Which of the following mental status changes may occur when a client with pneumonia is first experiencing hypoxia?

The respiratory system provides oxygen to and removes carbon dioxide from the body; however, the inability to perform either or both of these tasks results in respiratory failure. Type 1 respiratory failure occurs when the respiratory system cannot adequately provide oxygen to the body, leading to hypoxemia, and can be caused by alveolar hypoventilation, low atmospheric pressure/fraction of inspired oxygen, diffusion defect, ventilation/perfusion mismatch, and right-to-left shunt. Type 2 respiratory failure occurs when the respiratory system is unable to adequately remove carbon dioxide from the body, leading to hypercapnia, and can be caused by respiratory pump failure and increased carbon dioxide production. This activity reviews the evaluation and management of respiratory failure and highlights the role of the healthcare team in evaluating and treating patients with this condition.

Objectives:

• Review the etiology of respiratory failure.

• Explain the pathophysiology of respiratory failure.

• Review the physical exam findings associated with respiratory failure.

• Summarize the treatment considerations for patients with respiratory failure.

The respiratory system allows gas exchange between the environment and the body, facilitating the process of aerobic metabolism. Specifically, the respiratory system provides oxygen and removes carbon dioxide from the body. The inability of the respiratory system to perform either or both of these tasks results in respiratory failure. Type 1 respiratory failure occurs when the respiratory system cannot adequately provide oxygen to the body, leading to hypoxemia. Type 2 respiratory failure occurs when the respiratory system is unable to sufficiently remove carbon dioxide from the body, leading to hypercapnia. Respiratory failure can further be classified based on chronicity (i.e., acute, chronic, and acute on chronic). A thorough understanding of respiratory failure is crucial to managing this disorder.

Respiratory failure can occur if there is an abnormality with any component of the respiratory system. Components of the respiratory system include the upper and lower respiratory tracts, the central and peripheral nervous systems, in addition to the chest wall and muscles of respiration.[1] The pathophysiology section of this article will review specific etiologies of respiratory failure.

Respiratory failure is a syndrome caused by a multitude of pathological states; therefore, the epidemiology of this disease process is difficult to ascertain. In 2017 in the United States of America, however, the incidence of respiratory failure was found to be 1,275 cases per 100,000 adults. The case definition used in this study included all diagnosis codes that included respiratory failure as a component.[2]

T ype 1 respiratory failure:

The distinguishing characteristic of Type 1 respiratory failure is a partial pressure of oxygen (PaO2) < 60 mmHg with a normal or decreased partial pressure of carbon dioxide (PaCO2); Depending on the cause of hypoxemia, the alveolar-arterial (A-a) gradient may be normal or increased. Formulas of the A-a gradient and alveolar gas equation are provided below, as these concepts are helpful in the understanding of the pathophysiology of respiratory failure.

     A-a gradient:

• A-a gradient = PAO2 - PaO2, where

  • PAO2 = Alveolar partial pressure of oxygen

  • PaO2 = Arterial partial pressure of oxygen

     Alveolar gas equation:

• PAO2 = FiO2 (Patm - Pwater) - PaCO2/0.8, where

  • PAO2 = Alveolar partial pressure of oxygen

  • FiO2 = Fraction of inspired oxygen

  • Patm = Atmospheric pressure

  • Pwater = Partial pressure of water at body temperature

  • PaCO2 = Partial pressure of arterial carbon dioxide

 Etiologies of Type 1 respiratory failure with normal A-a gradients include:

• Alveolar hypoventilation: Alveolar hypoventilation increases the arterial partial pressure of carbon dioxide (PaCO2). The alveolar gas equation demonstrates that an increase in PaCO2 causes a decrease in the alveolar partial pressure of oxygen (PAO2). In this situation, the A-a gradient is normal, as the PAO2 and PaO2 decrease in equal magnitudes. When severe, alveolar hypoventilation may progress to Type 2 respiratory failure.[3] Etiologies of alveolar hypoventilation include:

  • Central nervous system depression (i.e., central sleep apnea, coma, hypothyroidism, obesity hypoventilation syndrome, and toxic metabolic encephalopathy)

  • Decreased chest wall compliance (i.e., flail chest and kyphoscoliosis)

  • Neuromuscular disease (i.e., amyotrophic lateral sclerosis, Guillain-Barré syndrome, and myasthenia gravis)

• Low atmospheric pressure/fraction of inspired oxygen: The alveolar gas equation demonstrates that the alveolar partial pressure of oxygen (PAO2) decreases with low atmospheric pressures (Patm) and with low levels of inspired oxygen (FiO2). In either situation, the A-a gradient remains normal, and the PaCO2 is decreased, given the response to hypoxia is hyperventilation. Clinically, this cause of respiratory failure only occurs at high altitudes.[4]

 Etiologies of Type 1 respiratory failure with increased A-a gradients include:

• Diffusion defect: Gas exchange between the environment and the body occurs at the alveolar-capillary interface. Structural changes to the alveolar component of the alveolar-capillary interface, such as decreased surface area or increased thickness, may result in diffusion defects across the membrane. Additionally, reducing pulmonary capillary transit time through the alveolar-capillary interface may result in diffusion defects across the membrane. In either situation, hypercapnia does not occur, as carbon dioxide diffuses more readily across the alveolar-capillary membrane than oxygen.[5] Etiologies of diffusion defects include:

  • Emphysema

  • Exercise

  • Interstitial lung disease

• Ventilation/perfusion (V/Q) mismatch: The alveolar gas composition depends on the balance of alveolar ventilation and pulmonary capillary blood flow that occurs at the alveolar-capillary interface. When perfectly matched, the V/Q ratio is equal to one. When ventilation is excessive to perfusion, the V/Q ratio is greater than one; Dead space ventilation occurs when the V/Q ratio reaches infinity. When perfusion is excessive to ventilation, the V/Q ratio is less than one; Shunt occurs when the V/Q ratio reaches zero. In healthy subjects, however, the V/Q ratio is approximately 0.8, as the balance between ventilation and perfusion differs from the apex to the base of the lungs. V/Q mismatch is the most common cause of Type 1 respiratory failure.[6] Etiologies of V/Q mismatch include:

  • Acute respiratory distress syndrome

  • Atelectasis

  • Chronic obstructive pulmonary disease

  • Congestive heart failure

  • Pneumonia

  • Pulmonary embolism

• Right-to-left shunt: As discussed above, shunt occurs when the V/Q ratio reaches zero. The absence of gas exchange at the alveolar-capillary interface represents a true shunt and is analogous to intracardiac right-to-left shunting seen in atrial septal defect and patent foramen ovale. Unlike V/Q mismatch, true shunt does not improve with supplemental oxygen therapy.[7] Etiologies of pulmonary right-to-left shunts include:

  • Arteriovenous malformation

  • Complete atelectasis

  • Severe pneumonia

  • Severe pulmonary edema

Type 2 respiratory failure:

The distinguishing characteristic of Type 2 respiratory failure is a partial pressure of carbon dioxide (PaCO2) > 45 mmHg with a pH < 7.35; Depending on the cause of respiratory failure, the partial pressure of oxygen (PaO2) may be normal or decreased. The inability to ventilate can result from respiratory pump failure or increased carbon dioxide (CO2) production. While respiratory pump failure is more common than increased carbon dioxide (CO2) production, both etiologies are discussed below:

• Respiratory pump failure: The respiratory pump is comprised of the chest wall, the pulmonary parenchyma, the muscles of respiration, as well as the central and peripheral nervous systems. The inability to ventilate can occur if any of the aforementioned components of the respiratory pump fails.

• • Altered neural and neuromuscular transmission: Conditions such as amyotrophic lateral sclerosis, botulism, Guillain-Barre syndrome, myasthenia graves, organophosphate poisoning, poliomyelitis, spinal cord trauma, tetanus, and transverse myelitis may impair the function of the respiratory pump, resulting in hypoventilation.

  • Chest wall and pleural disorders: Flail chest, kyphoscoliosis, hyperinflation, large pleural effusions, obesity, and thoracoplasty may impair the function of the respiratory pump, resulting in hypoventilation.

  • Dead space ventilation: Conditions that increase the V/Q ratio, such as acute respiratory distress syndrome, bronchitis, bronchiectasis, emphysema, and pulmonary embolism, can result in hypoventilation. Hypoventilation typically occurs once dead space ventilation exceeds 50% of total ventilation.

  • Decreased central dive: Sedatives (i.e., alcohol, benzodiazepines, and opiates) and diseases of the central nervous system (i.e., encephalitis, stroke, tumor, and trauma) may impair the respiratory drive, resulting in hypoventilation.

  • Muscle abnormalities: Diaphragmatic paralysis, diffuse atrophy, muscular dystrophy, and ruptured diaphragm may impair the function of the respiratory pump, resulting in hypoventilation.

• Increased carbon dioxide (CO2) production: Carbon dioxide (CO2) is a by-product of oxidative metabolism, and increased carbon dioxide (CO2) production may occur due to fever, exercise, hyperalimentation, sepsis, and thyrotoxicosis. Increased carbon dioxide (CO2) production becomes pathologic if the compensatory increase in minute ventilation mechanism fails.[8] 

Respiratory failure is a syndrome with a myriad of etiologies; therefore, a thorough history and physical examination are required to narrow the differential diagnosis.

History: 

Patients typically present with respiratory symptoms (i.e., dyspnea, cough, hemoptysis, sputum production, and wheezing); however, symptoms from other organ systems (i.e., chest pain, decreased appetite, heartburn, and significant weight loss) may be important.

For patients already diagnosed with airway disease, it is important to assess inhaler compliance and technique, recent steroid use, as well as exposure to environmental triggers. For patients with hypertension and chronic cough, the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers should be investigated.

Social history is also crucial when considering respiratory failure. Alcohol use and sexually transmitted diseases may lead to an immunocompromised state, making patients more susceptible to certain infections, while a sedentary lifestyle may increase the risk of pulmonary embolism. Hobbies such as diving and flying may have implications when considering the diagnosis of pneumothorax. Most importantly, a patient's smoking history should be investigated, including exposure to second-hand smoke.

Finally, an occupational history may be helpful when considering work-related lung disease (i.e., hypersensitivity pneumonitis and pneumoconiosis), while a family history may be beneficial when considering atopic, genetic (i.e., alpha-1-antitrypsin deficiency and cystic fibrosis), and infectious diseases (i.e., tuberculosis).[9]

Physical examination: 

Signs of respiratory failure may be present throughout the body. Physical examination findings by region appear below:

• General inspection: Accessory muscle use, altered mental status, cachectic, conversational dyspnea, diaphoresis, fever, respiratory distress (i.e., at rest or with exertion), obesity, and purse-lipped breathing

• Head: Cushingoid appearance, central cyanosis, Horner's syndrome, and pale conjunctiva

• Neck: Jugular venous distention, lymphadenopathy, and tracheal deviation

• Chest/thorax: Asymmetrical chest expansion, bradypnea, bronchial breath sounds, Cheyne-Stoke breathing, crackles, decreased breath sounds, dullness to percussion, hyper-resonance to percussion, Kussmaul breathing, kyphoscoliosis, loud P2, paradoxical breathing, pectus carinatum, pectus excavatum, pleural rub, reduced chest expansion, rhonchi, stridor, tachypnea, tactile vocal fremitus, vesicular breath sounds, vocal resonance, wheezes, and whispering pectoriloquy

• Abdomen: Hepatomegaly

• Upper extremities: Asterixis, digital clubbing, peripheral cyanosis, tobacco staining, and tremor

• Lower extremities: Edema, peripheral cyanosis, and unilateral swelling[10][11][12]

 As discussed above, respiratory failure is a syndrome caused by a multitude of pathological states. As such, a single algorithm for evaluating respiratory failure does not exist. Appropriate diagnostic studies may include laboratory assays (i.e., complete blood count with differential, comprehensive metabolic panel with magnesium/phosphorous, procalcitonin, troponin, and thyroid-stimulating hormone), infectious workup (i.e., blood cultures, sputum cultures, respiratory pathogen panel test, and urinary antigen test), and 12-lead electrocardiography. Evaluation of respiratory failure with arterial blood gas, capnometry, radiography, pulse oximetry, and ultrasonography are discussed below.

Arterial blood gas:

 Arterial blood gas (ABG) is the gold standard for diagnosing respiratory failure. At a minimum, the information obtained from an ABG includes pH, partial pressure of arterial oxygen (PaO2), partial pressure of arterial carbon dioxide (PaCO2), and serum bicarbonate (HCO3). It should be noted that the HCO3 obtained from an ABG is a calculated value and may therefore be inaccurate. Analysis of an ABG should instead be performed using a measured HCO3 obtained from a basic metabolic panel.

Oxygenation is assessed through the interpretation of the PaO2. Hypoxemia is defined as a PaO2 less than 60 mmHg. Ventilation is assessed through the interpretation of the PaCO2. Hypercapnia is defined as a PaCO2 greater than 45 mmHg.

Information from the ABG can also be used to differentiate acute from chronic respiratory failure by evaluating the renal response to PaCO2. In respiratory acidosis, the kidneys respond by increasing the absorption of HCO3 in the proximal convoluted tube. As this is a slow process, the magnitude of HCO3 absorption in acute respiratory acidosis is less than the magnitude of HCO3 absorption in chronic respiratory acidosis. This difference allows for the distinction between the chronicity in acute and chronic respiratory failure.[13]

Capnometry:

Capnometry, the measurement of carbon dioxide in exhaled gas, may be qualitative or quantitative. Colorimetric capnometry is a qualitative measure of carbon dioxide in exhaled gas that relies on the color change of a pH-sensitive indicator. Infrared capnometry is a quantitative measure of carbon dioxide in exhaled gas that relies on measuring the partial pressure of carbon dioxide (pCO2). Quantitative capnometry provides more information than qualitative capnometry.[14]

In the non-pathological state, the partial pressure of carbon dioxide at the end of expiration, or end-tidal pCO2 (PETCO2), approximates the partial pressure of carbon dioxide in the arterial blood (PaCO2). The PaCO2 is typically 2 to 3 mmHg greater than the PETCO2. In the pathological state, where gas exchange is impaired, the difference between the PaCO2 and PETCO2 becomes greater than 3 mmHg due to increased dead space ventilation.[15]

Values obtained from quantitative capnometry can be plotted graphically and displayed as waveform capnography. Analysis of these waveforms allows for detecting pathological states (i.e., apnea, bronchospasm, hyperventilation, and hypoventilation).[16] This topic, however, is beyond the scope of this article.

Radiography:

Various imaging modalities are available for the evaluation of respiratory failure. Such options include plain films, computed tomography, magnetic resonance, nuclear medicine, angiography, and ultrasonography.[17] This topic, however, is beyond the scope of this article. 

Pulse oximetry:

Pulse oximetry relies on spectrophotometry, the process of identifying the composition of a substance via measurement of the absorption of specific wavelengths of light transmitted through the substance in question. The composition and structural configuration of hemoglobin are dependent upon molecular oxygen. In the tense state, oxygenated hemoglobin has a lower affinity for oxygen. In the relaxed state, deoxygenated hemoglobin has a higher affinity for oxygen. Pulse oximetry takes advantage of the conformational states of the hemoglobin molecule as deoxygenated hemoglobin absorbs light at wavelengths of 660 nm and oxygenated hemoglobin absorbs light at wavelengths of 940 nm. Measurement of arterial oxygenation is ensured through the analysis of pulsatile blood. Proprietary algorithms allow for the conversion of light absorption to the fraction of hemoglobin saturated with oxygen, known as oxygen saturation (SpO2). This non-invasive modality is greatly useful in diagnosing and managing respiratory failure.[18]

Ultrasonography:

The bedside lung ultrasound in emergency (BLUE)-protocol is the bedside gold standard for the immediate diagnosis of acute respiratory failure. The protocol, which allows for reproducible analysis, relies on standardized thoracic locations (BLUE points) and 10 ultrasonographic signs or profiles. The BLUE protocol is performed by analyzing the ultrasonographic profiles obtained at each of the three BLUE points on each side of the body. The standardized BLUE points are known as the Upper BLUE point, the Lower BLUE point, and the postero-lateral alveolar and/or pleural syndrome (PLAPS)-point. In total, there are six BLUE points. The theory behind and the application of the BLUE protocol are beyond the scope of this article; however, the ten ultrasonographic profiles are grouped with their corresponding clinical states below:

• Normal lung surface: Bat sign, lung sliding, and A-lines

• Interstitial syndrome: Lung rockets

• Lung consolidations: Fractal and tissue-like signs

• Pleural effusions: Quad and sinusoid sign

• Pneumothorax: Stratosphere sign and the lung point[19]

Bronchoscopy, echocardiography, nocturnal polysomnography, and pulmonary function tests may also be included in evaluating respiratory failure. Pulmonary consultation is warranted if the aforementioned diagnostic studies are required.

Treatment of respiratory failure should be directed towards the underlying cause while providing support with oxygenation and ventilation, if necessary. The treatment and management of the various etiologies of respiratory failure are beyond the scope of this article; however, the following StatPearls articles provide excellent insight into available therapies: Oxygen administration, Noninvasive ventilation, and Mechanical ventilation. 

The differential diagnosis for respiratory failure is broad and includes, but is not limited to, the following:

• Acute respiratory distress syndrome

• Aspiration pneumonia

• Aspiration pneumonitis

• Asthma

• Atelectasis

• Bacterial pneumonia

• Bronchitis

• Cardiogenic pulmonary edema

• Cardiogenic shock

• Central sleep apnea

• Cervical cord injury

• Cor pulmonale

• Diaphragmatic paralysis

• Distributive shock

• Drug overdose

• Emphysema

• Fat embolism

• Granulomatous lung disease

• Idiopathic pulmonary arterial hypertension

• Kyphoscoliosis

• Myxedema

• Myocardial infarction

• Neurogenic pulmonary edema

• Obesity hypoventilation syndrome

• Obstructive shock

• Obstructive sleep apnea

• Pleural effusion

• Pneumothorax

• Pulmonary fibrosis

• Restrictive lung disease

• Pneumoconiosis

• Primary muscle disorders

• Pulmonary arterial hypertension

• Pulmonary embolism

• Viral pneumonia

 Respiratory failure is a syndrome caused by a multitude of pathological states; therefore, the prognosis of this disease process is difficult to ascertain. In 2017 in the United States of America, however, the in-hospital respiratory failure mortality rate was 12%. The case definition used in this study included all diagnosis codes, which included respiratory failure.[2] In-hospital mortality rates for patients requiring intubation with mechanical ventilation for asthma exacerbation, acute exacerbation of chronic obstructive pulmonary disease, and pneumonia were found to be 9.8%, 38.3%, and 48.4%, respectively.[20][21][22] Lastly, the in-hospital mortality rate for acute respiratory distress syndrome was found to be 44.3%.[23]

 Respiratory failure is associated with both pulmonary and extrapulmonary complications, especially in the acute setting. Pulmonary complications include bronchopleural fistula, nosocomial pneumonia, pneumothorax, pulmonary embolism, and pulmonary fibrosis while extrapulmonary complications include acid-base disturbances, decreased cardiac output, gastrointestinal hemorrhage, hepatic failure, ileus, infection, increased intracranial pressure, malnutrition, pneumoperitoneum, renal failure, and thrombocytopenia. Clinicians should be aware of the conditions mentioned earlier and be prepared to offer prophylactic therapy or proper treatment for such complications when applicable.[24][25]

Depending on the severity of the respiratory failure, consultation with a Pulmonary specialist may be warranted in the patient's care.

While patients should be educated on the symptoms of respiratory failure, they should also be aware of the importance of device and medication compliance as well as modifiable risk factors and how they relate to disease prevention. For instance, the following strategies are efficacious in preventing acute exacerbations of chronic obstructive pulmonary disease: Adherence to pharmacological therapy, pulmonary rehabilitation, smoking cessation, and vaccination (i.e., influenza and pneumococcal).[26] Unfortunately, not all causes of respiratory failure are preventable. Patients should seek prompt evaluation and treatment if they become symptomatic.

Diagnosing the underlying cause of respiratory failure and its treatment is challenging as this syndrome can result from numerous pulmonary and extrapulmonary causes. As such, consultation with other specialties (i.e., cardiology and neurology) may be mandatory. Moreover, discussing radiographic findings with a radiologist can sometimes be necessary. Additionally, complications from respiratory failure may be due to improper patient positioning and poor adherence to infection control policies. Fortunately, nurses are vital members of the interprofessional healthcare team, assuring appropriate patient positioning. Nursing is also responsible for feeding, monitoring, and suctioning the patient. Since patients with respiratory failure may require multiple medications, the pharmacist is instrumental in ensuring safe medication administration. Finally, respiratory therapists also care for a patient with respiratory failure (i.e., administration of oxygen and chest physiotherapy). All interprofessional team members must engage in meticulous documentation and report any changes in patient status to the appropriate team members for possible corrective action. This interprofessional team works to improve patient care and outcomes through collaborative activity and open communication. [Level 5]

Review Questions

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