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

项目摘要/摘要 X-COR治疗公司正在创造第一个体外二氧化碳清除(ECCO2R)设备，该设备使用 类似透析的方法可方便地治疗高碳酸血症呼吸衰竭(HRF)患者。人力资源管理局是一种 慢性阻塞性肺疾病(COPD)引起的危重肺病的破坏性后果 以及其他呼吸系统疾病，包括常见的并发症--急性呼吸窘迫综合征(ARDS 新冠肺炎。目前对严重疾病的护理标准是有创机械通气，这导致 死亡率约为30%，增加了ARDS的易感性。在使用保护性呼吸策略的同时 降低死亡率，保护性通风导致的高碳酸血症类似于COPD等疾病。在这两个地方 在某些情况下，通风障碍会导致二氧化碳(CO2)水平增加，从而导致酸中毒、昏迷和 死亡。对于高碳酸血症患者，提供氧气和清除气体的体外技术 二氧化碳(如ECMO)提供了可能的替代方案，但具有高度的侵入性和成本。它们需要高血流量 费率(&gt；1 L/分钟)和大口径插管只能在专门的设施中部署。 在这里，我们建议研究一种类似于血液透析的血液滤芯的混合设备，它 包含两种用于碳酸氢盐透析和气态二氧化碳捕集的新型过滤纤维。高 高效的二氧化碳清除使血液流速降低到250毫升/分钟，从而允许小导管(13.5毫升) 更换目前大多数体外治疗中使用的28-30Fr套管。侵入性和标准性较低 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。通过平行治疗，建议的设备可以预防因保护性疾病而导致的高碳酸血症。 并能更安全地使用早期拔管的有创机械通气法。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。 此第一阶段SBIR项目的目标是优化并随后调查使用 混合式膜过滤装置，可从超低体外血流中去除二氧化碳。目标1是 确定最佳设备几何结构和操作参数(例如，大小、光纤包密度和光纤比率) 通过迭代修改使用可扩展的新型设计来满足所需的二氧化碳捕获要求 制作方法。每一次迭代都将使用台式体外灌流测试进行评估。目标2是 探讨体外二氧化碳捕获对患者自主呼吸机和辅助呼吸机的影响 要求使用一系列使用患者特定边界条件的生理学计算模型。 该项目的成功完成将导致制造准备就绪的设备，具有候选几何形状和 用于临床前测试的操作参数。该装置将能够：1)将产生的二氧化碳去除30%；2) 可使用可扩展制造来生产；以及3)可与现有的血液透析平台互操作。这 是推进支持FDA批准的未来临床前和临床研究的关键一步。

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.