Argatroban for anticoagulation in continuous renal replacement therapy*

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. DESIGN: Prospective, dose finding study. SETTING: Two intensive care units (medical and surgical) of a university hospital. PATIENTS: Medical and surgical patients (n = 30) with acute or histories of heparin-induced thrombocytopenia type II and acute renal failure with necessity for CRRT. INTERVENTION: CRRT with argatroban for anticoagulation. MEASUREMENTS AND MAIN 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. CONCLUSION: 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.