Distribution of mechanical energy intensity during mechanical ventilation: An investigation on the mechanisms of ventilator induced lung injury

• Applicant: Professor Dr. Marcelo Gama de Abreu
• Subject Area: Anaesthesiology
• Term: from 2020 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 438791011

Mechanical ventilation requires the setting of lung distending pressures, tidal volume, airway flow (or inspiratory-to-expiratory ratio), respiratory rate and positive end-expiratory pressure (PEEP). Together, all those variables contribute to the mechanical energy that is transferred from the ventilator to the respiratory system. Depending upon the amount of mechanical energy that is dissipated in the lungs, ventilator-induced lung injury (VILI) may result. Current ways to calculate mechanical power, that is the amount of mechanical energy over time, are flawed due to inclusion of a PEEP term. On the other hand, PEEP causes a shift in the volume-pressure curve of the respiratory system, and results in static stress-and-strain, both of which contribute importantly to VILI. Also, it is usually neglected that VILI may differ regionally depending on the distribution of energy across lungs, so-called energy intensity. The two projects proposed in this application are intended to fulfill this gap in knowledge. The first project deals with the innovative concept of mechanical energy intensity and its distribution across the lungs at different protective mechanical ventilation settings in an experimental model of the acute respiratory distress syndrome (ARDS) in pigs. The second project addresses the isolated (without tidal ventilation) and the combined (with tidal ventilation) contribution of PEEP to mechanical energy intensity and VILI also in an experimental model of ARDS in pigs, whereby the use of extracorporeal lung support will be required to obtain the appropriate mechanical ventilation settings. Both projects include a combination of sophisticated lung imaging techniques that permit the determination of regional lung mechanics and inflammation, namely computed tomography (CT), and positron emission tomography (PET) with mathematical modeling of 18F-fluorodeoxyglucose (18F-FDG, inflammation marker) kinetics. In addition, state-of-the-art measurements of inflammation and lung damage using molecular biology and histology techniques will take place. Theoretically, by solving the inconsistencies in the computation of mechanical power, and specially by expanding the concept to static and dynamic energy as well as static and dynamic intensity, both globally and regionally, a unifying mechanism of VILI might result. Also, by estimating the contribution of the energy due to PEEP, strategies aiming at protecting lungs during mechanical ventilation could be decisively improved. Therefore, the results of these investigations would represent a substantial advance in basic science and translational aspects of mechanical ventilation, with impact on clinical practice as well.

• DFG Programme: Research Grants
• International Connection: Brazil, Italy, Netherlands
• Cooperation Partners: Professor Dr. Paolo Pelosi; Professorin Patricia Rieken Macêdo Rocco, Ph.D.; Professor Marcus Schultz, Ph.D.; Professor Dr. Ary Serpa Neto
• Co-Investigator: Professor Dr. Jörg Kotzerke