The additive interactions between ondansetron and droperidol for preventing postoperative nausea and vomiting

Prophylactic ondansetron or droperidol reduces the incidence of postoperative nausea and vomiting (PONV). Previous studies showed that the combination of these two drugs produced better antiemetic effect than either drug alone. We present a nonparametric method to determine the pharmacologic interaction between ondansetron and droperidol and compared the observed response of the drug combination with that predicted from additivity. This is calculated as the product of the individual drug response, normalized to that of the controls. Five minutes before induction of anesthesia, 400 patients scheduled for laparoscopic gynecologic surgery were randomly assigned to receive 1) saline IV; 2) ondansetron 4 mg IV; 3) droperidol 1.25 mg IV; or 4) a combination of droperiodol 1.25 mg and ondansetron 4 mg IV. A standardized anesthetic technique and postoperative analgesic regimen were used. Patients were reviewed regularly for 48 h. Changes in the heart rate adjusted QT (QTc) interval were measured from electrocardiograms recorded before and 5 min after study drug administration. In a subgroup of 160 patients, QTc intervals were measured again at 2-3 h after surgery. During the first 48 h after the surgery, the proportion of patients experiencing PONV was 68% (95% CI 58-77) in the control group. A single dose of ondansetron or droperidol decreased the incidence of PONV to 30% (95% CI 21-40) and 28% (95% CI 20-38), respectively. The predicted incidence of PONV after drug combination, 11.8% (7.1-11.9), was similar to that observed, 12.1% (6.4-20.2), P = 0.94. The corresponding predicted and observed treatment responses in the combination group were 88.2% and 87.9%, respectively. There was a modest and transient increase in QTc interval after administration of ondansetron, droperidol, or their combination. The changes were however similar among groups. We conclude that the interaction between ondansetron and droperiodol was additive. Both drugs acted independently of each other through their specific mechanisms of action. The incidence of QTc prolongation did not increase with the drug combination.