title: Early airway pressure release ventilation prevents ARDS-a novel preventive approach to lung injury.
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.
authors.affiliation: Cardiopulmonary and Critical Care Laboratory, Department of Surgery, Upstate Medical University, Syracuse, NY, USA. roys@upstate.edu
authors.forename: Shreyas
authors.initials: S
authors.lastname: Roy
authors.forename: Nader
authors.initials: N
authors.lastname: Habashi
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sadowitz
authors.forename: Penny
authors.initials: P
authors.lastname: Andrews
authors.forename: Lin
authors.initials: L
authors.lastname: Ge
authors.forename: Guirong
authors.initials: G
authors.lastname: Wang
authors.forename: Preyas
authors.initials: P
authors.lastname: Roy
authors.forename: Auyon
authors.initials: A
authors.lastname: Ghosh
authors.forename: Michael
authors.initials: M
authors.lastname: Kuhn
authors.forename: Joshua
authors.initials: J
authors.lastname: Satalin
authors.forename: Louis A
authors.initials: LA
authors.lastname: Gatto
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
authors.forename: David A
authors.initials: DA
authors.lastname: Dean
authors.forename: Yoram
authors.initials: Y
authors.lastname: Vodovotz
authors.forename: Gary
authors.initials: G
authors.lastname: Nieman
mesh_terms: D055371:Acute Lung Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015820:Cadherins / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood; D045422:Continuous Positive Airway Pressure / Q000379:methods*; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D008170:Lung Compliance / Q000502:physiology; D009102:Multiple Organ Failure / Q000517:prevention & control; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011654:Pulmonary Edema / Q000517:prevention & control; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D012720:Severity of Illness Index; D034421:Sus scrofa; D013990:Tidal Volume / Q000502:physiology; D013997:Time Factors; D014882:Water-Electrolyte Balance / Q000502:physiology
chemical_list: D015820:Cadherins; D037662:Pulmonary Surfactant-Associated Protein A; D002245:Carbon Dioxide; D010100:Oxygen