Personalized Mechanical Ventilation for the Injured Lung

针对受损肺部的个性化机械通气

• 批准号: 9026498
• 负责人: Jason HT Bates
• 金额: $ 58.72万
• 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/9026498
• 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; Health; Individual; Infection; Injury; Lead; Liquid substance; Lung; Measures; Mechanical ventilation; Mechanics; Modality; Modeling; Nature; 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; improved outcome; individual patient; injured; lung injury; mechanical behavior; mortality; mouse model; novel; novel therapeutics; patient population; personalized approach; personalized strategies; pressure; prevent; 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）是一种常见且常常致命的疾病，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伤的肺组织造成损伤，导致呼吸机相关性肺损伤（VILI）。因此，治疗 ARDS 的主要目标是以避免或至少最大限度地减少 VILI 的方式进行机械通气。 ARDS 的护理标准包括使用小潮气量 (Vt)（目前理想的潮气量为 6 毫升/公斤理想体重）以及呼气末正压 (PEEP)，以防止肺萎陷并改善氧合。这些策略改善了结果，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部进行机械通气。不幸的是，继续寻找针对异质性 ARDS 患者群体的一刀切的机械通气方法很快就会变得徒劳无功，因为需要大量患者才能获得比当前策略具有统计学意义的显着改善。因此，寻找改进的 ARDS 机械通气方法必须侧重于可以根据个体患者的病理生理学特征量身定制的策略。此外，此类策略必须适应 ARDS 不断变化的性质和严重程度。这些考虑因素使我们提出，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循环内进行：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) 根据步骤 1 和 2 中提供的信息优化通气，使其伤害最小。 机械通气方案能够满足患者的通气需求，同时最大限度地减少 VILI 的产生量，从而使患者自身的修复过程有最大的成功机会。我们之前进行了广泛的研究，表明我们可以通过测量肺的机械特性因持续的肺复张和解除肺复张而随时间变化的情况，最有效地评估肺的当前损伤状态。我们还开发了计算模型，展示了原则上如何预测给定机械通气方案产生的 VILI 量。我们在该提案中的首要目标是利用这些发现来优化针对受伤肺部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。