Inconsistent Methods Used to Set Airway Pressure Release Ventilation in ARDS: A Systematic Review and Meta-Regression Analysis

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Abstract

Airway pressure release ventilation (APRV) is a protective mechanical ventilation mode for patients with acute respiratory distress syndrome (ARDS) that theoretically may reduce ventilator-induced lung injury (VILI) and ARDS-related mortality. However, there is no standard method to set and adjust the APRV mode shown to be optimal. Therefore, we performed a meta-regression analysis to evaluate how the four individual APRV settings impacted the outcome in these patients.
Methods: Studies investigating the use of the APRV mode for ARDS patients were searched from electronic databases. We tested individual settings, including (1) high airway pressure (PHigh); (2) low airway pressure (PLow); (3) time at high airway pressure (THigh); and (4) time at low pressure (TLow) for association with PaO2/FiO2 ratio and ICU length of stay.
Results: There was no significant difference in PaO2/FiO2 ratio between the groups in any of the four settings (PHigh difference −12.0 [95% CI −100.4, 86.4]; PLow difference 54.3 [95% CI −52.6, 161.1]; TLow difference −27.19 [95% CI −127.0, 72.6]; THigh difference −51.4 [95% CI −170.3, 67.5]). There was high heterogeneity across all parameters (PhHgh I2 = 99.46%, PLow I2 = 99.16%, TLow I2 = 99.31%, THigh I2 = 99.29%).
Conclusions: None of the four individual APRV settings independently were associated with differences in outcome. A holistic approach, analyzing all settings in combination, may improve APRV efficacy since it is known that small differences in ventilator settings can significantly alter mortality. Future clinical trials should set and adjust APRV based on the best current scientific evidence available.

Key Points

  1. Variability in APRV Application: The study highlights significant heterogeneity in how APRV is applied across clinical trials, with inconsistent settings for pressure levels and inspiratory/expiratory times.
  2. No Independent Effect of Individual Settings: Meta-regression analysis found that variations in PHigh, PLow, THigh, and TLow were not independently associated with significant differences in PaO₂/FiO₂ ratio or ICU length of stay.
  3. High Heterogeneity Among Studies: The included studies exhibited substantial differences in APRV protocols, contributing to inconsistent results and limiting generalizability.
  4. Potential for Synergistic Effects: The authors suggest that APRV may be most effective when all settings are optimized together rather than focusing on a single parameter.
  5. Role of TLow in Lung Protection: TLow, which regulates expiratory time, is critical for maintaining alveolar stability. However, most studies applied arbitrary TLow values without physiologic justification.
  6. PLow and Alveolar Stability: Setting PLow at 0 cmH₂O can help prevent alveolar collapse, but its effects depend on appropriately adjusted TLow settings.
  7. Recruitment and Mean Airway Pressure: APRV increases mean airway pressure, which may enhance lung recruitment while reducing cyclic alveolar collapse and overdistension.
  8. Lack of Standardization in Clinical Trials: Despite potential benefits, the absence of a universal APRV protocol has hindered its widespread adoption in ARDS management.
  9. Need for Personalized APRV Strategies: The study emphasizes that APRV should be tailored to patient-specific lung mechanics rather than relying on fixed settings.
  10. Future Research Directions: Further large-scale trials are needed to establish evidence-based APRV protocols that optimize lung protection and patient outcomes.

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