Background: Sepsis remains a leading cause of mortality in intensive care units (ICUs) worldwide despite advances in critical care. Early recognition and intervention are crucial for improving outcomes. This systematic review evaluates the current evidence on established and emerging biomarkers for sepsis in ICU settings, focusing on their diagnostic and prognostic value, implementation challenges, and future directions. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a comprehensive literature search across MEDLINE, Embase, Cochrane Library, and Web of Science from January 2015 to October 2024 (PROSPERO ID: CRD420251012434). We included randomized controlled trials, meta-analyses, systematic reviews, and prospective studies evaluating biomarkers in adult sepsis patients in ICU settings. Results: This review analyzed 45 key studies examining 23 distinct biomarkers. Procalcitonin and C-reactive protein remain the most extensively validated biomarkers, with high-quality evidence supporting their use in antimicrobial stewardship. Emerging biomarkers including presepsin, soluble triggering receptor expressed on myeloid cells-1, and novel multi-biomarker panels show potential for improved diagnostic and prognostic capabilities, though require further validation. Cell-free DNA, micro-RNAs, and metabolomic signatures represent innovative approaches under early investigation for personalized sepsis management. Conclusion: While no single ideal biomarker exists for sepsis, combining established and novel biomarkers with clinical parameters may offer a more comprehensive approach to sepsis management. Integration of biomarker-guided algorithms into clinical decision support systems represents a promising strategy requiring prospective validation to improve sepsis outcomes. Further large-scale, multicenter studies are needed to validate emerging biomarkers before widespread clinical implementation.
Shibu Sasidharan (Wed,) studied this question.