Laird Harrison

January 13, 2014

SAN FRANCISCO — Blood–brain barrier injury and endothelial dysfunction are independently associated with acute brain dysfunction in patients in the intensive care unit (ICU), a new study shows.

If supported by further research, this finding could lead to new treatments, lead investigator Christopher Hughes, MD, assistant professor of anesthesia at Vanderbilt University in Nashville, Tennessee, told Medscape Medical News.

"There haven't been many studies in humans," said Dr. Hughes, who presented the study here at the Society of Critical Care Medicine 43rd Critical Care Congress. "This could help us figure out which patients are at high risk."

Delirium affects about two thirds of patients in the ICU, Dr. Hughes explained, and current preventive measures — such as turning lights off at night, giving patients activities that require them to think, prompting patients to exercise, and monitoring drug reactions — have had limited success.

By trying to understand the biologic mechanisms of the condition, Dr. Hughes and his team say they hope to eventually improve outcomes.

In 134 patients with respiratory failure or shock, the researchers measured plasma concentrations of S100B, which is a marker of blood–brain barrier injury. They also looked at PAI-1, E-selectin, and Ang-2, which are biomarkers for endothelial dysfunction. Investigators conducted daily assessments of patients for delirium and coma using the Confusion Assessment Method for the ICU and the Richmond Agitation Sedation Scale.

The median age of the patient cohort was 57 years, and median Acute Physiology and Chronic Health Evaluation (APACHE) II score was 26.

The investigators used statistical methods to analyze the correlation of these biomarkers with delirium- and coma-free days and delirium duration, and adjusted for confounders such as age, illness severity, and sepsis. They found an independent correlation between fewer delirium- and coma-free days and higher PAI-1 concentrations (P = .002) and higher S100B concentrations (P < .001).

They also found a significantly longer duration of delirium in patients with higher concentrations of PAI-1 (P = .01) and S100B (P = .01).

Adjustment for S100B did not affect the independent association between acute brain dysfunction and endothelial vascular reactivity, PAI-1, or E-selectin, contradicting the hypothesis that blood–brain barrier injury mediates the effects of endothelial dysfunction.

New Blood–Brain or Endothelium Target

The results of this study could lead to therapies that target either the blood–brain barrier or the endothelium, such as statins, angiotensin-receptor blockers, and early exercise. But before making such recommendations, Dr. Hughes and his team say they want to conduct a study with a much larger cohort.

Charles Hobson, MD, from the University of Florida in Gainesville, who served as discussion moderator for the poster presentation, asked about the effects of any other drugs that the patients may have been taking.

Dr. Hughes explained that the team has not studied correlations between these biomarkers and drugs such as sedatives that can cause cognitive dysfunction. "We want to look at that in the future," he said.

Dr. Hughes has disclosed no relevant financial interests. Dr. Hobson reports that his wife receives support from Astute Medical.

Society of Critical Care Medicine (SCCM) 43rd Critical Care Congress: Abstract 595. Presented January 10, 2014.

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