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Association of Central Nervous System-Related Biomarkers With Hospital Delirium in Patients With Respiratory Failure in the ICU
Journal article   Open access   Peer reviewed

Association of Central Nervous System-Related Biomarkers With Hospital Delirium in Patients With Respiratory Failure in the ICU

Andrew T. Pham, Ryan A. Peterson, Suzanne Slaughter, Morgan Martin, Joseph A. Hippensteel and Ellen L. Burnham
CHEST critical care, Vol.3(2), p.100143
06/01/2025
DOI: 10.1016/j.chstcc.2025.100143
PMCID: PMC12201967
PMID: 40575577
url
https://doi.org/10.1016/j.chstcc.2025.100143View
Published (Version of record) Open Access

Abstract

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. In critically ill patients with respiratory failure, are central nervous system (CNS)-related biomarkers measured at admission associated with delirium diagnosis? 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. 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. 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.
 alcohol brain-derived neurotrophic factor critical illness neurofilament light chain

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