Technical Indicators to Evaluate the Degree of Large Clot Formation Inside the Membrane Fiber Bundle of an Oxygenator in an In Vitro Setup.

The most common technical complication during ECMO is clot formation. A large clot inside a membrane oxygenator reduces effective membrane surface area and therefore gas transfer capabilities, and restricts blood flow through the device, resulting in an increased membrane oxygenator pressure drop (dpMO). The reasons for thrombotic events are manifold and highly patient specific. Thrombus formation inside the oxygenator during ECMO is usually unpredictable and remains an unsolved problem. Clot sizes and positions are well documented in literature for the Maquet Quadrox-i Adult oxygenator based on CT data extracted from devices after patient treatment. Based on this data, the present study was designed to investigate the effects of large clots on purely technical parameters, for example, dpMO and gas transfer. Therefore, medical grade silicone was injected into the fiber bundle of the devices to replicate large clot positions and sizes. A total of six devices were tested in vitro with silicone clot volumes of 0, 30, 40, 50, 65, and 85 mL in accordance with ISO 7199. Gas transfer was measured by sampling blood pre and post device, as well as by sampling the exhaust gas at the devices' outlet at blood flow rates of 0.5, 2.5, and 5.0 L/min. Pre and post device pressure was monitored to calculate the dpMO at the different blood flow rates. The dpMO was found to be a reliable parameter to indicate a large clot only in already advanced "clotting stages." The CO2 concentration in the exhaust gas, however, was found to be sensitive to even small clot sizes and at low blood flows. Exhaust gas CO2 concentration can be monitored continuously and without any risks for the patient during ECMO therapy to provide additional information on the endurance of the oxygenator. This may help detect a clot formation and growth inside a membrane oxygenator during ECMO even if the increase in dpMO remains moderate.

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.

Novel Size-Variable Dedicated Rodent Oxygenator for ECLS Animal Models-Introduction of the "RatOx" Oxygenator and Preliminary In Vitro Results.

The overall survival rate of extracorporeal life support (ECLS) remains at 60%. Research and development has been slow, in part due to the lack of sophisticated experimental models. This publication introduces a dedicated rodent oxygenator ("RatOx") and presents preliminary in vitro classification tests. The RatOx has an adaptable fiber module size for various rodent models. Gas transfer performances over the fiber module for different blood flows and fiber module sizes were tested according to DIN EN ISO 7199. At the maximum possible amount of effective fiber surface area and a blood flow of 100 mL/min, the oxygenator performance was tested to a maximum of 6.27 mL O2/min and 8.2 mL CO2/min, respectively. The priming volume for the largest fiber module is 5.4 mL, while the smallest possible configuration with a single fiber mat layer has a priming volume of 1.1 mL. The novel RatOx ECLS system has been evaluated in vitro and has demonstrated a high degree of compliance with all pre-defined functional criteria for rodent-sized animal models. We intend for the RatOx to become a standard testing platform for scientific studies on ECLS therapy and technology.

In Vitro and In Vivo Feasibility Study for a Portable VV-ECMO and ECCO2R System.

Extracorporeal membrane oxygenation (ECMO) is an established rescue therapy for patients with chronic respiratory failure waiting for lung transplantation (LTx). The therapy inherent immobilization may result in fatigue, consecutive deteriorated prognosis, and even lost eligibility for transplantation. We conducted a feasibility study on a novel system designed for the deployment of a portable ECMO device, enabling the physical exercise of awake patients prior to LTx. The system comprises a novel oxygenator with a directly connected blood pump, a double-lumen cannula, gas blender and supply, as well as control and energy management. In vitro experiments included tests regarding performance, efficiency, and blood damage. A reduced system was tested in vivo for feasibility using a novel large animal model. Six anesthetized pigs were first positioned in supine position, followed by a 45° angle, simulating an upright position of the patients. We monitored performance and vital parameters. All in vitro experiments showed good performance for the respective subsystems and the integrated system. The acute in vivo trials of 8 h duration confirmed the results. The novel portable ECMO-system enables adequate oxygenation and decarboxylation sufficient for, e.g., the physical exercise of designated LTx-recipients. These results are promising and suggest further preclinical studies on safety and efficacy to facilitate translation into clinical application.

Extracorporeal Hyperoxygenation Therapy (EHT) for Carbon Monoxide Poisoning: In-Vitro Proof of Principle.

Carbon monoxide (CO) poisoning is the leading cause of poisoning-related deaths globally. The currently available therapy options are normobaric oxygen (NBO) and hyperbaric oxygen (HBO). While NBO lacks in efficacy, HBO is not available in all areas and countries. We present a novel method, extracorporeal hyperoxygenation therapy (EHT), for the treatment of CO poisoning that eliminates the CO by treating blood extracorporeally at elevated oxygen partial pressure. In this study, we proof the principle of the method in vitro using procine blood: Firstly, we investigated the difference in the CO elimination of a hollow fibre membrane oxygenator and a specifically designed batch oxygenator based on the bubble oxygenator principle at elevated pressures (1, 3 bar). Secondly, the batch oxygenator was redesigned and tested for a broader range of pressures (1, 3, 5, 7 bar) and temperatures (23, 30, 37 °C). So far, the shortest measured carboxyhemoglobin half-life in the blood was 21.32 min. In conclusion, EHT has the potential to provide an easily available and effective method for the treatment of CO poisoning.

How Computational Modeling can Help to Predict Gas Transfer in Artificial Lungs Early in the Design Process.

Wearable extracorporeal membrane oxygenation (ECMO) circuits may soon become a viable alternative to conventional ECMO treatment. Common device-induced complications, however, such as blood trauma and oxygenator thrombosis, must first be addressed to improve long-term reliability, since ambulatory patients cannot be monitored as closely as intensive care patients. Additionally, an efficient use of the membrane surface can reduce the size of the devices, priming volume, and weight to achieve portability. Both challenges are linked to the hemodynamics in the fiber bundle. While experimental test methods can often only provide global and time-averaged information, computational fluid dynamics (CFD) can give insight into local flow dynamics and gas transfer before building the first laboratory prototype. In this study, we applied our previously introduced micro-scale CFD model to the full fiber bundle of a small oxygenator for gas transfer prediction. Three randomized geometries as well as a staggered and in-line configuration were modeled and simulated with Ansys CFX. Three small laboratory oxygenator prototypes were built by stacking fiber segments unidirectionally with spacers between consecutive segments. The devices were tested in vitro for gas transfer with porcine blood in accordance with ISO 7199. The error of the predicted averaged CFD oxygen saturations of the random 1, 2, and 3 configurations relative to the averaged in-vitro data (over all samples and devices) was 2.4%, 4.6%, 3.1%, and 3.0% for blood flow rates of 100, 200, 300, and 400 ml/min, respectively. While our micro-scale CFD model was successfully applied to a small oxygenator with unidirectional fibers, the application to clinically relevant oxygenators will remain challenging due to the complex flow distribution in the fiber bundle and high computational costs. However, we will outline our future research priorities and discuss how an extended mass transfer correlation model implemented into CFD might enable an a priori prediction of gas transfer in full size oxygenators.

Impact of hyperthermal rotary blood pump surfaces on blood clotting behavior: an approach.

The influence of heat dissipating systems, such as rotary blood pumps, was investigated. Titanium cylinders as rotary blood pump housing dummies were immersed in porcine blood and constantly tempered at specific temperatures (37-60 degrees C) over a defined period of time. The porcine blood was anticoagulated either by low heparin dosage or citrate. At frequent intervals, samples were taken for blood analysis and the determination of the plasmatic coagulation cascade. Blood parameters do not alter at surface temperatures below 50 degrees C. Hyperthermia-induced hemolysis could be confirmed. The plasmatic coagulation cascade is terminated at surface temperatures exceeding 55 degrees C. The adhesion of blood constituents on surfaces is temperature and time dependent, and structural changes of adhesions and blood itself were detected.

Particle Image Velocimetry Used to Qualitatively Validate Computational Fluid Dynamic Simulations in an Oxygenator: A Proof of Concept.

Computational fluid dynamics (CFD) is used to simulate blood flow inside the fiber bundles of oxygenators. The results are interpreted in terms of flow distribution, e.g., stagnation and shunt areas. However, experimental measurements that provide such information on the local flow between the fibers are missing. A transparent model of an oxygenator was built to perform particle image velocimetry (PIV), to perform the experimental validation. The similitude theory was used to adjust the size of the PIV model to the minimal resolution of the PIV system used (scale factor 3.3). A standard flow of 80 mL/min was simulated with CFD for the real oxygenator and the equivalent flow of 711 mL/min, according to the similitude theory, was investigated with PIV. CFD predicts the global size of stagnation and shunt areas well, but underestimates the streamline length and changes in velocities due to the meandering flow around the real fibers in the PIV model. Symmetrical CFD simulation cannot consider asymmetries in the flow, due to manufacturing-related asymmetries in the fiber bundle. PIV could be useful for validation of CFD simulations; measurement quality however must be improved for a quantitative validation of CFD results and the investigation of flow effects such as tortuosity and anisotropic flow behavior.

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.