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Why No O's: Part 3 of 3

Why No O's: Part 3 of 3


Because of these and other findings the AHA 2010 guidelines reads as follows: “EMS providers administer oxygen during the initial assessment of patients with suspected ACS. However, there is insufficient evidence to support its routine use in uncomplicated ACS. If the patient is dyspneic, hypoxemic, or has obvious signs of heart failure, providers should titrate therapy, based on monitoring of oxyhemoglobin saturation, to equal to or greater than 94% (Class I, LOE C).”

As long ago as 1950, it was demonstrated that the administration of pure oxygen via a non rebreather mask not only failed to reduce the duration of angina pain but also prolonged the electrocardiographic changes indicative of an AMI (Russek 1950).   A systematic review of human studies that included non-randomized studies did not confirm that oxygen administration diminishes acute myocardial ischemia (Nicholson 2004). Indeed, some evidence suggested that oxygen may increase myocardial ischemia (Nicholson 2004). Another recent narrative review on oxygen therapy (Beasley 2007) also sounded a cautionary note. It referenced a randomized controlled trial (RCT) conducted in 1976 (Rawles 1976) showing that the relative risk of death was 2.89 (95% CI 0.81 to 10.27) in patients receiving oxygen com- pared to those breathing air. While this suggested that oxygen may be harmful, the increased risk of death could easily have been a chance finding. A recent review (Wijesinghe 2009) looked at the effect of oxygen on infarct size inpatients with AMI and concluded that, “There is little evidence by which to determine the efficacy and safety of high flow oxygen therapy in MI. The evidence that does exist suggests that the routine use of high flow oxygen in uncomplicated MI may result in a greater infarct size and possibly increase the risk of mortality”.

Oxygen is also a free radical, meaning that it is a highly reactive species owing to its two unpaired electrons. From a physics perspective, free radicals have potential to do harm in the body. The sun, chemicals in the atmosphere, radiation, drugs, viruses and bacteria, dietary fats, and stress all produce free radicals. Cells in the body endure thousands of hits from free radicals daily. Normally, the body fends off free radical attacks using antioxidants.

Free radicals are a type of unstable, reactive, short-lived chemical species that have one or more unpaired electrons and may possess a net charge or be neutral. The species is termed free because the unpaired electron in the outer orbit is free to interact with surrounding molecules. Cells generate free radicals, or ROS, by the reduction of molecular O2 to water (H2O).  Hypoxic cells are greatly susceptible to ROS. These can damage tissues throughout the body, but of particular concern are lung, heart and brain tissues.

The alveolar epithelial and alveolar capillary endothelial cells are vulnerable targets forO2 free radical induced injury caused by hyperoxia. In acute lung injury (ALI) caused by hyperoxia, hyper- permeability of the pulmonary microvasculature causes flooding of the alveolus with plasma      extravasations leading to pulmonary edema and abnormalities in the coagulation and fibrinolysis pathways promoting fibrin deposition.  Type II alveolar epithelial cells are injured by O2 free radicals leading to impairment of surfactant production.  Cellular survival and adaptation in an oxidative atmosphere are dependent upon sufficient antioxidant defenses to counteract the effects of ROS on cells and tissues.

Hyperoxia is a state of excess supply of O2 in tissues and organs. Oxygen toxicity occurs when the partial pressure of alveolar O2 (PAO2) exceeds that which is breathed under normal conditions.  With continuous exposure to supraphysiologic concentrations of O2, a state of hyperoxia develops. Under hyperoxic pathological conditions, a large influx of reactive O2 species (ROS) are produced. In intracellular and extracellular biological systems, the mass effect of ROS elevation, caused by O2 overexposure, disrupts the balance between oxidants and antioxidants, and this disruption of homeostasis can result in damage to cells and tissues.

Exposure time, atmospheric pressure, and fraction of inspired O2 (FIO2) determine the cumulative O2 dose leading to toxicity. Oxygen is toxic to the lungs when high FIO2 (>0.60) is administered over extended exposure time (≥24 hours) at normal barometric pressure (1 atmospheres absolute (ATA)). This type of exposure is referred to as low pressure O2 poisoning, pulmonary toxicity, or the Lorraine Smith effect. Oxygen exposure after approximately 12 hours leads to lung passageway congestion, pulmonary edema, and atelectasis caused by damage to the linings of the bronchi and alveoli. The formation of fluid in the lungs causes a feeling of shortness of breath combined with a burning of the throat and chest, and breathing becomes very painful [12]. The reason for this effect in the lungs but not in other tissues is that the air spaces of the lungs are directly exposed to the highO2 pressure.  Pulmonary capillary endothelial and alveolar epithelial cells are targets for ROS resulting in injury-induced lung edema, alveolar flooding, hemorrhage, and collagen, elastin, and hyaline membrane deposits [11, 21, 22]. Above a critical PAO2, the hemoglobin-O2 buffering mechanism fails and the tissue PO2 can rise to hundreds or thousands of mmHg. At high levels of O2, protective endogenous antioxidant enzyme systems become consumed by ROS leading to cell death [16, 23]. 

Oxygen toxicity caused by ROS progresses in overlapping phases based on degree of severity and reversibility of injury. The phases are initiation, inflammation, proliferation, and fibrosis. Initially, there are increased ROS and depleted antioxidant levels, and the lung fails to clear itself of mucous. The inflammation phase or exudative phase is characterized by the destruction of the pulmonary lining and migration of leukocyte derived inflammatory mediators to the sites of injury. The proliferative phase is sub-acute and there are cellular hypertrophy, increased secretions from surfactant secreting alveolar type II cells, and increased monocytes.  This increase in the level of monocytes has a direct effect on the body’s immune system as well as its ability to fight disease. 

With aging and in cases of trauma, stroke, heart attack or other tissue injury, the balance of free radicals to antioxidants shifts. Cell damage occurs when free radicals outnumber antioxidants, a condition called oxidative stress. Many disease processes including arthritis, cancer, diabetes, Alzheimer’s and Parkinson’s result from oxidative stress.

The role of oxygen in chronic obstructive pulmonary disease (COPD) patients has been debated for decades. Issues such as a theoretical “hypoxic drive” in patients with COPD and chronic hypercarbia have led to controversies over how much oxygen to give them. While hypoxia must be corrected quickly when it exists, the definition of hypoxia in terms of oxygen saturation has been unclear. For example, a normal person without a respiratory condition breathing room air will usually have a saturation varying from 97%–99%, depending on tidal volume and other normal respiratory variances. It is almost impossible to achieve 100% saturation by breathing room air. We know a saturation of 90% correlates to approximately 60 mmHg pressure, and that is the normal threshold of respiratory distress. However, COPD patients may be accustomed to less saturation, and they typically do well at 88%–92%.

In a study of 405 patients in Australia published in 2010, Dr. Michael Austin and colleagues compared the outcomes of COPD patients who were given standard high-flow oxygen treatment with those given titrated oxygen treatment by paramedics. Titrated oxygen treatment reduced mortality compared with high-flow oxygen by 58% for all patients.

In addition, the role of oxygen after cardiac resuscitation must be mentioned. At one time we attempted to push as much oxygen as possible into cardiac arrest patients on the theory that myocardial oxygen supplies were quickly dwindling, and that if we wanted to save people we had to replenish the missing oxygen. During arrest, and if we were fortunate enough to get a return of spontaneous circulation, we bagged patients as fast and hard as we could, thinking we were restoring oxygen to ischemic cardiac and brain cells.

I can remember as a young paramedic delivering cardiac arrest patients to the ER with an FIO2 of 150% or higher and congratulating myself on what a great job that I had done.  Keep in mind that this was the same era when we gave cases and cases of sodium bicarb.  It didn’t really work, but we looked just like Johnny and Roy popping off the tops of the ampules!

Now we know that while ischemia is responsible for most cases of cardiac arrest, managing reperfusion of ischemic cardiac cells is more complicated than we thought. Because of the role of ROS (free radicals), we now understand that a flood of oxygen into previously ischemic cardiac cells is harmful. 

The latest post-cardiac arrest care guidelines from AHA recommend the following: Avoid excessive ventilation. Start at 10–12 breaths/min and titrate to target PetCO2 of 35–40 mmHg. When feasible, titrate FiO2 to minimum necessary to achieve SpO2 equal to or greater than 94%.  Hence the change from airway, breathing and circulation to that of today…circulation, airway and breathing.  I predict that when the 2015 AHA guidelines are published that ventilations for cardiac arrest patients will be set as low as 6-8 ventilations per minute. This also goes to prove the importance of understanding the role that CO2 and qualitative capnography plays in the resuscitation of the cardiac arrest patient. 

The concept of free radical damage suggests the old EMS notion that, “high flow oxygen won’t hurt anyone in the initial period of resuscitation” may be dead wrong. Tissue damage is directly proportionate to the quantity of free radicals present at the site of injury. Supplemental oxygen administration during the initial moments of a stroke, myocardial infarct (MI) or major trauma may well increase tissue injury by flooding the injury site with free radicals. Finally, consider this: five minutes of supplemental oxygen by non-rebreather decreases coronary blood flow by 30 percent, increases coronary resistance by 40 percent due to coronary artery constriction, and blunts the effect of vasodilator medications like nitroglycerine. These effects were demonstrated dramatically in cath lab studies 1213 published in 2005.

Wonder why the 2010 ECC Guidelines recommended against supplemental oxygen for chest pain patients without hypoxia? Now you know: supplemental oxygen reduces coronary blood flow and renders the vasodilators ALS providers use to treat chest pain ineffective. Where do we go from here? Knowing that both hypoxia and hyperoxia are bad, EMS providers must stop giving oxygen routinely. Oxygen saturations should be measured on every patient. Protocols need to be aligned to reflect the 2010 ECC guidelines: administer oxygen to keep saturations between 94 and 96 percent. No patient needs oxygen saturations above 97 percent and in truth, there is little to no evidence suggesting any clinical benefit of oxygen saturations above 90 percent in any patient.

Part of the reason for the failure to fund such a fundamental study may be the strong a priori belief (Cabello 2009; Danchin 2009), based on pathophysiological reasoning, that oxygen administration must reduce both the oxygen deficit in ischemic myocardial tissue and consequent tissue death. Indeed, both the medical profession and the public are so familiar with the use of oxygen that the general attitude may be that even if it is not doing any good it is not going to be of any harm.  In other words, maybe there is a placebo effect that “might” help the patient. 

Modifications in prehospital equipment will be inherent in controlling oxygen doses administered to patients. In the early days of EMS, venturi masks were popular and routinely used for COPD and cardiac patients. How many of you have even used a venturi mask?  Following the 1994 revision of the EMT National Standard Curriculum, these were largely abandoned because it was felt high concentrations of oxygen were an acceptable risk, given the curriculum’s time limitations.  In all likelihood, the venturi mask will make a comeback, allowing EMS providers to deliver varied concentrations of oxygen as needed to keep oxygen saturations between 94 and 96 percent. Few patients will require non-rebreather masks which are prone to deliver too much oxygen (hyperoxia). CPAP (Continuous Positive Airway Pressure) devices will also need redesign as most conventional EMS CPAP delivers 100 percent oxygen.

In a 2012 study of prehospital noninvasive ventilation in patients with pulmonary edema and/or COPD, asthma and pneumonia, a team led by Dr. Bryan Bledsoe found that use of CPAP with a low oxygen percentage (FiO2) of 28%–32% was highly effective in treatment of respiratory emergencies by medics. Since most CPAP setups deliver 100% oxygen, it may be worthwhile for services to explore the value of using setups with a lower oxygen percentage. 

Author Bill Young is the program director of the EKU Emergency Medical program. He will receive his doctorate in Educational Leadership this May.  CAAHEP-accredited since 1978, EKU offers top quality degree programs in emergency medical care.


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Published on April 06, 2016

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