Respiratory Failure

Definitions

  • Respiratory Failure: defined as the occurrence of one or both the following
    • Decreased pO2 as Predicted for the Patient’s Age (Hypoxemia)
    • Increased pCO2 (Hypercapnia) in the Setting of a Normal Serum Bicarbonate
      • A Normal Serum Bicarbonate is Specified Here Since a Primary Metabolic Alkalosis (with Increased Serum Bicarbonate) Would Be Expected to Result in a Normal Compensatory Increase in pCO2: this normal compensatory mechanism functions to maintain a normal serum pH and would not be considered “respiratory failure”
  • Hypoxemia: decreased hemoglobin saturation (as assessed by pulse oximetry: SaO2 or SpO2) or decreased arterial pO2 (as assessed by arterial blood gas)
    • In Specific Clinical Circumstances, a Patient May Be Hypoxemic, But Not Be Hypoxic
      • Example: a young hypoxemic patient can significantly increase cardiac output to maintain tissue oxygen delivery
  • Hypoxia: state of impaired tissue oxygenation
    • In Specific Clinical Circumstances, a Patient May Be Hypoxic, But Not Be Hypoxemic
      • Example: in cyanide intoxication, SaO2 can be normal, but tissues may be hypoxic (see Cyanide)
  • Anoxia: compelete tissue deprivation of oxygen supply
  • Hypercapnia (see Hypercapnia): increased arterial pCO2
  • Acidemia: acidic serum pH (due to either metabolic or respiratory acidosis)
  • Alkalemia: alkaline serum pH (due to either metabolic or respiratory alkalosis)
  • Acidosis: presence of acid-producing acid-base disturbance (with or without concomitant acidemia)
    • Clinical Scenarios in Which an Acidosis is Present, But in Which the pH is Not Acidemic
      • Presence of a Metabolic Acidosis May Not Necessarily Result in an Acidemic pH (pH <7.4), Since Respiratory Compensation (Hyperventilation) Occurs, Resulting in an Increase in the Serum pH
      • Presence of a (Chronic) Respiratory Acidosis May Not Necessarily Result in an Acidemic pH (pH <7.4), Since Metabolic Compensation (Renal Bicarbonate Retention) Generally Occurs Over a Period of Days, Resulting in an Increase in the Serum pH
  • Alkalosis: presence of alkali-producing acid-base disturbance (with or without concomitant alkalemia)
    • Clinical Scenarios in Which an Alkalosis is Present, But in Which the pH is Not Alkalemic
      • Presence of a Metabolic Alkalosis May Not Necessarily Result in an Alkelemic pH (pH >7.4), Since Respiratory Compensation (Hypoventilation) Occurs Rapidly, Resulting in a Decrease in the Serum pH
      • Presence of a (Chronic) Respiratory Alkalosis May Not Necessarily Result in an Alkalemic pH (pH >7.4), Since Metabolic Compensation (Renal Bicarbonate Wasting) Generally Occurs Over a Period of Days, Resulting in a Decrease in the Serum pH
  • PaO2: arterial pO2 (arterial oxygen tension)
    • Usually Referred to Simply as pO2
  • PAO2: alveolar PO2 (alveolar oxygen tension)
  • SpO2: pulse oximetry, as determined by peripheral pulse oximeter (see Pulse Oximetry)
  • SaO2: pulse oximetry, as determined by arterial blood gas co-oximeter (see Arterial Blood Gas)

Epidemiology

  • Study of Patients with Acute Hypoxemic, Hypercapnic Respiratory Failure Requiring Intensive Care Unit (ICU) Admission (Am J Respir Crit Care Med, 2017) [MEDLINE]
    • Presence of Comorbid Conditions
      • Approximately 67% (52/78) of Patients Had Chronic Obstructive Pulmonary Disease (COPD): however, only 24% (19/78) had been previously diagnosed with COPD
      • Patients without COPD were Predominantly Obese
      • Severe Obstructive Sleep Apnea (OSA) was Present in 51% of COPD Patients and 81% of Non-COPD Patients
      • Previously Undiagnosed Chronic Diastolic Congestive Heart Failure was Present in 44% of Cases
      • Previously Undiagnosed Hypertension was Present in 67% of Cases
    • Number of Comorbid Conditions
      • More than 50% of the Patients Had ≥3 Comorbidities Which were Known to Precipitate Acute Hypoxemic, Hypercapnic Respiratory Failure
      • Multiple Morbidities were Associated with Increased Hospital Length of Stay
    • Prognosis
      • Hospital Readmission or Death Occurred in 46% of Patients Over an Average of 3.5 mo After Discharge

Classification Schemes for Respiratory Failure

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

Type 1-Hypoxemic Respiratory Failure

  • Subtypes
    • Acute Hypoxemic Respiratory Failure (see Hypoxemia)
    • Chronic Hypoxemic Respiratory Failure (see Hypoxemia)

Type II-Hypoxemic, Hypercapnic Respiratory Failure)

  • Subtypes: the accompanying pH depends on the level of serum bicarbonate (which is dependent on the duration of the hypercapnia)
    • Acute Hypoxemic, Hypercapnic Respiratory Failure: pH may be more decreased (due to inadequate time for renal reabsorption of bicarbonate)
    • Chronic Hypoxemic, Hypercapnic Respiratory Failure: 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 of Acute/Chronic Type I-Hypoxemic Respiratory Failure

Pseudohypoxemia

  • Mechanism
    • ABG Left at Room Temperature (Particularly with Elevated White Blood Cell Count), Resulting in In Vitro Oxygen Consumption by White Blood Cells in the Sample
  • Diagnosis

Normal A-a Gradient Hypoxemia

Decreased Inspired PO2 (PiO2)

  • Mechanism: decreased PiO2 results in decreased oxygen delivery to the alveoli (with decreased alveolar pO2)
    • PiO2 = FIO2 x (Patm – PH20)
      • Patm: atmospheric pressure
      • PH20: partial pressure of water (equal to 47 mm Hg at 37 degrees C)
  • Etiology
    • Fire in Enclosed Space
    • High Altitude (with Decreased Barometric Pressure)
      • Sea Level (0 ft): FIO2 = 21%, PIO2= 150, pATM = 760, pH2O = 47 (at 37 degree C)
      • Denver (5280 ft): FIO2 = 21%, PIO2= 125, pATM = 640, pH2O = 47 (at 37 degree C)
    • Inadvertent Administration of Low FIO2 During Mechanical Ventilation: due to circuit leak, clinician error, etc

Decreased Mixed Venous Oxygen Saturation

  • Mechanism: blood returns to the right side of the heart in a severely deoxygenated state and cardiopulmonary system is incapable of re-oxygenating the blood
    • Low Mixed Venous Oxygen Saturation Usually Only Results in Arterial Hypoxemia in the Setting of Coexistent Anemia, V/Q Mismatch, or Right-to-Left Shunt: these result in the impaired ability to re-oxygenate the blood
  • Etiology
    • Decreased Cardiac Output State/Cardiogenic Shock (see Cardiogenic Shock)
    • Increased Tissue Oxygen Extraction
      • Anxiety (see Anxiety)
      • Fever (see Fever)
      • Increased Work of Breathing

Elevated A-a Gradient Hypoxemia

Worsened V/Q Mismatch (Above Levels Observed as Part of Normal Physiology)

Intrapulmonary Right-to-Left Shunt (see Intracardiac and Extracardiac Shunt)

  • Mechanism
    • Shunting of Unoxygenated Blood Through the Lung, Without Undergoing Oxygenation
    • Since a Large Intrapulmonary Shunt Can Produce a Region of Near Zero V/Q Ratio, Intrapulmonary Shunt Really Represents the Most Extreme Form of V/Q Mismatch
    • Shunt is Classically Characterized by Poor Response of pO2 (or SaO2) to the Administration of Supplemental Oxygen
  • Quantification of Shunt Fraction: perform on 100% FIO2 for at least 20 min (to allow nitrogen washout)
    • Qs/Qt = (CcO2-CaO2) / (CcO2-CvO2)
      • PIO2 = FIO2 x pATM -> at sea level and on 100% FIO2, PIO2 = 760
      • PAO2 = PIO2 – (PCO2 x 1.25) -> at sea level and on 100% FIO2, PAO2 = 760 – (PCO2 x 1.25)
      • CcO2: end-capillary oxygen content = Hb x 1.39 + (0.003 x PAO2)
      • CaO2: arterial oxygen content = Hb x SaO2 x 1.39 + (0.003 x PaO2)
        • Use values from ABG
      • CvO2: mixed venous oxygen content = Hb x SvO2 x 1.39 + (0.003 x PvO2)
        • Use values from Swan-Ganz Catheter
    • Normal Shunt Fraction: <5% (this accounts for the normal physiologic degree of anatomical shunt that exists, due to the bronchial and Thebesian circulations)
  • Etiology

Intracardiac Right-to-Left Shunt (see Intracardiac and Extracardiac Shun)

  • Mechanism
    • Shunting of Unoxygenated Blood from the Right to the Left Side of the Heart, Bypassing the Pulmonary Vascular Bed
  • Etiology

Diffusion Limitation

  • Mechanism
    • Limitation of Oxygen Exchange Across the Pulmonary Alveolar-Capillary Membrane
      • Thickening of the Alveolar-Capillary Membrane (Associated with Interstitial Fibrosis, Cryptogenic Organizing Pneumonia, ARDS, Asbestos Exposure, etc) Results in Inadequate Red Blood Cell Transit Time in the Pulmonary Circulation, Not Allowing Adequate Equilibration of pO2 Between the Alveolar Gas and Pulmonary Capillary Blood
      • Note: diffusion limitation is absent in normal subjects at rest
  • Etiology
    • Heavy Exercise
      • Due to Increased Cardiac Output (with Transient Pulmonary Interstitial Fluid Accumulation) with Decreased Time Available for Oxygen Diffusion
      • Effect of Hypoxia: humans will freqently demonstrate diffusion limitation in setting of normoxia, but almost all will demonstrate diffusion limitation in setting of hypoxia
      • Race Horses Develop Diffusion Limitation During Severe Exercise (Explaining the Common Practice of Administering Furosemide Prior to Races, with the Goal of Decreasing the Accumulation of High Cardiac Output-Associated Interstitial Pulmonary Edema)
    • Severe Interstitial Lung Disease with Exercise (see Interstitial Lung Disease)
      • Due to Increased Cardiac Output with Decreased time Available for Oxygen Diffusion Combined with Thickening of the Alveolar-Capillary Membrane

Etiology of Type II-Hypoxemic, Hypercapnic Respiratory Failure

Acute Type II-Hypoxemic, Hypercapnic Respiratory Failure

Disorders with Decreased Ventilatory Drive

  • Metabolic Alkalosis (see 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)
      • Bilateral Carotid Endarterectomy with Inadvertent Destruction of Peripheral Chemoreceptors (see Carotid Endarterectomy)
        • Clinical: decreased hypoxic ventilatory response and a slight increase in the resting arterial pCO2
      • Carotid Body Resection (Glomectomy) (see Carotid Body Resection)
        • Epidemiology: historically used a treatment for asthma and dyspnea in severe COPD
    • Hypercapnia (“CO2 Narcosis”) (see Hypercapnia)
      • Mechanism: worsens central hypoventilation
    • Hypothyroidism (see Hypothyroidism)
      • Mechanism: combination of decreased central respiratory drive, phrenic neuropathy, and respiratory muscle myopathy
      • Clinical: manifests as both inspiratory and expiratory muscle weakness
  • Acute Brainstem Disease

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)
      • Atlantoaxial Subluxation/Instability (see Atlantoaxial Instability)
      • Cervical Disk Disease with Cord Compression
      • Cervical Osteoarthritis
      • Cervical Space-Occupying Lesions
      • Cervical Spinal Cord Infarction (see Spinal Cord Infarction)
      • Cervical Spine Trauma with Cord Injury
      • Diastematomyelia (Bony Spur in Spinal Canal, Which May Compress the Cervical Spinal Cord)
      • Post-Cervical Cordotomy: procedure done to achieve pain control may damage ascending and descending tracts
      • Spondylolisthesis/Cervical Spondylosis
      • Syringomelia (Cavitation of Central Spinal Cord) (see Syringomelia)
      • Thoracic Outlet Syndrome (see Thoracic Outlet Syndrome)
      • Transverse Myelitis (see Transverse Myelitis)
    • Cervical Root Disease (see Cervical Root Disease)
      • Cervical Osteoarthritis (with Bilateral C3-C5 Involvement)
      • Cervical Spine Manipulation (with Bilateral C3-C5 Involvement)
      • Cervical Mass Lesion (with Bilateral C3-C5 Involvement)
      • Herpes Zoster (with Bilateral C3-C5 Involvement) (see Varicella-Zoster Virus)
      • Multiple Sclerosis (with Bilateral C3-C5 Involvement) (see Multiple Sclerosis)
      • Neuralgic Amyotrophy (with Bilateral C3-C5 Involvement): usually affects the brachial plexus
  • Acute Motor Neuron Disease
    • Amyotrophic Lateral Sclerosis (ALS) (see Amyotrophic Lateral Sclerosis)
      • Mechanism: upper and lower motor neuron disease
      • Acute Ventilatory Failure May Be the Initial Presentation of ALS
    • Kennedy Disease
      • Epidemiology: age of onset from adolescence-old age in males
      • Mechanism: X-linked lower motor neuron disease due to androgen receptor mutation
    • Poliomyelitis (see Poliomyelitis)
    • Post-Polio Syndrome (see Poliomyelitis)
    • Primary Lateral Sclerosis
      • Mechanism: upper motor neuron disease
    • Progressive Muscular Atrophy (PMA)
      • Mechanism: lower motor neuron disease
    • Spinal Muscular Atrophies
      • Mechanism: lower motor neuron disease
    • Strychnine Intoxication (see 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)
      • Mechanism: damaged upper motor neurons can no longer inhibit lower motor neurons
  • Acute Peripheral Neuropathy (see Phrenic Neuropathy)
    • Infection/Toxin
    • Alcoholic Neuropathy (see Alcoholic Neuropathy)
    • Buckthorn Berry Intoxication (see Buckthorn Berry Intoxication)
    • Diphtheria (see Diphtheria)
    • Lyme Disease (see Lyme Disease)
    • Neurotoxic Shellfish Poisoning (see Neurotoxic Shellfish)
      • Physiology: ingestion of brevetoxin-contaminated bivalve shellfish
      • Clinical: descending paralysis (similar to botulism and in contrast to ascending paralysis seen in Guillain-Barre syndrome and tick paralysis)
    • Paralytic Shellfish Poisoning (see Paralytic Shellfish)
      • Physiology: 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)
      • Clinical: descending paralysis (similar to botulism and in contrast to ascending paralysis seen in Guillain-Barre syndrome and tick paralysis)
    • Poisonous Lizard Bite (see Poisonous Lizard Bite)
    • Rabies (see Rabies): ascending paralysis (may mimic that of Guillian-Barre syndrome)
    • Widow Spider Bite (see Widow Spider Bite)
    • Other
      • Acute Intermittent Porphyria (see Acute Intermittent Porphyria)
      • Chronic Inflammatory Demyelinating Polyneuropathy (see Chronic Inflammatory Demyelinating Polyneuropathy)
      • Critical Illness Polyneuropathy (see ICU-Acquired Weakness)
      • Diabetic Neuropathy (see Diabetic Neuropathy)
      • Guillain-Barre Syndrome (GBS) (see 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)
        • Mechanism: combination of decreased central respiratory drive, phrenic neuropathy, and respiratory muscle myopathy
        • Clinical: manifests as both inspiratory and expiratory muscle weakness
      • Idiopathic Peripheral Neuropathy
      • Mediastinal/Esophageal Surgical Injury or Traumatic Injury of Bilateral Phrenic Nerves
        • Epidemiology
        • Phrenic Nerve Injury Occurs in 2-20% of Open Heart Surgery Cases
        • L>R Sided Injury
        • Mechanisms
        • Cold Cardioplegia
        • Dissection of Left Internal Mammary Artery (LIMA)
        • Stretching of Phrenic Nerve
      • Multiple Sclerosis (see Multiple Sclerosis)
      • Neurofibromatosis (see Neurofibromatosis)
        • Epidemiology: case report of bilateral diaphragmatic paralysis
      • Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus)
        • Physiology: neuropathy with vasculitis of phrenic nerves and myopathy
  • Acute Neuromuscular Junction Disease (Involving the Respiratory Muscles)
    • Myasthenia Gravis (MG) (see Myasthenia Gravis)
      • Clinical: acute ventilatory failure may be the initial presentation of myasthenia gravis
    • Lambert-Eaton Myasthenic Syndrome (LEMS) (see Lambert-Eaton Myasthenic Syndrome)
    • Botulism (see Botulism)
      • Physiology: botulinum toxin blocks acetylcholine release at neuromuscular junction
      • Clinical: descending paralysis (similar to paralytic-neurotoxic shellfish poisoning)
    • Tick Paralysis (see Tick Paralysis)
      • Physiology: toxin probably impairs acetylcholine mobilization at motor nerve terminal
      • Clinical: ascending paralysis (Similar to Guillain-Barre Syndrome)
    • Snake Bite: due to various types of neurotoxins in venom
      • Mojave Rattlesnake (Crotalus Scutulatus) (see 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/Carbamate Intoxication (see Organophosphates-Carbamates) (PLoS Med, 2008) [MEDLINE]
    • VX Nerve Agent (see VX Nerve Agent)
    • Pharmacologic Neuromuscular Junction Antagonists
      • Aminoglycosides (see Aminoglycosides): usually clinically relevant only in the presence of other neuromuscular junction disease
      • Anticholinergics (see Anticholinergic Agents): usually clinically relevant only in the presence of other neuromuscular disease
      • Fluoroquinolones (see Fluoroquinolones): usually clinically relevant only in the presence of other neuromuscular disease
      • Procainamide (see Procainamide): usually clinically relevant only in the presence of other neuromuscular disease
      • Polymyxin B (see Polymyxins): usually clinically relevant only in the presence of other neuromuscular disease
      • Sodium Colistimethate (aka Colistin, Polymyxin E) (see 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)

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)
    • Bilateral Vocal Fold Immobility (BVFI) (see Bilateral Vocal Fold Immobility) (Select Etiologies Shown)
      • Cricoarytenoid Arthritis (see Cricoarytenoid Arthritis)
      • Laryngeal Inflammation
      • Laryngospasm (see Laryngospasm)
      • Neurologic Disease/Dysfunction Involving the Vocal Folds (Select Etiologies Shown)
        • Altered Mental Status with Inability to Protect Upper Airway
        • Airway Obstruction Occurs Due to Tongue Prolapse into the Posterior Pharynx and/or Decreased Soft Palate Muscular Tone
        • Amyotrophic Lateral Sclerosis (ALS) (see Amyotrophic Lateral Sclerosis)
        • Idiopathic Bilateral Vocal Cord Paralysis
        • Paradoxical Vocal Fold Motion (Vocal Cord Dysfunction) (see Paradoxical Vocal Fold Motion)
      • Intubation Injury to Vocal Folds
      • Mechanical/Iatrogenic Injury to Vocal Folds
    • Other Upper Airway Disease (see Obstructive Lung Disease)
  • Acute Obstructive Lung Disease (with Increased Work of Breathing) (see Obstructive Lung Disease)
    • Acute Tracheobronchial Obstruction
      • Tracheobronchial Infection
      • Tracheobronchial Neoplasm
      • Extrinsic Tracheobronchial Compression
      • Other Tracheobronchial Obstructive Process
    • Asthma Exacerbation (see Asthma)
    • Bronchiectasis Exacerbation (see Bronchiectasis)
    • Chronic Obstructive Pulmonary Disease (COPD) Exacerbation (see Chronic Obstructive Pulmonary Disease)
    • Cystic Fibrosis Exacerbation (see Cystic Fibrosis)
  • Acute Parenchymal Lung Disease (with Increased Work of Breathing)
  • 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): very low V/Q and/or intrapulmonary shunt
    • End-Stage Interstitial Lung Disease (ILD) (see Interstitial Lung Disease): due to increased physiologic dead space
    • Hyperinflation States
      • Asthma Exacerbation (see Asthma): very high V/Q with dynamic hyperinflation
      • COPD Exacerbation (see Chronic Obstructive Pulmonary Disease): very high V/Q with dynamic hyperinflation
      • Pulmonary Hyperinflation (Excessive Exogenous PEEP or Auto-PEEP): generalized pulmonary hypoperfusion
    • Pulmonary Vascular Disease (Severe)
      • Acute Pulmonary Embolism (Severe) (see Acute Pulmonary Embolism: localized pulmonary hypoperfusion with increased physiologic dead space
      • Air Embolism (see Air Embolism: venous air ambolism -> localized pulmonary hypoperfusion with increased physiologic dead space
      • Sickle Cell Acute Chest Syndrome (see Sickle Cell Disease)
    • Shallow Breathing: due to anatomic dead space
    • Shock States
  • Increased Carbon Dioxide Production: disorders which increase carbon dioxide production are usually not the primary or sole etiology of hypercapnia (since the usual response to increased pCO2 is to increase minute ventilation), but they can be contributors in patients with decreased ventilatory reserve (patients with chronic lung disease, respiratory muscle weakness, other conditions which increase the VD/VT ratio, etc)
  • Exogenous Carbon Dioxide Inhalation
    • Carbon Dioxide Rebreathing
    • Industrial/Laboratory Accident

Chronic Type II-Hypoxemic, Hypercapnic Respiratory Failure

Disorders with Decreased Ventilatory Drive

  • Metabolic Alkalosis (see Metabolic Alkalosis)
    • Mechanism: 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)
      • Bilateral Carotid Endarterectomy with Inadvertent Destruction of Peripheral Chemoreceptors (see Carotid Endarterectomy)
        • Clinical: decreased hypoxic ventilatory response and a slight increase in the resting arterial pCO2
      • Carotid Body Resection (Glomectomy) (see Carotid Body Resection)
        • Epidemiology: historically used a treatment for asthma and dyspnea in severe COPD
    • Central Sleep Apnea (see Central Sleep Apnea)
    • Chronic Mountain Sickness (Monge Disease) (see Chronic Mountain Sickness)
      • Mechanism: loss of ventilatory acclimatization to high altitude-associated hypoxia, leading to central hypoventilation
    • Hypercapnia (“CO2 Narcosis”) (see Hypercapnia
      • Mechanism: worsens central hypoventilation
    • Hypothyroidism (see Hypothyroidism)
      • Mechanism: combination of decreased central respiratory drive, phrenic neuropathy, and respiratory muscle myopathy
      • Clinical: manifests as both inspiratory and expiratory muscle weakness
  • Chronic Brainstem Disease

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)
      • Atlantoaxial Subluxation/Instability (see Atlantoaxial Instability)
      • Cervical Disk Disease with Cord Compression
      • Cervical Osteoarthritis
      • Cervical Space-Occupying Lesions
      • Cervical Spinal Cord Infarction (see Spinal Cord Infarction)
      • Cervical Spine Trauma with Cord Injury
      • Diastematomyelia (Bony Spur in Spinal Canal, Which May Compress the Cervical Spinal Cord)
      • Post-Cervical Cordotomy: procedure done to achieve pain control may damage ascending and descending tracts
      • Spondylolisthesis/Cervical Spondylosis
      • Syringomelia (Cavitation of Central Spinal Cord) (see Syringomelia)
      • Thoracic Outlet Syndrome (see Thoracic Outlet Syndrome)
      • Transverse Myelitis (see Transverse Myelitis)
    • Cervical Root Disease (see Cervical Root Disease)
      • Cervical Osteoarthritis (with Bilateral C3-C5 Involvement)
      • Cervical Spine Manipulation (with Bilateral C3-C5 Involvement)
      • Cervical Mass Lesion (with Bilateral C3-C5 Involvement)
      • Herpes Zoster (with Bilateral C3-C5 Involvement) (see Varicella-Zoster Virus)
      • Multiple Sclerosis (with Bilateral C3-C5 Involvement) (see Multiple Sclerosis)
      • Neuralgic Amyotrophy (with Bilateral C3-C5 Involvement): usually affects the brachial plexus
  • Motor Neuron Disease
    • Amyotrophic Lateral Sclerosis (ALS) (see Amyotrophic Lateral Sclerosis)
      • Mechanism: upper and lower motor neuron disease
      • Clinical: acute ventilatory failure may be the initial presentation of ALS
    • Kennedy Disease
      • Epidemiology: age of onset from adolescence-old age in males
      • Mechanism: X-linked lower motor neuron disease due to androgen receptor mutation
    • Poliomyelitis (see Poliomyelitis)
    • Post-Polio Syndrome (see Poliomyelitis)
    • Primary Lateral Sclerosis
      • Mechanism: upper motor neuron disease
    • Progressive Muscular Atrophy (PMA)
      • Mechanism: lower motor neuron disease
    • Spinal Muscular Atrophies
      • Mechanism: lower motor neuron disease
    • Strychnine Intoxication (see 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)
      • Mechanism: damaged upper motor neurons can no longer inhibit lower motor neurons
  • Peripheral Neuropathy (see Phrenic Neuropathy)
    • Infection/Toxin
    • Alcoholic Neuropathy (see Alcoholic Neuropathy)
    • Buckthorn Berry Intoxication (see Buckthorn Berry Intoxication)
    • Diphtheria (see Diphtheria)
    • Lyme Disease (see Lyme Disease)
    • Neurotoxic Shellfish Poisoning (see Neurotoxic Shellfish)
      • Physiology: ingestion of brevetoxin-contaminated bivalve shellfish
      • Clinical: descending paralysis (similar to botulism and in contrast to ascending paralysis seen in Guillain-Barre syndrome and tick paralysis)
    • Paralytic Shellfish Poisoning (see Paralytic Shellfish)
      • Physiology: 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)
      • Clinical: descending paralysis (similar to botulism and in contrast to ascending paralysis seen in Guillain-Barre syndrome and tick paralysis)
    • Poisonous Lizard Bite (see Poisonous Lizard Bite)
    • Rabies (see Rabies)
      • Clinical: ascending paralysis (may mimic that of Guillian-Barre syndrome)
    • Widow Spider Bite (see Widow Spider Bite)
    • Other
      • Acute Intermittent Porphyria (see Acute Intermittent Porphyria)
      • Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (see Chronic Inflammatory Demyelinating Polyneuropathy)
      • Critical Illness Polyneuropathy (see ICU-Acquired Weakness)
      • Diabetic Neuropathy (see Diabetic Neuropathy)
      • Guillain-Barre Syndrome (GBS) (see 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)
        • Mechanism: combination of decreased central respiratory drive, phrenic neuropathy, and respiratory muscle myopathy
        • Clinical: manifests as both inspiratory and expiratory muscle weakness
      • Idiopathic Peripheral Neuropathy
      • Mediastinal/Esophageal Surgical Injury or Traumatic Injury of Bilateral Phrenic Nerves
        • Epidemiology
        • Phrenic Nerve Injury Occurs in 2-20% of Open Heart Surgery Cases
        • L>R Sided Injury
        • Mechanisms
        • Cold Cardioplegia
        • Dissection of Left Internal Mammary Artery (LIMA)
        • Stretching of Phrenic Nerve
      • Multiple Sclerosis (see Multiple Sclerosis)
      • Neurofibromatosis (see Neurofibromatosis)
        • Epidemiology: case report of bilateral diaphragmatic paralysis
      • Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus)
        • Physiology: neuropathy with vasculitis of phrenic nerves and myopathy
  • Neuromuscular Junction Disease (Involving the Respiratory Muscles)
    • Myasthenia Gravis (MG) (see Myasthenia Gravis)
      • Clinical: acute ventilatory failure may be the initial presentation of myasthenia gravis
    • Lambert-Eaton Myasthenic Syndrome (LEMS) (see Lambert-Eaton Myasthenic Syndrome)
    • Botulism (see Botulism)
      • Physiology: botulinum toxin blocks acetylcholine release at neuromuscular junction
      • Clinical: descending paralysis (similar to paralytic-neurotoxic shellfish poisoning)
    • Tick Paralysis (see Tick Paralysis)
      • Physiology: toxin probably impairs acetylcholine mobilization at motor nerve terminal
      • Clinical: ascending paralysis (Similar to Guillain-Barre Syndrome)
    • Organophosphate/Carbamate Intoxication (see Organophosphates-Carbamates) (PLoS Med, 2008) [MEDLINE]
    • Pharmacologic Neuromuscular Junction Antagonists
      • Aminoglycosides (see Aminoglycosides): usually clinically relevant only in the presence of other neuromuscular junction disease
      • Anticholinergic Agents (see Anticholinergic Agents): usually clinically relevant only in the presence of other neuromuscular disease
      • Fluoroquinolones (see Fluoroquinolones): usually clinically relevant only in the presence of other neuromuscular disease
      • Procainamide (see Procainamide): usually clinically relevant only in the presence of other neuromuscular disease
      • Polymyxin B (see Polymyxins): usually clinically relevant only in the presence of other neuromuscular disease
      • Sodium Colistimethate (aka Colistin, Polymyxin E) (see Polymyxins): usually clinically relevant only in the presence of other neuromuscular disease
  • Acute Myopathy/Muscle Dysfunction (Involving Respiratory Muscles) (see Myopathy

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)
    • Bilateral Vocal Fold Immobility (BVFI) (see Bilateral Vocal Fold Immobility)
      • Cricoarytenoid Arthritis (see Cricoarytenoid Arthritis)
      • Laryngeal Inflammation
      • 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)
      • Infection
      • Neurologic
        • Essential Tremor (see Essential Tremor): typically mild upper airway obstruction
        • Parkinson’s Disease (see Parkinson’s Disease): may cause acute upper airway obstruction in the postoperative 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): typically mild upper airway obstruction
        • Laryngeal Cyst/Laryngocele: typically mild upper airway obstruction
        • Laryngeal Rheumatoid Nodule (see Rheumatoid Arthritis): typically progressive
        • Macroglossia: typically mild upper airway obstruction
        • Nasal Polyps (see Nasal Polyps): typically mild upper airway obstruction
        • Obstructive Sleep Apnea (OSA) (see Obstructive Sleep Apnea): may cause acute upper airway obstruction in the postoperative setting
        • Thermal Injury/Burns of Upper Airway (see Smoke Inhalation): thermal injury is usually supraglottic (typically, laryngeal injury) and may be acute
        • Thyromegaly/Goiter (see Goiter): typically progressive
        • Tracheal Cyst: typically progressive
        • Tracheobronchomalacia (see Tracheobronchomalacia): typically progressive
        • Tonsillar/Adenoid Enlargement: typically progressive
        • Unilateral Vocal Cord Paralysis (see Unilateral Vocal Fold Immobility): typically mild upper airway obstruction
  • Obstructive Lung Disease (with Increased Work of Breathing) (see Obstructive Lung Disease)
    • Bronchiectasis (see Bronchiectasis)
    • Chronic Obstructive Pulmonary Disease (COPD) (see Chronic Obstructive Pulmonary Disease)
    • Chronic Tracheobronchial Obstruction
      • Tracheobronchial Infection
      • Tracheobronchial Neoplasm
      • Extrinsic Tracheobronchial Compression
      • Other Tracheobronchial Obstructive Process
    • Cystic Fibrosis (CF) (see Cystic Fibrosis)
  • Increased Dead Space Ventilation (Increased VD/VT Ratio)
  • Parenchymal Lung Disease (with Increased Work of Breathing)
    • Any Etiology of Pulmonary Fibrosis
    • Idiopathic Pulmonary Fibrosis (IPF) (see Idiopathic Pulmonary Fibrosis)
      • Acute Ventilatory Failure May Be Manifested as the End-Stage of 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)

Physiology

  • 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

Diagnosis

General

  • Arterial Blood Gas (ABG) (see Arterial Blood Gas)
    • Arterial Blood Gas is an Essential Diagnostic Procedure in Respiratory Failure, as it Provides Information Regarding the Arterial pH, Arterial pCO2, Arterial pO2, and the Serum Bicarbonate
  • Pulmonary Function Tests (PFT’s) (see Pulmonary Function Tests)
    • Pulmonary Function Tests are Useful to Diagnose Underlying Obstructive and Restrictive Lung Disease
  • Pulse Oximetry (see Pulse Oximetry)
    • Pulse Oximetry Only Measures Oxygen Saturation and Does Not Provide the pH and pCO2 (the Latter Two of Which are Required to Diagnose Acidemia and Hypercapnia)
  • End-Tidal Carbon Dioxide (Capnography) (see Capnography)
    • Capnography May Be Used to Diagnose Hypercapnia
  • Transcutaneous Carbon Dioxide
    • Transcutaneous Carbon Dioxide Measurement May Be Used to Diagnose Hypercapnia
  • Chest X-Ray (see Chest X-Ray)
    • Chest X-Ray is Standardly Used to Diagnose Underlying Lung Disease
  • Chest CT (see Chest Computed Tomography)
    • Chest CT is Standardly Used to Diagnose Underlying Lung Disease
  • Thyroid Function Tests (TFT’s) (see Thyroid Function Tests)
    • Thyroid Function Tests areUseful to Diagnose Both Hypothyroidism and Hyperthyroidism (see Hypothyroidism)

Diagnosis of Chronic Type II-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

  • Patients with Acute Respiratory Failure Typically Progress Through a Defined Sequence of Clinical Stages (Am J Med, 1982) [MEDLINE]
    • Study Involved 12 Postextubation Patients with Intact Ventilatory Drive, But Decreased Ventilatory Output
    • 6 of the Patients Manifested EMG Evidence of Inspiratory Muscle Fatigue
    • Importantly, the Stages were of Variable Duration and Some Patients Skipped Some Stages Altogether
    • Main Conclusion is that Respiratory Arrest is Typically Heralded by Preceding Clinical Events

Clinical Manifestations of Hypercapnia

  • General Comments
    • Normal (Normocapnic) Patients Generally Do Not Develop Altered Mental Status Until the pCO2 Exceeds 75-80 mm Hg
    • Chronically Hypercapnic Patients Do Not Develop Altered Mental Status Until the pCO2 Exceeds 90-100 mm Hg
  • Mild-Moderate Hypercapnia (Which Develops Gradually)
    • Anxiety (see Anxiety)
    • Dyspnea (see Dyspnea)
      • Mechanisms
        • Hypercapnia-Associated Decreased Diaphragmatic Contractility: this decrease in diaphragmatic contractility may contribute further to the development of respiratory failure
        • Hypercapnia-Associated Decreased Myocardial Contractility
        • Hypercapnia-Associated with Acidemia (with Stimulation of Central and Peripheral Chemoreceptors)
        • Hypercapnia-Induced Increase in Respiratory Drive
    • Excessive Daytime Somnolence (see Excessive Daytime Somnolence)
    • Headache (see Headache)
    • Respiratory Acidosis (see Respiratory Acidosis)
  • Moderate (or Rapidly Developing) Hypercapnia
    • Delirium/Confusion (see Delirium)
    • Depression (see Depression)
    • Increased Intracranial Pressure (ICP) (see Increased Intracranial Pressure)
      • Due to Increased Cerebral Blood Flow
    • Obtundation/Coma (“CO2 Narcosis”) (see Obtundation/Coma)
      • Acute Hypercapnia Initially Causes Increased Respiratory Drive with the Subsequent Development of Decreased Respiratory Drive (Leading to Worsening Hypercapnia with “CO2 Narcosis”) (Anesthesiology, 1960) [MEDLINE] (NEJM, 1984) [MEDLINE]: the subsequent development of increased brain glutamine, increased brain gamma-aminobutyric acid (GABA), decreased brain glutamate, and decreased brain aspartate may be responsible for decreased respiratory drive and depressed mental status
    • Paranoia (see Paranoia)
    • Rightward Shift of the Oxyhemoglobin Dissociation Curve (Due to Hypercapnia and/or Acidemia): this results in increased oxygen release at the tissues (Bohr Effect)
  • Severe Hypercapnia

Clinical Recognition of Respiratory Failure

  • Clinicians are Generally Poor at Recognizing the Clinical Signs of Respiratory Failure
    • In a Study of Clinical Assessment of Patients Requiring CPR, Physicians were Poor at Recognizing a Lack of Respiratory Effort (Ann Emerg Med, 1999) [MEDLINE]
      • Approximately 89.7% of Emergency Personnel Accurately Recognized Failure of Respiratory Effort
      • Approximately 84.5% of Physicians Accurately Recognized Failure of Respiratory Effort
      • Approximately 78.4% of Medical Students Accurately Recognized Failure of Respiratory Effort
    • In a Study of Automated Graphical Assessment of Respiratory Activity During Endoscopy, Visual Recognition of Changes Respiratory Activity (Which Might Precede the Development of Hypoxemia) was Poor (Gastrointest Endosc, 2002) [MEDLINE]
      • Capnography was an Excellent Indicator of Respiratory Rate, as Compared to Auscultation (r = 0.967, p < 0.001)
      • Fifty Four Episodes of Apnea or Disordered Respiration Occurred in 28 Patients (Mean Duration: 70.8 sec)
      • Only 50% of the Apnea or Disordered Respiration Episodes were Detected by Pulse Oximetry and None were Detected by Visual Assessment (p < 0.0010)

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)
  • Consequences of Hypoventilation-Associated Hypercapnia
    • Metabolic Compensation: elevated bicarbonate
  • Consequences of Hypoventilation-Associated Hypoxemia

Treatment

Site of Care

  • Criteria for Intensive Care Unit Admission in Patients with Respiratory Failure: no established guidelines exist
    • Need for Endotracheal Intubation/Mechanical Ventilation: this is the only criterion which mandates ICU admission
    • Altered Mental Status
    • Neuromuscular Disease (Particularly with Vital Capacity <1L)
    • Severe Acidosis (pH < 7.25)
    • Hemodynamic Instability
    • Need for Active Titration of Supplemental Oxygen
    • Need for Close Monitoring of Noninvasive Positive-Pressure Ventilation (NIPPV)
  • Carefully Selected Patients with Respiratory Failure May Be Cared for Outside of the Intensive Care Unit (For Example, on Stepdown Units
    • Patients with Do Not Resuscitate (DNR) Status Who Require Palliative Noninvasive Positive-Pressure Ventilation

Supplemental Oxygen Therapy (see Oxygen)

Considerations

  • First Priority is to Ensure Adequate Oxygenation
  • However, Provider Should Judiciously Use Supplemental Oxygen in Patients with Type II-Hypoxemic, Hypercapnic Respiratory Failure: generally titrated to achieve SpO2 90-94%
    • Risk Factors for Oxygen-Induced Worsening of Hypercapnia in Chronically Hypercapnic Patients with COPD (Am J Med, 1978) [MEDLINE]
      • History of Baseline Hypercapnia with/without Oxygen Administration
      • Low Initial pH (<7.33) and/or Low Arterial pO2
    • Mechanisms by Which Supplemental Oxygen May Worsen Hypercapnia
      • Hyperoxia Blunts Hypoxic Respiratory Drive (Lancet, 1977) [MEDLINE]
      • Hyperoxia Causes Oxygen-Induced Bronchodilation in Poorly-Perfused Lung Units, Worsening V/Q Mismatch and Increasing Physiologic Dead Space
      • Haldane Effect Oxyhemoglobin Binds Carbon Dioxide Less Avidly than Deoxyhemoglobin, Increasing Blood Carbon Dioxide Levels
    • Examples of Patients in Whom Supplemental Oxygen Should Be Used Judiciously
      • Chronic Obstructive Pulmonary Disease (COPD) with Chronic Hypercapnia (i.e. Chronic Hypoventilation) (see Chronic Obstructive Pulmonary Disease)
      • Neuromuscular Disease with Chronic Hypercapnia (Mayo Clin Proc, 1995) [MEDLINE]

Oxygen Delivery Methods

  • Nasal Cannula (NC)
  • High-Flow Nasal Cannula (HFNC)
  • Ventimask
  • Rebreather Mask
  • Non-Rebreather Mask
  • Transtracheal Catheter
  • Noninvasive Mechanical Ventilation (NIPPV) (see Noninvasive Mechanical Ventilation)
  • Bag-Valve-Mask Ventilation (see Airway Management)
    • May Be Used Temporarily for Hypoxemia and/or Hypercapnia, Typically Prior to Endotracheal Intubation with Invasive Mechanical Ventilation
  • Endotracheal Intubation with Invasive Mechanical Ventilation

Management of Pharmacologic Respiratory System Depressants

  • Discontinuation of General Anesthesia (see General Anesthesia)
  • Discontinuation of Opiates (see Opiates)
  • Discontinuation of Sedatives
  • Reversal of Opiates (see Opiates)
  • Reversal of Paralytic Agents
  • Reversal of Benzodiazepines
    • Benzodiazepines (Selected) (see Benzodiazepines)
    • Reversal Agents
    • Specific Treatment of Patients with Respiratory Depressant Intoxication
      • Specific Antidote to Intoxication
      • Gastric Decontamination Techniques: may be used in select sedative overdoses (and generally only in an intubated patient, where the risk of aspiration has been minimized

Treat Other Underlying Etiology (if Present)

Examples

  • Myasthenia Gravis (see Myasthenia Gravis)
    • Corticosteroids, Plasmapheresis, and Intravenous Immunoglobulin (IVIG) (see Myasthenia Gravis)
  • Severe Hypokalemia (see Hypokalemia)
    • Potassium Replacement: in patients who require significant replacement over a shorter period of time, central venous catheter (CVC) may be required

Respiratory Stimulants

  • General Comments
    • These Agents Have No Proven Benefit in the Management of Acute/Chronic Type II-Hypoxemic, Hypercapnic Respiratory Failure: no longer recommended
  • Agents

Heliox (see Heliox)

Bag-Valve-Mask Ventilation (see Airway Management)

  • Indications
    • Temporary Ventilation While Preparing for Endotracheal Intubation with Invasive Mechanical Ventilation
    • Temporary Ventilation While Treating an Etiology Which is Expected to Rapidly Resolve (Such as Opiate Intoxication)

Noninvasive Positive-Pressure Ventilation (NIPPV) (see Noninvasive Positive-Pressure Ventilation)

  • Clinical Indications (Selected)

Endotracheal Intubation with Invasive Mechanical Ventilation (see Airway Management, Endotracheal Intubation, and Mechanical Ventilation-General)

Prone Ventilation

Venovenous Extracorporeal Membrane Oxygenation (VV-ECMO) (see Venovenous Extracorporeal Membrane Oxygenation)

Management of Specific Disorders

  • Specific Management of Hypothyroidism (see 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)
    • Evaluation/Treatment of Concomitant Sleep-Disordered Breathing/Obstructive Sleep Apnea (OSA): 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 (Chest, 2005) [MEDLINE]
    • Evaluation/Treatment of Concomitant Congestive Heart Failure (CHF): if present
    • Weight Loss
  • Management of Chest Trauma
    • In Subset of Chest Trauma Patients with Persistent Hypoxemia, NIPPV Has Been Demonstrated to Decrease the Need for Intubation and Shorten Hospital Length of Stay (Chest, 2010) [MEDLINE]

References

General

  • 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]
  • Comorbidities and Subgroups of Patients Surviving Severe Acute Hypercapnic Respiratory Failure in the Intensive Care Unit. Am J Respir Crit Care Med. 2017;196(2):200 [MEDLINE]

Clinical

  • Effects of carbon dioxide on the cardiovascular system. Anesthesiology. 1960;21:652 [MEDLINE]
  • Effect of carbon dioxide on diaphragmatic function in human beings. N Engl J Med. 1984;310(14):874 [MEDLINE]
  • Checking for breathing: evaluation of the diagnostic capability of emergency medical services personnel, physicians, medical students, and medical laypersons. Ann Emerg Med. 1999;34(6):720 [MEDLINE]
  • Automated graphic assessment of respiratory activity is superior to pulse oximetry and visual assessment for the detection of early respiratory depression during therapeutic upper endoscopy. Gastrointest Endosc. 2002;55(7):826 [MEDLINE]

Treatment

  • The J. Burns Amberson Lecture. The management of acute respiratory failure in chronic bronchitis and emphysema. Am Rev Respir Dis. 1967;96(4):626 [MEDLINE]
  • Hypercapnia during oxygen therapy in acute exacerbations of chronic respiratory failure. Hypothesis revisited. Lancet. 1977;2(8036):483 [MEDLINE]
  • Controlled oxygen administration in acute respiratory failure in chronic obstructive pulmonary disease: a reappraisal. Am J Med. 1978;65(6):896 [MEDLINE]
  • Severe hypercapnia after low-flow oxygen therapy in patients with neuromuscular disease and diaphragmatic dysfunction. Mayo Clin Proc. 1995;70(4):327 [MEDLINE]
  • Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J. 2004;23(6):932 [MEDLINE]
  • Initial oxygen management in patients with an exacerbation of chronic obstructive pulmonary disease. QJM. 2005;98(7):499 [MEDLINE]
  • The effects of oxygen therapy in patients presenting to an emergency department with exacerbation of chronic obstructive pulmonary disease. Med J Aust. 2007;186(5):235 [MEDLINE]
  • Extracorporeal carbon dioxide removal: the future of lung support lies in the history. Blood Purif. 2012;34(2):94-106 [MEDLINE]
  • BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017;72(Suppl 1):ii1 [MEDLINE]