Phase II, Head Up Cardiopulmonary Resuscitation Device

摘要 心脏骤停（SCA）是美国的主要死因，只有3-20%的患者神经系统完好 每年超过350，000名院外SCA患者的生存率。即使在病人最初复苏后，许多人 一周内死于严重的脑损伤这项应用的目的是提高神经系统完整的生存率 院前和院内SCA后的比率。I期临床前研究显示：1）头部抬高 在使用阻抗阈值装置（ITD）的主动加压减压（ACD）CPR期间， 在平躺位置时，脑血流量比ACD+ITD CPR增加一倍，2）受控和顺序头部， 与对照组相比，ACD+ITD CPR胸部抬高导致神经系统完整生存率增加6倍。 传统的心肺复苏术这种新的CPR方法被称为抬头位（Head Up Position，HUP）CPR。它的工作 通过利用重力来增强从大脑到心脏的静脉血流量，降低颅内压， 增强心输出量第一台人体HUP CPR设备EleGARDTM是由 第一阶段资金支持。EleGARD随后获得FDA 510 k许可，并已用于帮助 迄今为止治疗了超过400名SCA患者。基于这些积极成果，第二阶段的目标是：1）设计， 开发和构建改进的EleGARD-2，以加快器械应用的时间并提高采用率 通过a）减小尺寸和重量以及改进的用户界面，B）增加局部脑血氧测定， （rSO 2）和，c）纳入自动正压呼吸输送，以提高年龄段的机组人员安全性 Covid-19; 2）证明ACD+ITD HUP CPR与ACD+ITD相比具有上级神经系统完整生存率 在猪模型中进行CPR平板，包括采用皮质外膜氧合（ECMO）进行补救，以评估 随着ECMO在SCA中的快速发展，HUP CPR的潜在受益;以及3）证明HUP CPR 利用先进的成像技术，利用EleGARD-2减少SCA猪模型中的脑损伤。下一 第二代HUP CPR设备将更容易储存、携带和部署，将提供rSO 2以更好地指导护理， 并提供自动呼吸输送，以提高机组人员的安全性，减少救援人员的数量， 做心肺复苏动物研究将有助于确定HUP CPR延长生理生存能力的潜力 在难治性室颤复苏期间， 可用，并帮助确定是否HUP CPR减少脑损伤，如通过MRI和测量 生化标志物总体而言，第二阶段的资金将支持下一代HUP的开发 CPR平台，并加速采用这项创新技术，以提高神经系统完好的生存率 SCA之后的价格。

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.