[1] It is generally regarded, based on animal models and human studies, that volutrauma is the most harmful aspect of mechanical ventilation.

[5][6] During positive pressure ventilation, atelectatic regions will inflate, however, the alveoli will be unstable and will collapse during the expiratory phase of the breath (atelectotrauma).

Finally oxygen toxicity contributes to ventilator-associated lung injury through several mechanisms including oxidative stress.

Possible reasons for predisposition to VALI include: Overdistension of alveoli and cyclic atelectasis (atelectotrauma) are the primary causes for alveolar injury during positive pressure mechanical ventilation.

[citation needed] Alveolar overdistension is mitigated by using small tidal volumes, maintaining a low plateau pressure, and most effectively by using volume-limited ventilation.

A 2018 systematic review by The Cochrane Collaboration provided evidence that low tidal volume ventilation reduced post operative pneumonia and reduced the requirement for both invasive and non invasive ventilation after surgery[9] Applied positive end-expiratory pressure (PEEP) is the principal method used to keep the alveoli open and lessen cyclic atelectasis.