Brain Temperature Influences Intracranial Pressure and Cerebral Perfusion Pressure After Traumatic Brain Injury: A CENTER-TBI Study
Authors: Birg Tatiana , Ortolano Fabrizio , Wiegers Eveline J. A. , Smielewski Peter , Savchenko Yan , Ianosi Bogdan A. , Helbok Raimund , Rossi Sandra , Carbonara Marco , Zoerle Tommaso , Stocchetti Nino ,   the CENTER-TBI Investigators and Participants, Anke Audny , Beer Ronny , Bellander Bo-Michael , Beqiri Erta , Buki Andras , Cabeleira Manuel , Chieregato Arturo , Citerio Giuseppe , Clusmann Hans , Czeiter Endre , Czosnyka Marek , Depreitere Bart , Ercole Ari , Frisvold Shirin , Jankowski Stefan , Kondziella Danile , Koskinen Lars-Owe , Kowark Ana , Menon David K. , Meyfroidt Geert , Moeller Kirsten , Nelson David , Piippo-Karjalainen Anna , Radoi Andreea , Ragauskas Arminas , Raj Rahul , Rhodes Jonathan , Rocka Saulius , Rossaint Rolf , Sahuquillo Juan , Sakowitz Oliver , Sundström Nina , Takala Riikka , Tamosuitis Tomas , Tenovuo Olli , Vajkoczy Peter , Vargiolu Alessia , Vilcinis Rimantas , Wolf Stefan , Younsi Alexander , Zeiler Frederick A. 
Published: July 2021

Abstract
Background
After traumatic brain injury (TBI), fever is frequent. Brain temperature (BT), which is directly linked to body temperature, may influence brain physiology. Increased body and/or BT may cause secondary brain damage, with deleterious effects on intracranial pressure (ICP), cerebral perfusion pressure (CPP), and outcome.

Methods
Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI), a prospective multicenter longitudinal study on TBI in Europe and Israel, includes a high resolution cohort of patients with data sampled at a high frequency (from 100 to 500 Hz). In this study, simultaneous BT, ICP, and CPP recordings were investigated. A mixed-effects linear model was used to examine the association between different BT levels and ICP. We additionally focused on changes in ICP and CPP during the episodes of BT changes (Δ BT ≥ 0.5 °C lasting from 15 min to 3 h) up or downward. The significance of ICP and CPP variations was estimated with the paired samples Wilcoxon test (also known as Wilcoxon signed-rank test).

Results
Twenty-one patients with 2,435 h of simultaneous BT and ICP monitoring were studied. All patients reached a BT of 38 °C and experienced at least one episode of ICP above 20 mm Hg. The linear mixed-effects model revealed an association between BT above 37.5 °C and higher ICP levels that was not confirmed for lower BT. We identified 149 episodes of BT changes. During BT elevations (n = 79) ICP increased, whereas CPP was reduced; opposite ICP and CPP variations occurred during episodes of BT reduction (n = 70). All these changes were of moderate clinical relevance (increase of ICP of 4.5 and CPP decrease of 7.5 mm Hg for BT rise, and ICP reduction of 1.7 and CPP elevation of 3.7 mm Hg during BT defervescence), even if statistically significant (p < 0.0001). It has to be noted, however, that a number of therapeutic interventions against intracranial hypertension was documented during those episodes.

Conclusions
Patients after TBI usually develop BT > 38 °C soon after the injury. BT may influence brain physiology, as reflected by ICP and CPP. An association between BT exceeding 37.5 °C and a higher ICP was identified but not confirmed for lower BT ranges. The relationship between BT, ICP, and CPP become clearer during rapid temperature changes. During episodes of temperature elevation, BT seems to have a significant impact on ICP and CPP.