PULM2: Combining Extracorporeal Lung and Kidney Support: Evaluation of Fibre Configurations on Gas Exchange Preservation for the Development of a Novel Highly Integrated Device (RenOx)

Abstract

Background: Combined lung and kidney dysfunction are frequent in extracorporeal membrane oxygenation (ECMO) patients affecting up to 70% of them. Current treatment relies on the use of two separate circuits combining ECMO and renal replacement therapy, increasing infection risks and the use of artificial surfaces. Therefore, we aim to develop a novel artificial lung that integrates lung and kidney support in a single device combining oxygenation and hemodialysis fibers. Thus, we analyzed how many oxygenation fibers could be substituted by hemodialysis fibers while still maintaining 90% of the oxygenator’s gas exchange capacity and the effect fiber configuration has on oxygen (O2) and carbon dioxide (CO2) transfer. Methods: Fiber bundles were composed of oxygenation fiber mats (Oxyplus™ 90/200, 3M) stacked perpendicularly at a 90° angle and/or crossed at a 24° angle on top of each other. We manufactured bundles with all oxygenation fibers open and bundles with oxygenation fibers closed in a way that they could not contribute to gas exchange, simulating hemodialysis fibers. Bundles in perpendicular configuration had 100% of fibers open (Oxy100P), 50% of fibers closed (Oxy50P), or 25% of fibers closed (Oxy75P), Figure 1. Bundles in crossed configuration had all fibers open (Oxy100C) or 33% of fibers closed (Oxy67C). Bundles were tested for gas exchange performance following in-vitro blood tests according to ISO 7199:2016. Results: Our results show that bundles with 25% of oxygenation fibers closed in perpendicular configuration were able to still maintain 90% of the O2 exchange and 80% of the CO2 exchange capacity of our oxygenator. Bundles with 25% oxygenation fibers closed had no statistically significant difference in O2 or CO2 transfer compared to a fully open oxygenator with the same fiber configuration, Figure 2. Additionally, Oxy75P bundles were able to keep O2 delivery above 55 mL/LBlood flow and CO2 removal above 52 mL/LBlood flow up to 140 mL/min. Fiber configuration did not affect gas exchange for fully open bundles, however, configuration significantly influenced O2 and CO2 exchange for bundles with closed fiber layers. Closing fibers in perpendicular configuration resulted in a lower decrease in gas transfer. Below 140 mL/min, this was demonstrated by a similar decrease in O2 transfer of 20% when 50% of perpendicular fibers or 33% of crossed fibers were closed Conclusions: We analyzed the effect of replacing oxygenation fibers with hemodialysis fibers on gas exchange efficiency. Our results demonstrate that 25% of oxygenation fibers in a perpendicular configuration could be replaced by hemodialysis fibers while still maintaining 90% of the O2 exchange of our oxygenator. Moreover, this type of bundle kept O2 delivery above 55 mL/LBlood flow up to 140 mL/min. This shows that gas exchange can be preserved to a desirable extent when oxygenation fiber layers are replaced. This is a step towards combining lung and kidney support in a single device.Figure 1. Illustration of a device combining extracorporeal lung and kidney support. Oxygen flows through the lumen of oxygenation fibers and dialysate flows inside hemodialysis fibers. In this work, fiber bundles were manufactured with a perpendicular and/or crossed configuration having a varying number of oxygenation fiber layers closed, simulating hemodialysis fibers (open fibers in white and closed fibers in blue). Perpendicular bundles had 50% of fibers closed (Oxy50P), 25% of fibers closed (Oxy75P), or 100% of fibers open (Oxy100P), while crossed bundles had 33% of fibers closed (Oxy67C), or all fibers open (Oxy100C).Figure 2. Oxygen exchange performance mL/LBlood flow ± standard deviation from the mean (n = 10) for bundles with different fiber configurations. We found no statistically significant difference in mean oxygen exchange between Oxy75P and the fully open oxygenator Oxy100P (ANOVA p > 0.38).