REBEL Cast Ep114: High Flow O2, Suspected ACS, and Mortality?

Background: Historically, we have treated acute coronary syndrome with supplemental oxygen regardless of the patient’s oxygen saturation.  This intervention was based on the belief that pushing the patient’s PaO2 to supra therapeutic levels would increase O2 delivery to ischemic myocardium and help reduce myocardial injury.  More recent evidence, however, demonstrates that too much oxygen could be harmful (AVOID Trial) by causing coronary vasoconstriction and increasing oxidative stress.

The DETO2X-AMI trial (Link is HERE) was a randomized trial of patients with suspected acute myocardial infarction and showed no difference in one year mortality in patients given 12 hours of high flow O2 compared with limited O2. Based on recent studies, current guidelines recommend that O2 should not be given to non-hypoxemic patients with STEMI or NSTEMI [2,3].

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Paper: Stewart, RAH et al. High Flow Oxygen and Risk of Mortality in Patients with a Suspected Acute Coronary Syndrome: Pragmatic, Cluster Randomised, Crossover Trial. BMJ 2021. PMID: 33653685

Clinical Question: Is there an association between high flow supplementary oxygen and 30-day mortality in patients presenting with a suspected acute coronary syndrome (ACS)?

What They Did:

• Pragmatic, cluster randomized, crossover trial performed in 4 regions in New Zealand
• The four geographical regions were randomly allocated to each of two oxygen protocols in six-month blocks over 2 years
  • High O2 protocol: Recommended O2 at 6 to 8L/min by face mask or 4L/min by nasal cannula for ischemic symptoms or EKG changes, irrespective of oxygen saturation (SpO2)
  • Low O2protocol: Recommended oxygen only if SpO2 was less than 90%, with a target SpO2 of <95%

Outcomes:

• Primary: 30d all-cause mortality
• Pre-Specified Secondary Outcomes:
  • 1-year all-cause mortality
  • Length of hospital stay

Inclusion:

• Patients presenting with suspected ACS
• Patients presenting to the ambulances and hospitals in the ANZACS-QI or ambulance ACS registries
• Presenting during the defined study periods over 2 years

Exclusion:

• None stated in the manuscript

Results:

• 40,872 patients with suspected or confirmed ACS were included in the All New Zealand Acute Coronary Syndrome Quality Improvement registry or ambulance ACS pathway
  • 20,304 patients managed using high oxygen protocol
  • 20,568 patients were managed using low oxygen protocol
• 10% had STEMI, 25% had NSTEMI, and 8% had unstable angina 30d
• Mortality:
  • High O2 protocol: 3.0%
  • Low O2 protocol: 3.1%
  • aOR 0.96, 95% CI 0.86 to 1.08
• 4159 patients (10% of total population) had STEMI
  • 30d Mortality:
  • High O2 protocol: 8.8%
  • Low O2 protocol: 10.6%
  • aOR 0.78; 95% CI 0.63 to 0.97
• 10,218 patients (25% of total population) had NSTEMI
  • High O2 protocol: 3.6%
  • Low O2 protocol: 3.5%
  • OR 1.02; 95% CI 0.83 to 1.27

Strengths:

• Groups were equally balanced in terms of baseline characteristics
• Asks a clinically important question

Limitations:

• There were a significant number of protocol violations in a randomly selected group of patients that were audited
• It is unclear what treatments outside of oxygen were given to either group
• Low statistical power for a modest (0.6% absolute difference in all cause 30d mortality) effect of oxygen is a major limitation of this trial
• Very little granular detail on treatments given to both groups, reinfarction rates, hospital admission for heart failure, troponin levels, or echocardiographic outcomes
• Protocol non-adherence could have biased results toward no difference and decreased statistical power of the trial
• The duration of oxygen use was not documented, and it is unclear if one group received oxygen for a longer duration of time than the other

Discussion:

• Groups were destined to look alike because neither had an intervention in most cases. Of the charts that were audited, most did not get O2. Does this study even achieve what it intended to?
  • When looking at final diagnosis of patients over 50% of patients in both groups had either a non-ACS condition or were not classified. The fact that >50% of patients had a non-ACS condition could explain the findings of no increase or decrease in 30d mortality. Why would patients without an ACS condition be included in a study that is evaluating the use of oxygen in ACS?
  • Another reason there is no surprise to the fact that this study didn’t show a difference in 30d mortality is simply looking at the SpO2 achieved: 98% in the high O2 group vs 96% in the low O2 group. Essentially there was no difference, meaning we wouldn’t expect to find a difference in outcomes
  • Although not patient oriented, why is there no breakdown of how many patients had cardiogenic shock, congestive heart failure, echocardiographic findings, or even troponin levels. Although death is a hard objective outcome, there are other outcomes worth knowing the results of and do impact patients quality of life
• There does appear to be a small trend toward better outcomes in the STEMI cohort of patients with high O2 protocol compared to the low O2 protocol (8.8% vs 10.%) that was barely statistically significant. However, this was not the primary outcome of this trial and no definitive conclusions can be drawn.  This is essentially a hypothesis generating outcome

Author Conclusion: “In a large patient cohort presenting with suspected ACS, high flow oxygen was not associated with an increase or decrease in 30 day mortality.”

Clinical Take Home Point: Unfortunately, this is a completely flawed trial that did not achieve any difference in SpO2 between groups (98% vs 96%), included >50% of patients without ACS, and had no granular details (troponin levels, echo findings, quality of life, treatments given between groups). Until further better evidence is produced, I recommend continuing to not use oxygen in patients with ACS who are normoxemic.

For More Thoughts on This Topic Checkout:

• REBEL EM: The DETO2X Trial: Do Patients with AMI Need Supplemental O2?
• REBEL EM: The Death of MONA in ACS – Part II – Oxygen
• REBEL Cast: Ep13 – The AVOID Trial & The FLORALI Trial

References:

1. Stewart, RAH et al. High Flow Oxygen and Risk of Mortality in Patients with a Suspected Acute Coronary Syndrome: Pragmatic, Cluster Randomised, Crossover Trial. BMJ 2021. PMID: 33653685
2. Amsterdam EA et al. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014. PMID: 25260718
3. Ibanez B et al. 2017 ESC Guidelines for the Management of Acute Myocardial Infarction in Patients Presenting with ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 2018. PMID: 28886621