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Background: Reduction in sedation exposure is an important metric in intensive care unit (ICU) patients. However, challenges arose during the coronavirus disease-2019 (COVID-19) pandemic in adhering to this practice, driven by concerns on transmission and disease severity issues. Accordingly, diverse sedation approaches emerged, although the effect on mortality has not been studied thoroughly. Methods: Retrospective cohort study in the medical ICU of seven hospitals within a major Health System in Northeast Ohio. We included all adult patients admitted with COVID-19 requiring invasive mechanical ventilation (IMV) from March 2020 to December 2021. Results: Study included 2394 COVID-19 patients requiring IMV. Across waves, sample included 55-63% male subjects, with an average age of 61-68 years (P < 0.001), Acute Physiologic and Chronic Health Evaluation (APACHE)-III score 65.8-68.9 (P = 0.37), median IMV duration 8-10 days (P = 0.14), and median ICU duration 9.8-11.6 days (P = 0.084). Propofol remained the primary sedative (84-92%; P = 0.089). Ketamine use increased from the first (9.7%) to fourth (19%) wave (P = 0.002). Midazolam use decreased from the first (27.4%) to third (9.4%) wave (P = 0.001). Dexmedetomidine use declined from 35% to 27-28% (P = 0.002) after the first wave. A multivariable regression analysis indicated clinical variables explained 34% of the variation in hospital mortality (R2). Factors associated with higher mortality included age [aOR = 1.059 (95% CI 1.049-1.069); P < 0.001], COVID-19 wave, especially fourth wave [aOR = 2.147, (95% CI 1.370-3.365); P = 0.001], and higher number of vasopressors [aOR = 31.636, (95% CI 17.603-56.856); P < 0.001]. Addition of sedative medications to a second model led to an increase in the R2 by only 1.6% to 35.6% [aOR = 1 (95% CI 1-1); P > 0.05] for propofol, ketamine, and midazolam. Dexmedetomidine demonstrated a decrease in the odds of mortality [aOR = 0.96 (95% CI 0.94-0.97); P < 0.001]. Conclusion: Mortality in critical COVID-19 patients was mostly driven by illness severity, and the choice of sedation might have minimal impact when other factors are controlled. [ABSTRACT FROM AUTHOR]

Objectives: The immunomodulators tocilizumab and baricitinib improve outcomes in severely ill patients with coronavirus disease 2019 (COVID‐19); however, comparative analyses of clinical outcomes related to these agents are lacking. A tocilizumab national shortage shifted treatment to baricitinib in critically ill patients, allowing for an outcome comparison in a similar population. The purpose of this study is to compare clinical outcomes in critically ill COVID‐19 patients who received tocilizumab and those who received baricitinib. Design: Retrospective, observational cohort study using generalized estimating equation models, accounting for clustering by hospital and known confounders, to estimate the proportional odds of the ordinal World Health Organization Clinical Progression Scale (WHO‐CPS) score at day 14, the primary outcome. Secondary outcomes included WHO‐CPS score at day 7. Setting: Multiple hospitals within the Cleveland Clinic Health System. Patients: Adult patients admitted for COVID‐19 between January 2021 and November 2021. Interventions: Receipt of tocilizumab, before its shortage, or baricitinib, during shortage. Measurements and Main Results: In total, 507 patients were included; 217 received tocilizumab and 290 received baricitinib. Over 96% of patients required ICU admission and 98% received concomitant dexamethasone. Tocilizumab recipients had higher (worse) baseline WHO‐CPS scores. After adjustment, tocilizumab use was associated with higher odds of a worse day 14 WHO‐CPS score compared with baricitinib (adjusted odds ratio [OR] 1.65 [95% confidence interval (CI) 1.10–2.48]). Similarly, after adjustment, tocilizumab use was associated with higher odds of a worse day 7 WHO‐CPS score (adjusted OR 1.65 [95% CI 1.22–2.24]). Conclusions: Baricitinib use was associated with better WHO‐CPS scores at day 14 and day 7 compared with tocilizumab in a cohort of critically ill patients with COVID‐19. The odds of having a one unit increase in WHO‐CPS score at day 14 was 71% higher with tocilizumab than baricitinib. No difference in mortality or adverse effects was noted. [ABSTRACT FROM AUTHOR]