A comparative study of varying doses of enoxaparin for thromboprophylaxis in critically ill patients: double-blinded, randomised controlled trial.
Crit Care. 2013 Apr 19;17(2):R75
Authors: Robinson S, Zincuk A, Larsen UL, Ekstrom C, Nybo M, Rasmussen B, Toft P
INTRODUCTION: Critically ill patients are predisposed to venous thromboembolism. We hypothesized that higher doses of enoxaparin would improve thromboprophylaxis without increasing the risk of bleeding. Peak anti-factor Xa (anti-Xa) levels of 0.1- 0.4 IU/ml, reflect adequate thromboprophylaxis for general ward patients. Studies conducted in orthopaedic patients demonstrated a statistically significant relationship between anti-Xa levels and wound haematoma and thrombosis. Corresponding levels for critically ill patients may well be higher, but have never been validated in large studies. METHODS: 80 critically ill patients weighing 50 - 90 kilograms were randomised in a double-blinded study to receive subcutaneous (sc) enoxaparin: 40 mg once daily (QD), 30 mg twice daily (BID), 40mg BID, or 1mg/kg QD, each administered for three days. Anti-Xa activity was measured at baseline, and daily at 4, 12, 16 and 24 hours post administration. Antithrombin, fibrinogen, and platelets were measured at baseline and twice daily thereafter. RESULTS: Two patients were transferred prior to participation. On day 1, doses of 40 mg QD (n= 20) and 40 mg BID (n=19) yielded mean peak anti-Xa of 0.20 IU/ml and 0.17 IU/ml respectively. A dose of 30 mg BID (n= 20) resulted in much lower levels (0.08 IU/ml). Patients receiving 1 mg/kg QD (n=19) achieved near steady state mean peak anti-Xa levels from day 1 (0.34 IU/ml). At steady state (day 3), mean peak anti-Xa levels of 0.13 IU/ml and 0.15 IU/ml were achieved with doses of 40 mg QD and 30 mg BID respectively. This increased significantly to 0.33 IU/ml and 0.40 IU/ml for doses of 40 mg BID and 1 mg/kg QD respectively. Thus anti-Xa response profiles differed significantly over the three days between enoxaparin treatment groups (p <0.0001). Doses of 40 mg BID and1mg/kg QD enoxaparin yielded target anti-Xa levels for over 80% of the study period. There were no adverse effects. CONCLUSIONS: 40 mg QD enoxaparin (Europe) or 30 mg BID (North America) yield levels of anti-Xa which may be inadequate for critically ill patients. A weight-based dose yielded the best anti-Xa levels without bioaccumulation, and allowed the establishment of near steady state levels from the first day of enoxaparin administration. Trial registration: Current Controlled Trials ISRCTN91570009.
PMID: 23601744 [PubMed - as supplied by publisher]