• Josef Dankiewicz, Tobias Cronberg, Gisela Lilja, Janus C Jakobsen, Helena Levin, Susann Ullén, Christian Rylander, Matt P Wise, Mauro Oddo, Alain Cariou, Jan Bělohlávek, Jan Hovdenes, Manoj Saxena, Hans Kirkegaard, Paul J Young, Paolo Pelosi, Christian Storm, Fabio S Taccone, Michael Joannidis, Clifton Callaway, Glenn M Eastwood, MorganMatt P GMPGFrom the Department of Clinical Sciences Lund, Sections of Cardiology (J. Dankiewicz, D.E.), Neurology (T. Cronberg, G.L.), and Anesthesiology and Intensive Care (H. Levin, O.B.), Skåne University Hospital Lund, Lund University and Clinic, Per Nordberg, David Erlinge, Alistair D Nichol, Michelle S Chew, Jacob Hollenberg, Matthew Thomas, Jeremy Bewley, Katie Sweet, Anders M Grejs, Steffen Christensen, Matthias Haenggi, Anja Levis, Andreas Lundin, Joachim Düring, Simon Schmidbauer, Thomas R Keeble, Grigoris V Karamasis, Claudia Schrag, Edith Faessler, Ondrej Smid, Michal Otáhal, Marco Maggiorini, Pedro D Wendel Garcia, Paul Jaubert, Jade M Cole, Miroslav Solar, Ola Borgquist, Christoph Leithner, Samia Abed-Maillard, Leanlove Navarra, Martin Annborn, Johan Undén, Iole Brunetti, Akil Awad, Peter McGuigan, Bjørkholt OlsenRoyRFrom the Department of Clinical Sciences Lund, Sections of Cardiology (J. Dankiewicz, D.E.), Neurology (T. Cronberg, G.L.), and Anesthesiology and Intensive Care (H. Levin, O.B.), Skåne University Hospital Lund, Lund University and Clin, Tiziano Cassina, Philippe Vignon, Halvor Langeland, Theis Lange, Hans Friberg, Niklas Nielsen, and TTM2 Trial Investigators.
• From the Department of Clinical Sciences Lund, Sections of Cardiology (J. Dankiewicz, D.E.), Neurology (T. Cronberg, G.L.), and Anesthesiology and Intensive Care (H. Levin, O.B.), Skåne University Hospital Lund, Lund University and Clinical Studies Sweden - Forum South, Skåne University Hospital (S.U.), Lund; the Department of Clinical Sciences Lund, Section of Anesthesia and Intensive Care, Skåne University Hospital Malmö, Malmö, (J. Düring, S.S., H.F.); the Department of Clinical Sciences Lund, Sections of Anesthesiology and Intensive Care (M.A., N.N.) and Clinical Sciences Helsingborg (N.N.), Helsingborg Hospital, Helsingborg; the Department of Clinical Sciences Lund, Section of Anesthesiology and Intensive Care Lund, Hallands Hospital, Halmstad (J.U.); the Department of Anesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg (C.R., A. Lundin); the Department of Clinical Science and Education, Center for Resuscitation Science, Karolinska Institutet, Södersjukhuset, Stockholm (P.N., J. Hollenberg, A.A.); and the Department of Anesthesiology, Intensive Care, and Acute Medicine, Linköping University, Linköping (M.S.C.) - all in Sweden; Copenhagen Trial Unit, Center for Clinical Intervention Research, Copenhagen University Hospital (J.C.J.), and the Section of Biostatistics, Faculty of Health and Medical Sciences (T.L.), University of Copenhagen, Copenhagen, the Department of Regional Health Research, the Faculty of Health Sciences, University of Southern Denmark, Odense (J.C.J.), the Research Center for Emergency Medicine, the Department of Clinical Medicine (H.K.), and the Department of Intensive Care (A.M.G., S.C.), Aarhus University Hospital, Aarhus - all in Denmark; Adult Critical Care, University Hospital of Wales, Cardiff (M.P.W., M.P.G.M., J.M.C.), the Department of Intensive Care, Bristol Royal Infirmary, Bristol (M.T., J. Bewley, K.S.), Essex Cardiothoracic Centre, Basildon (T.R.K., G.V.K.), Anglia Ruskin University School of Medicine, Chelmsford, Essex (T.R.K., G.V.K.), and the Department of Anesthesiology and Intensive Care, Royal Victoria Hospital, Belfast (P.M.) - all in the United Kingdom; Neuroscience Critical Care Research Group and Adult Intensive Care Medicine Service, Centre Hospitalier Universitaire Vaudois-Lausanne University Hospital and University of Lausanne, Lausanne (M. Oddo, S.A.-M.), the Departments of Intensive Care Medicine (M.H.) and Anesthesiology and Pain Medicine, Inselspital (A. Levis), Bern University Hospital, University of Bern, Bern, the Intensive Care Department, Kantonsspital St. Gallen, St. Gallen (C. Schrag, E.F.), the Institute of Intensive Care Medicine, University Hospital Zurich, Zurich (M.M., P.D.W.G.), and the Cardiac Anesthesia and Intensive Care Department, Instituto Cardiocentro Ticino, Lugano (T. Cassina) - all in Switzerland; Descartes University of Paris and Cochin University Hospital, Paris (A.C., P.J.), Medical-Surgical Intensive Care Unit, Dupuytren Teaching Hospital, Limoges (P.V.) - all in France; the 2nd Department of Medicine (J. Bělohlávek, O.S.), and the Department of Anesthesiology and Intensive Care Medicine (M. Otáhal), General University Hospital and First Faculty of Medicine, Charles University, Prague, the 1st Department of Internal Medicine-Cardioangiology, University Hospital Hradec Králové, and Faculty of Medicine, Charles University, Hradec Králové (M. Solar) - all in the Czech Republic; the Department of Anesthesiology, Division of Emergencies and Critical Care, Oslo University Hospital, Rikshospitalet, Oslo (J. Hovdenes), the Department of Anesthesiology, Sørlandet Hospital, Arendal (R.B.O.), the Department of Anesthesiology and Intensive Care Medicine, St. Olav's University Hospital, and the Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim (H. Langeland) - all in Norway; the Division of Critical Care and Trauma, George Institute for Global Health, and Bankstown-Lidcombe Hospital, South Western Sydney Local Health District, Sydney (M. Saxena), and the Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine (G.M.E., A.D.N.), and the Department of Intensive Care, Alfred Health (A.D.N.), Monash University, Melbourne - all in Australia; the Medical Research Institute of New Zealand, Intensive Care Unit, Wellington Hospital, Wellington (P.J.Y., L.N.); the Departments of Surgical Sciences and Integrated Diagnostics (P.P.) and Anesthesiology and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience (P.P., I.B.), University of Genoa, Genoa, Italy; the Department of Nephrology and Medical Intensive Care (C. Storm), and Klinik und Hochschulambulanz für Neurologie (C.L.), Charité Universitätzmedizin, Berlin, Germany; the Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels (F.S.T.); the Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria (M.J.); the Department of Emergency Medicine, University of Pittsburgh, Pittsburgh (C.C.); and University College Dublin Clinical Research Centre at St. Vincent's University Hospital, Dublin, Ireland (A.D.N.).
• N. Engl. J. Med. 2021 Jun 17; 384 (24): 2283-2294.

BackgroundTargeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty.MethodsIn an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33°C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, ≥37.8°C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device.ResultsA total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P = 0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score ≥4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups.ConclusionsIn patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, NCT02908308.).Copyright © 2021 Massachusetts Medical Society.

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