Abstract
BACKGROUND: Delirium commonly occurs in critical illness and is associated with significant morbidity and mortality. Although risk reduction measures can mitigate the risk of delirium, identifying patients in whom delirium will develop remains clinically challenging. RESEARCH QUESTION: In critically ill patients with respiratory failure, are central nervous system (CNS)-related biomarkers measured at admission associated with delirium diagnosis? STUDY DESIGN AND METHODS: We performed a secondary analysis of a cohort of patients with respiratory failure in the medical ICU enrolled at a single medical center. Using serum collected at ICU admission, we measured CNS-related biomarkers including brain-derived neurotrophic factor (BDNF), chitinase-3-like protein 1, glial fibrillary acidic protein, neurofilament light chain (NF-L), neurogranin, S100 calcium-binding protein B, and triggering receptor expressed on myeloid cells 2 via a multiplex immunoassay. The primary outcome was diagnosis of in-hospital delirium, defined using validated methods. Associations between individual biomarkers and delirium diagnosis were examined using multivariable logistic regressions, adjusting for factors known to predispose and precipitate delirium. Secondary outcomes included in-hospital mortality, ventilator-free days, ICU-free days, and hospital-free days. RESULTS: Serum biomarkers were measured in 100 patients. Delirium occurred in 73% of the cohort. Patients with vs without delirium did not differ significantly in terms of age, sex, comorbidities, severity of illness, or unhealthy alcohol use. After adjustment, NF-L was associated positively with delirium diagnosis (adjusted OR, 1.86; 95% CI, 1.09-3.43), whereas BDNF was associated negatively with delirium (adjusted OR, 0.43; 95% CI, 0.15-0.82). No associations were found between other measured biomarkers and delirium diagnosis. NF-L levels were associated negatively with ICU-free and hospital-free days. INTERPRETATION: Our results indicate that CNS-related biomarkers measured at ICU admission are associated with delirium diagnosis in critically ill patients. Prospective investigations are necessary to validate the role of these biomarkers in predicting delirium.