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.

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）的成功率平均只有10%左右。此外，器官短缺 是器官移植面临的最大挑战，捐献者远远少于需求， 等待移植。这些方法可以提高心脏骤停的存活率， 因此，迫切需要大量的器官捐赠者。一种方法是实施系统， 心脏骤停期间的血流，因为增强的血流增加了存活率。即使经过50分钟的心脏 体外膜氧合（ECMO）可以使患者的存活率比传统的 心肺复苏然而，超过一半接受ECMO治疗的心脏骤停患者没有自发恢复。 ROSC是一种脑循环疾病，一些患有ROSC的患者是脑死亡。患者正在进行ECMO，但没有 ROSC，或脑死亡，代表了大量可行的供体。然而，目前的ECMO系统需要 血管通路的大量特殊培训和灌注师，限制了其广泛使用。更新ECMO 正在开发允许比现有系统更大流量通过更短套管的系统。不 然而，我们知道生存需要多少流量。如果能够达到所需的临界流量， 较短的套管与较新的系统配合使用，然后是更短、更容易放置和更少病态的套管 可以常规使用，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。 我们已经开发了一种MRI兼容的ECMO系统，并在获取实时磁共振成像时使用它。 共振衍生的脑血流、氧代谢和代谢物水平。对这些大脑参数的研究 因为脑功能是心脏骤停后存活的最重要决定因素。的假设 我们正在测试的是：1）代谢参数和脑血流量将保留临界量 2）在复苏过程中需要临界水平的血流; 复苏的神经完整的生存; 3）有关键水平的代谢参数，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， 神经系统完好的生存; 4）增加CPR将减少生存所需的ECMO流量; 5） 停搏内低温将减少存活所需的流量;以及6）活性氧种类 在复苏过程中产生的血流可以被临界水平的血流和体温过低所抑制。其中一个目标是 该项目旨在研究使用ECMO系统的血流动力学和代谢效应，该系统可以在没有 一个灌注师，并且使用可以通过显著增加的池灌注插入的套管。 医生另一个目标是了解生存的决定因素和ECMO流量的最小值 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， 心脏骤停后神经系统完好的存活率，并增加可用于移植的器官数量。