• Morphine 6-glucronide;
  • Post-operative;
  • Pain;
  • Nausea;
  • PONV;
  • M6G;
  • Morphine


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 (M6 g), 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 M6 g 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 24–48h. Pain intensity, nausea, vomiting and sedation scores were collected at regular intervals.

In the study 268 patients were randomised to M6 g and 249 to morphine. Withdrawal due to insufficient pain relief occurred predominantly just after surgery and was higher in the M6 g group (16.8%) than in the morphine group (8.8%), suggesting a slower onset of analgesia for M6 g compared to morphine. Subjects who continued on PCA remained equi-analgesic throughout the study.

During the first 24 h, nausea levels showed a 27% difference in favour of M6 g which narrowly failed to reach statistical significance (P =0.052). Sub-analysis showed a significant reduction in nausea levels in females on M6 g (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 M6 g, persisting for the first 24 h postoperatively. Reductions in sedation were observed in the first 4 h post-operative period for M6 g patients.