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

Crit Care Med. 2021 Sep 1;49(9):1524-1534. doi: 10.1097/CCM.0000000000005053.


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.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Analgesics / therapeutic use
  • Brain / diagnostic imaging
  • Brain / pathology
  • COVID-19 / complications
  • COVID-19 / mortality
  • COVID-19 Drug Treatment*
  • Coma / etiology*
  • Female
  • Hospital Mortality*
  • Humans
  • Hypnotics and Sedatives / administration & dosage*
  • Hypnotics and Sedatives / adverse effects
  • Logistic Models
  • Male
  • Middle Aged
  • Neuromuscular Blocking Agents / therapeutic use
  • Propensity Score
  • Respiration, Artificial*
  • Respiratory Distress Syndrome / etiology*
  • Respiratory Distress Syndrome / mortality
  • Respiratory Distress Syndrome / therapy
  • Retrospective Studies


  • Analgesics
  • Hypnotics and Sedatives
  • Neuromuscular Blocking Agents