Publications

OBJECTIVES: Invasive mechanical ventilation (IMV) is crucial for acute respiratory distress syndrome (ARDS) management, but mortality remains high. While spontaneous breathing is key to weaning, excessive respiratory effort may injure the lung and diaphragm. Most existing data on respiratory effort during IMV are based on brief periods of observation, potentially underestimating the burden of inappropriate efforts. This study aims to characterize the evolution of respiratory effort over time in ARDS patients and its relation to survival. We hypothesized that nonsurvivors would spend a greater proportion of time in the high-effort range during the active breathing phase compared with survivors. DESIGN, SETTING, AND PATIENTS: In this prospective cohort study, we continuously recorded airway pressure, flow, esophageal, and gastric pressures in ARDS patients on mechanical ventilation during 7 days after the onset of spontaneous breathing. We analyzed physiologic respiratory effort variables, focusing on the proportion of time spent within defined effort ranges, and compared these data between ICU survivors and nonsurvivors. Statistical analysis was conducted using variance weighted methods to account for variability in the number of respiratory cycles analyzed per patient. This study is registered at ClinicalTrials.gov under identifier NCT06490523. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 1,485,405 respiratory cycles were analyzed from 26 ARDS patients (19 survivors, seven nonsurvivors). Nonsurvivors spent significantly more time in high effort (12% vs. 3%; p = 0.006). In contrast, survivors spent more time in the moderate-effort range (50% vs. 5%; p < 0.001). The time spend with high dynamic transpulmonary driving pressure (> 25 cm H2O) was also significantly different between groups (32% survivors vs. 74% nonsurvivors; p = 0.001). CONCLUSIONS: Patients who die of ARDS are more likely to be exposed to high respiratory effort for prolonged periods of time compared with survivors.

JTD Keywords: Acute respiratory distress syndrome, Adult patients, Epidemiology, Esophageal, Esophageal pressure, Evolution, Lung injury, Mechanical ventilation, Mortality, Pressure support ventilation, Pulmonary, Respiratory effort, Transpulmonary pressure

Introduction: Application of lipopolysaccharide (LPS) is a widely employed model to mimic acute respiratory distress syndrome (ARDS). Available data regarding LPS-induced biomechanical changes on pulmonary epithelial cells are limited only to P. aeruginosa LPS. Considering that LPS from different bacteria could promote a specific mechanical response in epithelial cells, we aim to assess the effect of E. coli LPS, widely employed as a model of ARDS, in the biomechanics of alveolar epithelial cells. Methods: Young’s modulus (E) of alveolar epithelial cells (A549) was measured by atomic force microscopy every 5 min throughout 60 min of experiment after treatment with LPS from E. coli (100 μg/mL). The percentage of cells presenting actin stress fibers (F-actin staining) was also evaluated. Control cells were treated with culture medium and the values obtained were compared with LPS-treated cells for each time-point. Results: Application of LPS induced significant increase in E after 20 min (77%) till 60 min (104%) in comparison to controls. Increase in lung epithelial cell stiffness induced by LPS was associated with a higher number of cells presenting cytoskeletal remodeling. Conclusions: The observed effects of E. coli LPS on alveolar epithelial cells suggest that this widely-used LPS is able to promote a quick formation of actin stress fibers and stiffening cells, thereby facilitating the disruption of the pulmonary epithelial barrier.

JTD Keywords: Acute respiratory distress syndrome model, Alveolar epithelium, Biomechanics, E. coli, Lipopolysaccharide