Bhushan H Katira, Doreen Engelberts, Gail Otulakowski, Regan E Giesinger, Takeshi Yoshida, Martin Post, Wolfgang M Kuebler, Kim A Connelly, Brian P Kavanagh

Ventilator management in ARDS focuses on 'setting' parameters and not on ventilator disconnection. To determine if abrupt deflation after sustained inflation causes lung injury. Male Sprague-Dawley rats were ventilated (6 mL·kg-1) and randomized to Control (n=6, PEEP 3 cmH2O; 100 min) or Intervention (n=6, PEEP 3 to 11 cmH2O over 70 min; abrupt deflation to zero PEEP; ventilation for 30 mins). Lung function and injury was assessed, scanning electron microscopy performed, and microvascular leak timed by Evans Blue dye (n=4/group at 0, 2, 5, 10 & 20 min post deflation). Hemodynamic assessment included systemic arterial pressure (n=6), echocardiography (n=4), and right (n=6) and left ventricular pressures (n=6). Abrupt deflation following sustained inflation (vs. control) caused acute lung dysfunction (compliance 0.48±1.0 vs. 0.82±0.2 mL·cmH20-1) and injury (wet/dry ratio 6.1±0.6 vs. 4.6±0.4: P<0.01). Vascular leak was absent before deflation and maximal 5-10 min thereafter; injury was predominantly endothelial. At deflation, left ventricular preload, systemic blood pressure and LVEDP increased precipitously in proportion to the degree of injury. Injury caused later right ventricular failure. Sodium nitroprusside prevented the increase in systemic blood pressure and LVEDP associated with deflation, and prevented injury. Injury did not occur with gradual deflation. Abrupt deflation after sustained inflation can cause acute lung injury. It appears to be mediated by acute LV decompensation (increased LV preload and afterload) that elevates pulmonary microvascular pressure; this injures the endothelium and causes edema, which is potentiated by the surge in pulmonary perfusion.