Original Investigation 

Caring for the Critically Ill Patient

March 19, 2024

Lower vs Higher Oxygenation Target and Days Alive Without Life Support in COVID-19: The HOT-COVID Randomized Clinical Trial

Frederik M. Nielsen, Thomas L. Klitgaard, Martin Siegemund, et al

JAMA. Published online March 19, 2024. doi:10.1001/jama.2024.2934

Key Points

Question  Does targeting a Pao₂ of 60 mm Hg vs 90 mm Hg affect the number of days alive without life support in intensive care unit patients with COVID-19 and severe hypoxemia?

Findings  In this randomized trial including 726 patients, targeting a Pao₂ of 60 mm Hg resulted in 80.0 days alive without support at 90 days compared with 72.0 days when targeting a Pao₂ of 90 mm Hg. This difference was statistically significant.

Meaning  A Pao₂ target of 60 mm Hg vs 90 mm Hg resulted in more days alive without life support in intensive care unit patients with COVID-19 and severe hypoxemia.

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