title: A factorial trial of six interventions for the prevention of postoperative nausea and vomiting.
abstract: BACKGROUND
  Untreated, one third of patients who undergo surgery will have postoperative nausea and vomiting. Although many trials have been conducted, the relative benefits of prophylactic antiemetic interventions given alone or in combination remain unknown.
  
  
  METHODS
  We enrolled 5199 patients at high risk for postoperative nausea and vomiting in a randomized, controlled trial of factorial design that was powered to evaluate interactions among as many as three antiemetic interventions. Of these patients, 4123 were randomly assigned to 1 of 64 possible combinations of six prophylactic interventions: 4 mg of ondansetron or no ondansetron; 4 mg of dexamethasone or no dexamethasone; 1.25 mg of droperidol or no droperidol; propofol or a volatile anesthetic; nitrogen or nitrous oxide; and remifentanil or fentanyl. The remaining patients were randomly assigned with respect to the first four interventions. The primary outcome was nausea and vomiting within 24 hours after surgery, which was evaluated blindly.
  
  
  RESULTS
  Ondansetron, dexamethasone, and droperidol each reduced the risk of postoperative nausea and vomiting by about 26 percent. Propofol reduced the risk by 19 percent, and nitrogen by 12 percent; the risk reduction with both of these agents (i.e., total intravenous anesthesia) was thus similar to that observed with each of the antiemetics. All the interventions acted independently of one another and independently of the patients' baseline risk. Consequently, the relative risks associated with the combined interventions could be estimated by multiplying the relative risks associated with each intervention. Absolute risk reduction, though, was a critical function of patients' baseline risk.
  
  
  CONCLUSIONS
  Because antiemetic interventions are similarly effective and act independently, the safest or least expensive should be used first. Prophylaxis is rarely warranted in low-risk patients, moderate-risk patients may benefit from a single intervention, and multiple interventions should be reserved for high-risk patients.
authors.affiliation: Julius-Maximilians Universitat, Wurzburg, Germany. apfel@ponv.org
authors.forename: Christian C
authors.initials: CC
authors.lastname: Apfel
authors.forename: Kari
authors.initials: K
authors.lastname: Korttila
authors.forename: Mona
authors.initials: M
authors.lastname: Abdalla
authors.forename: Heinz
authors.initials: H
authors.lastname: Kerger
authors.forename: Alparslan
authors.initials: A
authors.lastname: Turan
authors.forename: Ina
authors.initials: I
authors.lastname: Vedder
authors.forename: Carmen
authors.initials: C
authors.lastname: Zernak
authors.forename: Klaus
authors.initials: K
authors.lastname: Danner
authors.forename: Ritva
authors.initials: R
authors.lastname: Jokela
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Pocock
authors.forename: Stefan
authors.initials: S
authors.lastname: Trenkler
authors.forename: Markus
authors.initials: M
authors.lastname: Kredel
authors.forename: Andreas
authors.initials: A
authors.lastname: Biedler
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Sessler
authors.forename: Norbert
authors.initials: N
authors.lastname: Roewer
mesh_terms: D000768:Anesthesia, General; D000771:Anesthesia, Intravenous; D000772:Anesthesia, Local; D018686:Anesthetics, Intravenous; D000932:Antiemetics / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D004329:Droperidol / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005163:Factor Analysis, Statistical; D005260:Female; D005283:Fentanyl; D006801:Humans; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D009584:Nitrogen; D009609:Nitrous Oxide; D017294:Ondansetron / Q000627:therapeutic use*; D010880:Piperidines; D020250:Postoperative Nausea and Vomiting / Q000517:prevention & control*; D011292:Premedication; D015742:Propofol; D000077208:Remifentanil; D016037:Single-Blind Method
chemical_list: D018686:Anesthetics, Intravenous; D000932:Antiemetics; D010880:Piperidines; D017294:Ondansetron; D003907:Dexamethasone; D009609:Nitrous Oxide; D009584:Nitrogen; D004329:Droperidol; D000077208:Remifentanil; D005283:Fentanyl; D015742:Propofol