title: Edrophonium increases mivacurium concentrations during constant mivacurium infusion, and large doses minimally antagonize paralysis.
abstract: 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.
authors.affiliation: Department of Anesthesia, University of California, San Francisco 94143-0648, USA.
authors.forename: P S
authors.initials: PS
authors.lastname: Hart
authors.forename: P M
authors.initials: PM
authors.lastname: Wright
authors.forename: R
authors.initials: R
authors.lastname: Brown
authors.forename: M
authors.initials: M
authors.lastname: Lau
authors.forename: M L
authors.initials: ML
authors.lastname: Sharma
authors.forename: R D
authors.initials: RD
authors.lastname: Miller
authors.forename: L
authors.initials: L
authors.lastname: Gruenke
authors.forename: D M
authors.initials: DM
authors.lastname: Fisher
mesh_terms: D000293:Adolescent; D000328:Adult; D002802:Cholinesterases / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004491:Edrophonium / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D007546:Isoquinolines / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000097:blood*; D008875:Middle Aged; D000077590:Mivacurium; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology*; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors* / Q000097:blood*; D010243:Paralysis / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D004491:Edrophonium; D000077590:Mivacurium; D002802:Cholinesterases