Evaluation of the relationship between slow-waves of intracranial pressure, mean arterial pressure and brain tissue oxygen in TBI: a CENTER-TBI exploratory analysis
Authors: Zeiler Frederick A. , Cabeleira Manuel , Hutchinson Peter J. , Stocchetti Nino , Czosnyka Marek , Smielewski Peter , Ercole Ari ,   the CENTER-TBI High-Resolution ICU (HR ICU) Sub-Study Participants and Investigators, Anke Audny , Beer Ronny , Bellander Bo-Michael , Beqiri Erta , Buki Andras , Cabeleira Manuel , Carbonara Marco , Chieregato Arturo , Citerio Giuseppe , Clusmann Hans , Czeiter Endre , Czosnyka Marek , Depreitere Bart , Ercole Ari , Frisvold Shirin , Helbok Raimund , 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 , Smielewski Peter , Stocchetti Nino , Sundström Nina , Takala Riikka , Tamosuitis Tomas , Tenovuo Olli , Vajkoczy Peter , Vargiolu Alessia , Vilcinis Rimantas , Wolf Stefan , Younsi Alexander , Zeiler Frederick A. 
Published: May 2020

Brain tissue oxygen (PbtO2) monitoring in traumatic brain injury (TBI) has demonstrated strong associations with global outcome. Additionally, PbtO2 signals have been used to derive indices thought to be associated with cerebrovascular reactivity in TBI. However, their true relationship to slow-wave vasogenic fluctuations associated with cerebral autoregulation remains unclear. The goal of this study was to investigate the relationship between slow-wave fluctuations of intracranial pressure (ICP), mean arterial pressure (MAP) and PbtO2 over time. Using the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) high resolution ICU sub-study cohort, we evaluated those patients with recorded high-frequency digital intra-parenchymal ICP and PbtO2 monitoring data of a minimum of 6 h in duration. Digital physiologic signals were processed for ICP, MAP, and PbtO2 slow-waves using a moving average filter to decimate the high-frequency signal. The first 5 days of recording were analyzed. The relationship between ICP, MAP and PbtO2 slow-waves over time were assessed using autoregressive integrative moving average (ARIMA) and vector autoregressive integrative moving average (VARIMA) modelling, as well as Granger causality testing. A total of 47 patients were included. The ARIMA structure of ICP and MAP were similar in time, where PbtO2 displayed different optimal structure. VARIMA modelling and IRF plots confirmed the strong directional relationship between MAP and ICP, demonstrating an ICP response to MAP impulse. PbtO2 slow-waves, however, failed to demonstrate a definite response to ICP and MAP slow-wave impulses. These results raise questions as to the utility of PbtO2 in the derivation of cerebrovascular reactivity measures in TBI. There is a reproducible relationship between slow-wave fluctuations of ICP and MAP, as demonstrated across various time-series analytic techniques. PbtO2 does not appear to reliably respond in time to slow-wave fluctuations in MAP, as demonstrated on various VARIMA models across all patients. These findings suggest that PbtO2 should not be utilized in the derivation of cerebrovascular reactivity metrics in TBI, as it does not appear to be responsive to changes in MAP in the slow-waves. These findings corroborate previous results regarding PbtO2 based cerebrovascular reactivity indices.