Abstract Rationale Dexmedetomidine, an α2-adrenergic agonist, is commonly used for sedation in mechanically ventilated (MV) patients. Limited data exist on its safety in patients with substance use disorders (SUDs), a population with unique neurobiological and pharmacologic sensitivities. Understanding how sedation choices affect outcomes in this group is essential to improving critical care management. This study aimed to evaluate outcomes in patients with a history of SUD sedated with dexmedetomidine while requiring mechanical ventilation. Methods This retrospective cohort study utilized the TriNetX Research Network, incorporating electronic health records from 112 healthcare organizations. Adults with a documented history of SUD who underwent MV between January 1, 2010, and present were identified and stratified by exposure to dexmedetomidine. Propensity score matching (PSM) balanced age, sex, race, BMI, healthcare utilization, and Charlson Comorbidity Index. Outcomes compared between matched cohorts included mortality, delirium/disorientation, exposure to adjunct sedatives (propofol, midazolam, fentanyl), emergent re-intubation, hospitalization, and emergency visits within 1 and 3 months following the MV index event. Results A total of 23,912 patients with SUD were identified (20,816 non-dexmedetomidine; 3,096 dexmedetomidine). After PSM, 3,092 patients remained in each cohort. Dexmedetomidine use was associated with higher mortality at 1 month (HR 1.39, 95% CI 1.12-1.74) and 3 months (HR 1.26, 95% CI 1.06-1.50). Disorientation was more frequent in patients exposed to dexmedetomidine at 1 month (RR 2.34, 95% CI 1.61-3.41) and 3 months (RR 1.91, 95% CI 1.41-2.57). Dexmedetomidine use had greater concomitant exposure to propofol (RR 2.00, 1.82-2.20), midazolam (RR 1.72, 1.58-1.88), and fentanyl (RR 1.67, 1.54-1.80) at 1 month, with similar trends at 3 months. The dexmedetomidine cohort also had higher risk of emergent re-intubation (RR 2.34, 1.88-2.91) and hospitalization (RR 1.19, 1.11-1.28), while emergency visit rates were not significantly different. Conclusion Among mechanically ventilated patients with SUD, dexmedetomidine exposure was associated with increased risks of mortality, delirium, additional sedative needs, emergent re-intubation, and rehospitalization at both 1 and 3 months post-MV. These findings suggest that sedation with dexmedetomidine in this population may reflect more complex or refractory clinical courses and highlight the need for prospective studies to clarify causality and optimize sedation practices in patients with substance use disorders. This abstract is funded by: None
Fiore et al. (Fri,) studied this question.