Development of a Hyperbaric Intravascular Membrane Oxygenator Catheter

Acute Respiratory Distress Syndrome (ARDS), a form of acute lung injury resulting in hypoxic respiratory failure is a frequent and often lethal indication for admission to both adult and pediatric intensive care units (ICUs). Currently, patients in need of oxygen support must rely on conventional methods that use a patient’s lungs to deliver oxygen, such as mechanical ventilation. In severe cases where patients’ lungs are damaged to a point that they are unable to be supported with mechanical ventilation, currently the only option is extracorporeal membrane oxygenation (ECMO). This method of oxygenation bypasses the lungs and directly oxygenates the blood. However, this is a costly, highly sophisticated treatment typically only available in select large hospitals who have the required resources. The onset of the COVID-19 pandemic made clear that the need for alternative, lung-independent, oxygen delivery methods for patients is a dire need in the medical field. Smaller devices that can be easily deployed, used in more hospitals, and are cheaper to manufacture and administer, would find immediate use in the medical field to help patients who would otherwise not have access to ECMO. The hyperbaric intravascular oxygenator catheter is a concept that Dr. Tobias Straube (Duke University) conceived in response to this need. The idea behind this device is to deliver critical levels of oxygen to patients in need with easy to deploy catheter-based devices. The primary objective of this dissertation was to develop the concept of this hyperbaric intravascular oxygenation catheter as a future treatment option in patients with ARDS. The work consisted of the development of a proof-of-concept device using hollow fiber dense membranes and hyperbaric oxygen to diffuse oxygen at transfer rates greater than previous works. A conceptually accurate mathematical model was developed to investigate system limitations in the early prototype, and guide future investigations. Blood mixing methodologies were developed and tested at the bench scale to determine the feasibility of angular oscillation-based mixing on both transport efficiencies and impacts on bubble formation, and the previous model was used to evaluate the system. Finally, an investigation on the mechanisms behind the angular oscillation was conducted using computational fluid dynamics. Initial work demonstrated the technical feasibility of providing oxygen to a bulk medium, such as blood, via diffusion across non-porous hollow fiber membranes (HFM) using hyperbaric oxygen. The oxygen transfer across Teflon AF 2400 membranes was characterized at oxygen pressures up to 2 bars in both a stirred tank vessel (CSTR) and a tubular device mimicking intravenous application. Fluxes over 550 mL min-1 m-2 were observed in well-mixed systems, and just over 350 mL mL min-1 m-2 in flow through tubular systems. Oxygen flux was proportional to the oxygen partial pressure inside the HFM over the tested range and increased with mixing of the bulk liquid. Some bubbles were observed at the higher pressures (1.9 bar) and when bulk liquid dissolved oxygen concentrations were high. High frequency ultrasound was applied to detect and count individual bubbles, but no increase from background levels was detected during lower pressure operation. A conceptual model of the oxygen transport was developed and validated. Model parametric sensitivity studies demonstrated that diffusion through the thin fiber walls was a significant resistance to mass transfer. Promoting convection around the fibers should enable physiologically relevant oxygen supply. This work indicated that a device is within reach that is capable of delivering greater than 10% of a patient’s basal oxygen needs in a configuration that readily fits intravascularly. Proof-of-concept work highlighted the need for an active mixing method that would both improve flux while also limiting conditions favoring bubble formation in such a hyperbaric device. We demonstrated that the introduction of angular oscillation as a form of active mixing allowed for fluxes of up to 400 mL min-1 m-2 at lower pressures than our previous work. This increase of almost 150 mL min-1 m-2 was achieved despite the use of water maintained at body temperature (37 C°) and at the viscosity of blood (3.5 cP), both of which reduce oxygen transfer rates when compared to the 20 C water used in the previous work. Adaptation of the previously developed mathematical model indicated continued improvements maybe achieved with more active mixing. Future work in blood will investigate the effects of angular oscillation on oxygen transport and bubble formation in an in vitro system, and to determine if this method of active mixing has any deleterious effects on red blood cells. A computational fluid dynamics analysis using COMSOL was undertaken on the micro and macro-oscillations used in the active mixing schemes. This analysis revealed reasons why micro-oscillations were reducing the incidence of bubbles on fiber walls in bench testing when the fibers were undergoing rapid small motions, while also producing less overall flux as compared to the large oscillations. This result lends itself to future work to optimize the conditions of micro-oscillations such that bubble formation is reduced in bench top prototypes. Additionally, there is potential to optimize the range of motions used in micro-oscillations to reduce the impact of overall oxygen flux as compared to large consistent motion in real world testing. Overall, this work demonstrated the feasibility of using hyperbaric pressures in an oxygen delivery catheter and that a mixing methodology using angular oscillation could be employed that would increase flux rates while also limiting bubble formation. Mathematical models were developed that gave insight to a hypothetical catheter’s mass transport limitations, and can be used to investigate hypothetical changes to the device. Finally, a CFD model was developed to better understand the angular oscillation mixing that was able to reduce bubble formation in this system.