The Neuromuscular Blocking and Cardiovascular Effects of Doxacurium Chloride in Patients Receiving Nitrous Oxide Narcotic Anesthesia

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Abstract
The purpose of this study was to evaluate neuromuscular and cardiovascular effects of doxacurium chloride, a new long-acting neuromuscular blocking agent, during a stable state of nitrous oxide and narcotic anesthesia. Ninety-three ASA physical status I or II patients were studied after informed written consent had been obtained. Eighty-one patients (group A) received doxacurium. The 81 patients were divided into nine subgroups according to the dose of doxacurium administered (0.01–0.06 mg·kg-1). Patients in a control group (group B) (n=12) received pancuronium. To assess neuromuscular responses, a force displacement transducer recorded the twitch response of the adductor pollicis muscle following ulnar nerve stimulation. The ED50 and ED95 for doxacurium were estimated to be 0.013 mg·kg-1 and 0.023 mg·kg-1, respectively. The time to maximum twitch suppression following a dose of 1.0 (ED95) and 1.7 (ED95) was 10.3 ± 1.3 min and 7.6 ± 0.8 min, respectively. After an ED95 dose of doxacurium the time to spontaneous recovery to 95% of control twitch height was 73.7 ± 8.7 min. With larger doses of doxacurium, 0.04 mg·kg-1 (1.7 × ED95) and 0.05 mg·kg-1 (2.2 × ED95), the time to spontaneous recovery to 95% of control twitch height was 125.8 ± 24.8 and 204.0 ± 21.2 minutes, respectively. When 25% twitch height recovery or more was present the reversal of doxacurium induced neuromuscular blockade was prompt. After administration of 0.04 mg · kg-1 of doxacurium or 0.08 mg · kg-1 of pancuronium, the time for spontaneous recovery to 25% of control twitch height recovery was 77.4 ± 7.5 min (n = 23) and 71.4 ± 6.7 min (n = 10), respectively. When identical multiple maintenance doses of doxacurium were administered, the subsequent neuromuscular block following each maintenance dose was of similar magnitude and duration. At 1,2, and 5 min following pancuronium, heart rate and mean blood pressure increased. Following doxacurium small decreases in mean blood pressure occurred at 2 and 5 min, while heart rate decreased 5 min following drug injection. Doxacurium is a new, long-acting, nondepolarizing relaxant. Further study is warranted to assess the cardiovascular effects of this neuromuscular blocking drug in patients with cardiovascular disease.