Abstract
<title>Abstract</title> <p>Sepsis-associated delirium is a common form of acute brain dysfunction in critically ill patients and is closely linked to adverse clinical outcomes. Although endothelial injury and systemic stress have been increasingly recognised as important contributors to brain dysfunction during sepsis, simple clinical markers that reflect these processes and help identify patients at high risk of delirium remain limited. The endothelial activation and stress index (EASIX), calculated using lactate dehydrogenase, creatinine, and platelet count, may provide an objective measure of endothelial damage and systemic stress. In this retrospective cohort study using the MIMIC-IV database, we investigated the association between EASIX and delirium in septic ICU patients while taking death into account as a competing event. EASIX was calculated using the average values of laboratory indicators within the first 24 hours after ICU admission and was log-transformed for analysis. Delirium was identified using CAM-ICU assessments and nursing records among patients with adequate arousal levels. Of the 6,111 septic ICU patients included, 31.2% developed delirium within 28 days. Higher log-EASIX was independently associated with an increased risk of delirium after adjustment for potential confounders. Each one-unit increase in log-EASIX was associated with a 5%, 6%, and 5% higher risk of delirium within 7, 14, and 28 days, respectively. Cumulative incidence curves and dose-response analyses showed a consistent positive association between EASIX and delirium risk, and the findings remained robust across subgroup and sensitivity analyses. These results suggest that EASIX is independently associated with the development of delirium in septic ICU patients. As a simple and readily available index based on routine laboratory tests, EASIX may help clinicians identify septic patients at higher risk of delirium at an early stage, supporting timely monitoring and preventive strategies.</p>