A factorial trial of six interventions for the prevention of postoperative nausea and vomiting.
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.
Apfel
Christian C
CC
Julius-Maximilians Universitat, Wurzburg, Germany. apfel@ponv.org
Korttila
Kari
K
Abdalla
Mona
M
Kerger
Heinz
H
Turan
Alparslan
A
Vedder
Ina
I
Zernak
Carmen
C
Danner
Klaus
K
Jokela
Ritva
R
Pocock
Stuart J
SJ
Trenkler
Stefan
S
Kredel
Markus
M
Biedler
Andreas
A
Sessler
Daniel I
DI
Roewer
Norbert
N
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
D018686:Anesthetics, Intravenous; D000932:Antiemetics; D010880:Piperidines; D017294:Ondansetron; D003907:Dexamethasone; D009609:Nitrous Oxide; D009584:Nitrogen; D004329:Droperidol; D000077208:Remifentanil; D005283:Fentanyl; D015742:Propofol