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      The impact of hypertonic saline on cerebrovascular reactivity and compensatory reserve in traumatic brain injury: an exploratory analysis

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          Abstract

          Background

          Intravenous hypertonic saline is utilized commonly in critical care for treatment of acute or refractory elevations of intracranial pressure (ICP) in traumatic brain injury (TBI) patients. Though there is a clear understanding of the general physiological effects of a hypertonic saline solution over long periods of time, smaller epoch effects of hypertonic saline (HTS) have not been thoroughly analyzed. The aim of this study was to perform a direct evaluation of the high-frequency response of HTS on the cerebrovascular physiological responses in TBI.

          Methods

          We retrospectively reviewed our prospectively maintained adult TBI database for those with archived high-frequency cerebral physiology and available HTS treatment information. We evaluated different epochs of physiology around HTS bolus dosing, comparing pre- with post-HTS. We assessed for changes in slow fluctuations in ICP, pulse amplitude of ICP (AMP), cerebral perfusion pressure (CPP), mean arterial pressure (MAP), cerebrovascular reactivity (as measured through pressure reactivity index (PRx)), and cerebral compensatory reserve (correlation (R) between AMP (A) and ICP (P)). Comparisons of mean measures and percentage time above clinically relevant thresholds for the physiological parameters were compared pre- and post-HTS using descriptive statistics and Mann-Whitney U testing. We assessed for subgroups of physiological responses using latent profile analysis (LPA).

          Results

          Fifteen patients underwent 69 distinct bolus infusions of hypertonic saline. Apart from the well-documented decrease in ICP, there was also a reduction in AMP. The analysis of cerebrovascular reactivity response to HTS solution had two main effects. For patients with grossly impaired cerebrovascular reactivity pre-HTS (PRx > + 0.30), HTS bolus led to improved reactivity. However, for those with intact cerebrovascular reactivity pre-HTS (PRx < 0), HTS bolus demonstrated a trend towards more impaired reactivity. This indicates that HTS has different impacts, dependent on pre-bolus cerebrovascular status. There was no significant change in metrics of cerebral compensatory reserve. LPA failed to demonstrate any subgroups of physiological responses to HTS administration.

          Conclusions

          The direct decrease in ICP and AMP confirms that a bolus dose of a HTS solution is an effective therapeutic agent for intracranial hypertension. However, in patients with intact autoregulation, hypertonic saline may impair cerebral hemodynamics. These findings regarding cerebrovascular reactivity remain preliminary and require further investigation.

          Electronic supplementary material

          The online version of this article (10.1007/s00701-020-04579-0) contains supplementary material, which is available to authorized users.

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          Most cited references35

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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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              Visualizing the pressure and time burden of intracranial hypertension in adult and paediatric traumatic brain injury.

              To assess the impact of the duration and intensity of episodes of increased intracranial pressure on 6-month neurological outcome in adult and paediatric traumatic brain injury.
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                Author and article information

                Contributors
                log.froese@gmail.com
                dianj@myumanitoba.ca
                leenbatson@gmail.com
                gomeza35@myumanitoba.ca
                bertram.j.unger@gmail.com
                Frederick.Zeiler@umanitoba.ca
                Journal
                Acta Neurochir (Wien)
                Acta Neurochir (Wien)
                Acta Neurochirurgica
                Springer Vienna (Vienna )
                0001-6268
                0942-0940
                21 September 2020
                : 1-11
                Affiliations
                [1 ]GRID grid.21613.37, ISNI 0000 0004 1936 9609, Biomedical Engineering, Faculty of Engineering, , University of Manitoba, ; Winnipeg, Canada
                [2 ]GRID grid.21613.37, ISNI 0000 0004 1936 9609, Section of Neurosurgery, Department of Surgery, Rady Faculty of Health Sciences, , University of Manitoba, ; Winnipeg, MB Canada
                [3 ]GRID grid.21613.37, ISNI 0000 0004 1936 9609, Department of Anatomy and Cell Science, Rady Faculty of Health Sciences, , University of Manitoba, ; Winnipeg, Canada
                [4 ]GRID grid.21613.37, ISNI 0000 0004 1936 9609, Section of Critical Care, Department of Medicine, Rady Faculty of Health Sciences, , University of Manitoba, ; Winnipeg, Canada
                [5 ]GRID grid.21613.37, ISNI 0000 0004 1936 9609, Centre on Aging, , University of Manitoba, ; Winnipeg, Canada
                [6 ]GRID grid.5335.0, ISNI 0000000121885934, Division of Anaesthesia, Department of Medicine, Addenbrooke’s Hospital, , University of Cambridge, ; Cambridge, UK
                Author information
                http://orcid.org/0000-0003-1737-0510
                Article
                4579
                10.1007/s00701-020-04579-0
                7505542
                32959342
                28f23a85-6285-4641-96e4-7063b372ef77
                © Springer-Verlag GmbH Austria, part of Springer Nature 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 24 June 2020
                : 7 September 2020
                Categories
                Original Article - Brain trauma

                Surgery
                cerebrovascular circulation,cerebrovascular response,hypertonic saline,intracranial pressure,pressure reactivity index,sodium chloride

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