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Commentary

Taking the Air Out of Oxygen Supplementation in Individuals With Diabetes and Acute Coronary Syndromes

  1. David Aguilar1⇑ and
  2. Vijay Nambi2,3
  1. 1Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, and Division of Cardiology, University of Texas McGovern Medical School, Houston, TX
  2. 2Michael E. Debakey Veterans Affairs Medical Center, Houston, TX
  3. 3Center for Cardiometabolic Disease Prevention, Department of Medicine, Baylor College of Medicine, Houston, TX
  1. Corresponding author: David Aguilar, david.aguilar{at}uth.tmc.edu
Diabetes Care 2019 Nov; 42(11): 2019-2021. https://doi.org/10.2337/dci19-0035
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Oxygen supplementation has been a cornerstone in the initial treatment of individuals with acute coronary syndrome. While consensus for oxygen supplementation exists for patients with hypoxia, oxygen supplementation has also been routinely used in those presenting with acute myocardial infarction (MI) with normal oxygen saturations based on the rationale that oxygen therapy could improve oxygen supply to the ischemic myocardium, thereby reducing the infarct size and complications. Indeed, reports of oxygen supplementation to relieve angina pectoris were described as early as 1900 (1). These reports were followed by small studies that suggested benefit with oxygen supplementation in acute MI, but these studies were limited by lack of randomization and unblinded end point ascertainment (2–4). Nonetheless, supplemental oxygen was incorporated into routine clinical practice, as evidenced in 2007 cardiology practice guidelines that recommended routine supplemental oxygen to all patients with acute coronary syndrome during the first 6 h after presentation (5). This widespread belief in oxygen was highlighted in a survey of emergency department, cardiology, and ambulance staff in which 98% of respondents reported using oxygen supplementation for suspected MI and 55% believed oxygen reduced the risk of death (6).

Despite the ubiquitous use of oxygen, there were early reports of potential harm with high-dose oxygen supplementation in individuals with acute MI (7). Over 40 years ago, the first randomized trial of high-dose oxygen in patients with an acute MI demonstrated that oxygen-treated patients had increased cardiac enzymes and a trend toward increased mortality compared with those not treated with oxygen (8). More recently, a study of 441 patients with ST-segment elevation MI, but without hypoxia, demonstrated that supplemental oxygen therapy (8 L/min) was associated with increased markers of myocardial injury, increased rate of early MI, and larger myocardial infarct size at 6 months compared with ambient air (9). In this setting, the DETO2X-AMI (Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction) trial was performed (10). The DETO2X-AMI trial was an open-label, registry-based clinical trial that randomized 6,629 patients with suspected acute MI and oxygen saturation ≥90% to receive supplemental oxygen at 6 L/min for 6–12 h or ambient air (10). While supplemental oxygen prevented hypoxemia compared with the control group, supplemental oxygen did not improve the primary outcome of 1-year mortality (hazard ratio 0.97, 95% CI 0.79–1.21; P = 0.80). A subsequent meta-analysis of randomized clinical trials, including the DETO2X-AMI trial, demonstrated that supplemental oxygen therapy did not reduce the risk of in-hospital (odds ratio 1.11, 95% CI 0.69–1.77) or 30-day mortality (odds ratio 1.09, 95% CI 0.80–1.50) in those with suspected acute MI without hypoxia (11).

In this issue of Diabetes Care, Nyström et al. (12) present results of a prespecified analysis of the DETO2X-AMI trial among individuals with diabetes and a confirmed MI, a particularly high-risk cohort. Of the 5,010 individuals with confirmed MI enrolled in the DETO2X-AMI trial, 19% had diabetes. In the group with diabetes, the incidence of the primary composite outcome (total mortality, rehospitalization for MI, or rehospitalization for heart failure) at 1 year and the incidences of individual components of the composite outcome were similar in those treated with supplemental oxygen compared with ambient air. There was no statistical interaction between treatment and diabetes status for any of the outcomes. However, although not observed in individuals without diabetes and not statistically significant, the short-term adverse outcomes were numerically greater in patients with diabetes receiving oxygen supplementation compared with those breathing ambient air. For example, in-hospital death occurred in 13 (2.9%) patients receiving oxygen compared with 7 (1.4%) who were randomized to ambient air. Similar numerical trends were seen for in-hospital cardiogenic shock, cardiac arrest, and 30-day all-cause mortality, although conclusions are limited by very small numbers of events. As anticipated, individuals with diabetes had worse clinical outcomes following MI than those without diabetes, including increased risk of death at 1 year.

Previous randomized trials of oxygen supplementation in acute MI have been limited by small sample size and, thus, have been unable to identify particular subgroups that may receive benefit or harm. Although the current study provides new and needed information regarding oxygen supplementation for those with diabetes, it remains limited in power for this subgroup. As described in the main publication on the DETO2X-AMI trial (10), mortality was lower than anticipated, potentially related to the exclusion of hypoxemic patients, a higher-risk subset. Future and ongoing studies, such as an oxygen supplementation trial of 21,000 individuals with suspected acute coronary syndrome, should provide further subgroup information (13). Nonetheless, the current analysis from the DETO2X-AMI trial does not support the use of supplemental oxygen in individuals with diabetes and acute MI who have normal oxygen saturations. Furthermore, albeit limited by small number of early events (<30 days), the study does not exclude the possibility of harm from oxygen supplementation during the early period of an acute MI in those with diabetes.

How might oxygen be harmful in individuals with diabetes and acute MI? Several studies have shown detrimental effects of hyperoxia, including increased coronary vascular resistance, reduced coronary artery blood flow, and regional decrease in myocardial function (14–16). Hyperoxia may also increase production of oxygen free radicals and oxidative stress, which in turn may lead to cardiac injury (15,17). Importantly, endothelial dysfunction, microvascular abnormalities, increased oxidative stress, and cardiac cellular metabolic dysregulation are all hallmarks of diabetic cardiovascular disease (18) that may be further exacerbated by hyperoxia. Hyperoxia has also been recognized to reduce heart rate, reduce cardiac output, and increase systemic vascular resistance (19). Of note, the majority of these studies have used high concentrations of oxygen, achieving arterial partial pressure of oxygen values ranging from 273 to 600 mmHg (14,19); the cardiac effects with more modest oxygen supplementation as may happen in clinical practice have not been well studied.

In 1775, the clergyman and chemist Joseph Priestly, one of the discoverers of oxygen, recognized the potential therapeutic use of oxygen (“dephlogisticated air”) but warned of possible danger: “… for, as a candle burns out much faster in dephlogisticated than in common air, so we might, as may be said, live out too fast and the animal power be too soon exhausted in this pure kind of air. A moralist, at least, may say that the air which nature has provided for us is as a good as we deserve” (20). Recent data are consistent with this observation that “natural” ambient air is sufficient in those presenting with acute MI and normal oxygen saturation, a recommendation reflected in recent treatment guidelines for acute MI (21).

Article Information

Duality of Interest. V.N. was the site principal investigator of a study sponsored by Merck and holds a provisional patent along with Baylor College of Medicine and Roche on use of biomarkers in prediction of heart failure. No other potential conflicts of interest relevant to this article were reported.

Footnotes

  • See accompanying article, p. 2032.

  • © 2019 by the American Diabetes Association.
http://www.diabetesjournals.org/content/license

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.

References

  1. ↵
    1. Steele C
    . Severe angina pectoris relieved by oxygen inhalations. BMJ 1900;2:1568
    OpenUrl
  2. ↵
    1. Madias JE,
    2. Madias NE,
    3. Hood WB Jr
    . Precordial ST-segment mapping. 2. Effects of oxygen inhalation on ischemic injury in patients with acute myocardial infarction. Circulation 1976;53:411–417
    OpenUrlAbstract/FREE Full Text
    1. Maroko PR,
    2. Radvany P,
    3. Braunwald E,
    4. Hale SL
    . Reduction of infarct size by oxygen inhalation following acute coronary occlusion. Circulation 1975;52:360–368
    OpenUrlAbstract/FREE Full Text
  3. ↵
    1. Horvat M,
    2. Yoshida S,
    3. Prakash R,
    4. Marcus HS,
    5. Swan HJ,
    6. Ganz W
    . Effect of oxygen breathing on pacing-induced angina pectoris and other manifestations of coronary insufficiency. Circulation 1972;45:837–844
    OpenUrlAbstract/FREE Full Text
  4. ↵
    1. Anderson JL,
    2. Adams CD,
    3. Antman EM, et al.; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; American College of Emergency Physicians; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; American Association of Cardiovascular and Pulmonary Rehabilitation; Society for Academic Emergency Medicine
    . ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol 2007;50:e1–e157
    OpenUrlFREE Full Text
  5. ↵
    1. Burls A,
    2. Emparanza JI,
    3. Quinn T,
    4. Cabello JB
    . Oxygen use in acute myocardial infarction: an online survey of health professionals’ practice and beliefs. Emerg Med J 2010;27:283–286
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Russek HI,
    2. Regan FD,
    3. Naegele CF
    . One hundred percent oxygen in the treatment of acute myocardial infarction and severe angina pectoris. J Am Med Assoc 1950;144:373–375
    OpenUrlCrossRefPubMedWeb of Science
  7. ↵
    1. Rawles JM,
    2. Kenmure AC
    . Controlled trial of oxygen in uncomplicated myocardial infarction. BMJ 1976;1:1121–1123
    OpenUrlAbstract/FREE Full Text
  8. ↵
    1. Stub D,
    2. Smith K,
    3. Bernard S, et al.; AVOID Investigators
    . Air versus oxygen in ST-segment-elevation myocardial infarction. Circulation 2015;131:2143–2150
    OpenUrlAbstract/FREE Full Text
  9. ↵
    1. Hofmann R,
    2. James SK,
    3. Jernberg T, et al.; DETO2X-SWEDEHEART Investigators
    . Oxygen therapy in suspected acute myocardial infarction. N Engl J Med 2017;377:1240–1249
    OpenUrlCrossRefPubMed
  10. ↵
    1. Sepehrvand N,
    2. James SK,
    3. Stub D,
    4. Khoshnood A,
    5. Ezekowitz JA,
    6. Hofmann R
    . Effects of supplemental oxygen therapy in patients with suspected acute myocardial infarction: a meta-analysis of randomised clinical trials. Heart 2018;104:1691–1698
    OpenUrlAbstract/FREE Full Text
  11. ↵
    1. Nyström T,
    2. James SK,
    3. Lindahl B, et al
    .; DETO2X-SWEDEHEART Investigators. Oxygen therapy in myocardial infarction patients with or without diabetes: a predefined subgroup analysis from the DETO2X-AMI trial. Diabetes Care 2019;42:2032–2041
    OpenUrlAbstract/FREE Full Text
  12. ↵
    1. Australian New Zealand Clinical Trials Registry
    . Oxygen therapy in acute coronary syndromes trial. Available from https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12616000461493. Accessed 28 July 2019
  13. ↵
    1. Farquhar H,
    2. Weatherall M,
    3. Wijesinghe M, et al
    . Systematic review of studies of the effect of hyperoxia on coronary blood flow. Am Heart J 2009;158:371–377
    OpenUrlCrossRefPubMedWeb of Science
  14. ↵
    1. McNulty PH,
    2. King N,
    3. Scott S, et al
    . Effects of supplemental oxygen administration on coronary blood flow in patients undergoing cardiac catheterization. Am J Physiol Heart Circ Physiol 2005;288:H1057–H1062
    OpenUrlCrossRefPubMedWeb of Science
  15. ↵
    1. Guensch DP,
    2. Fischer K,
    3. Shie N,
    4. Lebel J,
    5. Friedrich MG
    . Hyperoxia exacerbates myocardial ischemia in the presence of acute coronary artery stenosis in swine. Circ Cardiovasc Interv 2015;8:e002928
    OpenUrlAbstract/FREE Full Text
  16. ↵
    1. Norouzirad R,
    2. Gholami H,
    3. Ghanbari M, et al
    . Dietary inorganic nitrate attenuates hyperoxia-induced oxidative stress in obese type 2 diabetic male rats. Life Sci 2019;230:188–196
    OpenUrl
  17. ↵
    1. Low Wang CC,
    2. Hess CN,
    3. Hiatt WR,
    4. Goldfine AB
    . Clinical update: cardiovascular disease in diabetes mellitus: atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus – mechanisms, management, and clinical considerations. Circulation 2016;133:2459–2502
    OpenUrlAbstract/FREE Full Text
  18. ↵
    1. Smit B,
    2. Smulders YM,
    3. van der Wouden JC,
    4. Oudemans-van Straaten HM,
    5. Spoelstra-de Man AME
    . Hemodynamic effects of acute hyperoxia: systematic review and meta-analysis. Crit Care 2018;22:45
    OpenUrl
  19. ↵
    1. Priestley J
    . Experiments and Observations on Different Kinds of Air. Vol 2. London, St. Paul’s Church-Yard, 1775
  20. ↵
    1. Ibanez B,
    2. James S,
    3. Agewall S, et al
    . 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Rev Esp Cardiol (Engl Ed) 2017;70:1082
    OpenUrl
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Taking the Air Out of Oxygen Supplementation in Individuals With Diabetes and Acute Coronary Syndromes
David Aguilar, Vijay Nambi
Diabetes Care Nov 2019, 42 (11) 2019-2021; DOI: 10.2337/dci19-0035

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Taking the Air Out of Oxygen Supplementation in Individuals With Diabetes and Acute Coronary Syndromes
David Aguilar, Vijay Nambi
Diabetes Care Nov 2019, 42 (11) 2019-2021; DOI: 10.2337/dci19-0035
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