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

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          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.


          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.


          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.


          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.

          Electronic supplementary material

          The online version of this article (10.1007/s00701-019-03980-8) contains supplementary material, which is available to authorized users.

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          Most cited references 20

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          Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI): a prospective longitudinal observational study.

          Current classification of traumatic brain injury (TBI) is suboptimal, and management is based on weak evidence, with little attempt to personalize treatment. A need exists for new precision medicine and stratified management approaches that incorporate emerging technologies.
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            Continuous monitoring of cerebrovascular pressure reactivity allows determination of optimal cerebral perfusion pressure in patients with traumatic brain injury.

            To define optimal cerebral perfusion pressure (CPPOPT) in individual head-injured patients using continuous monitoring of cerebrovascular pressure reactivity. To test the hypothesis that patients with poor outcome were managed at a cerebral perfusion pressure (CPP) differing more from their CPPOPT than were patients with good outcome. Retrospective analysis of prospectively collected data. Neurosciences critical care unit of a university hospital. A total of 114 head-injured patients admitted between January 1997 and August 2000 with continuous monitoring of mean arterial blood pressure (MAP) and intracranial pressure (ICP). MAP, ICP, and CPP were continuously recorded and a pressure reactivity index (PRx) was calculated online. PRx is the moving correlation coefficient recorded over 4-min periods between averaged values (6-sec periods) of MAP and ICP representing cerebrovascular pressure reactivity. When cerebrovascular reactivity is intact, PRx has negative or zero values, otherwise PRx is positive. Outcome was assessed at 6 months using the Glasgow Outcome Scale. A total of 13,633 hrs of data were recorded. CPPOPT was defined as the CPP where PRx reaches its minimum value when plotted against CPP. Identification of CPPOPT was possible in 68 patients (60%). In 22 patients (27%), CPPOPT was not found because it presumably lay outside the studied range of CPP. Patients' outcome correlated with the difference between CPP and CPPOPT for patients who were managed on average below CPPOPT (r =.53, p <.001) and for patients whose mean CPP was above CPPOPT (r = -.40, p <.05). CPPOPT could be identified in a majority of patients. Patients with a mean CPP close to CPPOPT were more likely to have a favorable outcome than those whose mean CPP was more different from CPPOPT. We propose use of the criterion of minimal achievable PRx to guide future trials of CPP oriented treatment in head injured patients.
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              Regulation of cerebral autoregulation by carbon dioxide.

              Cerebral autoregulation describes a mechanism that maintains cerebral blood flow stable despite fluctuating perfusion pressure. Multiple nonperfusion pressure processes also regulate cerebral perfusion. These mechanisms are integrated. The effect of the interplay between carbon dioxide and perfusion pressure on cerebral circulation has not been specifically reviewed. On the basis of the published data and speculation on the aspects that are without supportive data, the authors offer a conceptualization delineating the regulation of cerebral autoregulation by carbon dioxide. The authors conclude that hypercapnia causes the plateau to progressively ascend, a rightward shift of the lower limit, and a leftward shift of the upper limit. Conversely, hypocapnia results in the plateau shifting to lower cerebral blood flows, unremarkable change of the lower limit, and unclear change of the upper limit. It is emphasized that a sound understanding of both the limitations and the dynamic and integrated nature of cerebral autoregulation fosters a safer clinical practice.

                Author and article information

                Acta Neurochir (Wien)
                Acta Neurochir (Wien)
                Acta Neurochirurgica
                Springer Vienna (Vienna )
                25 June 2019
                25 June 2019
                : 161
                : 9
                : 1955-1964
                [1 ]ISNI 0000000121885934, GRID grid.5335.0, Division of Anaesthesia, Addenbrooke’s Hospital, , University of Cambridge, ; Cambridge, UK
                [2 ]ISNI 0000 0004 1936 9609, GRID grid.21613.37, Department of Surgery, Rady Faculty of Health Sciences, , University of Manitoba, ; Winnipeg, MB R3A 1R9 Canada
                [3 ]ISNI 0000000121885934, GRID grid.5335.0, Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke’s Hospital, , University of Cambridge, ; Cambridge, UK
                [4 ]ISNI 0000 0004 0480 1382, GRID grid.412966.e, Department of Intensive Care, , Maastricht UMC, ; Maastricht, Netherlands
                [5 ]ISNI 0000 0004 1757 8749, GRID grid.414818.0, Neuro ICU Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, ; Milan, Italy
                [6 ]ISNI 0000 0004 1757 2822, GRID grid.4708.b, Department of Physiopathology and Transplantation, , Milan University, ; Milan, Italy
                [7 ]ISNI 0000000099214842, GRID grid.1035.7, Institute of Electronic Systems, , Warsaw University of Technology, ; Warsaw, Poland
                [8 ]ISNI 0000 0004 1936 9609, GRID grid.21613.37, Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, , University of Manitoba, ; Winnipeg, Canada
                [9 ]ISNI 0000 0004 1936 9609, GRID grid.21613.37, Department of Biomedical Engineering, Faculty of Engineering, , University of Manitoba, ; Winnipeg, Canada
                © The Author(s) 2019

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                Funded by: European Union 7th Framework program
                Award ID: 602150
                Award Recipient :
                Original Article - Brain trauma
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                © Springer-Verlag GmbH Austria, part of Springer Nature 2019


                therapeutic intensity, til, prx, tbi, cerebrovascular reactivity


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