Argatroban dosing in intensive care patients with acute renal failure and liver dysfunction

Study Objective. To demonstrate dosing adjustment difficulties of argatroban encountered in critically ill patients with acute liver dysfunction who are receiving continuous renal replacement therapy. Design. Case description. Setting. Medical and surgical intensive care unit in a tertiary care, university-affiliated hospital. Patients. Four consecutive patients with proven heparin-induced thrombocytopenia (HIT), acute renal failure requiring continuous renal replacement therapy, and various levels of transient hepatic impairment. Intervention. Argatroban, a direct synthetic thrombin inhibitor, was given continuously and stabilized at 0.125-0.85 mug/kg/minute to attain an activated partial thromboplastin time (aPTT) 1.5-2.5 times the normal value for periods of 6-36 days. Measurements and Results. Argatroban was started at the usual dosage of 2 mug/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. Conclusion. 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.