BACKGROUND: The evidence for temperature control for comatose survivors of cardiac arrest is inconclusive. Controversy exists as to whether the effects of hypothermia differ per the circumstances of the cardiac arrest or patient characteristics. METHODS: An individual patient data meta-analysis of the Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest (TTM) and Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trials was conducted. The intervention was hypothermia at 33°C and the comparator was normothermia. The primary outcome was all-cause mortality at 6 months. Secondary outcomes included poor functional outcome (modified Rankin scale score of 4 to 6) at 6 months. Predefined subgroups based on the design variables in the original trials were tested for interaction with the intervention as follows: age (older or younger than the median), sex (female or male), initial cardiac rhythm (shockable or nonshockable), time to return of spontaneous circulation (above or below the median), and circulatory shock on admission (presence or absence). RESULTS: The primary analyses included 2800 patients, with 1403 assigned to hypothermia and 1397 to normothermia. Death occurred for 691 of 1398 participants (49.4%) in the hypothermia group and 666 of 1391 participants (47.9%) in the normothermia group (relative risk with hypothermia, 1.03; 95% confidence interval [CI], 0.96 to 1.11; P=0.41). A poor functional outcome occurred for 733 of 1350 participants (54.3%) in the hypothermia group and 718 of 1330 participants (54.0%) in the normothermia group (relative risk with hypothermia, 1.01; 95% CI, 0.94 to 1.08; P=0.88). Outcomes were consistent in the predefined subgroups. CONCLUSIONS: Hypothermia at 33°C did not decrease 6-month mortality compared with normothermia after out-of-hospital cardiac arrest. (Funded by Vetenskapsrådet; ClinicalTrials.gov numbers NCT02908308 and NCT01020916.)

Adult Critical Care University Hospital of Wales Cardiff United Kingdom

Adult Intensive Care Medicine Service Neuroscience Critical Care Research Group Vaud University Hospital Center University of Lausanne Lausanne Switzerland

Anesthesia and Intensive Care Department of Clinical Sciences Skåne University Hospital Malmö Lund University Lund Sweden

Anesthesiology and Critical Care San Martino Policlinico Hospital Scientific Institute for Research Hospitalization and Healthcare for Oncology and Neurosciences University of Genoa Genoa Italy

Anesthesiology and Intensive Care Department of Clinical Sciences Helsingborg Hospital Lund Lund University Lund Sweden

Anesthesiology and Intensive Care Department of Clinical Sciences Skåne University Hospital Lund Lund University Lund Sweden

Anglia Ruskin School of Medicine Chelmsford Essex United Kingdom

Australian and New Zealand Intensive Care Research Centre Monash University Melbourne Australia

Cardiology Department of Clinical Sciences Skåne University Hospital Lund Lund University Lund Sweden

Cardiovascular Medicine 2nd Department of Medicine General University Hospital 1st Faculty of Medicine Charles University Prague Czech Republic

Clinical Studies Sweden Forum South Skåne University Hospital Lund Sweden

Cochin University Hospital Descartes University of Paris Paris

Copenhagen Trial Unit Center for Clinical Intervention Research Copenhagen University Hospital Copenhagen

Department of Anesthesiology and Intensive Care Medicine Institute of Clinical Sciences Sahlgrenska Academy University of Gothenburg Gothenburg Sweden

Department of Cardiology The Heart Centre Copenhagen University Hospital Rigshospitalet Copenhagen

Department of Clinical Medicine Research Center for Emergency Medicine Aarhus University Hospital Aarhus University Aarhus Denmark

Department of Clinical Science and Education Center for Resuscitation Science Karolinska Institutet Södersjukhuset Stockholm

Department of Emergency Medicine University of Pittsburgh Pittsburgh

Department of Intensive Care Academic Medical Center Amsterdam

Department of Intensive Care Bristol Royal Infirmary Bristol United Kingdom

Department of Intensive Care Erasme University Hospital Université Libre de Bruxelles Brussels

Department of Intensive Care Liverpool Hospital Sydney

Department of Intensive Care Medical Center Leeuwarden Leeuwarden The Netherlands

Department of Intensive Care Medicine Centre Hospitalier de Luxembourg Luxembourg Luxembourg

Department of Intensive Care Medicine Inselspital Bern University Hospital University of Bern Bern Switzerland

Department of Life Sciences and Medicine Faculty of Science Technology and Medicine University of Luxembourg Esch sur Alzette Luxembourg

Department of Nephrology and Medical Intensive Care Charité Universitätsmedizin Berlin Berlin

Department of Regional Health Research Faculty of Health Sciences University of Southern Denmark Odense Denmark

Department of Surgical Sciences and Integrated Diagnostics University of Genoa Genoa Italy

Division of Critical Care and Trauma George Institute for Global Health Sydney

Division of Emergencies and Critical Care Department of Anesthesiology Oslo University Hospital Rikshospitalet Oslo

Division of Intensive and Emergency Medicine Department of Internal Medicine Medical University Innsbruck Innsbruck Austria

Essex Cardiothoracic Centre Basildon United Kingdom

Intensive Care Department Kantonspital St Gallen St Gallen Switzerland

Intensive Care Unit Medical Research Institute of New Zealand Wellington Hospital Wellington New Zealand

Intensive Care Unit Santa Maria degli Angeli Pordenone Italy

Klinik und Hochschulambulanz für Neurologie Charité Universitätzmedizin Berlin

Neurology Department of Clinical Sciences Skåne University Hospital Lund Lund University Lund Sweden

School of Public Health and Preventive Medicine Australian and New Zealand Intensive Care Research Centre Monash University Melbourne Australia

University College Dublin Clinical Research Centre St Vincent's University Hospital Dublin

References provided by Crossref.org

Fever management with or without a temperature control device after out-of-hospital cardiac arrest and resuscitation (TEMP-CARE): A study protocol for a randomized clinical trial

See more in PubMed

ClinicalTrials.gov
NCT02908308, NCT01020916