title: Argatroban dosing in intensive care patients with acute renal failure and liver dysfunction.
abstract: OBJECTIVE
  To demonstrate dosing adjustment difficulties of argatroban encountered in critically ill patients with acute liver dysfunction who are receiving continuous renal replacement therapy.
  
  
  METHODS
  Case description.
  
  
  METHODS
  Medical and surgical intensive care unit in a tertiary care, university-affiliated hospital.
  
  
  METHODS
  Four consecutive patients with proven heparin-induced thrombocytopenia (HIT), acute renal failure requiring continuous renal replacement therapy, and various levels of transient hepatic impairment.
  
  
  METHODS
  Argatroban, a direct synthetic thrombin inhibitor, was given continuously and stabilized at 0.125-0.85 microg/kg/minute to attain an activated partial thromboplastin time (aPTT) 1.5-2.5 times the normal value for periods of 6-36 days.
  
  
  RESULTS
  Argatroban was started at the usual dosage of 2 microg/kg/minute, which resulted in significant overshooting of the aPTT and international normalized ratio (INR). No patient experienced bleeding or thrombotic complications. All patients were stabilized with reduced dosages such as those recommended for patients with chronic hepatic impairment.
  
  
  CONCLUSIONS
  We recommend argatroban therapy for intensive care patients with HIT, especially those with renal failure. However, in all patients with suspected liver dysfunction due to recent elevation of liver transaminase levels and combined renal failure, a decrease in the initial dosage and careful titration of the infusion are mandatory. Further studies are needed to fully elucidate argatroban elimination and dosage adjustments for intensive care patients.
authors.affiliation: Department of Pharmacy Services, Hôpital du Sacré-Coeur de Montréal, Montréal, Québec, Canada. david.williamson@umontreal.ca
authors.forename: David R
authors.initials: DR
authors.lastname: Williamson
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boulanger
authors.forename: Mariline
authors.initials: M
authors.lastname: Tardif
authors.forename: Martin
authors.initials: M
authors.lastname: Albert
authors.forename: Geneviève
authors.initials: G
authors.lastname: Grégoire
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives; D003422:Critical Care; D016638:Critical Illness; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007263:Infusions, Parenteral; D019934:International Normalized Ratio; D008107:Liver Diseases / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010875:Pipecolic Acids / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D017582:Renal Replacement Therapy / Q000379:methods; D013449:Sulfonamides; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control; D000637:Transaminases / Q000097:blood
chemical_list: D010875:Pipecolic Acids; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; D000637:Transaminases; C031942:argatroban