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: 10371978
• 负责人: HENRY R HALPERIN
• 金额: $ 81.06万
• 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/10371978
• 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.

在美国，每年有超过350,000名院外心脏骤停的受害者， 心肺复苏（CPR）的成功率平均仅约10％。另外，器官短缺 是器官移植面临的最大挑战，捐助者少得多，许多患者 垂死等待移植。可以提高心脏骤停生存的方法，也可以增加 因此，非常需要器官捐献者的数量。一种方法是实施系统以增强 心脏骤停过程中的血流，因为增强的流量会增加生存率。即使经过50分钟的心脏 逮捕，体外膜氧合（ECMO）可以比常规的生存率两倍 CPR。但是，超过一半的心脏逮捕受害者接受了ECMO治疗的人没有自发的回归 循环（ROSC）和一些ROSC患者大脑死亡。正在进行的ECMO的患者，但没有 ROSC或脑死亡，代表了大量可行的捐助者。但是，当前的ECMO系统需要 对血管通道的大量特殊培训和灌注者限制了它们的广泛使用。较新的ECMO 与当前系统相比，正在开发系统，该系统使经过较短的插管的流动更多。它不是 然而，已知生存需要多少流动。如果可以实现所需的关键流量 随着较短的插管与较新的系统一起使用，然后较短，更易于放置，并且病态较少 可以定期使用，将ECMO的使用扩展到更广泛的患者人群，包括服务不足的地区。 我们已经开发了MRI兼容的ECMO系统，并在获取实时磁性的同时使用了它 共振衍生的大脑流，氧代谢和代谢产物水平。这些大脑参数的研究是 关键，因为大脑功能是心脏骤停生存的最重要决定因素。假设 我们正在测试：1）代谢参数和脑血流将通过关键量保留 复苏期间产生的血流； 2）在 神经学完整生存的复苏； 3）代谢参数的关键水平，脑损伤 在复苏期间测量的生物标志物，炎症标志物和活性氧 神经系统完整的生存； 4）增加心肺复苏术将减少生存所需的ECMO流量； 5） 征收的体温过低会减少存活所需的流量； 6）活性氧 复苏期间产生的临界水平和体温过低可以抑制。一个目标 程序是研究使用可以使用的ECMO系统的血液动力学和代谢作用 一种灌注者，它使用可以通过明显增加的库插入的插管 医师。另一个目标是了解生存的决定因素和ECMO流量的最低量 需要提高生存。如果成功，这些系统应该能够提供足够的流程以增加 心脏骤停的神经学完整生存，并增加可用于移植的器官的数量。