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Oxygen therapy for acute myocardial infarction

Clinical Summary

The World Health Organisation estimates that more than 30 million people suffer a heart attack each year worldwide. In the UK, over 100,000 people a year die from coronary heart disease with about one-third of these dying from an acute myocardial infarction. Oxygen has been used in acute myocardial infarction for many decades and it has become a classic part of the management of this condition. Most guidelines for the treatment of people who are having a heart attack recommend that the patient should be given oxygen to breathe, and many medical students will be familiar with the mnemonic used to remember the initial treatment of myocardial infarction: MONA, Morphine Oxygen Nitrates Aspirin.

The rationale for providing supplemental oxygen to a patient with an acute myocardial infarction is that it may improve the oxygenation of the part of the heart muscle which has had its oxygen supply reduced by the heart attack, and thereby reduce pain, infarct size and, consequently, morbidity and mortality. This pathophysiological reasoning has face validity. However, it is also biologically plausible that oxygen may be harmful. It might reduce coronary artery blood flow and increase coronary vascular resistance, leading to reduced stroke volume and cardiac output. There might also be other adverse haemodynamic consequences, such as increased vascular resistance from hyperoxia and reperfusion injury from increased oxygen free radicals.

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Both of these arguments are mechanism-based and fit well with ideas from their period, because oxygen was introduced into clinical settings before the current emphasis on evidence-based health care. The O2 team who embarked on the Cochrane review featured in this Journal Club share a passion for evidence-based practice. They got together spontaneously to do this review, without funding, in response to national newspaper headlines in 2007 declaring “Oxygen is Harmful”. This followed the publication of a narrative review on oxygen, which highlighted the findings of one randomised trial from the 1970s. At that time, the O2 team were surprised not to find any existing systematic review of this very widely adopted intervention for this common condition.

The Cochrane review evaluates the effects of inhaled oxygen compared to normal air on patient centred outcomes, principally death and pain, in people who are suffering a myocardial infarction. The authors checked through more than 2500 articles, but found only three pieces of research that met the inclusion criteria for the review. These three studies took place in the UK and Russia in the 1970s, 1990s and 2000s. They randomly allocated patients into one of two groups: one received oxygen and the other received air, either through a face mask or by breathing normally. One of the trials was double blinded.

In total, the trials recruited 387 patients, of whom 14 died. Some patients entered the studies with a suspected acute myocardial infarction, but were later shown to be suffering from something else. Therefore, the meta-analyses were done separately for all randomized patients and just for those known to have had an acute myocardial infarction. The pooled estimate for all patients showed a non-statistically significant increase in deaths in hospital in the oxygen treated group. The relative risk was 2.88 (95% CI 0.88 to 9.39). This increased further, to 3.03 (95% CI 0.93 to 9.83) for patients confirmed as having had a myocardial infarction. These findings are suggestive of harm from oxygen but, because of the small number of deaths, may have been due to chance. Pain was not explicitly measured in the trials but the Cochrane reviewers were able to examine it by using the data on the use of pain-relieving drugs. Their meta-analysis found almost no difference between the groups who breathed oxygen or air. The relative risk for all randomized patients was 0.97 (95% CI 0.78 to 1.20). For patients with a proven acute myocardial infarction, it was very similar (0.99, 95% CI 0.83 to 1.18).

This Cochrane review is the most comprehensive systematic review yet undertaken of oxygen for acute myocardial infarction. It can be considered the definitive, up-to-date review of this topic, and given the need for reliable knowledge to guide practice it highlights the urgent need for a new, adequately powered randomized trial to resolve the uncertainty. Until then, the main conclusion of the review is that there is no evidence from randomised trials to support the use of inhaled oxygen in patients with acute myocardial infarction.

Read the Paper

Oxygen therapy for acute myocardial infarction
Juan B Cabello, Amanda Burls, José I Emparanza, Sue Bayliss, Tom Quinn

Background: Oxygen (O2) is widely recommended for patients with myocardial infarction yet a narrative review has suggested it may do more harm than good. Systematic reviews have concluded that there was insufficient evidence to know whether oxygen reduced, increased or had no effect on the heart ischaemia or infarct size.

Objectives: To review the evidence from randomised controlled trials to establish whether routine use of inhaled oxygen in acute myocardial infarction (AMI) improves patient-centred outcomes, in particular pain and death.

Search Strategy: The following bibliographic databases were searched (to the end of February 2010): Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, MEDLINE In-Process, EMBASE, CINAHL, LILACS and PASCAL, British Library ZETOC, Web of Science ISI Proceedings. Experts were also contacted to identify any studies. No language restrictions were applied.

Selection Criteria: Randomised controlled trials of people with suspected or proven AMI, less than 24 hours after onset, in which the intervention was inhaled oxygen (at normal pressure) compared to air and regardless of co-therapies provided these were the same in both arms of the trial.

Data collection and analysis: Two review authors independently reviewed the titles and abstracts of identified studies to see if they met the inclusion criteria and independently undertook the data extraction. The quality of studies and the risk of bias were assessed according to guidance in the Cochrane Handbook. The primary outcomes were death, pain and complications. The measure of effect used was the relative risk (RR).

Main results: OThree trials involving 387 patients were included and 14 deaths occurred. The pooled RR of death was 2.88 (95% CI 0.88 to 9.39) in an intention-to-treat analysis and 3.03 (95% CI 0.93 to 9.83) in patients with confirmed AMI. While suggestive of harm, the small number of deaths recorded meant that this could be a chance occurrence. Pain was measured by analgesic use. The pooled RR for the use of analgesics was 0.97 (95% CI 0.78 to 1.20).

Authors' conclusions: There is no conclusive evidence from randomised controlled trials to support the routine use of inhaled oxygen in patients with acute AMI. A definitive randomised controlled trial is urgently required given the mismatch between trial evidence suggestive of possible harm from routine oxygen use and recommendations for its use in clinical practice guidelines.

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Author Profile

The O2 Team

The O2 Team comprises:

  • Sue Bayliss is an Information Specialist with the West Midlands Health Technology Assessment Collaboration at the University of Birmingham in England, who has extensive experience of searching for studies to inform systematic reviews.
  • Juan B. Cabello is a Consultant Cardiologist and Clinical Epidemiologist who works at the Hospital General Universitario de Alicante in Spain. He is the National Director of CASP Spain (CASPe).
  • Tom Quinn is Professor of Clinical Practice at the University of Surrey, England. He has a background in cardiac nursing and was regional Head of Research in a NHS ambulance Trust.
  • Jose Emparanza is a Consultant Paediatrician and Clinical Epidemiologist and works at the Hospital Donostia in Spain, where he leads the Unidad de Epidemiología Clínica e Investigación (the Clinical Epidemiology and Research Unit). He is Director of CASPe in the Basque Country.
  • Amanda Burls is a Consultant Public Health Physician who is a Senior Clinical Research Fellow and Director of Postgraduate Programmes in Evidence-Based Health Care at the University of Oxford, England. She is a Senior Fellow of the Centre for Evidence-Based Medicine and led this Cochrane review.

Discussion points: a critical appraisal

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