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ANTICOAGULATION

Argatroban Anticoagulation in Critically Ill Patients

Staff Anesthesiologist, Klinik für Anästhesiologie, Universitätsklinikum der Heinrich-Heine-Universität, Düsseldorf, Germany

Tanja A Treschan, Dr med MD

Staff Anesthesiologist, Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum der Universität Duisburg-Essen, Essen, Germany

Klaus Görlinger, Dr med MD

Staff Anesthesiologist, Klinik für Anästhesiologie und Intensivmedizin Universitätsklinikum der Universität Duisburg-Essen

Jürgen Peters, Prof Dr med MD

Director and Chair, Klinik für Anästhesiologie und Intensivmedizin Universitätsklinikum der Universität Duisburg-Essen

Reprints: Dr. Beiderlinden, Klinik für Anästhesiologie, Universität-sklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany, fax 49 201 81-16253, martin. beiderlinden{at}med.uni-duesseldorf.de

BACKGROUND: Despite long-term use of argatroban in clinical practice, no dosing recommendations exist for critically ill patients with multiple organ dysfunction (MODS) and suspected or proven heparin-induced thrombocytopenia (HIT).

OBJECTIVE: To determine the suitability of argatroban use in critically ill patients with MODS and HIT.

METHODS: We conducted prospective observation of 24 consecutive patients with suspected HIT who were being anticoagulated with argatroban (target activated partial thromboplastin time [aPTT] 1.5–2 times normal or 50–60 sec) using 2 µg/kg/min in the first 5 patients and 0.2 µg/kg/min in the subsequent 19 patients.

RESULTS: Infusion of argatroban 2 µg/kg/min over 4 hours caused bleeding complications in 3 patients as aPTT increased from 51 ± 18 to 86 ± 34 seconds (p = 0.02), prothrombin time (PT) decreased from 76 ± 27% to 33 ± 12% of normal reference values, and international normalized ratio (INR) increased from 1.4 ± 0.4 to 2.5 ± 0.9 (p = 0.007). Infusion of argatroban 0.2 µg/kg/min over 4 hours provided sufficient anticoagulation without bleeding complications. The aPTT in this population increased from 44 ± 9 to 59 ± 13 seconds (p < 0.001), and PT and INR remained unchanged (76 ± 22% and 69 ± 23% of normal reference values, 1.3 ± 0.3 and after 1.3 ± 0.3, respectively [p = 0.4]). Coagulation variables (aPTT, PT, INR) were significantly different between both dosing regimens after 4 hours of infusion (p = 0.042 and p = 0.003, respectively). The maintenance dose for target aPTT averaged 0.22 ± 0.15 µg/kg/min in both groups.

CONCLUSIONS: In critically ill patients with MODS, argatroban 2 µg/kg/min, as recommended by the manufacturer, resulted in extensive anticoagulation. A tenfold lower starting dose is sufficient and safe for effective anticoagulation in this specific patient population.

Key Words: argatroban, heparin-induced thrombocytopenia, multiple organ failure

Published Online, April 17, 2007. www.theannals.com, DOI 10.1345/aph.1H569

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