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.