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Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest

PURPOSE: The majority of unconscious patients after cardiac arrest (CA) do not fulfill guideline criteria for a likely poor outcome, their prognosis is considered “indeterminate”. We compared brain injury markers in blood for prediction of good outcome and for identifying false positive predictions...

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Autores principales: Moseby-Knappe, Marion, Mattsson-Carlgren, Niklas, Stammet, Pascal, Backman, Sofia, Blennow, Kaj, Dankiewicz, Josef, Friberg, Hans, Hassager, Christian, Horn, Janneke, Kjaergaard, Jesper, Lilja, Gisela, Rylander, Christian, Ullén, Susann, Undén, Johan, Westhall, Erik, Wise, Matt P., Zetterberg, Henrik, Nielsen, Niklas, Cronberg, Tobias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421280/
https://www.ncbi.nlm.nih.gov/pubmed/34417831
http://dx.doi.org/10.1007/s00134-021-06481-4
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author Moseby-Knappe, Marion
Mattsson-Carlgren, Niklas
Stammet, Pascal
Backman, Sofia
Blennow, Kaj
Dankiewicz, Josef
Friberg, Hans
Hassager, Christian
Horn, Janneke
Kjaergaard, Jesper
Lilja, Gisela
Rylander, Christian
Ullén, Susann
Undén, Johan
Westhall, Erik
Wise, Matt P.
Zetterberg, Henrik
Nielsen, Niklas
Cronberg, Tobias
author_facet Moseby-Knappe, Marion
Mattsson-Carlgren, Niklas
Stammet, Pascal
Backman, Sofia
Blennow, Kaj
Dankiewicz, Josef
Friberg, Hans
Hassager, Christian
Horn, Janneke
Kjaergaard, Jesper
Lilja, Gisela
Rylander, Christian
Ullén, Susann
Undén, Johan
Westhall, Erik
Wise, Matt P.
Zetterberg, Henrik
Nielsen, Niklas
Cronberg, Tobias
author_sort Moseby-Knappe, Marion
collection PubMed
description PURPOSE: The majority of unconscious patients after cardiac arrest (CA) do not fulfill guideline criteria for a likely poor outcome, their prognosis is considered “indeterminate”. We compared brain injury markers in blood for prediction of good outcome and for identifying false positive predictions of poor outcome as recommended by guidelines. METHODS: Retrospective analysis of prospectively collected serum samples at 24, 48 and 72 h post arrest within the Target Temperature Management after out-of-hospital cardiac arrest (TTM)-trial. Clinically available markers neuron-specific enolase (NSE) and S100B, and novel markers neurofilament light chain (NFL), total tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were analysed. Normal levels with a priori cutoffs specified by reference laboratories or defined from literature were used to predict good outcome (no to moderate disability, Cerebral Performance Category scale 1–2) at 6 months. RESULTS: Seven hundred and seventeen patients were included. Normal NFL, tau and GFAP had the highest sensitivities (97.2–98% of poor outcome patients had abnormal serum levels) and NPV (normal levels predicted good outcome in 87–95% of patients). Normal S100B and NSE predicted good outcome with NPV 76–82.2%. Normal NSE correctly identified 67/190 (35.3%) patients with good outcome among those classified as “indeterminate outcome” by guidelines. Five patients with single pathological prognostic findings despite normal biomarkers had good outcome. CONCLUSION: Low levels of brain injury markers in blood are associated with good neurological outcome after CA. Incorporating biomarkers into neuroprognostication may help prevent premature withdrawal of life-sustaining therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00134-021-06481-4.
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spelling pubmed-84212802021-09-09 Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest Moseby-Knappe, Marion Mattsson-Carlgren, Niklas Stammet, Pascal Backman, Sofia Blennow, Kaj Dankiewicz, Josef Friberg, Hans Hassager, Christian Horn, Janneke Kjaergaard, Jesper Lilja, Gisela Rylander, Christian Ullén, Susann Undén, Johan Westhall, Erik Wise, Matt P. Zetterberg, Henrik Nielsen, Niklas Cronberg, Tobias Intensive Care Med Original PURPOSE: The majority of unconscious patients after cardiac arrest (CA) do not fulfill guideline criteria for a likely poor outcome, their prognosis is considered “indeterminate”. We compared brain injury markers in blood for prediction of good outcome and for identifying false positive predictions of poor outcome as recommended by guidelines. METHODS: Retrospective analysis of prospectively collected serum samples at 24, 48 and 72 h post arrest within the Target Temperature Management after out-of-hospital cardiac arrest (TTM)-trial. Clinically available markers neuron-specific enolase (NSE) and S100B, and novel markers neurofilament light chain (NFL), total tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were analysed. Normal levels with a priori cutoffs specified by reference laboratories or defined from literature were used to predict good outcome (no to moderate disability, Cerebral Performance Category scale 1–2) at 6 months. RESULTS: Seven hundred and seventeen patients were included. Normal NFL, tau and GFAP had the highest sensitivities (97.2–98% of poor outcome patients had abnormal serum levels) and NPV (normal levels predicted good outcome in 87–95% of patients). Normal S100B and NSE predicted good outcome with NPV 76–82.2%. Normal NSE correctly identified 67/190 (35.3%) patients with good outcome among those classified as “indeterminate outcome” by guidelines. Five patients with single pathological prognostic findings despite normal biomarkers had good outcome. CONCLUSION: Low levels of brain injury markers in blood are associated with good neurological outcome after CA. Incorporating biomarkers into neuroprognostication may help prevent premature withdrawal of life-sustaining therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00134-021-06481-4. Springer Berlin Heidelberg 2021-08-21 2021 /pmc/articles/PMC8421280/ /pubmed/34417831 http://dx.doi.org/10.1007/s00134-021-06481-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial 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-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Original
Moseby-Knappe, Marion
Mattsson-Carlgren, Niklas
Stammet, Pascal
Backman, Sofia
Blennow, Kaj
Dankiewicz, Josef
Friberg, Hans
Hassager, Christian
Horn, Janneke
Kjaergaard, Jesper
Lilja, Gisela
Rylander, Christian
Ullén, Susann
Undén, Johan
Westhall, Erik
Wise, Matt P.
Zetterberg, Henrik
Nielsen, Niklas
Cronberg, Tobias
Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest
title Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest
title_full Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest
title_fullStr Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest
title_full_unstemmed Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest
title_short Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest
title_sort serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest
topic Original
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421280/
https://www.ncbi.nlm.nih.gov/pubmed/34417831
http://dx.doi.org/10.1007/s00134-021-06481-4
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