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.

项目总结 大约16,000名患者通过体外膜氧合接受了人工肺支持 (ECMO)在2019年。在ECMO过程中，中空纤维膜(HFM)气体交换器要求表面积为~2 M2来实现治疗性气体转移；然而，这种与血液的大接触区域激活了 需要全身抗凝才能抑制的凝血级联反应，通常使用肝素。虽然 肝素降低凝血频率，它不能有效地抑制血小板的表面沉积和 蛋白质。这些关键凝血成分的消耗，以及持续给药 全身抗凝剂，会增加ECMO期间出血的风险，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较少的凝血和所需的较少 使用抗凝剂，减少血栓形成和出血的发生率。为了实现这一点，无界 科学家正在开发一种新的血液氧合系统，该系统使用超声波来显著增强气体 传递效率高，从而减少了所需的气体交换器面积。较小的气体交换器将导致 凝血更少，需要更少的抗凝和相关的出血风险。另一个好处是， 更小的表面积将使我们能够开发一个小得多的ECMO系统，提供 动态心肺复苏术。我们超声增强ECMO(US-ECMO)的初步结果显示，超声(US) 将氧在平面纳米多孔聚丙烯膜上的传输速度提高4-6.4倍。 我们假设美国通过两种机制加强运输。首先，美国人对旅游的吸纳 通过血液会产生一种体积力，进而产生称为体积流的流动。第二，美国 在膜表面摆动气体/血液半月板，迅速将膜附近的血液混合成 这一过程称为微流。这些机制产生的血液混合破坏了边界层 血-膜界面，使氧梯度变陡，推动更快的扩散。 这项建议旨在确定美国和膜的配置，以最大限度地增加气体交换 临床上相关的HFM。我们将限制美国的参数，以避免血液损伤。我们将朝着这一目标前进 目的通过以下具体目标。目的1)确定特定的超声参数(幅度， 频率、占空比、脉冲持续时间和换能器几何结构)，分别优化批量流和 微流，同时避免溶血、惯性空化、过热和气泡的产生。目标2) 确定声流和微流在其上有效的最大纤维束厚度。 目的3)制造和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传输 至少是七倍。成功的结果不仅将显示US-ECMO的潜力，而且将为 必要的设计指南以推动临床可行的US-ECMO系统的开发。