Mechanical power ratio threshold for ventilator-induced lung injury

Abstract

Rationale: Mechanical power (MP) is a summary variable incorporating all causes of ventilator-induced-lung-injury (VILI). We expressed MP as the ratio between observed and normal expected values (MP_ratio).

Objective: To define a threshold value of MP_ratio leading to the development of VILI.

Methods: In a population of 82 healthy pigs, a threshold of MP_ratio for VILI, as assessed by histological variables and confirmed by using unsupervised cluster analysis was 4.5. The population was divided into two groups with MP_ratio above or below the threshold.

Measurements and main results: We measured physiological variables every six hours. At the end of the experiment, we measured lung weight and wet-to-dry ratio to quantify edema. Histological samples were analyzed for alveolar ruptures, inflammation, alveolar edema, atelectasis. An MP_ratio threshold of 4.5 was associated with worse injury, lung weight, wet-to-dry ratio and fluid balance (all p < 0.001). After 48 h, in the two MP_ratio clusters (above or below 4.5), respiratory system elastance, mean pulmonary artery pressure and physiological dead space differed by 32%, 36% and 22%, respectively (all p < 0.001), being worse in the high MP_ratio group. Also, the changes in driving pressure, lung elastance, pulmonary artery occlusion pressure, central venous pressure differed by 17%, 64%, 8%, 25%, respectively (all p < 0.001).

Limitations: The main limitation of this study is its retrospective design. In addition, the computation for the expected MP in pigs is based on arbitrary criteria. Different values of expected MP may change the absolute value of MP ratio but will not change the concept of the existence of an injury threshold.

Conclusions: The concept of MP_ratio is a physiological and intuitive way to quantify the risk of ventilator-induced lung injury. Our results suggest that a mechanical power ratio > 4.5 MP_ratio in healthy lungs subjected to 48 h of mechanical ventilation appears to be a threshold for the development of ventilator-induced lung injury, as indicated by the convergence of histological, physiological, and anatomical alterations. In humans and in lungs that are already injured, this threshold is likely to be different.

Fig. 1

Histological findings. A Severely damaged lung parenchyma with massive alveolar ruptures (H&E, 40×). B Diffuse interalveolar exudation by neutrophils (H&E, 100×). C Lung parenchyma characterized by severe septal blood congestion associated with interalveolar edema (H&E, 40×). D Extensive lung atelectasis involving almost the whole parenchyma in histological section; note also emphysematous area in the left upper corner of the microphotograph (H&E, 40×). E Massive parenchymal blood septal congestion with interalveolar hemorrhages (H&E, 100×). F Extensive blood congestion of septa and vessel of different size (H&E, 40×). G Medium sized artery with edema and focal inflammatory infiltration of the wall (H&E, 40×). H Medium size artery with occlusive recent thrombosis of the lumen; note also marked parenchymal congestion and interalveolar edema (H&E, 40×)

Fig. 2

Histological damage and mechanical power ratio. Histological score for alveolar ruptures (A), inflammation (B), alveolar edema (C) and atelectasis (D) as a function of mechanical power ratio. This has been expressed in deciles (x-axis) including 8–9 animals each, whose upper limits are the following: decile 1: MP_ratio 2.40; decile 2: MP_ratio 2.94; decile 3: MP_ratio 3.12; decile 4: MP_ratio 3.54; decile 5: MP_ratio 4.46; decile 6: MP_ratio 6.13; decile 7: MP_ratio 7.28; decile 8: MP_ratio 10.3; decile 9: MP_ratio 12.5; decile 10: MP_ratio 24.6. As shown, upon visual inspection, at MP_ratio greater than 4.46 (rounded to 4.5, upper limit of the fifth decile), the histological scores markedly increased, suggesting a more severe parenchymal damage (see also Supplement, Table E1)

Fig. 3

Lung edema and mechanical power ratio. Lung wet-to-dry ratio (A), lung weight (kg⁻¹) (B) and fluid balance (C) as a function of the MP_ratio deciles. The MP_ratio limits of each decile are the same as in Fig. 1. Upon visual inspection, at MP_ratio greater than 4.5, lung wet-to-dry ratio, lung weight and fluid balance also markedly increased

Fig. 4

Time-course of normalized respiratory system elastance (A), mean pulmonary arterial pressure (B) and physiological dead space (C), in the high (red circles) and low (blue circles) MP_ratio groups. At the two-way ANOVA analysis: Respiratory system elastance: p_GROUP < 0.001, p_TIME = 0.039, and p_INTERACTION < 0.001. Mean pulmonary artery pressure: p_GROUP = 0.003, p_TIME < 0.001, and p_INTERACTION < 0.001. Physiological dead space: p_GROUP = 0.550, p_TIME = 0.097, and p_INTERACTION = 0.039. See also Table E4 for the complete sets of variables

Fig. 5

Possible sequences leading to ventilator-induced lung injury in healthy lung. Sequence 1, the intensity of mechanical ventilation is such as to induce structural anatomical modifications, which in turn lead to inflammatory reaction. The physiological variables in theory more associated with these alterations should be the physiological dead space and the inflammatory cytokines, both not specific for lung injury. Sequence 2: the intensity of mechanical ventilation is not such as to induce anatomical damage, but sufficient to interfere with normal hemodynamics. In theory, the first event is the increased intrathoracic pressure followed by all the hemodynamic consequences. The estimate of change of intrathoracic pressure requires the esophageal balloon, while several methods are available to assess the hemodynamic status. Both “direct” and “indirect” lung injury sequences convey in the same final pattern, characterized by water retention, alveolar edema and atelectasis. In the figure we report the common physiological variables which should be more associate with these events