SGEM#192: Sometimes, All You Need is the Air that You Breathe

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Date: October 19th, 2017

Reference: Hofmann et al. Oxygen Therapy in Suspected Acute Myocardial Infarction. NEJM Sept 2017.

Guest Skeptic: Marcus Prescott is a nurse in Norway. He is also now a first-year medical student.

Case: A 68-year-old man with a history of hypertension and dyslipidemia develops chest pain while grocery shopping. Emergency medical services are called, arrive quickly and find a man with 7/10 chest pain. His vitals are: heart rate of 72 beats per minute, blood pressure of 150/90, respiratory rate of 14 breaths per minute and oxygen saturation of 93%. The ECG shows an inferior ST-Elevated Myocardial Infarction (STEMI). They give him 180mg of ASA to chew and package him for transportation to the hospital. While preparing to depart, they wonder if they should provide him with supplemental oxygen?

Background: Oxygen is a drug and like all drugs can have potential benefits and potential harms depending on how and when it is used. Studies have shown that oxygen can cause vasoconstriction, increase blood pressure and decrease coronary artery blood flow (Kones et al AM J Med 2011).

A systematic review by Wijesinge et al from 2009 found only two randomized control trials looking at supplemental oxygen. One study of 200 patients demonstrated increased mortality (4% in controls vs. 11% in oxygen treatment group).

A second smaller study of 50 patients did not look at mortality but showed less ventricular tachycardia (VT) with supplemental oxygen (23% vs. 25%). However, this difference between the two groups was not statistically significant (relative risk 0.9; 0.3 to 2.7, p = 0.86). What would you rather have, more death or less VT?

Oxygen supplementation in non-hypoxemic patients with acute myocardial infarction has been a hot topic since the publication of the AVOID-trial (Stub et al Circulation 2014). The AVOID trial showed no benefit, and possible harm, to patients with an oxygen saturation over 94% when given supplemental high-flow oxygen. Their conclusion was: “Supplemental oxygen therapy in patients with ST-elevation–myocardial infarction but without hypoxia may increase early myocardial injury and was associated with larger myocardial infarct size assessed at 6 months.”

A 2016 Cochrane review by Cabello et al found five RCTs in patients with suspected or confirmed acute myocardial infarction. They found “There is no evidence from randomised controlled trials to support the routine use of inhaled oxygen in people with AMI, and we cannot rule out a harmful effect.”

The Cochrane authors said that a well-designed RCT is needed due to the uncertainty of routinely using supplemental oxygen in patients with acute myocardial infarctions. They felt this would help inform guideline writers on making recommendations in this area.

The American Heart Association (AHA) Guidelines were updated in 2015 and did not provide a strong recommendation on the issue. The say supplemental oxygen may be withheld in normoxic patients with suspected or confirmed acute coronary syndrome

The usefulness of supplementary oxygen therapy has not been established in normoxic patients. In the prehospital, ED, and hospital settings, the withholding of supplementary oxygen therapy in normoxic patients with suspected or confirmed acute coronary syndrome may be considered. (Class IIb, LOE C-LD)

Clinical Question: Does routine administration of supplemental oxygen in patients with suspected or confirmed acute myocardial infarction who are not hypoxic provide a patient oriented benefit?

Reference: Hofmann et al. Oxygen Therapy in Suspected Acute Myocardial Infarction. NEJM Sept 2017.

Population: Patients 30 years and older with symptoms suggestive of myocardial infarction for less than six hours, oxygen saturation greater than 89%, and either evidence of ischemia on ECG or elevated cardiac troponin on admission.
- Exclusion: Patients in cardiac arrest, oxygen saturation less than 90% or who were receiving ongoing oxygen therapy.
Intervention: Supplemental oxygen at 6L/min for 6-12 hours through open face mask
Comparison: Ambient air
Outcome:
- Primary: Death from any cause within one year
- Secondary: Death for any causes within 30 days, rehospitalisation with myocardial infarction or heart failure and cardiovascular death and composite endpoints at 30 days and one year.

Authors’ Conclusions: “Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1-year all-cause mortality.”

Quality Checklist for Randomized Clinical Trials:

The study population included or focused on those in the emergency department. No
The patients were adequately randomized. Yes
The randomization process was concealed. Yes
The patients were analyzed in the groups to which they were randomized. Yes
The study patients were recruited consecutively (i.e. no selection bias). Unsure
The patients in both groups were similar with respect to prognostic factors. Yes
All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No
All groups were treated equally except for the intervention. No
Follow-up was complete (i.e. at least 80% for both groups). Yes
All patient-important outcomes were considered. No
The treatment effect was large enough and precise enough to be clinically significant. No

Key Results: There were 6,629 patients included in the study for the intention-to-treat analysis. Around 2/3 arrived via ambulance, the median age was 68 years and slightly more than 2/3 of the patients were male. Patients were on oxygen therapy for a median duration of almost 12 hours. In addition, the supplemental oxygen did result in a statistically significant increase in oxygen saturation (99% vs. 97%, p<0.001).

No difference in death from any cause within one year

Kaplan-Meier Curve Death Any Cause

Primary Outcome: Death any cause at one year was 5.1% vs 5.0%, CI 0.79-1.21, p=0.80
- Per-protocol: Mortality was no difference 4.75% vs. 5.1%, CI 0.72-1.14, p=0.40
- Consistent over all subgroups
Secondary Outcomes: No difference in the secondary outcomes reported
- Death from any cause at 30 days was 2.2% vs 2.0%, CI 0.77-1.50, p=0.67
- Rehospitalization with acute myocardial infarction at 30 days was 1.4% vs 0.9%, CI 0.92-2.31, p=0.11
- Rehospitalization with acute myocardial infarction at one year was 3.8% vs. 3.3%, CI 0.88-1.46, p=0.33
- Heart failure data has a 12-month lag time and thus was not included

1) Consecutive Emergency Department Patients: We are unsure if these were consecutive patients because it was not explicitly stated. This has the potential to introduce selection bias. They also recruited patients from the ambulance services, emergency departments, coronary care units, or catheterization laboratories. However, more than 2/3 of the patients arrived at the hospital by ambulance suggesting this would represent a similar population to what we see. This broad inclusion criteria would also increase the validity of these results other clinical settings.

2) Blinding: This was an open label trial not a double-blinded trial. They said it was not feasible or ethical to have a sham comparison group. However, this lack of blinding should have favoured the treatment group. This strengthens our confidence in the results not demonstrating benefit of supplemental oxygen.

3) Treated Equally: We were unsure whether the patients were treated equally. This is because of the pragmatic study design, physicians decided any treatments to use outside of the protocol. Table 2 reports the management was the same except for inotropes being used more often in the oxygen group. There could have also been unmeasured cofounders. In addition, the physician could provide supplemental oxygen to patients based clinically necessary. This happened more often in the ambient-air group (8%) vs. the oxygen group (2%) making the data a little harder to interpret.

4) Under Powered: This study ended up being underpowered for the primary outcome. They had based their power calculation on estimated one year total mortality of 14.4% among patients with myocardial infarctions. Death from any cause at one year was only 5%. They provide three possible explanations for the lower observed mortality. Sicker patients were excluded (hypoxic and those with altered mental status) and healthier patients were included (¼ had a diagnosis other than acute myocardial infarction). This means that there still could be a statistical difference between the two groups if the study had enough patients enrolled. In other words, a Type II error could be made by concluding that there is no difference between the two groups when in fact there is a difference.

5) Clinical vs. Statistical Significance: Even if there was a statistical difference, they did not report one important clinical: outcome, survival with good neurologic function. We would not want to have more patients survive with poor neurologic status.

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusions.

SGEM Bottom Line: Routine administration of supplemental oxygen in patients with suspected or confirmed acute myocardial infarction who are not hypoxic does not appear to provide a patient oriented benefit?

Case Resolution: This patient is not hypoxic with an oxygen saturation of 93%. The paramedics load him up and head to the hospital notifying them that an inferior STEMI is on the way.

Clinical Application: This study agrees with the Cochrane review of five RCTs failing to demonstrate benefit of supplemental oxygen in these patients. As such, I will not provide oxygen to these patients routinely. I also plan to talk with my EMS director about changing their protocol to only administer oxygen to patients with suspected or confirmed acute myocardial infarctions who are hypoxic.

Marcus Prescott

What do I tell my patient? It looks like you are having a heart attack. We have given you ASA and will take you quickly and safely to a hospital that can treat your heart attack. Your vital signs are good right now. We will monitor them on the way to the hospital. Specifically, your oxygen level is fine and we do not need to give you any extra oxygen.

Keener Kontest: Last weeks’ winner was Dr. Drew Watters a Clinical Assistant Professor of Medicine at Indiana University School of Medicine but currently working in Gisborne, New Zealand. Drew knew that it was Gabe Mirkin who coined the mnemonic R.I.C.E. back in 1978. The mnemonic stood for Rest, Ice, Compression and Elevation and it should be noted that he has since recanted his support for the R.I.C.E. regimen.

Listen to the SGEM podcast on iTunes to hear this weeks’ keener question. If you know the answer, then send an email to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

ACEP is coming up at the end of the month. I will be in Washington, DC to debate Chris Carpenter at the Rural Section meeting on October 29^th between 11a-1pm. Please come by and watch the guy in the ivory tower sweat when facing a Rural ACE. Or if you just see me in the hallway, stop and say hello.

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