Respiratory Failure

Definition and Classification

Definition

Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation.

Classification

Respiratory failure may be classified based on: 

The time course:

• Acute respiratory failure: occurs within minutes to hours.
• Chronic respiratory failure: 
  • Occurs over months to years 
  • Often due to a chronic lung disease process

The underlying issue:

• Hypoxemic respiratory failure (type 1): 
  • Most common form of respiratory failure
  • Results from a ↓ ability to oxygenate the blood
• Hypercapnic respiratory failure (type 2):
  • Results from a ↓ ability to eliminate carbon dioxide (CO₂) 
  • ↓ pH of the blood → respiratory acidosis

Etiology

Etiology of hypoxemic respiratory failure

• Right-to-left shunt:
  • Pulmonary edema (cardiogenic and noncardiogenic)
  • Pneumonia
  • Pulmonary hemorrhage
  • Aspiration
  • Atelectasis
  • ARDS
• V/Q mismatch:
  • Pulmonary embolism
  • Asthma
  • Chronic obstructive pulmonary disease (COPD)
  • Cystic fibrosis
  • Interstitial lung disease
  • Pulmonary hypertension
• Low inspired oxygen: high altitude
• Hypoventilation:
  • Sedative medications
  • Neuromuscular conditions

Etiology of hypercapnic respiratory failure

• Diminished respiratory drive:
  • Sedative medications (opioids, benzodiazepines)
  • Brain stem lesions (affecting the central respiratory center)
  • Multiple sclerosis
  • Hypothermia
• Impaired respiratory muscle function:
  • Guillain–Barré syndrome
  • Myasthenia gravis
  • Amyotrophic lateral sclerosis
  • Multiple sclerosis
  • Botulism
  • Tetanus
  • Spinal cord lesions
  • Muscle fatigue (seen with hypoxemic respiratory failure)
  • Malnutrition
  • Myopathy
• Airway obstruction:
  • COPD
  • Asthma
  • Obstructive sleep apnea
  • Cystic fibrosis
  • Airway edema
• Diminished lung elasticity:
  • Alveolar edema
  • Pneumonia
  • Atelectasis
  • ARDS
• Diminished chest wall elasticity:
  • Pleural effusion
  • Obesity
  • Kyphoscoliosis
  • Abdominal distention
  • Pneumothorax

Pathophysiology

Right-to-left shunt

• Blood is shunted from the right side of the lung to the left side without oxygenation.
• Deoxygenated blood mixes with oxygenated blood → ↓ arterial pressure of O₂
• This can be caused by:
  • Cardiac shunting (e.g., congenital malformations of the heart that allow blood to bypass the respiratory system) 
  • Pulmonary shunting (e.g., fluid fills the alveoli, preventing oxygen diffusion)
• Note: 100% oxygen administration will not change oxygenation.

Ventilation-to-perfusion inequality

A mismatch between ventilation and perfusion occurs from a disease process resulting in either:

• Low V/Q ratio:
  • May occur from:
    • Diminished oxygen entry into alveoli with normal blood flow 
    • Overperfusion of alveoli with normal ventilation (e.g., diversion of blood flow)
  • Results in: 
    • Hypoxemia 
    • Hypercapnia
• High V/Q ratio:
  • Results from diminished blood flow to alveoli with normal ventilation
  • Ventilation is wasted.
  • Must be severe for gas exchange to be affected

Note: 100% oxygen administration can correct oxygenation in V/Q mismatch.

Clinical Presentation

General signs and symptoms

• Vitals:
  • Tachypnea
  • Tachycardia
• Dyspnea
• Diaphoresis
• Altered mental status:
  • Restlessness and anxiety
  • Confusion
  • Somnolence
  • Coma

Hypoxemia

• Fatigue (inability to speak in complete sentences)
• Use of accessory muscles of respiration
• Cyanosis

Hypercapnia

• Headache
• Asterixis
• Change in breathing pattern:
  • Shallow
  • Irregular
  • Gasping

Diagnosis

Arterial blood gas

An arterial blood gas (ABG) analysis is required in the diagnosis of respiratory failure. It measures and calculates components in arterial blood:

• Measured:
  • pH
  • Partial pressure of oxygen (PaO₂)
  • Partial pressure of CO₂ (PaCO₂)
• Calculated:
  • Bicarbonate (HCO₃)
  • Base excess
  • Oxygen saturation (SaO₂)

Criteria

The following parameters are used to define hypoxemic and hypercapnic respiratory failure:

Hypoxemic respiratory failure:

• PaO₂ < 60 mmHg on a supplemental O₂ concentration ≥ 50% 
• PaO₂ < 40 mmHg with any O₂ concentration
• SaO₂ < 90%

Hypercapnic respiratory failure:

• PaCO₂ > 50 mmHg
• In patients with chronic hypercapnia:
  • PaCO₂ acutely above a patient’s normal baseline
  • Concurrent ↓ in pH < 7.3

Alveolar–arterial gradient

Once hypoxemic respiratory failure is established, the alveolar–arterial (A-a) gradient can be used to help in understanding the potential underlying etiology.

• Defined as the difference between the oxygen concentration in the alveoli (PAO₂) and arterial blood (PaO₂):
  • A-a gradient = PAO₂ – PaO₂ 
  • PAO₂: calculated from the alveolar gas equation
  • PaO₂: measured in an ABG
• Interpretation:
  • Normal: 5–10 mmHg
  • Increased in etiologies that cause:
    • Right-to-left shunting
    • V/Q mismatch

Supporting workup

The following can be done to evaluate for potential causes of respiratory failure. The workup should be tailored to the patient’s presentation and clinical suspicion.

Laboratory evaluation:

• CBC
  • Anemia
  • Polycythemia → seen in chronic respiratory failure
  • ↑ WBC → infection
• Troponin and BNP → cardiogenic pulmonary edema
• Blood and sputum cultures → pneumonia
• Creatine kinase → myositis
• Urine drug screen → sedation from opioids or benzodiazepines

Pulmonary function tests:

• More useful in chronic respiratory failure
• Used for assessing and monitoring the severity of obstructive and restrictive lung disease
• Predictive of ventilatory failure in patient with neuromuscular disease

Imaging:

• Chest X-ray:
  • Atelectasis
  • Pneumonia
  • Pulmonary edema
  • ARDS
  • Pleural effusion
  • Pneumothorax
• CT chest:
  • Pulmonary embolism
  • Interstitial lung disease
  • Pulmonary hemorrhage

Management

Management of respiratory failure is supportive and focuses on maintaining adequate oxygenation and ventilation until the underlying condition can be treated.

Supplemental oxygen

General principles:

• In hypoxemic respiratory failure, use the lowest concentration of oxygen that provides sufficient oxygenation to avoid oxygen toxicity.
• In hypercapnic respiratory failure, excessive administration of oxygen may result in V/Q mismatch and loss of the hypoxemic respiratory drive.

Options:

• Nasal cannula:
  • Used in mild hypoxemia
  • Low flow
  • Provides low amounts of oxygen (24%–50%)
• Simple face mask: 
  • Slightly higher flow than nasal cannula
  • Delivers low to moderate amounts of oxygen (40%–60%)
• Venturi mask: 
  • Especially helpful when overoxygenation is a potential concern
  • Delivers a known concentration of oxygen (24%–60%)
• Nonrebreather mask:
  • Used for severe hypoxemia, often as a transition to other ventilatory measures
  • Contains a reservoir bag for oxygen
  • Requires a higher flow
  • Allows high concentrations of oxygen (60%–90%)
  • Exhaled air is released through a 1-way valve (prevents re-inhalation).
• High-flow nasal cannula:
  • Provides high volumes of oxygen (up to approximately 100%)
  • Humidified
  • Can provide a small amount of positive pressure

Noninvasive positive-pressure ventilation (NPPV)

Noninvasive positive-pressure ventilation provides ventilatory support without placing an artificial airway.

Indications:

• Ideally for conscious patients 
• Moderate to severe hypoxemia or hypercapnia
• Increased respiratory effort and tachypnea:
  • Accessory muscle use, pursed-lip breathing
  • Goal is to prevent fatigue.

Best suited for:

• Pulmonary edema
• COPD

Options:

• BiPAP:
  • Most commonly used form of NPPV
  • Provides positive inspiratory pressure (assists with active inhalation)
  • Delivers constant PEEP
  • Used acutely for hypoxemic and hypercapnic failure
• CPAP (continuous positive airway pressure):
  • Delivers essentially constant PEEP
  • Used for hypoxemic failure
  • Patients may use long term for sleep apnea.

Invasive ventilation

Indications: 

• Severe respiratory distress 
• Patient is obtunded and is unable to protect the airway (absent gag or cough reflex).
• Severe hypoxemia 
• Severe hypercapnia (especially for a pH < 7.2)
• Worsening condition despite NPPV support
• Impending respiratory fatigue

General principles:

• Applies positive pressure breaths
• Volumes and pressures given are dependent on the resistance and compliance of the airways.

Parameters:

• To improve oxygenation:
  • ↑ Fraction of inspired oxygen (FiO₂)
  • ↑ PEEP
• To improve ventilation:
  • ↑ Respiratory rate 
  • ↑ Tidal volume

ECMO

ECMO is an advanced therapy utilizing prolonged cardiopulmonary bypass to oxygenate blood and remove CO₂.

• Considered in respiratory failure that remains refractory despite mechanical ventilation (e.g., ARDS)
• Can be done only at specialized centers with a dedicated, multidisciplinary team