The TRAUMOX2 Trial: Early Restrictive vs Liberal Oxygen Strategies in Adult Trauma Patients

🧭 REBEL Rundown

📌 Key Points

  • 🫁 Restrictive is safe – Targeting SpO₂ around 94% in trauma patients was feasible and not inferior to liberal oxygen for death or major respiratory complications.
  • 💨 No benefit from liberal oxygen – Routine high-flow oxygen did not improve outcomes and may add unnecessary risk of hyperoxia.
  • 🚑 Early initiation matters – Strategies were applied prehospital or at trauma center arrival, making findings directly relevant to real-world trauma care.
  • ⚖️ Balance is key – Clinicians should weigh hypoxia vs hyperoxia risk; restrictive oxygen is a reasonable alternative but requires careful titration.
  • 📊 Limitations remain – The composite primary outcome, short (8-hour) intervention, and homogeneous study population leave unanswered questions for broader practice.

📝 Introduction

Supplemental oxygen is routinely administered to severely injured trauma patients to prevent hypoxia, but the optimal oxygen strategy remains uncertain. While traditional Advanced Trauma Life Support (ATLS) guidelines recommend universal oxygen supplementation for these patients, concerns about potential harm from hyperoxia have led to investigation of more restrictive oxygen targets. Existing evidence from critically ill populations is mixed, with some trials suggesting harm from liberal oxygen use1, while others find no difference in outcomes2. However, data specifically addressing oxygen therapy in trauma patients in the early post-injury phase is scarce.

The TRAUMOX2 trial was an open-label pragmatic, international randomized controlled trial designed to evaluate whether a restrictive oxygen strategy targeting lower oxygen saturation reduces death and/or major respiratory complications compared with a liberal oxygen strategy in adult trauma patients.

🧾 Paper

Arleth T. et al, TRAUMOX2 Trial Group. Early Restrictive vs Liberal Oxygen for Trauma Patients: The TRAUMOX2 Randomized Clinical Trial. JAMA. Feb 2025. PMID: 39657224

👀Previously Covered on REBEL EM

⚙️ What They Did

Does an early, 8-hour restrictive oxygen strategy compared with a liberal oxygen strategy in severely injured trauma patients reduce mortality and/or major respiratory complications?

  • Pragmatic, international, multicenter, randomized controlled trial
  • Patients were incapable of providing informed consent, so an initial proxy consent was obtained and granted by an independent physician upon enrollment.
  • Informed consent from the patient, patient’s relatives or proxy was sought at the earliest opportunity
  • Patients were allocated to either a restrictive or liberal oxygen strategy for 8 hours as soon as possible following trauma either in the pre-hospital setting or upon admission to the trauma center
  • High level of oxygen for a brief duration was permitted in both groups at the discretion of the treating physician (ie. Preoxygenation prior to intubation)

Outcome Assessment Method

  • Each site had two blinded outcome assessors (anesthesiology or intensive care specialists).
  • Assessors were blinded to group allocation, with redacted documentation (e.g., SpO₂, FiO₂, PaO₂) to prevent bias.

Assessments were based entirely on:

  • Medical records
  • Imaging (CT, X-ray)
  • Laboratory results
  • Clinical notes through day 30 or hospital discharge, whichever came first

Disagreements between assessors were resolved by discussion or, if needed, by a third blinded adjudicator.

Inclusion Criteria:

    • Adult patients over 18 years old
    • Who experienced blunt or penetrating trauma and transported directly to participating trauma centers
    • Patients who triggered a full trauma team activation
    • Enrolling physician had to anticipate a hospital stay of at least 24 hours

Exclusion Criteria:

  • No or minor injuries after secondary survey in trauma resuscitation bay
  • Suspicion of carbon monoxide intoxication
  • Cardiac arrest prior to randomization
  • Expected to be discharged within 24 hours

Intervention:

  • Restrictive oxygen strategy group targeted a minimum SpO₂ of 94%.
  • Supplemental oxygen was administered only at the lowest possible dose needed to maintain SpO₂ at or above 94%.
  • Oxygen delivery methods included:
    • Room air if SpO₂ was ≥94%
    • Nasal cannula, non-rebreather mask, or mechanical ventilation as required
  • For intubated patients, FiO₂ was titrated down to maintain SpO₂ ≥94%, with median FiO₂ ~0.35 during the intervention period.
  • The intervention was initiated in the prehospital setting or upon trauma center admission, lasting for a total of 8 hours.
  • Arterial blood gases were drawn at 1 hour ±15 min and 6 hours ±2 hours post-randomization to monitor adherence.
  • Temporary use of high FiO₂ (e.g., for preoxygenation before intubation) was allowed at the physician’s discretion.

Control:

  • Liberal oxygen strategy group received 15 liters per minute (LPM) of oxygen via a non-rebreather mask for non-intubated patients.
  • Intubated patients received 100% FiO₂ (FiO₂ 1.0) in the prehospital setting, trauma resuscitation room, and during intrahospital transport.
  • In the operating room (OR), post-anesthesia care unit (PACU), ICU, or hospital wards, the oxygen flow or FiO₂ could be reduced to 12 LPM or FiO₂ 0.6 if SpO₂ was ≥98%.
  • Brief use of high oxygen concentrations was permitted in both arms at the treating physician's discretion (e.g., preoxygenation for intubation).

Primary Outcome:

  • Composite of death and/or major respiratory complications within 30 days

Secondary Outcomes:

  • Death within 30 days
  • Major respiratory complications withing 30 days (assessed separately from the composite)

Exploratory outcomes (full list in supplemental information):

    • Episodes of hypoxemia during 8-hour intervention
    • ICU readmission
    • Sepsis
    • Surgical site infection
    • Pneumonia post-discharge

📈 Results

💪 Strengths

  • Multicenter RCT: Took place at 15 pre-hospital bases and 5 major trauma centers allowing for better variability, generalizability, and external validity 
  • Accurate and realistic inclusion criteria: Aligned with ATLS guidelines reflecting typical trauma populations.
  • Early with EMS in mind: Early randomization, including prehospital enrollment at multiple prehospital bases
  • Bias reduction through blinding: Blinded primary outcome assessment to minimize bias.
  • Strict record keeping: Detailed reporting of protocol adherence and adverse events.
  • Prior evidence justification: Utilized TRAUMOX1 pilot trial and other evidence to justify the intervention period of 8 hours
  • Large sample size: Enrolled (1508) which helps provide sufficient power for the study.
  • Patient-orientated in real-time: Focus was on SpO2 rather than PaO2 due hyperacute setting of trauma and time sensitivity precluding obtaining ABG
  • Similar illness severity: Patients were moderate to severely injured with similar severity to previous trials
  • Well balanced baseline characteristics: Patients across both groups were fairly well-balanced (Subgroup and adjusted analyses showed similar results.)

⚠️ Limitations

  • Bias Possibility: Open-label design potentially influenced treatment decisions and post-randomization exclusions may have introduced bias.
  • Unclear injury types: Heterogeneous trauma population; no analysis by specific injury types.
  • Problematic Primary Outcome: Composite primary outcome combined endpoints with opposite trends. A composite may also combine events of varying severity or one less important event may drive the result one way or the other
  • Timing too short: Intervention duration of 8 hours may be too short to detect differences in mortality.
  • Diversity data lacking: No data on race or skin pigmentation to assess pulse oximetry accuracy.
  • 25% of patients received supplemental oxygenation for more than 50 minutes before randomization.
  • Homogenous patient population: Conducted in three European countries with a fairly homogeneous ethnic background; thus, may be difficult to apply studies to more heterogenous populations like the United States.
  • Unclear practice environment: Did not specify if conducted at Academic vs Community hospitals and thus unable to extract the results to a particular type of institution.
  • Protocol adherence issues: Major protocol violations occurred more often in the liberal oxygen group.

🗣️ Discussion

Trial Impact and Context
  • The TRAUMOX2 trial adds vital data to the ongoing debate on oxygen therapy in trauma patients.
  • Despite concerns about hyperoxia-related harm, the trial found no significant difference in death or major respiratory complications between restrictive and liberal oxygen strategies applied early after trauma.
Feasibility and Safety of Restrictive Oxygen
  • Targeting lower oxygen saturation levels (~94%) is both feasible and safe in trauma patients.
  • This challenges the entrenched practice of automatically administering liberal oxygen to all severely injured patients.
  • Such liberal oxygen use may unnecessarily increase harm without improving outcomes.
Strengths and Limitations
  • The trial’s pragmatic, real-world design supports external validity and applicability.
  • However, the open-label design and protocol deviations underscore challenges in implementing restrictive oxygen strategies consistently in practice.
Clinical Implications
  • Clinicians should balance the risks of hypoxia and hyperoxia, recognizing that restrictive oxygen strategies are a reasonable alternative to liberal oxygen in early trauma care.
  • Caution is warranted as requiring providers to decide whether oxygen is necessary during high-stress trauma resuscitations adds cognitive load.
  • This additional decision step may detract from addressing more immediate, life-threatening interventions.

📘 Author's Conclusion

“In adult trauma patients, a restrictive oxygen strategy compared with a liberal oxygen strategy initiated in the prehospital setting or on trauma center admission for a duration of 8 hours did not significantly reduce death and/or major respiratory complications within 28 days.”

💬 Our Conclusion

The TRAUMOX2 trial suggests that targeting a restrictive oxygen saturation of approximately 94% is safe and not inferior to liberal oxygen therapy in preventing death or major respiratory complications after trauma. However, interpretation is limited by the trial’s composite primary outcome, which combined mortality and respiratory complications—two events of unequal clinical significance that trended in opposite directions. This approach may have obscured more nuanced differences between the two strategies. Additionally, the 8-hour intervention period was pragmatic and aligned with real-world practice, however it may have been too brief to detect longer-term effects such as ARDS or late mortality.

Further research is needed to identify optimal oxygen targets, especially for specific injury subgroups like traumatic brain injury or thoracic trauma. The ongoing Mega-ROX trial, may offer more definitive guidance for oxygenation strategies in critically ill and trauma populations.5

In the meantime, clinicians can reasonably move away from a one-size-fits-all liberal oxygen strategy and instead adopt a more targeted, patient-centered approach to oxygen therapy in trauma.

🚨 Clinical Bottom Line

For adult trauma patients, a restrictive oxygen strategy targeting SpO2 ~94% is a reasonable and safe alternative to liberal oxygen therapy during the initial 8 hours post-injury without increased risk of death or major respiratory complications.

📚 References

  1. Chu DK, et al.
    Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis.     Lancet. 2018 Apr 28;391(10131):1693–1705.
    PMID:     29628388
  2. Martin DS, Grocott MP.
    Oxygen therapy and anaesthesia: too much of a good thing?     Anaesthesia. 2013 Jan;68(1):52–62.
    PMID:     23157457
  3. Young PJ, et al.
    The Mega-ROX trial: a protocol for a randomised trial of conservative versus liberal oxygen therapy in intensive care.     Crit Care Resusc. 2022 Dec;24(4):326-334.
    PMID:     36546435
  4. Arleth T. et al, TRAUMOX2 Trial Group.
    Early Restrictive vs Liberal Oxygen for Trauma Patients: The TRAUMOX2 Randomized Clinical Trial.     JAMA. Feb 2025.
    PMID:    39657224
  5. Young PJ, et al.
    Mega-ROX Management Committee; Australian and New Zealand Intensive Care Society Clinical Trials Group; Crit Care Asia and Africa Network; Irish Critical Care Clinical Trials Group; Alberta Health Services Critical Care Strategic Clinical Network. Protocol and statistical analysis plan for the mega randomised registry trial research program comparing conservative versus liberal oxygenation targets in adults receiving unplanned invasive mechanical ventilation in the ICU (Mega-ROX). Crit Care Resusc. 2023 Oct 19;.OA4.
    PMID: 38045600

Post Peer Reviewed By: Mark Ramzy, DO (X/IG: @MRamzyDO), and Marco Propersi, DO (X: @Marco_Propersi)

👤 Guest Author

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Cite this article as: May Ali, DO, "The TRAUMOX2 Trial: Early Restrictive vs Liberal Oxygen Strategies in Adult Trauma Patients", REBEL EM blog, October 20, 2025. Available at: https://rebelem.com/traumox2-trial/.
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