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

Clinical guidelines are designed to provide recommendations to clinicians based on best available data. Frequently, these guidelines are based on inadequate or insufficient information and at times are found to be incorrect. Supplemental oxygen has routinely been used in the initial treatment of patients with acute coronary syndromes, including both myocardial infarction and post-cardiac-arrest patients. A number of recent trials have focused attention on not only the lack of evidence for supplemental oxygen but also the potential adverse effects.^1-3

The largest and best-designed study, AVOID (Air Versus Oxygen in Myocardial Infarction Study), was a multi-center, prospective, open-label randomized trial conducted in 12 hospitals in Melbourne, Australia, that enrolled 441 pre-hospital normoxic patients with confirmed ST-segment elevation myocardial infarction (STEMI) (638 were randomized).⁴ This trial studied the effect of supplemental oxygen on the primary endpoint of myocardial infarct size assessed by peak cardiac enzyme values and secondary endpoints of recurrent myocardial infarction, arrhythmia and infarct size at 6 months. The 218 patients randomized to the high-flow oxygen group received supplemental oxygen via face mask at 8 liters/minute, and the 223 patients randomized to the no supplemental oxygen group received oxygen only if the oxygen saturation fell below 94%, in which case oxygen was administered by nasal cannula (4 liters/minute) or face mask (8 liters/minute) to achieve an oxygen saturation of 94%. The study showed similar mean peak troponin levels between the groups but higher peak creatinine kinase (1948 u/L vs. 1543 u/L) in the oxygen group, as well as a larger infarct size at 6 months in the high-flow oxygen group as measured by cardiac magnetic resonance.

Although the authors should be applauded for conducting a well-designed trial designed to challenge conventional wisdom, we need to AVOID overreaction and extrapolation beyond the design of the trial. To begin, this was still a relatively small trial, and more than 30% of patients screened were excluded. In addition, the high-flow oxygen group received oxygen at 8 liters/minutes by face mask, a relatively high dose for a normoxic patient; many pre-hospital and hospital protocols provide 2-4 liters/minute via nasal cannula. Although the vast majority of patients in the no supplemental oxygen group did not receive any oxygen on route to the hospital, a significant minority (over 35%) received oxygen 2 hours post-procedure compared with nearly 80% in the high-flow oxygen group, this despite a small difference in PO2 on arrival to the catheterization laboratory (97 vs. 99%). The trial failed to detect a significant difference between the two groups in the troponin primary endpoint. Although cardiac magnetic resonance data suggested larger infarct sizes in the high-flow oxygen group, the result was nonsignificant when adjusted for left ventricular mass. The authors emphasize a reduction in recurrent myocardial infarction and arrhythmias, but there was actually a trend toward an increase in mortality in the no supplemental oxygen group (1.8 vs. 4.5% in-hospital and 3.8 vs. 5.9% at 6 months). A larger-powered study may have better highlighted this difference. Most interesting were the 6-month follow-up data on the rates of adverse outcomes showing no difference between the groups with appropriate medical therapy. Overall results, although provocative, were certainly not definitive.

The most recent STEMI guidelines to address oxygen were in 2004.⁵ At that time, the recommendation was for oxygen to be administered to hypoxic STEMI patients (arterial oxygen saturation <90%, Class I, Level of Evidence B). The guidelines noted that it was reasonable to administer supplemental oxygen to patients during the first 6 hours (Class IIa, Level of Evidence C) but included no guidelines regarding how much oxygen to administer. In contrast, the 2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes recommended to administer supplemental oxygen only with oxygen saturation <90%, respiratory distress, or other high-risk features for hypoxemia.⁶ The 2015 American Heart Association Guideline Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care offered more specific direction on oxygen therapy.⁷ The systematic review identified observational studies suggesting that excessively high arterial oxygen concentrations (hyperoxia defined at PaO2 > 300 mmHg) may harm various organs or worsen outcomes. Yet it also notes that other studies did not confirm this finding. The guidelines define hypoxia as oxygen saturation <94% and comment that it is more important to prevent hypoxic episodes than avoid any potential risk of hyperoxia. The bottom line recommendation was to use the highest available oxygen concentration until the arterial oxyhemoglobin saturation or the partial pressure of arterial oxygen can be measured (Class IIa, Level of Evidence C-EO). The guidelines also note the "it is reasonable to decrease the FIO₂ when the oxyhemoglobin saturation is 100% providing that it can be maintained at >94%."

We clearly need better evidence to inform clinical practices, but until then we need to AVOID a tendency to overreach beyond the evidence.

References

1. Farquhar H, Weatherall M, Wijesinghe M, et al. Systematic review of studies of the effect of hyperoxia on coronary blood flow. Am Heart J 2009;158:371-7.
2. McNulty PH, Robertson BJ, Tulli MA, et al. Effect of hyperoxia and vitamin C on coronary blood flow in patients with ischemic heart disease. J Appl Physiol 2007;102:2040-5.
3. Cabello JB, Burls A, Emparanza JI, Bayliss SE, Quinn T. Oxygen therapy for acute myocardial infarction. Cochrane Database Syst Rev 2010;6:CD007160.
4. Stub D, Smith K, Bernard S, et al. Air Versus Oxygen in ST-Segment-Elevation Myocardial Infarction. Circulation 2015;131:2143-50.
5. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). Circulation 2004;110:588-636.
6. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;130:2354-94.
7. Callaway CW, Donnino MW, Fink EL, et al. 2015 Part 8: Post-Cardiac Arrest Care: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S465-82.

Keywords: Acute Coronary Syndrome, Myocardial Infarction, Oxygen, Oxygen Inhalation Therapy, Arrhythmias, Cardiac, Cardiopulmonary Resuscitation, Catheterization, Creatinine, Hyperoxia, Magnetic Resonance Spectroscopy, Oxyhemoglobins, Troponin

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