Neuromuscular effects of doxacurium chloride in isoflurane-anesthetized dogs

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. Paco(2) 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 mu g/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 (T-1%) 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 mu g/kg) and ED50 (3.5 mu g/kg) for doxacurium in isoflurane-anesthetized dogs. Mean +/- SD values for T-1% (first twitch tension compared with baseline) at maximal depression after drug administration, onset (time from drug administration to maximal depression of T-1%), duration (time from maximal depression of T-1% to 25% recovery of T-1%), and recovery (time from 25% to 75% recovery of T-1%) times were 92% +/- 4%, 40 +/- 5 minutes, 108 +/- 31 minutes, and 42 +/- 11 minutes for dogs treated with 3.5 mu g/kg of doxacurium and 94% +/- 7%, 41 +/- 8 minutes, 111 +/- 33 minutes, and 37 +/- 10 minutes for dogs treated with 4.5 mu g/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. (C) Copyright 1998 by The American College of Veterinary Surgeons.