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

机械通气过程中机械能强度的分布：呼吸机所致肺损伤机制的研究

• 批准号: 438791011
• 负责人: Professor Dr. Marcelo Gama de Abreu
• 金额: --
• 依托单位: Klinik und Poliklinik für Anästhesiologie und Intensivtherapie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2020
• 资助国家: 德国
• 起止时间: 2019-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/438791011?language=en
• 关键词: Distribution; mechanical; energy; intensity; during

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.

机械通气需要设定肺扩张压、潮气量、呼吸道流量(或吸气/呼气比)、呼吸频率和呼气末正压(PEEP)。所有这些变量加在一起，导致机械能从呼吸机转移到呼吸系统。根据机械能在肺中的消散程度，可能会导致呼吸机诱发肺损伤(VILI)。目前计算机械能的方法，即一段时间内机械能的量，由于包含了PEEP项而存在缺陷。另一方面，PEEP引起呼吸系统容量-压力曲线的移动，并导致静态应力和应变，这两者都对VILI有重要贡献。此外，通常被忽视的是，VILI可能会因能量在肺部的分布而有所不同，即所谓的能量强度。本申请中提出的两个项目旨在填补这一知识缺口。第一个项目涉及在猪急性呼吸窘迫综合征(ARDS)的实验模型中，在不同的保护性机械通风设置下，机械能强度的创新概念及其在肺中的分布。第二个项目是在猪ARDS的实验模型中研究PEEP对机械能强度和VILI的单独(无潮气通风)和联合(有潮气通风)贡献，因此需要使用体外肺支持来获得适当的机械通风设置。这两个项目都结合了先进的肺部成像技术，可以确定局部肺力学和炎症，即计算机断层扫描(CT)和正电子发射断层扫描(PET)，并建立了18F-氟代脱氧葡萄糖(18F-FDG，炎症标志物)动力学的数学模型。此外，还将使用分子生物学和组织学技术对炎症和肺损伤进行最先进的测量。从理论上讲，通过解决机械功率计算中的不一致问题，特别是通过将概念扩展到静态和动态能量以及静态和动态强度，在全球和区域范围内，可能会产生VILI的统一机制。此外，通过估计PEEP所产生的能量贡献，可以决定性地改进旨在保护机械通气期间肺的策略。因此，这些研究的结果将代表着在机械通气的基础科学和翻译方面的实质性进展，并对临床实践产生影响。