Atypical Antipsychotic Use for Weaning Sedation in Mechanically Ventilated ICU Patients

Introduction: Atypical antipsychotics (AAPs) are commonly used in mechanically ventilated ICU patients to decrease agitation and assist in the transition off continuous infusion sedatives prior to successful extubation. Quetiapine and olanzapine are both agents that can be used for these indications, however agent selection and dosing strategies are not well defined. Previous studies assessing AAP use with the goal of reducing sedation requirements have been small and provided mixed results. This study aims to evaluate the efficacy of quetiapine and olanzapine in mechanically ventilated patients.


Methods: This retrospective, single-center cohort study included mechanically ventilated adult ICU patients on continuous sedative infusions who received either scheduled quetiapine or olanzapine for at least 48 hours between March 2020 to February 2025. The primary outcome was the change in propofol or dexmedetomidine doses from initiation of AAP to 24 and 48 hours after initiation via linear mixed effects regression. Secondary outcomes included RASS score percentage time in therapeutic range (TTR) 48 hours before versus after AAP initiation.


Results: A total of 27 patients were included; 17 patients received quetiapine (62.9%) and 10 patients received olanzapine (37.1%). The mean propofol infusion rate (mcg/kg/min) significantly decreased over time (p=0.047) from AAP initiation (20.6 [95% CI 11.3–29.9]) to 24- (26.4 [95% CI 17.1–35.6]), and 48-hours (10.6 [95% CI 1.3–19.9]) after initiation. The mean dexmedetomidine infusion rate (mcg/kg/hr) also decreased significantly over time (p=0.004) from AAP initiation (0.669 [95% CI 0.534–0.805]) to 24- (0.407 [95% CI 0.262–0.553]) and 48-hours (0.384 [95% CI 0.238–0.529]) after initiation. RASS TTR range was increased 48 hours after AAP initiation compared to 48 hours prior to AAP initiation in 12 (44.4%) patients. There were no reported adverse events directly attributed to AAPs that required AAP discontinuation.


Conclusions: The use of AAPs in mechanically ventilated ICU patients was associated with a decrease in continuous infusion propofol and dexmedetomidine dose requirements over 48 hours after AAP initiation. AAP use may result in a higher RASS TTR following initiation compared to before initiation.