. 2021 Jan;47(1):39-48.

doi: 10.1007/s00134-020-06218-9. Epub 2020 Aug 27.

Neurofilament light as an outcome predictor after cardiac arrest: a post hoc analysis of the COMACARE trial

Lauri Wihersaari¹, Nicholas J Ashton^{2

3

4

5}, Matti Reinikainen¹, Pekka Jakkula⁶, Ville Pettilä⁶, Johanna Hästbacka⁶, Marjaana Tiainen⁷, Pekka Loisa⁸, Hans Friberg⁹, Tobias Cronberg¹⁰, Kaj Blennow^{2

11}, Henrik Zetterberg^{2

11

12

13}, Markus B Skrifvars¹⁴; COMACARE STUDY GROUP

Collaborators, Affiliations

Collaborators

COMACARE STUDY GROUP:
Raili Laru-Sompa, Anni Pulkkinen, Mikko Reilama, Sinikka Tolmunen, Minna Bäcklund, Jonna Heinonen, Johanna Hästbacka, Pekka Jakkula, Nina Lundbom, Marcus Norrgård, Marjatta Okkonen, Ville Pettilä, Markus B Skrifvars, Tarja Suhonen, Marjaana Tiainen, Tuukka Tikka, Marjut Timonen, Jussi Toppila, Miia Valkonen, Erika Wilkman, Teemu Hult, Tuomas Oksanen, Stepani Bendel, Elina Halonen, Sari Rahikainen, Saija Rissanen, Eija Vaskelainen, Tanja Eiserbeck, Sirkku Heino, Helena Jyrkönen, Matti Reinikainen, Johanna Räsänen, Tero Surakka, Talvikki Koskue, Petteri Kujala, Pekka Loisa, Marika Lähde, Jari Kalliomäki, Sari Karlsson, Atte Kukkurainen, Simo Varila

Affiliations

¹ Department of Anaesthesiology and Intensive Care, Kuopio University Hospital, Kuopio, Finland.
² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
³ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
⁴ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁵ NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
⁶ Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁷ Department of Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁸ Department of Intensive Care, Päijät-Häme Central Hospital, Lahti, Finland.
⁹ Department of Clinical Sciences Lund, Anesthesiology and Intensive Care, Lund University, Skane University Hospital, Malmö, Sweden.
¹⁰ Department of Clinical Sciences Lund, Neurology, Lund University, Skane University Hospital, Lund, Sweden.
¹¹ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹² UK Dementia Research Institute at UCL, London, UK.
¹³ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
¹⁴ Department of Emergency Care and Services, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. markus.skrifvars@hus.fi.

PMID: 32852582
PMCID: PMC7782453
DOI: 10.1007/s00134-020-06218-9

Neurofilament light as an outcome predictor after cardiac arrest: a post hoc analysis of the COMACARE trial

Lauri Wihersaari et al. Intensive Care Med. 2021 Jan.

. 2021 Jan;47(1):39-48.

doi: 10.1007/s00134-020-06218-9. Epub 2020 Aug 27.

Authors

Collaborators

COMACARE STUDY GROUP:
Raili Laru-Sompa, Anni Pulkkinen, Mikko Reilama, Sinikka Tolmunen, Minna Bäcklund, Jonna Heinonen, Johanna Hästbacka, Pekka Jakkula, Nina Lundbom, Marcus Norrgård, Marjatta Okkonen, Ville Pettilä, Markus B Skrifvars, Tarja Suhonen, Marjaana Tiainen, Tuukka Tikka, Marjut Timonen, Jussi Toppila, Miia Valkonen, Erika Wilkman, Teemu Hult, Tuomas Oksanen, Stepani Bendel, Elina Halonen, Sari Rahikainen, Saija Rissanen, Eija Vaskelainen, Tanja Eiserbeck, Sirkku Heino, Helena Jyrkönen, Matti Reinikainen, Johanna Räsänen, Tero Surakka, Talvikki Koskue, Petteri Kujala, Pekka Loisa, Marika Lähde, Jari Kalliomäki, Sari Karlsson, Atte Kukkurainen, Simo Varila

Affiliations

¹ Department of Anaesthesiology and Intensive Care, Kuopio University Hospital, Kuopio, Finland.
² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
³ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
⁴ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁵ NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
⁶ Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁷ Department of Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁸ Department of Intensive Care, Päijät-Häme Central Hospital, Lahti, Finland.
⁹ Department of Clinical Sciences Lund, Anesthesiology and Intensive Care, Lund University, Skane University Hospital, Malmö, Sweden.
¹⁰ Department of Clinical Sciences Lund, Neurology, Lund University, Skane University Hospital, Lund, Sweden.
¹¹ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹² UK Dementia Research Institute at UCL, London, UK.
¹³ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
¹⁴ Department of Emergency Care and Services, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. markus.skrifvars@hus.fi.

PMID: 32852582
PMCID: PMC7782453
DOI: 10.1007/s00134-020-06218-9

Abstract

Purpose: Neurofilament light (NfL) is a biomarker reflecting neurodegeneration and acute neuronal injury, and an increase is found following hypoxic brain damage. We assessed the ability of plasma NfL to predict outcome in comatose patients after out-of-hospital cardiac arrest (OHCA). We also compared plasma NfL concentrations between patients treated with two different targets of arterial carbon dioxide tension (PaCO₂), arterial oxygen tension (PaO₂), and mean arterial pressure (MAP).

Methods: We measured NfL concentrations in plasma obtained at intensive care unit admission and at 24, 48, and 72 h after OHCA. We assessed neurological outcome at 6 months and defined a good outcome as Cerebral Performance Category (CPC) 1-2 and poor outcome as CPC 3-5.

Results: Six-month outcome was good in 73/112 (65%) patients. Forty-eight hours after OHCA, the median NfL concentration was 19 (interquartile range [IQR] 11-31) pg/ml in patients with good outcome and 2343 (587-5829) pg/ml in those with poor outcome, p < 0.001. NfL predicted poor outcome with an area under the receiver operating characteristic curve (AUROC) of 0.98 (95% confidence interval [CI] 0.97-1.00) at 24 h, 0.98 (0.97-1.00) at 48 h, and 0.98 (0.95-1.00) at 72 h. NfL concentrations were lower in the higher MAP (80-100 mmHg) group than in the lower MAP (65-75 mmHg) group at 48 h (median, 23 vs. 43 pg/ml, p = 0.04). PaCO₂ and PaO₂ targets did not associate with NfL levels.

Conclusions: NfL demonstrated excellent prognostic accuracy after OHCA. Higher MAP was associated with lower NfL concentrations.

Keywords: Biomarkers; Cardiac arrest; Neurofilament light (NfL); Prognostication.

PubMed Disclaimer

Conflict of interest statement

Markus Skrifvars reports speakers’ fees and travel grants from BARD Medical (Ireland) and a research grant from GE Healthcare. Kaj Blennow has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, 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. Henrik Zetterberg has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed and CogRx, has given lectures in symposia sponsored by 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.

Figures

**Fig. 1**
Flowchart of the study population. *ICU* intensive care unit

**Fig. 2**
Scatter plots and box plots presenting neurofilament light (NfL) concentrations at intensive care unit admission (0 h) and 24, 48 and 72 h after cardiac arrest for patients with good outcome (Cerebral Performance Category [CPC] 1–2) and those with poor outcome (CPC 3–5) with a 10-based logarithmic scale. Dots present concentrations for individual patients. Each box depicts the interquartile range, the line inside the box shows the median value, and the whiskers show the range of values

**Fig. 3**
Receiver operating characteristic curves and areas under the curves (AUROC) with 95% confidence intervals (CI) for NfL, NSE and S100B at intensive care unit (ICU) admission and 24, 48 and 72 h after cardiac arrest, presenting these biomarkers’ ability to discriminate between patients with good outcome (Cerebral Performance Category [CPC] 1–2) and those with poor outcome (CPC 3–5) at six months. *NfL* neurofilament light, *NSE* neuron-specific enolase

See this image and copyright information in PMC

Comment in

Neurofilament to predict post-anoxic neurological outcome: are we ready for the prime time?
Taccone FS, Nolan JP, Hoedemaekers CWE. Taccone FS, et al. Intensive Care Med. 2021 Jan;47(1):77-79. doi: 10.1007/s00134-020-06309-7. Epub 2020 Nov 9. Intensive Care Med. 2021. PMID: 33169216 No abstract available.

References

1. Nolan JP, Berg RA, Callaway CW, Morrison LJ, Nadkarni V, Perkins GD, Sandroni C, Skrifvars MB, Soar J, Sunde K, Cariou A. The present and future of cardiac arrest care: international experts reach out to caregivers and healthcare authorities. Intensive Care Med. 2018;44:823–832. doi: 10.1007/s00134-018-5230-9. - DOI - PubMed
1. Sandroni C, Combes A, Nolan JP. Focus on post-resuscitation care. Intensive Care Med. 2019;45:1283–1287. doi: 10.1007/s00134-019-05666-2. - DOI - PubMed
1. Efendijev I, Folger D, Raj R, Reinikainen M, Pekkarinen PT, Litonius E, Skrifvars MB. Outcomes and healthcare-associated costs 1 year after intensive care-treated cardiac arrest. Resuscitation. 2018;131:128–134. doi: 10.1016/j.resuscitation.2018.06.028. - DOI - PubMed
1. Sandroni C, Soar J, Friberg H. Does this comatose survivor of cardiac arrest have a poor prognosis? Intensive Care Med. 2016;42:104–106. doi: 10.1007/s00134-015-4082-9. - DOI - PubMed
1. Nolan JP, Soar J, Cariou A, Cronberg T, Moulaert VR, Deakin CD, Bottiger BW, Friberg H, Sunde K, Sandroni C, European Resuscitation C, European Society of Intensive Care M European Resuscitation Council and European Society of Intensive Care Medicine 2015 guidelines for post-resuscitation care. Intensive Care Med. 2015;41:2039–2056. doi: 10.1007/s00134-015-4051-3. - DOI - PubMed

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Neurofilament light as an outcome predictor after cardiac arrest: a post hoc analysis of the COMACARE trial

Collaborators

Affiliations

Neurofilament light as an outcome predictor after cardiac arrest: a post hoc analysis of the COMACARE trial

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources