INHIBITION OF THE ENZYMATIC DEGRADATION OF SUXAMETHONIUM AND MIVACURIUM INCREASES THE ONSET TIME OF SUBMAXIMAL NEUROMUSCULAR BLOCK

Background: The factors that influence the onset time of submaximal (< 100%) neuromuscular block are not fully known. The authors hypothesize d that differences in the rate of decrease in the plasma concentration result in differences in the rate of equilibration between plasma and biophase and thus in different onset times. If this hypothesis is val id inhibition of the enzymic degradation of muscle relaxants should in crease the onset time of neuromuscular block Methods: Twenty pigs rece ived either suxamethonium or mivacurium Dose finding (70% block) was d one for each pig. The enzymic degradation of the muscle relaxant was r andomly inhibited by selective inhibition of plasma cholinesterase act ivity by tetraisopropyl pyrophosphoramide (10 pigs) or was not inhibit ed (10 pigs). Plasma cholinesterase activities and the mechanomyograph ic muscle response after peroneal nerve stimulation (0.1 Hz) were meas ured. Results: Inhibition of plasma cholinesterase activity (by 93% an d 89%, respectively) increased the onset time of suxamethonium from a median of 40 s (range, 20-45 s) to 131 s (range, 114-166 s; P = 0.009) and of mivacurium from a median of 52 s (range, 40-59 s) to 105 s (ra nge, 90-125 s; P = 0.009). Inhibition of degradation decreased the eff ective dose of suxamethonium that resulted in 70% depression of the in itial twitch height from 900 mu g/kg (range, 400-1,000 mu g/kg) to 150 mu g/kg (range, 135-150 mu g/kg) and of mivacurium from 100 mu g/kg ( range, 80-150 mu g/kg) to 35 mu g/kg (range, 20-50 mu g/kg). Conclusio ns: Inhibition of the enzymic degradation of suxamethonium and mivacur ium increases the onset time of submaximal neuromuscular block Therefo re, pharmacokinetics influence the onset time of submaximal neuromuscu lar block. These results imply that to obtain an ultrashort onset time , muscle relaxants should be developed that not only have a low affini ty for the receptor but also rapidly disappear from plasma.