Effect of Atypical Antipsychotics on Sedatives and Analgesics in Mechanically Ventilated Patients

INTRODUCTION: Sedatives and analgesics are commonly used as continuous infusions in the intensive care unit (ICU) to treat pain and anxiety and facilitate patient-ventilator synchrony, but are associated with complications, including an increase in mechanical ventilation days, ICU length of stay, and incidence of delirium. Atypical antipsychotics (AAP) affect a variety of receptors that may allow them to act as adjunctive agents for sedation, and therefore allow weaning of continuous infusions.

METHODS : A single-center, retrospective study was conducted at Brigham and Women’s Hospital from 1/1/2018 to 12/31/2019. Patients were included if they were mechanically ventilated for at least 48 hours before and following the first dose of an AAP (quetiapine or olanzapine), were receiving at least one sedative via continuous infusion, and received an AAP for at least 48 hours. The major endpoint of this study was the percentage of patients with at least a 20% reduction in the dose of midazolam, propofol, or opioids, using morphine mg equivalent (MME), within 48 hours from AAP initiation. Minor endpoints included median changes in cumulative dose (CD) at 24 and 48 hours, and assessments using the Richmond Agitation-Sedation Scale (RASS), and Critical Care Pain Observation Tool (CPOT).

RESULTS: A total of 1,177 encounters were screened and 107 were included. The median age was 63 years, most were admitted to the medical ICU, and the median APACHE II and SOFA scores were 30 and 9, respectively. Most patients (96.3%) received quetiapine with a median starting dose of 25 mg and frequency of 8 hours. During the 48-hours after initiation, 77.6% had ≥ 20% reduction in the CD of a sedative or analgesic. There was a significant reduction in propofol, and no change in MME CD at 24- and 48-hours following AAP initiation. Dexmedetomidine CD was significantly increased at 48-hours, but not at the 24-hour mark. There was no difference in pain scores, but patients had significantly lighter sedation scores in the 48 hours after AAP were started. Subgroup analysis showed a significant reduction in propofol CD regardless of whether dexmedetomidine was administered.

CONCLUSIONS: AAP use was associated with a significant reduction in sedative doses at 24 and 48 hours. Future studies are warranted to confirm the results of this study.