Ferritin-Based Biomarkers for Prediction of 28-Day Mortality in Septic Shock: A Prospective, Single-Centre, Observational Study From South India

Abstract

Introduction Septic shock is a life-threatening condition with high mortality despite advances in critical care. Ferritin, an acute-phase reactant involved in iron metabolism and inflammation, along with its derived biomarkers, has emerged as a potential biomarker of disease severity in sepsis. Methods This prospective observational study was conducted in an Intensive Care Unit in a Tertiary Care Hospital from December 2024 to October 2025. Adult patients meeting Sepsis-3 criteria for septic shock were included. Serum ferritin was measured on Day 1 and Day 3. Ferritin index, Delta ferritin and Ferritin-albumin ratio were calculated. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the discriminatory performance of serum ferritin, Ferritin Index (FI), delta ferritin (ΔFerritin), and ferritin-albumin ratio (FAR). Optimal cutoffs were determined using the ROC curves, and pairwise comparisons of the areas under the curves (AUCs) were performed using DeLong’s test. Univariate and multivariable logistic regression analyses were performed to identify predictors of 28-day mortality. Results A total of 79 patients were included, with a 28-day mortality rate of 64.6%. All ferritin-based biomarkers were significantly associated with 28-day mortality. Among these, the ferritin-albumin ratio demonstrated the best predictive performance (AUC: 0.849), with a sensitivity of 82.5% and specificity of 81.8% at a cutoff value of ≥239. Day 1 ferritin also showed excellent predictive ability (AUC: 0.840), with 94.1% sensitivity and 60.7% specificity at a cutoff of ≥574 µg/L. The ferritin index showed good discrimination (AUC: 0.795; sensitivity: 72.6%; specificity: 78.6% at ≥5.45), while delta ferritin demonstrated acceptable predictive performance (AUC: 0.737; sensitivity: 96.0%; specificity: 67.5% at ≥305 µg/L). DeLong pairwise comparison demonstrated that FAR was significantly superior to Ferritin Index, but its performance did not differ significantly from Day 1 serum ferritin or delta ferritin. On univariate analysis, Day 1 ferritin, Ferritin Index, FAR, SOFA, qSOFA, and lactate were associated with mortality; however, SOFA remained the only independent predictor in multivariable analysis. Conclusion Ferritin-derived biomarkers serve as valuable prognostic tools for risk stratification in septic shock. While the ferritin-albumin ratio demonstrated high diagnostic accuracy, the ferritin index and delta ferritin also show clinical utility. These inexpensive and widely available markers may aid early risk stratification in critically ill patients, though their prognostic value is closely aligned with baseline clinical severity scores.