Open lung approach with low tidal volume mechanical ventilation attenuates lung injury in rats with massive brain damage

INTRODUCTION: The ideal ventilation strategy for patients with massive brain damage requires better elucidation. We hypothesized that in the presence of massive brain injury, a ventilation strategy using low (6 milliliters per kilogram ideal body weight) tidal volume (V(T)) ventilation with open lung positive end-expiratory pressure (LV(T)/OLPEEP) set according to the minimal static elastance of the respiratory system, attenuates the impact of massive brain damage on gas-exchange, respiratory mechanics, lung histology and whole genome alterations compared with high (12 milliliters per kilogram ideal body weight) V(T) and low positive end-expiratory pressure ventilation (HV(T)/LPEEP). METHODS: In total, 28 adult male Wistar rats were randomly assigned to one of four groups: 1) no brain damage (NBD) with LV(T)/OLPEEP; 2) NBD with HV(T)/LPEEP; 3) brain damage (BD) with LV(T)/OLPEEP; and 4) BD with HV(T)/LPEEP. All animals were mechanically ventilated for six hours. Brain damage was induced by an inflated balloon catheter into the epidural space. Hemodynamics was recorded and blood gas analysis was performed hourly. At the end of the experiment, respiratory system mechanics and lung histology were analyzed. Genome wide gene expression profiling and subsequent confirmatory quantitative polymerase chain reaction (qPCR) for selected genes were performed. RESULTS: In NBD, both LV(T)/OLPEEP and HV(T)/LPEEP did not affect arterial blood gases, as well as whole genome expression changes and real-time qPCR. In BD, LV(T)/OLPEEP, compared to HV(T)/LPEEP, improved oxygenation, reduced lung damage according to histology, genome analysis and real-time qPCR with decreased interleukin 6 (IL-6), cytokine-induced neutrophil chemoattractant 1 (CINC)-1 and angiopoietin-4 expressions. LV(T)/OLPEEP compared to HV(T)/LPEEP improved overall survival. CONCLUSIONS: In BD, LV(T)/OLPEEP minimizes lung morpho-functional changes and inflammation compared to HV(T)/LPEEP.