The predictive value of highly malignant EEG patterns after cardiac arrest: evaluation of the ERC-ESICM recommendations

Sara Turella; Josef Dankiewicz; Hans Friberg; Janus Christian Jakobsen; Christoph Leithner; Helena Levin; Gisela Lilja; Marion Moseby-Knappe; Niklas Nielsen; Andrea O Rossetti; Claudio Sandroni; Frédéric Zubler; Tobias Cronberg; Erik Westhall; TTM2-trial investigators

doi:10.1007/s00134-023-07280-9

The predictive value of highly malignant EEG patterns after cardiac arrest: evaluation of the ERC-ESICM recommendations

Intensive Care Med. 2024 Jan;50(1):90-102. doi: 10.1007/s00134-023-07280-9. Epub 2024 Jan 3.

Authors

Sara Turella¹, Josef Dankiewicz², Hans Friberg³, Janus Christian Jakobsen^{4

5}, Christoph Leithner⁶, Helena Levin⁷, Gisela Lilja^{8

9}, Marion Moseby-Knappe¹⁰, Niklas Nielsen¹¹, Andrea O Rossetti¹², Claudio Sandroni¹, Frédéric Zubler¹³, Tobias Cronberg⁸, Erik Westhall¹⁴; TTM2-trial investigators

Collaborators

TTM2-trial investigators:
Jan Bělohlávek, Clifton Callaway, Alain Cariou, Tobias Cronberg, Glenn Eastwood, David Erlinge, Jan Hovdenes, Michael Joannidis, Hans Kirkegaard, Matt P G Morgan, Alistair D Nichol, Per Nordberg, Mauro Oddo, Paolo Pelosi, Christian Rylander, Manoj Saxena, Christian Storm, Fabio S Taccone, Susann Ullén, Matt P Wise, Paul J Young, Kathy Rowan, Paul Mouncey, Manu Shankar-Hari, Duncan Young, Susann Ullén, Theis Lange, Karolina Palmér, Susann Ullén, Ulla-Britt Karlsson, Simon Heissler, Manoj Saxena, Frances Bass, Naomi Hammond, John Myburgh, Colman Taylor, Alain Cariou, Adele Bellino, Marwa Abel-All, Ben Finfer, Carolyn Koch, Yang Li, Anne O'Connor, Julia Pilowsky, Tina Schneider, Anna Tippett, Bridget Ady, Tessa Broadley, Amanda Brown, Liz Melgaard, Mimi Morgan, Vanessa Singh, Rebecca Symons, Kathrin Becker, Nathalie Van Sante, Vendula Saleova, Silvie Zerzanova, Samia Sefr-Kribel, Ute Lübeck, Martina Carrara, Kathryn Fernando, Diane Mackle, Leanlove Navarra, Judith Riley, Elin Westerheim, Marianne Flatebø, Ameldina Ceric, Zana Haxhija, Lovisa Terling, Lena Bossmar, Liz Jergle, Helén Holm Månsson, Samia Abed Maillard, Andreja Vujicic Zagar, Christina Jodlauk, Helen Hill, Jennifer Scrivens, Kate Ainscough, Ciara Fahey, Rinaldo Bellomo, Glenn Eastwood, Leah Peck, Helen Young, Winston Cheung, Rosalba Cross, Michael Hayes, Nitin Jain, Mark Kol, Asim Shah, Atul Wagh, Helen Wong, F Eduardo Martinez, Gail Brinkerhof, Dustin Bush, Antony Stewart, Anders Aneman, Lien Lombardo, Peter McCanny, James Penketh, Ian Seppelt, Rebecca Gresham, Julie Lowrey, Kristy Masters, Christina Whitehead, James Walsham, Meg Harward, Josephine Mackay, Jason Meyer, Emma Saylor, Ellen Venz, Krista Wetzig, Wade Stedman, Angela Ashelford, Frances Bass, Naomi Hammond, Sharon Mar, Julia Pilowsky, Miyuki Tokumitsu, Elizabeth Yarad, Hergen Buscher, Claire Reynolds, Andrew Udy, Aidan Burrell, Jasmin Collins, Dashiell Gantner, Victoria Emma-Leah Martin, Phoebe Mccracken, Vinodh Nanjayya, Alistair Nichol, Alexander Sacha Richardson, Meredith Young, Angaj Ghosh, Simone Said, Michael Joannidis, Ronny Beer, Frank Hartig, Raimund Helbok, Sebastian Klein, Andreas Peer, Fabio S Taccone, Jacques Creteur, Dominique Durand, Matthias Dupont, Sigrid Christiaens, Carola Claes, Sebastiaan Deckx, Bert Ferdinande, Sanne Lenaerts, Wilifred Mullens, Sarah Stroobants, Evi Theunissen, David Verhaert, Ondřej Šmíd, Marek Flaksa, David Kemlink, Jan Malík, Michal Otáhal, Jan Rulíšek, Michal Šíranec, Zdeněk Stach, Anna Valeriánová, Petra Zavadilova, Miroslav Solař, Róber Bánszky, Jana Červená, Renata Černá Pařízková, Libor Šimůnek, Filip Varhaník, Jiří Karásek, Matěj Strýček, Anders Grejs, Stefen Christensen, Peter Juhl-Olsen, Ida Katrine Thomsen, Lisa Gregersen Østergaard, Alain Cariou, Albert Cao, Pierre Dupland, Ariane Gavaud, Paul Jaubert, Mathieu Jozwiak, Nathalie Marin, Guillaume Savary, Nicolas Deye, Bruno Megarbane, Pierre Mora, Laetitia Sutterlin, Stephane Legriel, Hugo Bellut, Alexis Ferre, Guillaume Lacave, Marine Paul, Jean-Baptiste Lascarrou, Emmanuel Canet, Charlotte Garret, Arnaud Felix Miaihle, Jean Reignier, Philippe Vignon, Thomas Daix, Arnaud Desachy, Bruno Evrard, Bruno Francois, Anne-Laure Fedou, Marine Goudelin, Christian Storm, Gabriele Kress, Jens Nee, Kaspar Josche Streitberger, Iole Brunetti, Lorenzo Ball, Denise Battaglini, Giulia Bonatti, Iacopo Firpo, Paolo Frisoni, Arianna Iachi, Simona Maiani, Maura Mandelli, Chiara Robba, Fabio Tarantino, Alberto Barbieri, Elisabetta Bertellini, Enrico Giuliani, Gabriele Melegari, Erik Roman-Pognuz, Giorgio Berlot, Umberto Lucangelo, Elisabetta Macchini, Jan Hovdenes, Vibeke Aune, Tomas Drægni, Simon Jacobsen, Søren Pieschke, Åse Rasmussen, Gro Ringstad Akselsen, Halvor Langeland, Daniel Bergum, Therese M Erbe, Pål Klepstad, Helle M Næss, Roy Bjørkholt Olsen, Lena Eriksen Skjelnes, Marius Holen, Joakim Iver Post, Rune Fanebust, Linda Hårteig Sørensen, Ken Åge Kårstad, Carsten Fredrik Wickman, Paul Young, Colin Barnes, Ben Barry, Nina Beehre, Dick Dinsdale, Sam Edney, Anna Hunt, Harriet Judd, Charlotte Latimer-Bell, Cassie Lawrence, James Moore, Shaanti Olatunji, Alex Psirides, Chelsea Robinson, Kate Tietjens, Jason Wright, David Knight, Brandon Birker, David Bowie, Tara Burke, David Closey, Rosalind Crombie, Neil Davidson, Seton Henderson, Louise Hitchings, James McKay, Jan Mehrtens, Emmeline Minto, Stacey Morgan, Anna Morris, Jay Ritzemar-Carter, Jessica Roberts, Geofrey Shaw, Katherine Townend, Kymbalee Vander Heyden, Christian Rylander, Marita Ahlqvist, Roman Desta Lindgren, Ingrid Eiving, Andreas Lundin, Patrik Martner, Elisabeth Myhrman, Birgitta Ryding, Joachim Düring, Mattias Bergström, Mattias Bohm, Ingrid Didriksson, Petrea Frid, Katarina Heimburg, Marina Larsson, Oscar Lundberg, Stefan Olsson Hau, Simon Schmidbauer, Ola Borgquist, Anne Adolfsson, Anna Bjärnroos, Erik Blennow-Nordström, Irina Dragancea, Thomas Kander, Anna Lybeck, Gustav Mattiasson, Olof Persson, Malin Rundgren, Susann Schrey, Martin Annborn, Sara Andertun, Florian Ebner, Nerida Gustavsson, Lisa Hassel, Jesper Johnsson, Marie Nelderup, Heléne Petersson, Jörgen Petersson, Frideriki Staflidou, Johan Undén, Frida Antonsson, Git Bergman, Jörgen Gamroth, Maria Meirik, Katarina Rudolfsson, Helena Sandberg, Martin Thorsson, Kristin Savolainen, Maria Hansbo, Malin Helliksson, Björne Nödtveidt, Johan Sanner, Victoria Sem, Camilla Sund Lindquist, Per Nordberg, Akil Awad, Anna-Sofa Börjesson, Malin Hedberg, Mia Henning, Jacob Hollenberg, Per Petersen, Emelia Dahlberg, Johan Forshammar, Veronica Svensson, Michael Wanecek, Håkan Eskilsson, Daniel Rodriguez-Santos, Åsa Appelqvist, Henrietta Jidbratt, Elisabeth Johansson, Lars Kiszakiewicz, Åsa Nilsson, Sinnika Olsson, Anders Paulsson, Urszula Stempel, Andreas Thoren, Stefan Persson, Ida Berglund, Eric Bergström, Cathrine Törnqvist, Ingela Östman, Sten Rubertsson, Ing-Marie Larsson, Elin Söderman, Ewa Wallin, Joanna Wessbergh, Thomas Halliday, Filippa Engvall, Mauro Oddo, Nawfel Ben-Hamouda, Adriano Bernini, Pierre-Nicolas Carron, Philippe Eckert, Eva Favre, John-Paul Miroz, Paola Morelli, Olivier Muller, Jan Novi, Andrea Rosseti, Madeleine Schnorf, Matthias Haenggi, Anja Levis, Sandra Nansoz, Marianne Roth, Nicole Söll, Claudia Schrag, Mensur Alicajic, Philipp Baier, Joel Dütschler, Dominique Flügel, Edith Fässler, Ruth Gamio-Veis, Marc Güpfert, Yvonne Hilpertshauser, Stefan Hägele-Link, Gian-Reto Kleger, Peter Krähenmann, Maria Elisabeth Mair, Nadja Schai, Christoph Strohmaier, Peter Tangl, Dominik Zieglgänsberger, Marco Maggiorini, Gabriele Claus, Gabi Consani Vogel, Lukas Imbach, Samira Kaiser, Eva-Maria Kleinert, Pedro David Wendel Garcia, Tiziano Cassina, Pamela Agazzi, Bruno Capelli, Gabriele Casso, Martino Regazzi, Hervé Schlotterbeck, Gabriele Via, Michele Villa, Matt P Wise, Jenny Brooks, Eve Cocks, Jade Cole, Jacqueline Curtin, Michelle Davies, Rhys Davies, Stephen Fernandez, Julie Highfeld, Helen Hill, Matt P G Morgan, Lydia Pennant, Sofa Rose, Emma Thomas, Angharad Williams, Peter McGuigan, Stephen Hafey, Aisling O'Neill, Kathryn Ward, Matthew Thomas, Jeremy Bewley, Anna Chillingworth, Julie Cloake, Libby Cole, Hilary Galvin, Zoe Garland, Lisa Grimmer, Bethany Gumbrill, Lucy Howie, Rebekah Johnson, Chloe Searles, Agnieszka Skorko, Katie Sweet, Victoria Taylor, Denise Webster, Thomas Keeble, Gill Adams, Rajesh K Aggarwal, Jo-Anne Cartwright, Steven Church, Gerald J Clesham, John R Davies, Kelly Farrell, Reto Gamma, Jane Harding, Rohan Jagathesan, Alamgir Kabir, Paul A Kelly, Lauren Kittridge, Maria Maccaroni, Gracie Maloney, Marco Mion, Naveen Nain, Raghunath Nalgirkar, Gyanesh Namjoshi, Stacey Pepper, Emily Redman, Nicholas M Robinson, Jeremy Sayer, Amanda Solesbury, Kare H Tang, Sali Urovi, Kunal Waghmare, Noel Watson, Teresa Webber, Peter Isherwood, Conor Bentley, Colin Bergin, Ronald Carrera, Amy Clark, Lauren Cooper, Liesl Despy, Natalie Dooley, Karen Ellis, Emma Fellows, Stephanie Goundry, Samantha Harkett, Christopher McGhee, Aoife Neal, Hazel Smith, Catherine Snelson, Elaine Spruce, Tony Whitehouse, Kamal Yakoub, Andrew Walden, Shauna Bartley, Parminder Bhuie, Matthew Frise, Nicola Jacques, Liza Keating, David Pogson, Zoe Daly, Steve Rose, Jonathan Bannard-Smith, Rachael Quayle, Nigel Chee, Nina Barratt, Katie Bowman, Debbie Branney, Elizabeth Howe, Maria Letts, Sally Pitts, Luke Vamplew, Clifton W Callaway, Sara Difore Sprouse, Ankur A Doshi, Jennifer Fugate, Amy M Headlee, Eelco F M Wijdicks

Affiliations

¹ Department of Intensive Care, Emergency Medicine and Anesthesiology, Fondazione Policlinico Universitario "Agostino Gemelli", IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
² Department of Clinical Sciences Lund, Cardiology, Lund University, Lund, Sweden.
³ Department of Clinical Sciences Lund, Anaesthesia and Intensive Care, Lund University, Lund, Sweden.
⁴ Copenhagen Trial Unit, Capital Region, Copenhagen, Denmark.
⁵ Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
⁶ Department of Neurology and Experimental Neurology, Charité, Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
⁷ Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
⁸ Department of Clinical Sciences Lund, Neurology, Lund University, Lund, Sweden.
⁹ Skane University Hospital, Lund, Sweden.
¹⁰ Department of Clinical Sciences Lund, Neurology and Rehabilitation, Lund University, Lund, Sweden.
¹¹ Department of Clinical Sciences Lund, Anesthesiology and Intensive Care Medicine, Helsingborg Hospital, Helsingborg, Sweden.
¹² Department of Neurology, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
¹³ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
¹⁴ Department of Clinical Sciences, Clinical Neurophysiology, Lund University, S-221 85, Lund, Sweden. erik.westhall@med.lu.se.

Abstract

Purpose: The 2021 guidelines endorsed by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) recommend using highly malignant electroencephalogram (EEG) patterns (HMEP; suppression or burst-suppression) at > 24 h after cardiac arrest (CA) in combination with at least one other concordant predictor to prognosticate poor neurological outcome. We evaluated the prognostic accuracy of HMEP in a large multicentre cohort and investigated the added value of absent EEG reactivity.

Methods: This is a pre-planned prognostic substudy of the Targeted Temperature Management trial 2. The presence of HMEP and background reactivity to external stimuli on EEG recorded > 24 h after CA was prospectively reported. Poor outcome was measured at 6 months and defined as a modified Rankin Scale score of 4-6. Prognostication was multimodal, and withdrawal of life-sustaining therapy (WLST) was not allowed before 96 h after CA.

Results: 845 patients at 59 sites were included. Of these, 579 (69%) had poor outcome, including 304 (36%) with WLST due to poor neurological prognosis. EEG was recorded at a median of 71 h (interquartile range [IQR] 52-93) after CA. HMEP at > 24 h from CA had 50% [95% confidence interval [CI] 46-54] sensitivity and 93% [90-96] specificity to predict poor outcome. Specificity was similar (93%) in 541 patients without WLST. When HMEP were unreactive, specificity improved to 97% [94-99] (p = 0.008).

Conclusion: The specificity of the ERC-ESICM-recommended EEG patterns for predicting poor outcome after CA exceeds 90% but is lower than in previous studies, suggesting that large-scale implementation may reduce their accuracy. Combining HMEP with an unreactive EEG background significantly improved specificity. As in other prognostication studies, a self-fulfilling prophecy bias may have contributed to observed results.

Keywords: Brain injury; Cardiac arrest; Coma; EEG; Outcome; Prognosis.

MeSH terms

Cardiopulmonary Resuscitation* / methods
Clinical Trials as Topic
Critical Care
Electroencephalography / methods
Heart Arrest* / diagnosis
Heart Arrest* / therapy
Humans
Hypothermia, Induced* / methods
Multicenter Studies as Topic
Prognosis