Correlation of brain injury biomarkers with brain dysfunction, brain injury, and outcomes in critically ill patients: a post hoc exploratory analysis

PURPOSE: Clinical assessment of brain dysfunction in critically ill patients is frequently limited by impaired consciousness and poor compliance. Blood-based biomarkers may facilitate detection of neurocognitive impairment, quantify structural brain injury, and improve prognostication. This study evaluated the potential diagnostic role of validated brain injury biomarkers compared with routine diagnostics in critically ill patients. METHODS: We performed a single-center post hoc analysis of a prospective observational sepsis study conducted in two perioperative ICUs. Critically ill patients with and without sepsis were included. Delirium was assessed using validated tools and structural brain injury was evaluated from radiology reports. Biomarkers-neurofilament light chain (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP) and Tau-were measured at two time points (enrollment and day 7). Neurological outcome was assessed using the modified Rankin Scale (mRS). 90-day mortality was recorded. RESULTS: 90 patients were analyzed (60 with, 30 without sepsis). Delirium occurred in 54.4% and structural brain injury in 42.2%. At ICU discharge, 23.3% had favorable neurological outcomes. NfL levels were higher in septic patients with delirium (p = 0.038). GFAP was significantly elevated in patients with structural brain injury (p < 0.001). All biomarkers showed prognostic potential; GFAP demonstrated the strongest association with unfavorable outcome (aOR 5.11, 95% CI 1.57-22.33). GFAP and UCH-L1 improved AUC in reference model 1 (age + SOFA), while all four biomarkers improved AUC in models 2 (age + GCS) and 3 (APACHE-II) for predicting poor outcome and 90-day mortality. CONCLUSION: Brain injury biomarkers correlate with delirium and structural injury and may enhance outcome prediction in heterogeneous critically ill patients. TRIAL REGISTRATION: ClinicalTrials.gov. NCT06749483. Study Registration Date: 23 December 2024.