Acidic sweep gas with carbonic anhydrase coated hollow fiber membranes synergistically accelerates CO2 removal from blood

Abstract

The use of extracorporeal carbon dioxide removal (ECCO2R) is well established as a therapy for patients suffering from acute respiratory failure. Development of next generation low blood flow (< 500 mL/min) ECCO2R devices necessitates more efficient gas exchange devices. Since over 90% of blood CO2 is transported as bicarbonate (HCO3−), we previously reported development of a carbonic anhydrase (CA) immobilized bioactive hollow fiber membrane (HFM) which significantly accelerates CO2 removal from blood in model gas exchange devices by converting bicarbonate to CO2 directly at the HFM surface. This present study tested the hypothesis that dilute sulfur dioxide (SO2) in oxygen sweep gas could further increase CO2 removal by creating an acidic microenvironment within the diffusional boundary layer adjacent to the HFM surface, facilitating dehydration of bicarbonate to CO2. CA was covalently immobilized onto poly (methyl pentene) (PMP) HFMs through glutaraldehyde activated chitosan spacers, potted in model gas exchange devices (0.0151m2) and tested for CO2 removal rate with oxygen (O2) sweep gas and a 2.2% SO2 in oxygen sweep gas mixture. Using pure O2 sweep gas, CA-PMP increased CO2 removal by 31% (258 mL/min/m2) compared to PMP (197 mL/min/m2) (P < 0.05). Using 2.2% SO2 acidic sweep gas increased PMP CO2 removal by 17% (230 mL/min/m2) compared to pure oxygen sweep gas control (P < 0.05); device outlet blood pH was 7.38 units. When employing both CA-PMP and 2.2% SO2 sweep gas, CO2 removal increased by 109% (411 mL/min/m2) (P < 0.05); device outlet blood pH was 7.35 units. Dilute acidic sweep gas increases CO2 removal, and when used in combination with bioactive CA-HFMs has a synergistic effect to more than double CO2 removal while maintaining physiologic pH. Through these technologies the next generation of intravascular and paracorporeal respiratory assist devices can remove more CO2 with smaller blood contacting surface areas.

A mathematical model of CO2, O2 and N2 exchange during venovenous extracorporeal membrane oxygenation

“…Gas exchange across the membranes used for extracorporeal CO 2 removal is often limited by incomplete diffusion [ 21 ], and this may be exacerbated by the high gas sweep to blood flow ratios that are used to facilitate CO 2 removal. A range of techniques have been tried to enhance CO 2 removal including using carbonic anhydrase [ 23 ], acidification of blood or dialysate [ 24 ] and electrodialysis [ 25 ]. Further modelling of the factors affecting gas exchange during extracorporeal CO 2 removal may prove enlightening.…”

Development of zwitterionic sulfobetaine block copolymer conjugation strategies for reduced platelet deposition in respiratory assist devices

“…The mini-modules were scaled from full sized oxygenator devices manufactured by Medtronic, Terumo and Capiox and simulate the surface area to volume ratio for gas exchange. 31,34 The estimated blood wall shear rate experienced in these modules was estimated to be comparable to commercially available devices. Mini-modules with open ports were sterilized using a standard ethylene oxide (EtO) sterilization cycle.…”

“…Fiber mats were potted directly into polycarbonate mini‐modules using 5 min epoxy (Devcon, Danvers, MA). The mini‐modules were scaled from full sized oxygenator devices manufactured by Medtronic, Terumo and Capiox and simulate the surface area to volume ratio for gas exchange . The estimated blood wall shear rate experienced in these modules was estimated to be comparable to commercially available devices.…”

Extracorporeal carbon dioxide removal for lowering the risk of mechanical ventilation: research questions and clinical potential for the future

“…Mechanisms to improve the effectiveness of ECCO 2 R have been investigated in pre-clinical studies using blood acidification (to increase carbon dioxide release) and respiratory electrodialysis combining a haemofilter, electrodialysis, and ECCO 2 R. [35][36][37][38] Other experimental techniques include coating the membrane lung with carbonic anhydrase, the enzyme responsible for splitting carbonic acid into carbon dioxide and water. Pre-clinical studies suggest this technique can significantly augment carbon dioxide removal across membrane lungs.…”