PURPOSE: Hyperoxemia is common in patients resuscitated after out-of-hospital cardiac arrest (OHCA) admitted to the intensive care unit (ICU) and may increase the risk of mortality. However, the effect of hyperoxemia on functional outcome, specifically related to the timing of exposure to hyperoxemia, remains unclear. METHODS: The secondary analysis of the Target Temperature Management 2 (TTM-2) randomized trial. The primary aim was to identify the best cut-off of partial arterial pressure of oxygen (PaO2) to predict poor functional outcome within the first 24 h from admission, with this period further separated into 'very early' (0-4 h), 'early' (8-24 h), and 'late' (28-72 h) periods. Hyperoxemia was defined as the highest PaO2 recorded during each period. Poor functional outcome was defined as a 6 months modified Rankin Score (mRS) of 4 to 6. RESULTS: A total of 1,631 patients were analysed for the 'very early' and 'early' periods, and 1,591 in the 'late period'. In a multivariate logistic regression model, a PaO2 above 245 mmHg during the very early phase was independently associated with a higher probability of poor functional outcome (Odds Ratio, OR = 1.63, 95 % Confidence Interval, CI 1.08-2.44, p = 0.019). No significant associations were found for the later periods. CONCLUSIONS: Very early hyperoxemia after ICU admission is associated with higher risk of poor functional outcome after OHCA. Avoiding hyperoxia in the initial hours after resuscitation should be considered.

Adult Critical Care University Hospital of Wales Cardiff UK

Anesthesia and Critical Care San Martino Policlinico Hospital IRCCS for Oncology and Neuroscience Genoa Italy

Anesthesia and Critical Care San Martino Policlinico Hospital IRCCS for Oncology and Neuroscience Genoa Italy; Department of Surgical Sciences and Integrated Diagnostics University of Genoa Genoa Italy

Australian and New Zealand Intensive Care Research Centre Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne VIC Australia; Department of Intensive Care Austin hospital Melbourne Australia

Copenhagen Trial Unit Centre for Clinical Intervention Research Copenhagen University Hospital Rigshospitalet Copenhagen Denmark; Department of Regional Health Research Faculty of Health Sciences University of Southern Denmark Odense Denmark

Department of Anaesthesia and Intensive Care A O U Policlinico San Marco Catania Italy; Anesthesia and Critical Care San Martino Policlinico Hospital IRCCS for Oncology and Neuroscience Genoa Italy

Department of Anaesthesia and Intensive Care Biomedical and Clinical Sciences Linköping University Linköping Sweden

Department of Anaesthesiology and Intensive Care Medicine Institute of Clinical Sciences Sahlgrenska Academy University of Gothenburg 423 45 Gothenburg Sweden

Department of Biomedical Engineering Wroclaw University of Science and Technology Wrocław Poland

Department of Clinical Medicine Anaesthesiology and Intensive Care Lund University Lund Sweden

Department of Clinical Science and Education Södersjukhuset Centre for Resuscitation Science Karolinska Institute Stockholm Sweden

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

Department of Clinical Sciences Lund Anesthesia and Intensive Care Lund University Helsingborg Hospital S 251 87 Helsingborg Sweden

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

Department of Clinical Sciences Lund Neurology Skåne University Hospital Lund University Getingevägen 4 222 41 Lund Sweden

Department of Clinical Sciences Malmö Lund University Malmö Sweden; Department of Operation and Intensive Care Lund University Hallands Hospital Halmstad Halland Sweden

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

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

Department of Intensive Care Medicine Université Libre de Bruxelles Hopital Erasme Bruxelles Belgium

Department of Internal Medicine Cardioangiology University Hospital Hradec Kralove Hradec Kralove Czech Republic; Faculty of Medicine Charles University Hradec Králové Czech Republic

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

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

Institute of Intensive Care Medicine University Hospital of Zurich Rämistrasse 100 8091 Zurich Switzerland

Intensive Care Unit St George Hospital Sydney Australia

Malcolm Fisher Department of Intensive Care Royal North Shore Hospital Critical Care Division The George Institute for Global Health Faculty of Medicine UNSW Sydney Sydney Australia

Medical Research Institute of New Zealand Private Bag 7902 Wellington 6242 New Zealand; Intensive Care Unit Wellington Regional Hospital Wellington New Zealand; Australian and New Zealand Intensive Care Research Centre Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne VIC Australia; Department of Critical Care University of Melbourne Parkville VIC Australia

University Hospitals Bristol NHS Foundation Trust Bristol UK

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