EAST 2012 PLENARY PAPERS

Early stabilizing alveolar ventilation prevents acute respiratory distress syndrome

A novel timing-based ventilatory intervention to avert lung injury

Roy, Shreyas MD, CM; Sadowitz, Benjamin MD; Andrews, Penny RN; Gatto, Louis A. PhD; Marx, William DO; Ge, Lin PhD; Wang, Guirong PhD; Lin, Xin PhD; Dean, David A. PhD; Kuhn, Michael BA; Ghosh, Auyon BSc; Satalin, Joshua BA; Snyder, Kathy BA; Vodovotz, Yoram PhD; Nieman, Gary BA; Habashi, Nader MD

Author Information

From Cardiopulmonary & Critical Care Laboratory, Department of Surgery (S.R., B.S., L.G., G.W., M.K., A.G., J.S., K.S., G.N.), SUNY Upstate Medical University, Syracuse, New York; Division of Surgical Critical Care (P.A., N.H.), R. Adams Cowley Shock Trauma Center, Baltimore, Maryland; Department of Biology (L.A.G.), SUNY Cortland, Cortland, New York; Division of General Surgery (W.M.), Veterans Administration Medical Center, Syracuse, New York; University Department of Pediatrics, Neonatology (X.L., D.A.D.), University of Rochester Medical Center, Rochester, New York; Department of Surgery and Department of Immunology (Y.V.), University of Pittsburgh, Pittsburgh, Pennsylvania.

Submitted: December 1, 2011; Revised: April 26, 2012; Accepted: April 26, 2012.

This work was presented at the 25th annual meeting of the Eastern Association for the Surgery of Trauma, January 10–14, 2012, in Lake Buena Vista, Florida.

Address for reprints: Shreyas Roy, MD, CM, Department of Surgery, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210; email: [email protected].

Journal of Trauma and Acute Care Surgery 73(2):p 391-400, August 2012. | DOI: 10.1097/TA.0b013e31825c7a82

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.

HYPOTHESIS

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 (T_high), and time duration of release phase (T_low). 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.

CONCLUSION

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.

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Early stabilizing alveolar ventilation prevents acute respiratory distress syndrome

A novel timing-based ventilatory intervention to avert lung injury