Marion Moseby-Knappe1, Niklas Mattsson1,2, Niklas Nielsen3, Henrik Zetterberg4,5,6,7, Kaj Blennow4,5, Josef Dankiewicz8, Irina Dragancea1, Hans Friberg9, Gisela Lilja1, Philip S Insel2, Christian Rylander10, Erik Westhall11, Jesper Kjaergaard12, Matt P Wise13, Christian Hassager12, Michael A Kuiper14, Pascal Stammet15, Michael C Jaeger Wanscher16, Jørn Wetterslev17, David Erlinge8, Janneke Horn18, Tommaso Pellis19, Tobias Cronberg1. 1. Department of Clinical Sciences Lund, Neurology, Lund University, Skåne University Hospital, Lund, Sweden. 2. Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden. 3. Department of Clinical Sciences Lund, Anesthesia and Intensive Care, Lund University, Helsingborg Hospital, Lund, Sweden. 4. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. 5. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 6. Department of Molecular Neuroscience, University College of London Institute of Neurology, London, United Kingdom. 7. United Kingdom Dementia Research Institute, London, United Kingdom. 8. Department of Clinical Sciences Lund, Cardiology, Lund University, Skåne University Hospital, Lund, Sweden. 9. Department of Clinical Sciences Lund, Anesthesia and Intensive Care, Lund University, Skåne University Hospital, Lund, Sweden. 10. Department of Anesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 11. Department of Clinical Sciences Lund, Clinical Neurophysiology, Skåne University Hospital, Lund, Sweden. 12. Departments of Cardiology, Rigshospitalet and Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. 13. Adult Critical Care, University Hospital of Wales, Cardiff, United Kingdom. 14. Department of Intensive Care, Medical Center Leeuwarden, Leeuwarden, the Netherlands. 15. National Rescue Services, Luxembourg City, Luxembourg. 16. Department of Cardiothoracic Anaesthesia, The Heart Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. 17. Copenhagen Trial Unit, Centre for Clinical Intervention Research Department, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 18. Department of Intensive Care, Academic Medical Center, Amsterdam, the Netherlands. 19. Anesthesia and Intensive Care, Card. G. Panico Hospital Agency, Tricase, Italy.
Abstract
Importance: Prognostication of neurologic outcome after cardiac arrest is an important but challenging aspect of patient therapy management in critical care units. Objective: To determine whether serum neurofilament light chain (NFL) levels can be used for prognostication of neurologic outcome after cardiac arrest. Design, Setting and Participants: Prospective clinical biobank study of data from the randomized Target Temperature Management After Cardiac Arrest trial, an international, multicenter study with 29 participating sites. Patients were included between November 11, 2010, and January 10, 2013. Serum NFL levels were analyzed between August 1 and August 23, 2017, after trial completion. A total of 782 unconscious patients with out-of-hospital cardiac arrest of presumed cardiac origin were eligible. Exposures: Serum NFL concentrations analyzed at 24, 48, and 72 hours after cardiac arrest with an ultrasensitive immunoassay. Main Outcomes and Measures: Poor neurologic outcome at 6-month follow-up, defined according to the Cerebral Performance Category Scale as cerebral performance category 3 (severe cerebral disability), 4 (coma), or 5 (brain death). Results: Of 782 eligible patients, 65 patients (8.3%) were excluded because of issues with aliquoting, missing sampling, missing outcome, or transport problems of samples. Of the 717 patients included (91.7%), 580 were men (80.9%) and median (interquartile range [IQR]) age was 65 (56-73) years. A total of 360 patients (50.2%) had poor neurologic outcome at 6 months. Median (IQR) serum NFL level was significantly increased in the patients with poor outcome vs good outcome at 24 hours (1426 [299-3577] vs 37 [20-70] pg/mL), 48 hours (3240 [623-8271] vs 46 [26-101] pg/mL), and 72 hours (3344 [845-7838] vs 54 [30-122] pg/mL) (P < .001 at all time points), with high overall performance (area under the curve, 0.94-0.95) and high sensitivities at high specificities (eg, 69% sensitivity with 98% specificity at 24 hours). Serum NFL levels had significantly greater performance than the other biochemical serum markers (ie, tau, neuron-specific enolase, and S100). At comparable specificities, serum NFL levels had greater sensitivity for poor outcome compared with routine electroencephalogram, somatosensory-evoked potentials, head computed tomography, and both pupillary and corneal reflexes (ranging from 29.2% to 49.0% greater for serum NFL level). Conclusions and Relevance: Findings from this study suggest that the serum NFL level is a highly predictive marker of long-term poor neurologic outcome at 24 hours after cardiac arrest and may be a useful complement to currently available neurologic prognostication methods.
RCT Entities:
Importance: Prognostication of neurologic outcome after cardiac arrest is an important but challenging aspect of patient therapy management in critical care units. Objective: To determine whether serum neurofilament light chain (NFL) levels can be used for prognostication of neurologic outcome after cardiac arrest. Design, Setting and Participants: Prospective clinical biobank study of data from the randomized Target Temperature Management After Cardiac Arrest trial, an international, multicenter study with 29 participating sites. Patients were included between November 11, 2010, and January 10, 2013. Serum NFL levels were analyzed between August 1 and August 23, 2017, after trial completion. A total of 782 unconscious patients with out-of-hospital cardiac arrest of presumed cardiac origin were eligible. Exposures: Serum NFL concentrations analyzed at 24, 48, and 72 hours after cardiac arrest with an ultrasensitive immunoassay. Main Outcomes and Measures: Poor neurologic outcome at 6-month follow-up, defined according to the Cerebral Performance Category Scale as cerebral performance category 3 (severe cerebral disability), 4 (coma), or 5 (brain death). Results: Of 782 eligible patients, 65 patients (8.3%) were excluded because of issues with aliquoting, missing sampling, missing outcome, or transport problems of samples. Of the 717 patients included (91.7%), 580 were men (80.9%) and median (interquartile range [IQR]) age was 65 (56-73) years. A total of 360 patients (50.2%) had poor neurologic outcome at 6 months. Median (IQR) serum NFL level was significantly increased in the patients with poor outcome vs good outcome at 24 hours (1426 [299-3577] vs 37 [20-70] pg/mL), 48 hours (3240 [623-8271] vs 46 [26-101] pg/mL), and 72 hours (3344 [845-7838] vs 54 [30-122] pg/mL) (P < .001 at all time points), with high overall performance (area under the curve, 0.94-0.95) and high sensitivities at high specificities (eg, 69% sensitivity with 98% specificity at 24 hours). Serum NFL levels had significantly greater performance than the other biochemical serum markers (ie, tau, neuron-specific enolase, and S100). At comparable specificities, serum NFL levels had greater sensitivity for poor outcome compared with routine electroencephalogram, somatosensory-evoked potentials, head computed tomography, and both pupillary and corneal reflexes (ranging from 29.2% to 49.0% greater for serum NFL level). Conclusions and Relevance: Findings from this study suggest that the serum NFL level is a highly predictive marker of long-term poor neurologic outcome at 24 hours after cardiac arrest and may be a useful complement to currently available neurologic prognostication methods.
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