Personalized Mechanical Ventilation for the Injured Lung

针对受损肺部的个性化机械通气

基本信息

批准号：
9232202
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
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9232202
关键词：
Address Adult Respiratory Distress Syndrome Algorithms Biological Blood gas Body Weight Characteristics Clinical 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 Patients Pharmacologic Substance Pharmacy (field)Process Prone Position Proteins Randomized Clinical Trials Recruitment Activity Regimen Respiratory Failure Running Seminal Severities Stress Structure of parenchyma of lung Supportive care Testing Tidal Volume Time Tissues 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 mechanical properties mortality mouse model novel novel therapeutics patient population personalized approach personalized strategies pressure prevent public health relevance response standard of care translation to humans

项目摘要

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）是一种常见且通常是致命的疾病，除了以机械通气为中心的支持护理外，没有其他有效的治疗方法。但是，机械通气本身很容易对已经受伤的肺组织造成损害，从而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中的护理标准涉及使用小潮汐体积（VT），当前的理想是6 mL/kg的理想体重，以及正面的末端爆炸压力（PEEP），以防止肺塌陷并改善氧合。这些策略导致了进步的改善，但ARDS死亡率仍然很高，因此迫切需要机械通风肺部的更好的方法。不幸的是，由于非常异构的ARDS患者群体的机械通气，继续寻找一种适合的方法，因为患者迅速变得徒劳无功，因为需要大量的患者来获得比当前策略的统计显着改善。因此，在ARDS中寻找改进的机械通气方法必须集中于可以量身定制以适合各个patiens的病理生理特征的策略。此外，这些策略必须适应ARDS的发展性质和严重性。这些考虑因素使我们提出，ARDS患者的个性化机械通气必须发生在持续的反馈回路中，涉及三个相互依存的过程：1）评估给定肺的伤害状态，2）预测该肺部将通过机械通气的指定允许在该肺中引起多少VILI，并在此方面提供了这一允许的步骤，并在此方面提供了2）最小化的效果，并在2）上进行了2），并确定了这一较小的不利性不利的信息。机械通气方案可以响应患者的通风需求，同时最大程度地减少了产生的VILI量，以便患者自己的修复过程有最好的机会。我们已经进行了广泛的先前研究，这些研究表明我们可以通过衡量其机械性能如何随着时间的流逝而导致的持续募集和降级来评估肺的当前损伤状态。我们还开发了计算模型，以原则上的方式预测给定的机械通气方案将产生的VILI量。我们在此提案中的总体目标是利用这些发现来优化受伤肺部机械通气策略的个性化设计。该目标将在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部力学和VILI开发的计算模型中，从而在计算中进行实验。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Dynamic Mechanical Interactions Between Neighboring Airspaces Determine Cyclic Opening and Closure in Injured Lung.

DOI：
10.1097/ccm.0000000000002234
发表时间：
2017-04
期刊：
Critical care medicine
影响因子：
8.8
作者：
Broche L;Perchiazzi G;Porra L;Tannoia A;Pellegrini M;Derosa S;Sindaco A;Batista Borges J;Degrugilliers L;Larsson A;Hedenstierna G;Wexler AS;Bravin A;Verbanck S;Smith BJ;Bates JH;Bayat S
通讯作者：
Bayat S

Entropy Production and the Pressure-Volume Curve of the Lung.