Ventilator - Induced Lung Injury

Mechanisms and Pathogenesis of VILI

Alveolar Overdistention and the Development of Lung Injury

The normal human lung is fully inflated when transalveolar pressures are approximately 30 to 35 cm H₂O. The risk for VILI has been shown in multiple studies to increase when this distention threshold is exceeded.^1,4-25 In the animal experiments inducing VILI, this pressure generation is usually produced by delivering high tidal volumes. In disease states, however, lung injury is often heterogeneous with very abnormal lung units interspersed with much healthier units. Under these conditions, tidal volumes of gas delivered by PPV will preferentially be distributed to the healthier units. A seemingly normal-sized tidal volume delivered to the trachea could thus create abnormally high regional tidal volumes (Fig 2) and consequent regional overdistention, even in the setting of a normal overall end-inspiratory distention.

There is compelling evidence that limiting end-inspiratory distention during PPV reduces lung injury and improves outcome.^16-18,22-29 This was most dramatically shown by the large National Institutes of Health (NIH) ARDS Network trial in over 800 patients in whom a low-stretch strategy (tidal volume, 6 mL/kg; mean plateau pressures from days 1 to 7, 25 to 26 cm H₂O) had improved survival as compared with a high-stretch strategy (tidal volume, 12 mL/kg; mean plateau pressure from days 1 to 7, 33 to 37 cm H₂O).²⁷ Moreover, the low-stretch group also had lower blood levels of interleukin 6 and fewer organ failures, which speaks to the systemic nature of VILI. Interestingly, earlier smaller trials addressing this issue did not find much benefit to this "lung-protective" concept.^30,31 However, these other trials generally had smaller numbers and less stretch separation between the two groups, and the high-stretch groups usually had end-inspiratory plateau pressures generally considered in the safe range (ie, <35 cm H₂O).

Recent studies have addressed not only the magnitude of the end-inspiratory distention but also the pattern of distention. Two studies have suggested that a rapid rate of lung distention may be as important as, or even more important than, the magnitude of the distention in producing VILI.^32,33 This would suggest that stretch injury may be significantly influenced by a shear stress phenomenon induced by rapid flows in addition to the ultimate maximal stretch. The frequency of the stretch (respiratory rate) and the duration of the stretch (inspiratory time) have also been assessed as risk factors for VILI. Increasing stretch frequency may increase the risk of VILI but this finding is not consistent among studies.^33,34 Interestingly, increasing inspiratory time for the same tidal volume, inspiratory flow pattern, and respiratory frequency does not appear to affect VILI development.³³

The pulmonary circulation may also play a role in the development of VILI. Studies have shown that VILI is increased as pulmonary vascular pressures and flows are increased.³⁴ This effect is no doubt compounded if a capillary leak syndrome is already present.^35,36