Pulmonary lesion induced by low and high positive end-expiratory pressure levels during protective ventilation in experimental acute lung injury

Abstract

To investigate the effects of low and high levels of positive end-expiratory pressure (PEEP), without recruitment ma neuvers, during lung protective ventilation in an experimental model of acute lung injury (ALI). Design: Prospective, randomized, and controlled experimental study. Setting: University research laboratory. Subjects: Wistar rats were randomly assigned to control (C) saline (0.1 mL), intraperitoneally] and ALI paraquat (15 mg/kg), intraperitoneally] groups. Measurements and Main Results: After 24 hours, each group was further randomized into four groups (six rats each) at differ ent PEEP levels 1.5, 3, 4.5, or 6 cm H2O and ventilated with a constant tidal volume (6 mL/kg) and open thorax. Lung mechanics static elastance (Est, L) and viscoelastic pressure ( P2, L)] and arterial blood gases were measured before (Pre) and at the end of 1-hour mechanical ventilation (Post). Pulmonary histology (light and electron microscopy) and type III procollagen (PCIII) messen ger RNA (mRNA) expression were measured after 1 hour of mechanical ventilation. In ALI group, low and high PEEP levels induced a greater percentage of increase in Est, L (44% and 50%) and P2, L (56% and 36%) in Post values related to Pre. Low PEEP yielded alveolar collapse whereas high PEEP caused overdisten sion and atelectasis, with both levels worsening oxygenation and increasing PCIII mRNA expression. Conclusions: In the present nonrecruited ALI model, protective mechanical ventilation with lower and higher PEEP levels than required for better oxygenation increased Est, L and P2, L, the amount of atelectasis, and PCIII mRNA expression. PEEP selection titrated for a minimum elastance and maximum oxygenation may prevent lung injury while deviation from these settings may be harmful. (Crit Care Med 2009; 37:1011–1017.