Potentiation of Mivacurium Blockade by Low Dose of Pancuronium

Background Mivacurium is potentiated by pancuronium to a much greater extent than other relaxants. In a previous investigation we suggested that this potentiation could be due to the ability of pancuronium to inhibit plasma cholinesterase activity, but we did not measure plasma concentrations of mivacurium. In the current study we performed a pharmacokinetic analysis by measuring the plasma concentration of mivacurium when preceded by administration of a low dose of pancuronium. Methods After induction of general anesthesia with propofol and fentanyl and orotracheal intubation, 10 patients (pancuronium-mivacurium group) received 15 microg/kg pancuronium followed 3 min later by 0.1 mg/kg mivacurium, whereas 10 other patients (mivacurium group) received saline followed by 0.13 mg/kg mivacurium 3 min later. Plasma cholinesterase activity was measured before and 3 and 30 min after pancuronium dosing in the pancuronium-mivacurium group and was measured before and after administration of saline in the mivacurium group. Arterial plasma concentrations of mivacurium and its metabolites were measured at 0.5, 1, 1.5, 2, 4, 10, 20, and 30 min after injection. Neuromuscular blockade was assessed by mechanomyography. Results Plasma cholinesterase activity decreased by 26% in the pancuronium-mivacurium group 3 min after injection of pancuronium (P < 0.01) and returned to baseline values 30 min later; however, no significant variation was observed in the mivacurium group. The clearances of the two most active isomers (Cis-Trans and Trans-Trans) were lower in the pancuronium-mivacurium group (17.6 +/- 5.1, 14.7 +/- 5.3 ml. min-1. kg-1, respectively) than in the mivacurium group (32.4 +/- 20.2, 24.8 +/- 13.5 ml. min-1. kg-1; P < 0.05). Conclusions A subparalyzing dose of pancuronium decreased plasma cholinesterase activity and the clearance of the two most active isomers of mivacurium. Pancuronium potentiates mivacurium more than other neuromuscular blocking agents because, in addition to its occupancy of postsynaptic acetylcholine receptors, it slows down the hydrolysis of mivacurium.

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The Effect of Neostigmine on Twitch Tension and Muscle Relaxant Concentration during Infusion of Mivacurium or Vecuronium

Anesthesiology ◽

10.1097/00000542-199507000-00010 ◽

1995 ◽

Vol 83 (1) ◽

pp. 83-87. ◽

Cited By ~ 13

Author(s):

Janos Szenohradszky ◽

Marie Lau ◽

Ronald Brown ◽

Manohar L. Sharma ◽

Dennis M. Fisher

Keyword(s):

Cholinesterase Activity ◽

Plasma Concentrations ◽

Neuromuscular Function ◽

Plasma Cholinesterase ◽

Constant Infusion ◽

Plasma Cholinesterase Activity ◽

Limited Efficacy ◽

Before And After ◽

Neuromuscular Effect

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.

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Edrophonium Increases Mivacurium Concentrations during Constant Mivacurium Infusion, and Large Doses Minimally Antagonize Paralysis

Anesthesiology ◽

10.1097/00000542-199504000-00014 ◽

1995 ◽

Vol 82 (4) ◽

pp. 912-918. ◽

Cited By ~ 14

Author(s):

Paul S. Hart ◽

Peter M. C. Wright ◽

Ronald Brown ◽

Marie Lau ◽

Manohar L. Sharma ◽

...

Keyword(s):

Cholinesterase Activity ◽

Plasma Concentrations ◽

Plasma Cholinesterase ◽

Constant Infusion ◽

Dependent Manner ◽

Plasma Cholinesterase Activity ◽

Limited Efficacy ◽

Before And After ◽

Dose Dependent ◽

Nondepolarizing Muscle Relaxant

Background Mivacurium, a nondepolarizing muscle relaxant, is metabolized by plasma cholinesterase. Although edrophonium does not alter plasma 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 might after metabolism of mivacurium, thereby hindering antagonism of paralysis. Accordingly, we determined the effect of edrophonium on neuromuscular function and plasma mivacurium concentrations during constant mivacurium infusion. Methods We infused mivacurium to maintain 90% depression of adductor pollicis twitch tension and then gave edrophonium in doses ranging from 125-2,000 micrograms/kg without altering the mivacurium 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 mivacurium concentrations before and after edrophonium were measured. Additional subjects were given 500 micrograms/kg edrophonium to antagonize continuous infusions of d-tubocurarine and vecuronium. Results With mivacurium, edrophonium increased twitch tension in a dose-dependent manner: the dose of edrophonium antagonizing 50% of twitch depression was 2,810 micrograms/kg. The largest dose of edrophonium (2,000 micrograms/kg) produced only 45 +/- 7% antagonism. Edrophonium, 500 micrograms/kg, antagonized mivacurium markedly less than it antagonized d-tubocurarine and vecuronium. Edrophonium increased plasma concentrations of the two potent stereoisomers of mivacurium 48% and 79%, these peaking at 1-2 min; plasma cholinesterase activity was unchanged. Conclusions Edrophonium doses that antagonize d-tubocurarine and vecuronium are less effective in antagonizing the neuromuscular effects of mivacurium during constant infusion. Edrophonium increases plasma mivacurium concentrations, partly or completely explaining its limited efficacy; the mechanism by which edrophonium increases mivacurium concentrations remains unexplained. Our results demonstrate that antagonism of mivacurium by edrophonium is impaired, and therefore we question whether edrophonium should be used to antagonize mivacurium.

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Variation in Human Plasma Cholinesterase Activity During Low-Dose Cocaine Administration

Journal of Toxicology Clinical Toxicology ◽

10.3109/15563659809162576 ◽

1998 ◽

Vol 36 (1-2) ◽

pp. 3-9 ◽

Cited By ~ 5

Author(s):

Robert S. Hoffman ◽

Tim Thompson ◽

Glendon C. Henry ◽

Dorothy K. Hatsukami ◽

Paul R. Pentel

Keyword(s):

Human Plasma ◽

Low Dose ◽

Cholinesterase Activity ◽

Plasma Cholinesterase ◽

Plasma Cholinesterase Activity ◽

Cocaine Administration ◽

Human Plasma Cholinesterase

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Pharmacodynamics and the Plasma Concentration of Mivacurium during Spontaneous Recovery and Neostigmine-facilitated Recovery

Anesthesiology ◽

10.1097/00000542-199907000-00019 ◽

1999 ◽

Vol 91 (1) ◽

pp. 119-126 ◽

Cited By ~ 6

Author(s):

Cynthia A. Lien ◽

Matthew R. Belmont ◽

Doreen L. Wray Roth ◽

Michiko Okamoto ◽

Amy Abalos ◽

...

Keyword(s):

Plasma Concentration ◽

Trans Isomer ◽

Cholinesterase Activity ◽

Spontaneous Recovery ◽

Neuromuscular Block ◽

Statistical Significance ◽

Plasma Concentrations ◽

Plasma Cholinesterase ◽

T Test ◽

Plasma Cholinesterase Activity

Background The authors examined the plasma concentrations of the isomers of mivacurium and its pharmacodynamics during spontaeous and neostigmine-facilitated recovery after a mivacurium infusion. Methods Sixteen patients receiving nitrous oxide-opioid anesthesia received 0.25 mg/kg mivacurium. Patient response to neuromuscular stimulation was determined using a mechanomyograph Once T1 had recovered to 25% of its baseline height, a mivacurium infusion was begun and adjusted to maintain 95-99% neuromuscular block. The infusion was discontinued after 90 min and muscle strength allowed to recover either spontaneously or after neostigmine/glycopyrrolate (0.05/0.01 mg/kg). Plasma concentrations of the isomers of mivacurium after discontinuation of the infusion were determined using an HPLC assay. Differences between the groups were determined using a one-way analysis of variance with a Bonferroni-corrected t test or Student t test as appropriate. P < or = 0.05 was considered significant. Results Differences in the times for recovery to a train-of-four ratio of 70% did not achieve statistical significance (mean+/-SD, 13.3+/-6.0 vs. 16.3+/-2.5 min for the neostigmine and spontaneous groups, respectively). Plasma cholinesterase activity decreased significantly from baseline values after administration of neostigmine (5.88+/-0.21 vs. 0.43+/-0.04 U/ml plasma). Plasma concentrations of the trans-trans isomer were significantly greater in the neostigmine group than in the spontaneous recovery group 5, 6, 8, and 10 min after discontinuation of the infusion. Differences in the plasma concentration of the cis-trans isomer did not achieve statistical significance. Conclusions Although administration of neostigmine decreased plasma cholinesterase activity and caused the trans-trans isomer to remain in the plasma at higher concentration, it did not delay recovery from mivacurium-induced block.

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