Plasma anti-FXa concentration after continuous intravenous infusion and subcutaneous dosing of enoxaparin for thromboprophylaxis in critically ill patients. A randomized clinical trial

Introduction: In intensive care unit (ICU) patients, subcutaneous low-molecular weight heparin thromboprophylaxis results in lower plasma anti-factor Xa (anti-FXa) levels compared to general ward patients. The aim of this study was to examine whether enoxaparin thromboprophylaxis given as a continuous intravenous infusion (CII) results in more constant and predictable anti-FXa concentration than standard subcutaneous bolus (SCB) administration.

Materials and methods: This was a prospective, single-blind, multicenter, randomized controlled trial where ICU patients requiring thromboprophylaxis received enoxaparin either 40mg as a SCB once daily or 40mg as a CII over 24h for three consecutive days. The primary outcome was maximum serum anti-FXa concentration (C_max24h) within the first 24h; the secondary outcome was anti-FXa area under the curve (AUC)_(0-24h). Trough level was measured at 72h.

Results: Thirty-nine patients were included in the intention to treat analysis. The median anti-FXa C_max24h was 0.05 (interquartile range, IQR, 0.05-0.18) IU/ml in the CII group and 0.18 (IQR, 0.12-0.33) IU/ml in the SCB group (p=0.05). Median anti-FXa AUC_(0-24h) was 1.20 (IQR, 0.98-2.88) in the CII and 1.54 (IQR, 1.22-4.12) in the SCB group (p=0.095). After 72h, 66.7% of patients in the CII group had a detectable anti-FXa concentration of >0.1IU/ml, compared with 16.7% in the SCB group (p=0.019).

Conclusions: Continuous infusion of enoxaparin led to lower anti-FXa C_max24h than standard SCB administration. No difference in anti-FXa AUC_0-24h was detected.