PumpKIN PreClinical

Ension小儿心肺辅助系统（pCAS）是作为下一代体外膜肺氧合（ECMO）-也称为体外生命支持（ECLS）-系统设计和开发的，可提供更高的功能和血液相容性。pCAS的预期用途是使用单个一次性血液接触泵-氧合器为2 kg至25 kg的患者提供长达两周的部分或完全心肺支持。该系统经过专门设计，可通过在不到5分钟的时间内快速更换泵-氧合器来提供超过两周的长期支持。该系统提供了优于当前可用系统的关键优势，特别是改善的血液相容性、更小的表面积和预充体积、快速部署以及便于亲子结合和患者运输的紧凑配置。 pCAS系统由泵-氧合器、控制台和辅助组件（包括静脉和动脉插管以及除泡器）组成。pCAS泵-氧合器是一种紧凑型器械，由通过旋转扩散器直接与血液氧合器集成的离心叶轮组成。氧合器由中空纤维膜（Celgard聚丙烯微孔编织阵列）组成，并结合了专门设计用于增强血液相容性的肝素基工程表面。pCAS控制台的功能包括泵速调节、所有操作参数显示、故障状态监测、报警显示和供应至血液密封的清洗液控制。控制台包含一个内部备用电池，能够在交流电源丢失或患者运输过程中提供超过两小时的连续运行。 原型pCAS泵氧合器和控制台已在pCAS项目的开发阶段进行了广泛的制造和测试（主要由NIH儿科循环中心支持 支助合同HHSN 268200448189 C，2004年4月开始，目前正在执行。根据功能、生物相容性、临床和成本要求以及试验数据、正式危害分析、人为因素评价、计算流体动力学（CFD）分析和可靠性考虑，对集成泵-氧合器和控制台的候选设计以及后续改进进行了指导。作为产品开发和原型生产过程的一部分，已经建立、完善和验证了制造过程。Ension准备在符合ISO 13485以及21 CFR 820.30中规定的设计控制法规的质量体系下组装和测试所有必要的pCAS系统组件。这包括持续使用深入的风险和可靠性分析、管理和缓解。 Ension的pCAS系统在开发过程中已进行了广泛的体外和体内测试。体外数据已证明pCAS泵-氧合器能够实现所需的血液流速和压力，并交换氧气和二氧化碳。额外的体外数据证实了最小的血液损伤，如低水平的红细胞、白色细胞和血小板消耗所证明的，与目前可用的中空纤维膜氧合器相比，血浆泄漏显著改善，以及血液相容性改善。Ension已在仔猪中进行了体内系统试验，证明pCAS系统可为目标人群中的小型患者提供适当的血流动力学支持，并在小牛中进行了长期器械功能性和血液相容性试验。

The Ension pediatric cardiopulmonary assist system (pCAS) has been designed and developed as a next-generation extracorporeal membrane oxygenation (ECMO) - also called extracorporeal life support (ECLS) - system that provides increased functionality and blood compatibility. The intended use of the pCAS is to provide partial or complete cardiopulmonary support to patients from 2 kg to 25 kg for periods of up to two weeks using a single disposable blood-contacting pump-oxygenator. The system has been specifically designed to accommodate extended support beyond this two-week period by rapid change-out of the pump-oxygenator in a procedure that can be completed in less than five minutes. The system offers key advantages over currently available systems, specifically improved blood compatibility, smaller surface area and priming volume, rapid deployment, and a compact configuration that facilitates parent-child bonding and patient transport. The pCAS system consists of a pump-oxygenator, a control console, and ancillary components that include venous and arterial cannulae and a bubble trap. The pCAS pump-oxygenator is a compact device consisting of a centrifugal impeller directly integrated with a blood oxygenator via a turning diffuser. The oxygenator is comprised of hollow fiber membranes (Celgard polypropylene microporous knitted array) incorporating a heparin-based engineered surface specifically designed to enhance blood compatibility. The pCAS control console functionality includes regulation of pump speed, display of all operational parameters, monitoring for fault conditions, display of alarms, and control of purge fluid supplied to the blood seal. The control console incorporates an internal backup battery capable of providing over two hours of continuous operation should AC power be lost or during patient transport. Prototype pCAS pump-oxygenators and control consoles have been fabricated and tested extensively during the development phase of the pCAS project (primarily supported by NIH Pediatric Circulatory Support contract HHSN268200448189C beginning in April 2004 and ongoing). Candidate designs for the integrated pump-oxygenator and control console, as well as subsequent refinements, were guided by functionality, biocompatibility, clinical, and cost requirements as well as test data, formal hazards analysis, human factors evaluations, computational fluid dynamics (CFD) analyses, and reliability considerations. Manufacturing processes have been established, refined, and validated as part of the product development and prototype production processes. Ension is prepared to assemble and test all necessary pCAS system components under a Quality System compliant with ISO 13485 as well as the design control regulations articulated in 21 CFR 820.30. This includes the continued use of in-depth risk and reliability analysis, management, and mitigation. Ension's pCAS system has been extensively tested in vitro and in vivo during development. In vitro data have demonstrated the pCAS pump-oxygenator's ability to achieve required blood flow rates and pressures and to exchange oxygen and carbon dioxide. Additional in vitro data have confirmed minimal blood damage as evidenced by low levels of red cell, white cell, and platelet consumption, significant improvement in plasma leakage over currently available hollow fiber membrane oxygenators, and improvement in blood compatibility. Ension has conducted in vivo system testing in piglets demonstrating that the pCAS system provides appropriate hemodynamic support for the small patients in the target population and in calves demonstrating longer-term device functionality and blood compatibility.