ObjectiveMany studies have investigated the protective role of positive end-expiratory pressure (PEEP) on ventilator-induced lung injury. Most assessed lung injury in protocols involving different ventilation strategies applied for the same length of time. This study, however, set out to investigate the protective role of PEEP with respect to the time needed to reach similar levels of lung injury.DesignProspective, randomized laboratory animal investigation.SettingThe University Laboratory of Ospedale Maggiore, Milano, IRCCS.SubjectsAnesthetized, paralyzed, and mechanically ventilated Sprague-Dawley rats.InterventionsThree groups of five Sprague-Dawley rats were ventilated using zero end-expiratory pressure ZEEP (PEEP of 0 cm H2O) and PEEP of 3 and 6 cm H2O and a similar index of lung overdistension (Pawp/P100≅ 1.1; where Pawpis peak airway pressure and P100is the pressure corresponding to total lung capacity). To obtain this, tidal volume was reduced depending on the PEEP. To reach similar levels of lung injury, we measured respiratory system elastance while ventilating the animals and killed them when respiratory system elastance was 150% of baseline. Once target respiratory system elastance was reached, the lung wet-to-dry ratio was obtained.ResultsRats were ventilated with comparable high airway pressure (Pawpof 42.8 ± 3.1, 43.5 ± 2.6, and 46.2 ± 4.4, respectively, for PEEP 0, 3, and 6) obtaining similar overdistension (Pawp/P100− index of overdistension: 1.17 ± 0.2, 1.06 ± 0.1, and 1.19 ± 0.2). The respiratory system elastance target was reached and wet-to-dry ratio was not different in the three groups, suggesting a similar degree of lung damage. The time taken to achieve the target respiratory system elastance was three times longer with PEEP 3 and 6 (55 ± 14 mins and 60 ± 17) as compared with zero end-expiratory pressure (18 ± 3 mins,p< .001).ConclusionThese findings confirm that PEEP is protective against ventilator-induced lung injury and may enable the clinician to “buy time” in the progression of lung injury.