Morphine is the first choice of treatment of severe post-operative pain, despite the occurrence of often discomforting (post-operative nausea or vomiting (PONV)) and sometimes dangerous (sedation, respiratory depression) side effects. Literature data indicate that morphine's active metabolite, morphine-6-glucuronide (M6G), is a powerful analgesic with a possibly more favourable side-effect profile. In this multi-centre randomised controlled clinical trial patients undergoing major abdominal surgery were randomised to M6G or morphine treatment. Treatment started 30-60 min prior to the end of surgery and was continued postoperatively, after patients were titrated to comfort, via patient-controlled analgesia (PCA) for 24-48 h. Pain intensity, nausea, vomiting and sedation scores were collected at regular intervals. In the study 268 patients were randomised to M6G and 249 to morphine. Withdrawal due to insufficient pain relief occurred predominantly just after surgery and was higher in the M6G group (16.8%) than in the morphine group (8.8%), suggesting a slower onset of analgesia for M6G compared to morphine. Subjects who continued on PCA remained equi-analgesic throughout the study. During the first 24h, nausea levels showed a 27% difference in favour of M6G which narrowly failed to reach statistical significance (P=0.052). Sub-analysis showed a significant reduction in nausea levels in females on M6G (30% difference, P=0.034). In all patients, similar reductions of 30-35% were observed in anti-emetic use, vomiting, PONV (a combined measure of nausea and vomiting) in favour of M6G, persisting for the first 24h postoperatively. Reductions in sedation were observed in the first 4h post-operative period for M6G patients.

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The anti-emetic effects of ondansetron and droperidol were evaluated in 134 ASA Grade I and II female patients, scheduled for laparoscopic cholecystectomy and minor gynaecological laparoscopic surgery, who were randomly assigned to receive ondansetron 4 mg or droperidol 75 micrograms kg-1 intravenously immediately after induction of anaesthesia. The patients were assessed 1, 6, 12 and 24 h after surgery for intensity of nausea and number of vomiting episodes. In the case of the patients undergoing laparoscopy, vomiting episodes occurred in a similar proportion in patients treated with ondansetron or droperidol, with the probability of the Type I error of 0.05 and the Type error II of 0.1. Although there was no difference between the two groups in emetic episodes following all laparoscopic procedures and gynaecological laparoscopic surgery, there was a significant difference between these parameters after laparoscopic cholecystectomy. The patients treated with ondansetron experienced a lower intensity of nausea (P = 0.04) after laparoscopic cholecystectomy, less frequent severe nausea (P = 0.02) and episodes of vomiting (P = 0.04) when compared with those in the droperidol group. We conclude, that despite the result the droperidol prophylaxis appears to be an effective alternative to ondansetron in all patients undergoing laparoscopy, the ondansetron prophylaxis is superior to droperidol in patients undergoing laparoscopic cholecystectomy.