The neuromuscular blocking and cardiovascular effects of doxacurium chloride in patients receiving nitrous oxide narcotic anesthesia

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 x ED₉₅) and 0.05 mg·kg^-1 (2.2 x 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.