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Respiratory Failure

Respiratory Failure

Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. A number of etiologies exist, including diseases of the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy, cardiovascular, and nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with respiratory failure may present with dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, tachypnea Tachypnea Increased respiratory rate. Pulmonary Examination, and altered mental status Altered Mental Status Sepsis in Children. The diagnosis is made through measurement of arterial blood gas Arterial blood gas Respiratory Alkalosis and supplemented with laboratory and imaging studies to elicit an etiology. Management involves treating the underlying cause, supplemental oxygen administration, and mechanical ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing for severe cases.

Last updated: 17 May, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Contents

Definition and Classification

Definition

Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing.

Classification

Respiratory failure may be classified based on: 

The time course:

  • Acute respiratory failure: occurs within minutes to hours of an inciting incident.
  • Chronic respiratory failure: 
    • Occurs over months to years 
    • Often due to a chronic lung disease process

The underlying issue:

  • Hypoxemic respiratory failure ( type 1 Type 1 Spinal Muscular Atrophy): 
    • Most common form of respiratory failure
    • Results from a ↓ ability to oxygenate the blood
  • Hypercapnic respiratory failure ( type 2 Type 2 Spinal Muscular Atrophy):
    • Results from a ↓ ability to eliminate carbon dioxide (CO₂) 
    • ↓ pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance of the blood → respiratory acidosis Respiratory acidosis The respiratory system is responsible for eliminating the volatile acid carbon dioxide (CO2), which is produced via aerobic metabolism. In the setting of hypoventilation, this acid load is not adequately blown off, and respiratory acidosis occurs. Renal compensation occurs after 3-5 days, as the kidneys attempt to increase the serum bicarbonate levels. Respiratory Acidosis

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Respiratory Failures: Introduction

Etiology

Etiology of hypoxemic respiratory failure

  • Right-to-left shunt:
    • Pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema (cardiogenic and noncardiogenic)
    • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
    • Pulmonary hemorrhage
    • Aspiration
    • Atelectasis Atelectasis Atelectasis is the partial or complete collapse of a part of the lung. Atelectasis is almost always a secondary phenomenon from conditions causing bronchial obstruction, external compression, surfactant deficiency, or scarring. Atelectasis
    • ARDS ARDS Acute respiratory distress syndrome is characterized by the sudden onset of hypoxemia and bilateral pulmonary edema without cardiac failure. Sepsis is the most common cause of ARDS. The underlying mechanism and histologic correlate is diffuse alveolar damage (DAD). Acute Respiratory Distress Syndrome (ARDS)
  • V/Q mismatch:
    • Pulmonary embolism Pulmonary Embolism Pulmonary embolism (PE) is a potentially fatal condition that occurs as a result of intraluminal obstruction of the main pulmonary artery or its branches. The causative factors include thrombi, air, amniotic fluid, and fat. In PE, gas exchange is impaired due to the decreased return of deoxygenated blood to the lungs. Pulmonary Embolism
    • Asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma
    • Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD) ( COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD))
    • Cystic fibrosis Cystic fibrosis Cystic fibrosis is an autosomal recessive disorder caused by mutations in the gene CFTR. The mutations lead to dysfunction of chloride channels, which results in hyperviscous mucus and the accumulation of secretions. Common presentations include chronic respiratory infections, failure to thrive, and pancreatic insufficiency. Cystic Fibrosis
    • Interstitial lung disease
    • Pulmonary hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Low inspired oxygen: high altitude
  • Hypoventilation:
    • Sedative medications
    • Neuromuscular conditions

Etiology of hypercapnic respiratory failure

  • Diminished respiratory drive:
    • Sedative medications ( opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics, benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines)
    • Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification stem lesions (affecting the central respiratory center)
    • Multiple sclerosis Multiple Sclerosis Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis (bulbar dysfunction leading to central respiratory drive depression)
    • Hypothermia Hypothermia Hypothermia can be defined as a drop in the core body temperature below 35°C (95°F) and is classified into mild, moderate, severe, and profound forms based on the degree of temperature decrease. Hypothermia
  • Impaired respiratory muscle function:
    • Guillain–Barré syndrome
    • Myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis
    • Amyotrophic lateral sclerosis Amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a sporadic or inherited neurodegenerative disease of upper motor neurons (UMNs) and lower motor neurons (LMNs). ALS is the most common progressive motor neuron disease in North America, primarily affecting men and individuals of Caucasian ethnicity. Amyotrophic Lateral Sclerosis
    • Multiple sclerosis Multiple Sclerosis Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis
    • Botulism Botulism Botulism is a rare, neuroparalytic syndrome caused by Clostridium botulinum (C. botulinum). A fatal neurotoxin (botulinum toxin) is released causing varying degrees of muscle paralysis and distinct clinical syndromes. The most common types of botulism are foodborne and infant. Botulism
    • Tetanus Tetanus Tetanus is a bacterial infection caused by Clostridium tetani, a gram-positive obligate anaerobic bacterium commonly found in soil that enters the body through a contaminated wound. C. tetani produces a neurotoxin that blocks the release of inhibitory neurotransmitters and causes prolonged tonic muscle contractions. Tetanus
    • Spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy lesions
    • Muscle fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia (seen with hypoxemic respiratory failure)
    • Malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries
    • Myopathy Myopathy Dermatomyositis
  • Airway obstruction Airway obstruction Airway obstruction is a partial or complete blockage of the airways that impedes airflow. An airway obstruction can be classified as upper, central, or lower depending on location. Lower airway obstruction (LAO) is usually a manifestation of chronic disease, such as asthma or chronic obstructive pulmonary disease (COPD). Airway Obstruction:
    • COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD)
    • Asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma
    • Obstructive sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep apnea
    • Cystic fibrosis Cystic fibrosis Cystic fibrosis is an autosomal recessive disorder caused by mutations in the gene CFTR. The mutations lead to dysfunction of chloride channels, which results in hyperviscous mucus and the accumulation of secretions. Common presentations include chronic respiratory infections, failure to thrive, and pancreatic insufficiency. Cystic Fibrosis
    • Airway Airway ABCDE Assessment edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • Diminished lung elasticity Elasticity Resistance and recovery from distortion of shape. Skeletal Muscle Contraction/ compliance Compliance Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. Veins: Histology:
    • Alveolar edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
    • Atelectasis Atelectasis Atelectasis is the partial or complete collapse of a part of the lung. Atelectasis is almost always a secondary phenomenon from conditions causing bronchial obstruction, external compression, surfactant deficiency, or scarring. Atelectasis
    • ARDS ARDS Acute respiratory distress syndrome is characterized by the sudden onset of hypoxemia and bilateral pulmonary edema without cardiac failure. Sepsis is the most common cause of ARDS. The underlying mechanism and histologic correlate is diffuse alveolar damage (DAD). Acute Respiratory Distress Syndrome (ARDS)
  • Diminished chest wall Chest wall The chest wall consists of skin, fat, muscles, bones, and cartilage. The bony structure of the chest wall is composed of the ribs, sternum, and thoracic vertebrae. The chest wall serves as armor for the vital intrathoracic organs and provides the stability necessary for the movement of the shoulders and arms. Chest Wall: Anatomy elasticity Elasticity Resistance and recovery from distortion of shape. Skeletal Muscle Contraction:
    • Pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion
    • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
    • Kyphoscoliosis Kyphoscoliosis Osteomalacia and Rickets
    • Abdominal distention Abdominal distention Megacolon
    • Pneumothorax Pneumothorax A pneumothorax is a life-threatening condition in which air collects in the pleural space, causing partial or full collapse of the lung. A pneumothorax can be traumatic or spontaneous. Patients present with a sudden onset of sharp chest pain, dyspnea, and diminished breath sounds on exam. Pneumothorax

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Acute Hypoxemic
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Acute Hypercapnic

Pathophysiology

Right-to-left shunt

  • Blood is shunted from the right side of the heart to the left side without undergoing oxygenation.
  • Deoxygenated blood mixes with oxygenated blood → ↓ arterial pressure of O₂
  • This can be caused by:
    • Cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) shunting (e.g., congenital Congenital Chorioretinitis malformations of the heart that allow blood to bypass the respiratory system) 
    • Pulmonary shunting (e.g., fluid fills the alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS), preventing oxygen diffusion Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport. Peritoneal Dialysis and Hemodialysis)
  • Note: 100% oxygen 100% Oxygen Cluster Headaches administration will not change oxygenation.
Diagram of a right-to-left shunt resulting in hypoxemia

Diagram of a right-to-left shunt resulting in hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome:
A cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) or pulmonary issue causes deoxygenated blood to skip gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange. When this later mixes with oxygenated blood, the arterial pressure of O2 is reduced.
PA: alveolar partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange
PI: inspired partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange
Pv PV Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the overproduction of rbcs. In addition, the wbc and platelet counts are also increased, which differentiate pv from erythrocytosis seen with chronic hypoxia and other chronic conditions. Polycythemia Vera: venous partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange
Ppv PPV The positive predictive value is the percentage of people with a positive test result who actually have the disease among all people with a positive result, regardless of whether or not they have the disease. Epidemiological Values of Diagnostic Tests: pulmonary venous partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange

Image by Lecturio.

Ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing-to-perfusion inequality

A mismatch between ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing and perfusion occurs from a disease process resulting in either:

  • Low V/Q ratio:
    • May occur from:
      • Diminished oxygen entry into alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) with normal blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure 
      • Overperfusion of alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) with normal ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing (e.g., diversion of blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure)
    • Results in: 
  • High V/Q ratio:
    • Results from diminished blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure to alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) with normal ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing
    • Ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing is wasted.
    • Must be severe for gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange to be affected

Note: 100% oxygen 100% Oxygen Cluster Headaches administration can correct oxygenation in V/Q mismatch.

Ventilation to perfusion mismatch

Diagrammatic examples of ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing (V) to perfusion (Q) mismatch:

The left side of the diagram shows an example of low ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing to an alveolus and normal perfusion, resulting in an oxygen saturation Oxygen Saturation Basic Procedures of 79% (low V/Q ratio).
In the middle, perfusion and ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing are matched, which allows appropriate oxygenation of the blood.
On the right, there is normal ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing, but low perfusion (high V/Q ratio), which provides more complete oxygenation, but there is less blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure.
When the blood from these vessels combine, the oxygenation from the middle and right alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) is not enough to compensate for the poor ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing of the left alveolus.

Image by Lecturio.

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Clinical Presentation

General signs and symptoms

  • Vitals:
  • Dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea
  • Increased work of breathing Work of breathing Respiratory muscle contraction during inhalation. The work is accomplished in three phases: lung compliance work, that required to expand the lungs against its elastic forces; tissue resistance work, that required to overcome the viscosity of the lung and chest wall structures; and airway resistance work, that required to overcome airway resistance during the movement of air into the lungs. Work of breathing does not refer to expiration, which is entirely a passive process caused by elastic recoil of the lung and chest cage. Pulmonary Examination and use of accessory muscles of breathing
  • Diaphoresis
  • Altered mental status Altered Mental Status Sepsis in Children:
    • Restlessness and anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder
    • Confusion
    • Somnolence
    • Coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma

Hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome

  • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia (inability to speak in complete sentences)
  • Use of accessory muscles of respiration Respiration The act of breathing with the lungs, consisting of inhalation, or the taking into the lungs of the ambient air, and of exhalation, or the expelling of the modified air which contains more carbon dioxide than the air taken in. Nose and Nasal Cavity: Anatomy
  • Cyanosis Cyanosis A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. Pulmonary Examination
Hypoxemia

Cyanosis Cyanosis A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. Pulmonary Examination on a patient’s face due to hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome

Image: “Clinical signs of chronic hypoxaemia” by Maximilian Patzig et al AL Amyloidosis. License: CC BY 4.0, edited by Lecturio.

Hypercapnia Hypercapnia A clinical manifestation of abnormal increase in the amount of carbon dioxide in arterial blood. Neonatal Respiratory Distress Syndrome

  • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
  • Asterixis Asterixis Hepatic Encephalopathy
  • Lethargy Lethargy A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction. Hyponatremia
  • Change in breathing pattern:
    • Shallow
    • Irregular
    • Gasping

Diagnosis

Arterial blood gas Arterial blood gas Respiratory Alkalosis

An arterial blood gas Arterial blood gas Respiratory Alkalosis (ABG) analysis is required in the diagnosis of respiratory failure. It measures and calculates components in arterial blood:

  • Measured:
    • pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance
    • Partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange of oxygen (PaO₂)
    • Partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange of CO₂ (PaCO₂)
  • Calculated:
    • Bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes (HCO₃)
    • Base excess
    • Oxygen saturation Oxygen Saturation Basic Procedures (SaO₂)

Criteria

The following parameters are used to define hypoxemic and hypercapnic respiratory failure:

Hypoxemic respiratory failure:

  • PaO₂ < 60 mmHg on a supplemental O₂ concentration ≥ 50% 
  • PaO₂ < 40 mmHg with any O₂ concentration
  • SaO₂ < 90%

Hypercapnic respiratory failure:

  • PaCO₂ > 50 mmHg
  • In patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with chronic hypercapnia Hypercapnia A clinical manifestation of abnormal increase in the amount of carbon dioxide in arterial blood. Neonatal Respiratory Distress Syndrome:
    • PaCO₂ acutely above a patient’s normal baseline
    • Concurrent ↓ in pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance < 7.3

Alveolar–arterial gradient

Once hypoxemic respiratory failure is established, the alveolar–arterial (A-a) gradient can be used to help in understanding Understanding Decision-making Capacity and Legal Competence the potential underlying etiology.

  • Defined as the difference between the oxygen concentration in the alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) (PAO2) and arterial blood (PaO₂):
    • A-a gradient = PAO₂ – PaO₂ 
    • PAO₂: calculated from the alveolar gas equation
    • PaO₂: measured in an ABG
  • Interpretation:
    • Normal: 5–10 mmHg
    • Increased in etiologies that cause:
      • Right-to-left shunting
      • V/Q mismatch

Supporting workup

The following can be done to evaluate potential causes of respiratory failure. The workup should be tailored to the patient’s presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor and clinical suspicion.

Laboratory evaluation:

  • CBC
    • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
    • Polycythemia Polycythemia An increase in the total red cell mass of the blood. Renal Cell Carcinoma → seen in chronic respiratory failure
    • ↑ WBC → infection
  • Troponin and BNP BNP A peptide that is secreted by the brain and the heart atria, stored mainly in cardiac ventricular myocardium. It can cause natriuresis; diuresis; vasodilation; and inhibits secretion of renin and aldosterone. It improves heart function. It contains 32 amino acids. Renal Sodium and Water Regulation → cardiogenic pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema
  • Blood and sputum cultures Cultures Klebsiella → pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
  • Creatine kinase Creatine kinase A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: the mm type from skeletal muscle, the mb type from myocardial tissue and the bb type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. Skeletal Muscle Contraction → myositis
  • Urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat drug screen → sedation from opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics or benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines

Pulmonary function tests:

  • More useful in chronic respiratory failure
  • Used for assessing and monitoring the severity of obstructive and restrictive lung disease
  • Predictive of ventilatory failure in patient with neuromuscular disease

Imaging:

  • Chest X-ray Chest X-ray X-ray visualization of the chest and organs of the thoracic cavity. It is not restricted to visualization of the lungs. Pulmonary Function Tests:
    • Atelectasis Atelectasis Atelectasis is the partial or complete collapse of a part of the lung. Atelectasis is almost always a secondary phenomenon from conditions causing bronchial obstruction, external compression, surfactant deficiency, or scarring. Atelectasis
    • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
    • Pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema
    • ARDS ARDS Acute respiratory distress syndrome is characterized by the sudden onset of hypoxemia and bilateral pulmonary edema without cardiac failure. Sepsis is the most common cause of ARDS. The underlying mechanism and histologic correlate is diffuse alveolar damage (DAD). Acute Respiratory Distress Syndrome (ARDS)
    • Pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion
    • Pneumothorax Pneumothorax A pneumothorax is a life-threatening condition in which air collects in the pleural space, causing partial or full collapse of the lung. A pneumothorax can be traumatic or spontaneous. Patients present with a sudden onset of sharp chest pain, dyspnea, and diminished breath sounds on exam. Pneumothorax
  • CT chest:
    • Pulmonary embolism Pulmonary Embolism Pulmonary embolism (PE) is a potentially fatal condition that occurs as a result of intraluminal obstruction of the main pulmonary artery or its branches. The causative factors include thrombi, air, amniotic fluid, and fat. In PE, gas exchange is impaired due to the decreased return of deoxygenated blood to the lungs. Pulmonary Embolism
    • Interstitial lung disease
    • Pulmonary hemorrhage

Related videos

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Alveolar Gas Equation – Hypoxemia and Hypercapnia
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Practice Calculation – Hypoxemia and Hypercapnia

Management

Management of respiratory failure is supportive and focuses on maintaining adequate oxygenation and ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing until the underlying condition can be treated.

Supplemental oxygen

General principles:

  • In hypoxemic respiratory failure, use the lowest concentration of oxygen that provides sufficient oxygenation to avoid oxygen toxicity Toxicity Dosage Calculation.
  • In hypercapnic respiratory failure, excessive administration of oxygen may result in V/Q mismatch and loss of the hypoxemic respiratory drive.

Options:

  • Nasal cannula:
    • Used in mild hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome
    • Low flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure
    • Provides low amounts of oxygen (24%–50%)
  • Simple face mask: 
    • Slightly higher flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure than nasal cannula
    • Delivers low to moderate amounts of oxygen (40%–60%)
  • Venturi mask: 
    • Especially helpful when over oxygenation is a potential concern
    • Delivers a known concentration of oxygen (24%–60%)
  • Non-rebreather mask:
    • Used for severe hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome, often as a transition to other ventilatory measures
    • Contains a reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli bag for oxygen
    • Requires a higher flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure
    • Allows high concentrations of oxygen (60%–90%)
    • Exhaled air is released through a 1-way valve (prevents re-inhalation).
  • High- flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure nasal cannula:
    • Provides high volumes of oxygen (up to approximately 100%)
    • Humidified
    • Can provide a small amount of positive pressure

Noninvasive positive-pressure ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing (NPPV)

Noninvasive positive-pressure ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing provides ventilatory support without placing an artificial airway Airway ABCDE Assessment.

Indications:

Best suited for:

  • Pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema
  • COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD)

Options:

Invasive ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing

Indications: 

General principles:

  • Applies positive pressure breaths
  • Volumes and pressures given are dependent on the resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing and compliance Compliance Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. Veins: Histology of the airways.

Parameters:

Extracorporeal membrane oxygenation (ECMO)

Extracorporeal membrane oxygenation is an advanced therapy utilizing prolonged cardiopulmonary bypass to oxygenate blood and remove CO₂.

  • Considered in respiratory failure that remains refractory despite mechanical ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing (e.g., ARDS ARDS Acute respiratory distress syndrome is characterized by the sudden onset of hypoxemia and bilateral pulmonary edema without cardiac failure. Sepsis is the most common cause of ARDS. The underlying mechanism and histologic correlate is diffuse alveolar damage (DAD). Acute Respiratory Distress Syndrome (ARDS))
  • Can be done only at specialized centers with a dedicated, multidisciplinary team
Ecmo

Diagram of venovenous ECMO for respiratory failure:
The patient is put on a cardiopulmonary bypass circuit, where venous blood is extracted, oxygenated, and returned to the body.
IVC IVC The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy: inferior vena cava Inferior vena cava The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy
SVC: superior vena cava Superior vena cava The venous trunk which returns blood from the head, neck, upper extremities and chest. Mediastinum and Great Vessels: Anatomy

Image: “ECMO for isolated respiratory failure” by Van Meurs et al AL Amyloidosis., Extracorporeal Life Support Organization. License: CC BY 2.5

Related videos

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References

  1. Shebl E, Burns B. (2020). Respiratory failure. [online] StatPearls. Retrieved March 28, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK526127/
  2. Castro, D., Patil, S.M., Keenaghan, M. (2021). Arterial blood gas. [online] StatPearls. Retrieved March 28, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK536919/
  3. Brinkman, J.E., Sharma, S. (2020). Physiology, pulmonary. [online] StatPearls. Retrieved March 28, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK482426/
  4. Hickey, S.M., Giwa, A.O. (2020). Mechanical ventilation. [online] StatPearls. Retrieved March 29, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK539742/
  5. Patel, B.K. (2020). Acute hypoxemic respiratory failure (AHRF, ARDS). [online] MSD Manual Professional Version. Retrieved March 28, 2021, from https://www.msdmanuals.com/professional/critical-care-medicine/respiratory-failure-and-mechanical-ventilation/acute-hypoxemic-respiratory-failure-ahrf,-ards
  6. Patel, B.K. (2020). Ventilatory failure. [online] MSD Manual Professional Version. Retrieved March 28, 2021, from https://www.msdmanuals.com/professional/critical-care-medicine/respiratory-failure-and-mechanical-ventilation/ventilatory-failure
  7. Kaynar, A.M., Sharma, S. (2020). Respiratory failure. In Pinksy, M. R. (Ed.), Medscape. Retrieved March 28, 2021, from https://emedicine.medscape.com/article/167981-overview
  8. Soo Hoo, G.W. (2020). Noninvasive ventilation. In Mosenifar, Z. (Ed.), Medscape. Retrieved March 29, 2021, from https://emedicine.medscape.com/article/304235-overview

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