title: Atracurium infusions in patients with fulminant hepatic failure awaiting liver transplantation.
abstract: OBJECTIVE
  To determine the pharmacokinetics and pharmacodynamics of the neuromuscular blocking agent atracurium besylate in patients with fulminant hepatic failure (FHF).
  
  
  METHODS
  Open study of patients receiving atracurium infusions to facilitate mechanical ventilation.
  
  
  METHODS
  Intensive care unit in a tertiary referral university teaching hospital.
  
  
  METHODS
  Ten encephalopathic patients with FHF requiring mechanical ventilation while awaiting orthotopic liver transplantation. Three patients died before transplantation could be performed, three died after transplantation, and four survived following successful transplantation.
  
  
  METHODS
  Plasma, urine and dialysate fluid were analysed for atracurium and its metabolites using HPLC. Neuromuscular blockade was measured using transcutaneous ulnar nerve stimulation and an accelerometer. Electroencephalography and liver function tests were performed daily.
  
  
  RESULTS
  Patients received atracurium infusions for a period ranging from 38 to 217 h. Six patients required continuous arteriovenous haemodiafiltration (CAVHD) to replace renal function. Atracurium mean steady state clearance was 8.6 ml/min/kg, and train-of-four recovery ratio to 75% took 63 min (range 32-108). Laudanosine clearance was markedly reduced in the non-survivors; the half-life was 38.5 hrs compared with 5.3 h in the 4 patients who underwent successful transplantation. Laudanosine accumulation could be observed in all patients before transplantation, but kinetics returned to normal after successful transplantation. The highest laudanosine level recorded was 6,860 ng/ml. There was no evidence of adverse central neurological effects attributable to laudanosine. CAVHD did not contribute significantly to clearance of atracurium or its metabolites.
  
  
  CONCLUSIONS
  Atracurium kinetics and dynamics are near-normal even in patients with fulminant hepatic failure and renal failure; laudanosine accumulation will occur, but this is not associated with measurable central neurological effects. Implantation of a functioning liver graft results in clearance of laudanosine, which seems to be independent of renal function. Atracurium is an appropriate choice for producing neuromuscular blockade for periods of several days in patients with fulminant hepatic failure and renal impairment.
authors.affiliation: Intensive Care Unit, Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: J F
authors.initials: JF
authors.lastname: Bion
authors.forename: M I
authors.initials: MI
authors.lastname: Bowden
authors.forename: B
authors.initials: B
authors.lastname: Chow
authors.forename: L
authors.initials: L
authors.lastname: Honisberger
authors.forename: B C
authors.initials: BC
authors.lastname: Weatherley
mesh_terms: D000328:Adult; D001279:Atracurium / Q000097:blood / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use* / Q000652:urine; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006440:Hemofiltration; D006501:Hepatic Encephalopathy / Q000097:blood / Q000378:metabolism / Q000401:mortality / Q000628:therapy* / Q000652:urine; D006801:Humans; D007262:Infusions, Intravenous; D007546:Isoquinolines / Q000493:pharmacokinetics / Q000627:therapeutic use; D016031:Liver Transplantation / Q000401:mortality; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009294:Narcotics / Q000493:pharmacokinetics / Q000627:therapeutic use; D012121:Respiration, Artificial; D015996:Survival Rate; D014850:Waiting Lists
chemical_list: D007546:Isoquinolines; D009294:Narcotics; D001279:Atracurium; C001522:laudanosine