Association Between Cumulative Sedative Exposure and ICU Length of Stay Without a Significant Association with Mortality

Background: Sedative medications are widely used in intensive care units (ICUs) to facilitate patient management; however, their association with clinical outcomes remains incompletely understood. This study aimed to evaluate the association of cumulative sedative exposure with ICU length of stay (LOS) in a large cohort of critically ill adult patients. Methods: A retrospective observational study was conducted using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Adult ICU patients (≥18 years) with documented sedative administration were included. Total sedative exposure was quantified as the cumulative dose administered during the ICU stay. The primary outcome was ICU LOS, while the secondary outcome was in-hospital mortality. Patients were stratified into quartiles according to cumulative sedative dose. Multivariable regression analysis was performed to assess the association between total sedative exposure and ICU LOS. Results: A total of 2953 ICU stays were analyzed. Higher cumulative sedative exposure was associated with significantly prolonged ICU LOS. Mean ICU LOS increased from 68.75 h in the lowest quartile to 250.65 h in the highest quartile (p < 0.001). A weak positive correlation was observed between log-transformed total sedative dose and ICU LOS (r = 0.33, p < 0.001). In multivariable analysis, cumulative sedative exposure remained significantly associated with ICU LOS (β = 15.79, 95% CI 14.17–17.41, p < 0.001). No consistent association was identified between sedative exposure and in-hospital mortality. Conclusions: Higher cumulative sedative exposure was associated with longer ICU LOS but not with increased in-hospital mortality. These findings support the importance of carefully tailored sedation strategies in critically ill patients. However, due to the retrospective observational design, causality cannot be inferred, and residual confounding related to illness severity and treatment duration may remain.