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.


METHODS
Randomized, controlled trial.


METHODS
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.


CONCLUSIONS
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.
Martinez
E A
EA
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, USA.
Wooldridge
A A
AA
Hartsfield
S M
SM
Mealey
K L
KL
D018685:Anesthetics, Inhalation; D000818:Animals; D004285:Dogs / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007530:Isoflurane; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects*; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D018685:Anesthetics, Inhalation; D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D007530:Isoflurane; C049429:doxacurium