Abstract

Introduction:Ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa (PA) is a common intensive care unit-acquired nosocomial infection. Early prone positioning (PP) during mechanical ventilation (MV) has been proven beneficial in severe ARDS patients. The potential effect of PP on the development of VAP is currently unknown.

Aims:To investigate the role of PP during MV on PA-VAP severity.

Methods:C57BL/6J mice were subjected to high tidal volume MV for 4h either in supine (SP) or prone position and PA was instilled via the endotracheal tube. Sedation was antagonized and mice breathed spontaneously for 24h after extubation. Lung function was measured at the start and end of MV. Lung permeability, inflammatory responses, histology, and bacterial load in lung, blood, and liver were analyzed 24h post-infection.

Results:PP mice exhibited decreased mean airway pressure and increased lung compliance after 4h MV. PP mice showed significantly decreased lung permeability, reduced BAL and plasma levels of inflammatory mediators, and lower blood neutrophil counts compared to infected SP mice. Pulmonary and extra-pulmonary bacterial loads were significantly lower in mice subjected to PP than SP. Histopathologic analysis showed significantly attenuated neutrophil infiltration and lung injury in infected PP mice compared to the SP mice. Analysis of dorsal and ventral lung sections revealed a significant reduction of ventral overinflation and neutrophil infiltration in PP mice.

Conclusion:In our novel murine VAP model, prone positioning prevented worsening of lung function due to MV and was associated with decreased susceptibility to PA infection and reduced systemic spread of bacteria.