexamethasone), antihistamines (e.g. cyclizine) and anticholinergics (e.g. scopolamine). In addition, acupressure was effective in reducing some nausea but not vomiting.

Few studies assessed the possible side effects such as headaches, dizziness, low blood pressure, skin rashes and breathing difficulties.

In addition to this review, there will be two further reviews on nausea and vomiting at caesarean section. The first will look at interventions given to reduce nausea and vomiting after general anaesthesia (as opposed to regional anaesthesia). The second will explore interventions given as a treatment to women who do suffer nausea and vomiting during regional anaesthesia.

Background

Nausea and vomiting are common symptoms experienced during caesarean section under regional anaesthesia and can also occur in the postoperative period following caesarean section under either regional or general anaesthesia. Nausea and vomiting during and after the birth of a baby are distressing for both the woman and her family. In addition, when vomiting occurs intraoperatively under regional anaesthesia, it offers significant challenge to the operating surgeon, potentially increasing the duration of the procedure and the risk of bleeding and inadvertent associated surgical trauma. There is also the potential risk of aspiration of gastric contents when vomiting occurs intraoperatively (Paranjothy 2010).

Caesarean section is a very commonly performed surgical procedure. The World Health Organization data indicate the caesarean section rate varies widely from less than 5% of births in low‐income countries (e.g. 5% in Zimbabwe) to 20% to 30% in high‐income countries (e.g. 22% in Germany) (WHO 2008). There are approximately 4.40 million live births in Central Europe and 4.43 million in the United States each year. This equates to approximately 1.7 million caesarean sections performed each year in Europe and the United States alone. Also, rates have risen considerably in high‐income countries in recent years, and still continue to rise. In the UK the rate was 21.3% in 2000 (Thomas 2001) and 23.8% in 2006 (Redshaw 2007). In a recent study of NHS trusts, the caesarean section rate ranged from 14.9% to 32.1% (Bragg 2010). The majority of caesarean sections these days are carried out under regional analgesia, though some need to be carried out under general anaesthesia, particularly in emergency situations or when there is a contraindication to the use of regional anaesthesia.

There are multiple underlying causes of nausea and vomiting at caesarean section and several different modes of intervention are in common use. Many different studies have evaluated these interventions, either compared with one another or with placebo. In some countries, for example in the UK (NICE 2011), there is a recommendation for the routine administration of drugs (antiemetics) or acupressure to try to prevent nausea and vomiting at caesarean section. However, it is probably more common clinical practice to give antiemetic medication as treatment, rather than as prophylaxis. It is not known to what extent medications which are efficacious as treatment are also efficacious as prophylaxis (and vice versa). All such interventions are associated with increased healthcare costs and potential risks to the woman (and potentially to the neonate, via breastfeeding) and therefore, their use should be evidence‐based. The aim of this review is to assess the effectiveness of these interventions given as prophylaxis during caesarean section to prevent nausea and vomiting. Studies aiming to assess interventions for secondary treatment of nausea and vomiting will be assessed in a separate review. A further review will also evaluate studies investigating the treatment of nausea and vomiting following caesarean section under general anaesthesia.

Description of the condition

Nausea is the unpleasant subjective urge to vomit. In contrast, vomiting is the propulsive abdominal muscular spasms associated with the expulsion of gastric contents. Retching is the same propulsive muscular spasms as vomiting (but without the expulsion of gastric contents).

The exact incidence of nausea and vomiting during caesarean section, and in the ensuing postoperative period, is uncertain as few prospective observational studies or audit data have been published. It is also likely that the baseline rate will vary depending on the anaesthetic and analgesic regimen used. However, it would seem reasonable to use the rates of nausea and vomiting in the placebo arms of well‐designed randomised trials as an indication of the baseline rate. Published placebo data show rates of nausea or vomiting ranging from 23% (Fujii 1998a) to 79% (Abouleish 1999). Most studies recruit women in the setting of elective caesarean section, and it is possible that rates are higher in the setting of emergency caesarean section.

Several aetiological factors contribute to the incidence of nausea and vomiting. These include hypotension (a frequent side effect of regional anaesthesia), reduced cardiac output from aorto‐caval compression (Cooke 1979), surgical stimulation from visceral traction such as exteriorisation of the uterus (Wahab 1999) and intraoperative medications including opiates and administered uterotonics including syntocinon and particularly ergometrine (De Groot 1998). Postoperative nausea and vomiting are also common, and can affect women who received regional or general anaesthesia. In most types of surgery, the use of regional anaesthesia is thought to be associated with lower rates of postoperative nausea and vomiting than general anaesthesia (Gan 2003); however, this difference may not be apparent following caesarean section. Almost all postoperative analgesia regimens involve the use of opioid type medications, either by oral, intravenous or neuraxial (spinal or epidural) routes, all of which can contribute to nausea and vomiting.

Description of the intervention

In this review, we have included pharmacological and non‐pharmacological interventions given specifically for the purpose of preventing nausea and vomiting in women undergoing caesarean section. Whilst hypotension is clearly an important cause of these symptoms during caesarean section, treatment for hypotension during regional anaesthesia has already been specifically addressed in another Cochrane review (Cyna 2006). Sometimes interventions can be given for other reasons, but may have an impact on nausea and vomiting. For example, interventions to reduce the risk of acid aspiration may well affect nausea and vomiting. These interventions have also been addressed in another Cochrane review (Paranjothy 2010).

The pharmacological interventions available include medications from a wide range of drug classes including dopamine and serotonin receptor antagonists, corticosteroids, antihistamines, sedatives and anticholinergics (Flake 2004).

A number of non‐pharmacological approaches have also been used to treat intraoperative nausea and vomiting including acupuncture or acupressure (Ho 2006), supplemental oxygen (Ghods 2005; Phillips 2007) and boluses of intravenous fluids (Morgan 2001).

This review has assessed the efficacy of interventions specifically used as prophylaxis to prevent the occurrence of nausea and vomiting in women undergoing caesarean section under regional anaesthesia. We define prophylaxis as an intervention that is commenced prior to, and without regard for, the onset of symptoms. Treatment is defined as an intervention which is commenced following, and in response to, the onset of symptoms. Interventions given as treatment to reduce established nausea and/or vomiting will be assessed in a different review.

How the intervention might work

Pharmacological interventions

The exact mechanism of action of many of the recognised interventions for the prevention of nausea and vomiting is not well understood. However, most treatments can be classed pharmacologically based on their receptor target. Nausea and vomiting caused by visceral stimulation is thought to be mediated predominantly via serotonin and dopamine, whereas nausea and vomiting caused by central nervous system and vestibular mechanisms are thought to be mediated mainly via histamine and acetylcholine. The chemoreceptor trigger zone (CTZ), a small region within the brainstem (responsible for medication and toxin related emesis symptoms) is mediated by serotonin and dopamine.

The main classes of medications in use include the following (Flake 2004; Gan 2003).

Serotonin (5‐HT) receptor subtype‐3 antagonists (e.g. ondansetron, granisetron) antagonise the emetic effects of serotonin in the small bowel, vagus nerve and CTZ (Peixoto 2006). They are effective and have few side effects. The most common adverse effects include headache and gastrointestinal symptoms (including diarrhoea).
Dopamine receptor antagonists (e.g. metoclopramide, prochlorperazine, droperidol, domperidone) antagonise the effects of dopamine at the D2 receptors in the CTZ. They have a wide variety of associated side effects including sedation, agitation, and extra‐pyramidal effects (Chestnut 1989). Droperidol has been associated with very rare, but potentially life threatening, cardiac arrhythmias.
Corticosteroids (most commonly dexamethasone) are regarded as being highly effective but the mechanism of action is not clear (Tzeng 2000). Whilst long‐term steroid use can lead to a wide variety of side effects (such as fluid and electrolyte changes, obesity, and diabetes), single antiemetic doses are well tolerated.
Antihistamines (e.g. phenergan [Habib 2007] and cyclizine [Nortcliffe 2003]) can cause a variety of adverse effects including sedation and dry mouth.
Anticholinergic agents (e.g. glycopyrrolate [Ure 1999], scopolamine [Kotelko 1989]) are mainly useful for nausea and vomiting caused via the vestibular system.
Sedatives. Low doses of sedatives such as midazolam or propofol (Numazaki 2003; Warwick 1997) seem to have efficacy.The mechanism of action is unclear, but may relate to the contribution of psychological factors such as stress and anxiety to the incidence of emetic symptoms
Opioids. A number of studies have attempted to demonstrate the beneficial effects of opioids. Whilst generally considered to be a cause (rather than a treatment) of nausea and vomiting, it is possible that when two opioids are administered together, one of them may reduce the opioid‐induced emetic symptoms caused by the other. This may be due to one drug being an opioid antagonist or partial agonist (such as nalbuphine) (Charuluxananan 2003), or if one drug is given by an alternative route (such as intrathecal fentanyl) (Manullang 2000).

Non‐pharmacological interventions

Supplemental oxygen: hypoxia has been proposed as a contributor to nausea and vomiting (Ghods 2005). At low or moderate concentrations, supplemental oxygen is associated with few side effects.
Intravenous fluids: dehydration has also been proposed as a contributor to nausea and vomiting, perhaps by increasing the incidence and severity of hypotension. Supplemental fluids may assist in treatment of this. Excessive fluid supplementation may theoretically cause volume overload, cardiac failure and electrolyte abnormalities.
Acupuncture or acupressure: a number of trials have proposed efficacy of acupressure or acupuncture (Duggal 1998; Harmon 2000) at the P6 point at the wrist, although the mechanism of action of acupuncture and acupressure is not well understood. Potential adverse effects of acupuncture includes infection or trauma from acupuncture needles.

Why it is important to do this review

Nausea and vomiting are very common symptoms experienced both during and following caesarean section, with significant associated morbidity, and can be very distressing for women and their families. Many interventions are available and routine prophylactic treatment has been proposed (NICE 2011). The available interventions have widely varying cost and significant side‐effect profiles. This review is important to ensure that women undergoing caesarean section are offered interventions to prevent nausea and vomiting which are safe, efficacious and cost effective.

Objectives

To assess the efficacy of pharmacological and non‐pharmacological treatments given prophylactically to prevent nausea and vomiting at caesarean section under regional anaesthesia.

Methods

Criteria for considering studies for this review

Types of studies

We included published and unpublished randomised controlled trials (RCTs), including cluster‐randomised trials. Quasi‐RCTs and cross‐over studies were excluded.

Types of participants

Pregnant women undergoing elective or emergency caesarean section under regional anaesthesia.

Types of interventions

We included studies where the intervention was given with the express purpose of preventing either intraoperative or postoperative nausea and vomiting, or both. We compared the various interventions with placebo or no treatment, and with each other.

We excluded studies where the express purpose was to treat another problem which may impact upon the development of nausea or vomiting, such as studies assessing agents for treating hypotension. Studies which assess the efficacy of these interventions for treatment (rather than prevention) of nausea and vomiting will be included in a separate review.

Interventions included the following categories.

Serotonin (5‐HT₃) receptor antagonists (e.g. ondansetron, granisetron).
Dopamine receptor antagonists (e.g. metoclopramide, prochlorperazine, droperidol, domperidone).
Corticosteroids (e.g. dexamethasone).
Antihistamines (e.g. promethazine, cyclizine).
Anticholinergic agents (e.g. glycopyrrolate, scopolamine).
Sedatives (e.g. midazolam, propofol).
Opioids (e.g. nalbuphine)
Supplemental oxygen.
Intravenous fluids.
Acupuncture/acupressure.

We compared the different drug classes against placebo and against each other, setting out individual drugs and doses as subgroups. We compared different drugs within the same class in separate comparisons and we considered differing doses of the same drug, also in separate comparisons.

Types of outcome measures

Primary outcomes

Nausea intraoperatively.
Vomiting (and/or retching) intraoperatively.
Nausea postoperatively.
Vomiting (and/or retching) postoperatively

Secondary outcomes

Maternal adverse effects: e.g. sedation, restlessness, extra‐pyramidal effects, surgical bleeding, hypotension, atonic uterus.
Neonatal morbidity: e.g. Apgar scores less than seven at five minutes.
Initiation of breastfeeding.
Duration of exclusive breastfeeding.
Maternal satisfaction (using a validated questionnaire).

In this review, when authors reported retching and vomiting separately, we combined these data, as we believe retching is more pathophysiologically analogous to vomiting than nausea.

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 (27 February 2012).

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

monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL);
weekly searches of MEDLINE;
weekly searches of EMBASE;
handsearches of 30 journals and the proceedings of major conferences;
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.

Searching other resources

We searched for further studies in the reference list of the studies identified.

We did not apply any language restrictions.

Data collection and analysis

The methodology for data collection and analysis was based on the Cochrane Handbook of Systematic Reviews of Interventions (Higgins 2011).

Selection of studies

Two review authors independently assessed for inclusion all the potential studies we identified as a result of the search strategy. We resolved any disagreement through discussion or, if required, we consulted a third review author.

Data extraction and management

We designed a form to extract data. For eligible studies, at least two review authors extracted the data using the agreed form. We resolved discrepancies through discussion or, if required, we consulted a third author. Data were entered into Review Manager software (RevMan 2011) and checked for accuracy.

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

Assessment of risk of bias in included studies

Two review authors independently assessed the risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Any disagreement was resolved by discussion or by involving a third author.

(1) Sequence generation (checking for possible selection bias)

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

We assessed the methods 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 have described for each included study the method used to conceal the allocation sequence in sufficient detail and determine 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) Blinding (checking for possible performance bias)

We have described for each included study all the methods used, if any, to blind study participants and personnel from knowledge of which intervention a participant received. We have also provided information on whether the intended blinding was effective. We noted where there was partial blinding (e.g. where it was not been possible to blind participants but where outcome assessment was carried out without knowledge of group assignment). Where blinding was not possible, we assessed whether the lack of blinding was likely to have introduced bias.

We assessed the methods as:

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

Where blinding was considered high risk or of unclear risk, we then assessed to what extent the outcome measurement was likely to have been influenced by lack of blinding.

(4) Incomplete outcome data (checking for possible attrition bias through withdrawals, dropouts, protocol deviations)

We have 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 have stated whether attrition and exclusions were reported, 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 supplied by the trial authors, we re‐included missing data in the analyses which we undertook. We assessed methods as:

low risk of bias;
high risk of bias;
unclear risk of bias.

We discussed whether missing data greater than 20% might impact on outcomes acknowledging that with long‐term follow‐up, complete data are difficult to attain.

(5) Selective reporting bias

We have described for each included study how the possibility of selective outcome reporting bias was examined by us and what we found.

We assessed the methods as:

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

(6) Other sources of bias

We have described for each included study any important concerns we have had about other possible sources of bias. For example, was there a potential source of bias related to the specific study design? Was the trial stopped early due to some data‐dependent process? Was there extreme baseline imbalance? Has the study been claimed to be fraudulent?

We assessed whether each study was free of other problems that could put it at risk of bias:

low risk of bias;
high risk of bias;
unclear risk of bias.

(7) Overall risk of bias

We made explicit judgements about whether studies are at high risk of bias, according to the criteria given in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). With reference to (1) to (6) above, we assessed the likely magnitude and direction of the bias and whether we consider it was likely to impact on the findings. We planned to explore the impact of the level of bias through undertaking sensitivity analyses ‐ seeSensitivity analysis.

Measures of treatment effect

Dichotomous data

For dichotomous data, we presented results as summary risk ratio with 95% confidence intervals.

Continuous data

For continuous data, we used the mean difference if outcomes were measured in the same way between trials. We used the standardised mean difference to combine trials that measured the same outcome, but used different methods. Where nausea and/or vomiting were presented as a clear scale or ordinal outcome, we converted this to a dichotomous outcome (e.g. a nausea score of zero = 0, and a nausea score greater than zero = 1). However, when this was not clear, or where data were only presented graphically, we wrote to the authors to request clarification.

Unit of analysis issues

Cluster‐randomised trials

Had we found any cluster‐randomised trials, we would have included them along with the individually‐randomised trials. Their sample sizes would have been adjusted using the methods described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) using an estimate of the intracluster correlation co‐efficient (ICC) derived from the trial (if possible), or from another source.

Dealing with missing data

For included studies, we noted levels of attrition. The impact of including studies with high levels of missing data in the overall assessment of treatment effect would have been explored by using sensitivity analysis had we found any such studies.

For all outcomes, analyses were carried out, 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. 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 (tau‐squared), I² and Chi² statistics. We regarded heterogeneity as substantial if the I² was greater than 30% and either T² was greater than zero or there was a low P value (less than 0.10) in the Chi² test for heterogeneity. Where we found heterogeneity and used a random‐effects meta‐analysis, we reported the average risk ratio, or average mean difference or average standardised mean difference.

Assessment of reporting biases

Had there been 10 or more studies in a meta‐analysis, we would have investigated reporting biases (such as publication bias) using funnel plots. We would have assessed funnel plot asymmetry visually, and used formal tests for funnel plot asymmetry if advised by the group's statistician. For continuous outcomes we would have used the test proposed by Egger 1997, and for dichotomous outcomes we would have used the tests proposed by Harbord 2006. If asymmetry had been detected by any of these tests or been suggested by a visual assessment, we would have performed exploratory analyses to investigate it.

Data synthesis

We carried out statistical analysis using the Review Manager software (RevMan 2011).

We used random‐effects meta‐analyses for combining data because we considered that there was clinical heterogeneity sufficient to expect that the underlying treatment effects differed between trials,. Or, if substantial statistical heterogeneity was detected, we used random‐effects meta‐analysis to produce an overall summary if an average treatment effect across trials was considered clinically meaningful. The random‐effects summary was treated as the average range of possible treatment effects and we discussed the clinical implications of treatment effects differing between trials. If we had considered that the average treatment effect was not clinically meaningful, we would not have combined trials. Where we used random‐effects analyses, the results are presented as the average treatment effect with its 95% confidence interval, and the estimates of T², Chi² P value and I² (Higgins 2011). We found significant clinical and/or methodological heterogeneity between studies sufficient to suggest that treatment effects might differ between trials, which supported our choice of random‐effects meta‐analysis.

We used fixed‐effect analysis in subgroup comparisons of different doses of individual drugs.

Subgroup analysis and investigation of heterogeneity

We conducted planned subgroup analyses classifying whole trials by interaction tests as described by Deeks 2001.

We had planned to carry out the following subgroup analysis, assessing all outcomes.

Elective versus emergency caesarean section.
Individual drug versus Individual drug.
Differing drug doses.

We did not undertake subgroup analysis by elective versus emergency caesarean section as the vast majority of included studies specifically excluded emergency cases. Those studies that did not include non‐elective caesarean cases did not stratify their data based on this exposure, and hence the data were not amenable to this analysis.

For fixed‐effect meta‐analyses, we conducted planned subgroup analyses classifying whole trials by interaction tests as described by Deeks 2001. For random‐effects meta‐analyses, we assessed differences between subgroups by inspection of the subgroups’ confidence intervals; non‐overlapping confidence intervals indicate a statistically significant difference in treatment effect between the subgroups.

Sensitivity analysis

There were insufficient data in any one comparison to undertake sensitivity analysis to assess the effect of missing data or trial quality.

Results

Description of studies

Results of the search

Our searches (February 2012) revealed 178 studies relevant to the outcomes of nausea, vomiting and aspiration prophylaxis at caesarean section. Of these, 111 were excluded, 14 are in the section Studies awaiting classification and there is one ongoing trial (Brody 2008). Many of these excluded studies were included in the review of aspiration prophylaxis (Paranjothy 2010).

Included studies

Of the 52 studies remaining, 41 (involving 5046 women), provided usable data for this review (Abouleish 1999; Apiliogullari 2007; Duman 2010; Biswas 2003; Caba 1997; Charuluxananan 2003; Cherian 2001; Chestnut 1987; Chestnut 1989; Duggal 1998; El‐Deeb 2011; Gaiser 2002; Habib 2006; Harmon 2000; Harnett 2007; Ho 1996; Ho 2006; Huang 1992; Jaafarpour 2008; Kasodekar 2006; Kotelko 1989; Lussos 1992; Mandell 1992; Mukherjee 2006; Nortcliffe 2003; Owczarzak 1997; Pan 1996; Pan 2001; Pan 2003; Pecora 2009; Peixoto 2006; Phillips 2007; Rudra 2004a; Sahoo 2012; Shahriari 2009; Stein 1997; Tarhan 2007; Tzeng 2000; Ure 1999; Wang 2001; Wu 2007). Three studies reported data in conference proceedings only (Apiliogullari 2007; Gaiser 2002; Kasodekar 2006). We could not use data from 11 of the included studies because the data were either presented in a graphical format only, or the data for nausea and vomiting were combined as a single score (Birnbach 1993; Biwas 2002; Boone 2002; Chaudhuri 2004; Imbeloni 1986; Manullang 2000; Munnur 2008; Quiney 1995; Sanansilp 1998; Weiss 1995; Yazigi 2002). We have written to these authors requesting further information.

Seven studies were placed in the category of Characteristics of studies awaiting classification whilst we attempted to contact the authors for further information. A further seven studies (Fujii 1998a; Fujii 1998b; Fujii 1999; Fujii 2002; Fujii 2004; Numazaki 2000; Numazaki 2003) were placed in the category of Characteristics of studies awaiting classification pending investigation into research authenticity (Carlisle 2012). There is one ongoing study (Brody 2008).

Elective versus emergency caesarean sections

Of all our included studies, the vast majority were specifically restricted to elective caesarean sections. Only one study mentioned including both elective and emergency caesareans (Caba 1997), but they did not present the data separately. One other study specifically included only women undergoing emergency caesarean section (Huang 1992). Most of the remaining studies did not mention whether they included elective or emergency caesareans. We have, therefore, not been able to consider the subgroup comparison of elective versus emergency caesarean section.

Excluded studies

The excluded studies are listed in the reference section under excluded studies and the table Characteristics of excluded studies states the reasons for exclusion from this review. Most of the studies that were excluded assessed interventions for reducing the risk of aspiration pneumonitis at caesarean section rather than reducing the risk of nausea and vomiting, as the search strategy included both these circumstances in the original protocol which remains part of the aspiration pneumonitis review (Paranjothy 2010). The studies looking at aspiration prophylaxis are included in the review of interventions for reducing aspiration prophylaxis at caesarean section (Paranjothy 2010).

Although our review assesses interventions for prevention (rather than treatment) of nausea and vomiting, our current search would identify treatment studies too. There were, in fact, no RCTs identified which specifically assessed interventions for treatment (rather than prevention) of nausea and vomiting.

Risk of bias in included studies

Overall risk of bias is reported in Figure 1 and Figure 2.

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Allocation

Random sequence generation was judged to be of low risk of bias in 26 studies, with 26 studies being judged of unclear risk. Allocation concealment was judged to be of low risk of bias in 11 studies and of unclear risk in 41 studies. There were 10 studies where both sequence generation and allocation concealment were judged to be of low risk (Abouleish 1999; Charuluxananan 2003; Cherian 2001; Chestnut 1987; Manullang 2000; Mukherjee 2006; Peixoto 2006; Phillips 2007; Stein 1997; Tarhan 2007).

Blinding

Blinding was assessed as of low risk of bias in 32 studies and of unclear bias in 19 studies. Blinding was considered at high risk of bias in one study (Rudra 2004a) because the treating anaesthetist was not blinded to the study drug.

Incomplete outcome data

Incomplete outcome data were addressed adequately and so at low risk of bias in 31 studies. In 19 studies, it was judged to be of unclear bias, and at high risk of bias in two studies (Duman 2010; Phillips 2007). In these two studies, data on women had been excluded and we were unable to be re‐include on an intention‐to‐treat basis.

Selective reporting

As we did not assess study protocols, all the studies were judged to be unclear in regards to selective reporting bias, with the exception of one study which clearly showed high risk of bias (Shahriari 2009). This study did not report the pre‐specified outcome of sedation, when this was likely to be an important side effect of the intervention.

Other potential sources of bias

Thirty‐four studies were judged to be free of other potential sources of bias, with 18 being unclear.

Effects of interventions

A. 5‐HT₃ receptor antagonists (Comparisons 1, 2, 3)

1) 5‐HT₃ receptor antagonists (A) versus placebo (10 studies, 980 women, Comparison 1)

Thirteen studies assessed this comparison with 10 providing data on outcomes (Abouleish 1999; Charuluxananan 2003; Cherian 2001; Harnett 2007; Kasodekar 2006; Pan 1996; Pan 2001; Pan 2003; Peixoto 2006, Sahoo 2012). Three studies provided no data which could be included in our analyses (Boone 2002; Munnur 2008; Yazigi 2002). Of the studies that provided data, nine studied ondansetron (4 mg or 8 mg) (Abouleish 1999; Charuluxananan 2003; Cherian 2001; Harnett 2007; Pan 1996; Pan 2001; Pan 2003; Peixoto 2006, Sahoo 2012) and one examined granisetron (1 mg) (Kasodekar 2006). Of the 10 studies providing data, only three were judged to have had both adequate sequence generation and allocation concealment (Abouleish 1999; Charuluxananan 2003; Cherian 2001), and seven were considered to have adequate blinding (and the remainder being unclear) seeFigure 1 and Figure 2 .

Primary outcomes

Intraoperative nausea

We found that overall, 5‐HT₃ antagonists were more effective than placebo at reducing intraoperative nausea (average risk ratio (RR) 0.64, 95% confidence interval (CI) 0.46 to 0.88, eight studies, 720 women, random‐effects [T² = 0.10, Chi² P = 0.02, I² = 57%], Analysis 1.1). but there was substantial heterogeneity (I² = 57%). In a subgroup analysis by type of drug and dose, there was no evidence of differences in treatment effect between the subgroups (Chi² = 3.79 , P = 0.15, I² = 47.2%). The ondansetron 4 mg subgroup was the only one to show a statistically significant effect, likely because this subgroup contained the most trials.

1.1 — Comparison 1 5‐HT₃ antagonists (A) vs placebo, Outcome 1 Nausea ‐ intraoperative.

Intraoperative vomiting

For the outcome of intraoperative vomiting, we were unable to demonstrate a significant difference compared with placebo with 5‐HT₃ antagonists (average RR 0.56, 95% CI 0.31 to 1.00, seven studies, 668 women, random‐effects [T² = 0.33, Chi² P = 0.02 , I² = 61%], Analysis 1.2) but again, there was substantial heterogeneity (I² = 61%). In the subgroup analysis by type and dose of drug, there was no evidence of differences in treatment effect between the subgroups (Chi² = 1.94, P = 0.38, I² = 0%).

1.2 — Comparison 1 5‐HT₃ antagonists (A) vs placebo, Outcome 2 Vomiting ‐ intraoperative.

Postoperative nausea

There was a reduction in postoperative nausea using 5‐HT₃ antagonists versus placebo (average RR 0.40, 95% CI 0.25 to 0.64, four studies, 405 women, random‐effects [T² = 0.08, Chi² P = 0.24, I² = 27%], Analysis 1.3) but again there was significant heterogeneity (I² = 27%).

1.3 — Comparison 1 5‐HT₃ antagonists (A) vs placebo, Outcome 3 Nausea ‐ postoperative.

Postoperative vomiting

Postoperative vomiting was also reduced (average RR 0.50, 95% CI 0.32 to 0.77, five studies, 565 women, random‐effects [T² = 0.07, Chi² P = 0.27, I² = 21%], Analysis 1.4). Significant heterogeneity was observed (I² = 21%).

1.4 — Comparison 1 5‐HT₃ antagonists (A) vs placebo, Outcome 4 Vomiting ‐ postoperative.

Secondary outcomes

We identified two differing results in women's satisfaction between 5‐HT₃ receptor antagonist drugs and placebo. One study showed a benefit from the ondansetron and the other showed no difference (Analysis 1.9).

1.9 — Comparison 1 5‐HT₃ antagonists (A) vs placebo, Outcome 9 Maternal satisfaction.

Outcomes not pre‐specified

Although there were no estimates of a composite outcome of adverse effects, a few studies did measure headaches/dizziness. hypotension and pruritis but there were insufficient data to make a statement about adverse effects (seeAnalysis 1.10 to Analysis 1.12).

1.10 — Comparison 1 5‐HT₃ antagonists (A) vs placebo, Outcome 10 Headache/dizziness (not pre‐specified).

1.12 — Comparison 1 5‐HT₃ antagonists (A) vs placebo, Outcome 12 Pruritus (not pre‐specified).

2) 5‐HT₃ antagonists (A) versus other 5 HT₃ antagonists (A) (no studies, Comparison 2)

There was only one study comparing two different 5‐HT₃ receptor antagonists, ondansetron versus granisetron, but we were unable to use the data as the authors reported a composite outcome (Munnur 2008). We have written to the authors for further information.

3) 5‐HT₃ antagonist (A) ‐ ondansetron 8 mg versus 4 mg (one study, 120 women, Comparison 3)

There was only one study comparing differing doses of 5‐HT₃ antagonists (Charuluxananan 2003). This study reported the outcomes of postoperative nausea, postoperative vomiting and pruritis. We did not identify any differences between the groups (seeAnalysis 3.3, Analysis 3.4 and Analysis 3.10).

3.3 — Comparison 3 5‐HT₃ antagonists (A) ‐ Ondansetron 8mg vs 4mg, Outcome 3 Nausea ‐ postoperative.

3.4 — Comparison 3 5‐HT₃ antagonists (A) ‐ Ondansetron 8mg vs 4mg, Outcome 4 Vomiting ‐ postoperative.

3.10 — Comparison 3 5‐HT₃ antagonists (A) ‐ Ondansetron 8mg vs 4mg, Outcome 10 Pruritus (not pre‐specified).

B. Dopamine antagonists (Comparisons 4‐6)

1) Dopamine antagonists (B) versus placebo (12 studies, 899 women, Comparison 4)

Fifteen studies compared dopamine antagonists with placebo, of which 12 studies provided data for analysis (Biswas 2003; Chestnut 1987; Duman 2010; Huang 1992; Lussos 1992; Mandell 1992; Pan 1996; Pan 2001; Peixoto 2006; Stein 1997; Tzeng 2000; Wu 2007). Three studies provided no data which could be included in our analyses (Birnbach 1993; Imbeloni 1986; Sanansilp 1998). Of the studies providing data, seven studied metoclopramide (10 mg, 20 mg, 0.15 mg/kg) (Biswas 2003; Chestnut 1987; Duman 2010; Huang 1992; Lussos 1992; Pan 2001; Stein 1997) and five examined droperidol (0.5 mg, 0.625 mg, or 1.25 mg) (Mandell 1992; Pan 1996; Peixoto 2006; Tzeng 2000; Wu 2007).

Overall, the studies were of uncertain quality. Of the 14 studies which provided data, only three were judged to have had both adequate sequence generation and allocation concealment (Chestnut 1987; Peixoto 2006; Stein 1997). Nine were judged to have had adequate blinding with the remaining being unclear (Figure 1).

Primary outcomes

Dopamine antagonists were found to be more effective than placebo at reducing intraoperative nausea (average RR 0.38, 95% CI 0.25 to 0.57, nine studies, 636 women, random‐effects [T² = 0.19, Chi² P = 0.04, I² = 51%], Analysis 4.1), and intraoperative vomiting (RR 0.39, 95% CI 0.24 to 0.64, eight studies, 536 women, random‐effects, T² = 0.00, Chi² P = 0.64, I² = 0%, Analysis 4.2). Dopamine antagonists were found to be more effective than placebo at reducing postoperative nausea (average RR 0.60, 95% CI 0.40 to 0.91, five studies, 412 women, random‐effects T² = 0.08, Chi² P = 0.17, I² = 37%, Analysis 4.3), and postoperative vomiting (average RR 0.57, 95% CI 0.36 to 0.91, six studies, 472 women, random‐effects [T² = 0.13, Chi² P = 0.14, I² = 40%], Analysis 4.4). These findings were persistent when the individual interventions of metoclopramide and droperidol were assessed separately.

4.1 — Comparison 4 Dopamine antagonists (B) vs placebo, Outcome 1 Nausea ‐ intraoperative.

4.2 — Comparison 4 Dopamine antagonists (B) vs placebo, Outcome 2 Vomiting ‐ intraoperative.

4.3 — Comparison 4 Dopamine antagonists (B) vs placebo, Outcome 3 Nausea ‐ postoperative.

4.4 — Comparison 4 Dopamine antagonists (B) vs placebo, Outcome 4 Vomiting ‐ postoperative.

Secondary outcomes

We identified no overall difference in women's satisfaction between dopamine antagonists and placebo (RR 1.42, 95% CI 0.91 to 2.21, one study, 102 women, Analysis 4.9). None of the studies looked at a composite outcome of adverse effects.

4.9 — Comparison 4 Dopamine antagonists (B) vs placebo, Outcome 9 Maternal satisfaction.

Outcomes not pre‐specified

Although there were no estimates of a composite outcome of adverse effects, a few studies did measure anxiety, headaches/dizziness, hypotension and pruritus. There were no differences identified (Analysis 4.10; Analysis 4.11; Analysis 4.12; Analysis 4.13).

4.10 — Comparison 4 Dopamine antagonists (B) vs placebo, Outcome 10 Anxiety (not pre‐specified).

4.11 — Comparison 4 Dopamine antagonists (B) vs placebo, Outcome 11 Headache/dizziness (not pre‐specified).

4.12 — Comparison 4 Dopamine antagonists (B) vs placebo, Outcome 12 Hypotension (not pre‐specified).

4.13 — Comparison 4 Dopamine antagonists (B) vs placebo, Outcome 13 Pruritus (not pre‐specified).

Subgroup analyses

For variations between individual drugs, seeAnalysis 4.1 to Analysis 4.5.

2) Dopamine antagonists (B) versus 5‐HT₃ antagonists (A) (four studies, 307 women, Comparison 5)

Four studies assessed and provided data on this comparison and involved 307 women (Owczarzak 1997; Pan 1996; Pan 2001; Peixoto 2006). The studies compared various doses of metoclopramide and droperidol, both dopamine antagonists, against various doses of ondansetron and granisetron, both 5‐HT₃ antagonists. Overall, the studies were of uncertain quality. Only one study was judged to have adequate sequence generation and allocation concealment (Peixoto 2006). Blinding was judged as adequate for all four studies.

We found an increase in postoperative nausea with dopamine antagonists compared with 5‐HT3 antagonists (RR 1.84, 95% CI 1.13 to 2.98, two studies, 185 women, Analysis 5.3). We did not detect any other significant differences (Analysis 5.1, Analysis 5.2, Analysis 5.4).

5.3 — Comparison 5 Dopamine antagonists (B) vs 5‐HT₃ antagonists (A), Outcome 3 Nausea ‐ postoperative.

5.1 — Comparison 5 Dopamine antagonists (B) vs 5‐HT₃ antagonists (A), Outcome 1 Nausea ‐ intraoperative.

5.2 — Comparison 5 Dopamine antagonists (B) vs 5‐HT₃ antagonists (A), Outcome 2 Vomiting ‐ intraoperative.

5.4 — Comparison 5 Dopamine antagonists (B) vs 5‐HT₃ antagonists (A), Outcome 4 Vomiting ‐ postoperative.

3) Dopamine antagonists (B) versus other dopamine antagonists (B) (one study, 81 women, Comparison 6)

One study involving 81 women assessed this comparison and provided data for analysis (Chestnut 1989). The study was judged to have adequate sequence generation and adequate blinding. We did not find any significant differences between the different dopamine antagonists for our outcomes (Analysis 6.1 to Analysis 6.4 and Analysis 6.10).

6.1 — Comparison 6 Dopamine antagonist (B) vs dopamine antagonist (B), Outcome 1 Nausea ‐ intraoperative.

6.4 — Comparison 6 Dopamine antagonist (B) vs dopamine antagonist (B), Outcome 4 Vomiting ‐ postoperative.

6.10 — Comparison 6 Dopamine antagonist (B) vs dopamine antagonist (B), Outcome 10 Restlessness (not‐pre‐specified).

C. Corticosteroids (Comparisons 7‐14)

1) Corticosteroids (C) versus placebo (six studies, 490 women, Comparison 7)

Six studies involving 490 women compared corticosteroids against placebo, all studied dexamethasone but in various doses from 2.5 mg to 10 mg (Biswas 2003; Jaafarpour 2008; Nortcliffe 2003; Tzeng 2000; Wang 2001; Wu 2007). Three of the studies addressed intraoperative symptoms (Biswas 2003; Jaafarpour 2008; Tzeng 2000), and three assessed postoperative symptoms (Nortcliffe 2003; Wang 2001; Wu 2007). The studies were of questionable quality with none judged as having adequate sequence generation and allocation concealment. Three had adequate blinding (Tzeng 2000; Wang 2001; Wu 2007). One study (Abdel‐Aleem 2012) is in Studies awaiting classification because the authors excluded women after randomisation if they suffered intraoperative nausea or vomiting and this amounted to 31%. We will write to the authors in an attempt to obtain these data for re‐inclusion.

Primary outcomes

The three studies assessing intraoperative symptoms found a reduction in nausea (average RR 0.31, 95% CI 0.15 to 0.64, three studies, 195 women, random‐effects [T² = 0.00, Chi² P = 0.92, I² = 0%], Analysis 7.1) and vomiting (RR 0.35, 95% CI 0.14 to 0.86, three studies,195 women, random‐effects [T² = 0.00, Chi² P = 0.44, I² = 0%], Analysis 7.2). The studies assessing postoperative symptoms showed no reduction in nausea (average RR 0.75, 95% CI 0.52 to 1.07, two studies, 235 women, random‐effects [T² = 0.01, Chi² P = 0.37, I² = 4%], Analysis 7.3) or vomiting (average RR 0.78, 95% CI 0.54 to 1.12, three studies, 295 women, random‐effects [T² = 0.03, Chi² P = 0.33, I² = 14%], Analysis 7.4).

7.1 — Comparison 7 Corticosteroids (C) vs placebo, Outcome 1 Nausea ‐ intraoperative.

7.2 — Comparison 7 Corticosteroids (C) vs placebo, Outcome 2 Vomiting ‐ intraoperative.

7.3 — Comparison 7 Corticosteroids (C) vs placebo, Outcome 3 Nausea ‐ postoperative.

7.4 — Comparison 7 Corticosteroids (C) vs placebo, Outcome 4 Vomiting ‐ postoperative.

Secondary outcomes

No data reported.

Outcomes not pre‐specified

Although there were no estimates of a composite outcome of adverse effects, a few studies did measure hypotension and pruritis but there were insufficient data to make any firm statement about adverse effects (Analysis 7.10; Analysis 7.11).

7.10 — Comparison 7 Corticosteroids (C) vs placebo, Outcome 10 Hypotension (not pre‐specified).

7.11 — Comparison 7 Corticosteroids (C) vs placebo, Outcome 11 Pruritus (not pre‐specified).

2) Corticosteroids (C) versus 5‐HT₃ antagonists (A) (no studies, Comparison 8)

There were no studies that made this comparison.

3) Corticosteroids (C) versus dopamine antagonists (B) (three studies, 176 women, Comparison 9)

There were three studies involving 176 women that assessed this comparison (Biswas 2003; Tzeng 2000; Wu 2007). Two studies had adequate sequence generation and blinding (Tzeng 2000; Wu 2007) but all were unclear with regard to allocation concealment. We did not detect any significant differences between corticosteroids and 5 HT₃ antagonists (Analysis 9.1 to Analysis 9.11).

9.1 — Comparison 9 Corticosteroids (C) vs dopamine antagonists (B), Outcome 1 Nausea ‐ intraoperative.

9.11 — Comparison 9 Corticosteroids (C) vs dopamine antagonists (B), Outcome 11 Pruritus (not pre‐specified).

4) Corticosteroids (C) versus other steroids (C) (no studies, Comparison 10)

There were no studies that made this comparison.

5) Corticosteroid (C) ‐ dexamethasone 2.5 mg versus 5 mg (one study, 88 women, Comparison 11)

One study (Wang 2001) involving 88 women studied this comparison. The outcomes of postoperative nausea and postoperative vomiting were reported, however, there were no differences detected between the groups (Analysis 11.3; Analysis 11.4).

11.3 — Comparison 11 Corticosteroids (C) ‐ Dexamethasone 2.5 mg vs 5 mg, Outcome 3 Nausea ‐ postoperative.

11.4 — Comparison 11 Corticosteroids (C) ‐ Dexamethasone 2.5 mg vs 5 mg, Outcome 4 Vomiting ‐ postoperative.

6) Corticosteroid (C) ‐ dexamethasone 2.5 mg versus 10 mg (one study, 87 women, Comparison 12)

One study (Wang 2001) involving 87 women studied this comparison. The outcomes of postoperative nausea and postoperative vomiting were reported. However, there no differences detected between the groups (Analysis 12.3; Analysis 12.4).

12.3 — Comparison 12 Corticosteroids (C) ‐ Dexamethasone 2.5 mg vs 10 mg, Outcome 3 Nausea ‐ postoperative.

12.4 — Comparison 12 Corticosteroids (C) ‐ Dexamethasone 2.5 mg vs 10 mg, Outcome 4 Vomiting ‐ postoperative.

7) Corticosteroid (C) ‐ dexamethasone 5 mg versus 10 mg (one study, 88 women, Comparison 13)

One study (Wang 2001) involving 88 women studied this comparison. The outcomes of postoperative nausea and vomiting were reported. However, we did not detect any differences between the groups (Analysis 13.3; Analysis 13.4).

13.3 — Comparison 13 Corticosteroids (C) ‐ Dexamethasone 5 mg vs 10 mg, Outcome 3 Nausea ‐ postoperative.

13.4 — Comparison 13 Corticosteroids (C) ‐ Dexamethasone 5 mg vs 10 mg, Outcome 4 Vomiting ‐ postoperative.

D. Antihistamines (Comparisons 14‐19)

1) Antihistamines (D) versus placebo (three studies, 365 women, Comparison 14)

Three studies compared the intervention of antihistamines with placebo (Apiliogullari 2007; Duman 2010; Nortcliffe 2003). Only one study had adequate sequence generation (Duman 2010) and all three studies were unclear with regard to allocation concealment. Two out of three had adequate blinding (Apiliogullari 2007; Duman 2010).

Primary outcomes

We found a reduction in postoperative nausea compared with placebo (average RR 0.39, 95% CI 0.26 to 0.59, three studies, 365 women, random‐effects [T² = 0.01, Chi² P = 0.37, I² = 4%], Analysis 14.3). We also found a reduction in postoperative vomiting (average RR 0.50, 95% CI 0.30 to 0.86, two studies, 184 women, random‐effects [T² = 0.00, Chi² P = 0.96, I² = 0%], Analysis 14.4). Intraoperative symptoms were not assessed by any of the three studies.

14.3 — Comparison 14 Antihistamines (D) vs placebo, Outcome 3 Nausea ‐ postoperative.

14.4 — Comparison 14 Antihistamines (D) vs placebo, Outcome 4 Vomiting ‐ postoperative.

Secondary outcomes

Not assessed in the trials.

2) Antihistamines (D) versus 5 HT₃ antagonists (A) (no studies, Comparison 15)

There were no studies that made this comparison.

3) Antihistamines (D) versus dopamine antagonists (B) (one study, 119 women, Comparison 16)

One study assessed this comparison (Duman 2010). Although the study had adequate sequence generation, it was unclear if there was adequate allocation concealment or blinding. Also there were potentially significant missing data.

Primary outcomes

No differenced was identified in postoperative nausea (RR 0.52, 95% CI 0.21 to 1.31, one study, 119 women, Analysis 16.3) but there was a reduction in postoperative vomiting (RR 0.37, 95% CI 0.14 to 0.96, one study, 119 women, Analysis 16.4).

16.3 — Comparison 16 Antihistamines (D) vs dopamine antagonists (B), Outcome 3 Nausea ‐ postoperative.

16.4 — Comparison 16 Antihistamines (D) vs dopamine antagonists (B), Outcome 4 Vomiting ‐ postoperative.

Secondary outcomes

None were assessed in this study.

4) Antihistamines (D) versus corticosteroids (C) (one study, 60 women, Comparison 17)

There was one study involving 60 women that assessed this comparison (Nortcliffe 2003). Sequence generation and allocation concealment were unclear. We did not detect a reduction in postoperative nausea (Analysis 17.3), however, a possible reduction in postoperative vomiting was detected (RR 0.53, 95% CI 0.28 to 0.99, one study, 60 women, Analysis 17.4).

17.3 — Comparison 17 Antihistamines (D) vs corticosteroids (C), Outcome 3 Nausea ‐ postoperative.

17.4 — Comparison 17 Antihistamines (D) vs corticosteroids (C), Outcome 4 Vomiting ‐ postoperative.

5) Antihistamines (D) versus other antihistamines (D) (no studies, Comparison 18)

There were no studies that made this comparison.

6) Antihistamone (D) ‐ demethylate 50 mg versus 100 mg (one study, 122 women, Comparison 19)

One study (Apiliogullari 2007) involving 122 participants studied this comparison. The outcome of postoperative nausea was reported. However, no significant difference was detected (Analysis 19.3).

19.3 — Comparison 19 Antihistamines (D) ‐ Dimenhydrate 100 mg vs 50 mg, Outcome 3 Nausea ‐ postoperative.

E. Anticholinergics (Comparisons 20‐25)

1) Anticholenergics (E) versus placebo (four studies, 453 women, Comparison 20)

Five studies compared the intervention of anticholinergics with placebo with four of these studies (involving 453 women) reporting data that we could use in the review (Biswas 2003; Harnett 2007; Kotelko 1989; Ure 1999). One study provided no data (Quiney 1995) as it presented a combined outcome for nausea and vomiting. One study had adequate sequence generation (Harnett 2007) and the other three were unclear. All four studies were unclear with regard to allocation concealment. Two studies described adequate blinding (Harnett 2007; Kotelko 1989).

Primary outcomes

We found a significant reduction in intraoperative nausea with anticholinergics (average RR 0.67, 95% CI 0.51 to 0.87, four studies, 453 women, random‐effects [T² = 0.03, Chi² P = 0.13, I² = 47%], Analysis 20.1) but we identified no difference in intraoperative vomiting (average RR 0.79, 95% CI 0.40 to 1.54, four studies, 453 women, random‐effects [T² = 0.22, Chi² P = 0.10, I² = 52%], Analysis 20.2). These findings were persistent in the scopolamine subgroup, but not the glycopyrrolate subgroup, however, there were much smaller numbers in the glycopyrrolate subgroup. None of the studies assessed postoperative nausea, however, there was a reduction in postoperative vomiting (RR 0.55, 95% CI 0.41 to 0.74, one study, 161 women, (Analysis 20.4).

20.1 — Comparison 20 Anticholinergics (E) vs placebo, Outcome 1 Nausea ‐ intraoperative.

20.2 — Comparison 20 Anticholinergics (E) vs placebo, Outcome 2 Vomiting ‐ intraoperative.

20.4 — Comparison 20 Anticholinergics (E) vs placebo, Outcome 4 Vomiting ‐ postoperative.

Secondary outcomes

None of the studies assessed any of our secondary outcomes.

Outcomes not pre‐specified

Some studies did assess specific adverse effects, but there are insufficient data to be able to report specifically (Analysis 20.10 to Analysis 20.14).

20.14 — Comparison 20 Anticholinergics (E) vs placebo, Outcome 14 Pruritus (not pre‐specified).

2) Anticholenergics (E) versus 5‐HT₃ antagonists (A) (one study, 159 women, Comparison 21)

One study involving 159 women assessed this comparison (Harnett 2007). The study was judged to have adequate sequence generation and blinding but it was unclear when assessed on allocation concealment. No differences were detected between anticholinergics and 5‐HT₃ antagonists (Analysis 21.1 to Analysis 21.9).

21.1 — Comparison 21 Anticholinergic (E) vs 5‐HT₃ antagonist (A), Outcome 1 Nausea ‐ intraoperative.

3) Anticholenergics (E) versus dopamine antagonists (B) (one study, 40 women, Comparison 22)

Two studies involving 80 women assessed this comparison (Biswas 2003; Biwas 2002), however, we were unable to use the composite outcome data for one study (Biwas 2002). The study with included data (Biswas 2003) was unclear with regard to sequence generation, allocation concealment and blinding.

There were insufficient data to make adequate comparisons between anticholinergics and dopamine antagonists (Analysis 22.1 to Analysis 22.11 ).

22.1 — Comparison 22 Anticholenergic (E) vs dopamine antagonist (B), Outcome 1 Nausea ‐ intraoperative.

4) Anticholenergics (E) versus corticosteroids (C) (one study, 40 women, Comparison 23)

One study involving 40 women assessed this comparison (Biswas 2003). The study was assessed as being unclear with regard to sequence generation, allocation concealment and blinding.

There were insufficient data to make adequate comparisons between anticholinergics and steroids (Analysis 23.1 to Analysis 23.10).

23.1 — Comparison 23 Anticholenergic (E) vs corticosteroids (C), Outcome 1 Nausea ‐ intraoperative.

5) Anticholenergics (E) versus antihistamines (D) (no studies, Comparison 24)

There were no studies that made this comparison.

6) Anticholenergics (E) versus other anticholinergics (E) (no studies, Comparison 25)

There were no studies that made this comparison.

F. Sedatives (Comparisons 26‐35)

1) Sedatives (F) versus placebo (four studies, 285 women, Comparison 26)

Five studies assessed the intervention of sedatives versus placebo, with four providing data, and all assessed propofol but at differing doses (Caba 1997; Mukherjee 2006; Rudra 2004a; Tarhan 2007). One study also assessed midazolam (Tarhan 2007) and one study provided data in graphical form only (Weiss 1995). Two studies assessed intraoperative and post operative nausea and vomiting (Caba 1997; Tarhan 2007) and two studies assessed intraoperative nausea and vomiting only (Mukherjee 2006; Rudra 2004a). The studies were of reasonable quality with all five having adequate random sequence generation and two out of four having adequate allocation concealment. Three of the five studies had adequate blinding, with one study rated as inadequate (Rudra 2004a) because the treating anaesthetist was not blinded to the intervention and one study was unclear (Tarhan 2007).

Primary outcomes

We found a reduction in intraoperative nausea compared with placebo (average RR 0.71, 95% CI 0.52 to 0.96, four studies, 285 women, random‐effects [T² = 0.00, Chi² P = 0.56, I² = 0%], Analysis 26.1). These studies also found a reduction in intraoperative vomiting compared with placebo (average RR 0.42, 95% CI 0.26 to 0.68, four studies, 285 women, random‐effects [T² = 0.00, Chi² P = 0.77, I² = 0%], Analysis 26.2). Two studies found propofol reduced both postoperative nausea (average RR 0.25, 95% CI 0.09 to 0.71, two studies, 145 women, [T² = 0.47, Chi² P = 0.09, I² = 58%] Analysis 26.3) and vomiting (average RR 0.09, 95% CI 0.03 to 0.28, two studies, 145 women, [T² = 0.00, Chi² P = 0.39, I² = 0%], Analysis 26.4).

26.1 — Comparison 26 Sedatives (F) vs placebo, Outcome 1 Nausea ‐ intraoperative.

26.2 — Comparison 26 Sedatives (F) vs placebo, Outcome 2 Vomiting ‐ intraoperative.

26.3 — Comparison 26 Sedatives (F) vs placebo, Outcome 3 Nausea ‐ postoperative.

26.4 — Comparison 26 Sedatives (F) vs placebo, Outcome 4 Vomiting ‐ postoperative.

Secondary outcomes

None of our secondary outcomes were assessed.

2. Sedatives (F) versus 5‐HT₃ antagonists (A) (no studies, Comparison 27)

There were no studies that made this comparison.

3) Sedatives (F) versus dopamine antagonists (B) (one study, 80 women, Comparison 28)

One study involving 80 women assessed this comparison (Shahriari 2009). The study had adequate sequence generation but allocation concealment was unclear (Shahriari 2009).

Primary outcomes

We found a reduction in intraoperative nausea (average RR 0.29, 95% CI 0.13 to 0.63, one study, 80 women, Analysis 28.1) There was no difference detected in the incidence of intraoperative vomiting (Analysis 28.2).

28.1 — Comparison 28 Sedatives (F) vs dopamine antagonists (B), Outcome 1 Nausea ‐ intraoperative.

28.2 — Comparison 28 Sedatives (F) vs dopamine antagonists (B), Outcome 2 Vomiting ‐ intraoperative.

Secondary outcomes

None of our secondary outcomes were assessed in the included trials.

Outcomes not pre‐specified.

The authors did assess some adverse outcomes. There were insufficient data to detect a difference in hypotension (Analysis 28.10), however, an increase in respiratory depression was reported (RR 35.0, 95% CI 2.18 ‐ 562.8, one study, 80 women, Analysis 28.11).

28.11 — Comparison 28 Sedatives (F) vs dopamine antagonists (B), Outcome 11 Respiratory depression (not pre‐specified).

4) Sedatives (F) versus corticosteroids (C) (no studies, Comparison 29)

There were no studies that made this comparison.

5) Sedatives (F) versus antihistamines (D) (no studies, Comparison 30)

There were no studies that made this comparison.

6) Sedatives (F) versus anticholinergics (E) (no studies, Comparison 31)

There were no studies that made this comparison.

7) Sedatives (F) versus other sedatives (F) (one study, 60 women, Comparison 32)

One study involving 60 women assessed this comparison and compared midazolam versus propofol (Tarhan 2007). The study had adequate sequence generation, allocation concealment and blinding.

There were insufficient data to make adequate comparisons between different sedatives (Analysis 32.1 to Analysis 32.10).

32.1 — Comparison 32 Sedative (F) vs sedative (F), Outcome 1 Nausea ‐ intraoperative.

8) Sedative (F) ‐ propofol 0.5 mg/kg/hr versus 1.0 mg/kg/hr (one study, 40 women, Comparison 33)

One study (Mukherjee 2006) involving 40 participants assessed this comparison. The authors reported intraoperative nausea and vomiting. There were insufficient data to make adequate comparisons (Analysis 33.1; Analysis 33.2).

33.1 — Comparison 33 Sedatives (F) ‐ Propofol 0.5 mg/kg/hr vs 1 mg/kg/hr, Outcome 1 Nausea ‐ intraoperative.

33.2 — Comparison 33 Sedatives (F) ‐ Propofol 0.5 mg/kg/hr vs 1 mg/kg/hr, Outcome 2 Vomiting ‐ intraoperative.

9) Sedative (F) ‐ propofol 0.5 mg/kg/hr versus 1.5 mg/kg/hr (one study, 40 women, Comparison 34)

34.1 — Comparison 34 Sedatives (F) ‐ Propofol 0.5 mg/kg/hr vs 1.5 mg/kg/hr, Outcome 1 Nausea ‐ intraoperative.

34.2 — Comparison 34 Sedatives (F) ‐ Propofol 0.5 mg/kg/hr vs 1.5 mg/kg/hr, Outcome 2 Vomiting ‐ intraoperative.

10) Sedative (F) ‐ propofol 1.0 mg/kg/hr versus 1.5 mg/kg/hr (one study, 40 women, Comparison 35)

35.1 — Comparison 35 Sedatives (F) ‐ Propofol 1.0 mg/kg/hr vs 1.5 mg/kg/hr, Outcome 1 Nausea ‐ intraoperative.

35.2 — Comparison 35 Sedatives (F) ‐ Propofol 1.0 mg/kg/hr vs 1.5 mg/kg/hr, Outcome 2 Vomiting ‐ intraoperative.

G. Opioids (Comparisons 36‐7)

1) Opioids (G) versus placebo (one study, 120 women, Comparison 36)

There was one study that compared opioids with placebo (Charuluxananan 2003). The study was judged to be at low risk of bias.

Primary outcomes

The study found no difference in postoperative nausea (RR 0.75, 95% CI 0.39 to 1.45, one study, 120 women, Analysis 36.3) or vomiting (RR 1.25, 95% CI 0.35 to 4.43, one study, 120 women, Analysis 36.4). There were no data reported on intraoperative symptoms.

36.3 — Comparison 36 Opioid (G) vs placebo, Outcome 3 Nausea ‐ postoperative.

36.4 — Comparison 36 Opioid (G) vs placebo, Outcome 4 Vomiting ‐ postoperative.

Secondary outcomes

There was a small decrease in pruritis with the intervention (RR 0.86, 95% CI 0.74 to 0.99, one study, 120 women, Analysis 36.10. The one study in this comparison used intrathecal (spinal) nalbuphine as the opioid intervention. Nalbuphine is an opioid partial agonist, which may explain the observed small decrease in pruritis.

2) Opioids (G) versus 5‐HT₃ antagonists (A) (one study, 180 women, Comparison 37)

One study provided data which compared opioids against 5‐HT₃ antagonists (Charuluxananan 2003). A second study looked at this comparison but provided a cumulative score outcome (Manullang 2000). The study was well designed, judged as adequate on all criteria except freedom from other bias which was judged as unclear. The study looked at one dose of opioids (nalbuphine 4 mg) against two different doses of 5‐HT₃ antagonist (ondansetron 4 mg and 8 mg). We looked at these in different subgroups.

Primary outcomes

There was no difference detected between the two interventions for intraoperative nausea and vomiting and pruritus (Analysis 37.1; Analysis 37.2).

37.1 — Comparison 37 Opioids (G) vs 5‐HT antagonists (A), Outcome 1 Nausea ‐ intraoperative.

37.2 — Comparison 37 Opioids (G) vs 5‐HT antagonists (A), Outcome 2 Vomiting ‐ intraoperative.

Secondary outcomes

None of our secondary outcomes were measured.

Not pre‐specified

The study also reported on pruritus but there were insufficient data to report findings (Analysis 37.10).

H. Supplemental oxygen (Comparison 38)

1) Supplemental oxygen (H) versus placebo (two studies, 294 women, Comparison 38)

Two studies compared supplemental oxygen with placebo under regional anaesthesia (Pecora 2009; Phillips 2007). One study was of good quality with the randomisation, allocation concealment and blinding all judged as adequate (Phillips 2007). However, some participants did not receive the allocated intervention and their data were not able to be re‐included. The other study was unclear on all 'Risk of bias' criteria.

Primary outcome

We found no difference between placebo and the treatment group in terms of intraoperative nausea (average RR 0.78, 95% CI 0.53 to 1.15, two studies, 294 women, random‐effects [T² = 0.02, Chi² P = 0.27, I² = 19%], Analysis 38.1), intraoperative vomiting (RR 0.42, 95% CI 0.14 to 1.25, one study, 89 women, Analysis 38.2), postoperative nausea (RR 0.65, 95% CI 0.31 to 1.36, one study, 89 women, Analysis 38.3) and intraoperative vomiting (RR 1.56, 95% CI 0.40 to 6.13, one study, 89 women, Analysis 38.4).

38.1 — Comparison 38 Supplemental oxygen (H) vs placebo, Outcome 1 Nausea ‐ intraoperative.

38.2 — Comparison 38 Supplemental oxygen (H) vs placebo, Outcome 2 Vomiting ‐ intraoperative.

38.3 — Comparison 38 Supplemental oxygen (H) vs placebo, Outcome 3 Nausea ‐ postoperative.

38.4 — Comparison 38 Supplemental oxygen (H) vs placebo, Outcome 4 Vomiting ‐ postoperative.

Secondary outcomes

None of our secondary outcomes were assessed.

Not pre‐specified outcomes

There was no difference identified in maternal satisfaction (RR 0.96, 95% CI 0.89 to 1.03, one study, 89 women, Analysis 38.9).

38.9 — Comparison 38 Supplemental oxygen (H) vs placebo, Outcome 9 Maternal satisfaction.

J. Intravenous fluids (Comparison 39)

1) Intravenous fluids (J) versus placebo (one study, 10 women, Comparison 39)

One very small study compared supplemental intravenous fluid with placebo in regional anaesthesia (Gaiser 2002). The study was of uncertain quality, with random sequence generation, blinding, missing data, selective reporting and other bias all judged as 'Unclear'. Allocation concealment was assessed as adequate.

Primary outcomes

The primary outcomes of postoperative nausea and vomiting were assessed. No difference was detected in either the outcome of postoperative nausea or postoperative vomiting (Analysis 39.3; Analysis 39.4).

39.3 — Comparison 39 IV fluids (J) vs placebo, Outcome 3 Nausea ‐ postoperative.

39.4 — Comparison 39 IV fluids (J) vs placebo, Outcome 4 Vomiting ‐ postoperative.

Secondary outcomes

None of our secondary outcomes were assessed.

K. Acupressure/acupuncture (Comparison 40‐42)

1) Acupressure/acupuncture (K) versus placebo (six studies, 649 women, Comparison 40)

Seven studies compared acupressure/acupuncture with placebo, with six studies providing data on 649 women (Duggal 1998; Habib 2006; Harmon 2000; Ho 1996; Ho 2006; Stein 1997). One study addressed this question but provided graphical data only (Birnbach 1993). The studies providing data were of reasonable quality with five out of six describing adequate blinding and one rated as unclear (Harmon 2000). However, only three of six described adequate random sequence generation and only one of six adequate allocation concealment (Stein 1997). All six studies assessed intraoperative symptoms. Only three studies (Duggal 1998; Habib 2006; Harmon 2000) also assessed postoperative symptoms.

Primary outcomes

The six studies comparing the intervention with placebo found a reduction in intraoperative nausea (average RR 0.59, 95% CI 0.38 to 0.90, six studies, 649 women, random‐effects [T² = 0.18, Chi² P = 0.004, I² = 71%], Analysis 40.1). No significant difference was seen in intraoperative vomiting (average RR 0.74, 95% CI 0.46 to 1.18, six studies, 649 women, random‐effects [T² = 0.05, Chi² P = 0.33, I² = 13%], Analysis 40.2). The three studies assessing postoperative symptoms identified no reduction in nausea (average RR 0.83, 95% CI 0.68 to 1.00, three studies, 429 women, random‐effects [T² = 0.00, Chi² P = 0.42, I² = 0%], Analysis 40.3), or vomiting (average RR 0.69, 95% CI 0.45 to 1.06, three studies, 429 women, random‐effects [T² = 0.08, Chi² P = 0.10, I² = 57%], Analysis 40.4).

40.1 — Comparison 40 Acupressure/acupuncture (K) vs placebo, Outcome 1 Nausea ‐ intraoperative.

40.2 — Comparison 40 Acupressure/acupuncture (K) vs placebo, Outcome 2 Vomiting ‐ intraoperative.

40.3 — Comparison 40 Acupressure/acupuncture (K) vs placebo, Outcome 3 Nausea ‐ postoperative.

40.4 — Comparison 40 Acupressure/acupuncture (K) vs placebo, Outcome 4 Vomiting ‐ postoperative.

Secondary outcomes

Only two studies (Ho 1996; Stein 1997) assessed adverse effects and found no difference between the groups for anxiety, dizziness, hypotension and pruritus Analysis 40.10 to Analysis 40.13).

40.10 — Comparison 40 Acupressure/acupuncture (K) vs placebo, Outcome 10 Anxiety (not pre‐specified).

40.13 — Comparison 40 Acupressure/acupuncture (K) vs placebo, Outcome 13 Pruritus (not pre‐specified).

2) Acupressure/acupuncture (K) versus 5‐HT₃ antagonists (A) (no studies, Comparison 41)

There were no studies that made this comparison.

3) Acupressure/acupuncture (K) versus dopamine antagonists (B) (one study, 50 women, Comparison 42)

Two studies assessed this question (Birnbach 1993, Stein 1997) but only one provided useable data (Stein 1997). The study was of good quality.

Primary outcomes

The primary outcomes of intraoperative nausea and vomiting were assessed. No difference was detected in either outcome (Analysis 42.1; Analysis 42.2).

42.1 — Comparison 42 Acupuncture/acupressure (K) vs dopamine antagonist (B), Outcome 1 Nausea ‐ intraoperative.

42.2 — Comparison 42 Acupuncture/acupressure (K) vs dopamine antagonist (B), Outcome 2 Vomiting ‐ intraoperative.

Secondary outcomes

No data.

Not pre‐specified outcomes

See analyses Analysis 42.10 and Analysis 42.11.

Combinations of interventions (comparisons 43‐47)

There were seven comparisons of combinations of drugs with only one study for each comparison. These are reported below.

1) Droperidol + dexamethasone (B+C) versus placebo (one study, 60 women, Comparison 43)

One study involving 60 women looked at the combination of droperidol plus dexamethasone against placebo (Wu 2007). The study had adequate random sequence generation and blinding, however, it was unclear whether there was adequate concealment allocation. The only outcome assessed was postoperative vomiting which was reduced with the drug combination (RR 0.40, 95% CI 0.18 to 0.89, one study, 60 women, Analysis 43.4).

43.4 — Comparison 43 Dopamine antagonists + corticosteroids (B+C) vs placebo, Outcome 4 Vomiting ‐ postoperative.

2) Droperidol + dexamethasone (B+C) versus droperidol (B) alone (one study, 60 women, Comparison 44)

The same study involving 60 women looked at the combination of droperidol plus dexamethasone versus droperidol (Wu 2007). The only outcome assessed was postoperative vomiting and no difference was identified (RR 0.67, 95% CI 0.27 to 1.64, one study, 60 women, Analysis 44.4).

44.4 — Comparison 44 Dopamine antagonists + corticosteroids (B+C) vs dopamine antagonists (B), Outcome 4 Vomiting ‐ postoperative.

3) Droperidol + dexamethasone (B+C) versus dexamethasone (C) alone (one study, 60 women. Comparison 45)

The same study involving 60 women looked at the combination of droperidol plus dexamethasone against droperidol (Wu 2007). The only outcome assessed was postoperative vomiting and no difference was identified (RR 0.46, 95% CI 0.20 to 1.05, one study, 60 women, Analysis 45.4).

45.4 — Comparison 45 Dopamine antagonists + corticosteroids (B+C) vs corticosteroids (C), Outcome 4 Vomiting ‐ postoperative.

4) Metoclopramide + glycopyrrolate (B+E) versus metoclopramide (B) alone (no studies, Comparison 46)

Although there was one small study, we were unable to use the combined outcome data (Biwas 2002).

5) Metaclopramide + glycopyrrolate (B+E) versus glycopyrrolate (E) alone (no studies, Comparison 47)

Although there was one small study, we were unable to use the combined outcome data (Biwas 2002).

Discussion

Summary of main results

The included studies included in this review fall into three broad groups ‐ those comparing agents with placebo, those comparing different single agents with one another, and those comparing combinations of therapy.

Placebo controlled studies

A. 5‐HT₃ antagonists. Using data from 10 studies involving 980 women, overall we found that 5‐HT₃ antagonists were effective in reducing intraoperative nausea, and postoperative nausea and vomiting. However, there were insufficient data to determine if there were significant adverse effects like headaches, dizziness, hypotension and pruritus.

B. Dopamine antagonists In 12 studies involving 899 women, we found that dopamine antagonists (both metoclopramide and droperidol) were effective in reducing both intraoperative nausea and vomiting, and postoperative nausea and vomiting. However, there were insufficient data to determine if there were significant adverse effects like headaches, dizziness, hypotension and pruritus.

C. Corticosteroids. In six studies involving 490 women, corticosteroids were found to be effective at reducing intraoperative nausea and vomiting. However, we did not identify any benefit for postoperative nausea and vomiting.

D. Antihistamines. In three studies involving 365 women, antihistamines were effective at reducing postoperative nausea and vomiting, but none of the studies assessed intraoperative nausea and vomiting. There are no data on possible adverse effects.

E. Anticholenergic drugs. In four studies involving 453 women, we found that anticholinergic drugs were effective at reducing intraoperative nausea but not intraoperative vomiting. No study assessed postoperative nausea, however, there was a reduction in postoperative vomiting in one study involving 161 women but there were insufficient data to be sure of other outcomes, including potential adverse effects.

F. Sedatives. In four studies involving 285 women, we found a reduction in intraoperative and postoperative nausea and vomiting. There were insufficient data on potential adverse effects.

G. Opioids. There was just one study involving 120 women and this found no difference in postoperative nausea or vomiting.

H. Supplemental oxygen. There were two studies involving 294 women and these studies found no difference in our primary outcomes.

J. Intravenous fluids. There was just one small study involving 10 women and this provided insufficient data to be able to report findings with any degree of assurance.

K. Acupressure/acupuncture. In six studies involving 649 women, we found a reduction in intraoperative nausea but we identified no difference in postoperative nausea or intraoperative and postoperative vomiting, although there is likely to be insufficient data to be able to say there is no difference. There were insufficient data on potential adverse effects.

Comparison studies

A number of studies compared the efficacy of different single drugs with one another. These included studies comparing different medications within the same class, such as comparing different dopamine antagonists (one study, 81 women) or different doses of 5‐HT₃ antagonists (one study, 120 women). Some studies also compared medication of different classes, such as studies comparing a 5‐HT3 antagonist with a dopamine antagonist (four studies, 307 women) or a dopamine antagonist with a steroid (three studies, 176 women).

In our primary outcomes, postoperative nausea was found to be reduced with 5‐HT3 antagonists compared with dopamine antagonists. Postoperative vomiting was found to be reduced with antihistamines compared with dopamine antagonists, and with antihistamines compared with steroids. Sedatives were found to decrease intraoperative nausea compared with dopamine antagonists.

In non‐prespecified outcomes, respiratory depression was found to be significantly increased with sedatives compared with dopamine antagonists.

Combination studies

A number of small combination studies were included in the review. These included the combination of metoclopramide/glycopyrrolate compared with metoclopramide or glycopyrrolate alone, the combination of 5‐HT₃/dexamethasone with 5‐HT₃ antagonists or droperidol alone, and the combination of 5‐HT₃/droperidol and 5‐HT₃ antagonists alone.

No difference was detected between any combination of treatment for any of our primary outcomes. However, the combination of dopamine antagonists and corticosteroids was assessed against placebo in one study and found to be effective in reducing postoperative vomiting.

Overall completeness and applicability of evidence

There are good data assessing the efficacy of most classes of antiemetic compared with placebo in preventing nausea and vomiting during and following caesarean section under regional anaesthesia. There are limited data comparing different classes of antiemetics, and very limited data comparing combinations of therapy.

There were no studies identified that assessed the efficacy of antiemetics given for treatment (rather than prevention) of established nausea and vomiting although these would be dealt with in a separate review.

Quality of the evidence

The quality of the evidence in this review varied widely. The 'Risk of bias' assessment ranged from seven studies which assessed as low risk on all criteria (apart from Selective Bias) to five studies assessed as unclear on all criteria. Only four studies were rated as inadequate on any criteria ‐ Duman 2010 and Phillips 2007 for management of missing data, Rudra 2004a for inadequate blinding and Shahriari 2009 for selective reporting.

Of the 52 included studies, 31 described adequate blinding, and 26 described adequate random sequence generation, however only 11 described adequate allocation concealment.

Potential biases in the review process

The possibility of introducing bias was present at every stage of reviewing process. We attempted to minimise bias in a number of ways; two review authors assessed eligibility for inclusion, carried out data extraction and assessed risk of bias. Each worked independently. Nevertheless, the process of assessing risk of bias, for example, is not an exact science and includes many personal judgements.

Agreements and disagreements with other studies or reviews

The findings of this study are consistent with previously published reviews of nausea and vomiting at caesarean section (Balki 2005).

Authors' conclusions

Implications for practice.

This study indicates that many agents, from a diverse range of pharmacological classes, have efficacy in preventing intraoperative and postoperative emetic symptoms at caesarean section. This is perhaps consistent with the multi‐factorial pathogenesis of the condition. Of the included interventions, 5 HT₃ antagonists, dopamine antagonists and sedatives all showed a reduction in the majority of our primary outcomes. The other classes of drugs and interventions show effects on some of these outcomes only, for example, acupuncture/acupressure was found to reduce intraoperative nausea, but was not found to affect vomiting or postoperative nausea. This may reflect the amount of data available.

There is little evidence that combinations of treatment are superior to single agents but few studies looked at these aspects.

The studies suggest that emetic symptoms are common both during and following caesarean section. Placebo arms of trials included in this review suggest an intraoperative incidence of nausea in the order of 20% to 60%. This gives some weight to published guidelines recommending prophylaxis rather than treatment of emesis at caesarean section (NICE 2011).

Implications for research.

Whilst there is good evidence that many single agents are efficacious in preventing nausea and vomiting, there is a paucity of good quality data comparing different interventions, nor is there good data comparing combinations of treatment. There are no data comparing the efficacy of agents for treatment of established nausea and vomiting although these would be dealt with in a separate review. Future studies should assess potential adverse effects and women's views.

Acknowledgements

Dr Eugene HC Liu Department of Anaesthesia, National University Hospital, Singapore.

Eugene Liu (EL) and Shantini Paranjothy (SP) wrote the first drafts of the combined protocol (Drugs at caesarean section for preventing nausea, vomiting and aspiration pneumonitis), which was subsequently split into this review and Paranjothy 2010.

Several papers considered for inclusion in the review were not reported in English. Thanks to Edgardo Abalos for translating Caba 1997; Liza Abraham for translating Maranhao 1988; Julie Arbon for translating Jasson 1987; Alex Balistreri for translating Karamanlioglu 1995, von Braun 1994 and Zoroglu 1999; Elizabeth Dumford Chavez for translating Imbeloni 1986; Samiye Godel for translating Ozkan 2000; Gillian Kenyon for translating Tryba 1983; Alison Ledward for translating Jasson 1989b and Zue 1999; Almira Opardija for translating Avramovic 1979; and Sara Roden‐Scott for translating Bifarini 1990 and Bifarini 1992.

As part of the pre‐publication editorial process, this review has been commented on by two peers (an editor and referee who is 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

Comparison 1. 5‐HT₃ antagonists (A) vs placebo.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Nausea ‐ intraoperative	8	720	Risk Ratio (M‐H, Random, 95% CI)	0.64 [0.46, 0.88]
1.1 Ondansetron ‐ 4 mg	6	512	Risk Ratio (M‐H, Random, 95% CI)	0.60 [0.40, 0.89]
1.2 Ondansetron ‐ 8 mg	1	32	Risk Ratio (M‐H, Random, 95% CI)	0.45 [0.20, 1.01]
1.3 Granisetron ‐ 1 mg	1	176	Risk Ratio (M‐H, Random, 95% CI)	1.14 [0.59, 2.20]
2 Vomiting ‐ intraoperative	7	668	Risk Ratio (M‐H, Random, 95% CI)	0.56 [0.31, 1.00]
2.1 Ondansetron ‐ 4 mg	5	460	Risk Ratio (M‐H, Random, 95% CI)	0.60 [0.30, 1.18]
2.2 Ondansetron ‐ 8 mg	1	32	Risk Ratio (M‐H, Random, 95% CI)	0.14 [0.02, 1.03]
2.3 Granisetron ‐ 1 mg	1	176	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.19, 2.28]
3 Nausea ‐ postoperative	4	405	Risk Ratio (M‐H, Random, 95% CI)	0.40 [0.25, 0.64]
3.1 Ondansetron ‐ 4 mg	4	315	Risk Ratio (M‐H, Random, 95% CI)	0.39 [0.21, 0.75]
3.2 Ondansetron ‐ 8 mg	1	90	Risk Ratio (M‐H, Random, 95% CI)	0.44 [0.18, 1.09]
3.3 Granisetron ‐ 1 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.4 Granisetron ‐ 3 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4 Vomiting ‐ postoperative	5	565	Risk Ratio (M‐H, Random, 95% CI)	0.50 [0.32, 0.77]
4.1 Ondansetron ‐ 4 mg	5	475	Risk Ratio (M‐H, Random, 95% CI)	0.45 [0.27, 0.77]
4.2 Ondansetron ‐ 8 mg	1	90	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.19, 5.15]
4.3 Granisetron ‐ 1 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.4 Granisetron ‐ 3 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5 Maternal adverse effects	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.1 Ondansetron ‐ 4 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.2 Ondansetron ‐ 8 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.3 Granisetron ‐ 1 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.4 Granisetron ‐ 3 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6 Apgar < 7 at 5 min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.1 Ondansetron ‐ 4 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.2 Ondansetron ‐ 8 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.3 Granisetron ‐ 1 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.4 Granisetron ‐ 3 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7 Initiaition of breastfeeding	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.1 Ondansetron ‐ 4 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.2 Ondansetron ‐ 8 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.3 Granisetron ‐ 1 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.4 Granisetron ‐ 3 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8 Duration of exclusive breastfeeding	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.1 Ondansetron ‐ 4 mg	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.2 Ondansetron ‐ 8 mg	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.3 Granisetron ‐ 1 mg	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.4 Granisetron ‐ 3 mg	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Maternal satisfaction	2		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
9.1 Ondansetron ‐ 4 mg	2		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.2 Ondansetron ‐ 8 mg	0		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.3 Granisetron ‐ 1 mg	0		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.4 Granisetron ‐ 3 mg	0		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10 Headache/dizziness (not pre‐specified)	1	105	Risk Ratio (M‐H, Random, 95% CI)	2.83 [0.30, 26.36]
10.1 Ondansetron ‐ 4 mg	1	105	Risk Ratio (M‐H, Random, 95% CI)	2.83 [0.30, 26.36]
10.2 Ondansetron ‐ 8 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.3 Granisetron ‐ 1 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.4 Granisetron ‐ 3 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11 Hypotension (not pre‐specified)	3	290	Risk Ratio (M‐H, Random, 95% CI)	1.22 [0.72, 2.08]
11.1 Ondansetron ‐ 4 mg	2	114	Risk Ratio (M‐H, Random, 95% CI)	1.44 [0.48, 4.34]
11.2 Ondansetron ‐ 8 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11.3 Granisetron ‐ 1 mg	1	176	Risk Ratio (M‐H, Random, 95% CI)	3.0 [0.12, 72.65]
11.4 Granisetron ‐ 3 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
12 Pruritus (not pre‐specified)	1	180	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.85, 1.03]
12.1 Ondansetron ‐ 4 mg	1	90	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.81, 1.07]
12.2 Ondansetron ‐ 8 mg	1	90	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.83, 1.08]
12.3 Granisetron ‐ 1 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
12.4 Granisetron ‐ 3 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Nausea ‐ intraoperative	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Vomiting ‐ intraoperative	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Nausea ‐ postoperative	1	120	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.37, 2.68]
4 Vomiting ‐ postoperative	1	120	Risk Ratio (M‐H, Fixed, 95% CI)	1.33 [0.31, 5.70]
5 Maternal adverse effects	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Apgar < 7 at 5 min	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Initiation of breastfeeding	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Duration of exclusive breastfeeding	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9 Maternal satisfaction	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
10 Pruritus (not pre‐specified)	1	120	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.89, 1.17]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Nausea ‐ intraoperative	9	636	Risk Ratio (M‐H, Random, 95% CI)	0.38 [0.25, 0.57]
1.1 Metoclopramide ‐ 10 mg	4	234	Risk Ratio (M‐H, Random, 95% CI)	0.36 [0.13, 0.96]
1.2 Metoclopramide ‐ 20 mg	1	100	Risk Ratio (M‐H, Random, 95% CI)	0.27 [0.10, 0.75]
1.3 Metoclopramide ‐ 0.15 mg/kg	1	67	Risk Ratio (M‐H, Random, 95% CI)	0.32 [0.12, 0.90]
1.4 Droperidol ‐ 0.5 mg	1	128	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.17, 0.65]
1.5 Droperidol ‐ 0.625 mg	1	32	Risk Ratio (M‐H, Random, 95% CI)	0.36 [0.15, 0.90]
1.6 Droperidol ‐ 1.25 mg	1	75	Risk Ratio (M‐H, Random, 95% CI)	0.44 [0.17, 1.15]
2 Vomiting ‐ intraoperative	8	536	Risk Ratio (M‐H, Random, 95% CI)	0.39 [0.24, 0.64]
2.1 Metoclopramide ‐ 10 mg	4	234	Risk Ratio (M‐H, Random, 95% CI)	0.45 [0.20, 0.99]
2.2 Metoclopramide ‐ 20 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.3 Metoclopramide ‐ 0.15 mg/kg	1	67	Risk Ratio (M‐H, Random, 95% CI)	0.09 [0.01, 1.54]
2.4 Droperidol ‐ 0.5 mg	1	128	Risk Ratio (M‐H, Random, 95% CI)	0.34 [0.09, 1.23]
2.5 Droperidol ‐ 0.625 mg	1	32	Risk Ratio (M‐H, Random, 95% CI)	0.29 [0.07, 1.17]
2.6 Droperidol ‐ 1.25 mg	1	75	Risk Ratio (M‐H, Random, 95% CI)	0.37 [0.10, 1.27]
3 Nausea ‐ postoperative	5	412	Risk Ratio (M‐H, Random, 95% CI)	0.60 [0.40, 0.91]
3.1 Metoclopramide ‐ 10 mg	3	265	Risk Ratio (M‐H, Random, 95% CI)	0.58 [0.36, 0.94]
3.2 Metoclopramide ‐ 20 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.3 Metoclopramide ‐ 0.15 mg/kg	1	67	Risk Ratio (M‐H, Random, 95% CI)	0.40 [0.16, 1.02]
3.4 Droperidol ‐ 0.5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.5 Droperidol ‐ 0.625 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.6 Droperidol ‐ 1.25 mg	1	80	Risk Ratio (M‐H, Random, 95% CI)	1.67 [0.43, 6.51]
4 Vomiting ‐ postoperative	6	472	Risk Ratio (M‐H, Random, 95% CI)	0.57 [0.36, 0.91]
4.1 Metoclopramide ‐ 10 mg	3	265	Risk Ratio (M‐H, Random, 95% CI)	0.65 [0.24, 1.73]
4.2 Metoclopramide ‐ 20 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.3 Metoclopramide ‐ 0.15 mg/kg	1	67	Risk Ratio (M‐H, Random, 95% CI)	0.32 [0.12, 0.90]
4.4 Droperidol ‐ 0.5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.5 Droperidol ‐ 0.625 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.6 Droperidol ‐ 1.25 mg	2	140	Risk Ratio (M‐H, Random, 95% CI)	0.55 [0.32, 0.94]
5 Maternal adverse effects	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.1 Metoclopramide ‐ 10 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.2 Metoclopramide ‐ 20 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.3 Metoclopramide ‐ 0.15 mg/kg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.4 Droperidol ‐ 0.5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.5 Droperidol ‐ 0.625 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.6 Droperidol ‐ 1.25 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6 Apgar < 7 at 5 min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.1 Metoclopramide ‐ 10 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.2 Metoclopramide ‐ 20 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.3 Metoclopramide ‐ 0.15 mg/kg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.4 Droperidol ‐ 0.5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.5 Droperidol ‐ 0.625 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.6 Droperidol ‐ 1.25 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7 Initiation of breastfeeding	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.1 Metoclopramide ‐ 10 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.2 Metoclopramide ‐ 20 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.3 Metoclopramide ‐ 0.15 mg/kg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.4 Droperidol ‐ 0.5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.5 Droperidol ‐ 0.625 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.6 Droperidol ‐ 1.25 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8 Duration of exclusive breastfeeding	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.1 Metoclopramide ‐ 10 mg	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.2 Metoclopramide ‐ 20 mg	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.3 Metoclopramide ‐ 0.5 mg/kg	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.4 Droperidol ‐ 0.5 mg	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.5 Droperidol ‐ 0.625 mg	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.6 Droperidol ‐ 1.25 mg	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Maternal satisfaction	1	102	Risk Ratio (M‐H, Random, 95% CI)	1.42 [0.91, 2.21]
9.1 Metoclopramide ‐ 10 mg	1	102	Risk Ratio (M‐H, Random, 95% CI)	1.42 [0.91, 2.21]
9.2 Metoclopramide ‐ 20 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.3 Metoclopramide ‐ 0.15 mg/kg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.4 Droperidol ‐ 0.5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.5 Droperidol ‐ 0.625 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.6 Droperidol ‐ 1.25 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10 Anxiety (not pre‐specified)	1	50	Risk Ratio (M‐H, Random, 95% CI)	4.0 [0.48, 33.33]
10.1 Metoclopramide ‐ 10 mg	1	50	Risk Ratio (M‐H, Random, 95% CI)	4.0 [0.48, 33.33]
10.2 Metoclopramide ‐ 20 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.3 Metoclopramide ‐ 0.15 mg/kg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.4 Droperidol ‐ 0.5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.5 Droperidol ‐ 0.625 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.6 Droperidol ‐ 1.25 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11 Headache/dizziness (not pre‐specified)	1	102	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.01, 8.00]
11.1 Metoclopramide ‐ 10 mg	1	102	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.01, 8.00]
11.2 Metoclopramide ‐ 20 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11.3 Metoclopramide ‐ 0.15 mg/kg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11.4 Droperidol ‐ 0.5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11.5 Droperidol ‐ 0.625 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11.6 Droperidol ‐ 1.25 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
12 Hypotension (not pre‐specified)	4	285	Risk Ratio (M‐H, Random, 95% CI)	1.05 [0.84, 1.31]
12.1 Metoclopramide ‐ 10 mg	2	90	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.68, 1.28]
12.2 Metoclopramide ‐ 20 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
12.3 Metoclopramide ‐ 0.15 mg/kg	1	67	Risk Ratio (M‐H, Random, 95% CI)	1.62 [0.66, 3.95]
12.4 Droperidol ‐ 0.5 mg	1	128	Risk Ratio (M‐H, Random, 95% CI)	1.13 [0.80, 1.60]
12.5 Droperidol ‐ 0.625 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
12.6 Droperidol ‐ 1.25 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
13 Pruritus (not pre‐specified)	1	75	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.55, 1.53]
13.1 Metoclopramide ‐ 10 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
13.2 Metoclopramide ‐ 20 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
13.3 Metoclopramide ‐ 0.15 mg/kg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
13.4 Droperidol ‐ 0.5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
13.5 Droperidol ‐ 0.625 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
13.6 Droperidol ‐ 1.25 mg	1	75	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.55, 1.53]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Nausea ‐ intraoperative	2	137	Risk Ratio (M‐H, Random, 95% CI)	1.39 [0.67, 2.90]
1.1 Metoclopramide (10 mg) vs ondansetron (4 mg)	1	105	Risk Ratio (M‐H, Random, 95% CI)	1.79 [1.01, 3.16]
1.2 Metoclopramide (10 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.3 Metoclopramide (10 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.4 Droperidol (0.625 mg) vs ondansetron (8 mg)	1	32	Risk Ratio (M‐H, Random, 95% CI)	0.8 [0.26, 2.45]
1.5 Droperidol (1.25 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.6 Droperidol (1.25 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2 Vomiting ‐ intraoperative	2	137	Risk Ratio (M‐H, Random, 95% CI)	1.30 [0.55, 3.10]
2.1 Metoclopramide (10 mg) vs ondansetron (4 mg)	1	105	Risk Ratio (M‐H, Random, 95% CI)	1.21 [0.47, 3.10]
2.2 Metoclopramide (10 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.3 Metoclopramide (10 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.4 Droperidol (0.625 mg) vs ondansetron (8 mg)	1	32	Risk Ratio (M‐H, Random, 95% CI)	2.0 [0.20, 19.91]
2.5 Droperidol (1.25 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.6 Droperidol (1.25 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3 Nausea ‐ postoperative	2	185	Risk Ratio (M‐H, Random, 95% CI)	1.84 [1.13, 2.98]
3.1 Metoclopramide (10 mg) vs ondansetron (4 mg)	1	105	Risk Ratio (M‐H, Random, 95% CI)	1.97 [1.16, 3.32]
3.2 Metoclopramide (10 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.3 Metoclopramide (10 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.4 Droperidol (0.625 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.5 Droperidol (1.25 mg) vs ondansetron (4 mg)	1	80	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.36, 4.32]
3.6 Droperidol (1.25 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4 Vomiting ‐ postoperative	3	275	Risk Ratio (M‐H, Random, 95% CI)	2.09 [0.94, 4.64]
4.1 Metoclopramide (10 mg) vs ondansetron (4 mg)	1	105	Risk Ratio (M‐H, Random, 95% CI)	1.19 [0.50, 2.85]
4.2 Metoclopramide (10 mg) vs ondansetron (8 mg)	1	90	Risk Ratio (M‐H, Random, 95% CI)	2.63 [1.30, 5.30]
4.3 Metoclopramide (10 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.4 Droperidol (0.625 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.5 Droperidol (1.25 mg) vs ondansetron (4 mg)	1	80	Risk Ratio (M‐H, Random, 95% CI)	11.00 [0.63, 192.56]
4.6 Droperidol (1.25 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5 Maternal adverse effects	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.1 Metoclopramide (10 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.2 Metoclopramide (10 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.3 Metoclopramide (10 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.4 Droperidol (0.625 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.5 Droperidol (1.25 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.6 Droperidol (1.25 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6 Apgar < 7 at 5 min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.1 Metoclopramide (10 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.2 Metoclopramide (10 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.3 Metoclopramide (10 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.4 Droperidol (0.625 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.5 Droperidol (1.25 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.6 Droperidol (1.25 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7 Initiation of breastfeeding	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.1 Metoclopramide (10 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.2 Metoclopramide (10 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.3 Metoclopramide (10 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.4 Droperidol (0.625 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.5 Droperidol (1.25 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.6 Droperidol (1.25 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8 Duration of exclusive breastfeeding	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.1 Metoclopramide (10 mg) vs ondansetron (4 mg)	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.2 Metoclopramide (10 mg) vs ondansetron (8 mg)	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.3 Metoclopramide (10 mg) vs granisetron (3 mg)	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.4 Droperidol (0.625 mg) vs ondansetron (8 mg)	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.5 Droperidol (1.25 mg) vs ondansetron (4 mg)	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.6 Droperidol (1.25 mg) vs granisetron (3 mg)	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Maternal satisfaction	1	105	Risk Ratio (M‐H, Random, 95% CI)	0.71 [0.53, 0.97]
9.1 Metoclopramide (10 mg) vs ondansetron (4 mg)	1	105	Risk Ratio (M‐H, Random, 95% CI)	0.71 [0.53, 0.97]
9.2 Metoclopramide (10 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.3 Metoclopramide (10 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.4 Droperidol (0.625 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.5 Droperidol (1.25 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.6 Droperidol (1.25 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10 Headache/dizziness (not pre‐specified)	1	105	Risk Ratio (M‐H, Random, 95% CI)	0.15 [0.01, 2.85]
10.1 Metoclopramide (10 mg) vs ondansetron (4 mg)	1	105	Risk Ratio (M‐H, Random, 95% CI)	0.15 [0.01, 2.85]
10.2 Metoclopramide (10 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.3 Metoclopramide (10 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.4 Droperidol (0.625 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.5 Droperidol (1.25 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.6 Droperidol (1.25 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11 Pruritus < 8 hours (not pre‐specified)	1	90	Risk Ratio (M‐H, Random, 95% CI)	1.23 [0.90, 1.68]
11.1 Metoclopramide (10 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11.2 Metoclopramide (10 mg) vs ondansetron (8 mg)	1	90	Risk Ratio (M‐H, Random, 95% CI)	1.23 [0.90, 1.68]
11.3 Metoclopramide (10 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11.4 Droperidol (0.625 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11.5 Droperidol (1.25 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11.6 Droperidol (1.25 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
12 Pruritus > 8 hours (not pre‐specified)	1	90	Risk Ratio (M‐H, Random, 95% CI)	4.29 [2.10, 8.73]
12.1 Metoclopramide (10 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
12.2 Metoclopramide (10 mg) vs ondansetron (8 mg)	1	90	Risk Ratio (M‐H, Random, 95% CI)	4.29 [2.10, 8.73]
12.3 Metoclopramide (10 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
12.4 Droperidol (0.625 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
12.5 Droperidol (1.25 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
12.6 Droperidol (1.25 mg) vs granisetron (3 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Nausea ‐ intraoperative	1	81	Risk Ratio (M‐H, Random, 95% CI)	1.54 [0.70, 3.36]
1.1 Metoclopramide (10 mg) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.2 Metoclopramide (15 mg) vs droperidol (0.5 mg)	1	81	Risk Ratio (M‐H, Random, 95% CI)	1.54 [0.70, 3.36]
2 Vomiting ‐ intraoperative	1	81	Risk Ratio (M‐H, Random, 95% CI)	0.51 [0.05, 5.43]
2.1 Metoclopramide (10 mg) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.2 Metoclopramide (15 mg) vs droperidol (0.5 mg)	1	81	Risk Ratio (M‐H, Random, 95% CI)	0.51 [0.05, 5.43]
3 Nausea ‐ postoperative	1	81	Risk Ratio (M‐H, Random, 95% CI)	1.03 [0.32, 3.27]
3.1 Metoclopramide (10 mg) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.2 Metoclopramide (15 mg) vs droperidol (0.5 mg)	1	81	Risk Ratio (M‐H, Random, 95% CI)	1.03 [0.32, 3.27]
4 Vomiting ‐ postoperative	1	81	Risk Ratio (M‐H, Random, 95% CI)	1.03 [0.22, 4.78]
4.1 Metoclopramide (10 mg) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.2 Metoclopramide (15 mg) vs droperidol (0.5 mg)	1	81	Risk Ratio (M‐H, Random, 95% CI)	1.03 [0.22, 4.78]
5 Maternal adverse effects	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.1 Metoclopramide (10 mg) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.2 Metoclopramide (15 mg) vs droperidol (0.5 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6 Apgar < 7 at 5 min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.1 Metoclopramide (10 mg) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.2 Metoclopramide (15 mg) vs droperidol (0.5 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7 Initiaition of breastfeeding	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.1 Metoclopramide (10 mg) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.2 Metoclopramide (15 mg) vs droperidol (0.5 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8 Duration of exclusive breastfeeding	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.1 Metoclopramide (10 mg) vs droperidol (1.25 mg)	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.2 Metoclopramide (15 mg) vs droperidol (0.5 mg)	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Maternal satisfaction	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.1 Metoclopramide (10 mg) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.2 Metoclopramide (15 mg) vs droperidol (0.5 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10 Restlessness (not‐pre‐specified)	1	81	Risk Ratio (M‐H, Random, 95% CI)	0.51 [0.05, 5.43]
10.1 Metoclopramide (10 mg) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.2 Metoclopramide (15 mg) vs droperidol (0.5 mg)	1	81	Risk Ratio (M‐H, Random, 95% CI)	0.51 [0.05, 5.43]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Nausea ‐ intraoperative	3	195	Risk Ratio (M‐H, Random, 95% CI)	0.31 [0.15, 0.64]
1.1 Dexamethasone ‐ 2.5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.2 Dexamethasone ‐ 5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.3 Dexamethasone ‐ 8 mg	3	195	Risk Ratio (M‐H, Random, 95% CI)	0.31 [0.15, 0.64]
1.4 Dexamethasone ‐ 10 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2 Vomiting ‐ intraoperative	3	195	Risk Ratio (M‐H, Random, 95% CI)	0.35 [0.14, 0.86]
2.1 Dexamethasone ‐ 2.5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.2 Dexamethasone ‐ 5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.3 Dexamethasone ‐ 8 mg	3	195	Risk Ratio (M‐H, Random, 95% CI)	0.35 [0.14, 0.86]
2.4 Dexamethasone ‐ 10 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3 Nausea ‐ postoperative	2	235	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.52, 1.07]
3.1 Dexamethasone ‐ 2.5 mg	1	58	Risk Ratio (M‐H, Random, 95% CI)	0.56 [0.19, 1.63]
3.2 Dexamethasone ‐ 5 mg	1	59	Risk Ratio (M‐H, Random, 95% CI)	0.43 [0.13, 1.38]
3.3 Dexamethasone ‐ 8 mg	1	60	Risk Ratio (M‐H, Random, 95% CI)	0.9 [0.61, 1.32]
3.4 Dexamethasone ‐ 10 mg	1	58	Risk Ratio (M‐H, Random, 95% CI)	0.44 [0.13, 1.41]
4 Vomiting ‐ postoperative	3	295	Risk Ratio (M‐H, Random, 95% CI)	0.78 [0.54, 1.12]
4.1 Dexamethasone ‐ 2.5 mg	1	58	Risk Ratio (M‐H, Random, 95% CI)	0.74 [0.22, 2.49]
4.2 Dexamethasone ‐ 5 mg	1	59	Risk Ratio (M‐H, Random, 95% CI)	0.34 [0.08, 1.51]
4.3 Dexamethasone ‐ 8 mg	2	120	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.65, 1.28]
4.4 Dexamethasone ‐ 10 mg	1	58	Risk Ratio (M‐H, Random, 95% CI)	0.26 [0.07, 1.04]
5 Maternal adverse effects	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.1 Dexamethasone ‐ 2.5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.2 Dexamethasone ‐ 5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.3 Dexamethasone ‐ 8 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.4 Dexamethasone ‐ 10 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6 Apgar < 7 at 5 min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.1 Dexamethasone ‐ 2.5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.2 Dexamethasone ‐ 5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.3 Dexamethasone ‐ 8 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.4 Dexamethasone ‐ 10 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7 Initiaition of breastfeeding	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.1 Dexamethasone ‐ 2.5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.2 Dexamethasone ‐ 5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.3 Dexamethasone ‐ 8 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.4 Dexamethasone ‐ 10 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8 Duration of exclusive breastfeeding	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.1 Dexamethasone ‐ 2.5 mg	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.2 Dexamethasone ‐ 5 mg	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.3 Dexamethasone ‐ 8 mg	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.4 Dexamethasone ‐ 10 mg	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Maternal satisfaction	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9.1 Dexamethasone ‐ 2.5 mg	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9.2 Dexamethasone ‐ 5 mg	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9.3 Dexamethasone ‐ 8 mg	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9.4 Dexamethasone ‐ 10 mg	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
10 Hypotension (not pre‐specified)	1	40	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.32, 1.77]
10.1 Dexamethasone ‐ 2.5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.2 Dexamethasone ‐ 5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.3 Dexamethasone ‐ 8 mg	1	40	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.32, 1.77]
10.4 Dexamethasone ‐ 10 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11 Pruritus (not pre‐specified)	1	75	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.59, 1.60]
11.1 Dexamethasone ‐ 2.5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11.2 Dexamethasone ‐ 5 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11.3 Dexamethasone ‐ 8 mg	1	75	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.59, 1.60]
11.4 Dexamethasone ‐ 10 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Nausea ‐ intraoperative	2	116	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.25, 1.77]
1.1 Dexamethasone (8 mg) vs metoclopramide (10 mg)	1	40	Risk Ratio (M‐H, Random, 95% CI)	0.5 [0.10, 2.43]
1.2 Dexamethasone (8 mg) vs droperidol (1.25 mg)	1	76	Risk Ratio (M‐H, Random, 95% CI)	0.8 [0.23, 2.75]
2 Vomiting ‐ intraoperative	2	116	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.31, 3.27]
2.1 Dexamethasone (8 mg) vs metoclopramide (10 mg)	1	40	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.16, 6.42]
2.2 Dexamethasone (8 mg) vs droperidol (1.25 mg)	1	76	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.22, 4.65]
3 Nausea ‐ postoperative	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.1 Dexamethasone (8 mg) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.2 Dexamethasone (8 mg) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4 Vomiting ‐ postoperative	1	60	Risk Ratio (M‐H, Random, 95% CI)	1.44 [0.73, 2.86]
4.1 Dexamethasone (8 mg) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.2 Dexamethasone (8 mg) vs droperidol (1.25 mg)	1	60	Risk Ratio (M‐H, Random, 95% CI)	1.44 [0.73, 2.86]
5 Maternal adverse effects	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.1 Dexamethasone (8 mg) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.2 Dexamethasone (8 mg) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6 Apgar < 7 at 5 min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.1 Dexamethasone (8 mg) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.2 Dexamethasone (8 mg) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7 Initiaition of breastfeeding	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.1 Dexamethasone (8 mg) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.2 Dexamethasone (8 mg) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8 Duration of exclusive breastfeeding	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.1 Dexamethasone (8 mg) vs metoclopramide (10 mg)	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.2 Dexamethasone (8 mg) vs droperidol (1.25 mg)	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Maternal satisfaction	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.1 Dexamethasone (8 mg) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.2 Dexamethasone (8 mg) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10 Hypotension (not pre‐specified)	1	40	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.29, 1.52]
10.1 Dexamethasone (8 mg) vs metoclopramide (10 mg)	1	40	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.29, 1.52]
10.2 Dexamethasone (8 mg) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11 Pruritus (not pre‐specified)	1	76	Risk Ratio (M‐H, Random, 95% CI)	1.06 [0.64, 1.78]
11.1 Dexamethasone (8 mg) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11.2 Dexamethasone (8 mg) vs droperidol (1.25 mg)	1	76	Risk Ratio (M‐H, Random, 95% CI)	1.06 [0.64, 1.78]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Nausea ‐ intraoperative	4	453	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.51, 0.87]
1.1 Glycopyrrolate ‐ 0.2 mg	2	89	Risk Ratio (M‐H, Random, 95% CI)	0.49 [0.22, 1.09]
1.2 Scopolamine patch	2	364	Risk Ratio (M‐H, Random, 95% CI)	0.71 [0.51, 0.97]
2 Vomiting ‐ intraoperative	4	453	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.40, 1.54]
2.1 Glycopyrrolate ‐ 0.2 mg	2	89	Risk Ratio (M‐H, Random, 95% CI)	0.45 [0.12, 1.62]
2.2 Scopolamine patch	2	364	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.36, 2.59]
3 Nausea ‐ postoperative	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.1 Glycopyrrolate ‐ 0.2 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.2 Scopolamine patch	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4 Vomiting ‐ postoperative	1	161	Risk Ratio (M‐H, Random, 95% CI)	0.55 [0.41, 0.74]
4.1 Glycopyrrolate ‐ 0.2 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.2 Scopolamine patch	1	161	Risk Ratio (M‐H, Random, 95% CI)	0.55 [0.41, 0.74]
5 Maternal adverse effects	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.1 Glycopyrrolate ‐ 0.2 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.2 Scopolamine patch	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6 Apgar < 7 at 5 min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.1 Glycopyrrolate ‐ 0.2 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.2 Scopolamine patch	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7 Initiaition of breastfeeding	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.1 Glycopyrrolate ‐ 0.2 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.2 Scopolamine patch	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8 Duration of exclusive breastfeeding	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.1 Glycopyrrolate ‐ 0.2 mg	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.2 Scopolamine patch	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Maternal satisfaction	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.1 Glycopyrrolate ‐ 0.2 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.2 Scopolamine patch	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10 Blurred vision (not pre‐specified)	1	203	Risk Ratio (M‐H, Random, 95% CI)	1.98 [0.37, 10.57]
10.1 Glycopyrrolate ‐ 0.2 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.2 Scopolamine patch	1	203	Risk Ratio (M‐H, Random, 95% CI)	1.98 [0.37, 10.57]
11 Disorientation (not pre‐specified)	1	203	Risk Ratio (M‐H, Random, 95% CI)	2.97 [0.12, 72.08]
11.1 Glycopyrrolate ‐ 0.2 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11.2 Scopolamine patch	1	203	Risk Ratio (M‐H, Random, 95% CI)	2.97 [0.12, 72.08]
12 Dizziness (not pre‐specified)	1	203	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.39, 2.54]
12.1 Glycopyrrolate ‐ 0.2 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
12.2 Scopolamine patch	1	203	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.39, 2.54]
13 Hypotension (not pre‐specified)	2	89	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.50, 1.26]
13.1 Glycopyrrolate ‐ 0.2 mg	2	89	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.50, 1.26]
13.2 Scopolamine patch	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
14 Pruritus (not pre‐specified)	1	203	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.66, 1.28]
14.1 Glycopyrrolate ‐ 0.2 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
14.2 Scopolamine patch	1	203	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.66, 1.28]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Nausea ‐ intraoperative	1	159	Risk Ratio (M‐H, Random, 95% CI)	1.06 [0.80, 1.40]
1.1 Scopolamine 1.5 mg vs Ondansetron 4 mg	1	159	Risk Ratio (M‐H, Random, 95% CI)	1.06 [0.80, 1.40]
2 Vomiting ‐ intraoperative	1	159	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.49, 1.74]
2.1 Scopolamine 1.5 mg vs Ondansetron 4 mg	1	159	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.49, 1.74]
3 Nausea ‐ postoperative	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.1 Scopolamine 1.5 mg vs Ondansetron 4 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4 Vomiting ‐ postoperative	1	159	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.66, 1.39]
4.1 Scopolamine 1.5 mg vs Ondansetron 4 mg	1	159	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.66, 1.39]
5 Maternal adverse effects	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.1 Scopolamine 1.5 mg vs Ondansetron 4 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6 Apgar < 7 at 5min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.1 Scopolamine 1.5 mg vs Ondansetron 4 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7 Initiaition of breastfeeding	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.1 Scopolamine 1.5 mg vs Ondansetron 4 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8 Duration of exclusive breastfeeding	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.1 Scopalamine 1.5 mg vs Ondansetron 4 mg	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Maternal satisfaction	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.1 Scopolamine 1.5 mg vs Ondansetron 4 mg	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Nausea ‐ intraoperative	4	285	Risk Ratio (M‐H, Random, 95% CI)	0.71 [0.52, 0.96]
1.1 Propofol ‐ 0.5 mg/kg/hr	1	26	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.19, 2.93]
1.2 Propofol ‐ 1.0 mg/kg/hr	2	87	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.11, 0.96]
1.3 Propofol ‐ 1.5 mg/kg/hr	1	27	Risk Ratio (M‐H, Random, 95% CI)	0.35 [0.09, 1.35]
1.4 Propofol ‐ 2.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.5 Propofol ‐ 10 mg IV ‐ single dose	1	57	Risk Ratio (M‐H, Random, 95% CI)	1.19 [0.39, 3.67]
1.6 Propofol ‐ 20 mg + 1.0 mg/kg/hr	1	44	Risk Ratio (M‐H, Random, 95% CI)	0.78 [0.46, 1.32]
1.7 Midazolam ‐ 1.0 mg + 1.0 mg/hr	1	44	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.47, 1.20]
2 Vomiting ‐ intraoperative	4	285	Risk Ratio (M‐H, Random, 95% CI)	0.42 [0.26, 0.68]
2.1 Propofol ‐ 0.5 mg/kg/hr	1	26	Risk Ratio (M‐H, Random, 95% CI)	0.9 [0.24, 3.35]
2.2 Propofol ‐ 1.0 mg/kg/hr	2	87	Risk Ratio (M‐H, Random, 95% CI)	0.34 [0.15, 0.78]
2.3 Propofol ‐ 1.5 mg/kg/hr	1	27	Risk Ratio (M‐H, Random, 95% CI)	0.23 [0.05, 1.12]
2.4 Propofol ‐ 2.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.5 Propofol ‐ 10 mg IV ‐ single dose	1	57	Risk Ratio (M‐H, Random, 95% CI)	0.60 [0.06, 6.21]
2.6 Propofol ‐ 20 mg + 1.0 mg/kg/hr	1	44	Risk Ratio (M‐H, Random, 95% CI)	0.28 [0.08, 1.01]
2.7 Midazolam ‐ 1.0 mg + 1.0 mg/hr	1	44	Risk Ratio (M‐H, Random, 95% CI)	0.56 [0.21, 1.53]
3 Nausea ‐ postoperative	2	145	Risk Ratio (M‐H, Random, 95% CI)	0.25 [0.09, 0.71]
3.1 Propofol ‐ 0.5 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.2 Propofol ‐ 1.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.3 Propofol ‐ 1.5 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.4 Propofol ‐ 2.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.5 Propofol ‐ 10 mg IV ‐ single dose	1	57	Risk Ratio (M‐H, Random, 95% CI)	2.38 [0.23, 24.83]
3.6 Propofol ‐ 20 mg + 1.0 mg/kg/hr	1	44	Risk Ratio (M‐H, Random, 95% CI)	0.16 [0.06, 0.40]
3.7 Midazolam ‐ 1.0 mg + 1.0 mg/hr	1	44	Risk Ratio (M‐H, Random, 95% CI)	0.18 [0.08, 0.40]
4 Vomiting ‐ postoperative	2	145	Risk Ratio (M‐H, Random, 95% CI)	0.09 [0.03, 0.28]
4.1 Propofol ‐ 0.5 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.2 Propofol ‐ 1.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.3 Propofol ‐ 1.5 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.4 Propofol ‐ 2.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.5 Propofol ‐ 10 mg IV ‐ single dose	1	57	Risk Ratio (M‐H, Random, 95% CI)	0.40 [0.02, 9.31]
4.6 Propofol ‐ 2 0 mg + 1.0 mg/kg/hr	1	44	Risk Ratio (M‐H, Random, 95% CI)	0.02 [0.00, 0.37]
4.7 Midazolam ‐ 1.0 mg + 1.0 mg/hr	1	44	Risk Ratio (M‐H, Random, 95% CI)	0.09 [0.02, 0.37]
5 Maternal adverse effects	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.1 Propofol ‐ 0.5 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.2 Propofol ‐ 1.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.3 Propofol ‐ 1.5 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.4 Propofol ‐ 2.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.5 Propofol ‐ 10 mg IV ‐ single dose	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.6 Propofol ‐ 20 mg + 1.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.7 Midazolam ‐ 1.0 mg + 1.0 mg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6 Apgar < 7 at 5 min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.1 Propofol ‐ 0.5 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.2 Propofol ‐ 1.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.3 Propofol ‐ 1.5 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.4 Propofol ‐ 2.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.5 Propofol ‐ 10 mg IV ‐ single dose	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.6 Propofol ‐ 20 mg + 1.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.7 Midazolam ‐ 1.0 mg + 1.0 mg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7 Initiaition of breastfeeding	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.1 Propofol ‐ 0.5 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.2 Propofol ‐ 1.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.3 Propofol ‐ 1.5 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.4 Propofol ‐ 2.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.5 Propofol ‐ 10 mg IV ‐ single dose	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.6 Propofol ‐ 20 mg + 1.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.7 Midazolam ‐ 1.0 mg + 1.0 mg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8 Duration of exclusive breastfeeding	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.1 Propofol ‐ 0.5 mg/kg/hr	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.2 Propofol ‐ 1.0 mg/kg/hr	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.3 Propofol ‐ 1.5 mg/kg/hr	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.4 Propofol ‐ 2.0 mg/kg/hr	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.5 Propofol ‐ 10 mg IV ‐ single dose	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.6 Propofol ‐ 20 mg + 1.0mg/kg/hr	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.7 Midazolam ‐ 1.0 mg + 1.0 mg/kg	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Maternal satisfaction	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.1 Propofol ‐ 0.5 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.2 Propofol ‐ 1.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.3 Propofol ‐ 1.5 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.4 Propofol ‐ 2.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.5 Propofol ‐ 10 mg IV ‐ single dose	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.6 Propofol ‐ 20 mg + 1.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.7 Midazolam ‐ 1.0 mg + 1.0 mg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10 Respiratory depression (not pre‐specified)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.1 Propofol ‐ 0.5 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.2 Propofol ‐ 1.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.3 Propofol ‐ 1.5 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.4 Propofol ‐ 2.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.5 Propofol ‐ 10 mg IV ‐ single dose	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.6 Propofol ‐ 20 mg + 1.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.7 Midazolam ‐ 1.0 mg + 1.0 mg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Nausea ‐ intraoperative	1	80	Risk Ratio (M‐H, Random, 95% CI)	0.29 [0.13, 0.63]
1.1 Propofol (1 mg/kg/hr) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.2 Propofol (1 mg/kg/hr) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.3 Midazolam (2 mg) vs metoclopramide (10 mg)	1	80	Risk Ratio (M‐H, Random, 95% CI)	0.29 [0.13, 0.63]
2 Vomiting ‐ intraoperative	1	80	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.1 Propofol (1 mg/kg/hr) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.2 Propofol (1 mg/kg/hr) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.3 Midazolam (2 mg) vs metoclopramide (10 mg)	1	80	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3 Nausea ‐ postoperative	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.1 Propofol (1 mg/kg/hr) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.2 Propofol (1 mg/kg/hr) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.3 Midazolam (2 mg) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4 Vomiting ‐ postoperative	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.1 Propofol (1 mg/kg/hr) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.2 Propofol (1 mg/kg/hr) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.3 Midazolam (2 mg) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5 Maternal adverse effects	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.1 Propofol (1 mg/kg/hr) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.2 Propofol (1 mg/kg/hr) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.3 Midazolam (2 mg) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6 Apgar < 7 at 5 min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.1 Propofol (1 mg/kg/hr) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.2 Propofol (1 mg/kg/hr) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.3 Midazolam (2 mg) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7 Initiaition of breastfeeding	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.1 Propofol (1 mg/kg/hr) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.2 Propofol (1 mg/kg/hr) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.3 Midazolam (2 mg) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8 Duration of exclusive breastfeeding	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.1 Propofol (1 mg/kg/hr) vs metoclopramide (10 mg)	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.2 Propofol (1 mg/kg/hr) vs droperidol (1.25 mg)	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.3 Midazolam (2 mg) vs metoclopramide (10 mg)	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Maternal satisfaction	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.1 Propofol (1 mg/kg/hr) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.2 Propofol (1 mg/kg/hr) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.3 Midazolam (2 mg) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10 Hypotension (not pre‐specified)	1	80	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.36, 4.32]
10.1 Propofol (1 mg/kg/hr) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.2 Propofol (1 mg/kg/hr) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.3 Midazolam (2mg) vs metoclopramide (10mg)	1	80	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.36, 4.32]
11 Respiratory depression (not pre‐specified)	1	80	Risk Ratio (M‐H, Random, 95% CI)	35.00 [2.18, 562.81]
11.1 Propofol (1 mg/kg/hr) vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11.2 Propofol (1 mg/kg/hr) vs droperidol (1.25 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11.3 Midazolam (2 mg) vs metoclopramide (10 mg)	1	80	Risk Ratio (M‐H, Random, 95% CI)	35.00 [2.18, 562.81]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Nausea ‐ intraoperative	1	60	Risk Ratio (M‐H, Random, 95% CI)	1.07 [0.65, 1.74]
1.1 Midazolam (1 mg/kg/hr) vs propofol (20 mg + 1 mg/kg/hr)	1	60	Risk Ratio (M‐H, Random, 95% CI)	1.07 [0.65, 1.74]
2 Vomiting ‐ intraoperative	1	60	Risk Ratio (M‐H, Random, 95% CI)	2.0 [0.55, 7.27]
2.1 Midazolam (1 mg/kg/hr) vs propofol (20 mg + 1 mg/kg/hr)	1	60	Risk Ratio (M‐H, Random, 95% CI)	2.0 [0.55, 7.27]
3 Nausea ‐ postoperative	1	60	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.37, 4.21]
3.1 Midazolam (1 mg/kg/hr) vs propofol (20 mg + 1 mg/kg/hr)	1	60	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.37, 4.21]
4 Vomiting ‐ postoperative	1	60	Risk Ratio (M‐H, Random, 95% CI)	5.0 [0.25, 99.95]
4.1 Midazolam (1 mg/kg/hr) vs propofol (20 mg + 1 mg/kg/hr)	1	60	Risk Ratio (M‐H, Random, 95% CI)	5.0 [0.25, 99.95]
5 Maternal adverse effects	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.1 Midazolam (1 mg/kg/hr) vs propofol (20 mg + 1 mg/kg/hr)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6 Apgar < 7 at 5 min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.1 Midazolam (1 mg/kg/hr) vs propofol (20 mg + 1 mg/kg/hr)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7 Initiaition of breastfeeding	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.1 Midazolam (1 mg/kg/hr) vs propofol (20 mg + 1 mg/kg/hr)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8 Duration of exclusive breastfeeding	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.1 Midazolam (1 mg/kg/hr) vs propofol (20 mg + 1 mg/kg/hr)	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Maternal satisfaction	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.1 Midazolam (1 mg/kg/hr) vs propofol (20 mg + 1 mg/kg/hr)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10 Respiratory depression (not pre‐specified)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.1 Propofol ‐ 0.5 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.2 Propofol ‐ 1.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.3 Propofol ‐ 1.5 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.4 Propofol ‐ 2.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.5 Propofol ‐ 20 mg + 1.0 mg/kg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10.6 Midazolam ‐ 1.0 mg + 1.0 mg/hr	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Nausea ‐ intraoperative	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	1.67 [0.46, 6.06]
2 Vomiting ‐ intraoperative	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.58, 6.91]
3 Nausea ‐ postoperative	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Vomiting ‐postoperative	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Maternal adverse effects	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Apgar < 7 at 5 min	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Initiation of breastfeeding	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Duration of breastfeeding	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9 Maternal satisfaction	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Nausea ‐ intraoperative	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.23, 4.37]
2 Vomiting ‐ intraoperative	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	1.5 [0.28, 8.04]
3 Nausea ‐ postoperative	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Vomiting ‐ postoperative	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Maternal adverse effects	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Apgar < 7 at 5 min	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Initiation of breastfeeding	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Duration of breastfeeding	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9 Maternal satisfaction	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Nausea ‐ intraoperative	1	180	Risk Ratio (M‐H, Random, 95% CI)	1.71 [0.85, 3.47]
1.1 Nalbuphine (4 mg) vs ondansetron (4 mg)	1	90	Risk Ratio (M‐H, Random, 95% CI)	1.71 [0.63, 4.65]
1.2 Nalbuphine (4 mg) vs ondansetron (8 mg)	1	90	Risk Ratio (M‐H, Random, 95% CI)	1.71 [0.63, 4.65]
2 Vomiting ‐ intraoperative	1	180	Risk Ratio (M‐H, Random, 95% CI)	1.43 [0.47, 4.31]
2.1 Nalbuphine (4 mg) vs ondansetron (4 mg)	1	90	Risk Ratio (M‐H, Random, 95% CI)	1.33 [0.24, 7.56]
2.2 Nalbuphine (4 mg) vs ondansetron (8 mg)	1	90	Risk Ratio (M‐H, Random, 95% CI)	1.5 [0.36, 6.28]
3 Nausea ‐ postoperative	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.1 Nalbuphine (4 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.2 Nalbuphine (4 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4 Vomiting ‐ postoperative	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.1 Nalbuphine (4 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.2 Nalbuphine (4 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5 Maternal adverse effects	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.1 Nalbuphine (4 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.2 Nalbuphine (4 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6 Apgar < 7 at 5 min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.1 Nalbuphine (4 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.2 Nalbuphine (4 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7 Initiaition of breastfeeding	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.1 Nalbuphine (4 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.2 Nalbuphine (4 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8 Duration of exclusive breastfeeding	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.1 Nalbuphine (4 mg) vs ondansetron (4 mg)	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.2 Nalbuphine (4 mg) vs ondansetron (8 mg)	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Maternal satisfaction	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.1 Nalbuphine (4 mg) vs ondansetron (4 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.2 Nalbuphine (4 mg) vs ondansetron (8 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10 Pruritus (not pre‐specified)	1	180	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.79, 1.06]
10.1 Nalbuphine (4 mg) vs ondansetron (4 mg)	1	90	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.75, 1.13]
10.2 Nalbuphine (4 mg) vs ondansetron (8 mg)	1	90	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.74, 1.11]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Nausea ‐ intraoperative	2	294	Risk Ratio (M‐H, Random, 95% CI)	0.78 [0.53, 1.15]
1.1 Oxygen ‐ 4 L/min	1	89	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.56, 1.76]
1.2 Oxygen ‐ 15 L/min	1	205	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.43, 1.03]
2 Vomiting ‐ intraoperative	1	89	Risk Ratio (M‐H, Random, 95% CI)	0.42 [0.14, 1.25]
2.1 Oxygen ‐ 4 L/min	1	89	Risk Ratio (M‐H, Random, 95% CI)	0.42 [0.14, 1.25]
2.2 Oxygen ‐ 15 L/min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3 Nausea ‐ postoperative	1	89	Risk Ratio (M‐H, Random, 95% CI)	0.65 [0.31, 1.36]
3.1 Oxygen ‐ 4 L/min	1	89	Risk Ratio (M‐H, Random, 95% CI)	0.65 [0.31, 1.36]
3.2 Oxygen ‐ 15 L/min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4 Vomiting ‐ postoperative	1	89	Risk Ratio (M‐H, Random, 95% CI)	1.56 [0.40, 6.13]
4.1 Oxygen ‐ 4 L/min	1	89	Risk Ratio (M‐H, Random, 95% CI)	1.56 [0.40, 6.13]
4.2 Oxygen ‐ 15 L/min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5 Maternal adverse effects	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.1 Oxygen ‐ 4 L/min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.2 Oxygen ‐ 15 L/min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6 Apgar < 7 at 5 min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.1 Oxygen ‐ 4 L/min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.2 Oxygen ‐ 15 L/min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7 Initiaition of breastfeeding	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.1 Oxygen ‐ 4 L/min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.2 Oxygen ‐ 15 L/min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8 Duration of exclusive breastfeeding	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.1 Oxygen ‐ 4 L/min	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.2 Oxygen ‐ 15 L/min	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Maternal satisfaction	1	89	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.89, 1.03]
9.1 Oxygen ‐ 4 L/min	1	89	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.89, 1.03]
9.2 Oxygen ‐ 15 L/min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Nausea ‐ intraoperative	6	649	Risk Ratio (M‐H, Random, 95% CI)	0.59 [0.38, 0.90]
1.1 Acupressure	6	649	Risk Ratio (M‐H, Random, 95% CI)	0.59 [0.38, 0.90]
1.2 Acupuncture	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2 Vomiting ‐ intraoperative	6	649	Risk Ratio (M‐H, Random, 95% CI)	0.74 [0.46, 1.18]
2.1 Acupressure	6	649	Risk Ratio (M‐H, Random, 95% CI)	0.74 [0.46, 1.18]
2.2 Acupuncture	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3 Nausea ‐ postoperative	3	429	Risk Ratio (M‐H, Random, 95% CI)	0.83 [0.68, 1.00]
3.1 Acupressure	3	429	Risk Ratio (M‐H, Random, 95% CI)	0.83 [0.68, 1.00]
3.2 Acupuncture	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4 Vomiting ‐ postoperative	3	429	Risk Ratio (M‐H, Random, 95% CI)	0.69 [0.45, 1.06]
4.1 Acupressure	3	429	Risk Ratio (M‐H, Random, 95% CI)	0.69 [0.45, 1.06]
4.2 Acupuncture	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5 Maternal adverse effects	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.1 Acupressure	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.2 Acupuncture	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6 Apgar < 7 at 5 min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.1 Acupressure	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.2 Acupuncture	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7 Initiaition of breastfeeding	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.1 Acupressure	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.2 Acupuncture	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8 Duration of exclusive breastfeeding	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.1 Acupressure	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.2 Acupuncture	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Maternal satisfaction	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.1 Acupressure	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.2 Acupuncture	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10 Anxiety (not pre‐specified)	1	50	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.07, 15.12]
10.1 Acupressure	1	50	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.07, 15.12]
10.2 Acupuncture	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11 Dizziness (not pre‐specified)	1	60	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.07, 15.26]
11.1 Acupressure	1	60	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.07, 15.26]
11.2 Acupuncture	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
12 Hypotension (not pre‐specified)	1	50	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.54, 1.16]
12.1 Acupressure	1	50	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.54, 1.16]
12.2 Acupuncture	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
13 Pruritus (not pre‐specified)	1	60	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.67, 1.99]
13.1 Acupressure	1	60	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.67, 1.99]
13.2 Acupuncture	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Nausea ‐ intraoperative	1	50	Risk Ratio (M‐H, Random, 95% CI)	1.5 [0.48, 4.68]
1.1 Acupressure vs metoclopramide (10 mg)	1	50	Risk Ratio (M‐H, Random, 95% CI)	1.5 [0.48, 4.68]
2 Vomiting ‐ intraoperative	1	50	Risk Ratio (M‐H, Random, 95% CI)	3.0 [0.33, 26.92]
2.1 Acupressure vs metoclopramide (10 mg)	1	50	Risk Ratio (M‐H, Random, 95% CI)	3.0 [0.33, 26.92]
3 Nausea ‐ postoperative	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.1 Acupressure vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4 Vomiting ‐ postoperative	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.1 Acupressure vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5 Maternal adverse effects	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.1 Acupressure vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6 Apgar < 7 at 5 min	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.1 Acupressure vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7 Initiaition of breastfeeding	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.1 Acupressure vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8 Duration of exclusive breastfeeding	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.1 Acupressure vs metoclopramide (10 mg)	0	0	Std. Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Maternal satisfaction	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9.1 Acupressure vs metoclopramide (10 mg)	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10 Anxiety (not pre‐specified)	1	50	Risk Ratio (M‐H, Random, 95% CI)	0.25 [0.03, 2.08]
10.1 Acupressure vs metoclopramide (10 mg)	1	50	Risk Ratio (M‐H, Random, 95% CI)	0.25 [0.03, 2.08]
11 Hypotension (not pre‐specified)	1	50	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.58, 1.34]
11.1 Acupressure vs metoclopramide (10 mg)	1	50	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.58, 1.34]

Methods	RCT.
Participants	74 women 18‐40 years undergoing elective CS at term under spinal anaesthesia, ASA 1‐2, no significant maternal medical conditions.
Interventions	Intervention: 5‐HT₃antagonist (A) Ondansetron IV ‐ 4 mg. N = 36. Comparison: Placebo Normal saline 2 mL. N = 38.
Outcomes	Nausea ‐ presence/absence and severity. Vomiting ‐ severity, frequency.
Notes	Setting: Texas, USA.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random number table.
Allocation concealment (selection bias)	Low risk	Syringes produced by pharmacy.
Blinding (performance bias and detection bias)   All outcomes	Low risk	Double blind.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	8 participants withdrawn, 5 withdrew consent, 2 had an exclusion criteria (oesophageal reflux), 1 failed spinal converted to GA. Data not re‐included.
Selective reporting (reporting bias)	Unclear risk	We did not assess the trial protocol.
Other bias	Low risk	Mild increase in BP in the control group, not significant.

Methods	Individual RCT.
Participants	ASA 1‐2, uncomplicated pregnancy, elective CS under spinal.
Interventions	Intervention 1: Steroid + sedative (C+F) Dexamethasone 8 mg + 2 mg midazolam post‐cord clamping. N = 80. Intervention 2: Steroid + 5‐HT₃ antagonist (C+A) Dexamethasone 8 mg + 2 mg granisetron post‐cord clamping. N = 80. Comparison: Placebo Saline. N = 80.
Outcomes	Nausea score, vomiting, antiemetic use, drowsiness, headache, blurred vision, allergy, women's satisfaction.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation code.
Allocation concealment (selection bias)	Unclear risk	No information given.
Blinding (performance bias and detection bias)   All outcomes	Low risk	Drugs prepared by anaesthetist not otherwise involved in the conduct of women's care or outcome assessment.
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	None described.
Selective reporting (reporting bias)	Unclear risk	We did not assess the trial protocol.
Other bias	Low risk	Nil apparent.

Study	Reason for exclusion
Abboud 1984	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Ackerman 1987	Study assessed drugs given for analgesia, not for prevention of nausea and vomiting.
Ackerman 1988	Study assessed drugs given for analgesia, not for prevention of nausea and vomiting.
Ackerman 1989	Study assessed drugs given for analgesia, not for prevention of nausea and vomiting.
Atkinson 1980	Not an RCT.
Avramovic 1979	Study assesses an intervention given to reduce abdominal discomfort, not to reduce nausea and vomiting.
Ayorinde 2001	Study assessing drugs given for blood pressure control, not prevention of nausea and vomiting.
Belzarena 1993	Study assessing drugs given for blood pressure control, not prevention of nausea and vomiting.
Bifarini 1990	Following translation, study assessed drugs given for aspiration prophylaxis, not for prevention of nausea and vomiting.
Bifarini 1992	Following translation, study assessed drugs given for aspiration prophylaxis, not for prevention of nausea and vomiting.
Boschi 1984	Not an RCT; women were divided into groups.
Brock‐Utne 1989	Not an RCT; women were allocated to groups.
Bylsma‐Howell 1983	Study was assessing the effect of metoclopramide on gastric emptying and aspiration prophylaxis not for reducing nausea and vomiting.
Chan 1992	Study was a quasi‐RCT.
Chan 1997	Study assessing drugs given for blood pressure control, not prevention of nausea and vomiting.
Chen 2005	Not an RCT; women were assigned to groups.
Chung 1998	Study assessed drugs given for analgesia, not for prevention of nausea and vomiting.
Cohen 1984	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting. No information on how women were allocated to groups.
Colman 1988	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting. No information on how women were allocated to groups.
Connelly 1997	Study assessed drugs given for analgesia, not for prevention of nausea and vomiting.
Cooper 2002	Study assessed drugs given for manipulation of blood pressure, not for prevention of nausea and vomiting.
Cowan 2002	Study assessed drugs given for analgesia, not for prevention of nausea and vomiting.
Dahlgren 1997	Study assessed drugs given for analgesia, not for prevention of nausea and vomiting.
Dailey 1988	Studied effect of cimetidine and ranitidine on lignocaine concentrations in the blood.
Datta 1982	Study assessing drugs given for blood pressure control, not prevention of nausea and vomiting. No information on how women were allocated to groups.
Dewan 1982	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting. Not described as an RCT; women were assigned to groups.
Dewan 1984	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Dewan 1985	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Dundee 1979	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting. No information on how women were allocated to groups.
Elhakim 2005	Study assess medication given for the purpose of pain relief not reduction of nausea and vomiting.
Ewart 1990	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Fan 1994	Study assessed drugs given for analgesia, not for prevention of nausea and vomiting.
Flynn 1989a	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting. Study of effect of 400 mg cimetidine or 150 mg ranitidine or placebo on plasma levels of bupivacaine at caesarean section.
Flynn 1989b	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting. Study of effect of 200 mg cimetidine plasma levels of lignocaine at caesarean section.
Flynn 1989c	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting. Study of effect of 400 mg cimetidine or 150 mg ranitidine or placebo on plasma levels of lidocaine at caesarean section.
Fogarty 1992	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Frank 1984	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Freeman 1999	Study assessed the use of sodium citrate (normally used for reducing aspiration pneumonitis during general anaesthesia) for spinal anaesthesia at caesarean section. Although the study assessed nausea and vomiting, this was not the primary purpose.
Ghods 2005a	Intervention was given in the postoperative period for prevention of nausea and vomiting. Protocol includes studies only where interventions were given during the caesarean section.
Gutsche 1976	Study assessing drugs given for blood pressure control, not prevention of nausea and vomiting.
Han 2007	Study is assessing different routes of administration, not the efficacy of the medication itself.
Hildyard 2000	Data presented graphically, but without numerical results. Wrote to authors (June 2008), no response.
Hodgkinson 1983	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting. Not ITT analysis for primary outcome and high exclusion rates post randomisation.
Holdsworth 1974	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting. Not an RCT.
Holdsworth 1978	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting. Quasi‐RCT.
Holdsworth 1980	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting. Not an RCT. Assessing women's positions for GA.
Hong 2004	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Hunt 1989	Study assessed drugs given for analgesia, not for prevention of nausea and vomiting.
Husemeyer 1980	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Iqbal 2000	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Ishiyama 2001	Study assessed drugs given for analgesia, not for prevention of nausea and vomiting.
Jasson 1989a	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Kang 1982	Study assessing drugs given for blood pressure control, not prevention of nausea and vomiting.
Kangas‐Saarela 1990	Study assessing drugs given for blood pressure control, not prevention of nausea and vomiting.
Karamanlioglu 1995	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
King 1998	Study assessing drugs given for blood pressure control, not prevention of nausea and vomiting.
Kjaer 2006	In this review, we are assessing the efficacy of medication given for the specific purpose of reducing nausea and vomiting at caesarean section. In this study, the medication is given for the purpose of aspiration prophylaxis, and the incidence of emetic side effects is being studied.
Kocamanoglu 2005	Study looked at prevention of postoperative nausea and vomiting after general anaesthesia for cesarean section not regional anaesthesia.
Lim 1991	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting. Not randomised.
Lim 2001a	Data presented as combined nausea and vomiting. Wrote to authors July 09, unable to contact.
Lim 2001b	Data presented as combined nausea and vomiting. Wrote to authors July 09, unable to contact.
Lin 1996	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Loughrey 2002	Study assessing drugs given for blood pressure control, not prevention of nausea and vomiting.
McCaughey 1981	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting. Not a randomised study.
Mebazaa 2003	Study assessing the anaesthetic drug, not intervention for prevention of nausea and vomiting.
Murphy 1984	Study assessed interventions on gastric emptying for reducing nausea and vomiting.
Ngan 2000	Study assessing drugs given for blood pressure control, not prevention of nausea and vomiting.
Ngan 2001	Study assessing drugs given for blood pressure control, not prevention of nausea and vomiting.
Ngan 2004a	Study assessing drugs given for blood pressure control, not prevention of nausea and vomiting.
Ngan 2004b	Study assessing drugs given for blood pressure control, not prevention of nausea and vomiting.
O'Sullivan 1985	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
O'Sullivan 1988	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Olsen 1994	Study assessing interventions for blood pressure control, not prevention of nausea and vomiting.
Ormezzano 1990	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Orr 1993	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Osman 1995	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting. No information on the number of women in each group.
Ostheimer 1982	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Ouyang 2002	Study assessed drugs given for analgesia, not for prevention of nausea and vomiting.
Ozkan 2000	Study investigates medication given for aspiration prophylaxis not nausea and vomiting prevention.
Palmer 1991	In this review, we are assessing the efficacy of medication given for the specific purpose of reducing nausea and vomiting at caesarean section. In this study, the medication is given for the purpose of aspiration prophylaxis, and the incidence of emetic side effects is being studied.
Palmer 1995	Study assessing fentanyl for pain relief.
Pellegrini 2001	Study assessed drugs given with regard to analgesia, not for prevention of nausea and vomiting. Opioid antagonists were not included in the protocol as possible interventions for reducing nausea and vomiting.
Pickering 1980	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Prakash 2006	Study assessed drugs given for analgesia, not for prevention of nausea and vomiting.
Qvist 1983	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting. Not randomised.
Qvist 1985	Studied effect of placental transfer of cimetidine given prior to induction of anaesthesia.
Ramanathan 1983	Study assessing interventions given for blood pressure control, not prevention of nausea and vomiting.
Ramin 1994	Study assessing drugs given for blood pressure control, not prevention of nausea and vomiting.
Rocke 1994	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Rout 1992	Study assessing drugs given for blood pressure control, not prevention of nausea and vomiting.
Rout 1993	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Rudra 2004b	Assesses medication given predominantly for the purpose of achieving surgical analgesia, not for the purpose of reducing nausea and vomiting.
Santos 1984	Study did not appear to randomise women to each intervention.
Sen 2001	Study assessed drugs given for analgesia, not for prevention of nausea and vomiting.
Seyedhejazi 2007	Assess medication given for the purpose of achieving surgical anaesthesia, not for the purpose of reducing nausea and vomiting.
Shende 1998	Study assessed drugs given for analgesia, not for prevention of nausea and vomiting.
Shifman 2010	The study compared 2 different doses of the same drug (4 mg versus 12 mg dexamethasone).
Siddik‐Sayyid 2002	Study assessed drugs given for analgesia, not for prevention of nausea and vomiting.
Stuart 1996	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting. Not ITT.
Tanaka 2007	Not an RCT but a dose response study.
Taylor 1966	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting. Not an RCT.
Tettambel 1983	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting. Quasi‐RCT.
Tripathi 1995	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Tryba 1983	Assesses medication given for the purpose of aspiration prophylaxis not nausea and vomiting.
Tshibangu 2010	The study assessed the impact of intrathecal morphine given primarily for postoperative analgesia.
Vercauteren 2000	Study assessing drugs given for blood pressure control, not prevention of nausea and vomiting.
von Braun 1994	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting. Number of women in each group not reported.
Wig 1987	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Yau 1992	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Zoroglu 1999	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.
Zue 1999	Study assessed interventions for reducing aspiration pneumonitis at caesarean section not for reducing nausea and vomiting.

PERMALINK

Interventions for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

James D Griffiths

Gillian ML Gyte

Shantini Paranjothy

Heather C Brown

Hannah K Broughton

Jane Thomas

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Background

Description of the condition

Description of the intervention

How the intervention might work

Pharmacological interventions

Non‐pharmacological interventions

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

(1) Sequence generation (checking for possible selection bias)

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

(3) Blinding (checking for possible performance bias)

(4) Incomplete outcome data (checking for possible attrition bias through withdrawals, dropouts, protocol deviations)

(5) Selective reporting bias

(6) Other sources of bias

(7) Overall risk of bias

Measures of treatment effect

Dichotomous data

Continuous data

Unit of analysis issues

Cluster‐randomised trials

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Results

Description of studies

Results of the search

Included studies

Elective versus emergency caesarean sections

Excluded studies

Risk of bias in included studies

1.

2.

Allocation

Blinding

Incomplete outcome data

Selective reporting

Other potential sources of bias

Effects of interventions

A. 5‐HT3 receptor antagonists (Comparisons 1, 2, 3)

1) 5‐HT3 receptor antagonists (A) versus placebo (10 studies, 980 women, Comparison 1)

Primary outcomes

Intraoperative nausea

1.1. Analysis.

Intraoperative vomiting

1.2. Analysis.

A. 5‐HT₃ receptor antagonists (Comparisons 1, 2, 3)

1) 5‐HT₃ receptor antagonists (A) versus placebo (10 studies, 980 women, Comparison 1)

2) 5‐HT₃ antagonists (A) versus other 5 HT₃ antagonists (A) (no studies, Comparison 2)

3) 5‐HT₃ antagonist (A) ‐ ondansetron 8 mg versus 4 mg (one study, 120 women, Comparison 3)

2) Dopamine antagonists (B) versus 5‐HT₃ antagonists (A) (four studies, 307 women, Comparison 5)

2) Corticosteroids (C) versus 5‐HT₃ antagonists (A) (no studies, Comparison 8)

2) Antihistamines (D) versus 5 HT₃ antagonists (A) (no studies, Comparison 15)

Trial name or title	Study of the effect of intramuscular ephedrine on the incidence of nausea and vomiting during elective cesarean section.
Methods	RCT.
Participants	Women having an elective caesarean section under spinal anaesthesia.
Interventions	Ephedrine ‐ 25 mg, IM vs placebo ‐ saline.
Outcomes	Nausea, vomiting, blood pressure, cord blood gasses.
Starting date	February 2007.
Contact information	Rachel Brody, RN. +1 212 746 2952; rab9029@med.cornell.edu Sharon Abremovitz, MD. +1 212 746 2679; sea2003@med.cornell.edu
Notes	ClinicalTrials.gov identifier: NCT00432991