Association Between Stress Hyperglycemia Ratio and 72-Hour Delirium in Critically Ill Patients: A Retrospective Cohort Study from the MIMIC-IV Database

: Background Stress hyperglycemia, quantified by the stress hyperglycemia ratio (SHR), reflects the acute glycemic response relative to chronic glycemic status. Its association with intensive care unit (ICU)-acquired delirium and the mechanistic pathway linking SHR to mortality remain poorly characterized. Methods In this retrospective cohort study of 7,397 critically ill adults from the MIMIC-IV database, we examined the association between SHR and 72-hour delirium using multivariable Cox proportional-hazards regression. Restricted cubic spline analysis was used to characterize the dose-response relationship. Mediation analyses were employed to evaluate whether delirium mediates the effect of SHR on 28-day and 365-day all-cause mortality, with E-value analysis to assess robustness to unmeasured confounding. Results Overall, 1,259 patients developed delirium within 72 hours of ICU admission, with a median onset of 11.25 hours. Patients in the highest SHR quartile had a significantly higher hazard of delirium than those in the lowest quartile (HR 1.23, 95% CI 1.04-1.45; P = 0.014), with an approximately linear dose-response relationship. The association was consistent across GCS thresholds, glucose-measurement windows, diabetes/HbA1c strata, and subgroups. Delirium significantly mediated the indirect effect of SHR on both 28-day and 365-day mortality, whereas no significant direct effect of SHR on mortality was observed. Conclusions Elevated SHR is independently associated with an increased risk of ICU-acquired delirium in a linear, dose-dependent manner, and delirium fully mediates the indirect effect of SHR on short- and long-term mortality. These findings support SHR as a readily obtainable biomarker for early delirium risk stratification among critically ill patients.