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

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.

Keywords: Biomarker; Cerebral performance; Neuroprognostication; Prognosis; S100.

Figures

Fig. 1

Study flowchart. Number of patients enrolled in the TTM trial and included in this substudy a; Number of samples included in this study and reasons for eliminating serum samples from analysis b. TTM Target Temperature Management after Out-of-Hospital Cardiac Arrest trial, CPC Cerebral Performance Categories Scale

Fig. 2

S100 time course. Box plots of S100 over the first 72 h after return of spontaneous circulation. Data are presented as median, quartile 1, quartile 3, and lower fence (i.e., lowest value above [quartile 1–1.5 {quartile3 − quartile1}]) and upper fence (i.e., greater value below [quartile 3 + 1.5 {quartile3 − quartile1}]). A statistical difference was found only for S100 values of patients with good outcomes, with higher values in the 33 °C group and between good and poor outcome groups. * p < 0.05. CPC Cerebral Performance Categories Scale

Fig. 3

ROC curves with AUCs for S100 at 24 h (a), 48 h (b), and 72 h (c) after return of spontaneous circulation for outcome prediction according to Cerebral Performance Categories Scale score at 6 months

Fig. 4

Kaplan-Meier curves for prediction of survival at the end of the trial (primary endpoint of the Target Temperature Management after Out-of-Hospital Cardiac Arrest trial) for S100 values at 24 h (a), 48 h (b), and 72 h (c) after return of spontaneous circulation. Separation into quartiles of serum S100 levels