Pre-admission polypharmacy burden and intensive care unit outcomes in patients with sepsis: A retrospective cohort study using the MIMIC-IV-ED linked database

Purpose: Polypharmacy is highly prevalent among critically ill patients, yet it's independent impact on intensive care unit (ICU) outcomes in sepsis remains critically unexplored. We aimed to evaluate whether pre-admission polypharmacy independently predicts ICU mortality and provides incremental prognostic value using the medication reconciliation module of the MIMIC-IV-ED linked database. Materials and Methods: We conducted a retrospective cohort study of 3,347 adults admitted to the ICU who met Sepsis-3 criteria. Pre-admission polypharmacy was categorized as none (0-4), standard (5-9), or high (>=10 medications). Multivariable logistic regression, propensity score matching, and reclassification analyses (NRI/IDI) were performed. The primary outcome was in-hospital ICU mortality. Results: High polypharmacy was present in 58.9% of patients. Crude ICU mortality increased sequentially: 18.5% (none), 26.0% (standard), and 27.5% (high; p < 0.001). After multivariable adjustment, high polypharmacy independently predicted in-hospital ICU mortality (aOR 1.45, 95% CI (1.10-1.91)), and 28-day mortality (aOR 1.47). Drug-class analysis identified statins as significantly protective (aOR 0.56), whereas RAS blockers combined with diuretics increased acute kidney injury risk (aOR 1.49). Propensity matching confirmed the primary mortality association (matched aOR 1.28). Conclusions: By utilizing the ED medication reconciliation table, this study proves high polypharmacy represents a distinct 'pharmacologic frailty', independent of acute severity. Available instantly at triage, this zero-latency metric provides significant early prognostic value (SOFA NRI = 0.24) and identifies actionable high-risk interactions (e.g., RAS blockers plus diuretics) for immediate, targeted pharmacist-led intervention upon ICU admission.