Optimizing cerebral perfusion and hemodynamics during cardiopulmonary bypass through cannula design combining in silico, in vitro and in vivo input.

Cardiopulmonary bypass (CPB) is a standard technique for cardiac surgery, but comes with the risk of severe neurological complications (e.g. stroke) caused by embolisms and/or reduced cerebral perfusion. We report on an aortic cannula prototype design (optiCAN) with helical outflow and jet-splitting dispersion tip that could reduce the risk of embolic events and restores cerebral perfusion to 97.5% of physiological flow during CPB in vivo, whereas a commercial curved-tip cannula yields 74.6%. In further in vitro comparison, pressure loss and hemolysis parameters of optiCAN remain unaffected. Results are reproducibly confirmed in silico for an exemplary human aortic anatomy via computational fluid dynamics (CFD) simulations. Based on CFD simulations, we firstly show that optiCAN design improves aortic root washout, which reduces the risk of thromboembolism. Secondly, we identify regions of the aortic intima with increased risk of plaque release by correlating areas of enhanced plaque growth and high wall shear stresses (WSS). From this we propose another easy-to-manufacture cannula design (opti2CAN) that decreases areas burdened by high WSS, while preserving physiological cerebral flow and favorable hemodynamics. With this novel cannula design, we propose a cannulation option to reduce neurological complications and the prevalence of stroke in high-risk patients after CPB.

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.

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.

Impact of membrane lung surface area and blood flow on extracorporeal CO2 removal during severe respiratory acidosis.

BACKGROUND: Veno-venous extracorporeal CO2 removal (vv-ECCO2R) is increasingly being used in the setting of acute respiratory failure. Blood flow rates through the device range from 200 ml/min to more than 1500 ml/min, and the membrane surface areas range from 0.35 to 1.3 m2. The present study in an animal model with similar CO2 production as an adult patient was aimed at determining the optimal membrane lung surface area and technical requirements for successful vv-ECCO2R. METHODS: Four different membrane lungs, with varying lung surface areas of 0.4, 0.8, 1.0, and 1.3m2 were used to perform vv-ECCO2R in seven anesthetized, mechanically ventilated, pigs with experimentally induced severe respiratory acidosis (pH 7.0-7.1) using a 20Fr double-lumen catheter with a sweep gas flow rate of 8 L/min. During each experiment, the blood flow was increased stepwise from 250 to 1000 ml/min. RESULTS: Amelioration of severe respiratory acidosis was only feasible when blood flow rates from 750 to 1000 ml/min were used with a membrane lung surface area of at least 0.8 m2. Maximal CO2 elimination was 150.8 ml/min, with pH increasing from 7.01 to 7.30 (blood flow 1000 ml/min; membrane lung 1.3 m2). The membrane lung with a surface of 0.4 m2 allowed a maximum CO2 elimination rate of 71.7 mL/min, which did not result in the normalization of pH, even with a blood flow rate of 1000 ml/min. Also of note, an increase of the surface area above 1.0 m2 did not result in substantially higher CO2 elimination rates. The pressure drop across the oxygenator was considerably lower (<10 mmHg) in the largest membrane lung, whereas the smallest revealed a pressure drop of more than 50 mmHg with 1000 ml blood flow/min. CONCLUSIONS: In this porcine model, vv-ECCO2R was most effective when using blood flow rates ranging between 750 and 1000 ml/min, with a membrane lung surface of at least 0.8 m2. In contrast, low blood flow rates (250-500 ml/min) were not sufficient to completely correct severe respiratory acidosis, irrespective of the surface area of the membrane lung being used. The converse was also true, low surface membrane lungs (0.4 m2) were not capable of completely correcting severe respiratory acidosis across the range of blood flows used in this study.

First In Vivo Results of a Novel Pediatric Oxygenator with an Integrated Pulsatile Pump.

Extracorporeal membrane oxygenation (ECMO) is a pivotal bridge to recovery for cardiopulmonary failure in children. Besides its life-saving quality, it is often associated with severe system-related complications, such as hemolysis, inflammation, and thromboembolism. Novel oxygenator and pump systems may reduce such ECMO-related complications. The ExMeTrA oxygenator is a newly designed pediatric oxygenator with an integrated pulsatile pump minimizing the priming volume and reducing the surface area of blood contact. The aim of our study was to investigate the feasibility and safety of this new ExMeTrA (expansion mediated transport and accumulation) oxygenator in an animal model. During 6 h of extracorporeal circulation (ECC) in pigs, parameters of the hemostatic system including coagulation, platelets and complement activation, and flow rates were investigated. A nonsignificant trend in C3 consumption, thrombin-antithrombin-III (TAT) complex formation and a slight trend in hemolysis were detected. During the ECC, the blood flow was constantly at 500 ml/min using only flexible silicone tubes inside the oxygenator as pulsatile pump. Our data clearly indicate that the hemostatic markers were only slightly influenced by the ExMeTrA oxygenator. Additionally, the oxygenator showed a constant quality of blood flow. Therefore, this novel pediatric oxygenator shows the potential to be used in pediatric and neonatal support with ECMO.

Gas exchange efficiency of an oxygenator with integrated pulsatile displacement blood pump for neonatal patients.

Oxygenators have been used in neonatal extracorporeal membrane oxygenation (ECMO) since the 1970s. The need to develop a more effective oxygenator for this patient cohort exists due to their size and blood volume limitations. This study sought to validate the next design iteration of a novel oxygenator for neonatal ECMO with an integrated pulsatile displacement pump, thereby superseding an additional blood pump. Pulsating blood flow within the oxygenator is generated by synchronized active air flow expansion and contraction of integrated silicone pump tubes and hose pinching valves located at the oxygenator inlet and outlet. The current redesign improved upon previous prototypes by optimizing silicone pump tube distribution within the oxygenator fiber bundle; introduction of an oval shaped inner fiber bundle core, and housing; and a higher fiber packing density, all of which in combination reduced the priming volume by about 50% (50 to 27 mL and 41 to 20 mL, respectively). Gas exchange efficiency was tested for two new oxygenators manufactured with different fiber materials: one with coating and one with smaller pore size, both capable of long-term use (OXYPLUS® and CELGARD®). Results demonstrated that the oxygen transfer for both oxygenators was 5.3-24.7 mlO2/min for blood flow ranges of 100-500 mlblood/min. Carbon dioxide transfer for both oxygenators was 3.7-26.3 mlCO2/min for the same blood flow range. These preliminary results validated the oxygenator redesign by demonstrating an increase in packing density and thus in gas transfer, an increase in pumping capacity and a reduction in priming volume.

In vitro performance testing of a pediatric oxygenator with an integrated pulsatile pump.

For different lung and heart diseases (e.g., acute respiratory distress syndrome, congenital heart failure, and cardiomyopathy) extracorporeal membrane oxygenation is a well-established therapy, particularly in the field of neonatal and pediatric medicine. To reduce the priming volume of the extracorporeal circuit, different components can be combined. In this study, an oval-shaped oxygenator (called ExMeTrA) with integrated pulsatile pump was tested in vitro using porcine blood. A feasibility study regarding the performance of collapsing and expanding silicone tubes within an oxygenator fiber bundle as a pulsatile pump was previously completed with successful results. The findings of this study improve upon the previous feasibility results, particularly in terms of gas exchange and filling volume. Five modules were manufactured in sizes of 20 ± 2.2 ml (priming volume) with fiber surface areas of 0.24 ± 0.027 m(2) and an analytically calculated volume pumping capacity of 692 ± 75 ml/min. The modules were made of polymethylpentene fibers with dense outer layer to permit long-term applications. The gas exchange rates at a gas/blood flow ratio of 2:1 were between 64 and 72.7 ml(O)(2)/l(blood) and between 62.5 and 81.5 ml/l(blood), depending on the blood flow. The individual module's pumping capacity ranged from 200-500 ml/min thus providing room for further improvements. In order to enhance the pumping capacity while maintaining sufficient gas exchange rates future optimization, adjustments will be made to the inlet and outlet geometries.

A validated CFD model to predict O2 and CO2 transfer within hollow fiber membrane oxygenators.

Hollow fiber oxygenators provide gas exchange to and from the blood during heart surgery or lung recovery. Minimal fiber surface area and optimal gas exchange rate may be achieved by optimization of hollow fiber shape and orientation (1). In this study, a modified CFD model is developed and validated with a specially developed micro membrane oxygenator (MicroMox). The MicroMox was designed in such a way that fiber arrangement and bundle geometry are highly reproducible and potential flow channeling is avoided, which is important for the validation. Its small size (V(Fluid)=0.04 mL) allows the simulation of the entire bundle of 120 fibers. A non-Newtonian blood model was used as simulation fluid. Physical solubility and chemical bond of O2 and CO2 in blood was represented by the numerical model. Constant oxygen partial pressure at the pores of the fibers and a steady state flow field was used to calculate the mass transport. In order to resolve the entire MicroMox fiber bundle, the mass transport was simulated for symmetric geometry sections in flow direction. In vitro validation was achieved by measurements of the gas transfer rates of the MicroMox. All measurements were performed according to DIN EN 12022 (2) using porcine blood. The numerical simulation of the mass transfer showed good agreement with the experimental data for different mass flows and constant inlet partial pressures. Good agreement could be achieved for two different fiber configurations. Thus, it was possible to establish a validated model for the prediction of gas exchange in hollow fiber oxygenators.