Ultrasound Enhanced Extracorporeal Membrane Oxygenation

项目摘要 约16，000例患者通过体外膜肺氧合接受人工肺支持 2019年的ECMO。在ECMO期间，中空纤维膜（HFM）气体交换器需要约2 m2来实现治疗气体转移;然而，与血液的这种大接触面积激活了 需要全身抗凝抑制的凝血级联反应，通常使用肝素。虽然 肝素降低了凝血的频率，它不能有效地抑制血小板的表面沉积， proteins.这些关键凝血成分的消耗，以及持续给予 全身抗凝剂，导致ECMO期间出血风险增加， 并发症和死亡率。 我们建议减少HFM气体交换器的表面积将导致较少的凝血，并且需要较少的 抗凝剂的使用，降低血栓形成和出血的发生率。为了实现这一目标， 科学正在开发一种新的血液氧合系统，该系统使用超声波来显着增强气体 传输效率，从而减少所需的气体交换器面积。较小的气体交换器将导致 更少的凝血，需要更少的抗凝和相关的出血风险。一个额外的好处是， 更小的表面积将使我们能够开发一个更小的ECMO系统， 动态ECMO。我们对超声增强ECMO（US-ECMO）的初步结果显示，超声（US） 将氧气通过平面纳米多孔聚丙烯膜的传输速率提高4-6.4倍。 我们假设，美国通过两种机制提高运输。第一，美国旅游的吸引力 通过血液产生体积力，该体积力又产生称为体积流的流动。二是美国 在膜表面振荡气体/血液混合物，在膜附近快速混合血液， 这个过程被称为微流。来自这些机制的血液混合破坏了在血液中的边界层。 血液-膜界面，使氧梯度变陡并驱动更快的扩散。 该提案旨在确定美国和膜配置，最大限度地提高气体交换内 临床相关HFM。我们将限制US参数以避免血液损伤。我们将朝着这个方向前进 通过以下具体目标。目的1）确定特定的超声参数（振幅， 频率、占空比、脉冲持续时间和换能器几何形状），分别优化批量流， 微流，同时避免溶血、惯性空化、过度加热和气泡产生。目标2） 确定声流和微流有效的最大纤维束厚度。 目的3）制造和评估一种定制的超声输送系统，通过以下方式安全地增强氧气输送： 至少七倍。成功的结果不仅显示了US-ECMO的潜力， 必要的设计指南，以推动临床可行的US-ECMO系统的开发。

PROJECT SUMMARY Approximately 16,000 patients received artificial pulmonary support via extra-corporeal membrane oxygenation (ECMO) in 2019. During ECMO, hollow fiber membrane (HFM) gas exchangers require a surface area of ~2 m2 to achieve therapeutic gas transfer; however, this large contact area with the blood activates the coagulation cascade that requires systemic anticoagulation for suppression, usually with heparin. Although heparin reduces the frequency of clotting, it does not effectively inhibit the surface deposition of platelets and proteins. The consumption of these critical clotting components, as well as continuous administration of systemic anticoagulant, results in an increased risk of bleeding during ECMO and increases the risk of complications and mortality. We propose that reducing the surface area of the HFM gas exchanger will lead to less clotting and require less anticoagulant use, reducing the incidence of both thrombosis and hemorrhage. To achieve this, Boundless Science is developing a novel blood oxygenation system that uses ultrasound to dramatically enhance gas transfer efficiency, and thereby reduce the required gas exchanger area. A smaller gas exchanger will induce less clotting and require less anticoagulation and associated bleeding risks. An additional benefit is that a smaller surface area will allow us to develop a dramatically smaller ECMO system, offering the potential for ambulatory ECMO. Our initial results with ultrasound-enhanced ECMO (US-ECMO) show that ultrasound (US) enhances the rate of oxygen transport across a planar nano-porous polypropylene membrane by 4–6.4-fold. We hypothesize that US enhances transport through two mechanisms. First, the absorption of US travelling through the blood induces a bulk force, which in turn generates flow known as bulk streaming. Second, US oscillates gas/blood menisci at the membrane surface, rapidly mixing the blood near the membrane in a process known as microstreaming. Blood mixing from these mechanisms disrupts the boundary layer at the blood-membrane interface, steepening the oxygen gradient and driving faster diffusion. This proposal seeks to identify the US and membrane configurations that maximize gas exchange within clinically relevant HFM. We will constrain US parameters to avoid blood damage. We will progress toward this objective through the following specific aims. Aim 1) Determine the specific ultrasound parameters (amplitude, frequency, duty cycle, pulse duration, and transducer geometry) that separately optimize bulk streaming and microstreaming, while avoiding hemolysis, inertial cavitation, excessive heating, and bubble generation. Aim 2) Determine the maximal fiber bundle thickness over which acoustic streaming and microstreaming are effective. Aim 3) Fabricate and evaluate a custom ultrasound delivery system that safely enhances oxygen transport by at least seven-fold. Successful results will not only show the potential of US-ECMO but will provide the necessary design guidelines to drive the development of a clinically viable US-ECMO system.