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.
