Lancet Respiratory Medicine 2021.01.08

Key national and international societies have endorsed critical care guidelines for mechanically ventilated patients, which include well-calibrated pain management with timely discontinuation of analgesics and sedatives, daily spontaneous awakening and breathing trials, delirium assessments throughout the day, early mobility and exercise, and family engagement.

However, evidence from small cohorts of mechanically ventilated patients with COVID-19 has shown that recommendations were not being followed, with higher levels of sedatives and analgesics being prescribed for these patients compared with their counterparts without COVID-19.


According to a recent multicenter cohort study, acute brain dysfunction occurred frequently and was prolonged in critically ill COVID-19 patients.

Of more than 2,000 patients with COVID-19 in the ICU, 82% were comatose for a median of 10 days and 55% experienced delirium for a median of 3 days, reported Rafael Badenes, MD, PhD, of the University of Valencia in Spain, and colleagues in the Lancet Respiratory Medicine.

In addition, they found benzodiazepine infusion and family visits to be the two strongest modifiable risk factors for COVID-19 delirium.

The study included 2,088 patients with COVID-19 admitted to 69 ICUs across 14 countries before April 28, 2020. The researchers used electronic health records to examine patient characteristics, care practices, and findings from clinical assessments.

Median patient age was 64 years, and most were men (71.7%) and white (76.5%). They had a median Charlson comorbidity score of 1.0 and were moderately ill on admission, with a median Simplified Acute Physiology Score [SAPS] II of 40.

Nearly all the institutions (94%) in the study were teaching hospitals. Most (84%) increased their ICU bed capacity during the pandemic, and 42% reported resource shortages, mostly of critical care providers, personal protective equipment, ventilators, ICU beds, and sedatives.

Overall, 87.5% of patients monitored during the study were invasively mechanically ventilated at some point during hospitalization, 66.9% of them on day 1 of ICU admission. About 63% of patients were placed in the prone position for a median of 4 days. Median score on the Richmond Agitation-Sedation Scale while on invasive mechanical ventilation was -4.

Most patients received continuous sedative infusions while on mechanical ventilation: 64.0% of patients received benzodiazepines for a median of 7 days, and 70.9% received propofol for a median of 7 days.

Sedative benzodiazepine infusions (OR 1.59), antipsychotics (OR 1.59), invasive mechanical ventilation (OR 1.48), continuous opioid infusions (OR 1.39), restraint use (OR 1.32), and vasopressors (OR 1.25) each were associated with a higher risk of delirium the next day (all P≤0.04). Family interactions, including virtual visits, lowered delirium risk (OR 0.73, P<0.0001).

The following factors at baseline were independently associated with fewer days alive and free of delirium and coma (all P<0.01): older age, higher SAPS II scores, male sex, smoking or alcohol abuse, use of vasopressors on day 1, and invasive mechanical ventilation on day 1.

More than 50% of patients had hyperactive delirium, up from a reported incidence of 13% seen for critically ill adults prior to the COVID-19 pandemic.

The study had several limitations, the researchers acknowledged. Routine care of severe COVID-19 patients may have changed after the study was completed. Neuroimaging data were not collected, nor was information about acute kidney injury. Sedative doses, sedation goals, and rationales for drug choices were also not assessed.