Dolasetron in the prevention of postoperative nausea and vomiting - A meta-analysis of randomized controlled trials

Objective: The aim of the present study was to conduct a meta-analysis to synthesize and assess the results from randomized controlled trials investigating the efficacy of dolasetron versus placebo in the prevention of postoperative nausea and/or vomiting. Methods: A systematic literature search for relevant studies was performed (identification of study material via MEDLINE, EMBASE, and the Cochrane-Library as well as by scrutinization of the reference lists of matching articles and narrative reviews and a manual screening of current issues of locally available anaesthesia journals and anaesthesia conference proceedings dated up to Mai 2001, updated October 2001). The numbers of patients in whom postoperative nausea, postoperative vomiting, or both (postoperative nausea and vomiting, PONV) occurred within the period of 6 or 24 hours after anaesthesia were extracted. Another extraction criterion was the need for rescue antiemetics and the incidence of undesirable side-effects. The pooled relative risk (RR) and the number-needed-to-treat (NNT) with its corresponding 95% confidence interval (given in parentheses) were calculated using a random effects model. Analysis was performed according to the recommendations of the QUORUM statement. Results: 11 trials with a total number of 3,875 patients were included in the analysis. 948 patients received a placebo and 2,927 patients received dolasetron. Differences in the reporting of outcome data required a unification of outcome measures in order to calculate a common effect. The first analyses were performed on smaller patient groups that were homogeneous with respect to the way and dose of administration. Since these analyses showed very similar results, several subgroups were combined and assessed in aggregate. The RR of postoperative vomiting under dolasetron prophylaxis was 0.75 (95% - CI: 0.70 - 0.80) for the first 24 hours after anaesthesia (data from 27 comparisons). An initial incidence of 60% would thus require dolasetron treatment in about 6 patients to prevent vomiting in one patient who would otherwise suffer from postoperative vomiting if a placebo was given. The RR for postoperative nausea (data from 11 comparisons) was 0.85 (95% - CI: 0.79 - 0.92), (NNT=10; 95% - CI: 7 - 17). The RR for PONV (data from 15 comparisons) and postoperative antiemetic treatment (data from 14 comparisons) was 0.78 (95% - CI: 0.73 - 0.84; NNT = 6; 95% - CI: 5 - 8) and 0.73 (95% - CI: 0.67 - 0.80; NNT = 9; 95% - CI: 7 - 13) respectively. Conclusion: The present study shows that dolasetron is significantly superior to placebo in the prevention of postoperative nausea and vomiting if it is administered at a minimum dose of 12.5 mg (intravenously) or 25 mg (orally). However, the data available so far do not suggest that increasing these doses will also notably increase the beneficial effect of dolasetron.