Circulating and Respiratory Biomarkers in Sepsis-Induced ARDS: Diagnostic and Prognostic Insights – A Narrative Review

Abstract: Sepsis affects around 50 million people annually and is a significant contributor to acute respiratory distress syndrome (ARDS), leading to high morbidity and mortality. Sepsis-induced ARDS is the leading cause of ARDS globally and has worse outcomes compared to other causes, with mortality rates up to 40% in severe instances. Geographic variability in ARDS prevalence is notable, with rates of 27% among septic patients in China, 6– 7% in Western countries, and up to 31% in sub-Saharan African Intensive Care Units, highlighting significant disparities in disease burden and outcomes. Management of sepsis-induced ARDS generally necessitates mechanical ventilation, yet extended ventilatory support can lead to negative outcomes. Weaning from ventilation is complicated by the inflammatory response and multiorgan dysfunction seen in sepsis. Traditional weaning predictors, like the rapid shallow breathing index, show inadequate sensitivity and specificity, indicating a requirement for more effective predictive tools. Recent studies have identified several biomarkers, including Pancreatic Stone Protein, soluble receptor for advanced glycation end-products, and soluble urokinase plasminogen activator receptor, as promising tools for enhancing the prediction of mechanical ventilation outcomes in sepsis-induced ARDS. Despite the identification of multiple biomarkers, a major clinical gap remains: there is currently no consensus on their routine use to guide weaning, largely due to inconsistent findings, heterogeneity in study designs, and limited large-scale validation. This review explores the role of circulating and respiratory biomarkers in improving outcomes for patients with sepsis-induced ARDS, particularly in predicting successful mechanical ventilation weaning. It appraises the evidence surrounding these biomarkers against traditional weaning indices and identifies gaps in existing research. The review emphasizes the strengths and limitations of current studies, suggesting that validated biomarker-guided strategies could significantly enhance clinical management by reducing ventilation duration, preventing extubation failures, and improving survival rates in this vulnerable patient group. Keywords: sepsis, ARDS, biomarker, mechanical ventilation, weaning