Assessing the prognostic value of Age-adjusted EASIX for predicting mortality in critically ill surgical patients: a retrospective cohort study

Purpose: Critically ill surgical patients face high mortality rates, necessitating early and accurate risk stratification. The Age-Adjusted Endothelial Activation and Stress Index (aEASIX), a simple biomarker for endothelial dysfunction, has shown promise in other cohorts but remains uninvestigated in a broad surgical intensive care unit (SICU) population. This study aimed to evaluate the association between the aEASIX upon SICU admission and short-term mortality in critically ill surgical patients. Patients and methods: This retrospective cohort study utilized data from the MIMIC-IV database. We included 4,394 adult patients with a first-time admission to a SICU. Because the aEASIX distribution was markedly skewed, we applied a natural-log transformation (LnaEASIX). The primary outcome was 28-day ICU mortality, and the secondary outcome was 28-day in-hospital mortality. Multivariable logistic regression, restricted cubic splines, and receiver operating characteristic (ROC) curve analyses were performed. A mediation analysis explored the role of the SOFA score. Results: The overall 28-day ICU and 28-day in-hospital mortality rates were 18.0% and 17.09%, respectively. After adjusting for confounders, a higher LnaEASIX was independently associated with an increased risk of both 28-day ICU mortality (OR 1.348, 95% CI 1.259-1.445, P < 0.001) and 28-day in-hospital mortality (OR 1.367, 95% CI 1.275-1.465, P < 0.001). A non-linear, dose-response relationship was observed for both outcomes. In predictive performance analysis, aEASIX demonstrated significantly better discrimination than the SOFA score for both 28-day ICU mortality (AUC: 0.653 vs. 0.625) and 28-day in-hospital mortality (AUC: 0.649 vs. 0.614). Mediation analysis revealed that the SOFA score mediated 17.6% and 14.7% of the total effect of LnaEASIX on 28-day ICU and 28-day in-hospital mortality, respectively. Conclusion: The aEASIX is a significant and independent predictor of short-term mortality in a large, heterogeneous cohort of critically ill surgical patients. As a simple, readily available tool, aEASIX outperforms the SOFA score in predicting both ICU and in-hospital mortality and may serve as a valuable instrument for early bedside risk stratification in the SICU.