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lunes, 6 de agosto de 2012

Oxygen Toxicity. EMSWORLD


Oxygen Toxicity

What EMS providers need to know about possible complications from oxygen administration

This CE activity is approved by EMS World Magazine, an organization accredited by the Continuing Education Coordinating Board for Emergency Medical Services (CECBEMS), for 1.5 CEUs. There are two ways to take the CE test that accompanies this article and receive 1.5 hours of CE credit accredited by CECBEMS: 1. Click here to download a PDF of the test. The PDF has instructions for completing the test. 2. Or go towww.rapidce.com to take the test and immediately receive your CE credit. Questions? E-maileditor@EMSWorld.com.
  • Review oxygen absorption and consumption physiology
  • Introduce complications including oxygen toxicity, absorbative atelectasis and carbon dioxide narcosis
  • Explain unique situations of oxygen toxicity in hyperbaric medicine and neonatology
  • Identify techniques to prevent complications
Oxygen is an essential tool in prehospital care and the most commonly administered drug in the out-of-hospital setting. Prehospital providers administer oxygen to correct hypoxemia and hypoxia, and also as an adjunctive treatment in pain management. When administered, oxygen can decrease both the work of breathing and myocardial workload. However, like all drugs, oxygen has side effects. Used incorrectly, oxygen can cause serious harm.

Oxygen Absorption

Adequate oxygen delivery and absorption is essential for proper function at the cellular, tissue and organ levels. The body tolerates inadequate oxygen availability for a short period; however, when demand exceeds oxygen availability for greater than a few minutes, hypoxia will develop, leading to cellular and organ dysfunction, including eventual cellular death.
When a breath is taken or artificial ventilation is delivered, air passes through the mouth and the trachea entering the respiratory system. The tracheobronchial tree first divides at the carina; there are a total of 23 divisions in each branch before finally reaching the alveoli. Air that does not pass though all 23 divisions does not participate in gas exchange and constitutes the “dead space.” Gas exchange occurs when air reaches the alveoli; oxygen diffuses into the bloodstream while carbon dioxide diffuses from the bloodstream into the alveoli. Recall from the EMS classroom that both oxygen (~21%) and carbon dioxide (\< 1%) make up only a small percentage of the air we breathe. By far, nitrogen makes up the majority of the air at nearly 79%. This nitrogen is actually quite important to oxygen absorption, for nitrogen is not as easily absorbed by the body and is the primary gas that creates the pressure inside the alveoli which allows it to stay inflated. Alveoli experiencing atelectasis are not inflated and do not participate in oxygen or carbon dioxide exchange. Pulmonary surfactant, excreted by alveolar cells, coats the alveoli, making it easier to remain open.
It is possible to measure the amount of oxygen absorbed by the body. The majority of the body’s oxygen is attached to hemoglobin as oxyhemoglobin and is measured via arterial oxygen saturation (SaO2). Pulse oximetry (SpO2) is very similar but cannot distinguish between oxygen and carbon monoxide attached to hemoglobin. In prehospital care, in the absence of suspected carbon monoxide cases, SpO2and SaO2 should be essentially the same. Normally less than 5% of oxygen available in the bloodstream is not attached to hemoglobin; rather it is dissolved in the plasma. This dissolved oxygen is measured as the pressure of arterial oxygen, called PaO2, and is measured in millimeters of mercury (mm Hg). A normal PaO2 is 80–100 mm Hg but can decrease to as little as 60 mm Hg without significant clinical symptoms. Under normal conditions, a PaO2 of 60 mm Hg is associated with a SpO2 of 90%. When supplemental oxygen is administered, more and more oxygen is dissolved into the bloodstream increasing the PaO2. There is no maximum PaO2 value when supplemental oxygen is applied.
Oxygen consumption, abbreviated VO2, is the total amount of oxygen used by the body and is determined by oxygen demand, oxygen availability, and the body’s ability to extract oxygen from hemoglobin and plasma. The inability to extract oxygen from hemoglobin occurs in sickle-cell anemia and other similar conditions, but is otherwise beyond the scope of this article. For more information on anemia, review the previous EMS World CE articles.
Unfortunately it is not possible to precisely measure cellular oxygen demand. However it is well understood that oxygen demand increases when the body is stressed, such as during serious injury or illness, following surgery, due to infection and while experiencing pain and/or anxiety. Oxygen demand decreases whenever metabolism slows; this is one reason why patients are cooled following cardiac arrest. More information on the benefits of therapeutic hypothermia will be in a CE article later this year.
Cellular oxygen consumption depends on an adequate oxygen supply. Cells do not function as effectively when oxygen supplies become inadequate because the cells must then shift to anaerobic metabolism. Anaerobic metabolism creates a cellular oxygen debt, which exacerbates tissue dysfunction and hypoxia. Clinically there are several signs and symptoms of oxygen debt, including: anxiety, shortness of breath, tachypnea, tachycardia, hypertension, confusion and cyanosis (late).2
Some progressive EMS systems have begun carrying an iSTAT, which allows paramedics to determine certain lab values. Two of these, lactic acid and pH, can help identify an oxygen debt. In anaerobic metabolism, which occurs when cells are hypoxic, the metabolism byproduct lactic acid rises significantly. The consequence of a rising lactic is a decline in pH, which is why over time anaerobic metabolism leads to the development of a metabolic acidosis. When capable, determine a lactic acid level as well as a pH; lactic acid is considered elevated at levels exceeding 2.2 mm/L, and a pH consistent with acidosis is \
Not surprisingly, cells function poorly in low oxygen environments, and extremely efficiently in oxygen-rich environments. As oxygen availability increases, cellular function increases until they are functioning at full capacity. Essentially, the more oxygen that is available, the better the cell functions. However, there is a point of oxygen administration where additional oxygen does not provide any additional benefit, and over time this supplemental oxygen can become harmful.
The point at which additional oxygen is unnecessary can be estimated in the prehospital setting. To begin, administer supplemental oxygen to restore a normal SpO2, which the American Heart Association currently recommends as at least 94%.3 Once SpO2 is normal, slowly decrease the amount of oxygen being administered and identify the lowest oxygen delivery rate that maintains SpO2 at 94%.1 When a patient can maintain an SpO2 of 94% on room air, supplemental oxygen is generally unnecessary.3
In the hospital setting, cellular oxygen consumption is determined by comparing oxygen content in the arteries and veins. The difference between the two is the amount of oxygen the body takes from the blood for use. These blood draws are referred to as arterial and venous blood gasses respectively.
There is a reason to go through all of this information about what happens to the cells in a hypoxic environment, and how to determine how much oxygen to give to patients. Supplemental oxygen is needed to prevent hypoxia and keep cells functioning properly. However, during normal cellular metabolism oxygen is systematically changed and an O2molecule is produced as a byproduct, which is oxygen with an extra negatively charged electron. This oxygen molecule is considered a free radical “toxic” molecule because it has the ability to damage cell membranes. Normally the body avoids damage from these toxic oxygen molecules because enzymes within each cell are produced that quickly destroy the “toxic” oxygen molecule.4 However, these enzymes are produced at a fixed rate that does not increase when metabolism (oxygen consumption) increases.

Complications of Oxygen Delivery

Like every other drug, oxygen administration has complications. Common complications include skin irritation and breakdown as well as a drying of the mucous membranes. Less common but more serious complications include oxygen toxicity, absorbative atelectasis and carbon dioxide narcosis.
The most common complications are a consequence of the delivery systems. Plastic systems, oxygen masks and nasal cannulas are used, and all of these devices are skin irritants which can cause significant skin irritation and breakdown when used long term. Patients who are on long-term oxygen systems often try to prevent skin irritation by padding their delivery systems, such as by padding their nasal cannula behind the ears with nasal tissues. Other common areas of skin breakdown are across the bridge of the nose and beneath the nares.
Typically oxygen systems deliver oxygen that has nearly zero moisture content. When this oxygen passes through the mucous membranes in the mouth and nose, it is humidified by pulling moisture from the mucous membranes so it is humid by the time it reaches the alveoli. While this protects the alveoli and bronchioles, the nasal and oral mucous membranes quickly dry out. Dry mucous membranes lose their ability to humidify the air we breathe and also become uncomfortable. Applying oxygen via a humidifier can help prevent this from occurring.

Oxygen Toxicity

Recall from earlier in this article that under high oxygen environments, cells metabolize oxygen more quickly. This is because there is an increased pressure from the dissolved oxygen, the PaO2, forcing oxygen into the cell, thereby increasing oxygen consumption and the production of the toxic oxygen molecule byproduct O2-. Since production of the enzyme to eliminate O2- is fixed, the toxic molecules build up over time.4 After roughly 24 hours of this oxygen-rich environment, enough toxic molecules accumulate to clinically see evidence of cellular damage.1
An oxygen-rich environment is determined by looking at how much oxygen a patient receives. Delivering less than 60% oxygen to otherwise healthy lungs is generally considered a low oxygen delivery rate and typically is not associated with the development of clinical oxygen toxicity. However, diseased or injured lungs have been shown to develop symptoms of oxygen toxicity when receiving 50% oxygen or more.4
An early result of oxygen toxicity is capillary leakage, which leads to edema throughout the body, particularly pulmonary edema. Pulmonary edema generally appears first and when untreated can lead to acute lung injury and acute respiratory distress syndrome (ARDS).1 Central nervous system symptoms include altered mental status, respiratory depression and seizures. When awake, some patients also experience visual and auditory disturbances.
Oxygen toxicity has been well documented since the early 1900s and still today remains clinically significant for patients on ventilator support, premature infants and patients receiving hyperbaric oxygen treatment.4 A detailed discussion of ventilator management is beyond the scope of this article. However, EMS is seeing a rise in patients being managed with hyperbaric oxygen and newborns are regularly born outside of the hospital setting.

Toxicity in Hyperbaric Medicine

Hyperbaric oxygen therapy is an important tool in modern medicine for management in a variety of situations including diving emergencies, wound management and carbon monoxide toxicity. Regardless of what hyperbaric medicine is being used to manage, its goal is to increase oxygen availability to organ tissues by increasing oxygen dissolved in the plasma through an increase in the atmospheric pressure. To illustrate this, administering 100% oxygen at sea level, or 1 atmospheric pressure, can produce a maximum PaO2 of 510 mm Hg. By increasing the environment to 3 atmospheric pressures, PaO2 can be increased to 1,530 mm Hg.4 This increase speeds healing by allowing tissues to have increased oxygen available for metabolism. Specifically in diving-related emergencies, hyperbaric medicine compresses nitrogen bubbles that may have formed in the patient’s body tissues to allow the body to more easily eliminate nitrogen that may cause pain (i.e., the bends) and emboli.
While hyperbaric oxygen has true benefits, there are legitimate dangers to its utilization as well. As stated above, hyperbaric oxygen increases oxygen available at the tissue level. Also recall from earlier that the more oxygen available, the faster the cell will metabolize oxygen, and over time this can lead to an accumulation of free oxygen radicals. At normal atmospheric pressures (1 atmosphere) this takes 12 to 16 hours of constant 100% oxygen exposure; this timeframe is reduced to 3 to 6 hours at 2 atmospheres.4This is significant because the same valuable treatments can become dangerous; thus the utilization of hyperbaric oxygen must be closely monitored and controlled.

Neonatal Oxygen Administration

A host of changes occur during and shortly after the birth of a neonate. The neonate’s fetal hemoglobin has a higher affinity for oxygen than adult hemoglobin, which allows them to tolerate lower measured oxygen levels better.4 In reality, measured blood gasses are quite different for the neonate than in the adult and the normal blood gasses are summarized in Table I. The most significant numbers for EMS providers to note are that the neonate’s normal SaO2 and PO2 are much lower than normal adult values. Healthy neonates tolerate these low values well and transition to adult values within about a week.4
Administering supplemental oxygen to neonatal patients has been common, particularly during resuscitation. However, supplemental oxygen can bring the neonate’s oxygen levels well beyond their established normal levels; one of the side effects of this is vascular constriction. This vascular constriction can cause a temporary loss of blood flow in the neonatal retina, leading to long-term vision problems. This occurs in addition to traditional oxygen toxicity, which is also a risk for the neonate because they are not capable of managing increased PO2 levels as well as an adult.4
In response to this risk, and based on fairly recently published data that showed neonates resuscitated with room air had a higher survivability than those resuscitated with 100% oxygen, the American Heart Association changed their recommendations in regards to oxygen administration during neonatal resuscitation. Immediate 100% oxygen is no longer recommended. Instead, they suggest initiating resuscitation with room air, and only administer oxygen if the neonate’s heart rate stays 60 after 90 seconds of resuscitation. Once it’s administered, continue administering oxygen until the heart rate normalizes.5

Absorbative Atelectasis

Not all alveoli are used on a minute-to-minute basis. For example, when resting and sleeping fairly shallow breaths are taken and only a fraction of the body’s alveoli participate in gas exchange. When exercising more oxygen is needed so deeper breaths are taken to increase the volume of air inhaled, and thus more alveoli participate in gas exchange.
As mentioned earlier, nitrogen helps create pressure inside the lungs to keep alveoli propped open because nitrogen does not easily pass though the alveolar membranes. Inactive alveoli, which are those not being ventilated with the average resting breath, contract and have a reduced air volume. However, some nitrogen still remains in these alveoli to keep them open and ready for use.
When supplemental oxygen is administered, less nitrogen is inhaled. At 50% oxygen, there is still roughly 50% nitrogen in inhaled air. However, once greater than 50% oxygen is delivered, oxygen replaces nitrogen as the primary gas in the lungs. The term for this is nitrogen washout, because the oxygen literally pushes out the nitrogen over time. Complete nitrogen washout takes 15 minutes when breathing 100% oxygen.
With the nitrogen washed out, the gas helping keep alveoli inflated is eliminated and alveoli begin to collapse. Absorbative atelectasis, also called denitrogenation absorption atelectasis, is the collapse of the alveoli due to the loss of the partial pressure of nitrogen within the lungs.4 Thus at higher oxygen levels fewer alveoli are available to participate in gas exchange.
Absorbative atelectasis has clinically significant applications for prehospital providers. It is difficult to identify when absorbative atelectasis has occurred since the only sign is a decreased inspiratory volume. However, there are clues that it may be taking place. Patients who are breathing spontaneously may complain of increased shortness of breath or anxiety when oxygen levels are increased. Another clue may be that an increased ventilator rate is needed when delivering 100% oxygen compared to when using lower oxygen levels. While these subtle changes are unlikely to be noticed during short transports, providers whose systems include longer transport times (greater than 30 minutes), and those who participate in interfacility transports, may observe these changes, indicating a need to decrease oxygen delivery rates.

Carbon Dioxide Narcosis/Oxygen-Induced Hypercapnia

Chemoreceptors are discussed in both EMT and paramedic classes. Peripheral chemoreceptors, located in the carotid arteries and the aortic arch, are sensitive to oxygen changes and trigger breaths when PaO2drops below 60 mm Hg. Central chemoreceptors have primary control over breathing and are located in the medulla of the brain and bathed in cerebral spinal fluid. When the CO2 levels rise, hydrogen ion levels rise, causing a pH decrease, and the brain’s respiratory center is triggered to “blow off” carbon dioxide via respiration. In patients with chronically high CO2 levels and low PaO2 levels, such as patients with advanced COPD, the central chemoreceptors can become desensitized because their pH is persistently low due to excessive hydrogen ions in their cerebral spinal fluid. When this occurs, their respirations are triggered, in theory, by peripheral chemoreceptors sensing hypoxia.2
Patients who have chronic ventilatory failure, defined as a chronically increased PaCO2 exceeding 50 mm Hg and decreased PaO2 below 55 mm Hg, need oxygen when their oxygen levels fall below the patient’s established baseline.They also need titrated oxygen when they present in respiratory distress. A recent synopsis of research on patients experiencing an exacerbation of COPD found that 45 minutes of prehospital-administered high-flow oxygen (8 liters per minute) increased patient mortality. The research found decreased mortality when SpO2 was maintained between 88%–92% using titrated oxygen via nasal cannula alone instead of high-flow oxygen and led to recommendations of avoiding high-flow oxygen during prehospital care of patients with advanced COPD.6,7
On occasion, a relatively rare condition known as oxygen-induced hypercapnia can develop in these patients, which results from oxygen administration. When oxygen is administered for an extended period (hours to days) the patient’s already high carbon dioxide levels rise even further, which leads to lethargy and slow and shallow breathing. Without intervention, respiratory arrest develops. Although the exact mechanism for oxygen-induced hypercapnia is not clearly known, it is thought to be a combination of the suppression of the theoretical hypoxic drive as well as an oxygen-induced pulmonary perfusion mismatch.2 Other texts suggest that when oxygen is applied to the asymptomatic patient with a history of an advanced COPD, their lungs are exposed to an increased oxygen saturation. The body quickly recognizes that it can maintain the same PaO2 without having to work as hard, and over time the body adjusts to the alveolar oxygen levels to maintain their arterial oxygen levels as their baseline. The net result of this can be a decreased respiratory rate.4
The well documented and clinically important piece of this condition is that oxygen-induced hypercapnia most commonly occurs in otherwise asymptomatic, relaxed and unstimulated patients, such as a patient who is sleeping. It does not occur in patients with acute respiratory distress, who often are experiencing a catecholamine release stimulating increased respiratory and circulatory rates.2
Clinical symptoms of oxygen-induced hypercapnia include a rising CO2 level, which can be measured with a side-stream CO2 device, altered mental status including confusion, complaints of headaches, and a somnolent appearance.1

Prevention of Complications

Preventing complications from oxygen administration is fairly straightforward. To start, whenever possible, pad the straps and tubing of oxygen delivery systems, particularly on patients who receive oxygen long term. Also, consider increasing the use of humidified oxygen to prevent drying out mucous membranes. Oxygen humidifiers are inexpensive and greatly increase patient comfort. Also, elevating a patient’s head and chest at least 30 degrees promotes lung expansion and helps prevent aspiration.
Never withhold oxygen from patients who are in respiratory distress or hypoxic. Oxygen is truly a lifesaving drug. During major resuscitations, such as cardiac arrest and major traumas, 100% oxygen is indicated. However, for most all other patients, consider limiting oxygen to maintain SpO2 in the 90%–95% range; this also keeps the PaO2 above 60 mm Hg.1Research has consistently shown that oxygen’s maximum benefit is obtained when delivered in the 22%–50% range4, and its benefit is limited after 6 hours of administration.3
Neonatal patient management requires special consideration. Whenever possible, utilize room air when initiating resuscitation. Only administer oxygen when the neonate remains bradycardic after 90 seconds of resuscitation efforts.5


The administration of oxygen is safe and effective for patients who are in respiratory distress or who are hypoxic. Never feel that oxygen needs to be withheld. However, keep in mind that there are real consequences to the long term utilization of high-flow oxygen. To help prevent potential complications from oxygen administration, reach for the nasal cannula before the non-rebreather mask, and apply just enough oxygen to maintain normal saturations.
1. Morton PG, et al, eds., Critical Care Nursing, a Holistic Approach, 8th edition. Philadelphia, PA: Lippincott, Williams & Wilkins, 2005.
2. Des Jardins T, Burton GG. Clinical Manifestations and Assessment of Respiratory Disease, 5th edition. St. Louis, MO: Elsevier, 2006.
3. O’Connor RE, et al. Acute Coronary Syndromes: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.Circulation 122: S787–817, 2010.
4. Shapiro BA, et al. Clinical Application of Blood Gases, 5th Edition. St. Louis, MO: Elsevier, 1994.
5. Kattwinkel J, et al, Neonatal Resuscitation: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.Circulation 122: S909–S919, 2010.
6. Ntoumenopolus G. Using titrated oxygen instead of high flow oxygen during an acute exacerbation of chronic obstructive pulmonary disease (COPD) saves lives. J Physiother57(1):55, 2011.
7. Austin MA, et al. Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomized controlled trial. BMJ 341: c5462, 2010.
Kevin T. Collopy, BA, FP-C, CCEMT-P, NREMT-P, WEMT, is an educator, e-learning content developer and author of numerous articles and textbook chapters. He is also the performance improvement coordinator for Vitalink/Airlink in Wilmington, NC, and a lead instructor for Wilderness Medical Associates. Contact him at kcollopy@colgatealumni.org.
Sean M. Kivlehan, MD, MPH, NREMT-P, is an emergency medicine resident at the University of California San Francisco and a former New York City paramedic for 10 years. Contact him atsean.kivlehan@gmail.com.
Scott R. Snyder, BS, NREMT-P, is the EMS education manager for the San Francisco Paramedic Association in San Francisco, CA. Scott has worked on numerous publications as an editor, contributing author and author, and enjoys presenting on both clinical and EMS educator topics. Contact him atscottrsnyder@me.com.