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Refurbishing single use extracorporeal membrane oxygenation (ECMO) oxygenators for in vitro research applications is common. However, the refurbishment protocols that are established in respective laboratories have never been evaluated. In the present study, we aim at proving the relevance of a well-designed refurbishing protocol by quantifying the burden of repeatedly reused oxygenators. We used the same three oxygenators in 5 days of 6 hours whole blood experiments. During each experiment day, the performance of the oxygenators was measured through the evaluation of gas transfer. Between experiment days, each oxygenator was refurbished applying three alternative refurbishment protocols based on purified water, pepsin and citric acid, and hydrogen peroxide solutions, respectively. After the last experiment day, we disassembled the oxygenators for visual inspection of the fiber mats. The refurbishment protocol based on purified water showed strong degeneration with a 40-50 %-performance drop and clearly visible debris on the fiber mats. Hydrogen peroxide performed better; nevertheless, it suffered a 20% decrease in gas transfer as well as clearly visible debris. Pepsin/citric acid performed best in the field, but also suffered from 10% performance loss and very few, but visible debris. The study showed the relevance of a well-suited and well-designed refurbishment protocol. The distinct debris on the fiber mats also suggests that reusing oxygenators is ill-advised for many experiment series, especially regarding hemocompatibility and in vivo testing. Most of all, this study revealed the relevance of stating the status of test oxygenators and, if refurbished, comment on the implemented refurbishment protocol in detail.

Blood stream infection (BSI) is a potentially lethal complication in patients receiving extracorporeal membrane oxygenation (ECMO). It may be particularly common in patients with veno-venous ECMO due to their long hospitalization in the intensive care unit. Given that these patients have concurrent indwelling central venous catheters (CVC), it is unclear whether the ECMO circuit, CVC, or both, contribute to BSI. This study evaluated the risk factors associated with BSI in patients receiving veno-venous ECMO in a single institution study of 61 patients from 2016 through 2019. All ECMO catheters and the circuit oxygenator fluid were aseptically collected and analyzed for microorganisms at the time of decannulation. New BSI was diagnosed in 15 (24.6%) patients and increased mortality by threefold. None of the ECMO catheters or oxygenator fluid were culture positive. BSI increased with CVC use of over 8 days and was significantly lowered when CVC were exchanged by day 8 compared with patients with exchanges at later points (15.0% vs. 42.8%, p = 0.02). Median length of CVC use in the BSI-negative and BSI-positive group were 6.3 ± 5.0 and 9.4 ± 5.1, respectively (p = 0.04). In summary, BSI is a potentially lethal complication in patients receiving ECMO. Indwelling CVC, not the ECMO circuitry, is the likely contributor for BSI, and exchanging CVC by day 8 can reduce the incidence of BSI.

Volatile anesthetics (VAs) protect myocardial cells during cardiovascular surgeries, including cardiopulmonary bypass (CPB). In CPB, blood is gradually transferred from the body to a CPB unit until the target cardiac index is achieved, following which human lung (HL) ventilation is stopped. This pilot study aimed to evaluate changes in the blood sevoflurane concentrations 5 min after the start of CPB when its delivery to the oxygenator began after HL ventilation with sevoflurane was completed. Six patients were recruited and participated in this study. For each patient, the equilibrated blood sample, collected 20 min after starting the delivery of 1.7% sevoflurane (HL group), and another blood sample, collected 5 min after starting the CPB, were analyzed using gas chromatography equipped with a flame ionization detector. The mean (± standard deviation) sevoflurane concentrations in the HL and 5 min after starting CPB groups were 58.6 ± 4.7 and 14.5 ± 5.0 μg/ml, respectively (P < 0.01). In conclusion, the equilibrated blood sevoflurane concentrations showed a rapid decrease when switching from sevoflurane ventilation for the HL to CPB unless it was introduced to the oxygenator until completion of the switch., This is an Open Access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. To view the details of this license, please visit (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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.

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.

Background. Innovative advances in cardiac surgery to reduce the negative impact of cardiopulmonary bypass (CPB) require a comprehensive solution. The ultimate questions of present interest remain the prevention of hypoxia, the composition of the priming volume of the oxygenator, the state of erythrocytes and their energy potential, the level of hemolysis, the pathogenetic approach to the correction of electrolytes during perfusion, as well as the biocompatibility of the extracorporeal circuit. The study aimed to create the protocol for cardiopulmonary bypass, which includes the possibility of reducing the negative effects of synthetic polymers of the extracorporeal circuit; reducing the hydrodynamic load on the tissue; carrying out a more physiological correction of the acid-base state; improving the energy potential of cells; correction of electrolyte balance during cardiopulmonary bypass ta­king into account the stages of the surgical operation. Materials and methods. The study included 225 patients who underwent cardiac surgery using cardiopulmonary bypass. The patients were divided into three groups. The first group consisted of 75 people, whose extracorporeal contour was treated with the adaptive composition by a special technique. After centrifuging the patient’s blood, serum was obtained, which was diluted in a solution of 0.9% NaCl and treated with the oxygenator circuit. The second group included patients (n = 75) in whom fructose-1,6-diphosphate (FPD) was used in the perfusion regimen. The drug was administered intravenously at a dose of 10 g at a rate of 10 ml/min in two stages: 5 g of FPD were injected immediately before the start of perfusion and 5 g before the patient was warmed up. The third group was the control group. Perfusion was performed using a membrane oxygenator in a non-pulsating blood flow mode with a prime of 1.3–1.6 L to achieve moderate hemodilution (Ht — 25 ± 2 g/L). A hyperosmolar priming volume with a total osmolarity of up to 510.6 mmol/L was used. The basic solutions were volutens, reosorbilact, mannitol 15%, Soda-buffer 4.2%. Hemogram (Hb, Ht, MCV, MCH, MCHC, RDWa, RDW%, hemolysis), oxygen transport: saturation of arterial (SaO2%) and venous blood (SvO2%), partial pressure of oxygen in arterial (PaO2) and venous blood (PvO2), oxygen delivery index (IDO2), oxygen consumption index (IVO2), oxygen extraction (O2ER), and oxygen extraction index (O2EI) were studied. The research of morphological changes in erythrocytes was carried out. Results. Our study aimed to develop and implement into practice an optimized cardiopulmonary bypass protocol based on the results obtained. The previous studies have shown that treatment of the oxy-genator circuit with the adaptive composition creates a protective layer of autoalbumin on the inner surface of the extracorporeal circuit, and the use of a drug with the active fructose-1,6-diphosphate ingredient during perfusion allows correcting hypophosphatemia, reducing the energy deficiency of the cells. In these two groups, in comparison with the control one, after CPB, there was a lower level of hemolysis, a lower number of echinocytes, and spherocytes. The three groups used the hyperosmolar priming ­volume. Before perfusion, there were the following indices: IDO2 — 332.00 ± ± 84.84 ml/(min • m2), IVO2 — 76.07 ± 28.34 ml/(min • m2), O2ЕR — 22.91 ± 6.33 %, O2EI — 22.47 ± 6.32 %, BE = –0.78 ± 2.13 mmol/L. At 10 min after CPB, there were the following indices: IDO2 — 579.7 ± 112.3 ml/(min • m2), IVO2 — 30.91 ± 13.31 ml / (min • m2), O2ER — 5.35 ± 2.07 %, O2EI — 5.26 ± ± 2.08 %, BE = 0.82 ± 2.03 mmol/L. IDO2 increased due to the oxygenator gas exchange, and the decrease in IVO2, O2ЕR, O2EI can be explained by the patient’s cooling. At the warming stage, there were the indices: IDO2 — 598.8 ± 114.9 ml/(min • m2), IVO2 — 108.10 ± 33.11 ml/(min • m2), O2ER — 18.04 ± 4.14 %, O2EI — 17.95 ± 4.15 %, BE = –0.11 ± 8.88 mmol/L. IDO2 — 305.7 ± 60.9 ml / min • m2), IVO2 — 77.15 ± 24.29 ml/(min • m2), O2ЕR — 25.36 ± 6.5 %, O2EI — 25.34 ± 6.5 %, BE = –0.36 ± 2.20 mmol/L. After CPB, the rate of diuresis was 11.88 ± 5.31 ml/kg/h, the relative hydrobalance after CPB was 9.67 ± 8.12 ml/kg. Our proposed protocol for cardiopulmonary bypass includes the basic points: 1) treatment of the oxygenator contour with the adaptive composition; 2) in patients with an initially low level of phosphorus, administration of the drug of fructose-1,6-diphosphate by the scheme; 3) the use of a hyperosmolar priming volume of the oxygenator; 4) correction of electrolytes taking into account the stages of cardiac surgery. Conclusions. The proposed procedure for the treatment of the extracorporeal oxygenator circuit is simple and affordable, improves the biocompatibility of the oxygenator. The use of a hyperosmolar priming volume avoids the volume load and provides an adequate gas transport function of the blood. The application of FPD makes it possible to reduce hemolysis and protect erythrocytes, correct electrolytes by taking into account the stages of operations and the peculiarities of CPB., Актуальність. Сучасний підхід до зменшення негативного впливу штучного кровообігу (ШК) вимагає комплексного вирішення. Найбільш актуальними питаннями залишаються профілактика й усунення гіпоксії, склад первинного об’єму заповнення оксигенатора, стан еритроцитів і їх енергетичний потенціал, рівень гемолізу, патогенетичний підхід до корекції електролітів під час перфузії, а також біосумісність екстракорпорального контура. Мета: створити протокол проведення штучного кровообігу, який включав би можливість зниження негативного впливу синтетичних полімерів екстракорпорального контура; зменшення гідродинамічного навантаження на тканини; проведення більш фізіологічної корекції кислотно-лужного стану; усунення енергетичного дефіциту клітин; проведення корекції електролітного балансу під час штучного кровообігу з урахуванням етапів операції. Матеріали та методи. У дослідження увійшло 225 хворих, яким виконані кардіохірургічні операції з використанням штучного кровообігу. Пацієнти були розподілені на 3 групи. У першу групу ввійшли пацієнти (n = 75), у яких екстракорпоральний контур оброблявся адаптуючою композицією за спеціальною методикою. У результаті центрифугування крові пацієнта отримували сироватку, яку розводили в розчині 0,9% NaCl, і обробляли контур оксигенатора. До другої групи були включені пацієнти (n = 75), у яких у схемі проведення перфузії використовувався препарат фруктозо-1,6-дифосфат (ФДФ). Препарат вводили внутрішньовенно в дозі 10 г зі швидкістю 10 мл/хв у два етапи: 5 г ФДФ вводилися безпосередньо перед початком перфузії і 5 г — перед зігріванням пацієнта. Третя група була контрольною. Перфузія проводилась за допомогою мембранного оксигенатора в режимі непульсуючого кровотоку з первинним об’ємом заповнен-ня 1,3–1,6 л для досягнення помірної гемодилюції (Ht – 25 ± 2 г/л). Використовували гіперосмолярний первинний об’єм заповнення оксигенатора із загальною осмолярністю до 510,6 ммоль/л. Базисними розчинами були волютенз, реосорбілакт, маніт 15%, сода-буфер 4,2%. Досліджували гемограму (Hb, Ht, MCV, MCH, MCHC, RDWa, RDW%, гемоліз), кисневий транспорт: сатурацію артеріальної (SaO2) і венозної крові (SvO2), парціальний тиск кисню в артеріальній (PaO2) і венозній крові (PvO2), індекс доставки кисню (IDO2), індекс споживання кисню (IVO2), екстракцію кисню (O2ER) та індекс екстракції кисню (O2EI). Відповідно до мазків крові проводили вивчення морфологічних змін еритроцитів. Результати. Наші дослідження були спрямовані на те, щоб за їх результатом розробити й увести в практику оптимізований протокол проведення штучного кровообігу. У попередніх роботах було показано, що обробка контура оксигенатора адаптуючою композицією створює захисний шар з автоальбуміну на внутрішній поверхні екстракорпорального контура, а використання під час перфузії препарату з діючою речовиною фруктозо-1,6-дифосфат дозволяє скорегувати гіпофосфатемію, усунути енергетичний дефіцит клітини. У цих двох групах порівняно з контрольною після закінчення перфузії був менший рівень гемолізу, менша кількість ехіноцитів і сфероцитів. У трьох групах використовували гіперосмолярний первинний об’єм заповнення оксигенатора. До перфузії показники були такими: IDO2 — 332,0 ± ± 84,84 мл/(хв ∙ м2), IVO2 — 76,07 ± 28,34 мл/(хв ∙ м2), O2ЕR — 22,91 ± 6,33 %, O2EI — 22,47 ± 6,32 %, BE = –0,78 ± 2,13 ммоль/л. На 10-й хвилині ШК IDO2 — 579,7 ± 112,3 мл/(хв ∙ м2), IVO2 — 30,91 ± ± 13,31мл/(хв ∙ м2), O2ЕR — 5,35 ± 2,07 %, O2EI — 5,26 ± 2,08 %, BE = 0,82 ± 2,03 ммоль/л. IDO2 виріс за рахунок роботи оксигенатора, а зниження IVO2, O2ЕR, O2EI можна пояснити охолодженням хворого. На етапі зігрівання: IDO2 — 598,8 ± 114,9 мл/(хв ∙ м2), IVO2 — 108,1 ± 33,11 мл/(хв ∙ м2), O2ЕR — 18,04 ± ± 4,14 %, O2EI — 17,95 ± 4,15 %, BE = –0,11 ± 8,88 ммоль/л. Після ШК: IDO2 — 305,7 ± ± 60,90 мл/(хв ∙ м2), IVO2 — 77,15 ± 24,29 мл/(хв ∙ м2), O2ЕR — 25,36 ± 6,5 %, O2EI — 25,34 ± 6,5 %,BE = –0,36 ± 2,20 ммоль/л. Після перфузії темп діурезу становив 11,88 ± 5,31 мл/кг/год, відносний гідробаланс — 9,67 ± 8,12 мл/кг. Запропонований нами протокол проведення штучного кровообігу включає основні ланки: 1) обробка контура оксигенатора адаптуючою композицією; 2) введення за схемою препарату фруктозо-1,6-дифосфату пацієнтам з початковим низьким рівнем фосфору; 3) використання гіпер-осмолярного первинного об’єму заповнення оксигенатора; 4) корекція електролітів з урахуванням етапів кардіохірургічної операції. Висновки. Запропонована методика обробки екстракорпорального контура оксигенатора є простою і доступною, вона покращує біосумісність оксигенатора, застосування гіперосмолярного первинного об’єму заповнення оксигенатора дозволяє уникнути волемічного навантаження й забезпечує адекватну газотранспортну функцію крові, використання фруктозо-1,6-дифосфату сприяє зменшенню гемолізу й захисту еритроцитів, корекція електролітів з урахуванням етапів операцій враховує особливості штучного кровообігу.

Thrombosis in extracorporeal membrane oxygenation (ECMO) circuits remains a frequent complication. We characterize the location, extent, structure, and clinical implications of thrombi in 53 ECMO circuits from 46 pediatric patients. The tubing, pump, and oxygenator were examined for visible thrombi. Representative samples of thrombi were collected for histologic, immunofluorescence, and immunohistochemical analysis. Thrombi were found in 81% of ECMO circuits. The most clinically significant were inflow oxygenator membrane surface thrombi (11% of circuits), arterial tubing thrombi (30%), and venous tubing (26%) or connector thrombi (26%). Oxygenator membrane surface thrombi resulted in rapidly increasing delta pressure across the oxygenator over 1-2 days, oxygenator failure, and circuit replacement. Oxygenator membrane surface thrombi were associated with intravascular venous thrombosis and bacterial infection before starting ECMO. Arterial cannula/tubing thrombi led in one case to aortic and mesenteric artery thrombosis followed by bowel infarction. In 11% of cases, venous tubing thrombi grew large enough to break off and embolize to the pump, resulting in increased hemolysis. Antifibrinolytic therapy during ECMO was associated with an increased risk of pump thromboembolism. Other less clinically significant thrombi included pump axle thrombi with thrombus fragments trapped in the oxygenator (45%), and deep oxygenator membrane thrombi (15%). Examination of ECMO circuits after removal is a useful quality improvement tool that can elucidate the cause of circuit problems, indicate patients at increased risk of thrombosis, and suggest areas for possible improvements.

Rapid reductions in P a CO 2 during extracorporeal membrane oxygenation (ECMO) are associated with poor neurologic outcomes. Understanding what factors determine P a CO 2 may allow a gradual reduction, potentially improving neurologic outcome. A simple and intuitive arithmetic expression was developed, to describe the interactions between the major factors determining P a CO 2 during venovenous ECMO. This expression was tested using a wide range of input parameters from clinically feasible scenarios. The difference between P a CO 2 predicted by the arithmetic equation and P a CO 2 predicted by a more robust and complex in-silico mathematical model, was10 mm Hg for more than 95% of the scenarios tested. With no CO 2 in the sweep gas, P a CO 2 is proportional to metabolic CO 2 production and inversely proportional to the "total effective expired ventilation" (sum of alveolar ventilation and oxygenator ventilation). Extracorporeal blood flow has a small effect on P a CO 2 , which becomes more important at low blood flows and high recirculation fractions. With CO 2 in the sweep gas, the increase in P a CO 2 is proportional to the concentration of CO 2 administered. P a CO 2 also depends on the fraction of the total effective expired ventilation provided via the oxygenator. This relationship offers a simple intervention to control P a CO 2 using titration of CO 2 in the sweep gas.

Resumen: Una placenta artificial es una plataforma de soporte vital para bebés prematuros o que tuvieron menos de 37 semanas de gestación completa. Aunque existe la posibilidad de utilizar esta plataforma para la reparación intraoperatoria de anomalías congénitas (p. ej., hernia diafragmática congénita) en bebés prematuros tardíos, o para el estudio del desarrollo fetal, el objetivo principal de esta tecnología es actualmente el tratamiento de bebés extremadamente prematuros, o aquellos nacidos durante el período peri-viable entre las 21-24 semanas de gestación completa.Los bebés que nacen en este período peri-viable, generalmente tienen malos resultados debido a la necesidad de ventilar mecánicamente sus pulmones extremadamente inmaduros, a menudo a altas presiones máximas. Las plataformas de soporte vital basadas en placenta artificial están diseñadas para evitar la necesidad de ventilar como un medio para facilitar el intercambio de gases y así evitar lesiones en el pulmón prematuro inmaduro. En cambio, el intercambio de gases altamente eficiente y fácilmente regulado se realiza mediante dispositivos de intercambio de gases conectados a la vasculatura fetal. Dependiendo de la forma del sistema utilizado, se han probado diseños de circuitos venoso-venosos y arterio-venosos, con los prototipos arterio-venosos más recientes que utilizan el corazón fetal, en lugar de una bomba externa, para generar la presión del circuito.A pesar de tener la apariencia de un concepto futurista, el trabajo de desarrollar una placenta artificial se ha llevado a cabo de forma intermitente desde al menos finales de los años 50. El hecho de que la tecnología aún no haya entrado en servicio clínico, a pesar de que han pasado más de 60 años, refleja los desafíos técnicos que rodean el desarrollo y uso de la placenta artificial. Esta demora en la introducción también refleja el panorama cambiante de la atención neonatal y, en particular, los avances en la ventilación mecánica y los modos de soporte respiratorio no invasivo, como la presión positiva continua en las vías respiratorias, la introducción de esteroides prenatales y la disponibilidad de terapia con surfactante exógeno.Como tal, es razonable argumentar que el grupo demográfico objetivo para la tecnología de placenta artificial ha cambiado significativamente desde que comenzó su desarrollo. Los bebés que antes se consideraban peri-viables y probables candidatos para la terapia con placenta artificial (es decir, los que nacieron antes de las 28 semanas de gestación) ahora tienen tasas mucho mejores de supervivencia libre de enfermedad con la tecnología disponible en la actualidad. El grupo demográfico con los peores resultados, y los posibles candidatos para la terapia de placenta artificial contemporánea, son aquellos nacidos de embarazos significativamente comprometidos (por ejemplo, infección intrauterina, sepsis, preeclampsia severa, insuficiencia placentaria severa) a las 21-24 semanas de gestación y con un peso de aprox. 300 gramos.Este artículo proporcionará una revisión del historial de desarrollo de la placenta artificial, un resumen de la situación actual y concluirá discutiendo los desafíos restantes que deberán abordarse antes de que esta tecnología pueda introducirse en la práctica clínica. Summary: An artificial placenta is a life support platform for babies born preterm, or prior to 37 weeks’ completed gestation. Although there is potential to use this platform for the intraoperative repair of congenital abnormalities (e.g. congenital diaphragmatic hernia) in late preterm babies, or for the study of fetal development, the primary target for this technology is currently treatment of extremely preterm infants, or those delivered during the peri-viable period between 21-24 weeks’ completed gestation.Babies born in this peri-viable period generally have poor outcomes due to the need to mechanically ventilate their extremely immature lungs–often at high peak pressures. Artificial placenta-based life support platforms are designed to obviate the need to ventilate as a means of facilitating gas exchange, and thus avoid injury to the immature preterm lung. Instead, highly efficient, and easily regulated gas exchange is performed by gas-exchange devices connected to the fetal vasculature. Depending on the form of the system used, venous-venous and arterio-venous circuit designs have been trialled, with the more recent arterio-venous prototypes using the fetal heart, rather than an external pump, to generate circuit pressure.Despite having the appearance of a futuristic concept, work to develop an artificial placenta has been undertaken intermittently since at least the late 1950s. That the technology is yet to enter clinical service, despite 60-plus years of work, reflects the technical challenges surrounding the development and use of the artificial placenta. This delay in introduction also reflects the changing neonatal care landscape, and notably advances in mechanical ventilation and non-invasive respiratory support modes such as continuous positive airway pressure, the introduction of antenatal steroids, and the availability of exogenous surfactant therapy.As such, it is reasonable to argue that the target demographic for artificial placenta technology has changed significantly since development first began. Babies once considered peri-viable and a probable candidate for artificial placenta therapy (i.e. those born below 28 weeks’ gestation) now have much improved rates of disease-free survival using currently available technology. The demographic with the poorest outcomes, and the likely candidates for contemporary artificial placenta therapy, are those born from significantly compromised pregnancies (e.g. intrauterine infection, sepsis, severe pre-eclampsia, severe placental insufficiency) at 21-24 weeks’ gestation and weighing as little as 300 grams.This paper will provide a review of the development history of the artificial placenta, a summary of the current state-of-play, and conclude by discussing the remaining challenges that will need to be addressed before this technology might be introduced to clinical practice.

Towards the establishment of a long-term lung-assist device to be used both as a bridge and as an alternative to lung transplantation according to final destination therapy, we develop the biohybrid lung (BHL) on the technical basis of contemporary extracorporeal membrane oxygenation (ECMO). Here, to overcome the significant drawbacks of ECMO, in particular the missing hemocompatibility of the artificial surfaces, all blood-contacting areas need to be endothelialized sufficiently. In continuation of our recent accomplishments, demonstrating the feasibility of establishing a physiological acting endothelial cell (EC) monolayer on the hollow fiber membranes (HFMs) of the ECMO in vitro, the next step towards BHL translation is the endothelialization of the complete oxygenator, consisting of HFMs and the surrounding housing. Therefore, we assessed EC seeding inside our model oxygenator (MOx), which simulated the conditions in the assembled HFM oxygenators in order to identify the most important factors influencing efficient endothelialization, such as cell seeding density, cell distribution, incubation time and culture medium consumption. Overall, upon adjusting the concentration of infused ECs to 15.2 × 104/cm2 and ensuring optimal dispersion of cells in the MOx, viable and confluent EC monolayers formed on all relevant surfaces within 24 h, even though they comprised different polymers, i.e., the fibronectin-coated HFMs and the polysulfone MOx housing. Periodic medium change ensured monolayer survival and negligible apoptosis rates comparable to the reference within the assembled system. By means of these results, revealing essential implications for BHL development, their clinical translation is coming one step closer to reality.

Oxygenator thrombosis during extracorporeal membrane oxygenation (ECMO), is a complication that necessitates component replacement. ECMO centers monitor clot burden by intermittent measurement of pressure drop across the oxygenator. An increase in pressure drop at a preset flow rate suggests an increase in resistance/clot formation within the oxygenator. This monitoring method comes with inherent disadvantages such as monitoring gaps, and increased risk of air embolism and infection. We explored utilizing flow measurement, which avoids such risks, as an indicator of ECMO circuit obstructions. The hypothesis that flow rate through a shunt tube in the circuit will increase as distal resistances in the circuit increases was tested. We experimentally simulated controlled levels of oxygenator obstructions using glass microspheres in an ex vivo veno-venous ECMO circuit and measured the change in shunt flow rate using over the tube ultra-sound flow probes. A mathematical model was also used to study the effect of distal resistances in the ECMO circuit on shunt flow. Results of both the mathematical model and the experiments showed a clear and measurable increase in shunt flow with increasing levels of oxygenator obstruction. Therefore, flow monitoring appears to be an effective non-contact and continuous method to monitor for obstruction during ECMO.

Thrombocytosis has been feared as a source of thrombotic complications during the conduct of cardiopulmonary bypass (CPB) for patients undergoing cardiac procedures. We present a patient urgently requiring repair/replacement of three heart valves that had preexisting myelofibrosis with thrombocytosis (platelet count of 800,000 per µl) and neutrophilia (40,000 per µl). Despite achieving an activated clotting time > 500 s with heparin and antithrombin concentrate administration prior to CPB, the pump oxygenator and reservoir demonstrated significant clot just prior to restoration of the patient’s circulation. The patient subsequently suffered a severe protamine reaction that was successfully managed. A review of the literature of similar patients and the relevant cellular and biochemical mechanisms in this setting are presented, with potential therapeutic approaches to prevent such complications noted.

Introduction: A high-pressure excursion (HPE) is a sudden increase in oxygenator inlet pressure during cardiopulmonary bypass (CPB). The aims of this study were to identify factors associated with HPE, to describe a treatment protocol utilizing epoprostenol in severe cases, and to assess early outcome in HPE patients. Methods: Patients who underwent cardiac surgery with cardiopulmonary bypass at Sahlgrenska University Hospital 2016–2018 were included in a retrospective observational study. Pre- and post-operative data collected from electronic health records, local databases, and registries were compared between HPE and non-HPE patients. Factors associated with HPE were identified with logistic regression models. Results: In total, 2024 patients were analyzed, and 37 (1.8%) developed HPE. Large body surface area (adjusted Odds Ratio (aOR): 1.43 per 0.1 m2; 95% confidence interval (CI): 1.16–1.76, p < 0.001), higher hematocrit during CPB (aOR: 1.20 per 1%; (1.09–1.33), p < 0.001), acute surgery (aOR: 2.98; (1.26–6.62), p = 0.018), and previous stroke (aOR: 2.93; (1.03–7.20), p = 0.027) were independently associated with HPE. HPE was treated with hemodilution ( n = 29, 78.4%), and/or extra heparin ( n = 23, 62.2%), and/or epoprostenol ( n = 12, 32.4%). No oxygenator change-out was necessary. While there was no significant difference in 30-day mortality (2.7% vs 3.2%, p = 1.0), HPE was associated with a higher perioperative stroke rate (8.1% vs 1.8%, aOR 5.09 (1.17–15.57), p = 0.011). Conclusions: Large body surface area, high hematocrit during CPB, previous stroke and acute surgery were independently associated with HPE. A treatment protocol including epoprostenol appears to be a safe option. Perioperative stroke rate was increased in HPE patients.

Background Pulsatile extracorporeal circulation (ECC) may improve perfusion of critical organs during cardiac surgery. This study analyzed the influence of the components of a minimal invasive ECC (MiECC) on the transfer of pulsatile energy into the pseudo-patient of a mock circulation. Methods An aortic model with human-like geometry and compliance was perfused by a diagonal pump. Surplus hemodynamic energy (SHE) was determined from flow and pressure data. Five adult-size oxygenator models and three sizes of cannulas were compared. Pulsatile pump settings were optimized, and parallel dual-pump configurations were evaluated. Results Oxygenator models showed up to twofold differences in pressure gradients and influenced SHE at flow rates up to 2.0 L min−1. Adjustments of frequency, systole duration, and rotational speed gain significantly improved SHE compared with empirical settings, with SHE above 21% of mean arterial pressure at flow rates of 1.0 L min−1 to 1.5 L min−1 and SHE above 5% at 3.5 L min−1. Small diameter cannula (15 Fr) limited SHE compared with larger cannula (21 Fr and 23 Fr). Two diagonal pumps did not provide higher SHE than a single pump, but permitted additional control over pulse pressure and SHE by varying the total fraction of pulsatile flow and the fraction of flow bypassing the oxygenator. Conclusions Proper selection of components and optimizations of pump settings significantly improved pulse pressure and SHE of pulsatile MiECC. Surplus hemodynamic energy depended on flow rate with a maximum at 1.0 L min−1–1.5 L min−1. Pulsatile MiECC may specifically assist organ perfusion during phases of low flow., publishedVersion

Artificial organs (2022). doi:10.1111/aor.14465, Published by Wiley-Blackwell, Oxford [u.a.]

Cardiopulmonary bypass (CPB) circuits can significantly sequester intravenous anesthetics. Adsorption of medications by our institution's standard circuit (Terumo CAPIOX FX05 oxygenator; noncoated polyvinylchloride tubing) has not been described. We prepared ex vivo CPB circuits with and without oxygenators. Medication combinations studied included midazolam (0.5 mg), fentanyl (50 [micro]g), midazolam (0.5 mg) with morphine (0.5 mg), and midazolam (0.5 mg) with fentanyl (50 [micro]g). Medications were administered after obtaining baseline samples. Samples were drawn at 2, 5, 15, 30, 60, 120, and 180 minutes, and analyzed for concentration of injected medications. Midazolam demonstrated no sequestration after 180 minutes. Fentanyl concentration at 180 minutes was lower with an oxygenator (52.7 +/- 12.5 vs. 110.9 +/- 12.0 ng/ml, P = 0.00432). More fentanyl was found in solution after 180 minutes when given with midazolam compared to fentanyl given alone in the presence of an oxygenator (101 +/- 22.3 vs. 52.7 +/- 12.5 ng/ml, P = 0.044). Less midazolam was present after 180 minutes when given with morphine compared to midazolam given alone in the absence of an oxygenator (1264.9 +/- 425.6 vs. 2124 +/- 254 ng/ml, P = 0.037). We successfully characterized the adsorption of various combinations of midazolam, fentanyl, and morphine to our CPB circuit, showing that fentanyl and midazolam behave differently based on other medications present.

Acute lung injury and acute respiratory distress syndrome are characterized by rapid-onset respiratory failure following a variety of direct and indirect insults to the parenchyma or vasculature of the lungs. Extracorporeal membrane oxygenation is a form of extracorporeal life support where an external artificial circulator carries venous blood from the patient to a gas exchange device (oxygenator) where blood becomes enriched with oxygen and has carbon dioxide removed. This blood then re-enters the patients circulation. The potential advantages of ECMO over conventional manajement may extend beyond its role in supporting patients with ARDS. ECMO may facilitate and enhance the application of lung-protective ventilation by minimizing ventilator-induced lung injury.

Introduction: To determine the oxygenator impact on alterations of meropenem (MEM)/vaborbactam (VBR) in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extra corporeal membrane oxygenation (ECMO) circuit including the Quadrox-i® oxygenator. Methods: 1/4-inch and 3/8-inch, simulated closed-loop ECMO circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. Additionally, 1/4-inch and 3/8-inch circuits were also prepared without an oxygenator in series. A one-time dose of MEM/VBR was administered into the circuits and serial pre- and post-oxygenator concentrations were obtained at 5 minutes, 1, 2, 3, 4, 5, 6, 8, 12, and 24-hour time points. MEM/VBR was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation. Results: For the 1/4-inch circuit, there was an approximate mean 55% MEM loss with the oxygenator in series and a mean 33%–40% MEM loss without an oxygenator in series at 24 hours. For the 3/8-inch circuit, there was an approximate mean 70% MEM loss with the oxygenator in series and a mean 30%–38% MEM loss without an oxygenator in series at 24 hours. For both the 1/4-inch circuit and 3/8-inch circuits with and without an oxygenator, there was Conclusions: This ex-vivo investigation demonstrated substantial MEM loss within an ECMO circuit with an oxygenator in series with both sizes of the Quadrox-i oxygenator at 24 hours and no significant VBR loss. Further evaluations with multiple dose in-vitro and in-vivo investigations are needed before specific MEM/VBR dosing recommendations can be made for clinical application with ECMO.

The objective of this study was to determine if propofol administration to veno-venous (VV) extracorporeal membrane oxygenation (ECMO) patients was associated with more incidents of oxygenator failure when compared to patients who did not receive propofol. This was a single center, retrospective cohort study. The primary outcome of the study is oxygenator exchanges per ECMO day in patients who received propofol versus those who did not receive propofol. Patients were 18 years or older on VV-ECMO support between January 1, 2015 and January 31, 2018. Patients were excluded if they required ECMO support for less than 48 h or greater than 21 days. There were five patients in the propofol arm that required oxygenator exchanges and seven patients in the control arm. The total number of oxygenator exchanges per ECMO day was not significantly different between groups ( p = 0.50). When comparing those who required an oxygenator exchange and those who did not, there was no difference in the cumulative dose of propofol received per ECMO hour (0.64 mg/kg/h vs 0.96 mg/kg/h; p = 0.16). Propofol use in patients on VV-ECMO does not appear to increase the number of oxygenator exchanges.

Since extracorporeal membrane oxygenator (ECMO) has been utilized to save countless lives by providing continuous extracorporeal breathing and circulation to patients with severe cardiopulmonary failure. In particular, it has played an important role during the COVID-19 epidemic. One of the important composites of ECMO is membrane oxygenator, and the core composite of the membrane oxygenator is hollow fiber membrane, which is not only a place for blood oxygenation, but also is a barrier between the blood and gas side. However, the formation of blood clots in the oxygenator is a key problem in the using process. According to the study of the mechanism of thrombosis generation, it was found that improving the hemocompatibility is an efficient approach to reduce thrombus formation by modifying the surface of materials. In this review, the corresponding modification methods (surface property regulation, anticoagulant grafting, and bio-interface design) of hollow fiber membranes in ECMO are classified and discussed, and then, the research status and development prospects are summarized. Graphical abstract

Extracorporeal membrane oxygenation (ECMO) plays an important role in the coronavirus disease 2019 (COVID-19) pandemic. Management of thrombi in ECMO is generally an important issue; especially in ECMO for COVID-19 patients who are prone to thrombus formation, the thrombus formation in oxygenators is an unresolved issue, and it is very difficult to deal with. To prevent thromboembolic complications, it is necessary to develop a method for early thrombus detection. We developed a novel method for detailed real-time observation of thrombi formed in oxygenators using indocyanine green (ICG) fluorescence imaging. The purpose of this study was to verify the efficacy of this novel method through animal experiments. The experiments were performed three times using three pigs equipped with veno-arterial ECMO comprising a centrifugal pump (CAPIOX SL) and an oxygenator (QUADROX). To create thrombogenic conditions, the pump flow rate was set at 1 L/min without anticoagulation. The diluted ICG (0.025 mg/mL) was intravenously administered at a dose of 10 mL once an hour. A single dose of ICG was 0.25mg. The oxygenator was observed with both an optical detector (PDE-neo) and the naked eye every hour after measurement initiation for a total of 8 hours. With this dose of ICG, we could observe it by fluorescence imaging for about 15 minutes. Under ICG imaging, the inside of the oxygenator was observed as a white area. A black dot suspected to be the thrombus appeared 6-8 hours after measurement initiation. The thrombus and the black dot on ICG imaging were finely matched in terms of morphology. Thus, we succeeded in real-time thrombus detection in an oxygenator using ICG imaging. The combined use of ICG imaging and conventional routine screening tests could compensate for each other's weaknesses and significantly improve the safety of ECMO.

Guanhua Li,1,2 Jianfeng Zeng,3 Zhaoyuan Liu,4 Yu Zhang,5,* Xiaoping Fan6,* 1Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People’s Republic of China; 2Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 3Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People’s Republic of China; 4Department of Hepatobiliary Surgery, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, People’s Republic of China; 5Department of Pathology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 6Department of Cardiovascular Surgery, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoping FanDepartment of Cardiovascular Surgery, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 55, Neihuan Xi Road, Panyu District, Guangzhou, 510006, People’s Republic of ChinaTel/Fax +86 20-81887233Email fukui-hanson@hotmail.comYu ZhangDepartment of Pathology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 111, Dade Road, Guangzhou, 510120, People’s Republic of ChinaTel/Fax +86 20-81887233Email zyddyf@126.comBackground: COVID-19 is still a worldwide pandemic and extracorporeal membrane oxygenation (ECMO) is vital for extremely critical COVID-19 patients. Pulsatile flow impacts greatly on organ function and microcirculation, however, the effects of pulsatile flow on hemodynamics and inflammatory responses during ECMO are unknown. An in vivo study was launched aiming at comparing the two perfusion modes in ECMO.Methods: Fourteen beagles were randomly allocated into two groups: the pulsatile group (n=7) and the non-pulsatile group (n=7). ECMO was conducted using the i-Cor system for 24 hours. Hemodynamic parameters including surplus hemodynamic energy (SHE), energy equivalent pressure (EEP), oxygenator pressure drop (OPD), and circuit pressure drop (CPD) were monitored. To assess inflammatory responses during ECMO, levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8, and transforming growth factor-β 1 (TGF-β 1) were measured.Results: EEP and SHE were markedly higher in pulsatile circuits when compared with the conventional circuits. Between-group differences in both OPD and CPD reached statistical significance. Significant decreases in TNF-α were seen in animals treated with pulsatile flows at 2 hours, 12 hours, and 24 hours as well as a decrease in IL-1β at 24 hours during ECMO. The TGF-β 1 levels were significantly higher in pulsatile circuits from 2 hours to 24 hours. The changes in IL-6 and IL-8 levels were insignificant.Conclusion: The modification of pulsatility in ECMO generates more hemodynamic energies and attenuates inflammatory responses as compared to the conventional non-pulsatile ECMO.Keywords: pulsatile flow, extracorporeal membrane oxygenation, inflammatory response, COVID-19

Extra Corporeal membrane oxygenation (ECMO) is one of the most advanced forms of life support therapy in the Intensive Care Unit. It relies on the principle where an external artificial circuit carries venous blood from the patient to a gas exchange device (oxygenator) within which blood becomes enriched with oxygen and has carbon dioxide removed. The blood is then returned to the patient via a central vein or an artery. The goal of ECMO is to provide a physiologic milieu for recovery in refractory cardiac/respiratory failure. The technology is not a definitive treatment for a disease, but provides valuable time for the body to recover. In that way it can be compared to a bridge, where patients are initiated on ECMO as a bridge to recovery, bridge to decision making, bridge to transplant or bridge to diagnosis. The use of this modality in children is not backed by a lot of randomized controlled trials, but the use has increased dramatically in our country in last 10 years. This article is not intended to provide an in-depth overview of ECMO, but outlines the basic principles that a pediatric intensive care physician should know in order to manage a kid on ECMO support.

Extracorporeal carbon dioxide removal (ECCO2R) is increasingly considered a viable therapeutic approach in the management of hypercapnic lung failure to avoid intubation or to allow lung-protective ventilator settings. This study aimed to analyze efficacy and safety of a minimal-invasive ECCO2R device, the Homburg lung. The Homburg lung is a pump-driven system for veno-venous ECCO2R with ¼″ tubing and a 0.8 m surface oxygenator. Vascular access is usually established via a 19F/21 cm bilumen cannula in the right internal jugular vein. For this work, we screened patient registries from two German centers for patients who underwent ECCO2R with the Homburg lung because of hypercapnic lung failure since 2013. Patients who underwent extracorporeal membrane oxygenation before ECCO2R were excluded. Patients who underwent ECCO2R more than one time were only included once. In total, 24 patients (aged 53.86 ± 12.49 years; 62.5% male) were included in the retrospective data analysis. Ventilatory failure occurred because of chronic obstructive pulmonary disease (50%), cystic fibrosis (16.7%), acute respiratory distress syndrome (12.5%), and other origins (20.8%). The system generated a blood flow of 1.18 ± 0.23 liters per minute (lpm). Sweep gas flow was 3.87 ± 2.97 lpm. Within 4 hours, paCO2 could be reduced significantly from 82.05 ± 15.57 mm Hg to 59.68 ± 12.27 mm Hg, thereby, increasing pH from 7.23 ± 0.10 to 7.36 ± 0.09. Cannulation-associated complications were transient arrhythmia (1/24 patients) and air embolism (1/24). Fatal complications did not occur. In conclusion, the Homburg lung provides effective carbon dioxide removal in hypercapnic lung failure. The cannulation is a safe procedure, with complication rates comparable to those in central venous catheter implantation.

Objective: In this study, we aimed to share our first experiences about the extracorporeal membrane oxygenator (ECMO) system that we have just started to use and compare it with the system we used before. Methods: Between January 2019 and December 2019, 27 consecutive patients under the age of 18 who were operated for congenital heart disease and needed ECMO support were retrospectively analyzed. İn this period The Medos Deltastream diagonal pump and Sorin Revolution ECMO systems were used. Results: Successful wean was observed in six (42.9%) patients in Medos ECMO group and two (15.4%) in Sorin ECMO group. Five (35.7%) patients discharged in the Medos ECMO group. In Sorin ECMO group all patients died. The difference between the groups in terms of the number of patients discharged was statistically significant (p = 0.02). Lactate clearance was 14 hours in Medos ECMO and 48 hours in Sorin ECMO (p = 0.02). Conclusion: In this study, in which we shared our first experiences regarding the first use of the Sorin ECMO system in the postcardiac pediatric patient group, we observed slower lactate clearance, lower succesful wean and higher mortaly rates. Therefore, this should be taken into account during the use of this system.

Therapeutic plasma exchange in children is increasingly recognized as a life-saving treatment and is challenged by some technical considerations. As extracorporeal membrane oxygenation has been used for nearly half a century for refractory reversible respiratory and/or cardiac failure in both pediatric and adult populations, it may serve as an extracorporeal platform for therapeutic plasma exchange. It is most commonly described in patients with sepsis with multiple organ failure or thrombocytopenia associated multi organ failure. Additional pathophysiological processes of inflammatory and immunological storms might benefit from the combination of extracorporeal membrane oxygenation and plasma exchange. This is a nonmethodological review of English-language reports of therapeutic plasma exchange performed in patients supported by extracorporeal membrane oxygenation, both pediatric and adult, searching six databases, MEDLINE, Clinical Key, GOOGLE SCHOLAR, CINAHL, Cochrane library, and EMBASE.

Background Extracorporeal membrane oxygenation (ECMO) support can be life-saving in critically ill COVID-19 patients. However, there are many complications associated with this procedure, including Heparin-induced thrombocytopenia (HIT.) Despite its rarity in ECMO cases, HIT can lead to devastating consequences and is difficult to manage. Case presentation In this report, we present a case of a COVID-19 patient on ECMO support who was diagnosed with HIT and required intensive treatment. Initially, HIT was only suspected due to newly-developed thrombocytopenia and oxygenator dysfunction, with thrombi observed later. Regarding his treatment, since there was no recommended replacement to heparin available to us at the time of diagnosis, we decided to use rivaroxaban temporarily. No adverse events were recorded during that period. The patient was able to make a full recovery. Conclusion HIT may jeopardize patient’s care during ECMO. As COVID-19 may bring about a surge in the number of patients requiring ECMO support, we need consented guidance to optimize treatment in this specific situation.

Summary. The study highlights a method of treatment extracorporeal circuit with «adaptation composition» (AdC) for the reduction of negative impact on state of erythrocytes. Materials and methods. A total of 90 patients were enrolled, they were divided into two groups. The group 1 (45 patients, 39/6 male/female) included patients who underwent surgical procedures without treatment of an extracorporeal circuit with AdC. The group 2 (45 patients, 39/6 male/female) included patients who underwent surgery with the treatment of an extracorporeal circuit with AdC. According to the study protocol, patient blood was sampling for complete blood cell count (CBC) and erythrocyte morphology at 4 stages of surgery: before surgery, at 10 min. CPB-time, at 60 min. CPB-time and after separation from CPB. Results. The albumin of AdC creates a protective nanolayer on the surface of the oxygenator membrane and tubes. There were no statistically significant differences of parameters in the groups before CPB. Level of Ht 2 (group 2) at 60 min CPB-time and after CPB, were lower than Ht 1 (group 1) (p=0.021 and p=0.035 correspondingly) because MCV1 was higher (р=0.025 and p

Venovenous and venoarterial extracorporeal membrane oxygenation (ECMO) remains a crucial lifesaving therapy for critically ill neonates with severe cardiorespiratory failure. Both the roller pump as well as the centrifugal pump are safe and efficient systems, and some red blood cell breakdown and hemolysis occurs in all ECMO systems. The roller pump functions by gravity whereas the centrifugal pump promotes the flow of blood by a magnetically driven spinning rotor to generate negative pressure. Extracorporeal Life Support Organization data indicate a significant increase in intravascular hemolysis in neonatal and pediatric patients receiving ECMO when the centrifugal pump is used compared with its use in adults. Risk factors for developing hemolysis during ECMO are small cannula size, high negative inlet pressure in the pump head, and thrombosis in the pump head and oxygenator. Excessive red blood cell breakdown and release of plasma free hemoglobin (pfHb) saturate physiologic neutralizing mechanisms such as haptoglobin and hemopexin. The increase in pro-oxidant and proinflammatory pfHb levels causes endothelial dysfunction in a dose-dependent manner. Hemolysis also increases the risk of in-hospital morbidities such as renal injury, direct hyperbilirubinemia, and thrombosis without an increase in mortality in patients receiving ECMO. Hemolysis is an unavoidable side effect of current ECMO technology and there are no approved treatments or treatment guidelines for the neonatal population. Therefore, increased vigilance, recognition of the severity of the hemolytic process, and prompt management are essential to prevent severe endothelial injury leading to proinflammatory and prothrombotic events.

Left ventricular (LV) distention and pulmonary congestion are major complications inherent to venoarterial extracorporeal membrane oxygenation (ECMO). This study aimed to quantitatively compare the hemodynamic differences between common circulatory unloading methods for ECMO. Ten circulatory unloading techniques were evaluated on a mock circulatory loop simulating acute LV failure supported by ECMO. Simulated unloading techniques included: surgical and percutaneous pulmonary artery (PA) venting, surgical left atrial venting, surgical and percutaneous LV venting, atrial septal defect, partial support ventricular assist device, intraaortic balloon pump, and temporary VAD with inline oxygenator (tVAD). The most LV unloading occurred with the surgically placed LV vent and tVAD, which reduced LV end-diastolic volume from 295 to 167 ml and 82 ml, respectively. Meanwhile, the PA surgical vent was the most effective at reducing mean PA pressure from 21.0 to 10.6 mm Hg, and the tVAD was most effective at reducing left atrial pressure from 13.3 to 4.4 mm Hg. The major limitation of this study was the use of a mock circulatory loop, which simulated lower left atrial pressure than is typically seen clinically. This study identified clinically significant hemodynamic variability between the different circulatory unloading techniques evaluated. However, the applicability of these techniques will vary with different patient disease etiology. Further studies on ECMO unloading will help to quantify hemodynamic benefits and establish treatment guidelines.

Purpose: Purpose: Condensation that clogs the hollow fibers of the oxygenation and accumulation of plasma leaks reduces oxygenated lung capacity. In this study, artificial We evaluated whether monitoring changes in lung gas inlet pressure was a way to predict these complications. Methods: Changes in gas inlet pressure and oxygenation capacity of three different prostheses (BIOCUBE6000, EXCELUNG PRIME, and Capiox-LX) Evaluated the relationship. When simulating plasma leakage using BIOCUBE6000, sodium dodecyl sulfate (SDS) (1%, 0.1%, A solution of 0.01%, and RO water) reduced surface tension. During 120 minutes of circulation, changes in gas inlet pressure and leakage from the membrane into the gas flow path The amount of fluid was measured. Results: There was a significant negative correlation between the gas inlet pressure changes and the oxygenation capacity of all three oxygenators (BIOCUBE6000: R2 = 0.957, EXCELUNG PRIME: R2 = 0.946, Capiox-LX: R2 = 0.878). After 120 min of SDS solution circulation using the BIOCUBE6000, both the gas inlet pressure and the volume of fluid leaking from the membrane into the gas flow path increased in proportion to the SDS solution concentration: RO water (0.56 ± 0.11 mmHg and 16.67 mL ± 0.94 mL), 0.01% SDS (0.98 ± 0.11 mmHg and 23.3 ± 0.47 mL,) 0.1% SDS (1.64 ± 0.21 mmHg and 29.0 ± 1.63 mL), and 1%SDS (14.3 ± 0.27 mmHg and 36.7 ± 0.47 mL) (n = 3). Conclusion: This study confirmed that monitoring the gas inlet pressure changes of an oxygenator during ECMO is clinically useful.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) serves as a conventional short-term mechanical circulatory assist to support heart and lung functions. The short-term ventricular assist devices (ST-VAD) can, on the contrary, offer only circulatory support. A combination of VAD and oxygenator (Oxy-VAD) could help overcome this potential disadvantage. This is a retrospective case note study of patients supported on ST-VAD which required adding an oxygenator for extra respiratory support. The oxygenator was introduced in the ST-VAD circuit, either on the left or the right side. Twenty-two patients with the etiology of refractory cardiogenic shock in decompensation were supported on Oxy-VAD between years 2009 and 2019 at tertiary care . All patients were classified into class-I INTERMACS with a mean SOFA Score of 14 ± 2.58. 86.4% of patients were already on mechanical support pre-ST-VAD implant, 80% on VA-ECMO. The BiVAD implant accounted for 63.6%, followed by LVAD and RVAD with 27.3% and 9.1%. Mean duration of the ST-VAD was 8.5 days. The oxygenator was introduced in 14 RVAD and 8 LVAD circuits. The oxygenator was successfully weaned in 54.5% while ST-VAD was explanted in 31.8%. Discharge to home survival was 22.7%. Oxy-VAD proves a viable, and probably, a better option to VA-ECMO in acute cardiorespiratory decompensation. It offers organ-specific tailor-made support to the right and/or left heart and/or lungs. While on Oxy-VAD support, each organ performance can be assessed independently, and the assistance of the specifically improved organ can be weaned off without discontinuing the support for the rest.

Objectives The main objective of the study was to determine the prevalence of venous thromboembolism events in patients infected with severe acute respiratory syndrome coronavirus 2 requiring venovenous extracorporeal membrane oxygenation. The secondary objective was to compare venous thromboembolism events and coagulation variables in patients requiring venovenous extracorporeal membrane oxygenation according to the pathogen. Design Retrospective observational analysis at a single center. Setting Tertiary referral university teaching hospital. Patients Patients with severe acute respiratory syndrome coronavirus 2-related severe acute respiratory distress syndrome requiring venovenous extracorporeal membrane oxygenation therapy with an injected CT scan performed after extracorporeal membrane oxygenation retrieval. Interventions None. Measurements and main results We included 13 severe acute respiratory syndrome coronavirus 2 patients requiring venovenous extracorporeal membrane oxygenation. All of these patients experienced venous thromboembolism: 10 patients (76.9%) had isolated cannula-associated deep vein thrombosis, two patients (15.4%) had isolated pulmonary embolism, and one patient (7.7%) had both cannula-associated deep vein thrombosis and pulmonary embolism. Eleven patients (84.6%) had cannula-associated deep vein thrombosis. A jugular associated cannula-associated deep vein thrombosis was identified in seven patients (53.8%), a femoral associated cannula-associated deep vein thrombosis was identified in 10 patients (76.9%), and six patients (46.2%) had both femoral and jugular cannula-associated deep vein thrombosis. A pulmonary embolism was found in three patients (23.1%). No patient had central venous catheter-related deep vein thrombosis. One patient had thrombotic occlusion of the centrifugal pump, and one had oxygenator thrombosis requiring circuit replacement. Three patients (23.1%) had significant bleeding. Three patients (23.1%) had laboratory-confirmed heparin-induced thrombocytopenia, and all of them developed cannula-associated deep vein thrombosis. These three patients had femoral cannula-associated deep vein thrombosis, and two had an oxygenator or pump thrombosis. The mean activated partial thromboplastin time ratio was higher in the severe acute respiratory syndrome coronavirus 2 group than in the influenza group and the community-acquired pneumonia group (1.91 vs 1.48 vs 1.53; p = 0.001), which was also found in regard to the percentage of patients with an activated partial thromboplastin time ratio greater than 1.8 (47.8% vs 20% vs 20.9%; p = 0.003) and the mean prothrombin ratio (86.3 vs 61.6 vs 67.1; p = 0.003). There was no difference in baseline characteristics or venous thromboembolism events. Conclusions We report a 100% occurrence of venous thromboembolism in critically ill patients supported by venovenous extracorporeal membrane oxygenation for severe acute respiratory syndrome coronavirus 2-related acute respiratory distress syndrome using CT scan imaging despite a high target and close monitoring of anticoagulation.

Objectives: To assess the in vivo hemodynamic effects on the pressure overloaded right ventricle of RAS-Q® technology, the world’s first gas exchanger with a fully integrated compliance. Methods: In six acute in vivo trials RAS-Q was implanted in sheep between the pulmonary artery and left atrium. Right ventricular pressure overload was induced by pulmonary artery banding. Pressures and flows were recorded in baseline, moderate and severe pulmonary hypertension conditions. In one trial, RAS-Q was benchmarked against the pediatric Quadrox-i®. Results: With 1.00 and 1.17 L/min, RAS-Q delivered 31% and 39% of the total cardiac output in moderate and severe pulmonary hypertension, respectively. Pulmonary artery pressures and mean pulmonary artery pressure/mean arterial blood pressure ratio successfully decreased, implying a successful right ventricular unloading. Cardiac output was restored to normal levels in both pulmonary hypertension conditions. With both devices in parallel, RAS-Q provided three times higher flow rates and a 10 times higher pressure relief, compared to the pediatric Quadrox-i. Conclusion: A gas exchanger with a fully integrated compliance better unloads the right ventricle compared to a non-compliant gas exchanger and it can restore cardiac output to normal levels in cases of severe pulmonary hypertension.

It is very important to observe all the parameters of cardioplegia when protecting myocardium during cardiac surgery. To perform this task, it is necessary to have clear understanding of properties of the elements of the extracorporeal circuit of cardiopulmonary bypass. The objective : to develop a test model and using it to evaluate technical capabilities of blood cardioplegic system reducing the filling volume of the heat exchange chamber and the system supplying solution to the myocardium. Subjects and methods . A model of a neonatal cardiopulmonary bypass circuit was tested, it included an oxygenator and the cardioplegic system with a 7-ml heat exchange chamber; changes in the pressure and temperature in key nodes of the extracorporeal and cardioplegic circuits were assessed when the pump velocity, ambient temperature and fluid temperature in the main circuit were changed. Results . This modification provides a wide range of liquid volumetric velocities. Maintaining the selected variant of blood cardioplegia and safe pressure within the cardioplegic circuit is ensured at the perfusion rate of up to 350 ml/min. With normothermal circulation and air temperature in the operating room of 23°C, parameters of the cardioplegic circuit and solution delivery system allows maintaining the solution temperature within the range from 16 to 19°C. When the solution is cooled in a heat exchanger down to 4°C, the temperature of the final cardioplegic solution is maintained within 12-17°C; and with normothermal perfusion, air temperature in the operating room of 15°C and the solution temperature in the heat exchange chamber of 4°C, the temperature of the final cardioplegic solution can be within 6‒13°C. With perfusion in the mode of moderate hypothermia (32°C), air temperature in the operating room 15°C and temperature in the heat exchange chamber 4°C, the final cardioplegic solution can be delivered at the temperature from 5 to 9°C. Conclusions . The proposed test model allows investigating aimed to find out additional characteristics of the cardioplegic circuit. Ambient air temperature, cardioplegic pump velocity and main circuit fluid temperature are the main factors influencing the final cardioplegic solution temperature. When using the studied variant of the cardioplegic circuit assembly, the maintenance of the selected variant of blood cardioplegia and safe pressure inside the cardioplegic circuit are ensured at a perfusion rate of up to 350 ml/min.

Rationale: Mesenchymal stromal cell (MSC) therapy is a promising intervention for acute respiratory distress syndrome (ARDS), although trials to date have not investigated its use alongside extracorporeal membrane oxygenation (ECMO). Recent preclinical studies have suggested that combining these interventions may attenuate the efficacy of ECMO.Objectives: To determine the safety and efficacy of MSC therapy in a model of ARDS and ECMO.Methods: ARDS was induced in 14 sheep, after which they were established on venovenous ECMO. Subsequently, they received either endobronchial induced pluripotent stem cell-derived human MSCs (hMSCs) (n = 7) or cell-free carrier vehicle (vehicle control; n = 7). During ECMO, a low Vt ventilation strategy was employed in addition to protocolized hemodynamic support. Animals were monitored and supported for 24 hours. Lung tissue, bronchoalveolar fluid, and plasma were analyzed, in addition to continuous respiratory and hemodynamic monitoring.Measurements and Main Results: The administration of hMSCs did not improve oxygenation (PaO2/FiO2 mean difference = -146 mm Hg; P = 0.076) or pulmonary function. However, histological evidence of lung injury (lung injury score mean difference = -0.07; P = 0.04) and BAL IL-8 were reduced. In addition, hMSC-treated animals had a significantly lower cumulative requirement for vasopressor. Despite endobronchial administration, animals treated with hMSCs had a significant elevation in transmembrane oxygenator pressure gradients. This was accompanied by more pulmonary artery thromboses and adherent hMSCs found on explanted oxygenator fibers.Conclusions: Endobronchial hMSC therapy in an ovine model of ARDS and ECMO can impair membrane oxygenator function and does not improve oxygenation. These data do not recommend the safe use of hMSCs during venovenous ECMO.

Introduction: Extracorporeal membrane oxygenation circuit performance can be compromised by oxygenator thrombosis. Stagnant blood flow in the oxygenator can increase the risk of thrombus formation. To minimize thrombogenic potential, computational fluid dynamics is frequently applied for identification of stagnant flow conditions. We investigate the use of computed tomography angiography to identify flow patterns associated with thrombus formation. Methods: A computed tomography angiography was performed on a Quadrox D oxygenator, and video densitometric parameters associated with flow stagnation were measured from the acquired videos. Computational fluid dynamics analysis of the same oxygenator was performed to establish computational fluid dynamics–based flow characteristics. Forty-one Quadrox D oxygenators were sectioned following completion of clinical use. Section images were analyzed with software to determine oxygenator clot burden. Linear regression was used to correlate clot burden to computed tomography angiography and computational fluid dynamics–based flow characteristics. Results: Clot burden from the explanted oxygenators demonstrated a well-defined pattern, with the largest clot burden at the corner opposite the blood inlet and outlet. The regression model predicted clot burden by region of interest as a function of time to first opacification on computed tomography angiography (R2 = 0.55). The explanted oxygenator clot burden map agreed well with the computed tomography angiography predicted clot burden map. The computational fluid dynamics parameter of residence time, when summed in the Z-direction, was partially predictive of clot burden (R2 = 0.35). Conclusion: In the studied oxygenator, clot burden follows a pattern consistent with clinical observations. Computed tomography angiography–based flow analysis provides a useful adjunct to computational fluid dynamics–based flow analysis in understanding oxygenator thrombus formation.

Introduction: To determine the oxygenator impact on alterations of voriconazole in a contemporary neonatal/pediatric (1/4 inch) and adolescent/adult (3/8 inch) extracorporeal membrane oxygenation circuit including the Quadrox-i® oxygenator. Methods: Simulated closed-loop extracorporeal membrane oxygenation circuits (1/4 and 3/8 inch) were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. In addition, 1/4- and 3/8-inch circuits were also prepared without an oxygenator in series. A one-time dose of voriconazole was administered into the circuits, and serial pre- and post-oxygenator concentrations were obtained at 5 minutes, 1, 2, 3, 4, 5, 6, and 24 hour time points. Voriconazole was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation Results: For the 1/4-inch circuit, there was an approximate mean of 64-67% voriconazole loss with the oxygenator in series and mean of 15-20% voriconazole loss without an oxygenator in series at 24 hours. For the 3/8-inch circuit, there was an approximate mean of 44-51% voriconazole loss with the oxygenator in series and a mean of 8-12% voriconazole loss without an oxygenator in series at 24 hours. The reference voriconazole concentrations remained relatively constant during the entire study period demonstrating that the drug loss in each size of the extracorporeal membrane oxygenation circuit with or without an oxygenator was not a result of spontaneous drug degradation. Conclusion: This ex vivo investigation demonstrated substantial voriconazole loss within an extracorporeal membrane oxygenation circuit with an oxygenator in series with both sizes of the Quadrox-i oxygenator at 24 hours and no significant voriconazole loss in the absence of an oxygenator. Further evaluations with multiple dose in vitro and in vivo investigations are needed before specific voriconazole dosing recommendations can be made for clinical application with extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) requires constant management of coagulation. Whereas unfractionated heparin remains the anticoagulant of choice, experienced centers report high bleeding rates. Biocompatibility of the extracorporeal circuit enables management of anticoagulation with subcutaneous low-molecular-weight heparins only. The aim of this study was to evaluate the safety and feasibility of anticoagulation with subcutaneous nadroparin compared with unfractionated heparin during respiratory ECMO in patients. We assessed for thrombotic complications and number of bleeding and life-threatening bleeding events. Additionally, we evaluated the change in resistance to flow in the oxygenator and the number of transfused blood products. Nadroparin and unfractionated heparin were comparable in terms of number of bleeding (34 vs. 53%; p = 0.12), life-threatening bleeding (2.8 vs. 9.3%; p = 0.26) events, and daily red blood cell transfusion rates (0.79 units/patient/day vs. 0.71 units/patient/day in nadroparin group; p = 0.87) during respiratory ECMO. The relative change in resistance to flow in the oxygenator was similar between groups (8.03 vs. 11.6%; p = 0.27). Nadroparin seemed equivalent to unfractionated heparin in the number of thrombotic and hemorrhagic events as well as in the daily red blood cell transfusion rates during venovenus-ECMO.

While hypercapnia is typically well treated with modern membrane oxygenators, there are cases where respiratory acidosis persists despite maximal extracorporeal membrane oxygenation support. To better understand the physiology of gas exchange within the membrane oxygenator, CO2 clearance within an adult Maquet Quadrox-iD oxygenator was evaluated at varying blood CO2 tensions and V/Q ratios in an ex vivo extracorporeal membrane oxygenation circuit. A closed blood-primed circuit incorporating two Maquet Quadrox-iD oxygenators in series was attached to a Maquet PLS Rotaflow pump. A varying blend of CO2 and air was connected to the first oxygenator to provide different levels of pre-oxygenator blood CO2 levels (PvCO2) to the second oxygenator. Varying sweep gas flows of 100% O2 were connected to the second oxygenator to provide different V/Q ratios. Exhaust CO2 was directly measured, and then VCO2 and oxygenator dead space fraction (VD/VT) were calculated. VCO2 increased with increasing gas flow rates with plateauing at V/Q ratios greater than 4.0. Exhaust CO2 increased with PvCO2 in a linear fashion with the slope of the line decreasing at high V/Q ratios. Oxygenator dead space fraction varied with V/Q ratio—at lower ratios, dead space fraction was 0.3-0.4 and rose to 0.8-0.9 at ratios greater than 4.0. Within the Maquet Quadrox-iD oxygenator, CO2 clearance is limited at high V/Q ratios and correlated with elevated oxygenator dead space fraction. These findings have important implications for patients requiring high levels of extracorporeal membrane oxygenation support.

Extracorporeal membrane oxygenation (ECMO) is a well-known therapy for refractory cardiac and respiratory failure. Stem cell therapy has been investigated as an adjunctive treatment for use during ECMO, but little is known about the viability of stem cells during ECMO support. We evaluated the viability and activity of mesenchymal stem cells (MSCs) in ex vivo circulation (EVC) conditions. The experimental groups were divided into two subgroups: EVC with oxygenator (OXY group) and EVC without oxygenator (Non-OXY group). Mesenchymal stem cells (1.0 × 10) were injected into the EVC system. Cell counting, a lactate dehydrogenase (LDH) cytotoxicity assay, and the mitochondrial functions of viable MSCs were analyzed. The post-EVC oxygen consumption rate (OCR) was significantly lower than the pre-EVC OCR, regardless of whether the oxygenator was used. The LDH levels were significantly higher in the OXY group than in the Non-OXY group. The cellular loss was mainly due to lysis of the cells whereas the loss of cellular activity was attributed to the nonphysiologic condition itself, as well as the oxygenator. We concluded that direct infusion of MSCs during ECMO support did not serve as adjunctive therapy. Further studies are needed to improve the viability in an ECMO setting.

Objectives To determine the oxygenator impact on alterations of ceftolozane/tazobactam in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extracorporeal membrane oxygenation circuit including the Quadrox-i oxygenator (Maquet, Wayne, NJ). Design A 1/4-inch and 3/8-inch, simulated closed-loop extracorporeal membrane oxygenation circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. Additionally, 1/4-inch and 3/8-inch circuits were also prepared without an oxygenator in series. A one-time dose of ceftolozane/tazobactam was administered into the circuits and serial preoxygenator and postoxygenator concentrations were obtained at 5 minutes, 1, 2, 3, 4, 5, 6, and 24-hour time points. Ceftolozane/tazobactam was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation SETTING:: A free-standing extracorporeal membrane oxygenation circuit. Patients None. Interventions Single-dose administration of ceftolozane/tazobactam into closed-loop extracorporeal membrane oxygenation circuits prepared with and without an oxygenator in series with serial preoxygenator, postoxygenator, and reference samples obtained for concentration determination over a 24-hour study period. Measurements and main results For the 1/4-inch circuit, there was approximately 92% ceftolozane and 22-25% tazobactam loss with the oxygenator in series and 19-30% ceftolozane and 31-34% tazobactam loss without an oxygenator in series at 24 hours. For the 3/8-inch circuit, there was approximately 85% ceftolozane and 29% tazobactam loss with the oxygenator in series and 25-27% ceftolozane and 23-26% tazobactam loss without an oxygenator in series at 24 hours. The reference ceftolozane and tazobactam concentrations remained relatively constant during the entire study period demonstrating the drug loss in each size of the extracorporeal membrane oxygenation circuit with or without an oxygenator was not a result of spontaneous drug degradation. Conclusions This ex vivo investigation demonstrated substantial ceftolozane loss within an extracorporeal membrane oxygenation circuit with an oxygenator in series with both sizes of the Quadrox-i oxygenator at 24 hours and significant ceftolozane loss in the absence of an oxygenator. Tazobactam loss was similar regardless of the presence of an oxygenator. Further evaluations with multiple dose in vitro and in vivo investigations are needed before specific drug dosing recommendations can be made for clinical application with extracorporeal membrane oxygenation.

OBJECTIVE: The roles of the large membrane surface of the oxygenator and the high mechanical shear stress (HMSS) of the pump in the ECMO circuit were examined under a pediatric support setting. METHODS: A clinical centrifugal pump and a pediatric oxygenator were used to construct the ECMO circuit. An identical circuit without the oxygenator was constructed for comparison. Fresh human blood was circulated in the two circuits for 4 hours under the identical pump speed and flow. Blood samples were collected hourly for blood damage assessment, including platelet activation, generation of platelet-derived microparticles (PDMP), losses of key platelet hemostasis receptors (glycoprotein (GP) Ibα (GPIbα) and GPVI) and high molecular weight multimers (HMWM) of von Willebrand factor (VWF) and plasma free hemoglobin (PFH). Platelet adhesion on fibrinogen, VWF and collagen was further examined. RESULTS: The levels of platelet activation and generation of PDMP and PFH exhibited an increasing trend with circulation time while the expression levels of GPIbα and GPVI receptors on the platelet surface decreased. Correspondingly, the platelets in the blood samples exhibited increased adhesion capacity to fibrinogen and decreased adhesion capacities on VWF and collagen with circulation time. Loss of HMWM of VWF occurred in both circuits. No statistically significant differences were found in all the measured parameters for blood damage and platelet adhesion function between the two circuits. CONCLUSIONS: The results indicate that HMSS from the pump played a dominant role in blood damage associated with ECMO and the impact of the large surface of the oxygenator on blood damage was insignificant.

The recent demonstration of normal development of preterm sheep in an artificial extrauterine environment has renewed interest in artificial placenta (AP) systems as a potential treatment strategy for extremely preterm human infants. However, the feasibility of translating this technology to the human preterm infant remains unknown. Here we report the support of 13 preterm fetal pigs delivered at 102 ± 4 days (d) gestation, weighing 616 ± 139 g with a circuit consisting of an oxygenator and a centrifugal pump, comparing these results with our previously reported pumpless circuit (n = 12; 98 ± 4 days; 743 ± 350 g). The umbilical vessels were cannulated, and fetuses were supported for 46.4 ± 46.8 h using the pumped AP versus 11 ± 13 h on the pumpless AP circuit. Upon initiation of AP support on the pumped system, we observed supraphysiologic circuit flows, tachycardia, and hypertension, while animals maintained on a pumpless AP circuit exhibited subphysiologic flows. On the pumped AP circuit, there was a progressive decline in umbilical vein (UV) flow and oxygen delivery. We conclude that the addition of a centrifugal pump to the AP circuit improves survival of preterm pigs by augmenting UV flow through the reduction of right ventricular afterload. However, we continued to observe the development of heart failure within a matter of days.

Η ιδέα της εξωσωματικής κυκλοφορίας οδήγησε την επιστήμη της καρδιοχειρουργικής σε σπουδαία ιατρικά επιτεύγματα, με την ανάπτυξη της μηχανής εξωσωματικής κυκλοφορίας να αποτελεί το κύριο μέσο για τη διενέργεια επιτυχών χειρουργείων ανοικτής καρδιάς με ασφάλεια και αποτελεσματικότητα. Σκοπός της παρούσας μελέτης είναι η ιστορική ανασκόπηση της εξωσωματικής κυκλοφορίας και οι πιθανότητες μέσω της ραγδαίας εξέλιξης των κλινικών πρακτικών για περαιτέρω πρόοδο και ανάπτυξη. Παρουσιάζεται αρχικά η έννοια της καρδιοπνευμονικής παράκαμψης, οι μέθοδοι μέσω των οποίων πραγματοποιείται η εξωσωματική κυκλοφορία και η αρκετά ενδιαφέρουσα ιστορική της εξέλιξη, καθώς γίνεται αναφορά στις τροποποιήσεις που πραγματοποιήθηκαν στο σύντομο διάστημα που εφαρμόζεται η καρδιοπνευμονική παράκαμψη στην καρδιοχειρουργική. Στα επόμενα κεφάλαια αναλύονται βασικά μέρη της μηχανής, τα οποία είναι απαραίτητα για τη σωστή λειτουργία της συσκευής και για την επιτυχή έκβαση της καρδιοχειρουργικής επέμβασης. Αναφέρονται οι τύποι των συσκευών οξυγόνωσης και άντλησης του αίματος, οι οποίες είναι υπεύθυνες για τον καθαρισμό του αίματος από το διοξείδιο του άνθρακα και τον εμπλουτισμό του με οξυγόνο και τη μετακίνησή του με τη βοήθεια αντλιών από τον ασθενή προς τη μηχανή και την επαναπροώθησή του σε αυτόν, με την μικρότερη πιθανότητα τραυματισμού του αίματος. Στο τελευταίο κεφάλαιο παρουσιάζεται η μηχανή εξωσωματικής οξυγόνωσης με μεμβράνη (ECMO), της οποίας η λειτουργία βασίζεται στη μηχανή εξωσωματικής κυκλοφορίας του Dr. Γκίμπον, ο οποίος θεωρείται “πατέρας” της εξωσωματικής κυκλοφορίας και η χρήση της για την υποβοήθηση της καρδιοπνευμονικής λειτουργίας ασθενών σε μονάδες εντατικής θεραπείας μέχρι να μπορέσει το δικό τους καρδιαγγειακό ή αναπνευστικό σύστημα να διατελέσει τις λειτουργίες που τους αναλογούν, αλλά και στην αντιμετώπιση σύγχρονων ασθενειών, όπως ο Covid 19., The idea of extracorporeal circulation led the science of cardiac surgery to great medical achievements, with the development of the extracorporeal circulation machine being the main means for performing successful open heart surgeries safely and effectively.The purpose of this study is the historical review of extracorporeal circulation and the possibilities through the rapid evolution of clinical practices for further progress and development.The concept of cardiopulmonary bypass is first introduced, the methods through which the extracorporeal circulation takes place and its quite interesting historical development, as reference is made to the modifications made in the short time that cardiopulmonary bypass is applied in cardiac surgery. In the following chapters, key parts of the machine are analyzed, which are necessary for the proper operation of the device and for the successful outcome of the heart surgery. Indicate the types of oxygenation and blood pumping devices that are responsible for purifying the blood of carbon dioxide and enriching it with oxygen and moving it with the help of pumps from the patient to the machine and returning it to him, with the least chance of blood injury. The last chapter presents the extracorporeal oxygenation machine with membrane (ECMO), whose operation is based on the extracorporeal circulation machine of Dr. Gibbon, who is considered the "father" of extracorporeal circulation and its use to assist patients with cardiopulmonary function in intensive care units until their own cardiovascular or respiratory system can perform their functions, but also in the treatment of modern diseases , such as Covid 19.

Einleitung: Durch den Einsatz von Pulsation während der extrakorporalen Zirkulation ist eine verbesserte Durchblutung kritischer Organe möglich. Dies liegt vor allem an der durch die Pulsation zusätzlich erzeugten hämodynamischen Energie. Das Ziel der Doktorarbeit war es, verschiedene Komponenten der minimal invasiven extrakorporalen Zirkulation (MiECC) hinsichtlich der Übertragung hämodynamischer Energie zu testen. Methoden: Als Pseudopatient diente ein Aortenperfusionsmodell, das eine Silikonaorta besitzt, welche die Geometrie und Compliance einer menschlichen Aorta hat. Die MiECC bestand aus einer Diagonalpumpe, einem Oxygenator und Schläuchen als Verbindung zwischen den Komponenten. Für den Vergleich der Schlaucharten wurden entweder PVC- oder Silikonschläuche in der EKZ verwendet und um den Einfluss des Pseudopatienten darzustellen wurden die Messungen einmal mit starrem und einmal mit physiologischem Aortenmodell durchgeführt. Die Messungen wurden bei 37°C erhoben. Zudem wurden 5 verschiedene Oxygenatoren in der MiECC verglichen. Die Messungen hierfür wurden bei 26,9°C und 37°C erhoben, um die Auswirkungen bei hypothermen und normothermen Patienten darzustellen. Zuletzt wurden die Pulsationsparameter systematisch verändert, um eine möglichst hohe Energieübertragung auf den Pseudopatienten zu erreichen. Druckabfall, energy equivalent pressure (EEP) und surplus hemodynamic energy (SHE) wurden aus erhobenen Druck- und Flusskurven berechnet. Ergebnisse: Bei Verwendung der PVC-Schläuche und dem physiologischen Aortenmodell konnte bei allen Flussraten eine signifikant höhere SHE gemessen werden. Mit dem starren Modell wurde dieser Unterschied erst ab 1,5 l·min-1 signifikant. Beim starren Modell konnten zudem bis zu 6 Prozentpunkte höhere SHE-Werte gemessen werden. Beim Quadrox-i und Affinity Fusion wurde der geringste Druckabfall gemessen. Der des Inspire 8FM war signifikant am höchsten und fast doppelt so hoch, wie der des Quadrox-i und Affinity Fusion. Bei allen Oxygenatoren fand sich das Maximum der gemessenen SHE bei 1,5 bis 2 l·min-1. Für die Erzeugung von Pulsation wurde die höchste SHE bei einer Drehzahldifferenz von 2500 Umdrehungen·min-1, einer Frequenz von 40 min-1 und bei einer Flussrate bis 1,5 l·min-1 bei 30%, ab 2 l·min-1 bei 40% Systolenanteil gemessen. Kombinierte man diese optimalen Einstellungen wurde die SHE fast verdreifacht. Das Maximum wurde allerdings in eine geringere Flussrate verschoben und auch bei 3,5 l·min-1 konnte nur eine SHE von 5% gemessen werden. Schlussfolgerung: Die Compliance des Perfusionsmodells hat einen großen Einfluss auf die Messergebnisse. PVC-Schläuche übertragen die hämodynamische Energie in dem verwendeten Perfusionsmodell besser als flexible Silikon-Schläuche. Hinsichtlich der Energieübertragung spielt die Wahl des Oxygenators keine Rolle, die Unterschiede im Druckabfall müssen aber beachtet werden. Durch gute Kombination der Pulsationsparameter ist es möglich mehr Energie in höheren Flussraten zu übertragen. Die Weiterentwicklung der Pumpen ist notwendig, um die Übertragung in den, für den Erwachsenen notwendigen, höheren Flussraten zu optimieren.

BACKGROUND Cefepime is a first-line therapy for gram-negative infections in children on extracorporeal membrane oxygenation. Cefepime pharmacokinetics (PK) in children on extracorporeal membrane oxygenation still needs to be better established. METHODS This was a prospective single-center PK study. A maximum of 12 PK samples per patient were collected in children

Background: Extracorporeal membrane oxygenation (ECMO) provides cardiopulmonary support for critically ill patients. Portable ECMO devices can be applied in both in-hospital and out-of-hospital emergency conditions. We evaluated the safety and biocompatibility of a novel centrifugal pump and ECMO device of the OASSIST ECMO System (Jiangsu STMed Technologies Co., Suzhou, China) in a 168-h ovine ECMO model.Methods: The portable OASSIST ECMO system consists of the control console, the pump drive, and the disposable centrifugal pump. Ten healthy sheep were used to evaluate the OASSIST ECMO system. Five were supported on veno-venous ECMO and five on veno-arterial ECMO, each for 168 h. The systemic anticoagulation was achieved by continuous heparin infusion to maintain the activated clotting time (ACT) between 220 and 250 s. The rotary speed was set at 3,200–3,500 rpm. The ECMO configurations and ACT were recorded every 6 hours (h). The free hemoglobin (fHb), complete blood count, and coagulation action test were monitored, at the 6th h and every 24 h after the initiation of the ECMO. The dissection of the pump head and oxygenator were conducted to explore thrombosis.Results: Ten sheep successfully completed the study duration without device-related accidents. The pumps ran stably, and the ECMO flow ranged from 1.6 ± 0.1 to 2.0 ± 0.11 L/min in the V-V group, and from 1.8 ± 0.1 to 2.4 ± 0.14 L/min in the V-A group. The anticoagulation was well-performed. The ACT was maintained at 239.78 ± 36.31 s, no major bleeding or thrombosis was observed during the ECMO run or in the autopsy. 3/5 in the V-A group and 4/5 in the V-V group developed small thrombus in the bearing pedestal. No obvious thrombus formed in the oxygenator was observed. The hemolytic blood damage was not significant. The average fHb was 0.17 ± 0.12 g/L. Considering hemodilution, the hemoglobin, white blood cell, and platelets didn't reduce during the ECMO runs.Conclusions: The OASSIST ECMO system shows satisfactory safety and biocompatibility for the 168-h preclinical evaluation in the ovine model. The OASSIST ECMO system is promising to be applied in clinical conditions in the future.

RATIONALE Increased cytokine response is common in patients receiving extracorporeal life support and is often a poor prognostic indicator. There is interest in using adjunctive cytokine adsorption technologies to reduce inflammatory burden, However, it is debated whether extracorporeal membrane oxygenation (ECMO) itself provides therapeutic benefit beyond gas exchange. Thus, we sought to characterize the inflammatory profile of ECMO in the first 72-96 h of and quantify its effect on cytokine levels in a case series of patients undergoing ECMO. METHODS Eight patients initiating ECMO were studied. Of these, we measured cytokines pre- and post-oxygenator over 96 h. Comparisons of cytokine levels were made across the oxygenator and over time. RESULTS The average age of patients was 64.3 years with 62% being male. Centrally cannulated patients had higher IL-6 levels (820.43 vs. 6907.53 pg/ml, p