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Published in: Critical Care 1/2017

Open Access 01-12-2017 | Research

Protein S100 as outcome predictor after out-of-hospital cardiac arrest and targeted temperature management at 33 °C and 36 °C

Authors: Pascal Stammet, Josef Dankiewicz, Niklas Nielsen, François Fays, Olivier Collignon, Christian Hassager, Michael Wanscher, Johan Undèn, Jorn Wetterslev, Tommaso Pellis, Anders Aneman, Jan Hovdenes, Matt P. Wise, Georges Gilson, David Erlinge, Janneke Horn, Tobias Cronberg, Michael Kuiper, Jesper Kjaergaard, Yvan Gasche, Yvan Devaux, Hans Friberg, Target Temperature Management after Out-of-Hospital Cardiac Arrest (TTM) trial investigators

Published in: Critical Care | Issue 1/2017

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Abstract

Background

We aimed to investigate the diagnostic performance of S100 as an outcome predictor after out-of-hospital cardiac arrest (OHCA) and the potential influence of two target temperatures (33 °C and 36 °C) on serum levels of S100.

Methods

This is a substudy of the Target Temperature Management after Out-of-Hospital Cardiac Arrest (TTM) trial. Serum levels of S100 were measured a posteriori in a core laboratory in samples collected at 24, 48, and 72 h after OHCA. Outcome at 6 months was assessed using the Cerebral Performance Categories Scale (CPC 1–2 = good outcome, CPC 3–5 = poor outcome).

Results

We included 687 patients from 29 sites in Europe. Median S100 values were higher in patients with a poor outcome at 24, 48, and 72 h: 0.19 (IQR 0.10–0.49) versus 0.08 (IQR 0.06–0.11) μg/ml, 0.16 (IQR 0.10–0.44) versus 0.07 (IQR 0.06–0.11) μg/L, and 0.13 (IQR 0.08–0.26) versus 0.06 (IQR 0.05–0.09) μg/L (p < 0.001), respectively. The ability to predict outcome was best at 24 h with an AUC of 0.80 (95% CI 0.77–0.83). S100 values were higher at 24 and 72 h in the 33 °C group than in the 36 °C group (0.12 [0.07–0.22] versus 0.10 [0.07–0.21] μg/L and 0.09 [0.06–0.17] versus 0.08 [0.05–0.10], respectively) (p < 0.02). In multivariable analyses including baseline variables and the allocated target temperature, the addition of S100 improved the AUC from 0.80 to 0.84 (95% CI 0.81–0.87) (p < 0.001), but S100 was not an independent outcome predictor. Adding S100 to the same model including neuron-specific enolase (NSE) did not further improve the AUC.

Conclusions

The allocated target temperature did not affect S100 to a clinically relevant degree. High S100 values are predictive of poor outcome but do not add value to present prognostication models with or without NSE. S100 measured at 24 h and afterward is of limited value in clinical outcome prediction after OHCA.

Trial registration

ClinicalTrials.gov identifier: NCT01020916. Registered on 25 November 2009.
Appendix
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Literature
1.
go back to reference Lemiale V, Dumas F, Mongardon N, Giovanetti O, Charpentier J, Chiche JD, et al. Intensive care unit mortality after cardiac arrest: the relative contribution of shock and brain injury in a large cohort. Intensive Care Med. 2013;39(11):1972–80.CrossRefPubMed Lemiale V, Dumas F, Mongardon N, Giovanetti O, Charpentier J, Chiche JD, et al. Intensive care unit mortality after cardiac arrest: the relative contribution of shock and brain injury in a large cohort. Intensive Care Med. 2013;39(11):1972–80.CrossRefPubMed
2.
go back to reference Dragancea I, Rundgren M, Englund E, Friberg H, Cronberg T. The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest. Resuscitation. 2013;84(3):337–42.CrossRefPubMed Dragancea I, Rundgren M, Englund E, Friberg H, Cronberg T. The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest. Resuscitation. 2013;84(3):337–42.CrossRefPubMed
3.
go back to reference Laver S, Farrow C, Turner D, Nolan J. Mode of death after admission to an intensive care unit following cardiac arrest. Intensive Care Med. 2004;30(11):2126–8.CrossRefPubMed Laver S, Farrow C, Turner D, Nolan J. Mode of death after admission to an intensive care unit following cardiac arrest. Intensive Care Med. 2004;30(11):2126–8.CrossRefPubMed
4.
go back to reference Donato R. Functional roles of S100 proteins, calcium-binding proteins of the EF-hand type. Biochim Biophys Acta. 1999;1450(3):191–231.CrossRefPubMed Donato R. Functional roles of S100 proteins, calcium-binding proteins of the EF-hand type. Biochim Biophys Acta. 1999;1450(3):191–231.CrossRefPubMed
5.
go back to reference Zimmer DB, Cornwall EH, Landar A, Song W. The S100 protein family: history, function, and expression. Brain Res Bull. 1995;37(4):417–29.CrossRefPubMed Zimmer DB, Cornwall EH, Landar A, Song W. The S100 protein family: history, function, and expression. Brain Res Bull. 1995;37(4):417–29.CrossRefPubMed
6.
go back to reference Schafer BW, Heizmann CW. The S100 family of EF-hand calcium-binding proteins: functions and pathology. Trends Biochem Sci. 1996;21(4):134–40.CrossRefPubMed Schafer BW, Heizmann CW. The S100 family of EF-hand calcium-binding proteins: functions and pathology. Trends Biochem Sci. 1996;21(4):134–40.CrossRefPubMed
7.
go back to reference Sandroni C, Cavallaro F, Callaway CW, Sanna T, D’Arrigo S, Kuiper M, et al. Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: a systematic review and meta-analysis. Part 1: Patients not treated with therapeutic hypothermia. Resuscitation. 2013;84(10):1310–23.CrossRefPubMed Sandroni C, Cavallaro F, Callaway CW, Sanna T, D’Arrigo S, Kuiper M, et al. Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: a systematic review and meta-analysis. Part 1: Patients not treated with therapeutic hypothermia. Resuscitation. 2013;84(10):1310–23.CrossRefPubMed
8.
go back to reference Sandroni C, Cavallaro F, Callaway CW, D’Arrigo S, Sanna T, Kuiper MA, et al. Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: a systematic review and meta-analysis. Part 2: Patients treated with therapeutic hypothermia. Resuscitation. 2013;84(10):1324–38.CrossRefPubMed Sandroni C, Cavallaro F, Callaway CW, D’Arrigo S, Sanna T, Kuiper MA, et al. Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: a systematic review and meta-analysis. Part 2: Patients treated with therapeutic hypothermia. Resuscitation. 2013;84(10):1324–38.CrossRefPubMed
9.
go back to reference Sandroni C, Cariou A, Cavallaro F, Cronberg T, Friberg H, Hoedemaekers C, et al. Prognostication in comatose survivors of cardiac arrest: an advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine. Resuscitation. 2014;85(12):1779–89.CrossRefPubMed Sandroni C, Cariou A, Cavallaro F, Cronberg T, Friberg H, Hoedemaekers C, et al. Prognostication in comatose survivors of cardiac arrest: an advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine. Resuscitation. 2014;85(12):1779–89.CrossRefPubMed
10.
go back to reference Steiner J, Bernstein HG, Bielau H, Berndt A, Brisch R, Mawrin C, et al. Evidence for a wide extra-astrocytic distribution of S100B in human brain. BMC Neurosci. 2007;8:2.CrossRefPubMedPubMedCentral Steiner J, Bernstein HG, Bielau H, Berndt A, Brisch R, Mawrin C, et al. Evidence for a wide extra-astrocytic distribution of S100B in human brain. BMC Neurosci. 2007;8:2.CrossRefPubMedPubMedCentral
11.
go back to reference Unden J, Bellner J, Eneroth M, Alling C, Ingebrigtsen T, Romner B. Raised serum S100B levels after acute bone fractures without cerebral injury. J Trauma. 2005;58(1):59–61.CrossRefPubMed Unden J, Bellner J, Eneroth M, Alling C, Ingebrigtsen T, Romner B. Raised serum S100B levels after acute bone fractures without cerebral injury. J Trauma. 2005;58(1):59–61.CrossRefPubMed
12.
go back to reference Unden J, Christensson B, Bellner J, Alling C, Romner B. Serum S100B levels in patients with cerebral and extracerebral infectious disease. Scand J Infect Dis. 2004;36(1):10–3.CrossRefPubMed Unden J, Christensson B, Bellner J, Alling C, Romner B. Serum S100B levels in patients with cerebral and extracerebral infectious disease. Scand J Infect Dis. 2004;36(1):10–3.CrossRefPubMed
13.
go back to reference Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, et al. Targeted temperature management at 33 °C versus 36 °C after cardiac arrest. N Engl J Med. 2013;369(23):2197–206.CrossRefPubMed Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, et al. Targeted temperature management at 33 °C versus 36 °C after cardiac arrest. N Engl J Med. 2013;369(23):2197–206.CrossRefPubMed
14.
go back to reference Nielsen N, Wetterslev J, al-Subaie N, Andersson B, Bro-Jeppesen J, Bishop G, et al. Target Temperature Management after out-of-hospital cardiac arrest—a randomized, parallel-group, assessor-blinded clinical trial—rationale and design. Am Heart J. 2012;163(4):541–8.CrossRefPubMed Nielsen N, Wetterslev J, al-Subaie N, Andersson B, Bro-Jeppesen J, Bishop G, et al. Target Temperature Management after out-of-hospital cardiac arrest—a randomized, parallel-group, assessor-blinded clinical trial—rationale and design. Am Heart J. 2012;163(4):541–8.CrossRefPubMed
15.
go back to reference Nielsen N, Winkel P, Cronberg T, Erlinge D, Friberg H, Gasche Y, et al. Detailed statistical analysis plan for the target temperature management after out-of-hospital cardiac arrest trial. Trials. 2013;14:300.CrossRefPubMedPubMedCentral Nielsen N, Winkel P, Cronberg T, Erlinge D, Friberg H, Gasche Y, et al. Detailed statistical analysis plan for the target temperature management after out-of-hospital cardiac arrest trial. Trials. 2013;14:300.CrossRefPubMedPubMedCentral
16.
17.
go back to reference Stammet P, Collignon O, Hassager C, Wise MP, Hovdenes J, Aneman A, et al. Neuron-specific enolase as a predictor of death or poor neurological outcome after out-of-hospital cardiac arrest and targeted temperature management at 33 °C and 36 °C. J Am Coll Cardiol. 2015;65(19):2104–14.CrossRefPubMed Stammet P, Collignon O, Hassager C, Wise MP, Hovdenes J, Aneman A, et al. Neuron-specific enolase as a predictor of death or poor neurological outcome after out-of-hospital cardiac arrest and targeted temperature management at 33 °C and 36 °C. J Am Coll Cardiol. 2015;65(19):2104–14.CrossRefPubMed
18.
go back to reference Pfeifer R, Franz M, Figulla HR. Hypothermia after cardiac arrest does not affect serum levels of neuron-specific enolase and protein S-100b. Acta Anaesthesiol Scand. 2014;58(9):1093–100.CrossRefPubMed Pfeifer R, Franz M, Figulla HR. Hypothermia after cardiac arrest does not affect serum levels of neuron-specific enolase and protein S-100b. Acta Anaesthesiol Scand. 2014;58(9):1093–100.CrossRefPubMed
19.
go back to reference Tiainen M, Roine RO, Pettila V, Takkunen O. Serum neuron-specific enolase and S-100B protein in cardiac arrest patients treated with hypothermia. Stroke. 2003;34(12):2881–6.CrossRefPubMed Tiainen M, Roine RO, Pettila V, Takkunen O. Serum neuron-specific enolase and S-100B protein in cardiac arrest patients treated with hypothermia. Stroke. 2003;34(12):2881–6.CrossRefPubMed
20.
go back to reference Rundgren M, Karlsson T, Nielsen N, Cronberg T, Johnsson P, Friberg H. Neuron specific enolase and S-100B as predictors of outcome after cardiac arrest and induced hypothermia. Resuscitation. 2009;80(7):784–9.CrossRefPubMed Rundgren M, Karlsson T, Nielsen N, Cronberg T, Johnsson P, Friberg H. Neuron specific enolase and S-100B as predictors of outcome after cardiac arrest and induced hypothermia. Resuscitation. 2009;80(7):784–9.CrossRefPubMed
21.
go back to reference Stammet P, Wagner DR, Gilson G, Devaux Y. Modeling serum level of s100β and bispectral index to predict outcome after cardiac arrest. J Am Coll Cardiol. 2013;62(9):851–8.CrossRefPubMed Stammet P, Wagner DR, Gilson G, Devaux Y. Modeling serum level of s100β and bispectral index to predict outcome after cardiac arrest. J Am Coll Cardiol. 2013;62(9):851–8.CrossRefPubMed
22.
go back to reference Einav S, Kaufman N, Algur N, Kark JD. Modeling serum biomarkers S100β and neuron-specific enolase as predictors of outcome after out-of-hospital cardiac arrest: an aid to clinical decision making. J Am Coll Cardiol. 2012;60(4):304–11.CrossRefPubMed Einav S, Kaufman N, Algur N, Kark JD. Modeling serum biomarkers S100β and neuron-specific enolase as predictors of outcome after out-of-hospital cardiac arrest: an aid to clinical decision making. J Am Coll Cardiol. 2012;60(4):304–11.CrossRefPubMed
23.
go back to reference Bottiger BW, Mobes S, Glatzer R, Bauer H, Gries A, Bartsch P, et al. Astroglial protein S-100 is an early and sensitive marker of hypoxic brain damage and outcome after cardiac arrest in humans. Circulation. 2001;103(22):2694–8.CrossRefPubMed Bottiger BW, Mobes S, Glatzer R, Bauer H, Gries A, Bartsch P, et al. Astroglial protein S-100 is an early and sensitive marker of hypoxic brain damage and outcome after cardiac arrest in humans. Circulation. 2001;103(22):2694–8.CrossRefPubMed
24.
go back to reference Martens P, Raabe A, Johnsson P. Serum S-100 and neuron-specific enolase for prediction of regaining consciousness after global cerebral ischemia. Stroke. 1998;29(11):2363–6.CrossRefPubMed Martens P, Raabe A, Johnsson P. Serum S-100 and neuron-specific enolase for prediction of regaining consciousness after global cerebral ischemia. Stroke. 1998;29(11):2363–6.CrossRefPubMed
25.
go back to reference Larsson IM, Wallin E, Kristofferzon ML, Niessner M, Zetterberg H, Rubertsson S. Post-cardiac arrest serum levels of glial fibrillary acidic protein for predicting neurological outcome. Resuscitation. 2014;85(12):1654–61.CrossRefPubMed Larsson IM, Wallin E, Kristofferzon ML, Niessner M, Zetterberg H, Rubertsson S. Post-cardiac arrest serum levels of glial fibrillary acidic protein for predicting neurological outcome. Resuscitation. 2014;85(12):1654–61.CrossRefPubMed
26.
go back to reference Shinozaki K, Oda S, Sadahiro T, Nakamura M, Abe R, Nakada TA, et al. Serum S-100B is superior to neuron-specific enolase as an early prognostic biomarker for neurological outcome following cardiopulmonary resuscitation. Resuscitation. 2009;80(8):870–5.CrossRefPubMed Shinozaki K, Oda S, Sadahiro T, Nakamura M, Abe R, Nakada TA, et al. Serum S-100B is superior to neuron-specific enolase as an early prognostic biomarker for neurological outcome following cardiopulmonary resuscitation. Resuscitation. 2009;80(8):870–5.CrossRefPubMed
27.
go back to reference Westaby S, Johnsson P, Parry AJ, Blomqvist S, Solem JO, Alling C, et al. Serum S100 protein: a potential marker for cerebral events during cardiopulmonary bypass. Ann Thorac Surg. 1996;61(1):88–92.CrossRefPubMed Westaby S, Johnsson P, Parry AJ, Blomqvist S, Solem JO, Alling C, et al. Serum S100 protein: a potential marker for cerebral events during cardiopulmonary bypass. Ann Thorac Surg. 1996;61(1):88–92.CrossRefPubMed
28.
go back to reference Undén J, Ingebrigtsen T, Romner B, Scandinavian Neurotrauma Committee (SNC). Scandinavian guidelines for initial management of minimal, mild and moderate head injuries in adults: an evidence and consensus-based update. BMC Med. 2013;11:50.CrossRefPubMedPubMedCentral Undén J, Ingebrigtsen T, Romner B, Scandinavian Neurotrauma Committee (SNC). Scandinavian guidelines for initial management of minimal, mild and moderate head injuries in adults: an evidence and consensus-based update. BMC Med. 2013;11:50.CrossRefPubMedPubMedCentral
29.
go back to reference Zandbergen EG, Hijdra A, Koelman JH, Hart AA, Vos PE, Verbeek MM, et al. Prediction of poor outcome within the first 3 days of postanoxic coma. Neurology. 2006;66(1):62–8.CrossRefPubMed Zandbergen EG, Hijdra A, Koelman JH, Hart AA, Vos PE, Verbeek MM, et al. Prediction of poor outcome within the first 3 days of postanoxic coma. Neurology. 2006;66(1):62–8.CrossRefPubMed
30.
go back to reference Nolan JP, Soar J, Cariou A, Cronberg T, Moulaert VR, Deakin CD, et al. European Resuscitation Council and European Society of Intensive Care Medicine Guidelines for Post-resuscitation Care 2015: Section 5 of the European Resuscitation Council Guidelines for Resuscitation 2015. Resuscitation. 2015;95:202–22.CrossRefPubMed Nolan JP, Soar J, Cariou A, Cronberg T, Moulaert VR, Deakin CD, et al. European Resuscitation Council and European Society of Intensive Care Medicine Guidelines for Post-resuscitation Care 2015: Section 5 of the European Resuscitation Council Guidelines for Resuscitation 2015. Resuscitation. 2015;95:202–22.CrossRefPubMed
Metadata
Title
Protein S100 as outcome predictor after out-of-hospital cardiac arrest and targeted temperature management at 33 °C and 36 °C
Authors
Pascal Stammet
Josef Dankiewicz
Niklas Nielsen
François Fays
Olivier Collignon
Christian Hassager
Michael Wanscher
Johan Undèn
Jorn Wetterslev
Tommaso Pellis
Anders Aneman
Jan Hovdenes
Matt P. Wise
Georges Gilson
David Erlinge
Janneke Horn
Tobias Cronberg
Michael Kuiper
Jesper Kjaergaard
Yvan Gasche
Yvan Devaux
Hans Friberg
Target Temperature Management after Out-of-Hospital Cardiac Arrest (TTM) trial investigators
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2017
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-017-1729-7

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