Dose-response relationships for edrophonium and neostigmine antagonism of atracurium and cisatracurium-induced neuromuscular block.
OBJECTIVE
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 x kg(-1) atracurium or 0.1 mg x 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 x kg(-1)) or neostigmine (0.005, 0.01, 0.02, or 0.05 mg x 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 T1 recovery. The neostigmine T1-ED50 was 10.3 +/- 1.06 (SEM) microg x kg(-1) after atracurium and 11.2 +/- 1.06) microg x kg(-1) after cisatracurium. The edrophonium ED50 was 157 +/- 1.07 microg x kg(-1) with atracurium and 47.4 +/- 1.07 microg x 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.
Naguib
M
M
Department of Anesthesia at the University of Iowa College of Medicine, Iowa City 52242-1009, USA.
Riad
W
W
D000293:Adolescent; D000328:Adult; D001279:Atracurium / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004491:Edrophonium / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009388:Neostigmine / Q000494:pharmacology*; D009466:Neuromuscular Blocking Agents / Q000037:antagonists & inhibitors*; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology
D002800:Cholinesterase Inhibitors; D009466:Neuromuscular Blocking Agents; D001279:Atracurium; D009388:Neostigmine; D004491:Edrophonium; C101584:cisatracurium