Use of Oxygen in MI Patients Questioned by New Cochrane Review

June 16, 2010

June 16, 2010 (Alicante, Spain and Guildford, United Kingdom) — There is no conclusive evidence from randomized controlled trials to support the routine use of inhaled oxygen in patients with acute MI, a new analysis in the Cochrane Database of Systematic Reviews concludes [1]. In fact, the review of available clinical-trial data suggests that oxygen might actually be harmful.

"A definitive randomized 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," the authors state.

For the review, published online June 16, 2010, researchers led by Dr Juan Cabello (Hospital General Universitario de Alicante, Spain) and Prof Tom Quinn (University of Surrey, Guildford, UK) pooled the results of three randomized trials involving 387 MI patients. There were a total of only 14 deaths. Results showed that oxygen use was associated with a relative risk of death of 2.88 (95% CI 0.88–9.39) in an intention-to-treat analysis and 3.03 (95% CI 0.93–9.83) in patients with confirmed MI. While suggestive of harm, the small number of deaths recorded meant that this could be a chance occurrence, the authors stress.

Pain, measured by analgesic use, did not appear to be affected by oxygen use, with a relative risk for analgesic use of 0.97 (95% CI 0.78–1.20).

Quinn commented to heartwire : "There is no hard evidence supporting the use of oxygen in MI. It is used for pathophysiological reasons. People think that because MI is caused by a lack of oxygen to the heart, giving more oxygen must be a good thing. But it is always a problem moving from that reasoning to clinical-trial evidence."

He added: "While it may seem like common sense, sometimes these things are not beneficial. Cardiology is littered with examples where an intervention has seemed like a good idea in theory, but when large trials are done it has turned out to be of no benefit or even harmful, like the prophylactic use of antiarrhythmics."

If oxygen really is associated with a threefold increased risk of dying, it could be responsible for hundreds of thousands of unnecessary deaths.

While most clinical guidelines recommend the use of oxygen on the basis of expert opinion, some have noted that the use of oxygen is not evidence based and that there have been suggestions that it could be harmful, Quinn explained. He believes that guidelines should state that the benefits of oxygen are unknown and that its use is based only on expert opinion.

"If oxygen were being introduced today as a new treatment, it wouldn't be accepted, as there are no data to support its use. But we have been using it for decades based on just three small trials that, if anything, suggest an excess of deaths in patients given oxygen. Yes, these trials are far from perfect, and the number of deaths is very low, so no conclusions can be drawn, but if oxygen really is associated with a threefold increased risk of dying, it could be responsible for hundreds of thousands of unnecessary deaths," he commented.

Quinn said he does not know how oxygen could be causing harm but that some studies have suggested that administration of high doses could cause a constriction of the coronary artery and increase infarct size.

Funding Needed for Definitive Trial

"We need a large clinical trial with about 10 000 patients in each group to sort this issue out. We are trying to plan such a trial, but funding will be difficult," Quinn said. "Also, because the use of oxygen has become so routine, with it being given to 98% of Mi patients, usually in the ambulance, it might be difficult to persuade doctors to enroll patients. The trouble is, oxygen is not a sexy subject. If it were some brand-new technology, we would probably have a lot more interest."

In the review, the authors say: "The evidence in this area is sparse [and] of poor quality and predates the advances in reperfusion techniques and trial methods. The evidence available is suggestive of harm but lacks power, so this could be due to chance. Current evidence neither supports nor clearly refutes the routine use of oxygen in patients with AMI."

They point out that as long ago as 1950, it was demonstrated that the administration of pure oxygen not only failed to reduce the duration of angina pain but also prolonged the electrocardiographic changes indicative of an MI. "This finding was explicitly identified as requiring further research over three decades ago," the authors note, adding that, given that a study published in 1976 subsequently suggested possible harm, "It is surprising that a definitive study to rule out the possibility that oxygen may do more harm than good has not been done." They conclude: "Given the widespread use of oxygen in AMI, the inconsistency in recommendations about when and to whom it should be given, and the fact that the best current evidence is suggestive of potential clinically significant harm, the need to clarify this uncertainty is urgent."