Meaning of Intracranial Pressure-to-Blood Pressure Fisher-Transformed Pearson Correlation–Derived Optimal Cerebral Perfusion Pressure: Testing Empiric Utility in a Mechanistic Model

Objectives: Time-averaged intracranial pressure-to-blood pressure Fisher-transformed Pearson correlation (PRx) is used to assess cerebral autoregulation and derive optimal cerebral perfusion pressure. Empirically, impaired cerebral autoregulation is considered present when PRx is positive; greater difference between time series median cerebral perfusion pressure and optimal cerebral perfusion pressure (ΔCPP) is associated with worse outcomes. Our aims are to better understand: 1) the potential strategies for targeting optimal cerebral perfusion pressure; 2) the relationship between cerebral autoregulation and PRx; and 3) the determinants of greater ΔCPP. Design: Mechanistic simulation using a lumped compartmental model of blood pressure, intracranial pressure, cerebral autoregulation, cerebral blood volume, PaCO2, and cerebral blood flow. Setting: University critical care integrative modeling and precision physiology research group. Subjects: None, in silico studies. Interventions: Simulations in blood pressure, intracranial pressure, PaCO2, and impairment of cerebral autoregulation, with examination of "output" cerebral perfusion pressure versus PRx-plots, optimal cerebral perfusion pressure, and ΔCPP. Measurements and Main Results: In regard to targeting optimal cerebral perfusion pressure, a shift in mean blood pressure or mean intracranial pressure with no change in mean blood pressure, with intact cerebral autoregulation, impacts optimal cerebral perfusion pressure. Second, a positive PRx occurs even with intact cerebral autoregulation. In relation to ΔCPP, for a given input blood pressure profile, with constant intracranial pressure, altering the degree of impairment in cerebral autoregulation or the level of PaCO2 maintains differences to within ±5 mm Hg. Change in intracranial pressure due to either an intermittently prolonged pattern of raised intracranial pressure or terminal escalation shows ΔCPP greater than 10 mm Hg and less than –10 mm Hg, respectively. Conclusions: These mechanistic simulations provide insight into the empiric basis of optimal cerebral perfusion pressure and the significance of PRx and ΔCPP. PRx and optimal cerebral perfusion pressure deviations do not directly reflect changes in cerebral autoregulation but are, in general, related to the presence of complex states involving well-described clinical progressions with raised intracranial pressure. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by a Trailblazer award from the Department of Anesthesiology, Critical Care and Pain Medicine, at Boston Children's Hospital, Boston, MA. Dr. Akhondi-Asl received other support from a Trailblazer Award. Dr. Tasker received funding from a "Trailblazer Award" from the Department of Anesthesiology, Perioperative and Pain Medicine, at Boston Children's Hospital, Boston, MA. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Robert.tasker@childrens.harvard.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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