Early restrictive versus liberal oxygen for trauma patients: does it make a difference?
The authors’ conclusion from the TRAUMAOX2 study was that 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 (1). The conclusion that an oxygen therapy intervention of 8 hours did not change death or respiratory outcomes judged 30 days later, is not a surprise, due to limitations in details of the methodology and lack of additional data. Hypoxemia in trauma patients occurs from ventilation-perfusion mismatch, increased shunt, diffusion impairment, and alveolar hypoventilation, all of which can occur in hemorrhagic shock and head injury. A challenge in interpreting this study is the heterogeneity of the study trauma population and the lack of detail about what injuries were sustained and what treatment was given (e.g., transfusion, acute hemorrhage control procedures) in the 30 days after the oxygen therapy intervention, in those trauma patients who died. We also are unsure what may have caused hypoxemia in the individual patients given the oxygen therapy intervention.
In previous studies of major trauma patients, traumatic hemorrhage is the leading cause of preventable death. Approximately half of all patient deaths in the first 24-h after trauma are due to hemorrhage; survival from major traumatic hemorrhage is poor. Trauma patients with hemorrhagic shock who require substantial transfusion have a mortality greater than 30% in some studies. About 14% of patients in the TRAUMOX2 study were in hemorrhagic shock [systolic blood pressure (SBP) <90 mmHg, heart rate (HR) >110/min]. Reversal of hypoxemia in the first 8 hours of trauma care will acutely increase oxygen transport in trauma patients due to hemorrhage, by maintaining hemoglobin saturation and oxygen dissolved in the plasma. If hemorrhagic shock causes acute anemia and transfusion occurs to maintain/increase hemoglobin, cardiac output and tissue oxygen delivery will increase. The approach of reversing hemorrhagic shock by controlling bleeding and transfusion is recognized as a cornerstone to reduce death in trauma patients, one of the primary outcomes of the study. The authors have not told us the full story about the injuries or the interventions administered to the trauma patients they enrolled in each oxygen strategy. Despite a pulse oximetry oxygen saturation >94% (the metric used in the restricted oxygen category), sudden decompensation and death can occur in young, previously healthy adults with acute trauma, who develop ventilation-perfusion mismatch, and increased shunt, as lung blood flow decreases and hypoxemia increases with shock. In the TRAUMOX2 study, the heterogeneity of the population is evidenced by the minority that required any surgery (about 20%), and only 1/3rd required intensive care. The 30-day follow-up for mortality is generally considered standard for drug safety testing studies. However, the intervention was an 8-hour inspired oxygen difference on day 1, with primary study outcomes of death and respiratory complication 30 days after injury. The impact of the brief early intervention is confounded by multiple interval treatment variables.
The ongoing Mega-ROX trial, which will enroll 40,000 patients, including a subset of trauma patients, may validate the findings of the current TRAUMOX2 randomized clinical trial (2). Mega-ROX should consider differences in individual patient characteristics (e.g., age, weight, illicit drug use) and sites of trauma (traumatic brain injury, isolated injury versus multiple injuries, etc.). Perhaps, rather than using an all or none liberal versus restrictive oxygen strategy, after a brief initial liberal oxygen strategy during resuscitation, the inspired oxygen should be titrated downwards to maintain optimal oxygen saturation of 97–99%. This approach to oxygen therapy would account for the dynamic changes in an individual trauma patient’s physiological state, during initial reception and resuscitation. Titration of oxygen administration to oxygen saturation is what occurs in clinical practice. We cannot judge the outcome of the restricted compared to liberal oxygen strategy in these trauma patients without knowing the hemoglobin concentration. The hemoglobin concentration and cardiac output are major factors determining tissue oxygenation and survival, the 30 days interval respiratory issues are unknown, once the 8-hour oxygen therapy intervention was completed. The authors do not provide either hemoglobin levels or interval respiratory issues after the 8 hours of oxygen therapy randomization. Without these, the authors have not demonstrated whether different oxygen therapies for 8 hours after admission did, or did not, make a difference.
Acknowledgments
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References
- Arleth T, Baekgaard J, Siersma V, et al. Early Restrictive vs Liberal Oxygen for Trauma Patients: The TRAUMOX2 Randomized Clinical Trial. JAMA 2025;333:479-89. [Crossref] [PubMed]
- Young PJ, Arabi YM, Bagshaw SM, et al. 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 2022;24:137-49. [Crossref] [PubMed]
