Pharmacokinetic Comparison of Subcutaneous and Intravenous Nadroparin Administration for Thromboprophylaxis in Critically Ill Patients on Vasopressors


CIHLÁŘ Radek ŠRÁMEK Vladimír PAPIEŽ Adriána PENKA Miroslav SUK Pavel

Year of publication 2020
Type Article in Periodical
Magazine / Source PHARMACOLOGY
MU Faculty or unit

Faculty of Medicine

Keywords Low molecular weight heparin; Pharmacokinetics; Anti-factor Xa activity; Thromboembolism; Prophylaxis; Vasopressors
Description Introduction: Critically ill patients are exposed to a high risk of developing thromboembolism. Moreover, standard prophylaxis with subcutaneous (SC) heparin is less efficient in patients requiring vasopressors. The aim is a comparison of pharmacokinetics between SC and intravenous (IV) applied nadroparin. Methods: Thirty-eight ventilated ICU patients requiring vasopressor support were randomized into a single dose of nadroparin 3,800 IU (0.4 mL) subcutaneously (SC group) or 1,900 IU (0.2 mL) intravenously (IV group). Anti-factor Xa activity (anti-Xa) was observed over 24 h; data are stated as median (IQR). Results: Peak anti-Xa was significantly higher in the IV group 0.42 (0.39-0.43) IU/mL than in the SC group 0.16 (0.09-0.18) IU/mL (p < 0.001). There was a trend towards higher area under the curve (AUC) of anti-Xa in the SC group 1.41 (0.41-1.80) IU/mL x h than in the IV group 1.04 (0.93-1.13) IU/mL x h (p = 0.08). In the SC group, there was a negative correlation between anti-Xa AUC and both capillary refill time Xa (r = -0.86) and norepinephrine dose (r = -0.68). In the IV group, anti-Xa decrease half-life was 1.6 (1.4-2.0) h. Conclusions: IV administration of 1,900 IU of nadroparin led to a predictable effective peak anti-Xa. After SC administration, anti-Xa was heterogeneous and significantly influenced by peripheral perfusion.

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