Cerebrovascular reactivity is not associated with therapeutic intensity in adult traumatic brain injury: a CENTER-TBI analysis

Frederick A. Zeiler*, Ari Ercole, Erta Beqiri, Manuel Cabeleira, Marcel Aries, Tommaso Zoerle, Marco Carbonara, Nino Stocchetti, Peter Smielewski, Marek Czosnyka, David K. Menon, Audny Anke, Ronny Beer, Bo-Michael Bellander, Andras Buki, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Endre Czeiter, Bart DepreitereGeorge Eapen, Shirin Frisvold, Raimund Helbok, Stefan Jankowski, Daniel Kondziella, Lars-Owe Koskinen, Geert Meyfroidt, Kirsten Moeller, David Nelson, Anna Piippo-Karjalainen, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Jonathan Rhodes, Saulius Rocka, Rolf Rossaint, Juan Sahuquillo, Oliver Sakowitz, Ana Stevanovic, Nina Sundstrom, Riikka Takala, Tomas Tamosuitis, Olli Tenovuo, Peter Vajkoczy, Alessia Vargiolu, Rimantas Vilcinis, Stefan Wolf, Alexander Younsi, CENTER-TBI High Resolution ICU (HR ICU) Sub-Study Participants and Investigators

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background Impaired cerebrovascular reactivity in adult traumatic brain injury (TBI) is known to be associated with poor outcome. However, there has yet to be an analysis of the association between the comprehensively assessed intracranial hypertension therapeutic intensity level (TIL) and cerebrovascular reactivity. Methods Using the Collaborative European Neuro Trauma Effectiveness Research in TBI (CENTER-TBI) high-resolution intensive care unit (ICU) cohort, we derived pressure reactivity index (PRx) as the moving correlation coefficient between slow-wave in ICP and mean arterial pressure, updated every minute. Mean daily PRx, and daily % time above PRx of 0 were calculated for the first 7 days of injury and ICU stay. This data was linked with the daily TIL-Intermediate scores, including total and individual treatment sub-scores. Daily mean PRx variable values were compared for each TIL treatment score via mean, standard deviation, and the Mann U test (Bonferroni correction for multiple comparisons). General fixed effects and mixed effects models for total TIL versus PRx were created to display the relation between TIL and cerebrovascular reactivity. Results A total of 249 patients with 1230 ICU days of high frequency physiology matched with daily TIL, were assessed. Total TIL was unrelated to daily PRx. Most TIL sub-scores failed to display a significant relationship with the PRx variables. Mild hyperventilation (p <0.0001), mild hypothermia (p = 0.0001), high levels of sedation for ICP control (p = 0.0001), and use vasopressors for CPP management (p <0.0001) were found to be associated with only a modest decrease in mean daily PRx or % time with PRx above 0. Conclusions Cerebrovascular reactivity remains relatively independent of intracranial hypertension therapeutic intensity, suggesting inadequacy of current TBI therapies in modulating impaired autoregulation. These findings support the need for investigation into the molecular mechanisms involved, or individualized physiologic targets (ICP, CPP, or Co2) in order to treat dysautoregulation actively.

Original languageEnglish
Pages (from-to)1955-1964
Number of pages10
JournalActa Neurochirurgica
Issue number9
Publication statusPublished - Sept 2019


  • Cerebrovascular reactivity
  • PRx
  • TBI
  • Therapeutic intensity
  • TIL

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