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

Abstract

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-iso flurane 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) μg kg⁻¹ and 4.7 (4.1–5.4) μg kg⁻¹ (mean (95% confidence intervals)), respectively. Corresponding ED₅₀ and ED₇₀ values for edrophonium were 2.8 (0.75–10.2) pg kg⁻¹ and 9.2 (3.6–23.6) μg kg⁻¹, respectively. These values corresponded to neostigmine :edrophonium potency ratios of 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) μg kg⁻¹ and edrophonium 26.9 (14.6–49.6) pg kg⁻¹. These values corresponded to a potency ratio of 10.4 (0.7–20). (Br. J. Anaesth. 1993; 71: 709–714)