Download Oxygen Toxicity

Oxygen Toxicity
BY KEVIN T. COLLOPY, BA, FP-C, CCEMT-P, NREMT-P, WEMT, SEAN M. KIVLEHAN, MD, MPH, NREMTP, SCOTT R. SNYDER, BS, NREMT-P ON JAN 17, 2012
Photo credit: Ray Kemp
Photo credit: Ray Kemp
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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 CEU. To take the CE test that accompanies this
article, go to www.rapidce.com to take the test and immediately receive your CE credit. Questions? [email protected].
Objectives

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 (SaO 2). 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, SpO2 and 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 PaO 2. There is no maximum PaO2 value when
supplemental oxygen is applied.
Oxygen Consumption
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 previousEMS 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 O2- molecule
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 PaO 2, forcing oxygen into the cell, thereby
increasing oxygen consumption and the production of the toxic oxygen molecule byproduct O 2-. 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. 4 This 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 SaO 2 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 PO2levels 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 PaO2 drops 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 CO 2 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.4 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
Summary
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.
References
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 Physiother 57(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. BMJ341: 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 [email protected].
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 at [email protected].
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 [email protected].