Novel Stimulation to Improve Respiratory Function in ARDS and Severe COVID-19 Patients

项目概要/摘要 急性呼吸窘迫综合征（ARDS）是一种常见的致命性呼吸衰竭。与最近的 冠状病毒大流行，大多数2019年严重冠状病毒病（COVID-19）患者 急性呼吸窘迫综合征和需要机械通气和重症监护病房入院，给医疗系统带来严重的压力。使用 在COVID-19等病例的ARDS期间，机械通气（MV）是支持性的，直到感染发生 解决可能需要长达20天。虽然MV对于通风和维持生命是有用的，但它会导致严重的 延迟拔管的呼吸肌萎缩。此外，MV延长会导致大量发病率 和死亡率（即肺损伤、肺炎、喉损伤等）因此，调节呼吸系统的策略 在插管过程中防止肌肉萎缩可能会减少MV时间，从而降低发病率， 与MV相关的死亡率，并减少呼吸机需求和宝贵资源的消耗。 在慢性高颈段脊髓损伤期间，已经开发出调节或激活膈肌的策略。 脊髓损伤与植入物刺激膈神经或隔膜;然而，这种侵入性的策略， 与急性呼吸窘迫综合征的急性和暂时性质不相容。进入神经网络的主要障碍 控制呼吸的神经机制存在于大脑深处， 脑干，手术很危险最近，我们阐明了一种新的呼吸途径， 通过刺激脊髓来调节。我们收集了大量数据，证明这一点。 策略可以恢复或增强呼吸。该项目的主要目标是提供安全性和可行性 在ARDS患者中使用这种方法的数据。第二个目标是提供概念的证明， 策略可以改善呼吸机依赖患者的呼吸功能，并定义刺激参数 最有效地防止MV期间呼吸肌萎缩。本项目的可交付成果包括 确定经皮脊髓刺激用于ARDS呼吸康复的安全性和可行性， 初步疗效数据，完善原型设计，并为后续阶段的器械提供支持 发展

PROJECT SUMMARY/ABSTRACT Acute respiratory distress syndrome (ARDS) is an often-fatal form of respiratory failure. Relevant to the recent coronavirus pandemic, the majority of patients with severe Coronavirus Disease of 2019 (COVID-19) develop ARDS and need mechanical ventilation and ICU admission, placing severe strains on the medical system. Use of mechanical ventilation (MV) during ARDS for cases such as COVID-19 is supportive until the infection has resolved which may take up to 20 days. While MV is useful for ventilation and supporting life, it causes severe atrophy of respiratory muscles that delays extubation. Furthermore, prolonged MV causes substantial morbidity and mortality (i.e. lung injury, pneumonia, laryngeal injury, etc.) Therefore, strategies to condition the respiratory muscles to prevent atrophy during intubation will likely decrease MV time, thereby decrease morbidity and mortality associated with MV, and decrease ventilator need and consumption of valuable resources. Strategies have been developed to condition or activate the diaphragm muscle during chronic high cervical spinal cord injury with implants that stimulate the phrenic nerve or diaphragm; however, such an invasive strategy is incompatible with the acute and temporary nature of ARDS. The main hurdle to accessing the neural network for breathing for therapeutic purposes is that the neural mechanisms controlling respiration reside deep in the brainstem, which is dangerous to access surgically. Recently, we elucidated a novel breathing pathway that can be modulated by stimulation of the spinal cord. We have compiled significant data demonstrating that this strategy can restore or augment breathing. The main objective of this project is to provide safety and feasibility data for this approach in patients with ARDS. The second objective is to provide proof of the concept that this strategy can improve respiratory function in ventilator-dependent patients and define the stimulation parameters that most effectively prevent respiratory muscle atrophy during MV. The deliverables for this project include establishing the safety and feasibility of transcutaneous spinal stimulation for respiratory rehabilitation in ARDS, preliminary efficacy data, refining the prototype design, and creating support for subsequent phases of device development.