Factors influencing enoxaparin anti-Xa activity in surgical critically ill patients.

STUDY OBJECTIVE: The objectives of the present study were to describe the incidence of low anti-Xa levels defined as below 0.1 IU/mL in a general surgical intensive care unit population and to evaluate factors independently influencing anti-Xa activity. DESIGN: A prospective study was undertaken. SETTING: Thirty-six patients admitted to a general intensive care unit and receiving subcutaneous (SC) enoxaparin 30 mg twice daily for thromboprophylaxis between November 2003 and August 2005 were included in the study. MEASUREMENTS AND MAIN RESULTS: After reaching steady state, anti-Xa activity was determined by chromogenic assay at 0, 3, 6, and 9 hours after injection. Anti-Xa levels below 0.1 IU/mL at any time were considered subtherapeutic. Areas under the curve (AUCs) for a 12-hour dosing interval were estimated. Factors influencing anti-Xa AUC were evaluated using linear regression. Two patients (5.6%) did not attain therapeutic levels defined as anti-Xa more than 0.1 IU/mL at 3 hours post dose. Median AUC was 1.84 IU·h/mL (interquartile range, 1.47 IU·h/mL). In the linear regression analysis, sex and creatinine clearance were significant predictors of anti-Xa AUC(0-12h) levels. CONCLUSION: In the study, prophylactic SC enoxaparin in critically ill patients at the current 30 mg SC twice daily dosage attained an anti-Xa level more than 0.1 U/mL in nearly all patients. In addition, low creatinine clearances and female sex are associated with higher anti-Xa activity AUC(0-12h).

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 microg/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 microg/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.