Droperidol and 5-HT3-receptor antagonists, alone or in combination, for prophylaxis of postoperative nausea and vomiting - A meta-analysis of randomised controlled trials

Background: Droperidol and 5-HT3-receptor antagonists are among the most po tent antiemetics to prevent postoperative nausea and vomiting (PONV). Combi nations of these drugs have been used to increase the efficacy of antiemeti c treatment. However, so far the quantitative effect of this combination ha s not been evaluated systematically. Methods: Results from randomised controlled trials investigating the effica cy of 5-HT3-receptor antagonists or droperidol alone versus the combination of both drugs to prevent PONV were included in a meta-analysis. Studies we re systematically searched using Medline, EMBASE, the Cochrane-Library, and by manually screening the reference lists of matching review articles and current issues of locally available peer-reviewed anaesthesia journals. Sev en papers with data on granisetron published by Fujii and co-workers were n ot considered. The main end point in each study was defined as occurrence o f nausea, retching, or vomiting within 6 h ("early PONV") and within 48 h ( "late PONV") after surgery. The relative risks (RR) and the numbers needed to treat (NNT) of the pooled data with their corresponding 95% confidence i ntervals (given in parentheses) were calculated using a random effects mode l. Results: Eight studies with 881 patients (adults: n=801; children (mean age : 8 yr): n=80) were included in the analysis. Droperidol was applied to 340 patients, 5-HT3-receptor antagonists to 198, and 343 were treated with a c ombination of both drugs. Seven out of these eight studies reported increas ed antiemetic efficacy of the combination group compared with the single dr ugs (droperidol and 5-HT3-receptor antagonists respectively). However, in n one of the trials did this difference reach statistical significance. When a meta-analytic analysis based on these results was performed the combinati on of droperidol with a 5HT(3)-recpetor antagonist was not associated with a significantly increased antiemetic efficacy. In 12 to 13 patients a 5-HT3 -receptor antagonist has to be added to droperidol proyhylaxis to prevent o ne additional patient from PONV who would have had suffered from PONV when treated with droperidol alone (RR "early PONV": 1.52 (0.95-2.44); RR "late PONV": 1.24 (0.89-1.74)). Similar results were obtained when the antiemetic effect of adding droperidol to a prophylaxis with 5-HT3-receptor antagonis ts was analysed. In this case 10 to 12 patients have to be treated with the 5-HT3-droperidol combination instead of with a 5-HT3-receptor antagonist a lone to prevent one additional patient from PONV (RR "early PONV": 1.55 (0. 68-3.52); RR "late PONV": 1.29 (0.77-2.17)). There were no reports of an in creased incidence of adverse effects. Conclusion: The data on the combination of droperidol with 5-HT3-receptor a ntagonists suggest that there is a trend towards increased efficacy of the combination therapy compared to the single drugs. However, so far there are insufficient data to recommend this combination treatment for proyhylaxis.