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Background: Mivacurium is hydrolyzed by plasma cholinesterase (pChe). The purpose of this study was to evaluate the pharmacodynamics and the pharmacokinetics of the three isomers of mivacurium in patients phenotypically heterozygous for the usual and the atypical pChe variant (UA)., Methods: Thirty-two patients were included in a dose-response study, in which the patients received one of four doses of mivacurium. An additional bolus dose of mivacurium, to a total of 0.1 mg kg-1, was given followed by a continuous infusion adjusted to maintain 91-99% neuromuscular block. The times to different levels of recovery following the infusion were measured using mechanomyography and train-of-four (TOF) nerve stimulation. Twelve of the patients with an estimated duration of anaesthesia of more than 90 min were (randomly) selected for the pharmacokinetic part of the study. Venous samples were taken for determination of the three isomers of mivacurium. These results were compared with results from a previous study in phenotypically normal patients (UU)., Results: The estimated ED50 and ED95 were 24 and 69 microg kg-1, respectively. The median (range) infusion rate was 3.7 microg kg-1 min-1 (1.2-2.9) and the time to a TOF ratio of 0.7 was 29.8 min (16.1-44.8). The median clearances of the cis-cis, cis-trans and trans-trans isomers were 3.7, 29 and 28 ml kg-1 min-1, respectively. The elimination half-lives of the isomers were 45, 6.7 and 6.3 min, respectively., Conclusion: In patients heterozygous for the usual and the atypical variant (UA), the potency of mivacurium is higher, the infusion requirements lower and the rate of spontaneous recovery prolonged, compared with phenotypically normal patients. The clearances of the active isomers are significantly lower and the elimination half-lives longer in heterozygous patients than in phenotypically normal patients (UU). The pharmacokinetics of the inactive cis-cis isomer was not affected.

Background: Mivacurium is hydrolyzed by plasma cholinesterase, and is therefore less dependent on liver metabolism and renal elimination than other neuromuscular blocking drugs. This might favor the use of mivacurium in elderly patients. The purpose of this study was to compare the pharmacodynamics and the pharmacokinetics of the three isomers of mivacurium and their metabolites in young adult and elderly patients., Methods: Sixty-four patients were included in a dose-response study, in which 32 young adults and 32 elderly patients received one of four doses of mivacurium. An additional bolus dose of mivacurium to a total of 0.1 mg/kg was given followed by a continuous infusion adjusted to maintain a 91-99% neuromuscular block. The times to maximum block and different levels of recovery were measured using mechanomyography and train-of-four (TOF) nerve stimulation. Thirty-two patients were randomly selected for the pharmacokinetic study. Venous samples were taken for determination of the three mivacurium isomers and the metabolites., Results: The estimated ED95 were 0.053 and 0.061 mg/kg in young adults and elderly patients, respectively (NS). The median infusion rate did not differ, but duration to a TOF ratio of 0.7 was significantly longer in elderly patients than in young adult patients (21.0 vs. 16.5 min). No statistically significant difference between the age groups in clearance and elimination half-life of the isomers was seen. The half-lives of the metabolites were significantly prolonged in the elderly patients., Conclusion: There were no significant differences in the potency or infusion requirements between the adult and elderly patients, but the rate of recovery was significantly, though only moderately prolonged, in the elderly patients. No significant difference in clearance was seen but the elimination half-lives of the metabolites was longer in the elderly patients.

Introduction: The aim of this investigation was to compare the use of a continuous infusion of mivacurium or atracurium guided by tactile evaluation of the neuromuscular block., Materials and Methods: Forty-five patients were randomly allocated to three groups of patients. Group M and MN received a bolus dose of mivacurium 0.15 mg/kg followed by a continuous infusion and group AN a bolus dose of atracurium 0.4 mg/kg followed by an infusion., Results: The neuromuscular blockade recovered spontaneously in group M and was antagonised in group MN and AN. The level of block was quantified by tactile evaluation. The time to full recovery was significantly shorter in patients receiving mivacurium compared to patients given atracurium, 14.5, 12.0 and 18.0 min, respectively. Further, reversal with neostigmine significantly enhanced recovery following mivacurium., Conclusion: A continuous infusion of mivacurium and atracurium can easily be performed, guided by tactile evaluation of the neuromuscular block and the effect can be reversed by neostigmine.

Background: The short duration of action of mivacurium results from its rapid hydrolysis by plasma cholinesterase. Bambuterol, an oral bronchodilator, has an inhibiting effect on plasma cholinesterase. The purpose of this study was to evaluate the effect of bambuterol-induced low plasma cholinesterase activity on the pharmacokinetics and pharmacodynamics of mivacurium., Methods: Fourteen patients received 20 mg bambuterol and 14 patients received placebo orally 2 h before induction of anesthesia. During anesthesia the neuromuscular block was monitored at the thumb using train-of-four nerve stimulation every 12 s and mechanomyography. The times to different levels of neuromuscular recovery after 0.2 mg/kg mivacurium were measured. The concentrations in venous blood of the three isomers and the metabolites of mivacurium were measured using high-performance liquid chromatography., Results: Plasma cholinesterase activity was inhibited a median of 90% (range, 67-97%) after bambuterol. The time to first response to train-of-four nerve stimulation was 15 min (range, 9-21 min) and 59 min (range, 32-179 min) in patients receiving placebo and bambuterol, respectively. The estimated clearances of the isomers were significantly lower and the elimination half-lives of all three isomers significantly prolonged in patients receiving bambuterol. No difference was seen in elimination half-lives of the metabolites. The elimination rate constant from the effect compartment and the potency of mivacurium was not affected by bambuterol., Conclusion: A 90% inhibition of plasma cholinesterase activity significantly reduced clearance of the isomers of mivacurium. Correspondingly, the duration of action of 0.2 mg/kg mivacurium was prolonged three- to fourfold, compared with patients not administered bambuterol.