THE EFFECT OF NEOSTIGMINE ON TWITCH TENSION AND MUSCLE-RELAXANT CONCENTRATION DURING INFUSION OF MIVACURIUM OR VECURONIUM

Background: An investigation suggested that neostigmine may not effect ively antagonize mivacurium, presumably because neostigmine impairs mi vacurium's metabolism. However, the effect of neostigmine on mivacuriu m's metabolism in vivo has not been reported. Therefore, the effect of neostigmine on neuromuscular function and plasma mivacurium concentra tions during constant mivacurium infusion was determined. Methods: Miv acurium was infused in five patients to maintain 90% depression of add uctor pollicis twitch tension, then 50 mu g/kg intravenous neostigmine was administered without altering the mivacurium infusion. Peak twitc h tension after neostigmine, plasma cholinesterase activity, and mivac urium concentrations before and after neostigmine were measured. Five additional patients were given 50 mu g/kg neostigmine to antagonize bl ock due to continuous infusions of vecuronium. Results: Neostigmine pr oduced less antagonism of mivacurium (39 +/- 11%) than of vecuronium ( 54 +/- 9%, P < 0.05). Neostigmine decreased plasma cholinesterase acti vity and increased plasma concentrations of the trans-trans and cis-tr aits stereoisomers of mivacurium (P < 0.05). Conclusions: Neostigmine is less effective at antagonizing the neuromuscular effect of mivacuri um than that of vecuronium during constant infusion. Neostigmine incre ases plasma mivacurium concentrations, likely explaining its limited e fficacy. Our results confirm that neostigmine impairs the metabolism o f mivacurium ill vivo and may explain the observation that neostigmine may not effectively antagonize mivacurium-induced block.