SBIR-STTR Award

Ventilation with perfluorocarbon (PFC) liquids preserves the lungs and maintains gas exchange during end-stage adult and infant respiratory failure. The applicants propose to develop a new type of liquid ventilator with greatly enhanced gas exchange capability. The ventilator uses a recently patented mode of liquid delivery which circumvents the gas exchange limitation imposed by the slower diffusion of gases in PFC liquid, compared to air. A continuous intratracheal circulation of PFC liquid through a double lumen catheter with superimposed delivery of liquid tidal volume removes airway dead space ventilation and facilitates respiratory gas diffusion through airway eddy currents. Preliminary data in piglets indicate an increase in CO2 clearance using this mode of liquid delivery. During phase I, Mallard Medical Company which has extensive experience in ventilator development and production, will develop and deliver a prototype ventilator with high output capability and precise wave form control. The investigators propose to optimize ventilatory parameters to maximize CO2 clearance and compare maximal CO2 clearances and blood gas values between the new mode of ventilation and conventional tidal liquid ventilation in newborn piglets. They will also ventilate piglets for 6 hours at optimal settings and examine the lungs for histologic evidence of tissue injury.

We have developed and patented (U.S. Pat No. 5,706,830) a new type of closed circuit perfluorocarbon (PFC) liquid ventilator with enhanced capabilities for gas exchange and exudates clearance from the lungs. This system has potential application to rescue of patients in acute respiratory failure and treatment of cystic fibrosis. The system employs a continuous isovolumetric perfusion (bias flow) of oxygenated PFC through one lumen of a double lumen endotracheal catheter that is superimposed on tidal liquid ventilation (liv). Phase I studies in newborn piglets indicate that bias flow significantly improved blood gases and increased the clearance of a five percent albumin solution from the lung by over 3-fold. During Phase II we propose to finalize the prototype design and control system software for ventilatory parameters and a feedback control of lung liquid volume based on measurements of end-expiratory stop-flow pressures. High performance pulseless pumps, an oxygenator and vapor recovery system will be included as well as protective algorithms and relief valves to limit airway pressure excursions. Phase II experimental studies in piglets and rabbits will examine novel applications of TLV with bias flow for sustaining arterial blood gases during oleic acid lung injury, increasing the clearance rate of five percent albumin solution and mucus-like gels from the lung, and enhancing the homogeneity of gene expression for a reporter gene introduced during TLV. We will also apply for an Investigational Device Exemption (IDE) from the Food and Drug Administration during Phase II to distribute ventilator prototypes to research institutions. PROPOSED COMMERCIAL APPLICATION: This liquid ventilator will be used in infant and adult intensive care units to treat end-stage respiratory failure as a lower cost alternative to extracorporeal oxygenation. Other applications include continuous intrapulmonary administration of drugs and anesthetics and clearance of material from the lungs.