The Hemodynamic and Metabolic Effects of Advanced Circulatory Support for Resuscitation

高级循环支持对复苏的血流动力学和代谢效应

• 批准号: 10097790
• 负责人: HENRY R HALPERIN
• 金额: $ 81.86万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10097790
• 关键词: Biological Markers; Blood Circulation; Blood Vessels; Blood flow; Brain; Brain Death; Brain Injuries; Caliber; Cannulas; Cardiopulmonary Resuscitation; Cerebrovascular Circulation; Cerebrum; Childhood; Data; Donor person; Emergency Situation; Evolution; Extracorporeal Membrane Oxygenation; Goals; Heart Arrest; Inflammatory; Intervention; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Metabolic; Metabolism; Molecular; Morbidity - disease rate; Neurologic; Organ; Organ Donor; Organ Preservation; Organ Transplantation; Oxygen; Patients; Pediatrics; Physicians; Postoperative Period; Reactive Oxygen Species; Resources; Resuscitation; Surgeon; Survival Rate; Survivors; System; Technology; Testing; Time; Training; Transplantation; United States; brain circulation; hemodynamics; improved; inflammatory marker; metabolic rate; metabolomics; natural hypothermia; out-of-hospital cardiac arrest; outcome prediction; patient population; preservation; programs; success; survival prediction; underserved area

There are over 350,000 victims of out-of-hospital cardiac arrest each year in the United States, and the success rates from cardiopulmonary resuscitation (CPR) average only about 10%. In addition, organ shortage is the greatest challenge facing organ transplantation, with far fewer donors than needed, and many patients dying awaiting transplant. Approaches that could enhance survival from cardiac arrest, and also increase the number of organ donors, are, therefore, critically needed. One approach is implementing systems to enhance blood flow during cardiac arrest, since enhanced flow increases survival. Even after 50 minutes of cardiac arrest, Extracorporeal Membrane Oxygenation (ECMO) can double survival rates over those from conventional CPR. More than half of cardiac arrest victims treated with ECMO do not, however, have return of spontaneous circulation (ROSC), and some patients with ROSC are brain dead. Patients with ongoing ECMO, but without ROSC, or with brain death, represent a large pool of viable donors. Current ECMO systems, however, require substantial special training for vascular access, and a perfusionist, limiting their widespread use. Newer ECMO systems are being developed that allow more flow through shorter cannulas than with current systems. It is not known, however, how much flow is needed for survival. If the critical amount of flow needed can be achieved with the shorter cannulas used with the newer systems, then shorter, easier to place, and less morbid cannulas can be used routinely, extending the use of ECMO to wider patient populations, including underserved areas. We have developed an MRI compatible ECMO system and are using it while acquiring real-time magnetic resonance derived cerebral flow, oxygen metabolism, and metabolite levels. Study of these brain parameters is critical since brain function is the most important determinant of survival from cardiac arrest. The hypotheses we are testing are that: 1) Metabolic parameters and cerebral blood flow will be preserved by critical amounts of blood flow generated during resuscitation; 2) There are critical levels of blood flow that are needed during resuscitation for neurologically intact survival; 3) There are critical levels of metabolic parameters, brain injury biomarkers, inflammatory markers, and reactive oxygen species, measured during resuscitation, that predict neurologically intact survival; 4) Adding CPR will reduce the amount of ECMO flow needed for survival; 5) Intra-arrest hypothermia will reduce the amount of flow needed for survival; and 6) Reactive oxygen species generated during resuscitation can be suppressed by critical levels of flow and hypothermia. One goal of this program is to study the hemodynamic and metabolic effects of using an ECMO system that can be used without a perfusionist, and that uses cannulas that can be inserted percutaneously by a markedly increased pool of physicians. Another goal is to understand the determinants of survival and the minimum amount of ECMO flow needed to improve survival. If successful, these systems should be able to deliver sufficient flow to increase neurologically intact survival from cardiac arrest and increase the number of organs available for transplant.

美国每年有超过 350,000 名院外心脏骤停受害者， 心肺复苏 (CPR) 的成功率平均仅为 10% 左右。此外，器官短缺 是器官移植面临的最大挑战，捐献者远少于所需，而且患者众多 等待移植时死亡。可以提高心脏骤停生存率并增加死亡率的方法 因此，迫切需要一定数量的器官捐献者。一种方法是实施系统来增强 心脏骤停期间的血流量，因为血流量增加可以提高生存率。即使心脏骤停 50 分钟后 逮捕时，体外膜肺氧合 (ECMO) 可使存活率比传统方法翻倍 心肺复苏。然而，超过一半接受 ECMO 治疗的心脏骤停患者并未恢复自发性心跳。 循环（ROSC），一些 ROSC 患者脑死亡。正在进行 ECMO 但没有进行 ECMO 治疗的患者 ROSC（或脑死亡）代表了大量可行的捐赠者。然而，当前的 ECMO 系统需要 血管通路和灌注师的大量特殊培训，限制了它们的广泛使用。较新的 ECMO 正在开发的系统比现有系统允许更多的流量通过更短的插管。它不是 然而，我们知道生存需要多少流量。如果可以达到所需的临界流量 新系统使用较短的插管，然后使用更短、更容易放置且病态更少的插管 可以常规使用，将 ECMO 的使用范围扩大到更广泛的患者群体，包括服务不足的地区。 我们开发了一种兼容 MRI 的 ECMO 系统，并在获取实时磁力时使用它 共振产生的脑流量、氧代谢和代谢水平。对这些大脑参数的研究是 至关重要，因为大脑功能是心脏骤停存活的最重要决定因素。假设 我们正在测试的是：1）代谢参数和脑血流量将保持临界量 复苏期间产生的血流量； 2) 手术期间需要达到临界血流量水平 神经系统完整存活的复苏； 3）代谢参数达到临界水平，脑损伤 在复苏过程中测量的生物标志物、炎症标志物和活性氧物种可以预测 神经系统完整存活； 4）增加CPR将减少生存所需的ECMO流量； 5） 逮捕期间体温过低会减少生存所需的流量； 6) 活性氧 复苏过程中产生的热量可以通过临界流量和低温来抑制。这一目标之一 计划的目的是研究使用 ECMO 系统对血流动力学和代谢的影响，该系统可以在不使用 ECMO 的情况下使用 灌注师，使用可以通过显着增加的池经皮插入的插管 医生。另一个目标是了解生存的决定因素和最小 ECMO 流量 需要提高生存率。如果成功，这些系统应该能够提供足够的流量来增加 心脏骤停后神经系统完好无损，并增加可用于移植的器官数量。