Temporal increase in the endothelial activation and stress index before brain death

Brain death (BD) is accompanied by systemic inflammation and endothelial dysfunction, but temporal changes in endothelial injury during progression to BD remain insufficiently characterized. This study aimed to evaluate serial changes in the Endothelial Activation and Stress Index (EASIX) during the clinical course leading to BD. This retrospective, single-center study included patients diagnosed with BD in the intensive care unit (ICU) between January 2019 and June 2025. EASIX, calculated from lactate dehydrogenase (LDH), serum creatinine, and platelet count, was assessed at ICU admission, 24 hours before BD, 12 hours before BD, and at BD diagnosis. Temporal differences were analyzed using the Friedman test, followed by Wilcoxon signed-rank tests with Bonferroni adjustment. Of 222 patients diagnosed with BD, 52 met the inclusion criteria. EASIX values differed significantly across the four time points (p < 0.001), with significant differences observed between ICU admission and BD diagnosis and between 24 and 12 hours before BD. These findings indicate that EASIX increases during the clinical course leading to BD and may reflect progressive systemic endothelial activation and worsening critical illness rather than a BD-specific process. Prospective comparative studies are needed to validate its clinical utility.