Early Restrictive vs Liberal Oxygen for Trauma Patients: The TRAUMOX2 Randomized Clinical Trial

Abstract

Importance: Early administration of supplemental oxygen for all severely injured trauma patients is recommended, but liberal oxygen treatment has been associated with increased risk of death and respiratory complications.

Objective: To determine whether an early 8-hour restrictive oxygen strategy compared with a liberal oxygen strategy in adult trauma patients would reduce death and/or major respiratory complications.

Design, setting, and participants: This randomized controlled trial enrolled adult trauma patients transferred directly to hospitals, triggering a full trauma team activation with an anticipated hospital stay of a minimum of 24 hours from December 7, 2021, to September 12, 2023. This multicenter trial was conducted at 15 prehospital bases and 5 major trauma centers in Denmark, the Netherlands, and Switzerland. The 30-day follow-up period ended on October 12, 2023. The primary outcome was assessed by medical specialists in anesthesia and intensive care medicine blinded to the randomization.

Interventions: In the prehospital setting or on trauma center admission, patients were randomly assigned 1:1 to a restrictive oxygen strategy (arterial oxygen saturation target of 94%) (n = 733) or liberal oxygen strategy (12-15 L of oxygen per minute or fraction of inspired oxygen of 0.6-1.0) (n = 724) for 8 hours.

Main outcomes and measures: The primary outcome was a composite of death and/or major respiratory complications within 30 days. The 2 key secondary outcomes, death and major respiratory complications within 30 days, were assessed individually.

Results: Among 1979 randomized patients, 1508 completed the trial (median [IQR] age, 50 [31-65] years; 73% male; and median Injury Severity Score was 14 [9-22]). Death and/or major respiratory complications within 30 days occurred in 118 of 733 patients (16.1%) in the restrictive oxygen group and 121 of 724 patients (16.7%) in the liberal oxygen group (odds ratio, 1.01 [95% CI, 0.75 to 1.37]; P = .94; absolute difference, 0.56 percentage points [95% CI, -2.70 to 3.82]). No significant differences were found between groups for each component of the composite outcome. Adverse and serious adverse events were similar across groups, with the exception of atelectasis, which was less common in the restrictive oxygen group compared with the liberal oxygen group (27.6% vs 34.7%, respectively).

Conclusions and relevance: In adult trauma patients, an early restrictive oxygen strategy compared with a liberal oxygen strategy initiated in the prehospital setting or on trauma center admission for 8 hours did not significantly reduce death and/or major respiratory complications within 30 days.

Trial registration: ClinicalTrials.gov Identifier: NCT05146700.

Figure 1.. Screening, Randomization, and Follow-Up of Patients in the TRAUMOX2 Trial

In this pragmatic trial, prehospital information on assessment for eligibility was not possible. ^aIncluded in other trials that prohibited coenrollment, previously enrolled patients, acute medical calls incorrectly labeled as trauma team activation, and unknown time of trauma.

Figure 2.. Patient Outcomes

Trial outcomes for trauma patients randomized to either a restrictive oxygen strategy or liberal oxygen strategy. The odds ratios were adjusted for stratification variables. Further adjusted analyses are presented in eTables 4 and 5 in Supplement 2. Death and/or major respiratory complications, surgical site infection, and pneumonia postdischarge were evaluated within 30 days. Hypoxemic episode(s) were defined as the presence of any Spo₂ less than 90% during the 8-hour intervention from the hourly collected Spo₂ values. ICU readmission and sepsis were evaluated during the initial hospital admission (not at hospital readmission). ICU indicates intensive care unit; and Spo₂, arterial oxygen saturation measured by pulse oximetry.

Figure 3.. Cumulative Incidence of Death and/or Major Respiratory Complications

Visualization of data using Kaplan-Meier curves of the incidences of the primary outcome (A) and key secondary outcomes (B, C) during the 30-day follow-up period for trauma patients randomized to either a restrictive oxygen strategy or liberal oxygen strategy.

Figure 4.. Subgroup Analysis of Death and/or Major Respiratory Complications Within 30 Days

The odds ratios were adjusted for stratification variables. Further adjusted analyses are presented in eTable 7 in Supplement 2. AIS indicates Abbreviated Injury Scale; ICU, intensive care unit; and TBI, traumatic brain injury. ^aAIS scores range from 0 to 6 and are based on injuries in different anatomical regions. A head score below 3 indicates mild TBI and a score of 3 or higher indicates moderate or severe TBI. Only the AIS codes for isolated brain injury were selected, thereby excluding neck injuries. ^bInjury Severity Score ranges from 0 to 75, used to assess anatomical injury severity. Scores below 15 indicate mild to moderate trauma, while scores higher than 15 are considered severe trauma.