Researchers at the UW School of Medicine and Public Health discovered that delirium following severe surgery may be associated with brain injury.

Delirium is an acute state of confusion that results in inattention and cognitive failure. Medical or surgical conditions can often trigger delirium. A UW study involving 114 surgical patients showed that delirium is linked to nervous tissue injury in the brain that could lead to loss of cognitive ability. The research was led by Robert Sanders, MD, assistant professor of anesthesiology at the UW School of Medicine and Public Health.

Robert Sanders
Robert Sanders

“For a long time, it has been thought that delirium, a state of confusion that can arise in sick patients, may lead to dementia and long-term cognitive problems,” he said. “However, it has been impossible to prove that delirium causes these problems, our study directly links inflammation during delirium with nerve injury.”

The paper is featured as an Editor’s Choice article in the January issue of the journal Brain.

The research team demonstrated that a protein called neurofilament light, which indicates brain injury, increased in the presence of diagnosed delirium in patients following severe surgery.

Sanders’ study examined 114 patients, with an average age of 71, whose blood plasma neurofilament light levels were tested prior to surgery. Six subjects were excluded from the study due to canceled or halted surgeries, or because delirium was associated with alcohol withdrawal rather than medical treatment. Four hundred eighty-seven blood samples were collected, and data were analyzed for 93 of those patients with paired blood samples collected before and after surgery to establish the change in neurofilament light and inflammatory markers.

Of the 108 participants, 39 experienced delirium, particularly those who underwent vascular or higher-risk surgeries. Overall there was a rise in neurofilament light with surgery, but the increase was more profound in the group who experienced delirium. More severe delirium was associated with higher levels of neurofilament light and inflammation. Using a linear regression model, the research showed that neuronal injury was associated with increases in delirium severity independent of inflammation.

The proportional change of neurofilament light with severity of delirium provides further information to suggest a causal link of delirium and brain injury, according to Sanders.

“However, we don’t yet know for certain whether there is a cause-and-effect relationship between these changes in neurofilament light and long-term changes in cognition,” he said. “We also don’t know whether they are related to onset of dementia; further research is needed.”

The severity of any cognitive decline after experiencing delirium that is attributable to brain injury is not known, but should be explored in future studies, according to Sanders.

“We recommend a study that examines a large observational group, or registry of studies, that explores all the possible causes of delirium to confirm our observations, identify the role of neuronal injury in inflammation-driven delirium, as well as other causes, and to link to long-term cognitive outcomes,” he said.

This study could inform future efforts to educate patients about the risks of surgery, especially major surgery in patients older than 65 years of age, Sanders said.