Hypoxia is a state in which oxygen is not available in sufficient amounts at the tissue level to maintain adequate homeostasis; this can result from inadequate oxygen delivery to the tissues either due to low blood supply or low oxygen content in the blood (hypoxemia). Hypoxia can vary in intensity from mild to severe and can present in acute, chronic, or acute and chronic forms. This activity reviews the etiology, pathophysiology, and presentation of hypoxia and highlights the role of the interprofessional team in the management of affected patients.
Hypoxia is a state in which oxygen is not available in sufficient amounts at the tissue level to maintain adequate homeostasis; this can result from inadequate oxygen delivery to the tissues either due to low blood supply or low oxygen content in the blood (hypoxemia).
Hypoxia can vary in intensity from mild to severe and can present in acute, chronic, or acute and chronic forms. The response to hypoxia is variable; while some tissues can tolerate some forms of hypoxia/ischemia for a longer duration, other tissues are severely damaged by low oxygen levels.[rx][rx][rx]
Hypoxia is a condition in which tissues of the body do not receive sufficient oxygen (O2) supply. The imbalance between tissue O2 supply and consumption results in an insufficient O2 supply to maintain cellular function. Hypoxia is defined as an O2 saturation (SpO2) < 90%. Hypoxemia is a decrease in oxygen tension in the arterial blood (PaO2) and is defined as a PaO2 < 60 mmHg. A SpO2 < 90% or a PaO2 < 60 mmHg places a patient on the “steep” area of the oxygen–hemoglobin dissociation curve, where small changes in PaO2 cause large changes in SpO2 and rapid clinical deterioration
Types of Hypoxia
- Asphyxia – condition of severely deficient supply of oxygen to the body caused by abnormal breathing
- Cerebral hypoxia – Oxygen shortage of the brain or cerebral anoxia, a reduced supply of oxygen to the brain
- Erotic asphyxiation – Intentional restriction of oxygen to the brain for sexual arousal or autoerotic hypoxia, intentional restriction of oxygen to the brain for sexual arousal
- Fink effect – Changes of oxygen partial pressure in the pulmonary alveoli caused by a soluble anesthetic gas, or diffusion hypoxia, a factor that influences the partial pressure of oxygen within the pulmonary alveolus
- G-LOC cerebral hypoxia induced by excessive g-forces
- histotoxic hypoxia, the inability of cells to take up or utilize oxygen from the bloodstream
- Hyperoxia – exposure of tissues to abnormally high concentrations of oxygen.
- Hypoventilation training – Physical training method in which reduced breathing frequency are interspersed with periods with normal breathing
- Hypoxemia – Abnormally low level of oxygen in the blood or hypoxemic hypoxia, a deficiency of oxygen in arterial blood
- Hypoxia in fish – Response of fish to environmental hypoxia, responses of fish to hypoxia
- Hypoxia-inducible factors
- Hypoxic hypoxia, a result of insufficient oxygen available to the lungs
- Hypoxic ventilatory response
- Hypoxicator a device intended for hypoxia acclimatisation in a controlled manner
- Intermittent hypoxic training
- Intrauterine hypoxia, when a fetus is deprived of an adequate supply of oxygen
- Latent hypoxia – Tissue oxygen concentration which is sufficient to support consciousness at depth, but not at surface pressure or deep water blackout, loss of consciousness on ascending from a deep freedive
- Pseudohypoxia, increased cytosolic ratio of free NADH to NAD+ in cells
- Sleep apnea – Disorder involving pauses in breathing during sleep
- Time of useful consciousness
- Tumor hypoxia, the situation where tumor cells have been deprived of oxygen
Causes of Hypoxia
In order to understand the mechanism of hypoxia, we have to know that in order to have the oxygen carried by hemoglobin, direct interaction between red blood cells in pulmonary capillaries and the air in the alveoli is needed. This process can be compromised at any one of the following three points: blood flow to the lung (perfusion), airflow to the alveoli (ventilation), and the gas exchange through the interstitial tissue (diffusion).
The brain depends on the blood to provide it with a constant supply of oxygen. Thus disruptions to any part of the body that plays a role in blood or oxygen supply can lead to hypoxia. The four primary causes of hypoxia are:
- No blood supply to the brain – This occurs when the blood vessels that supply the brain with blood are completely obstructed. This is extremely rare and usually fatal.
- Low blood supply to the brain – Low blood supply can occur when even a single blood vessel is blocked or partially obstructed, as often happens with a stroke. This form of hypoxia frequently affects a specific region of the brain, interfering with functions governed by that region.
- No blood oxygen – When the body can’t take in oxygen, or the heart or lungs can’t properly provide the blood with oxygen, the brain — and all other organs — suffer from hypoxia. This is quickly fatal.
- Low blood oxygen – When the body can’t properly oxygenate the blood, often due to illnesses such as emphysema or a crisis such as a heart attack, the brain gets less oxygen than it needs to properly function.
Reduced Oxygen Tension
As in cases of high altitude.
Airway obstruction can be proximal as in laryngeal edema or foreign body inhalation, or distal as in bronchial asthma or chronic obstructive pulmonary disease (COPD).
Impaired respiratory drive as in cases of deep sedation or coma.
Restricted movement of the chest wall as in obesity hypoventilation syndrome, circumferential burns, massive ascites, or ankylosing spondylitis.
Neuromuscular diseases, such as myasthenia gravis, muscular dystrophy, amyotrophic lateral sclerosis, or phrenic nerve injuries.
Ventilation-Perfusion Mismatch (V/Q Mismatch)
Decreased V/Q Ratio (impaired ventilation or high perfusion) such as chronic bronchitis, obstructive airway disease, mucus plugs, pulmonary edema impair the ventilation and therefore decrease the ratio of ventilation to perfusion.
Increased V/Q Ratio (impaired perfusion): such as in cases of pulmonary embolism or increased ventilation as in emphysema (large bullae in the lungs) the surface area available for gas exchange is decreased, which causes higher ventilation in comparison to perfusion leading to a high V/Q ratio.
- Hypoxemic Hypoxia – Low oxygen tension in the arterial blood (PaO2) is due to the inability of the lungs to properly oxygenate the blood. Causes include hypoventilation, impaired alveolar diffusion, and pulmonary shunting.
- Circulatory Hypoxia – It is due to pump failure (heart is unable to pump enough blood, and therefore oxygen delivery is impaired).
- Anemic Hypoxia – It is because of a decrease in oxygen-carrying capacity due to low hemoglobin leading to inadequate oxygen delivery.
- Histotoxic Hypoxia (Dysoxia) – Cells are unable to utilize oxygen effectively, the best example of this is Cyanide poisoning which inhibits the enzyme cytochrome C oxidase in the mitochondria, blocking the use of oxygen to make ATP.
- Traveling to high altitudes, especially for people in poor health and for those who quickly rise to high altitudes.
- Carbon monoxide poisoning.
- Strangulation or smothering. For example, the choke holds that some law enforcement officers use can cause hypoxia if held too long.
- Very low blood pressure, which is usually caused by something else, such as a hemorrhage.
- Smoke inhalation.
- Heart attack or stroke.
- Medical conditions such as a heart attack or stroke.
- Allergic reactions that lead to anaphylactic shock.
- Severe cases of asthma.
- In infants, improper sleep positions or unsafe sleep environments. For example, young babies can be smothered in crib bumpers, or get inadequate oxygen while sleeping on their stomachs.
Right to Left Shunt
The blood crosses from the right to the left side of the heart without being oxygenated. Causes include:
Anatomic Shunts: Blood bypasses the alveoli, e.g., intracardiac shunts (ASD, VSD, PDA), pulmonary arteriovenous malformations, fistulas, and hepato-pulmonary syndrome.
Physiologic Shunting: Blood passes through non-ventilated alveoli, for example, pneumonia, atelectasis, and ARDS.
Impaired Diffusion of Oxygen
Oxygen diffusion is impaired between the alveolus and the pulmonary capillaries. Causes are usually interstitial edema, interstitial inflammation, or fibrosis. Clinical examples include pulmonary edema and interstitial lung disease.
This includes the factors that decrease the percentage of oxygen in the alveoli, either due to obstruction of the airways or an increase in partial pressure of alveolar gases other than oxygen. Carbon dioxide is one example. Hypoventilation can also occur due to impaired respiratory drive as in cases of deep sedation or because of restricted movement of the chest wall as in obesity hypoventilation syndrome or ankylosing spondylitis. In this setting, the A-a gradient will be normal as the oxygen is deficient in both alveoli and the bloodstream.
In alveoli, an increase in partial pressure of one gas will be on the cost of the other gases composing the air, e.g., an increase in carbon dioxide partial pressure results in a decrease of partial pressure of oxygen, both at alveolar as well as the arterial level. This type of hypoxemia is easily corrected with supplemental oxygen.
Ventilation-Perfusion Mismatch (V/Q Mismatch)
This occurs when there is an imbalance between lung ventilation and blood flow. Even in the normal lung, there is a V/Q mismatch. In an upright individual, the V/Q ratio is higher in the apices than at the lung base. This difference is responsible for the normal A-a gradient. V/Q mismatch increases in pulmonary vascular disease, thromboembolic disease, or atelectasis to name a few. Such a process ultimately results in hypoxemia which is more difficult to correct with supplemental oxygen.
Right to Left Shunt
Occurs when blood passes from the right to the left side of the heart without being oxygenated. Anatomic abnormalities, such as atrial or ventricular septal defects as well as pulmonary arteriovenous malformations can cause hypoxemia that is notoriously difficult to correct with supplemental oxygen. Similar physiology is observed in hepato-pulmonary syndrome. Physiologic right-to-left shunt exists when the blood passes through non-ventilated alveoli in cases of atelectasis, pneumonia, and acute respiratory distress syndrome (ARDS).
Impaired Diffusion of Oxygen Across the Alveoli into Blood
The usual causes are interstitial edema, lung tissue inflammation, or fibrosis. Depending on the disease’s extent, a moderate to a large amount of supplemental oxygen may be required to correct this type of hypoxemia. Exercise can worsen hypoxemia resulting from impaired diffusion. An increase in cardiac output with exercise results in accelerated blood flow through alveoli, reducing the time available for gas exchange. In the case of the abnormal pulmonary interstitium, gas exchange time becomes insufficient, and hypoxemia ensues.
Symptoms of Hypoxia
Oxygen plays an important part in your body’s cells and tissues. The only way for your body to get oxygen is through your lungs.
COPD results in inflammation and swelling of your airways. It also causes the destruction of the lung tissue called alveoli. COPD causes a restricted flow of oxygen in your body as well.
Symptoms of hypoxia often include:
- shortness of breath while resting
- severe shortness of breath after physical activity
- decreased tolerance to physical activity
- waking up out of breath
- feelings of choking
- frequent cough
- bluish discoloration of the skin
- Changes in the color of your skin, ranging from blue to cherry red
- Fast heart rate
- Rapid breathing
- Shortness of breath
- Slow heart rate
Symptoms of oxygen deprivation include
- Something obstructing the face, mouth, or nose; increased carbon monoxide exposure can be a problem in enclosed areas, so a person in a very small space or whose face is covered may suffer from oxygen deprivation even if they can breathe.
- Changes in mood or personality; the victim may seem confused.
- Loss of consciousness, including fainting or seizures.
- Blue or white lips, tongue, or face.
- Tingling in the extremities.
- Pupils that don’t respond normally to light.
- Not breathing, or not expelling air when exhaling.
- Hyperventilating or gasping for air.
- Unable to speak; a person who is truly choking may not cough.
COPD is a chronic condition, so you may experience any of these symptoms on an ongoing basis. If you experience any of these symptoms, it’s considered a medical emergency.
You should call your local emergency services, or go to an emergency room, if you experience a change from your baseline or if your symptoms worsen. This is especially important if the symptoms are associated with chest pain, fever, fatigue, or confusion.
Diagnosis of Hypoxia
The presentation of hypoxia can be acute or chronic; acutely the hypoxia may present with dyspnea and tachypnea. Symptom severity usually depends on the severity of hypoxia. Sufficiently severe hypoxia can result in tachycardia to provide sufficient oxygen to the tissues. Some of the signs are very evident on physical exam; stridor can be heard once the patient arrives in cases of upper airway obstruction. Skin can be cyanotic, which might indicate severe hypoxia.
When oxygen delivery is severely compromised, organ function will start to deteriorate. Neurologic manifestations include restlessness, headache, and confusion with moderate hypoxia. In severe cases, altered mentation and coma can occur, and if not corrected quickly may lead to death.
The chronic presentation is usually less dramatic, with dyspnea on exertion as the most common complaint. Symptoms of the underlying condition that induced the hypoxia can help in narrowing the differential diagnosis. For instance, productive cough and fever will be seen in cases of lung infection, leg edema, and orthopnea in cases of heart failure, and chest pain and unilateral leg swelling may point to pulmonary embolism as a cause of hypoxia.
The physical exam may show tachycardia, tachypnea, and low oxygen saturation. Fever may point to infection as the cause of hypoxia.
Lung auscultation can yield a lot of useful information. Bilateral basilar crackles may indicate pulmonary edema or volume overload, other signs of that includes jugular venous distention and lower limb edema. Wheezing and rhonchi can be found in obstructive lung disease. Absent unilateral air entry can be caused by either massive pleural effusion or pneumothorax. Chest percussion can help differentiate the two and will reveal dullness in cases of pleural effusion and hyper-resonance in cases of pneumothorax. Clear lung fields in a setting of hypoxia should raise suspicion of pulmonary embolism, especially if the patient is tachycardic and has evidence of deep vein thrombosis (DVT).
Lab Test And Imaging
Evaluation of Acute Hypoxia
Pulse Oximetry to Evaluate Arterial Oxygen Saturation (SaO2)
The arterial oxygen saturation (SaO2) refers to the amount of oxygen bound to hemoglobin in arterial blood. The measurement is given as a percentage. Resting SaO2 less than or equal to 95% or exercise desaturation greater than or equal to 5% is considered abnormal. However, clinical correlation is always necessary as the exact cutoff below which tissue hypoxia ensues has not been defined.[rx][rx][rx]
Arterial Blood Gas
It is a useful tool to evaluate hypoxemia. Aside from the diagnosis of hypoxemia, additional information obtained, such as PCO2, can shed light on the etiology of the process.
Arterial oxygen tension (PaO2): Partial pressure of oxygen is the amount of oxygen dissolved in the plasma. A PaO2 less than 80 mmHg is considered abnormal. However, this should be in line with the clinical situation.
The partial pressure of CO2: It is an indirect measure of exchange of CO2 with the air via the alveoli, its level is related to minute ventilation. PCO2 is elevated in hypoventilation like in obesity hypoventilation, deep sedation, or maybe in the setting of acute hypoxia secondary to tachypnea and washout of CO2.
PaO2:FiO2 ratio (Normal ratio is 300 to 500), if this ratio drops this may indicate a deterioration in gas exchange, this is particularly important in defining ARDS.
Imaging studies of the chest, such as chest x-rays or CT help in identifying the cause of the hypoxia, e.g., pneumonia, pulmonary edema, hyperinflated lungs in COPD, and other conditions. CT chest can give more detailed images that outline the exact pathology, CT angiogram of the chest is of particular importance in detecting the pulmonary embolism. Another modality is the VQ scan which can detect the ventilation-perfusion mismatch, which is helpful in diagnostics of acute or chronic pulmonary embolism. VQ scan can be particularly useful when renal failure or allergy to iodinated contrast increases the risks of CT angiography.
The first step in evaluating the hypoxia is to calculate the A-a gradient of oxygen. This is the difference in the amount of oxygen between the Alveoli “A” and the amount of oxygen in the blood “a.” In other terms, the A-a oxygen gradient = PAO2 – PaO2.
PaO2 can be obtained from the arterial blood gas; however, PAO2 is calculated using the alveolar gas equation:
PAO2 = (FiO2 x [760-47]) – PaCO2/0.8)
760 is the atmospheric pressure at the sea level in mmHg, 47 is the partial pressure of water at a temperature of 37 C, and 0.8 is the steady-state respiratory quotient.
The A-a gradient changes with age, and thus it is corrected for age using this equation; A-a gradient = (age/4+4).
If the A-a gradient is normal, then the cause of hypoxia is low oxygen content in the alveoli, either due to low O2 content in the air (low FiO2, as in the high altitude) or more commonly due to hypoventilation like the central nervous system (CNS) depression, OHS, or obstructed airways as in COPD exacerbation.
If the gradient is height then the cause of hypoxia is either due to a diffusion defect or perfusion defect (VQ mismatch), an alternative explanation is shunting of blood flow around the alveolar circulation, administering 1.0 FiO2 may help differentiate the two, as the oxygenation will improve in VQ mismatch in contrast to cases where shunt physiology is present.
This ratio is another way to measure the degree of hypoxia. A normal PaO2/FiO2 ratio is about 300 to 500 mmHg. The ratio of less than 300 indicates abnormal gas exchange, and values less than 200 mmHg indicate severe hypoxemia. The PaO2/FiO2 ratio is used mostly as a definition of acute respiratory distress syndrome severity.
Evaluation of Chronic Hypoxia
Pulmonary Function Test (PFT)
PFT provides a direct measure of the lung volumes, bronchodilator response, and diffusion capacity, which can help in establishing the diagnosis and guiding the treatment of lung disorders. Aiding the history and physical exam, PFTs can be used to differentiate between the obstructive (bronchial asthma, COPD, upper airway obstruction) versus restrictive lung diseases (interstitial lung diseases, chest wall abnormalities). PFTs play a role in the assessment of airway obstruction severity as well as a response to therapy. One has to keep in mind that PFTs are effort-dependent and require the patient’s ability to cooperate and understand instructions.
Nocturnal (overnight) Trend Oximetry
It provides information about oxyhemoglobin saturation over a period (usually overnight). This test is primarily used to assess adequacy or need for oxygen supplementation at night. Use of overnight trend oximetry as a surrogate for a diagnostic sleep study is possible, however, is discouraged. A formal sleep study should be used whenever possible.
Six-Minute Walk Test
This test provides information on oxyhemoglobin saturation response to exercise as well as the total distance a patient can walk in 6 minutes on a ground level. This information can be used to titrate oxygen supplementation as well as evaluate the response to therapy. The 6-minutes walk test is frequently used in the preoperative pulmonary evaluation, pulmonary hypertension treatment and assessment of supplemental oxygen need with exercise.
Secondary polycythemia can be an indicator of chronic hypoxia.
Treatment of Hypoxia
Maintaining Patent Airways
Ensure patency of the upper airways with good suctioning, maneuvers that prevent occlusion of the throat (head tilt and jaw thrust if necessary), sometimes the placement of an endotracheal tube or tracheostomy is necessary.
In chronic conditions like obesity hyperventilation syndrome, maintaining patent airways can be achieved with positive pressure ventilation like CPAP or BiPAP.
Bronchodilators and aggressive pulmonary hygiene, such as chest physiotherapy, the flutter valve, and incentive spirometry can be used to maintain the patency of the lower airways.
Increase Fraction of the Inspired O2 (FiO2)
This is indicated for low PaO2 less than 60 or SaO2 less than 90, and this can be achieved by increasing the percentage of oxygen in the inspired air that reaches the alveoli.
Use: mild hypoxia (with FiO2 approximately 92%)
Flow rate: up to 6 L per minute
FiO2 delivered: up to 45% (0.45)
Advantage: Easy to use and more convenient to the patient (can be used during eating, drinking, talking)
Disadvantage: Dry nasal mucosa (humidify if the flow is greater than or equal to 4 L per minute), FiO2 being delivered varies greatly. Mouth breathers derive less benefit from using a nasal cannula.
The following formula can be used to approximate the percentage of FiO2; FiO2 = 20% + (4 times oxygen flow liters) For example, oxygen flow 2L/min would deliver approximately FiO2 of 0.3, 6 L per minute would deliver approximately FiO2 of 0.45 (more commonly known as 45%).
Use: Moderate to severe hypoxia, initial treatment
Flow rate: up to 10 L per minute
FiO2 delivered: 35% to 50%
Advantage: provides higher FiO2, no pressures involved, well tolerated by patients
Disadvantage: Dry oral mucosa (needs humidification), the flow must be at least 5 L per minute to flush CO2, not high flow. Also, the mask itself can interfere with activities of daily living.
The device uses a reservoir space, which stores O2 during expiration, making it available as a bolus during the next inspiration. This way the patient gets a higher oxygen delivery without increasing flow.
Flow rate: up to 16 L per minute.
FiO2 = up to 90% (0.9)
Reservoir cannulas are available as mustache configuration (Oxymizer), where the reservoir is located directly beneath the nose, pendant configuration (Oxymizer Pendant) which is connected to a plastic reservoir on the anterior chest
Has a 300 to 500 mL reservoir bag and 2 one-way valves to prevent exhaling into the reservoir
Use: Moderate to severe hypoxia, initial treatment
Flow rate: 6 to 10 L per minute (flow must be sufficient to keep reservoir bag from collapse during inspiration)
FiO2 delivered: 50% to 70%
Advantage: Higher FiO2 can be delivered
Disadvantage: Interferes with activities of daily living
Has a 300 to 500 mL reservoir bag and 2 one-way valves
Use: Moderate to severe acute hypoxia, initial treatment
Flow rate: 10 to 15 (at least 10 L per minute to avoid bag collapse during inspiration)
FiO2 delivered: 85% to 90%
Advantage: even higher FiO2 can be achieved
Disadvantage: Interferes with activities of daily living
Usually, this requires an oxygen blender, humidifier, and heated tubing.
Mask attached an air entrainment valve
Use: Moderate to severe hypoxia, initial treatment
The flow rate and FiO2: (depends on the color). (Blue = 2 to 4 L per minute = 24% O2, White = 4 to 6 L per minute = 28% O2, Yellow = 8 to 10 L per minute = 35% O2, Red = 10 to 12 L per minute = 40% O2, Green = 12 to 15 L per minute = 60% O2)
Advantage: provides the most accurate O2 delivery, high flow
Disadvantage: need to be removed for eating. Less accurate at high flow rates
Does not guarantee the total flow with O2 percentages above 35% in patients with high inspiratory flow demands; the problem with air entrainment systems is that as this is increased, the air to oxygen ratio decreases
High-flow oxygen (HFO) consists of a heated, humidified O2
Flow rate: 10 to 60 L per minute
FiO2 delivered: Up to 100%
Advantages: More convenient, Can deliver up to 100% heated and humidified oxygen at a maximum flow of 60 L
Disadvantages: Fairly large cannula, can be a source of (although usually rather minimal) discomfort
Provides accurate oxygen delivery independent of the patient’s inspiratory flow demands
Positive end-expiratory pressure may be generated
For approximately every 10 liters of flow delivered, about 1 cm/HO of positive pressure is obtained
Positive Pressure Ventilation
It allows for accurate delivery of any necessary FiO2 and includes the following:
It is usually used as the last resort to avoid the intubation
Mainly used in patients with obstructive sleep apnea or in acute pulmonary edema.
Delivers oxygen (or air) under pre-determined high pressure via a tightly fitting face mask.
Positive pressure is continuous, to ensure that the airways are open (split them)
Mainly used in patients with acute Hypercarbia as in patients with COPD exacerbation and ARDS patients.
High positive pressure on inspiration and lower positive pressure on expiration.
Pressure delivery is variable throughout the respiratory cycle, with high positive pressure on inspiration and lower positive pressure on expiration.
Positive pressure ventilator attached to (usually) endotracheal tube.
Allows for accurate delivery of predetermined minute ventilation as well as accurate FiO2 and positive end-expiratory pressure.
Can be used electively during surgery.
Improve the Diffusion of Oxygen through the Alveolar Interstitial Tissue
The overall idea s to treat the underlying cause of respiratory failure:
Diuretics can be used in cases of pulmonary edema.
Steroids in certain cases of interstitial lung disease.
Extracorporeal membrane oxygenation (ECMO) can be used as an ultimate method of increasing oxygenation.
Hypoventilation presents with an elevated PaCO2 with a normal A-a gradient.
Low-inspired oxygen presents with a normal PaC02 plus normal A-a gradient.
Shunting presents with a normal PaC02 and elevated A-a gradient that does not correct with the administration of 100% oxygen.
V/Q mismatch presents with a normal PaC02 and elevated A-a gradient that does correctly with 100% oxygen.
Oxygen supplementation varies between FiO2 of 0.21 and 1.00. A variety of low and high flow devices exist to facilitate this process, each with unique advantages and disadvantages.
The delivery of oxygen depends on two variables:
There are several devices designed to deliver oxygen at different rates and concentrations as described above.
Oxygen toxicity may result if oxygen is delivered at a higher concentration for a long duration of time.
Decreased body temperature decreases metabolic rate, which lowers oxygen consumption and minimizes the adverse effects of tissue hypoxia (especially brain) Therapeutic hypothermia is based on this principle.
Long-term oxygen therapy can reduce mortality, and it is indicated in these patient populations:
Group 1 (Absolute): PaO2 55 mm Hg or SaO2 88%
Group 2 (In the presence of cor pulmonale): PaO2 55 to 59 mm Hg or SaO2 89%, ECG evidence of right atrial enlargement, hematocrit greater than 55%, congestive heart failure