Sedative Selection Led to More Brain Dysfunction in COVID-19 ICU Patients

Whether because of drug shortages or other reasons, many ICUs apparently reverted to older protocols in treating early COVID-19 patients. That included choice of sedatives which, combined with other factors such as lack of family visitation, increased rates of coma and delirium over what is usually seen with acute respiratory failure, according to a new international study.

NASHVILLE, TN – Why did COVID-19 patients admitted to intensive care in the early months of the pandemic have a much higher rate of delirium and coma than usually identified in acute respiratory failure patients?

An international study suggests that choice of sedative medications and limits on family visitation increased acute brain dysfunction in those patients.

The report in The Lancet Respiratory Medicine, led by researchers at Vanderbilt University Medical Center in coordination with researchers in Spain, was on the results of a study tracking the incidence of delirium and coma in 2,088 COVID-19 patients admitted before April 28, 2020, to 69 adult intensive care units across 14 countries.

The authors report that about 82% of patients in the observational study were comatose for a median of 10 days, and 55% were delirious for a median of three days. Acute brain dysfunction – whether coma or delirium -- lasted for a median of 12 days.

"This is double what is seen in non-COVID ICU patients," said Vanderbilt’s Brenda Pun, DNP, RN, co-first author on the study with Rafael Badenes MD, PhD, of the University of Valencia in Spain.

Between Jan 20 and April 28, 2020, 4,530 patients with COVID-19 were admitted to 69 ICUs, of whom 2088, with a median age of 64, were included in the study cohort. Nearly 70% of the patients were invasively mechanically ventilated on the day of ICU admission, and more than 87% were invasively mechanical ventilated at some point during hospitalization.

The authors note that Infusion with sedatives while on mechanical ventilation was common: 1337 (64·0%) of 2088 patients were given benzodiazepines for a median of 7·0 days (4·0 to 12·0) and 1481 (70·9%) were given propofol for a median of 7·0 days (4·0 to 11·0).

The study determined that mechanical ventilation, use of restraints, and benzodiazepine, opioid, and vasopressor infusions, and antipsychotics were each associated with a higher risk of delirium the next day (all p≤0·04). On the other hand, family visitation (in person or virtual) was associated with a lower risk of delirium (p<0·0001).

In addition, researchers report that, at baseline, 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 were independently associated with fewer days alive and free of delirium and coma (all p<0·01). Slightly more than a fourth, 28.8%, of the patients died within 28 days of admission, mostly in the ICU.

“Acute brain dysfunction was highly prevalent and prolonged in critically ill patients with COVID-19,” researchers advise. “Benzodiazepine use and lack of family visitation were identified as modifiable risk factors for delirium, and thus these data present an opportunity to reduce acute brain dysfunction in patients with COVID-19.”

One problem, according to the authors, is that issues such as shortages of drugs led to a reversion to outmoded critical care practices. Those included deep sedation, widespread use of benzodiazepine infusions, immobilization, and isolation from families.

"It is clear in our findings that many ICUs reverted to sedation practices that are not in line with best practice guidelines," Pun said, "and we're left to speculate on the causes. Many of the hospitals in our sample reported shortages of ICU providers informed about best practices. There were concerns about sedative shortages, and early reports of COVID-19 suggested that the lung dysfunction seen required unique management techniques including deep sedation. In the process, key preventive measures against acute brain dysfunction went somewhat by the boards."

One of the senior authors, Pratik Pandharipande, MD, MSCI, professor of Anesthesiology and Surgery at Vanderbilt and part of the Veterans Affairs Anesthesiology Service, explained, "These prolonged periods of acute brain dysfunction are largely avoidable. Our study sounds an alarm: as we enter the second and third waves of COVID-19, ICU teams need above all to return to lighter levels of sedation for these patients, frequent awakening and breathing trials, mobilization and safe in-person or virtual visitation."

Go Back