Abstract
BACKGROUND: Delirium is a common and serious neurocognitive complication in critically ill patients, particularly those with chronic kidney disease (CKD), who are predisposed due to systemic inflammation, metabolic dysregulation, and polypharmacy. Statins, widely used for their cardiovascular benefits, also possess anti-inflammatory and neuroprotective properties that may influence delirium risk. However, their impact on delirium incidence and short-term prognosis in CKD patients remains unclear. METHODS: We conducted a retrospective cohort study using the MIMIC-IV database, identifying 3218 adult patients with CKD admitted to the intensive care units (ICU). Patients were stratified based on statin exposure during the 3 days before and after ICU admission. The primary outcome was the incidence of delirium, which was assessed using the Confusion Assessment Method for the ICU (CAM-ICU). Secondary outcomes included all-cause mortality at 30 days and 90 days. Propensity score matching (PSM) was employed to balance baseline characteristics, and multivariable logistic and Cox regression models were utilized to estimate associations. RESULTS: Before matching, statin use was associated with significantly lower delirium incidence (25.0% vs. 34.4%, p < 0.001) and lower 30-day mortality (20.4% vs. 28.7%, p < 0.001). After 1:1 PSM (n = 2132), these associations remained significant: statin use correlated with reduced odds of delirium (adjusted OR 0.60, 95% CI 0.49-0.74, p < 0.001), and lower 30-day (HR 0.82, 95% CI 0.69-0.97, p = 0.019) and 90-day mortality (HR 0.80, 95% CI 0.69-0.93, p = 0.003). Subgroup analyses showed consistent findings across CKD stages and comorbidity profiles, with notable interaction observed in benzodiazepine users (interaction for p = 0.009). CONCLUSION: Among critically ill patients with CKD, statin use is independently associated with a lower risk of delirium and improved short-term survival. These findings support the potential neuroprotective role of statins in this high-risk population and warrant further investigation through prospective studies and randomized controlled trials.