Mechanisms of Pathophysiological Benefits in ARDS Management
Prone Positioning
Prone positioning works through multiple biomechanical mechanisms that redistribute ventilation-perfusion matching and reduce ventilator-induced lung injury, making it a cornerstone therapy for severe ARDS. 1, 2
Primary Mechanisms:
Redistribution of pleural pressure gradients: Prone positioning eliminates the gravitational gradient that causes dorsal lung compression in supine position, allowing previously collapsed dorsal alveoli to re-expand and participate in gas exchange 2
Homogenization of ventilation distribution: The prone position creates more uniform distribution of tidal volume across lung regions, reducing regional overdistension in ventral areas while recruiting dorsal zones 2
Improved ventilation-perfusion matching: Blood flow in ARDS remains preferentially distributed to dorsal lung regions regardless of position; prone positioning aligns ventilation with this perfusion pattern, dramatically improving oxygenation 2
Reduction in ventilator-induced lung injury: By promoting more homogeneous lung inflation, prone positioning reduces focal stress concentrations that drive inflammatory injury and barotrauma 2
Enhanced secretion drainage: Gravitational effects facilitate clearance of inflammatory debris and secretions from dependent lung regions 2
Clinical Application: The American Thoracic Society recommends implementing prone positioning for >12 hours daily in severe ARDS (PaO₂/FiO₂ <100 mmHg), as this intervention demonstrates significant mortality reduction 1, 3, 4
Corticosteroids
Corticosteroids attenuate the dysregulated inflammatory cascade in ARDS by suppressing pro-inflammatory mediator release and stabilizing the alveolar-capillary membrane, with moderate certainty evidence supporting their use. 5
Primary Mechanisms:
Suppression of inflammatory mediators: Corticosteroids inhibit nuclear factor-kappa B (NF-κB) signaling, reducing production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8) that drive alveolar epithelial and vascular endothelial injury 6
Stabilization of alveolar-capillary barrier: By reducing inflammatory cell infiltration and cytokine-mediated damage, steroids decrease capillary permeability and reduce protein-rich edema fluid accumulation in alveolar spaces 6
Inhibition of inflammatory cell recruitment: Corticosteroids suppress expression of adhesion molecules on endothelial cells, preventing neutrophil and macrophage migration into lung parenchyma 6
Reduction of fibroproliferative response: Early steroid administration may prevent progression to the fibrotic phase of ARDS by inhibiting fibroblast proliferation and collagen deposition 6
Clinical Application: The American Thoracic Society suggests using corticosteroids for patients with ARDS (conditional recommendation, moderate certainty of evidence), with particular benefit demonstrated in COVID-19 ARDS 5, 1
Critical Caveat: Timing matters—late administration (>14 days after ARDS onset) may increase mortality, so initiate early in the disease course 6
Positive End-Expiratory Pressure (PEEP)
Higher PEEP prevents end-expiratory alveolar collapse and reduces cyclic recruitment-derecruitment injury, which is the primary driver of ventilator-induced lung injury in ARDS. 5, 7
Primary Mechanisms:
Prevention of alveolar collapse: PEEP maintains positive pressure throughout the respiratory cycle, preventing end-expiratory collapse of injured alveoli that have reduced surfactant function and increased closing pressures 7
Reduction of atelectrauma: By preventing cyclic opening and closing of alveoli with each breath, PEEP eliminates the shear stress injury (atelectrauma) that occurs at the interface between collapsed and open lung units 7
Recruitment of collapsed alveoli: PEEP can reopen previously collapsed alveolar units, increasing the functional lung volume available for gas exchange and reducing the concentration of tidal volume in fewer alveoli 7
Reduction of tidal lung stress and strain: By increasing end-expiratory lung volume, PEEP shifts the tidal breath to a more compliant portion of the pressure-volume curve, reducing regional overdistension 7
Improved oxygenation: Increased functional residual capacity and reduced intrapulmonary shunt improve arterial oxygenation, potentially allowing reduction in toxic FiO₂ levels 8, 7
More homogeneous ventilation distribution: PEEP promotes more uniform lung inflation, reducing regional stress concentrations that drive inflammatory injury 9, 7
Balancing Benefits and Risks:
Potential harm from overdistension: Excessive PEEP can overdistend already-open alveoli, particularly in non-dependent lung regions, causing volutrauma and hemodynamic compromise 7
Individual variability in recruitability: The net benefit of PEEP depends on the balance between recruited alveoli versus overdistended lung; patients with high recruitability benefit most from higher PEEP 7
Clinical Application: The American Thoracic Society suggests using higher PEEP (typically 10-15 cmH₂O) without prolonged lung recruitment maneuvers in moderate to severe ARDS (conditional recommendation, low to moderate certainty), while strongly recommending against prolonged recruitment maneuvers (strong recommendation, moderate certainty) 5, 1, 3
Important Distinction: While the ALVEOLI trial showed no mortality difference between higher versus lower PEEP strategies overall, subsequent analyses suggest benefit in more severe ARDS (PaO₂/FiO₂ <200 mmHg) 8, 7
Integrated Pathophysiological Framework
These three interventions work synergistically through complementary mechanisms:
- Prone positioning optimizes the mechanical environment for ventilation 2
- PEEP prevents cyclic injury within that optimized mechanical environment 7
- Corticosteroids dampen the inflammatory response triggered by the initial insult and any ongoing ventilator-induced injury 6
For exam preparation, remember: All three interventions fundamentally aim to break the cycle of ventilator-induced lung injury while supporting gas exchange—prone positioning and PEEP through mechanical means, steroids through anti-inflammatory effects 5, 1, 4