Conservative oxygen therapy for mechanically ventilated adults with sepsis: a post hoc analysis of data from the intensive care unit randomized trial comparing two approaches to oxygen therapy (ICU-ROX)

PURPOSE: Sepsis is a common reason for intensive care unit (ICU) admission and mortality in ICU patients. Despite increasing interest in treatment strategies limiting oxygen exposure in ICU patients, no trials have compared conservative vs. usual oxygen in patients with sepsis. METHODS: We undertook a post hoc analysis of the 251 patients with sepsis enrolled in a trial that compared conservative oxygen therapy with usual oxygen therapy in 1000 mechanically ventilated ICU patients. The primary end point for the current analysis was 90-day mortality. Key secondary outcomes were cause-specific mortality, ICU and hospital length of stay, ventilator-free days, vasopressor-free days, and the proportion of patients receiving renal replacement therapy in the ICU. RESULTS: Patients with sepsis allocated to conservative oxygen therapy spent less time in the ICU with an SpO(2) ≥ 97% (23.5 h [interquartile range (IQR) 8–70] vs. 47 h [IQR 11–93], absolute difference, 23 h; 95% CI 8–38), and more time receiving an FiO(2) of 0.21 than patients allocated to usual oxygen therapy (20.5 h [IQR 1–79] vs. 0 h [IQR 0–10], absolute difference, 20 h; 95% CI 14–26). At 90-days, 47 of 130 patients (36.2%) assigned to conservative oxygen and 35 of 120 patients (29.2%) assigned to usual oxygen had died (absolute difference, 7 percentage points; 95% CI − 4.6 to 18.6% points; P = 0.24; interaction P = 0.35 for sepsis vs. non-sepsis). There were no statistically significant differences between groups for secondary outcomes but point estimates of treatment effects consistently favored usual oxygen therapy. CONCLUSIONS: Point estimates for the treatment effect of conservative oxygen therapy on 90-day mortality raise the possibility of clinically important harm with this intervention in patients with sepsis; however, our post hoc analysis was not powered to detect the effects suggested and our data do not exclude clinically important benefit or harm from conservative oxygen therapy in this patient group. CLINICAL TRIALS REGISTRY: ICU-ROX Australian and New Zealand Clinical Trials Registry number ACTRN12615000957594. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05857-x) contains supplementary material, which is available to authorized users.