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Randomized Controlled Trial
. 2025 Mar 3;8(3):e252093.
doi: 10.1001/jamanetworkopen.2025.2093.

Targeted Normoxemia and Supplemental Oxygen-Free Days in Critically Injured Adults: A Stepped-Wedge Cluster Randomized Clinical Trial

David J Douin  1 , John D Rice  2 , Erin L Anderson  3 , Conner L Jackson  4 , Alex C Cheng  5 , Mengli Xiao  4 , Jessica Cwik  3 , Laurel E Beaty  4 , Jessica L Wild  4 , Mohamud R Daya  6 , Pratik B Doshi  7 , Shannon C Eastham  8 , Michael D Goodman  9 , Scott R Gunn  10 , Jason S Haukoos  11 , Jessica A Hudson  7 , Jan O Jansen  12 , Jason T McMullan  13 , Julie A Rizzo  14 , Martin A Schreiber  15 , Wesley H Self  16 , Matthew W Semler  17 , Aimee Steinwand  3 , Nicole Werner  18   19 , Vikhyat S Bebarta  3   20 , Steven G Schauer  21   22 , Adit A Ginde  3 ; Strategy to Avoid Excessive Oxygen (SAVE-O2) Investigators
Collaborators, Affiliations
Randomized Controlled Trial

Targeted Normoxemia and Supplemental Oxygen-Free Days in Critically Injured Adults: A Stepped-Wedge Cluster Randomized Clinical Trial

David J Douin et al. JAMA Netw Open. .

Abstract

Importance: Supplemental oxygen is fundamental to caring for critically injured adults but can expose them to excess inspired oxygen.

Objective: To determine the safety and effectiveness of targeting normoxemia in critically ill trauma patients.

Design, setting, and participants: This multicenter, stepped-wedge, cluster randomized clinical trial compared targeted normoxemia (defined as a peripheral oxygen saturation [Spo2] of 90% to 96%) with usual care among adult trauma patients admitted to an intensive care unit (ICU) at 8 level I trauma centers across the US. These trauma centers were randomized at 3-month intervals when they crossed over from usual care to targeting normoxemia. Eligible patients were enrolled between July 15, 2020, and November 14, 2022. All statistical analyses were performed from April 2023 to November 2024 according to intention-to-treat approach.

Intervention: In the usual care group, supplemental oxygen was determined by treating clinicians. In the targeted normoxemia group, a multimodal educational and informatics intervention encouraged decreasing the supplemental oxygen administered whenever Spo2 exceeded 96%.

Main outcomes and measures: The primary outcome was supplemental oxygen-free days (SOFDs), defined as the number of days alive and not receiving supplemental oxygen through day 28. Safety outcomes included hypoxemia (defined as Spo2 <88%) during the ICU admission, in-hospital mortality, and adverse events.

Results: A total of 12 487 patients were enrolled (mean [SD] age, 51.7 [21.1] years; 8799 males [70.5%]; mean [SD] Injury Severity Score, 19.6 [12.0]). The proportion of ICU time spent in normoxemia increased from 56.2% in the usual care group to 71.6% in the targeted normoxemia group. Hyperoxemia (defined as Spo2 >96%) decreased from 42.4% in the usual care group to 26.7% in the targeted normoxemia group, and hypoxemia was similar between groups (1.1% vs 1.1%). The raw mean (SD) number of SOFDs was 19.6 (10.3) days for the targeted normoxemia group and 17.5 (10.4) days for the usual care group (adjusted mean difference [AMD], 0.32 [95% CI, -0.37 to 1.00] days; P = .30). Among patients not receiving mechanical ventilation at ICU admission, mean SOFDs were greater in the targeted normoxemia group than in the usual care group (22.6 [8.30] days vs 20.6 [8.86] days; AMD, 0.75; 95% CI, 0.00-1.50 days). The mean (SD) time for weaning to room air was 1.6 (3.2) days for the targeted normoxemia group and 2.7 (4.0) days for the usual care group (adjusted hazard ratio [AHR], 1.23; 95% CI, 1.13-1.33 days). In-hospital mortality to day 90 occurred in 563 patients (9.9%) in the targeted normoxemia and 732 patients (10.7%) in the usual care group (AHR, 1.05; 95% CI, 0.83-1.33). No adverse events were reported in either group.

Conclusions and relevance: This randomized clinical trial showed that targeting normoxemia did not increase the number of SOFDs but safely reduced supplemental oxygen use among critically ill trauma patients.

Trial registration: ClinicalTrials.gov Identifier: NCT04534959.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Douin reported receiving grants from the National Heart, Lung, and Blood Institute (NHLBI) during the conduct of the study. Dr Rice reported receiving grants from the US Department of Defense (DOD) Joint Warfighter Medical Research Program (JWMRP) during the conduct of the study. Ms Anderson reported receiving grants from the DOD during the conduct of the study. Dr Cheng reported receiving grants from the DOD, National Center for Advancing Translational Sciences, National Library of Medicine, and the Patient Centered Outcomes Research Network during the conduct of the study. Dr Xiao reported receiving grants from the DOD and the National Institutes of Health (NIH) during the conduct of the study. Dr Daya reported receiving grants from the DOD and the NIH during the conduct of the study. Dr Doshi reported receiving grants to the institution from the DOD during the conduct of the study. Dr Goodman reported receiving grants from the DOD during the conduct of the study. Dr Jansen reported receiving grants from the NHLBI, National Institute for Health and Care Research, Medical Technology Enterprise Consortium, the DOD, Infrascan, and CSL Behring; clinical devices for a trial donated by RevMedX; and personal fees from Infrascan, CSL Behring, and Octapharma outside the submitted work. Dr Schreiber reported receiving grants to the institution from the DOD during the conduct of the study. Dr Self reported receiving grants from the DOD during the conduct of the study. Dr Semler reported receiving grants to the institution from the DOD during the conduct of the study and receiving personal fees from Baxter Healthcare Inc and serving on a medical advisory board outside the submitted work. Dr Schauer reported receiving grants from the DOD during the conduct of the study and outside the submitted work. Dr Ginde reported receiving grants from the DOD, the NIH, the Centers for Disease Control and Prevention, and the Patient Centered Outcomes Research Institute during the conduct of the study; grants from O2matic and consulting fees from SeaStar and Biomeme outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study FlowDiagram
Enrollment of patients was based on prespecified inclusion and exclusion criteria. A total of 294 patients were excluded after eligibility was determined due to missing data, which made analysis of the primary outcome (supplemental oxygen–free days) impossible. ED indicates emergency department; ICU, intensive care unit.
Figure 2.
Figure 2.. Mean FIO2 and Oxygen Saturation Measured by Pulse Oximetry (SpO2) Values During Intensive Care Unit (ICU) Admission for Modifiable Patient Time
Shaded areas represent 95% CIs. Patient time was considered nonmodifiable if the patient was receiving FIO2 of 21% (ie, room air) but had SpO2 greater than 96% (ie, hyperoxemia range). All other patient time is included.
Figure 3.
Figure 3.. Proportion of Patients Alive and Not Receiving Supplemental Oxygen Through Day 28, by Intervention Group
The top curve is a Kaplan-Meier mortality plot. The bottom curve is time to room air (ie, receiving no supplemental oxygen).
See this image and copyright information in PMC

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