title: A comparative study of varying doses of enoxaparin for thromboprophylaxis in critically ill patients: a double-blinded, randomised controlled trial.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  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 and 1 mg/kg QD enoxaparin yielded target anti-Xa levels for over 80% of the study period. There were no adverse effects.
  
  
  CONCLUSIONS
  Doses of 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.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN91570009.
authors.forename: Sian
authors.initials: S
authors.lastname: Robinson
authors.forename: Aleksander
authors.initials: A
authors.lastname: Zincuk
authors.forename: Ulla Lei
authors.initials: UL
authors.lastname: Larsen
authors.forename: Claus
authors.initials: C
authors.lastname: Ekstrøm
authors.forename: Mads
authors.initials: M
authors.lastname: Nybo
authors.forename: Bjarne
authors.initials: B
authors.lastname: Rasmussen
authors.forename: Palle
authors.initials: P
authors.lastname: Toft
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000925:Anticoagulants / Q000008:administration & dosage; D016638:Critical Illness / Q000453:epidemiology / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D017984:Enoxaparin / Q000008:administration & dosage; D011446:Prospective Studies; D012307:Risk Factors; D013927:Thrombosis / Q000453:epidemiology / Q000517:prevention & control
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin