A 2024 systematic review and meta-analysis of 15 retrospective studies, randomized controlled trials (RCTs), and case series, evaluated individualized dosing strategies for enoxaparin in critically ill pediatric patients. Significant interindividual variability was identified in enoxaparin pharmacokinetics, with evidence suggesting higher initial doses may be necessary, particularly in neonates and infants, to achieve therapeutic anti-Xa levels. Intravenous (IV) administration was noted as an alternative to subcutaneous (SC) dosing, with numerous studies demonstrating comparable safety and efficacy when comparing IV infusions over 30 minutes and SC dosing in critically ill patients. However, another study did find that 56% of neonates experienced localized reactions at the site of the indwelling SC catheter when receiving enoxaparin for thrombosis treatment. [1]
The route of administration is often determined based on the severity of the condition, the patient’s stability, or the risk of drug interactions, with critically ill pediatric patients usually receiving SC dosing due to the ease and lower risk of infection. While the recommended prophylactic venous thromboembolism (VTE) treatment with enoxaparin in pediatrics ranges from 0.5 to 1.5 mg/kg/12 hours, the treatment of deep vein thrombosis (DVT) or pulmonary embolism is 1 to 1.5 mg/kg/12 hours. However, opposing evidence suggested that patients younger than one year of age require a higher initial treatment dose of 1.5 to 2.7 mg/kg/12 hours instead, although this was administered subcutaneously. The findings emphasize the importance of therapeutic drug monitoring and population pharmacokinetic modeling for optimizing enoxaparin dosing in this vulnerable population, underscoring the need for further prospective research to establish pediatric-specific guidelines. [1]
A 2014 retrospective study evaluated the pharmacodynamics, safety, and therapeutic utility of intravenous (IV) enoxaparin delivered as a 30-minute infusion in critically ill neonatal and pediatric patients. This study included 45 individuals, 15 cases receiving IV enoxaparin and 30 controls receiving subcutaneous (SC) enoxaparin, between January 2009 and June 2012. Key inclusion criteria required patients to have at least one anti-Factor Xa level measured, with therapeutic ranges defined as 0.3-0.5 U/mL for prophylaxis and 0.5-1 U/mL for treatment. Cases and controls were matched in a 1:2 ratio based on age and ICU location to standardize potential confounding variables. A 30-minute IV infusion of enoxaparin was utilized in response to concerns about impaired SC absorption due to edema or to mitigate procedural pain, particularly in smaller or critically ill children. IV enoxaparin demonstrated comparable pharmacodynamic efficacy to SC administration, as therapeutic anti-Factor Xa levels were achieved in 100% of the cases and controls. [2]
Although IV dosing required a higher mean initial dose (1.14 ± 0.38 mg/kg/dose) than SC dosing (0.85 ± 0.2 mg/kg/dose; p= 0.003), cases requiring dose adjustments achieved therapeutic levels significantly faster (mean of 2.7 ± 1.3 days) than controls (mean of 4.4 ± 1.4 days; p= 0.007). Notably, no adverse events related to bleeding, thrombosis, or hypersensitivity were reported in either group. Additionally, the study highlighted lower perceived pain and distress with IV administration and outlined potential benefits in patients with compromised SC absorption due to factors such as edema, peripheral vasoconstriction, or reduced regional blood flow. The findings suggest that 30-minute IV enoxaparin infusions may be a viable, effective, and potentially more comfortable alternative for anticoagulation in critically ill pediatric populations, warranting further investigation and prospective pharmacokinetic and pharmacodynamic analyses. [2]