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）是一种常见且通常致命的疾病，除了以机械通气为中心的支持性护理外，没有有效的治疗方法。然而，机械通气本身很容易对已经受损的肺组织造成损伤，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的方式进行机械通气。ARDS的护理标准涉及使用小潮气量（Vt），目前的理想值为6 ml/kg理想体重，以及呼气末正压（PEEP），以防止肺萎陷并改善氧合。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来机械通气受伤的肺。不幸的是，继续寻找一个尺寸适合所有的方法，以机械通气的非常异质性的ARDS患者群体正在迅速成为徒劳的，因为将需要大量的患者，以获得统计学显着改善目前的战略。因此，寻求改善ARDS机械通气方法的研究必须集中在能够适应个体患者病理生理特征的策略上。此外，这些策略必须适应急性呼吸窘迫综合征（ARDS）发展过程中不断变化的性质和严重程度。这些考虑使我们提出，ARDS患者的个性化机械通气必须在涉及三个相互依赖的过程的持续反馈回路中进行：1）评估给定肺部的损伤状态，2）预测给定机械通气方案将在该肺部引起多少VILI，以及3）基于步骤1和2中提供的信息优化通风以使其伤害最小。这将允许所施加的机械通气方案响应于患者的呼吸需要，同时使产生的VILI的量最小化，使得患者自身的修复过程具有最佳的获胜机会。我们已经进行了广泛的先前研究，表明我们可以通过测量其机械性能如何随着时间的推移而变化，作为持续招募和去招募的结果，最有效地评估肺损伤的当前状态。我们还开发了计算模型，显示在原则上如何能够预测由给定的机械通气方案产生的VILI的量。我们在这项提案中的首要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的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发展的计算模型来进行计算。