New research shows that in COVID-19 patients admitted to the intensive care unit (ICU), episodes of brain dysfunction are more common and prolonged than normally associated with severe respiratory failure.

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Based on the study’s findings, critically ill COVID-19 patients experienced brain dysfunction for an average of 12 days.

“This is double what we see in non-COVID ICU patients,” says Brenda Pun, DNP, RN. Pun, who works at Vanderbilt University Medical Center in Nashville, TN, is co-first author on the study with Dr. Rafael Badenes, Ph.D., of the University of Valencia in Spain.

The researchers say elements of the disease itself may be responsible for this heightened risk. However, they found evidence that some clinicians are not using current protocols designed to reduce brain dysfunction. Instead, they have reverted to using outdated and potentially harmful treatment strategies associated with increased incidences of delirium and coma.

“It is clear in our findings that many ICUs reverted to sedation practices that are not in line with best practice guidelines, and we are left to speculate on the causes,” says Pun. “In the process, key preventive measures against acute brain dysfunction went somewhat by the boards.”

This finding means ICU healthcare professionals need to ensure they are following current critical care guidelines to reduce the risk of brain dysfunction.

The results could also inspire doctors and researchers to develop new ways to lessen ICU-related brain dysfunction in critically ill COVID-19 patients.

The study appears in The Lancet Respiratory Medicine.

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People who require mechanical ventilation are at a high risk of developing brain dysfunction, specifically coma and delirium. In addition, ICU-related delirium leads to higher medical costs and increases the risk of long-term ICU-related dementia and death.

So far, 750,000 people with COVID-19, globally, have received ventilation.

Therefore, people severely ill with COVID-19 have an increased risk of developing brain dysfunction. In the recent study, researchers wanted to uncover the prevalence and risk factors associated with brain dysfunction in COVID-19 patients admitted to the ICU.

The Vanderbilt University Medical Center (VUMC) have been producing influential research exploring ICU-related delirium for almost 20 years. Their work has helped shape critical care guidelines endorsed by medical authorities in several countries.

Some of the current critical care guidelines that healthcare professionals have produced based on the VUMC’s delirium research include:

  • proper, effective pain management
  • early discontinuation of analgesics and sedatives
  • daily spontaneous breathing and awakening trials
  • delirium assessments throughout the day
  • family engagement
  • early mobility and exercise

In the recent study, researchers used electronic health records to examine details about severely ill COVID-19 patients’ characteristics, the care they received, and findings from clinical assessments.

The study, the largest of its kind to date, included information from 2,088 critically ill COVID-19 patients admitted to 69 ICUs in 14 countries before the end of April 2020.

In the study, 82% of patients were comatose for a median of 10 days, while 55% of patients were delirious for a median of 3 days. Acute brain dysfunction — in the form of delirium or coma — occurred in patients for an average of 12 days.

According to the study’s authors, these rates are double those typically associated with severe, non-COVID infections treated in the ICU.

In a previous, large-scale, multi-site study led by VUMC, acute brain dysfunction lasted a median of 5 days, while most people were comatose for 4 days and delirious for 1 day.

The researchers claim disease processes associated with COVID-19 contribute to this heightened risk. However, based on their findings, patient care also appears to have a strong impact on the risk of brain dysfunction.

In the study, healthcare professionals were practicing outdated critical care protocols on a broad scale, including:

  • deep sedation
  • widespread use of nervous system depressants such as benzodiazepine infusions
  • isolation from family
  • immobilization

Pan says a mixture of pandemic and non-pandemic related factors likely fueled this trend.

“Many of the hospitals in our sample reported shortages of ICU providers informed about best practices,” she says.

“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 study, patients receiving the sedative benzodiazepine were 59% more likely to develop delirium.

The study also found family visitation, either in person or virtually, lowered the risk of delirium by 30%. In addition, due to COVID-19 protocols, family visitation for critically ill patients has been greatly reduced or banned in many ICUs. In the study, family visitation took place on less than 20% of eligible days.

The authors cite several limitations to their research. The study analyzed information from early in the pandemic, so critical care protocols may have already changed.

Researchers also relied on clinical assessments to identify brain dysfunction and did not confirm their findings using neuroimaging tools. They also did not collect information about sedation dosages, treatment goals, when treatments stopped, or when they conducted the delirium assessments.

The researchers claim they may also have under-reported rates of brain dysfunction by excluding patients with a history of brain conditions and not tracking discharged patients.

More large-scale studies using up-to-date patient data are necessary to identify, validate, and address additional risk factors influencing the risk of coma and delirium with severe COVID-19.

But the study authors say their findings could help researchers and healthcare professionals reevaluate and modify their care guidelines now, potentially improving patient outcomes.

“These prolonged periods of acute brain dysfunction are largely avoidable,” says one of the study’s senior authors, Dr. Pratik Pandharipande, MSCI, professor of anesthesiology.

“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.”

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