Ultrasound Enhanced Extracorporeal Membrane Oxygenation

超声增强体外膜氧合

• 批准号: 10323520
• 负责人: Andrew Jones
• 金额: $ 29.99万
• 依托单位: BOUNDLESS SCIENCE, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10323520
• 关键词: Acoustics; Adult; Advanced Development; Animals; Anticoagulants; Anticoagulation; Area; Automobile Driving; Biocompatible Materials; Blood; Blood Platelets; Blood coagulation; Blood gas; Capital; Childhood; Clinical; Coagulation Process; Consumption; Custom; Deep Vein Thrombosis; Deposition; Development; Devices; Diffusion; Disease; Entrepreneurship; Extracorporeal Membrane Oxygenation; Fiber; Frequencies; Funding; Gases; Generations; Geometry; Guidelines; Heating; Hemolysis; Hemorrhage; Heparin; Incidence; Injury; International; Intracranial Hemorrhages; Lung; Medical; Membrane; Meniscus structure of joint; Nanoporous; Oxygen; Oxygenators; PF4 Gene; Patient-Focused Outcomes; Patients; Phase; Physiologic pulse; Polypropylenes; Positioning Attribute; Process; Proteins; Pulmonary Embolism; Quality of life; Recording of previous events; Registries; Reporting; Risk; Safety; Science; Sonication; Stream; Surface; System; Therapeutic; Thick; Thrombosis; Transducers; Travel; Ultrasonography; Venous Thrombosis; Work; absorption; blood damage; clinically relevant; design; heart function; improved; mortality; neonate; novel; oxygen transport; pulmonary function; safety outcomes; success; ventricular assist device

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.

项目摘要 大约16,000名患者通过体外膜氧合获得了人工肺部支持 （ECMO）在2019年。在ECMO期间，空心纤维膜（HFM）气体交换器需要〜2的表面积 M2实现热气体转移；但是，与血液的大型接触区域激活 凝血级联反应需要全身性抗凝治疗抑制，通常用肝素抑制。虽然 肝素降低了衣服的频率，它不会有效地抑制血小板的表面沉积 蛋白质。这些关键的凝血组件的消费以及连续给药 全身性抗凝剂，导致ECMO期间出血的风险增加，并增加 并发症和死亡率。 我们建议减少HFM气体交换器的表面积会导致衣服更少，并且需要更少 抗凝剂的使用，减少了血栓形成和出血的事件。为了实现这一目标，无限 科学正在开发一种新型的血液氧合系统，该系统使用超声波大大增强气体 转移效率，从而降低所需的气体交换器区域。较小的汽油交换器将诱发 较少的衣服，需要更少的抗凝治疗和相关的出血风险。另一个好处是 较小的表面积将使我们能够开发一个动态较小的ECMO系统，从而提供了潜力 门诊经济。我们使用超声增强的ECMO（US-ECMO）的最初结果表明，超声（US） 以4-6.4倍的速度提高氧气转运速率。 我们假设美国通过两种机制增强了运输。首先，我们旅行的吸收 通过血液诱导巨大力，进而产生称为散装流的流动。第二，我们 在膜表面振荡气体/血液半月板，迅速将血液迅速混合 被称为微流的过程。这些机制的血液混合破坏了边界层 血膜界面，使氧梯度陡峭并驱动更快的扩散。 该建议旨在确定美国和膜配置，以最大程度地提高气体交换 临床相关的HFM。我们将限制我们的参数以避免血液损害。我们将进步 通过以下特定目的进行客观。目标1）确定特定的超声参数（振幅， 频率，占空比，脉搏持续时间和换能器几何形状）分别优化散装流和 微流避免溶血，惯性空化，过量加热和产生气泡。目标2） 确定声流和微流有效的最大纤维束厚度。 目标3）制造和评估自定义的超声输送系统，该系统可以安全地通过 至少七倍。成功的结果不仅会显示美国ECMO的潜力，而且还将提供 推动临床可行的US-ECMO系统开发的必要设计指南。