Lower vs Higher Oxygenation Target and Days Alive Without Life Support in COVID-19
Authors: Nielsen Frederik M. , Klitgaard Thomas L. , Siegemund Martin , Laake Jon H. , Thormar Katrin M. , Cole Jade M. , Aagaard Søren R. , Bunzel Anne-Marie G. , Vestergaard Stine R. , Langhoff Peter K. , Pedersen Caroline H. , Hejlesen Josefine Ø. , Abdelhamid Salim , Dietz Anna , Gebhard Caroline E. , Zellweger Nuria , Hollinger Alexa , Poulsen Lone M. , Weihe Sarah , Andersen-Ranberg Nina C. , Pedersen Ulf G. , Mathiesen Ole , Andreasen Anne Sofie , Brix Helene , Thomsen Jonas J. , Petersen Christina H. , Bestle Morten H. , Wichmann Sine , Lund Martin S. , Mortensen Karoline M. , Brand Björn A. , Haase Nicolai , Iversen Susanne A. , Marcussen Klaus V. , Brøchner Anne C. , Borup Morten , Grøfte Thorbjørn , Hildebrandt Thomas , Kjær Maj-Brit N. , Engstrøm Janus , Lange Theis , Perner Anders , Schjørring Olav L. , Rasmussen Bodil S. ,   HOT-COVID Trial Group, Eriksen Anne S. B. , Jørgensen Tina , Lauitzen Sanne , Valbjørn Lone , Christensen Ann B. , Foldager Niels , Sørensen Henrik S. , Haberlandt Trine , Vennegaard Annette , Aslam Tayyba N. , Hill Helen , Wise Matthew P. 
Published: March 2024

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