A recent publication in the NEJM by Hofmann et al (1) serves as a nice reminder that so many of our therapeutic staples while based on sound physiological reasoning fail to translate into clinically important realities when empirically tested.
This mammoth undertaking, entitled the DETO2X trial, randomized 6629 adult patients (>30 years old) presenting to 35 hospitals in Sweden with signs concerning for a myocardial infarction and EKG changes or an elevated troponin to either oxygen therapy (6L via a standard face mask) or ambient air for a period of 6-12 hours after enrollment. If determined clinically necessary by the treating clinician, the use of supplemental oxygen was permitted outside the trial’s protocol.
Using a novel registry-based randomized design, the authors utilized the previously established SWEDEHEART registry to prospectively collect data on the patients enrolled and randomized into the DETO2X Trial. The registry compiled data for 106 variables, including patient demographics, admission logistics, risk factors, past medical history, medical treatment prior to admission, electrocardiographic changes, biochemical markers, other clinical features and investigations, medical treatment in hospital, interventions, hospital outcome, discharge diagnoses and discharge-medications. Additionally, for all patients registered into SWEDEHEART a follow-up visit wass performed after 6-10 weeks and again after 12-14 months.
The authors reported no difference in their primary outcome, one year mortality, between patients randomized to oxygen therapy and those who received ambient air (5.0% vs 5.1%). Nor was there a difference in the composite endpoint of death from any cause, re-hospitalization with myocardial infarction (8.3% vs 8.0%), or 30-day mortality.
While clearly negative, unlike past literature, DETO2X did not show any signal of harm associated with the use of supplemental oxygen. This is in contrast to the previously published AVOID trial, which suggested an increase in infarct size in patients exposed to supplemental oxygen (2). These findings were based off cardiac MR imaging and no significant difference in clinically important outcomes were observed. Such images were not assessed in the DETO2X cohort, but the authors found no clinical signs of deleterious outcomes in patients randomized to the supplemental oxygen arm. And so the suggestion of harm observed in the statistically smaller AVOID trial were due to either random sampling error or representative of a surrogate measure that does not translate into clinically important outcomes.
Supplemental oxygen has long been considered a universally beneficial intervention. Applied with great enthusiasm to a vast majority of patients transported to the Emergency Department by ambulance. And while the authors powered their study expecting a one year mortality of approximately 14%, this is a fairly robust demonstration of oxygen’s lack of utility in patients experiencing a myocardial infarction. Yet another physiological fairytale to add to our considerable list of therapeutically futile endeavors.
- Hofmann R, James SK, Jernberg T, et al. Oxygen therapy in suspected acute myocardial infarction. N Engl J Med. DOI: 10.1056/NEJMoa1706222
- Stub D, Smith K, Bernard S, et al. Air versus oxygen in ST-segment-elevation myocardial infarction. Circulation 2015;131: 2143-50
University of Maryland
Resuscitation Fellowship Graduate