Early systemic insults following traumatic brain injury: association with biomarker profiles, therapy for intracranial hypertension, and neurological outcomes—an analysis of CENTER-TBI data
Chiara Robba, Francesca Graziano, Edoardo Picetti, Cecilia Åkerlund, Alberto Addis, Giuseppe Pastore, Mattia Sivero, Paola Rebora, Stefania Galimberti, Nino Stocchetti, Andrew I.R. Maas, David K. Menon, Giuseppe Citerio, Cecilia Åkerlund, Krisztina Amrein, Nada Anđelić, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo‐Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Bražinová, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, András Büki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Hans Clusmann, Mark Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot‐Fizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Françesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens P. Dreier, Guy‐Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubović, Pedro A. Gómez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton
Abstract
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.