The Effects of Sedation on Brain Function in COVID-19 Patients

Although treatment for those with COVID-19 has improved, concerns about neurological complications continue to proliferate. Neurological symptoms such as loss of smell, confusion and headaches have been reported over the course of the pandemic. 

However, the impact of COVID-19 treatment on the brain and related cognitive dysfunction (such as problems with memory and attention) is an area of concern for physicians. This has prompted physicians and researchers at Massachusetts General Hospital to study the effects of sedation on neurological outcomes in COVID-19 patients.

The Need for Prolonged Ventilation in COVID-19 Patients

Coronavirus infection starts with inhalation of the virus and its eventual spread to the lungs. Because the virus has the potential to cause extensive damage to the lungs, some patients may be unable to breathe on their own, and require intubation and subsequent ventilation in order to bring oxygen into the body. Ventilation, which requires sedation to prevent injury, has become a common part of respiratory treatment in those with COVID-19. 

Early during the pandemic, clinicians did not have the experience in treating the virus and had to learn how to best manage COVID-19 symptoms.

“Everybody was reaching in the dark because they hadn't seen anything like this before,” says Emery Brown, MD, PhD, anesthesiologist in the Department of Anesthesia, Critical Care and Pain Medicine.

In many cases, sedation was prolonged and sometimes for several weeks; this was much longer than for common treatments requiring sedation, such as surgery.

Soon, there were reports of new issues facing those with COVID-19.

“When things were calming down in the Northeast, there were reports of patients who were not waking up,” says Dr. Brown. “Their respiratory systems improved, but they were comatose.”

Being ventilated increases the prevalence of hypoxia—a state wherein the body is deprived of oxygen, causes blood clots and alters the way the body metabolizes medication. 

Dr. Brown notes that “all were likely contributing to these patients not waking up.”

A Missing Link Between Coronavirus and Hypoxic Injury

Further perplexing neurologists and neuroscientists are the unknown ways that COVID-19 may be impacting the brain directly.

Shibani Mukerji, MD, PhD is the associate director of the Neuro-Infectious Diseases Unit at Mass General and co-author of a recently published article on neuropathological findings from the autopsies of COVID-19 patients in the New England Journal of Medicine. In this autopsy series, there was no evidence of the virus that causes COVID-19 in the brain tissue of ventilated COVID-19 patients. This suggests that other causes besides the virus directly infecting the brain were the reason for neurological symptoms during infection.

“The evidence we have currently does not indicate a direct central nervous system infection for the majority of cases with neurological symptoms,” says Dr. Mukerji.

Dr. Mukerji does find that those with COVID-19 had hypoxic injury—meaning that brain cells in these patients died due to lack of oxygen. Answers to questions of what’s leading to this hypoxic injury, and whether it’s specifically due to coronavirus infection, are obscured by the fact that prolonged ventilation increases hypoxic injury. 

“You're more likely to have hypoxic injury in people who needed prolonged ventilation regardless of source,” notes Dr. Mukerji.

There is much debate in the medical community as to what is causing the observed hypoxic injury, neurological symptoms and cognitive dysfunction in those with COVID-19. Blood clots are thought to be a critical factor in brain trauma and symptoms.

“There is data to suggest there's these micro-bleeds when looking at magnetic resonance imaging, but that doesn't speak to whether or not these micro-clots result in hypoxic changes,” says Dr. Mukerji. “The infection potentially leads to an increase in blood clots in other organs, and whether micro-clots occur in the brain remains up for debate and is still a consideration.” 

Bringing Connections Into Focus

As with finding patients being unable to fully awake and having significant cognitive dysfunction, COVID-19 is expected to bring about the unexpected.

Dr. Brown relates, “I think that where we're going to see residual effects, over the next several years we will see patients with a broad range of symptoms.” 

Physicians and researchers at Mass General will continue to work on disentangling the effects of sedation on the neurological impacts of COVID-19 and to improve patient treatment. 

“We will optimize the therapies going forward so that we can reduce consequences down the line and help mitigate the effects,” says Dr. Brown.

The enigmatic links between COVID-19, neurological symptoms and underlying brain dysfunction are complex. Time and research efforts have offered some perspective on these links, though many key questions remain unanswered. Mass General researchers will continue improving neurological outcomes while identifying the impact of COVID-19 on the brain.