Kirsten Helwig1, Florian Seeger2, Hans Hölschermann3, Volker Lischke4, Tibo Gerriets5,6, Marion Niessner7, Christian Foerch8. 1. Department of Neurology, Goethe University, Schleusenweg 2-16, 60528, Frankfurt am Main, Germany. 2. Department of Cardiology, Goethe University, Frankfurt am Main, Germany. 3. Department of Cardiology, Hochtaunus-Kliniken, Bad Homburg, Germany. 4. Department of Anesthesiology, Hochtaunus-Kliniken, Bad Homburg, Germany. 5. Department of Neurology, Justus Liebig University, Giessen, Germany. 6. Department of Neurology, Gesundheitszentrum Wetterau, Friedberg, Germany. 7. Roche Diagnostics, Penzberg, Germany. 8. Department of Neurology, Goethe University, Schleusenweg 2-16, 60528, Frankfurt am Main, Germany. foerch@em.uni-frankfurt.de.
Abstract
BACKGROUND: The neurological prognosis of patients after cardiopulmonary resuscitation (CPR) is difficult to assess. GFAP is an astrocytic intermediate filament protein released into bloodstream in case of cell death. We performed a prospective study aiming to compare the predictive potential of GFAP after resuscitation to the more widely used biomarker neuron-specific enolase (NSE). METHODS: One hundred patients were included at 48 h (tolerance interval ±12 h) after cardiac arrest. A serum sample was collected immediately after study inclusion. We determined serum levels of GFAP and NSE by means of immunoassays. Primary outcome was the modified Glasgow outcome scale at 4 weeks. Values below four were considered as a poor functional outcome. RESULTS: Median GFAP levels in poor outcome (n = 61) and good outcome (n = 39) patients were 0.03 μg/L (interquartile range 0.01-0.07 μg/L) and 0.02 μg/L (0.01-0.03 μg/L; p = 0.014), respectively. GFAP revealed a sensitivity of 60.7% and a specificity of 66.7% to predict a poor functional outcome. All patients having a GFAP level >0.08 µg/L had a poor functional outcome. For NSE, sensitivity was 44.3% and specificity was 100.0% for predicting a poor outcome. Multivariate regression analysis revealed GFAP, NSE, and the Karnofsky index to be independent predictors of outcome. CONCLUSIONS: The release patterns of GFAP and NSE after CPR show differences. GFAP levels above 0.08 µg/L were associated with a poor outcome in all cases, and patients with strongly elevated values (>3 µg/L) consistently had severe brain damage on brain imaging. Both biomarkers independently contribute to outcome prediction after CPR.
BACKGROUND: The neurological prognosis of patients after cardiopulmonary resuscitation (CPR) is difficult to assess. GFAP is an astrocytic intermediate filament protein released into bloodstream in case of cell death. We performed a prospective study aiming to compare the predictive potential of GFAP after resuscitation to the more widely used biomarker neuron-specific enolase (NSE). METHODS: One hundred patients were included at 48 h (tolerance interval ±12 h) after cardiac arrest. A serum sample was collected immediately after study inclusion. We determined serum levels of GFAP and NSE by means of immunoassays. Primary outcome was the modified Glasgow outcome scale at 4 weeks. Values below four were considered as a poor functional outcome. RESULTS: Median GFAP levels in poor outcome (n = 61) and good outcome (n = 39) patients were 0.03 μg/L (interquartile range 0.01-0.07 μg/L) and 0.02 μg/L (0.01-0.03 μg/L; p = 0.014), respectively. GFAP revealed a sensitivity of 60.7% and a specificity of 66.7% to predict a poor functional outcome. All patients having a GFAP level >0.08 µg/L had a poor functional outcome. For NSE, sensitivity was 44.3% and specificity was 100.0% for predicting a poor outcome. Multivariate regression analysis revealed GFAP, NSE, and the Karnofsky index to be independent predictors of outcome. CONCLUSIONS: The release patterns of GFAP and NSE after CPR show differences. GFAP levels above 0.08 µg/L were associated with a poor outcome in all cases, and patients with strongly elevated values (>3 µg/L) consistently had severe brain damage on brain imaging. Both biomarkers independently contribute to outcome prediction after CPR.
Authors: Johann Reisinger; Kurt Höllinger; Wolfgang Lang; Christoph Steiner; Thomas Winter; Eduard Zeindlhofer; Michael Mori; Alexandra Schiller; Alexander Lindorfer; Kurt Wiesinger; Peter Siostrzonek Journal: Eur Heart J Date: 2006-10-23 Impact factor: 29.983
Authors: Christian Foerch; Marion Niessner; Tobias Back; Michael Bauerle; Gian Marco De Marchis; Andreas Ferbert; Holger Grehl; Gerhard F Hamann; Andreas Jacobs; Andreas Kastrup; Sven Klimpe; Frederick Palm; Götz Thomalla; Hans Worthmann; Matthias Sitzer Journal: Clin Chem Date: 2011-11-28 Impact factor: 8.327
Authors: Christoph A Mayer; Robert Brunkhorst; Marion Niessner; Waltraud Pfeilschifter; Helmuth Steinmetz; Christian Foerch Journal: PLoS One Date: 2013-04-23 Impact factor: 3.240
Authors: Claudio Sandroni; Sonia D'Arrigo; Sofia Cacciola; Cornelia W E Hoedemaekers; Marlijn J A Kamps; Mauro Oddo; Fabio S Taccone; Arianna Di Rocco; Frederick J A Meijer; Erik Westhall; Massimo Antonelli; Jasmeet Soar; Jerry P Nolan; Tobias Cronberg Journal: Intensive Care Med Date: 2020-09-11 Impact factor: 17.440
Authors: Jerry P Nolan; Claudio Sandroni; Bernd W Böttiger; Alain Cariou; Tobias Cronberg; Hans Friberg; Cornelia Genbrugge; Kirstie Haywood; Gisela Lilja; Véronique R M Moulaert; Nikolaos Nikolaou; Theresa Mariero Olasveengen; Markus B Skrifvars; Fabio Taccone; Jasmeet Soar Journal: Intensive Care Med Date: 2021-03-25 Impact factor: 17.440
Authors: Ahmed Abdelhak; Matteo Foschi; Samir Abu-Rumeileh; John K Yue; Lucio D'Anna; Andre Huss; Patrick Oeckl; Albert C Ludolph; Jens Kuhle; Axel Petzold; Geoffrey T Manley; Ari J Green; Markus Otto; Hayrettin Tumani Journal: Nat Rev Neurol Date: 2022-02-03 Impact factor: 44.711
Authors: Jaana Humaloja; Marika Lähde; Nicholas J Ashton; Matti Reinikainen; Johanna Hästbacka; Pekka Jakkula; Hans Friberg; Tobias Cronberg; Ville Pettilä; Kaj Blennow; Henrik Zetterberg; Markus B Skrifvars Journal: Resuscitation Date: 2021-12-01 Impact factor: 5.262
Authors: Jude Savarraj; Eun S Park; Gabriela D Colpo; Sarah N Hinds; Diego Morales; Hilda Ahnstedt; Atzhiry S Paz; Andres Assing; Fudong Liu; Shivanki Juneja; Eunhee Kim; Sung-Min Cho; Aaron M Gusdon; Pramod Dash; Louise D McCullough; H Alex Choi Journal: J Neuroinflammation Date: 2021-11-27 Impact factor: 8.322
Authors: Jasmeet Soar; Katherine M Berg; Lars W Andersen; Bernd W Böttiger; Sofia Cacciola; Clifton W Callaway; Keith Couper; Tobias Cronberg; Sonia D'Arrigo; Charles D Deakin; Michael W Donnino; Ian R Drennan; Asger Granfeldt; Cornelia W E Hoedemaekers; Mathias J Holmberg; Cindy H Hsu; Marlijn Kamps; Szymon Musiol; Kevin J Nation; Robert W Neumar; Tonia Nicholson; Brian J O'Neil; Quentin Otto; Edison Ferreira de Paiva; Michael J A Parr; Joshua C Reynolds; Claudio Sandroni; Barnaby R Scholefield; Markus B Skrifvars; Tzong-Luen Wang; Wolfgang A Wetsch; Joyce Yeung; Peter T Morley; Laurie J Morrison; Michelle Welsford; Mary Fran Hazinski; Jerry P Nolan Journal: Resuscitation Date: 2020-10-21 Impact factor: 5.262