Definition and Pathophysiology of Respiratory Failure
Respiratory failure is defined as the inability of the respiratory system to maintain adequate gas exchange, characterized by PaO₂ <8 kPa (60 mmHg) with or without PaCO₂ >6 kPa (45 mmHg), resulting from failure of oxygenation, ventilation, or both. 1, 2
Core Definition
Respiratory failure represents a breakdown in the cardiopulmonary system's ability to maintain adequate oxygen delivery to tissues and/or adequate carbon dioxide removal from tissues. 3, 4 The condition is diagnosed when arterial blood gas analysis reveals:
- PaO₂ <60 mmHg (8 kPa) while breathing room air 1, 2, 5
- With or without elevated PaCO₂ depending on the type 2, 6
Classification System
Type 1 (Hypoxemic) Respiratory Failure
- Defined by PaO₂ <8 kPa (60 mmHg) with normal or low PaCO₂ (≤6 kPa or 45 mmHg) 1, 2
- Results from failure to maintain adequate oxygenation despite normal or increased ventilatory effort 1
- Hypoxemia is the dominant feature with preserved ventilatory capacity 6
Type 2 (Hypercapnic) Respiratory Failure
- Defined by PaO₂ <8 kPa (60 mmHg) AND PaCO₂ >6 kPa (45 mmHg) 1, 2
- Represents failure of the ventilatory pump to eliminate CO₂ produced by metabolism 1, 2
- Both hypoxemia and hypercapnia are present 2
Pathophysiological Mechanisms
Type 1 Respiratory Failure Mechanisms
Ventilation-perfusion (V/Q) mismatch is the primary mechanism, where blood flows through poorly ventilated lung regions, preventing adequate oxygenation. 1, 2, 6
Intrapulmonary shunting occurs when blood bypasses ventilated alveoli entirely, flowing through completely unventilated or fluid-filled lung units—this does not respond to supplemental oxygen. 1
Diffusion impairment results from thickened alveolar-capillary membranes, limiting oxygen transfer across the interface. 1, 6
Common clinical causes include:
- ARDS: Bilateral infiltrates with increased pulmonary capillary permeability, classified as mild (PaO₂/FiO₂ 200-300 mmHg), moderate (100-200 mmHg), or severe (≤100 mmHg) 7, 1
- Pneumonia: Creates consolidated lung regions with shunt physiology 1
- Pulmonary edema: Fills alveoli with fluid from increased vascular permeability or hydrostatic pressure 7, 1
Type 2 Respiratory Failure Mechanisms
Alveolar hypoventilation is the fundamental mechanism, where minute ventilation is insufficient relative to CO₂ production. 1, 2, 6
Increased mechanical workload develops from:
- Increased airway resistance requiring greater inspiratory effort 1, 8
- Dynamic hyperinflation with intrinsic PEEP (PEEPi) trapping air and flattening the diaphragm 1, 8
- Inspiratory muscle dysfunction from fatigue or weakness 1, 8
Increased dead space ventilation occurs when ventilated alveoli are not perfused, wasting ventilatory effort. 8 This shifts breathing to a rapid shallow pattern (high respiratory rate, low tidal volume) that increases the dead space/tidal volume ratio of each breath. 8
Common clinical causes include:
- COPD exacerbations: Airflow obstruction with air trapping and V/Q mismatch 7, 1, 8
- Neuromuscular disorders: Respiratory muscle weakness preventing adequate ventilation 7, 1
- Chest wall deformities: Restrictive defects limiting lung expansion 1
Sepsis-Related Respiratory Dysfunction
Sepsis creates a spectrum of respiratory abnormalities from subclinical changes to full ARDS. 7, 1 Multiple factors increase work of breathing:
- Increased dead space ventilation from vascular bed obliteration 7, 1
- Respiratory muscle dysfunction 1
- Decreased thoracic compliance from edema 1
- Bronchoconstriction 1
Both increased physiological dead space and intrapulmonary shunting drive tachypnea and elevated minute ventilation. 1
Clinical Course and Natural History
ARDS Progression
The natural history is dominated by the inciting event rather than lung injury itself. 7 Death from refractory respiratory failure is unusual; the most common cause of death is multiple organ failure or recurrent sepsis. 7
In patients resolving rapidly (10-14 days):
- Minute ventilation and dead-space ventilation decrease with improving oxygenation 7
- The lung withstands higher forces in early ARDS without evident barotrauma 7
In severe ARDS with fibrosis development:
- Minute ventilatory requirements remain high despite improving oxygenation 7
- Progressive vascular bed obliteration increases dead-space ventilation 7
- Mortality was historically 60-70% but has declined to approximately 40% 7
Acute vs. Chronic Respiratory Failure
Acute respiratory failure develops suddenly with rapid arterial blood gas deterioration. 1
Chronic respiratory failure develops gradually with compensatory mechanisms like renal bicarbonate retention buffering the acidosis. 1
Acute-on-chronic respiratory failure presents unique challenges due to altered baseline physiology and limited physiological reserve. 1
Critical Diagnostic Pitfalls
Standard chest radiographs are poor predictors of oxygenation defect severity or clinical outcome. 7, 1 Classic ARDS findings may be asymmetric, patchy, or focal rather than diffuse and bilateral. 7, 1
Clinical recognition of hypoxemia is unreliable—continuous pulse oximetry is essential, though it may be unreliable with poor peripheral perfusion, carbon monoxide poisoning, or methemoglobinemia. 7
Administering high-flow oxygen without monitoring CO₂ can precipitate CO₂ narcosis and respiratory arrest in Type 2 respiratory failure. 1 Controlled oxygen with target saturation 88-92% is mandatory. 7, 1