Association of Sedation, Coma, and In-Hospital Mortality in Mechanically Ventilated Patients With Coronavirus Disease 2019–Related Acute Respiratory Distress Syndrome: A Retrospective Cohort Study*

Abstract

OBJECTIVES: In patients with coronavirus disease 2019–associated acute respiratory distress syndrome, sedatives and opioids are commonly administered which may lead to increased vulnerability to neurologic dysfunction. We tested the hypothesis that patients with coronavirus disease 2019–associated acute respiratory distress syndrome are at higher risk of in-hospital mortality due to prolonged coma compared with other patients with acute respiratory distress syndrome matched for disease severity. DESIGN: Propensity-matched cohort study. SETTING: Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA). PATIENTS: All mechanically ventilated coronavirus disease 2019 patients between March and May 2020 were identified and matched with patients with acute respiratory distress syndrome of other etiology. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using clinical data obtained from a hospital registry, we matched 114 coronavirus disease 2019 patients to 228 noncoronavirus disease 2019–related acute respiratory distress syndrome patients based on baseline disease severity. Coma was identified using the Richmond Agitation Sedation Scale less than or equal to –3. Multivariable logistic regression and mediation analyses were used to assess the percentage of comatose days, sedative medications used, and the association between coronavirus disease 2019 and in-hospital mortality. In-hospital mortality (48.3% vs 31.6%, adjusted odds ratio, 2.15; 95% CI, 1.34–3.44; p = 0.002), the percentage of comatose days (66.0% ± 31.3% vs 36.0% ± 36.9%, adjusted difference, 29.35; 95% CI, 21.45–37.24; p < 0.001), and the hypnotic agent dose (51.3% vs 17.1% of maximum hypnotic agent dose given in the cohort; p < 0.001) were higher among patients with coronavirus disease 2019. Brain imaging did not show a higher frequency of structural brain lesions in patients with coronavirus disease 2019 (6.1% vs 7.0%; p = 0.76). Hypnotic agent dose was associated with coma (adjusted coefficient, 0.61; 95% CI, 0.45–0.78; p < 0.001) and mediated (p = 0.001) coma. Coma was associated with in-hospital mortality (adjusted odds ratio, 5.84; 95% CI, 3.58–9.58; p < 0.001) and mediated 59% of in-hospital mortality (p < 0.001). CONCLUSIONS: Compared with matched patients with acute respiratory distress syndrome of other etiology, patients with coronavirus disease 2019 received higher doses of hypnotics, which was associated with prolonged coma and higher mortality.

High sedation needs of critically ill COVID-19 ARDS patients—A monocentric observational study

“…In our retrospective observational study, we found evidence of unusually high sedative medication requirements as well as of multiple use as combination therapies, leading to a challenging sedation in patients with moderate to severe C-ARDS. Our results are consistent with the repeatedly raised suspicion of aggravated sedation with previously published results from other study groups [2,3]. In our study, we found a high mortality (46.6%) comparable to international data among mechanically ventilated severely affected C-ARDS patients [20].…”

“…This observation is especially meaningful when taking into account that esketamine was only administered in combination with a sedative that had already been used at its optimum dose. Such frequent use of esketamine as a substance rarely used in modern intensive care was similarly found in another study [2]. For effective sedation with midazolam, a mean dosage of 0.15 (±0.1) mg�kg -1 �h -1 was found necessary in several studies [31][32][33][34].…”

“…However, our in-hospital standards appear to be consistent with previously published regimens for severe COVID-19 patients in terms of the classes of agents used. Previously published reports also describe the predominant use of propofol, benzodiazepines, central α 2 -agonists and potent opioids, as well as the use of esketamine to achieve the prescribed depth of sedation [2,3].…”

“…Recently, Wongtangman et al published a first retrospective comparison between ARDS patients with and without causative COVID-19 pneumonia. They demonstrated a significantly increased need for sedation and analgesics on the basis of a sedative burden index [2]. In addition, Kapp et al were able to demonstrate a significant association between sedation depth and mortality [3].…”

Reasons for the Overuse of Sedatives and Deep Sedation for Mechanically Ventilated Coronavirus Disease 2019 Patients

“…We read with great interest the study by Wongtangman et al ( 1 ) published in a recent issue of Critical Care Medicine , which investigated the potential mediators of high mortality rate of coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS). Sophisticated statistical methods including mediation analysis and propensity score matching were leveraged to make causal inference from observational dataset ( 2 ).…”