Predicting membrane oxygenator pressure drop using computational fluid dynamics

Three-dimensional computational fluid dynamic (CFD) simulations of membrane oxygenators should allow prediction of spatially dependent variables and subsequent shape optimization. Fiber bed complexity and current computational limitations require the use of approximate models to predict fiber drag effects in complete device simulations. A membrane oxygenator was modified to allow pressure measurement along the fiber bundle in all cardinal axes. Experimental pressure drop information with water perfusion was used to calculate the permeability of the fiber bundle. A three-dimensional CFD model of a commercial membrane oxygenator was developed to predict pressure drops throughout the device. Darcy's Law was used to account for the viscous drag of the fibers and was incorporated as a momentum loss term in the conservation equations. Close agreement was shown between experimental and simulated pressure drops at lower flow rates, but the simulated pressure drops were lower than experimental results at higher flows. Alternate models of fiber drag effects and flow field visualization are suggested as means to potentially improve the accuracy of the flow simulation. Computational techniques coupled with experimental verification offer insight into model validity and show promise for the development of accurate three-dimensional simulations of membrane oxygenators.     

Improving oxygenator performance using computational simulation and flow field-based parameters

Current goals in the development of oxygenators are to reduce extrinsic surface contact area, thrombus formation, hemolysis, and priming volume. To achieve these goals and provide a favorable concentration gradient for the gas exchange throughout the fiber bundle, this study attempts to find an optimized inlet and outlet port geometry to guide the flow of a hexagonal-shaped oxygenator currently under development. Parameters derived from numerical flow simulations allowed an automated quantitative evaluation of geometry changes of flow distribution plates. This led to a practical assessment of the quality of the flow. The results were validated qualitatively by comparison to flow visualization results. Two parameters were investigated, the first based on the velocity distribution and the second calculated from the residence time of massless particles representing erythrocytes. Both approaches showed significant potential to improve the flow pattern in the fiber bundle, based on one of the parameters of up to 66%. Computational fluid dynamics combined with a parameterization proved to be a powerful tool to quickly improve oxygenator designs.     

Uniformity of the fluid flow velocities within hollow fiber membranes of blood oxygenation devices

A finite volume-based computational model was developed to investigate the uniformity of the fluid flow across the hollow fiber membranes in blood oxygenation devices. A two-dimensional annular cross section of a blood oxygenation device including about 3,300 hollow fiber membranes was used in the computation model. The equations governing the steady incompressible laminar flow in the blood oxygenation device were solved numerically and the results were compared with those obtained from the equivalent porous medium approximation. For the porous medium approximation, the Ergun equation was used for evaluating the permeability. The simulation results showed that the fluid molecules spend about six times longer in the fiber bundle region than that in its equivalent porous medium approximation model. The computational model also provides a more detailed fluid flow pattern in the membrane compartment of the blood oxygenator.     

The development of the modern oxygenator

From 1953 when Gibbon first successfully supported a patient with extracorporeal circulation to about 1980 many different types of oxygenators were developed. Since their introduction in the early 1980s, microporous hollow fiber oxygenators with blood flow outside the fiber have become the dominant type of oxygenator in use. Their success has been due to both the ability to specify the required properties for a good oxygenator and the application of modern design tools, especially computational fluid dynamics, to the design process. The result has been the availability of many oxygenators from different manufacturers that differ to some extent in their performance but all of which provide adequate performance for successful and safe clinical use.     

Development of a new hollow fiber silicone membrane oxygenator for ECMO: the recent progress.

Throughout the last 50 years, many improvements have been made for a more effective oxygenator. A large plate type membrane oxygenator, used by Clowes, and a coil type, used by Kolff, has evolved into the small hollow fiber oxygenator. The complex bubble oxygenator, or rotating disk oxygenator, has become a small disposable bubble oxygenator. The currently available oxygenators are extremely small, efficient, and can be used for extended periods of time. However, there are some problems with extracorporeal membrane oxygenation (ECMO). Currently in the United States, there are no clinically applicable hollow fiber ECMO oxygenators available, in spite of the extended ECMO application. Therefore, the development of a small, yet efficient, silicone hollow fiber membrane oxygenator for long-term ECMO usage was attempted. Based on the results of many experimental models, preclinical oxygenator models for long-term ECMO were developed in our laboratory using an ultra-thin silicone rubber hollow fiber membrane.     

Modeling flow effects on thrombotic deposition in a membrane oxygenator

The hypothesis that regions of low blood velocity in a membrane oxygenator, as predicted by computational fluid dynamics (CFD), would correspond with regions of clinical thrombotic deposition was investigated. Twenty heparin-coated oxygenators were sectioned following use in adult extracorporeal membrane oxygenation. The activated clotting time (ACT) was maintained at approximately 180 s via heparin infusion throughout the support period. Cross-sections were systematically photographed, and slides made to allow image projection upon a digitizing pad. Thrombotic deposition was traced to allow creation of a device cross-section image with an overlaid color scale representing thrombotic deposition frequency. A two-dimensional CFD model was developed to predict blood velocities throughout the oxygenator cross-section. Direct spatial comparisons were made between maps of CFD modeled blood speed and thrombotic deposition. Theoretical oxygenator design modification was performed within the CFD model to investigate flow paths which might minimize regions of low blood velocity. CFD results demonstrated that low velocity regions qualitatively matched regions with a high incidence of thrombotic deposition. Thrombotic deposition was also correlated to longer perfusion periods. This technique of coupling clinical data and CFD offers the potential to relate flow characteristics to thrombotic deposition and represents a potentially powerful new methodology for the optimization of oxygenator flow-related biocompatibility.     

Pressure drop, shear stress, and activation of leukocytes during cardiopulmonary bypass: a comparison between hollow fiber and flat sheet membrane oxygenators

The membrane oxygenator is known to be superior to the bubble oxygenator, but little information is available about the difference between the hollow fiber and flat sheet membrane oxygenators with regard to pressure drop, shear stress, and leukocyte activation. In this study, we compared these 2 types of membrane oxygenators in patients undergoing cardiopulmonary bypass (CPB) surgery with special focus on leukocyte activation and pressure drop across the oxygenators. Plasma concentration of elastase, a marker indicating leukocyte activation, increased to 593+/-68% in the flat sheet oxygenator group versus 197+/-42% in the hollow fiber oxygenator group (p<0.01) at the end of CPB compared to their respective baseline concentrations before CPB. Pressure drop across the oxygenator was significantly higher in the flat sheet group than in the hollow fiber group throughout the entire period of CPB (p<0.01). High pressure drop across the oxygenator as well as the calculated shear stress was positively correlated with the release of elastase at the end of CPB (r = 0.760, p<0.01, r = 0.692, p<0.01). However, this positive correlation existed in the flat sheet oxygenator but not in the hollow fiber oxygenator. Clinically, both membrane oxygenators have satisfactory performance in O2 and CO2 transfer. These results suggest that a higher pressure drop across the flat sheet oxygenator is associated with more pronounced activation of leukocytes in patients undergoing cardiopulmonary bypass.     

Description of a flow optimized oxygenator with integrated pulsatile pump

Extracorporeal membrane oxygenation (ECMO) is a well-established therapy for several lung and heart diseases in the field of neonatal and pediatric medicine (e.g., acute respiratory distress syndrome, congenital heart failure, cardiomyopathy). Current ECMO systems are typically composed of an oxygenator and a separate nonpulsatile blood pump. An oxygenator with an integrated pulsatile blood pump for small infant ECMO was developed, and this novel concept was tested regarding functionality and gas exchange rate. Pulsating silicone tubes (STs) were driven by air pressure and placed inside the cylindrical fiber bundle of an oxygenator to be used as a pump module. The findings of this study confirm that pumping blood with STs is a viable option for the future. The maximum gas exchange rate for oxygen is 48mL/min/L(blood) at a medium blood flow rate of about 300mL/min. Future design steps were identified to optimize the flow field through the fiber bundle to achieve a higher gas exchange rate. First, the packing density of the hollow-fiber bundle was lower than commercial oxygenators due to the manual manufacturing. By increasing this packing density, the gas exchange rate would increase accordingly. Second, distribution plates for a more uniform blood flow can be placed at the inlet and outlet of the oxygenator. Third, the hollow-fiber membranes can be individually placed to ensure equal distances between the surrounding hollow fibers.     

Spontaneous gas bubbling in microporous oxygenators

During operation of the microporous membrane oxygenators at some conditions, gas microbubbles penetrate into the blood. This effect, so-called spontaneous bubbling, takes place even when the blood pressure is higher than the gas pressure. This phenomenon was confirmed experimentally both in a model cell with hydrophobic microporous hollow fibers being used in the oxygenators and in in vitro tests on the actual microporous hollow fiber oxygenator. We proposed a mechanism of spontaneous gas bubbling into liquid that contains dissolved gases. Because of a partial pressure gradient, the dissolved gases and water vapors are transported from blood into the gas pore. This causes Stefans gas flow directed from the liquid-gas interface. Because of the high hydraulic resistance of the micropores, gas pressure at the meniscus increases up to gas bubbling. A mishandled priming of the oxygenator as well as the blood pressure pulsation caused by the roller pump operation contribute to spontaneous gas bubbling in the microporous oxygenators. The flow and pressure in the hydrophobic pores were calculated for various gases.     

Development of a new silicone membrane oxygenator for ECMO.

Two types small and efficient ECMO oxygenators were developed utilizing the most up to date hollow fiber technology. Newly silicone hollow fibers possess sufficient mechanical strength while maintaining ultra thin walls of 50 micro meter. Two types of oxygenators were made with this fiber. The fiber length for the type 1 module is 150mm with a priming volume 194 cc (surface area 1.3 m(2)) and type 2 has a fiber length of 100 mm with a 144 cc priming volume (the surface area 0.8 m(2)). The studies were performed at 0.5, 1.0 and 2.0 L/min of blood flow and these oxygenators demonstrated. O(2) gas transfer rate of 69+/-4 ml/min/L for type 1 and 68+/-6 ml/min/L for type 2. The CO(2) gas transfer rate was 25+/-2 ml/min/L for type 1 and 32+/-2 ml/min/L for type 2. These results demonstrate type 2 oxygenator has similar gas exchange capabilities to those of Kolobows' oxygenator which has about 2.0 times larger surface area. Additionally, comparative hemolysis tests were preformed with this new oxygenator and the Kolbow. The NIH value was 0.006 (g/100 L) for the type 1 oxygenator and 0.01 (g/100 L) for the Kolbow oxygenator. These results suggested that this ECMO oxygenator had sufficient gas exchange performance in spite of being smaller and induced minimal blood damage.     

Experimental Approach to Visualize Flow in a Stacked Hollow Fiber Bundle of an Artificial Lung With Particle Image Velocimetry

Flow distribution is key in artificial lungs, as it directly influences gas exchange performance as well as clot forming and blood damaging potential. The current state of computational fluid dynamics (CFD) in artificial lungs can only give insight on a macroscopic level due to model simplification applied to the fiber bundle. Based on our recent work on wound fiber bundles, we applied particle image velocimetry (PIV) to the model of an artificial lung prototype intended for neonatal use to visualize flow distribution in a stacked fiber bundle configuration to (i) evaluate the feasibility of PIV for artificial lungs, (ii) validate CFD in the fiber bundle of artificial lungs, and (iii) give a suggestion how to incorporate microscopic aspects into mainly macroscopic CFD studies. To this end, we built a fully transparent model of an artificial lung prototype. To increase spatial resolution, we scaled up the model by a factor of 5.8 compared with the original size. Similitude theory was applied to ensure comparability of the flow distribution between the device of original size and the scaled‐up model. We focused our flow investigation on an area (20 × 70 × 43 mm) in a corner of the model with a Stereo‐PIV setup. PIV data was compared to CFD data of the original sized artificial lung. From experimental PIV data, we were able to show local flow acceleration and declaration in the fiber bundle and meandering flow around individual fibers, which is not possible using state‐of‐the‐art macroscopic CFD simulations. Our findings are applicable to clinically used artificial lungs with a similar stacked fiber arrangement (e.g., Novalung iLa and Maquet QUADROX‐I). With respect to some limitations, we found PIV to be a feasible experimental flow visualization technique to investigate blood‐sided flow in the stacked fiber arrangement of artificial lungs.     

Retrospective analysis comparing hollow fiber and silicone membrane oxygenators for neonates on ECMO

There is little information showing the use of microporous polypropylene hollow fiber oxygenators during extra-corporeal life support (ECLS). Recent surveys have shown increasing use of these hollow fibers amongst ECLS centers in the United States. We performed a retrospective analysis comparing the Terumo BabyRx hollow fiber oxygenator to the Medtronic 800 silicone membrane oxygenator on 14 neonatal patients on extracorporeal membrane oxygenation (ECMO). The aim of this study was to investigate the similarities and differences when comparing pressure drops, prime volumes, oxygenator endurance, and gas transfer capabilities between the two groups.     

Development of an Intravenous Membrane Oxygenator: Enhanced Intravenous Gas Exchange Through Convective Mixing of Blood around Hollow Fiber Membranes

Abstract: In vitro testing of a new prototype intravenous membrane oxygenator (IMO) is reported. The new IMO design consists of matted hollow fiber membranes arranged around a centrally positioned tripartite balloon. Short gas flow paths and consistent, reproducible fiber geometry after insertion of the device result in an augmented oxygen flux of up to 800% with balloon activation compared with the static mode (balloon off). Operation of the new IMO device with the balloon on versus the balloon off results in a 400% increase in carbon dioxide flux. Gas flow rates of up to 9. 5 L/min through the 14–cm–long hollow fibers have been achieved with vacuum pressures of 250 mm Hg. Gas exchange efficiency for intravenous membrane oxygenators can be increased by emphasizing the following design features: short gas flow paths, consistent and reproducible fiber geometry, and most importantly, an active means of enhancing convective mixing of blood around the hollow fiber membranes     

Extracorporeal membrane oxygenator compatible with centrifugal blood pumps

Coil-type silicone membrane oxygenators can only be used with roller blood pumps due to the resistance from the high blood flow. Therefore, during extracorporeal membrane oxygenation (ECMO) treatment, the combination of a roller pump and an oxygenator with a high blood flow resistance will induce severe hemolysis, which is a serious problem. A silicone rubber, hollow fiber membrane oxygenator that has a low blood flow resistance was developed and evaluated with centrifugal pumps. During in vitro tests, sufficient gas transfer was demonstrated with a blood flow less than 3 L/min. Blood flow resistance was 18 mm Hg at 1 L/min blood flow. This oxygenator module was combined with the Gyro C1E3 (Kyocera, Japan), and veno-arterial ECMO was established on a Dexter strain calf. An ex vivo experiment was performed for 3 days with stable gas performance and low blood flow resistance. The combination of this oxygenator and centrifugal pump may be advantageous to enhance biocompatibility and have less blood trauma characteristics.     

Silicone-Coated Polypropylene Hollow-Fiber Oxygenator: Experimental Evaluation and Preliminary Clinical Use

Background. A membrane oxygenator consisting of a microporous polypropylene hollow fiber with a 0.2-μm ultrathin silicone layer (cyclosiloxane) was developed. Animal experimental and preliminary clinical studies evaluated its reliability in bypass procedures.

Methods. Five 24-hour venoarterial bypass periods were conducted on dogs using the oxygenator (group A). In 5 controls, bypass periods were conducted using the same oxygenator without silicone coating (group B). As a preliminary clinical study, 14 patients underwent cardiopulmonary bypass with the silicone-coated oxygenator.

Results. Eight to 16 hours (mean, 12.2 hours) after initiation of bypass, plasma leakage occurred in all group B animals, but none in group A. The O₂ and CO₂ transfer rates after 24 hours in group A were significantly higher than at termination of bypass in group B (p < 0.005 and p < 0.03, respectively). Scanning electron microscopy of silicone-coated fibers after 24 hours of bypass revealed no damage to the silicone coating of the polypropylene hollow fibers. In the clinical study, the oxygenator showed good gas transfer, acceptable pressure loss, low hemolysis, and good durability.

Conclusions. This oxygenator is more durable and offers greater gas transfer capabilities than the previous generation of oxygenators.     

A clinical evaluation of the Terumo Capiox SX18R hollow fiber oxygenator

The Terumo Capiox SX18R is a commercially available, low prime, reverse phase, hollow fiber membrane oxygenator. The oxygenator consists of a 1.8 m2 microporous polypropylene hollow fiber bundle, a 2200 cm2 tubular stainless steel heat exchanger, and an open hard shell venous reservoir with integral cardiotomy filter. The Terumo Capiox SX18R oxygenator was evaluated to determine its clinical oxygenating performance. Blood samples were drawn from 25 patients yielding 114 data points. The following parameters were recorded: blood flow, cardiac index, gas flow, gas to blood flow ratio, and oxygen fraction. Samples were assayed for hematocrit, hemoglobin, arterial and venous blood gas values, and venous oxygen saturation. The data and assay results were used to calculate arterial, venous, and membrane gas oxygen content, oxygen transfer, shunt fraction, and oxygen diffusion capacity. The Terumo Capiox SX18R oxygenator performed adequately with sufficient oxygen transfer reserve and carbon dioxide clearance under a variety of clinical conditions for the tested population.     

Development of a New Hollow Fiber Silicone Membrane Oxygenator: In Vitro Study

An experimental silicone hollow fiber membrane oxygenator for long-term extracorporeal membrane oxygenation (ECMO) was developed in our laboratory using an ultrathin silicone hollow fiber. However, the marginal gas transfer performances and a high-pressure drop in some cases were demonstrated in the initial models. In order to improve performance the following features were incorporated in the most recent oxygenator model: increasing the fiber length and total surface area, decreasing the packing density, and modifying the flow distributor. The aim of this study was to evaluate the gas transfer performances and biocompatibility of this newly improved model with in vitro experiments. According to the established method in our laboratory, in vitro studies were performed using fresh bovine blood. Gas transfer performance tests were performed at a blood flow rate of 0.5 to 6 L/min and a V/Q ratio (V = gas flow rate, Q = blood flow rate) of 2 and 3. Hemolysis tests were performed at a blood flow rate of 1 and 5 L/min. Blood pressure drop was also measured. At a blood flow rate of 1 L/min and V/Q = 3, the O2 and CO2 gas transfer rates were 72.45 +/- 1.24 and 39.87 +/- 2.92 ml/min, respectively. At a blood flow rate of 2 L/min and V/Q = 3, the O2 and CO2 gas transfer rates were 128.83 +/- 1.09 and 47.49 +/- 5.11 ml/min. Clearly, these data were superior to those obtained with previous models. As for the pressure drop and hemolytic performance, remarkable improvements were also demonstrated. These data indicate that this newly improved oxygenator is superior to the previous model and may be clinically acceptable for long-term ECMO application.     

Non-destructive evaluation of membrane lung gas exchange performance

This paper describes a method of evaluating the gas exchange effectiveness of hollow fiber oxygenators utilizing gas on both sides of the membrane. The goal of the study was to develop an evaluation technique which was accurate, reliable, and did not harm or contaminate a new, sterile oxygenator. Three pediatric oxygenators were tested and compared: the Medtronic Minimax Plus, the Terumo Capiox 320, and the Sorin Masterflo 34 (all with rated blood flows of 2-2.5 L/min). Gas entering the "blood" side was a mixture of CO2, O2, and N2 in a mixture matching typical venous blood partial pressures. The "blood" flows used were 0.5, 1, 1.5, or 2 L/min. Gas entering the gas port had an FiO2 of 0.4 flowing at 0.5, 1, 1.5, 2, 2.5, 3, or 3.5 L/min. Fractional contents of CO2 and O2 at all inlets and outlets were determined using a gas analyzer and converted to partial pressures. Efficacy indices and gas transfer rates were calculated and compared. Of the devices studied, the Masterflo 34 had the highest gas transport rates and effectiveness followed by the Minimax-Plus and the Capiox 320. Reversing the direction of the flow through the "blood" phase of the Minimax-Plus greatly changed its gas exchange effectiveness. The techniques described in this study should allow for a more uniform and consistent evaluation of gas exchange by membrane lungs which can be made inexpensively and relatively quickly. In addition, these methods should allow manufactures to evaluate gas exchange effectiveness and transfer rates of individual units during production as well as reduce the complexity involved when evaluating newly developed oxygenators.     

From the spinning disc to the membrane oxygenator for open-heart surgery

Gibbon's rotating cylinder could not be enlarged to oxygenate an animal larger than a cat. The spinning disc oxygenator, introduced in 1947, had the capacity to perfuse a dog and the potential to increase oxygenation capacity by addition of more discs. When centers began to do three to four open-heart operations per day, the disposable bubble oxygenator was more practical. Bubble size was optimized to decrease the flow of oxygen relative to the blood flow and reduce trauma to blood. The bubble oxygenator is the type most commonly used today. Use of deep hypothermia with whole blood at an esophageal temperature of 10 degrees C was initially complicated by brain damage due to aggregation of white blood corpuscles and platelets. The introduction of hemodilution permitted safe utilization of hypothermic perfusion. Perfusion of infants should not be carried out at hematocrit below 25 ml/100 m. Early membrane oxygenators used nonporous silicone, or modified silicone membranes. High priming volumes, high pressure drop and marginal gas transfer efficiency characterized these devices. Recent advances in membrane technology have spawned a new generation of membrane oxygenators utilizing microporous polypropylene. In these new oxygenators, with either microporous hollow fibers or sheet membrane, the gas transfer characteristics are far superior to those of types produced in the past. The hollow-fiber devices typically have larger surface areas and higher pressure drop than in the new state-of-the-art flat plate models. An evaluation of one of these new-generation membrane oxygenators gave optimal oxygen and carbon dioxide exchange at a gas flow of 1 l/min of 60% oxygen in air at 30 degrees C and 2 l/min of 80% oxygen in air at normal temperature and rewarming for an adult. Today, after almost 40 years of oxygenator development, these new membrane device can offer better platelet preservation and reduced blood trauma as compared with types developed in the past. The new membrane oxygenators are fast becoming the preferred choice for use in infants and in protracted perfusion.     

Computational Design and In Vitro Characterization of an Integrated Maglev Pump-Oxygenator

For the need for respiratory support for patients with acute or chronic lung diseases to be addressed, a novel integrated maglev pump-oxygenator (IMPO) is being developed as a respiratory assist device. IMPO was conceptualized to combine a magnetically levitated pump/rotor with uniquely configured hollow fiber membranes to create an assembly-free, ultracompact system. IMPO is a self-contained blood pump and oxygenator assembly to enable rapid deployment for patients requiring respiratory support or circulatory support. In this study, computational fluid dynamics (CFD) and computer-aided design were conducted to design and optimize the hemodynamics, gas transfer, and hemocompatibility performances of this novel device. In parallel, in vitro experiments including hydrodynamic, gas transfer, and hemolysis measurements were conducted to evaluate the performance of IMPO. Computational results from CFD analysis were compared with experimental data collected from in vitro evaluation of the IMPO. The CFD simulation demonstrated a well-behaved and streamlined flow field in the main components of this device. The results of hydrodynamic performance, oxygen transfer, and hemolysis predicted by computational simulation, along with the in vitro experimental data, indicate that this pump-lung device can provide the total respiratory need of an adult with lung failure, with a low hemolysis rate at the targeted operating condition. These detailed CFD designs and analyses can provide valuable guidance for further optimization of this IMPO for long-term use.