Forskning ved Københavns Universitet - Københavns Universitet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Marion Moseby-Knappe
  • Niklas Mattsson-Carlgren
  • Pascal Stammet
  • Sofia Backman
  • Kaj Blennow
  • Josef Dankiewicz
  • Hans Friberg
  • Hassager, Christian
  • Janneke Horn
  • Jesper Kjaergaard
  • Gisela Lilja
  • Christian Rylander
  • Susann Ullén
  • Johan Undén
  • Erik Westhall
  • Matt P. Wise
  • Henrik Zetterberg
  • Niklas Nielsen
  • Tobias Cronberg

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.

OriginalsprogEngelsk
TidsskriftIntensive Care Medicine
Vol/bind47
Sider (fra-til)984–994
ISSN0342-4642
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
Open access funding provided by Lund University. Funding for the study was provided by the Swedish Research Council, Swedish Heart Lung Foundation, Arbetsmarknadens Försäkringsaktiebolag Insurance Foundation, the Skåne University Hospital Foundations, the Gyllenstierna-Krapperup Foundation, and governmental funding of clinical research within the Swedish National Health System, the County Council of Skåne; the Swedish Society of Medicine; the Koch Foundation; TrygFonden (Denmark); European Clinical Research Infrastructures Network; Thelma Zoega Foundation; Stig and Ragna Gorthon Foundation; Thure Carlsson Foundation; Hans-Gabriel and Alice Trolle-Wachtmeister Foundation for Medical Research; Lions Research fund Skåne; South Swedish Hospital Region Research Funds; the Swedish Brain Foundation; the Lundbeck Foundation; and the Torsten Söderberg foundation at the Royal Swedish Academy of Sciences. HZ is a Wallenberg Scholar. NMC is a Wallenberg Molecular Medicine Fellow.Role of the Funder/Sponsor: the funding organizations had no role in the design and conduct. of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Funding Information:
MMK, NMC, PS, SB, JD, HF, CH, JH, GL, CR, SU, JH, EW, MW, NN and TC report no conflicts of interest. HZ has served at scientific advisory boards for Eisai, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies and CogRx, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). KB has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, JOMDD/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. JK reports funding from NovoNordisk foundation NNF17OC0028706, for work outside the present manuscript.

Publisher Copyright:
© 2021, The Author(s).

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