Early systemic insults following traumatic brain injury: association with biomarker profiles, therapy for intracranial hypertension, and neurological outcomes—an analysis of CENTER-TBI data

• Published in: Intensive care medicine Vol. 50; no. 3; pp. 371 - 384
• Main Authors: Robba, Chiara, Graziano, Francesca, Picetti, Edoardo, Åkerlund, Cecilia, Addis, Alberto, Pastore, Giuseppe, Sivero, Mattia, Rebora, Paola, Galimberti, Stefania, Stocchetti, Nino, Maas, Andrew, Menon, David K., Citerio, Giuseppe
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2024; Springer Nature B.V
• Subjects: Anesthesiology; Biomarkers; Brain; Calcium-binding protein; Critical Care Medicine; Emergency Medicine; Glial fibrillary acidic protein; Head injuries; Hypertension; Hypotension; Hypoxemia; Hypoxia; Impact analysis; Injury analysis; Intensive; Intensive care; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Neuronal-glial interactions; Original; Pain Medicine; Pediatrics; Phosphopyruvate hydratase; Pneumology/Respiratory System; Protein B; Protein gene product 9.5; Proteins; Risk factors; S100b protein; Tau protein; Trauma; Traumatic brain injury; Ubiquitin carboxy-terminal hydrolase; Traumatic brain injury; Hypoxemia; Serum biomarkers; Systemic insults; Outcome; Hypotension
• ISSN: 0342-4642; 1432-1238; 1432-1238
• DOI: 10.1007/s00134-024-07324-8

Purpose We analysed the impact of early systemic insults (hypoxemia and hypotension, SIs) on brain injury biomarker profiles, acute care requirements during intensive care unit (ICU) stay, and 6-month outcomes in patients with traumatic brain injury (TBI). Methods From patients recruited to the Collaborative European neurotrauma effectiveness research in TBI (CENTER-TBI) study, we documented the prevalence and risk factors for SIs and analysed their effect on the levels of brain injury biomarkers [S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and protein Tau], critical care needs, and 6-month outcomes [Glasgow Outcome Scale Extended (GOSE)]. Results Among 1695 TBI patients, 24.5% had SIs: 16.1% had hypoxemia, 15.2% had hypotension, and 6.8% had both. Biomarkers differed by SI category, with higher S100B, Tau, UCH-L1, NSE and NfL values in patients with hypotension or both SIs. The ratio of neural to glial injury (quantified as UCH-L1/GFAP and Tau/GFAP ratios) was higher in patients with hypotension than in those with no SIs or hypoxia alone. At 6 months, 380 patients died (22%), and 759 (45%) had GOSE ≤ 4. Patients who experienced at least one SI had higher mortality than those who did not (31.8% vs. 19%, p  < 0.001). Conclusion Though less frequent than previously described, SIs in TBI patients are associated with higher release of neuronal than glial injury biomarkers and with increased requirements for ICU therapies aimed at reducing intracranial hypertension. Hypotension or combined SIs are significantly associated with adverse 6-month outcomes. Current criteria for hypotension may lead to higher biomarker levels and more negative outcomes than those for hypoxemia suggesting a need to revisit pressure targets in the prehospital settings.