Association between polypharmacy at the emergency department and long-term mortality in critically ill older patients receiving mechanical ventilation: a single-center retrospective cohort study

Abstract Background Polypharmacy is increasingly prevalent among older adults, and is associated with adverse health outcomes. However, its prognostic impact in emergency care settings remains unclear, particularly in critically ill older patients requiring mechanical ventilation. Therefore, this study aimed to evaluate the association between polypharmacy at the emergency department and long-term mortality in critically ill older patients who required mechanical ventilation. Methods We conducted a retrospective cohort study of emergency department patients aged ≥ 65 years who received mechanical ventilation at a Japanese university hospital between April 2015 and December 2024. Patients were categorized into a polypharmacy group (≥ 5 regular medications at admission) or a non-polypharmacy group (fewer medications at admission). Survival was comparatively analyzed using Kaplan–Meier curves and the log-rank test. Cox proportional hazards regression analysis was performed to examine the association between polypharmacy at admission (reference: non-polypharmacy) and long-term mortality while adjusting for age, Charlson comorbidity index, and the Sequential Organ Failure Assessment (SOFA) score modeled as a continuous variable. In addition, we similarly analyzed the association between polypharmacy status at discharge among patients discharged alive and long-term mortality. Results The study cohort comprised 533 patients (non-polypharmacy: 207 patients, polypharmacy: 326 patients). The median follow-up duration was 2.1 months (interquartile range [IQR], 0.6–11.7 months; maximum, 112.7 months). Among patients discharged alive, the median follow-up duration was 3.6 months (IQR, 1.0–19.6 months). After adjustment for age, Charlson comorbidity index, and SOFA score, patients with polypharmacy at admission were not independently associated with all-cause mortality (hazard ratio [HR]: 1.17, 95% confidence interval [CI]: 0.85–1.60). In contrast, among patients discharged alive, polypharmacy at hospital discharge showed a borderline association with increased all-cause mortality (HR, 1.67; 95% CI, 0.98–2.85). Conclusions In critically ill older patients requiring mechanical ventilation, polypharmacy at emergency department admission was not independently associated with long-term mortality after adjustment for acute illness severity. Polypharmacy at hospital discharge showed a borderline association with increased long-term mortality, suggesting that medication burden at discharge may reflect underlying clinical vulnerability rather than a direct causal effect.