Objective  To explore the impact of statins on the risk of sepsis-associated delirium (SAD) in critically ill patients.

Methods  This retrospective cohort study analyzed data of adult intensive care unit (ICU) patients from the MIMIC-IV database who met the inclusion criteria. The association between before ICU admission (pre-ICU) statin use and the incidence of SAD was examined by univariate and multivariable Logistic regression analysis, propensity score matching (PSM), inverse probability weighting (IPW), and subgroup analysis employing propensity score matching and inverse probability weighting to adjust for potential confounders. The adjusted odds ratio (OR) with 95% CI was calculated in corresponding cohorts.

Results  A total of 6,649 critically ill patients were included in the analysis, among whom 35.1% developed SAD. Patients with pre-ICU statin use showed a lower incidence of SAD compared to those without (27.6% vs. 38.0% in origin cohort, 27.2% vs. 33.9% in the PSM cohort). Pre-ICU statin use showed a stable protective effect against SAD across different analyses: in original cohort [OR=0.562, 95%CI (0.491, 0.642), P<0.001], the PSM cohort [OR=0.707, 95%CI (0.630, 0.794), P<0.001] and the IPW cohort [OR=0.627, 95%CI (0.573, 0.686), P<0.001]. Subgroup analyses indicated that the protective effects of statins were more pronounced in the population aged (≥65 years) [OR=0.622, 95%CI (0.525, 0.736), P<0.001], and that lipophilic statins demonstrated a significant protective effect against SAD [OR=0.527, 95%CI (0.454, 0.609), P<0.001]. E-value analysis indicated that this association was robust to unmeasured confounding factors.

Conclusion  Pre-ICU statin use is associated with a reduced incidence of SAD, particularly among elderly patients and those receiving lipophilic statins. These findings support the potential role of statins administration in the management of delirium in septic patients and underscore the importance of maintaining statin therapy during critical illness. Future prospective studies are needed to confirm these results and guide clinical practice.

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