EvidenceAlerts

Nielsen FM, Klitgaard TL, Siegemund M, et al. Lower vs Higher Oxygenation Target and Days Alive Without Life Support in COVID-19: The HOT-COVID Randomized Clinical Trial. JAMA. 2024 Apr 9;331(14):1185-1194. doi: 10.1001/jama.2024.2934. (Original study)
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.

Ratings
Discipline Area Score
Internal Medicine 7 / 7
Infectious Disease 6 / 7
Intensivist/Critical Care 6 / 7
Respirology/Pulmonology 5 / 7
Comments from MORE raters

Infectious Disease rater

This study suggests that higher oxygen targets are not necessarily better; but like many issues in critical care, questions remain.

Intensivist/Critical Care rater

Relevant and well done. Supportive of using this for an ACPJC

Intensivist/Critical Care rater

This study is well-designed and has novel results that defy current treatment belief/wisdom and may change clinical practice.

Respirology/Pulmonology rater

This multicenter RCT found that in adult patients admitted to the ICU with COVID-19 and severe hypoxemia, a strategy using a lower oxygenation target (PaO2 60 mmHg) achieved more days alive without life support than a higher oxygenation target (PaO2 90 mmHg), with no significant differences in overall mortality or adverse events. The difference was driven mostly by less use of mechanical ventilation. Results were influenced heavily by a small number of patients with shock at baseline who experienced a huge benefit from lower oxygenation. Among the remaining participants, differences were more modest and not statistically significant.

Respirology/Pulmonology rater

Well conducted clinical trial showing a clinically important change in outcome with a readily deliverable intervention (changing a ventilator setting). It is likely applicable to a much broader group of patients beyond COVID-19.
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