Implications of the AVOID study

The AVOID study results go against everything doctors have been taught about using oxygen in treating AMI

---

 

For over a century oxygen therapy has been the mainstay of initial treatment in patients with suspected acute myocardial infarction.

However, over the past decade, an increasing number of studies have challenged the wisdom of this. One of the largest of these is the AVOID (Air Verses Oxygen In myocarDial infarction) study¹. An Australian initiative, the results of this study go against everything doctors have been taught about the role of oxygen in treating AMI.

The bottom line is: in patients without hypoxia, there is limited evidence suggesting oxygen therapy is beneficial.

In fact, it may even cause harm as we will see.

Hyperoxaemia can cause coronary vasoconstriction², so giving too much oxygen during an acute infarction may worsen oxygen delivery to the cardiac muscle.

High-flow oxygen has been associated with increased reperfusion injury, infarct size and mortality in myocardial infarction^{3, 4}. Theoretically, hyperoxaemia may have similar effects on cerebral blood flow. One randomised controlled trial found that in minor or moderate stroke, oxygen administration was linked to increased mortality when compared with room air⁵.

Why AVOID?

Given the prevalence of heart disease in the community, and associated increased risk of a serious cardiovascular event, knowing what works is important. However, knowing can require unlearning the gospel of our medical training.

The data on the effects of hyperoxaemia on ischaemic myocardium is conflicting. The few available clinical trials that have looked at oxygen’s role in AMI did not occur in the contemporary context of emergent reperfusion and associated advanced medical management.

The AVOID study was a prospective, multi-centre, randomised, controlled trial conducted by Ambulance Victoria and participating metropolitan Melbourne hospitals with primary percutaneous coronary intervention (PCI) capabilities. The purpose of the study was to determine whether withholding routine supplemental oxygen therapy in patients with acute ST-elevation myocardial infarction (STEMI) but without hypoxia prior to reperfusion decreased myocardial infarct size. AVOID enrolled 490 patients, over 18 years of age with acute STEMI of less than 12 hours duration. Approximately 79% of subjects in each arm of the study were male.

Patients with ST elevation in two contiguous ECG leads and intended for primary PCI were randomised 1:1 pre-hospital by paramedics. They then either received 8L/min via facemask or no oxygen unless their Sa02 fell below 94%. The oxygen arm went on to receive oxygen at the same flow rate in the cath lab during PCI. The no oxygen group received no oxygen in the cath lab unless, once again, their Sa02 fell below 94%.

The primary endpoints in the AVOID study were:

• Myocardial infarct size as assessed on cardiac enzymes
• Mean peak creatine kinase
• Mean peak troponin I
•  Area under curve of creatine kinase and troponin I

And the pre-specified clinical secondary endpoints:

• ST-segment resolution (12 lead ECG)
• Survival to hospital discharge
• MACCE: Death, MI, revascularisation, stroke at six months
• Myocardial infarct size on CMR (cardiovascular magnetic resonance) at six months

The AVOID study concluded that supplemental oxygen therapy in patients with STEMI but without hypoxia increased myocardial injury, recurrent myocardial infarction and major cardiac arrhythmia, and was associated with larger myocardial infarction size assessed at six months. The  increased risk of reinfarction in the oxygen arm was fivefold.

AVOID contradicted the much publicised OPTIMISE study⁶. This was a pilot study, in which 163 patients with STEMI were randomised to either high-flow oxygen 6L/min via facemask or controlled oxygen with target saturation of 94% to 98% prior to emergency PCI. No difference was found between the two arms of the study in 30-day mortality or infarct size. The problem with the OPTIMISE study was that patients were randomised to treatment in hospital, and most had received high-flow oxygen in the ambulance en route to hospital. Therefore, the results only applied to the short period of time between admission to hospital and primary PCI.

Old habits

It seems counterintuitive to avoid giving oxygen to a patient with chest pain and a likely AMI, with the myocardium experiencing hypoxic damage. However, the latest recommendation, now taught in Advanced Life Support courses is to use the <94% Sa02 threshold.

Dr Ursula King is Medical Editor, The Medical Republic.

References:

1. Stub D, Smith K, Bernard S, et al. A randomised controlled trial of oxygen therapy in acute myocardial infarction Air Verses Oxygen In myocarDial infarction study (AVOID Study). Am Heart J 2012; 163: 339–345.
2. McNulty PH, King N, Scott S, et al. Effects of supplemental oxygen administration on coronary blood flow in patients undergoing cardiac catheterisation. Am J Physiol Heart Circ Physiol 2005; 288: H1057–H1062
3. 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: 371–377.
4. Kaneda T, Ku K, Inoue T, et al. Postischemic reperfusion injury can be attenuated by oxygen tension control. Jpn Circ J 2001; 65: 213–218.
5. Rønning OM, Guldvog B. Should stroke victims routinely receive supplemental oxygen? A quasi-randomised controlled trial. Stroke 1999; 30: 2033–2037.
6. Ranchord AM, Argyle R, Beynon R, et al. High-concentration versus titrated oxygen therapy in ST-elevation myocardial infarction: a pilot randomised controlled trial. Am Heart J 2012; 163: 168–175.