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Dose-Response Relationships for Edrophonium and Neostigmine as Antagonists of Moderate and Profound Atracurium Blockade

Received from the Departments of Anaesthesia, Royal Victoria Hospital and McGill University, Montreal, Quebec, Canada.

Abstract

To measure the ability of neostigmine and edrophonium to reverse moderate and profound atracurium blockade, dose-response relationships were established for these reversal agents given at 1% and 10% twitch height recovery. Eighty-five ASA I and II adult patients received atracurium, 0.4 mg/kg, during a thiopental-nitrous oxide-en-flurane anesthetic. Train-of-four stimulation was applied every 12 seconds, and the force of contraction of the adductor pollicis muscle was recorded. Edrophonium, 0.1, 0.2, 0.4, or 1 mg/kg; neostigmine, 0.005, 0.01, 0.02 or 0.05 mg/kg; or no reversal agent was given when there was either 1% or 10% recovery of the first twitch response. With profound blockade, the slope of the edrophonium dose-response relationship was significantly flatter (P < 0.05) than that of neostigmine. The dose of neostigmine required to achieve 80% first twitch recovery (ED₈₀) after 10 minutes was 0.013 ± 0.003 mg/kg (mean ± SEM) if given at 10% recovery, and 0.032 ± 0.004 mg/kg if given at 1% recovery. The ED₈₀for edrophonium was 0.22 ± 0.04 mg/kg and 1.14 ± 0.33 mg/kg, respectively. These values corresponded to neostigmine edrophonium potency ratios of 16.6 ± 3.5 and 35.3 ± 8.9 at 90% and 99% blockade respectively (P < 0.006). We conclude that the relative potency of neostigmine is greater than that of edrophonium for antagonism of profound atracurium blockade.

Key Words: ANTAGONISTS, NEUROMUSCULAR RELAXANTS—edrophonium, neostigmine • MONITORING—neuromuscular transmission, train-of-four • NEUROMUSCULAR RELAXANTS—atracurium, vecuronium

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