Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/33469
Title: Effects of Hypothermia vs Normothermia on Societal Participation and Cognitive Function at 6 Months in Survivors After Out-of-Hospital Cardiac Arrest: A Predefined Analysis of the TTM2 Randomized Clinical Trial.
Austin Authors: Lilja, Gisela;Ullén, Susann;Dankiewicz, Josef;Friberg, Hans;Levin, Helena;Nordström, Erik Blennow;Heimburg, Katarina;Jakobsen, Janus Christian;Ahlqvist, Marita;Bass, Frances;Belohlavek, Jan;Olsen, Roy Bjørkholt;Cariou, Alain;Eastwood, Glenn M ;Fanebust, Hans Rune;Grejs, Anders M;Grimmer, Lisa;Hammond, Naomi E;Hovdenes, Jan;Hrecko, Juraj;Iten, Manuela;Johansen, Henriette;Keeble, Thomas R;Kirkegaard, Hans;Lascarrou, Jean-Baptiste;Leithner, Christoph;Lesona, Mildred Eden;Levis, Anja;Mion, Marco;Moseby-Knappe, Marion;Navarra, Leanlove;Nordberg, Per;Pelosi, Paolo;Quayle, Rachael;Rylander, Christian;Sandberg, Helena;Saxena, Manoj;Schrag, Claudia;Siranec, Michal;Tiziano, Cassina;Vignon, Philippe;Wendel-Garcia, Pedro David;Wise, Matt P;Wright, Kim;Nielsen, Niklas;Cronberg, Tobias
Affiliation: Clinical Studies Sweden, Forum South, Skane University Hospital, Lund, Sweden.
Cardiology, Department of Clinical Sciences Lund, Lund University, Skane University Hospital, Lund, Sweden.
Anesthesia and Intensive Care, Department of Clinical Sciences Lund, Lund University, Skane University Hospital, Malmö, Sweden.
Neurology, Department of Clinical Sciences Lund, Lund University, Skane University Hospital, Lund, Sweden.
Copenhagen Trial Unit, Center for Clinical Intervention Research, Copenhagen University Hospital, Copenhagen, Denmark.;Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Denmark.
Department of Anaesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
Critical Care Program, The George Institute for Global Health and UNSW Sydney, Sydney, New South Wales, Australia.;Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, Sydney, New South Wales, Australia.
2nd Department of Medicine-Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic.
Department of Anesthesiology, Sørlandet Hospital, Arendal, Norway.
Cochin University Hospital (APHP) and Paris Cité University (medical school), Paris, France.
Intensive Care
Cardiac Intensive Care Unit, Haukeland University Hospital, Bergen, Norway.
Department of Intensive Care Medicine and Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
University Hospitals Bristol and Weston NHS Trust, Bristol, United Kingdom.
Critical Care Program, The George Institute for Global Health and UNSW Sydney, Sydney, New South Wales, Australia.;Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, Sydney, New South Wales, Australia.
Department of Anesthesiology, Division of Emergencies and Critical Care, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
The 1st Department of Internal Medicine, Cardioangiology, Medical Faculty of Charles University in Hradec Králové and University Hospital Hradec Králové, Hradec Králové, Czech Republic.
Department of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Department of Neurology, Rikshospitalet, Oslo University Hospital, Oslo, Norway.
Essex Cardio Thoracic Centre, Basildon, Essex, UK Thurrock University Hospitals, Basildon, United Kingdom.;MTRC, Anglia Ruskin University Faculty of Health Education Medicine & Social Care, Chelmsford, Essex, United Kingdom.
Research Center for Emergency Medicine, Emergency Department Aarhus University Hospital and Department of Clinical Medicine Aarhus University, Aarhus, Denmark.
Medecine Intensive Reanimation, CHU Nantes, Nantes, France.
Charité- Universitätsmedizin Berlin, coroporate member of Freie Universität Berlin and Humboldt- Universität-zu-Berlin, Department of Neurology, Berlin, Germany.
Intensive Care Unit, Wellington hospital, Wellington, New Zealand.
Department of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.;Department of Anesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Essex Cardio Thoracic Centre, Basildon, Essex, UK Thurrock University Hospitals, Basildon, United Kingdom.;MTRC, Anglia Ruskin University Faculty of Health Education Medicine & Social Care, Chelmsford, Essex, United Kingdom.
Neurology, Department of Clinical Sciences Lund, Lund University, Skane University Hospital, Lund, Sweden.
Medical Research Institute of New Zealand, Wellington, New Zealand.
Center for Resuscitation Sciences, Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.;Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy.;Anesthesia and Critical Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy.
Manchester Foundation Trust, Manchester, United Kingdom.;The Greater Manchester NIHR Clinical Research Network, Manchester, United Kingdom.
Department of Surgical Sciences, Anaesthesiology and Intensive Care Medicine, Uppsala University, Sweden.
Hallands hospital, Halmstad, Sweden.
St George Hospital Clinical School, The George institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.
Intensive Care Department, Kantonspital St Gallen, St Gallen, Switzerland.
2nd Department of Medicine-Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic.
Cardiac anesthesia and Intensive Care department, Istituto Cardiocentro Ticino, Lugano, Switzerland.
Medical-surgical ICU and Inserm CIC 1435, Dupuytren University hospital, Limoges, France.
Institute of Intensive Care Medicine, University Hospital Zurich, Zurich, Switzerland.
Adult Critical Care, University Hospital of Wales, Cardiff, United Kingdom.
University Hospitals Bristol and Weston NHS Trust, Bristol, United Kingdom.
Department of Clinical Sciences Lund, Anaesthesia and Intensive Care and Clinical Sciences Helsingborg, Helsingborg Hospital, Lund University, Lund, Sweden.
Neurology, Department of Clinical Sciences Lund, Lund University, Skane University Hospital, Lund, Sweden.
Issue Date: 7-Aug-2023
Date: 2023
Publication information: JAMA Neurology 2023-08-07
Abstract: The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. Randomization 1:1 to temperature control with targeted hypothermia at 33 °C or targeted normothermia and early treatment of fever (37.8 °C or higher). Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes. At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P = .46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,-0.33 to 1.05; P = .37) and SDMT (mean difference, 0.06; 95% CI,-0.16 to 0.27; P = .62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%). In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common. ClinicalTrials.gov Identifier: NCT02908308.
URI: https://ahro.austin.org.au/austinjspui/handle/1/33469
DOI: 10.1001/jamaneurol.2023.2536
ORCID: 
Journal: JAMA Neurology
PubMed URL: 37548968
ISSN: 2168-6157
Type: Journal Article
Appears in Collections:Journal articles

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