EDROPHONIUM INCREASES MIVACURIUM CONCENTRATIONS DURING CONSTANT MIVACURIUM INFUSION, AND LARGE DOSES MINIMALLY ANTAGONIZE PARALYSIS

Background: Mivacurium, a nondepolarizing muscle relaxant, is metaboli zed by plasma cholinesterase. Although edrophonium does not alter plas ma cholinesterase activity, we have observed that doses of edrophonium that antagonize paralysis from other nondepolarizing muscle relaxants are less effective with mivacurium. We speculated that edrophonium mi ght alter metabolism of mivacurium, thereby hindering antagonism of pa ralysis. Accordingly, we determined the effect of edrophonium on neuro muscular function and plasma mivacurium concentrations during constant mivacurium infusion. Methods: We infused mivacurium to maintain 90% d epression of adductor pollicis twitch tension and then gave edrophoniu m in doses ranging from 125-2,000 mu g/kg without altering the mivacur ium infusion. Peak twitch tension after edrophonium was determined to estimate the dose of edrophonium antagonizing 50% of twitch depression for antagonism of mivacurium; plasma cholinesterase activity and miva curium concentrations before and after edrophonium were measured. Addi tional subjects were given 500 mu g/kg edrophonium to antagonize conti nuous infusions of d-tubocurarine and vecuronium. Results: With mivacu rium, edrophonium increased twitch tension in a dose-dependent manner: the dose of edrophonium antagonizing 50% of twitch depression was 2,8 10 mu g/kg. The largest dose of edrophonium (2,000 mu g/kg) produced o nly 45 +/- 7% antagonism. Edrophonium, 500 mu g/kg, antagonized mivacu rium markedly less than it antagonized d-tubocurarine and vecuronium. Edrophonium increased plasma concentrations of the two potent stereois omers of mivacurium 48% and 79%, these peaking at 1-2 min; plasma chol inesterase activity was unchanged. Conclusions: Edrophonium doses that antagonize ci-tubocurarine and vecuronium are less effective in antag onizing the neuromuscular effects of mivacurium during constant infusi on. Edrophonium increases plasma mivacurium concentrations, partly or completely explaining its limited efficacy; the mechanism by which edr ophonium increases mivacurium concentrations remains unexplained. Our results demonstrate that antagonism of mivacurium by edrophonium is im paired, and therefore we question whether edrophonium should be used t o antagonize mivacurium.