Respiratory Failure is defined as the incapacity of the respiratory system to deliver sufficient oxygen to the bloodstream and. or adequately eliminate carbon dioxide.
There are several pathophysiological mechanisms for the production of respiratory failure, which can divide into type I or hypoxemic respiratory failure and type II or hypercapnic respiratory failure.
Patients with respiratory failure may present with cough, dyspnea, wheezing, sputum production, and hemoptysis, along with signs and symptoms pointing to other organ systems, such as chest pain, fever, weight loss, or muscle weakness.
The gold standard for diagnosis and classification of respiratory failure is the Acid-Base and Gases panel. There are other diagnostic methods used to assess a patient with respiratory failure, which are used in accordance with the suspected underlying etiology, that also dictate the appropriate management.
Definition of Respiratory Failure
Respiratory failure is a serious and life-threatening condition characterized by the incapacity of the respiratory system to deliver sufficient oxygen to the bloodstream and/or adequately eliminate carbon dioxide from the body.
Classification of Respiratory Failure
There are two types of respiratory failure:
- Hypoxemic Respiratory Failure (Type 1) Hypoxemic respiratory failure: the main problem is inadequate blood oxygenation, which leads to hypoxemia with normocapnia or hypocapnia. (1)
- Hypercapnic Respiratory Failure (Type 2) Hypercapnic respiratory failure: the main issue is an excess of carbon dioxide in the blood, which results in hypercapnia with normoxia or hypoxemia and acid-base balance abnormalities. (1, 2)
However, it is possible for both forms of respiratory failure to occur simultaneously. This is the case in patients with chronic obstructive pulmonary disease (COPD) with carbon dioxide build-up, or in those experiencing severe pulmonary edema or an asthmatic crisis, where they may initially experience hypoxemia, but as the disease continues or worsens, hypercapnia may also become evident. (1, 3-5)
Respiratory failure can be further classified as acute or chronic, depending on the levels of bicarbonate (HCO3) in the blood. During respiratory acidosis, the renal response to PaCO2 is to increase the absorption of HCO3 slowly; therefore, the extent of HCO3 absorption in chronic respiratory acidosis is greater than it is during acute respiratory acidosis. (6)
Pathophysiology of Respiratory Failure
Hypoxemic Respiratory Failure (Type 1)
Hypoxemic respiratory failure, also called type 1 respiratory failure, is characterized by a low partial pressure of arterial oxygen in the blood (PaO2) < 60 mmHg, while the partial pressure of carbon dioxide (PaCO2) is normal or low. (1)
Causes of hypoxemic respiratory failure include:
- Ventilation-perfusion mismatch
Ventilation-perfusion mismatch occurs when there is an imbalance between the amount of air that goes into the lungs and the amount of blood that flows to the lungs. It can be caused by conditions such as pulmonary embolism, pneumonia, and acute respiratory distress syndrome (ARDS). (3)
- Diffusion impairment
Diffusion impairment happens when the oxygen is not able to cross properly from the alveoli into the bloodstream. It can be caused by conditions like pulmonary fibrosis and interstitial lung disease. (3)
- Righ-to-left shunt
In this case, the ventilation/perfusion ratio becomes zero. The blood bypasses the lungs and does not become oxygenated. It can be caused by conditions such as congenital heart defects, severe pulmonary edema, severe pneumonia, complete atelectasis, and pulmonary hypertension. (7, 8)
- Alveolar hypoventilation
Alveolar hypoventilation occurs when there is a decrease in the amount of air reaching the alveoli in the lungs, which impairs the exchange of oxygen and carbon dioxide. It can be caused due to obstructive sleep apnea (OSA), COPD, obesity, neuromuscular disorders, alcohol intake, and some medications like opioids or sedatives. (1, 3, 7, 9, 10)
- Low atmospheric pressure/fraction of inspired oxygen
This happens at high altitudes, where the air pressure and oxygen levels are lower, making it difficult for the respiratory system to obtain enough oxygen.
Hypercapnic Respiratory Failure (Type 2)
Hypercapnic respiratory failure, also called type 2 respiratory failure, is characterized by a high partial pressure of carbon dioxide (PaCO2) > 45 mmHg along with a pH < 7.35, while the partial pressure of arterial oxygen (PaO2) is normal or low. (1, 2)
Decreased alveolar ventilation is the most common cause of hypercapnic respiratory failure, being increased carbon dioxide production a very rare cause.
Causes of hypercapnic respiratory failure include:
- Respiratory pump failure
The inability to ventilate can arise from failure in any of the components that comprise the respiratory pump, which includes the chest wall, respiratory muscles, pulmonary parenchyma, and the central and peripheral nervous systems. (3, 6, 11)
In this case, hypoventilation can result from a decrease in the central drive caused by sedatives (such as alcohol, benzodiazepines, and opiates) or diseases of the central nervous system, including encephalitis, stroke, and tumors. (1, 6)
Additionally, respiratory pump failure can also happen due to other conditions that alter neural and neuromuscular transmission, such as Guillain-Barre syndrome, amyotrophic lateral sclerosis, tetanus, botulism, myasthenia graves, spinal cord injury (SCI), organophosphate poisoning, poliomyelitis, and transverse myelitis. (1, 6, 12)
Various disorders of the pleura and chest wall, as well as a wide number of respiratory muscle abnormalities, can hinder the respiratory pump function. Such conditions include muscular dystrophy, kyphoscoliosis, flail chest, diffuse atrophy, hyperinflation, large pleural effusions, thoracoplasty, ruptured diaphragm, and obesity. (1, 3)
Lastly, hypoventilation can also result from conditions that increase the ventilation/perfusion ratio, leading to dead space ventilation exceeding 50% of total ventilation. Such conditions include bronchitis, emphysema, bronchiectasis, pulmonary embolism, and acute respiratory distress syndrome. (3, 13)
- Increased dead space
Dead space happens when any area of the lung is unable to exchange gas, either for anatomical or physiological reasons.
In patients with COPD, the main mechanism for hypercapnia development is high alveolar ventilation and the corresponding ventilation-perfusion mismatch. (11,13,14)
- Increased carbon dioxide production
Increased carbon dioxide production may occur due to thyrotoxicosis, sepsis, fever, hyperalimentation, fever, and exercise. When there is a failure in the compensatory increase in minute ventilation mechanism, excessive carbon dioxide production becomes pathologic. (3, 7, 11)
Signs and Symptoms of Respiratory Failure
Typical symptoms of respiratory failure include dyspnea, persistent cough, wheezing, sputum production, and hemoptysis. However, it is imperative also to consider symptoms from other organ systems, such as chest pain, hyporexia, heartburn, fever, and significant weight loss. (3)
Suspecting COVID-19 infection and associated respiratory failure is crucial in patients with loss of smell and/or exposure to sick people, especially for those at high risk, such as the elderly, morbidly obese, immunocompromised, and those patients taking immunosuppressants. (11, 15, 16)
For patients already diagnosed with airway disease, it is imperative to assess recent exposure to environmental triggers, recent steroid use, and inquire about inhaler compliance and technique. For patients with chronic cough and diagnosed hypertension, the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers should be investigated. (3,5)
Furthermore, when assessing the risk for respiratory failure, it is imperative to inquire about the patient’s smoking history, including exposure to second-hand smoke, marijuana, e-cigarettes, and vaping, as well as investigate the patient’s habits and social history because alcohol use and sexually transmitted diseases may lead to an immunocompromised immune system, which in turn makes patients more susceptible to certain infections; while a sedentary lifestyle increases the risk of pulmonary embolism. (3, 5, 17)
It is also necessary to perform an occupational history to help identify work-related lung diseases, such as hypersensitivity pneumonitis and pneumoconiosis. (3)
Physical Examination in the Patient with Respiratory Failure
Signs of respiratory failure are varied and can be noted in several systems. At general inspection, the patient may appear cachectic, have conversational dyspnea, purse-lipped breathing, respiratory distress, diaphoresis, and fever. (1, 3, 11)
Central cyanosis, jugular venous distention, and tracheal deviation may be noted upon close inspection of the patient’s head and neck. (3)
During the evaluation of the thorax, common findings may include bradypnea or tachypnea, asymmetrical or reduced chest expansion, kyphoscoliosis, pectus carinatum or excavatum, dullness or hyper-resonance to percussion, decreased breath sounds, vocal resonance, bronchial breath sounds, loud P2, stridor, crackles, rhonchi, pleural rub, wheezes, whispering pectoriloquy, Cheyne-Stoke breathing, Kussmaul breathing, and paradoxical breathing. (1, 3)
Other common findings may include hepatomegaly, asterixis, tremor, peripheral cyanosis, digital clubbing, tobacco staining, and edema in the lower extremities.
Diagnosis of Respiratory Failure
The diagnosis of respiratory failure is typically made based on clinical presentation and arterial blood gas analysis. However, other appropriate diagnostic tests to further investigate the cause of respiratory failure are also warranted.
Arterial Blood Gas (ABG)
This test is the gold standard for diagnosing respiratory failure. An ABG test includes information about pH, PaO2, PaCO2, and HCO3.
However, since the HCO3 values from this test are calculated, a measured HCO3 obtained from a basic metabolic panel is preferred to perform an ABG analysis accurately. (18,19)
Pulse oximetry is a non-invasive test that relies on spectrophotometry to measure arterial oxygenation through the analysis of pulsatile blood. However, this is not a completely accurate method, and certain factors can affect the reading, including the use of nail polish, poor circulation, skin temperature, skin thickness and pigmentation, and current tobacco use. (20,21)
Nevertheless, pulse oximetry constitutes a useful tool to help diagnose and monitor patients with respiratory failure.
Capnometry is the measurement of exhaled carbon dioxide, it can be either qualitative (using a pH-sensitive indicator) or quantitative (using an infrared method). (22, 23)
Under normal conditions, the end-tidal partial pressure of carbon dioxide (PETCO2) at the end of exhalation is similar to the PaCO2 in the arterial blood. The PaCO2 is usually slightly higher than the PETCO2, by around 2 to 3 mmHg. However, if gas exchange is compromised, as in a pathological state, the difference between PaCO2 and PETCO2 can exceed 3 mmHg. (19, 23)
Different imaging techniques can be used to assess respiratory failure, including radiography, computed tomography, magnetic resonance, ultrasonography, nuclear medicine, and angiography. (24)
Among these, the bedside lung ultrasound in emergency (BLUE)-protocol is considered the bedside gold standard for quickly diagnosing acute respiratory failure. The BLUE protocol employs a set of standardized thoracic locations (BLUE points) and ten ultrasonographic signs or profiles, which provide reliable and reproducible results. (24, 25)
Further testing, such as bronchoscopy, echocardiography, electrocardiography, nocturnal polysomnography, and pulmonary function tests, may be employed to further investigate the causes of respiratory failure. (12)
Treatment of Respiratory Failure
The initial management of patients with respiratory failure consists of ABC (airway, breathing, and circulation) assessment, and treatment should be aimed at improving oxygenation and addressing the underlying cause.
The goal is to improve tissue oxygenation, characterized by a PaO2 of 60 mm Hg or arterial oxygen saturation (SaO2) of about 90%. In the absence of hypoxemia, hypercapnia is usually well tolerated and is unlikely to impair organ function unless it is accompanied by severe acidosis. (6)
The specific treatment of respiratory failure is a complex and multidisciplinary process that requires prompt and tailored interventions based on the underlying cause, the severity of the condition, and the patient’s overall health status. In general, treatment options may include:
Controlled oxygen therapy is the first-line treatment and should be used to achieve optimal saturation levels and help decrease the workload on the respiratory system. It must be adjusted to be delivered at a higher concentration or under higher pressure to improve oxygenation and can be administered via nasal cannula, face mask, or mechanical ventilation. Extracorporeal membrane oxygenation (ECMO) may be warranted in refractory cases. (26-28)
The following are common indications for mechanical ventilation:
- Tachypnea with a respiratory rate greater than 30 breaths per minute.
- Altered consciousness or coma.
- Apnea with respiratory arrest.
- Hemodynamic instability.
- Respiratory muscle fatigue.
- Failure of supplemental oxygen to increase PaO2 to 55 to 60 mmHg.
- Hypercapnia with arterial pH less than 7.25.
Although noninvasive ventilation (NIV) is typically preferred. The decision to use invasive or noninvasive ventilatory support relies on the clinical situation, the underlying cause, and the severity and chronicity of the condition. (4, 27-31)
Depending on the underlying cause, drugs like bronchodilators, corticosteroids, and diuretics may need to be used to help improve the patient’s respiratory status. (4,31)
Other supportive measures, such as positioning, suctioning, and hydration, may also be necessary to optimize respiratory function.
Treatment of the underlying cause
The main goal of controlling respiratory failure is the treatment of underlying causes to prevent further complications and improve outcomes for the patient. For instance, using anticoagulant therapy in case of pulmonary embolism or antibiotics to treat pneumonia. (14)
Complications of Respiratory Failure
Acute respiratory failure can lead to both pulmonary and extrapulmonary complications.
Pulmonary complications may involve pneumothorax, pulmonary embolism, cor pulmonale, bronchopleural fistula, nosocomial pneumonia, pulmonary hypertension, and pulmonary fibrosis.
Meanwhile, extrapulmonary complications may include infections, pneumoperitoneum, acid-base imbalances, renal failure, hepatic failure, reduced cardiac output, gastrointestinal bleeding, ileus, thrombocytopenia, increased intracranial pressure, malnutrition, and multiorgan dysfunction syndrome. (32)
The author does not report any conflict of interest.
This information is for educational purposes and is not intended to treat disease or supplant professional medical judgment. Physicians should follow local policy regarding the diagnosis and management of medical conditions.
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Krystie Linares is a physician with 10 years of experience as a family practitioner and occupational health specialist. She has collaborated with several companies, startups, and individuals, by doing research, developing educational content, managing medical libraries, and working as a database curator.