Oxygen targets and 6-month outcome after out of hospital cardiac arrest: a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial
Chiara Robba,
Rafael Badenes,
Denise Battaglini,
Lorenzo Ball,
Filippo Sanfilippo,
Iole Brunetti,
Janus Christian Jakobsen,
Gisela Lilja,
Hans Friberg,
Pedro David Wendel-Garcia,
Paul J. Young,
Glenn Eastwood,
Michelle S. Chew,
Johan Unden,
Matthew Thomas,
Michael Joannidis,
Alistair Nichol,
Andreas Lundin,
Jacob Hollenberg,
Naomi Hammond,
Manoj Saxena,
Annborn Martin,
Miroslav Solar,
Fabio Silvio Taccone,
Josef Dankiewicz,
Niklas Nielsen,
Anders Morten Grejs,
Florian Ebner,
Paolo Pelosi,
TTM2 Trial collaborators
Affiliations
Chiara Robba
Anesthesia and Critical Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience
Rafael Badenes
Department of Anesthesiology and Surgical-Trauma Intensive Care, Hospital Clínic Universitari de Valencia
Denise Battaglini
Anesthesia and Critical Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience
Lorenzo Ball
Anesthesia and Critical Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience
Filippo Sanfilippo
Department of Anaesthesia and Intensive Care, A.O.U. “Policlinico-San Marco”
Iole Brunetti
Anesthesia and Critical Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience
Janus Christian Jakobsen
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital - Rigshospitalet
Gisela Lilja
Department of Clinical Sciences Lund, Neurology, Skåne University Hospital, Lund University
Hans Friberg
Department of Clinical Sciences Lund, Anesthesia and Intensive Care, Lund University
Pedro David Wendel-Garcia
Institute of Intensive Care Medicine, University Hospital of Zurich
Paul J. Young
Medical Research Institute of New Zealand
Glenn Eastwood
Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University
Michelle S. Chew
Department of Anaesthesia and Intensive Care, Biomedical and Clinical Sciences, Linköping University
Johan Unden
Department of Clinical Sciences Malmö, Lund University
Matthew Thomas
University Hospitals Bristol NHS Foundation Trust
Michael Joannidis
Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck
Alistair Nichol
Monash University
Andreas Lundin
Department of Anaesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg
Jacob Hollenberg
Department of Clinical Science and Education, Södersjukhuset, Centre for Resuscitation Science, Karolinska Institutet
Naomi Hammond
Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, Critical Care Division, The George Institute for Global Health, Faculty of Medicine, UNSW Sydney
Manoj Saxena
Intensive Care Unit, St George Hospital
Annborn Martin
Department of Clinical Medicine, Anaesthesiology and Intensive Care, Lund University
Miroslav Solar
Department of Internal Medicine, Faculty of Medicine in Hradec Králové, Charles University
Fabio Silvio Taccone
Department of Intensive Care Medicine, Université Libre de Bruxelles, Hopital Erasme
Josef Dankiewicz
Department of Clinical Sciences Lund, Cardiology, Skåne University Hospital, Lund University
Niklas Nielsen
Department of Clinical Sciences Lund, Anaesthesia and Intensive Care and Clinical Sciences Helsingborg, Helsingborg Hospital, Lund University
Anders Morten Grejs
Department of Intensive Care Medicine, Aarhus University Hospital
Florian Ebner
Department of Clinical Sciences Lund, Anesthesia and Intensive Care, Helsingborg Hospital, Lund University
Paolo Pelosi
Anesthesia and Critical Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience
Abstract 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 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.
