麻豆传媒

Acute brain dysfunction -- coma or delirium -- occurred frequently and was prolonged in critically ill COVID-19 patients, a large multicenter cohort study showed.

Of more than 2,000 COVID-19 ICU patients in 14 countries, 82% were comatose for a median of 10 days, reported Rafael Badenes, MD, PhD, of the University of Valencia in Spain, and co-authors in . For the 55% showing delirium, the median duration was 3 days.

Acute brain dysfunction lasted a median of 12 days, twice what's usually seen with other ICU patients. Benzodiazepine use and family visits were identified as modifiable risk factors for COVID-19 delirium.

Prolonged acute brain dysfunction is "a harbinger of bad outcomes," said co-author Wes Ely, MD, of Vanderbilt University Medical Center in Nashville. Earlier research has shown that delirium duration is a predictor of mortality, length of stay, cost of care, and acquired dementia, he noted.

"What we're learning is that COVID in the ICU is like a delirium factory," Ely told 麻豆传媒. "It's a reason to have our hackles up and say OK, what are we going to do about it?"

The study looked at 2,088 COVID-19 patients admitted to 69 ICUs before April 28, 2020. Median patient age was 64, with median Simplified Acute Physiology Score of 40 on admission; most were men (71.7%) and white (76.5%). Patients who were moribund or who had life-support measures withdrawn within 24 hours of ICU admission and those with pre-existing mental illness, neurodegenerative disorders, or brain damage were excluded.

Invasive mechanical ventilation was started on day one of ICU admission for two-thirds of patients (66.9%). Overall, 87.5% received mechanical ventilation at some point during their hospital stay and 63.1% were placed in the prone position for a median of 4 days. Median score on the while on invasive mechanical ventilation was –4.

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

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.

Before the COVID-19 pandemic, the reported incidence of new agitated delirium was up to 13% in adults with critical illness, with an overall prevalence of up to 20%, noted Valerie Page, MB BCh, of Watford General Hospital in England, in an .

"The optimal approach to sedation in COVID-19 remains uncertain, although available evidence-based practice outside the context of COVID-19 should form the basis of the approach to delirium management," Page wrote. "As the severity of COVID-19 illness is modified with reduced viral load, reduction in risk factors, and earlier presentation, and more is understood about encephalopathy caused by COVID-19, clinicians might be able to safely manage the majority of these patients without the use of deep sedation."

ICU delirium rates had been declining before COVID-19, due in large part to protocols like the (A2F) bundle that re-evaluate sedation frequently, Ely noted. "We lost a lot of ground with COVID," he said. "Not since 2005 have we had this kind of benzodiazepine use."

The study had several limitations, the researchers observed. 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 also were not assessed.

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