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

We have studied the dose-response relationships for neostigmine and edrophonium during antagonism of neuromuscular block induced by pipecuronium bromide. Fifty-six ASA physical status I or II adults were given pipecuronium 70 mu g/kg during fentanyl thiopental-nitrous oxide-halothane anesthesia. Train-of-four (TOF) stimulation 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 20% of its initial control value, edrophonium (0.125, 0.25, 0.75, or 1 mg/kg) or neostigmine (0.015, 0.03, 0.045, or 0.06 mg/kg) was administered by random allocation. Neuromuscular function in another seven subjects was allowed to recover spontaneously. This study demonstrated that the dose-response curves for these two drugs for reversal of first twitch and TOF ratio were not parallel. The doses of neostigmine required to achieve 50% (ED(50)) and 80% (ED(80)) recovery of the first twitch after 10 min were 8.5 (7.3-9.7) and 17.4 (16.2-18.7) mu g/kg [mean (95% confidence intervals)], respectively. Corresponding ED(50) and ED(80) values for edrophonium were 84.1 (72.9-96.9) and 233 (215.7-253.3) mu g/kg, respectively. These values corresponded to neostigmine:edrophonium potency ratios of 9.89 (7.4-12.3) and 13.4 (11.8-14.9) for first twitch ED(50) and ED(80) height, respectively. The calculated doses producing 50% (ED,,) recovery of the TOF ratio at 10 min were 18.8 (17.5-20.2) and 271.3 (246.5-298.6) mu g/kg for neostigmine and edrophonium, respectively. These values corresponded to a potency ratio of 14.4 (12.8-15.9). We conclude that both edrophonium and neostigmine were able to reverse a pipecuronium neuromuscular block although their dose-response curves were not parallel.