Experience with Intravenous Enoxaparin in Critically Ill Infants and Children.

The use of subcutaneous (SC) low molecular weight heparin (LMWH), such as enoxaparin, in pediatric patients for treatment or prevention of thromboembolism is now considered standard practice; however, SC administration is often difficult in special populations such as premature neonates, children with minimal subcutaneous tissue, and critically ill children with severe edema. Impaired SC absorption may lead to difficulty achieving adequate anticoagulation, as measured by anti-Xa levels 4 to 6 hr after the second or third dose. Intravenous (IV) administration of enoxaparin has, therefore, been employed in our intensive care unit (ICU) in an attempt to achieve adequate anticoagulation. However, the published experience of IV dosing and its monitoring consists of one brief manuscript and one abstract describing one preterm infant each. Therefore, we retrospectively evaluated dosing, monitoring, and clinical outcomes of pediatric patients receiving IV enoxaparin in our ICU between April 1, 2005 and March 31, 2006. Seven patients, all with congenital heart defects, were identified using hospital pharmacy records. Five were switched to IV enoxaparin after having difficulty achieving therapeutic anti-Xa levels with SC administration, primarily due to marked edema. Two others were empirically started on IV enoxaparin. Five children were treated with enoxaparin for thrombosis and 2 were treated prophylactically. Median age at the initiation of IV enoxaparin was 4 mo (range, 18 d – 3 yr). Dosing of the enoxaparin was every 8 hr for the 5 children under 1 yr of age and every 12 hr for the 2 children over 1 yr of age. Of the total 64 anti-Xa levels obtained, 19 monitored the 12 hr dosing schedule and 45 the 8 hr schedule. In order to evaluate the anti-Xa levels drawn following different doses (mg/kg) and dosing regimens (q8h or q12h) we transformed the data by the following equation: anti-Xa level (IU/ml)/total daily dose of enoxaparin· kg⁻¹. These transformed values were averaged and grouped by the time of the anti-Xa level after enoxaparin, as follows:

The average enoxaparin dose necessary to achieve the therapeutic target (anti-Xa 0.5–1.0 IU/ml) at 1–2 hr for the 3 children < 1 yr of age was 2.4 mg/kg (± s.d. 0.58) q8h. The average dose to achieve the prophylactic target (anti-Xa 0.3–0.5 IU/ml) at 1–2 hr for the 2 children <1 yr of age was 0.93 mg/kg (± s.d. 0.43) q8h. In the 2 children > 1yr of age, the average dose to achieve the therapeutic target at 1–2 hr was 1.11 mg/kg (± s.d. 0.13) q12h. No serious bleeding complications occurred in any patient. In conclusion, IV enoxaparin dosing appears to exhibit different pharmacodynamics than SC dosing, with higher anti-Xa levels at 1 to 2 hr after administration rather than at 4 to 6 hr. More frequent administration may be indicated as the levels decrease substantially 6 to 8 hr following an IV dose. The average dose needed for therapeutic levels may be higher than with SC administration (especially in the younger child). Future prospective studies should be conducted to determine the pharmacodynamics of IV enoxaparin, its safety and its clinical indications.