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Spontaneous Breathing Activity Correlates with Regional Lung Inflammation at Inappropriate Low Positive End-Expiratory Pressure in Experimental Moderate ARDS

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A5125 - Spontaneous Breathing Activity Correlates with Regional Lung Inflammation at Inappropriate Low Positive End-Expiratory Pressure in Experimental Moderate ARDS
Author Block: J. J. Wittenstein1, T. Kiss1, T. Bluth1, A. Braune1, R. Huhle1, M. Herzog1, L. Vivona2, A. Bergamaschi3, M. Andreef4, M. Scharffenberg1, M. V. Melo5, T. Koch1, P. R. Rocco6, P. Pelosi3, J. Kotzerke4, M. Gama de Abreu1; 1Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus Dresden, Dresden, Germany, 2Department of Anesthesiology and Intensive Care, University of Naples, Napoli, Italy, 3Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy, 4Institute of Nuclear Medicine, University Hospital Carl Gustav Carus Dresden, Dresden, Germany, 5Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, United States, 6Laboratory of Pulmonary Investigation, Federal University of Rio de Janeiro, Rio De Janeiro, Brazil.
INTRODUCTION: The impact of positive end-expiratory pressure (PEEP) during mechanical ventilation with and without spontaneous breathing (SB) activity on inflammation in acute lung injury is poorly described. We hypothesized that, in moderate ARDS, SB activity combined with inappropriate low PEEP-levels increases regional lung inflammation.
METHODS: In 24 anesthetized pigs, intrapleural pressure sensors were placed in ventral, dorsal and caudal regions of the left hemithorax. Lung injury was induced by saline lung lavage followed by injurious ventilation (ΔP=30cmH2O). During airway pressure release ventilation (APRV) with low tidal volumes (Vt=6ml/kg), PEEP was set 4 cmH2O above the level to reach a positive transpulmonary pressure in caudal regions at end-expiration (best PEEP). Animals were randomly assigned to one of four groups (n=6/group; 12 hours): 1) no SB activity and PEEP=best PEEP-4 cmH2O(C-); 2) no SB activity and PEEP=best PEEP+4 cmH2O (C+); 3) SB activity and PEEP=best PEEP-4 cmH2O (SB-); 4) SB activity and PEEP=best PEEP+4 cmH2O (SB+). After 12 hours, lung aeration was determined by static and dynamic computed tomography (CT). In addition, positron emission tomography (PET) was used to assess regional lung [18F]fluorodeoxyglucose ([18F]FDG) uptake as well as perfusion using 68Ga-labeled microspheres.
RESULTS: Global lung inflammation, assessed by specific [18F]-fluorodeoxyglucose uptake rate (Kis) [median (25% percentile – 75% percentile), min-1], was decreased with higher compared to lower PEEP without SB activity [0.029(0.027-0.030) vs. 0.044(0.041-0.065), P=0.004] and with SB activity [0.032(0.028-0.043) vs. 0.057(0.042-0.075), P=0.016], mainly in ventral regions. SB activity did not increase global lung inflammation, independent of the PEEP level. However, regional lung inflammation correlated with dorsal transpulmonary driving pressures from spontaneous breaths at lower (r=0.850, P=0.032) but not higher PEEP (r=0.018, P=0.972). Higher PEEP resulted in a more homogeneous distribution of regional transpulmonary pressures at end-expiration. In ventral lung regions, tidal hyperaeration was higher with S+ compared to S-. In mid-ventral regions, tidal reaeration was more pronounced
with C- compared to C+. In S+ compared to S-, the centers of aeration and perfusion were shifted towards dependent lung. The centers of ventilation along the ventral-dorsal gradient did not differ significantly among groups.
CONCLUSION: In experimental moderate ARDS, PEEP levels that stabilize dependent lung regions reduce global lung inflammation during mechanical ventilation, independent from SB activity. SB activity has the potential to increase dorsal lung inflammation when inappropriate low PEEP is used.
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