The Clinical Neuromuscular Pharmacology of 51W89 in Patients Receiving Nitrous Oxide/Opioid/Barbiturate Anesthesia

Abstract

Background Atracurium is a mixture of ten stereoisomers. 51W89, one of these isomers, is a potent nondepolarizing intermediate-duration neuromuscular blocking agent. Preclinical studies have shown 51W89 to be significantly more potent than atracurium but with a similar neuromuscular blocking profile. This study was undertaken to establish the neuromuscular blocking potency and pharmacodynamics of 51W89 in patients undergoing elective surgical procedures. Methods Ninety-nine ASA physical status 1 or 2 patients undergoing elective surgical procedures under nitrous oxide/opioid/barbiturate anesthesia were studied. The neuromuscular blocking effect of 51W89 was assessed after administration of bolus doses from 0.015 to 0.4 mg/kg, as well as during and after continuous infusions from 11 to 249 min in length. Results The calculated ED95 for inhibition of adductor pollicis twitch evoked at 0.15 Hz was 0.048 mg/kg. At 0.10 mg/kg, maximum block developed within 5.2 +/- 0.3 min, and recovery to 95% twitch height occurred 64.4 +/- 3.9 min after injection. At 0.4 mg/kg, onset was 1.9 +/- 0.1 min, and 95% recovery developed within 121.0 +/- 5.9 min. Comparative recovery indexes from 5% to 95% or from 25% to 75% twitch heights did not differ significantly among all dosage groups from 0.1 to 0.4 mg/kg (means ranged from 29.6 to 32.3 min and from 12.6 to 14.3 min, respectively). The average infusion rate necessary to maintain approximately 95% twitch suppression was 1.35 micrograms/kg/min. Recovery indexes from infusions were 5-95% 33.2 +/- 1.8 min and 25-75% 15.0 +/- 0.6 min, not differing significantly from recovery indexes from single bolus doses. Twenty-five patients received neostigmine (0.06 mg/kg) with atropine (0.03 mg/kg) at twitch height recovery of between 6% and 21%. Antagonism to 95% control twitch height developed within 6.8 +/- 0.3 min, and the neostigmine-accelerated 25-75% recovery index was 2.8 +/- 0.2 min. Conclusions 51W89 is a potent nondepolarizing neuromuscular blocking agent that shows noncumulative intermediate-duration neuromuscular blocking pharmacodynamics.