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Prone positioning associated with high-frequency oscillatory ventilation and conventional protective mechanical ventilation in an acute respiratory distress syndrome rabbit model.

Grant number: 10/19942-8
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2011
Effective date (End): January 31, 2012
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal Investigator:José Roberto Fioretto
Grantee:Thalissa Herminia Baio
Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil


Mechanical ventilation (MV) is an essential method of support in acute respiratory distress syndrome (ARDS). There are two ventilatory methods of lung protection, protective conventional mechanical ventilation (CMV) and, more recently, high frequency oscillatory ventilation (HFOV). HFOV is a ventilatory method that uses lower tidal volume than the volume of anatomical dead space, often well above the physiological, avoiding the high pressures and alveolar volumes typical of CMV. Due to the high mortality in ARDS, other therapeutic strategies have being developed in addition to MV, especially the prone position. Prone position can improve gas exchange for several reasons: 1) redistribution of ventilation to dorsal lung areas which are better perfused, with improvement of ventilation/perfusion ratio in these regions, 2) homogenization of the distribution of tidal volume, 3) alveolar recruitment, 4) redirection of compressive forces exerted by the weight of the heart on the lungs and 5) facilitating the removal of secretions. Considering the protective features of the HFOV and the ability to redistribution of ventilation to better perfused lung areas, and the potential recruitment of the prone position, our hypothesis is that beneficial effects of HFOV and prone position provide greater improvement in oxygenation, more homogeneous and less severe histopathological damage, and attenuate lung injury and oxidative tissue inflammation compared to HFOV alone and protective CMV with or without prone position. Objectives: The objective of this study will be investigate the effects of prone position associated with HFOV and protective CMV on oxygenation, inflammation, histology and oxidative lung damage, compared to supine position in an experimental model of ARDS induced in rabbits. The outcomes will be pathophysiological indexes of acute lung injury: gas exchange and oxygenation, histological and oxidative damage of lung tissue, serum and brochoalveolar lavage TNF-alpha and IL-6, polymorphonuclear count in lung lavage fluid and expression of mRNA for IL-6 and TNF-alpha through the polymerase chain reaction in real time (real time PCR). Methods: Eighty rabbits will be instrumented and randomly assigned to six experimental groups: 1) healthy instrumented animals submitted to protective CMV (control - GC, n = 15), 2) animals with ARDS submitted to protective CMV in supine position (MVS, n = 15), 3) animals with ARDS submitted to CMV protective in prone position (MVP n = 15), 4) animals with ARDS submitted to HFOV in supine position (HFS n = 15), 5) animals with ARDS submitted to HFOV in prone position (HFP n = 15) and 6) healthy animals not instrumented (healthy - GH, n = 5). Acute lung injury will be induced by repeated lung lavage with warm saline at 37oC - 38oC at a rate of 30 mL/kg, in maximum pressure of 30 cmH2O. The animals remain on mechanical ventilation for four hours, being closely monitored in terms of ventilatory and hemodynamic parameters during this period.

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