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

Moseby-Knappe, Marion LU ; Mattsson-Carlgren, Niklas LU orcid ; Stammet, Pascal ; Backman, Sofia LU ; Blennow, Kaj LU ; Dankiewicz, Josef LU orcid ; Friberg, Hans LU ; Hassager, Christian ; Horn, Janneke and Kjaergaard, Jesper , et al. (2021) In Intensive Care Medicine 47(9). p.984-994
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Blood biomarkers, Cardiac arrest, ERC/ESICM guidelines, Good neurological outcome, Neurofilament light, Prognostication
in
Intensive Care Medicine
volume
47
issue
9
pages
984 - 994
publisher
Springer
external identifiers
  • scopus:85113165680
  • pmid:34417831
ISSN
0342-4642
DOI
10.1007/s00134-021-06481-4
language
English
LU publication?
yes
id
5db9dd9c-e2ff-46fe-ab87-3bcebb900c80
date added to LUP
2021-09-06 10:52:38
date last changed
2024-06-16 18:20:41
@article{5db9dd9c-e2ff-46fe-ab87-3bcebb900c80,
  abstract     = {{<p>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.</p>}},
  author       = {{Moseby-Knappe, Marion and Mattsson-Carlgren, Niklas and Stammet, Pascal and Backman, Sofia and Blennow, Kaj and Dankiewicz, Josef and Friberg, Hans and Hassager, Christian and Horn, Janneke and Kjaergaard, Jesper and Lilja, Gisela and Rylander, Christian and Ullén, Susann and Undén, Johan and Westhall, Erik and Wise, Matt P. and Zetterberg, Henrik and Nielsen, Niklas and Cronberg, Tobias}},
  issn         = {{0342-4642}},
  keywords     = {{Blood biomarkers; Cardiac arrest; ERC/ESICM guidelines; Good neurological outcome; Neurofilament light; Prognostication}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{984--994}},
  publisher    = {{Springer}},
  series       = {{Intensive Care Medicine}},
  title        = {{Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest}},
  url          = {{http://dx.doi.org/10.1007/s00134-021-06481-4}},
  doi          = {{10.1007/s00134-021-06481-4}},
  volume       = {{47}},
  year         = {{2021}},
}