Is the clinical efficacy of epidural diamorphine concentration-dependent when used as analgesia for labour?

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 =05 cm cervical dilatation were recruited to determine whether the mode of action of diamorphine in the epidural space is concentration-dependent. After insertion of a lumbar epidural catheter, patients received epidural diamorphine 3 mg either as a high-volume, low-concentration solution (group A) or a low-volume, high-concentration solution (group B). The concentration of diamorphine was determined by the response of the previous patient in the same group using updown sequential allocation. Pain corresponding to the previous contraction was assessed using a 100-mm visual analogue score and effective analgesia was defined as =10 mm within 30 min of epidural injection. Results. There was no significant difference in EC50 for diamorphine between the groups: the difference was 15.0 µg ml (95% CI -40.3 to 10.3). The EC50 for group A was 237.5 µg ml (95% CI 221.2 to 253.8) and the EC50 for group B was 252.5 µg ml (95% CI 232.2 to 272.8). The EC50 ratio was 0.95 (95% CI 0.87 to 1.06). The groups exhibited parallelism (P=0.98). The overall EC50 for all data was 244.2 µg ml (95% CI 230.8 to 257.2). Conclusion. We conclude that diamorphine provides analgesia in labour by a concentration-dependent effect.