A 66-year-old man presents with substernal chest pressure and dyspnea that has been present for 45 minutes. He has nausea. Vital signs: blood pressure, 110/60; pulse, 100; oxygen saturation, 92%. Neck: elevated jugular venous pressure. Chest: clear. Cardiac: normal S1 S2, no murmurs. ECG: ST elevation in 2, 3, and aVF leads.

Which of these treatments do you recommend?

A. Morphine, oxygen, nitroglycerin, and aspirin (ASA).

B. Oxygen, morphine, ASA.


For many years, a standard treatment of providing morphine, oxygen, nitroglycerin, and aspirin (MONA) was the standard initial treatment approach for all patients presenting with chest pain due to suspected myocardial ischemia.

In this patient, I think the correct approach would be to just give aspirin. Nitroglycerin would be problematic, as it appears that this patient might be having a right ventricular infarct, and lowering right-sided filling pressures with nitroglycerin may lead to severe hypotension.

There is controversy over the safety of routine morphine use for patients with chest pain.

Trip J. Meine, MD, and colleagues found that use of morphine either alone or in combination with nitroglycerin for patients presenting with non–ST-elevation acute coronary syndrome (NSTE-ACS) was associated with higher mortality.1 Cian P. McCarthy, MD, and colleagues found the same results, with morphine use associated with larger infarct size, a longer hospital stay, and a trend toward increased mortality in invasively managed NSTE-ACS patients.2 Suzanne de Waha and colleagues found that morphine use in patients with ST-segment elevation MIs had larger infarct size and less reperfusion success, as measured by cardiac MRI.3

Not all recent studies show a detrimental effect of morphine. Etienne Puymirat et al. reviewed in-hospital complications (death, nonfatal re-MI, stroke, stent thrombosis, and bleeding) and 1-year survival according to prehospital morphine use in 2,438 ST-elevation MI (STEMI) patients from the French Registry of Acute ST-elevation and non–ST-elevation Myocardial Infarction (FAST-MI).4 They found no increase in in-hospital complications or 1-year mortality.

The practice of using supplemental oxygen to treat all patients with MI became standard nearly a century ago, after oxygen was found in 1900 to relieve angina, and led to clinical improvement in four MI patients in a 1930 case series.5,6

It was not studied in a controlled trial until 1976, when J.M. Rawles, MD, and colleagues randomized 157 patients with MI to 24 hours of oxygen at 8 L/min or to ambient air. They found no difference in mortality between the groups, but they did find a higher burden of MI in the intervention arm receiving supplemental oxygen, as measured by mean serum aspartate aminotransferase levels.7

The topic was not addressed again in a significant randomized trial until this century. Most notably, two recent studies again demonstrated no benefit of supplemental oxygen in normoxemic patients with MI.

In the AVOID trial in 2015, Dion Stub, MD, PhD, and colleagues randomized 441 patients with STEMI to oxygen at 8 L/min – from diagnosis in an ambulance until after cardiac catheterization – or to ambient air. They found no difference in death at 6 months, but did find an increased rate of in-hospital recurrent MIs, with 0.9% of the control group and 5.5% of the oxygen intervention arm suffering recurrence (P = .006).8 They also showed a larger area of myocardial infarct in the oxygen group, as measured by peak creatine kinase levels and cardiac MRI at 6 months.

Proposed mechanisms of increased myocardial injury from hyperoxia include increased coronary vascular resistance resulting in decreased myocardial perfusion, and increased reperfusion injury from formation of free radicals.9

This year, a large randomized trial of 6,629 patients across 35 Swedish hospitals was published by Robin Hofmann, MD, and colleagues.10 The DETO2X-AMI study compared 6 L/min of oxygen delivered for an average of 11.6 hours to ambient air in normoxemic patients with suspected MI (76% with ultimately confirmed MI). They found no difference in death at 30 days or 1 year. While this finding reinforced the lack of benefit of supplemental oxygen shown in the AVOID trial, the findings by Dr. Stub and colleagues of increased tissue damage were not borne out: Both groups showed similar troponin levels.

Where does all this leave us in the treatment of suspected MI?

Morphine should only be used when the patient has pain, and is probably best reserved for severe pain, as the safety of its use is not clear. While hypoxemia is a common consequence of MI – and may correlate with worse outcomes – treatment with supplemental oxygen in the absence of hypoxemia is not supported by current evidence, and may carry risk of harm. Nitroglycerin should be avoided in patients with right ventricular infarcts, and in patients who present with hypotension.

Dr. Tubbesing is a senior resident in medicine at the University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu .


1. Am Heart J. 2005 Jun;149(6):1043-9 .

2. J Interv Cardiol. 2017 Nov 22. doi: 10.1111/joic.12464 .

3. Clin Res Cardiol. 2015 Sep;104(9):727-34 .

4. Eur Heart J. 2016 Apr 1;37(13):1063-71 .

5. BMJ. 1900 Dec 1;2(2083):1568 .

6. JAMA. 1930 May 3;94(18):1363-5 .

7. Br Med J. 1976 May 8;1(6018):1121-3 .

8. Circulation. 2015 Jun 16;131(24):2143-50 .

9. Cochrane Database Syst Rev. 2016 Dec 19;12:CD007160 .

10. N Engl J Med. 2017 Sep 28;377(13):1240-9 .


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