Background We investigated delirium prevalence and potential effects of long-term sedation in critically ill COVID-19 patients; to identify opportunities for improving sedation practices and delirium prevention.

Methods This prospective, single-center, observational cohort study was conducted from April-June 2020. Adult COVID-19 patients were eligible if admitted to an ICU with mechanical ventilation/intravenous sedation; or a general care unit with brain monitoring due to altered mental status. Patients were evaluated daily until discharge using the Richmond Agitation-Sedation Scale, Confusion Assessment Method for the ICU, and CAM-Severity. Cumulative doses of sedation and paralytic medications were recorded. At three months post-enrollment, cognition, mood, and quality of life were measured by the Telephone Interview for Cognitive Status (TICS), Center for Epidemiologic Studies Depression Scale 10-item (CES-10), and EuroQol 5-Dimension-3 Level (EQ-5D-3L), respectively.

Results 67 patients were enrolled, with a mean (SD) age of 59 (12) years, 30 (45%) Hispanic, 43 (64%) developing acute respiratory distress syndrome, 55 (82%) mechanically ventilated (mean duration of 22.9 days), and 5 comatose for the entire study. Of the 62 patients assessed for delirium, 61 (98%) had delirium at least once, with a mean (SD) of 12.7 (13.0) days. >90% of patients received opioids, benzodiazepines, or propofol at least once; median (IQR) total dose of 37.4 (78.9) mg (fentanyl equivalents), 52.5 (813.3) mg (midazolam equivalents), and 46 (53) g (propofol), respectively. At follow-up, 40 (60%) patients were reached, while 16 (24%) were deceased/comfort measures. Patients showed reductions in cognition, mood, and quality of life with median (IQR) scores for TICS (0-41): 30 (26-33); CES-D-10 (0-30): 6 (4-12); EQ-5D-3L (1-3): 2 (mobility, self-care, usual activities, pain/discomfort).

Conclusion Critically and acutely ill patients with COVID-19 early in the pandemic experienced a high rate of delirium and sedation. Large doses of sedatives may contribute to greater delirium burden during hospitalization, and lead to poor clinical outcomes.

Dr. Westover is a co-founder, serves as a scientific advisor and consultant, and has a personal equity interest in Beacon Biosignals.

MBW was supported by the Glenn Foundation for Medical Research and American Federation for Aging Research (Breakthroughs in Gerontology Grant); American Academy of Sleep Medicine (AASM Foundation Strategic Research Award); Football Players Health Study (FPHS) at Harvard University; Department of Defense through a subcontract from Moberg ICU Solutions, Inc; and NIH (1R01NS102190, 1R01NS102574, 1R01NS107291, 1RF1AG064312, RF1NS120947, R01AG073410 R01HL161253, R01NS126282, R01AG073598), and NSF (2014431).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

According to the Partners Human Research Committee, it qualified for an exemption from formal oversight by the Mass General Brigham Institutional Review Board and met the criteria for a waiver of informed consent. The study was performed in compliance with the ethical principles outlined in the 1964 Declaration of Helsinki, its subsequent amendments, and comparable ethical standards.

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↵* Co-first authors

↵** Co-senior authors

Conflicts of interest: Dr. Westover is a co-founder, serves as a scientific advisor and consultant, and has a personal equity interest in Beacon Biosignals.

Funding: MBW was supported by the Glenn Foundation for Medical Research and American Federation for Aging Research (Breakthroughs in Gerontology Grant); American Academy of Sleep Medicine (AASM Foundation Strategic Research Award); Football Players Health Study (FPHS) at Harvard University; Department of Defense through a subcontract from Moberg ICU Solutions, Inc; and NIH (1R01NS102190, 1R01NS102574, 1R01NS107291, 1RF1AG064312, RF1NS120947, R01AG073410, R01HL161253, R01NS126282, R01AG073598), and NSF (2014431).