Entrainment-based mechanical ventilation to improve patient-ventilator synchrony

基于夹带的机械通气可改善患者与呼吸机的同步性

• 批准号: 9144423
• 负责人: CHI-SANG POON
• 金额: $ 24.88万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9144423
• 关键词: Accident and Emergency department; Acute; Acute respiratory failure; Address; Adult Respiratory Distress Syndrome; Age; Award; Basic Life Support; Bennett model; Biomedical Engineering; Brain; Breathing; Chronic; Clinical; Clinical Research; Clinical Trials; Collaborations; Complex; Computer software; Coupled; Cross-Over Studies; Dancing; Dependency; Devices; Economic Inflation; Effectiveness; Eligibility Determination; Engineering; Environmental air flow; FDA approved; Future; Generations; Goals; Grant; Health Care Costs; Home environment; Hospitalization; Hour; Incidence; Individual; Intensive Care Units; Interdisciplinary Study; Intuition; Investigation; Lead; Learning; Legal patent; Length of Stay; Letters; Life; Long-Term Care; Lung; Mechanical Ventilators; Mechanical ventilation; Mediating; Medical; Memory; Modeling; Multicenter Trials; Muscle; National Heart, Lung, and Blood Institute; Nosocomial Infections; Operating Rooms; Outcome; Paralysed; Patients; Persons; Phase; Phase III Clinical Trials; Physics; Pilot Projects; Probability; Procedures; Reflex action; Rehabilitation therapy; Research; Research Design; Research Personnel; Respiratory Failure; Risk; Safety; Secure; Sedation procedure; Slave; Techniques; Technology; Testing; Tracheostomy procedure; Translating; United States National Institutes of Health; Ventilator; Ventilator Weaning; Weaning; Work of Breathing; base; computerized; cost; cost effective; design; improved; innovation; mortality; next generation; novel; patient population; prospective; prototype; public health relevance; research clinical testing; respiratory; risk minimization; safety and feasibility; simulation; theories

 DESCRIPTION (provided by applicant): A fundamental question during assisted ventilation in the ICU is how to synchronize the ventilator rhythm with the patient's breathing effort smoothly and effectively. Dyssynchrony could lead to increased/wasted work of breathing, patient discomfort, increased need for sedation, higher rate of tracheostomy, longer durations of mechanical ventilation and reduced number of ventilator-free days, longer ICU and hospital stay, and lower probabilities of survival and home discharge. Current generation ventilators either dictate the breathing rhythm completely with the use of heavy sedation/muscle paralysis (ventilator-based ventilation) or let the patient trigger the ventilator breath by breath (patient-based ventilation). Neither extreme is optimal. We propose a next generation of ventilatory assist (entrainment-based mechanical ventilation, EMV) that is based on the classical physics theory of mutual entrainment between coupled oscillators, which may provide a cost-effective solution to this clinical problem. This innovative technique is motivated by our recent discovery that the brain circuits controlling breathing are capable of entraining to a ventilator and adaptin to it through learning and memory of the Hering-Breuer inflation reflex. In EMV, the patient's spontaneous respiratory rhythm and the ventilator rhythm are phase-locked to one another on the same tempo, just like two individuals dancing together. Under a previous NIH ARRA Challenge Grant (RC1) award we have implemented a prototype of EMV on a widely used mechanical ventilator (Puritan-Bennett Model 840) and demonstrated the feasibility of this novel technique on a computerized lung simulator. Based on these simulation results, a conditional approval for investigational device exemption has been recently granted by the FDA for initial clinical research of the EMV mode. To transition the base technology from the bench top to the bedside, a multidisciplinary research team comprised of a basic researcher/bioengineer (Dr. Poon, PI), a clinician (Dr. Harris, Co-I), a biostatistician (Dr. Schoenfeld, statistical consultan) and a technology developer (Covidien/Puritan-Bennett) has been formed to address the underlying scientific, engineering, statistical and clinical problems. The goal of this pilot projet is to first establish that the proposed EMV mode is both safe and effective in entraining the patient's breathing rhythm over a short (4-hour) period (Aim 1). This phase I clinical research wil allow us to fine-tune the parameters of the EMV mode in order to further minimize risks and maximize the effectiveness of the EMV mode in improving patient-ventilator synchrony over a long period. The second phase (Aim 2) is to establish that the EMV mode is safe and feasible in providing improved synchrony in ARDS patients when used over a patient's entire ventilation weaning period. The proposed phase I/phase II research are both necessary and sufficient for securing FDA approval of a full-scale phase III multicenter trial to be conducted in the future in order to test whether improved patient-ventilator synchrony with the EMV mode may lead to materially beneficial clinical outcomes during ventilator weaning.

 描述（由申请人提供）：ICU辅助通气期间的一个基本问题是如何使呼吸机节律与患者的呼吸努力平稳有效地同步。不同步可能导致呼吸功增加/浪费、患者不适、镇静需求增加、气管造口术率升高、机械通气持续时间延长和无呼吸机天数减少、ICU和住院时间延长以及生存和出院概率降低。当前一代呼吸机要么通过使用重度镇静/肌肉麻痹（基于呼吸机的通气）完全控制呼吸节律，要么让患者逐个呼吸触发呼吸机（基于患者的通气）。两个极端都不是最优的。我们提出了下一代的辅助呼吸（基于呼吸的机械通气，EMV），这是基于耦合振荡器之间的相互夹带的经典物理理论，这可能会提供一个具有成本效益的解决方案，这个临床问题。这项创新技术的动机是我们最近发现，控制呼吸的大脑回路能够通过学习和记忆Hering-Breuer充气反射来吸引呼吸机并适应呼吸机。在EMV中，患者的自主呼吸节律和呼吸机节律以相同的克里思彼此锁相，就像两个人一起跳舞一样。根据先前的NIH ARRA挑战资助（RC 1）奖，我们在广泛使用的机械呼吸机（Puritan-Bennett Model 840）上实现了EMV原型，并在计算机化肺模拟器上证明了这种新技术的可行性。基于这些模拟结果，FDA最近批准了EMV模式初步临床研究的试验用器械豁免条件。为了将基础技术从实验室转移到床边，成立了一个多学科研究团队，由基础研究员/生物工程师（Poon博士，PI）、临床医生（Harris博士，Co-I）、生物统计学家（Schoenfeld博士，统计咨询师）和技术开发人员（Covidien/Puritan-Bennett）组成，以解决基础科学、工程、统计和临床问题。该试点项目的目标是首先确定所提出的EMV模式在短时间（4小时）内对患者的呼吸节律既安全又有效（目标1）。该I期临床研究将使我们能够微调EMV模式的参数，以进一步降低风险并最大限度地提高EMV模式在长期改善患者-呼吸机同步方面的有效性。第二阶段（目标2）是确定EMV模式在患者的整个通气撤机期间使用时，在为ARDS患者提供改善的同步性方面是安全可行的。拟议的I期/II期研究对于确保FDA批准未来进行的全规模III期多中心试验是必要的和充分的，以便测试在呼吸机脱机期间改善患者-呼吸机与EMV模式的同步是否可能导致实质性有益的临床结局。