Phase II, Head Up Cardiopulmonary Resuscitation Device

摘要 在美国，心脏骤停(SCA)是主要的死亡原因，神经学上只有3%-20%的人完好无损 每年350,000名出院SCA患者的存活率。即使在患者最初被复苏后，许多人 在一周内死于严重的脑损伤。这项应用的目标是提高神经功能完好的存活率。 院前和院内SCA后的比率。I期临床前研究显示：1)头部抬高 使用阻抗阈值装置(ITD)的主动压缩减压(ACD)CPR期间的胸部 与ACD+ITD CPR相比，平卧位的脑血流量增加了一倍，2)控制和顺序的头部和 ACD+ITD CPR胸腔抬高术导致神经功能完整存活率增加6倍 常规心肺复苏为平卧位。这种新的心肺复苏方法被称为抬头位心肺复苏(HUP)。它起作用了 通过利用重力来增加从大脑到心脏的静脉血流量，降低颅内压，以及 提高心输出量。第一个人类HUP CPR设备EleGARDTM是设计、制造和测试的 第一阶段资金支持。EleGARD随后获得了FDA 510k的批准，并已被用于帮助 到目前为止治疗了400名SCA患者。基于这些积极的结果，第二阶段的目标是1)设计， 开发和构建改进的EleGARD-2，以加快设备应用的时间并提高采用率 通过a)缩小尺寸和重量并改进用户界面，b)增加局部脑氧仪 (RSO2)和(C)采用自动正压呼气，以提高#岁船员的安全 新冠肺炎；2)证明ACD+ITD HUP CPR组神经功能完整的存活率高于ACD+ITD组 在包括体外膜氧合(ECMO)抢救的猪模型中进行CPR平坦评估 随着ECMO用于SCA的快速发展，HUP CPR的潜在好处；以及3)演示HUP CPR 利用EleGARD-2减少使用先进成像技术的猪SCA模型的脑损伤。下一个 新一代HUP CPR设备将更易于存储、携带和部署，将提供rSO2以更好地指导护理， 并提供自动呼气输送，以提高船员安全并减少所需的救援人员数量 进行心肺复苏。动物研究将有助于确定HUP CPR延长生理活性的可能性 在难治性室颤的复苏期间，直到以ECMO的形式提供更好的血流动力学支持 可用，并帮助确定HUP CPR是否减少了脑损伤，通过MRI和测量 生化标记物。总体而言，第二阶段资金将支持下一代HUP的发展 CPR平台，并加速采用这项创新技术，以提高神经功能完整的存活率 SCA后的费率。

Abstract Sudden cardiac arrest (SCA) is a leading cause of death in the USA, with only 3-20% neurologically intact survival for >350,000 out-of-hospital SCA patients each year. Even after patients are initially resuscitated, many die within a week from severe brain injury. The goal of this application is to improve neurologically-intact survival rates after pre-hospital and in-hospital SCA. The Phase I pre-clinical studies showed 1) elevation of the head and thorax during active compression decompression (ACD) CPR with an impedance threshold device (ITD) doubled brain blood flow versus ACD+ITD CPR in the flat position and, 2) controlled and sequential head and thorax elevation with ACD+ITD CPR resulted in a 6-fold increase in neurologically-intact survival versus conventional CPR in the flat position. This novel method of CPR is called Head Up Position (HUP) CPR. It works by harnessing gravity to enhance venous blood flow from the brain to the heart, lower intracranial pressure, and enhance cardiac output. The first human HUP CPR device, the EleGARDTM, was designed, built, and tested with Phase I funding support. The EleGARD subsequently received FDA 510k clearance and has been used to help treat >400 SCA patients to date. Based upon these positive outcomes, the Phase II objectives are to 1) Design, develop, and build an improved EleGARD-2 to accelerate time to device application and increase adoption rates through a) a reduction in size and weight and an improved user interface, b) addition of regional cerebral oximetry (rSO2) and, c) incorporation of automated positive pressure breath delivery to increase crew safety in the age of Covid-19; 2) Demonstrate neurologically-intact survival is superior with ACD+ITD HUP CPR versus ACD+ITD CPR flat in a pig model that includes salvage with extra-corporeal membrane oxygenation (ECMO) to evaluate the potential benefit of HUP CPR with the rapidly evolving use of ECMO for SCA; and 3) Demonstrate HUP CPR utilizing EleGARD-2 reduces brain injury in a pig model of SCA utilizing advanced imaging techniques. The next generation HUP CPR device will be easier to store, carry, and deploy, will provide rSO2 to better guide care, and provide automated breath delivery to increase crew safety and reduce the number of rescuers needed to perform CPR. The animal studies will help determine the potential for HUP CPR to extend physiologic viability during resuscitation in refractory ventricular fibrillation until better hemodynamic support in the form of ECMO is available, and help determine if HUP CPR reduces brain injury, as determined by MRI and measurement of biochemical markers. Collectively, Phase II funding will support the development of the next generation HUP CPR platform and accelerate adoption of this innovative technology to improve neurologically-intact survival rates after SCA.