Association between Endothelial Dysfunction and Acute Brain Dysfunction during Critical Illness

Background: Acute brain dysfunction (delirium and coma) during critical illness is prevalent and costly, but the pathophysiology remains unclear. The relationship of acute brain dysfunction with endothelial function, which is impaired in critical illness and may contribute to alterations in cerebral blood flow and blood-brain barrier permeability, has not been studied. This study sought to determine whether systemic endothelial dysfunction is associated with acute brain dysfunction during critical illness. Methods: In this prospective cohort study, adult medical/surgical intensive care unit patients in shock and/or respiratory failure were enrolled. Endothelial function was assessed at enrollment using peripheral artery tonometry to calculate the reactive hyperemia index, with lower reactive hyperemia index indicative of worse endothelial function. Patients were assessed for coma and delirium with the Richmond Agitation-Sedation Scale and Confusion Assessment Method for the Intensive Care Unit. Multivariable linear regression was used to analyze the association between reactive hyperemia index and (1) delirium/coma-free days among all patients and (2) delirium duration among survivors, both over a 14-day period. Results: One hundred forty-seven patients with median age of 57 yr and median Acute Physiology and Chronic Health Evaluation II score of 26 were enrolled. After adjusting for age, severity of illness, severe sepsis, preexisting cognitive function, medical versus surgical intensive care unit admission, and prehospital statin use, lower reactive hyperemia index (worse systemic endothelial function) was associated with fewer delirium/coma-free days (P = 0.02) and more delirium days (P = 0.05). Conclusions: In this study, critically ill patients with lower vascular reactivity indicative of worse systemic endothelial function had increased duration of acute brain dysfunction.