TY - JOUR
T1 - Cerebrovascular reactivity is not associated with therapeutic intensity in adult traumatic brain injury
T2 - a CENTER-TBI analysis
AU - Zeiler, Frederick A.
AU - Ercole, Ari
AU - Beqiri, Erta
AU - Cabeleira, Manuel
AU - Aries, Marcel
AU - Zoerle, Tommaso
AU - Carbonara, Marco
AU - Stocchetti, Nino
AU - Smielewski, Peter
AU - Czosnyka, Marek
AU - Menon, David K.
AU - Anke, Audny
AU - Beer, Ronny
AU - Bellander, Bo-Michael
AU - Buki, Andras
AU - Chevallard, Giorgio
AU - Chieregato, Arturo
AU - Citerio, Giuseppe
AU - Czeiter, Endre
AU - Depreitere, Bart
AU - Eapen, George
AU - Frisvold, Shirin
AU - Helbok, Raimund
AU - Jankowski, Stefan
AU - Kondziella, Daniel
AU - Koskinen, Lars-Owe
AU - Meyfroidt, Geert
AU - Moeller, Kirsten
AU - Nelson, David
AU - Piippo-Karjalainen, Anna
AU - Radoi, Andreea
AU - Ragauskas, Arminas
AU - Raj, Rahul
AU - Rhodes, Jonathan
AU - Rocka, Saulius
AU - Rossaint, Rolf
AU - Sahuquillo, Juan
AU - Sakowitz, Oliver
AU - Stevanovic, Ana
AU - Sundstrom, Nina
AU - Takala, Riikka
AU - Tamosuitis, Tomas
AU - Tenovuo, Olli
AU - Vajkoczy, Peter
AU - Vargiolu, Alessia
AU - Vilcinis, Rimantas
AU - Wolf, Stefan
AU - Younsi, Alexander
AU - CENTER-TBI High Resolution ICU (HR ICU) Sub-Study Participants and Investigators
N1 - Funding Information:
Funding Data used in preparation of this manuscript were obtained in the context of CENTER-TBI, a large collaborative project with the support of the European Union 7th Framework program (EC grant 602150). Additional funding was obtained from the Hannelore Kohl Stiftung (Germany), from OneMind (USA) and from Integra LifeSciences Corporation (USA).
Funding Information:
FAZ has received salary support for dedicated research time, during which this project was completed. FAZ receives research support from the University of Manitoba Thorlakson Chair in Surgical Research Establishment Fund, the University of Manitoba VPRI Research Investment Fund (RIF), the University of Manitoba Rudy Falk Clinician-Scientist Professorship, and the Health Sciences Centre Foundation Winnipeg.
Funding Information:
DKM was also supported by funding from the National Institute for Health Research (NIHR, UK) through a Senior Investigator award and the Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust. The study also received additional support from the NIHR Clinical Research network. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care, UK.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/9
Y1 - 2019/9
N2 - 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.
AB - 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.
KW - Cerebrovascular reactivity
KW - PRx
KW - TBI
KW - Therapeutic intensity
KW - TIL
KW - CEREBRAL PERFUSION-PRESSURE
KW - MODERATE HYPOTHERMIA
KW - AUTOREGULATION
KW - ISOFLURANE
KW - MANAGEMENT
KW - SUPPRESSION
U2 - 10.1007/s00701-019-03980-8
DO - 10.1007/s00701-019-03980-8
M3 - Article
C2 - 31240583
SN - 0001-6268
VL - 161
SP - 1955
EP - 1964
JO - Acta Neurochirurgica
JF - Acta Neurochirurgica
IS - 9
ER -