BACKGROUND: The aim of this study was to assess whether hypothermia increased survival and improved functional outcome when compared with normothermia in out-of-hospital cardiac arrest (OHCA) patients with similar characteristics than in previous randomized studies showing benefits for hypothermia. METHODS: Post hoc analysis of a pragmatic, multicenter, randomized clinical trial (TTM-2, NCT02908308). In this analysis, the subset of patients included in the trial who had similar characteristics to patients included in one previous randomized trial and randomized to hypothermia at 33 °C or normothermia (i.e. target < 37.8 °C) were considered. The primary outcome was survival at 6 months; secondary outcomes included favorable functional outcome at 6 months, defined as a modified Rankin scale of 0-3. Time-to-death and the occurrence of adverse events were also reported. RESULTS: From a total of 1891 included in the TTM-2 study, 600 (31.7%) were included in the analysis, 294 in the hypothermia and 306 in the normothermia group. At 6 months, 207 of the 294 patients (70.4%) in the hypothermia group and 220 of the 306 patients (71.8%) in the normothermia group had survived (relative risk with hypothermia, 0.96; 95% confidence interval [CI], 0.81 to 1.15; P = 0.71). Also, 198 of the 294 (67.3%) in the hypothermia group and 202 of the 306 (66.0%) in the normothermia group had a favorable functional outcome (relative risk with hypothermia, 1.03; 95% CI, 0.87 to 1.23; P = 0.79). There was a significant increase in the occurrence of arrythmias in the hypothermia group (62/294, 21.2%) when compared to the normothermia group (43/306, 14.1%-OR 1.49, 95% CI 1.05-2.14; p = 0.026). CONCLUSIONS: In this study, hypothermia at 33˚C did not improve survival or functional outcome in a subset of patients with similar cardiac arrest characteristics to patients in whom benefit from hypothermia was shown in prior studies.

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

Adult Critical Care University Hospital of Wales Cardiff UK

After ROSC Network Paris France

Anglia Ruskin School of Medicine MTRC Chelmsford UK

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

Cardiology Department Lund University Skåne University Hospital Lund Lund Sweden

Copenhagen Trial Unit Centre for Clinical Intervention Research The Capital Region Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Department of Anesthesiology and Critical Care IRCCS Policlinico San Martino Genoa Italy

Department of Cardiology Essex Cardiothoracic Centre MSE Essex UK

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

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

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

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

Department of Critical Care University of Melbourne Melbourne VIC Australia

Department of Intensive Care Hôpital Universitaire de Bruxelles Brussels Belgium

Department of Intensive Care Liverpool Hospital Sydney Australia

Department of Intensive Care Medicine and Clinical Medicine Aarhus University Hospital Aarhus Denmark

Department of Intensive Care Wellington Regional Hospital Te Whatu Ora Capital Coast and Hutt Valley Wellington New Zealand

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

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

Institute for Heart Diseases Wroclaw Medical University Wrocław Poland

Institute of Intensive Care Medicine University Hospital Zurich Zurich Switzerland

Intensive and Perioperative Care Skåne University Hospital Malmö Sweden

Medical Intensive Care Unit AP HP Centre Cochin Hospital Université Paris Cité Paris France

Medical Research Institute of New Zealand Wellington New Zealand

Oslo University Hospital Rikshospitalet Oslo Norway

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