Bupivacaine has a chiral centre and is currently available as a racemic mixture of its two enantiomers: R(+)-bupivacaine and S(-)-bupivacaine. Preclinical studies have demonstrated that there is enantiomer selectivity of action with the bulk of central nervous system and cardiovascular toxicity residing with the R(+) isomer. The aim of this study was to compare the clinical efficacy and safety of S(-)-bupivacaine with racemic RS-bupivacaine for extradural anaesthesia. We studied 88 patients undergoing elective lower limb surgery under lumbar extradural anaesthesia who received 15 ml of 0.5% or 0.75% S(-)-bupivacaine, or 0.5% RS-bupivacaine in a randomized, double-blind study. There was no difference in onset time, maximum spread of sensory block or intensity of motor block between the three groups. Duration of sensory block was significantly longer for 0.75% S(-)-bupivacaine. We conclude that S(-)-bupivacaine has similar local anaesthetic characteristics to RS-bupivacaine when used for extradural anaesthesia.

Ninety-one patients were allocated randomly to three groups to receive 1% ropivacaine 10 ml, 0.5% ropivacaine 20 ml or 0.5% bupivacaine 20 ml extradurally. Intermittent sensory (pinprick) and motor (Bromage scale) assessments of the block produced were recorded, with an assessment of the quality of the block and the requirement for supplementary analgesia. There was little difference between the groups in frequency, onset, duration or spread of sensory block. However, the motor block produced by 0.5% ropivacaine was less intense and of shorter duration than that with bupivacaine. The block produced by the smaller volume of ropivacaine was less reliable clinically than the larger, more dilute, solution and more anaesthetic supplements were required in that group. Cardiovascular changes were similar in all three groups. The peak plasma concentration of ropivacaine was significantly greater and T1/2 significantly shorter than those of bupivacaine, although no patient showed any features of systemic toxicity. The systemic kinetics of ropivacaine were not influenced significantly by varying the concentration or volume administered.

Patients given dextromethorphan before and after surgery had a significant reduction in some pain scores at rest, but not on movement. There was a trend to lower morphine requirements in the first 24 h. Over the next 48 h, oral analgesic usage was significantly reduced.

We have compared the efficacy of 0.25% S(-)-bupivacaine with 0.25% RS-bupivacaine in providing epidural analgesia for labour in a randomized, multicentre, double-blind study. Analgesia was initiated with 10 ml of the study solution and maintained with 10-ml top-ups. We studied 137 women and treatments were found to be equivalent for onset, duration and quality of block. Median onset of pain relief was 12 min for both drugs and median duration was 49 (range 3-129) min and 51 (7-157) min for S(-)-bupivacaine and RS bupivacaine, respectively. The estimated treatment difference for duration of pain relief was -4 (90% CI -13, 6) min. Thirty patients failed to achieve pain relief after the first injection (20 patients after S(-)-bupivacaine and 10 after RS-bupivacaine; P = 0.039). However, median duration of pain relief from the first top-up was 82 (range 3-164) min for S(-)-bupivacaine and 76 (22-221) min for RS-bupivacaine. There were no significant differences in the quality of analgesia, as assessed by the investigators. There were no significant differences in the extent of sensory block, percentage of patients with motor block or incidence of adverse events.

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.