Philip 2000.

Study characteristics
Methods	Study design: randomized controlled trial Study grouping: 5 groups, monoprophylaxis, dose‐finding study
Participants	Baseline characteristics Placebo Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): 208 Received treatment (n): NA Analysed (n): 208 Age (mean ± SD, median (IQR), median (range)): 37.6 ± 12.4 Weight (mean ± SD, median (IQR), median (range)): 77.1 ± 17.7 BMI (mean ± SD, median (IQR), median (range)): NA ASA I/II/III/IV (n): 110/91/0/0 Gender (female in %): 70 Non‐smoker (%): NA History of PONV/motion sickness (%): 15/22 Type of general anaesthesia: balanced anaesthesia (isoflurane, N₂O, fentanyl/alfentanil) Duration of anaesthesia or surgery (in min; as mean or median): 66 Use of perioperative opioids (if yes, which?): NA Type of surgery: ear/nose/throat, ophthalmological, orthopaedic, urologic, breast, other Dolasetron (12.5 mg group) Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): 206 Received treatment (n): NA Analysed (n): 206 Age (mean ± SD, median (IQR), median (range)): 37.0 ± 13.4 Weight (mean ± SD, median (IQR), median (range)): 73.4 ± 17.2 BMI (mean ± SD, median (IQR), median (range)): NA ASA I/II/III/IV (n): 113/87/0/0 Gender (female in %): 71 Non‐smoker (%): NA History of PONV/motion sickness (%): 22/20 Type of general anaesthesia: balanced anaesthesia (isoflurane, N₂O, fentanyl/alfentanil) Duration of anaesthesia or surgery (in min; as mean or median): 66 Use of perioperative opioids (if yes, which?): NA Type of surgery: ear/nose/throat, ophthalmological, orthopaedic, urologic, breast, other Dolasetron (50 mg group) Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): 205 Received treatment (n): NA Analysed (n): 205 Age (mean ± SD, median (IQR), median (range)): 35.9 ± 11.8 Weight (mean ± SD, median (IQR), median (range)): 74.7 ± 16.6 BMI (mean ± SD, median (IQR), median (range)): NA ASA I/II/III/IV (n): 102/98/0/0 Gender (female in %): 71 Non‐smoker (%): NA History of PONV/motion sickness (%): 28/26 Type of general anaesthesia: balanced anaesthesia (isoflurane, N₂O, fentanyl/alfentanil) Duration of anaesthesia or surgery (in min; as mean or median): 66 Use of perioperative opioids (if yes, which?): NA Type of surgery: ear/nose/throat, ophthalmological, orthopaedic, urologic, breast, other Dolasetron (25 mg group) Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): 203 Received treatment (n): NA Analysed (n): 203 Age (mean ± SD, median (IQR), median (range)): 35.6 ± 10.6 Weight (mean ± SD, median (IQR), median (range)): 74.2 ± 16.7 BMI (mean ± SD, median (IQR), median (range)): NA ASA I/II/III/IV (n): 102/98/0/0 Gender (female in %): 69 Non‐smoker (%): NA History of PONV/motion sickness (%): 25/23 Type of general anaesthesia: balanced anaesthesia (isoflurane, N₂O, fentanyl/alfentanil) Duration of anaesthesia or surgery (in min; as mean or median): 66 Use of perioperative opioids (if yes, which?): NA Type of surgery: ear/nose/throat, ophthalmological, orthopaedic, urologic, breast, other Dolasetron (100 mg group) Assessed for eligibility (n): ‐ Enrolled (n): ‐ Randomized (n): 208 Received treatment (n): NA Analysed (n): 208 Age (mean ± SD, median (IQR), median (range)): 36.9 ± 11.9 Weight (mean ± SD, median (IQR), median (range)): 72.1 ± 17.4 BMI (mean ± SD, median (IQR), median (range)): NA ASA I/II/III/IV (n): 112/91/0/0 Gender (female in %): 70 Non‐smoker (%): NA History of PONV/motion sickness (%): 23/19 Type of general anaesthesia: balanced anaesthesia (isoflurane, N₂O, fentanyl/alfentanil) Duration of anaesthesia or surgery (in min; as mean or median): 72 Use of perioperative opioids (if yes, which?): NA Type of surgery: ear/nose/throat, ophthalmological, orthopaedic, urologic, breast, other Included criteria: male and female, 18 years of age or older, ASA I to III, undergoing outpatient surgery with general anaesthesia Excluded criteria: had received any drug with potential antiemetic activity within 24 hours of surgery, had received previous treatment with dolasetron, had any clinically significant cardiovascular abnormality (complete bundle‐branch block, cardiomyopathy, congestive heart failure, arrhythmia, second‐ or third‐degree heart block), exceeded ideal body weight by over 100%, had any clinically significant laboratory abnormalities or major organ system dysfunction, undergoing liver or gastrointestinal surgery, experienced nausea and/or vomiting within 24 hours of the present surgery, had taken an investigational drug within 30 days Pretreatment: baseline characteristics (age, weight, ASA): no. Potential effect modifiers (gender, duration of anaesthesia, history of motion sickness): no; (non‐smoker, perioperative opioids): unclear; (history of PONV): yes
Interventions	Intervention characteristics Placebo Dose: saline Time point of administration: approximately 15 minutes before cessation of nitrous oxide Route of administration: IV Rescue antiemetics (if yes, which?): droperidol and metoclopramide most frequently given Dolasetron (12.5 mg group) Dose: 12.5 mg Time point of administration: approximately 15 minutes before cessation of nitrous oxide Route of administration: IV Rescue antiemetics (if yes, which?): droperidol and metoclopramide most frequently given Dolasetron (50 mg group) Dose: 50 mg Time point of administration: approximately 15 minutes before cessation of nitrous oxide Route of administration: IV Rescue antiemetics (if yes, which?): droperidol and metoclopramide most frequently given Dolasetron (25 mg group) Dose: 25 mg Time point of administration: approximately 15 minutes before cessation of nitrous oxide Route of administration: IV Rescue antiemetics (if yes, which?): droperidol and metoclopramide most frequently given Dolasetron (100 mg group) Dose: 100 mg Time point of administration: approximately 15 minutes before cessation of nitrous oxide Route of administration: IV Rescue antiemetics (if yes, which?): droperidol and metoclopramide most frequently given
Outcomes	Nausea (0 to 24 hours) Outcome type: dichotomous outcome Complete response (no PONV) in 24 hours Outcome type: dichotomous outcome Arrhythmia (0 to 24 hours) Outcome type: dichotomous outcome Headache (0 to 24 hours) Outcome type: dichotomous outcome Sedation/drowsiness (0 to 24 hours) Outcome type: dichotomous outcome
Identification	Sponsorship source: NA Country: USA Setting: outpatient, multi‐centre (17) Author's name: B.K. Philip Institution: Brigham and Women's Hospital, Department of Anesthesiology Email: NA Address: Brigham and Women's Hospital, Department of Anesthesiology, Perioperative and Pain Medicine, 75 Francis St., Boston, MA 02115, USA Duration of study: NA Language: English Study's primary outcome: complete response, defined as no emetic episodes and no rescue antiemetic medication during the 24‐hour study period Trial registry number: NA
Notes	Study included in a pooled analysis (secondary publication)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "all were randomized, double‐blind, placebo‐controlled, multicenter trials with 24‐hour monitoring periods" Judgement comment: no further information on randomization method 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	Judgement comment: no missing outcome data
Selective reporting (reporting bias)	Unclear risk	Judgement comment: no reference to a study protocol or trial registry number reported
Other bias	High risk	Judgement comment: baseline characteristics (age, weight, ASA): no. Potential effect modifiers (gender, duration of anaesthesia, history of motion sickness): no; (non‐smoker, perioperative opioids): unclear; (history of PONV): yes