Comparison between effects of pressure support and pressure-controlled ventilation on lung and diaphragmatic damage in experimental emphysema.

Gisele De A Padilha,Marcelo M Morales,Isalira P Ramos,Vera Luiza Capelozzi,Pedro L Silva,Patricia R M Rocco,Marcelo Gama De Abreu,Lucas F B Horta,Paolo Pelosi,Milena V Oliveira,Cíntia L Santos,Regina C S Goldenberg,Lillian Moraes,Cassia L Braga

doi:10.1186/s40635-016-0107-0

Abstract

BackgroundIn patients with emphysema, invasive mechanical ventilation settings should be adjusted to minimize hyperinflation while reducing respiratory effort and providing adequate gas exchange. We evaluated the impact of pressure-controlled ventilation (PCV) and pressure support ventilation (PSV) on pulmonary and diaphragmatic damage, as well as cardiac function, in experimental emphysema.MethodsEmphysema was induced by intratracheal instillation of porcine pancreatic elastase in Wistar rats, once weekly for 4 weeks. Control animals received saline under the same protocol. Eight weeks after first instillation, control and emphysema rats were randomly assigned to PCV (n = 6/each) or PSV (n = 6/each) under protective tidal volume (6 ml/kg) for 4 h. Non-ventilated control and emphysema animals (n = 6/group) were used to characterize the model and for molecular biology analysis. Cardiorespiratory function, lung histology, diaphragm ultrastructure alterations, extracellular matrix organization, diaphragmatic proteolysis, and biological markers associated with pulmonary inflammation, alveolar stretch, and epithelial and endothelial cell damage were assessed.ResultsEmphysema animals exhibited cardiorespiratory changes that resemble human emphysema, such as increased areas of lung hyperinflation, pulmonary amphiregulin expression, and diaphragmatic injury. In emphysema animals, PSV compared to PCV yielded: no changes in gas exchange; decreased mean transpulmonary pressure (Pmean,L), ratio between inspiratory and total time (Ti/Ttot), lung hyperinflation, and amphiregulin expression in lung; increased ratio of pulmonary artery acceleration time to pulmonary artery ejection time, suggesting reduced right ventricular afterload; and increased ultrastructural damage to the diaphragm. Amphiregulin correlated with Pmean,L (r = 0.99, p < 0.0001) and hyperinflation (r = 0.70, p = 0.043), whereas Ti/Ttot correlated with hyperinflation (r = 0.81, p = 0.002) and Pmean,L (r = 0.60, p = 0.04).ConclusionsIn the model of elastase-induced emphysema used herein, PSV reduced lung damage and improved cardiac function when compared to PCV, but worsened diaphragmatic injury.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-016-0107-0) contains supplementary material, which is available to authorized users.

Highlights

In patients with emphysema, invasive mechanical ventilation settings should be adjusted to minimize hyperinflation while reducing respiratory effort and providing adequate gas exchange
Tidal volume (VT), Ti/Ttot, and PPeak,L remained unaltered in pressure support ventilation (PSV) compared to pressure-controlled ventilation (PCV) animals at T4 (Table 1)
PSV compared to PCV: decreased Pmean,L, hyperinflation, mean linear intercept, and amphiregulin messenger RNA (mRNA) expression in the lung; reduced right ventricular afterload; and increased ultrastructural damage to the diaphragm without inducing changes in biomarkers associated with proteolysis

Summary

Introduction

Invasive mechanical ventilation settings should be adjusted to minimize hyperinflation while reducing respiratory effort and providing adequate gas exchange. We evaluated the impact of pressure-controlled ventilation (PCV) and pressure support ventilation (PSV) on pulmonary and diaphragmatic damage, as well as cardiac function, in experimental emphysema. When providing ventilatory support to patients with emphysema, the main goals are to improve gas exchange and avoid or prevent further aggravation of hyperinflation, cardiovascular dysfunction, and diaphragmatic atrophy. Pressure support ventilation requires less sedation, no paralysis, and has been associated with improved gas exchange and lung mechanics (due to decreased time-constant inhomogeneity), as well as with less hemodynamic deterioration and diaphragmatic damage, in experimental [6, 9, 10] and clinical [11] reports. No study has evaluated the impact of pressure support ventilation (PSV) and pressure-controlled ventilation (PCV) on lung damage, diaphragmatic injury, and cardiovascular function in experimental emphysema

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