Potentiation of mivacurium blockade by low dose of pancuronium: a pharmacokinetic study.
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.
Motamed
Cyrus
C
Service d' Anesthésie Réanimation, Hôpital Henri Mondor, Créteil, France.
Menad
Riad
R
Farinotti
Robert
R
Kirov
Krassen
K
Combes
Xavier
X
Bouleau
Daniel
D
Feiss
Pierre
P
Duvaldestin
Philippe
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D001711:Biotransformation; D002802:Cholinesterases / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D000077590:Mivacurium; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D003473:Neuromuscular Nondepolarizing Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D019637:Orthopedic Procedures; D010197:Pancuronium / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D014656:Vascular Surgical Procedures
D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D000077590:Mivacurium; D002802:Cholinesterases; D010197:Pancuronium