PEEP in ARDS : is it really protective?

Various forms of ventilator-induced lung injury (VILI) have been described since the definition of Adult Respiratory Distress Syndrome. The barotrauma was the first to be recognized as a form of stress at rupture, leading to pneumothorax, pneumoperitoneum etc. In the following years the concept of volutrauma (excessive strain) emerged and, years later, the atelectrauma and its associated inflammatory reaction was recognized, first ex-vivo and, afterwards, in clinical settings. Excessive tidal volume is now recognized as the first source of VILI, supporting the concept of volutrauma, while the airway pressure limitations to ≈30 cmH2O, in patients with normal chest wall, is used as a surrogate of the maximal stress (transpulmonary pressure ) tolerable.
The protective effects of positive end expiratory pressure (PEEP) on VILI were described by Webb and Tierney in their seminal experiments. Although dramatically effective in experimental ARDS, higher PEEP failed to show clear benefits in human ARDS compared to lower PEEP. Possible benefits were only suggested by meta-analysis in the subgroups of the most severe ARDS patients. Therefore, while the association between higher tidal volume and VILI is robust and largely accepted, the protective effects of PEEP are not so consistent.
The tidal change in lung volume is associated with a cyclic energy load to the lung parenchyma, being the energy equal to the pressure applied multiplied the change in volume (PdV, summed along the inspiratory volume-pressure curve). In contrast, PEEP, once applied, does not cause any cyclic energy load as the volume due to PEEP application is constant (dV=0). Therefore, considering both the lung volume distortion and the energy load to the lung parenchyma, we aimed to answer the following question: is there any threshold of volume distortion/energy load producing VILI? Is the application of PEEP protective per se or is it just an indirect effect, due to the concomitant reduction in tidal volume when PEEP is applied?
We conducted, over the years, a series of long term animal experiments in which we tested different tidal volumes (strain), transpulmonary pressure (stress) and levels of PEEP. In the present study we added further experiments, covering a wider range of tidal volumes and PEEP levels, to define the interaction between the anatomical limits of lung expansion, as assessed by CT scan, the inspiratory volumes applied (tidal volume + PEEP volume) and the dynamic and static energy used to produce VILI in healthy animals.