RCT: In critically ill adults receiving mechanical ventilation and supplemental oxygen, conservative vs usual oxygen therapy did not reduce all-cause mortality at 90 d.
Martin DS, Gould DW, Shahid T, et al. Conservative Oxygen Therapy in Mechanically Ventilated Critically Ill Adult Patients: The UK-ROX Randomized Clinical Trial. JAMA. 2025 Jun 12. doi: 10.1001/jama.2025.9663.
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IMPORTANCE: Supplemental oxygen is frequently given to patients in intensive care units (ICUs); however, there is insufficient evidence to guide its therapeutic use and to minimize the potential harm caused by administering too little or too much.

OBJECTIVE: To determine whether reducing exposure to supplemental oxygen through a strategy of conservative oxygen therapy by using a peripheral oxygen saturation (Spo2) target of 90% (range, 88%-92%) reduces mortality at 90 days in mechanically ventilated adult patients receiving supplemental oxygen in the ICU.

DESIGN, SETTING, AND PARTICIPANTS: Multicenter, pragmatic, randomized clinical trial conducted in 97 ICUs in the UK including 16?500 mechanically ventilated patients receiving supplemental oxygen. Participants were enrolled between May 2021 and November 2024. Follow-up was completed in February 2025.

INTERVENTIONS: Participants randomized to conservative oxygen therapy (n = 8258) received the lowest fraction of inspired oxygen possible to maintain their Spo2 at 90%. Participants randomized to usual oxygen therapy (n = 8242) received oxygen therapy at the discretion of the treating clinician.

MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause mortality at 90 days. Secondary outcomes included duration of ICU and acute hospital stay among survivors, days alive and free from organ support at 30 days, and mortality at other time points.

RESULTS: Of 16?500 randomized patients, primary outcome data were available for 16?394 (8211 in the conservative and 8183 in the usual oxygen therapy group). Randomized groups were similar (median age, 60 [IQR, 48-71] years and 38.2% females in both groups [n = 5652]). Exposure to supplemental oxygen was 29% lower for participants in the conservative oxygen therapy group compared with the usual oxygen therapy group. By 90 days, 2908 participants (35.4%) in the conservative oxygen therapy group had died compared with 2858 (34.9%) in the usual oxygen therapy group. After adjustment for prespecified baseline variables, the risk difference was 0.7 percentage points (95% CI, -0.7 to 2.0; P = .28). There were no significant differences in durations in ICU or hospital stay, days alive and free from organ support at 30 days, or mortality at other time points.

CONCLUSIONS AND RELEVANCE: In adult patients receiving mechanical ventilation and supplemental oxygen in the ICU, minimizing oxygen exposure through conservative oxygen therapy did not significantly reduce all-cause mortality at 90 days.

TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN13384956.

Ratings
Specialty Area Score
Hospital Doctor/Hospitalists
Internal Medicine
Intensivist/Critical Care
Respirology/Pulmonology
Comments from MORE raters

Intensivist/Critical Care

Well done and important work that is consistent with previous studies. Also, MEGA-ROX is pending and will be the final word on this issue.

This is a large well-conducted clinical trial on a topic relevant to all practicing ICU physicians. It supports the hypothesis that lower O2 targets are safe, but not superior to higher O2 targets (it is possible these may vary by subgroup). Future evidence on the topic is forthcoming; however, for many clinicians this will reaffirm (not change) current practice.

Respirology/Pulmonology

Intriguing results about lower oxygen use in MV patients with similar outcomes to higher thresholds. This may impact lower baro/volutrauma.

Very large multicenter trial found no advantage to reducing oxygen exposure to mechanically ventilated ICU patients. However, the 'usual care' comparator group resulted in a less marked difference in mean SpO2 between the study groups. This may have limited the study results.

In this large RCT of 16,500 ICU patients on mechanical ventilation, conservative oxygen therapy (SpO2 88–92%) did not significantly reduce 90-day mortality vs usual care (35.4% vs 34.9%; risk difference 0.7%, 95% CI -0.7% to 2.0%; P = .28). NNT was 143 (95% CI: NNT harm 143 to 8 to NNT benefit 50), showing no clear benefit. No significant differences were seen in ICU/hospital stay or organ support-free days. Routine use of conservative oxygen targets in this population is not supported; individualized oxygen therapy based on clinical judgment remains appropriate.

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