Pathophysiology and Early Recognition of Sepsis in Critically Ill Patients

Abstract

Introduction: Sepsis remains one of the leading causes of mortality in intensive care units in Brazil and worldwide, accounting for approximately 11 million deaths annually and a lethality rate exceeding 40% in severe cases. Late diagnosis is the main determinant of poor prognosis, making early recognition imperative. Methodology: Narrative review of articles published between 2015 and 2025, selected from the PubMed/MEDLINE, Scopus, SciELO, and LILACS databases, prioritizing experimental studies, high-impact reviews, and international consensus statements (Sepsis-3), without a formal systematic search. Pathophysiology: sepsis results from a dysregulated inflammatory response to infection, with a cytokine storm, immunothrombosis, and, subsequently, profound immunoparalysis with lymphocyte apoptosis and elevated PD-L1 expression. Early Recognition: qSOFA and SOFA remain the most widely used clinical criteria, but with limitations in sensitivity and delay. Promising biomarkers include Ang-2, Syndecan-1, NETs, absolute lymphocyte count, miRNAs, lactation-related genes, and artificial intelligence/machine learning models. Discussion: The integration of pathophysiology and diagnostic tools allows sepsis to be identified before obvious organ failure, but gaps remain in validation in underrepresented populations, limited access to advanced testing in Brazil, and false alarms in AI systems. Conclusion: The future of sepsis diagnosis lies in the combination of simple clinical signs, biomarkers of endothelial damage, and artificial intelligence. Until advanced resources are widely available, continuous training of teams and rigorous use of qSOFA/SOFA and existing protocols remain the most effective and realistic strategies for reducing high mortality from sepsis in the Brazilian context.