Pulmonary Assist Device for Destination Therapy

用于目的地治疗的肺辅助装置

• 批准号: 9347492
• 负责人: Keith E Cook
• 金额: $ 22.43万
• 依托单位: ADVANCED RESPIRATORY TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9347492
• 关键词: Acute; Anticoagulants; Area; Biological Assay; Blood; Blood Platelets; Blood Volume; Blood flow; Carbon Dioxide; Cattle; Cells; Cessation of life; Chronic Obstructive Airway Disease; Chronic lung disease; Clinical; Coagulation Process; Consumption; Coupled; Cystic Fibrosis; Dangerousness; Destinations; Device Designs; Devices; Disease; Drops; Dyes; Extracorporeal Membrane Oxygenation; Fiber; Floor; Gases; Glycerol; Goals; Hemoglobin concentration result; Hemolysis; Home environment; Hospitals; Hour; Housing; Interstitial Lung Diseases; Lead; Lung; Lung Transplantation; Measures; Methylene blue; Monitor; Oxygenators; Oxyhemoglobin; Patients; Phase; Physiological; Physiology; Plasma; Platelet Count measurement; Polypropylenes; Positioning Attribute; Preclinical Testing; Pulmonary Hypertension; Pump; Resistance; Respiratory physiology; Sampling; Schedule; Sheep; Surface; System; Technology; Testing; Time; Transplantation; Venous; artificial lung; base; biomaterial compatibility; design; improved; in vitro testing; indexing; innovation; protein activation; prototype; respiratory; shear stress; success; ventricular assist device

Abstract The purpose of this proposal is to develop a highly biocompatible pulmonary assist device (PAD) to support patients with chronic lung disease for months to years. Over 12 million patients suffer from chronic lung disease in the US. These patients suffer from a gradual decline in respiratory function coupled with acute exacerbations that lead to a transient, but dangerous, worsening of their disease state. In the US, this results in over 700,000 hospital discharges per year, and approximately 180,000 deaths. Less than 2,000 of these patients will undergo lung transplantation, where 5-year survival is under 50%. For the remaining transplant ineligible patients, there is no means of destination therapy. The PAD is a compact, highly biocompatible gas exchanger for venovenous or venoarterial respiratory support lasting months to years. The PAD is coupled with a small ventricular assist device quality pump to allow for compact, mobile respiratory support. Our initial clinical goal is to use the PAD to move chronic lung disease patients from the ICU to the floor in an ambulatory bridge to transplant setting. After accomplishing this preliminary goal, the PAD system would transition toward destination therapy lasting years. During this time, the patient would be discharged home with planned monitoring and return to the hospital every 2-3 months for scheduled PAD replacement. Accordingly, the PAD must be designed with far greater biocompatibility than current oxygenators. Previous artificial lung designs from our lab have demonstrated minimal clot formation and no increase in resistance over two weeks of testing, despite using no anticoagulant coatings, by using an innovative gas exchange fiber bundle that slows clot formation and eliminates shear damage and activation of blood. The PAD will utilize a similar design while further improving biocompatibility by i) shrinking the device surface area and ii) utilizing a unique housing design that eliminates stagnant or recirculating flows. Lastly, the PAD is designed to operate with 1-2 modules. This allows for partial support during device replacement and allows for adjustment of support level based on the patient’s physiologic needs. With appropriate coating technology, a single device should function normally for months. This proposal will focus on prototyping and in vitro testing. The Phase I Specific Aims are to 1) determine PAD gas exchange and blood flow resistance, 2) quantify the blood damage of the PAD and compare to the Quadrox oxygenator, and 3) quantify the presence of blood flow stagnation in the PAD and compare it to the Quadrox. The success criteria are that a the PAD must: i) convert 2 L/min of venous blood to > 95% oxyhemoglobin saturation and transfer > 100 ml/min of CO2 with a single module, ii) have a blood flow resistance < 2.5 mmHg/(L/min) at 2 L/min of blood flow to a single module, iii) have lower or equal hemolysis and platelet consumption than the Quadrox when testing at 4 L/min of blood flow with 2 PAD modules in parallel, and iv) possess equal or superior dye washout than the Quadrox. Together, these results will position the PAD for success during long-term, Phase II testing.

抽象的 该提案的目的是开发一种高度生物相容性的肺辅助装置（PAD）来支持 慢性肺病患者数月至数年 超过 1200 万患者患有慢性肺病。 在美国，这些患者的呼吸功能逐渐下降，并伴有急性加重。 这导致他们的疾病状况短暂但危险地恶化，在美国，这导致了超过 700,000 人的死亡。 每年约有 18 万名患者出院，其中不到 2,000 人死亡。 肺移植，5年生存率低于50% 对于其余不符合移植条件的患者，有。 PAD 是一种紧凑型、高度生物相容性的静脉气体交换器。 或持续数月至数年的静脉动脉呼吸支持，并配有小型心室辅助。 我们最初的临床目标是使用 PAD 来提供紧凑、移动的呼吸支持。 将慢性肺病患者从 ICU 转移到移动桥的地板上进行移植。 为了实现这一初步目标，PAD 系统将过渡到持续数年的目标治疗。 在此期间，患者将出院回家并进行有计划的监测，并每隔一段时间返回医院一次。 定期 PAD 更换需要 2-3 个月，因此，PAD 的设计必须具有更大的性能。 我们实验室之前的人工肺设计已证明具有比现有氧合器更好的生物相容性。 尽管未使用抗凝剂，但在两周的测试中，血栓形成最少，阻力也没有增加 涂层，通过使用创新的气体交换纤维束来减缓凝块形成并消除剪切力 PAD 将采用类似的设计，同时通过以下方式进一步提高生物相容性。 i) 缩小设备表面积 ii) 采用独特的外壳设计，消除停滞或 最后，PAD 设计为可与 1-2 个模块一起运行，从而在运行期间提供部分支持。 设备更换并允许根据患者的生理需求调整支撑水平。 适当的涂层技术，单个设备应该可以正常运行数月。本提案将重点关注。 原型设计和体外测试 第一阶段的具体目标是 1) 确定 PAD 气体交换和血液。 流动阻力，2) 量化 PAD 的血液损伤并与 Quadrox 氧合器进行比较，以及 3) 量化 PAD 中血流停滞的情况并将其与 Quadrox 的成功标准进行比较。 PAD 必须： i) 将 2 L/min 的静脉血转化为 > 95% 氧合血红蛋白饱和度并转移 > 单个模块的 100 ml/min CO2，ii) 在 2 L/min 血液时血流阻力 < 2.5 mmHg/(L/min) 流至单个模块，iii) 比 Quadrox 具有更低或相同的溶血和血小板消耗 使用 2 个 PAD 模块并行进行 4 L/min 血流测试，并且 iv) 具有相同或更好的染料冲洗能力 综合起来，这些结果将使 PAD 在长期 II 期测试中取得成功。