The impact of fluid status and decremental PEEP strategy on cardiac function and lung and kidney damage in mild-moderate experimental acute respiratory distress syndrome.

Abstract

Background We evaluated the effects of abrupt versus gradual positive end-expiratory pressure (PEEP) decrease, combined with standard versus high-volume fluid administration, on lung, heart, and kidney damage in an established model of acute respiratory distress syndrome (ARDS). Methods Thirty-five Wistar rats received endotoxin intratracheally. After 24 h, they were treated with Ringer´s lactate [standard (10 mL/kg/h) or high (30 mL/kg/h) fluids]. For 30 min, all animals were mechanically ventilated with tidal volume = 6 mL/kg and PEEP = 9 cmH2O (to keep alveoli open), then randomized to undergo abrupt or gradual (0.2 cmH2O/min for 30 min) PEEP decrease, from 9 to 3 cmH2O. After this period, animals were further ventilated for 10 minutes at PEEP = 3 cmH2O, euthanized, and then lungs and kidney removed for molecular biology analysis. Results At the end of the experiment, left and right ventricular end-diastolic areas were greater in animals treated with high compared to standard fluid administration, regardless of PEEP decrease rate. The PAT (pulmonary acceleration time)/PET (pulmonary ejection time) ratio was lower in abrupt compared to gradual PEEP decrease, independent of fluid status, suggesting higher pulmonary arterial pressure in rats undergo abrupt PEEP decrease. Animals treated with high fluids and abrupt PEEP decrease exhibited greater diffuse alveolar damage and higher expression of interleukin-6 (pro-inflammatory marker) and vascular endothelial growth factor (endothelial cell damage marker) compared to the other groups. Standard fluid administration associated with gradual PEEP decrease increased zonula occludens-1 expression, suggesting epithelial cell preservation. Club cell-16 protein expression, an alveolar epithelial cell damage marker, was higher in abrupt compared to gradual PEEP decrease, regardless of fluid status. Acute kidney injury score and gene expression of kidney injury molecule-1 was higher in high compared to standard fluid administration, independent of PEEP strategy. Conclusion In experimental mild-moderate ARDS, decreasing PEEP abruptly increased pulmonary arterial hypertension, independent of fluid status. The combination of abrupt PEEP decrease and high fluid administration led to greater lung and kidney damage. This information adds to the growing body of evidence that supports gradual transitioning of ventilatory patterns and warrants directing additional investigative effort into vascular and deflation issues that impact lung protection.