Distribution of lung inflammation during assisted mechanical ventilation with titrated end-expiratory transpulmonary pressures in experimental acute respiratory distress syndrome
Thomas Kiss1, Thomas Bluth1, Anja Braune1, Luigi Vivona1,2, Robert Huhle1, Marcelo Gama de Abreu1

1Department of Anesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Carl Gustav Carus, Technische Universität Dresden, Germany
2Department of Anesthesia and Intensive Care, University of Naples, Naples, Italy

BACKGROUND AND GOAL OF STUDY
Evidence of lung injury due to spontaneous breathing activity (SB) in acute respiratory lung injury (ARDS) has been obtained during inappropriate settings of positive end-expiratory pressure (PEEP) and artificially high respiratory drive.  
In this study, we investigated the correlation between a PEEP setting based on transpulmonary pressure (TP) and assisted SB in experimental severe adult respiratory distress syndrome (ARDS) in pigs.
We hypothesized that in severe ARDS, 12 hours of assisted SB with titrated positive end-expiratory TP levels in all lung regions, compared to a group with negative TP values, reduces lung inflammation measured by positron emission tomography (PET).
MATERIAL AND METHODS
In 10 anesthetized pigs, custom-made intrapleural pressure sensors were placed in non-dependent and dependent lung regions by video-assisted thoracoscopy. Experimental ARDS was induced by saline lung lavage and injurious high tidal volume mechanical ventilation, until PaO2 < 100 mmHg. Following a lung recruitment maneuver and a decremental PEEP trial (26 cmH2O - 6 cmH2O) respiratory system mechanics and regional TP was determined for each PEEP level. The best-PEEP level was defined as the lowest PEEP yielding positive end-expiratory TP in  all lung regions. Animals were then randomly assigned to airway pressure release ventilation with best PEEP + 4 cmH2O (Group 1, “high PEEP”, n=5) or best PEEP – 4 cmH2O (Group 2, “low PEEP”, n=5). SB was induced (proportion of SB being 40 to 60% of total minute ventilation) gas exchange, hemodynamics and lung mechanics were assessed for a time period of 12 hours. At the end lung inflammation was determined as the specific uptake rate (Ki,S) of Fluor-18-deoxyglucose using PET (Patlak model).
RESULTS AND DISCUSSION
There were no significant differences in bodyweight and age. A two tailed Mann Whitney U test showed a significantly lower Ki,S for the high PEEP group (median 0.031, interquartile range 0.038-0.026) compared to the low PEEP group (median 0.048; interquartile range 0.070-0.039) (p=0.032). Repeated measures two-way ANOVA showed no differences between groups for hemodynamics, gas exchange and lung mechanics. The best- PEEP level did not differ significantly from the PEEP level resulting in lowest lung elastance.  
CONCLUSION
In a model of severe ARDS in pigs, assisted SB with titrated positive end-expiratory TP levels in all lung regions, attenuated lung inflammation.

Distribution of lung inflammation during assisted mechanical ventilation with titrated end-expiratory transpulmonary pressures in experimental acute respiratory distress syndrome