Novel bundled mechanical and pharmacological CPR platform

新颖的捆绑式机械和药物心肺复苏平台

• 批准号: 8308832
• 负责人: Anja Kohler Metzger
• 金额: $ 25.73万
• 依托单位: RESQSYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8308832
• 关键词: Acute Disease; American; Animal Model; Blood; Blood Circulation; Blood Pressure; Blood flow; Brain; Cardiac; Cardiac Output; Cardiopulmonary Resuscitation; Caring; Cause of Death; Cerebral perfusion pressure; Cerebrovascular Circulation; Chest; Chest wall structure; Clinical; Clinical Trials; Combined Modality Therapy; Complex; Devices; Disease; Disodium Salt Nitroprusside; Effectiveness; Electric Countershock; Emergency Situation; Environmental air flow; Family suidae; Foundations; Funding; Goals; Grant; Heart; Heart Arrest; Heart Atrium; Hospitals; Hour; Hypotension; Intracranial Pressure; Life; Lifting; Manuals; Mechanics; Medical; Methods; Modeling; Morbidity - disease rate; Multi-Institutional Clinical Trial; Nervous System Physiology; Organ; Outcome; Outcome Measure; Patients; Perfusion; Phase; Physiological; Physiology; Process; Pulmonary artery structure; Regulation; Relative (related person); Reperfusion Therapy; Research; Research Proposals; Resistance; Rest; Resuscitation; Small Business Innovation Research Grant; Source; Suction; Survival Rate; Survivors; System; Techniques; Technology; Testing; Time; Transference; Translating; United States; Vacuum; Vasodilator Agents; Venous; Ventricular Fibrillation; Work; base; design; electric impedance; hemodynamics; improved; mortality; novel; novel strategies; phase 1 study; pressure; sudden cardiac death

DESCRIPTION (provided by applicant): On average, >90% of patients who suffer from a cardiac arrest die. Nearly all die unexpectedly from this leading cause of death, in part, because the essential components of standard CPR (S-CPR): manual chest compressions at a rate of 100/min, 1 to 1.5 inches in depth and positive pressure ventilations, are an inherently inefficient process, providing less than 25% of normal blood flow to the heart and brain. Despite intensive research, little or no improvement in outcomes has been observed for over half a century. This application builds upon our new understanding of ways to optimize blood flow to the heart and brain during CPR and promises to provide new hope for patients who suffer from sudden cardiac death. The proposed research is focused on using more recently developed intrathoracic pressure regulation (IPR) technology to test the hypothesis that by using a combination of sodium nitroprusside (SNP), a potent vasodilator, and mechanical, non-invasive CPR adjuncts like Active Compression Decompression (ACD) CPR and IPR (the combination of which we term "e- CPR"), we can significantly and further improve CPR-generated blood flow to the heart and brain when compared with currently available CPR techniques. ACD CPR utilizes a suction cup to actively lift the chest wall during the decompression phase to enhance the refilling of the heart in between compressions. IPR generates a continuous negative intrathoracic pressure between positive pressure ventilations which creates a vacuum within the thorax relative to the rest of the body that enhances venous blood return to the heart, increases cardiac output and systemic arterial blood pressure, lowers right atrial and pulmonary artery pressures, lowers intracranial pressure by immediate transference of the negative intrathoracic pressure to the brain, and increases cerebral perfusion pressure. A potent vasodilator like SNP can be used with ACD CPR and IPR devices in this setting only because of the marked increase in circulation and blood pressure afforded with the mechanical adjuncts. The specific aims of this research proposal are to: 1) further develop and refine the IPR device from a mechanical device requiring an external suction source, to a new device (eIPR) with an internal suction source that does not need to be removed post return of spontaneous circulation (ROSC) which enhances circulation post-ROSC by augmenting venous return, and 2) determine the effectiveness of eCPR using the novel eIPR device on hemodynamics and survival outcomes measures in an established animal model of a) ventricular fibrillation cardiac arrest and b) pulseless electrical activity (PEA). This unique combination of mechanical and pharmacological mechanisms has the potential to provide normal levels of circulation during cardiac arrest which can significantly improve long-term neurologically-intact survival rates. If successful, this theray will result in saving >10,000 more Americans each year from out of hospital cardiac arrest and a similar number of in- hospital survivors based upon the superior blood flow and the ability afforded by eCPR to perform prolonged CPR with normal physiology. PUBLIC HEALTH RELEVANCE: Based upon a combination of multiple newly discovered mechanisms to enhance circulation during CPR, the goal of this SBIR phase 1 application is to optimize an intrathoracic pressure regulation device for use with a novel pharmacological approach to improving brain and heart blood flow during cardiac arrest with the goal of improving neurologically intact survival. This technology is needed because high quality STD CPR provides less than 20% of normal blood flow to the heart and little more to the brain. Even in the most efficient emergency medical systems, less than 20% of all patients with an out-of-hospital cardiac arrest are discharged from the hospital with intact neurological function. Strikingly, the average national survival to hospital discharge after out-of-hospital cardiac arres has remained less than 5% for decades. This complex disease state remains the nation's #1 killer, claiming more than 1000 lives outside the hospital and 1000 lives inside the hospital each day in the United States alone. Improved circulation to the brain and other vital organs during CPR, especially when combined in an overall systems-based approach to pre and post-resuscitation care, has the potential to significantly reduce morbidity and mortality from cardiac arrest.

描述（由申请人提供）：平均而言，>90% 的心脏骤停患者会死亡。几乎所有人都因这一主要原因而意外死亡，部分原因在于标准心肺复苏 (S-CPR) 的基本组成部分：以 100 次/分钟的速度、深度为 1 至 1.5 英寸的手动胸外按压以及正压通气，本质上是低效率的 过程中，向心脏和大脑提供的血流量低于正常血流量的 25%。尽管进行了深入的研究，但半个多世纪以来，观察到的结果很少或根本没有改善。该应用程序建立在我们对心肺复苏期间优化心脏和大脑血流的新理解的基础上，有望为心源性猝死的患者带来新的希望。拟议的研究重点是使用最近开发的胸内压力调节 (IPR) 技术来检验以下假设：通过使用强效血管扩张剂硝普钠 (SNP) 和机械、非侵入性 CPR 辅助剂（如主动加压减压）的组合（ ACD）CPR和IPR（我们将其组合称为“e-CPR”），与目前可用的CPR相比，我们可以显着并进一步改善CPR产生的流向心脏和大脑的血液技术。 ACD CPR 在减压阶段利用吸盘主动抬起胸壁，以增强心脏在两次按压之间的再充盈。 IPR 在正压通气之间产生连续的胸腔内负压，从而在胸腔内相对于身体其他部位形成真空，从而增强静脉血回流心脏，增加心输出量和全身动脉血压，降低右心房和肺动脉压力，通过将胸内负压立即转移到大脑来降低颅内压，并增加脑灌注压。在这种情况下，像 SNP 这样的强效血管扩张剂可以与 ACD CPR 和 IPR 设备一起使用，只是因为机械辅助装置可以显着增加循环和血压。本研究提案的具体目标是：1）进一步开发和完善IPR装置，从需要外部抽吸源的机械装置，到具有内部抽吸源且返回后无需移除的新装置（eIPR）自主循环 (ROSC)，通过增加静脉回流来增强 ROSC 后的循环，以及 2) 使用新型 eIPR 设备确定 eCPR 在已建立的动物模型中的血流动力学和生存结果测量的有效性 a) 心室颤动心脏骤停和 b) 无脉电活动 (PEA)。这种机械和药理机制的独特组合有可能在心脏骤停期间提供正常的循环水平，从而显着提高长期神经完整的存活率。如果成功，这种疗法每年将导致超过 10,000 名美国人免于院外心脏骤停，并根据 eCPR 的优越血流和在正常生理状态下进行长时间心肺复苏的能力，拯救类似数量的住院幸存者。 公共健康相关性：基于多种新发现的增强心肺复苏期间循环的机制的组合，SBIR 第一阶段应用的目标是优化胸内压力调节装置，与一种新颖的药理学方法一起使用，以改善心肺复苏过程中的大脑和心脏血流。心脏骤停，目的是提高神经系统完整的生存率。之所以需要这项技术，是因为高质量的 STD CPR 提供的心脏血流量不到正常血流量的 20%，而流向大脑的血流量也很少。即使在最高效的紧急医疗系统中，只有不到 20% 的院外心脏骤停患者出院时神经功能完好。引人注目的是，数十年来，全国院外心脏骤停后出院的平均生存率一直低于 5%。这种复杂的疾病状态仍然是美国第一大杀手，仅在美国，每天就有 1000 多人在医院外死亡，在医院内死亡 1000 多人。在心肺复苏期间改善大脑和其他重要器官的循环，特别是与基于整体系统的复苏前和复苏后护理方法相结合，有可能显着降低心脏骤停的发病率和死亡率。