Editor's Note: This is Part Two article of a two-part Expert Analysis. Click here for Part One.

Following the first report of supplemental oxygen for angina in 1900,¹ oxygen therapy has been commonly used in the initial treatment of patients with acute coronary syndromes (ACS). Other medical practices from the early 1900s, such as starvation diets for aneurysms and mercury as a treatment for syphilis infections, were quickly discarded, but the routine use of oxygen in cardiac emergencies has remained a pervasive component of first medical response. Given the paucity of evidence highlighting routine oxygen's clinical efficacy and the ever-increasing clinical and physiological data indicating the dangers of routine oxygen leading to hyperoxemia, it is time to cast off this century-old practice and limit the use of oxygen in ACS to only patients who are hypoxic.

Despite its potential adverse physiological effects, supplemental oxygen continues to be administered to almost 90% of patients with suspected ACS.² This has been based on the belief that supplemental oxygen may increase oxygen delivery to ischemic myocardium and hence reduce myocardial injury and is supported by laboratory studies,^3,4 an older clinical trial,⁵ the apparent benefit of hyperbaric oxygen,⁶ and clinical trials of intracoronary aqueous oxygen.⁷ Although no clinician would doubt the efficacy of oxygen supplementation for hypoxemic patients, there is increasing awareness of the potential adverse physiologic effect of supplemental oxygen causing significant hyperoxemia, reduced coronary blood flow,⁸ increased coronary vascular resistance,⁹ and the production of reactive oxygen species contributing to vasoconstriction and reperfusion injury.^10,11

A recent meta-analysis of three small randomized trials suggested a possible increase in adverse outcomes with supplemental oxygen administration.¹² More recently, a small study comparing high-concentration oxygen with titrated oxygen in patients with suspected ST-segment elevation myocardial infarction (STEMI) found no difference in myocardial infarct size on cardiac magnetic resonance imaging (CMR).¹³

The most recent randomized trial of supplemental oxygen therapy in the setting of contemporary therapy for STEMI is AVOID (Air Versus Oxygen in Myocardial Infarction Study).¹⁴ This study randomized 638 patients with STEMI in the pre-hospital setting to high-flow oxygen or no supplemental oxygen. Mean peak troponin was similar in both groups, but there was a 27% increase in creatine kinase (CK) compared with patient's breathing room air and an increase in the rate of recurrent myocardial infarction in the oxygen group compared with the no-oxygen group. At 6 months, the oxygen group had an increase in myocardial infarct size on CMR.¹⁴ We now have data from 4 randomized trials highlighting no significant benefit of routine oxygen therapy with a signal toward increased adverse clinical outcomes.

The effect of the dose and duration of oxygen exposure on myocardial injury is not known in patients suffering STEMI. A secondary analysis of AVOID revealed that for every 100-litre increase of supplemental oxygen administered in the first 12 hours of a STEMI, there was an associated 1.4% and 1.2% increase in the mean peak cardiac troponin I and CK, respectively (Figure 1).¹⁵ It remains unclear, therefore, what oxygen saturation target is ideal for patients with STEMI. Most studies have targeted an oxygen saturation of >93%. The safety of a lower saturations such as >90% oxygen saturation threshold is currently being evaluated by a Swedish-based clinical trial,¹⁰ and this will help determine the safety and feasibility of further reducing the need for oxygen therapy in the treatment of patients with STEMI.

Further supporting the notion that oxygen should not be routinely given to all ACS patients is the association of routine oxygen therapy leading to adverse outcomes in other emergency patient cohorts. A recent randomized trial of conservative oxygen therapy versus high-flow oxygen in patients admitted to the intensive care unit revealed worse mortality in the high-flow oxygen group (relative risk 0.57, p = .01).¹⁶ Similarly, poor outcomes have been seen in routine oxygen therapy for stroke¹⁷ and cardiac arrest.¹⁸

In conclusion, although routine oxygen may benefit the hypoxemic patient with complicated acute myocardial infarction, evidence supporting its routine use in normoxemic patients is of low quality and predates contemporary reperfusion practices. Recent physiological studies have highlighted the potential adverse effects of supplemental oxygen, and randomized trials have not demonstrated any significant benefit of routine oxygen use in terms of myocardial infarct size, patient hemodynamics, or reported symptoms. Instead, these trials have identified a signal for increased myocardial injury during uncomplicated acute myocardial infarction with the routine use of supplemental oxygen. Oxygen should be treated like all other medical therapies, for which physicians balance efficacy and side-effect profiles. Until larger studies are available, oxygen should not be routinely administered to patients unless oxygen saturations are <94%.

Figure 1¹⁵

References

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13. Ranchord AM, Argyle R, Beynon R, et al. High-concentration versus titrated oxygen therapy in ST-elevation myocardial infarction: a pilot randomized controlled trial. Am Heart J 2012;163:168-75.
14. Stub D, Smith K, Bernard S, et al. Air Versus Oxygen in ST-Segment-Elevation Myocardial Infarction. Circulation 2015;131:2143-50.
15. Nehme Z, Stub D, Bernard S, et al. Effect of supplemental oxygen exposure on myocardial injury in ST-elevation myocardial infarction. Heart 2016;102:444-51.
16. Girardis M, Busani S, Damiani E, et al. Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial. JAMA 2016;316:1583-9.
17. Rønning OM, Guldvog B. Should stroke victims routinely receive supplemental oxygen? A quasi-randomized controlled trial. Stroke 1999;30:2033-7.
18. Kilgannon JH, Jones AE, Parrillo JE, et al. Relationship between supranormal oxygen tension and outcome after resuscitation from cardiac arrest. Circulation 2011;123:2717-22.

Keywords: Acute Coronary Syndrome, Aneurysm, Angina Pectoris, Creatine Kinase, Heart Arrest, Hyperbaric Oxygenation, Magnetic Resonance Imaging, Mercury, Myocardial Infarction, Myocardium, Oxygen, Oxygen Inhalation Therapy, Prednisolone, Reactive Oxygen Species, Reperfusion Injury, Risk, Shock, Cardiogenic, Stroke, Troponin I, Vascular Resistance, Vasoconstriction

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