Hyper-protective mechanical ventilation by gas exchange-optimizing ventilation profiles

当患者处于全身麻醉或患有肺部疾病时，机械通气是主要的救命方法。高潮气量及其相关的高压力、高流速、不均匀的气体分布以及肺组织的潮气性呼吸充盈/去充盈会导致周期性机械负荷，从而覆盖肺实质。在常规机械通气中，无论是强制呼吸还是增加自主呼吸，呼气过程遵循快速指数衰减函数，其时间常数由呼吸系统(视情况而定)的顺应性和阻力来确定。我们研究组开发的“流量控制呼气”(FLEX)和正弦通风(SINE)的特点是对总通气期进行主动控制。在呼吸系统的大小动物模型中，FLEX和SINE与被动呼气的传统呼吸机相比，肺损伤较小，局灶性炎症减少，顺应性改善，气体交换更有效。在前期工作的基础上，我们设计了一种新的方法来优化换气的时间模式，目的是改善肺气体交换。通过将线性和正弦模式相结合，我们创建了Linus通风模式。在这个项目中，我们研究了Linus通风模式在改善气体交换及其肺保护潜力方面的效果。因此，研究的重点是潮气量和呼吸频率的减少以及减速通风模式本身的肺保护作用。为了全面了解新通风模式的潜在机制和肺保护潜力，我们将在机械通气健康呼吸系统和急性肺衰竭时呼吸系统的小动物模型上进行一系列实验。

Mechanical ventilation is the main life-saving therapy when a patient is under general anaesthesia or suffers from a lung disease. High tidal volumes and associated high pressures, high flow rates, inhomogeneous gas distribution and tidal respiratory recruitment/de-recruitment of lung tissue lead to cyclic mechanical load that can overburden the lung parenchyma. Under conventional mechanical ventilation, mandatory or provided as augmented spontaneous breathing, the course of expiration follows a rapid exponential decay function, the time constant of which is determined by compliance and resistance of the (as the case may be pathologically altered) respiratory system. The "flow-controlled expiration" (FLEX) and the sinusoidal ventilation (SINE) developed in our research group are characterised by active control of the total ventilation period.In small and large animal models of the ventilated respiratory system, FLEX and SINE resulted in less lung damage and reduced focal inflammation, as well as improved compliance and more efficient gas exchange compared to conventional ventilation with passive expiration. Based on our preliminary work, we designed a new approach to optimise the temporal pattern of ventilation with the aim of improving pulmonary gas exchange. By combining a linear with a sinusoidal pattern we created the LINUS ventilation pattern. In this project we investigate the effects of the LINUS ventilation pattern with regard to improving gas exchange and its lung-protective potential. Thereby, the focus is on the reduction of tidal volume and respiratory rate as well as on the lung-protective effects of the decelerated ventilation pattern itself.In order to gain comprehensive insights into the underlying mechanisms and the lung-protective potential of the new ventilation pattern, series of experiments will be conducted in small animal models of the mechanically ventilated healthy respiratory system and the respiratory system in acute lung failure.