The clinical neuromuscular pharmacology of 51W89 in patients receiving nitrous oxide/opioid/barbiturate anesthesia

Anesthesiology. 1995 May;82(5):1139-45. doi: 10.1097/00000542-199505000-00008.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anesthesia
  • Atracurium / pharmacology*
  • Barbiturates / administration & dosage
  • Dose-Response Relationship, Drug
  • Humans
  • Narcotics / administration & dosage
  • Neostigmine / pharmacology
  • Neuromuscular Junction / drug effects*
  • Nitrous Oxide / administration & dosage
  • Stereoisomerism

Substances

  • Barbiturates
  • Narcotics
  • Atracurium
  • Neostigmine
  • Nitrous Oxide