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Clinical Pharmacy Specialist, Critical Care, Department of Pharmacy Services, The University Hospital; Adjunct Clinical Instructor of Clinical Pharmacy, Division of Pharmacy Practice, James L Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH
PGY2 Oncology Pharmacy Resident, Department of Pharmacy Services, The University Hospital, Cincinnati
Clinical Pharmacy Specialist, Critical Care, Department of Pharmacy Services, The University Hospital; Adjunct Clinical Instructor of Clinical Pharmacy, Division of Pharmacy Practice, James L Winkle College of Pharmacy, University of Cincinnati
Clinical Pharmacy Specialist, Cardiology, Department of Pharmacy Services, The University Hospital; Adjunct Clinical Instructor of Clinical Pharmacy, Division of Pharmacy Practice, James L Winkle College of Pharmacy, University of Cincinnati
Clinical Pharmacy Specialist, Critical Care, Department of Pharmacy Services, The University Hospital; Adjunct Assistant Professor of Clinical Pharmacy, Division of Pharmacy Practice, James L Winkle College of Pharmacy, University of Cincinnati
Reprints: Dr. Keegan, The University Hospital, 234 Goodman Ave., Mail Location 0791, Cincinnati, OH 45219, fax 513/584-1790, Shaun.keegan{at}healthall.com
BACKGROUND: Critically ill patients often require therapeutic argatroban dosages lower than those recommended in package labeling. The magnitude of dosage alteration in relation to severity of organ failure is unknown.
OBJECTIVE: To compare therapeutic argatroban dosages between critically ill and noncritically ill patients with confirmed or suspected heparin-induced thrombocytopenia and investigate the relationship between total Sequential Organ Failure Assessment (SOFA) score and therapeutic argatroban dosage.
METHODS: This retrospective cohort study was conducted at an urban academic medical center. Adults without Child-Pugh class C hepatic dysfunction who received argatroban for more than 24 hours over a 3-year period were included. Therapeutic argatroban dosage was that resulting in 2 consecutive activated partial thromboplastin time (aPTT) values 1.5–3 times the patient-specific baseline obtained at least 4 hours apart. Initial argatroban dosages were at the discretion of the managing service.
RESULTS: Fifty-three patients (critically ill, n = 34; noncritically
ill, n = 19) were included. Critically ill patients had higher median
[interquartile range] Acute Physiology and Chronic Health Evaluation (APACHE
II) (17 [12–21] vs 10 [3.25–17.75]; p = 0.007) and SOFA (11
[7–13] vs 2 [0–2.75]; p < 0.001) scores. Critically ill
patients required lower mean ± SD therapeutic argatroban dosage (0.6
± 0.5 vs 1.4 ± 0.9 µg/kg/min; p < 0.001). There was no
significant difference in time to therapeutic aPTT or proportion of aPTTs
within therapeutic range. Argatroban dosage was inversely related to SOFA
score tertiles (<6: 1.34 ± 0.82 µg/kg/min; 6–9: 0.93
± 0.54; 
10: 0.40 ± 0.27; p < 0.001). Total SOFA score at
the time of argatroban initiation was independently associated with an
argatroban dosage less than 0.75 µg/kg/min (OR 1.5, 95% CI 1.2 to 1.8; p
< 0.001). Adverse events were similar between groups.
CONCLUSIONS: Critically ill patients with single or multiple organ failure require lower therapeutic argatroban dosages compared with noncritically ill patients. Because of an inverse relationship with SOFA score, initial argatroban dosage in critically ill patients should be based on the presence and magnitude of organ failure.
Key Words: argatroban, multiple organ failure, thrombocytopenia
Published Online, December 30, 2008. www.theannals.com, DOI 10.1345/aph.1L224
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  W. E Dager Dosing Nomograms: Silos on a Slope Ann. Pharmacother., January 1, 2009; 43(1): 114 - 117. [Abstract] [Full Text] [PDF]
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