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Association of deranged cerebrovascular reactivity with brain injury following cardiac arrest: a post-hoc analysis of the COMACARE trial

BACKGROUND: Impaired cerebrovascular reactivity (CVR) is one feature of post cardiac arrest encephalopathy. We studied the incidence and features of CVR by near infrared spectroscopy (NIRS) and associations with outcome and biomarkers of brain injury. METHODS: A post-hoc analysis of 120 comatose OHC...

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Autores principales: Laurikkala, Johanna, Aneman, Anders, Peng, Alexander, Reinikainen, Matti, Pham, Paul, Jakkula, Pekka, Hästbacka, Johanna, Wilkman, Erika, Loisa, Pekka, Toppila, Jussi, Birkelund, Thomas, Blennow, Kaj, Zetterberg, Henrik, Skrifvars, Markus B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477475/
https://www.ncbi.nlm.nih.gov/pubmed/34583763
http://dx.doi.org/10.1186/s13054-021-03764-6
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author Laurikkala, Johanna
Aneman, Anders
Peng, Alexander
Reinikainen, Matti
Pham, Paul
Jakkula, Pekka
Hästbacka, Johanna
Wilkman, Erika
Loisa, Pekka
Toppila, Jussi
Birkelund, Thomas
Blennow, Kaj
Zetterberg, Henrik
Skrifvars, Markus B.
author_facet Laurikkala, Johanna
Aneman, Anders
Peng, Alexander
Reinikainen, Matti
Pham, Paul
Jakkula, Pekka
Hästbacka, Johanna
Wilkman, Erika
Loisa, Pekka
Toppila, Jussi
Birkelund, Thomas
Blennow, Kaj
Zetterberg, Henrik
Skrifvars, Markus B.
author_sort Laurikkala, Johanna
collection PubMed
description BACKGROUND: Impaired cerebrovascular reactivity (CVR) is one feature of post cardiac arrest encephalopathy. We studied the incidence and features of CVR by near infrared spectroscopy (NIRS) and associations with outcome and biomarkers of brain injury. METHODS: A post-hoc analysis of 120 comatose OHCA patients continuously monitored with NIRS and randomised to low- or high-normal oxygen, carbon dioxide and mean arterial blood pressure (MAP) targets for 48 h. The tissue oximetry index (TO(x)) generated by the moving correlation coefficient between cerebral tissue oxygenation measured by NIRS and MAP was used as a dynamic index of CVR with TO(x) > 0 indicating impaired reactivity and TO(x) > 0.3 used to delineate the lower and upper MAP bounds for disrupted CVR. TO(x) was analysed in the 0–12, 12–24, 24–48 h time-periods and integrated over 0–48 h. The primary outcome was the association between TO(x) and six-month functional outcome dichotomised by the cerebral performance category (CPC1-2 good vs. 3–5 poor). Secondary outcomes included associations with MAP bounds for CVR and biomarkers of brain injury. RESULTS: In 108 patients with sufficient data to calculate TO(x), 76 patients (70%) had impaired CVR and among these, chronic hypertension was more common (58% vs. 31%, p = 0.002). Integrated TO(x) for 0–48 h was higher in patients with poor outcome than in patients with good outcome (0.89 95% CI [− 1.17 to 2.94] vs. − 2.71 95% CI [− 4.16 to − 1.26], p = 0.05). Patients with poor outcomes had a decreased upper MAP bound of CVR over time (p = 0.001), including the high-normal oxygen (p = 0.002), carbon dioxide (p = 0.012) and MAP (p = 0.001) groups. The MAP range of maintained CVR was narrower in all time intervals and intervention groups (p < 0.05). NfL concentrations were higher in patients with impaired CVR compared to those with intact CVR (43 IQR [15–650] vs 20 IQR [13–199] pg/ml, p = 0.042). CONCLUSION: Impaired CVR over 48 h was more common in patients with chronic hypertension and associated with poor outcome. Decreased upper MAP bound and a narrower MAP range for maintained CVR were associated with poor outcome and more severe brain injury assessed with NfL. Trial registration ClinicalTrials.gov, NCT02698917. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-021-03764-6.
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spelling pubmed-84774752021-09-28 Association of deranged cerebrovascular reactivity with brain injury following cardiac arrest: a post-hoc analysis of the COMACARE trial Laurikkala, Johanna Aneman, Anders Peng, Alexander Reinikainen, Matti Pham, Paul Jakkula, Pekka Hästbacka, Johanna Wilkman, Erika Loisa, Pekka Toppila, Jussi Birkelund, Thomas Blennow, Kaj Zetterberg, Henrik Skrifvars, Markus B. Crit Care Research BACKGROUND: Impaired cerebrovascular reactivity (CVR) is one feature of post cardiac arrest encephalopathy. We studied the incidence and features of CVR by near infrared spectroscopy (NIRS) and associations with outcome and biomarkers of brain injury. METHODS: A post-hoc analysis of 120 comatose OHCA patients continuously monitored with NIRS and randomised to low- or high-normal oxygen, carbon dioxide and mean arterial blood pressure (MAP) targets for 48 h. The tissue oximetry index (TO(x)) generated by the moving correlation coefficient between cerebral tissue oxygenation measured by NIRS and MAP was used as a dynamic index of CVR with TO(x) > 0 indicating impaired reactivity and TO(x) > 0.3 used to delineate the lower and upper MAP bounds for disrupted CVR. TO(x) was analysed in the 0–12, 12–24, 24–48 h time-periods and integrated over 0–48 h. The primary outcome was the association between TO(x) and six-month functional outcome dichotomised by the cerebral performance category (CPC1-2 good vs. 3–5 poor). Secondary outcomes included associations with MAP bounds for CVR and biomarkers of brain injury. RESULTS: In 108 patients with sufficient data to calculate TO(x), 76 patients (70%) had impaired CVR and among these, chronic hypertension was more common (58% vs. 31%, p = 0.002). Integrated TO(x) for 0–48 h was higher in patients with poor outcome than in patients with good outcome (0.89 95% CI [− 1.17 to 2.94] vs. − 2.71 95% CI [− 4.16 to − 1.26], p = 0.05). Patients with poor outcomes had a decreased upper MAP bound of CVR over time (p = 0.001), including the high-normal oxygen (p = 0.002), carbon dioxide (p = 0.012) and MAP (p = 0.001) groups. The MAP range of maintained CVR was narrower in all time intervals and intervention groups (p < 0.05). NfL concentrations were higher in patients with impaired CVR compared to those with intact CVR (43 IQR [15–650] vs 20 IQR [13–199] pg/ml, p = 0.042). CONCLUSION: Impaired CVR over 48 h was more common in patients with chronic hypertension and associated with poor outcome. Decreased upper MAP bound and a narrower MAP range for maintained CVR were associated with poor outcome and more severe brain injury assessed with NfL. Trial registration ClinicalTrials.gov, NCT02698917. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-021-03764-6. BioMed Central 2021-09-28 /pmc/articles/PMC8477475/ /pubmed/34583763 http://dx.doi.org/10.1186/s13054-021-03764-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Laurikkala, Johanna
Aneman, Anders
Peng, Alexander
Reinikainen, Matti
Pham, Paul
Jakkula, Pekka
Hästbacka, Johanna
Wilkman, Erika
Loisa, Pekka
Toppila, Jussi
Birkelund, Thomas
Blennow, Kaj
Zetterberg, Henrik
Skrifvars, Markus B.
Association of deranged cerebrovascular reactivity with brain injury following cardiac arrest: a post-hoc analysis of the COMACARE trial
title Association of deranged cerebrovascular reactivity with brain injury following cardiac arrest: a post-hoc analysis of the COMACARE trial
title_full Association of deranged cerebrovascular reactivity with brain injury following cardiac arrest: a post-hoc analysis of the COMACARE trial
title_fullStr Association of deranged cerebrovascular reactivity with brain injury following cardiac arrest: a post-hoc analysis of the COMACARE trial
title_full_unstemmed Association of deranged cerebrovascular reactivity with brain injury following cardiac arrest: a post-hoc analysis of the COMACARE trial
title_short Association of deranged cerebrovascular reactivity with brain injury following cardiac arrest: a post-hoc analysis of the COMACARE trial
title_sort association of deranged cerebrovascular reactivity with brain injury following cardiac arrest: a post-hoc analysis of the comacare trial
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477475/
https://www.ncbi.nlm.nih.gov/pubmed/34583763
http://dx.doi.org/10.1186/s13054-021-03764-6
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