Gesztesi 2000‐1.

Study characteristics
Methods	Study design: randomized controlled trial Study grouping: 4 groups, dose‐finding study, monoprophylaxis
Participants	Baseline characteristics Placebo (to 100 mg) Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): NA Received treatment (n): NA Analysed (n): 21 Age (mean ± SD, median (IQR), median (range)): 43 ± 7 Weight (mean ± SD, median (IQR), median (range)): 63 ± 7 BMI (mean ± SD, median (IQR), median (range)): NA ASA I/II/III/IV (n): NA/NA/0/0 Gender (female in %): 100 Non‐smoker (%): NA History of PONV/motion sickness (%): NA Type of general anaesthesia: inhalational anaesthesia (isoflurane, N₂O) Duration of anaesthesia or surgery (in min; as mean or median): 97 Use of perioperative opioids (if yes, which?): 2 µg/kg to 4 µg/kg fentanyl at induction, 50 mg morphine intraoperatively and postoperatively via PCA Type of surgery: total abdominal hysterectomy CP‐122,721 (100 mg group) Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): NA Received treatment (n): NA Analysed (n): 21 Age (mean ± SD, median (IQR), median (range)): 43 ± 11 Weight (mean ± SD, median (IQR), median (range)): 69 ± 12 BMI (mean ± SD, median (IQR), median (range)): NA ASA I/II/III/IV (n): NA/NA/0/0 Gender (female in %): 100 Non‐smoker (%): NA History of PONV/motion sickness (%): NA Type of general anaesthesia: inhalational anaesthesia (isoflurane, N₂O) Duration of anaesthesia or surgery (in min; as mean or median): 95 Use of perioperative opioids (if yes, which?): 2 µg/kg to 4 µg/kg fentanyl at induction, 53 mg morphine intraoperatively and postoperatively via PCA Type of surgery: total abdominal hysterectomy Placebo (to 200 mg) Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): NA Received treatment (n): NA Analysed (n): 24 Age (mean ± SD, median (IQR), median (range)): 43 ± 7 Weight (mean ± SD, median (IQR), median (range)): 74 ± 18 BMI (mean ± SD, median (IQR), median (range)): NA ASA I/II/III/IV (n): NA/NA/0/0 Gender (female in %): 100 Non‐smoker (%): NA History of PONV/motion sickness (%): NA Type of general anaesthesia: inhalational anaesthesia (isoflurane, N₂O) Duration of anaesthesia or surgery (in min; as mean or median): 81 Use of perioperative opioids (if yes, which?): 2 µg/kg to 4 µg/kg fentanyl at induction, 47 mg morphine intraoperatively and postoperatively via PCA Type of surgery: total abdominal hysterectomy CP‐122,721 (200 mg group) Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): NA Received treatment (n): NA Analysed (n): 20 Age (mean ± SD, median (IQR), median (range)): 42 ± 8 Weight (mean ± SD, median (IQR), median (range)): 78 ± 11 BMI (mean ± SD, median (IQR), median (range)): NA ASA I/II/III/IV (n): NA/NA/0/0 Gender (female in %): 100 Non‐smoker (%): NA History of PONV/motion sickness (%): NA Type of general anaesthesia: inhalational anaesthesia (isoflurane, N₂O) Duration of anaesthesia or surgery (in min; as mean or median): 108 Use of perioperative opioids (if yes, which?): 2 µg/kg to 4 µg/kg fentanyl at induction, 45 mg morphine intraoperatively and postoperatively via PCA Type of surgery: total abdominal hysterectomy Included criteria: healthy, ASA I or II, nonpregnant women presenting for total abdominal hysterectomy procedures Excluded criteria: had received any antiemetic medications within 24 hours before induction of anaesthesia, had received an investigational drug within the past 30 days, had vomited or retched within the preceding 24 hours, more than 60% above their ideal body weight Pretreatment: baseline characteristics (age, weight, ASA): no. Potential effect modifiers (gender, duration of anaesthesia): no; (history of PONV/motion sickness, non‐smoker, perioperative opioids): unclear
Interventions	Intervention characteristics Placebo (to 100 mg) Dose: placebo Time point of administration: 60 to 90 minutes before induction of general anaesthesia Route of administration: PO Rescue antiemetics (if yes, which?): droperidol CP‐122,721 (100 mg group) Dose: 100 mg Time point of administration: 60 to 90 minutes before induction of general anaesthesia Route of administration: PO Rescue antiemetics (if yes, which?): droperidol Placebo (to 200 mg) Dose: placebo Time point of administration: 60 to 90 minutes before induction of general anaesthesia Route of administration: PO Rescue antiemetics (if yes, which?): droperidol CP‐122,721 (200 mg group) Dose: 200 mg Time point of administration: 60 to 90 minutes before induction of general anaesthesia Route of administration: PO Rescue antiemetics (if yes, which?): droperidol
Outcomes	Vomiting (0 to 24 hours) Outcome type: dichotomous outcome Vomiting (0 to 2 hours) Outcome type: dichotomous outcome Adverse events (general notes in the publication, 72 hours' observation) Outcome type: general notes on side effects
Identification	Sponsorship source: supported by Pfizer Central Research, Groton, Connecticut, USA Country: USA Setting: inpatient, multi‐centre Author's name: Paul F. White Institution: Departments of Anaesthesiology, Departments of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, USA Email: pwhite@mednet.swmed.edu Address: Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, 5363 Harry Hines Boulevard, F 2.208, Dallas, Texas, USA Duration of study: NA Language: English Study's primary outcome: incidence of postoperative emesis Trial registry number: NA
Notes	Two studies: dose‐ranging study (study I), interaction study (study II) Groups with same interventions pooled for analysis
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "in the interaction study, patients were randomly assigned to one of three treatment groups using a computer‐generated random number table" Judgement comment: "low risk of bias" for the interaction study. Missing information for the dose‐ranging study, but we assume similar performance
Allocation concealment (selection bias)	Unclear risk	Quote: "all study medications were prepared by the manufacturer (Pfizer, Inc., Groton, CT) in identical capsules" Quote: "the oral study drug was supplied by Pfizer Inc., in blinded containers, whereas the parenteral (intravenous) solution was prepared by a local pharmacist who was not otherwise involved in the conduct of the study" Judgement comment: insufficient information on allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "the patients, anesthesiologists, and observers were all blinded to the study medications being administered"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "the patients, anesthesiologists, and observers were all blinded to the study medications being administered"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "of the 277 patients enrolled in the two studies, 34 were withdrawn because of protocol violations (e.g., inadvertent administration of a drug with antiemetic properties during surgery), failure to receive the study medication at the appropriate time, or cancellation of the surgical procedure"
Selective reporting (reporting bias)	Unclear risk	Judgement comment: no reference to a study protocol or trial registry number reported
Other bias	Unclear risk	Quote: "the treatment groups were comparable with respect to age, weight, height, history of PONV and motion sickness, day of menstrual cycle, duration of surgery, and PCA morphine usage during the first 72 h postoperatively (tables 1 and 2)" Judgement comment: baseline characteristics (age, weight, ASA): no. Potential effect modifiers (gender, duration of anaesthesia): no; (history of PONV/motion sickness, non‐smoker, perioperative opioids): unclear