Pascal Stammet1, Olivier Collignon2, Christian Hassager3, Matthew P Wise4, Jan Hovdenes5, Anders Åneman6, Janneke Horn7, Yvan Devaux8, David Erlinge9, Jesper Kjaergaard3, Yvan Gasche10, Michael Wanscher11, Tobias Cronberg12, Hans Friberg13, Jørn Wetterslev14, Tommaso Pellis15, Michael Kuiper16, Georges Gilson17, Niklas Nielsen18. 1. Department of Anesthesia and Intensive Care, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg. Electronic address: stammet.pascal@chl.lu. 2. Competence Centre for Methodology and Statistics, Luxembourg Institute of Health, Luxembourg, Luxembourg. 3. Department of Cardiology B, The Heart Centre, Rigshospitalet University Hospital, Copenhagen, Denmark. 4. Department of Intensive Care, University Hospital of Wales, Cardiff, United Kingdom. 5. Department of Anesthesia and Intensive Care, Oslo University Hospital, Rikshospitalet, Oslo, Norway. 6. Department of Intensive Care, Liverpool Hospital, Sydney, Australia. 7. Department of Intensive Care, Academic Medical Centrum, Amsterdam, the Netherlands. 8. Laboratory of Cardiovascular Research, Luxembourg Institute of Health, Luxembourg, Luxembourg. 9. Department of Cardiology, Skåne University Hospital, Lund, Sweden. 10. Department of Intensive Care, Geneva University Hospital, Geneva, Switzerland. 11. Department of Cardiothoracic Anesthesiology RT, The Heart Centre, Rigshospitalet University Hospital, Copenhagen, Denmark. 12. Department of Clinical Sciences, Division of Neurology, Lund University, Lund, Sweden. 13. Department of Anesthesia and Intensive Care, Skåne University Hospital, Lund University, Lund, Sweden. 14. Copenhagen Trial Unit, Centre of Clinical Intervention Research, Rigshospitalet, Copenhagen, Denmark. 15. Department of Intensive Care, Santa Maria degli Angeli, Pordenone, Italy. 16. Department of Intensive Care, Leeuwarden Medical Centrum, Leeuwarden, the Netherlands. 17. Department of Clinical Biology, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg. 18. Department of Anesthesia and Intensive Care, Helsingborg Hospital, Helsingborg, Sweden.
Abstract
BACKGROUND:Neuron-specific enolase (NSE) is a widely-used biomarker for prognostication of neurological outcome after cardiac arrest, but the relevance of recommended cutoff values has been questioned due to the lack of a standardized methodology and uncertainties over the influence of temperature management. OBJECTIVES: This study investigated the role of NSE as a prognostic marker of outcome after out-of-hospital cardiac arrest (OHCA) in a contemporary setting. METHODS: A total of 686 patients hospitalized after OHCA were randomized to targeted temperature management at either 33°C or 36°C. NSE levels were assessed in blood samples obtained 24, 48, and 72 h after return of spontaneous circulation. The primary outcome was neurological outcome at 6 months using the cerebral performance category score. RESULTS:NSE was a robust predictor of neurological outcome in a baseline variable-adjusted model, and target temperature did not significantly affect NSE values. Median NSE values were 18 ng/ml versus 35 ng/ml, 15 ng/ml versus 61 ng/ml, and 12 ng/ml versus 54 ng/ml for good versus poor outcome at 24, 48, and 72 h, respectively (p < 0.001). At 48 and 72 h, NSE predicted neurological outcome with areas under the receiver-operating curve of 0.85 and 0.86, respectively. High NSE cutoff values with false positive rates ≤5% and tight 95% confidence intervals were able to reliably predict outcome. CONCLUSIONS: High, serial NSE values are strong predictors of poor outcome after OHCA. Targeted temperature management at 33°C or 36°C does not significantly affect NSE levels. (Target Temperature Management After Cardiac Arrest [TTM]; NCT01020916).
RCT Entities:
BACKGROUND:Neuron-specific enolase (NSE) is a widely-used biomarker for prognostication of neurological outcome after cardiac arrest, but the relevance of recommended cutoff values has been questioned due to the lack of a standardized methodology and uncertainties over the influence of temperature management. OBJECTIVES: This study investigated the role of NSE as a prognostic marker of outcome after out-of-hospital cardiac arrest (OHCA) in a contemporary setting. METHODS: A total of 686 patients hospitalized after OHCA were randomized to targeted temperature management at either 33°C or 36°C. NSE levels were assessed in blood samples obtained 24, 48, and 72 h after return of spontaneous circulation. The primary outcome was neurological outcome at 6 months using the cerebral performance category score. RESULTS:NSE was a robust predictor of neurological outcome in a baseline variable-adjusted model, and target temperature did not significantly affect NSE values. Median NSE values were 18 ng/ml versus 35 ng/ml, 15 ng/ml versus 61 ng/ml, and 12 ng/ml versus 54 ng/ml for good versus poor outcome at 24, 48, and 72 h, respectively (p < 0.001). At 48 and 72 h, NSE predicted neurological outcome with areas under the receiver-operating curve of 0.85 and 0.86, respectively. High NSE cutoff values with false positive rates ≤5% and tight 95% confidence intervals were able to reliably predict outcome. CONCLUSIONS: High, serial NSE values are strong predictors of poor outcome after OHCA. Targeted temperature management at 33°C or 36°C does not significantly affect NSE levels. (Target Temperature Management After Cardiac Arrest [TTM]; NCT01020916).