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 M. Eastwood, Michelle S. Chew, Johan Undén, Matthew Thomas, Michael Joannidis, Alistair Nichol, Andreas Lundin, Jacob Hollenberg, Naomi Hammond, Manoj Saxena, Martin Annborn, Miroslav Solař, Fabio Silvio Taccone, Josef Dankiewicz, Niklas Nielsen, Anders Morten Grejs, Florian Ebner, Paolo Pelosi, TTM2 Trial collaborators, Jan Bělohlávek, Clifton W. Callaway, Alain Cariou, Tobias Cronberg, David Erlinge, Jan Hovdenes, Hans Kirkegaard, Helena Levin, Matt Morgan, Per Nordberg, Mauro Oddo, Christian Rylander, Christian Storm, Susann Ullén, Matt P. Wise, Kathy Rowan, David A Harrison, Paul Mouncey, Manu Shankar‐Hari, Duncan Young, Theis Lange, Karolina Palmér, Ulla-Britt Karlsson, Simon Heissler, Frances Bass, John Myburgh, Colman Taylor, Adele Bellino, Marwa Abel-all, Ben Finfer, Carolyn Koch, Yang Li, Anne O’Connor, Julia Pilowsky, Tina Schneider, Anna Tippett, Bridget Ady, Tessa Broadley, Amanda Brown, Liz Melgaard, Mimi Morgan, Vanessa Singh, Rebecca Symons, Kathrin Becker, Nathalie Van Sante, Vendula Saleova, Silvie Zerzanova, Samia Sefir-Kribel, Ute Lübeck, Martina Carrara, Kathryn Fernando, Diane Mackle, Leanlove Navarra, Judith Riley, Elin Westerheim, Marianne Flatebø, Ameldina Ceric, Zana Haxhija, Lovisa Terling, Lena Bossmar, Liz Jergle, Helén Holm Månsson, Samia Abed Maillard, Andreja Vujičić Žagar, Christina Jodlauk, Jennifer Scrivens, Kate Ainscough, Ciara Fahey, Rinaldo Bellomo, Leah Peck
Abstract
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 (PaO 2 ) 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 PaO 2 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 PaO 2 < 60 mmHg and severe hyperoxemia as PaO 2 > 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 (PaO 2 -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.