Association of thiamine supplementation with 30-day mortality among ICU patients with sepsis-associated delirium

Sepsis-associated delirium (SAD) is a common and severe complication in critically ill patients and is associated with increased mortality. Thiamine is an essential coenzyme in mitochondrial energy metabolism, and deficiency is frequent in critical illness. However, the association between thiamine supplementation and survival in ICU patients with SAD remains unclear. We conducted a retrospective cohort study using the MIMIC-IV (v3.1) database. Adult ICU patients meeting Sepsis-3 criteria and diagnosed with delirium during ICU stay were included. Patients were categorized according to thiamine supplementation during ICU admission. Propensity score-based methods, including matching, adjustment, and multiple weighting approaches, were applied to balance baseline covariates. The primary outcome was 30-day all-cause mortality. We performed survival, subgroup, and sensitivity analyses. We also conducted duration-response and dose-response analyses to evaluate whether thiamine treatment duration and average daily dose were associated with prognosis. In the MIMIC-IV cohort, 332 ICU patients with sepsis-associated delirium received thiamine supplementation, while 956 did not. Thirty-day mortality was significantly lower in the thiamine group compared with the non-thiamine group (P < 0.001). Thiamine use was associated with improved survival in crude analysis and remained significantly associated with lower 30-day mortality after multivariable adjustment (HR, 0.51; 95% CI, 0.33-0.79; P = 0.002). Consistent associations were observed across propensity score analyses, including propensity score-adjusted analysis (HR, 0.59; 95% CI, 0.40-0.85; P = 0.005), propensity score matching (HR, 0.59; 95% CI, 0.39-0.90; P = 0.015), inverse probability of treatment weighting (HR, 0.54; 95% CI, 0.38-0.77; P = 0.002), standardized mortality ratio weighting (HR, 0.68; 95% CI, 0.47-0.98; P = 0.052), pairwise algorithmic weighting (HR, 0.63; 95% CI, 0.40-0.97; P = 0.016), and overlap weight (HR, 0.60; 95% CI, 0.36-1.02; P = 0.008). Weighted subgroup analyses demonstrated consistent associations across clinical strata, with a significant interaction by illness severity indicating a survival benefit of thiamine among patients with SOFA scores < 4. Duration-response and dose-response analyses suggested greater benefit with longer treatment courses and lower daily dosing. Thiamine supplementation was associated with reduced 30-day mortality in ICU patients with sepsis-associated delirium, with an observed interaction in the SOFA score subgroup, where a SOFA score below 4 was associated with survival benefit. Duration-response and dose-response analyses suggested greater benefit with longer treatment courses and lower daily dosing.