Tandem extracorporeal blood purification therapies for sepsis and acute kidney injury in critically ill children: a state-of-the-art review

Tandem extracorporeal blood purification and support therapies integrate established therapies such as continuous renal replacement therapies (CRRT), extracorporeal membrane oxygenation (ECMO), intermittent or prolonged renal replacement therapies with emerging adsorptive, immunomodulatory, and organ-support technologies. These approaches are increasingly applied in critically ill children with complex multi-organ dysfunction, particularly in the settings of severe sepsis, hyperinflammatory syndromes, acute kidney injury, liver failure, and refractory cardiorespiratory compromise. Despite growing clinical adoption, most tandem applications remain off-label in pediatrics, with evidence largely limited to case reports, single-center experiences, and small observational cohorts, and with few standardized protocols to guide practice.This state-of-the-art review synthesizes available pediatric and relevant adult literature to examine the mechanistic rationale, technical integration, clinical indications, and reported outcomes of tandem extracorporeal strategies beyond conventional CRRT-ECMO-therapeutic plasma exchange combinations. We focus on under-reported and emerging modalities, including hemoperfusion and adsorptive hemofilters integrated with CRRT or ECMO, leukapheresis combined with renal replacement or extracorporeal life support, selective cytopheretic and immunomodulatory devices, extracorporeal liver support platforms, and novel miniaturized and translational technologies. Practical considerations related to circuit configuration, anticoagulation strategies, and extracorporeal volume are discussed, alongside safety considerations unique to pediatric populations. While early experiences suggest feasibility and potential benefit, current evidence is insufficient to establish definitive efficacy or survival benefit. This review highlights critical knowledge gaps, implementation barriers, and research priorities, and aims to support the development of standardized, evidence-based guidelines to promote safe, effective, and reproducible use of tandem extracorporeal therapies in pediatric critical care.