Original Investigation 

Caring for the Critically Ill Patient

Conservative Oxygen Therapy in Mechanically Ventilated Critically Ill Adult Patients: The UK-ROX Randomized Clinical Trial

Daniel S. Martin, Doug W. Gould, Tasnin Shahid, et al

JAMA Published Online: June 12, 2025

doi: 10.1001/jama.2025.9663

Key Points

Question  Does reducing exposure to supplemental oxygen by using a reduced peripheral oxygen saturation (Spo₂) target of 90% (range, 88%-92%) decrease 90-day all-cause mortality in mechanically ventilated adult patients receiving supplemental oxygen in intensive care units?

Findings  This randomized clinical trial of 16 500 participants found no statistically significant difference between the groups with 35.4% of patients randomized to conservative oxygen therapy having died by 90 days compared with 34.9% of patients receiving usual oxygen therapy.

Meaning  The findings do not support an approach of reducing oxygen exposure by targeting an Spo₂ of 90% in mechanically ventilated adults receiving oxygen in an intensive care unit.

Abstract

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