Respiratory failure

Respiratory failure is the acute or chronic inability of the respiratory system to maintain gas exchange (PaO₂ of < 60 mmHg, PaCO₂ > 50 mmHg). Causes can be extrapulmonary (e.g., CNS depression due to narcotic overdose) as well as pulmonary (e.g., acute exacerbation of COPD). Respiratory failure can be classified as hypoxemic (type 1) or hypercapnic (type 2). Clinical features of hypoxemia include respiratory distress, cyanosis, tachycardia, and altered mental status. Clinical features of hypercapnia include hypoventilation, headache, warm extremities, and asterixis. Diagnostics include arterial blood gas analysis and possibly chest imaging to detect the underlying disease. Treatment includes supportive measures (oxygen delivery and/or ventilator support) and treatment of the underlying condition. Complications may arise due to prolonged hypoxemia and can affect various organs (e.g., renal/heart failure, brain damage).

Respiratory failure is the acute or chronic inability of the respiratory system to maintain gas exchange. This leads to: ^[1]

• Failure to oxygenate the body: defined as a PaO₂ of < 60 mmHg (8 kPa)
• Failure to eliminate carbon dioxide: defined as a PaCO₂ of > 50 mmHg (6.5 kPa)

• Pulmonary causes
  • Airway obstruction (hypoventilation) and/or increased physiologic dead space (e.g., due to exacerbation of COPD, acute severe bronchial asthma, bronchiolitis)
  • Impaired alveolar diffusion (e.g., due to pulmonary edema, severe pneumonia, pulmonary hemorrhage , idiopathic pulmonary fibrosis)
  • Right-to-left shunt
    • Pulmonary right-to-left shunt (e.g., due to ARDS, pulmonary contusions/hemorrhage, lung collapse)
    • Intracardiac right-to-left shunt (e.g., due to atrial septal defect, VSD, PDA)
  • V/Q mismatch (e.g., due to severe pneumonia, pulmonary edema, pulmonary embolism, atelectasis)
  • Decreased FiO₂ (e.g., due to asphyxiant gas exposure, high altitude)
• Extrapulmonary causes
  • CNS depression (e.g., due to narcotic or sedative overdose, brain trauma/herniation, stroke)
  • Respiratory muscle weakness (e.g., due to myasthenia gravis, Guillain-Barre syndrome, myopathies, ALS, high cervical spinal cord injury, poliomyelitis)
  • Decreased chest wall compliance (e.g., due to rib fractures, tension pneumothorax, tetanus, seizures, fibrothorax)
  • Increased O₂ consumption and/or CO₂ production (e.g., due to severe sepsis, toxic shock syndrome, cardiogenic shock, multiorgan dysfunction)
  • Electrolyte disturbances (e.g., anorexia nervosa)

• Clinical features of hypoxemia
  • Tachypnea, dyspnea
  • Cyanosis
  • Pleuritic chest pain
  • Tachycardia, arrhythmia
  • Confusion, somnolence
• Clinical features of hypercapnia
  • Hypoventilation
  • Headache, daytime sleepiness
  • Anxiety
  • Warm extremities
  • Papilledema
  • Asterixis
  • Coma
  • Paralytic ileus
• Clinical features of the underlying condition
  • Fever, e.g., due to sepsis, pneumonia
  • Cough, e.g., due to pneumonia, COPD
  • Chest pain, e.g., due to pneumonia, pulmonary embolism
  • Signs of general muscle weakness, e.g., due to myasthenia gravis, Guillain-Barre syndrome, myopathies, ALS
  • Pain on inspiration, e.g., due to rib fracture
  • CNS depression, e.g., due to opioid use

• Arterial blood gas analysis (ABG): to confirm diagnosis
  • Alveolar-arterial gradient: ([P_atm - 47] × FiO₂ - [PaCO₂/0.8]) - PaO₂
  • Normal Aa gradient: hypoventilation or ↓ oxygen uptake
  • ↑ Aa gradient: V/Q mismatch or shunting

• Chest imaging (x-ray, CT): to assess for chest wall, pleural, and/or lung lesions (e.g., trauma, ARDS, pneumonia, pneumothorax, atelectasis, pleural effusion)
• Assessment for underlying conditions
  • Leukocytosis (and/or thrombocytopenia) in sepsis or pneumonia: CBC
  • COPD or asthma: pulmonary function tests
  • Heart defects (e.g., atrial septal defect, VSD, PDA): ECG, echocardiography

Supportive measures ^[1]

• Nonmechanical ventilation/oxygen support
  • Via nasal cannula or face mask
  • Goal
    • Correction of hypoxemia
    • Maintain adequate tissue oxygenation (PaO₂ of 60 mmHg or SaO₂ of > 90%)
• Mechanical ventilation
  • Goal
    • Correct hypercapnia and possible hypoxemia
    • Support weak/fatigued respiratory muscles
  • Oxygenation and ventilation are affected via change of the following mechanical ventilator parameters:
    • ↑ Respiratory rate and/or ↑ tidal volume → ↑ ventilation
    • ↑ FiO₂ and/or ↑ PEEP → ↑ oxygenation
    • Apnea
    • Tachypnea of > 30 breaths per minute
    • Disturbed consciousness, coma
    • Respiratory muscle fatigue
    • Hemodynamic instability (e.g., arrhythmia)
    • Failure of supplemental oxygen to increase PaO₂ to > 55 mm Hg
    • Hypercapnia with arterial pH < 7.25
  • See “Mechanical ventilation” for more details.

Treatment of underlying conditions

• Airway obstruction (COPD, asthma): bronchodilators and/or inhaled corticosteroids:
• Infection (e.g., pneumonia, sepsis, bronchiolitis): antibiotic or antiviral treatment
• Pulmonary embolism: empiric parenteral anticoagulation
• Narcotic or sedative overdose: antidote
• Brain trauma/herniation: surgical decompression
• Ischemic stroke: reperfusion therapy
• Pneumothorax: chest tube placement

• Pulmonary: e.g., irreversible lung scarring after pulmonary embolism or pneumonia, ventilator dependence
• Cardiac: e.g., arrhythmias, heart failure
• Neurological: e.g., irreversible brain damage, brain death
• Renal: e.g., acute renal failure
• Gastrointestinal: e.g., stress ulcer, ileus
• Nutritional: e.g., hypoglycemia, electrolyte disturbances

We list the most important complications. The selection is not exhaustive.