Limiting Overdistention or Collapse When Mechanically Ventilating Injured Lungs: A Randomized Study in a Porcine Model

Rationale: It is unknown whether preventing overdistention or collapse is more important when titrating positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS). Objective: To compare PEEP targeting either minimal overdistention, minimal collapse or using a compromise between collapse and overdistention in a randomized trial, and assess the impact on respiratory mechanics, gas exchange, inflammation, and hemodynamics. Methods: In a porcine model of ARDS, lung collapse and overdistention were estimated by electrical impedance tomography during a decremental PEEP titration. Pigs were randomized to three groups and ventilated for 12 hours: PEEP set at ≤3% of overdistention (low overdistention); ≤3% of collapse (low collapse); and crossing point of collapse and overdistention (crossing-point). Measurements and main results: Thirty-six pigs (12/group) were included. Median PEEP were 7(IQR:6-8)cmH2O, 11(10-11)cmH2O, and 15(12-16)cmH2O in the three groups, p<0.001. With low overdistension, 6(50%) pigs died whereas survival was 100% in both other groups. Cause of death was hemodynamic in nature, with high transpulmonary gradient and high epinephrine requirements. Compared to the other groups, pigs surviving with low overdistension had worse respiratory mechanics and gas exchange during the entire protocol. Minimal differences existed between crossing-point and low collapse animals in physiological parameters but postmortem alveolar density was more homogeneous in crossing-point. Inflammatory markers were not significantly different. Conclusions: PEEP to minimize overdistention resulted in high mortality in an animal model of ARDS. Minimizing collapse or choosing a compromise between collapse and overdistention may result in less lung injury, with potential benefits of the compromise approach.