Pharmacokinetic profiles of intravenous versus subcutaneous administration of low molecular weight heparin for thromboprophylaxis in critically ill patients: A randomized controlled trial

Background: Low molecular weight heparins (LMWH) are recommended for thromboprophylaxis in ICU patients but often fail to reach adequate peak anti-Xa activity. Objective: To compare the pharmacokinetic profiles of intravenous (IV) versus subcutaneous (SC) route of administration of LMWH. Method: This was a prospective, monocentric, randomized trial. Patients were randomized to the IV route of administration with a 4-h infusion of nadroparin 3800 IU or to the SC route of administration. Randomization was stratified according to the need for vasopressor or not. Anti-Xa activity was measured at baseline, and at 1, 2, 4, 6, 8, 12 and 24 h after the administration was started. Results: Sixty patients were included, of whom 30 were randomized to the IV group and 30 to the SC route. Pharmacokinetic profiles were significantly different. Mean peak anti-Xa activity was 0.38 IU/ml in the IV group vs 0.20 IU/ml in the SC group (p < 0.001). Trough values and AUC (0-24 h) were similar in both groups. Pharmacokinetic profiles were similar whether patients received vasopressors or not. Conclusions: The IV route of administration with a 4-h infusion lead to a significantly higher peak anti-Xa activity without affecting trough value or the AUC (0-24 h). Whether the IV administration of LMWH might improve the efficacy of thromboprophylaxis requires further research. (c) 2022 Elsevier Inc. All rights reserved.