title: Neuromuscular pharmacodynamics of mivacurium in adults with major burns.
abstract: BACKGROUND
  Mivacurium is metabolized by plasma pseudocholinesterase (PChE) enzyme, which is decreased in burns. We tested whether the decreased metabolism of mivacurium due to decreased PChE activity can overcome the pharmacodynamic resistance to non-depolarizing relaxants previously seen in major burns.
  
  
  METHODS
  Thirty adults with 35 (13)% [mean (sd)] burn were studied at 5-91 post-burn days and 31 non-burns matched controls. Mivacurium 0.2 mg kg(-1) was administered as a single bolus. Neuromuscular block was monitored with single-twitch response using TOF-Watch™. Onset time (drug administration to maximal twitch suppression) and spontaneous recovery were measured.
  
  
  RESULTS
  Onset time was significantly prolonged in burns when compared with non-burns (115 vs 90 s; P<0.001). The PChE levels were lower in burns [1432 (916) vs 2866 (731) IU litre(-1); P<0.001] and the neuromuscular recovery to 50% of baseline twitch height was prolonged in burns (41 vs 26 min; P<0.001). There was a significant correlation between PChE and time to 50% recovery for the whole group together (r=-0.6; P<0.001). The dibucaine numbers were not different.
  
  
  CONCLUSIONS
  The prolonged onset time suggests resistance to neuromuscular effects, whereas the prolonged recovery suggests increased sensitivity. This divergent response can be explained by qualitative and quantitative changes in acetylcholine receptor expression causing resistance and decreased PChE activity causing sensitivity. Despite using a relatively large dose of mivacurium (0.2 mg kg(-1)) in the presence of decreased PChE levels, this did not overcome the resistance resulting from up-regulated receptors.
authors.affiliation: Department of Anesthesia #6505-3 JCP, Roy J. and Lucille A. Carver College of Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA. anthony-han@uiowa.edu
authors.forename: T-H
authors.initials: TH
authors.lastname: Han
authors.forename: J A J
authors.initials: JA
authors.lastname: Martyn
mesh_terms: D000293:Adolescent; D000328:Adult; D002056:Burns / Q000201:enzymology / Q000503:physiopathology* / Q000601:surgery; D002091:Butyrylcholinesterase / Q000097:blood; D016022:Case-Control Studies; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D000077590:Mivacurium; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000503:physiopathology; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*
chemical_list: D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D000077590:Mivacurium; D002091:Butyrylcholinesterase