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

Stammet, Pascal; Dankiewicz, Josef LU ; Nielsen, Niklas LU ; Fays, François; Collignon, Olivier; Hassager, Christian; Wanscher, Michael; Undén, Johan LU ; Wetterslev, Jorn and Pellis, Tommaso, et al. (2017) In Critical Care 21(1).
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... (More)

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.

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Biomarker, Cerebral performance, Neuroprognostication, Prognosis, S100
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Critical Care
volume
21
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85021054478
  • wos:000403589500001
ISSN
1364-8535
DOI
10.1186/s13054-017-1729-7
language
English
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yes
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e8833811-839c-4abd-b541-7a4f7f758975
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2017-08-11 11:40:53
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2018-01-07 12:14:28
@article{e8833811-839c-4abd-b541-7a4f7f758975,
  abstract     = {<p>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 &lt; 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 &lt; 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 &lt; 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.</p>},
  articleno    = {153},
  author       = {Stammet, Pascal and Dankiewicz, Josef and Nielsen, Niklas and Fays, François and Collignon, Olivier and Hassager, Christian and Wanscher, Michael and Undén, Johan and Wetterslev, Jorn and Pellis, Tommaso and Aneman, Anders and Hovdenes, Jan and Wise, Matt P and Gilson, Georges and Erlinge, David and Horn, Janneke and Cronberg, Tobias and Kuiper, Michael and Kjaergaard, Jesper and Gasche, Yvan and Devaux, Yvan and Friberg, Hans and , },
  issn         = {1364-8535},
  keyword      = {Biomarker,Cerebral performance,Neuroprognostication,Prognosis,S100},
  language     = {eng},
  month        = {06},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Critical Care},
  title        = {Protein S100 as outcome predictor after out-of-hospital cardiac arrest and targeted temperature management at 33 °C and 36 °C},
  url          = {http://dx.doi.org/10.1186/s13054-017-1729-7},
  volume       = {21},
  year         = {2017},
}