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 Depreitere; George 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

doi:10.1007/s00701-019-03980-8

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 journal › Article › Academic › peer-review

21 Citations (Web of Science)

Abstract

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 language	English
Pages (from-to)	1955-1964
Number of pages	10
Journal	Acta Neurochirurgica
Volume	161
Issue number	9
DOIs	https://doi.org/10.1007/s00701-019-03980-8
Publication status	Published - Sep 2019

Keywords

Cerebrovascular reactivity
PRx
TBI
Therapeutic intensity
TIL
CEREBRAL PERFUSION-PRESSURE
MODERATE HYPOTHERMIA
AUTOREGULATION
ISOFLURANE
MANAGEMENT
SUPPRESSION

Access to Document

10.1007/s00701-019-03980-8Licence: CC BY

Cite this

Zeiler, F. A., Ercole, A., Beqiri, E., Cabeleira, M., Aries, M., Zoerle, T., Carbonara, M., Stocchetti, N., Smielewski, P., Czosnyka, M., Menon, D. K., Anke, A., Beer, R., Bellander, B-M., Buki, A., Chevallard, G., Chieregato, A., Citerio, G., Czeiter, E., ... CENTER-TBI High Resolution ICU (HR ICU) Sub-Study Participants and Investigators (2019). Cerebrovascular reactivity is not associated with therapeutic intensity in adult traumatic brain injury: a CENTER-TBI analysis. Acta Neurochirurgica, 161(9), 1955-1964. https://doi.org/10.1007/s00701-019-03980-8

@article{beb0f756580843f8a97e69f2ddcdae78,

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

abstract = "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.",

keywords = "Cerebrovascular reactivity, PRx, TBI, Therapeutic intensity, TIL, CEREBRAL PERFUSION-PRESSURE, MODERATE HYPOTHERMIA, AUTOREGULATION, ISOFLURANE, MANAGEMENT, SUPPRESSION",

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

year = "2019",

month = sep,

doi = "10.1007/s00701-019-03980-8",

language = "English",

volume = "161",

pages = "1955--1964",

journal = "Acta Neurochirurgica",

issn = "0001-6268",

publisher = "Springer",

number = "9",

}

Zeiler, FA, Ercole, A, Beqiri, E, Cabeleira, M, Aries, M, Zoerle, T, Carbonara, M, Stocchetti, N, Smielewski, P, Czosnyka, M, Menon, DK, Anke, A, Beer, R, Bellander, B-M, Buki, A, Chevallard, G, Chieregato, A, Citerio, G, Czeiter, E, Depreitere, B, Eapen, G, Frisvold, S, Helbok, R, Jankowski, S, Kondziella, D, Koskinen, L-O, Meyfroidt, G, Moeller, K, Nelson, D, Piippo-Karjalainen, A, Radoi, A, Ragauskas, A, Raj, R, Rhodes, J, Rocka, S, Rossaint, R, Sahuquillo, J, Sakowitz, O, Stevanovic, A, Sundstrom, N, Takala, R, Tamosuitis, T, Tenovuo, O, Vajkoczy, P, Vargiolu, A, Vilcinis, R, Wolf, S, Younsi, A & CENTER-TBI High Resolution ICU (HR ICU) Sub-Study Participants and Investigators 2019, 'Cerebrovascular reactivity is not associated with therapeutic intensity in adult traumatic brain injury: a CENTER-TBI analysis', Acta Neurochirurgica, vol. 161, no. 9, pp. 1955-1964. https://doi.org/10.1007/s00701-019-03980-8

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

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

VL - 161

SP - 1955

EP - 1964

JO - Acta Neurochirurgica

JF - Acta Neurochirurgica

SN - 0001-6268

IS - 9

ER -