Respiratory failure

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

Respiratory failure is the result of inadequate gas exchange, that in turn results in hypoxemia, hypercapnia or both. There is always an underlying disease that results in respiratory failure. The cause must be identified in order two classify, diagnose and treat respiratory failure. In some instances it could result in persistent lung injury. Mortality rate increases with age. The incidence is approximately 137.1 per 100,000 individuals in the united states. Common risk factors include smoking, alcohol abuse, COPD exacerbation and obesity. If left untreated patients with respiratory failure may develop sepsis and multiple organ failure which could result in death. It is diagnosed based on clinical presentation, the hallmark being shortness of breath which could be correlated with arterial blood gases to classify and diagnose the patient. Correction of ABG’s by mechanical ventilation is the mainstay of treatment.

The diagnostic and treatment strategies for respiratory failure and it’s associated conditions have come a long way. Since the discovery of the stethoscope by René Laennec in 1816, to the work of Fenn and his team in 1946 on pulmonary gas exchange, the use of cuffed endotracheal tubes by Ibsen in 1954 to administer positive pressure ventilation to patients in respiratory failure who were admitted to the intensive care units, that became common in the United States in 1960.

Respiratory failure may be classified into several subtypes as follows; Type I, Type II, Type III, Type IV.

Respiratory failure is the result of inadequate gas exchange in the pulmonary circulation. This could result from lung failure or pump failure. Lung failure which is failure of gas exchange results in hypoxemia (<PaO2) and pump failure which is ventilatory failure would result in alveolar hypoventilation that causes hypercapnia (>PaCO2). Type I respiratory failure has a V/Q mismatch that causes hypoxemia. Type II respiratory failure is caused by alveolar hypoventilation which results in hypercapnia. Type III respiratory failure in the peri-operative period clinically progresses to Type I or Type II respiratory failure. Type IV respiratory failure results from an underlying circulatory collapse.

Common causes of respiratory failure include pneumonia, pulmonary edema, pulmonary embolism, acute respiratory distress syndrome, atelectasis, asthma, COPD, neuromuscular and chest wall disorders, inadequate post-operative analgesia, smoking, obesity and shock. Life-threatening causes of respiratory failure include chronic obstructive pulmonary disease, acute on chronic respiratory failure, pulmonary infection, pulmonary embolism, heart failure, cardiac arrhythmia and lung cancer.

As respiratory failure manifests in a variety of clinical forms, differentiation must be established in accordance with the particular type of respiratory failure. Type I respiratory failure must be differentiated from other disease that cause hypoxia, such as acute decompensated heart failure, adult respiratory distress syndrome, high altitude pulmonary edema, neurogenic pulmonary edema, pulmonary embolism, pneumonia and idiopathic chronic lung fibrosis. In contrast Type II respiratory failure must be differentiated from other diseases that cause hypercapnia, such as COPD, status asthmaticus, opioid toxicity, myasthenia crisis, Guillain-Barré syndrome. As well as Type III preoperative respiratory failure and Type IV respiratory failure.

The incidence of respiratory failure is approximately 137.1 per 100,000 individuals in the United States and the mortality rate is approximately 29%-42%. The incidence is higher among patients ≥ 65 years of age and the mortality rate is higher among African-Americans and Hispanics compared to Caucasians. Men and women are equally affected.

Common risk factors in the development of respiratory failure include smoking, alcohol abuse, COPD exacerbation, obesity.

There is insufficient evidence to recommend routine screening for respiratory failure.

Common complications of respiratory failure include, pulmonary emboli, barotrauma, fibrosis and pneumonia. If left untreated patients with respiratory failure may progress to develop sepsis and multiple organ failure which increases mortality. The mortality rate of respiratory failure is approximately 29%-42%.

Respiratory failure is mainly diagnosed based on clinical presentation. There is no single diagnostic study of choice for the diagnosis of respiratory failure, but respiratory failure can be diagnosed based on history, examination and arterial blood gases.

A positive history of sudden onset of shortness of breath, trauma to the neck or thorax and change in mental status is suggestive of respiratory failure. Common symptoms of respiratory failure include tachypnea , stridor and dyspnea. Less common symptoms of respiratory failure include anxiety, headache, and asterixis.

Patients with respiratory failure usually appear distressed with altered mental status. Physical examination of patients with respiratory failure is usually remarkable for dyspnea, stridor, and tachypnea.

Laboratory findings consistent with the diagnosis of respiratory failure include abnormal bicarbonate, oxygen, phosphate, and magnesium levels.

X-ray may be helpful in establishing the etiology of respiratory failure as it may detect underlying disease. Findings on x-ray suggestive of pre-existing COPD include hyperinflation and a flattened diaphragm. X-ray findings suggestive of interstitial lung disease include reticular nodular shadows. Findings on x-ray suggestive of acute respiratory distress include cardiomegaly, redistribution of vessels, peribronchial cuffing, pleural effusion, lines within the septum, and bat-wing distribution of perihilar infiltrates. Finally, thoracic cage abnormalities may be detected such as kyphosis, scoliosis, pectus excavatum, fractured ribs and ankylosing spondylitis, as well as diaphragmatic paralysis.

An ECG may be helpful in detecting underlying cardiovascular disease and to diagnose arrhythmia arising as a complication of severe hypoxemia and acidosis.

A CT scan may be helpful in establishing the etiology of respiratory failure as it may detect underlying disease. CT can also predict the incidence of respiratory failure after trauma to the spine. Findings on CT tend to be similar to those found on plain x-ray. Findings on CT scan suggestive of pre-existing COPD include hyperinflation and a flattened diaphragm. CT findings suggestive of interstitial lung disease include reticular nodular shadows. Findings on CT scan suggestive of acute respiratory distress include cardiomegaly, redistribution of vessels, peribronchial cuffing, pleural effusion, lines within the septum, and bat-wing distribution of perihilar infiltrates. CT may also reveal pathology of the neck, brainstem and peripheral nervous system, such as stroke, tumor and transection of the spinal cord.

MRI may be helpful in establishing the etiology of respiratory failure, in particular if the cause is due to a pathology of the neck, central or peripheral nervous system. MRI can predict the occurence of respiratory failure in a patient with cervical spine injury. MRI may suggest that stroke, tumor, spinal cord injury and/or complete spinal transection are the cause of respiratory failure. Findings on MRI may include embolism, thrombosis, and haemorrhage.

Echocardiography may be helpful in the diagnosis of a cardiac cause of respiratory failure. Findings on an echocardiography suggestive of cardiac cause of respiratory failure include dilatation of the left ventricle, focal or global wall motion irregularities, severe mitral regurgitation. If patients show a normal size of their heart and a normal blood pressure then this suggests an etiology of acute respiratory distress. Echocardiography is also useful in patients with chronic hypercapnic respiratory failure as the function of the right ventricle and the pulmonary artery pressure may be monitored. Thoracic ultrasound is a part of critical care ultrasonography and may be helpful in the diagnosis of acute cardiopulmonary respiratory failure. Findings on an ultrasound suggestive of respiratory failure include the presence of pneumothorax, alveolar and interstitial aeration abnormalities, and pleural effusion.

There are no other imaging findings associated with respiratory failure.

Despite most patients being unable to perform a pulmonary function test during acute respiratory failure, pulmonary function testing may be useful with chronic respiratory failure. Chronic respiratory failure is usually due to an underlying restrictive disease, pulmonary function test findings include a decrease in FEV1 and a significant decrease in FVC with an overall increase in the FEV1/FVC ratio. It is unlikely that an obstructive lung disease would cause respiratory failure. In respiratory failure with significant cardiac function compromise, a right side cardiac catheter may be used. Catheterization is controversially used to assess those patients with acute hypoxemic respiratory failure where cardiac function is uncertain.

There is no treatment for respiratory failure; however, medication may be used to allow for easier intubation and to ease anxiety in the patient. Recently, studies have demonstrated a strong recommendation against the use of sedatives or analgesics. The use of these agents has been implicated in decreasing the success rates of ventilation mechanisms.

A trial of non-invasive ventilation (NIV) may be carried out in order to achieve hypoxemic correction. NIV is advantageous in carrying less infection and mortality rates than traditional mechanical ventilation. ECMO is a cardiopulmonary support machine that is useful in cases of acute severe respiratory failure.

Mechanical ventilation aims to correct abnormalities in oxygenation of the blood and tissues, reduce the respiratory effort and prevent dynamic hyperinflation. Different modes of ventilation are available to suit each patient’s individual needs, such as assisted-control ventilation.

Effective measures for the primary prevention of respiratory failure include control of primary illness that may lead to respiratory failure. In addition, the administration of influenza and pneumococcal vaccinations to patients at risk such as COPD and asthma patients is very important in preventing respiratory failure. Finally, smoking cessation will help to minimize the risk for respiratory failure.

Effective measures for the secondary prevention of respiratory failure include monitoring and medical compliance of patients with chronic lung disease such as asthma.

Noninvasive pressure support ventilation (NPSV) using a new special helmet has undergone a pilot trial, where it successfully treated hypoxemic ARF, with a higher tolerance and less complications than a conventional face mask.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

The diagnostic and treatment strategies for respiratory failure and its associated conditions have come a long way. Since the discovery of the stethoscope by René Laennec in 1816, to the work of Fenn and his team in 1946 on pulmonary gas exchange, the use of cuffed endotracheal tubes by Ibsen in 1954 to administer positive pressure ventilation to patients in respiratory failure who were admitted to the intensive care units, that became common in the United States in 1960.

• In 1816 René Laennec invented the stethoscope.^[1]
• In 1821 René Laennec first described the gross pathology of idiopathic anasarca of the lungs; pulmonary edema without heart failure.
• In 1896 W.C. Roentgen had described X-rays.^[2]
• The limitation was that early chest X-rays required an exposure time of more than 20 minutes, hence they were not used until 1920.
• In 1946 Fenn and his team published their work on pulmonary gas exchange, relating PO2, PCO2, respiratory exchange ratio, arterial oxygen saturation, alveolar ventilation and altitude.^[3]
• In 1954 Clark first developed an electrode which was used for the measurement of PO2, showing the oxygen level in the blood.^[4]
• In 1960 the use of intensive care units became common in the United States.^[5]
• In 1967 Ashbaugh and his team identified acute respiratory distress syndrome.^[6]

• In 1936 Cortisone was first extracted.^[7]
• In 1950 Cortisone was used to treat asthma.
• In 1954 Ibsen used cuffed endotracheal tubes to administer positive pressure ventilation to patients in respiratory failure admitted to the ICU.^[8]
• In 1960 Moss and his coworkers discovered the benefits of using chest compressions to achieve artificial circulation.^[9]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

Respiratory failure may be classified into several subtypes as follows; Type I, Type II, Type III, Type IV.

The classification of respiratory failure is as follows:^[1]

Respiratory Failure

Type I

Type II

Type III

Type IV

Hypoxemic

Hypercapnic

Peri-operative

Shock

Respiratory failure patients may have a normal or increased A-a gradient depending upon the etiology of the respiratory failure. The following table outlines the major characteristics:

Respiratory Failure-decreased SaO2

Normal A-a gradient

Increased A-a gradient

Normal PaCO2

Increased PaCO2

Hypoxemia does not correct with 100% O2

Hypoxemia corrects with 100% O2

Decreased FiO2 or decreased PiO2

Hypoventilation (sedation, COPD, asthma, diaphragmatic paralysis or Neuromuscular disease)

True shunt (Left to right shunts, CHF, pneumonia, atelectasis)

Vascular disease (pulmonary embolism), airway disease (COPD, asthma), alveolar filling (CHF, pneumonia)

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

Respiratory failure is the result of inadequate gas exchange in the pulmonary circulation. This could result from lung failure or pump failure. Lung failure which is failure of gas exchange results in hypoxemia (<PaO2) and pump failure which is ventilatory failure would result in alveolar hypoventilation that causes hypercapnia (>PaCO2). Type I respiratory failure has a V/Q mismatch that causes hypoxemia. Type II respiratory failure is caused by alveolar hypoventilation which results in hypercapnia. Type III respiratory failure occurs in the peri-operative period clinically progresses to Type I or Type II respiratory failure. Type IV respiratory failure results from an underlying circulatory collapse.

Mechanics of the respiratory system

The pathogenesis of respiratory failure is as follows:^[1]

• The respiratory system comprises of 2 parts:
  • The gas exchanging organ, the lung
  • The pump that ventilates the lungs, the pump consists of:
    • Chest wall, the respiratory muscles
    • The respiratory control system in the central nervous system (CNS)
    • The spinal and peripheral pathways that connect the CNS control system with the respiratory muscles
• The respiratory system has 2 main functions oxygenation of mixed venous blood and elimination of carbon dioxide.

Respiratory failure

• Respiratory failure is a condition where there is loss of one or both of the functions of the respiratory system resulting in inadequate gas exchange.
• Respiratory failure is defined as:
  • Arterial oxygen tension (PaO2) < 60 mmHg
  • Arterial carbon dioxide (PaCO2) > 45 mmHg
• Respiratory failure can be caused by lung failure or pump failure.
• Lung failure, which is gas exchange failure resulting in hypoxemia (<PaO2).
• Pump failure, which is ventilatory failure resulting in alveolar hypoventilation which in turn results in hypercapnia (>PaCO2).
• Hypercapnic respiratory failure can be caused by:
  • Mechanical defects
  • Central nervous system depression
  • Imbalance of energy demands and supplies
  • Adaptation of central controllers
  • Neuromuscular transmission impairment
  • Mechanical defect of the rib cage
  • Fatigue of respiratory muscles
• Lung failure and pump failure can coexist in the same patient in cases of:
  • Chronic obstructive pulmonary disease (COPD) with carbon dioxide retention
  • Severe pulmonary edema
  • Asthmatic crisis
• Acute respiratory failure can develop in minutes to hours
• Chronic respiratory failure takes days to develop
• The ph drops below 7.35 in acute hypercapnic respiratory failure
• In underlying chronic respiratory failure, the PaCO2 rises unto 20mmHg above baseline
• Presentation of respiratory failure can be:
  • Acute
  • Chronic
  • Acute on chronic (COPD exacerbation)

Characteristics of Type I respiratory failure include:^[2][3]

• Severe oxygen-refractory hypoxemia (< PaO2)
• Ventilation/Perfusion (V/Q) mismatch
• A portion of total pulmonary blood flow is unable to pick oxygen
• Alveolar flooding (airspace filling)

Characteristics of Type II respiratory failure include:^[4][5][6][7]

• Hypercapnia (Increased PaCO2)
• Alveolar hypoventilation
• Alveolar minute ventilation (VA) is decreased
• Failure to adequately remove carbon dioxide
• Alveolar hypoventilation can be caused by:
  • Loss of CNS drive
  • Impaired neuromuscular competence
  • Excessive dead space
  • Increased mechanical load
• Hypoxemia can be present (corrected by supplemental oxygen)

Characteristics of Type III respiratory failure include:^[8][9][10]

• Progressive increased atelectasis due to a low functional residual capacity (FRC)
• Improper abdominal wall mechanics usually in the peri-operative or post-operative period
• Clinical progression is often either to Type I or Type II respiratory failure

Characteristics of Type IV respiratory failure include:^[11][12]

• Underlying cause is shock (inadequate oxygen delivery)
• Patients are often mechanically ventilated due to underlying shock
• Resolves when the underlying shock or circulatory collapse is corrected
• Poor prognosis, if superimposed by Type I or Type II respiratory failure

• Genetic variants that can influence susceptibility to acute respiratory distress syndrome include:^[13]
  • Functional single nucleotide polymorphism (SNP) in POPDC3 gene
  • Functional SNP in FAAH gene
• ARDS in severe sepsis is associated with the presence of allele D of the ACE gene^[14]

Conditions associated with respiratory failure include:^{[15][16][17][18][19][20][21][22][23][24][25]}

• Acute respiratory distress syndrome (ARDS)
• Chronic obstructive pulmonary disease (COPD)
• Opioid Toxicity
• Pulmonary edema
• Pulmonary embolism
• Pneumonia
• Idiopathic pulmonary fibrosis
• Asthma
• Myasthenia gravis
• Guillain-Barré syndrome
• Post-operative atelectasis
• Shock

Respiratory failure is an end stage disease that has many underlying causes. The gross pathology may thus vary according to the underlying disease. To review all the causes of respiratory failure click here.

Respiratory failure is an end stage disease that has many underlying causes. The microscopic pathology may thus vary according to the underlying disease. To review all the causes of respiratory failure click here.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

Common causes of respiratory failure include pneumonia, pulmonary edema, pulmonary embolism, acute respiratory distress syndrome, atelectasis, asthma, COPD, neuromuscular and chest wall disorders, inadequate post-operative analgesia, smoking, obesity and shock. Life-threatening causes of respiratory failure include chronic obstructive pulmonary disease, acute on chronic respiratory failure, pulmonary infection, pulmonary embolism, heart failure, cardiac arrhythmia and lung cancer.

• Life-threatening causes of respiratory failure include chronic obstructive pulmonary disease, acute on chronic respiratory failure, pulmonary infection, pulmonary embolism, heart failure, cardiac arrhythmia and lung cancer.^[1]

Causes of respiratory failure based on classification of disease include:^[2]

• Type I respiratory failure:
  • Pneumonia
  • Cardiogenic pulmonary edema
    • Caused by increased hydrostatic pressure in the pulmonary capillaries
  • Non-cardiogenic pulmonary edema
    • Caused by increased permeability in the pulmonary capillaries
    • Acute lung injury
    • Acute respiratory distress syndrome (ARDS)
  • Pulmonary embolism
  • Atelectasis
  • Pulmonary fibrosis

• Type II respiratory failure:
  • Central hypoventilation
  • Asthma
  • Chronic obstructive pulmonary disease (COPD)
    • Hypoxemia and hypercapnia often coexist
  • Neuromuscular and chest wall disorders
    • Myopathies
    • Neuropathies
    • Kyphoscoliosis
    • Myasthenia gravis ^[3]
  • Obesity hypoventilation syndrome

• Type III respiratory failure:
  • Inadequate post-operative analgesia
    • Upper abdominal incision
  • Obesity
  • Ascites
  • Pre-operative tobacco smoking
  • Excessive airway secretions

• Type IV respiratory failure:
  • Cardiogenic shock
  • Septic shock
  • Hypovolemic shock

Common drugs that can cause respiratory failure include:^[4][5]

• Azacitidine
• Codeine
• Clozapine
• Fentanyl
• Gamma-Hydroxybutyric acid
• Heroin
• Ketamine
• Lidocaine
• Labetalol
• Lorazepam
• Morphine
• Nitrazepam
• Opiate
• Oxymorphone
• Procainamide (patient information)
• Sodium thiopental
• Triazolam
• Zopiclone

Cardiovascular	Atrial septal defect (ostium primum), Ebstein anomaly, Eisenmenger syndrome, Fallot tetralogy, Pulmonary valve stenosis, Transposition of great arteries, Tricuspid valve stenosis, Ventricular septal defect, Heart failure, Cardiac arrhythmia, Shock
Chemical / poisoning	3-Quinuclidinyl benzilate, Abrin, Aldicarb, Alpha-amanitin, Barium nitrate, Bungarotoxin, Carbon monoxide poisoning, Ceritinib Cocaine, Cone snail, Furfural, Snakebites (Patient information)
Congenital	Atrial septal defect (ostium primum), Bland-White-Garland Syndrome, Congenital Central Hypoventilation Syndrome, Congenital diaphragmatic hernia, Fallot tetralogy, Fetal circulation, persistent, Respiratory distress syndrome (neonatal)
Dermatologic	No underlying causes
Drug Side Effect	Codeine, Clozapine, Crizotinib, Cyclophosphamide, Desmopressin, Dornase Alfa, Fentanyl, Gamma-Hydroxybutyric acid, galsulfase, Heroin, Idursulfase, interferon alfacon-1, Ixabepilone, Ketamine, Lidocaine, Labetalol, Lorazepam, Morphine, Nitrazepam, Opiate, Oxymorphone, Pegylated interferon alfa-2b, Pramipexole, Procainamide (patient information), Rasburicase, Sodium thiopental, Tretinoin, Triazolam, Vincristine sulfate liposome, Zopiclone
Ear Nose Throat	No underlying causes
Endocrine	No underlying causes
Environmental	Asbestosis, Coal worker pneumoconiosis, Smoke inhalation, Sulfur dioxide
Gastroenterologic	Hepatic failure, Hepatopulmonary syndrome
Genetic	Achondrogenesis, Acute Porphyria, Alpha 1-antitrypsin deficiency, Atelosteogenesis, type II, Becker’s muscular dystrophy, Carnitine palmitoyltransferase II deficiency, Cystic fibrosis, Duchenne’s Muscular Dystrophy, Familial dysautonomia, Hereditary haemorrhagic telangiectasia, Osteogenesis imperfecta, Thanatophoric dysplasia
Hematologic	Acute Porphyria, Cholesterol Emboli Syndrome, Fat embolism, Sepsis
Iatrogenic	Blood transfusion, EVAR
Infectious Disease	Babesiosis, Botulism, Crimean-Congo hemorrhagic fever, Hantavirus Pulmonary Syndrome, Heartworm, Post-polio syndrome, Rabies, Tetanus
Musculoskeletal / Ortho	Kyphoscoliosis
Neurologic	Amyotrophic Lateral Sclerosis, Meningitis, Polyrediculitis, Zellweger syndrome
Nutritional / Metabolic	Metabolic Acidosis
Obstetric/Gynecologic	No underlying causes
Oncologic	Malignant Mesothelioma
Ophthalmologic	No underlying causes
Overdose / Toxicity	Acetylsalicylic acid, Alcohol, Bufotenin, Clitocybe dealbata, Colchicine, Cytisine, Dicofol, Saxitoxin, Tetrodotoxin, Tick paralysis, Vinyl chloride
Psychiatric	No underlying causes
Pulmonary	Acute lung syndrome, Acute Respiratory Distress Syndrome, Alpha 1-antitrypsin deficiency, Atelectasis, Bronchial asthma, Bronchiectasis, Bronchiolitis, Bronchiolitis obliterans, Bronchogenic carcinoma, Bronchopulmonary dysplasia, Chronic Obstructive Pulmonary Disease, Cystic adenomatoid malformation of lung, Emphysema, Eosinophilic pneumonia, Fibrosing alveolitis, Flail chest, Interstitial fibrosis, Laryngo-/Bronchospasm, Legionella pneumophila, Pleural effusion, Pneumonia, Pneumothorax, Pulmonary alveolar proteinosis, Pulmonary arterio-venous malformation, Pulmonary edema, Pulmonary embolism, Pulmonary hypertension, Pulmonary oedema, Restrictive Lung Disease, Status asthmaticus, Lung cancer
Renal / Electrolyte	Electrolyte abnormalities
Rheum / Immune / Allergy	Acute motor axonal neuropathy, Anaphylaxis, Angioedema, Antiphospholipid Antibody Syndrome, Devic’s disease, Guillain-Barre syndrome, Hamman-Rich Syndrome, Myasthenia Gravis, Satoyoshi syndrome
Trauma	Ebstein anomaly, Flail chest
Urologic	No underlying causes
Miscellaneous	Aspiration, Foreign body, Malignant hyperpyrexia, Multiple organ dysfunction syndrome, Near-drowning, Reye’s syndrome

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vellayat Ali M.B.B.S[2] Karina Zavaleta, MD [3] M. Khurram Afzal, MD [4]

As respiratory failure manifests in a variety of clinical forms, differentiation must be established in accordance with the particular type of respiratory failure. Type I respiratory failure must be differentiated from other disease that cause hypoxia, such as acute decompensated heart failure, adult respiratory distress syndrome, high altitude pulmonary edema, neurogenic pulmonary edema, pulmonary embolism, pneumonia and idiopathic chronic lung fibrosis. In contrast Type II respiratory failure must be differentiated from other diseases that cause hypercapnia, such as COPD, status asthmaticus, opioid toxicity, myasthenia crisis, Guillain-Barré syndrome. As well as Type III preoperative respiratory failure and Type IV respiratory failure.

• As respiratory failure manifests in a variety of clinical forms, differentiation must be established in accordance with the particular type of respiratory failure. Type I respiratory failure must be differentiated from other disease that cause hypoxia, such as acute decompensated heart failure, adult respiratory distress syndrome, high altitude pulmonary edema, neurogenic pulmonary edema, pulmonary embolism, pneumonia and idiopathic chronic lung fibrosis. In contrast Type II respiratory failure must be differentiated from other diseases that cause hypercapnia, such as COPD, status asthmaticus, opioid toxicity, myasthenia crisis, Guillain-Barré syndrome. As well as Type III preoperative respiratory failure and Type IV respiratory failure.

Type of respiratory failure	Causes/Etiology		Onset	Clinical manifestations					Investigations		Gold standard	Other features
				Symptoms				Physical exam
				Dyspnea	Cough	Fever	Others findings		Imaging	Labs
Hypoxic respiratory failure (Type 1 respiratory failure)	Cardiogenic pulmonary edema	Acute decompensated heart failure[1][2] [3]	Acute	+	+ with frothy expectoration	+/-	nausea and anorexia confusion headaches	Wheezing Increased pulse rate Crackles Pedal edema Elevated JVP Obtundation Enlarged liver	Cardiomegaly and interstitial edema in chest radiograph Echocardiography	Pulse oximetry Assays for BNP (B-type natriuretic peptide) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) Cardiac troponin levels ST and T waves abnormalities in ECG	Clinical diagnosis	History of heart disease, hypertension
	Non cardiogenic pulmonary edema	Adult respiratory distress syndrome (ARDS) [4]	Acute	+	+/-	+/-	Cyanosis	Tachypnea Tachycardia Diffuse crackles	Diffuse, bilateral, alveolar infiltrates without cardiomegaly in chest radiograph Bilateral opacities in CT	Hypoxemia with acute respiratory alkalosis in arterial blood gases	Clinical diagnosis with supportive test	According to Berlin definition: One week of new or worse respiratory symptoms or clinical insult Symptoms can not be explained by cardiac disease Bilateral opacities in chest X-Ray or CT Compromised oxygenation
		High-Altitude Pulmonary edema (HAPE) [5]	Acute	+	+ with frothy expectoration	+	Chest tightness Decreased exercise performance	Wheezing	Chest X-ray may show patchy alveolar infiltrates, predominantly in the right central hemithorax, which become more confluent and bilateral as the illness progresses	High levels of white blood cell count Decreased of oxygen saturation	Clinical diagnosis with supportive test	Occurrs over 2500 m Descent is mandatory in >4000 m
		Neurogenic pulmonary edema [6] [7]	Acute	+	+/- with frothy expectoration	+/-	Hemoptysis	Rales Bilateral crackles	Bilateral hyperdense infiltration in chest X-Ray	CBC may show Leukocytosis Bilateral hyperdense infiltrations on chest X-Ray	Diagnosis of exclusion A proposed criteria is as follows Bilateral infiltrates PaO2/FiO2 ratio < 200 No evidence of left atrial hypertension Presence of CNS injury Absence of other common causes of acute respiratory distress or ARDS	Major causes of NPE are epileptic seizures, cerebral hemorrhages and brain injury
		Pulmonary embolism [8] [9]	Acute Sub-acute Chronic	+	+	+/-	Chest pain Orthopnea	Wheezing Tachypnea Edema Decreased breath sounds Tachycardia	Hamptom and Westermark sign may be seen in chest X-Ray	Leukocytosis, elevated erythrocyte sedimentation and lactic acid in complete blood count Hypoxemia in arterial blood gas D-dimer to rule out other diseases Tachycardia and abnormalities in ST-segment and T waves are observed in ECG VQ scan	Computed tomography pulmonary angiogram (CTPA) or catheter based pulmonary angiography	Venous thromboembolism (VTE)
	Pneumonia[10] [11]		Acute	+	+ with sputum production	+	Pleuritic chest pain	Egophony Crackles Tactile fremitus Bronchial breath sounds	Infiltration in chest X-Ray	Leukocytosis Sputum culture & sensitivity	Clinical manifestations and infiltration chest X-Ray with or without microbiological test	Community-acquired pneumonia Hospital-acquired pneumonia Healthcare-associated pneumonia Ventilator-associated pneumonia Aspiration pneumonia
	Idiopatic chronic lung fibrosis[12] [13] [14] [15]		Chronic	+	+ without any sputum production	+/-	symptoms suggestive of rheumatic diseases may be present	Clubbing of the digits Bibasilar Crackles	Reticular or nodular pattern in chest X-Ray HRCT may show reticular opacities, including honeycomb changes and traction bronchiectasis	Serological tests e.g. ANA, RF for underlying rheumatological diseases Reduced FEV1 and FVC on spirometry	Clinical presentation in combinations with HRCT findings Lung biopsy when lab, imaging and PFT do not yield enough evidence	History of cigarette smoking
Hypercapnic respiratory failure (Type 2 respiratory failure)	COPD [16] [17]		Acute Chronic Acute-on-chronic	+	+	+/-	Exercise intolerance Acute exacerbation may affect CNS, ranging from irritability to decreased responsiveness	Clubbing Tachypnea Barrel shaped chest Decreased breath sounds with prolonged expiration Rhonchi and Wheeze Use of accessory respiratory muscles Increased JVP, peripheral edema may manifest with right ventricular overload during an acute exacerbation	Chest X-ray may show hyperinflation, flattened diaphragm, rapid tapering of vascular markings  CT scan helps to correlate with COPD prognosis	PFTs: (FEV1/FVC) <70% of predicted    ABGs: Mild to moderate hypoxemia, hypercapnia with progression of disease, pH is around normal, < 7.3 points to respiratory acidosis	Clinical diagnosis with supportive test	CNS symptoms may be the only manifestation in elderly with baseline hypercapnia
	Severe Asthma/Status Asthmaticus [18] [19]		Acute	+	+	–	Chest tightness Audible wheeze	Tachypnea Tachycardia Wheezing Use of accessory respiratory muscles Unable to speak full sentences Orthopnea Pulsus paradoxus	Chest X-ray not required in acute conditions, may show hyperinflation	PEF <40 percent predicted or personal best Pulse oximetry ABGs	Clinical diagnosis	History of bronchial asthma
	Drug Overdose (opioid toxicity) [20] [21] [22]		Acute	+	–	–	Nausea and vomiting Constipation Seizures	Classic triad suggesting opioid toxicity consist of respiratory depression, pinpoint pupils, and altered mental state  Conjunctival injection, Decreased bowel sounds Euphoria	Chest X-ray usually not required, may show signs of acute lung injury	Urine toxicology screen: may reveal polysubstance abuse	Clinical diagnosis with supportive test	Toxicity from antipsychotics, anticonvulsants, ethanol, and sedatives can result in miosis and altered mentation, but respiratory depression is usually absent
	Myasthenic crisis [23] [24] [25] [26] [27]		Acute	+	+/-	+/-	Inability to cough Bulbar weakness: dysphagia, nasal regurgitation, a nasal quality to speech, staccato speech, jaw weakness, bi-facial paresis, and tongue weakness	Expressionless face with droopy eyelids and mouth Use of accessory muscles of respiration i.e. external intercostal muscles, sternocleidomastoid, scalene muscles Rapid and shallow breathing	Chest X-ray findings depicting bacterial pneumonia and/or aspiration may be observed	Pulse Oximetry ABGs CBC: Infective cause precipitating the crisis may be observed Tensilon (edorphonium) test	Clinical diagnosis with supportive test	Known case of Myasthenia Gravis In some cases, respiratory failure may be the presenting symptom
	Guillain-Barré syndrome [28] [29] [30] [31] [32] [33]		Acute	+	–	+/-	Difficulty walking (ascending symmetric muscular weakness) Paresthesias in hands and feet Back pain Pain in extremities	Dysautonomia (tachycardia/bradycardia, hypertension/hypotension, urinary retention) Diminished or absent deep tendon reflexes Limb weakness (first lower then upper limbs) Facial droop (Facial nerve palsy) Ophthalmoparesis (3rd & 6th nerve palsies) Decreased breath sounds Decreased bowel sounds	MRI Spine: thickening of intrathecal spinal nerve roots and cauda equina	CSF analysis: Albuminocytologic dissociation Nerve conduction studies may show conduction block, slowed motor conduction velocities and delayed latencies PFTs: Vital Capacity, maximum inspiratory pressure (PImax) and maximum expiratory pressure (PEmax) should be followed to determine appropriate timing of intubation and mechanical ventilation	Clinical diagnosis with supportive test	Signs depicting respiratory failure occur late, early manifestations are tachypnea, tachycardia, air hunger, broken sentences, and a need to pause between sentences Use of the accessory respiratory muscles, paradoxical breathing, and orthopnea indicate severe diaphragmatic weakness
Perioperative respiratory failure (Type 3 respiratory failure)	Post-operative atelectasis [34] [35] [36] [37] [38]		Acute	+	+/-	+/-	Asyptomatic or increase work of breathing	Tachypnea Tachycardia Decreased movement in the affected lung area Dullness percussion note Absent breath sounds Tracheal deviation to affected side	Chest X-ray may show increased density and reduced volume CT chest accurately shows the involved segment	Pulse oximetry ABGs	Clinical diagnosis with support of radiographic findings	History of abdominal or thoracic surgery
Type 4 respiratory failure	Shock[39] [40]		Acute	+	–	+/-	Oliguria Abnormal mental status Clammy skin Cool extremities	Hypotension Tachycardia Tachypnea Rales Gallop rythm	Visible congestion in chest X-Ray	Electrocardigogram Increased levels of lactic acid Low levels of Bicarbonate Echocardiography to identify any cardiac dysfunction	Clinical diagnosis with supportive test	Cardiac index decreased Troponin leves, chemestry screen, complete blood count Cardiogenic shock Septic shock Hypovolemic shock

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

The incidence of respiratory failure is approximately 137.1 per 100,000 individuals in the United States and the mortality rate is approximately 29%-42%. The incidence is higher among patients ≥ 65 years of age and the mortality rate is higher among African-Americans and Hispanics compared to Caucasians. Men and women are equally affected.

• The incidence of respiratory failure is approximately 137.1 per 100,000 individuals in the United States.^[1]

• The mortality rate of respiratory failure is approximately 29%-42%.^[2]

• The incidence of respiratory failure increases with age; the incidence is high among individuals ≥ 65 years of age.^[1]

• Respiratory failure usually has a higher mortality rate in African-Americans and Hispanics compared to Caucasians.^[3]

• Respiratory failure affects men and women equally.^[4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

Common risk factors in the development of respiratory failure include smoking, alcohol abuse, COPD exacerbation, obesity.

• Common risk factors in the development of respiratory failure include:^[1][2][3][4]
  • Smoking
  • Alcohol abuse
  • Exacerbation of COPD
  • Obesity

• Less common risk factors in the development of respiratory failure include:^[4]
  • Air pollution

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

There is insufficient evidence to recommend routine screening for respiratory failure.

There is insufficient evidence to recommend routine screening for respiratory failure.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

Common complications of respiratory failure include, pulmonary emboli, barotrauma, fibrosis and pneumonia. If left untreated patients with respiratory failure may progress to develop sepsis and multiple organ failure which increases mortality. The mortality rate of respiratory failure is approximately 29%-42%.

• If left untreated, patients with respiratory failure may progress to develop sepsis and multiple organ failure which increases mortality.^[1]
• The symptoms of respiratory failure have a higher incidence and are more severe in patients ≥ 65 years of age.^[2]

• Pulmonary complications of respiratory failure include:^[3]
  • Pulmonary emboli
  • Barotrauma
  • Fibrosis
  • Pneumonia

• Extra-pulmonary complications of respiratory failure include:^[3]
  • Gastrointestinal hemorrhage
  • Renal failure
  • Infection
  • Thrombocytopenia

• The resolution of pulmonary edema and inflammation are important for determining the recovery from lung injury.^[4]
• Long term prognosis of patients with respiratory failure depends on the severity of underlying disease.
• Recovery of pulmonary function is variable and determined by the severity of the acute episode.
• Acute respiratory failure has a poor prognosis when there is an underlying hematologic malignancy.
• The mortality rate of respiratory failure is approximately 29%-42%.^[5]

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