Respiratory Failure (see Respiratory Failure)

• Definition
  • Respiratory Failure is Defined as the Occurrence of One or Both of 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 (see Hypoxemia)

• Definition
  • Hypoxemia is Defined a Decrease in Hemoglobin Oxygen Saturation (as Assessed by Pulse Oximetry: SaO2 or SpO2) or Decrease in Arterial pO2 (as Assessed by Arterial Blood Gas)
• Note that a Patient May Be Hypoxemic, But Not Be Hypoxic
  • Example
    • A Young Hypoxemic Patient Can Significantly Increase Their Cardiac Output to Maintain Tissue Oxygen Delivery

Hypoxia (see Hypoxemia)

• Definition
  • Hypoxia is Defined as a State of Impaired Tissue Oxygenation
• Note that 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

• Definition
  • Anoxia is Defined as Complete Tissue Deprivation of Oxygen Supply

Hypercapnia (see Hypercapnia)

• Definition
  • Hypercapnia is Defined as Increase in Arterial pCO2 (i.e. Increased Arterial Blood Partial Pressure of Carbon Dioxide) to >40 mm Hg

Acidemia

• Definition
  • Acidemia is Defined as Decrease in Arterial pH < 7.40 (Due to Either Metabolic or Respiratory Acidosis)
• Note that a Patient Can Be Acidemic without having a Respiratory Acidosis
  • Example
    • Metabolic Acidosis Can Produce Acidemia without the Presence of a Respiratory Acidosis

Alkalemia

• Definition Alkalemia is Defined an Increase in Arterial pH to >7.40 (Due to Either Metabolic or Respiratory Alkalosis)

Acidosis

• Definition
  • Acidosis is Defined as the Presence of an 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

• Definition
  • Alkalosis is Defined as the Presence of an 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

Respiratory Acidosis (see Respiratory Acidosis)

• Definition
  • Respiratory Acidosis is Defined as a Disorder Which Results in Increase in Arterial pCO2 with an Associated Decrease in Arterial pH
• Note that a Patient Can Have a Respiratory Acidosis without Being Significantly Acidemic
  • Example
    • Via Normal Compensatory Mechanisms, Chronic Respiratory Acidosis Induces Metabolic (Predominantly Renal) Compensation (with a Increase in Serum Bicarbonate Over Time), Culminating in Minimal Acidemia

Terms

• 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)

Demographics of Patients with Acute Hypoxemic, Hypercapnic Respiratory Failure

• 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 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

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
  • Arterial Blood Gas (ABG) (see Arterial Blood Gas): decreased pO2

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)
    • Right Ventricular Dysfunction Due to Right Ventricular infarct (see Coronary Artery Disease)
    • Acute Cor Pulmonale Due to Acute Pulmonary Embolism (see Acute Pulmonary Embolism)
    • Tamponade (see Tamponade): unclear why this results in decreased mixed venous oxygen saturation
  • 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)

• Mechanism
  • Worsening of V/Q Mismatch, Aabove the Levels Which are Observed as Part of Normal Human Physiology
• Etiology
  • Acute Pulmonary Embolism (Acute PE) (see Acute Pulmonary Embolism)
    • Predominant Mechanism is V/Q Mismatch
    • Minor Mechanism is Shunt (Particularly Occurs Due to Coexistent Atelectasis)
  • Atelectasis (see Atelectasis)
  • Hemodialysis-Associated Hypoxemia (see Hemodialysis,)
  • Interstitial Lung Disease (ILD) (see Interstitial Lung Disease)
  • Leukostasis (see Leukostasis)
  • Obstructive Lung Disease (see Obstructive Lung Disease)
    • Asthma (see Asthma)
    • Chronic Obstructive Pulmonary Disease (COPD) (see Chronic Obstructive Pulmonary Disease)
  • Pneumonia
    • Community-Acquired Pneumonia (CAP) (see Community-Acquired Pneumonia)
    • Hospital-Acquired Pneumonia (HAP)/Ventilator-Associated Pneumonia (VAP) (see Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia
  • Pulmonary Vascular Disease (see Pulmonary Hypertension)

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
  • Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome): due to physiologic intrapulmonary shunt
  • Acute Pulmonary Embolism (PE) (see Acute Pulmonary Embolism)
    • Epidemiology
      • Case Report of a Patient with Platypnea-Orthodeoxia Due to Bilateral Lower Lobe Pulmonary Emboli (South Med J, 2011) [MEDLINE]
    • Physiology
      • Predominant Mechanism is V/Q Mismatch
      • Minor Mechanism is Shunt (Particularly Occurs Due to Coexistent Atelectasis)
  • Atelectasis (see Atelectasis): due to physiologic intrapulmonary shunt
  • Hepatopulmonary Syndrome (see Hepatopulmonary Syndrome): due to anatomic intrapulmonary shunt (which often increases with the patient in an upright position, resulting in orthodeoxia/platypnea)
  • Intralobar Pulmonary Sequestration (see Pulmonary Sequestration): one reported case of this resulting in an anatomic intrapulmonary shunt
  • Pneumonia: due to physiologic intrapulmonary shunt
    • Community-Acquired Pneumonia (CAP) (see Community-Acquired Pneumonia)
    • Hospital-Acquired Pneumonia (HAP) and Ventilator-Associated Pneumonia (VAP) (see Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia)
  • Pulmonary Arteriovenous Malformation (AVM) (see Pulmonary Arteriovenous Malformation (AVM)): due to anatomic intrapulmonary shunt

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
  • Acute Pulmonary Embolism (Acute PE) with Right to Left Shunt (see Acute Pulmonary Embolism): acutely increased pulmonary artery pressure may result in new or exacerbated right to left shunt through a pre-existing PFO, etc
  • Atrial Septal Defect with Right to Left Shunt (see Atrial Septal Defect)
  • Patent Ductus Arteriosus with Right to Left Shunt (see Patent Ductus Arteriosus)
  • Patent Foramen Ovale with Right to Left Shunt (see Patent Foramen Ovale)
  • Tetralogy of Fallot with Right to Left Shunt (see Tetralogy of Fallot): VSD + pulmonary artery stenosis
  • Ventricular Septal Defect (VSD) with Right to Left Shunt (see Ventricular Septal Defect)

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

Acute Type II-Hypoxemic, Hypercapnic Respiratory Failure

Disorders with Decreased Ventilatory Drive

• Metabolic Alkalosis (see Metabolic Alkalosis)
  • Mechanism
    • Elevated Serum Bicarbonate Increases the 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
  • Autonomic Insufficiency Syndrome (Dysautonomia) (see Autonomic Insufficiency Syndrome)
  • Brainstem Abscess (see Brain Abscess)
  • Brainstem Encephalitis (see Encephalitis)
  • Brainstem Hemorrhage (see Intracerebral Hemorrhage)
  • Brainstem Cerebrovascular Accident (CVA) (see Ischemic Cerebrovascular Accident)
  • Brainstem Multiple Sclerosis (see Multiple Sclerosis)
  • Brainstem Neoplasm
  • Brainstem Poliomyelitis (see Poliomyelitis)
  • Brainstem Sarcoidosis (see Sarcoidosis)
  • Hypogonadism with Testosterone Administration (see Hypogonadism)
  • Obesity Hypoventilation Syndrome (OHS) (see Obesity Hypoventilation Syndrome)
    • Mechanism: combination of chest wall restriction and decreased central respiratory drive
  • Prader-Willi Syndrome (see Prader-Willi Syndrome)
    • Mechanism: impaired hypoxic/hypercapnic ventilatory drive
  • Primary Alveolar Hypoventilation Syndrome (Ondine’s Curse) (see Primary Alveolar Hypoventilation Syndrome)
  • Pharmacologic Central Respiratory Depression
    • Opiates (see Opiates)
    • Benzodiazepines (see Benzodiazepines)
    • Barbiturates (see Barbiturates)
    • Etomidate (Amidate) (see Etomidate)
    • General Anesthesia (see General Anesthesia)
    • Intoxications
      • Propylene Glycol Intoxication (see Propylene Glycol)
      • Tricyclic Antidepressant Intoxication (see Tricyclic Antidepressants)
    • Ketamine (Ketalar) (see Ketamine): respiratory depression may occur with rapid administration or overdosage
    • Propofol (Diprivan) (see 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)
    • Atlantoaxial Subluxation/Instability (see Atlantoaxial Instability)
    • Cervical Disk Disease with Cord Compression
    • Cervical Osteoarthritis
    • Cervical Space-Occupying Lesions
      • Cervical Echinococcal Cyst (see Echinococcosis)
      • Cervical Epidural Abscess (see Spinal Epidural Abscess)
      • Cervical Gumma (see Syphilis)
      • Cervical Spinal Cord Hematoma (Hematomyelia) (see Spinal Cord Hematoma)
      • Cervical Tumor
    • 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)
  • Periodic Paralysis Syndromes
    • Hyperkalemic Periodic Paralysis (see Hyperkalemic Periodic Paralysis)
    • Hypokalemic Periodic Paralysis (see Hypokalemic Periodic Paralysis)
    • Thyrotoxic Periodic Paralysis (see Thyrotoxic Periodic Paralysis)
  • Rheumatologic
    • Mixed Connective Tissue Disease (see Mixed Connective Tissue Disease)
    • Polydermatomyositis (see Polydermatomyositis)
    • Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus): neuropathy and myopathy
  • Electrolyte-Related
    • Hyperkalemia (see Hyperkalemia): may cause respiratory muscle weakness
    • Hypomagnesemia (see Hypomagnesemia)
    • Hypophosphatemia (see Hypophosphatemia)
  • Other
    • Bilateral Diaphragmatic Paralysis (see Bilateral Diaphragmatic Paralysis)
    • Critical Illness Polymyopathy (see ICU-Acquired Weakness)
    • Necrotizing Myopathy from Steroids and Neuromuscular Junction Antagonists
    • Hyperthyroidism (see Hyperthyroidism)
      • Clinical: proximal and distal myopathy with both inspiratory and expiratory muscle weakness
    • 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

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)
    • Croup (see Croup): typically acute
    • Infection (Select Etiologies Shown)
      • Deep Neck Infection (see Deep Neck Infection): typically acute
      • Peritonsillar Abscess (see Peritonsillar Abscess): involving peritonsillar space
      • Pretracheal Abscess (see Pretracheal Abscess): involving pretracheal space
      • Retropharyngeal Abscess (see Retropharyngeal Abscess): involving retropharyngeal space
      • Submandibular Space Abscess/Ludwig’s Angina (see Ludwig’s Angina): involving submandibular space
    • Miscellaneous (Select Etiologies Shown)
      • Anaphylaxis (see Anaphylaxis): typically acute
      • Angioedema (see Angioedema): typically acute
• 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 Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome)
  • Aspiration Pneumonia (see Aspiration Pneumonia)
  • Cardiogenic Pulmonary Edema (see Congestive Heart Failure)
  • Diffuse Alveolar Hemorrhage (DAH) (see Diffuse Alveolar Hemorrhage)
  • 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
  • Pneumonia (see Pneumonia)
• Acute Pleural or Chest Wall Disease (with Increased Work of Breathing)
  • Ankylosing Spondylitis (see Ankylosing Spondylitis)
  • Chest Wall Trauma
  • Fibrothorax (see Fibrothorax)
  • Flail Chest (see Flail Chest,)
  • Hemothorax (see Pleural Effusion-Hemothorax)
  • Kyphoscoliosis (see Kyphoscoliosis)
  • Large Pleural Effusion (see Pleural Effusion-Transudate and Pleural Effusion-Exudate)
  • Large Pneumothorax (see Pneumothorax)
  • Obesity Hypoventilation Syndrome (OHS) (see Obesity Hypoventilation Syndrome)
    • Mechanism: combination of chest wall restriction and decreased central respiratory drive
  • Pectus Excavatum (see Pectus Excavatum)
  • Post-Thoracoplasty (see Thoracoplasty)
  • Severe Abdominal Distention
    • Ascites (see Ascites)
    • Abdominal Compartment Syndrome (see Abdominal Compartment Syndrome)
    • Pregnancy (see Pregnancy)
• 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)
    • Mechanism
      • 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
    • Cardiogenic Shock (see Cardiogenic Shock): generalized pulmonary hypoperfusion
    • Hypovolemic Shock (see Hypovolemic Shock): generalized pulmonary hypoperfusion
    • Ventilation During Cardiopulmonary Resuscitation (CPR) (see Cardiopulmonary Resuscitation): generalized pulmonary hypoperfusion
• 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)
  • Inflammation/Hypermetabolism
    • Corticosteroids (see Corticosteroids): due to catabolic state
    • Exercise
    • Fever (see Fever)
    • Metabolic Acidosis (see Metabolic Acidosis-General)
      • Burns (see Burns)
      • Severe Trauma
    • Sepsis (see Sepsis): due to catabolic state
    • Thyrotoxicosis (see Hyperthryoidism)
  • Muscle Activity
    • Shivering
    • Tetany
    • Seizures (see Seizures)
    • Malignant Hyperthermia (see Malignant Hyperthermia)
  • Excessive Caloric Intake/Overfeeding
    • Excessive Caloric Intake (see Enteral Nutrition): especially carbohydrates (which generate more carbon dioxide per calorie than fats)
• 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 the 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
  • Autonomic Insufficiency Syndrome (Dysautonomia) (see Autonomic Insufficiency Syndrome)
  • Brainstem Abscess (see Brain Abscess)
  • Brainstem Encephalitis (see Encephalitis)
  • Brainstem Intracerebral Hemorrhage (Hemorrhagic Cerebrovascular Accident) (see Intracerebral Hemorrhage)
  • Brainstem Ischemic Cerebrovascular Accident (CVA) (see Ischemic Cerebrovascular Accident)
  • Brainstem Multiple Sclerosis (see Multiple Sclerosis)
  • Brainstem Neoplasm
  • Brainstem Poliomyelitis (see Poliomyelitis)
  • Brainstem Sarcoidosis (see Sarcoidosis)
  • Hypogonadism with Testosterone Administration (see Hypogonadism)
  • Obesity Hypoventilation Syndrome (OHS) (see Obesity Hypoventilation Syndrome)
    • Mechanism: combination of chest wall restriction and decreased central respiratory drive
  • Prader-Willi Syndrome (see Prader-Willi Syndrome
    • Mechanism: impaired hypoxic/hypercapnic ventilatory drive
  • Primary Alveolar Hypoventilation Syndrome (Ondine’s Curse) (see Primary Alveolar Hypoventilation Syndrome)
  • Pharmacologic Central Respiratory Depression
    • Opiates (see Opiates)
    • Benzodiazepines (see Benzodiazepines)
    • Barbiturates (see Barbiturates)
  • 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)
    • Atlantoaxial Subluxation/Instability (see Atlantoaxial Instability)
    • Cervical Disk Disease with Cord Compression
    • Cervical Osteoarthritis
    • Cervical Space-Occupying Lesions
      • Cervical Echinococcal Cyst (see Echinococcosis)
      • Cervical Epidural Abscess (see Spinal Epidural Abscess)
      • Cervical Gumma (see Syphilis)
      • Cervical Spinal Cord Hematoma (Hematomyelia) (see Spinal Cord Hematoma)
      • Cervical Tumor
    • 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
  • Periodic Paralysis Syndromes
    • Hyperkalemic Periodic Paralysis (see Hyperkalemic Periodic Paralysis)
    • Hypokalemic Periodic Paralysis (see Hypokalemic Periodic Paralysis)
    • Thyrotoxic Periodic Paralysis (see Thyrotoxic Periodic Paralysis)
  • Rheumatologic
    • Mixed Connective Tissue Disease (see Mixed Connective Tissue Disease)
    • Polydermatomyositis (see Polydermatomyositis)
    • Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus): neuropathy and myopathy
  • Electrolyte-Related
    • Hyperkalemia (see Hyperkalemia): may cause respiratory muscle weakness
    • Hypomagnesemia (see Hypomagnesemia)
    • Hypophosphatemia (see Hypophosphatemia)
  • Other
    • Bilateral Diaphragmatic Paralysis (see Bilateral Diaphragmatic Paralysis)
    • Critical Illness Polymyopathy (see ICU-Acquired Weakness)
    • Necrotizing Myopathy from Steroids and Neuromuscular Junction Antagonists
    • Hyperthyroidism (see Hyperthyroidism)
      • Clinical: proximal and distal myopathy with both inspiratory and expiratory muscle weakness
    • 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

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
      • Coccidioidomycosis (see Coccidioidomycosis): typically mild upper airway obstruction
      • Cryptococcosis (see Cryptococcosis): typically mild upper airway obstruction
      • Histoplasmosis (see Histoplasmosis): typically mild upper airway obstruction
      • Syphilis (see Syphilis)
    • 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)
  • End-Stage Interstitial Lung Disease (ILD) (see Interstitial Lung Disease)
    • Mechanism
      • Due to Increased Physiologic Dead Space
• Parenchymal Lung Disease (with Increased Work of Breathing)
  • Any Etiology of Pulmonary Fibrosis
    • Progressive Massive Fibrosis (PMF) (see Progressive Massive Fibrosis)
    • Recurrent Diffuse Alveolar Hemorrhage (DAH) (see Diffuse Alveolar Hemorrhage)
  • 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)
  • Ankylosing Spondylitis (see Ankylosing Spondylitis)
  • Fibrothorax (see Fibrothorax)
  • Flail Chest (see Flail Chest)
  • Kyphoscoliosis (see Kyphoscoliosis)
  • Large Pleural Effusion (see Pleural Effusion-Transudate and Pleural Effusion-Exudate)
  • Obesity Hypoventilation Syndrome (OHS) (see Obesity Hypoventilation Syndrome)
    • Mechanism: combination of chest wall restriction and decreased central respiratory drive
  • Pectus Excavatum (see Pectus Excavatum)
  • Post-Thoracoplasty (see Thoracoplasty)
  • Severe Abdominal Distention
    • Ascites (see Ascites)
    • Pregnancy (see Pregnancy)

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

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 Manifestation of Hypoxemia (see Hypoxemia)

• General Comments
  • Hypoxemia May Be Asymptomatic, Since Compensatory Mechanisms (Such as Increase in Cardiac Output, Increase in Hemoglobin) May Act to Maintain Tissue Oxygen Delivery and Avoid Hypoxic End-Organ Dysfunction
  • In Contrast, Hypoxia is Defined as a State of Impaired Tissue Oxygenation and is Always Symptomatic (See Definition Above)
• Cardiovascular Manifestations
  • Angina (see Coronary Artery Disease)
  • Arrhythmia
    • Atrial Fibrillation (AF) (see Atrial Fibrillation)
    • Atrial Flutter (see Atrial Flutter)
    • Ventricular Tachycardia (VT) (see Ventricular Tachycardia)
      • Sleep-Disordered Breathing is Associated with an Increased Risk of Nocturnal Ventricular Arrhythmias (Am J Respir Crit Care Med, 2006) [MEDLINE]
      • In Patients with Heart Failure and Sleep Apnea, Treatment with CPAP Eliminates Sleep-Disordered Breathing and Decreases Ventricular Irritability (Circulation, 2000) [MEDLINE]
    • Ventricular Fibrillation (AF) (see Ventricular Fibrillation)
  • Atrioventricular Heart Block
    • First Degree Atrioventricular Block (see First Degree Atrioventricular Block)
    • Second Degree Atrioventricular Block-Mobitz Type I (Wenckebach) (see Second Degree Atrioventricular Block-Mobitz Type I)
    • Second Degree Atrioventricular Block-Mobitz Type II (see Second Degree Atrioventricular Block-Mobitz Type II)
    • Third Degree Atrioventricular Block (see Third Degree Atrioventricular Block)
  • Congestive Heart Failure (CHF) (see Congestive Heart Failure)
  • Hypotension/Pulseless Electrical Activity (PEA) (see Hypotension and Pulseless Electrical Activity)
    • Due to Hypoxia-Induced Systemic Vasodilation (Which Attempts to Maintain Tissue Perfusion with Oxygen Delivery)
  • Prolonged QT Interval (see Torsade)
    • Hypoxemia Has Been Demonstrated to Prolong the QT Interval During Sleep in Patients with Coronary Artery Disease (CAD) (Chest, 1982) [MEDLINE]
    • Nocturnal Hypoxemia Has Been Demonstrated to Prolong the QT Interval in Patients with Chronic Obstructive Pulmonary Disease (COPD) (NEJM, 1982) [MEDLINE]
    • Acute Hypoxia Has Been Demonstrated to Prolong the QT Interval in Normal Subjects (Am J Cardiol, 2003) [MEDLINE]
    • Severe Obstructive Sleep Apnea Has Been Demonstrated to Prolong the QTc Interval in Patients with Congenital Long QT Syndrome (Independent of Age, Sex, BMI, Use of β-Blockers, and History of Syncope), Which is a Biomarker for Sudden Cardiac Death (Sleep, 2015) [MEDLINE] (see Obstructive Sleep Apnea)
      • Severity of Obstructive Sleep Apnea (as Represented by the Apnea-Hypoxia Index and Apnea Index During Sleep) is Directly Related to the Degree of QT Prolongation in This Population
      • The Obstructive Sleep Apnea-Related Increase in the QT May Be Mediated by Hypoxic Episodes (Typically Immediately Following the Apnea), Sympathetic Activation (During the Apnea), and/or Vagal Bradyarrhythmias (During the Apnea)
  • Sinus Tachycardia (see Sinus Tachycardia)
• Neurologic Manifestations
  • Altered Mental Status
    • Confusion/Delirium (see Delirium)
    • Lethargy/Obtundation (see Obtundation-Coma)
  • Anxiety (see Anxiety)
  • Dizziness (see Dizziness)
  • Headache (see Headache)
  • Hypoxemia-Induced Cerebral Vasodilation with Increased Intracranial Pressure (ICP) (see Increased Intracranial Pressure)
    • This May Potentiate Neurologic Injury in Traumatic Brain Injury (TBI) (see Traumatic Brain Injury)
  • Irritability/Restlessness
• Pulmonary Manifestations
  • Dyspnea (see Dyspnea)
  • Pulmonary Vasoconstriction with Worsening of Pulmonary Hypertension (see Pulmonary Hypertension)
    • Hypoxic Pulmonary Vasoconstriction is Further Enhanced by Acidosis (see Metabolic Acidosis-General)
• Other Manifestations
  • Clubbing (see Clubbing): may occur with chronic hypoxemia
  • Cyanosis (see Cyanosis)
  • Polycythemia (see Polycythemia): may occur with chronic hypoxemia

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)
  • Decreased Alveolar pO2
  • 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
  • Both Stimulated and Depressed Cardiovascular System
    • Via Competing Effects to Decrease Systemic Vascular Resistance (SVR), Increase Cardiac Output (CO), etc
    • Hypercapnia Usually Results in Pulmonary Hypertension and an Increase in Cardiac Output (CO) Though
  • Confusion/Delirium (see Delirium)
  • Depression (see Depression)
  • Increased Intracranial Pressure (ICP) (see Increased Intracranial Pressure)
    • Hypercapnia Causes Cerebral Vasodilation with Increased Cerebral Blood Flow
  • Obtundation/Coma (“CO2 Narcosis”) (see Obtundation/Coma)
    • Acute Hypercapnia Initially Causes Increased Respiratory Drive with Hyperventilation (Anesthesiology, 1960) [MEDLINE] (NEJM, 1984) [MEDLINE]
      • Subsequently, There is Development of Decreased Respiratory Drive, Leading to Worsening Hypercapnia with Depressed Mental Status (“CO2 Narcosis”)
      • These Later Effects are Mediated Via Increased Brain Glutamine, Increased Brain γ-Aminobutyric Acid (GABA), Decreased Brain Glutamate, and Decreased Brain Aspartate
  • 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)
    • Decreased Hemoglobin Affinity for Oxygen in the Lungs (with Decreased Oxygen Loading) and Increased Oxygen Unloading at the Tissues (Bohr Effect)
• Severe Hypercapnia
  • Altered Action of Pharmacologic Agents
    • Due to Intracellular Acidosis, Not Due to the Hypercapnia Itself
  • Anesthesia
    • Observed with pCO2 >200 mm Hg
  • Asterixis (see Asterixis)
  • Decreased Renal Blood Flow
    • Observed with pCO2 >150 mm Hg
  • Leakage of Intracellular Potassium
    • Observed with pCO2 >150 mm Hg
  • Increased Intracranial Pressure (ICP) with Papilledema (see Increased Intracranial Pressure)
    • Hypercapnia Causes Cerebral Vasodilation with Increased Cerebral Blood Flow
    • The Increased Cerebral Blood Flow May Undesirably Potentiate Neurologic Injury in Traumatic Brain injury (TBI), etc (see Traumatic Brain injury)
  • Myoclonus (see Myoclonus)
  • Peripheral Venodilation with Hypotension (see Hypotension)
  • Seizures (see Seizures)

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
  • Cyanosis
  • Polycythemia
  • Pulmonary Hypertension/Cor Pulmonale (see Pulmonary Hypertension)

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)
  • Opiate Agents (Selected)
    • Hydromorphone (Dilaudid) (see Hydromorphone)
    • Morphine (see Morphine)
• Discontinuation of Sedatives
  • Sedative Agents
    • Benzodiazepines (see Benzodiazepines)
    • Propofol (Diprivan) (see Propofol)
• Reversal of Opiates (see Opiates)
  • Opiate Agents (Selected)
    • Hydromorphone (Dilaudid) (see Hydromorphone)
    • Morphine (see Morphine)
  • Reversal Agentes
    • Naloxone (Narcan) (see Naloxone)
• Reversal of Paralytic Agents
  • Sugammadex Sodium (Bridion) (see Sugammadex)
• Reversal of Benzodiazepines
  • Benzodiazepines (Selected) (see Benzodiazepines)
    • Diazepam (Valium) (see Diazepam)
    • Lorazepam (Ativan) (see Lorazepam)
    • Midazolam (Versed) (see Midazolam)
  • Reversal Agents
    • Flumazenil (Rmomazicon) (see Flumazenil)
  • Specific Treatment of Patients with Respiratory Depressant Intoxication
    • Specific Antidote to Intoxication
      • Example: organophosphate/carbamate intoxication (see Organophosphates-Carbamates)
    • 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
      • Nasogastric/Orogastric Suction (see Nasogastric-Orogastric Tube)
      • Activated Charcoal (see Activated Charcoa)

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
  • Acetazolamide (Diamox) (see Acetazolamide)
  • Medroxyprogesterone (see Medroxyprogesterone)
  • Theophylline (see Theophylline)

Heliox (see Heliox)

• Potential Indications
  • Acute Asthma Exacerbation (see Asthma)
  • Acute COPD Exacerbation (see Chronic Obstructive Pulmonary Disease)
  • Upper Airway Obstruction (see Obstructive Lung Disease)

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)
  • Chronic Obstructive Pulmonary Disease (COPD) Exacerbation (see Chronic Obstructive Pulmonary Disease)
  • Cardiogenic Pulmonary Edema Associated with Congestive Heart Failure (CHF) (see Congestive Heart Failure)
  • Community-Acquired Pneumonia (CAP)
  • Acute Respiratory Distress Syndrome (ARDS)

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

• Indications
  • Failure of Noninvasive Positive-Pressure Ventilation (NIPPV) (see Noninvasive Positive-Pressure Ventilation)
  • Contraindication to Noninvasive Positive-Pressure Ventilation (NIPPV) (see Noninvasive Positive-Pressure Ventilation)
    • Patients with Aspiration Risk
    • Patients with Inability to Manage Secretions
    • Patients with Inability to Protect Upper Airway

Prone Ventilation

• Indications
  • Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome)

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

• Indications
  • Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome)

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]