Analysis tracks depression in the ICU, confirming the lingering adverse impact of delirium on mental health and cognitive function.

For 15 years, the physicians, psychologists and staff at the Critical Illness, Brain Dysfunction and Survivorship (CIBS) Center at Vanderbilt University Medical Center have dedicated themselves to studying short- and long-term mental and physical outcomes for patients who experience delirium and coma while in intensive care.

One of several longitudinal studies, BRAIN-ICU, focuses on a variety of outcomes, from post-traumatic stress disorder to dementia, in a cohort of 826 patients. In a recent subanalysis, published in International Psychogeriatrics, first author and psychiatrist Patricia Andrews, M.D., reports on the worsening and chronic nature of depression in patients who enter the ICU with histories of depression and experience delirium during their stay.

“We found that patients with a depression history prior to their ICU stay exhibited a greater severity of depressive symptoms during the year after hospitalization,” Andrews said. “The ICU is one of the most stressful life events one can imagine. If someone has a preexisting vulnerability to depression, characterized by previous episodes, they are more likely to succumb to this stressor and develop more severe depressive symptoms.”

Exacerbated by COVID-related post-intensive care syndrome, the stakes for failing to recognize and address these mental health issues are escalating.

“Our mission is to study and test interventions in the ICU to reduce delirium, as well as find the most effective supports to minimize its impact on cognition and mental health after discharge,” said CIBS co-director and geriatric intensivist E. Wesley Ely, M.D.

A Vulnerable Brain

Delirium is characterized by acute fluctuations in attention and cognition, with a prevalence ranging from 60 to 87 percent in the ICU. It is a key negative prognostic indicator of poor post-ICU outcomes.

Ely and colleagues published a seminal study on the consequences of ICU delirium in the New England Journal of Medicine in 2013, finding that the proportion of patients with cognitive and executive function deficits rose from 6 percent prior to ICU delirium to 40 percent at three months post-discharge. These numbers tended to persist to the 12-month follow-up.

Since that time, myriad BRAIN-ICU studies have followed, seeking to elucidate the associations between delirium and different facets of mental health. Prior studies on depression report that its severity is associated with poorer cognitive performance and that cognitive deficits persist even after depression resolves.

Other studies have looked at the obverse and shown that patients with preadmission conditions like dementia and frailty have a higher likelihood of delirium in the ICU, demonstrating how risks feed upon themselves in a kind of vicious cycle.

Delirium and Depression

Depression is common following an ICU stay, with prior studies finding that nearly a third of ICU survivors experience depression up to 24 months after discharge.

“We are sorting through these associations, causes and effects through a series of analyses,” Ely said.

“This particular analysis by Dr. Andrews was important to establish that patients who have some history of depression going into an ICU experience represent a vulnerable population we should go to greater lengths to protect.”

Andrews looked at a total of 821 patients who had been admitted to the ICU at Vanderbilt or Saint Thomas Hospital and were enrolled in the BRAIN-ICU study between March of 2007 and May of 2012. Medical records or proxy reports indicated that 33 percent had some preadmission history of depression and 6 percent had cognitive impairment at baseline.

Patients were given the Beck Depression Inventory-II at three- and 12-month follow-ups, and Andrews confirmed that those reporting a history of depression scored higher on the depression inventory.

“What this shows us is that if someone comes into the ICU with a background of some elements of depression, they will likely have a worsening of that problem on the back end of their ICU stay,” she said.

Larger Web of Mental Health Problems

Earlier, Ely found that one in four patients experiencing ICU delirium had cognitive and executive function scores at three and 12 months that were similar to scores for patients with moderate traumatic brain injury or mild Alzheimer’s disease. And a longer duration of delirium was independently associated with poorer outcomes.

Adding COVID-era data, the Vanderbilt team will soon publish findings on the high proportion of COVID-19 ICU patients with delirium with dementia-like cognitive impairment one-year post-discharge.

“Inextricably bound with these cognitive deficits are the three major psychiatric problems we have focused on: post-traumatic stress disorder, anxiety disorder, and depression,” he said. “Cognitive impairment and depression, in particular, have a very high degree of overlap.”

Reduce Risk and Attenuate Loss

Delirium prevention comes first.

“Through the ICU Liberation collaborative in 2018, we showed that better compliance with the ABCDEF bundle saved lives, reduced the delirium and coma, reduced readmission and lowered the likelihood of transfer from hospital to nursing homes,” Ely said.

He says prehabilitation to gain strength is another approach gaining traction at Vanderbilt. For fragile patients with planned major surgeries, physical therapy may reduce the risk of delirium or lessen its impact.

To benefit those who develop or are at risk of post-intensive care syndrome, he recommends guided support groups to serve as mental health “medicine.”

“At Vanderbilt, we have both COVID survivor groups and ICU survivor groups – and of course there are patients who have been in the ICU with COVID, so there is overlap,” he said. “It’s been challenging, but for anxiety and depression, in particular, these groups are very therapeutic. We are also introducing brain games and encouraging other ways shown to help preserve people’s cognitive reserve.”

About the Expert

Patricia Andrews, M.D.

Patricia Andrews, M.D., is an assistant professor of psychiatry at Vanderbilt University Medical Center. Her research interests center around delirium and dementia.

E. Wesley Ely, M.D.

Wesley Ely, M.D., M.P.H., is the Grant W. Liddle Chair in Medicine, a professor of medicine in the Division of Allergy, Pulmonary, and Critical Care Medicine, and co-director of the Critical Illness, Brain Dysfunction and Survivorship (CIBS) Center. His research focuses on improving the care and outcomes of critically ill patients with ICU-acquired brain disease.