Development of a Pediatric Ventricular Assist Device

Ension正在提议开发一种集成的儿科心肺辅助系统(PCAS)，该系统可以为心脏病医生和外科医生治疗患有心肺衰竭的婴儿和儿童提供极大的灵活性。RFP提供了适合通过拟议系统进行治疗的广泛的患者情况。我们相信，随着全面发展，这一系统将满足这些条件中的大部分。这项提议最初的主要重点是为新生儿提供肺支持(据报道，约50%的最小患者需要)和循环支持。 该系统的独特技术是对流混合泵-氧合器的概念，Ension在过去三年里一直在开发这一概念。儿科大小的原型设备通常显示每平方米膜表面积的氧气转移率超过800毫升/分钟。对于最小的患者，这允许我们使用一个大约0.05m2的气体交换表面积的设备来传输40ml02/min。此外，即使在这些尺寸缩小的情况下，我们的泵-氧合器也被证明是一种非常有效的血泵。因此，我们的系统设计能够同时实现血液泵送和气体输送。在FACL中，泵浦效率的H/Q曲线很难与仅为血液泵送而优化的同类设备区分开来。在小羔羊中，使用搏动流量高达120次/分和流量高达1.0I/min的脉动流也被证明是有效的。 Ension与路易斯维尔大学合作，正在寻求开发一种系统，该系统以一个智能控制器和两个优化的泵送/质量传输模块为中心，使用弹药作为核心技术。该控制器将接受这些模块中的任何一个，并对每个模块做出独特的响应，自动设置该模块的功能，从而提供婴儿和临床医生的临床环境所需的灵活性。医生可选择的方法包括搏动或持续血流、纯心脏支持或心脏支持和气体转移(可在心脏支持开始几天后开始)，以及外周血管或胸腔内(心脏或大血管)插管。 最初的设备开发将集中在明确定义最小类别患者的需求，并开发一个满足这些需求的“模块”。将建立泵送/气体传输元件的计算模型，然后将其用作指导进一步改进装置的设计工具。同时，我们将开发一种越来越复杂的控制器，最终为临床医生提供最智能的操作灵活性。完全闭环控制器的最终开发需要来自第一次临床试验的投入。在计划的第四年和第五年，我们将开始开发一个模块来支持更大的孩子。 通过使用有机硅涂层纤维，在血液表面使用聚合物涂层，以及加入外部套管涂层以将感染降至最低，从而提高生物相容性。根据公认的血泵和氧合器开发实践，将通过一系列全面的体外和体内实验来衡量功能，以证明安全性、有效性和可靠性。作为最后的开发任务，我们建议执行一系列符合GMP和GLP要求的测试，以满足FDA的要求。开发工作将按照Ension的全面质量体系进行。Ension已经成功地完成了与BSI(我们的通知机构)的审核，并预计在2003年12月之前通过ISO认证。 其他任务包括最终确定和实施我们的质量控制系统，可靠性测试，包括故障模式和影响分析，以及在报告和科学论文中传播新的发展。这一研究和开发计划的最终产品将是一种安全有效的新生儿心肺支持系统，准备用于临床试验。

Ension is proposing to develop an Integrated Pediatric Cardiopulmonary Assist System (pCAS) that can provide great flexibility to cardiologists and surgeons treating infants and small children with cardiac and pulmonary failure. The RFP provides a wide range of patient conditions that are suitable for treatment by the proposed system. We believe that with full development, this system will meet most of these conditions. The initial major focus of this proposal is to provide pulmonary support (reportedly required by ~ 50% of the smallest patients) and circulatory support to neonates. The unique technology of the proposed system is the convective mixing pump-oxygenator concept, which Ension has been developing for the past three years. Prototype pediatric-sized devices have routinely demonstrated oxygen transfer rates in excess of 800 ml/min per m2 of membrane surface area. For the smallest patients this allows us to transfer 40 ml 02/min using a device with approximately 0.05m2 of gas exchange surface area. In addition, even in these reduced sizes, our pump-oxygenator has been shown to be a very effective blood pump. Hence, our system design is capable of achieving blood pumping and gas transfer simultaneously. In facl, H/Q curves of pumping efficiency are difficult to distinguish from comparable devices optimized only for blood pumping. Ventricular unloading in small lambs using pulsatile flow at beat rates up to 120 bpm and flow rates up to 1.0 I/min has also been demonstrated. Ension, in partnership with the University of Louisville, is seeking to develop a system that centers on a "smart" controller and two optimized pumping/mass transfer modules that use AMMO as the core technology. This controller will accept any of these modules and respond uniquely to each, automatically setting itself for that module's features, thus providing the flexibility that infant's and clinician's clinical circumstances require. Among the options available to the physician wil be pulsatile or continuous blood flow, pure cardiac support or cardiac support and gas transfer (which can be initiated days after cardiac support has commenced), and peripheral vascular or intrathoracic (cardiac or great vessels) cannulation. Initial device development will center on clearly defining the requirements of the smallest class of patients and developing a "module" to satisfy these needs. A computational model of the pumping/gas transfer element will be constructed and then used as a design tool to guide further device refinement. In parallel, we will be developing an increasingly sophisticated controller to ultimately provide the most intelligent operational flexibility to the clinician. Final development of completely closed loop controller requires input from the first clinical trials. In program years 4 & 5 we will begin developing a module to support larger children. Increased biocompatibility is addressed through the use of silicone-coated fibers, use of polymer coatings on blood surfaces and incorporation of external cannula coatings to minimize infection. Functionality will be measured by a comprehensive series of in vitro and in vivo experiments to demonstrate safety, efficacy, and reliability in accordance with accepted practices for blood pump and oxygenator development. As the final development task we propose to perform a series of GMP and GLP compliant tests designed to meet the requirements of the FDA. Development work will be conducted in accordance with Ension's comprehensive quality system. Ension has successfully completed an audit with BSI, our notified body, and expects ISO certification by December 2003. Additional tasks include finalization and implementation of our quality control system, reliability testing including a failure modes and effects analysis, and dissemination of new developments in reports and scientific papers. The end product of this research and development program will be a safe and effective neonatal cardiopulmonary support system ready for clinical trials.