Association between driving pressure, systemic inflammation and non-pulmonary organ dysfunction in patients with acute respiratory distress syndrome, a prospective pathophysiological study

Background: Driving pressure is thought to determine the effect of low tidal ventilation on survival in patients with acute respiratory distress syndrome. The leading cause of mortality in these patients is non-pulmonary multiorgan dysfunction, which is believed to worsen due to the biological response to mechanical ventilation (biotrauma). Therefore, we aimed to analyze the association between driving pressure, biotrauma, and non-pulmonary multiorgan dysfunction. Additionally, we analyzed this relationship for tidal volume/predicted body weight. Methods: Observational study that included adult patients with acute respiratory distress syndrome undergoing invasive mechanical ventilation admitted to the Hospital Clinic of Barcelona, Spain, between June 2019 and February 2021. We conducted mixed-effects models to assess the effects of driving pressure and tidal volume/predicted body weight on the evolution of 22 log-transformed biomarker variables during the first, third, and fifth days after study enrollment. These 22 systemic biomarkers characterized epithelial and endothelial pulmonary dysfunction, inflammation, and coagulation disorders in the included patients. In the same fashion, the association between driving pressure and non-pulmonary multiorgan dysfunction was evaluated by the non-pulmonary sequential organ failure assessment score (non-pulmonary SOFA) and its associated variables. Finally, we performed mediation analyses to assess whether the relationship between biomarkers and driving pressure was mediated by other ventilator-induced lung injury parameters. Results: Thirty-eight patients were included. Driving pressure was independently associated with soluble Receptor for advanced glycation end-products, Interleukin (IL)-8, IL-6, IL-10, IL-17, Interferon-ɣ, Chemokine (C-C motif)-2, Vascular endothelial growth factor, Tissue factor, Protein C, Protein S, and higher dose of norepinephrine. However, this relationship attenuated over time. In contrast, tidal volume/predicted body weight was not associated with any of the 22 biomarkers tested. A concomitant increase in positive end-inspiratory plateau pressure or tidal volume did not mediate the effect of driving pressure on biomarkers. Conversely, the association between compliance of the respiratory system and pulmonary epithelial dysfunction was primarily mediated by driving pressure. Conclusions: Driving pressure, but not tidal volume/predicted body weight, was correlated with epithelial and endothelial pulmonary dysfunction, inflammation, coagulation disorders, and hemodynamic dysfunction. However, this relationship diminished over time.