A comparative study of varying doses of enoxaparin for thromboprophylaxis in critically ill patients: a double-blinded, randomised controlled trial

• Published in: Critical care (London, England) England), 2013-04, Vol.17 (2), p.R75-R75, Article R75
• Main Authors: Robinson, Sian, Zincuk, Aleksander, Larsen, Ulla Lei, Ekstrøm, Claus, Nybo, Mads, Rasmussen, Bjarne, Toft, Palle
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Anticoagulants - administration & dosage; Care and treatment; Critical Illness - epidemiology; Critical Illness - therapy; Dosage and administration; Dose-Response Relationship, Drug; Double-Blind Method; Enoxaparin; Enoxaparin - administration & dosage; Female; Humans; Male; Middle Aged; Patients; Prospective Studies; Risk Factors; Thromboembolism; Thrombosis - epidemiology; Thrombosis - prevention & control
• ISSN: 1364-8535; 1466-609X; 1364-8535
• DOI: 10.1186/cc12684

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 to 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. Eighty critically ill patients weighing 50 to 90 kilograms were randomised in a double-blinded study to receive subcutaneous (sc) enoxaparin: 40 mg once daily (QD), 30 mg twice daily (BID), 40 mg BID, or 1 mg/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. 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