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

We have studied the dose-response relationships for neostigmine and ed rophonium during antagonism of neuromuscular block induced by mivacuri um chloride. Sixty-four ASA group I or II adults were given mivacurium 0.15 mg kg-1 during fentanyl-thiopentone-nitrous oxide-isoflurane ana esthesia. Train-of-four stimulation (TOF) was applied to the ulnar ner ve every 10 s, and the force of contraction of the adductor pollicis m uscle was recorded. When spontaneous recovery of first twitch height r eached 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 admin istered by random allocation. Neuromuscular function in another 16 sub jects 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 twit ch and train-of-four ratio) were parallel. The doses of neostigmine re quired to achieve 50% (ED50) and 70% (ED70) recovery of the first twit ch 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 neostigmi ne: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 neostigm ine 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).