Systematic review and meta-analysis of individualized enoxaparin dose optimization in critically ill pediatrics: A path towards enhanced therapeutic outcomes

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Mohammed Kanan
Nawaf M. Alotaibi
Khalid Bin Anzan
Hayat Yahya Alzahrani
Ghaliah Ibrahim
Fatmah Shamakhi
Anhar Al-Mohsin
Noura alhutarshi
Shaden Alotaibi
Renad Almutairi
Reem Alshammari
Asma Alshammari
Hanaa Almedali
Reem Alkhedair
Dalia Alhabeeb


systematic review, meta-analysis, enoxaparin, dose optimization, pediatrics, therapeutic outcome


Background: Critically ill pediatric patients face an increased risk of venous thromboembolism, and enoxaparin is commonly used for prophylaxis and treatment. However, optimal dosing in this population remains uncertain, and individualized dose optimization is seen as a promising approach. This systematic review aims to refine dosing strategies in critically ill pediatric patients, with the goal of improving outcomes and reducing VTE and bleeding complications. Methods: The study followed PRISMA guidelines and employed a comprehensive search strategy using relevant MeSH terms and keywords. Data extraction and management were performed using standardized protocols. The quality of the included studies was assessed using appropriate tools. The statistical analysis was performed using R software (Version 4.3.0, Vienna, Austria) and RStudio interface (Version 2023.03.0, Boston, MA, USA). Results: The systematic review included 15 studies on individualized dosing strategies of enoxaparin in critically ill pediatric patients. The studies revealed variations in dosing strategies, including higher initial doses for neonates and infants. The administration route (IV or SC) and dosing frequency were also explored, with some studies suggesting IV administration as an alternative to SC. Clinical outcomes such as time to therapeutic anti-Xa levels, bleeding events, side effects, and the development of venous thromboembolism were assessed. Anti-Xa level-directed dosing and weight-based dosing were found to yield optimal outcomes. Meta-analysis results showed low mortality rates, a low incidence of thrombotic events with therapeutic prophylactic doses, and a low frequency of bleeding events. Conclusion: This systematic review concluded that initial high dose of enoxaparin is required to achieve therapeutic levels. However, limited data regarding dose optimization of enoxaparin is available on critically ill pediatrics. Pharmacokinetic studies, therapeutic drug monitoring, and population pharmacokinetic modelling can guide personalized dosing decisions. The implementation of personalized dosing protocols in clinical practice has the potential to improve patient care, enhance safety, and optimize anticoagulation management in critically ill pediatrics. Further research including prospective studies and RCTs is essential to establish pediatric-specific dosing guidelines and target anti-factor Xa ranges for enoxaparin in critically ill pediatrics.

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