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Neuromuscular effects of doxacurium chloride in isoflurane-anesthetized dogs
E A Martinez1, A A Wooldridge, S M Hartsfield
1Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, USA.
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.