BACKGROUND: An investigation suggested that neostigmine may not effectively antagonize mivacurium, presumably because neostigmine impairs mivacurium's metabolism. However, the effect of neostigmine on mivacurium's metabolism in vivo has not been reported. Therefore, the effect of neostigmine on neuromuscular function and plasma mivacurium concentrations during constant mivacurium infusion was determined. METHODS: Mivacurium was infused in five patients to maintain 90% depression of adductor pollicis twitch tension, then 50 micrograms/kg intravenous neostigmine was administered without altering the mivacurium infusion. Peak twitch tension after neostigmine, plasma cholinesterase activity, and mivacurium concentrations before and after neostigmine were measured. Five additional patients were given 50 micrograms/kg neostigmine to antagonize block due to continuous infusions of vecuronium. RESULTS: Neostigmine produced less antagonism of mivacurium (39 +/- 11%) than of vecuronium (54 +/- 9%, P < 0.05). Neostigmine decreased plasma cholinesterase activity and increased plasma concentrations of the trans-trans and cis-trans stereoisomers of mivacurium (P < 0.05). CONCLUSIONS: Neostigmine is less effective at antagonizing the neuromuscular effect of mivacurium than that of vecuronium during constant infusion. Neostigmine increases plasma mivacurium concentrations, likely explaining its limited efficacy. Our results confirm that neostigmine impairs the metabolism of mivacurium in vivo and may explain the observation that neostigmine may not effectively antagonize mivacurium-induced block.
BACKGROUND: An investigation suggested that neostigmine may not effectively antagonize mivacurium, presumably because neostigmine impairs mivacurium's metabolism. However, the effect of neostigmine on mivacurium's metabolism in vivo has not been reported. Therefore, the effect of neostigmine on neuromuscular function and plasma mivacurium concentrations during constant mivacurium infusion was determined. METHODS:Mivacurium was infused in five patients to maintain 90% depression of adductor pollicis twitch tension, then 50 micrograms/kg intravenous neostigmine was administered without altering the mivacurium infusion. Peak twitch tension after neostigmine, plasma cholinesterase activity, and mivacurium concentrations before and after neostigmine were measured. Five additional patients were given 50 micrograms/kg neostigmine to antagonize block due to continuous infusions of vecuronium. RESULTS:Neostigmine produced less antagonism of mivacurium (39 +/- 11%) than of vecuronium (54 +/- 9%, P < 0.05). Neostigmine decreased plasma cholinesterase activity and increased plasma concentrations of the trans-trans and cis-trans stereoisomers of mivacurium (P < 0.05). CONCLUSIONS:Neostigmine is less effective at antagonizing the neuromuscular effect of mivacurium than that of vecuronium during constant infusion. Neostigmine increases plasma mivacurium concentrations, likely explaining its limited efficacy. Our results confirm that neostigmine impairs the metabolism of mivacurium in vivo and may explain the observation that neostigmine may not effectively antagonize mivacurium-induced block.