Prognostic values of different biomarkers in the prediction of sepsis-related prognosis and mortality: a systematic review and network meta-analysis

Accurate prediction of mortality remains a critical challenge in sepsis management. While various biomarkers have been studied, their comparative prognostic performance is unclear due to a lack of direct comparisons. This study aimed to systematically evaluate and rank the prognostic value of eight commonly investigated biomarkers for mortality risk in adult sepsis patients. A systematic review and network meta-analysis of observational studies was conducted. PubMed, EMBASE, Cochrane Library, and Web of Science were searched up to October 2025. Studies reporting hazard ratios (HRs) for the association between biomarkers (procalcitonin (PCT), albumin (ALB), C-reactive protein (CRP), interleukin-6 (IL-6), red cell distribution width (RDW), lactate, neutrophil-to-lymphocyte ratio (NLR), and lactate/albumin ratio (Lactate/ALB)) and mortality in adult sepsis were included. Pairwise meta-analysis and frequentist network meta-analysis were performed using random-effects models to explore the associations between these biomarkers and mortality. Biomarkers were ranked using P-scores. Heterogeneity, inconsistency, and publication bias were assessed. A total of 103 studies involving 191,561 patients were included. In the pairwise meta-analysis, the Lactate/ALB ratio demonstrated the strongest association with mortality (pooled HR = 2.94, 95% CI (1.09, 7.90)), followed by lactate, RDW, and NLR. CRP and ALB showed no significant association. The network meta-analysis, incorporating 193 pairwise comparisons, confirmed the superior prognostic performance of the Lactate/ALB ratio, which ranked first (P-score = 1.00) and showed a significantly higher mortality risk compared to lactate alone (HR = 2.58, 95% CI (1.82, 3.66)). Substantial heterogeneity was observed for most biomarkers, but sensitivity and subgroup analyses supported the robustness of the primary findings for the Lactate/ALB ratio. This comprehensive pairwise meta-analysis and network meta-analysis provides robust estimates of the univariable association between each of eight biomarkers and mortality in sepsis. The lactate/albumin ratio showed the strongest association with mortality among the evaluated biomarkers. The exploratory network meta-analysis, which should be interpreted with caution due to significant inconsistency and violation of transitivity assumptions, offers hypothesis-generating signals requiring confirmation through direct comparative studies. Future research should prioritize direct head-to-head comparisons using standardized methodologies to establish the clinical utility of the lactate/ALB ratio for risk stratification in sepsis.