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.

项目概要 大约 16,000 名患者通过体外膜氧合接受了人工肺支持 （ECMO）2019年。在ECMO期间，中空纤维膜（HFM）气体交换器需要〜2的表面积 m2 来实现治疗气体转移；然而，与血液的大接触面积会激活 需要全身抗凝来抑制的凝血级联反应，通常使用肝素。 肝素会降低凝血频率，不能有效抑制血小板表面沉积， 这些关键凝血成分的消耗以及持续施用。 全身抗凝，导致 ECMO 期间出血风险增加，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将导致更少的凝结并且需要更少的 抗凝剂的使用，减少血栓和出血的发生率 为了实现这一目标，Boundless。 科学正在开发一种新型血氧系统，利用超声波显着增强气体 传输效率，从而减少所需的气体交换器面积，从而导致较小的气体交换器。 凝血较少，需要较少的抗凝治疗和相关的出血风险。 更小的表面积将使我们能够开发出更小的 ECMO 系统，从而为 我们对超声增强型 ECMO (US-ECMO) 的初步结果表明，超声 (US) 使氧气穿过平面纳米多孔聚丙烯膜的传输速率提高 4-6.4 倍。 我们看到美国通过两个机制来加强交通：一是吸纳美国游客。 通过血液会产生体积力，进而产生称为体积流的流动。 在膜表面振荡气体/血液半月板，快速混合膜附近的血液 这些机制的血液混合过程被称为微流，破坏了边界层。 血膜界面，使氧梯度陡峭并驱动更快的扩散。 该提案旨在确定可最大化内部气体交换的美国和膜配置 临床相关的 HFM 我们将限制 US 参数以避免血液损伤。 目标 1) 确定具体的超声参数（振幅、 频率、占空比、脉冲持续时间和传感器几何形状），分别优化批量流和 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。 目标 3) 制造并评估定制的超声输送系统，该系统通过以下方式安全地增强氧气输送： 至少七倍的成功结果不仅会显示 US-ECMO 的潜力，而且会提供 必要的设计指南来推动临床上可行的 US-ECMO 系统的开发。