Clinical implications of ferroptosis in critical illness: a narrative review

Area of Science:

• Critical care medicine
• Molecular biology
• Pathophysiology

Background:

• Intensive care unit (ICU) patients face high mortality and poor functional outcomes despite advances in care.
• Innovative, mechanism-based approaches are needed to address the persistent burden in critical illness.
• Regulated cell death (RCD) pathways present a promising avenue for targeted interventions in critical care.

Purpose of the Study:

• To review the role of ferroptosis, an iron-dependent RCD, in critical care settings.
• To explore ferroptosis's contribution to organ dysfunction in conditions like sepsis, COVID-19, ischemia-reperfusion injury, and neurological emergencies.
• To discuss the translational potential of targeting ferroptosis for precision medicine in the ICU.

Main Methods:

• Narrative review of existing literature on ferroptosis and critical illness.
• Analysis of molecular mechanisms underlying ferroptosis.
• Examination of preclinical and emerging clinical data related to ferroptosis in critical care.

Main Results:

• Ferroptosis, characterized by lipid peroxidation, is mechanistically distinct and potentially reversible, making it relevant to acute critical illness.
• Ferroptosis plays a role in organ dysfunction across various critical care conditions.
• Preclinical data strongly suggest ferroptosis's involvement, with emerging clinical data indicating translational potential.

Conclusions:

• Ferroptosis represents a significant area of investigation for improving outcomes in critical illness.
• Targeting ferroptosis offers a potential strategy for precision medicine in the ICU.
• Further research into ferroptosis detection and therapeutic targeting is crucial for clinical application.