BACKGROUND: Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients' outcome. METHODS: Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 < 60 mmHg and severe hyperoxemia as PaO2 > 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. RESULTS: 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93-1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95-1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). CONCLUSIONS: In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. TRIAL REGISTRATION: clinicaltrials.gov NCT02908308 , Registered September 20, 2016.

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

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

Department of Anaesthesia and Intensive Care A O U Policlinico San Marco Catania 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 Anesthesiology and Surgical Trauma Intensive Care Hospital Clínic Universitari de Valencia Valencia Spain

Department of Clinical Medicine Aarhus University Aarhus Denmark

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

Department of Clinical Science and Education Södersjukhuset Centre for Resuscitation Science Karolinska Institutet Solna 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 Helsingborg Hospital Lund University 251 87 Helsingborg Sweden

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

Department of Clinical Sciences Malmö Lund University Malmö Sweden

Department of Critical Care University of Melbourne Parkville VIC Australia

Department of Intensive Care Austin Hospital Melbourne Australia

Department of Intensive Care Medicine Aarhus University Hospital Aarhus Denmark

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

Department of Internal Medicine Cardioangiology University Hospital Hradec Králové Hradec Králové Czech Republic

Department of Internal Medicine Faculty of Medicine in Hradec Králové Charles University Hradec Králové Czech Republic

Department of Medicine University of Barcelona Barcelona Spain

Department of Operation and Intensive Care Hallands Hospital Halmstad Lund University Halland Sweden

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

Department of Surgery University of Valencia Valencia Spain

Department of Surgical Sciences and Integrated Diagnostics University of Genoa Viale Benedetto XV 16 Genoa Italy

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

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

Intensive Care Unit St George Hospital Sydney Australia

Intensive Care Unit Wellington Regional Hospital Wellington New Zealand

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

Monash University Melbourne VIC Australia

University Hospitals Bristol NHS Foundation Trust Bristol UK

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ClinicalTrials.gov
NCT02908308