Florian Ebner1, Marion Moseby-Knappe2, Niklas Mattsson-Carlgren3, Gisela Lilja2, Irina Dragancea2, Johan Undén4, Hans Friberg5, David Erlinge6, Jesper Kjaergaard7, Christian Hassager7, Matt P Wise8, Michael Kuiper9, Pascal Stammet10, Michael Wanscher11, Janneke Horn12, Susann Ullén13, Tobias Cronberg2, Niklas Nielsen14. 1. Department of Clinical Sciences Lund, Anaesthesia and Intensive Care, Lund University, Helsingborg Hospital, Lund, Sweden. Electronic address: florian.ebner@med.lu.se. 2. Department of Clinical Sciences Lund, Neurology, Lund University, Skåne University Hospital, Lund, Sweden. 3. Department of Clinical Sciences Lund, Neurology, Lund University, Skåne University Hospital, Lund, Sweden; Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden; Wallenberg Centre for Molecular Medicine, Lund University, Sweden. 4. Department of Clinical Sciences Malmö, Anaesthesia and Intensive Care, Lund University, Hallands Hospital Halmstad, Halland, Sweden. 5. Department of Clinical Sciences Lund, Anaesthesia and Intensive Care, Lund University, Skåne University Hospital, Malmö, Sweden. 6. Department of Clinical Sciences Lund, Cardiology, Lund University, Skåne University Hospital, Lund, Sweden. 7. Department of Cardiology, Rigshospitalet, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. 8. Adult Critical Care, University Hospital of Wales, Cardiff, United Kingdom. 9. Department of Intensive Care, Medical Centre Leeuwarden, Leeuwarden, The Netherlands. 10. Medical and Health Directorate, National Fire and Rescue Corps, Luxembourg City, Luxembourg. 11. Department of Cardiothoracic Anaesthesia, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 12. Department of Intensive Care Medicine, Laboratory of Experimental Intensive Care and Anaesthesiology, Amsterdam UMC, AMC, University of Amsterdam, Amsterdam, The Netherlands. 13. Clinical Studies Sweden, Skane University Hospital, Lund, Sweden. 14. Department of Clinical Sciences Lund, Anaesthesia and Intensive Care, Lund University, Helsingborg Hospital, Lund, Sweden.
Abstract
OBJECTIVE: Neurological outcome prediction is crucial early after cardiac arrest. Serum biomarkers released from brain cells after hypoxic-ischaemic injury may aid in outcome prediction. The only serum biomarker presently recommended in the European Resuscitation Council prognostication guidelines is neuron-specific enolase (NSE), but NSE has limitations. In this study, we therefore analyzed the outcome predictive accuracy of the serum biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) in patients after cardiac arrest. METHODS: Serum GFAP and UCH-L1 were collected at 24, 48 and 72 h after cardiac arrest. The primary outcome was neurological function at 6-month follow-up assessed by the cerebral performance category scale (CPC), dichotomized into good (CPC1-2) and poor (CPC3-5). Prognostic accuracies were tested with receiver-operating characteristics by calculating the area under the receiver-operating curve (AUROC) and compared to the AUROC of NSE. RESULTS: 717 patients were included in the study. GFAP and UCH-L1 discriminated between good and poor neurological outcome at all time-points when used alone (AUROC GFAP 0.88-0.89; UCH-L1 0.85-0.87) or in combination (AUROC 0.90-0.91). The combined model was superior to GFAP and UCH-L1 separately and NSE (AUROC 0.75-0.85) at all time-points. At specificities ≥95%, the combined model predicted poor outcome with a higher sensitivity than NSE at 24 h and with similar sensitivities at 48 and 72 h. CONCLUSION: GFAP and UCH-L1 predicted poor neurological outcome with high accuracy. Their combination may be of special interest for early prognostication after cardiac arrest where it performed significantly better than the currently recommended biomarker NSE.
OBJECTIVE: Neurological outcome prediction is crucial early after cardiac arrest. Serum biomarkers released from brain cells after hypoxic-ischaemic injury may aid in outcome prediction. The only serum biomarker presently recommended in the European Resuscitation Council prognostication guidelines is neuron-specific enolase (NSE), but NSE has limitations. In this study, we therefore analyzed the outcome predictive accuracy of the serum biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) in patients after cardiac arrest. METHODS: Serum GFAP and UCH-L1 were collected at 24, 48 and 72 h after cardiac arrest. The primary outcome was neurological function at 6-month follow-up assessed by the cerebral performance category scale (CPC), dichotomized into good (CPC1-2) and poor (CPC3-5). Prognostic accuracies were tested with receiver-operating characteristics by calculating the area under the receiver-operating curve (AUROC) and compared to the AUROC of NSE. RESULTS: 717 patients were included in the study. GFAP and UCH-L1 discriminated between good and poor neurological outcome at all time-points when used alone (AUROC GFAP 0.88-0.89; UCH-L1 0.85-0.87) or in combination (AUROC 0.90-0.91). The combined model was superior to GFAP and UCH-L1 separately and NSE (AUROC 0.75-0.85) at all time-points. At specificities ≥95%, the combined model predicted poor outcome with a higher sensitivity than NSE at 24 h and with similar sensitivities at 48 and 72 h. CONCLUSION: GFAP and UCH-L1 predicted poor neurological outcome with high accuracy. Their combination may be of special interest for early prognostication after cardiac arrest where it performed significantly better than the currently recommended biomarker NSE.
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