title: Argatroban for anticoagulation in continuous renal replacement therapy.
abstract: OBJECTIVE
  Argatroban, a direct thrombin inhibitor, was evaluated for anticoagulation in continuous renal replacement therapy (CRRT) in critically ill patients with heparin-induced thrombocytopenia type II and acute renal failure. The investigation focused on predictors for the maintenance doses of argatroban with efficacy and safety of argatroban being secondary outcomes.
  
  
  METHODS
  Prospective, dose finding study.
  
  
  METHODS
  Two intensive care units (medical and surgical) of a university hospital.
  
  
  METHODS
  Medical and surgical patients (n = 30) with acute or histories of heparin-induced thrombocytopenia type II and acute renal failure with necessity for CRRT.
  
  
  METHODS
  CRRT with argatroban for anticoagulation.
  
  
  RESULTS
  Critical illness severity scores Acute Physiology and Chronic Health Evaluation (APACHE)-II, Simplified Acute Physiology Score (SAPS) II, and the indocyanine green plasma disappearance rate (ICG-PDR) were correlated to the argatroban maintenance doses. These diagnostic tools can help to identify patients with the necessity for decreased argatroban doses. The following recommendations for argatroban dosing during CRRT could be determined: a loading dose of 100 microg/kg followed by a maintenance infusion rate (microg/kg/min), which can be calculated from the scores as follows: for APACHE II: 2.15-0.06 x APACHE II (r = -.81, p < 0.001); for SAPS II: 2.06-0.03 x SAPS II (r = -.8, p < 0.001); and for ICG-PDR: -0.35 + 0.08 x ICG-PDR (r = .89, p < 0.001). The efficacy and safety of anticoagulation during CRRT were determined by the steady state of blood urea nitrogen (32.16 +/- 18.02 mg/dL), mean filter patency at 24 hrs (98%), and the rate of bleeding episodes. Only two patients developed minor bleeding; no patient developed severe bleeding episodes.
  
  
  CONCLUSIONS
  In critically ill patients with heparin-induced thrombocytopenia type II and necessity for CRRT critical illness scores (APACHE II, SAPS II) or ICG-PDR can help to predict the required argatroban maintenance dose for anticoagulation. These predictors identify decreased argatroban dosing requirements resulting in effective and safe CRRT.
authors.affiliation: Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes; D-66421Homburg/Saar, Germany. link@med-in.uni-saarland.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Link
authors.forename: Matthias
authors.initials: M
authors.lastname: Girndt
authors.forename: Simina
authors.initials: S
authors.lastname: Selejan
authors.forename: Alexander
authors.initials: A
authors.lastname: Mathes
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.forename: Hauke
authors.initials: H
authors.lastname: Rensing
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D001120:Arginine / Q000031:analogs & derivatives; D016638:Critical Illness; D005260:Female; D006493:Heparin / Q000009:adverse effects; D006801:Humans; D008297:Male; D010875:Pipecolic Acids / Q000008:administration & dosage*; D011446:Prospective Studies; D017582:Renal Replacement Therapy; D013449:Sulfonamides; D013921:Thrombocytopenia / Q000139:chemically induced / Q000150:complications
chemical_list: D000925:Anticoagulants; D010875:Pipecolic Acids; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban