Wagner 1996.

Study characteristics
Methods	Study design: randomized controlled trial Study grouping: 2 groups, monoprophylaxis
Participants	Baseline characteristics Placebo Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): NA Received treatment (n): NA Analysed (n): 50 Age (mean ± SD, median (IQR), median (range)): 34.2 ± 8.6 Weight (mean ± SD, median (IQR), median (range)): 68.7 ± 14.5 BMI (mean ± SD, median (IQR), median (range)): NA ASA I/II/III/IV (n): 39/11/0/0 Gender (female in %): 100 Non‐smoker (%): NA History of PONV/motion sickness (%): 26/28 Type of general anaesthesia: inhalational anaesthesia (en‐/isoflurane, N₂O) Duration of anaesthesia or surgery (in min; as mean or median): 119.4 Use of perioperative opioids (if yes, which?): 149.0 µg fentanyl intraoperative, 5.8 mg morphine postoperative Type of surgery: closed laparoscopic gynaecological surgery, cholecystectomy Metoclopramide Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): NA Received treatment (n): NA Analysed (n): 59 Age (mean ± SD, median (IQR), median (range)): 35.5 ± 7.6 Weight (mean ± SD, median (IQR), median (range)): 67.3 ± 14.2 BMI (mean ± SD, median (IQR), median (range)): NA ASA I/II/III/IV (n): 43/16/0/0 Gender (female in %): 100 Non‐smoker (%): NA History of PONV/motion sickness (%): 30.5/44.1 Type of general anaesthesia: inhalational anaesthesia (en‐/isoflurane, N₂O) Duration of anaesthesia or surgery (in min; as mean or median): 120.3 Use of perioperative opioids (if yes, which?): 143.5 µg fentanyl intraoperative, 6.3 mg morphine postoperative Type of surgery: closed laparoscopic gynaecological surgery, cholecystectomy Included criteria: female, 18 years of age or older, ASA I or II, scheduled for elective closed laparoscopic gynaecological surgery or cholecystectomy Excluded criteria: pregnant or nursing; required antiemetic therapy within 14 days before surgery; allergic to substituted benzamides, anaesthetics, or narcotics; history of significant gastrointestinal disease; required medications that could cause extrapyramidal side effects; had received emetogenic chemotherapy within 30 days before surgery; history of epistaxis or nasal passage abnormalities; history of chronic exposure to alcohol, barbiturates, or tranquilizers; had taken part in an investigational drug study within 30 days before surgery; suffering from rhinitis or nasal tissue inflammation Pretreatment: baseline characteristics (age, weight, ASA): no. Potential effect modifiers (gender, duration of anaesthesia, history of PONV/motion sickness, perioperative opioids): no; (non‐smoker): unclear
Interventions	Intervention characteristics Placebo Dose: 2 × 0.05 mL vehicle solution Time point of administration: approximately 15 minutes before expected emergence from anaesthesia Route of administration: intranasal, 1 spray in each nostril Rescue antiemetics (if yes, which?): droperidol in PACU, prochlorperazine and trimethobenzamide in ward Metoclopramide Dose: 20 mg (200 mg/mL in a buffered aqueous solution; 0.05 mL (10 mg) of solution with each spray) Time point of administration: approximately 15 minutes before expected emergence from anaesthesia Route of administration: intranasal, 1 spray in each nostril Rescue antiemetics (if yes, which?): droperidol in PACU, prochlorperazine and trimethobenzamide in ward
Outcomes	Nausea (0 to 24 hours) Outcome type: dichotomous outcome Subjects with any AE (0 to 24 hours) Outcome type: dichotomous outcome Sedation/drowsiness (0 to 24 hours) Outcome type: dichotomous outcome
Identification	Sponsorship source: supported in part by Naska Pharmacal, Lincolnton, North Carolina, USA Country: USA Setting: NA, single‐centre Author's name: Bertil K.J. Wagner Institution: College of Pharmacy, Rutgers University and the Department Anesthesiology, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey, USA Email: NA Address: Rutgers University, College of Pharmacy, Busch Campus, Piscataway, NJ 08855, USA Language: English Duration of study: NA Trial registry number: NA Study's primary outcome: incidence of PONV
Notes	None
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "patients were randomized to receive either metoclopramide 20 mg or placebo according to a randomized, block design" Judgement comment: no further information on sequence generation provided
Allocation concealment (selection bias)	Unclear risk	Judgement comment: no statement
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Judgement comment: insufficient information on blinding ("double‐blind")
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Judgement comment: insufficient information on blinding ("double‐blind")
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "a total of 119 patients were enrolled with 109 patients considered eligible for efficacy analysis. Ten patients were excluded from the statistical analysis due to protocol violations. Of these, six patients underwent other surgical procedures, two patients received unauthorized medications, and two patients did not receive the study drug (one in each group). The two patient groups (elective closed laparoscopic gynecological surgery and elective closed laparoscopic cholecystectomy) were combined since the laparoscopic procedure itself is a primary inciting event for the development of PONV"
Selective reporting (reporting bias)	Unclear risk	Judgement comment: no reference to a study protocol or trial registry number reported
Other bias	Unclear risk	Quote: "...are shown in parentheses. I demographics (Table 1) revealed no significant differences between the treatment groups. The frequency of a history..." Judgement comment: baseline characteristics (age, weight, ASA): no. Potential effect modifiers (gender, duration of anaesthesia, history of PONV/motion sickness, perioperative opioids): no; (non‐smoker): unclear