Dose-response relationships for edrophonium and neostigmine antagonism of atracurium and cisatracurium-induced neuromuscular block

Purpose: To study the dose-response relationships for neostigmine and edrophonium during antagonism of neuromuscular block induced by atracurium and cisatracurium. Methods: One hundred and twenty eight, ASA group 1 or 2 adults were given either 0.5 mg.kg(-1) atracurium or 0.1 mg.kg(-1) cisatracurium during fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. The neuromuscular block was measured by an acceleration-responsive transducer. Responses were defined in terms of percent depression in the first twitch (T1) and train-of-four (TOF) response. When spontaneous recovery of first twitch height reached 10% of its initial control value, edrophonium (0, 1, 0.2, 0,4, or 1 mg.kg(-1)) or neostigmine (0.005, 0.01, 0.02, or 0.05 mg.kg(-1)) was administered by random allocation, Neuromuscular function in another sixteen subjects was allowed to recover spontaneously Results: At five minutes, unlike edrophonium, neostigmine was equally effective against atracurium and cisatracurium with respect to TI recovery. The neostigmine TI-ED50 was 10.3 +/- 1.06 (SEM) mug.kg(-1) after atracurium and 11.2 +/- 1.06) mug.kg(-1) after cisatracurium. The edrophonium ED50 was 157 +/- 1.07 mug.kg(-1) with atracurium and 47.4 +/- 1.07 mug.kg(-1) with cisatracurium, giving a neostigmine:edrophonium potency ratios of 15.2 +/- 1.7 and 4.2 +/- 0.41 (P < 0.001)for atracurium and cisatracurium, respectively At 10 min neostigmine was 13 +/- 1.4 times as potent as edrophonium for achieving 50% TOF recovery after atracurium paralysis. After cisatracurium the potency ratio was 11.8 +/- 1.3 (NS). Conclusions: Although there were differences at five minutes, neostigmine:edrophonium potency ratios at 10 min, were similar in both relaxants studied.