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Neuromuscular Effects of Doxacurium Chloride in Isoflurane-Anesthetized Dogs
Authors:ELIZABETH A MARTINEZ DVM  Diplomate ACVA    ANNE A WOOLDRIDGE DVM    SANDEE M HARTSFIELD DVM  MS  Diplomate ACVA  KATRINA L MEALEY DVM  Dipiomate ACVCP
Institution:Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, TX
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 μg/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,%) 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 μg/kg) and ED90 (3.5 μg/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 μg/kg of doxacurium and 94%± 7%, 41 ± 8 minutes, 111 ± 33 minutes, and 37 ± 10 minutes for dogs treated with 4.5 μg/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.
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