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

Summary of findings 1. 5‐HT3 antagonists compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
5‐HT3 antagonists compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section
Patient or population: women undergoing regional anaesthesia for caesarean section Setting: hospitals across low‐, middle‐ and high‐income countries Intervention: 5‐HT3 antagonists Comparison: placebo
Outcomes	Risk with placebo	Risk with 5‐HT3 antagonists	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Nausea ‐ intraoperative	Study population		RR 0.55 (0.42 to 0.71)	1419 (12 RCTs)	⊕⊕⊝⊝ LOW ^{1 2}
Nausea ‐ intraoperative	479 per 1000	263 per 1000 (201 to 340)	RR 0.55 (0.42 to 0.71)	1419 (12 RCTs)	⊕⊕⊝⊝ LOW ^{1 2}
Vomiting ‐ intraoperative	Study population		RR 0.46 (0.29 to 0.73)	1414 (11 RCTs)	⊕⊝⊝⊝ VERY LOW ^{3 4 5}
Vomiting ‐ intraoperative	241 per 1000	111 per 1000 (70 to 176)	RR 0.46 (0.29 to 0.73)	1414 (11 RCTs)	⊕⊝⊝⊝ VERY LOW ^{3 4 5}
Nausea ‐ postoperative	Study population		RR 0.40 (0.30 to 0.54)	1340 (10 RCTs)	⊕⊕⊕⊝ MODERATE ⁶
Nausea ‐ postoperative	338 per 1000	135 per 1000 (101 to 183)	RR 0.40 (0.30 to 0.54)	1340 (10 RCTs)	⊕⊕⊕⊝ MODERATE ⁶
Vomiting ‐ postoperative	Study population		RR 0.47 (0.31 to 0.69)	1450 (10 RCTs)	⊕⊕⊝⊝ LOW ^{5 7}
Vomiting ‐ postoperative	228 per 1000	107 per 1000 (71 to 157)	RR 0.47 (0.31 to 0.69)	1450 (10 RCTs)	⊕⊕⊝⊝ LOW ^{5 7}
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
¹ Downgrade 1 for risk of bias: > 90% of data comes from studies with unclear selection bias ² Downgrade 1 for inconsistency: there may be substantial heterogeneity I² = 65%, Chi² P = 0.0009. 3 Downgrade 1 for risk of bias: > 80% of data comes from studies with unclear selection bias 4 Downgrade 1 for inconsistency: there may be substantial heterogeneity I² = 58%, Chi² P = 0.008. 5 Downgrade 1 for publication bias: there is some evidence of possible publication bias in the funnel plot. 6 Downgrade 1 for risk of bias: > 65% of data comes from studies with unclear selection bias 7 Downgrade 1 for risk of bias: > 70% of data comes from studies with unclear selection bias

Summary of findings 2. Dopamine antagonists compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Dopamine antagonists compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section
Patient or population: women undergoing regional anaesthesia for caesarean section Setting: hospitals across low‐, middle‐ and high‐income countries Intervention: dopamine antagonists Comparison: placebo
Outcomes	Risk with placebo	Risk with dopamine antagonists (B)	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Nausea ‐ intraoperative	Study population		RR 0.38 (0.27 to 0.52)	1180 (15 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2}
Nausea ‐ intraoperative	444 per 1000	169 per 1000 (120 to 231)	RR 0.38 (0.27 to 0.52)	1180 (15 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2}
Vomiting ‐ intraoperative	Study population		RR 0.41 (0.28 to 0.60)	942 (12 RCTs)	⊕⊕⊝⊝ LOW ¹
Vomiting ‐ intraoperative	211 per 1000	87 per 1000 (59 to 127)	RR 0.41 (0.28 to 0.60)	942 (12 RCTs)	⊕⊕⊝⊝ LOW ¹
Nausea ‐ postoperative	Study population		RR 0.61 (0.48 to 0.79)	601 (7 RCTs)	⊕⊕⊝⊝ LOW ¹
Nausea ‐ postoperative	393 per 1000	240 per 1000 (189 to 311)	RR 0.61 (0.48 to 0.79)	601 (7 RCTs)	⊕⊕⊝⊝ LOW ¹
Vomiting ‐ postoperative	Study population		RR 0.63 (0.44 to 0.92)	860 (9 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 3}
Vomiting ‐ postoperative	264 per 1000	167 per 1000 (116 to 243)	RR 0.63 (0.44 to 0.92)	860 (9 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 3}
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
¹ Downgrade 2 for risk of bias: all the data come from studies with unclear risk of selection bias. ² Downgrade 1 for inconsistency. Moderate to substantial heterogeneity, I² = 54%, Chi² P = 0.005 ³ Downgrade 1 for publication bias: evidence of some publication bias in the funnel plot

Summary of findings 3. Corticosteroids compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Corticosteroids compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section
Patient or population: women undergoing regional anaesthesia for caesarean section Setting: hospitals across low‐, middle‐ and high‐income countries Intervention: corticosteroids Comparison: placebo
Outcomes	Risk with placebo	Risk with corticosteroids (C)	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Nausea ‐ intraoperative	Study population		RR 0.56 (0.37 to 0.83)	609 (6 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2}
Nausea ‐ intraoperative	403 per 1000	226 per 1000 (149 to 334)	RR 0.56 (0.37 to 0.83)	609 (6 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2}
Vomiting ‐ intraoperative	Study population		RR 0.52 (0.31 to 0.87)	609 (6 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 3}
Vomiting ‐ intraoperative	141 per 1000	73 per 1000 (44 to 123)	RR 0.52 (0.31 to 0.87)	609 (6 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 3}
Nausea ‐ postoperative	Study population		RR 0.59 (0.49 to 0.73)	733 (6 RCTs)	⊕⊕⊕⊝ MODERATE ⁴
Nausea ‐ postoperative	491 per 1000	290 per 1000 (240 to 358)	RR 0.59 (0.49 to 0.73)	733 (6 RCTs)	⊕⊕⊕⊝ MODERATE ⁴
Vomiting ‐ postoperative	Study population		RR 0.68 (0.49 to 0.95)	793 (7 RCTs)	⊕⊕⊝⊝ LOW ^{5 6}
Vomiting ‐ postoperative	355 per 1000	241 per 1000 (174 to 337)	RR 0.68 (0.49 to 0.95)	793 (7 RCTs)	⊕⊕⊝⊝ LOW ^{5 6}
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
¹ Downgrade 2 for risk of bias: all the data comes from studies with unclear risk of selection bias ² Downgrade 1 for inconsistency: there is moderate heterogeneity I² = 50% and Chi² P = 0.06. ³ Downgrade 1 for imprecision: Wide CI close to line of no difference. Only 61 events out of 609 women. ⁴ Downgrade 1 for risk of bias: 69% of data comes from studies with unclear risk of selection bias. ⁵ Downgrade 1 for risk of bias: 83%% of data comes from studies with unclear risk of selection bias. ⁶ Downgrade 1 for inconsistency: may show moderate heterogeneity. I² = 52%. Chi² P = 0.03.

Summary of findings 4. Antihistamines compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Antihistamines compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section
Patient or population: preventing nausea and vomiting Setting: in women undergoing regional anaesthesia for caesarean section Intervention: antihistamines Comparison: placebo
Outcomes	Risk with Placebo	Risk with antihistamines	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Nausea ‐ intraoperative	Study population		RR 0.99 (0.47 to 2.11)	149 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{1 2}
Nausea ‐ intraoperative	155 per 1000	153 per 1000 (73 to 327)	RR 0.99 (0.47 to 2.11)	149 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{1 2}
Vomiting ‐ intraoperative	Study population		not estimable	149 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{1 3}	Only one RCT with no intraoperative vomiting events
Vomiting ‐ intraoperative	0 per 1000	0 per 1000 (0 to 0)	not estimable	149 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{1 3}	Only one RCT with no intraoperative vomiting events
Nausea ‐ postoperative	Study population		RR 0.44 (0.30 to 0.64)	514 (4 RCTs)	⊕⊕⊝⊝ LOW ⁴
Nausea ‐ postoperative	309 per 1000	136 per 1000 (93 to 198)	RR 0.44 (0.30 to 0.64)	514 (4 RCTs)	⊕⊕⊝⊝ LOW ⁴
Vomiting ‐ postoperative	Study population		RR 0.48 (0.29 to 0.81)	333 (3 RCTs)	⊕⊝⊝⊝ VERY LOW ^{4 5}
Vomiting ‐ postoperative	189 per 1000	91 per 1000 (55 to 153)	RR 0.48 (0.29 to 0.81)	333 (3 RCTs)	⊕⊝⊝⊝ VERY LOW ^{4 5}
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
¹ Downgrade 2 for risk of bias; only one study with unclear risk of bias across 6 domains and high risk for one domain ² Downgrade 2 for imprecision: wide CI, only 23 events out of 149 women in a single study. ³ Downgrade 2 for imprecision: there are no events. ⁴ Downgrade 2 for risk of bias: all data from studies with unclear risk of selection bias ⁵ Downgrade 1 for imprecision: only 45 events out of 333 women.

Summary of findings 5. Anticholinergics compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Anticholinergics compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section
Patient or population: women undergoing regional anaesthesia for caesarean section Setting: hospitals across low‐, middle‐ and high‐income countries Intervention: anticholinergics Comparison: placebo
Outcomes	Risk with placebo	Risk with anticholinergics	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Nausea ‐ intraoperative	Study population		RR 0.67 (0.51 to 0.87)	453 (4 RCTs)	⊕⊕⊝⊝ LOW ¹
Nausea ‐ intraoperative	665 per 1000	446 per 1000 (339 to 579)	RR 0.67 (0.51 to 0.87)	453 (4 RCTs)	⊕⊕⊝⊝ LOW ¹
Vomiting ‐ intraoperative	Study population		RR 0.79 (0.40 to 1.54)	453 (4 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2 3}
Vomiting ‐ intraoperative	304 per 1000	240 per 1000 (122 to 468)	RR 0.79 (0.40 to 1.54)	453 (4 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2 3}
Nausea ‐ postoperative	Study population		‐	(0 RCTs)	‐
Nausea ‐ postoperative	see comment	see comment	‐	(0 RCTs)	‐
Vomiting ‐ postoperative	Study population		RR 0.55 (0.41 to 0.74)	161 (1 RCT)	⊕⊕⊝⊝ LOW ^{4 5}
Vomiting ‐ postoperative	728 per 1000	401 per 1000 (299 to 539)	RR 0.55 (0.41 to 0.74)	161 (1 RCT)	⊕⊕⊝⊝ LOW ^{4 5}
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
¹ Downgrade 2 for risk of bias: all the data from studies with unclear selection bias. ² Downgrade 1 for inconsistency: there may be moderate heterogeneity I² = 52% Chi² P = 0.10. ³ Downgrade 1 for imprecision: wide CI, crossing the line of no difference. 120 events out of 453 women participants. ⁴ Downgrade 1 for risk of bias: only one study with unclear allocation concealment but adequate sequence generation ⁵ Downgrade 1 for imprecision: a single study shows a wide confidence interval away from the line of no difference but with 91 events out of 161 women participants.

Summary of findings 6. Sedatives compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Sedatives compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section
Patient or population: women undergoing regional anaesthesia for caesarean section Setting: hospitals across low‐, middle‐ and high‐income countries Intervention: sedatives Comparison: placebo
Outcomes	Risk with placebo	Risk with sedatives (F)	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Nausea ‐ intraoperative	Study population		RR 0.65 (0.51 to 0.82)	593 (8 RCTs)	⊕⊕⊕⊝ MODERATE ¹
Nausea ‐ intraoperative	375 per 1000	244 per 1000 (191 to 308)	RR 0.65 (0.51 to 0.82)	593 (8 RCTs)	⊕⊕⊕⊝ MODERATE ¹
Vomiting ‐ intraoperative	Study population		RR 0.35 (0.24 to 0.52)	593 (8 RCTs)	⊕⊕⊕⊝ MODERATE ²
Vomiting ‐ intraoperative	294 per 1000	103 per 1000 (71 to 153)	RR 0.35 (0.24 to 0.52)	593 (8 RCTs)	⊕⊕⊕⊝ MODERATE ²
Nausea ‐ postoperative	Study population		RR 0.25 (0.09 to 0.71)	145 (2 RCTs)	⊕⊝⊝⊝ VERY LOW ^{3 4}
Nausea ‐ postoperative	441 per 1000	110 per 1000 (40 to 313)	RR 0.25 (0.09 to 0.71)	145 (2 RCTs)	⊕⊝⊝⊝ VERY LOW ^{3 4}
Vomiting ‐ postoperative	Study population		RR 0.09 (0.03 to 0.28)	145 (2 RCTs)	⊕⊕⊝⊝ LOW ⁵
Vomiting ‐ postoperative	356 per 1000	32 per 1000 (11 to 100)	RR 0.09 (0.03 to 0.28)	145 (2 RCTs)	⊕⊕⊝⊝ LOW ⁵
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
¹ Downgrade 1 for risk of bias: 56% of data from studies with low risk of selection bias. 2 Downgrade 1 for risk of bias: 75% of data were from studies with unclear selection bias. ³ Downgrade 1 for inconsistency: moderate heterogeneity. I² = 58%. Chi² P = 0.09. ⁴ Downgrade 2 for imprecision: low number of events ‐ 37 and low number of participants 145. Wide CI though a reasonable distance from line of no difference. ⁵ Downgrade 2 for imprecision: low number of events ‐ 23 and low number of participants 145. Wide CI but a good distance from the line of no difference although the data of high effectiveness comes from just one study of 44 women.

Summary of findings 7. Opioid antagonists compared to placebo for preventing nausea and vomiting

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Opioid antagonists compared to placebo for preventing nausea and vomiting
Patient or population: preventing nausea and vomiting Setting: in women undergoing regional anaesthesia for caesarean section Intervention: opioid antagonists Comparison: placebo
Outcomes	Risk with placebo	Risk with opioid antagonists	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Nausea ‐ intraoperative	Study population		‐	(0 studies)	‐
Nausea ‐ intraoperative	see comment	see comment	‐	(0 studies)	‐
Vomiting ‐ intraoperative	Study population		‐	(0 study)	‐
Vomiting ‐ intraoperative	see comment	see comment	‐	(0 study)	‐
Nausea ‐ postoperative	Study population		RR 0.75 (0.39 to 1.45)	120 (1 RCT)	⊕⊕⊝⊝ LOW ¹
Nausea ‐ postoperative	267 per 1000	200 per 1000 (104 to 387)	RR 0.75 (0.39 to 1.45)	120 (1 RCT)	⊕⊕⊝⊝ LOW ¹
Vomiting ‐ postoperative	Study population		RR 1.25 (0.35 to 4.43)	120 (1 RCT)	⊕⊕⊝⊝ LOW ²
Vomiting ‐ postoperative	67 per 1000	83 per 1000 (23 to 295)	RR 1.25 (0.35 to 4.43)	120 (1 RCT)	⊕⊕⊝⊝ LOW ²
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
¹ Downgrade 2 for imprecision. Only 28 events out of 120 women in one study. Wide CI crossing line of no difference. ² Downgrade 2 for imprecision. Only 9 events out of 120 women in one study. Wide CI crossing line of no difference.

Summary of findings 8. Acupressure/acupuncture compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Acupressure/acupuncture compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section
Patient or population: women undergoing regional anaesthesia for caesarean section Setting: hospitals across low‐, middle‐ and high‐income countries Intervention: acupressure/acupuncture Comparison: placebo
Outcomes	Risk with placebo	Risk with acupressure/acupuncture (K)	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Nausea ‐ intraoperative	Study population		RR 0.55 (0.41 to 0.74)	1221 (9 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2}
Nausea ‐ intraoperative	466 per 1000	256 per 1000 (191 to 345)	RR 0.55 (0.41 to 0.74)	1221 (9 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2}
Vomiting ‐ intraoperative	Study population		RR 0.52 (0.33 to 0.80)	1221 (9 RCTs)	⊕⊕⊝⊝ LOW ¹
Vomiting ‐ intraoperative	236 per 1000	123 per 1000 (78 to 189)	RR 0.52 (0.33 to 0.80)	1221 (9 RCTs)	⊕⊕⊝⊝ LOW ¹
Nausea ‐ postoperative	Study population		RR 0.46 (0.27 to 0.75)	1069 (7 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 3}
Nausea ‐ postoperative	411 per 1000	189 per 1000 (111 to 308)	RR 0.46 (0.27 to 0.75)	1069 (7 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 3}
Vomiting ‐ postoperative	Study population		RR 0.52 (0.34 to 0.79)	1069 (7 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 4}
Vomiting ‐ postoperative	302 per 1000	157 per 1000 (103 to 239)	RR 0.52 (0.34 to 0.79)	1069 (7 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 4}
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
¹ Downgrade 2 for risk of bias: all the data comes from studies which are unclear risk of selection bias. ² Downgrade 1 for inconsistency: substantial heterogeneity I² = 69% Chi² P = 0.0010. ³ Downgrade 1 for inconsistency: substantial heterogeneity. I² = 81% and Chi² P = < 0.0001. Could be downgrade by 2, borderline decision ⁴ Downgrade 1 for inconsistency: moderate heterogeneity. I² = 62% and Chi² P = 0.01.

Summary of findings 9. Ginger compared to placebo for preventing nausea and vomiting

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Ginger compared to placebo for preventing nausea and vomiting
Patient or population: preventing nausea and vomiting Setting: in women undergoing regional anaesthesia for caesarean section? Intervention: ginger Comparison: placebo
Outcomes	Risk with placebo	Risk with ginger	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Nausea ‐ intraoperative	Study population		RR 0.66 (0.36 to 1.21)	331 (2 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2 3}
Nausea ‐ intraoperative	586 per 1000	387 per 1000 (211 to 709)	RR 0.66 (0.36 to 1.21)	331 (2 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2 3}
Vomiting ‐ intraoperative	Study population		RR 0.62 (0.38 to 1.00)	331 (2 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 4}
Vomiting ‐ intraoperative	408 per 1000	253 per 1000 (155 to 408)	RR 0.62 (0.38 to 1.00)	331 (2 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 4}
Nausea ‐ postoperative	Study population		RR 0.63 (0.22 to 1.77)	92 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{5 6}
Nausea ‐ postoperative	174 per 1000	110 per 1000 (38 to 308)	RR 0.63 (0.22 to 1.77)	92 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{5 6}
Vomiting ‐ postoperative	Study population		RR 0.20 (0.02 to 1.65)	92 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{5 7}
Vomiting ‐ postoperative	109 per 1000	22 per 1000 (2 to 179)	RR 0.20 (0.02 to 1.65)	92 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{5 7}
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
¹ Downgrade 2 for risk of bias: Only 2 studies both with unclear risk of selection bias ² Downgrade 1 for inconsistency. Substantial heterogeneity. I² = 74%, Chi² P = 0.05 ³ Downgrade 1 for imprecision. Very wide CI crossing the line of no difference. 170 events and 331 women participants ⁴ Downgrade 1 for imprecision: Wide CI. meeting the line of no difference. 112 events and 331 women participating ⁵ Downgrade 2 for risk of bias: Only 1 study with unclear risk of selection bias ⁶ Downgrade 2 for imprecision: Wide CI. Only 6 events out of 92 women ⁷ Downgrade 2 for imprecision: Wide CI crosses line of no difference. 5 events only and just 92 women included

Background

Nausea and vomiting are unpleasant symptoms commonly experienced by pregnant women during caesarean section under regional anaesthesia, and may also occur in the postpartum period following a caesarean under either regional or general anaesthesia. Nausea and vomiting around the time of the birth of a baby can be uncomfortable and distressing for the woman. If vomiting occurs intraoperatively during the caesarean under regional anaesthesia, it offers significant challenges to the operating surgeon, may increase the duration of surgery, the risk of bleeding, the risk of inadvertent surgical trauma and the risk of aspiration of gastric contents (Paranjothy 2014).

Caesarean section is one of the most commonly performed surgical procedures. World Health Organization data indicate that worldwide around 140 million babies are born each year. Globally caesarean rates vary widely; from less than 5% of births in low‐income countries (e.g. Zimbabwe) to above 30% in high‐income countries (e.g. Germany) (Boerma 2018) and in one study of NHS trusts the caesarean section rate ranged from 14.9% to 32.1% (Bragg 2010). These figures suggest the number of caesareans worldwide is at least 10 to 20 million per year. Caesarean section rates have also risen considerably in many countries in recent years and this trend is continuing (Chen 2018). There are several reasons why general anaesthesia should be avoided if possible in the later stages of pregnancy, and most women want to be awake for the birth of their child, so except where there is a contraindication or in some emergency situations, most caesareans are carried out under regional anaesthesia using spinal or epidural techniques.

Many factors can contribute to the development of nausea and vomiting at caesarean section. While some causes of nausea and vomiting are common to other non‐obstetric surgical procedures, many are unique to caesarean sections. There is a body of published literature, including consensus guidelines (Gan 2019), to help anaesthetists reduce the risk of postoperative nausea and vomiting. However, because some of the underlying causes of nausea and vomiting during caesarean section may be specific to the procedure, it is reasonable to assume that the choice of effective treatments may also differ from other types of surgery. Anaesthetists need to consider specific evidence in this setting. Since all interventions are associated with increased healthcare costs and potential risks to the woman (and potentially to the neonate, via either placental transfer or breastfeeding) it is clear that antiemetic use should be evidence‐based.

In some countries, for example in the United Kingdom, there is a recommendation that to reduce nausea and vomiting at caesarean delivery the routine administration of drugs (antiemetics ‐ drugs to reduce nausea and vomiting) or acupressure should be considered (NICE 2011). However, many anaesthetists may choose to give antiemetic medication only when nausea and vomiting occur (treatment) rather than as prophylaxis (prevention). It is not known to what extent medications which have been shown to be efficacious as treatment are also efficacious as prophylaxis (and vice versa).

The aim of this review is to assess the effectiveness of interventions to prevent nausea and vomiting given as prophylaxis during caesarean section under regional anaesthesia. Future reviews will be required to assess studies on interventions for treatment (rather than prevention) of nausea and vomiting, procedures performed as emergencies and caesarean deliveries performed under general anaesthesia.

Description of the condition

Nausea is the unpleasant subjective urge to vomit, while vomiting is the physiological process associated with propulsive abdominal muscular spasms leading to the expulsion of gastric contents. Retching involves the same propulsive muscular spasms as vomiting but without the expulsion of any gastric contents.

There are several aetiological factors (factors causing or contributing to the development of a condition or disease) which may contribute to the development of nausea and vomiting during caesarean section. These may include the following.

Haemodynamic changes (i.e. changes in blood flow) such as hypotension (low blood pressure ‐ a frequent side effect of regional anaesthesia, Chooi 2017) and reduced cardiac output from aorto‐caval compression resulting from placing the woman on her back (supine position) (Cooke 1979).
Surgical stimulation from visceral traction such as manual delivery of the baby and in particular, exteriorisation of the uterus(temporary removal of the uterus from the abdominal cavity to facilitate repairing the incision), Wahab 1999).
Intraoperative medications may contribute to nausea and include opiates, antibiotics and administered uterotonics such as oxytocin and particularly ergometrine (De Groot 1998).
Psychological factors such as stress, anxiety, fatigue and prolonged starvation should not be underestimated as contributors to nausea and vomiting. This may particularly be the case with emergency caesarean delivery.
Medications given prior to the caesarean, such as medications to reduce the risk of aspiration (Paranjothy 2014). If the woman has been in labour prior to surgery then pain relief already provided such as opioids and nitrous oxide may also have residual emetogenic effects.

Few prospective observational studies or audit data have been published and so the underlying incidence of nausea and vomiting during caesarean section is uncertain. It is also likely that the baseline rate will vary considerably depending on the anaesthetic, analgesic and vasopressor regimen that is being used. However, it would seem reasonable to use the rates in the placebo arms of well‐designed randomised trials as an indication of the baseline rate of nausea and vomiting. Published placebo data show rates of intraoperative nausea in the order of 48% (Habib 2013) to 79% (Abouleish 1999). Vomiting rates are typically lower than the rates of nausea, in the order of 15% (Voigt 2013) to 38% (El‐Deeb 2011a). Most studies recruit women in the setting of elective caesarean section, and it is likely that rates are higher in the setting of emergency caesarean section.

Nausea and vomiting in the postpartum period are also common, and can affect women who received either 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 2019); however, this difference may not be apparent following caesarean delivery. 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 under regional anaesthesia. Whilst hypotension is an important cause of these symptoms during a caesarean, treatment for hypotension during regional anaesthesia has already been specifically addressed in another Cochrane Review (Chooi 2017). Similarly, interventions to reduce the risk of acid aspiration may well affect nausea and vomiting and these interventions have also been addressed in another Cochrane Review (Paranjothy 2014).

The pharmacological interventions available include medications from a wide range of drug classes including serotonin and dopamine receptor antagonists, corticosteroids, antihistamines, sedatives and anticholinergics (Flake 2004). A number of non‐pharmacological approaches have also been used traditionally to treat nausea in pregnancy, and some of these have been studied in this setting. These include acupuncture or acupressure (Ho 2006) and oral ginger (Kalava 2013).

How the intervention might work

Pharmacological interventions

For many of the recognised interventions used for the prevention of nausea and vomiting, the mechanism of action is not well understood. However, most treatments can be classed pharmacologically based on their biochemical receptor target. Nausea and vomiting caused by visceral stimulation is thought to be mediated predominantly via serotonin (5‐HT) and dopamine receptors. The chemoreceptor trigger zone (CTZ) is a small region within the brainstem responsible for the symptoms of medication and toxin related emesis, including post anaesthetic nausea and vomiting, and is also mediated by serotonin and dopamine. In contrast, nausea and vomiting caused by central nervous system and vestibular mechanisms, such as motion sickness, are thought to be mediated mainly via histamine and acetylcholine.

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

Serotonin (5‐HT₃) 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 (George 2009) and have few side effects.
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 1987). Droperidol has been associated with very rare, but potentially life‐threatening, cardiac arrhythmias.
Corticosteroids also known as steroids (most commonly dexamethasone) are regarded as being highly effective, but their mechanism of action is unclear (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, even in diabetics.
Antihistamines (e.g. promethazine and cyclizine (Nortcliffe 2003) can cause a variety of adverse effects including sedation and dry mouth.
Anticholinergic agents (e.g. glycopyrrolate (Ure 1999) and scopolamine (Kotelko 1989) are mainly useful for nausea and vomiting caused via the vestibular system, i.e. motion sickness. They can also cause a dry mouth and potentially urinary retention.
Sedatives. Very low doses of sedatives such as midazolam or propofol (Mukherjee 2006; Tarhan 2007) seem to have antiemetic 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 antagonists or partial agonists. A number of studies have attempted to demonstrate the beneficial effects of opioids. Whilst opioids would generally be considered 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. If one drug is an opioid antagonist or partial agonist (such as naloxone or nalbuphine) (Charuluxananan 2003), then it may reduce the opioid‐related side effects (such as nausea, itch and constipation) without unduly reducing the analgesic benefits.

Non‐pharmacological interventions

Acupuncture or acupressure: acupressure or acupuncture at the P6 point at the wrist has long been a traditional treatment for nausea, particularly sea sickness. The mechanism of action of acupuncture and acupressure is not well understood (Duggal 1998; Harmon 2000). Potential adverse effects of acupuncture include infection or trauma from acupuncture needles.
Alternative natural therapies such as ginger (Kalava 2013; Zeraati 2016) and peppermint (Lane 2012; Niaki 2016) also have long histories of use as traditional treatments for reducing nausea in pregnancy. Although associated with minimal side effects, their efficacy is uncertain (Matthews 2015).

Why it is important to do this review

Nausea and vomiting are very common symptoms experienced both during and following caesarean section, may increase 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. Whilst guidelines exist for the prevention of nausea and vomiting after general anaesthesia in non‐pregnant patients (Gan 2019), the aetiology of emetic symptoms at caesarean section are clearly multifactorial and the current literature may not be directly applicable. 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 interventions versus placebo or no intervention given prophylactically to prevent nausea and vomiting in women undergoing regional anaesthesia for caesarean section.

Methods

Criteria for considering studies for this review

Types of studies

We included published and unpublished randomised controlled trials (RCTs), including conference abstracts. We planned to include cluster‐randomised trials, but none were identified. 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

In this updated review, we have included studies where the participants were women undergoing caesarean section under regional anaesthesia (either spinal, epidural or both) comparing interventions for nausea and vomiting against placebo or no intervention. Intervention versus intervention comparisons were excluded. We included studies where the intervention was given with the express purpose of preventing nausea and vomiting, either intraoperative, postoperative, or both.

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 antagonists or partial agonists (e.g. nalbuphine).
Acupressure/acupuncture.
Alternative therapies such as ginger or peppermint.

We compared the different drug classes against placebo, setting out individual drugs and doses as subgroups.

We excluded:

studies where the authors were comparing two different treatments (unless there was also a control/placebo arm) and studies investigating combinations of treatments;
studies where the intervention was for reducing aspiration pneumonitis, as this is the subject of another review (Paranjothy 2014);
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. This has also been studied in another review (Chooi 2017);
studies where a recognised antiemetic was given, but the focus of the study was on another effect of that medication (for example, studies on the haemodynamic effects of ondansetron);
studies which assessed the efficacy of interventions for treatment, rather than prevention, of nausea and vomiting. This may be the subject of a separate future review;
studies where the intervention was not recognised as an antiemetic and did not have a reasonable theoretical justification for affecting nausea and vomiting, e.g. supplemental oxygen; intravenous fluids; anticonvulsants; antidepressants, opioid agonists.

Types of outcome measures

Primary outcomes

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

Secondary outcomes

Nausea plus vomiting/retching.
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. In this update, we clarified our approach to the postoperative data. Where a paper reports a number of time epochs (for example, zero to four hours, four to eight hours, etc), we have included data from the earliest reported time period because we believe these data were most likely to reflect the efficacy of the intervention.

Search methods for identification of studies

The following methods section of this review is based on a standard template used by Cochrane Pregnancy and Childbirth.

Electronic searches

For this update, we searched Cochrane Pregnancy and Childbirth’s Trials Register by contacting their Information Specialist (16 April 2020).

The Register is a database containing over 25,000 reports of controlled trials in the field of pregnancy and childbirth. It represents over 30 years of searching. For full current search methods used to populate Pregnancy and Childbirth’s Trials Register including the detailed search strategies for CENTRAL, MEDLINE, Embase and CINAHL; the list of handsearched journals and conference proceedings, and the list of journals reviewed via the current awareness service, please follow this link.

Briefly, Cochrane Pregnancy and Childbirth’s Trials Register is maintained by their Information Specialist and contains trials identified from:

monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL);
weekly searches of MEDLINE (Ovid);
weekly searches of Embase (Ovid);
monthly searches of CINAHL (EBSCO);
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.

Search results are screened by two people and the full text of all relevant trial reports identified through the searching activities described above is reviewed. Based on the intervention described, each trial report is assigned a number that corresponds to a specific Pregnancy and Childbirth review topic (or topics), and is then added to the Register. The Information Specialist searches the Register for each review using this topic number rather than keywords. This results in a more specific search set that has been fully accounted for in the relevant review sections (Included studies, Excluded studies, Studies awaiting classification or Ongoing studies).

In addition, we searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) for unpublished, planned and ongoing trial reports (1 April 2020) using the search methods described in Appendix 1.

Searching other resources

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

We did not apply any language or date restrictions.

Data collection and analysis

For methods used in the previous version of this review, seeGriffiths 2012.

For this update, the following methods were used for assessing the 174 new studies that were identified as a result of the updated search.

The following methods section of this review is based on a standard template used by Cochrane Pregnancy and Childbirth.

Selection of studies

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

Data extraction and management

We designed a form to extract data. For eligible studies, two review authors extracted the data using the agreed form. We resolved discrepancies through discussion or, if required, we consulted the third review author. Data were entered into Review Manager software (RevMan 2020) and checked for accuracy.

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

Assessment of risk of bias in included studies

Two review authors independently assessed risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2019). Any disagreement was resolved by discussion or by involving a third assessor.

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

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

We assessed the method as:

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

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

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

We assessed the methods as:

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

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

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

We assessed the methods as:

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

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

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

We assessed methods used to blind outcome assessment as:

low, high or unclear risk of bias.

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

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

We assessed methods as:

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

(5) Selective reporting (checking for reporting bias)

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

We assessed the methods as:

low risk of bias (where it 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 bias (checking for bias due to problems not covered by (1) to (5) above)

We described for each included study any important concerns we had about other possible sources of bias.

(7) Overall risk of bias

We made explicit judgements about whether studies were at high risk of bias, according to the criteria given in the Handbook (Higgins 2019). With reference to (1) to (6) above, we planned to assess the likely magnitude and direction of the bias and whether we considered it is likely to impact on the findings. In future updates, we will 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. Where a random‐effects model has been used, we report this as an average risk ratio (aRR).

Continuous data

We planned to use mean difference if outcomes were measured in the same way between trials and standardised mean difference to combine trials that measured the same outcome, but used different methods.

Unit of analysis issues

Cluster‐randomised trials

We planned to include cluster‐randomised trials in the analyses along with individually‐randomised trials, but did not identify any. Had we identified any, we would have adjusted their standard error using the methods described in the Handbook[Section16.3.4 and 16.3.6] using an estimate of the intracluster correlation co‐efficient (ICC) derived from the trial (if possible), from a similar trial or from a study of a similar population. If we had used ICCs from other sources, we would have reported this and conduct sensitivity analyses to investigate the effect of variation in the ICC. If we had identify both cluster‐randomised trials and individually‐randomised trials, we planned to synthesise the relevant information. We would have considered it reasonable to combine the results from both if there is little heterogeneity between the study designs. We will also acknowledge heterogeneity in the randomisation unit and perform a sensitivity analysis to investigate the effects of the randomisation unit.

Cross‐over trials

We excluded cross‐over trials.

Other unit of analysis issues

Where we found multi‐arm studies, we assessed which arms were relevant to our question and included data taking care not to double count the data in the placebo group by dividing the placebo data equally amongst the relevant comparisons such that when the data were pooled, the correct number of events and participants were included.

Dealing with missing data

For included studies, we noted levels of attrition. In future updates, if more eligible studies are included, the impact of including studies with high levels of missing data in the overall assessment of treatment effect will be explored by using sensitivity analysis.

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 Tau², I² and Chi² statistics. We regarded heterogeneity as reported in the Cochrane Handbook (Higgins 2019):

0% to 40%: might not be important;
30% to 60%: may represent moderate heterogeneity*;
50% to 90%: may represent substantial heterogeneity*;
75% to 100%: considerable heterogeneity*.

and either a Tau² was greater than zero, or there was a low P value (less than 0.10) in the Chi² test for heterogeneity.

Assessment of reporting biases

In future updates, if there are 10 or more studies in the meta‐analysis we will investigate reporting biases (such as publication bias) using funnel plots. We will assess funnel plot asymmetry visually. If asymmetry is suggested by a visual assessment, we will perform exploratory analyses to investigate it.

Data synthesis

We carried out statistical analysis using the Review Manager software (RevMan 2020).

We used random‐effects meta‐analyses for combining data because we considered that there would be heterogeneity sufficient to expect that the underlying treatment effects would differ between trials because our question is around groups of drugs and so we are combining data from different drugs and different doses within the meta‐analyses.

The random‐effects summary was treated as the average range of possible treatment effects and we discuss the clinical implications of treatment effects differing between trials. If the average treatment effect was not clinically meaningful, we did not combine trials. The results are presented as the average treatment effect with 95% confidence intervals, and the estimates of Tau² and I².

Subgroup analysis and investigation of heterogeneity

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

We carried out the following subgroup analyses.

Different drugs with the same group of drugs
Difference doses of the drugs within the group of drugs

The following four primary outcomes were used in subgroup analyses.

intraoperative nausea
intraoperative vomiting
postoperative nausea
postoperative vomiting

We assessed subgroup differences by interaction tests available within RevMan (RevMan 2020). We reported the results of subgroup analyses quoting the Chi² statistic and P value, and the interaction test I² value.

Sensitivity analysis

We carried out sensitivity analyses to explore the effect of trial quality assessed by selection bias (sequence generation and allocation concealment) and attrition bias (incomplete outcome data), with poor‐quality studies (either high risk or unclear risk) being excluded from the analyses in order to assess whether this makes any difference to the overall result.

Summary of findings and assessment of the certainty of the evidence

For this update, the certainty of the evidence was assessed using the GRADE approach as outlined in the GRADE handbook to assess the certainty of the body of evidence relating to the following outcomes for the main comparisons. All nine comparisons were chosen as a specific focus as they represent the most clinically‐relevant comparisons in this updated review.

Comparisons for GRADE and Summary of findings

5‐HT3 antagonists versus placebo
Dopamine antagonists versus placebo
Corticosteroids versus placebo
Antihistamines versus placebo
Anticholinergics versus placebo
Sedatives versus placebo
Opioid antagonists/partial agonists versus placebo
Acupressure/acupuncture versus placebo
Ginger versus placebo

Outcomes for GRADE and Summary of findings

Incidence of intraoperative nausea
Incidence of intraoperative vomiting/retching
Incidence of postoperative nausea
Incidence of postoperative vomiting/retching

We used the GRADEpro Guideline Development Tool to import data from Review Manager 5.3 (RevMan 2020) in order to create ’Summary of findings’ tables. A summary of the intervention effect and a measure of certainty each of the above outcomes was produced using the GRADE approach. The GRADE approach uses five considerations (study limitations, consistency of effect, indirectness, imprecision and publication bias) to assess the quality of the body of evidence for each outcome. The evidence can be downgraded from 'high certainty' by one level for serious (or by two levels for very serious) limitations, depending on assessments for risk of bias, serious inconsistency, indirectness of evidence, imprecision of effect estimates or potential publication bias.

Results

Description of studies

Results of the search

We assessed 218 new trial reports, plus the change in scope meant we also reassessed the 204 trial reports referenced in the previous version of the review.

All in all in this 2021 update, there are 84 included studies (112 reports) (Characteristics of included studies) and 236 excluded studies (269 reports) (Characteristics of excluded studies). Ten studies are awaiting classification (Characteristics of studies awaiting classification). These are predominantly conference abstracts where we have been unable to contact the authors or studies in a non‐English language where we have been unable to obtain a translation as yet. There are 27 studies identified as ongoing (31 reports) (Characteristics of ongoing studies).

The change in scope meant we excluded nine studies from the 2012 publication, six of these studies had provided data (Chestnut 1989; Gaiser 2002; Owczarzak 1997; Pecora 2009; Phillips 2007; Shahriari 2009), and three had provided no data (Biwas 2002; Chaudhuri 2004; Manullang 2000).

In addition, there were eight comparisons in multi‐arm studies where, due to our change in scope, some arms were now excluded and the data from these women were not included in our review (Abdollahpour 2015; Habib 2013; Khalayleh 2005; Levin 2019; Mokini 2014; Shen 2012; Voigt 2013; Wu 2007).

(See: Figure 1)

Figure 1

Study flow diagram.

Included studies

Of the 84 included studies (involving 10,990 women), 69 studies involving 8928 women provided usable data for this review, taking into account the arms of the multi‐arm studies which are not included in our inclusion criteria (Abdel‐Aleem 2012; Abdollahpour 2015; Abouleish 1999; Ahn 2002; Apiliogullari 2007; Baciarello 2011; Biswas 2003; Caba 1997; Cardoso 2013; Carvalho 2010; Charuluxananan 2003; Cherian 2001; Chestnut 1987; Choi 1999; Dasgupta 2012; Direkvand‐Moghadam 2013; Duggal 1998; Duman 2010; El‐Deeb 2011a; Garcia‐Miguel 2000; Habib 2006; Habib 2013; Harmon 2000; Harnett 2007; Hassanein 2015; Ho 1996; Ho 2006; Huang 1992; Ibrahim 2019; Jaafarpour 2008; Kalava 2013; Kampo 2019; Kasodekar 2006; Khalayleh 2005; Koju 2015; Kotelko 1989; Levin 2019; Li 2012; Lussos 1992; Mandell 1992; Maranhao 1988; Mohammadi 2015; Mokini 2014; Mukherjee 2006; Munnur 2008; Niu 2018; Noroozinia 2013; Nortcliffe 2003; Pan 1996; Pan 2001; Pan 2003; Parra‐Guiza 2018; Peixoto 2006; Rasooli 2014; Rudra 2004a; Sahoo 2012; Selzer 2020; Shabana 2012; Shen 2012; Stein 1997; Tarhan 2007; Tkachenko 2019; Tzeng 2000; Uerpairojkit 2017; Ure 1999; Voigt 2013; Wang 2001; Wu 2007; Zeraati 2016).

Fifteen studies are included but do not contribute data to the meta‐analysis because the data were either presented in a graphical format only, or there was no information on the number of women in each outcome group (Birnbach 1993; Boone 2002; ; Imbeloni 1986; Jang 1997; Kim 1999; Lee 2002; Lim 2001a; Lim 2001b; Liu 2015a; Modir 2019; Pazoki 2018; Quiney 1995; Sanansilp 1998; Weiss 1995; Yazigi 2002). We have written to these authors requesting further information.

Multi‐arm studies

There are 41 multi‐arm studies, 31 are three‐arm studies (Abdollahpour 2015; Apiliogullari 2007; Baciarello 2011; Birnbach 1993; Choi 1999; Direkvand‐Moghadam 2013; Duman 2010; El‐Deeb 2011a; Garcia‐Miguel 2000; Habib 2013; Harnett 2007; Hassanein 2015; Kampo 2019; Khalayleh 2005; Levin 2019; Li 2012; Maranhao 1988; Modir 2019; Munnur 2008; Nortcliffe 2003; Pan 1996; Pan 2001; Parra‐Guiza 2018; Pazoki 2018; Peixoto 2006; Rasooli 2014; Sanansilp 1998; Stein 1997; Tarhan 2007; Tkachenko 2019; Tzeng 2000; Voigt 2013) and 10 studies are four‐arm studies (Ahn 2002; Biswas 2003; Charuluxananan 2003; Lee 2002; Mokini 2014; Mukherjee 2006; Shen 2012; Voigt 2013; Wang 2001; Wu 2007). Where two or more arms of a study fell within the same comparison, we treated the data as described in the Unit of analysis issues.

Of the multi‐arm studies which provided data, 18 compared more than one drug against placebo but the drugs were in different categories and so in different comparisons (Biswas 2003; Choi 1999; Direkvand‐Moghadam 2013; Duman 2010; El‐Deeb 2011a; Garcia‐Miguel 2000; Harnett 2007; Hassanein 2015; Kampo 2019; Nortcliffe 2003; Pan 1996; Pan 2001; Parra‐Guiza 2018; Peixoto 2006; Shen 2012; Stein 1997; Tzeng 2000; Wu 2007). Six multi‐arm studies providing data included arms with one of our excluded drugs or a combination of drugs, so data from these arms were excluded (Abdollahpour 2015; Habib 2013; Khalayleh 2005; Levin 2019; Li 2012; Voigt 2013). Seven multi‐arm studies providing data looked at different concentrations of the same drug or different routes of administration and we adjusted the placebo data accordingly (Ahn 2002; Apiliogullari 2007; Baciarello 2011; Lee 2002; Mukherjee 2006; Tkachenko 2019; Wang 2001). Four multi‐arm studies looked at different drugs from the same category and so were in the same comparison and here we adjusted the placebo data accordingly (Maranhao 1988; Munnur 2008; Rasooli 2014; Tarhan 2007). One four‐arm study looked at two drugs from different categories and for one of these drugs looked at two doses, the placebo data was dealt with accordingly (Charuluxananan 2003) and another four‐arm study one arm was excluded as it was a combination of drugs and the other two arms were drugs in different categories (Mokini 2014). Four of the multi‐arm studies provided no data that we could use in this review (Birnbach 1993; Pazoki 2018; Sanansilp 1998; Modir 2019).

Populations

The included studies covered women undergoing elective and emergency caesarean sections under regional anaesthesia, with either spinal or epidural anaesthesia. Most studies reported women in American Society of Anesthesiologists physical status classification (ASA) Grade 1 to 2, and so generally with no medical problems (Characteristics of included studies)

Interventions

The studies covered drugs in seven different classes of drugs. For 5‐HT3 antagonists (e.g. ondansetron, granisetron) there were 21 studies involving providing data on 2686 women; for dopamine antagonists (e.g. metoclopramide, droperidol) there were 20 studies providing data on 1880 women; for corticosteroids (e.g. dexamethasone) there were 12 studies providing data on 1182 women; for antihistamines (e.g. dimenhydrinate, cyclizine) there were four studies providing data on 514 women; for anticholinergics (e.g. glycopyrrolate, scopolamine) there were six studies providing data on 787 women; for sedatives (e.g. propofol, midazolam) there were 13 studies providing data on 1265 women; and for opioid antagonists/partial agonists (nalbuphine) there were two studies providing data on 197 women. Ten studies on acupressure/acupuncture provided data on 1401 women and two studies on ginger which provided data on 365 women (Characteristics of included studies).

Outcomes

Most studies reported intraoperative nausea, intraoperative vomiting, postoperative nausea and postoperative vomiting separately, but a few reported combines nausea and vomiting both intraoperative and postoperative. Some studies reported looking for side effects/adverse effects such as hypotension, itching, dizziness. Few studies looked at women's satisfaction (Characteristics of included studies).

Settings

The 84 studies were undertaken in a wide range of countries across the world (see Characteristics of included studies):

Americas (24 studies) ‐ USA 18 studies, South America four studies (including one from Columbia and two from Brazil), Canada two studies;

Asia (24 studies) ‐ India five studies, China five studies, Nepal one study, Thailand three studies, Taiwan three studies; South Korea five studies, Singapore two studies;

Middle East (14 studies) ‐ Iran 10 studies, Lebanon one study, Turkey three studies;

UK/Europe (10 studies) ‐ UK four studies, Germany one study, Ireland one study, Italy one study, Spain two studies; Ukraine one study;

Africa (seven studies) ‐ Egypt six studies, Ghana one study.

For two studies, there was no information provided on the setting, and three studies were conducted across multiple countries (e.g. USA and UK).

Dates of included studies

Fifty‐nine studies did not report the dates over which their studies were undertaken. The studies which reported dates covered 2001 to 2017 and publication dates range from 1987 to 2020 (Characteristics of included studies).

Funding sources of included studies

Seventy‐one studies did not report funding sources. Of the studies reporting this information, two studies reported commercial company funding (Abouleish 1999; Duggal 1998), one study specifically reported no commercial funding (Cherian 2001), nine studies reported finding from universities, hospitals and public funding bodies (Abdollahpour 2015; Cardoso 2013; Direkvand‐Moghadam 2013;Duggal 1998; Modir 2019; Parra‐Guiza 2018; Pazoki 2018; Selzer 2020; Zeraati 2016), and two studies reported specifically that they had no funding (Kampo 2019; Levin 2019).

Declarations of interest of authors of included studies

Seventy‐three studies did not report on declarations of interest of the authors. Eleven studies reported no conflict of interest for their authors (Abdel‐Aleem 2012; Abouleish 1999; Cardoso 2013;Kampo 2019; Koju 2015; Levin 2019; Niu 2018; Parra‐Guiza 2018; Selzer 2020; Uerpairojkit 2017; Voigt 2013).

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 but they did not present the data separately (Caba 1997). 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

We have excluded a total of 236 studies (269 reports). 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. Studies were excluded for a wide variety of reasons. Some studies were excluded for multiple reasons. Many 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 2004). Fifty‐four studies looking at aspiration prophylaxis and are included in the review of interventions for reducing aspiration prophylaxis at caesarean section (Paranjothy 2014). Seven studies (Fujii 1998a; Fujii 1998b; Fujii 1999; Fujii 2002; Fujii 2004; Numazaki 2000; Numazaki 2003) were excluded following investigation into research authenticity (Carlisle 2012).

Although our review assesses interventions for prevention (rather than treatment) of nausea and vomiting, our current search would identify treatment studies too. There were only three randomised controlled trials (RCTs) identified which specifically assessed interventions for treatment (rather than prevention) of nausea and vomiting (Fazel 2017; Kimura 2011; Lane 2012). Four studies were excluded because the women had their caesarean sections with general anaesthesia (Abadi 2018; Huseyinogclu 2016; Hussain 2014; Kocamanoglu 2005).

One hundred and seven studies were excluded because they studied aspects of anaesthesia other than interventions given for the prevention of nausea and vomiting. Many studies assessed antiemetic medication but were focused on the haemodynamic effects of the medication, or the quality and duration of anaesthesia (rather than the antiemetic effect). Some studies examined other medication such as analgesics, antidepressants or anticonvulsants, again not focused on their antiemetic effects. Some other studies compared different surgical techniques, or other interventions such as supplemental oxygen, intravenous fluids or prolonged fasting. These were also outside the inclusion criteria for our review (Characteristics of excluded studies).

Fifty studies were excluded as they compared different treatments, or combinations of treatments, without a placebo or control group.

Thirteen studies were excluded as they were deemed not to be an RCT (Atkinson 1980; Boschi 1984; Brock‐Utne 1989; Chen 2005; Colman 1988; Datta 1982; Dewan 1982; Dundee 1979; Fazel 2017; Qvist 1983; Santos 1984; Sultan 2014; Tanaka 2007).

Seven studies were excluded as the publications had been retracted since our previous review was published.

Risk of bias in included studies

Overall risk of bias is reported in Figure 2 and Figure 3.

Figure 2

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

Figure 3

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

Allocation

Of the 84 studies included in the review, random sequence generation was judged to be of low risk of bias in 38 studies, with 46 studies being judged of unclear risk. Many studies simply stated that "patients were randomised" without providing any further details.

Allocation concealment was generally poorly described. It was judged to be of low risk of bias in five studies and of unclear risk in 79 studies. There were only five studies where both sequence generation and allocation concealment were judged to be of low risk (Abdel‐Aleem 2012; Charuluxananan 2003; Cherian 2001; Tarhan 2007; Uerpairojkit 2017).

Blinding

Blinding was assessed in more detail in this updated review. Blinding was sometimes described poorly, with many studies simply describing a "double blind" design.

We judged blinding of participants and clinicians as of low risk of bias in 30 studies,and of unclear bias in 50studies. Blinding was considered at high risk of bias in four studies because the treating anaesthetist was likely not blinded to the study drug (Direkvand‐Moghadam 2013; Mokini 2014; Rasooli 2014; Rudra 2004a). In all these studies, it seemed some effort at blinding the treating clinician could have been made.

Blinding of outcome assessors was variably described, with 36 studies judged to be of low risk and 46 studies judged to be of unclear risk. Two studies were considered to be of high risk of bias in this regard (Ahn 2002; Mokini 2014).

Incomplete outcome data

Incomplete outcome data were addressed adequately and so at low risk of bias in 47 studies. In 34 studies, it was judged to be of unclear bias, and at high risk of bias in three studies (Baciarello 2011; Cardoso 2013; Duman 2010). In these three studies, data on a significant number of participants were excluded and we were unable to be re‐include on an intention‐to‐treat basis.

Selective reporting

As we were generally not able to assess study protocols, 76 studies were judged to be unclear about selective reporting bias with just one study assessed as low risk (Kalava 2013).. However, seven studies were judged to show a high risk of bias (Ahn 2002; Carvalho 2010; Ibrahim 2019; Jang 1997; Selzer 2020; Tkachenko 2019; Voigt 2013), generally because they did not report outcomes which were pre‐specified in the study methods.

Other potential sources of bias

Thirty‐six studies were judged to be free of other potential sources of bias, with 46 being unclear. Two studies were judged to be at high risk of bias (Habib 2013; Hassanein 2015). One study was conducted at two different centres. There seemed to be many differences in practice between the two centres and the study seemed poorly controlled (Habib 2013). Another study included an unspecified number of women undergoing additional surgical procedures (such as tubal ligation (Hassanein 2015).

Effects of interventions

1) 5‐HT₃ receptor antagonists versus placebo (25 studies, 3942 women, Comparison 1)

Whilst 25 studies assessed this comparison, only 21 provided usable data on outcomes involving 2686 women (Abouleish 1999; Charuluxananan 2003; Cherian 2001; Dasgupta 2012; El‐Deeb 2011a; Garcia‐Miguel 2000; Harnett 2007; Kasodekar 2006; Koju 2015; Mohammadi 2015; Munnur 2008; Pan 1996; Pan 2001; Pan 2003; Parra‐Guiza 2018; Peixoto 2006, Sahoo 2012; Shen 2012; Uerpairojkit 2017; Voigt 2013; Yazigi 2002). Four studies provided no data which could be included in our analyses (Boone 2002; Lee 2002; Pazoki 2018; Yazigi 2002). Of the studies that provided data, 17 studied ondansetron (Abouleish 1999; Charuluxananan 2003; Cherian 2001; El‐Deeb 2011a; Garcia‐Miguel 2000; Harnett 2007; Koju 2015; Munnur 2008; Pan 1996; Pan 2001; Pan 2003; Parra‐Guiza 2018; Peixoto 2006, Sahoo 2012; Shen 2012; Uerpairojkit 2017; Yazigi 2002), five examined granisetron (Dasgupta 2012; Kasodekar 2006; Lee 2002; Mohammadi 2015; Munnur 2008) and one studied tropisotron (Voigt 2013).

The studies which provided data were undertaken in: USA (six studies); Egypt (two studies); India (two studies); Iran (one study); Iran (one study); Spain (one study); Thailand (one study); and UK (one study).

Of the 21 studies providing data, only three were judged to have had both adequate sequence generation and allocation concealment (Abouleish 1999; Charuluxananan 2003; Cherian 2001). The remaining are unclear. Five studies were considered to have adequate and well‐described blinding (Dasgupta 2012; Mohammadi 2015; Pan 1996; Pan 2001; Peixoto 2006). The remainder are unclear in at least one element (seeFigure 2 and Figure 3).

Primary outcomes

Intraoperative nausea

5‐HT₃ antagonists may reduce the number of women having intraoperative nausea (average risk ratio (RR) 0.55, 95% confidence interval (CI) 0.42 to 0.71), 12 studies, 1419 women, random‐effects (T² = 0.11; Chi² P = 0.0009; I² = 65%), Analysis 1.1). The certainty of the evidence was low, downgraded for serious risk of bias and serious inconsistency (summary of findings Table 1).

In a subgroup analysis by drug and dose, there was significant difference in treatment effect between the subgroups (Chi² = 7.72, P = 0.05, I² = 61.1%).

The sensitivity analysis left only one study (with 81 women) at low risk of bias across selection and attrition bias and this showed no reduction and a wide CI crossing the line of no difference (average RR 1.11, 95% CI 0.45 to 2.79).

Intraoperative vomiting

5‐HT₃ antagonists may lead to a reduction in the number of women having intraoperative vomiting, but the results are very uncertain (average RR 0.46, 95% CI 0.29 to 0.73, 11 studies, 1414 women, random‐effects (T² = 0.27, Chi² P = 0.008, I² = 58%), Analysis 1.2).The certainty of the evidence is very low, downgraded for serious risk of bias, serious inconsistency and some evidence of publication bias (summary of findings Table 1).

In the subgroup analysis by dose of drug, there was no evidence of differences in treatment effect between the subgroups (Chi² = 4.33, P = 0.22, I² = 32.2%).

The sensitivity analysis left only one study (with 81 women) at low risk of bias across selection and attrition bias, it showed a similar result to the main analysis but a wider CI (RR 0.38, 95% CI 0.18 to 0.81).

Postoperative nausea

5‐HT₃ antagonists probably reduce the number of women having postoperative nausea (average RR 0.40, 95% CI 0.30 to 0.54, 10 studies, 1340 women, random‐effects (T² = 0.09, Chi² P = 0.10, I² = 37%) (Analysis 1.3). The certainty of the evidence was moderate, downgraded for serious risk of bias (summary of findings Table 1).

The subgroup analysis by drug and dose did not identify any heterogeneity (Chi² = 0.15, df = 3 (P = 0.99), I² = 0%).

The sensitivity analysis left only two studies (with 338 women) at low risk of bias across selection and attrition bias and this showed similar finding, with a wider CI (average RR 0.56, 95% CI 0.38 to 0.83).

Postoperative vomiting

5‐HT₃ antagonists may reduce the number of women having postoperative vomiting (average RR 0.47, 95% CI 0.31 to 0.69, 10 studies, 1450 women, random‐effects (T² = 0.13, Chi² P = 0.10, I² = 37%), Analysis 1.4). The certainty of the evidence was low, downgraded for serious risk of bias and some evidence of publication bias (summary of findings Table 1).

The subgroup analysis by drug and dose did not identify any differences (Chi² = 1.15, df = 3 (P = 0.76), I² = 0%).

The sensitivity analysis left only two studies (with 338 women) at low risk of bias across selection and attrition bias and this showed a wider CI crossing the line of no difference (average RR 0.94, 95% CI 0.53 to 1.67).

Secondary outcomes

Intraoperative nausea + vomiting

Only one small study (Voigt 2013) looked at this outcome and so there are insufficient data to make any judgement (Analysis 1.5).

Postoperative nausea + vomiting

5HT₃ antagonists may reduce the number of women having postoperative nausea plus vomiting (RR 0.57, 95% CI 0.41 to 0.80, five studies, 576 women), however, the certainty of the evidence is low due to unclear risk of bias on most aspects including selection and attrition bias. (Analysis 1.6).

Maternal satisfaction

We identified two differing results in women's satisfaction between the 5‐HT₃ receptor antagonist ondansetron and placebo. One study showed a benefit from the ondansetron (RR 1.99, 95%CI 1.35 to 2.94, 1 study, 105 women) (Pan 2001), and the other showed no difference (RR 0.98, 95% CI 0.82 to 1.16, 1 study 81 women) (Cherian 2001) (Analysis 1.7).

Adverse effects and side effects

There were no events in the one study involving 100 women that assessed a composite outcome of adverse effects. There was no indication of adverse effects for a number of outcome measures: headaches/dizziness (average RR 1.04, 95% CI 0.60 to 1.79, 4 studies, 433 women, Analysis 1.9); hypotension (average RR 1.22, 95% CI 0.72 to 2.08, 3 studies 290 women, Analysis 1.10); and pruritis/itching (RR 0.85, 95% CI 0.69 to 1.05, 4 studies 488 women, ,Analysis 1.11); dry mouth (RR 0.75, 95% CI 0.17 to 3.22, 1 study, 130 women, Analysis 1.12); drowsiness/sedation (RR 3.94, 95% CI 0.45 to 34.63, 2 studies, 170 women, Analysis 1.13). .

Rescue antiemetics used: 5HT₃ antagonist ondansetron may reduce the use of rescue antiemetics (RR 0.32, 95% CI 0.11 to 0.93, 1 study, 158 women, Analysis 1.14) but more data are needed.

2) Dopamine antagonists versus placebo (24 studies, 2965 women, Comparison 2)

Twenty‐four studies compared dopamine antagonists with placebo, of which 20 studies provided data for analysis involving 1880 women (Biswas 2003; Chestnut 1987; Choi 1999; Direkvand‐Moghadam 2013; Duman 2010; Garcia‐Miguel 2000; Habib 2013; Huang 1992; Kampo 2019; Khalayleh 2005; Lussos 1992; Mandell 1992; Maranhao 1988; Mokini 2014; Pan 1996; Pan 2001; Peixoto 2006; Stein 1997; Tzeng 2000; Wu 2007). Four studies provided no data which could be included in our analyses (Birnbach 1993; Imbeloni 1986; Kim 1999; Sanansilp 1998). Of the studies providing data, 15 studied metoclopramide (Biswas 2003; Chestnut 1987; Choi 1999; Direkvand‐Moghadam 2013; Duman 2010; Garcia‐Miguel 2000; Habib 2013; Huang 1992; Kampo 2019; Khalayleh 2005; Lussos 1992; Maranhao 1988; Mokini 2014; Pan 2001; Stein 1997). Five examined droperidol (Mandell 1992; Pan 1996; Peixoto 2006; Tzeng 2000; Wu 2007).

The 20 studies which provided data were undertaken in: USA (seven studies); one in the USA and Canada, Taiwan (two studies); India (one study); Iran (two studies); Spain (one study); Turkey (one study); Africa (one study) South America (two studies) and two studies where the setting was not described.

Overall, the studies were of uncertain or variable quality. Of the 20 studies which provided data, only three were judged to have had both adequate random sequence generation and allocation concealment (Chestnut 1987; Habib 2013; ; Stein 1997). Nine studies were judged to have had adequately described blinding (Chestnut 1987; Duman 2010; Habib 2013; ; Pan 1996; Pan 2001; Peixoto 2006; Stein 1997; Tzeng 2000; Wu 2007). All the remaining being unclear (Figure 2) except for one study where it seemed likely that the patient and clinicians would both have been aware of the group allocation (Direkvand‐Moghadam 2013). study appeared at high risk of bias due to missing data, where substantial numbers of patients were excluded after randomisation and weren't able to be re‐included (Duman 2010).

Primary outcomes

Intraoperative nausea

Dopamine antagonists may reduce the number of women having intraoperative nausea but the results are very uncertain (average RR 0.38, 95% CI 0.27 to 0.52, 15 studies, 1180 women, random‐effects (T² = 0.19, Chi² P = 0.005, I² = 54%), Analysis 2.1). The certainty of the evidence was very low, downgraded for very serious risk of bias and serious inconsistency (summary of findings Table 2).

In the subgroup analysis by dose and drug, there was no evidence of differences in treatment effects between the subgroups (Chi² = 0.79, df = 6 (P = 0.99), I² = 0%)..

We could not undertake a sensitivity analysis because none of the studies providing data were at low risk of bias across selection and attrition bias. .

Intraoperative vomiting

Dopamine antagonists may reduce the number of women with intraoperative vomiting (average RR 0.41, 95% CI 0.28 to 0.60, 12 studies, 942 women, random‐effects, T² = 00.02, Chi² P = 0.40, I² = 5%, Analysis 2.2). The certainty of the evidence was low, downgraded for very serious risk of bias.

In the subgroup analysis by drug and dose, there was no evidence of differences in treatment effects between the subgroups Chi² = 2.70, df = 5 (P = 0.75), I² = 0%.

We could not undertake a sensitivity analysis because none of the studies providing data were at low risk of bias across selection and reporting bias, and this also showed a reduced relative risk but a CI that crossed the line of no difference (average RR 0.34, 95% CI 0.10 to 1.23).

Postoperative nausea

Dopamine antagonists may reduce the number of women with postoperative nausea (average RR 0.61, 95% CI 0.48 to 0.79, 7 studies, 601 women, random‐effects, T² = 0.01, Chi² P = 0.35, I² = 10%, Analysis 2.3). The certainty of the evidence is low, downgraded for very serious risk of bias (summary of findings Table 2).

In the subgroup analysis by drug and dose, there was no evidence of differences in treatment effects between subgroups (Chi² = 2.84, df = 2 (P = 0.24), I² = 29.5%)

We could not undertake a sensitivity analysis because none of the studies providing data were at low risk of bias across selective and reporting bias,

Postoperative vomiting

Dopamine antagonists may lead to a reduction in the number of women having postoperative vomiting but the results are very uncertain (average RR 0.63, 95% CI 0.44 to 0.92, 9 studies, 860 women, T² = 0.13, Chi² P = 0.08, I² = 43%, Analysis 2.4). The certainty of the evidence is very low due to very serous risk of bias and some evidence of publication bias. (summary of findings Table 2), . These findings were broadly consistent when the individual interventions of metoclopramide and droperidol were assessed separately.

In the subgroup analysis by type and dose of drug, there was no evidence of differences in treatment effects between subgroups (Chi² = 2.03, df = 2 (P = 0.36), I² = 1.3%).

We could not undertake a sensitivity analysis because none of the studies providing data were at low risk of bias across selective and reporting bias.

Secondary outcomes

Intraoperative nausea + vomiting

There is only one small study with 98 women so the findings are very uncertain (average RR 0.12, 95% CI 0.02 to 0.88, Analysis 2.5).

Postoperative nausea + vomiting

There are four studies involving 450 women, so the findings are uncertain (average RR 0.23, 95% CI 0.05 to 1.02, Analysis 2.6). However, one study has a very extreme result (Kampo 2019). We have checked the paper and can find nothing to explain this result, so we also report the findings as well excluding these data (average (RR 0.49, 95% CI 0.32 to 0.75, 3 studies, 220 women).

Maternal satisfaction

We identified no overall difference in women's satisfaction between dopamine antagonists and placebo (RR 1.42, 95% CI 0.91 to 2.21, 1 study, 102 women, Analysis 2.7).

Adverse effects and side effects

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 2.8; Analysis 2.9; Analysis 2.10; Analysis 2.13).

Subgroup analyses

For possible variations between individual drugs, seeAnalysis 2.1 to Analysis 2.7.

3) Corticosteroids versus placebo (15 studies, 1830 women, Comparison 3)

Fifteen studies looked at corticosteroids versus placebo, of which 12 studies involving 1182 women provided data for the review. Studies compared corticosteroids against placebo, all studied dexamethasone but in various doses from 2.5 mg to 10 mg (Abdel‐Aleem 2012; Biswas 2003; Cardoso 2013; Hassanein 2015; Jaafarpour 2008; Nortcliffe 2003; Parra‐Guiza 2018; Selzer 2020; Tkachenko 2019; Tzeng 2000; Wang 2001; Wu 2007). Two included studies provided no data for the review (Lim 2001b; Modir 2019).

The studies were undertaken in: Taiwan (three studies); Egypt (two studies); Brazil (one study); India (one study); Iran (one study), Colombia (one study), Ukraine (one study), USA (one study)and UK (one study).

The studies were of questionable quality with only one being judged as having adequate sequence generation and allocation concealment (Abdel‐Aleem 2012; ). Six had adequate blinding (Abdel‐Aleem 2012; Hassanein 2015; Selzer 2020; Tzeng 2000; Wang 2001; Wu 2007). One study excluded many women after randomisation if they suffered intraoperative nausea or vomiting and this amounted to 31% of the enrolled subjects (Abdel‐Aleem 2012). Another study excluded 46% of women after randomisation if they were not the first patient of the day (Cardoso 2013).

Primary outcomes

Intraoperative nausea

Dexamethasone may reduce the number of women having intraoperative nausea but the results are very uncertain (average RR 0.56, 95% CI 0.37 to 0.83, 6 studies, 609 women, random‐effects (T² = 0.12, Chi² P = 0.06, I² = 50%), Analysis 3.1), The certainty of the evidence was very low, downgraded for very serious risk of bias and serious inconsistency (summary of findings Table 3).

In the subgroup analysis by dose of drug and route of administration (intravenous and intrathecal) , there was evidence of differences between the various doses and routes of administration (Chi² = 7.54, df = 2 (P = 0.02), I² = 73.5%).

The sensitivity analysis could not be undertaken as none of the included studies were low risk for selection.and attrition bias.

Intraoperative vomiting

Dexamethasone may reduce the number of women having intraoperative vomiting but the results are very uncertain (average RR 0.52, 95% CI 0.31 to 0.87, 6 studies, 609 women, random‐effects (T² = 0.00, Chi² P = 0.69, I² = 0%, Analysis 3.2). The certainty of the evidence being very low, downgraded for very serious risk of bias, and serious imprecision (summary of findings Table 3).

The subgroup analysis by dose of drug and route of administration (intravenous and intrathecal showed no difference between the subgroups (Chi² = 1.80, df = 2 (P = 0.41), I² = 0%).

The sensitivity analysis could not be undertaken as none of the included studies were low risk for selection and attrition bias.

Postoperative nausea

Dexamethasone probably reduces the number of women having postoperative vomiting (average RR 0.59, 95% CI 0.49 to 0.73, 6 studies, 733 women, random‐effects (T² = 0.01, Chi² P = 0.36, I² = 9%), Analysis 3.3). The certainty of the evidence was moderate, downgraded for serious risk of bias.

The subgroup analyses by dose of drug and route of administration (intravenous and intrathecal) showed no difference between the subgroups (Chi² = 6.87, df = 5 (P = 0.23), I² = 27.2%).

The sensitivity analysis could not be undertaken as none of the included studies were low risk for selection.and attrition bias. .

Postoperative vomiting

Dexamethasone may reduce the number of women having postoperative vomiting (average RR 0.68, 95% CI 0.49 to 0.95, 7 studies, 793 women, random‐effects (T² = 0.11, Chi² P = 0.03, I² = 52%) Analysis 3.4). The certainty of the evidence was low, downgraded for serious risk of bias and serious inconsistency (summary of findings Table 3).

The subgroup analysis by dose of drug and route of administration (intravenous and intrathecal) showed some variation (Chi² = 14.65, df = 5 (P = 0.01), I² = 65.9%).

The sensitivity analysis could not be undertaken as none of the included studies were low risk for selection.and attrition bias..

Secondary outcomes

Intraoperative nausea + vomiting

We identified only one study of 108 women (Selzer 2020) so the findings are very uncertain (average RR 1.65, 95% CI 0.96 to 2.84, Analysis 3.5).

Postoperative nausea + vomiting

We identified only one study of 108 women (Selzer 2020) so the findings are very uncertain (RR 0.94, 95% CI 0.79 to 1.12, Analysis 3.6).

Adverse effects and side effects

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 3.7; to Analysis 3.10).

4) Antihistamines versus placebo (4 studies, 654 women, Comparison 4)

Four studies compared antihistamines with placebo, all studies providing data on 514 women (Apiliogullari 2007; Carvalho 2010; Duman 2010; Nortcliffe 2003).

The studies were undertaken in: Iran (one study); Turkey (one study) Canada (one study) and UK (one study).

Only one study had adequate sequence generation (Duman 2010). All four studies were unclear with regard to allocation concealment. Only one study had adequate blinding (Duman 2010). Two studies were assessed as high risk of bias ‐ one due to missing data that could not be re‐included (Duman 2010) and one due to pre‐specified outcomes not reported (Carvalho 2010).

Primary outcomes

Intraoperative nausea

Antihistamines (e.g. dimenhydrinate ) may make little of no difference to intraoperative nausea (RR 0.99, 95% CI 0.47 to 2.11, 1 study, 149 women, Analysis 4.1). The certainty of the evidence was very low, downgraded for very serious risk of bias, and very serious imprecision summary of findings Table 4).

It was not possible to undertake subgroup analysis as only one study assessed this outcome (Carvalho 2010).

It was not possible to undertake sensitivity analysis as only one study (with unclear risk of selection and reporting bias) assessed this outcome (Carvalho 2010).

Intraoperative vomiting

Antihistamines (e.g. dimenhydrinate ) may make little of no difference to intraoperative nausea as there were no events in the one study of 149 women looking at this outcome and the GRADE assessment of this study was very low due to very serious risk of bias and very serious imprecision (Analysis 4.2, summary of findings Table 4).

It was not possible to undertake subgroup analysis as only one study assessed this outcome (Carvalho 2010).

It was not possible to undertake sensitivity analysis as only one study (with unclear risk of selection and reporting bias) assessed this outcome (Carvalho 2010).

Postoperative nausea

Antihistamines may lead to a reduction in postoperative nausea (average RR 0.44, 95% CI 0.30 to 0.64, 4 studies, 514 women, random‐effects (T² = 0.02, Chi² P = 0.34, I² = 11%), Analysis 4.3) as the certainty of the evidence is low, downgraded for very serious risk of bias. (summary of findings Table 4).

In the subgroup analysis by type and dose of drug, there was no evidence of differences in treatment effects between subgroups (Chi² = 3.98, df = 3 (P = 0.26), I² = 24.6%).

In the sensitivity analysis there were no studies with low risk of selection and attrition bias.

Postoperative vomiting

Antihistamines may lead to a reduction in postoperative vomiting but the results are very uncertain (average RR 0.48, 95% CI 0.29 to 0.81, 3 studies, 333 women, random‐effects (T² = 0.00, Chi² P = 0.66, I² = 0%), Analysis 4.4), The certainty of the evidence is very low, downgraded for very serious risk of bias and serious imprecision (summary of findings Table 4).

The subgroup analysis by type of drug or dose showed no difference between the subgroups (Chi² = 0.79, df = 2 (P = 0.67), I² = 0%).

In the sensitivity analysis there were no studies with low risk of selection and attrition bias.

Secondary outcomes

None of the studies looked at intraoperative 'nausea + vomiting nor postoperative 'nausea + vomiting'.

Adverse effects and side effects

Although there were no estimates of a composite outcome of adverse effects, one study involving 149 women looked at hypotension (Carvalho 2010, Analysis 4.5), but there were insufficient data to make any firm statement about hypotension.

5) Anticholenergics versus placebo (7 studies, 1088 women, Comparison 5)

Seven studies compared anticholinergics with placebo, with six of these studies (involving 787 women) reporting data that we could use in the review (Baciarello 2011; Biswas 2003; Harnett 2007; Kotelko 1989; Shen 2012; Ure 1999). One study provides no data for the review as they present data across multiple time periods and it is unclear if women have been counted multiple times (Quiney 1995).

The studies which provided data were undertaken in: USA (two studies); India (one study), Italy (one study), China (one study) and UK (one study).

Two studies had adequate sequence generation (Baciarello 2011; Harnett 2007). The other four were unclear. One study had adequate allocation concealment (Baciarello 2011) the others studies were unclear. Only one study described adequate blinding of participants and outcome assessment (Baciarello 2011). One study was judged to be at high risk of income data as 12 participants were excluded after randomisation (Baciarello 2011).

Primary outcomes

Intraoperative nausea

Anticholinergics may reduce intraoperative nausea (average RR 0.67, 95% CI 0.51 to 0.87, 4 studies, 453 women, random‐effects (T² = 0.03, Chi² P = 0.13, I² = 47%), Analysis 5.1). The certainty of the evidence was low, downgraded for very serious risk of bias (Analysis 5.1).

The subgroup analyses by type of drug or dose showed no difference between the subgroups (Chi² = 0.70, df = 1 (P = 0.40), I² = 0%).

In the sensitivity analysis there were no studies with low risk of selection and attrition bias.

Intraoperative vomiting

Anticholenergics may make little or no difference to intraoperative vomiting (average RR 0.79, 95% CI 0.40 to 1.54, 4 studies, 453 women, random‐effects (T² = 0.22, Chi² P = 0.10, I² = 52%), Analysis 5.2). The certainty of the evidence is very low, downgraded for very serious risk of bias, serious inconsistency and serious imprecision (summary of findings Table 5).

These findings were persistent in the scopolamine subgroup, but not the glycopyrrolate subgroup, however, there were much smaller numbers in the glycopyrrolate subgroup.

In a subgroup analysis by type of drug and dose, showed no difference between the subgroups (Chi² = 0.86, df = 1 (P = 0.35), I² = 0%)

In the sensitivity analysis there were no studies with low risk of selection and attrition bias.

Postoperative nausea

None of the studies assessed postoperative nausea.

Postoperative vomiting

Only one study of 161 women looked at this outcome (Harnett 2007). So we are very uncertain whether anticholinergics reduce postoperative vomiting (RR 0.55, 95% CI 0.41 to 0.74, 1 study, 161 women, (Analysis 5.4). The certainty of the evidence was low, downgraded for serious risk of bias and serious imprecision (summary of findings Table 5).

There were no assessments on subgroups nor sensitivity because there was only one study..

Secondary outcomes

Intraoperative 'nausea + vomiting'

None of the studies assessed this outcome.

Postoperative 'nausea + vomiting'

Anticholinergics may reduce the number of women with postoperative nausea and vomiting (average RR 0.46, 95% CI 0.25 to 0.85, 2 studies, 334 women, Analysis 5.6) but the certainty of the evidence is very low coming from just two small studies, so overall anticholinergics may make little or no difference.

Adverse effects and side effects

Although there were no estimates of a composite outcome of adverse effects, a few studies did measure a number of adverse and side effects, including blurred vision, anxiety/disorientation and dizziness, (Analysis 5.7 to Analysis 5.13) but we feel there are insufficient data to make any firm statement about adverse or side effects.

6) Sedatives versus placebo (17 studies, 1730 women, Comparison 6)

Seventeen studies assessed sedatives versus placebo, with 13 providing analysable data on 1265 women. Most studies assessed propofol but at differing doses (Ahn 2002; Caba 1997; Kampo 2019; Mokini 2014; Mukherjee 2006; Niu 2018; Rasooli 2014; Rudra 2004a; Tarhan 2007). Two studies assessed midazolam, two intravenous (Rasooli 2014; Tarhan 2007) and one intrathecal (Abdollahpour 2015). Two studies assessed ketamine (Hassanein 2015; Shabana 2012). One study provided data in graphical form only (Weiss 1995) and we have written to the authors to obtain the numerical data. One study provided outcome data as percentages and it was unclear how many women were in each group (Modir 2019).

The studies which provided data were undertaken in: India (two studies); Iran (two studies); Korea (one study) Egypt (two studies); Spain (one study) Ghana (one study), China (one study) and Turkey (one study). One study did not specify where it was conducted.

The 12 studies providing data appeared to be of reasonable quality with eight studies having adequate random sequence generation but only three having adequate allocation concealment. Only four of the 12 studies had adequate blinding (Hassanein 2015; Niu 2018; Mukherjee 2006; Tarhan 2007). Four studies were rated as inadequate blinding, where it was highly likely that the participants and/or clinicians would have been aware of the group allocation (Ahn 2002; Mokini 2014; Rasooli 2014; Rudra 2004a).

Primary outcomes

Intraoperative nausea

Sedatives probably reduce the number of women having intraoperative nausea (average RR 0.65, 95% CI 0.51 to 0.82, 8 studies, 593 women, random‐effects (T² = 0.00, Chi² P = 0.64, I² = 0%), Analysis 6.1). The certainty of the evidence was moderate, downgraded for serious risk of bias (summary of findings Table 6).

Subgroup analysis by type of drug and dose showed no difference between the subgroups (Chi² = 5.78, df = 7 (P = 0.57), I² = 0%).

The sensitivity analysis included one study (with 88 women) at low risk of bias of selection and attrition bias, and this showed similar findings to the main analysis although the lower CI now crosses the line of no difference (RR 0.76, 95% CI 0.53 to 1.08).

Intraoperative vomiting

Sedatives probably reduce the number of women with intraoperative vomiting (average RR 0.35, 95% CI 0.24 to 0.52, 8 studies, 593 women, random‐effects (T² = 0.00, Chi² P = 0.55, I² = 0%), Analysis 6.2). The certainty of the evidence was moderate, downgraded for serious risk of bias (summary of findings Table 6).

Subgroup analysis by type of drug and dose showed no difference between the subgroups (Chi² = 3.97, df = 7 (P = 0.78), I² = 0%).

The sensitivity analysis included one (with 88 women) at low risk of bias of selection and attrition bias, and this showed similar findings to the main analysis (RR 0.43, 95% CI 0.20 to 0.95).

Postoperative nausea

Sedatives may reduce the number of women with postoperative nausea but the results are very uncertain (average RR 0.25, 95% CI 0.09 to 0.71, 2 studies, 145 women, (T² = 0.47, Chi² P = 0.09, I² = 58%), Analysis 6.3) The certainty of the evidence was very low, downgraded for serious inconsistency and very serious imprecision (summary of findings Table 6).

Subgroup analysis by type of drug and dose showed some difference between the groups (Chi² = 4.64, df = 2 (P = 0.10), I² = 56.9%).

The sensitivity analysis included one study (with 88 women) at low risk of bias of selection and attrition bias, and this showed similar findings to the main analysis although the upper CI is further away from the line of no difference ( RR 0.17, 95% CI 0.09 to 0.31).

Postoperative vomiting

Sedatives may reduce the number of women with postoperative vomiting (average RR 0.09, 95% CI 0.03 to 0.28, 2 studies, 145 women, (T² = 0.00, Chi² P = 0.39, I² = 0%), Analysis 6.4). The certainty of the evidence was low, downgraded for very serious imprecision (summary of findings Table 6).

Subgroup analysis by type of drug and dose showed no difference between the groups (Chi² = 1.77, df = 2 (P = 0.41), I² = 0%).

The sensitivity analysis included one study (with 88 women) at low risk of bias of selection and attrition bias, and this showed similar findings to the main analysis although the upper CI is further away from the line of no difference ( (RR 0.07, 95% CI 0.02 to 0.24).

Secondary outcomes

Intraoperative 'nausea & vomiting'

None of the studies assessed this outcome.

Postoperative 'nausea & vomiting'

Sedatives may reduce the incidence of postoperative nausea and vomiting (average RR 0.06, 95% CI 0.02 to 0.22, 2 studies, 348 women, Analysis 6.6) . However, one study has a very extreme result (Kampo 2019). We have checked the paper and can find nothing to explain this result, so we also report the findings, as well excluding these data (average (RR 0.12, 95% CI 0.04 to 0.36, 1 study, 118 women).

Adverse and side effects:

Although there were no estimates of a composite outcome of adverse effects, a few studies did measure a number of maternal adverse and side effects (Analysis 6.7 to Analysis 6.9).

One study of 80 women (Niu 2018) reported no babies had Apgar scores less than seven at five minutes in either group. Also that all women in both groups initiated breastfeeding.

7) Opioids antagonists versus placebo (4 studies, 380 women, Comparison 7)

Four studies were eligible for inclusion in this comparison (Abdollahpour 2015; Charuluxananan 2003; Ibrahim 2019; Jang 1997), but only two provided data for analysis involving 197 women (Charuluxananan 2003; Ibrahim 2019). Three studies compared opioid antagonists with placebo (Abdollahpour 2015; Charuluxananan 2003; Ibrahim 2019): two studies assessed nalbuphine, one intravenously (Charuluxananan 2003) and the other intrathecally (Ibrahim 2019); and one study assessed intrathecal sufentanil (Abdollahpour 2015). The fourth study assessed butorphanol, and although the abstract was in English, we have been unable to get the full paper translated from Korean to analyse any of the data (Jang 1997).

The studies were undertaken in Iran, Thailand, Egypt and South Korea.

Both studies providing data were judged to have adequate random sequence generation, although blinding was not well described and judged to be unclear in both studies. The studies were also judged to be of unclear risk for other biases.

Primary outcomes

Intraoperative nausea

None of the studies assessed this outcome.

Intraoperative vomiting

None of the studies assessed this outcome.

Postoperative nausea

It is uncertain whether opioid antagonists may reduce, increase or may make little no difference to the number of women having postoperative nausea (RR 0.75, 95% CI 0.39 to 1.45, 1 study, 120 women, Analysis 7.3). The certainty of the evidence was low, downgraded due to very serious imprecision (summary of findings Table 7).

It was not possible to undertake a subgroup analysis by drug and dose because there was only one study reporting this outcome.,

It was not possible to undertake a sensitivity analysis as there was only one study assessing postoperative nausea and vomiting and this study was low risk for selection and attrition bias.

Postoperative vomiting

It is uncertain whether opioid antagonists may reduce the number of women having intraoperative vomiting (RR 1.25, 95% CI 0.35 to 4.43, 1 study, 120 women, Analysis 7.4). The certainty of the evidence was low, downgraded for very serious imprecision (summary of findings Table 7).

It was not possible to undertake a subgroup analysis by drug and dose because there was only one study reporting this outcome.,

It was not possible to undertake a sensitivity analysis as there was only one study assessing postoperative nausea and vomiting and this study was low risk for selection and attrition bias.

Secondary outcomes

Intraoperative 'nausea & vomiting'

No studies assessed this outcome.

Postoperative 'nausea & vomiting'

Nalbuphine (an opioid antagonist) may reduce postoperative nausea & vomiting (RR 0.09, 95% CI 0.02 to 0.37, 1 study, 77 women, nAnalysis 7.6), but the certainty of the evidence is very low and further data are needed.

Adverse effects and side effects

Only two studies assessed pruritis as a side effect (Analysis 7.7) with markedly different results, so we do not have enough data on which to make a meaningful assessment.

8) Acupressure/acupuncture versus placebo (14 studies, 1818 women, Comparison 8)

Fourteen studies compared acupressure/acupuncture with placebo, with 11 studies providing data on 1401 women (Direkvand‐Moghadam 2013; Duggal 1998; El‐Deeb 2011a; Habib 2006; Harmon 2000; Ho 1996; Ho 2006; Levin 2019; Li 2012; Noroozinia 2013; Stein 1997). One study addressed this question but provided graphical data only (Birnbach 1993). Data from two studies were not included as it was unclear how many women were allocated to each group (Lim 2001a; Lim 2001b). All eleven studies looked at acupressure, and none studies acupuncture.

The studies which provided data were undertaken in: USA (three studies); Iran (two studies); Canada (one study); China (two studies); Egypt (one study), Ireland (one study) and one study in the USA and Canada.

The studies providing data were of borderline quality with only four out of 11 describing adequate blinding of all relevant parties, and a further two studies providing an incomplete description of blinding. One study was judged at high risk of bias as it seemed likely the participants and treating clinicians were not blinded to group allocation (Direkvand‐Moghadam 2013). However, only four of the nine studies described adequate random sequence generation and only four adequate allocation concealment. We assessed the studies as low quality using GRADE criteria on the basis of inconsistency and imprecision.

Primary outcomes

Intraoperative nausea

Acupressure/acupuncture may reduce the number of women having intraoperative nausea but the results are very uncertain (average RR 0.55, 95% CI 0.41 to 0.74), 9 studies, 1221 women, random‐effects (T² = 0.12, Chi² P = 0.0001, I² = 69%), Analysis 8.1). The certainty of the evidence is very low, downgraded for very serious risk of bias and serious inconsistency (summary of findings Table 8).

It was not possible to undertake a subgroup analysis as all the studies used acupressure and we did not differentiate between the different types of acupressure.

It was not possible to undertake a sensitivity analysis as none of the studies providing data were at low risk of selection and reporting bias.

Intraoperative vomiting

Acupressure/acupuncture may reduce the number of women having intraoperative vomiting (average RR 0.52, 95% CI 0.33 to 0.80, 9 studies, 1221 women) (random‐effects (T² = 0.18, Chi² P = 0.05, I² = 47%), Analysis 8.2) . The certainty of the evidence is low, downgraded for very serious risk of bias (summary of findings Table 8).

It was not possible to undertake a subgroup analysis as all the studies used acupressure and we did not differentiate between the different types of acupressure.

It was not possible to undertake a sensitivity analysis as none of the studies providing data were at low risk of selection and reporting bias.

Postoperative nausea

Acupressure/acupuncture may reduce the number of women having postoperative nausea but the results are very uncertain (average RR 0.46, 95% CI 0.27 to 0.75, 7 studies, 1069 women, random‐effects (T² = 0.32, Chi² P = 0.0001, I² = 81%), Analysis 8.3). The certainty of the evidence is very low downgraded for very serious risk of bias and serious inconsistency (summary of findings Table 8).

It was not possible to undertake a subgroup analysis as all the studies used acupressure and we did not differentiate between the different types of acupressure.

It was not possible to undertake a sensitivity analysis as none of the studies were low risk for selection and attrition bias.

Postoperative vomiting

Acupressure/acupuncture may reduce the number of women having postoperative vomiting but the results are very uncertain (average RR 0.52, 95% CI 0.34 to 0.79, 7 studies, 1069 women, random‐effects (T² = 0.17, Chi² P = 0.01, I² = 62%), Analysis 8.4). The certainty of the evidence is very low downgraded for very serous risk of bias and serious inconsistency (summary of findings Table 8).

It was not possible to undertake a subgroup analysis as all the studies used acupressure and we did not differentiate between the different types of acupressure.

It was not possible to undertake a sensitivity analysis as none of the studies were low risk for selection and attrition bias.

Secondary outcomes

None of the studies reported intraoperative 'nausea + vomiting' nor postoperative 'nausea + vomiting'.

Adverse effects and side effects

It is uncertain whether acupressure/acupuncture increases side effects of anxiety, dizziness, hypotension or itching because the certainty of the evidence is very low (Analysis 8.5 to Analysis 8.8). Acupressure/acupuncture may reduce the use of rescue antiemetics (average RR 0.50, 95% CI 0.36 to 0.71, 2 studies, 240 women, Analysis 8.9) but the certainty of the evidence is very low downgraded for very severs risk of bias and very severe imprecision (summary of findings Table 8).

9) Ginger versus placebo (2 studies, 365 women, Comparison 9)

Two studies compared oral ginger with placebo included 365 women both provided data for the review (Kalava 2013; Zeraati 2016). One study described adequate random sequence generation, but both were unclear regarding allocation concealment and blinding. They were judged to be of low or unclear risk for other biases.

One study was undertaken in USA and one in Iran.

Primary outcomes

Intraoperative nausea

It is uncertain whether ginger reduces, increases or makes little to no difference in the number of women having intraoperative nausea (average RR 0.66, 95% CI 0.36 to 1.21, 2 studies, 331 women, random‐effects (T² = 0.15, Chi² P = 0.05, I² = 74%), Analysis 9.1. The certainty of the evidence is very low, downgraded for very serious risk of bias, serious inconsistency and serious imprecision (summary of findings Table 9).

In a subgroup analysis by dose, there was evidence of subgroup difference ( Chi² = 3.70, df = 1 (P = 0.05), I² = 73.0%).

The sensitivity analysis was not undertaken as neither of the studies were at low risk of bias of selection and attrition bias,

Intraoperative vomiting

Ginger may reduce the number of women having intraoperative vomiting or may make little or no difference (average RR 0.62, 95% CI 0.38 to 1.00, 2 studies, 331 women, random‐effects (T² = 0.06, Chi² P = 0.16, I² = 49%), Analysis 9.2). The certainty of the evidence was very low, downgraded for very serious risk of bias, and serious imprecision (summary of findings Table 9).

In a subgroup analysis by dose there was no evidence of a difference but more data are needed to be sure (Chi² = 1.97, df = 1 (P = 0.16), I² = 49.2%).

The sensitivity analysis was not undertaken as neither of the studies were at low risk of bias of selection and attrition bias,

Postoperative nausea

It is uncertain whether ginger reduces, increases or makes little to no difference to the number of women having postoperative nausea (average RR 0.63, 95% CI 0.22 to 1.77, 1 study, 92 women, Analysis 9.3). The certainty of the evidence was very low, downgraded for very serious risk of bias, and very serious imprecision (summary of findings Table 9).

There is no subgroup analysis nor sensitivity analysis as there was only one study.

Postoperative vomiting

It is uncertain whether ginger reduces increases, decreases or makes little to no difference to the number of women having postoperative vomiting (average RR 0.20, 95% CI 0.02 to 1.65, 1 study, 92 women, Analysis 9.4). The certainty of the evidence was very low, downgraded for very serious risk of bias and very serious imprecision (summary of findings Table 9).

There is no subgroup analysis nor sensitivity analysis as there was only one study.

Secondary outcomes

The studies did not report any of our secondary outcomes.

Discussion

Summary of main results

We found 84 included studies involving 10,990 women with 69 studies providing useable data on 8928 women, and this covered nine comparisons. The certainty of the data was generally low and very low, mainly due to many of the studies being quite old and undertaken in times when methodological information was not required in publications, hence risk of bias is generally unclear and also many studies are small.

Placebo‐controlled studies

1. 5‐HT₃ antagonists. In the 21 studies (involving 2686 women) that provided data, overall, we found that 5‐HT₃ antagonists (mainly ondansetron and granisetron) probably reduces postoperative nausea (moderate‐certainty evidence), may be effective in reducing intraoperative nausea and postoperative vomiting (low‐certainty evidence), but the effect on intraoperative vomiting is uncertain (very low‐certainty evidence) . There were no indications of adverse effects such as headaches, dizziness, hypotension and itchiness, although more data are needed.

2. Dopamine antagonists. In 20 studies (involving 1880 women) that provided data, we found that dopamine antagonists (both metoclopramide and droperidol) may be effective in reducing intraoperative vomiting and postoperative nausea (low‐certainty evidence), but it is uncertain whether they reduce intraoperative nausea and postoperative vomiting (very low‐certainty evidence). These results were broadly consistent with both metoclopramide and droperidol. However, there were insufficient data to determine if there were significant adverse effects like headaches, dizziness, hypotension and pruritus.

3. Corticosteroids. In 12 studies (involving 1182 women) that provided data, corticosteroids probably reduce postoperative nausea (moderate‐certainty evidence) and may reduce postoperative vomiting (low‐certainty evidence). We are uncertain whether corticosteroids reduce intraoperative nausea and vomiting (very low‐certainty evidence). There were limited data on adverse effects.

4. Antihistamines. In four studies (involving 514 women) that provided data, antihistamines (mainly dimenhydrinate and cyclizine) may reduce postoperative nausea (low‐certainty evidence) but may make little to no difference to intraoperative nausea, intraoperative vomiting (no events in the 149 women where this outcome was assessed) and postoperative vomiting (very low‐certainty evidence). Only one small study looked at the adverse effect of hypotension.

5. Anticholenergic drugs. In the six studies (involving 787 women) that provided data, we found that anticholinergic drugs (mainly glycopyrrolate and scopolamine) may be effective at reducing intraoperative nausea and postoperative vomiting (low‐certainty evidence) but may have little or no effect on intraoperative vomiting (very low‐certainty evidence). No study assessed postoperative nausea. There were few data on adverse effects.

6. Sedatives. In 13 studies (involving 1265 women) provided data and addressed sedatives as an intervention. Most studies included propofol, but some included midazolam and one study used ketamine. Overall, the use of sedatives probably reduces intraoperative nausea and intraoperative vomiting (moderate‐certainty evidence) and may reduce postoperative vomiting (low‐certainty evidence). It is uncertain if sedatives reduce postoperative nausea (very low‐certainty evidence). Reports generally provided insufficient data on potential adverse effects,in particular sedation.

7. Opioid antagonists/partial agonists. There were two studies that provided data involving 197 women assessing opioid antagonists used specifically to reduce nausea and vomiting. We found little to no difference in postoperative nausea or vomiting with these interventions (low‐certainty evidence) and there were no studies assessing intraoperative nausea and vomiting. Studies only looked at the side effect of itching and found no difference on limited data.

8. Acupressure/acupuncture. In the 10 studies (involving 1401 women) that provided data, we found acupressure/acupuncture may reduce the number of women having intraoperative vomiting (low‐certainty evidence) but it uncertain whether there is a reduction in intraoperative nausea, postoperative nausea and postoperative vomiting (very low‐certainty evidence). There were insufficient data on potential adverse effects. .

9. Ginger. In the two studies (involving 365 women) that provided data and compared ginger with placebo, it is uncertain whether ginger reduces, increases, or has no effect on intraoperative nausea and vomiting and postoperative nausea and vomiting (all very low‐certainty evidence). No side effects were assessed in either study.

Overall completeness and applicability of evidence

There are good data assessing the efficacy of most standard classes of antiemetic compared with placebo in preventing nausea and vomiting during and following caesarean section under regional anaesthesia. However, most of the trials are small and the certainty of evidence is generally low.

In this updated review we did not attempt to compare different classes of antiemetics or different combinations of therapy.

We excluded several studies that assessed the efficacy of antiemetics given for treatment (rather than prevention) of established nausea and vomiting and these would need to be dealt with in a separate review.

Quality of the evidence

The quality of the evidence in this review varied widely. Considering just the 69 studies providing data for the review, on standard 'Risk of bias' assessment, only five studies were rated as low risk on all criteria (apart from Selective Bias). In comparison, 14 studies were rated as 'unclear' or 'high risk' on some or all criteria. Seventeen studies were rated as high risk on at least one criteria ‐ including for management of missing data (Abdel‐Aleem 2012, Baciarello 2011; Cardoso 2013; Duman 2010) inadequate blinding (Ahn 2002; Direkvand‐Moghadam 2013; Levin 2019; Mokini 2014; Rasooli 2014; Rudra 2004a) or selective reporting (Ahn 2002; Carvalho 2010; Ibrahim 2019; Jang 1997; Selzer 2020; Tkachenko 2019; Voigt 2013). One study was rated as high risk for other bias due to a poorly controlled study protocol (Habib 2013).

Of the 84 studies providing data, 37 described adequate random sequence generation, however only 18 described adequate allocation concealment.

Using GRADE criteria for assessing the certainty of the evidence, we found the following.

Comparison 1: 5HT₃ antagonists: moderate‐certainty evidence for postoperative nausea (downgraded for serious risk of bias); low‐certainty evidence for intraoperative nausea (downgraded for serious risk of bias and serious inconsistency) and postoperative vomiting (downgraded for serious risk of bias and possible publication bias); very low‐certainty evidence for intraoperative vomiting (downgraded for serious risk of bias, serious inconsistency and possible publication bias). (summary of findings Table 1).

Comparison 2: dopamine antagonists: low‐certainty evidence for intraoperative vomiting and postoperative nausea and very low‐certainty evidence for intraoperative nausea and postoperative vomiting. Intraoperative nausea (downgraded for serious risk of bias and serious inconsistency; intraoperative vomiting (downgraded for serious risk of bias); postoperative nausea (downgraded for serious risk of bias) and postoperative vomiting (downgraded for serious risk of bias and possible publication bias) (summary of findings Table 2).

Comparison 3: corticosteroids: moderate‐certainty evidence for postoperative nausea (downgraded for serious risk of bias); low‐certainty evidence for postoperative vomiting (downgraded for serious risk of bias and serious inconsistency); very low‐certainty for intraoperative nausea (downgraded for very serious risk of bias and serious inconsistency) and intraoperative vomiting (downgraded for very serious risk of bias and serious imprecision) (summary of findings Table 3).

Comparison 4: antihistamines: very low‐certainty evidence for intraoperative nausea, intraoperative vomiting and postoperative vomiting (all downgraded for very serious risk of bias and very serious imprecision); and low‐certainty evidence for postoperative nausea (downgraded for very serious risk of bias) (summary of findings Table 4).

Comparison 5: anticholinergics: low‐certainty evidence for intraoperative nausea (downgraded for very serious risk of bias) and postoperative vomiting (downgraded for serious risk of bias and serious imprecision); very low‐certainty evidence for intraoperative vomiting (downgraded for very serious risk of bias, serious inconsistency and serious imprecision) (summary of findings Table 5).

Comparison 6: sedatives: moderate‐certainty evidence for intraoperative nausea (downgraded for serious risk of bias) and intraoperative vomiting (downgraded for serious risk of bias); low‐certainty evidence for postoperative vomiting (downgraded for very serious imprecision); very low‐certainty evidence for postoperative nausea (downgraded for serious inconsistence and very serious imprecision) (summary of findings Table 6).

Comparson 7: opioid antagonists: low‐certainty evidence for postoperative nausea (downgraded for very serious imprecision) and postoperative vomiting (downgraded for very serious imprecision) (summary of findings Table 7).

Comaprison 8: acupressure/acupuncture: low‐certainty evidence for intraoperative vomiting (downgraded for very serious risk of bias); very low‐certainty evidence for intraoperative nausea (downgraded for very serious risk of bias and serious inconsistency), postoperative nausea (downgraded for very serious risk of bias and serious inconsistency and postoperative vomiting (downgraded for very serious risk of bias and serious inconsistency) (summary of findings Table 8).

Comparison 9: ginger: very low‐certainty evidence for: intraoperative nausea (downgraded for risk of bias, serious inconsistency and serious imprecision), intraoperative vomiting (downgraded for risk of bias and serious imprecision); postoperative nausea (downgraded for serious risk of bias and very serious imprecision and postoperative vomiting (downgraded for serious risk of bias and very serious imprecision) (summary of findings Table 9).

Potential biases in the review process

The possibility of introducing bias was present at every stage of the review 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 broadly consistent with previously published reviews of nausea and vomiting at caesarean section (Balki 2005). Systematic reviews assessing specific medications such as ondansetron (George 2009; Zhou 2018) and metoclopramide (Mishriky 2012) have demonstrated efficacy, however a meta‐analysis of acupressure did not show a positive effect (Allen 2008).

Figure 1

Study flow diagram.

Figure 2

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

Figure 3

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

Comparison 1: 5‐HT3 antagonists vs placebo, Outcome 1: Nausea ‐ intraoperative

Analysis 1.1

Comparison 1: 5‐HT₃ antagonists vs placebo, Outcome 1: Nausea ‐ intraoperative

Comparison 1: 5‐HT3 antagonists vs placebo, Outcome 2: Vomiting ‐ intraoperative

Analysis 1.2

Comparison 1: 5‐HT₃ antagonists vs placebo, Outcome 2: Vomiting ‐ intraoperative

Comparison 1: 5‐HT3 antagonists vs placebo, Outcome 3: Nausea ‐ postoperative

Analysis 1.3

Comparison 1: 5‐HT₃ antagonists vs placebo, Outcome 3: Nausea ‐ postoperative

Comparison 1: 5‐HT3 antagonists vs placebo, Outcome 4: Vomiting ‐ postoperative

Analysis 1.4

Comparison 1: 5‐HT₃ antagonists vs placebo, Outcome 4: Vomiting ‐ postoperative

Comparison 1: 5‐HT3 antagonists vs placebo, Outcome 5: 'Nausea + Vomiting' ‐ intraoperative (not pre‐specified)

Analysis 1.5

Comparison 1: 5‐HT₃ antagonists vs placebo, Outcome 5: 'Nausea + Vomiting' ‐ intraoperative (not pre‐specified)

Comparison 1: 5‐HT3 antagonists vs placebo, Outcome 6: 'Nausea + Vomiting' ‐ postoperative ‐ (not pre‐specified)

Analysis 1.6

Comparison 1: 5‐HT₃ antagonists vs placebo, Outcome 6: 'Nausea + Vomiting' ‐ postoperative ‐ (not pre‐specified)

Comparison 1: 5‐HT3 antagonists vs placebo, Outcome 7: Maternal satisfaction

Analysis 1.7

Comparison 1: 5‐HT₃ antagonists vs placebo, Outcome 7: Maternal satisfaction

Comparison 1: 5‐HT3 antagonists vs placebo, Outcome 8: Maternal adverse outcomes

Analysis 1.8

Comparison 1: 5‐HT₃ antagonists vs placebo, Outcome 8: Maternal adverse outcomes

Comparison 1: 5‐HT3 antagonists vs placebo, Outcome 9: Headache/dizziness/vertigo

Analysis 1.9

Comparison 1: 5‐HT₃ antagonists vs placebo, Outcome 9: Headache/dizziness/vertigo

Comparison 1: 5‐HT3 antagonists vs placebo, Outcome 10: Hypotension

Analysis 1.10

Comparison 1: 5‐HT₃ antagonists vs placebo, Outcome 10: Hypotension

Comparison 1: 5‐HT3 antagonists vs placebo, Outcome 11: Pruritus/itching

Analysis 1.11

Comparison 1: 5‐HT₃ antagonists vs placebo, Outcome 11: Pruritus/itching

Comparison 1: 5‐HT3 antagonists vs placebo, Outcome 12: Dry mouth

Analysis 1.12

Comparison 1: 5‐HT₃ antagonists vs placebo, Outcome 12: Dry mouth

Comparison 1: 5‐HT3 antagonists vs placebo, Outcome 13: Drowsiness/sedation

Analysis 1.13

Comparison 1: 5‐HT₃ antagonists vs placebo, Outcome 13: Drowsiness/sedation

Comparison 1: 5‐HT3 antagonists vs placebo, Outcome 14: Rescue antiemetic (not pre‐specified)

Analysis 1.14

Comparison 1: 5‐HT₃ antagonists vs placebo, Outcome 14: Rescue antiemetic (not pre‐specified)

Analysis 2.1

Comparison 2: Dopamine antagonists vs placebo, Outcome 1: Nausea ‐ intraoperative

Analysis 2.2

Comparison 2: Dopamine antagonists vs placebo, Outcome 2: Vomiting ‐ intraoperative

Analysis 2.3

Comparison 2: Dopamine antagonists vs placebo, Outcome 3: Nausea ‐ postoperative

Analysis 2.4

Comparison 2: Dopamine antagonists vs placebo, Outcome 4: Vomiting ‐ postoperative

Analysis 2.5

Comparison 2: Dopamine antagonists vs placebo, Outcome 5: 'Nausea + vomiting' ‐ intraoperative (not pre‐specfied)

Analysis 2.6

Comparison 2: Dopamine antagonists vs placebo, Outcome 6: 'Nausea + vomiting' ‐ postoperative (not pre‐specified)

Analysis 2.7

Comparison 2: Dopamine antagonists vs placebo, Outcome 7: Maternal satisfaction

Analysis 2.8

Comparison 2: Dopamine antagonists vs placebo, Outcome 8: Anxiety

Analysis 2.9

Comparison 2: Dopamine antagonists vs placebo, Outcome 9: Headache/dizziness

Analysis 2.10

Comparison 2: Dopamine antagonists vs placebo, Outcome 10: Hypotension

Analysis 2.11

Comparison 2: Dopamine antagonists vs placebo, Outcome 11: Rescue antiemetics (not pre‐specified)

Analysis 2.12

Comparison 2: Dopamine antagonists vs placebo, Outcome 12: Sedation

Analysis 2.13

Comparison 2: Dopamine antagonists vs placebo, Outcome 13: Pruritus/itching

Analysis 3.1

Comparison 3: Corticosteroids vs placebo, Outcome 1: Nausea ‐ intraoperative

Analysis 3.2

Comparison 3: Corticosteroids vs placebo, Outcome 2: Vomiting ‐ intraoperative

Analysis 3.3

Comparison 3: Corticosteroids vs placebo, Outcome 3: Nausea ‐ postoperative

Analysis 3.4

Comparison 3: Corticosteroids vs placebo, Outcome 4: Vomiting ‐ postoperative

Analysis 3.5

Comparison 3: Corticosteroids vs placebo, Outcome 5: 'Nausea + Vomiting' ‐ intraoperative (not pre‐specified)

Analysis 3.6

Comparison 3: Corticosteroids vs placebo, Outcome 6: 'Nausea + Vomiting' ‐ postoperative ‐ (not pre‐specified)

Analysis 3.7

Comparison 3: Corticosteroids vs placebo, Outcome 7: Hypotension

Analysis 3.8

Comparison 3: Corticosteroids vs placebo, Outcome 8: Bradycardia

Analysis 3.9

Comparison 3: Corticosteroids vs placebo, Outcome 9: Shivering

Analysis 3.10

Comparison 3: Corticosteroids vs placebo, Outcome 10: Rescue antiemetics (not pre‐specified)

Analysis 4.1

Comparison 4: Antihistamines vs placebo, Outcome 1: Nausea ‐ intraoperative

Analysis 4.2

Comparison 4: Antihistamines vs placebo, Outcome 2: Vomiting ‐ intraoperative

Analysis 4.3

Comparison 4: Antihistamines vs placebo, Outcome 3: Nausea ‐ postoperative

Analysis 4.4

Comparison 4: Antihistamines vs placebo, Outcome 4: Vomiting ‐ postoperative

Analysis 4.5

Comparison 4: Antihistamines vs placebo, Outcome 5: Hypotension

Analysis 5.1

Comparison 5: Anticholinergics vs placebo, Outcome 1: Nausea ‐ intraoperative

Analysis 5.2

Comparison 5: Anticholinergics vs placebo, Outcome 2: Vomiting ‐ intraoperative

Analysis 5.3

Comparison 5: Anticholinergics vs placebo, Outcome 3: Nausea ‐ postoperative

Analysis 5.4

Comparison 5: Anticholinergics vs placebo, Outcome 4: Vomiting ‐ postoperative

Analysis 5.5

Comparison 5: Anticholinergics vs placebo, Outcome 5: 'Nausea + Vomiting' ‐ intraoperative (not pre‐specified)

Analysis 5.6

Comparison 5: Anticholinergics vs placebo, Outcome 6: 'Nausea + vomiting' ‐ postoperative (not pre‐specified)

Analysis 5.7

Comparison 5: Anticholinergics vs placebo, Outcome 7: Blurred vision

Analysis 5.8

Comparison 5: Anticholinergics vs placebo, Outcome 8: Anxiety/Disorientation

Analysis 5.9

Comparison 5: Anticholinergics vs placebo, Outcome 9: Dizziness

Analysis 5.10

Comparison 5: Anticholinergics vs placebo, Outcome 10: Hypotension

Analysis 5.11

Comparison 5: Anticholinergics vs placebo, Outcome 11: Pruritus/itching

Analysis 5.12

Comparison 5: Anticholinergics vs placebo, Outcome 12: Xerostomia/dry mouth

Analysis 5.13

Comparison 5: Anticholinergics vs placebo, Outcome 13: Drowsiness

Analysis 6.1

Comparison 6: Sedatives vs placebo, Outcome 1: Nausea ‐ intraoperative

Analysis 6.2

Comparison 6: Sedatives vs placebo, Outcome 2: Vomiting ‐ intraoperative

Analysis 6.3

Comparison 6: Sedatives vs placebo, Outcome 3: Nausea ‐ postoperative

Analysis 6.4

Comparison 6: Sedatives vs placebo, Outcome 4: Vomiting ‐ postoperative

Analysis 6.5

Comparison 6: Sedatives vs placebo, Outcome 5: 'Nausea + vomiting' ‐ intraoperative (not pre‐specified)

Analysis 6.6

Comparison 6: Sedatives vs placebo, Outcome 6: 'Nausea + vomiting' ‐ postoperative (not pre‐specified)

Analysis 6.7

Comparison 6: Sedatives vs placebo, Outcome 7: Pruritis/itching

Analysis 6.8

Comparison 6: Sedatives vs placebo, Outcome 8: Hypotension

Analysis 6.9

Comparison 6: Sedatives vs placebo, Outcome 9: Shivering

Analysis 6.10

Comparison 6: Sedatives vs placebo, Outcome 10: Apgar score < 7 at 5 mins

Analysis 6.11

Comparison 6: Sedatives vs placebo, Outcome 11: Initiation of breastfeeding

Analysis 7.1

Comparison 7: Opioid antagonist/partial agonist vs placebo, Outcome 1: Nausea ‐ intraoperative

Analysis 7.2

Comparison 7: Opioid antagonist/partial agonist vs placebo, Outcome 2: Vomiting ‐ intraoperative

Analysis 7.3

Comparison 7: Opioid antagonist/partial agonist vs placebo, Outcome 3: Nausea ‐ postoperative

Analysis 7.4

Comparison 7: Opioid antagonist/partial agonist vs placebo, Outcome 4: Vomiting ‐ postoperative

Analysis 7.5

Comparison 7: Opioid antagonist/partial agonist vs placebo, Outcome 5: 'Nausea + vomiting' ‐ intraoperative (not pre‐specified)

Analysis 7.6

Comparison 7: Opioid antagonist/partial agonist vs placebo, Outcome 6: 'Nausea + vomiting' ‐ postoperative (not pre‐specified)

Analysis 7.7

Comparison 7: Opioid antagonist/partial agonist vs placebo, Outcome 7: Pruritus/itching

Analysis 8.1

Comparison 8: Acupressure/acupuncture vs placebo, Outcome 1: Nausea ‐ intraoperative

Analysis 8.2

Comparison 8: Acupressure/acupuncture vs placebo, Outcome 2: Vomiting ‐ intraoperative

Analysis 8.3

Comparison 8: Acupressure/acupuncture vs placebo, Outcome 3: Nausea ‐ postoperative

Analysis 8.4

Comparison 8: Acupressure/acupuncture vs placebo, Outcome 4: Vomiting ‐ postoperative

Analysis 8.5

Comparison 8: Acupressure/acupuncture vs placebo, Outcome 5: Anxiety

Analysis 8.6

Comparison 8: Acupressure/acupuncture vs placebo, Outcome 6: Dizziness

Analysis 8.7

Comparison 8: Acupressure/acupuncture vs placebo, Outcome 7: Hypotension

Analysis 8.8

Comparison 8: Acupressure/acupuncture vs placebo, Outcome 8: Pruritus/itching

Analysis 8.9

Comparison 8: Acupressure/acupuncture vs placebo, Outcome 9: Rescue antiemetic (not pre‐specified)

Analysis 9.1

Comparison 9: Ginger vs placebo, Outcome 1: Nausea ‐ intraoperative

Analysis 9.2

Comparison 9: Ginger vs placebo, Outcome 2: Vomiting ‐ intraoperative

Analysis 9.3

Comparison 9: Ginger vs placebo, Outcome 3: Nausea ‐ postoperative

Analysis 9.4

Comparison 9: Ginger vs placebo, Outcome 4: Vomiting ‐ postoperative

Summary of findings 1. 5‐HT3 antagonists compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
5‐HT3 antagonists compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section
Patient or population: women undergoing regional anaesthesia for caesarean section Setting: hospitals across low‐, middle‐ and high‐income countries Intervention: 5‐HT3 antagonists Comparison: placebo
Outcomes	Risk with placebo	Risk with 5‐HT3 antagonists	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Nausea ‐ intraoperative	Study population		RR 0.55 (0.42 to 0.71)	1419 (12 RCTs)	⊕⊕⊝⊝ LOW ^{1 2}
Nausea ‐ intraoperative	479 per 1000	263 per 1000 (201 to 340)	RR 0.55 (0.42 to 0.71)	1419 (12 RCTs)	⊕⊕⊝⊝ LOW ^{1 2}
Vomiting ‐ intraoperative	Study population		RR 0.46 (0.29 to 0.73)	1414 (11 RCTs)	⊕⊝⊝⊝ VERY LOW ^{3 4 5}
Vomiting ‐ intraoperative	241 per 1000	111 per 1000 (70 to 176)	RR 0.46 (0.29 to 0.73)	1414 (11 RCTs)	⊕⊝⊝⊝ VERY LOW ^{3 4 5}
Nausea ‐ postoperative	Study population		RR 0.40 (0.30 to 0.54)	1340 (10 RCTs)	⊕⊕⊕⊝ MODERATE ⁶
Nausea ‐ postoperative	338 per 1000	135 per 1000 (101 to 183)	RR 0.40 (0.30 to 0.54)	1340 (10 RCTs)	⊕⊕⊕⊝ MODERATE ⁶
Vomiting ‐ postoperative	Study population		RR 0.47 (0.31 to 0.69)	1450 (10 RCTs)	⊕⊕⊝⊝ LOW ^{5 7}
Vomiting ‐ postoperative	228 per 1000	107 per 1000 (71 to 157)	RR 0.47 (0.31 to 0.69)	1450 (10 RCTs)	⊕⊕⊝⊝ LOW ^{5 7}
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
¹ Downgrade 1 for risk of bias: > 90% of data comes from studies with unclear selection bias ² Downgrade 1 for inconsistency: there may be substantial heterogeneity I² = 65%, Chi² P = 0.0009. 3 Downgrade 1 for risk of bias: > 80% of data comes from studies with unclear selection bias 4 Downgrade 1 for inconsistency: there may be substantial heterogeneity I² = 58%, Chi² P = 0.008. 5 Downgrade 1 for publication bias: there is some evidence of possible publication bias in the funnel plot. 6 Downgrade 1 for risk of bias: > 65% of data comes from studies with unclear selection bias 7 Downgrade 1 for risk of bias: > 70% of data comes from studies with unclear selection bias

Summary of findings 1. 5‐HT3 antagonists compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Summary of findings 2. Dopamine antagonists compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Dopamine antagonists compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section
Patient or population: women undergoing regional anaesthesia for caesarean section Setting: hospitals across low‐, middle‐ and high‐income countries Intervention: dopamine antagonists Comparison: placebo
Outcomes	Risk with placebo	Risk with dopamine antagonists (B)	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Nausea ‐ intraoperative	Study population		RR 0.38 (0.27 to 0.52)	1180 (15 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2}
Nausea ‐ intraoperative	444 per 1000	169 per 1000 (120 to 231)	RR 0.38 (0.27 to 0.52)	1180 (15 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2}
Vomiting ‐ intraoperative	Study population		RR 0.41 (0.28 to 0.60)	942 (12 RCTs)	⊕⊕⊝⊝ LOW ¹
Vomiting ‐ intraoperative	211 per 1000	87 per 1000 (59 to 127)	RR 0.41 (0.28 to 0.60)	942 (12 RCTs)	⊕⊕⊝⊝ LOW ¹
Nausea ‐ postoperative	Study population		RR 0.61 (0.48 to 0.79)	601 (7 RCTs)	⊕⊕⊝⊝ LOW ¹
Nausea ‐ postoperative	393 per 1000	240 per 1000 (189 to 311)	RR 0.61 (0.48 to 0.79)	601 (7 RCTs)	⊕⊕⊝⊝ LOW ¹
Vomiting ‐ postoperative	Study population		RR 0.63 (0.44 to 0.92)	860 (9 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 3}
Vomiting ‐ postoperative	264 per 1000	167 per 1000 (116 to 243)	RR 0.63 (0.44 to 0.92)	860 (9 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 3}
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
¹ Downgrade 2 for risk of bias: all the data come from studies with unclear risk of selection bias. ² Downgrade 1 for inconsistency. Moderate to substantial heterogeneity, I² = 54%, Chi² P = 0.005 ³ Downgrade 1 for publication bias: evidence of some publication bias in the funnel plot

Summary of findings 2. Dopamine antagonists compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Summary of findings 3. Corticosteroids compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Corticosteroids compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section
Patient or population: women undergoing regional anaesthesia for caesarean section Setting: hospitals across low‐, middle‐ and high‐income countries Intervention: corticosteroids Comparison: placebo
Outcomes	Risk with placebo	Risk with corticosteroids (C)	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Nausea ‐ intraoperative	Study population		RR 0.56 (0.37 to 0.83)	609 (6 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2}
Nausea ‐ intraoperative	403 per 1000	226 per 1000 (149 to 334)	RR 0.56 (0.37 to 0.83)	609 (6 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2}
Vomiting ‐ intraoperative	Study population		RR 0.52 (0.31 to 0.87)	609 (6 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 3}
Vomiting ‐ intraoperative	141 per 1000	73 per 1000 (44 to 123)	RR 0.52 (0.31 to 0.87)	609 (6 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 3}
Nausea ‐ postoperative	Study population		RR 0.59 (0.49 to 0.73)	733 (6 RCTs)	⊕⊕⊕⊝ MODERATE ⁴
Nausea ‐ postoperative	491 per 1000	290 per 1000 (240 to 358)	RR 0.59 (0.49 to 0.73)	733 (6 RCTs)	⊕⊕⊕⊝ MODERATE ⁴
Vomiting ‐ postoperative	Study population		RR 0.68 (0.49 to 0.95)	793 (7 RCTs)	⊕⊕⊝⊝ LOW ^{5 6}
Vomiting ‐ postoperative	355 per 1000	241 per 1000 (174 to 337)	RR 0.68 (0.49 to 0.95)	793 (7 RCTs)	⊕⊕⊝⊝ LOW ^{5 6}
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
¹ Downgrade 2 for risk of bias: all the data comes from studies with unclear risk of selection bias ² Downgrade 1 for inconsistency: there is moderate heterogeneity I² = 50% and Chi² P = 0.06. ³ Downgrade 1 for imprecision: Wide CI close to line of no difference. Only 61 events out of 609 women. ⁴ Downgrade 1 for risk of bias: 69% of data comes from studies with unclear risk of selection bias. ⁵ Downgrade 1 for risk of bias: 83%% of data comes from studies with unclear risk of selection bias. ⁶ Downgrade 1 for inconsistency: may show moderate heterogeneity. I² = 52%. Chi² P = 0.03.

Summary of findings 3. Corticosteroids compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Summary of findings 4. Antihistamines compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Antihistamines compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section
Patient or population: preventing nausea and vomiting Setting: in women undergoing regional anaesthesia for caesarean section Intervention: antihistamines Comparison: placebo
Outcomes	Risk with Placebo	Risk with antihistamines	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Nausea ‐ intraoperative	Study population		RR 0.99 (0.47 to 2.11)	149 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{1 2}
Nausea ‐ intraoperative	155 per 1000	153 per 1000 (73 to 327)	RR 0.99 (0.47 to 2.11)	149 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{1 2}
Vomiting ‐ intraoperative	Study population		not estimable	149 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{1 3}	Only one RCT with no intraoperative vomiting events
Vomiting ‐ intraoperative	0 per 1000	0 per 1000 (0 to 0)	not estimable	149 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{1 3}	Only one RCT with no intraoperative vomiting events
Nausea ‐ postoperative	Study population		RR 0.44 (0.30 to 0.64)	514 (4 RCTs)	⊕⊕⊝⊝ LOW ⁴
Nausea ‐ postoperative	309 per 1000	136 per 1000 (93 to 198)	RR 0.44 (0.30 to 0.64)	514 (4 RCTs)	⊕⊕⊝⊝ LOW ⁴
Vomiting ‐ postoperative	Study population		RR 0.48 (0.29 to 0.81)	333 (3 RCTs)	⊕⊝⊝⊝ VERY LOW ^{4 5}
Vomiting ‐ postoperative	189 per 1000	91 per 1000 (55 to 153)	RR 0.48 (0.29 to 0.81)	333 (3 RCTs)	⊕⊝⊝⊝ VERY LOW ^{4 5}
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
¹ Downgrade 2 for risk of bias; only one study with unclear risk of bias across 6 domains and high risk for one domain ² Downgrade 2 for imprecision: wide CI, only 23 events out of 149 women in a single study. ³ Downgrade 2 for imprecision: there are no events. ⁴ Downgrade 2 for risk of bias: all data from studies with unclear risk of selection bias ⁵ Downgrade 1 for imprecision: only 45 events out of 333 women.

Summary of findings 4. Antihistamines compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Summary of findings 5. Anticholinergics compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Anticholinergics compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section
Patient or population: women undergoing regional anaesthesia for caesarean section Setting: hospitals across low‐, middle‐ and high‐income countries Intervention: anticholinergics Comparison: placebo
Outcomes	Risk with placebo	Risk with anticholinergics	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Nausea ‐ intraoperative	Study population		RR 0.67 (0.51 to 0.87)	453 (4 RCTs)	⊕⊕⊝⊝ LOW ¹
Nausea ‐ intraoperative	665 per 1000	446 per 1000 (339 to 579)	RR 0.67 (0.51 to 0.87)	453 (4 RCTs)	⊕⊕⊝⊝ LOW ¹
Vomiting ‐ intraoperative	Study population		RR 0.79 (0.40 to 1.54)	453 (4 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2 3}
Vomiting ‐ intraoperative	304 per 1000	240 per 1000 (122 to 468)	RR 0.79 (0.40 to 1.54)	453 (4 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2 3}
Nausea ‐ postoperative	Study population		‐	(0 RCTs)	‐
Nausea ‐ postoperative	see comment	see comment	‐	(0 RCTs)	‐
Vomiting ‐ postoperative	Study population		RR 0.55 (0.41 to 0.74)	161 (1 RCT)	⊕⊕⊝⊝ LOW ^{4 5}
Vomiting ‐ postoperative	728 per 1000	401 per 1000 (299 to 539)	RR 0.55 (0.41 to 0.74)	161 (1 RCT)	⊕⊕⊝⊝ LOW ^{4 5}
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
¹ Downgrade 2 for risk of bias: all the data from studies with unclear selection bias. ² Downgrade 1 for inconsistency: there may be moderate heterogeneity I² = 52% Chi² P = 0.10. ³ Downgrade 1 for imprecision: wide CI, crossing the line of no difference. 120 events out of 453 women participants. ⁴ Downgrade 1 for risk of bias: only one study with unclear allocation concealment but adequate sequence generation ⁵ Downgrade 1 for imprecision: a single study shows a wide confidence interval away from the line of no difference but with 91 events out of 161 women participants.

Summary of findings 5. Anticholinergics compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Summary of findings 6. Sedatives compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Sedatives compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section
Patient or population: women undergoing regional anaesthesia for caesarean section Setting: hospitals across low‐, middle‐ and high‐income countries Intervention: sedatives Comparison: placebo
Outcomes	Risk with placebo	Risk with sedatives (F)	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Nausea ‐ intraoperative	Study population		RR 0.65 (0.51 to 0.82)	593 (8 RCTs)	⊕⊕⊕⊝ MODERATE ¹
Nausea ‐ intraoperative	375 per 1000	244 per 1000 (191 to 308)	RR 0.65 (0.51 to 0.82)	593 (8 RCTs)	⊕⊕⊕⊝ MODERATE ¹
Vomiting ‐ intraoperative	Study population		RR 0.35 (0.24 to 0.52)	593 (8 RCTs)	⊕⊕⊕⊝ MODERATE ²
Vomiting ‐ intraoperative	294 per 1000	103 per 1000 (71 to 153)	RR 0.35 (0.24 to 0.52)	593 (8 RCTs)	⊕⊕⊕⊝ MODERATE ²
Nausea ‐ postoperative	Study population		RR 0.25 (0.09 to 0.71)	145 (2 RCTs)	⊕⊝⊝⊝ VERY LOW ^{3 4}
Nausea ‐ postoperative	441 per 1000	110 per 1000 (40 to 313)	RR 0.25 (0.09 to 0.71)	145 (2 RCTs)	⊕⊝⊝⊝ VERY LOW ^{3 4}
Vomiting ‐ postoperative	Study population		RR 0.09 (0.03 to 0.28)	145 (2 RCTs)	⊕⊕⊝⊝ LOW ⁵
Vomiting ‐ postoperative	356 per 1000	32 per 1000 (11 to 100)	RR 0.09 (0.03 to 0.28)	145 (2 RCTs)	⊕⊕⊝⊝ LOW ⁵
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
¹ Downgrade 1 for risk of bias: 56% of data from studies with low risk of selection bias. 2 Downgrade 1 for risk of bias: 75% of data were from studies with unclear selection bias. ³ Downgrade 1 for inconsistency: moderate heterogeneity. I² = 58%. Chi² P = 0.09. ⁴ Downgrade 2 for imprecision: low number of events ‐ 37 and low number of participants 145. Wide CI though a reasonable distance from line of no difference. ⁵ Downgrade 2 for imprecision: low number of events ‐ 23 and low number of participants 145. Wide CI but a good distance from the line of no difference although the data of high effectiveness comes from just one study of 44 women.

Summary of findings 6. Sedatives compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Summary of findings 7. Opioid antagonists compared to placebo for preventing nausea and vomiting

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Opioid antagonists compared to placebo for preventing nausea and vomiting
Patient or population: preventing nausea and vomiting Setting: in women undergoing regional anaesthesia for caesarean section Intervention: opioid antagonists Comparison: placebo
Outcomes	Risk with placebo	Risk with opioid antagonists	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Nausea ‐ intraoperative	Study population		‐	(0 studies)	‐
Nausea ‐ intraoperative	see comment	see comment	‐	(0 studies)	‐
Vomiting ‐ intraoperative	Study population		‐	(0 study)	‐
Vomiting ‐ intraoperative	see comment	see comment	‐	(0 study)	‐
Nausea ‐ postoperative	Study population		RR 0.75 (0.39 to 1.45)	120 (1 RCT)	⊕⊕⊝⊝ LOW ¹
Nausea ‐ postoperative	267 per 1000	200 per 1000 (104 to 387)	RR 0.75 (0.39 to 1.45)	120 (1 RCT)	⊕⊕⊝⊝ LOW ¹
Vomiting ‐ postoperative	Study population		RR 1.25 (0.35 to 4.43)	120 (1 RCT)	⊕⊕⊝⊝ LOW ²
Vomiting ‐ postoperative	67 per 1000	83 per 1000 (23 to 295)	RR 1.25 (0.35 to 4.43)	120 (1 RCT)	⊕⊕⊝⊝ LOW ²
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
¹ Downgrade 2 for imprecision. Only 28 events out of 120 women in one study. Wide CI crossing line of no difference. ² Downgrade 2 for imprecision. Only 9 events out of 120 women in one study. Wide CI crossing line of no difference.

Summary of findings 7. Opioid antagonists compared to placebo for preventing nausea and vomiting

Summary of findings 8. Acupressure/acupuncture compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Acupressure/acupuncture compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section
Patient or population: women undergoing regional anaesthesia for caesarean section Setting: hospitals across low‐, middle‐ and high‐income countries Intervention: acupressure/acupuncture Comparison: placebo
Outcomes	Risk with placebo	Risk with acupressure/acupuncture (K)	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Nausea ‐ intraoperative	Study population		RR 0.55 (0.41 to 0.74)	1221 (9 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2}
Nausea ‐ intraoperative	466 per 1000	256 per 1000 (191 to 345)	RR 0.55 (0.41 to 0.74)	1221 (9 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2}
Vomiting ‐ intraoperative	Study population		RR 0.52 (0.33 to 0.80)	1221 (9 RCTs)	⊕⊕⊝⊝ LOW ¹
Vomiting ‐ intraoperative	236 per 1000	123 per 1000 (78 to 189)	RR 0.52 (0.33 to 0.80)	1221 (9 RCTs)	⊕⊕⊝⊝ LOW ¹
Nausea ‐ postoperative	Study population		RR 0.46 (0.27 to 0.75)	1069 (7 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 3}
Nausea ‐ postoperative	411 per 1000	189 per 1000 (111 to 308)	RR 0.46 (0.27 to 0.75)	1069 (7 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 3}
Vomiting ‐ postoperative	Study population		RR 0.52 (0.34 to 0.79)	1069 (7 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 4}
Vomiting ‐ postoperative	302 per 1000	157 per 1000 (103 to 239)	RR 0.52 (0.34 to 0.79)	1069 (7 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 4}
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
¹ Downgrade 2 for risk of bias: all the data comes from studies which are unclear risk of selection bias. ² Downgrade 1 for inconsistency: substantial heterogeneity I² = 69% Chi² P = 0.0010. ³ Downgrade 1 for inconsistency: substantial heterogeneity. I² = 81% and Chi² P = < 0.0001. Could be downgrade by 2, borderline decision ⁴ Downgrade 1 for inconsistency: moderate heterogeneity. I² = 62% and Chi² P = 0.01.

Summary of findings 8. Acupressure/acupuncture compared to placebo for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

Summary of findings 9. Ginger compared to placebo for preventing nausea and vomiting

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Ginger compared to placebo for preventing nausea and vomiting
Patient or population: preventing nausea and vomiting Setting: in women undergoing regional anaesthesia for caesarean section? Intervention: ginger Comparison: placebo
Outcomes	Risk with placebo	Risk with ginger	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Nausea ‐ intraoperative	Study population		RR 0.66 (0.36 to 1.21)	331 (2 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2 3}
Nausea ‐ intraoperative	586 per 1000	387 per 1000 (211 to 709)	RR 0.66 (0.36 to 1.21)	331 (2 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2 3}
Vomiting ‐ intraoperative	Study population		RR 0.62 (0.38 to 1.00)	331 (2 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 4}
Vomiting ‐ intraoperative	408 per 1000	253 per 1000 (155 to 408)	RR 0.62 (0.38 to 1.00)	331 (2 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 4}
Nausea ‐ postoperative	Study population		RR 0.63 (0.22 to 1.77)	92 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{5 6}
Nausea ‐ postoperative	174 per 1000	110 per 1000 (38 to 308)	RR 0.63 (0.22 to 1.77)	92 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{5 6}
Vomiting ‐ postoperative	Study population		RR 0.20 (0.02 to 1.65)	92 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{5 7}
Vomiting ‐ postoperative	109 per 1000	22 per 1000 (2 to 179)	RR 0.20 (0.02 to 1.65)	92 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{5 7}
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
¹ Downgrade 2 for risk of bias: Only 2 studies both with unclear risk of selection bias ² Downgrade 1 for inconsistency. Substantial heterogeneity. I² = 74%, Chi² P = 0.05 ³ Downgrade 1 for imprecision. Very wide CI crossing the line of no difference. 170 events and 331 women participants ⁴ Downgrade 1 for imprecision: Wide CI. meeting the line of no difference. 112 events and 331 women participating ⁵ Downgrade 2 for risk of bias: Only 1 study with unclear risk of selection bias ⁶ Downgrade 2 for imprecision: Wide CI. Only 6 events out of 92 women ⁷ Downgrade 2 for imprecision: Wide CI crosses line of no difference. 5 events only and just 92 women included

Summary of findings 9. Ginger compared to placebo for preventing nausea and vomiting

Comparison 1. 5‐HT3 antagonists vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Nausea ‐ intraoperative Show forest plot	12	1419	Risk Ratio (M‐H, Random, 95% CI)	0.55 [0.42, 0.71]

1.1.1 Ondansetron ‐ 4 mg	9	1111	Risk Ratio (M‐H, Random, 95% CI)	0.55 [0.41, 0.73]
1.1.2 Ondansetron ‐ 8 mg	1	32	Risk Ratio (M‐H, Random, 95% CI)	0.45 [0.20, 1.01]
1.1.3 Granisetron ‐ 1 mg	1	176	Risk Ratio (M‐H, Random, 95% CI)	1.14 [0.59, 2.20]
1.1.4 Granisetron 3 mg	1	100	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.18, 0.61]
1.2 Vomiting ‐ intraoperative Show forest plot	11	1414	Risk Ratio (M‐H, Random, 95% CI)	0.46 [0.29, 0.73]

1.2.1 Ondansetron ‐ 4 mg	8	1059	Risk Ratio (M‐H, Random, 95% CI)	0.51 [0.31, 0.84]
1.2.2 Ondansetron ‐ 8 mg	1	32	Risk Ratio (M‐H, Random, 95% CI)	0.14 [0.02, 1.03]
1.2.3 Granisetron ‐ 1 mg	1	176	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.19, 2.28]
1.2.4 Tropisotron 2 mg	1	147	Risk Ratio (M‐H, Random, 95% CI)	0.09 [0.01, 0.67]
1.3 Nausea ‐ postoperative Show forest plot	10	1340	Risk Ratio (M‐H, Random, 95% CI)	0.40 [0.30, 0.54]

1.3.1 Ondansetron ‐ 4 mg	8	1023	Risk Ratio (M‐H, Random, 95% CI)	0.39 [0.26, 0.58]
1.3.2 Ondansetron ‐ 8 mg	1	90	Risk Ratio (M‐H, Random, 95% CI)	0.44 [0.18, 1.09]
1.3.3 Granisetron ‐ 40 mcg/kg	1	80	Risk Ratio (M‐H, Random, 95% CI)	0.36 [0.14, 0.90]
1.3.4 Tropisotron ‐ 2 mg	1	147	Risk Ratio (M‐H, Random, 95% CI)	0.46 [0.12, 1.71]
1.4 Vomiting ‐ postoperative Show forest plot	10	1450	Risk Ratio (M‐H, Random, 95% CI)	0.47 [0.31, 0.69]

1.4.1 Ondansetron ‐ 4 mg	8	1133	Risk Ratio (M‐H, Random, 95% CI)	0.44 [0.27, 0.71]
1.4.2 Ondansetron ‐ 8 mg	1	90	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.19, 5.15]
1.4.3 Granisetron ‐ 40 mcg/kg	1	80	Risk Ratio (M‐H, Random, 95% CI)	0.43 [0.12, 1.54]
1.4.4 Tropisotron ‐ 2 mg	1	147	Risk Ratio (M‐H, Random, 95% CI)	0.21 [0.01, 4.38]
1.5 'Nausea + Vomiting' ‐ intraoperative (not pre‐specified) Show forest plot	1	147	Risk Ratio (M‐H, Random, 95% CI)	0.72 [0.53, 0.97]

1.5.1 Tropisotron ‐ 2 mg	1	147	Risk Ratio (M‐H, Random, 95% CI)	0.72 [0.53, 0.97]
1.6 'Nausea + Vomiting' ‐ postoperative ‐ (not pre‐specified) Show forest plot	5	576	Risk Ratio (M‐H, Random, 95% CI)	0.57 [0.41, 0.80]

1.6.1 Ondansetron ‐ 4 mg	3	255	Risk Ratio (M‐H, Random, 95% CI)	0.68 [0.40, 1.13]
1.6.2 Ondansetron ‐ 8 mg	1	100	Risk Ratio (M‐H, Random, 95% CI)	0.38 [0.19, 0.72]
1.6.3 Tropisotron ‐ 2 mg	1	147	Risk Ratio (M‐H, Random, 95% CI)	0.46 [0.12, 1.71]
1.6.4 Granisetron ‐ 0.1 mg	1	74	Risk Ratio (M‐H, Random, 95% CI)	0.72 [0.22, 2.31]
1.7 Maternal satisfaction Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

1.7.1 Ondansetron ‐ 4 mg	2		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
1.7.2 Ondansetron ‐ 8 mg	0		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
1.7.3 Granisetron ‐ 1 mg	0		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
1.7.4 Granisetron ‐ 3 mg	0		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
1.8 Maternal adverse outcomes Show forest plot	1	100	Risk Ratio (M‐H, Random, 95% CI)	Not estimable

1.8.1 Ondansetron ‐ 8 mg	1	100	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
1.9 Headache/dizziness/vertigo Show forest plot	4	433	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.60, 1.79]

1.9.1 Ondansetron ‐ 4 mg	4	433	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.60, 1.79]
1.10 Hypotension Show forest plot	3	290	Risk Ratio (M‐H, Random, 95% CI)	1.22 [0.72, 2.08]

1.10.1 Ondansetron ‐ 4 mg	2	114	Risk Ratio (M‐H, Random, 95% CI)	1.44 [0.48, 4.34]
1.10.2 Granisetron ‐ 1 mg	1	176	Risk Ratio (M‐H, Random, 95% CI)	3.00 [0.12, 72.65]
1.11 Pruritus/itching Show forest plot	4	488	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.69, 1.05]

1.11.1 Ondansetron ‐ 4 mg	3	298	Risk Ratio (M‐H, Random, 95% CI)	0.65 [0.36, 1.14]
1.11.2 Ondansetron ‐ 8 mg	2	190	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.84, 1.05]
1.12 Dry mouth Show forest plot	1	130	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.17, 3.22]

1.12.1 Ondansetron ‐ 4 mg	1	130	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.17, 3.22]
1.13 Drowsiness/sedation Show forest plot	2	170	Risk Ratio (M‐H, Random, 95% CI)	3.94 [0.45, 34.63]

1.13.1 Ondansetron ‐ 4 mg	2	170	Risk Ratio (M‐H, Random, 95% CI)	3.94 [0.45, 34.63]
1.14 Rescue antiemetic (not pre‐specified) Show forest plot	1	158	Risk Ratio (M‐H, Random, 95% CI)	0.32 [0.11, 0.93]

Comparison 1. 5‐HT3 antagonists vs placebo

Comparison 2. Dopamine antagonists vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Nausea ‐ intraoperative Show forest plot	15	1180	Risk Ratio (M‐H, Random, 95% CI)	0.38 [0.27, 0.52]

2.1.1 Metoclopramide ‐ 10 mg	10	748	Risk Ratio (M‐H, Random, 95% CI)	0.39 [0.24, 0.62]
2.1.2 Metoclopramide ‐ 20 mg	1	100	Risk Ratio (M‐H, Random, 95% CI)	0.27 [0.10, 0.75]
2.1.3 Metoclopramide ‐ 0.15 mg/kg	1	67	Risk Ratio (M‐H, Random, 95% CI)	0.32 [0.12, 0.90]
2.1.4 Droperidol ‐ 0.5 mg	1	128	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.17, 0.65]
2.1.5 Droperidol ‐ 0.625 mg	1	32	Risk Ratio (M‐H, Random, 95% CI)	0.36 [0.15, 0.90]
2.1.6 Droperidol ‐ 1.25 mg	1	75	Risk Ratio (M‐H, Random, 95% CI)	0.44 [0.17, 1.15]
2.1.7 Droperidol ‐ 5 mg	1	30	Risk Ratio (M‐H, Random, 95% CI)	0.30 [0.09, 1.01]
2.2 Vomiting ‐ intraoperative Show forest plot	12	942	Risk Ratio (M‐H, Random, 95% CI)	0.41 [0.28, 0.60]

2.2.1 Metoclopramide ‐ 10 mg	8	610	Risk Ratio (M‐H, Random, 95% CI)	0.45 [0.27, 0.76]
2.2.2 Metoclopramide ‐ 0.15 mg/kg	1	67	Risk Ratio (M‐H, Random, 95% CI)	0.09 [0.01, 1.54]
2.2.3 Droperidol ‐ 0.5 mg	1	128	Risk Ratio (M‐H, Random, 95% CI)	0.34 [0.09, 1.23]
2.2.4 Droperidol ‐ 0.625 mg	1	32	Risk Ratio (M‐H, Random, 95% CI)	0.29 [0.07, 1.17]
2.2.5 Droperidol ‐ 1.25 mg	1	75	Risk Ratio (M‐H, Random, 95% CI)	0.37 [0.10, 1.27]
2.2.6 Droperidol ‐ 5 mg	1	30	Risk Ratio (M‐H, Random, 95% CI)	0.13 [0.02, 0.98]
2.3 Nausea ‐ postoperative Show forest plot	7	601	Risk Ratio (M‐H, Random, 95% CI)	0.61 [0.48, 0.79]

2.3.1 Metoclopramide ‐ 10 mg	5	454	Risk Ratio (M‐H, Random, 95% CI)	0.63 [0.49, 0.80]
2.3.2 Metoclopramide ‐ 0.15 mg/kg	1	67	Risk Ratio (M‐H, Random, 95% CI)	0.40 [0.16, 1.02]
2.3.3 Droperidol ‐ 1.25 mg	1	80	Risk Ratio (M‐H, Random, 95% CI)	1.67 [0.43, 6.51]
2.4 Vomiting ‐ postoperative Show forest plot	9	860	Risk Ratio (M‐H, Random, 95% CI)	0.63 [0.44, 0.92]

2.4.1 Metoclopramide ‐ 10 mg	6	653	Risk Ratio (M‐H, Random, 95% CI)	0.72 [0.44, 1.20]
2.4.2 Metoclopramide ‐ 0.15 mg/kg	1	67	Risk Ratio (M‐H, Random, 95% CI)	0.32 [0.12, 0.90]
2.4.3 Droperidol ‐ 1.25 mg	2	140	Risk Ratio (M‐H, Random, 95% CI)	0.55 [0.32, 0.94]
2.5 'Nausea + vomiting' ‐ intraoperative (not pre‐specfied) Show forest plot	1	98	Risk Ratio (M‐H, Random, 95% CI)	0.12 [0.02, 0.88]

2.5.1 Metoclopramide ‐ 10 mg	1	98	Risk Ratio (M‐H, Random, 95% CI)	0.12 [0.02, 0.88]
2.6 'Nausea + vomiting' ‐ postoperative (not pre‐specified) Show forest plot	3	450	Risk Ratio (M‐H, Random, 95% CI)	0.23 [0.05, 1.02]

2.6.1 Metoclopramide ‐ 10 mg	3	360	Risk Ratio (M‐H, Random, 95% CI)	0.20 [0.02, 1.71]
2.6.2 Droperidol ‐ 0.625 mg	1	90	Risk Ratio (M‐H, Random, 95% CI)	0.30 [0.12, 0.75]
2.7 Maternal satisfaction Show forest plot	1	102	Risk Ratio (M‐H, Random, 95% CI)	1.42 [0.91, 2.21]

2.7.1 Metoclopramide ‐ 10 mg	1	102	Risk Ratio (M‐H, Random, 95% CI)	1.42 [0.91, 2.21]
2.8 Anxiety Show forest plot	1	50	Risk Ratio (M‐H, Random, 95% CI)	4.00 [0.48, 33.33]

2.8.1 Metoclopramide ‐ 10 mg	1	50	Risk Ratio (M‐H, Random, 95% CI)	4.00 [0.48, 33.33]
2.9 Headache/dizziness Show forest plot	1	102	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.01, 8.00]

2.9.1 Metoclopramide ‐ 10 mg	1	102	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.01, 8.00]
2.10 Hypotension Show forest plot	6	563	Risk Ratio (M‐H, Random, 95% CI)	1.08 [0.90, 1.30]

2.10.1 Metoclopramide ‐ 10 mg	4	278	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.77, 1.28]
2.10.2 Metoclopramide ‐ 0.15 mg/kg	1	67	Risk Ratio (M‐H, Random, 95% CI)	1.62 [0.66, 3.95]
2.10.3 Droperidol ‐ 0.5 mg	1	128	Risk Ratio (M‐H, Random, 95% CI)	1.13 [0.80, 1.60]
2.10.4 Droperidol ‐ 0.625 mg	1	90	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.69, 2.25]
2.11 Rescue antiemetics (not pre‐specified) Show forest plot	1	98	Risk Ratio (M‐H, Random, 95% CI)	0.26 [0.03, 2.25]

2.12 Sedation Show forest plot	2	220	Risk Ratio (M‐H, Random, 95% CI)	5.54 [2.78, 11.06]

2.12.1 Metoclopramide ‐ 10 mg	2	130	Risk Ratio (M‐H, Random, 95% CI)	4.24 [1.73, 10.41]
2.12.2 Droperidol ‐ 0.625 mg	1	90	Risk Ratio (M‐H, Random, 95% CI)	8.17 [2.77, 24.05]
2.13 Pruritus/itching Show forest plot	3	504	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.93, 1.03]

2.13.1 Metoclopramide ‐ 10 mg	2	429	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.93, 1.03]
2.13.2 Droperidol ‐ 1.25 mg	1	75	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.55, 1.53]

Comparison 2. Dopamine antagonists vs placebo

Comparison 3. Corticosteroids vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Nausea ‐ intraoperative Show forest plot	6	609	Risk Ratio (M‐H, Random, 95% CI)	0.56 [0.37, 0.83]

3.1.1 Dexamethasone ‐ 4 mg IV	1	200	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.68, 1.17]
3.1.2 Dexamethasone ‐ 4 mg IT	1	62	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.15, 0.75]
3.1.3 Dexamethasone ‐ 8 mg IV	5	347	Risk Ratio (M‐H, Random, 95% CI)	0.55 [0.37, 0.82]
3.2 Vomiting ‐ intraoperative Show forest plot	6	609	Risk Ratio (M‐H, Random, 95% CI)	0.52 [0.31, 0.87]

3.2.1 Dexamethasone ‐ 4 mg IV	1	200	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.33, 2.32]
3.2.2 Dexamethasone ‐ 4 mg IT	1	62	Risk Ratio (M‐H, Random, 95% CI)	0.24 [0.02, 2.47]
3.2.3 Dexamethasone ‐ 8 mg IV	5	347	Risk Ratio (M‐H, Random, 95% CI)	0.44 [0.23, 0.83]
3.3 Nausea ‐ postoperative Show forest plot	6	733	Risk Ratio (M‐H, Random, 95% CI)	0.59 [0.49, 0.73]

3.3.1 Dexamethasone ‐ 2.5 mg IV	1	58	Risk Ratio (M‐H, Random, 95% CI)	0.56 [0.19, 1.63]
3.3.2 Dexamethasone ‐ 4 mg IV	1	200	Risk Ratio (M‐H, Random, 95% CI)	0.52 [0.30, 0.88]
3.3.3 Dexamethasone ‐ 5 mg IV	1	59	Risk Ratio (M‐H, Random, 95% CI)	0.43 [0.13, 1.38]
3.3.4 Dexamethasone ‐ 8 mg IV	2	168	Risk Ratio (M‐H, Random, 95% CI)	0.82 [0.60, 1.13]
3.3.5 Dexamethasone ‐ 8 mg IT	1	120	Risk Ratio (M‐H, Random, 95% CI)	0.54 [0.39, 0.74]
3.3.6 Dexamethasone ‐ 10 mg IV	2	128	Risk Ratio (M‐H, Random, 95% CI)	0.43 [0.26, 0.69]
3.4 Vomiting ‐ postoperative Show forest plot	7	793	Risk Ratio (M‐H, Random, 95% CI)	0.68 [0.49, 0.95]

3.4.1 Dexamethasone ‐ 2.5 mg IV	1	58	Risk Ratio (M‐H, Random, 95% CI)	0.74 [0.22, 2.49]
3.4.2 Dexamethasone ‐ 4 mg IV	1	200	Risk Ratio (M‐H, Random, 95% CI)	0.14 [0.01, 2.73]
3.4.3 Dexamethasone ‐ 5 mg IV	1	59	Risk Ratio (M‐H, Random, 95% CI)	0.34 [0.08, 1.51]
3.4.4 Dexamethasone ‐ 8 mg IV	3	228	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.79, 1.31]
3.4.5 Dexamethasone ‐ 8 mg IT	1	120	Risk Ratio (M‐H, Random, 95% CI)	0.50 [0.31, 0.81]
3.4.6 Dexamethasone ‐ 10 mg IV	2	128	Risk Ratio (M‐H, Random, 95% CI)	0.44 [0.27, 0.73]
3.5 'Nausea + Vomiting' ‐ intraoperative (not pre‐specified) Show forest plot	1	108	Risk Ratio (M‐H, Random, 95% CI)	1.65 [0.96, 2.84]

3.5.1 Dexamethasone ‐ 8 mg IV	1	108	Risk Ratio (M‐H, Random, 95% CI)	1.65 [0.96, 2.84]
3.6 'Nausea + Vomiting' ‐ postoperative ‐ (not pre‐specified) Show forest plot	1	108	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.79, 1.12]

3.6.1 Dexamethasone ‐ 8 mg IV	1	108	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.79, 1.12]
3.7 Hypotension Show forest plot	1	124	Risk Ratio (M‐H, Random, 95% CI)	0.62 [0.34, 1.12]

3.7.1 Dexamethasone ‐ 4 mg IT	1	62	Risk Ratio (M‐H, Random, 95% CI)	0.44 [0.25, 0.78]
3.7.2 Dexamethasone ‐ 8 mg IV	1	62	Risk Ratio (M‐H, Random, 95% CI)	0.80 [0.53, 1.22]
3.8 Bradycardia Show forest plot	1	124	Risk Ratio (M‐H, Random, 95% CI)	0.58 [0.30, 1.16]

3.8.1 Dexamethasone ‐ 4 mg IT	1	62	Risk Ratio (M‐H, Random, 95% CI)	0.40 [0.14, 1.15]
3.8.2 Dexamethasone ‐ 8 mg IV	1	62	Risk Ratio (M‐H, Random, 95% CI)	0.77 [0.32, 1.87]
3.9 Shivering Show forest plot	1	124	Risk Ratio (M‐H, Random, 95% CI)	0.66 [0.41, 1.05]

3.9.1 Dexamethasone ‐ 4 mg IT	1	62	Risk Ratio (M‐H, Random, 95% CI)	0.53 [0.26, 1.09]
3.9.2 Dexamethasone ‐ 8 mg IV	1	62	Risk Ratio (M‐H, Random, 95% CI)	0.77 [0.42, 1.40]
3.10 Rescue antiemetics (not pre‐specified) Show forest plot	1	108	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.53, 1.57]

3.10.1 Dexamethasone 8 mg IV	1	108	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.53, 1.57]

Comparison 3. Corticosteroids vs placebo

Comparison 4. Antihistamines vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Nausea ‐ intraoperative Show forest plot	1	149	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.47, 2.11]

4.1.1 Dimenhydrinate ‐ 25 mg	1	149	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.47, 2.11]
4.2 Vomiting ‐ intraoperative Show forest plot	1	149	Risk Ratio (M‐H, Random, 95% CI)	Not estimable

4.2.1 Dimenhydrinate ‐ 25 mg	1	149	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
4.3 Nausea ‐ postoperative Show forest plot	4	514	Risk Ratio (M‐H, Random, 95% CI)	0.44 [0.30, 0.64]

4.3.1 Dimenhydrinate ‐ 25 mg	1	149	Risk Ratio (M‐H, Random, 95% CI)	0.68 [0.31, 1.52]
4.3.2 Dimenhydrate ‐ 50 mg	2	215	Risk Ratio (M‐H, Random, 95% CI)	0.38 [0.21, 0.69]
4.3.3 Dimenhydrate ‐ 100 mg	1	90	Risk Ratio (M‐H, Random, 95% CI)	0.17 [0.05, 0.57]
4.3.4 Cyclizine ‐ 50 mg	1	60	Risk Ratio (M‐H, Random, 95% CI)	0.50 [0.28, 0.88]
4.4 Vomiting ‐ postoperative Show forest plot	3	333	Risk Ratio (M‐H, Random, 95% CI)	0.48 [0.29, 0.81]

4.4.1 Dimenhydrinate ‐ 25 mg	1	149	Risk Ratio (M‐H, Random, 95% CI)	0.13 [0.01, 2.48]
4.4.2 Dimenhydrate ‐ 50 mg	1	124	Risk Ratio (M‐H, Random, 95% CI)	0.52 [0.19, 1.42]
4.4.3 Cyclizine ‐ 50 mg	1	60	Risk Ratio (M‐H, Random, 95% CI)	0.50 [0.27, 0.93]
4.5 Hypotension Show forest plot	1	149	Risk Ratio (M‐H, Random, 95% CI)	1.47 [0.90, 2.40]

4.5.1 Dimenhydrinate ‐ 25 mg	1	149	Risk Ratio (M‐H, Random, 95% CI)	1.47 [0.90, 2.40]

Comparison 4. Antihistamines vs placebo

Comparison 5. Anticholinergics vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
5.1 Nausea ‐ intraoperative Show forest plot	4	453	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.51, 0.87]

5.1.1 Glycopyrrolate ‐ 0.2 mg	2	89	Risk Ratio (M‐H, Random, 95% CI)	0.49 [0.22, 1.09]
5.1.2 Scopolamine patch	2	364	Risk Ratio (M‐H, Random, 95% CI)	0.71 [0.51, 0.97]
5.2 Vomiting ‐ intraoperative Show forest plot	4	453	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.40, 1.54]

5.2.1 Glycopyrrolate ‐ 0.2 mg	2	89	Risk Ratio (M‐H, Random, 95% CI)	0.45 [0.12, 1.62]
5.2.2 Scopolamine patch	2	364	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.36, 2.59]
5.3 Nausea ‐ postoperative Show forest plot	0	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable

5.4 Vomiting ‐ postoperative Show forest plot	1	161	Risk Ratio (M‐H, Random, 95% CI)	0.55 [0.41, 0.74]

5.4.1 Scopolamine patch	1	161	Risk Ratio (M‐H, Random, 95% CI)	0.55 [0.41, 0.74]
5.5 'Nausea + Vomiting' ‐ intraoperative (not pre‐specified) Show forest plot	0	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable

5.6 'Nausea + vomiting' ‐ postoperative (not pre‐specified) Show forest plot	2	334	Risk Ratio (M‐H, Random, 95% CI)	0.46 [0.25, 0.85]

5.6.1 Atropine ‐ 100 mcg IT	1	105	Risk Ratio (M‐H, Random, 95% CI)	0.27 [0.14, 0.52]
5.6.2 Atropine ‐ 100 mcg IV	1	99	Risk Ratio (M‐H, Random, 95% CI)	0.72 [0.45, 1.15]
5.6.3 Scopolamine 0.3 mg	1	130	Risk Ratio (M‐H, Random, 95% CI)	0.47 [0.22, 1.01]
5.7 Blurred vision Show forest plot	2	407	Risk Ratio (M‐H, Random, 95% CI)	0.84 [0.21, 3.40]

5.7.1 Scopolamine patch	1	203	Risk Ratio (M‐H, Random, 95% CI)	1.98 [0.37, 10.57]
5.7.2 Atropine ‐ 100 mcg intrathecal	1	105	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.18, 4.76]
5.7.3 Atropine ‐ 100 mcg intravenous	1	99	Risk Ratio (M‐H, Random, 95% CI)	0.10 [0.00, 1.96]
5.8 Anxiety/Disorientation Show forest plot	2	407	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.35, 2.58]

5.8.1 Scopolamine patch	1	203	Risk Ratio (M‐H, Random, 95% CI)	2.97 [0.12, 72.08]
5.8.2 Atropine ‐ 100 mcg intrathecal	1	105	Risk Ratio (M‐H, Random, 95% CI)	0.76 [0.19, 3.01]
5.8.3 Atropine ‐ 100 mcg intravenous	1	99	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.18, 4.95]
5.9 Dizziness Show forest plot	2	333	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.37, 2.24]

5.9.1 Scopolamine patch	1	203	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.39, 2.54]
5.9.2 Scopolamine 0.3 mg/5 mL IV	1	130	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.01, 8.03]
5.10 Hypotension Show forest plot	3	293	Risk Ratio (M‐H, Random, 95% CI)	0.81 [0.58, 1.13]

5.10.1 Glycopyrrolate ‐ 0.2 mg	2	89	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.50, 1.26]
5.10.2 Atropine ‐ 100 mcg intrathecal	1	105	Risk Ratio (M‐H, Random, 95% CI)	0.46 [0.07, 3.11]
5.10.3 Atropine ‐ 100 mcg intravenous	1	99	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.09, 10.15]
5.11 Pruritus/itching Show forest plot	2	407	Risk Ratio (M‐H, Random, 95% CI)	0.87 [0.65, 1.18]

5.11.1 Scopolamine patch	1	203	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.66, 1.28]
5.11.2 Atropine ‐ 100 mcg intrathecal	1	105	Risk Ratio (M‐H, Random, 95% CI)	0.53 [0.19, 1.47]
5.11.3 Atropine ‐ 100 mcg intravenous	1	99	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.36, 2.16]
5.12 Xerostomia/dry mouth Show forest plot	2	334	Risk Ratio (M‐H, Random, 95% CI)	0.82 [0.53, 1.27]

5.12.1 Atropine ‐ 100 mcg intrathecal	1	105	Risk Ratio (M‐H, Random, 95% CI)	0.82 [0.43, 1.59]
5.12.2 Atropine ‐ 100 mcg intravenous	1	99	Risk Ratio (M‐H, Random, 95% CI)	0.72 [0.36, 1.41]
5.12.3 Scopolamine 0.3 mg/5 mL IV	1	130	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.35, 4.45]
5.13 Drowsiness Show forest plot	1	130	Risk Ratio (M‐H, Random, 95% CI)	3.00 [0.12, 72.31]

5.13.1 Scopolamine 0.3 mg/5 mL IV	1	130	Risk Ratio (M‐H, Random, 95% CI)	3.00 [0.12, 72.31]

Comparison 5. Anticholinergics vs placebo

Comparison 6. Sedatives vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
6.1 Nausea ‐ intraoperative Show forest plot	8	593	Risk Ratio (M‐H, Random, 95% CI)	0.65 [0.51, 0.82]

6.1.1 Propofol ‐ 0.5 mg/kg/hr	1	26	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.19, 2.93]
6.1.2 Propofol ‐ 1.0 mg/kg/hr	3	135	Risk Ratio (M‐H, Random, 95% CI)	0.56 [0.26, 1.20]
6.1.3 Propofol ‐ 1.5 mg/kg/hr	1	27	Risk Ratio (M‐H, Random, 95% CI)	0.35 [0.09, 1.35]
6.1.4 Propofol ‐ 10 mg IV ‐ single dose	1	57	Risk Ratio (M‐H, Random, 95% CI)	1.19 [0.39, 3.67]
6.1.5 Propofol ‐ 20 mg + 1.0 mg/kg/hr	2	89	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.47, 1.32]
6.1.6 Propofol TCI target 1 ug/ml	1	80	Risk Ratio (M‐H, Random, 95% CI)	0.42 [0.23, 0.75]
6.1.7 Midazolam ‐ 1.0 mg + 1.0 mg/hr	2	89	Risk Ratio (M‐H, Random, 95% CI)	0.76 [0.48, 1.20]
6.1.8 Ketamine 0.4.mg/kg	1	90	Risk Ratio (M‐H, Random, 95% CI)	0.46 [0.19, 1.11]
6.1.9 Intrathecal midazolam 2 mg vs placebo	0	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
6.2 Vomiting ‐ intraoperative Show forest plot	8	593	Risk Ratio (M‐H, Random, 95% CI)	0.35 [0.24, 0.52]

6.2.1 Propofol ‐ 0.5 mg/kg/hr	1	26	Risk Ratio (M‐H, Random, 95% CI)	0.90 [0.24, 3.35]
6.2.2 Propofol ‐ 1.0 mg/kg/hr	3	135	Risk Ratio (M‐H, Random, 95% CI)	0.31 [0.15, 0.65]
6.2.3 Propofol ‐ 1.5 mg/kg/hr	1	27	Risk Ratio (M‐H, Random, 95% CI)	0.23 [0.05, 1.12]
6.2.4 Propofol ‐ 10 mg IV ‐ single dose	1	57	Risk Ratio (M‐H, Random, 95% CI)	0.60 [0.06, 6.21]
6.2.5 Propofol ‐ 20 mg + 1.0 mg/kg/hr	2	89	Risk Ratio (M‐H, Random, 95% CI)	0.17 [0.05, 0.65]
6.2.6 Propofol TCI target 1 ug/ml	1	80	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.10, 1.14]
6.2.7 Midazolam ‐ 1.0 mg + 1.0 mg/hr	2	89	Risk Ratio (M‐H, Random, 95% CI)	0.18 [0.01, 3.86]
6.2.8 Ketamine 0.4 mg/kg	1	90	Risk Ratio (M‐H, Random, 95% CI)	0.44 [0.15, 1.34]
6.2.9 Intrathecal midazolam 2 mg vs placebo	0	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
6.3 Nausea ‐ postoperative Show forest plot	2	145	Risk Ratio (M‐H, Random, 95% CI)	0.25 [0.09, 0.71]

6.3.1 Propofol ‐ 10 mg IV ‐ single dose	1	57	Risk Ratio (M‐H, Random, 95% CI)	2.38 [0.23, 24.83]
6.3.2 Propofol ‐ 20 mg + 1.0 mg/kg/hr	1	44	Risk Ratio (M‐H, Random, 95% CI)	0.16 [0.06, 0.40]
6.3.3 Midazolam ‐ 1.0 mg + 1.0 mg/hr	1	44	Risk Ratio (M‐H, Random, 95% CI)	0.18 [0.08, 0.40]
6.4 Vomiting ‐ postoperative Show forest plot	2	145	Risk Ratio (M‐H, Random, 95% CI)	0.09 [0.03, 0.28]

6.4.1 Propofol ‐ 10 mg IV ‐ single dose	1	57	Risk Ratio (M‐H, Random, 95% CI)	0.40 [0.02, 9.31]
6.4.2 Propofol ‐ 20 mg + 1.0 mg/kg/hr	1	44	Risk Ratio (M‐H, Random, 95% CI)	0.02 [0.00, 0.37]
6.4.3 Midazolam ‐ 1.0 mg + 1.0 mg/hr	1	44	Risk Ratio (M‐H, Random, 95% CI)	0.09 [0.02, 0.37]
6.5 'Nausea + vomiting' ‐ intraoperative (not pre‐specified) Show forest plot	0	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable

6.6 'Nausea + vomiting' ‐ postoperative (not pre‐specified) Show forest plot	2	348	Risk Ratio (M‐H, Random, 95% CI)	0.06 [0.02, 0.22]

6.6.1 Propofol ‐ 0.5 mg/kg	1	230	Risk Ratio (M‐H, Random, 95% CI)	0.02 [0.01, 0.08]
6.6.2 Propofol TCI target 1 ug/ml	1	39	Risk Ratio (M‐H, Random, 95% CI)	0.05 [0.00, 0.93]
6.6.3 Propofol TCI target 1.5 ug/ml	1	39	Risk Ratio (M‐H, Random, 95% CI)	0.17 [0.04, 0.80]
6.6.4 Propofol TCI target 2 ug/ml	1	40	Risk Ratio (M‐H, Random, 95% CI)	0.08 [0.01, 0.66]
6.7 Pruritis/itching Show forest plot	2	348	Risk Ratio (M‐H, Random, 95% CI)	0.04 [0.02, 0.12]

6.7.1 Propofol ‐ 0.5 mg/kg	1	230	Risk Ratio (M‐H, Random, 95% CI)	0.03 [0.01, 0.09]
6.7.2 Propofol TCI target 1 ug/ml	1	39	Risk Ratio (M‐H, Random, 95% CI)	0.12 [0.01, 2.78]
6.7.3 Propofol TCI target 1.5 ug/ml	1	39	Risk Ratio (M‐H, Random, 95% CI)	0.12 [0.01, 2.78]
6.7.4 Propofol TCI target 2 ug/ml	1	40	Risk Ratio (M‐H, Random, 95% CI)	0.12 [0.01, 2.69]
6.8 Hypotension Show forest plot	2	198	Risk Ratio (M‐H, Random, 95% CI)	1.29 [0.86, 1.93]

6.8.1 Propofol TCI target 1 ug/ml	2	119	Risk Ratio (M‐H, Random, 95% CI)	1.30 [0.83, 2.03]
6.8.2 Propofol TCI target 1.5 ug/ml	1	39	Risk Ratio (M‐H, Random, 95% CI)	0.86 [0.20, 3.76]
6.8.3 Propofol TCI target 2 ug/ml	1	40	Risk Ratio (M‐H, Random, 95% CI)	1.67 [0.44, 6.36]
6.9 Shivering Show forest plot	1	118	Risk Ratio (M‐H, Random, 95% CI)	0.24 [0.08, 0.72]

6.9.1 Propofol TCI target 1 ug/ml	1	39	Risk Ratio (M‐H, Random, 95% CI)	0.34 [0.06, 2.14]
6.9.2 Propofol TCI target 1.5 ug/ml	1	39	Risk Ratio (M‐H, Random, 95% CI)	0.17 [0.02, 1.70]
6.9.3 Propofol TCI target 2 ug/ml	1	40	Risk Ratio (M‐H, Random, 95% CI)	0.22 [0.04, 1.15]
6.10 Apgar score < 7 at 5 mins Show forest plot	1	80	Risk Ratio (M‐H, Random, 95% CI)	Not estimable

6.10.1 Propofol TCI target 1 ug/ml	1	80	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
6.11 Initiation of breastfeeding Show forest plot	1	80	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.95, 1.05]

6.11.1 Propofol TCI target 1 ug/ml	1	80	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.95, 1.05]

Comparison 6. Sedatives vs placebo

Comparison 7. Opioid antagonist/partial agonist vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
7.1 Nausea ‐ intraoperative Show forest plot	0	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable

7.2 Vomiting ‐ intraoperative Show forest plot	0	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable

7.3 Nausea ‐ postoperative Show forest plot	1	120	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.39, 1.45]

7.3.1 Nalbuphine ‐ 4 mg	1	120	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.39, 1.45]
7.4 Vomiting ‐ postoperative Show forest plot	1	120	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.35, 4.43]

7.4.1 Nalbuphine ‐ 4 mg	1	120	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.35, 4.43]
7.5 'Nausea + vomiting' ‐ intraoperative (not pre‐specified) Show forest plot	0	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable

7.6 'Nausea + vomiting' ‐ postoperative (not pre‐specified) Show forest plot	1	77	Risk Ratio (M‐H, Random, 95% CI)	0.09 [0.02, 0.37]

7.6.1 Nalbuphine ‐ 0.5 mg	1	77	Risk Ratio (M‐H, Random, 95% CI)	0.09 [0.02, 0.37]
7.7 Pruritus/itching Show forest plot	2	197	Risk Ratio (M‐H, Random, 95% CI)	0.34 [0.02, 5.27]

7.7.1 Nalbuphine ‐ 0.5 mg	1	77	Risk Ratio (M‐H, Random, 95% CI)	0.13 [0.04, 0.39]
7.7.2 Nalbuphine ‐ 4 mg	1	120	Risk Ratio (M‐H, Random, 95% CI)	0.86 [0.74, 0.99]

Comparison 7. Opioid antagonist/partial agonist vs placebo

Comparison 8. Acupressure/acupuncture vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
8.1 Nausea ‐ intraoperative Show forest plot	9	1221	Risk Ratio (M‐H, Random, 95% CI)	0.55 [0.41, 0.74]

8.1.1 Acupressure	9	1221	Risk Ratio (M‐H, Random, 95% CI)	0.55 [0.41, 0.74]
8.2 Vomiting ‐ intraoperative Show forest plot	9	1221	Risk Ratio (M‐H, Random, 95% CI)	0.52 [0.33, 0.80]

8.2.1 Acupressure	9	1221	Risk Ratio (M‐H, Random, 95% CI)	0.52 [0.33, 0.80]
8.3 Nausea ‐ postoperative Show forest plot	7	1069	Risk Ratio (M‐H, Random, 95% CI)	0.46 [0.27, 0.75]

8.3.1 Acupressure	7	1069	Risk Ratio (M‐H, Random, 95% CI)	0.46 [0.27, 0.75]
8.4 Vomiting ‐ postoperative Show forest plot	7	1069	Risk Ratio (M‐H, Random, 95% CI)	0.52 [0.34, 0.79]

8.4.1 Acupressure	7	1069	Risk Ratio (M‐H, Random, 95% CI)	0.52 [0.34, 0.79]
8.5 Anxiety Show forest plot	1	50	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.07, 15.12]

8.5.1 Acupressure	1	50	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.07, 15.12]
8.6 Dizziness Show forest plot	1	60	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.07, 15.26]

8.6.1 Acupressure	1	60	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.07, 15.26]
8.7 Hypotension Show forest plot	1	50	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.54, 1.16]

8.7.1 Acupressure	1	50	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.54, 1.16]
8.8 Pruritus/itching Show forest plot	3	395	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.85, 1.55]

8.8.1 Acupressure	3	395	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.85, 1.55]
8.9 Rescue antiemetic (not pre‐specified) Show forest plot	2	240	Risk Ratio (M‐H, Random, 95% CI)	0.50 [0.36, 0.71]

Comparison 8. Acupressure/acupuncture vs placebo

Comparison 9. Ginger vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
9.1 Nausea ‐ intraoperative Show forest plot	2	331	Risk Ratio (M‐H, Random, 95% CI)	0.66 [0.36, 1.21]

9.1.1 Ginger ‐ 1 g oral	1	239	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.68, 1.06]
9.1.2 Ginger ‐ 25 drops oral	1	92	Risk Ratio (M‐H, Random, 95% CI)	0.46 [0.26, 0.82]
9.2 Vomiting ‐ intraoperative Show forest plot	2	331	Risk Ratio (M‐H, Random, 95% CI)	0.62 [0.38, 1.00]

9.2.1 Ginger 1 g oral	1	239	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.52, 1.10]
9.2.2 Ginger ‐ 25 drops oral	1	92	Risk Ratio (M‐H, Random, 95% CI)	0.46 [0.26, 0.82]
9.3 Nausea ‐ postoperative Show forest plot	1	92	Risk Ratio (M‐H, Random, 95% CI)	0.62 [0.22, 1.77]

9.3.1 Ginger ‐ 25 drops oral	1	92	Risk Ratio (M‐H, Random, 95% CI)	0.62 [0.22, 1.77]
9.4 Vomiting ‐ postoperative Show forest plot	1	92	Risk Ratio (M‐H, Random, 95% CI)	0.20 [0.02, 1.65]

9.4.1 Ginger ‐ 25 drops oral	1	92	Risk Ratio (M‐H, Random, 95% CI)	0.20 [0.02, 1.65]

Comparison 9. Ginger vs placebo