Entrainment-based mechanical ventilation to improve patient-ventilator synchrony

 描述(申请人提供)：在ICU辅助呼吸机过程中的一个基本问题是如何平稳有效地使呼吸机节律与患者的呼吸努力同步。不同步可导致呼吸功增加/浪费、患者不适、需要更多镇静、更高的气管切开率、更长的机械通气时间和更少的无呼吸机天数、更长的ICU和住院时间以及更低的存活和出院概率。现代呼吸机要么通过使用重度镇静/肌肉麻痹来完全控制呼吸节奏(基于呼吸机的呼吸机)，要么让患者通过呼吸触发呼吸机(基于患者的呼吸机)。这两个极端都不是最优的。我们提出了一种基于耦合振荡器之间相互夹带的经典物理理论的新一代辅助呼吸机(基于夹带的机械通气，EMV)，它可能为这一临床问题提供一种经济有效的解决方案。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吸入呼吸器，并通过学习和记忆Hering-Breuer充气反射来适应呼吸器。在EMV中，患者的自发呼吸节律和呼吸机节律在同一节奏上彼此相锁，就像两个人一起跳舞。在之前的NIH ARRA挑战奖(RC1)下，我们在一种广泛使用的机械呼吸机(Puritan-Bennett840型)上实现了EMV的原型，并在计算机化的肺模拟器上演示了这种新技术的可行性。基于这些模拟结果，FDA最近有条件地批准了对EMV模式的初步临床研究的研究设备豁免。为了将基础技术从工作台转移到床边，成立了一个多学科研究小组，成员包括一名基础研究人员/生物工程师(潘博士，Pi)、一名临床医生(Harris博士，Co-I)、一名生物统计学家(Schoenfeld博士，统计顾问)和一名技术开发人员(Covidien/Puritan-Bennett)，以解决潜在的科学、工程、统计和临床问题。这个试点项目的目标是首先确定拟议的EMV模式在短时间(4小时)内引导患者的呼吸节律是安全和有效的(目标1)。这项I期临床研究将允许我们微调EMV模式的参数，以便进一步将风险降至最低，并最大限度地提高EMV模式在长期改善患者-呼吸机同步性方面的有效性。第二阶段(目标2)是确定EMV模式是安全和可行的，当在患者的整个机械通气撤机期间使用时，在ARDS患者中提供改善的同步性。拟议的I期/II期研究既是必要的，也是充分的，以确保FDA批准在未来进行一项全面的III期多中心试验，以测试改善的患者-呼吸机与EMV模式的同步性是否可能在呼吸机撤机期间带来实质性的临床结果。

 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.