DeOliveira 2016.

Study characteristics
Methods	Study design: randomized controlled trial Study grouping: 3 groups, monoprophylaxis and combination prophylaxis, dose‐finding study
Participants	Baseline characteristics Ondansetron Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): 30 Received treatment (n): 30 Analysed (n): 27 Age (mean ± SD, median (IQR), median (range)): 35 (30 to 43) Weight (mean ± SD, median (IQR), median (range)): NA BMI (mean ± SD, median (IQR), median (range)): 26.1 ± 3.8 ASA I/II/III/IV (n): 15/12/0/0 Gender (female in %): 100 Non‐smoker (%): NA History of PONV/motion sickness (%): NA Type of general anaesthesia: balanced anaesthesia (sevoflurane, remifentanil) Duration of anaesthesia or surgery (in min; as mean or median): 95 Use of perioperative opioids (if yes, which?): 438 µg intraoperative remifentanil, postoperative hydromorphone orally Type of surgery: gynaecological laparoscopy Diphenhydramine (25 mg group) + ondansetron Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): 30 Received treatment (n): 30 Analysed (n): 24 Age (mean ± SD, median (IQR), median (range)): 36.5 (29.5 to 44.5) Weight (mean ± SD, median (IQR), median (range)): NA BMI (mean ± SD, median (IQR), median (range)): 25.7 ± 6.3 ASA I/II/III/IV (n): 13/11/0/0 Gender (female in %): 100 Non‐smoker (%): NA History of PONV/motion sickness (%): NA Type of general anaesthesia: balanced anaesthesia (sevoflurane, remifentanil) Duration of anaesthesia or surgery (in min; as mean or median): 90.5 Use of perioperative opioids (if yes, which?): 544.5 µg intraoperative remifentanil, postoperative hydromorphone orally Type of surgery: gynaecological laparoscopy Diphenhydramine (50 mg group) + ondansetron Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): 30 Received treatment (n): 30 Analysed (n): 24 Age (mean ± SD, median (IQR), median (range)): 37 (33.5 to 43) Weight (mean ± SD, median (IQR), median (range)): NA BMI (mean ± SD, median (IQR), median (range)): 26.3 ± 4.8 ASA I/II/III/IV (n): 10/14/0/0 Gender (female in %): 100 Non‐smoker (%): NA History of PONV/motion sickness (%): NA Type of general anaesthesia: balanced anaesthesia (sevoflurane, remifentanil) Duration of anaesthesia or surgery (in min; as mean or median): 105 Use of perioperative opioids (if yes, which?): 528 µg intraoperative remifentanil, postoperative hydromorphone orally Type of surgery: gynaecological laparoscopy Included criteria: healthy women undergoing outpatient gynaecological laparoscopy Excluded criteria: history of allergy to diphenhydramine, long‐term use of an opioid analgesic or corticosteroid, pregnant subjects, conversion from a laparoscopic to an open incision Pretreatment: baseline characteristics (age, BMI, ASA): no. Potential effect modifiers (gender, duration of anaesthesia, perioperative opioids): no; (history of PONV/motion sickness, non‐smoker): unclear
Interventions	Intervention characteristics Ondansetron Dose: 4 mg Time point of administration: saline after anaesthesia induction, ondansetron at end of procedure Route of administration: IV Rescue antiemetics (if yes, which?): metoclopramide 10 mg IV, prochlorperazine 5 mg IV Diphenhydramine (25 mg group) + ondansetron Dose: diphenhydramine 25 mg, ondansetron 4 mg Time point of administration: diphenhydramine after anaesthesia induction, ondansetron at end of procedure Route of administration: IV Rescue antiemetics (if yes, which?): metoclopramide 10 mg IV, prochlorperazine 5 mg IV Diphenhydramine (50 mg group) + ondansetron Dose: diphenhydramine 50 mg, ondansetron 4 mg Time point of administration: diphenhydramine after anaesthesia induction, ondansetron at end of procedure Route of administration: IV Rescue antiemetics (if yes, which?): metoclopramide 10 mg IV, prochlorperazine 5 mg IV
Outcomes	Vomiting (PACU) Outcome type: dichotomous outcome
Identification	Sponsorship source: Department of Anesthesiology, Northwestern University Country: USA Setting: outpatient, single‐centre Author's name: Gildasio S. De Oliveira Institution: Department of Anesthesiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA Email: g‐jr@northwestern.edu Address: Department of Anesthesiology, Feinberg School of Medicine, Northwestern University, 241 E Huron St F5‐704, Chicago, IL 60611, USA Duration of study: September 2011 to September 2012 Language: English Study's primary outcome: Global Quality of Recovery–40 score at 24 hours Trial registry number: NCT01451762
Notes	None
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "using a computer‐generated table of random numbers"
Allocation concealment (selection bias)	Low risk	Quote: "group assignments were sealed in sequentially numbered, opaque envelopes that were opened by a research nurse not involved with patient care or data collection after the subject provided written informed consent"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "subject provided written informed consent. The same nurse prepared syringes labeled with study drug to blind the anesthesia personnel and the investigators collecting..."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "subject provided written informed consent. The same nurse prepared syringes labeled with study drug to blind the anesthesia personnel and the investigators collecting the data. All subjects were premedicated..."
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Quote: "the details of the conduct of the study are shown in Fig. 1. Ninety subjects were randomized, and 75 completed the study. Patients were enrolled consecutively from September 2011 through September 2012" Judgement comment: number of dropouts > 15%. Reasons described
Selective reporting (reporting bias)	Unclear risk	Judgement comment: NCT01451762 (retrospective registration)
Other bias	Unclear risk	Quote: "patient's baseline characteristics and surgical factors were not different between groups (Table 1)" Judgement comment: baseline characteristics (age, BMI, ASA): no. Potential effect modifiers (gender, duration of anaesthesia, perioperative opioids): no; (history of PONV/motion sickness, non‐smoker): unclear