Continuous Autoregulatory Indices Derived from Multi-Modal Monitoring: Each One Is Not Like the Other

Frederick A. Zeiler; Joseph Donnelly; David K. Menon; Peter Smielewski; Christian Zweifel; Kenneth Martin Brady; Marek Czosnyka

doi:10.1089/neu.2017.5129

Continuous Autoregulatory Indices Derived from Multi-Modal Monitoring: Each One Is Not Like the Other

Frederick A. Zeiler^*, Joseph Donnelly, David K. Menon, Peter Smielewski, Christian Zweifel, Kenneth Martin Brady, Marek Czosnyka

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

72 Scopus citations

Abstract

We assess the relationships between various continuous measures of autoregulatory capacity in a cohort of adults with traumatic brain injury (TBI). We assessed relationships between autoregulatory indices derived from intracranial pressure (ICP: PRx, PAx, RAC), transcranial Doppler (TCD: Mx, Sx, Dx), brain tissue-oxygenation (ORx), and spatially resolved near infrared spectroscopy (NIRS resolved: TOx, THx). Relationships between indices were assessed using Pearson correlation coefficient, Friedman test, principal component analysis (PCA), agglomerative hierarchal clustering (AHC) and k-means cluster analysis (KMCA). All analytic techniques were repeated for a range of temporal resolutions of data, including minute-by-minute averages, moving means of 30 samples, and grand mean for each patient. Thirty-seven patients were studied. The PRx displayed strong association with PAx/RAC across all the analytical techniques: Pearson correlation (r = 0.682/r = 0.677, p < 0.0001), PCA, AHC, and KMCA in the grand mean data sheet. Most TCD-based indices (Mx, Dx) were correlated and co-clustered on PCA, AHC, and KMCA. The Sx was found to be more closely associated with ICP-derived indices on Pearson correlation, PCA, AHC, and KMCA. The NIRS indices displayed variable correlation with each other and with indices derived from ICP and TCD signals. Of interest, TOx and THx co-cluster with ICP-based indices on PCA and AHC. The ORx failed to display any meaningful correlations with other indices in neither of the analytical method used. Thirty-minute moving average and minute-by-minute data set displayed similar results across all the methods. The RAC, Mx, and Sx were the strongest predictors of outcome at six months. Continuously updating autoregulatory indices are not all correlated with one another. Caution must be advised when utilizing less commonly described autoregulation indices (i.e., ORx) for the clinical assessment of autoregulatory capacity, because they appear to not be related to commonly measured/establish indices, such as PRx. Further prospective validation is required.

Original language	English (US)
Pages (from-to)	3070-3080
Number of pages	11
Journal	Journal of neurotrauma
Volume	34
Issue number	22
DOIs	https://doi.org/10.1089/neu.2017.5129
State	Published - Nov 15 2017

Funding

These studies were supported by the National Institute for Healthcare Research (NIHR, UK) through the Acute Brain Injury and Repair theme of the Cambridge NIHR Biomedical Research Centre, an NIHR Senior Investigator Award to DKM. Authors were also supported by a European Union Framework Program 7 grant (CENTER-TBI; Grant Agreement No. 602150). This work was made possible through salary support through the Cambridge Commonwealth Trust Scholarship, the Royal College of Surgeons of Canada—Harry S. Morton Travelling Fellowship in Surgery, the University of Manitoba Clinician Investigator Program, R. Samuel McLaughlin Research and Education Award, the Manitoba Medical Service Foundation, and the University of Manitoba Faculty of Medicine Dean’s Fellowship Fund. FAZ has received salary support for dedicated research time, during which this project was partially completed. Such salary support came from: the Cambridge Commonwealth Trust Scholarship, the Royal College of Surgeons of Canada—Harry S. Morton Travelling Fellowship in Surgery, the University of Manitoba Clinician Investigator Program, R. Samuel McLaughlin Research and Education Award, the Manitoba Medical Service Foundation, and the University of Manitoba—Faculty of Medicine Dean’s Fellowship Fund. DKM has consultancy agreements and/or research collaborations with GlaxoSmithKline Ltd; Ornim Medical; Shire Medical Ltd; Calico Inc.; Pfizer Ltd; Pressura Ltd; Glide Pharma Ltd; and NeuroTraumaSciences LLC. MC and PS have financial interest in a part of licensing fee for ICM+ software (Cambridge Enterprise Ltd, UK). MC is an honorary co-Director of Technicam Ltd-producer of Cranial Access Device used for CMD insertion. For the remaining authors, no competing financial interests exist.

Keywords

autoregulation
autoregulation index
co-variance
multi-modal monitoring

ASJC Scopus subject areas

Clinical Neurology

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10.1089/neu.2017.5129

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title = "Continuous Autoregulatory Indices Derived from Multi-Modal Monitoring: Each One Is Not Like the Other",

abstract = "We assess the relationships between various continuous measures of autoregulatory capacity in a cohort of adults with traumatic brain injury (TBI). We assessed relationships between autoregulatory indices derived from intracranial pressure (ICP: PRx, PAx, RAC), transcranial Doppler (TCD: Mx, Sx, Dx), brain tissue-oxygenation (ORx), and spatially resolved near infrared spectroscopy (NIRS resolved: TOx, THx). Relationships between indices were assessed using Pearson correlation coefficient, Friedman test, principal component analysis (PCA), agglomerative hierarchal clustering (AHC) and k-means cluster analysis (KMCA). All analytic techniques were repeated for a range of temporal resolutions of data, including minute-by-minute averages, moving means of 30 samples, and grand mean for each patient. Thirty-seven patients were studied. The PRx displayed strong association with PAx/RAC across all the analytical techniques: Pearson correlation (r = 0.682/r = 0.677, p < 0.0001), PCA, AHC, and KMCA in the grand mean data sheet. Most TCD-based indices (Mx, Dx) were correlated and co-clustered on PCA, AHC, and KMCA. The Sx was found to be more closely associated with ICP-derived indices on Pearson correlation, PCA, AHC, and KMCA. The NIRS indices displayed variable correlation with each other and with indices derived from ICP and TCD signals. Of interest, TOx and THx co-cluster with ICP-based indices on PCA and AHC. The ORx failed to display any meaningful correlations with other indices in neither of the analytical method used. Thirty-minute moving average and minute-by-minute data set displayed similar results across all the methods. The RAC, Mx, and Sx were the strongest predictors of outcome at six months. Continuously updating autoregulatory indices are not all correlated with one another. Caution must be advised when utilizing less commonly described autoregulation indices (i.e., ORx) for the clinical assessment of autoregulatory capacity, because they appear to not be related to commonly measured/establish indices, such as PRx. Further prospective validation is required.",

keywords = "autoregulation, autoregulation index, co-variance, multi-modal monitoring",

author = "Zeiler, {Frederick A.} and Joseph Donnelly and Menon, {David K.} and Peter Smielewski and Christian Zweifel and Brady, {Kenneth Martin} and Marek Czosnyka",

note = "Funding Information: These studies were supported by the National Institute for Healthcare Research (NIHR, UK) through the Acute Brain Injury and Repair theme of the Cambridge NIHR Biomedical Research Centre, an NIHR Senior Investigator Award to DKM. Authors were also supported by a European Union Framework Program 7 grant (CENTER-TBI; Grant Agreement No. 602150). Funding Information: This work was made possible through salary support through the Cambridge Commonwealth Trust Scholarship, the Royal College of Surgeons of Canada—Harry S. Morton Travelling Fellowship in Surgery, the University of Manitoba Clinician Investigator Program, R. Samuel McLaughlin Research and Education Award, the Manitoba Medical Service Foundation, and the University of Manitoba Faculty of Medicine Dean{\textquoteright}s Fellowship Fund. Funding Information: FAZ has received salary support for dedicated research time, during which this project was partially completed. Such salary support came from: the Cambridge Commonwealth Trust Scholarship, the Royal College of Surgeons of Canada—Harry S. Morton Travelling Fellowship in Surgery, the University of Manitoba Clinician Investigator Program, R. Samuel McLaughlin Research and Education Award, the Manitoba Medical Service Foundation, and the University of Manitoba—Faculty of Medicine Dean{\textquoteright}s Fellowship Fund. DKM has consultancy agreements and/or research collaborations with GlaxoSmithKline Ltd; Ornim Medical; Shire Medical Ltd; Calico Inc.; Pfizer Ltd; Pressura Ltd; Glide Pharma Ltd; and NeuroTraumaSciences LLC. MC and PS have financial interest in a part of licensing fee for ICM+ software (Cambridge Enterprise Ltd, UK). MC is an honorary co-Director of Technicam Ltd-producer of Cranial Access Device used for CMD insertion. For the remaining authors, no competing financial interests exist. Publisher Copyright: {\textcopyright} Copyright 2017, Mary Ann Liebert, Inc.",

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month = nov,

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doi = "10.1089/neu.2017.5129",

language = "English (US)",

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AU - Zeiler, Frederick A.

AU - Donnelly, Joseph

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AU - Smielewski, Peter

AU - Zweifel, Christian

AU - Brady, Kenneth Martin

AU - Czosnyka, Marek

N1 - Funding Information: These studies were supported by the National Institute for Healthcare Research (NIHR, UK) through the Acute Brain Injury and Repair theme of the Cambridge NIHR Biomedical Research Centre, an NIHR Senior Investigator Award to DKM. Authors were also supported by a European Union Framework Program 7 grant (CENTER-TBI; Grant Agreement No. 602150). Funding Information: This work was made possible through salary support through the Cambridge Commonwealth Trust Scholarship, the Royal College of Surgeons of Canada—Harry S. Morton Travelling Fellowship in Surgery, the University of Manitoba Clinician Investigator Program, R. Samuel McLaughlin Research and Education Award, the Manitoba Medical Service Foundation, and the University of Manitoba Faculty of Medicine Dean’s Fellowship Fund. Funding Information: FAZ has received salary support for dedicated research time, during which this project was partially completed. Such salary support came from: the Cambridge Commonwealth Trust Scholarship, the Royal College of Surgeons of Canada—Harry S. Morton Travelling Fellowship in Surgery, the University of Manitoba Clinician Investigator Program, R. Samuel McLaughlin Research and Education Award, the Manitoba Medical Service Foundation, and the University of Manitoba—Faculty of Medicine Dean’s Fellowship Fund. DKM has consultancy agreements and/or research collaborations with GlaxoSmithKline Ltd; Ornim Medical; Shire Medical Ltd; Calico Inc.; Pfizer Ltd; Pressura Ltd; Glide Pharma Ltd; and NeuroTraumaSciences LLC. MC and PS have financial interest in a part of licensing fee for ICM+ software (Cambridge Enterprise Ltd, UK). MC is an honorary co-Director of Technicam Ltd-producer of Cranial Access Device used for CMD insertion. For the remaining authors, no competing financial interests exist. Publisher Copyright: © Copyright 2017, Mary Ann Liebert, Inc.

PY - 2017/11/15

Y1 - 2017/11/15

N2 - We assess the relationships between various continuous measures of autoregulatory capacity in a cohort of adults with traumatic brain injury (TBI). We assessed relationships between autoregulatory indices derived from intracranial pressure (ICP: PRx, PAx, RAC), transcranial Doppler (TCD: Mx, Sx, Dx), brain tissue-oxygenation (ORx), and spatially resolved near infrared spectroscopy (NIRS resolved: TOx, THx). Relationships between indices were assessed using Pearson correlation coefficient, Friedman test, principal component analysis (PCA), agglomerative hierarchal clustering (AHC) and k-means cluster analysis (KMCA). All analytic techniques were repeated for a range of temporal resolutions of data, including minute-by-minute averages, moving means of 30 samples, and grand mean for each patient. Thirty-seven patients were studied. The PRx displayed strong association with PAx/RAC across all the analytical techniques: Pearson correlation (r = 0.682/r = 0.677, p < 0.0001), PCA, AHC, and KMCA in the grand mean data sheet. Most TCD-based indices (Mx, Dx) were correlated and co-clustered on PCA, AHC, and KMCA. The Sx was found to be more closely associated with ICP-derived indices on Pearson correlation, PCA, AHC, and KMCA. The NIRS indices displayed variable correlation with each other and with indices derived from ICP and TCD signals. Of interest, TOx and THx co-cluster with ICP-based indices on PCA and AHC. The ORx failed to display any meaningful correlations with other indices in neither of the analytical method used. Thirty-minute moving average and minute-by-minute data set displayed similar results across all the methods. The RAC, Mx, and Sx were the strongest predictors of outcome at six months. Continuously updating autoregulatory indices are not all correlated with one another. Caution must be advised when utilizing less commonly described autoregulation indices (i.e., ORx) for the clinical assessment of autoregulatory capacity, because they appear to not be related to commonly measured/establish indices, such as PRx. Further prospective validation is required.

AB - We assess the relationships between various continuous measures of autoregulatory capacity in a cohort of adults with traumatic brain injury (TBI). We assessed relationships between autoregulatory indices derived from intracranial pressure (ICP: PRx, PAx, RAC), transcranial Doppler (TCD: Mx, Sx, Dx), brain tissue-oxygenation (ORx), and spatially resolved near infrared spectroscopy (NIRS resolved: TOx, THx). Relationships between indices were assessed using Pearson correlation coefficient, Friedman test, principal component analysis (PCA), agglomerative hierarchal clustering (AHC) and k-means cluster analysis (KMCA). All analytic techniques were repeated for a range of temporal resolutions of data, including minute-by-minute averages, moving means of 30 samples, and grand mean for each patient. Thirty-seven patients were studied. The PRx displayed strong association with PAx/RAC across all the analytical techniques: Pearson correlation (r = 0.682/r = 0.677, p < 0.0001), PCA, AHC, and KMCA in the grand mean data sheet. Most TCD-based indices (Mx, Dx) were correlated and co-clustered on PCA, AHC, and KMCA. The Sx was found to be more closely associated with ICP-derived indices on Pearson correlation, PCA, AHC, and KMCA. The NIRS indices displayed variable correlation with each other and with indices derived from ICP and TCD signals. Of interest, TOx and THx co-cluster with ICP-based indices on PCA and AHC. The ORx failed to display any meaningful correlations with other indices in neither of the analytical method used. Thirty-minute moving average and minute-by-minute data set displayed similar results across all the methods. The RAC, Mx, and Sx were the strongest predictors of outcome at six months. Continuously updating autoregulatory indices are not all correlated with one another. Caution must be advised when utilizing less commonly described autoregulation indices (i.e., ORx) for the clinical assessment of autoregulatory capacity, because they appear to not be related to commonly measured/establish indices, such as PRx. Further prospective validation is required.

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Continuous Autoregulatory Indices Derived from Multi-Modal Monitoring: Each One Is Not Like the Other

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