Respiratory Failure

Definitions

  • Respiratory Failure: failure of respiratory system to maintain adequate gas exchange

    • Hypoxemia: decreased arterial pO2 (decreased hemoglobin saturation = SaO2, SpO2)
    • Hypoxia: impaired tissue oxygenation
    • Hypercapnia: increased arterial pCO2
    • Acidemia: acidic serum pH (due to either metabolic or respiratory acidosis)
    • Acidosis: present of acid-producing acid-base disturbance (with or without concomitant acidemia)
  • Acute Ventilatory Failure: exists when pCO2 increases enough (above the patient’s baseline pCO2) to produce a clinically significant decrease in pH (i.e. acidemia)

    • Note that the absolute pCO2 value alone does not necessarily indicate the presence of acute ventilatory failure (as increased pCO2 values can also be seen as part of physiologic respiratory compensation in metabolic alkalosis and in chronic hypoventilation)
    • The normal physiologic response to hypercapnia is renal reabsorption of bicarbonate (a process which usually takes a period of days)
    • Pre-Existing Chronic Hypoventilation: in the special clinical context of a patient with pre-existing chronic hypercapnia/chronic hypoventilation, the rise in pCO2 above the patient’s baseline must be large enough to produce a clinically significant decrease in pH to be considered concomitant acute ventilatory failure
      • In some patients with pre-existing chronic hypoventilation (with chronically elevated bicarbonate), an acute decrease in serum bicarbonate (due to an unrelated metabolic acidosis) may be sufficient to produce acidemia without technically being due to concomitant acute ventilatory failure -> in such cases, the clinical context of the combined acid-base disturbance is crucial to correctly interpret the respiratory component
        • Example: 50 y/o morbidly obese male with prior history of obstructive sleep apnea and associated chronic hypoventilation (baseline ABG: ph 7.40, pCO2 60 and serum bicarbonate: 36), now presents with superimposed diabetic ketoacidosis (current ABG: pH 7.22, pCO2 60, serum bicarbonate: 24) -> in this example, without a prior ABG (indicating the presence of chronic hypoventilation), the patient might be mistakenly interpreted to have acute ventilatory failure

Classification Schemes for Respiratory Failure

Classification Based on the Predominant Gas Exchange Abnormality and Time of Onset

Type 1-Hypoxemic Respiratory Failure

  • Etiology: associated with any type of lung disease which results in alveolar filling and/or atelectasis (collapse)
  • Subtypes
    • Acute Hypoxemic Respiratory Failure (see Hypoxemia, [[Hypoxemia]])
    • Chronic Hypoxemic Respiratory Failure (see Hypoxemia, [[Hypoxemia]])

Type II-Ventilatory/Hypercapnic Respiratory Failure (aka Hypoxemic-Hypercapnic Respiratory Failure)

  • Etiology: associated with only specific types of lung disease
  • Subtypes: the accompanying pH depends on the level of serum bicarbonate (which is dependent on the duration of the hypercapnia)
    • Acute Hypercapnic Respiratory Failure (see Acute Hypoventilation, [[Acute Hypoventilation]]): pH may be more decreased (due to inadequate time for renal reabsorption of bicarbonate)
    • Chronic Hypercapnic Respiratory Failure (see Chronic Hypoventilation, [[Chronic Hypoventilation]]): pH generally normal or only slightly decreased (due to prolonged duration, allowing for renal reabsorption of bicarbonate)

Potential Clinical Exceptions to This Classification Scheme

  • Exception: patient with prolonged, severe hypoxemia (initially classified as type I-acute hypoxemic respiratory failure), with the inability to maintain the required work of breathing, subsequently resulting in acute respiratory muscle fatigue with onset of acute hypercapnia (now classified as type II-hypercapnic/ventilatory failure) -> note that the classification of the patient’s respiratory failure changed during their clinical course
    • Example: 50 y/o WM with history of COPD and AIDS, presenting with PCP and severe acute hypoxemia
  • Exception: patient with increased work of breathing/increased minute ventilation (due to severe metabolic acidosis) without significant hypoxemia or hypercapnia -> note that such a patient may manifest imminent “respiratory failure”, although not technically fulfilling the criteria for either type I or type II respiratory failure
    • Example: 30 y/o WM with severe diabetic ketoacidosis (pH 6.9/pCO2 20/pO2 65/bicarb 3 + RR 36)

Classification Based on Anatomic Site of Dysfunction

  • Obstructive Lung Disease
    • Example: Airway Tumors
    • Example: Asthma
    • Example: Chronic Obstructive Pulmonary Disease (COPD)
    • Example: Mucous Plugging of Airway
  • Alveolar Disease
    • Example: Acute Lung Injury (ALI)/Adult Respiratory Distress Syndrome (ARDS)
    • Example: Diffuse Alveolar Hemorrhage (DAH)
    • Example: Pneumonia
    • Example: Pulmonary Alveolar Proteinosis (PAP)
    • Example: Pulmonary Edema
  • Interstitial Lung Disease (ILD)
    • Example: Acute Lung Injury (ALI)/Adult Respiratory Distress Syndrome (ARDS)
    • Example: Hypersensitivity Pneumonitis (HP)
    • Example: Idiopathic Pulmonary Fibrosis (IPF)
    • Example: Viral Pneumonia
  • Cardiac/Pulmonary Vascular Disease
    • Example: Congestive Heart Failure (CHF)
    • Example: Idiopathic Pulmonary Arterial Hypertension (IPAH)
    • Example: Intracardiac Shunt
    • Example: Intrapulmonary Shunt
    • Example: Pulmonary Edema
    • Example: Pulmonary Embolism
  • Pleural Disease
    • Example: Fibrothorax
    • Example: Pleural Effusion
    • Example: Pneumothorax
  • Neuromuscular Disease
    • Example: Guillain-Barre Syndrome (GBS)
    • Example: Myastenia Gravis
    • Example: Myopathy

Classification Based on Pathophysiologic Mechanism

  • Decreased Inspired Oxygen Pressure
    • ABG (typical)
      • pCO2: Normal-Decreased
      • pO2: Decreased
  • Acute Hypoventilation
    • ABG (typical)
      • pH: Decreased (acidemia)
      • pCO2: Increased
      • pO2: Decreased
      • Serum Bicarbonate: Normal
  • Chronic Hypoventilation
    • ABG (typical)
      • pH: Near Normal
      • pCO2: Increased
      • pO2: Decreased
      • Serum Bicarbonate: Increased
  • V/Q Mismatch
    • ABG (typical)
      • pCO2: Normal-Decreased
      • pO2: Decreased
  • Shunt
    • ABG (typical)
      • pCO2: Normal-Decreased
      • pO2: Decreased
  • Diffusion Impairment
    • ABG (typical)
      • pCO2: Normal-Decreased
      • pO2: Decreased

Etiology-Overview


Etiology of Type I-Hypoxemic Respiratory Failure

Type I-Acute Hypoxemic Respiratory Failure (Acute Hypoxemia) (see Hypoxemia, [[Hypoxemia]])

  • xxxx

Type I-Chronic Hypoxemic Respiratory Failure (Chronic Hypoxemia) (see Hypoxemia, [[Hypoxemia]])

  • xxxxx

Etiology of Type II-Hypoxemic, Hypercapnic Respiratory Failure

Type II-Acute Hypoxemic, Hypercapnic Respiratory Failure

Disorders with Decreased Ventilatory Drive

  • Metabolic Alkalosis (see Metabolic Alkalosis, [[Metabolic Alkalosis]]): elevated serum bicarbonate increases serum pH, resulting in a physiologic decrease in the central respiratory drive
  • Chemosensitivity Disorders
    • Carotid Body Dysfunction (see Carotid Body Dysfunction, [[Carotid Body Dysfunction]])
      • Bilateral Carotid Endarterectomy (see Carotid Endarterectomy, [[Carotid Endarterectomy]])
        • Physiology: destruction of peripheral chemoreceptors with resulting decreased hypoxic ventilatory response and a slight increase in the resting arterial pCO2
      • Carotid Body Resection (Glomectomy) (see Carotid Body Resection, [[Carotid Body Resection]])
        • Formerly Used as a Treatment for Asthma and Dyspnea in Severe COPD
    • Hypercapnia (“CO2 Narcosis”) (see Hypercapnia, [[Hypercapnia]]): worsens central hypoventilation
    • Hypothyroidism (see Hypothyroidism, [[Hypothyroidism]]): hypothyroidism-associated chronic hypoventilation is due to a combination of decreased central respiratory drive, phrenic neuropathy, and respiratory muscle myopathy
  • Acute Brainstem Disease
    • Autonomic Insufficiency Syndrome (Dysautonomia) (see Autonomic Insufficiency Syndrome, [[Autonomic Insufficiency Syndrome (Dysautonomia)]])
    • Brainstem Abscess (see Brain Abscess, [[Brain Abscess]])
    • Brainstem Encephalitis (see Encephalitis, [[Encephalitis]])
    • Brainstem Hemorrhage (see Intracerebral Hemorrhage, [[Intracerebral Hemorrhage]])
    • Brainstem Cerebrovascular Accident (CVA) (see Ischemic Cerebrovascular Accident, [[Ischemic Cerebrovascular Accident]])
    • Brainstem Multiple Sclerosis (see Multiple Sclerosis, [[Multiple Sclerosis]])
    • Brainstem Neoplasm
    • Brainstem Poliomyelitis (see Poliomyelitis, [[Poliomyelitis]])
    • Brainstem Sarcoidosis (see Sarcoidosis, [[Sarcoidosis]])
    • Hypogonadism with Testosterone Administration (see Hypogonadism, [[Hypogonadism]])
    • Obesity Hypoventilation Syndrome (see Obesity Hypoventilation Syndrome, [[Obesity Hypoventilation Syndrome]]): mechanism likely a combination of chest wall restriction + decreased central respiratory drive
    • Prader-Willi Syndrome (see Prader-Willi Syndrome, [[Prader-Willi Syndrome]]): impaired hypoxic/hypercapnic ventilatory drive
    • Primary Alveolar Hypoventilation Syndrome (Ondine’s Curse) (see Primary Alveolar Hypoventilation Syndrome, [[Primary Alveolar Hypoventilation Syndrome]])
    • Pharmacologic Central Respiratory Depression
      • Opiates (see Opiates, [[Opiates]])
      • Benzodiazepines (see Benzodiazepines, [[Benzodiazepines]])
      • Barbiturates (see Barbiturates, [[Barbiturates]])
      • Etomidate (Amidate) (see Etomidate, [[Etomidate]])
      • Intoxications
      • Ketamine (see Ketamine, [[Ketamine]]): respiratory depression may occur with rapid administration or overdosage
      • Propofol (Diprivan) (see Propofol, [[Propofol]])
    • Starvation
      • Physiology
        • Decreased Hypoxic Ventilatory Response: decreases approximately 40% in normal subjects after 10 days of 500 kcal/day dietary restriction (NEJM, 1976) [MEDLINE]
        • Little Change in Hypercapnic Ventilatory Response

Disorders with Decreased Ventilatory Output (Despite Increased Ventilatory Effort) Due to Neuromuscular Disease

  • Acute Spinal Cord Disease
    • High Cervical (Above C3) or Low-Mid Cervical (C3-C8) Spinal Cord Disease (see Cervical Spinal Cord Disease, [[Cervical Spinal Cord Disease]])
      • Atlantoaxial Subluxation/Instability (see Atlantoaxial Instability, [[Atlantoaxial Instability]]): associated with rheumatoid arthritis
      • Cervical Disk Disease with Cord Compression
      • Cervical Osteoarthritis
      • Cervical Space-Occupying Lesions
      • Cervical Spinal Cord Infarction (see Spinal Cord Infarction, [[Spinal Cord Infarction]])
      • Cervical Spine Trauma with Cord Injury
      • Diastematomyelia: bony spur in spinal canal, which may compress cervical spinal cord
      • Post-Cervical Cordotomy: procedure done to achieve pain control may damage ascending and descending tracts
      • Spondylolisthesis/Cervical Spondylosis
      • Syringomelia (see Syringomelia, [[Syringomelia]]): cavitation of central cord
      • Thoracic Outlet Syndrome (see Thoracic Outlet Syndrome, [[Thoracic Outlet Syndrome]])
      • Transverse Myelitis (see Transverse Myelitis, [[Transverse Myelitis]])
    • Cervical Root Disease (see Cervical Root Disease, [[Cervical Root Disease]])
      • Cervical Osteoarthritis
        • Clinical: with bilateral C3-C5 compression
      • Cervical Spine Manipulation
        • Clinical: with bilateral C3-C5 compression
      • Cervical Mass Lesion
        • Clinical: with bilateral C3-C5 compression
      • Herpes Zoster (see Varicella-Zoster Virus, [[Varicella-Zoster Virus]])
        • Clinical: bilaterally involving C3-C5
      • Multiple Sclerosis (see Multiple Sclerosis, [[Multiple Sclerosis]])
      • Clinical: bilaterally involving C3-C5
      • Neuralgic Amyotrophy
        • Clinical: bilaterally involving C3-C5 (usually affects brachial plexus)
  • Acute Motor Neuron Disease
    • Amyotrophic Lateral Sclerosis (ALS) (see Amyotrophic Lateral Sclerosis, [[Amyotrophic Lateral Sclerosis]])
      • Upper and lower motor neuron disease
      • Acute ventilatory failure may be the initial presentation of ALS
    • Kennedy Disease: lower motor neuron disease due to androgen receptor mutation (X-linked) with age of onset from adolescence-old age in males
    • Poliomyelitis (see Poliomyelitis, [[Poliomyelitis]])
    • Post-Polio Syndrome (see Poliomyelitis, [[Poliomyelitis]])
    • Primary Lateral Sclerosis: upper motor neuron disease
    • Progressive Muscular Atrophy (PMA): lower motor neuron disease
    • Spinal Muscular Atrophies: lower motor neuron disease
    • Strychnine Intoxication (see Strychnine, [[Strychnine]])
    • Survival of Motor Neuron (SMN) Protein-Associated Spinal Muscular Atrophy (all involve gene defect of the Survival of Motor Neuron protein)
      • Werdnig-Hoffman Disease (Type 1): lower motor neuron disease with onset at 0-6 mo
      • Type 2 Survival of Motor Neuron Protein-Associated Spinal Muscular Atrophy: lower motor neuron disease with onset at 7-18 mo
      • Kugelberg-Welander Disease (Type 3): lower motor neuron disease with onset at >18 mo
      • Adult-Onset (Type 4) Survival of Motor Neuron Protein-Associated Spinal Muscular Atrophy: lower motor neuron disease with adult onset
    • Tetanus (see Tetanus, [[Tetanus]])
      • Mechanism: damaged upper motor neurons can no longer inhibit lower motor neurons
  • Acute Peripheral Neuropathy (see Phrenic Neuropathy, [[Phrenic Neuropathy]])
    • Infection/Toxin
    • Alcoholic Neuropathy (see Alcoholic Neuropathy, [[Alcoholic Neuropathy]])
    • Buckthorn Berry Intoxication (see Buckthorn Berry Intoxication, [[Buckthorn Berry Intoxication]])
    • Diphtheria (see Diphtheria, [[Diphtheria]])
    • Lyme Disease (see Lyme Disease, [[Lyme Disease]])
    • Neurotoxic Shellfish Poisoning (see Neurotoxic Shellfish, [[Neurotoxic Shellfish]])
      • Epidemiology: associated with ingestion of brevetoxin-contaminated bivalve shellfish
      • Physiology: brevetoxins
      • Clinical: descending paralysis (similar to botulism and in contrast to ascending paralysis seen in GBS and tick paralysis)
    • Paralytic Shellfish Poisoning (see Paralytic Shellfish, [[Paralytic Shellfish]])
      • Epidemiology: associated with ingestion of saxitoxin-contaminated bivalve mollusks (cockles, salt and fresh water mussels, butter/little neck clams, scallops, oysters), gastropod mollusks (whelk, abalone, snails), crustaceans (dungeness crabs, shrimp, lobster), and zooplanktivorous fish (atlantic salmon, herring, mackerel)
      • Physiology: saxitoxins
      • Clinical: descending paralysis (similar to botulism and in contrast to ascending paralysis seen in GBS and tick paralysis)
    • Poisonous Lizard Bite (see Poisonous Lizard Bite, [[Poisonous Lizard Bite]])
    • Rabies (see Rabies, [[Rabies]]): ascending paralysis (may mimic that of Guillian-Barre syndrome)
    • Widow Spider Bite (see Widow Spider Bite, [[Widow Spider Bite]])
    • Other
      • Acute Intermittent Porphyria (see Acute Intermittent Porphyria, [[Acute Intermittent Porphyria]])
      • Chronic Inflammatory Demyelinating Polyneuropathy (see Chronic Inflammatory Demyelinating Polyneuropathy, [[Chronic Inflammatory Demyelinating Polyneuropathy]])
      • Critical Illness Polyneuropathy (see ICU-Acquired Weakness, [[ICU-Acquired Weakness]])
      • Diabetic Neuropathy (see Diabetic Neuropathy, [[Diabetic Neuropathy]])
      • Guillain-Barre Syndrome (see Guillain-Barre Syndrome, [[Guillain-Barre Syndrome]])
        • Epidemiology
        • GBS is the Most Common Etiology of Acute Paralysis and Neuromuscular Ventilatory Failure Presenting to Acute Care Hospitals
        • Clinical
        • Approximately 33% of Cases Develop Acute Ventilatory Failure
        • May Be Acute or Subacute
        • Ascending Paralysis (Similar to Tick Paralysis)
      • Hypothyroidism (see Hypothyroidism, [[Hypothyroidism]]): hypothyroidism-associated chronic hypoventilation is due to a combination of decreased central respiratory drive, phrenic neuropathy, and respiratory muscle myopathy
      • Idiopathic Peripheral Neuropathy
      • Mediastinal/Esophageal Surgical Injury or Traumatic Injury of Bilateral Phrenic Nerves
        • Phrenic nerve injury occurs in 2-20% of open heart surgery cases
        • L>R sided injury
        • Mechanisms: cold cardioplegia, dissection of LIMA, and/or stretching of phrenic nerve
      • Multiple Sclerosis (see Multiple Sclerosis, [[Multiple Sclerosis]])
      • Neurofibromatosis (see Neurofibromatosis, [[Neurofibromatosis]]): case report of bilateral diaphragmatic paralysis
      • Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus, [[Systemic Lupus Erythematosus]]): neuropathy with vasculitis of phrenic nerves + myopathy
  • Acute Neuromuscular Junction Disease (Involving the Respiratory Muscles)
    • Myasthenia Gravis (see Myasthenia Gravis, [[Myasthenia Gravis]]): acute ventilatory failure may be the initial presentation of myasthenia gravis
    • Lambert-Eaton Myasthenic Syndrome (LEMS)(see Lambert-Eaton Myasthenic Syndrome, [[Lambert-Eaton Myasthenic Syndrome]])
    • Botulism (see Botulism, [[Botulism]]): botulinum toxin blocks acetylcholine release at neuromuscular junction
      • Descending paralysis (similar to paralytic-neurotoxic shellfish poisoning)
    • Tick Paralysis (see Tick Paralysis, [[Tick Paralysis]]): toxin probably impairs acetylcholine mobilization at motor nerve terminal
      • Ascending paralysis (similar to Guillian-Barre syndrome)
    • Snake Bite: due to various types of neurotoxins in venom
      • Mojave Rattlesnake (Crotalus Scutulatus) (see Rattlesnake Bite, [[Rattlesnake Bite]]): Fasciculin toxin (destroys acetylcholinesterase, resulting in tetany)
      • Cobra/King Cobra: α-neurotoxins (inhibition at acetylcholine receptor)
      • Sea Snake: α-neurotoxins (inhibition at acetylcholine receptor)
      • Mamba: Fasciculin toxin (destroys acetylcholinesterase, resulting in tetany) and Dendrotoxin (blocks ion channels -> blocks nerve transmission)
    • Organophosphate Intoxication (see Organophosphates-Carbamates, [[Organophosphates-Carbamates]]) [MEDLINE]
    • Carbamate Intoxication (see Organophosphates-Carbamates, [[Organophosphates-Carbamates]]) [MEDLINE]
    • VX Nerve Agent (see VX Nerve Agent, [[VX Nerve Agent]])
    • Pharmacologic Neuromuscular Junction Antagonists
      • Aminoglycosides (see Aminoglycosides, [[Aminoglycosides]]): usually clinically relevant only in the presence of other neuromuscular junction disease
      • Anticholinergics (see xxxx, [[xxxx]]): usually clinically relevant only in the presence of other neuromuscular disease
      • Fluoroquinolones (see Fluoroquinolones, [[Fluoroquinolones]]): usually clinically relevant only in the presence of other neuromuscular disease
      • Procainamide (see Procainamide, [[Procainamide]]): usually clinically relevant only in the presence of other neuromuscular disease
      • Polymyxin B (see Polymyxins, [[Polymyxins]]): usually clinically relevant only in the presence of other neuromuscular disease
      • Sodium Colistimethate (aka Colistin, Polymyxin E) (see Polymyxins, [[Polymyxins]]): usually clinically relevant only in the presence of other neuromuscular disease
      • Paralytics: Succinylcholine, Aminosteroid Non-Depolarizing Blockers (Pancuronium, Vecuronium, etc), Benzylisoquinolone Non-Depolarizing Blockers (Atracurium, etc)
  • Acute Myopathy/Muscle Dysfunction (Involving Respiratory Muscles) (see Myopathy, [[Myopathy]])
    • Periodic Paralysis Syndromes
    • Rheumatologic
    • Electrolyte-Related
    • Other
      • Bilateral Diaphragmatic Paralysis (see Bilateral Diaphragmatic Paralysis, [[Bilateral Diaphragmatic Paralysis]])
      • Critical Illness Polymyopathy (see ICU-Acquired Weakness, [[ICU-Acquired Weakness]])
      • Necrotizing Myopathy from Steroids + Neuromuscular Junction Antagonists
      • Hyperthyroidism (see Hyperthyroidism, [[Hyperthyroidism]])
        • Proximal and Distal Myopathy: manifests as both inspiratory and expiratory muscle weakness
      • Hypothyroidism (see Hypothyroidism, [[Hypothyroidism]]): hypothyroidism-associated chronic hypoventilation is due to a combination of decreased central respiratory drive, phrenic neuropathy, and respiratory muscle myopathy
        • Manifests as Both Inspiratory and Expiratory Muscle Weakness

Disorders with Decreased Ventilatory Output (Despite Increased Ventilatory Effort) Due to Excessive Ventilatory Demand

  • Acute Upper Airway Obstruction (with Increased Work of Breathing) (see Obstructive Lung Disease, [[Obstructive Lung Disease]])
    • Bilateral Vocal Fold Immobility (BVFI) (see Bilateral Vocal Fold Immobility, [[Bilateral Vocal Fold Immobility]])
      • Cricoarytenoid Arthritis (see Cricoarytenoid Arthritis, [[Cricoarytenoid Arthritis]])
      • Laryngeal Inflammation
      • Laryngospasm (see Laryngospasm, [[Laryngospasm]])
      • Neurologic Disease/Dysfunction Involving the Vocal Folds (Vocal Cord Paralysis)
      • Developmental Abnormality or Neoplasm the Involving Vocal Folds
      • Intubation Injury to Vocal Folds
      • Mechanical/Iatrogenic Injury to Vocal Folds
      • Surgical Injury to Vocal Folds
    • Other Upper Airway Disease (see Obstructive Lung Disease, [[Obstructive Lung Disease]])
      • Infection
        • Coccidioidomycosis (see Coccidioidomycosis, [[Coccidioidomycosis]]): typically mild upper airway obstruction
        • Croup (see Croup, [[Croup]]): typically acute
        • Cryptococcosis (see Cryptococcosis, [[Cryptococcosis]]): typically mild upper airway obstruction
        • Deep Neck Infection (see Deep Neck Infection, [[Deep Neck Infection]]): typically acute
        • Peritonsillar Abscess (see Peritonsillar Abscess, [[Peritonsillar Abscess]]): involving peritonsillar space
        • Pretracheal Abscess (see Pretracheal Abscess, [[Pretracheal Abscess]]): involving pretracheal space
        • Retropharyngeal Abscess (see Retropharyngeal Abscess, [[Retropharyngeal Abscess]]): involving retropharyngeal space
        • Submandibular Space Abscess/Ludwig’s Angina (see Ludwig’s Angina, [[Ludwigs Angina]]): involving submandibular space
        • Diphtheria (see Diphtheria, [[Diphtheria]]): typically acute
        • Epiglottitis (see Epiglottitis, [[Epiglottitis]]): typically acute
        • Histoplasmosis (see Histoplasmosis, [[Histoplasmosis]]): typically mild upper airway obstruction
        • Syphilis (see Syphilis, [[Syphilis]])
      • Neurologic
        • Altered Mental Status with Inability to Protect Upper Airway: typically acute
        • Essential Tremor (see Essential Tremor, [[Essential Tremor]]): typically mild upper airway obstruction
        • Parkinson’s Disease (see Parkinson’s Disease, [[Parkinsons Disease]]): may cause acute upper airway obstruction in the post-operative setting or progressive upper airway dysfunction
      • Miscellaneous
        • Ammonia Inhalation (see Ammonia, [[Ammonia]]): typically acute
        • Anaphylaxis (see Anaphylaxis, [[Anaphylaxis]]): typically acute
        • Angioedema (see Angioedema, [[Angioedema]]): typically acute
        • Congenital Small Cricoid Cartilage: typically progressive
        • Esophageal Foreign Body: extrinsic compression of upper airway, typically progressive
        • Langerhans Cell Histiocytosis (see Langerhans Cell Histiocytosis, [[Langerhans Cell Histiocytosis]]): typically mild upper airway obstruction
        • Laryngeal Cyst/Laryngocele: typically mild upper airway obstruction
        • Laryngeal Rheumatoid Nodule (see Rheumatoid Arthritis, [[Rheumatoid Arthritis]]): typically progressive
        • Macroglossia: typically mild upper airway obstruction
        • Nasal Polyps (see Nasal Polyps, [[Nasal Polyps]]): typically mild upper airway obstruction
        • Obstructive Sleep Apnea (OSA) (see Obstructive Sleep Apnea, [[Obstructive Sleep Apnea]]): may cause acute upper airway obstruction in the post-operative setting
        • Thermal Injury/Burns of Upper Airway (see Smoke Inhalation, [[Smoke Inhalation]]): thermal injury is usually supraglottic (typically, laryngeal injury) and may be acute
        • Thyromegaly/Goiter (see Goiter, [[Goiter]]): typically progressive
        • Tracheal Cyst: typically progressive
        • Tracheobronchomalacia (see Tracheobronchomalacia, [[Tracheobronchomalacia]]): typically progressive
        • Tonsillar/Adenoid Enlargement: typically progressive
        • Unilateral Vocal Cord Paralysis (see Unilateral Vocal Fold Immobility, [[Unilateral Vocal Fold Immobility]]): typically mild upper airway obstruction
      • Upper Airway Foreign Body (see Foreign Body, [[Foreign Body]]): typically acute
  • Acute Obstructive Lung Disease (with Increased Work of Breathing) (see Obstructive Lung Disease, [[Obstructive Lung Disease]])
    • Acute Tracheobronchial Obstruction
      • Tracheobronchial Infection
      • Tracheobronchial Neoplasm
        • Primary Tracheobronchial Tumor
        • Endobronchial Metastases
      • Extrinsic Tracheobronchial Compression
      • Other Tracheobronchial Obstructive Process
    • Asthma Exacerbation (see Asthma, [[Asthma]])
    • Bronchiectasis Exacerbation (see Bronchiectasis, [[Bronchiectasis]])
    • Chronic Obstructive Pulmonary Disease (COPD) Exacerbation (see Chronic Obstructive Pulmonary Disease, [[Chronic Obstructive Pulmonary Disease]])
    • Cystic Fibrosis Exacerbation (see Cystic Fibrosis, [[Cystic Fibrosis]])
  • Acute Parenchymal Lung Disease (with Increased Work of Breathing)
    • Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]])
    • Aspiration Pneumonia (see Aspiration Pneumonia, [[Aspiration Pneumonia]])
    • Cardiogenic Pulmonary Edema (see Congestive Heart Failure, [[Congestive Heart Failure]])
    • Diffuse Alveolar Hemorrhage (DAH) (see Diffuse Alveolar Hemorrhage, [[Diffuse Alveolar Hemorrhage]])
    • Idiopathic Pulmonary Fibrosis (IPF) (see Idiopathic Pulmonary Fibrosis, [[Idiopathic Pulmonary Fibrosis]]: acute ventilatory failure may be manifested as the end-stage of the IPF or more commonly, in conjunction with pneumonia, surgery, or other illness
      • In end-stage IPF requiring mechanical ventilation, lung compliance has been noted to be significantly decreased
    • Pneumonia (see Pneumonia, [[Pneumonia]])
  • Acute Pleural or Chest Wall Disease (with Increased Work of Breathing)
  • Increased Dead Space Ventilation (Increased VD/VT Ratio)
    • Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]]): very low V/Q and/or intrapulmonary shunt
    • Acute Pulmonary Embolism (see Acute Pulmonary Embolism, [[Acute Pulmonary Embolism]]): localized pulmonary hypoperfusion
    • Air Embolism (see Air Embolism, [[Air Embolism]]): venous air ambolism -> localized pulmonary hypoperfusion
    • Cardiogenic Shock (see Cardiogenic Shock, [[Cardiogenic Shock]]): generalized pulmonary hypoperfusion
    • COPD Exacerbation (see Chronic Obstructive Pulmonary Disease, [[Chronic Obstructive Pulmonary Disease]]): very high V/Q
    • Hypovolemic Shock (see Hypovolemic Shock, [[Hypovolemic Shock]]): generalized pulmonary hypoperfusion
    • Pulmonary Hyperinflation (Excessive Exogenous PEEP or Auto-PEEP): generalized pulmonary hypoperfusion
    • Sickle Cell Acute Chest Syndrome (see Sickle Cell Disease, [[Sickle Cell Disease]])
    • Ventilation During Cardiopulmonary Resuscitation (CPR) (see Cardiopulmonary Resuscitation, [[Cardiopulmonary Resuscitation]]): generalized pulmonary hypoperfusion
  • Increased Carbon Dioxide Production
    • Inflammation/Hypermetabolism
      • Fever (see Fever, [[Fever]])
      • Burns (see Burns, [[Burns]])
      • Sepsis (see Sepsis, [[Sepsis]])
      • Severe Trauma
    • Muscle Activity
    • Excessive Caloric Intake
      • Excessive Caloric Intake: especially carbohydrates (which generate more carbon dioxide per calorie than fats)
  • Exogenous Carbon Dioxide Inhalation
    • Carbon Dioxide Rebreathing
    • Industrial/Laboratory Accident

Type II-Chronic Hypoxemic, Hypercapnic Respiratory Failure

Disorders with Decreased Ventilatory Drive

  • Metabolic Alkalosis (see Metabolic Alkalosis, [[Metabolic Alkalosis]]): elevated serum bicarbonate increases serum pH, resulting in a physiologic decrease in the central respiratory drive
  • Chemosensitivity Disorders
    • Carotid Body Dysfunction (see Carotid Body Dysfunction, [[Carotid Body Dysfunction]])
      • Bilateral Carotid Endarterectomy (see Carotid Endarterectomy, [[Carotid Endarterectomy]])
        • Physiology: destruction of peripheral chemoreceptors with resulting decreased hypoxic ventilatory response and a slight increase in the resting arterial pCO2
      • Carotid Body Resection (Glomectomy) (see Carotid Body Resection, [[Carotid Body Resection]])
        • Formerly Used as a Treatment for Asthma and Dyspnea in Severe COPD
    • Central Sleep Apnea (see Central Sleep Apnea, [[Central Sleep Apnea]])
    • Chronic Mountain Sickness (Monge Disease) (see Chronic Mountain Sickness, [[Chronic Mountain Sickness]]): chronic hypoxia
    • Hypercapnia (“CO2 Narcosis”) (see Hypercapnia, [[Hypercapnia]]): worsens central hypoventilation
    • Hypothyroidism (see Hypothyroidism, [[Hypothyroidism]]): hypothyroidism-associated chronic hypoventilation is due to a combination of decreased central respiratory drive, phrenic neuropathy, and respiratory muscle myopathy
  • Chronic Brainstem Disease
    • Autonomic Insufficiency Syndrome (Dysautonomia) (see Autonomic Insufficiency Syndrome, [[Autonomic Insufficiency Syndrome (Dysautonomia)]])
    • Brainstem Abscess (see Brain Abscess, [[Brain Abscess]])
    • Brainstem Encephalitis (see Encephalitis, [[Encephalitis]])
    • Brainstem Intracerebral Hemorrhage (Hemorrhagic Cerebrovascular Accident) (see Intracerebral Hemorrhage, [[Intracerebral Hemorrhage]])
    • Brainstem Ischemic Cerebrovascular Accident (CVA) (see Ischemic Cerebrovascular Accident, [[Ischemic Cerebrovascular Accident]])
    • Brainstem Multiple Sclerosis (see Multiple Sclerosis, [[Multiple Sclerosis]])
    • Brainstem Neoplasm
    • Brainstem Poliomyelitis (see Poliomyelitis, [[Poliomyelitis]])
    • Brainstem Sarcoidosis (see Sarcoidosis, [[Sarcoidosis]])
    • Hypogonadism with Testosterone Administration (see Hypogonadism, [[Hypogonadism]])
    • Obesity Hypoventilation Syndrome (see Obesity Hypoventilation Syndrome, [[Obesity Hypoventilation Syndrome]]): mechanism likely a combination of chest wall restriction + decreased central respiratory drive
    • Prader-Willi Syndrome (see Prader-Willi Syndrome, [[Prader-Willi Syndrome]]): impaired hypoxic/hypercapnic ventilatory drive
    • Primary Alveolar Hypoventilation Syndrome (Ondine’s Curse) (see Primary Alveolar Hypoventilation Syndrome, [[Primary Alveolar Hypoventilation Syndrome]])
    • Pharmacologic Central Respiratory Depression
    • Starvation
      • Physiology
        • Decreased Hypoxic Ventilatory Response: decreases approximately 40% in normal subjects after 10 days of 500 kcal/day dietary restriction (NEJM, 1976) [MEDLINE]
        • Little Change in Hypercapnic Ventilatory Response

Disorders with Decreased Ventilatory Output (Despite Increased Ventilatory Effort) Due to Neuromuscular Disease

  • Spinal Cord Disease
    • High Cervical (Above C3) or Low-Mid Cervical (C3-C8) Spinal Cord Disease (see Cervical Spinal Cord Disease, [[Cervical Spinal Cord Disease]])
      • Atlantoaxial Subluxation/Instability (see Atlantoaxial Instability, [[Atlantoaxial Instability]]): associated with rheumatoid arthritis
      • Cervical Disk Disease with Cord Compression
      • Cervical Osteoarthritis
      • Cervical Space-Occupying Lesions
      • Cervical Spinal Cord Infarction (see Spinal Cord Infarction, [[Spinal Cord Infarction]])
      • Cervical Spine Trauma with Cord Injury
      • Diastematomyelia: bony spur in spinal canal, which may compress cervical spinal cord
      • Post-Cervical Cordotomy: procedure done to achieve pain control may damage ascending and descending tracts
      • Spondylolisthesis/Cervical Spondylosis
      • Syringomelia (see Syringomelia, [[Syringomelia]]): cavitation of central cord
      • Thoracic Outlet Syndrome (see Thoracic Outlet Syndrome, [[Thoracic Outlet Syndrome]])
      • Transverse Myelitis (see Transverse Myelitis, [[Transverse Myelitis]])
    • Cervical Root Disease (see Cervical Root Disease, [[Cervical Root Disease]])
      • Cervical Osteoarthritis
        • Clinical: with bilateral C3-C5 compression
      • Cervical Spine Manipulation
        • Clinical: with bilateral C3-C5 compression
      • Cervical Mass Lesion
        • Clinical: with bilateral C3-C5 compression
      • Herpes Zoster (see Varicella-Zoster Virus, [[Varicella-Zoster Virus]])
        • Clinical: bilaterally involving C3-C5
      • Multiple Sclerosis (see Multiple Sclerosis, [[Multiple Sclerosis]])
      • Clinical: bilaterally involving C3-C5
      • Neuralgic Amyotrophy
        • Clinical: bilaterally involving C3-C5 (usually affects brachial plexus)
  • Motor Neuron Disease
    • Amyotrophic Lateral Sclerosis (ALS) (see Amyotrophic Lateral Sclerosis, [[Amyotrophic Lateral Sclerosis]])
      • Upper and lower motor neuron disease
      • Acute ventilatory failure may be the initial presentation of ALS
    • Kennedy Disease: lower motor neuron disease due to androgen receptor mutation (X-linked) with age of onset from adolescence-old age in males
    • Poliomyelitis (see Poliomyelitis, [[Poliomyelitis]])
    • Post-Polio Syndrome (see Poliomyelitis, [[Poliomyelitis]])
    • Primary Lateral Sclerosis: upper motor neuron disease
    • Progressive Muscular Atrophy (PMA): lower motor neuron disease
    • Spinal Muscular Atrophies: lower motor neuron disease
    • Strychnine Intoxication (see Strychnine, [[Strychnine]])
    • Survival of Motor Neuron (SMN) Protein-Associated Spinal Muscular Atrophy (all involve gene defect of the Survival of Motor Neuron protein)
      • Werdnig-Hoffman Disease (Type 1): lower motor neuron disease with onset at 0-6 mo
      • Type 2 Survival of Motor Neuron Protein-Associated Spinal Muscular Atrophy: lower motor neuron disease with onset at 7-18 mo
      • Kugelberg-Welander Disease (Type 3): lower motor neuron disease with onset at >18 mo
      • Adult-Onset (Type 4) Survival of Motor Neuron Protein-Associated Spinal Muscular Atrophy: lower motor neuron disease with adult onset
    • Tetanus (see Tetanus, [[Tetanus]])
      • Mechanism: damaged upper motor neurons can no longer inhibit lower motor neurons
  • Peripheral Neuropathy (see Phrenic Neuropathy, [[Phrenic Neuropathy]])
    • Infection/Toxin
    • Alcoholic Neuropathy (see Alcoholic Neuropathy, [[Alcoholic Neuropathy]])
    • Buckthorn Berry Intoxication (see Buckthorn Berry Intoxication, [[Buckthorn Berry Intoxication]])
    • Diphtheria (see Diphtheria, [[Diphtheria]])
    • Lyme Disease (see Lyme Disease, [[Lyme Disease]])
    • Neurotoxic Shellfish Poisoning (see Neurotoxic Shellfish, [[Neurotoxic Shellfish]])
      • Epidemiology: associated with ingestion of brevetoxin-contaminated bivalve shellfish
      • Physiology: brevetoxins
      • Clinical: descending paralysis (similar to botulism and in contrast to ascending paralysis seen in GBS and tick paralysis)
    • Paralytic Shellfish Poisoning (see Paralytic Shellfish, [[Paralytic Shellfish]])
      • Epidemiology: associated with ingestion of saxitoxin-contaminated bivalve mollusks (cockles, salt and fresh water mussels, butter/little neck clams, scallops, oysters), gastropod mollusks (whelk, abalone, snails), crustaceans (dungeness crabs, shrimp, lobster), and zooplanktivorous fish (atlantic salmon, herring, mackerel)
      • Physiology: saxitoxins
      • Clinical: descending paralysis (similar to botulism and in contrast to ascending paralysis seen in GBS and tick paralysis)
    • Poisonous Lizard Bite (see Poisonous Lizard Bite, [[Poisonous Lizard Bite]])
    • Rabies (see Rabies, [[Rabies]]): ascending paralysis (may mimic that of Guillian-Barre syndrome)
    • Widow Spider Bite (see Widow Spider Bite, [[Widow Spider Bite]])
    • Other
      • Acute Intermittent Porphyria (see Acute Intermittent Porphyria, [[Acute Intermittent Porphyria]])
      • Chronic Inflammatory Demyelinating Polyneuropathy (see Chronic Inflammatory Demyelinating Polyneuropathy, [[Chronic Inflammatory Demyelinating Polyneuropathy]])
      • Critical Illness Polyneuropathy (see ICU-Acquired Weakness, [[ICU-Acquired Weakness]])
      • Diabetic Neuropathy (see Diabetic Neuropathy, [[Diabetic Neuropathy]])
      • Guillain-Barre Syndrome (see Guillain-Barre Syndrome, [[Guillain-Barre Syndrome]])
        • Epidemiology
        • GBS is the Most Common Etiology of Acute Paralysis and Neuromuscular Ventilatory Failure Presenting to Acute Care Hospitals
        • Clinical
        • Approximately 33% of Cases Develop Acute Ventilatory Failure
        • May Be Acute or Subacute
        • Ascending Paralysis (Similar to Tick Paralysis)
      • Hypothyroidism (see Hypothyroidism, [[Hypothyroidism]]): hypothyroidism-associated chronic hypoventilation is due to a combination of decreased central respiratory drive, phrenic neuropathy, and respiratory muscle myopathy
      • Idiopathic Peripheral Neuropathy
      • Mediastinal/Esophageal Surgical Injury or Traumatic Injury of Bilateral Phrenic Nerves
        • Phrenic nerve injury occurs in 2-20% of open heart surgery cases
        • L>R sided injury
        • Mechanisms: cold cardioplegia, dissection of LIMA, and/or stretching of phrenic nerve
      • Multiple Sclerosis (see Multiple Sclerosis, [[Multiple Sclerosis]])
      • Neurofibromatosis (see Neurofibromatosis, [[Neurofibromatosis]]): case report of bilateral diaphragmatic paralysis
      • Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus, [[Systemic Lupus Erythematosus]]): neuropathy with vasculitis of phrenic nerves + myopathy
  • Neuromuscular Junction Disease (Involving the Respiratory Muscles)
    • Myasthenia Gravis (see Myasthenia Gravis, [[Myasthenia Gravis]]): acute ventilatory failure may be the initial presentation of myasthenia gravis
    • Lambert-Eaton Myasthenic Syndrome (LEMS)(see Lambert-Eaton Myasthenic Syndrome, [[Lambert-Eaton Myasthenic Syndrome]])
    • Botulism (see Botulism, [[Botulism]]): botulinum toxin blocks acetylcholine release at neuromuscular junction
      • Descending paralysis (similar to paralytic-neurotoxic shellfish poisoning)
    • Tick Paralysis (see Tick Paralysis, [[Tick Paralysis]]): toxin probably impairs acetylcholine mobilization at motor nerve terminal
      • Ascending paralysis (similar to Guillian-Barre syndrome)
    • Organophosphate Intoxication (see Organophosphates-Carbamates, [[Organophosphates-Carbamates]]) [MEDLINE]
    • Carbamate Intoxication (see Organophosphates-Carbamates, [[Organophosphates-Carbamates]]) [MEDLINE]
    • Pharmacologic Neuromuscular Junction Antagonists
      • Aminoglycosides (see Aminoglycosides, [[Aminoglycosides]]): usually clinically relevant only in the presence of other neuromuscular junction disease
      • Anticholinergics (see xxxx, [[xxxx]]): usually clinically relevant only in the presence of other neuromuscular disease
      • Fluoroquinolones (see Fluoroquinolones, [[Fluoroquinolones]]): usually clinically relevant only in the presence of other neuromuscular disease
      • Procainamide (see Procainamide, [[Procainamide]]): usually clinically relevant only in the presence of other neuromuscular disease
      • Polymyxin B (see Polymyxins, [[Polymyxins]]): usually clinically relevant only in the presence of other neuromuscular disease
      • Sodium Colistimethate (aka Colistin, Polymyxin E) (see Polymyxins, [[Polymyxins]]): usually clinically relevant only in the presence of other neuromuscular disease
  • Acute Myopathy/Muscle Dysfunction (Involving Respiratory Muscles) (see Myopathy, [[Myopathy]])
    • Periodic Paralysis Syndromes
    • Rheumatologic
    • Electrolyte-Related
    • Other
      • Bilateral Diaphragmatic Paralysis (see Bilateral Diaphragmatic Paralysis, [[Bilateral Diaphragmatic Paralysis]])
      • Critical Illness Polymyopathy (see ICU-Acquired Weakness, [[ICU-Acquired Weakness]])
      • Necrotizing Myopathy from Steroids + Neuromuscular Junction Antagonists
      • Hyperthyroidism (see Hyperthyroidism, [[Hyperthyroidism]])
        • Proximal and Distal Myopathy: manifests as both inspiratory and expiratory muscle weakness
      • Hypothyroidism (see Hypothyroidism, [[Hypothyroidism]]): hypothyroidism-associated chronic hypoventilation is due to a combination of decreased central respiratory drive, phrenic neuropathy, and respiratory muscle myopathy
        • Manifests as Both Inspiratory and Expiratory Muscle Weakness

Disorders with Decreased Ventilatory Output (Despite Increased Ventilatory Effort) Due to Excessive Ventilatory Demand

  • Progressive Upper Airway Obstruction (with Increased Work of Breathing) (see Obstructive Lung Disease, [[Obstructive Lung Disease]])
    • Bilateral Vocal Fold Immobility (BVFI) (see Bilateral Vocal Fold Immobility, [[Bilateral Vocal Fold Immobility]])
      • Cricoarytenoid Arthritis (see Cricoarytenoid Arthritis, [[Cricoarytenoid Arthritis]])
      • Laryngeal Inflammation
      • Laryngospasm (see Laryngospasm, [[Laryngospasm]])
      • Neurologic Disease/Dysfunction Involving the Vocal Folds (Vocal Cord Paralysis)
      • Developmental Abnormality or Neoplasm the Involving Vocal Folds
      • Intubation Injury to Vocal Folds
      • Mechanical/Iatrogenic Injury to Vocal Folds
      • Surgical Injury to Vocal Folds
    • Other Upper Airway Disease (see Obstructive Lung Disease, [[Obstructive Lung Disease]])
      • Infection
        • Coccidioidomycosis (see Coccidioidomycosis, [[Coccidioidomycosis]]): typically mild upper airway obstruction
        • Croup (see Croup, [[Croup]]): typically acute
        • Cryptococcosis (see Cryptococcosis, [[Cryptococcosis]]): typically mild upper airway obstruction
        • Deep Neck Infection (see Deep Neck Infection, [[Deep Neck Infection]]): typically acute
        • Peritonsillar Abscess (see Peritonsillar Abscess, [[Peritonsillar Abscess]]): involving peritonsillar space
        • Pretracheal Abscess (see Pretracheal Abscess, [[Pretracheal Abscess]]): involving pretracheal space
        • Retropharyngeal Abscess (see Retropharyngeal Abscess, [[Retropharyngeal Abscess]]): involving retropharyngeal space
        • Submandibular Space Abscess/Ludwig’s Angina (see Ludwig’s Angina, [[Ludwigs Angina]]): involving submandibular space
        • Diphtheria (see Diphtheria, [[Diphtheria]]): typically acute
        • Epiglottitis (see Epiglottitis, [[Epiglottitis]]): typically acute
        • Histoplasmosis (see Histoplasmosis, [[Histoplasmosis]]): typically mild upper airway obstruction
        • Syphilis (see Syphilis, [[Syphilis]])
      • Neurologic
        • Essential Tremor (see Essential Tremor, [[Essential Tremor]]): typically mild upper airway obstruction
        • Parkinson’s Disease (see Parkinson’s Disease, [[Parkinsons Disease]]): may cause acute upper airway obstruction in the post-operative setting or progressive upper airway dysfunction
      • Miscellaneous
        • Congenital Small Cricoid Cartilage: typically progressive
        • Esophageal Foreign Body: extrinsic compression of upper airway, typically progressive
        • Langerhans Cell Histiocytosis (see Langerhans Cell Histiocytosis, [[Langerhans Cell Histiocytosis]]): typically mild upper airway obstruction
        • Laryngeal Cyst/Laryngocele: typically mild upper airway obstruction
        • Laryngeal Rheumatoid Nodule (see Rheumatoid Arthritis, [[Rheumatoid Arthritis]]): typically progressive
        • Macroglossia: typically mild upper airway obstruction
        • Nasal Polyps (see Nasal Polyps, [[Nasal Polyps]]): typically mild upper airway obstruction
        • Obstructive Sleep Apnea (OSA) (see Obstructive Sleep Apnea, [[Obstructive Sleep Apnea]]): may cause acute upper airway obstruction in the post-operative setting
        • Thermal Injury/Burns of Upper Airway (see Smoke Inhalation, [[Smoke Inhalation]]): thermal injury is usually supraglottic (typically, laryngeal injury) and may be acute
        • Thyromegaly/Goiter (see Goiter, [[Goiter]]): typically progressive
        • Tracheal Cyst: typically progressive
        • Tracheobronchomalacia (see Tracheobronchomalacia, [[Tracheobronchomalacia]]): typically progressive
        • Tonsillar/Adenoid Enlargement: typically progressive
        • Unilateral Vocal Cord Paralysis (see Unilateral Vocal Fold Immobility, [[Unilateral Vocal Fold Immobility]]): typically mild upper airway obstruction
  • Obstructive Lung Disease (with Increased Work of Breathing) (see Obstructive Lung Disease, [[Obstructive Lung Disease]])
    • Asthma (see Asthma, [[Asthma]])
    • Bronchiectasis (see Bronchiectasis, [[Bronchiectasis]])
    • Chronic Obstructive Pulmonary Disease (COPD) (see Chronic Obstructive Pulmonary Disease, [[Chronic Obstructive Pulmonary Disease]])
    • Chronic Tracheobronchial Obstruction
      • Tracheobronchial Infection
      • Tracheobronchial Neoplasm
        • Primary Tracheobronchial Tumor
        • Endobronchial Metastases
      • Extrinsic Tracheobronchial Compression
      • Other Tracheobronchial Obstructive Process
    • Cystic Fibrosis (CF) (see Cystic Fibrosis, [[Cystic Fibrosis]])
  • Parenchymal Lung Disease (with Increased Work of Breathing)
    • Diffuse Alveolar Hemorrhage (DAH) (see Diffuse Alveolar Hemorrhage, [[Diffuse Alveolar Hemorrhage]])
    • Idiopathic Pulmonary Fibrosis (IPF) (see Idiopathic Pulmonary Fibrosis, [[Idiopathic Pulmonary Fibrosis]]: acute ventilatory failure may be manifested as the end-stage of the IPF or more commonly, in conjunction with pneumonia, surgery, or other illness
      • In end-stage IPF requiring mechanical ventilation, lung compliance has been noted to be significantly decreased
  • Pleural or Chest Wall Disease (with Increased Work of Breathing)

Diagnosis

General

  • Arterial Blood Gas (ABG): required

  • Pulse Oximetry: information provided is limited to oxygen saturation (but importantly neglects the pH and pCO2, which are crucial to allow the detection of hypercapnia)
  • End-Tidal CO2: may be useful to detect hypercapnia
  • Transcutaneous CO2: may be used
  • CXR/Chest CT: useful to identify underlying etiology

Diagnosis of Type II-Chronic Hypoxemic, Hypercapnic Respiratory Failure

  • Chemosensitivity Disorders
    • ABG: normal A-a gradient
    • PFT’s: normal spirometry and lung volumes (usually), normal MIP+MEP
  • Neuromuscular Disease
    • ABG: normal A-a gradient
    • PFT’s: restriction, decreased MIP+MEP
  • Upper Airway/Lower Airway/Chest Wall Disease
    • ABG: increased A-a gradient
    • PFT’s: restriction or obstruction, normal MIP+MEP

Clinical Manifestations

Acute Type II-Hypoxemic, Hypercapnic Respiratory Failure

Upper Airway/Proximal Tracheal Airway Obstruction

  • Characteristics of Upper Airway/Tracheal Obstruction
    • Role of Airway Diameter: progressive/gradual airway obstruction can be tolerated until upper airway/tracheal diameter reaches approximately 5-6 mm
    • Role of the Location of Airway Obstruction: impacts whether inspiratory and/or expiratory flows are more adversely affected by the obstructing lesion
      • Variable Extrathoracic Upper Airway Obstruction: adversely affects predominantly inspiratory flow (as inspiratory negative intraluminal pressures exacerbate the inspiratory airway narrowing, while expiratory positive intraluminal pressures splints the obstruction open)
        • Example: vocal cord paralysis -> inspiratory stridor with no expiratory obstruction
      • Variable Intrathoracic Upper Airway Obstruction: adversely affects predominantly expiratory flow (as inspiratory negative pressures decrease the inspiratory airway narrowing, while expiratory positive intrapleural pressures exacerbate the airway obstruction)
        • Example: tracheomalacia -> expiratory worsening of airway obstruction
      • Fixed Upper Airway Obstruction: adversely affects both inspiratory and espiratory flows
    • Complication by Negative Pressure Pulmonary Edema: negative pressure pulmonary edema may occur in cases with critical, acute upper airway obstruction (such as laryngospasm)

Clinical Manifestations of Inspiratory Muscle Fatigue

  • In a study of 12 patients with post-extubation respiratory failure (patients with intact ventilatory drive, but decreased ventilatory output), 6 patients manifested EMG evidence of inspiratory muscle fatigue characterized by a defined sequence of clinical stages [MEDLINE]
    • Note that the stages were of variable duration (with some patients skipping stages): however, this study suggests that the occurrence of respiratory arrest is typically heralded by preceding clinical events

INSPFATIGUE

Chronic Type II-Hypoxemic, Hypercapnic Respiratory Failure

  • Consequences of Hypoventilation-Associated Sleep-Disordered Breathing
    • Morning Headache: due to cerebral vasodilation
    • Sleep Disruption: due to cerebral vasodilation
    • Daytime Somnolence: due to cerebral vasodilation
    • Confusion: due to cerebral vasodilation
    • Pulmonary Hypertension/Cor Pulmonale (see Pulmonary Hypertension, [[Pulmonary Hypertension]])
  • Consequences of Hypoventilation-Associated Hypercapnia
    • Metabolic Compensation: elevated bicarbonate
  • Consequences of Hypoventilation-Associated Hypoxemia
    • Cyanosis
    • Polycythemia
    • Pulmonary Hypertension/Cor Pulmonale (see Pulmonary Hypertension, [[Pulmonary Hypertension]])

Treatment

Oxygen Therapy (see Oxygen, [[Oxygen]])

Nasal Cannula (NC)

  • xxx

High-Flow Nasal Cannula (HFNC)

  • Rationale: high-flow nasal cannula appears to decrease dead space [MEDLINE]
  • Contraindications
    • Hypercapnic Respiratory Failure
    • Mid-Maxillary Facial Trauma
    • Suspected Pneumothorax
  • French FLORALI Study Comparing High-Flow Nasal Cannula Oxygen with Standard Oxygen and Non-Invasive Ventilation in Hypoxemic, Non-Hypercapnic Respiratory Failure (NEJM, 2015) [MEDLINE]
    • No Difference in Intubation Rates
    • High-Flow Oxygen Group: improved 90-day mortality
    • High-Flow Oxygen Group: improved ventilator-free days
    • Criticisms of Study
      • Non-invasive ventilation group was unconventionally ventilated with 9 ml/kg PBW, possibly increasing lung injury int his group

Ventimask

  • xxx

Non-Rebreather Mask

  • xxx

Mechanical Ventilation (see Mechanical Ventilation-General, [[Mechanical Ventilation-General]])

  • xxx

Ventilation

Noninvasive Positive-Pressure Ventilation (NIPPV) (see Noninvasive Positive-Pressure Ventilation, [[Noninvasive Positive-Pressure Ventilation]]

  • Clinical Indications
    • Neuromuscular Disease
    • Congestive Heart Failure (CHF)
    • COPD Exacerbation

Invasive Mechanical Ventilation (see Mechanical Ventilation, [[Mechanical Ventilation]]

  • May be indicated for cases unresponsive or not amenable to NIPPV (especially cases with airway compromise, secretions, and/or aspiration risk)

Management of Specific Disorders

  • Specific Management of Hypothyroidism (see Hypothyroidism, [[Hypothyroidism]])
    • Hormone Replacement
    • Evaluation/Treatment of Concomitant Sleep-Disordered Breathing/Obstructive Sleep Apnea (OSA)
    • Evaluation/Treatment of Concomitant Congestive Heart Failure (CHF): if present
  • Specific Management of Obesity-Hypoventilation Syndrome (see Obesity Hypoventilation Syndrome, [[Obesity Hypoventilation Syndrome]])
    • Evaluation/Treatment of Concomitant Sleep-Disordered Breathing/Obstructive Sleep Apnea (OSA): if present
    • Evaluation/Treatment of Concomitant Congestive Heart Failure (CHF): if present
    • In retrospective study of 54 morbidly obese patients (mean BMI: 44), 87% of whom had concomitant OSA, chronic nocturnal nasal NIPPV improved gas exchange, dyspnea, and sleepiness [MEDLINE]
    • Weight Loss
  • Management of Chest Trauma
    • In subset of patients with persistent hypoxemia, NIPPV has been demonstrated to decrease the need for intubation and shorten hospital length of stay [MEDLINE]

References

  • The continuous inhalation of oxygen in cases of pneumonia otherwise fatal, and in other diseases. Boston Med J 1890;123:481-5
  • Clinical semi-starvation: depression of hypoxic ventilatory response. N Engl J Med. 1976;295(7):358 [MEDLINE]
  • Clinical manifestations of inspiratory muscle fatigue. Am J Med. 1982 Sep;73(3):308-16 [MEDLINE]
  • The spectrum of intermediate syndrome following acute organophosphate poisoning: a prospective cohort study from Sri Lanka. PLoS Med. 2008 Jul 15;5(7):e147. doi: 10.1371/journal.pmed.0050147 [MEDLINE]
  • Short-term and long-term effects of nasal intermittent positive pressure ventilation in patients with obesity-hypoventilation syndrome. Chest. 2005 Aug;128(2):587-94 [MEDLINE]
  • Noninvasive ventilation reduces intubation in chest trauma-related hypoxemia: a randomized clinical trial. Chest. 2010 Jan;137(1):74-80. doi: 10.1378/chest.09-1114. Epub 2009 Sep 11 [MEDLINE]
  • High-flow oxygen administration by nasal cannula for adult and perinatal patients. Respir Care 2013;58:98-122
  • Nasal high-flow versus Venturi mask oxygen therapy after extubation: effects on oxygenation, comfort, and clinical outcome. Am J Respir Crit Care Med 2014;190:282-8
  • Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE): a physiological method of increasing apnoea time in patients with difficult airways. Anaesthesia 2015;70:323-9 [MEDLINE]
  • FLORALI Study. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med 2015. DOI: 10.1056/NEJMoa1503326 [MEDLINE]
  • Saving lives with high-flow nasal oxygen. N Engl J Med. 2015 Jun 4;372(23):2225-6. doi: 10.1056/NEJMe1504852 [MEDLINE]
  • High-flow nasal cannula oxygen therapy in adults. J Intensive Care. 2015 Mar 31;3(1):15. doi: 10.1186/s40560-015-0084-5. eCollection 2015 [MEDLINE]