Development of a CO2-bicarbonate combined membrane capture system for accessible treatment of acute respiratory failure.

项目总结/摘要 X-COR Therapeutics正在创建第一个体外二氧化碳清除（ECCO 2 R）设备， 类似透析的方法，可用于治疗高碳酸血症性呼吸衰竭（HRF）患者。HRF是一个 慢性阻塞性肺疾病（COPD）导致的严重肺部疾病的毁灭性后果 和其他呼吸系统疾病，包括急性呼吸窘迫综合征（ARDS），一种常见的并发症 COVID-19目前治疗重症疾病的标准是有创机械通气， 死亡率约为30%，并增加了对ARDS的易感性。虽然使用保护性的补救策略， 降低死亡率，保护性通气导致的高碳酸血症类似于COPD等疾病。无论是 在某些情况下，通气功能受损会导致二氧化碳（CO2）水平升高，从而导致酸中毒、昏迷和 死亡对于高碳酸血症患者，提供氧气和去除气体的体外技术 CO2（例如ECMO）提供了可能的替代方案，但具有高度侵入性且成本高昂。它们需要高血流量 流速（>1 L/min）和大口径插管只能在专门设施中部署。 在这里，我们建议研究一种类似于血液透析样血液过滤盒的混合装置， 包含用于碳酸氢盐透析和气态CO2捕获的两种过滤纤维的新型配置。高 有效的CO2去除允许<250 ml/min的低血液速率，从而允许小导管（<13.5 Fr） 替换目前大多数体外治疗中使用的28-30 Fr插管。微创标准 血管通路使这种治疗变得容易，并使其能够与侵入性机械治疗并行使用。 通风.通过并行治疗，所提出的装置可以防止由保护性药物引起的高碳酸血症。 通气，并使更安全地使用有创机械通气与早期拔管。因为它可以使用 在现有的血液透析系统中，该设备可以与现有的工作流程和资本设备一起部署。 第一阶段SBIR项目的目标是优化，然后研究使用 混合膜过滤装置，用于从超低体外血流中去除CO2。目标1是 确定最佳的设备几何形状和操作参数（例如尺寸、纤维包密度和纤维比） 其通过使用可扩展的、可重复的改进的新颖设计来满足期望的CO2捕获要求， 生产方法。将使用实验室离体灌注试验评价每次迭代。目标二是 研究体外CO2捕获对患者自发和辅助呼吸的影响 使用一系列生理计算模型，使用患者特定的边界条件，满足要求。 该项目的成功完成将产生一个具有候选几何形状的可重复使用的设备， 临床前试验的操作参数。该装置将能够：1）去除产生的>30%的CO2; 2） 使用可扩展的制造来生产;以及3）可与现有的血液透析平台互操作。这 是推进未来临床前和临床研究以支持FDA批准的关键一步。

PROJECT SUMMARY/ABSTRACT X-COR Therapeutics is creating the first extracorporeal CO2 removal (ECCO2R) device that uses dialysis-like approaches to accessibly treat hypercapnic respiratory failure (HRF) patients. HRF is a devastating consequence of critical lung disease caused by chronic obstructive pulmonary disease (COPD) and other respiratory disorders including acute respiratory distress syndrome (ARDS), a common complication of COVID-19. The current standard of care for severe disease is invasive mechanical ventilation, which results in a ~30% mortality rate and increased susceptibility to ARDS. While use of protective ventilatory strategies reduces mortality, resultant hypercapnia from protective ventilation resembles diseases like COPD. In both cases, impaired ventilation causes increased carbon dioxide (CO2) levels that lead to acidosis, coma, and death. For patients with hypercapnia, extracorporeal technologies that deliver oxygen and remove gaseous CO2 (e.g. ECMO) present possible alternatives but are highly invasive and costly. They require high blood flow rates (>1 L/min) and large-bore cannula only deployable in specialized facilities. Here, we propose investigating a hybrid device that resembles a hemodialysis-like blood filtration cartridge that contains a novel configuration of two filtration fibers for bicarbonate dialysis and gaseous CO2 capture. High efficiency CO2 removal allows a low blood rate of <250 ml/min, thus allowing small catheters (<13.5 Fr) to replace the 28-30 Fr cannula used today in most extracorporeal therapies. Less invasive and standard vascular access makes this therapy accessible and enables its use in parallel with invasive mechanical ventilation. With parallel therapy, the proposed device can prevent hypercapnia that results from protective ventilation and enable safer use of invasive mechanical ventilation with earlier extubation. Because it can use existing hemodialysis systems, the device can be deployed with existing workflows and capital equipment. The objective of this Phase I SBIR project is to optimize and then investigate ventilatory benefits from using a hybrid membrane filtration device that removes CO2 from ultra-low extracorporeal blood flow. Aim 1 is to determine optimal device geometries and operating parameters (e.g. size, fiber pack density, and fiber ratio) that meet desired CO2 capture requirements through iterative modification of a novel design using scalable production methods. Each iteration will be evaluated using bench-top ex-vivo perfusion testing. Aim 2 is to investigate the impact that extracorporeal CO2 capture has on patient spontaneous and assisted ventilatory requirements using a series of physiologic computational models using patient-specific boundary conditions. Successful completion of this project will result in a manufacture-ready device with candidate geometries and operating parameters for pre-clinical testing. This device will be able to: 1) remove >30% of CO2 produced; 2) be produced using scalable manufacturing; and 3) be interoperable with existing hemodialysis platforms. This is a critical step for advancing toward future pre-clinical and clinical studies in support of FDA approval.