The Hemodynamic and Metabolic Effects of Advanced Circulatory Support for Resuscitation

在美国，每年有超过35万名院外心脏骤停的受害者，而 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，捐赠者远远少于所需，许多患者 在等待移植时垂死。可以提高心脏骤停存活率的方法，也可以增加 因此，迫切需要大量的器官捐赠者。一种方法是实施系统以增强 心脏骤停时的血液流动，因为血流增强可提高存活率。即使在心脏跳动50分钟后 停搏体外膜氧合(ECMO)可使存活率提高一倍 心肺复苏术。然而，接受ECMO治疗的心脏骤停患者中，超过一半的人没有自发恢复。 循环(ROSC)，一些ROSC患者脑死亡。患者正在进行体外反搏，但没有 ROSC，或脑死亡，代表了一大批有活力的捐赠者。然而，当前的ECMO系统需要 对血管通路进行了大量的特殊培训，以及一名灌注者，限制了它们的广泛使用。较新的ECMO 正在开发的系统允许更多的流量通过较短的套管，而不是目前的系统。它不是 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 较新的系统使用较短的插管，然后较短、更容易放置，且较少病态插管 可以常规使用，将ECMO的使用扩大到更广泛的患者群体，包括服务不足的地区。 我们已经开发了一个与MRI兼容的ECMO系统，并在采集实时磁场的同时使用该系统 磁共振引起的脑血流、氧代谢和代谢物水平。对这些大脑参数的研究是 关键是因为大脑功能是心脏骤停存活的最重要决定因素。假说 我们正在测试的是：1)代谢参数和脑血流量将被保存在临界量 在复苏过程中产生的血流量；2)在复苏过程中需要有临界水平的血流量 3)有代谢参数、脑损伤的临界水平 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，这些指标可以预测 神经学上完整的生存；4)加入CPR将减少生存所需的ECMO血流量；5) 停搏内低温将减少生存所需的血流量；以及6)活性氧 在复苏过程中产生的能量可被临界流量和低温抑制。其中一个目标就是 项目是研究使用ECMO系统的血液动力学和代谢影响，该系统可以在不使用的情况下使用 一位灌注者，使用的导管可以通过显著增加的 医生。另一个目标是了解存活率的决定因素和ECMO的最小流量 需要提高存活率。如果成功，这些系统应该能够提供足够的流量来增加 在神经学上完好无损地从心脏骤停中存活下来，并增加可供移植的器官数量。

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.