Prediction of good functional outcome decreases diagnostic uncertainty in unconscious survivors after out-of-hospital cardiac arrest

Alice Lagebrant; Claudio Sandroni; Jerry P Nolan; Jan Bělohlávek; Alain Cariou; Riccardo Carrai; Josef Dankiewicz; Anders Morten Grejs; Antonello Grippo; Christian Hassager; Janneke Horn; Matthias Haenggi; Janus C Jakobsen; Thomas R Keeble; Hans Kirkegaard; Jesper Kjaergaard; Michael A Kuiper; Byung Kook Lee; Dong Hun Lee; Helena Levin; Gisela Lilja; Andreas Lundin; Niklas Nielsen; Sang Hoon Oh; Kyu Nam Park; Tommaso Pellis; Chiara Robba; Christian Rylander; Seok Jin Ryu; Manoxj Saxena; Maenia Scarpino; Claudia Schrag; Pascal Stammet; Christian Storm; Fabio Silvio Taccone; Matthew Thomas; Erik Westhall; Matt P Wise; Chun Song Youn; Paul Young; Tobias Cronberg; Marion Moseby-Knappe

doi:10.1016/j.resuscitation.2025.110686

Prediction of good functional outcome decreases diagnostic uncertainty in unconscious survivors after out-of-hospital cardiac arrest

Resuscitation. 2025 Jun 16:214:110686. doi: 10.1016/j.resuscitation.2025.110686. Online ahead of print.

Authors

Alice Lagebrant¹, Claudio Sandroni², Jerry P Nolan³, Jan Bělohlávek⁴, Alain Cariou⁵, Riccardo Carrai⁶, Josef Dankiewicz⁷, Anders Morten Grejs⁸, Antonello Grippo⁶, Christian Hassager⁹, Janneke Horn¹⁰, Matthias Haenggi¹¹, Janus C Jakobsen¹², Thomas R Keeble¹³, Hans Kirkegaard¹⁴, Jesper Kjaergaard⁹, Michael A Kuiper¹⁵, Byung Kook Lee¹⁶, Dong Hun Lee¹⁶, Helena Levin¹⁷, Gisela Lilja¹⁸, Andreas Lundin¹⁹, Niklas Nielsen²⁰, Sang Hoon Oh²¹, Kyu Nam Park²¹, Tommaso Pellis²², Chiara Robba²³, Christian Rylander²⁴, Seok Jin Ryu¹⁶, Manoxj Saxena²⁵, Maenia Scarpino⁶, Claudia Schrag²⁶, Pascal Stammet²⁷, Christian Storm²⁸, Fabio Silvio Taccone²⁹, Matthew Thomas³⁰, Erik Westhall³¹, Matt P Wise³², Chun Song Youn²¹, Paul Young³³, Tobias Cronberg¹⁸, Marion Moseby-Knappe³⁴

Affiliations

¹ Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Department of Neurology, Skåne University Hospital, Malmö, Sweden. Electronic address: alice.lagebrant@med.lu.se.
² Department of Intensive Care, Emergency Medicine and Anaesthesiology, Fondazione Policlinico Universitario "Agostino Gemelli"-IRCCS, Largo Francesco Vito, 1, Rome, Italy; Institute of Anaesthesiology and Intensive Care Medicine, Università Cattolica del Sacro Cuore, Rome, Italy.
³ Warwick Clinical Trials Unit, University of Warwick, UK; Department of Anaesthesia and Intensive Care Medicine, Royal United Hospital, Bath, UK.
⁴ Department of Internal Medicine II, Cardiovascular Medicine, General University, 1st Faculty of Medicine, Charles University Prague, Czech Republic; Institute for Heart Diseases, Wroclaw Medical University, Wrocław, Poland Hospital.
⁵ Medical Intensive Care Unit, Cochin University Hospital, AP-HP Centre Université Paris Cité, Paris, France.
⁶ SODc Neurofisiopatologia, Neuroscience Department, Careggi University Hospital, Florence, Italy.
⁷ Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Department of Cardiology, Skåne University Hospital, Lund, Sweden.
⁸ Department of Intensive Care Medicine, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
⁹ Department of Cardiology, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
¹⁰ Department of Intensive Care, Amsterdam Neurosciences, Academic Medical Center, Amsterdam, The Netherlands.
¹¹ Institute of Intensive Care Medicine, University Hospital Zurich, Zurich, Switzerland.
¹² Copenhagen Trial Unit, Centre for Clinical Intervention Research, Capital Region of Denmark; Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Denmark.
¹³ Essex Cardiothoracic Centre, Nethermayne, Basildon, Essex, UK; ARU School of Medicine & MTRC, Chelmsford, Essex, UK.
¹⁴ Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Research Center for Emergency Medicine, Emergency Department, Aarhus University Hospital, Denmark.
¹⁵ Department of Intensive Care, Frisius Medical Center Leeuwarden, the Netherlands.
¹⁶ Department of Emergency Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea; Department of Emergency Medicine, Chonnam National University Hospital, Gwangju, Republic of Korea.
¹⁷ Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Department of Research, Development, Education and Innovation, Skåne University Hospital, Lund, Sweden.
¹⁸ Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Department of Neurology, Skåne University Hospital, Lund, Sweden.
¹⁹ Department of Anaesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
²⁰ Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Department of Anesthesia and Intensive Care, Intensive Care Unit, Helsingborg Hospital, Helsingborg, Sweden.
²¹ Department of Emergency Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
²² Department of Anesthesia and Intensive Care, Pordenone Hospital, Azienda Sanitaria Friuli Occidentale, Italy.
²³ IRCCS Policlinico San Martino Genova, Italy; Dipartimento di Scienze Chirurgiche Diagnostiche e Integrate, University of Genoa, Italy.
²⁴ Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden.
²⁵ Division of Critical Care and Trauma, George Institute for Global Health, Sydney, NSW, Australia; Intensive Care Unit, St George Hospital, Sydney, Australia.
²⁶ Clinic for Intensive Care Medicine, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
²⁷ Anaesthesia and Intensive Care Department, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg; Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
²⁸ Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin.
²⁹ Université Libre de Bruxelles, Brussels, Belgium; Department of Intensive Care, Hôpital Universitaire de Bruxelles, Brussels, Belgium.
³⁰ Dept of Intensive Care, University Hospitals Bristol and Weston, UK.
³¹ Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Department of Clinical Neurophysiology, Skåne University Hospital, Lund, Sweden.
³² Adult Critical Care, University Hospital of Wales, Cardiff, UK.
³³ Medical Research Institute of New Zealand, Wellington, New Zealand; Intensive Care Unit, Wellington Regional Hospital, Wellington, New Zealand; Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; Department of Critical Care, University of Melbourne, Parkville, VIC, Australia.
³⁴ Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Department of Rehabilitation, Skåne University Hospital, Lund, Sweden.

PMID: 40533052
DOI: 10.1016/j.resuscitation.2025.110686

Abstract

Purpose: To explore modifications of the 2021 European Resuscitation Council/European Society of Intensive Care Medicine (ERC/ESICM) guideline algorithm for neuroprognostication after cardiac arrest to improve its prognostic accuracy.

Methods: Post-hoc analysis of four prospective multicentre studies (TTM, TTM2, KORHN and ProNeCA). We raised the Glasgow Coma Scale motor (GCS-M) inclusion threshold at 72 h after cardiac arrest from the current GCS-M < 4 to GCS-M < 6 (all unconscious patients). Secondly, we included good outcome predictors (GCS-M 4-5, neuron-specific enolase < 17 µg/L, benign electroencephalography patterns ≤ 72 h post-arrest and normal magnetic resonance imaging at 72-168 h post-arrest) in the algorithm. Functional outcome was assessed dichotomously at six months, including modified Rankin Scale 0-3, Cerebral Performance Category 1-2 or Glasgow Outcome Scale 4-5 (no symptoms to moderate disability) as good outcome.

Results: We analysed 3,388 patients, of whom 2,079 had GCS-M < 4 at ≥ 72 h. Of the 874 patients identified by the 2021 ERC/ESICM poor outcome criteria, 870 had poor functional outcome (specificity: 99.6% [95%CI 99.0-99.9]). Using the GCS-M < 6 threshold, 366 more patients entered the algorithm (N = 2,445). Seven more patients with poor outcomes were identified, with close to identical specificity. Good outcome predictors thereafter identified 673 patients with potential recovery, of whom 411 (61%) had a good functional outcome at six months. With the updated algorithm, the number of prognosticated patients with an indeterminate prognosis decreased from 1,205/2,079 (58%) to 891/2,445 (36%).

Conclusion: Raising the GCS-M inclusion threshold and adding favourable predictors to the 2021 ERC/ESICM prognostication algorithm reduced prognostic uncertainty without increasing falsely pessimistic predictions.

Keywords: Cardiac Arrest; Functional Outcome; Good Outcome Prediction; Indeterminate Prognosis; Neurological Prognostication.