ENZYMATIC VERSUS PHARMACOLOGICAL ANTAGONISM OF PROFOUND MIVACURIUM-INDUCED NEUROMUSCULAR BLOCKADE

Background: Mivacurium, a nondepolarizing muscle relaxant, is hydrolyz ed by butyrylcholinesterase. The use of butyrylcholinesterase for anta gonism of profound mivacurium-induced blockade has not been studied in humans, In part 1 of this two-part study, the authors examined the re lationship between the posttetanic count (PTC) and recovery from profo und mivacurium-induced blockade, In part 2, an attempt was made to ant agonize a quantified level of profound mivacurium-induced blockade usi ng either butyrylcholinesterase, edrophonium, or neostigmine. Methods: Eighty-seven ASA physical status 1 or 2 adult patients were given 0.1 5 mg . kg(-1) mivacurium during fentanylthiopental-nitrous oxide-isofl urane anesthesia. They were randomly assigned to eight groups. Neuromu scular function was monitored by recording the mechanomyographic respo nse of the adductor pollicis to PTC and train-of-four (TOF) stimulatio n in all patients except those in group 1 where the TOF was the only p attern used. In part 1, neuromuscular function was allowed to recover spontaneously in ten patients (group 1; control-TOE) until TOF ratio ( the amplitude of the fourth evoked response as a fraction of the first evoked response: T4/T1) had reached 0.75. The temporal relationship b etween PTC and the first reaction to TOF stimulation was determined in another 21 patients, and neuromuscular function in 10 of these patien ts was allowed to recover spontaneously until TOF ratio had reached 0. 75 (group 2; control-PTC), In part 2, the antagonism of mivacurium-ind uced profound (PTC greater than or equal to 1; groups 3-6) and 90% blo ck (groups 7-8) of twitch height were investigated in another 56 patie nts. Groups 3 and 7 received neostigmine 0.06 mg . kg(-1) whereas grou ps 4 and 8 received edrophonium 1 mg . kg(-1), respectively, Groups 5 and 6 received exogenous human butyrylcholinesterase equivalent to act ivity present in 25 or 70 ml . kg(-1) of human plasma, respectively. R esults: Neither butyrylcholinesterase nor edrophonium shortened the ti mes from first PTC response to TOF = 0.75 compared to group 2. Neostig mine resulted in prolongation of recovery time, There was a linear rel ationship (r = -0.80; P = 0.00001) between PTC and time of onset of TO F response. Conclusions: There appears to be no clinical advantage in attempting to antagonize profound mivacurium-induced neuromuscular blo ckade.