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RESEARCH REPORTS |
1 Staff Anesthesiologist, Klinik für Anästhesiologie, Universitätsklinikum der Heinrich-Heine-Universität, Düsseldorf, Germany
2 Staff Anesthesiologist, Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum der Universität Duisburg-Essen, Essen, Germany
3 Staff Anesthesiologist, Klinik für Anästhesiologie und Intensivmedizin Universitätsklinikum der Universität Duisburg-Essen
4 Director and Chair, Klinik für Anästhesiologie und Intensivmedizin Universitätsklinikum der Universität Duisburg-Essen
* To whom correspondence should be addressed. E-mail: martin.beiderlinden{at}med.uni-duesseldorf.de.
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Abstract |
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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.
Reprints: Dr. Beiderlinden, Klinik für Anästhesiologie, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany, fax 49 201 81-16253, martin. beiderlinden@med.uni-duesseldorf.de
This article has been cited by other articles:
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  S. P Keegan, E. M Gallagher, N. E Ernst, E. J Young, and E. W Mueller Effects of Critical Illness and Organ Failure on Therapeutic Argatroban Dosage Requirements in Patients with Suspected or Confirmed Heparin-Induced Thrombocytopenia Ann. Pharmacother., January 1, 2009; 43(1): 19 - 27. [Abstract] [Full Text] [PDF]
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 T. E. Warkentin, A. Greinacher, A. Koster, and A. M. Lincoff Treatment and Prevention of Heparin-Induced Thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 340S - 380S. [Abstract] [Full Text] [PDF]
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W. D Hoffman, Y. Czyz, D. A McCollum, and M. J Hursting Reduced Argatroban Doses After Coronary Artery Bypass Graft Surgery Ann. Pharmacother., March 1, 2008; 42(3): 309 - 316. [Abstract] [Full Text] [PDF]
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