DOSE-RESPONSE RELATIONSHIPS FOR EDROPHONIUM AND NEOSTIGMINE ANTAGONISM OF MIVACURIUM-INDUCED NEUROMUSCULAR BLOCK

We have studied the dose-response relationships for neostigmine and edrophonium during antagonism of neuromuscular block induced by mivacurium chloride. Sixty-four ASA group I or II adults were given mivacurium 0.15 mg kg-1 during fentanyl-thiopentone-nitrous oxide-isoflurane anaesthesia. Train-of-four stimulation (TOF) was applied to the ulnar nerve every 10 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height reached 10% of its initial control value, edrophonium 0.1, 0.2, 0.4, or 1 mg kg-1 or neostigmine 0.005, 0.01, 0.02, or 0.05 mg kg-1 was administered by random allocation. Neuromuscular function in another 16 subjects was allowed to recover spontaneously. Spontaneous recovery from 90% mivacurium block to 95% twitch height and TOF ratio 0. 75 occurred within 15 min. This study demonstrated that the dose-response, curves for these two drugs for antagonism of neuromuscular block (first twitch and train-of-four ratio) were parallel. The doses of neostigmine required to achieve 50% (ED50) and 70% (ED70) recovery of the first twitch after 10 min were 2 (1.5-2.5) mug kg-1 and 4.7 (4.1-5.4) mug kg-1 (mean (95% confidence intervals)), respectively. Corresponding ED50 and ED70 values for edrophonium were 2.8 (0.75-10.2) mug kg-1 and 9.2 (3.6-23.6) mug kg-1, respectively. These values corresponded to neostigmine:edrophonium potency ratios bf 1.4 (0.4-2.4) and 1.95 (0.9-2.9) for first twitch ED50 and ED70 height, respectively. The calculated doses producing 50% (ED50) recovery of the TOF ratio at 10 min were neostigmine 2.57 (1.8-3.6) mug kg-1 and edrophonium 26.9 (14.6-49.6) mug kg-1. These values corresponded to a potency ratio of 10.4 (0.7-20).