呼气末正压与动态/静态机械能比值的相关性研究：针对不同肺损伤模型的动物实验及初步临床验证

Lung-protective ventilation has been extensively investigated in the treatment of acute respiratory distress syndrome (ARDS). Whereas, the setting of positive end-expiratory pressure (PEEP), an important composition of lung-protective ventilation, is far from conclusive. Recently, the concept of mechanical power has been introduced to clarify the relationship of ventilator-induced lung injury with the energy received by the lung. Current evidences showed that ventilator-induced lung injury was associated with the excessive mechanical power due to tidal volume, respiratory rate and inspiratory flow delivered by the ventilator. However, up to now, no study has been conducted to investigate the relationship between the mechanical power and PEEP. PEEP has dual-action of lung-protective and lung-injured effects, and mechanical power has the ability to differentiate the dynamic and static energy imposed during mechanical ventilation with PEEP. Therefore, we speculated that the ratio of dynamic and static mechanical power could reflect the dual-action of PEEP, and further, to be used as an indicator for the setting of PEEP in mechanically ventilated patients with ARDS. In the present project, we will first construct the relationship of dynamic-to-static mechanical power ratio with PEEP during PEEP titration trial in animal models with pulmonary and extra-pulmonary lung injury models. Lung-protective and lung-injured effects of mechanical power-derived PEEP will be investigated. We also preliminarily investigate the feasibility of mechanical power-derived PEEP settings in a small group of ARDS patients. Our results might provide important basic data for the research of mechanics of lung-protective and lung-injured effects of PEEP and methodological bases for individualized PEEP settings during the treatment of ARDS.

肺保护性通气是急性呼吸窘迫综合征研究的热点和前沿问题，其重要组成部分–呼气末正压，目前尚无确切方法以指导设定。新近研究发现，导致呼吸机相关肺损伤的机制与肺脏接受的机械能相关，致伤因素包括潮气量、呼吸频率和流速。但是，缺乏呼气末正压对机械能影响的研究。呼气末正压具有肺保护和损伤双重作用，而机械能可区分肺在机械通气时接受的静态和动态机械能。我们推测，动态/静态机械能比值可反映呼气末正压对肺的双重效应，从而进一步作为指导肺损伤时呼气末正压设定的指标。本项目首先在动物研究中构建了动态/静态机械能比值与呼气末正压之间的拟合关系，验证由该比值选择的呼气末正压，能否在提供肺保护作用的同时减轻损伤效应。进一步在临床研究中初步验证机械能在呼气末正压设定中的可行性。本研究结果将对探讨呼气末正压肺保护和损伤的病理生理学机制有较大帮助，也将为今后开展急性呼吸窘迫综合征患者呼气末正压个体化设定提供方法学基础。

急性呼吸窘迫综合征(acute respiratory distress syndrome，ARDS)是重症医学科中病死率较高的一种综合症，关于机械通气的研究是目前研究的热点和难点，其重要组成部分呼气末正压(positive end-expiratory pressure，PEEP)，目前尚无确切方法指导其设定。选择PEEP前需判断肺的复张性，其可能与ARDS的类型相关，ARDS根据其致病因素的不同，分为肺内源性ARDS和肺外源性ARDS。而导致呼吸机相关肺损伤的机制可能与机械能相关，机械能是一个综合因素，包含了致病因素潮气量、呼吸频率和流速等致病因素。呼气末正压具有肺保护和损伤双重作用，而机械能可区分肺在机械通气时接受的静态和动态机械能。本研究通过建立肺内源性和肺外源性ARDS动物模型模拟二种类型的ARDS，成功后进行PEEP滴定，从而计算出动态/静态机械能比值，首先拟合出动态/静态机械能比值与PEEP之间具有二项式的关系，肺内源性和肺外源性ARDS均具有二项式关系；再根据该拟合关系选择出最佳PEEP，并在最佳PEEP、大于和小于1.5倍最佳PEEP三个水平下进行机械通气，虽然通气后肺损伤的病理评分及氧合情况无统计学意义，但是有一定的趋势，因动物研究为小样本研究，可能需要更大的样本量及更多的临床研究进行验证。在数据分析中，本研究也发现在不同源性的ARDS模型中，PEEP对功能残气量无明显影响，且肺外源性ARDS的复张性比肺内源性ARDS的复张性好。应用分层电阻抗成像（electric impedance tomography, EIT）方法与流速积分法测量肺复张容积有显著的相关性和较好的一致性。EIT测量肺复张容积的优点是避免断开呼吸机，并且能够提供不同区域的通气和复张信息。EIT是床旁测量整体和局部肺复张容积的有效监测技术。本研究项目丰富了机械能关于PEEP的理论研究，也为EIT测量整体和局部肺复张容积提供了依据，仍需要更多的研究去完善和优化。

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