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

项目摘要/摘要 急性呼吸窘迫综合征(ARDS)是一种经常致命的呼吸衰竭形式。与最近的 冠状病毒大流行，2019年重症冠状病毒病(新冠肺炎)患者多数发病 ARDS和需要机械通风和ICU入院，给医疗系统带来了严重的压力。使用 对于新冠肺炎等ARDS患者，在ARDS期间进行机械通气(MV)是支持性的，直到感染 解决可能需要长达20天的时间。虽然MV对通风和维持生命有用，但它会导致严重的 呼吸肌萎缩延迟拔管。此外，长时间的机械通气会导致严重的发病率。 和死亡率(即肺损伤、肺炎、喉部损伤等)因此，调整呼吸道状况的策略 在插管过程中防止肌肉萎缩可能会减少机械通气时间，从而减少并发症和 减少与MV相关的死亡率，减少呼吸机需求和宝贵资源的消耗。 已经开发出在慢性高位颈椎期间调节或激活横隔肌的策略 脊髓损伤的植入物刺激膈神经或隔膜；然而，这种侵入性策略是 与急性呼吸窘迫综合征的急性和暂时性不相容。访问神经网络的主要障碍是 用于治疗目的的呼吸是控制呼吸的神经机制驻留在 脑干，通过手术接触是危险的。最近，我们阐明了一种新的呼吸途径，它可以 通过刺激脊髓来调节。我们收集了大量数据，证明了这一点 策略可以恢复或增加呼吸。该项目的主要目标是提供安全性和可行性。 ARDS患者采用这种方法的数据。第二个目标是提供这一概念的证据 策略可改善呼吸机依赖患者的呼吸功能并确定刺激参数 这是最有效地防止MV期间呼吸肌萎缩的药物。该项目的可交付成果包括 建立经皮脊髓刺激治疗ARDS呼吸康复的安全性和可行性， 初步疗效数据，改进原型设计，并为设备的后续阶段提供支持 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.