Neuromuscular effects of doxacurium chloride in isoflurane-anesthetized dogs

Abstract

Objective: To determine the neuromuscular effects of doxacurium chloride and to construct a dose-response curve for the drug in isoflurane-anesthetized dogs.

Design: Randomized, controlled trial.

Animals: Six healthy, adult, mixed-breed dogs (five female, one male) weighing 24.8 +/- 2.8 kg.

Methods: Anesthesia was induced with isoflurane in oxygen and maintained with 1.9% to 2.3% end-tidal isoflurane concentration. PaCO2 was maintained between 35 and 45 mm Hg with mechanical ventilation. Mechanomyography was used to quantitate the evoked twitch response of the paw after supramaximal train-of-four stimulation of the superficial peroneal nerve. After baseline values were recorded, the dogs received one of three doses of doxacurium (2.0, 3.5, 4.5 microg/kg of body weight) or a saline placebo intravenously in random order. All dogs received all treatments with at least 7 days between studies. After drug administration, the degree of maximal first twitch depression compared with baseline (T1%) was recorded. Dose-response relations of doxacurium were plotted in log dose-probit format and analyzed by linear regression to determine effective dose (ED50 and ED90) values for doxacurium.

Results: The median log dose-probit response curve showed good data correlation (r = .999) with estimates of the ED50 (2.1 microg/kg) and ED90 (3.5 microg/kg) for doxacurium in isoflurane-anesthetized dogs. Mean +/- SD values for T1% (first twitch tension compared with baseline) at maximal depression after drug administration, onset (time from drug administration to maximal depression of T1%), duration (time from maximal depression of T1% to 25% recovery of T1%), and recovery (time from 25% to 75% recovery of T1%) times were 92% +/- 4%, 40 +/- 5 minutes, 108 +/- 31 minutes, and 42 +/- 11 minutes for dogs treated with 3.5 microg/kg of doxacurium and 94% +/- 7%, 41 +/- 8 minutes, 111 +/- 33 minutes, and 37 +/- 10 minutes for dogs treated with 4.5 microg/kg of doxacurium.

Conclusion and clinical relevance: We conclude that doxacurium is a long-acting neuromuscular blocking agent with a slow onset of action. Doxacurium can be used to provide muscle relaxation for long surgical procedures in isoflurane-anesthetized dogs. Interpatient variability, particularly of duration of drug action, may exist in the neuromuscular response to the administration of doxacurium in dogs.