Prove It: Oxygen therapy improves outcomes following AMI

Recent study suggests it may be safe to withhold oxygen from normoxic patients who are suffering from AMI


Medic 12 and Engine 46 receive a report of chest pain on the 12th floor of a local office building. Engine 46 arrives on the scene first and finds a 42-year-old male sitting at his desk. The patient complains of an uncomfortable pressure in the center of the chest that started about 15 minutes ago. The patient rates the pain as a 7 on a 1 to 10 scale. The patient has no significant medical history, no allergies to medication, and no other complaints.

The patient’s heart rate is 96, the blood pressure is 132/84 mm Hg, the respiratory rate is 16 and the room-air pulse oximetry (RaSO2) value is 97 percent. The patient’s lung sounds are clear and equal. The crew of Engine 46 delivers supplemental oxygen at a rate of 8 lpm via a non-rebreather oxygen mask. The patient's pulse oximetry value quickly increases to 100 percent. Because the patient has no allergies to medications, one member of the engine company hands the patient four baby aspirins and asks the patient to chew, rather than swallow the aspirin.

Paramedics from Medic 12 arrive a few minutes later and place the patient on an electrocardiogram (ECG) monitor, which reveals a sinus tachycardia, with no ectopy. Paramedic Davis begins her attempt at IV access while paramedic Garcia acquires a 12-lead ECG. There is ECG evidence of an anterior ST-segment elevation myocardial infarction (STEMI). After determining there are no contraindications, paramedic Davis begins nitroglycerin therapy and asks the crew from Engine 46 to remove the oxygen mask.

During transport, the patient receives 100 micrograms of fentanyl and rests comfortably. Since the medics activated a STEMI Alert before arriving in the emergency department, the team in the coronary catheterization lab was ready and accepted the stable patient directly from the back of the ambulance.

Later, the medics meet with the crew from Engine 46. The lieutenant asks why the medics removed the oxygen when the patient was clearly having a heart attack. Paramedic Davis explains that oxygen is not necessary for patients who are not hypoxemic.

Study review: Supplemental oxygen for MI
Researchers in Australia recently evaluated the effect of supplemental oxygen therapy on myocardial infarction (MI) size [1]. The trial involved paramedics with Ambulance Victoria in Australia and nine different hospitals all capable of performing 24-hour percutaneous coronary intervention services.

Paramedics randomized patients with ECG evidence of ST-segment elevation MI (STEMI) and room-air pulse oximetry (RaSO2) values of 94 percent or greater to receive either 8 lpm oxygen via facemask or no oxygen. However, in the event the RaSO2 values of any patient in the no oxygen group fell below 94 percent, paramedics administered either 4 lpm via nasal cannula or 8 lpm via facemask. All oxygen therapy initiated in the field continued until the patient was admitted into the cardiac care unit (CCU).

The primary endpoints for this study were myocardial injury and infarct size. The researchers assessed myocardial injury by measuring cardiac troponin I (cTnI) and creatine kinase (CK) concentrations every six hours for the first 24 hours, then every 12 hours to 72 hours for the duration of the hospital stay. Cardiac troponin I is a protein released when heart muscle cells die and becomes detectable in the blood stream within 3-4 hours after symptoms begin [2]. CK is an enzyme released when all muscle cells are damaged, including skeletal and cardiac muscle.

To determine the extent of the MI six months after discharge, the research team offered free contrast-enhanced cardiac magnetic resonance (CMR) imaging to any patient willing to return to the research center. This test allowed the researchers to measure the amount of scar tissue present in heart muscle after the infarction.

Results for primary and secondary outcomes
During the 34-month study period, paramedics evaluated 836 patients with a chief complaint of chest pain; however, only randomized 626 patients into the trial. Of those 626 patients, 168 patients were excluded because of prehospital protocol violations, patient refusal to participate in the study, repeat patient, or the patient was determined not to be having a STEMI.

The remaining 470 patients all underwent emergent coronary angiography. By the time the statisticians began the analysis, outcome data was missing for 29 patients. This left 441 patients in the final analysis; 218 patients in the oxygen group and 223 patients in the no-oxygen group.

For secondary outcome measures (which are interesting but not the focus of the study), patients who received oxygen had an increased rate of recurrent MI when compared to the no-oxygen group (5.5% vs. 0.9%; p=0.006, respectively). Additionally, the oxygen group more frequently had arrhythmias after admission (defined as sustained or non-sustained ventricular or atrial tachyarrhythmia requiring medical intervention) than the no-oxygen group (40.4% vs. 31.4%; p=0.05, respectively).

For the primary outcome of myocardial injury, there was no significant difference in mean peak troponin levels between the oxygen and no-oxygen groups (57.4 µg/L vs. 48.0 µg/L; p=0.18, respectively). However, the oxygen group had significantly higher mean peak CK concentrations when compared to the no-oxygen group (1948 U/L vs. 1543 U/L, p=0.01, respectively).

Finally, six months after discharge from the hospital, patients who received oxygen had larger infarct sizes (measured in grams of infarcted heart muscle) when compared to the no-oxygen group (20.3 g vs. 13.1 g; p=0.04, respectively).

What this means for you
The practice of routinely administering oxygen to all patients with a complaint of chest pain is based on rational conjecture and research conducted before the era of coronary reperfusion therapy [3-5]. Oxygen administration increases the arterial oxygen levels and hemoglobin saturation. This in turn was thought to increase the amount of oxygen provided to the tissues and perhaps even to the injured heart muscle itself [6].

However, more recent evidence suggests that in the absence of hypoxemia, the administration of supplemental oxygen does not reduce infarct size or mortality when compared to no oxygen administration [7]. Although the Ranchord et al. study [7] seems to contradict the present study, it is important to note a major difference between the two. Ranchord et al. [7] did not randomize patients until they arrived at the hospital. Most of the patients had already received oxygen delivered by paramedics before arrival in the emergency department.

Other evidence suggests that attempts to keep oxygen saturations close to 100 percent may actually be harmful in the setting of acute coronary syndrome [8-10].

Oxygen administration produces a number of physiologic changes within the body that may help explain why some patients are harmed. Healthy individuals inhaling high concentrations of supplemental oxygen have reduced cardiac output and left ventricular perfusion [11]. Together, these effects reduce both systemic and coronary oxygen delivery. Hyperoxia also reduces coronary blood flow, along with an increase in coronary vascular resistance in patients with cardiac disease [12]. Further, during the reperfusion stage, oxygen has the potential to increases free radical production, which can damage myocardial tissue [13-15].

Study limitations
The methodology chosen for this investigation introduced several limitations that influence how one should interpret the results. For example, both the paramedics and the hospital team knew exactly who was getting oxygen and who was not. Ideally, one would chose to blind the care team to reduce any bias an individual might purposefully or accidently introduce into the investigation. Without blinding, anyone on the care team could treat the two groups differently, which could affect the results.

However, it appears unlikely the lack of blinding introduced significant bias into this investigation. Supplementary data provided by the research team showed that in the prehospital setting, the pain scores reported by patients in the two groups were not different, and there was no difference in nitroglycerin or opioid administration to patients in the two groups. Once at the hospital, there were differences between the two groups with respect to vital signs, pain scores, or the interval between hospital arrival and intervention.

Another limitation of the study is in the power analysis. A power analysis (conducted before the investigation begins) informs the researcher how many patients must be enrolled to detect a difference between the two groups, if a difference really exists. The study was only powered to detect whether oxygen administration altered myocardial injury or infarction size, not for clinical outcomes, such as major adverse cardiac events or mortality. Although the study did detect a 7-gram increase in infarct size associated with oxygen administration, the study could not determine the clinical significance of this increase.

A trial is currently underway in Europe that is adequately powered to detect morbidity and mortality associated with oxygen administration in patients having an AMI [16]. The results of that trial will provide greater insight into the role that oxygen should play in treating these patients.

Additionally, only about one-third of the patients who survived for at least six-months after the infarction agreed to return to the hospital to undergo the CMR imaging, which was used to determine the infarct size. CMR imaging of the remaining two-thirds could have significantly altered the results.

Finally, this study only compared 8 lpm oxygen administration to no oxygen administration. It is possible that low-flow oxygen administration (2 lpm via nasal cannula) may provide some benefit of increased oxygen delivery to the tissues without the harm associated with higher oxygen flow rates.

Summary
This study is another that suggests it may be safe to withhold oxygen from normoxic patients who were suffering from AMI. Oxygen administration to patients with no evidence of hypoxemia did not improve the patient’s symptoms. However, oxygen administration was associated with increases in infarct size at six months post event.

The 2015 AHA guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care acknowledges uncertainty in the role that supplemental oxygen plays in the management of uncomplicated ACS [17]. Despite the uncertainty, the AHA recommends that health care providers consider withholding supplemental oxygen from normoxic patients.

References

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  2. Burcu Bahadir, E., & Kemal Sezgintürk, M. (2015). Applications of electrochemical immunosensors for early clinical diagnostics. Talanta, 132, 162-174. doi:10.1016/j.talanta.2014.08.063
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  7. Ranchord, A. M., Argyle, R., Beynon, R., Perrin, K., Sharma, V., Weatherall, M., Simmonds, M., Heatlie, G., Brooks, N., & Beasley, R. (2012). High-concentration versus titrated oxygen therapy in ST-elevation myocardial infarction: A pilot randomized controlled trial. American Heart Journal, 163(2), 168–175. doi:10.1016/j.ahj.2011.10.013
  8. Cabello, J. B., Burls, A., Emparanza, J. I., Bayliss, S., & Quinn, T. (2013). Oxygen therapy for acute myocardial infarction. Cochrane Database of Systematic Reviews, 8, CD007160. doi:10.1002/14651858.CD007160.pub3
  9. Moradkhan, R., & Sinoway, L. I. (2010). Revisiting the role of oxygen therapy in cardiac patients. Journal of the American College of Cardiology, 56(13), 1013-1016. doi:10.1016/j.jacc.2010.04.052
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  11. Bodetoft, S., Carlsson, M., Arheden, H., & Ekelund, U. (2011). Effects of oxygen inhalation on cardiac output, coronary blood flow and oxygen delivery in healthy individuals, assessed with MRI. European Journal of Emergency Medicine, 18(1), 25-30. doi:10.1097/MEJ.0b013e32833a295e
  12. Farquhar, H., Weatherall, M., Wijesinghe, M., Perrin, K., Ranchord, A., Simmonds, M., & Beasley, R. (2009). Systematic review of studies of the effect of hyperoxia on coronary blood flow. American Heart Journal, 158(3), 371-377. doi:10.1016/j.ahj.2009.05.037
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