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Association of Outcomes with Model-Based Indices of Cerebral Autoregulation After Pediatric Traumatic Brain Injury

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An Invited Commentary to this article was published on 15 July 2021

Abstract

Background

We investigated whether model-based indices of cerebral autoregulation (CA) are associated with outcomes after pediatric traumatic brain injury.

Methods

This was a retrospective analysis of a prospective clinical database of 56 pediatric patients with traumatic brain injury undergoing intracranial pressure monitoring. CA indices were calculated, including pressure reactivity index (PRx), wavelet pressure reactivity index (wPRx), pulse amplitude index (PAx), and correlation coefficient between intracranial pressure pulse amplitude and cerebral perfusion pressure (RAC). Each CA index was used to compute optimal cerebral perfusion pressure (CPP). Time of CPP below lower limit of autoregulation (LLA) or above upper limit of autoregulation (ULA) were computed for each index. Demographic, physiologic, and neuroimaging data were collected. Primary outcome was determined using Pediatric Glasgow Outcome Scale Extended (GOSE-Peds) at 12 months, with higher scores being suggestive of unfavorable outcome. Univariate and multiple linear regression with guided stepwise variable selection was used to find combinations of risk factors that can best explain the variability of GOSE-Peds scores, and the best fit model was applied to the age strata. We hypothesized that higher GOSE-Peds scores were associated with higher CA values and more time below LLA or above ULA for each index.

Results

At the univariate level, CPP, dose of intracranial hypertension, PRx, PAx, wPRx, RAC, percent time more than ULA derived for PAx, and percent time less than LLA derived for PRx, PAx, wPRx, and RAC were all associated with GOSE-Peds scores. The best subset model selection on all pediatric patients identified that when accounting for CPP, increased dose of intracranial hypertension and percent time less than LLA derived for wPRx were independently associated with higher GOSE-Peds scores. Age stratification of the best fit model identified that in children less than 2 years of age or 8 years of age or more, percent time less than LLA derived for wPRx represented the sole independent predictor of higher GOSE-Peds scores when accounting for CPP and dose of intracranial hypertension. For children 2 years or younger to less than 8 years of age, dose of intracranial hypertension was identified as the sole independent predictor of higher GOSE-Peds scores when accounting for CPP and percent time less than LLA derived for wPRx.

Conclusions

Increased dose of intracranial hypertension, PRx, wPRx, PAx, and RAC values and increased percentage time less than LLA based on PRx, wPRx, PAx, and RAC are associated with higher GOSE-Peds scores, suggestive of unfavorable outcome. Reducing intracranial hypertension and maintaining CPP more than LLA based on wPRx may improve outcomes and warrants prospective investigation.

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Funding

This work was funded in part by the United States Department of Defense Congressionally Directed Medical Research Programs Epilepsy Research Program (W81XWH-19-1-0514).

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Authors and Affiliations

  1. Department of Neurosciences, Barrow Neurological Institute at Phoenix Children’s Hospital, 1919 E. Thomas Road, Ambulatory Building B, 4th Floor, Phoenix, AZ, USA

    Brian Appavu, M.’Hamed Temkit, Stephen Foldes, Brian T. Burrows, Austin Jacobson & P. David Adelson

  2. Department of Child Health, University of Arizona College of Medicine, Phoenix, 550 E. Van Buren Street, Phoenix, AZ, USA

    Brian Appavu, Stephen Foldes, Michael Kuwabara & P. David Adelson

  3. Department of Radiology, Phoenix Children’s Hospital, 1919 E. Thomas Road, Phoenix, AZ, USA

    Michael Kuwabara

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  1. Brian Appavu
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  2. M.’Hamed Temkit
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  4. Brian T. Burrows
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  7. P. David Adelson
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Contributions

BA, MT, SF, and PDA contributed to conception and design of this study. BA, MT, SF, BB, MK, AJ, and PDA contributed to acquisition and analysis of data and drafting a significant portion of the article and figures. All authors approved the final draft of this manuscript.

Corresponding author

Correspondence to Brian Appavu.

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Conflicts of Interest

Dr. Appavu previously received a completed research grant from Moberg ICU Solutions, outside the scope of this work. All other authors do not have relevant conflicts of interest.

Ethical Approval/Informed Consent

This study was performed under all ethical research guidelines at Phoenix Children’s Hospital, and the institutional review board (#19-284) at Phoenix Children’s Hospital approved this study.

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This article is related to the Invited Commentary available at https://link.springer.com/article/10.1007/s12028-021-01307-z.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplement 1

Age-stratified demographic and classic physiologic data. n, count; %, percent; CT, computed tomography; IQR, interquartile ratio; PRISM, Pediatric Risk of Mortality; mm, millimeters; mmHg, millimeters of mercury; ICP, intracranial pressure; CPP, cerebral perfusion pressure; ABP, arterial blood pressure; HR, heart rate; bpm, beats per minute; GOSE-Peds, Glasgow Outcome Scale Extended-Pediatrics. (DOCX 15 KB)

Supplement 2

Age-stratified characteristics of model-based indices of cerebral autoregulation. n, count; IQR, interquartile ratio; mmHg, millimeters of mercury; %, percent; PRx, pressure reactivity index; PAx, pulse amplitude index; wPRx, wavelet pressure reactivity index; RAC, correlation coefficient of intracranial pressure pulse amplitude and cerebral perfusion pressure; CPPOpt, optimal cerebral perfusion pressure; LLA, lower limit of autoregulation; ULA, upper limit of autoregulation. (DOCX 18 KB)

Supplement 3

Sex-based differences in model-based indices of cerebral autoregulation. SD, standard deviation; PRx, pressure reactivity index; PAx, pulse amplitude index; wPRx, wavelet pressure reactivity index; RAC; correlation coefficient of intracranial pressure pulse amplitude and cerebral perfusion pressure; %, percent; LLA, lower limit of autoregulation; ULA, upper limit of autoregulation. (DOCX 14 KB)

Supplement 4

Age-stratified univariate analysis of the association of demographic, neuroimaging and physiologic data with GOSE-Peds scores, 12 months post injury. Bold represent significant variables as related to global functional outcome determined by GOSE-Peds, Glasgow Outcome Scale Extended-Pediatrics (GOSE-Peds). RMSE, root mean square error; GCS, Glasgow Coma Scale; PRISM, pediatric risk of mortality; CT, computed tomography; dICH, dose of intracranial hypertension; CPP, cerebral perfusion pressure; ABP, arterial blood pressure; HR, heart rate; mmHg, millimeters of mercury; bpm, beats per minute; PRx, pressure reactivity index; PAx, pulse amplitude index; wPRx, wavelet pressure reactivity index; RAC; correlation coefficient of intracranial pressure pulse amplitude and cerebral perfusion pressure; %, percent; LLA, lower limit of autoregulation; ULA, upper limit of autoregulation. (DOCX 30 KB)

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Appavu, B., Temkit, M., Foldes, S. et al. Association of Outcomes with Model-Based Indices of Cerebral Autoregulation After Pediatric Traumatic Brain Injury. Neurocrit Care 35, 640–650 (2021). https://doi.org/10.1007/s12028-021-01279-0

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