Experimental ventilator-induced lung injury: exacerbation by positive end-expiratory pressure.

BACKGROUND Previous experimental studies of ventilator-induced lung injury have shown that positive end-expiratory pressure (PEEP) is protective. The authors hypothesized that the application of PEEP during volume-controlled ventilation with a moderately high tidal volume (VT) in previously healthy in vivo rats does not attenuate ventilator-induced lung injury if the peak airway pressure markedly increases during the application of PEEP. METHODS Sixty healthy, male Sprague-Dawley rats were anesthetized and randomized to be mechanically ventilated for 4 h at (1) VT of 6 ml/kg, (2) VT of 20 ml/kg, or (3) VT of 20 ml/kg plus 10 cm H2O of PEEP. Peak airway pressures, gas exchange, histologic evaluation, mortality, total lung tissue cytokine gene expression, and serum cytokine concentrations were analyzed. RESULTS Peak airway pressures exceeded 30 cm H2O with high VT plus PEEP. All lungs ventilated with high VT had perivascular edema and inflammatory infiltrates. In addition, those ventilated with PEEP had small hemorrhages foci. Five animals from the high VT plus PEEP group died (P = 0.020). Animals ventilated with high VT (with or without PEEP) had a substantial increase in serum interleukin-6 (P = 0.0002), and those ventilated with high VT plus PEEP had a 5.5-fold increase in systemic levels of tumor necrosis factor-alpha (P = 0.007). CONCLUSIONS In contrast to previous reports, PEEP exacerbated lung damage and contributed to fatal outcome in an in vivo, mild overdistension model of ventilator-induced lung injury in previously healthy rats. That is, the addition of high PEEP to a constant large VT causes injury in previously healthy animals.