Personalized Mechanical Ventilation for the Injured Lung

针对受损肺部的个性化机械通气

• 批准号: 8766263
• 负责人: Jason HT Bates
• 金额: $ 60.03万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8766263
• 关键词: Address; Adult Respiratory Distress Syndrome; Algorithms; Biological; Blood gas; Body Weight; Characteristics; Computer Simulation; Data; Development; Diagnosis; Disease; Environmental air flow; Epithelial; Feedback; Goals; Individual; Infection; Injury; Lead; Liquid substance; Lung; Measures; Mechanical ventilation; Mechanics; Modality; Modeling; Nature; Outcome; Patients; Pharmacologic Substance; Pharmacy (field); Process; Prone Position; Property; Proteins; Randomized Clinical Trials; Regimen; Respiratory Failure; Running; Seminal; Severities; Stress; Structure of parenchyma of lung; Supportive care; Testing; Tidal Volume; Time; Tissues; Translations; Trauma; Ventilator-induced lung injury; Volutrauma; Weight; atelectrauma; base; design; effective therapy; electric impedance; expiration; human subject; improved; injured; lung injury; mechanical behavior; mortality; mouse model; novel; novel therapeutics; patient population; pressure; prevent; public health relevance; response; standard of care

DESCRIPTION (provided by applicant): Acute respiratory distress syndrome (ARDS) is a common and often fatal condition for which there is no effective treatment other than supportive care centered on mechanical ventilation. Mechanical ventilation itself, however, can easily cause damage to already injured lung tissues, leading to ventilator-induced lung injury (VILI). The principle goal in managing ARDS is thus to administer mechanical ventilation in a manner that avoids, or at least minimizes, VILI. The standard of care in ARDS involves use of small tidal volumes (Vt), the current ideal being 6 ml/kg ideal body weight, together with positive end-expiration pressure (PEEP) to prevent lung collapse and improve oxygenation. These strategies have led to improved outcomes, but ARDS mortality remains high, so better approaches to mechanically ventilating the injured lung are desperately needed. Unfortunately, continuing to search for one-size-fits-all approaches to mechanical ventilation of the very heterogeneous ARDS patient population is rapidly becoming futile because of the huge number of patients that would be needed to obtain statistically significant improvements over current strategies. For this reason, the search for improved approaches to mechanical ventilation in ARDS must focus on strategies that can be tailored to suit the pathophysiological characteristics of individual patiens. Furthermore, such strategies must be adaptable to the evolving nature and severity of ARDS as it runs its course. These considerations lead us to propose that personalized mechanical ventilation of the ARDS patient must take place within an ongoing feedback loop involving three interdependent processes: 1) assessing the injury status of a given lung, 2) predicting how much VILI will be caused in that lung by a given regimen of mechanical ventilation, and 3) optimizing ventilation to be minimally injurious based on the information provided in steps 1 and 2. This will allow the imposed regimen of mechanical ventilation to be responsive to the ventilatory needs of the patient, while at the same time minimizing the amount of VILI that is produced so that the patient's own reparative processes have the best chances of prevailing. We have undertaken extensive prior studies that show we can assess the current state of injury of the lung most effectively by measuring how its mechanical properties change over time as a result of ongoing recruitment and derecruitment. We have also developed computational models showing how it is, in principle, possible to predict the amount of VILI that will be produced by a given regimen of mechanical ventilation. Our overarching goal in this proposal is to leverage these findings to optimize the personalized design of mechanical ventilation strategies for the injured lung. This goal will be pursued experimentally in mouse models of ARDS and VILI, and computationally by fitting the data obtained to computational models of lung mechanics and VILI development.

描述（由申请人提供）：急性呼吸窘迫综合征（ARDS）是一种常见且经常致命的疾病，除了以机械通气为中心的支持治疗外，没有有效的治疗方法。然而，机械通气本身很容易对已经损伤的肺组织造成损伤，导致呼吸机诱导的肺损伤（VILI）。因此，管理ARDS的主要目标是以避免或至少最小化VILI的方式管理机械通气。ARDS的标准护理包括使用小潮气量（Vt），目前理想的是6 ml/kg理想体重，同时使用正呼气末压（PEEP）来防止肺衰竭和改善氧合。这些策略改善了预后，但ARDS死亡率仍然很高，因此迫切需要更好的方法对受伤的肺进行机械通气。不幸的是，继续寻找一种适合所有异质性ARDS患者群体的机械通气方法正迅速变得徒劳，因为与目前的策略相比，需要大量患者才能获得统计上显着的改善。因此，在ARDS中寻找改进的机械通气方法必须侧重于能够适应个体患者病理生理特征的策略。此外，这些策略必须适应ARDS发展过程中不断变化的性质和严重程度。考虑到这些因素，我们提出，ARDS患者的个性化机械通气必须在一个持续的反馈循环中进行，涉及三个相互依存的过程：1)评估给定肺的损伤状态，2)预测给定机械通气方案会在该肺中引起多少VILI，以及3)根据步骤1和2提供的信息优化通气以使损伤最小。这将允许强制的机械通气方案对患者的通气需求做出反应，同时最大限度地减少VILI的产生，使患者自己的修复过程有最好的机会。我们已经进行了大量的前期研究，这些研究表明，我们可以通过测量肺的机械性能随着时间的推移而发生的变化来最有效地评估肺损伤的当前状态。我们还开发了计算模型，显示原则上如何可能预测给定机械通气方案将产生的VILI量。我们的总体目标是利用这些发现来优化受伤肺的机械通气策略的个性化设计。这一目标将在ARDS和VILI小鼠模型中进行实验，并通过将获得的数据拟合到肺力学和VILI发展的计算模型中进行计算。