Clinical implications of ferroptosis in critical illness: a narrative review

Despite major advances in care for patients admitted to the intensive care unit (ICU), mortality remains high and functional outcomes for ICU survivors are often poor. The persistent burden underscores the need for innovative, mechanism-based approaches. Precision medicine has emerged as a promising paradigm in critical illness, and regulated cell death (RCD) may offer a novel entry point for targeted interventions. Among the various RCD pathways, ferroptosis, an iron-dependent form of RCD driven by excessive lipid peroxidation within cellular membranes, has gained increasing attention. Its mechanistic distinctiveness from other RCDs and potential reversibility make it particularly relevant in acute, dynamic disease states. In this narrative review, we explore the role of ferroptosis in critical care, focusing on high-impact conditions such as sepsis, COVID-19, ischaemia-reperfusion injury, and neurological emergencies. We outline the molecular mechanisms of ferroptosis and discuss how it may contribute to organ dysfunction across systems. While most insights to date stem from preclinical models, emerging clinical data suggest translational potential. We highlight key studies, discuss current limitations in detection and therapeutic targeting, and consider how the evaluation of ferroptosis could help shape the future of precision medicine in the ICU.