[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
In a randomized, controlled trial of factorial design, 5,199 patients at high risk for postoperative nausea and vomiting were randomly assigned to 1 of 64 possible combinations of 6 prophylactic interventions: 1) 4 mg of ondansetron or no ondansetron; 2) 4 mg of dexamethasone or no dexamethasone; 3) 1.25 mg of droperidol or no droperidol; 4) propofol or a volatile anesthetic; 5) nitrogen or nitrous oxide; 6) remifentanil or fentanyl. The primary aim parameter was nausea and vomiting within 24 h after surgery, which was evaluated blindly.


RESULTS
Ondansetron, dexamethasone, and droperidol each reduced the risk of postoperative nausea and vomiting by about 26%, propofol reduced the risk by 19%, and nitrogen by 12%. The risk reduction with both of these agents (i.e., total intravenous anesthesia) was thus similar to that observed with each of the antiemetics alone. All the interventions acted independently of each other 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. However, absolute risk reduction 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
C C
CC
Klinik und Poliklinik für Anaesthesiologie, Julius-Maximilians Universität, Würzburg. apfel@ponv.org
Bacher
A
A
Biedler
A
A
Danner
K
K
Danzeisen
O
O
Eberhart
L H J
LH
Forst
H
H
Fritz
G
G
Hergert
M
M
Frings
G
G
Goebel
A
A
Hopf
H-B
HB
Kerger
H
H
Kranke
P
P
Lange
M
M
Mertzlufft
F
F
Motsch
J
J
Paura
A
A
Roewer
N
N
Schneider
E
E
Stoecklein
K
K
Wermelt
J
J
Zernak
C
C
D000701:Analgesics, Opioid / Q000009:adverse effects; D018685:Anesthetics, Inhalation / Q000009:adverse effects; D018686:Anesthetics, Intravenous / Q000009:adverse effects; D000932:Antiemetics / Q000191:economics / Q000627:therapeutic use*; D002985:Clinical Protocols; D003907:Dexamethasone / Q000627:therapeutic use; D004329:Droperidol / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005283:Fentanyl / Q000009:adverse effects; D006801:Humans; D008297:Male; D016017:Odds Ratio; D017294:Ondansetron / Q000627:therapeutic use; D010880:Piperidines / Q000009:adverse effects; D020250:Postoperative Nausea and Vomiting / Q000188:drug therapy* / Q000191:economics / Q000517:prevention & control; D015742:Propofol / Q000009:adverse effects; D000077208:Remifentanil; D012107:Research Design; D012306:Risk
D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D000932:Antiemetics; D010880:Piperidines; D017294:Ondansetron; D003907:Dexamethasone; D004329:Droperidol; D000077208:Remifentanil; D005283:Fentanyl; D015742:Propofol
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