Early airway pressure release ventilation prevents ARDS-a novel preventive approach to lung injury

Shreyas Roy*, Nader Habashi, Benjamin Sadowitz, Penny Andrews, Lin Ge, Guirong Wang, Preyas Roy, Auyon Ghosh, Michael Kuhn, Joshua Satalin, Louis A. Gatto, Xin Lin, David A. Dean, Yoram Vodovotz, Gary Nieman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

Abstract

Acute respiratory distress syndrome (ARDS) afflicts 200,000 patients annually with a mortality rate of 30% to 60% despite wide use of low tidal volume (LTV) ventilation, the present standard of care. High-permeability alveolar edema and instability occur early in the development of ARDS, before clinical signs of lung injury, and represent potential targets for therapy. We hypothesize that early application of a protective ventilation strategy (airway pressure release ventilation [APRV]) will stabilize alveoli and reduce alveolar edema, preventing the development of ARDS. Yorkshire pigs (30-40 kg) were anesthetized and subjected to two-hit injury: (a) intestinal ischemia-reperfusion, (b) peritoneal sepsis, or sham surgery. Following surgery, pigs were randomized into APRV (n = 4), according to current published guidelines for APRV; LTV ventilation (n = 3), using the current published ARDS Network guidelines (6 mL/kg); or sham (n = 5). The clinical care of all pigs was administered per the Surviving Sepsis Campaign guidelines. Animals were killed, and necropsy performed at 48 h. Arterial blood gases were measured to assess for the development of clinical lung injury. Lung tissue epithelial cadherin (E-cadherin) was measured to assess alveolar permeability. Bronchoalveolar lavage fluid (BALF) surfactant protein A was measured to assess alveolar stability. Lung edema content and histopathology were analyzed at 48 h. Airway pressure release ventilation pigs did not develop ARDS. In contrast, pigs in the LTV ventilation met ARDS criteria (PaO2/FIO2 ratio) (APRV: baseline = 471 ± 16; 48 h = 392 ± 8; vs. LTV ventilation: baseline = 551 ± 28; 48 h = 138 ± 88; P < 0.001). Airway pressure release ventilation preserved alveolar epithelial integrity demonstrated by higher levels of E-cadherin in lung tissue as compared with LTV ventilation (P < 0.05). Surfactant protein A levels were higher in BALF from the APRV group, suggesting APRV preserved alveolar stability. Quantitative histologic scoring showed improvements in all stigmata of ARDS in the APRV group versus the LTV ventilation (P < 0.05). Airway pressure release ventilation had significantly lower lung edema (wet-dry weight) than LTV ventilation (P < 0.05). Protective ventilation with APRV immediately following injury prevents development of ARDS. Reduction in lung edema, preservation of lung E-cadherin, and surfactant protein A abundance in BALF suggest that APRV attenuates lung permeability, edema, and surfactant degradation. Protective ventilation could change the clinical paradigm from supportive care for ARDS with LTV ventilation to preventing development of ARDS with APRV.

Original languageEnglish
Pages (from-to)28-38
Number of pages11
JournalShock
Volume39
Issue number1
DOIs
StatePublished - Jan 2013
Externally publishedYes

Keywords

  • ALI
  • ARDS
  • Acute respiratory distress syndrome
  • acute lung injury
  • airway pressure release ventilation
  • mechanical ventilation
  • sepsis
  • shock
  • systemic inflammatory response syndrome

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