Lower vs Higher Oxygenation Target and Days Alive Without Life Support in COVID-19
Frederik Mølgaard Nielsen, Thomas Klitgaard, Martin Siegemund, Jon Henrik Laake, Katrín Þormar, Jade Cole, Søren Rosborg Aagaard, Anne‐Marie Gellert Bunzel, Stine Rom Vestergaard, Peter K. Langhoff, Caroline H. Pedersen, Josefine Ø. Hejlesen, Salim Abdelhamid, Anna Dietz, Caroline E. Gebhard, Núria Zellweger, Alexa Hollinger, Lone Musaeus Poulsen, Sarah Weihe, Nina Christine Andersen‐Ranberg, U. G. Pedersen, Ole Mathiesen, Anne Sofie Andreasen, Helene Brix, J. Thomsen, Christina H. Petersen, Morten H. Bestle, Sine Wichmann, Martin S. Lund, Karoline M. Mortensen, Björn Brand, Nicolai Haase, Susanne Iversen, Klaus V. Marcussen, Anne Craveiro Brøchner, Morten Borup, Thorbjørn Grøfte, Thomas Hildebrandt, Maj-Brit N. Kjær, Janus Engstrøm, Theis Lange, Anders Perner, Olav Lilleholt Schjørring, Bodil Steen Rasmussen, HOT-COVID Trial Group, Anne Sofie Broberg Eriksen, Tina Jørgensen, Sanne Lauitzen, Lone Valbjørn, Ann B. Christensen, N. Foldager, Henrik S. Sørensen, Trine Haberlandt, Annette Vennegaard, Tayyba Naz Aslam, Helen Hill, Matt P. Wise
Abstract
Importance: Supplemental oxygen is ubiquitously used in patients with COVID-19 and severe hypoxemia, but a lower dose may be beneficial. Objective: To assess the effects of targeting a Pao2 of 60 mm Hg vs 90 mm Hg in patients with COVID-19 and severe hypoxemia in the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized clinical trial including 726 adults with COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 11 ICUs in Europe from August 2020 to March 2023. The trial was prematurely stopped prior to outcome assessment due to slow enrollment. End of 90-day follow-up was June 1, 2023. Interventions: Patients were randomized 1:1 to a Pao2 of 60 mm Hg (lower oxygenation group; n = 365) or 90 mm Hg (higher oxygenation group; n = 361) for up to 90 days in the ICU. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (mechanical ventilation, circulatory support, or kidney replacement therapy) at 90 days. Secondary outcomes included mortality, proportion of patients with serious adverse events, and number of days alive and out of hospital, all at 90 days. Results: Of 726 randomized patients, primary outcome data were available for 697 (351 in the lower oxygenation group and 346 in the higher oxygenation group). Median age was 66 years, and 495 patients (68%) were male. At 90 days, the median number of days alive without life support was 80.0 days (IQR, 9.0-89.0 days) in the lower oxygenation group and 72.0 days (IQR, 2.0-88.0 days) in the higher oxygenation group (P = .009 by van Elteren test; supplemental bootstrapped adjusted mean difference, 5.8 days [95% CI, 0.2-11.5 days]; P = .04). Mortality at 90 days was 30.2% in the lower oxygenation group and 34.7% in the higher oxygenation group (risk ratio, 0.86 [98.6% CI, 0.66-1.13]; P = .18). There were no statistically significant differences in proportion of patients with serious adverse events or in number of days alive and out of hospital. Conclusion and Relevance: In adult ICU patients with COVID-19 and severe hypoxemia, targeting a Pao2 of 60 mm Hg resulted in more days alive without life support in 90 days than targeting a Pao2 of 90 mm Hg. Trial Registration: ClinicalTrials.gov Identifier: NCT04425031.