Insights into Gradient and Anisotropic Pore Structures of Capiox® Gas Exchange Membranes for ECMO: Theoretically Verifying SARS-CoV-2 Permeability.

When using the extracorporeal capillary membrane oxygenator (sample A) for ECMO treatments of COVID-19 severely ill patients, which is dominantly used in Japan and worldwide, there is a concern about the risk of SARS-CoV-2 scattering from the gas outlet port of the membrane oxygenator. Terumo has launched two types of membranes (sample A and sample B), both of which are produced by the microphase separation processes using polymethylpentene (PMP) and polypropylene (PP), respectively. However, the pore structures of these membranes and the SARS-CoV-2 permeability through the membrane wall have not been clarified. In this study, we analyzed the pore structures of these gas exchange membranes using our previous approach and verified the SARS-CoV-2 permeation through the membrane wall. Both have the unique gradient and anisotropic pore structure which gradually become denser from the inside to the outside of the membrane wall, and the inner and outer surfaces of the membrane have completely different pore structures. The pore structure of sample A is also completely different from the other membrane made by the melt-extruded stretch process. From this, the pore structure of the ECMO membrane is controlled by designing various membrane-forming processes using the appropriate materials. In sample A, water vapor permeates through the coating layer on the outer surface, but no pores that allow SARS-CoV-2 to penetrate are observed. Therefore, it is unlikely that SARS-CoV-2 permeates through the membrane wall and scatter from sample A, raising the possibility of secondary ECMO infection. These results provide new insights into the evolution of a next-generation ECMO membrane.

Electron Microscopic Confirmation of Anisotropic Pore Characteristics for ECMO Membranes Theoretically Validating the Risk of SARS-CoV-2 Permeation.

The objective of this study is to clarify the pore structure of ECMO membranes by using our approach and theoretically validate the risk of SARS-CoV-2 permeation. There has not been any direct evidence for SARS-CoV-2 leakage through the membrane in ECMO support for critically ill COVID-19 patients. The precise pore structure of recent membranes was elucidated by direct microscopic observation for the first time. The three types of membranes, polypropylene, polypropylene coated with thin silicone layer, and polymethylpentene (PMP), have unique pore structures, and the pore structures on the inner and outer surfaces of the membranes are completely different anisotropic structures. From these data, the partition coefficients and intramembrane diffusion coefficients of SARS-CoV-2 were quantified using the membrane transport model. Therefore, SARS-CoV-2 may permeate the membrane wall with the plasma filtration flow or wet lung. The risk of SARS-CoV-2 permeation is completely different due to each anisotropic pore structure. We theoretically demonstrate that SARS-CoV-2 is highly likely to permeate the membrane transporting from the patient's blood to the gas side, and may diffuse from the gas side outlet port of ECMO leading to the extra-circulatory spread of the SARS-CoV-2 (ECMO infection). Development of a new generation of nanoscale membrane confirmation is proposed for next-generation extracorporeal membrane oxygenator and system with long-term durability is envisaged.

Newly Developed Pediatric Membrane Oxygenator that Suppresses Excessive Pressure Drop in Cardiopulmonary Bypass and Extracorporeal Membrane Oxygenation (ECMO).

This article developes a pediatric membrane oxygenator that is compact, high performance, and highly safe. This novel experimental approach, which imaging the inside of a membrane oxygenator during fluid perfusion using high-power X-ray CT, identifies air and blood retention in the local part of a membrane oxygenator. The cause of excessive pressure drop in a membrane oxygenator, which has been the most serious dysfunction in cardiovascular surgery and extracorporeal membrane oxygenation (ECMO), is the local retention of blood and air inside the oxygenator. Our designed blood flow channel for a membrane oxygenator has a circular channel and minimizes the boundary between laminated parts. The pressure drop in the blood flow channel is reduced, and the maximum gas transfer rates are increased by using this pediatric membrane oxygenator, as compared with the conventional oxygenator. Furthermore, it would be possible to reduce the incidents, which have occurred clinically, due to excessive pressure drop in the blood flow channel of the membrane oxygenator. The membrane oxygenator is said to be the "last stronghold" for patients with COVID-19 receiving ECMO treatment. Accordingly, the specification of our prototype is promising for low weight and pediatric patients.

Use of an extracorporeal circulation perfusion simulator: evaluation of its accuracy and repeatability.

Medical simulators have mainly been used as educational tools. They have been used to train technicians and to educate potential users about safety. We combined software for hybrid-type extracorporeal circulation simulation (ECCSIM) with a CPB-Workshop console. We evaluated the performance of ECCSIM, including its accuracy and repeatability, during simulated ECC. We performed a detailed evaluation of the synchronization of the software with the console and the function of the built-in valves. An S-III heart­lung machine was used for the open circuit. It included a venous reservoir, an oxygenator (RX-25), and an arterial filter. The tubes for venous drainage and the arterial line were connected directly to the ports of the console. The ECCSIM recorded the liquid level of the reservoir continuously. The valve in the console controlled the pressure load of the arterial line. The software made any adjustments necessary to both arterial pressure load and the venous drainage flow volume. No external flowmeters were necessary during simulation. We found the CPB-Workshop to be convenient, reliable, and sufficiently exact. It can be used to validate procedures by monitoring the controls and responses by using a combination of qualitative measures.

Evaluation of basic perfusion techniques, ECCSIM-Lite simulator.

Although serious accidents during extracorporeal circulation are infrequent, potential adverse events with both equipment and operation do still occur and require immediate and well-coordinated responses. Hence, perfusionists need to be well trained in both standard and emergency procedures, and this would be aided by the establishment of an official education and training curriculum. In particular, the establishment of a simulator-based educational program and corresponding evaluation methods will spur development of increasingly medical simulators. ExtraCorporeal Circulation SIMulator (ECCSIM-Lite) was used during repeated sessions of undergraduate students (n = 12) using a simple training scenario. Trainees aimed to maintain reservoir volume around a constant mean, and increase or decrease the arterial flow avoiding rapid variations, and their performance was monitored. Ability to prevent backflow was also recorded as a measure of accomplishment. Skills in performances were evaluated by using a scoring system based on task accomplishment. Accomplishment score was improved in all participants after 1 week of training. Accomplishment scores reflecting ability to maintain flow improved to an average of 78%; in the third and final practice session backflow was prevented in 100% of cases. The average reservoir level maintenance score in the flow-up phase was 75%, in the flow-maintenance phase was 92%, and in the flow-down phase was 58%. During skill training, in which trainees learn methods of avoiding adverse events, the use of simulators combined with tractable skills scores can ease the transition from training session to clinical practice. Use of these training scenarios within a perfusion education system also has the advantage of providing an index of trainees' current proficiency and improvement by providing tractable skill scores. In conclusion, the use of ECCSIM-Lite simulations, together with evaluation of task accomplishment over repeated training sessions, is an effective method of basic skill training for perfusionists.

Analysis of flow patterns in a ventricular assist device: a comparative study of particle image velocimetry and computational fluid dynamics.

In order to develop a diaphragm-type ventricular assist device (VAD), we studied the flow field change following structural modifications. We devised a center flow-type pump by putting a small projection on the center of the housing and/or diaphragm to provide a center in the flow field, and examined the following four types of VADs: N type without a projection, D type with a projection on the diaphragm, H type with a projection on the housing, and DH type with projections on both the diaphragm and housing. Computational fluid dynamics (CFD) was used for flow simulation. Particle image velocimetry (PIV) was also used to verify the reliability of the CFD method and to determine how the flow field changes in the presence of a projection. The results of the PIV and CFD analyses were comparable. The placement of a projection on the housing was most effective in rectifying the flow field.

Virtual patient simulator for the perfusion resource management drill.

Perfusionists require a detailed understanding of a patient's physiological status while comprehending the mechanics and engineering of the cardiopulmonary bypass system, so it is beneficial for them to obtain relevant practical skills using extracorporeal circulation technology and educational physiological simulators. We designed a perfusion simulator system (ECCSIM: Extracorporeal Circulation SIMulator system) based on a hybrid of a simple hydraulic mock circulation loop linked to a computer simulation model. Patient physiological conditions (height, weight, and cardiac indices) were determined by a parameter estimation procedure and used to accurately reproduce hemodynamic conditions. Extracorporeal circulation trainees in pre-clinical education were able to maintain venous oxygen saturation levels above 50%, except during cardiac standstill and a brief resumption of pulsation. Infant amplitudes of reservoir volume oscillation and flow rate were greatly increased compared with adult cardiovascular parameters, this enabled the instructor to control the difficulty level of the operation using different hemodynamic variations. High-fidelity simulator systems with controllable difficulty levels and high physiological reproducibility are useful in constructing a perfusion resource management environment that enable basic training and periodic crisis management drills to be performed.

Quantitative evaluation of hand cranking a roller pump in a crisis management drill.

The heart-lung machines for open-heart surgery have improved over the past 50 years; they rarely break down and are almost always equipped with backup batteries. The hand-cranking procedure only becomes necessary when a pump breaks down during perfusion or after the batteries have run out. In this study, the performance of hand cranking a roller pump was quantitatively assessed by an objective method using the ECCSIM-Lite educational simulator system. A roller pump connected to an extracorporeal circuit with an oxygenator and with gravity venous drainage was used. A flow sensor unit consisting of electromagnetic sensors was used to measure arterial and venous flow rates, and a built-in pressure sensor was used to measure the water level in the reservoir. A preliminary study of continuous cranking by a team of six people was conducted as a surprise drill. This system was then used at a perfusion seminar. At the seminar, 1-min hand-cranking drills were conducted by volunteers according to a prepared scenario. The data were calculated on site and trend graphs of individual performances were given to the participants as a handout. Preliminary studies showed that each person's performance was different. Results from 1-min drills showed that good performance was not related to the number of clinical cases experienced, years of practice, or experience in hand cranking. Hand cranking to maintain the target flow rate could be achieved without practice; however, manipulating the venous return clamp requires practice. While the necessity of performing hand cranking during perfusion due to pump failure is rare, we believe that it is beneficial for perfusionists and patients to include hand-cranking practice in periodic extracorporeal circulation crisis management drills because a drill allows perfusionists to mentally rehearse the procedures should such a crisis occur.

Development of an educational simulator system, ECCSIM-Lite, for the acquisition of basic perfusion techniques and evaluation.

A training system with quantitative evaluation of performance for training perfusionists is valuable for preparation for rare but critical situations. A simulator system, ECCSIM-Lite, for extracorporeal circulation (ECC) training of perfusionists was developed. This system consists of a computer system containing a simulation program of the hemodynamic conditions and the training scenario with instructions, a flow sensor unit, a reservoir with a built-in water level sensor, and an ECC circuit with a soft bag representing the human body. This system is relatively simple, easy to handle, compact, and reasonably inexpensive. Quantitative information is recorded, including the changes in arterial flow by the manipulation of a knob, the changes in venous drainage by handling a clamp, and the change in reservoir level; the time courses of the above parameters are presented graphically. To increase the realism of the training, a numerical-hydraulic circulatory model was applied. Following the instruction and explanation of the scenario in the form of audio and video captions, it is possible for a trainee to undertake self-study without an instructor or a computer operator. To validate the system, a training session was given to three beginners using a simple training scenario; it was possible to record the performance of the perfusion sessions quantitatively. In conclusion, the ECCSIM-Lite system is expected to be useful for perfusion training, since quantitative information about the trainee's performance is recorded and it is possible to use the data for assessment and comparison.