What are the considerations and settings for Airway Pressure Release Ventilation (APRV) trials in patients with severe lung injury or Acute Respiratory Distress Syndrome (ARDS)?

Airway Pressure Release Ventilation (APRV) in ARDS

Primary Recommendation

APRV should not be used as a primary ventilation mode for ARDS patients, as there is no high-quality evidence demonstrating mortality benefit, and current guidelines do not recommend it over conventional lung-protective ventilation strategies. 1

Evidence-Based Ventilation Strategy for ARDS

The established approach for ARDS ventilation prioritizes:

• Low tidal volume ventilation (4-8 ml/kg predicted body weight) with plateau pressure ≤30 cm H₂O remains the cornerstone of ARDS management (strong recommendation, moderate certainty). 1

• Higher PEEP strategies (without prolonged recruitment maneuvers) should be used in moderate to severe ARDS (conditional recommendation), as this approach probably reduces mortality (RR 0.77; 95% CI 0.60-0.96). 1

• Prone positioning for >12 hours/day in severe ARDS (PaO₂/FiO₂ <150 mmHg) is strongly recommended and reduces mortality (RR 0.74; 95% CI 0.56-0.99). 1, 2

• Driving pressure should be maintained ≤15 cm H₂O, as it predicts mortality better than tidal volume or plateau pressure alone. 3

Why APRV Is Not Recommended as Primary Mode

Lack of Definitive Evidence

• No randomized controlled trials demonstrate that APRV improves mortality or other patient-centered outcomes in ARDS compared to conventional lung-protective ventilation. 4

• APRV has greater potential for adversely affecting patient outcomes than improving them due to risks of volutrauma, variable performance across ventilators, and dependence on high-precision settings where small variations can lead to de-recruitment or excessive tidal volumes. 4

Technical Challenges

• APRV performance is highly operator-dependent and requires precise settings (P high, T high, P low, T low) that vary significantly across ventilators, making standardization difficult. 5

• Very short expiratory times (T low) required for optimal APRV function create risk for unintended consequences including lung injury if not precisely calibrated. 4

• Confusion exists regarding terminology, with APRV, biphasic positive airway pressure (BIPAP), and other modes often conflated in the literature. 5

Limited Role for APRV

Potential Rescue Therapy Consideration

• APRV may be considered as rescue therapy in difficult-to-oxygenate ARDS patients who have failed conventional lung-protective ventilation, higher PEEP strategies, and prone positioning. 5, 6

• Retrospective data suggest APRV may improve oxygenation (PaO₂/FiO₂ ratios higher on days 1,3,5,7; p<0.05) and showed a trend toward lower ICU mortality (31% vs 59%, p=0.050) compared to conventional ventilation in severe ARDS. 7

• Case reports demonstrate feasibility of combining APRV with prone positioning, potentially providing synergistic effects on gas exchange. 8

Theoretical Advantages (Unproven Clinically)

• APRV allows unrestricted spontaneous breathing throughout the ventilatory cycle, which may align with contemporary goals of reduced sedation and early mobility. 4, 5

• Animal studies suggest alveolar stability and recruitment with APRV, but these findings have not translated to improved human outcomes. 4

Critical Implementation Pitfall

The most important caveat is that major guidelines (American Thoracic Society 2024,2017) do not include APRV in their recommendations for ARDS management, focusing instead on proven strategies: low tidal volume ventilation, higher PEEP, prone positioning, and neuromuscular blockade in severe cases. 1

Algorithmic Approach to ARDS Ventilation

1. Initiate lung-protective ventilation: Tidal volume 4-8 ml/kg PBW, plateau pressure ≤30 cm H₂O 1

2. Apply higher PEEP strategy in moderate-severe ARDS (PaO₂/FiO₂ <200 mmHg) 1

3. Monitor driving pressure: Maintain ≤15 cm H₂O by adjusting tidal volume and PEEP 3

4. **If PaO₂/FiO₂ <150 mmHg despite optimization**: Implement prone positioning >12 hours/day 1, 2

5. Consider neuromuscular blockade in early severe ARDS 1

6. If refractory hypoxemia persists: Consider ECMO before experimental modes like APRV 1

APRV should only be considered after exhausting all evidence-based interventions, and only in centers with specific expertise in this mode, recognizing it remains investigational. 4, 6