title: Early stabilizing alveolar ventilation prevents acute respiratory distress syndrome: a novel timing-based ventilatory intervention to avert lung injury.
abstract: BACKGROUND
  Established acute respiratory distress syndrome (ARDS) is often refractory to treatment. Clinical trials have demonstrated modest treatment effects, and mortality remains high. Ventilator strategies must be developed to prevent ARDS.
  
  
  OBJECTIVE
  Early ventilatory intervention will block progression to ARDS if the ventilator mode (1) maintains alveolar stability and (2) reduces pulmonary edema formation.
  
  
  METHODS
  Yorkshire pigs (38-45 kg) were anesthetized and subjected to a "two-hit" ischemia-reperfusion and peritoneal sepsis. After injury, animals were randomized into two groups: early preventative ventilation (airway pressure release ventilation [APRV]) versus nonpreventative ventilation (NPV) and followed for 48 hours. All animals received anesthesia, antibiotics, and fluid or vasopressor therapy as per the Surviving Sepsis Campaign. Titrated for optimal alveolar stability were the following ventilation parameters: (1) NPV group--tidal volume, 10 mL/kg + positive end-expiratory pressure - 5 cm/H2O volume-cycled mode; (2) APRV group--tidal volume, 10 to 15 mL/kg; high pressure, low pressure, time duration of inspiration (Thigh), and time duration of release phase (Tlow). Physiological data and plasma were collected throughout the 48-hour study period, followed by BAL and necropsy.
  
  
  RESULTS
  APRV prevented the development of ARDS (p < 0.001 vs. NPV) by PaO₂/FIO₂ ratio. Quantitative histological scoring showed that APRV prevented lung tissue injury (p < 0.001 vs. NPV). Bronchoalveolar lavage fluid showed that APRV lowered total protein and interleukin 6 while preserving surfactant proteins A and B (p < 0.05 vs. NPV). APRV significantly lowered lung water (p < 0.001 vs. NPV). Plasma interleukin 6 concentrations were similar between groups.
  
  
  CONCLUSIONS
  Early preventative mechanical ventilation with APRV blocked ARDS development, preserved surfactant proteins, and reduced pulmonary inflammation and edema despite systemic inflammation similar to NPV. These data suggest that early preventative ventilation strategies stabilizing alveoli and reducing pulmonary edema can attenuate ARDS after ischemia-reperfusion and sepsis.
authors: Cardiopulmonary & Critical Care Laboratory, Department of Surgery, SUNY Upstate Medical University, Syracuse, New York 13210, USA. roys@upstate.edu
authors: Shreyas
authors: S
authors: Roy
authors: Benjamin
authors: B
authors: Sadowitz
authors: Penny
authors: P
authors: Andrews
authors: Louis A
authors: LA
authors: Gatto
authors: William
authors: W
authors: Marx
authors: Lin
authors: L
authors: Ge
authors: Guirong
authors: G
authors: Wang
authors: Xin
authors: X
authors: Lin
authors: David A
authors: DA
authors: Dean
authors: Michael
authors: M
authors: Kuhn
authors: Auyon
authors: A
authors: Ghosh
authors: Joshua
authors: J
authors: Satalin
authors: Kathy
authors: K
authors: Snyder
authors: Yoram
authors: Y
authors: Vodovotz
authors: Gary
authors: G
authors: Nieman
authors: Nader
authors: N
authors: Habashi
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D007150:Immunohistochemistry; D055370:Lung Injury / Q000401:mortality / Q000517:prevention & control* / Q000628:therapy; D011175:Positive-Pressure Respiration / Q000379:methods; D011659:Pulmonary Gas Exchange; D012123:Pulmonary Ventilation; D011897:Random Allocation; D012121:Respiration, Artificial / Q000379:methods*; D012128:Respiratory Distress Syndrome / Q000517:prevention & control*; D015656:Respiratory Mechanics; D012680:Sensitivity and Specificity; D015996:Survival Rate; D013552:Swine; D013990:Tidal Volume; D013997:Time Factors