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.

摘要 本提案的目的是开发一种高度生物相容性的肺辅助装置（PAD），以支持 慢性肺病患者数月至数年。超过1200万患者患有慢性肺部疾病 在美国.这些患者呼吸功能逐渐下降，并伴有急性加重 这会导致他们的疾病状态短暂但危险的恶化。在美国，这导致超过70万人 每年有180，000人出院，约180，000人死亡。其中不到2,000名患者将接受 肺移植，5年生存率低于50%。对于其余不符合移植资格的患者， 并不是目的地疗法PAD是一种紧凑型、高度生物相容性的静脉-静脉气体交换器， 或持续数月至数年的静脉动脉呼吸支持。PAD与小型心室辅助相结合 设备质量的泵，以允许紧凑的，移动的呼吸支持。我们最初的临床目标是使用PAD， 将慢性肺病患者从重症监护室转移到门诊桥的地板上，以进行移植。后 完成这一初步目标后，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，并接受计划的监测， 2-3按计划更换PAD的时间为3个月。因此，PAD的设计必须具有更大的 生物相容性优于当前氧合器。我们实验室以前的人工肺设计已经证明 尽管未使用抗凝剂，但在两周的测试中，血凝块形成最少，阻力未增加 涂层，通过使用创新的气体交换纤维束，减缓凝块形成并消除剪切 破坏和激活血液。PAD将采用类似的设计，同时通过以下方式进一步改善生物相容性： i）缩小装置表面积，以及ii）利用独特的壳体设计，其消除了停滞或 再循环流最后，PAD被设计为与1-2个模块一起操作。这允许在 设备更换，并允许根据患者的生理需求调整支撑水平。与 适当的涂层技术，一个单一的设备应该正常工作数月。该提案将重点关注 原型和体外测试。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中血流停滞的存在，并将其与Quadrox进行比较。成功标准 是指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CO2流量为100 ml/min，ii）在2 L/min血液流量下的血流阻力< 2.5 mmHg/（L/min） 流向单个模块，iii）在以下情况下，溶血和血小板消耗低于或等于Quadrox 在4 L/min血流条件下用2个PAD模块并行进行测试，以及iv）具有相等或上级染料洗脱 比Quadrox更好总之，这些结果将使PAD在长期的第二阶段测试中取得成功。