Relation between Respiratory Mechanics, Inflammation, and Survival in Experimental Mechanical Ventilation.
Pubmed ID: 30199644
Pubmed Central ID: PMC6376413
Journal: American journal of respiratory cell and molecular biology
Publication Date: 02/01/2019
Affiliation: 7 Department of Anesthesiology, Washington University in St. Louis, St. Louis, Missouri.
MeSH Terms: Humans, Clinical Trials as Topic, Animals, Pneumonia, Respiration, Artificial, Respiratory Function Tests, Cytokines, Interleukin-6, Mice, Inbred C57BL, Respiratory Mechanics
Grants: R01 HL094639, R01 GM117233
Authors: Szabari MV, Takahashi K, Feng Y, Locascio JJ, Chao W, Carter EA, Vidal Melo MF, Musch G
Cite As: Szabari MV, Takahashi K, Feng Y, Locascio JJ, Chao W, Carter EA, Vidal Melo MF, Musch G. Relation between Respiratory Mechanics, Inflammation, and Survival in Experimental Mechanical Ventilation. Am J Respir Cell Mol Biol 2019 Feb;60(2):179-188.
Low-tidal volume (Vt) ventilation might protect healthy lungs from volutrauma but lead to inflammation resulting from other mechanisms, namely alveolar derecruitment and the ensuing alveolar collapse and tidal reexpansion. We hypothesized that the different mechanisms of low- and high-volume injury would be reflected in different mechanical properties being associated with development of pulmonary inflammation and mortality: an increase of hysteresis, reflecting progressive alveolar derecruitment, at low Vt; an increase of elastance, as a result of overdistension, at higher Vt. Mice were allocated to "protective" (6 ml/kg) or "injurious" (15-20 ml/kg) Vt groups and ventilated for 16 hours or until death. We measured elastance and hysteresis; pulmonary IL-6, IL-1β, and MIP-2 (macrophage inflammatory protein 2); wet-to-dry ratio; and blood gases. Survival was greater in the protective group (60%) than in the injurious group (25%). Nonsurvivors showed increased pulmonary cytokines, particularly in the injurious group, with the increase of elastance reflecting IL-6 concentration. Survivors instead showed only modest increases of cytokines, independent of Vt and unrelated to the increase of elastance. No single lung strain threshold could discriminate survivors from nonsurvivors. Hysteresis increased faster in the protective group, but, contrary to our hypothesis, its change was inversely related to the concentration of cytokines. In this model, significant mortality associated with pulmonary inflammation occurred even for strain values as low as about 0.8. Low Vt improved survival. The accompanying increase of hysteresis was not associated with greater inflammation.