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Background: Few data describe the pharmacological interactions between local anaesthetics and opioids. The aim of this study was to measure the median effective concentration (MEC) of diamorphine and levobupivacaine when given separately and as mixtures for epidural analgesia, and determine whether the combination is additive or synergistic., Methods: One hundred and twenty patients were enrolled in this prospective randomized, two-phase, double-blind study. In the first phase, 60 women were randomized to receive a fixed 20 ml volume of either levobupivacaine or diamorphine epidurally . Dosing was determined using up-down sequential allocation with testing intervals, respectively, of 0.01%w/v and 12.5 microg ml(-1). After estimations of the MEC of levobupivacaine and diamorphine, a further 60 patients were randomized in the second phase to one of the three mixtures: (a) diamorphine 70 microg ml(-1) (fixed) and levobupivacaine (testing interval 0.004%w/v, starting at 0.044%w/v); (b) levobupivacaine 0.044%w/v (fixed) and diamorphine (testing interval 7 microg ml(-1), starting at 70 microg ml(-1)); and (c) bivariate diamorphine and levobupivacaine (testing intervals of 7 microg ml(-1) and 0.004%w/v starting at 70 microg ml(-1) and 0.044% w/v respectively)., Results: The MEC estimates from the first phase were 143.8 microg ml(-1) (95% CI 122.2-165.3) for diamorphine and 0.083%w/v (95% CI 0.071-0.095) for levobupivacaine. In the second phase, the MEC and interaction index (gamma) of the three combinations were: diamorphine 65.5 microg ml(-1) (56.8-74.2), gamma = 0.99; levobupivacaine 0.041%w/v (0.037-0.049), gamma = 0.98; and for the fixed combination diamorphine 69.5 microg ml(-1) (60.5-78.5) and levobupivacaine 0.044%w/v (0.039-0.049), gamma = 1.02., Conclusion: The combination of diamorphine and levobupivacaine is additive and not synergistic when used for epidural analgesia in the first stage of labour.

Background: Many years ago regular intermittent bolus administration of epidural local anaesthetic solution was recognized to produce more effective analgesia than continuous infusion, but only recently has the development of suitable pumps allowed the former technique's wider evaluation., Methods: In this randomized, double-blind trial, 40 primigravid patients had a lumbar epidural catheter inserted, and plain ropivacaine 0.2% 15-20 ml was titrated until analgesia and bilateral sensory block to T10 were produced (time zero). Patients were then given either an infusion of ropivacaine 2 mg ml(-1) with fentanyl 2 microg ml(-1) at 10 ml h(-1), or hourly boluses of 10 ml of the same solution. Pain, sensory block and motor block were measured frequently. If requested, additional 10 ml boluses of the study mixture were given for analgesia., Results: There were no differences between the two groups in patient characteristics, obstetric/neonatal outcome, or in sensory or motor block. A total of 12 (60%) patients in the continuous group required one or more additional boluses compared with 4 (20%) patients in the intermittent group (95% CI 9.6-61.7%, P=0.02). Therefore the intermittent group received a lower total drug dose than the infusion group (P=0.02). Duration of uninterrupted analgesia (time to first rescue bolus) was longer in the intermittent group (P<0.02)., Conclusions: The intermittent group required fewer supplementary injections and less drug to maintain similar pain scores, sensory and motor block compared with the continuous group. This represents a more efficacious mode of analgesia.

Background: In view of the wide variation in pain experience between patients, a clinical standard -- the time from the end of surgery to the first experience of pain -- was applied to 1359 consecutive patients in order to investigate whether the initial quality of epidural block has an effect on the overall quality of postoperative pain relief., Methods: Clinical data were recorded in 58,118 out of 72,412 h in 1359 patients, and transferred to a database. Data collected included pain scores on a four-point verbal rating scale; nausea and vomiting; motor block; sedation scores; systolic blood pressure <100 and <90 mm Hg; ventilatory frequency <10 and <8 bpm; and hourly epidural infusion rate., Results: As the time to first experience of pain increased from nil to >24 hours, the time from the first to last experience of pain shortened from 34 (19-50) h to 3 (1-12) h (p<0.001) and the proportion of patients receiving an epidural bolus decreased from 53 to 8% (p<0.001). Increases in the initial pain free time increased the proportion of patients with systolic BP<100 mmHg from 59 to 77%, (p<0.001) and increased the proportion of patients with respiratory rate <10 bpm from 13 to 26%, (p<0.001)., Conclusion: Extending pain relief for more than 12 h beyond the end of abdominal surgery significantly improves the overall quality of postoperative pain relief, but is associated with an increase in side-effects.

Background: The physicochemical properties of diamorphine (3,6-diacetylmorphine) enhance its bioavailability compared with more lipid-soluble opioids when administered into the epidural space. However, the influence of concentration, volume or mass on the clinical efficacy of diamorphine is not known., Method: In this double-blind, randomized, prospective study, 62 women in active labour and

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.