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Lung transplantation may be a final destination therapy in lung failure, but limited donor organ availability creates a need for alternative management, including artificial lung technology. This invited review discusses ongoing developments and future research pathways for respiratory assist devices and tissue engineering to treat advanced and refractory lung disease. An overview is also given on the aftermath of the coronavirus disease 2019 pandemic and lessons learned as the world comes out of this situation. The first order of business in the future of lung support is solving the problems with existing mechanical devices. Interestingly, challenges identified during the early days of development persist today. These challenges include device-related infection, bleeding, thrombosis, cost, and patient quality of life. The main approaches of the future directions are to repair, restore, replace, or regenerate the lungs. Engineering improvements to hollow fiber membrane gas exchangers are enabling longer term wearable systems and can be used to bridge lung failure patients to transplantation. Progress in the development of microchannel-based devices has provided the concept of biomimetic devices that may even enable intracorporeal implantation. Tissue engineering and cell-based technologies have provided the concept of bioartificial lungs with properties similar to the native organ. Recent progress in artificial lung technologies includes continued advances in both engineering and biology. The final goal is to achieve a truly implantable and durable artificial lung that is applicable to destination therapy., (© 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Background Methods Results Conclusions Veno‐arterial extracorporeal membrane oxygenation (V‐A ECMO) is increasingly utilized in pediatric patients. Failure to recognize membrane oxygenator failure can lead to critical complications due to rapid deterioration of membrane oxygenator function. Therefore, identifying the predictors for membrane oxygenator exchange is crucial. However, risk factors for membrane oxygenator exchange in pediatric V‐A ECMO remain unclear; therefore, this study aimed to evaluate these risk factors.This retrospective cohort study enrolled all pediatric patients aged <18 years who received V‐A ECMO between August 2018 and July 2023 at a tertiary‐care pediatric hospital in Japan. The Cox proportional hazards model was used to evaluate the predictors of membrane oxygenator failure within 72 h after initiation.During the study period, membrane oxygenator failure occurred in 18/55 (32.7%) children within 72 h; membrane oxygenator failure within 72 h occurred in 4/29 (13.8%) and 14/26 (53.8%) in the groups with ratio of blood flow divided by the blood flow limit of the membrane oxygenator (B/L) of <0.5 and ≥0.5, respectively (adjusted hazards ratio, 4.97 [95% confidence interval, 1.33–18.5]; p = 0.017). After adjusting for delta pressure of the oxygenator, an increase in body weight and aspartate aminotransferase levels were associated with an increase in early membrane oxygenator failure.This retrospective study demonstrated that a B/L ratio >0.5, an increase in body weight, and elevated aspartate aminotransferase were independent risk factors for early membrane oxygenator failure in pediatric V‐A ECMO. However, a prospective multicenter study with an appropriate sample size is warranted to mitigate potential bias, and enhance generalizability for further investigation of the association between a B/L ratio and early membrane oxygenator failure. [ABSTRACT FROM AUTHOR]

Background: As the pandemic progressed, the use of extracorporeal membrane oxygenation (ECMO) for COVID‐19‐related acute respiratory distress syndrome increased, and patient triage and transfer to ECMO centers became important to optimize patient outcomes. Our objectives are to identify predictors of patient transfer for veno‐venous extracorporeal membrane oxygenation (V‐V ECMO) evaluation as well as to describe the outcomes of accepted patients. Methods: This is a single‐center, retrospective analysis of V‐V ECMO transfer requests for adult patients with known or suspected COVID‐19 and respiratory failure from March 2020 until March 2021. Data were collected prospectively during the triage process for transfer requests as part of clinical patient care at our institution. Results: Of 341 referred patients, 112 (33%) were accepted for transfer to our facility, whereas 229 (67%) patients were declined for transfer. The Classification and Regression Tree analysis showed that patients' high pressure during airway pressure release ventilation (APRV) and age were the variables most significantly associated with the decision to accept or decline patients for transfer. Conclusions: Our triage process enabled one‐third of referred patients to be transferred for evaluation, with nearly 70% of those patients ultimately receiving ECMO support. High ventilator settings on APRV and young age were associated with acceptance for transfer. Accepted patients also had a higher incidence of adjunctive therapies (proning and paralysis) prior to transfer request, less cardiac or renal dysfunction, and a shorter duration of mechanical ventilation. Further research is warranted to investigate the outcomes of nontransferred patients. [ABSTRACT FROM AUTHOR]

Objective: Pulsatile‐flow veno‐arterial extracorporeal membrane oxygenation (V‐A ECMO) has shown encouraging results for microcirculation resuscitation and left ventricle unloading in patients with refractory cardiogenic shock. We aimed to comprehensively assess different V‐A ECMO parameters and their contribution to hemodynamic energy production and transfer through the device circuit. Methods: We used the i‐cor® ECMO circuit, which composed of Deltastream DP3 diagonal pump and i‐cor® console (Xenios AG), the Hilite 7000 membrane oxygenator (Xenios AG), venous and arterial tubing and a 1 L soft venous pseudo‐patient reservoir. Four different arterial cannulae (Biomedicus 15 and 17 Fr, Maquet 15 and 17 Fr) were used. For each cannula, 192 different pulsatile modes were investigated by adjusting flow rate, systole/diastole ratio, pulsatile amplitudes and frequency, yielding 784 unique conditions. A dSpace data acquisition system was used to collect flow and pressure data. Results: Increasing flow rates and pulsatile amplitudes were associated with significantly higher hemodynamic energy production (both p < 0.001), while no significant associations were seen while adjusting systole‐to‐diastole ratio (p = 0.73) or pulsing frequency (p = 0.99). Arterial cannula represents the highest resistance to hemodynamic energy transfer with 32%–59% of total hemodynamic energy generated being lost within, depending on pulsatile flow settings used. Conclusions: Herein, we presented the first study to compare hemodynamic energy production with all pulsatile ECLS pump settings and their combinations and widely used yet previously unexamined four different arterial ECMO cannula. Only increased flow rate and amplitude increase hemodynamic energy production as single factors, whilst other factors are relevant when combined. [ABSTRACT FROM AUTHOR]

Extreme prematurity, defined as a gestational age of fewer than 28 weeks, is a significant health problem worldwide. It carries a high burden of mortality and morbidity, in large part due to the immaturity of the lungs at this stage of development. The standard of care for these patients includes support with mechanical ventilation, which exacerbates lung pathology. Extracorporeal life support (ECLS), also called artificial placenta technology when applied to extremely preterm (EPT) infants, offers an intriguing solution. ECLS involves providing gas exchange via an extracorporeal device, thereby doing the work of the lungs and allowing them to develop without being subjected to injurious mechanical ventilation. While ECLS has been successfully used in respiratory failure in full-term neonates, children, and adults, it has not been applied effectively to the EPT patient population. In this review, we discuss the unique aspects of EPT infants and the challenges of applying ECLS to these patients. In addition, we review recent progress in artificial placenta technology development. We then offer analysis on design considerations for successful engineering of a membrane oxygenator for an artificial placenta circuit. Finally, we examine next-generation oxygenators that might advance the development of artificial placenta devices.

Background: The aim of this study was to assess the interdependence of extracorporeal blood flow (Qec) and gas flow (GF) in predicting CO2 removal and reduction of minute mechanical ventilation under extracorporeal respiratory support. Methods: All patients who benefited from V‐V ECMO and high‐flow ECCO2R in our intensive care unit over a period of 18 months were included. CO2 removal was calculated from inlet/outlet blood port gases during the first 7 days of oxygenator use. The relationship between the Qec × GF product (named decarboxylation index and expressed in L2/min2) and CO2 removal or expired minute mechanical ventilation reduction (ECMV ratio) was studied using linear regression models. Results: Eighteen patients were analyzed, corresponding to 24 oxygenators and 261 datasets. CO2 removal was 393 ml/min (IQR, 310–526) for 1.8 m2 oxygenators and 179 ml/min (IQR, 165–235) for 1.3 m2 oxygenators. The decarboxylation index was associated linearly with CO2 removal (R2 = 0.62 and R2 = 0.77 for the two oxygenators, respectively) and ECMV ratio (R2 = 0.72 and R2 = 0.62, respectively). The 20L2/min2 value (considering Qec = 2 L/min and GF = 10 L/min) was associated with an ECMV ratio between 61% and 29% for 1.8 m2 oxygenators, and between 62% and 38% for 1.3 m2 oxygenators. Conclusion: The decarboxylation index is a simple parameter to predict CO2 removal and ECMV ratio under extracorporeal respiratory support. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal membrane oxygenation (ECMO) became an accepted therapy for the treatment of severe acute respiratory distress syndrome and chronic obstructive pulmonary disease. However, ECMO systems are still prone to thrombus formation and decrease of gas exchange over time. Therefore, it is necessary to conduct qualified studies to identify parameters for optimization of ECMO systems, and especially the oxygenator. However, commercially marketed oxygenators are not always appropriate and available for certain research use cases. Therefore, we aimed to design an oxygenator, which is suitable for various test conditions such as blood tests, numerical simulation, and membrane studies, and can be modified in membrane area size and manufactured in laboratory. Methods: Main design criteria are a homogeneous blood flow without stagnation zones, low pressure drop, manufacturability in the lab, size variability with one set of housing parts and cost‐efficiency. Our newly designed oxygenator was tested comparatively regarding blood cell damage, gas transfer performance and pressure drop to prove the validity of the design in accordance with a commercial device. Results: No statistically significant difference between the tested oxygenators was detected and our new oxygenator demonstrated sufficient hemocompatibility. Furthermore, our variable oxygenator has proven that it can be easily manufactured in the laboratory, allows to use various membrane fiber configurations and can be reopened easily and non‐destructively for analysis after use, and the original geometry is available for numerical simulations. Conclusion: Therefore, we consider this newly developed device as a valuable tool for basic experimental and numerical research on the optimization of oxygenators. [ABSTRACT FROM AUTHOR]

Background: Antithrombogenicity of extracorporeal membrane oxygenation (ECMO) devices, particularly oxygenators, is a current problem, with numerous studies and developments underway. However, there has been limited progress in developing methods to accurately compare the antithrombogenicity of oxygenators. Animal experiments are commonly conducted to evaluate the antithrombogenicity of devices; however, it is challenging to maintain a steady experimental environment. We propose an innovative experimental animal model to evaluate different devices in a constant experimental environment in real‐time. Methods: This model uses two venous–arterial ECMO circuits attached to one animal (one by jugular vein and carotid artery, one by femoral vein and artery) and real‐time assessment of thrombus formation in the oxygenator by indocyanine green (ICG) fluorescence imaging. Comparison studies were conducted using three pigs: one to compare different oxygenators (MERA vs. CAPIOX) (Case 1), and two to compare antithrombotic properties of the oxygenator (QUADROX) when used under different hydrodynamic conditions (continuous flow vs. pulsatile flow) (Cases 2 and 3). Results: Thrombi, visualized using ICG imaging, appeared as black dots on a white background in each oxygenator. In Case 1, differences in the site of thrombus formation and rate of thrombus growth were observed in real‐time in two oxygenators. In Case 2 and 3, the thrombus region was smaller in pulsatile than in continuous conditions. Conclusions: We devised an innovative experimental animal model for comparison of antithrombogenicity in ECMO circuits. This model enabled simultaneous evaluation of two different ECMO circuits under the same biological conditions and reduced the number of sacrificed experimental animals. [ABSTRACT FROM AUTHOR]

Background: Training is an essential aspect of providing high‐quality treatment and ensuring patient safety in any medical practice. Because extracorporeal membrane oxygenation (ECMO) is a complicated operation with various elements, variables, and irregular situations, doctors must be experienced and knowledgeable about all conventional protocols and emergency procedures. The conventional simulation approach has a number of limitations. The approach is intrinsically costly since it relies on disposable medical equipment (i.e., oxygenators, heat exchangers, and pumps) that must be replaced regularly due to the damage caused by the liquid used to simulate blood. The oxygenator, which oxygenates the blood through a tailored membrane in ECMO, acts as a replacement for the patient's natural lung. For the context of simulation‐based training (SBT) oxygenators are often expensive and cannot be recycled owing to contamination issues. Methods: Consequently, it is advised that the training process include a simulated version of oxygenators to optimize reusability and decrease training expenses. Toward this goal, this article demonstrates a mock oxygenator for ECMO SBT, designed to precisely replicate the real machine structure and operation. Results: The initial model was reproduced using 3D modeling and printing. Additionally, the mock oxygenator could mimic frequent events such as pump noise and clotting. Furthermore, the oxygenator is integrated with the modular ECMO simulator using cloud‐based communication technology that goes in hand with the internet of things technology to provide remote control via an instructor tablet application. Conclusions: The final 3D modeled oxygenator body was tested and integrated with the other simulation modules at Hamad Medical Corporation with several participants to evaluate the effectiveness of the training session. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) is a life support system that circulates the blood through an oxygenating system to temporarily (days to months) support heart or lung function during cardiopulmonary failure until organ recovery or replacement. Currently, the need for high levels of systemic anticoagulation and the risk for bleeding are main drawbacks of ECMO that can be addressed with a redesigned ECMO system. Our lab has developed an approach using microelectromechanical systems (MEMS) fabrication techniques to create novel gas exchange membranes consisting of a rigid silicon micropore membrane (SμM) support structure bonded to a thin film of gas-permeable polydimethylsiloxane (PDMS). This study details the fabrication process to create silicon membranes with highly uniform micropores that have a high level of pattern fidelity. The oxygen transport across these membranes was tested in a simple water-based bench-top set-up as well in a porcine in vivo model. It was determined that the mass transfer coefficient for the system using SµM-PDMS membranes was 3.03 ± 0.42 mL O2 min-1 m-2 cm Hg-1 with pure water and 1.71 ± 1.03 mL O2 min-1 m-2 cm Hg-1 with blood. An analytic model to predict gas transport was developed using data from the bench-top experiments and validated with in vivo testing. This was a proof of concept study showing adequate oxygen transport across a parallel plate SµM-PDMS membrane when used as a membrane oxygenator. This work establishes the tools and the equipoise to develop future generations of silicon micropore membrane oxygenators.

Background: Severe COVID‐19 can necessitate multiple organ support including veno‐venous extracorporeal membrane oxygenation (vvECMO) and renal replacement therapy. The therapy can be complicated by venous thromboembolism due to COVID‐19‐related hypercoagulability, thus restricting vascular access beyond the vvECMO cannula. Although continuous renal replacement therapy can be performed via a vvECMO circuit, studies addressing sustained low‐efficiency dialysis (SLED) integration into vvECMO circuits are scarce. Here we address the lack of evidence by evaluating feasibility of SLED integration into vvECMO circuits. Methods: Retrospective cohort study on nine critically ill COVID‐19 patients, treated with integrated ECMO‐SLED on a single intensive care unit at a tertiary healthcare facility between December 2020 and November 2021. The SLED circuits were established between the accessory arterial oxygenator outlets of a double‐oxygenator vvECMO setup. Data on filter survival, quality of dialysis, and volume management were collected and compared with an internal control group receiving single SLED. Results: This study demonstrates general feasibility of SLED integration into existing vvECMO circuits. Filter lifespans of ECMO‐SLED compared with single SLED are significantly prolonged (median 18.3 h vs. 10.3 h, p < 0.01). ECMO‐SLED treatment is furthermore able to sufficiently normalize creatinine, blood urea nitrogen, and serum sodium, and allows for adequate ultrafiltration rates. Conclusions: We can show that ECMO‐SLED is practical, safe, results in adequate dialysis quality and enables sufficient electrolyte and volume management. Our data indicate that SLED devices can serve as potential alternative to continuous‐veno‐venous‐hemodialysis for integration in vvECMO circuits. [ABSTRACT FROM AUTHOR]

The increasing prevalence of chronic lung disease worldwide, combined with the emergence of multiple pandemics arising from respiratory viruses over the past century, highlights the need for safer and efficacious means for providing artificial lung support. Mechanical ventilation is currently used for the vast majority of patients suffering from acute and chronic lung failure, but risks further injury or infection to the patient's already compromised lung function. Extracorporeal membrane oxygenation (ECMO) has emerged as a means of providing direct gas exchange with the blood, but limited access to the technology and the complexity of the blood circuit have prevented the broader expansion of its use. A promising avenue toward simplifying and minimizing complications arising from the blood circuit, microfluidics‐based artificial organ support, has emerged over the past decade as an opportunity to overcome many of the fundamental limitations of the current standard for ECMO cartridges, hollow fiber membrane oxygenators. The power of microfluidics technology for this application stems from its ability to recapitulate key aspects of physiological microcirculation, including the small dimensions of blood vessel structures and gas transfer membranes. An even greater advantage of microfluidics, the ability to configure blood flow patterns that mimic the smooth, branching nature of vascular networks, holds the potential to reduce the incidence of clotting and bleeding and to minimize reliance on anticoagulants. Here, we summarize recent progress and address future directions and goals for this potentially transformative approach to artificial lung support. Correspondence between native blood vessel branching and the microfluidic blood vessel branching patterns that form the design basis for bio‐inspired artificial organs. As in the physiological vasculature, a large inlet vessel branches into multiple trunk lines, each of which leads to further branching into smaller microchannels. This design paradigm preserves a smooth distribution of blood flow throughout the microfluidic network. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the prevalence of 7‐, 30‐, 60‐, and 365‐day overall and cause‐specific mortality following extracorporeal membrane oxygenation (ECMO) support. Methods: The National Health Insurance claims database in South Korea was the data source for this population‐based cohort study. We enrolled all adult patients aged ≥18 years receiving intensive care unit ECMO support from January 1, 2005 to December 31, 2018. The study population was divided into three groups based on the main diagnoses during ECMO support: (1) cardiovascular, (2) respiratory, and (3) other diagnoses group (all other main diagnoses rather than cardiovascular or respiratory diseases). Results: A total of 18 697 patients were included in the final analysis (64.5%, 10.9%, and 24.6% in the cardiovascular, respiratory, and other groups, respectively). The corresponding 7‐, 30‐, 60‐, and 365‐day mortality rates in these groups were 33.1%, 56.1%, 62.4%, and 67.7%. Kaplan–Meier curves demonstrated that the median survival time was shortest in the cardiovascular group (12.0 days, 95% confidence interval [CI]: 11.3–12.7), with 31.0 (95% CI: 28.5–33.6) and 49.0 (95% CI: 44.4–57.6) day survival in the respiratory and other diagnoses groups (p < 0.001). Conclusions: Approximately one‐third of patients died within 7 days, half of the patients died within 30 days, and two‐thirds died within 365 days of ECMO support. Overall survival time was shortest in the cardiovascular group, followed by that of the respiratory group. [ABSTRACT FROM AUTHOR]

Background: During extracorporeal life support (ECLS), bleeding is one of the most frequent complications, associated with high morbidity and increased mortality, despite continuous improvements in devices and patient care. Risk factors for bleeding complications in veno‐venous (V‐V) ECLS applied for respiratory support have been poorly investigated. We aim to develop and internally validate a prediction model to calculate the risk for bleeding complications in adult patients receiving V‐V ECLS support. Methods: Data from adult patients reported to the extracorporeal life support organization (ELSO) registry between the years 2010 and 2020 were analyzed. The primary outcome was bleeding complications recorded during V‐V ECLS. Multivariable logistic regression with backward stepwise elimination was used to develop the predictive model. The performance of the model was tested by discriminative ability and calibration with receiver operating characteristic curves and visual inspection of the calibration plot. Results: In total, 18 658 adult patients were included, of which 3 933 (21.1%) developed bleeding complications. The prediction model showed a prediction of bleeding complications with an AUC of 0.63. Pre‐ECLS arrest, surgical cannulation, lactate, pO2, HCO3, ventilation rate, mean airway pressure, pre‐ECLS cardiopulmonary bypass or renal replacement therapy, pre‐ECLS surgical interventions, and different types of diagnosis were included in the prediction model. Conclusions: The model is based on the largest cohort of V‐V ECLS patients and reveals the most favorable predictive value addressing bleeding events given the predictors that are feasible and when compared to the current literature. This model will help identify patients at risk of bleeding complications, and decision making in terms of anticoagulation and hemostatic management. [ABSTRACT FROM AUTHOR]

Background: A paucity of evidence exists regarding risks and benefits of extracorporeal membrane oxygenation (ECMO) in adult liver transplantation. Methods: This was a systematic review conducted from January 1, 2000 to April 24, 2020 of adult liver transplant recipients (pre‐ or post‐transplant) and donors who underwent Veno‐arterial or Veno‐venous ECMO cannulation. Death was the primary outcome, with graft function and complications as secondary outcomes. Results: Forty‐one articles were identified that fit criteria. A total of 183 donors were placed on ECMO, with recipient complication profiles and mortality that mirrored rates from standard criteria donors. Sixty‐one recipients were placed on ECMO intraoperatively or postoperatively. Most patients experienced at least one complication with infections as the most common cause and minimal complications specifically related to ECMO use. Multisystem organ failure (MSOF) and infections were more common among liver recipients who died compared to those who survived. Overall mortality at 90 days was 45.9%. Causes of death were most commonly MSOF and infections. Conclusions: ECMO use in adult liver transplantation is a useful adjunct. Recipient morbidity and mortality from donors placed on ECMO parallel that of recipients from standard criteria donors, and morbidity and mortality of recipients placed on ECMO are similar to other ECMO populations. [ABSTRACT FROM AUTHOR]

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 < 0.03), whereas peripherally cannulated patients had higher IL‐12p70 levels (7.73 vs. 2.59 pg/ml, p < 0.05). Cytokine levels on day one included IL‐12p70 (4.17 ± 2.56), IL‐6 (4971.23 ± 8569.88), TNF (undetected), IL‐8 (346.68 ± 670.18), IL‐1B (undetected), and IL‐10 (72.27 ± 87.9). Cytokine levels increased over 96 h; however, no significant differences were appreciated despite blood product transfusion. On day 3, IL‐12p70 levels were significantly lower post‐oxygenator (p < 0.05). Conclusion: The inflammatory profile of ECMO does not change significantly over the early course of illness when accounting for transfusion. However, the decrease in IL‐12p70 specifically at day 3 of ECMO may indicate adsorption of specific inflammatory markers by the oxygenator although the clinical significance of this is still unknown. Further investigation of the oxygenator on cytokine response is warranted. [ABSTRACT FROM AUTHOR]

Background: Patients with combined circulatory shock and respiratory failure may benefit from veno‐arteriovenous (V‐AV) extracorporeal membrane oxygenation support (ECMO). We report our center's experience with V‐AV ECMO and propose an algorithm to help identify patients that may benefit from early V‐AV ECMO support. Methods: Clinical data were extracted from electronic medical records between November 1, 2016 and November 1, 2019. Results: Out of a total of 369 patients placed on extracorporeal life support (ECLS), we identified a total of 26 patients who underwent hybrid ECMO placement. Three patients were excluded from our analysis due to veno‐venoarterial extracorporeal membrane oxygenation (V‐VA ECMO) configuration, therefore 23 patients were included in our analysis. The median age was 53 (range 25–73) years. Hybrid ECMO support was instituted most commonly for differential hypoxemia in patients on venoarterial (V‐A) ECMO support, and cardiogenic shock in patients who were initially started on venovenous (V‐V) ECMO. The initial ECMO cannulation was V‐A in 12 patients, V‐V in 8 patients, and directly V‐AV in 3 patients. Nine out of 23 patients were successfully decannulated (39.1%) and survived until hospital discharge. The main ECMO‐related complications included bleeding (n = 10), circuit exchange either due to hemolysis or oxygenator failure (n = 4), ECMO cannula site infection (n = 2), deep venous thrombosis (n = 2), and death during ECMO cannula exchange (n = 1). Conclusions: V‐AV ECMO represents a rescue strategy in critically ill patients with combined respiratory failure and cardio‐circulatory shock. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Timing and causes of hospital mortality in adult patients undergoing veno‐arterial extracorporeal membrane oxygenation (V‐A ECMO) have been poorly described. Aim of the current review was to investigate the timing and causes of death of adult patients supported with V‐A ECMO and subsequently define the "V‐A ECMO gap," which represents the patients who are successfully weaned of ECMO but eventually die during hospital stay. A systematic search was performed using electronic MEDLINE and EMBASE databases through PubMed. Studies reporting on adult V‐A ECMO patients from January 1993 to December 2020 were screened. The studies included in this review were studies that reported more than 10 adult, human patients, and no mechanical circulatory support other than V‐A ECMO. Information extracted from each study included mainly mortality and causes of death on ECMO and after weaning. Complications and discharge rates were also extracted. Sixty studies with 9181 patients were included for analysis in this systematic review. Overall mortality was 38.0% (95% confidence intervals [CIs] 34.2%‐41.9%) during V‐A ECMO support (reported by 60 studies) and 15.3% (95% CI 11.1%‐19.5%, reported by 57 studies) after weaning. Finally, 44.0% of patients (95% CI 39.8‐52.2) were discharged from hospital (reported by 60 studies). Most common causes of death on ECMO were multiple organ failure, followed by cardiac failure and neurological causes. More than one‐third of V‐A ECMO patients die during ECMO support. Additionally, many of successfully weaned patients still decease during hospital stay, defining the "V‐A ECMO gap." Underreporting and lack of uniformity in reporting of important parameters remains problematic in ECMO research. Future studies should uniformly define timing and causes of death in V‐A ECMO patients to better understand the effectiveness and complications of this support. [ABSTRACT FROM AUTHOR]

Advances in microfluidics technologies have spurred the development of a new generation of microfluidic respiratory assist devices, constructed using microfabrication techniques capable of producing microchannel dimensions similar to those found in human capillaries and gas transfer films in the same thickness range as the alveolar membrane. These devices have been tested in laboratory settings and in some cases in extracorporeal animal experiments, yet none have been advanced to human clinical studies. A major challenge in the development of microfluidic oxygenators is the difficulty in scaling the technology toward high blood flows necessary to support adult humans; such scaling efforts are often limited by the complexity of the fabrication process and the manner in which blood is distributed in a three‐dimensional network of microchannels. Conceptually, a central advantage of microfluidic oxygenators over existing hollow‐fiber membrane‐based configurations is the potential for shallower channels and thinner gas transfer membranes, features that reduce oxygen diffusion distances, to result in a higher gas transfer efficiency defined as the ratio of the volume of oxygen transferred to the blood per unit time to the active surface area of the gas transfer membrane. If this ratio is not significantly higher than values reported for hollow fiber membrane oxygenators (HFMO), then the expected advantage of the microfluidic approach would not be realized in practice, potentially due to challenges encountered in blood distribution strategies when scaling microfluidic designs to higher flow rates. Here, we report on scaling of a microfluidic oxygenator design from 4 to 92 mL/min blood flow, within an order of magnitude of the flow rate required for neonatal applications. This scaled device is shown to have a gas transfer efficiency higher than any other reported system in the literature, including other microfluidic prototypes and commercial HFMO cartridges. While the high oxygen transfer efficiency is a promising advance toward clinical scaling of a microfluidic architecture, it is accompanied by an excessive blood pressure drop in the circuit, arising from a combination of shallow gas transfer channels and equally shallow distribution manifolds. Therefore, next‐generation microfluidic oxygenators will require novel design and fabrication strategies to minimize pressure drops while maintaining very high oxygen transfer efficiencies. [ABSTRACT FROM AUTHOR]

Weaning failure and mortality rates in veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) supported patients are significant. Small studies suggest the possible usefulness of levosimendan in this environment, especially in postcardiotomy shock. We performed a retrospective analysis of VA‐ECMO implants in a referral hospital comparing weaning failure and survival of patients treated with levosimendan with a control group. From 2013 to May 2020, 123 VA‐ECMO for several indications were implanted. Levosimendan was administered in 23 patients (18.7%) with good tolerance. Levosimendan was used more frequently in cardiogenic shock due to acute coronary syndrome indication, and in patients with lower left ventricular ejection fraction (LVEF) at the implant. No significant differences were found in success of ECMO weaning (60.9% levosimendan group vs. 44% non‐levosimendan group, P =.169) despite worse LVEF in levosimendan group. Survival at follow‐up (20.6 [58] months) was higher in the group that received levosimendan, although without finding statistically significant differences (47.8% vs. 32.0%, log rank P =.124). Levosimendan can be safely administered during VA‐ECMO support. Patients receiving levosimendan were weaned similarly from circulatory support despite worse LVEF. Its use did not influence in short‐ and medium‐term survival. Randomized studies are needed to evaluate the levosimendan impact in this indication. [ABSTRACT FROM AUTHOR]

Veno‐venous extracorporeal membrane oxygenation (V‐V ECMO) is used to sustain blood oxygenation and decarboxylation in severe acute respiratory distress syndrome (ARDS). It is under debate if V‐V ECMO is as appropriate for coronavirus disease 2019 (Covid‐19) ARDS as it is for influenza. In this retrospective study, we analyzed all patients with confirmed SARS‐CoV‐2 or influenza A/B infection, ARDS and V‐V ECMO, treated at our medical intensive care unit (ICU) between October 2010 and June 2020. Baseline and procedural characteristics as well as survival 30 days after ECMO cannulation were analyzed. A total of 62 V‐V ECMO patients were included (15 with Covid‐19 and 47 with influenza). Both groups had similar baseline characteristics at cannulation. Thirty days after ECMO cannulation, 13.3% of all patients with Covid‐19 were discharged alive from our ICU compared to 44.7% with influenza (P =.03). Patients with Covid‐19 had fewer ECMO‐free days (0 (0‐9.7) days vs. 13.2 (0‐22.1) days; P =.05). Cumulative incidences of 30‐day‐survival showed no significant differences (48.6% in Covid‐19 patients, 63.7% in influenza patients; P =.23). ICU treatment duration was significantly longer in ARDS patients with V‐V ECMO for Covid‐19 compared to influenza. Thirty‐day mortality was higher in Covid‐19, but not significant. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) represents a therapeutic option for cardiopulmonary support in patients with high‐risk pulmonary embolism (PE); however, no definite consensus exists on ECMO use in high‐risk PE. Hence, we aim to provide insights into its real‐world use pooling together all available published experiences. We performed a systematic review and pooled analysis of all published studies (up to April 17, 2020) investigating ECMO support in high‐risk PE. All studies including at least four patients were collectively analyzed. Study outcomes were early all‐cause death (primary endpoint) and relevant in‐hospital adverse events. A total of 21 studies were included in the pooled analysis (n = 635 patients). In this population (mean age 47.8 ± 17.3 years, 44.5% females), ECMO was indicated for cardiac arrest in 62.3% and immediate ECMO support was pursued in 61.9% of patients. Adjunctive reperfusion therapies were implemented in 57.0% of patients. Pooled estimate rate of early all‐cause mortality was 41.1% (95% CI 27.7%‐54.5%). The most common in‐hospital adverse event was major bleeding, with an estimated rate of 28.6% (95%CI 21.0%‐36.3%). At meta‐regression analyses, no significant impact of multiple covariates on the primary endpoint was found. In this systematic review of patients who received ECMO for high‐risk PE, pooled all‐cause mortality was 41.1%. Principal indication for ECMO was cardiac arrest, cannulation was chiefly performed at presentation, and major bleeding was the most common complication. [ABSTRACT FROM AUTHOR]

The role of extracorporeal membrane oxygenation (ECMO) in the management of critically ill COVID‐19 patients remains unclear. Our study aims to analyze the outcomes and risk factors from patients treated with ECMO. This retrospective, single‐center study includes 17 COVID‐19 patients treated with ECMO. Univariate and multivariate parametric survival regression identified predictors of survival. Nine patients (53%) were successfully weaned from ECMO and discharged. The incidence of in‐hospital mortality was 47%. In a univariate analysis, only four out of 83 pre‐ECMO variables were significantly different; IL‐6, PCT, and NT‐proBNP were significantly higher in non‐survivors than in survivors. The Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score was significantly higher in survivors. After a multivariate parametric survival regression, IL‐6, NT‐proBNP and RESP scores remained significant independent predictors, with hazard ratios (HR) of 1.069 [95%‐CI: 0.986‐1.160], P =.016 1.001 [95%‐CI: 1.000‐1.001], P =.012; and.843 [95%‐CI: 0.564‐1.260], P =.040, respectively. A prediction model comprising IL‐6, NT‐proBNP, and RESP score showed an area under the curve (AUC) of 0.87, with a sensitivity of 87.5% and 77.8% specificity compared to an AUC of 0.79 for the RESP score alone. The present study suggests that ECMO is a potentially lifesaving treatment for selected critically ill COVID‐19 patients. Considering IL‐6 and NT‐pro‐BNP, in addition to the RESP score, may enhance outcome predictions. [ABSTRACT FROM AUTHOR]

Modern extracorporeal life‐support (ECLS) technology has been successfully utilized to treat patients with diffuse alveolar damage (DAD) and diffuse alveolar hemorrhage (DAH); however, reports in the literature remain scarce. We sought to pool existing evidence to better characterize ECLS use in these patients. An electronic search was conducted to identify all studies in the English literature reporting the use of ECLS for DAD/DAH. Thirty‐two articles consisting of 38 patients were selected, and patient‐level data were extracted and pooled for analysis. Median patient age was 36 [IQR: 27, 48] years, and the majority (63.2%) were female. Most common etiological factors included granulomatosis with polyangiitis (8/38, 21.1%), systemic lupus erythematosus (8/38, 21.1%), Goodpasture's syndrome (4/38, 10.5%), and microscopic polyangiitis (4/38, 10.5%). Immunologic markers included anti‐neutrophil cytoplasmic antibody (ANCA) in 15/38 (39.5%), anti‐nuclear antibody (ANA) in 6/38 (15.8%), and anti‐glomerular basement membrane (anti‐GBM) antibodies in 4/38 (10.5%). DAH was present in 32/38 (84.2%) of cases and DAD without evidence of DAH was present in 6/38 (15.8%) of cases. ECLS strategies included extracorporeal membrane oxygenation of veno‐venous type (VV‐ECMO) in 28/38 (73.7%), veno‐arterial type (VA‐ECMO) in 5/38 (13.2%), and one case of right ventricular assist device with oxygenator (RVAD‐ECMO). Heparin was utilized in 18/38 (47.4%) of cases with no difference in use between DAH versus no DAH (P =.46) or VA‐ versus VV‐ECLS (P = 1). Median duration of ECLS was 10 [5, 14] days. Pre‐ versus post‐ECLS comparison of blood gases showed improvement in median PaO2 (49 [45, 59] mm Hg vs. 80 [70, 99] mm Hg, P <.001), PaO2:FiO2 ratio (48.2 [41.4, 54.8] vs. 182.0 [149.4, 212.2], P <.01), and pulse oximetry values (76% [72, 80] vs. 96% [94, 97], P =.086). Overall, 94.7% (36/38) of patients survived to decannulation while 30‐day mortality was 10.5% (4/38) with no differences between VA‐ and VV‐ECMO (P = 1 and P =.94, respectively). DAD/DAH occurs in a younger, predominantly female population, and tends to be associated with systemic autoimmune processes. ECLS, independent of its type, appears to result in favorable short‐term survival. [ABSTRACT FROM AUTHOR]

We report the case of a 12‐year old female patient with Friedreich's ataxia and diabetes mellitus. Due to a progressive multiorgan failure, a veno‐arterial extracorporeal membrane oxygenation was implanted through the axillary vessels. However, due to a lack of ejection and severe dilatation of the left ventricle, an Impella 2.5 was implanted. Due to the small diameter of the femoral arteries, we performed a trans‐aortic implantation through a median sternotomy via a Dacron tube graft. We report on the procedure and perioperative outcome. [ABSTRACT FROM AUTHOR]

We evaluated the benefit of left ventricular (LV) unloading using a percutaneous transseptal left atrial (LA) drain catheter via femoral vein incorporated into the ECMO venous circuit. This single‐center retrospective observational study analyzed clinical outcomes of the LA venting group (N = 62) who underwent percutaneous transseptal LA drain placement comparing with the conventionally treated control group (N = 62) with an arterial pulse pressure below 10 mm Hg for at least 24 hours from December 2012 to August 2018. The ECMO weaning rate (61.3% vs. 38.7%, P =.012) and cardiac transplantation rate (29.0% vs. 11.3%, P =.014) were higher in the LA venting group than in the control group. Inhospital mortality was not significantly different (56.5% vs. 69.4%, P =.191). Pulmonary congestion mostly improved after LA decompression (61.3%, P =.003). A serum lactate level at 24 hours after LA venting of more than 2.2 mmol/L was associated with poor outcomes. LA venting via transseptal cannula reduced pulmonary venous congestion and achieved higher rates of successful ECMO weaning and cardiac transplantation. Placement of a transseptal venous drain cannula should be considered in patients with uncontrolled pulmonary edema secondary to severe LV loading undergoing VA‐ECMO. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In serious novel coronavirus disease 2019 (COVID-19) with very severe acute respiratory distress syndrome (ARDS), even mechanical ventilation cannot provide satisfactory blood oxygenation and veno-venous extracorporeal membrane oxygenation (V-V ECMO) is necessary.1 Mortality in these patients is high, though reliable data are scarce. From the beginning on, we observed abnormal clotting in the ECMO circuit, even under PTT-monitored anticoagulation with heparin or argatroban within in the target range (PTT 60 seconds) and various parts of the system and the cytokine adsorber needed to be replaced during the treatment. While cytokine adsorption was effective and seemed to support stabilization of the patient, we observed severe clotting in the ECMO circuit even under full anticoagulation therapy as a serious therapeutic challenge. [Extracted from the article]

Limb ischemia is a major complication associated with peripheral venoarterial extracorporeal membrane oxygenation (VA‐ECMO). The high velocity jet from arterial cannulae can cause "sandblasting" injuries to the arterial endothelium, with the potential risk of distal embolization and end organ damage. The aim of this study was to identify, for a range of clinically relevant VA‐ECMO cannulae and flow rates, any regions of peak flow velocity on the aortic wall which may predispose to vascular injury, and any regions of low‐velocity flow which may predispose to thrombus formation. A silicone model of the aortic and iliac vessels was sourced and the right external iliac artery was cannulated. Cannulae ranged from 15 to 21 Fr in size. Simulated steady state ECMO flow rates were instituted using a magnetically levitated pump (CentriMag pump). Adaptive particle image velocimetry was performed for each cannula at 3, 3.5, 4, and 4.5 L/min. For all cannulae, in both horizontal and vertical side hole orientations, the peak velocity on the aortic wall ranged from 0.3 to 0.45 m/s, and the regions of lowest velocity flow were 0.05 m/s. The magnitude of peak velocity flow on the aortic wall was not different between a single pair versus multiple pairs of side holes. Maximum velocity flow on the aortic wall occurred earlier at a lower pump flow rate in the vertical orientation of distal side holes compared to a horizontal position. The presence of multiple paired side holes was associated with fewer low‐velocity flow regions, and some retrograde flow, in the distal abdominal aorta compared to cannulae with a single pair of side holes. From this in vitro visualization study, the selection of a cannula design with multiple versus single pairs of side holes did not change the magnitude of peak velocity flow delivered to the vessel wall. Cannulae with multiple side holes were associated with fewer regions of low‐velocity flow in the distal abdominal aorta. Further in vivo studies, and ideally clinical data would be required to assess any correlation of peak velocity flows with incidence of vascular injury, and any low‐velocity flow regions with incidence of thrombosis. [ABSTRACT FROM AUTHOR]

Mortality and morbidity of children received veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) support after cardiac surgery remain high despite remarkable advances in medical management and devices. The purpose of this study was to describe outcomes and risk factors of applying VA‐ECMO in the surgical pediatric population. We retrospectively analyzed 85 consecutive pediatric patients (aged <18 years) who received postcardiotomy VA‐ECMO from January 2010 to December 2018. Median (IQR) age at ECMO implantation in this cohort was 12.7 (6.4, 43.2) months, median weight was 8.5 (6.0, 12.8) kg, mean ECMO duration was 143.2 ± 81.6 hours and mean hospital length of stay was 48.4 ± 32.4 days. Seventy‐five patients (88.2%) were indicated for postcardiotomy cardiogenic shock. The successful ECMO weaning rate was 70.6% and in‐hospital mortality was 52.9%. The most common diagnosis was transposition of great arteries (n = 18, 21.2%), while acute kidney injury occurred most often (n = 64, 75.3%). Multivariate logistic regression analysis showed that thrombocytopenia, hemolysis, and nosocomial infection were positively correlated with in‐hospital mortality. Multivariate Cox proportional hazard regression analysis presented that thrombocytopenia significantly increased the 180‐day mortality in patients with successful weaning. Therefore, multiple factors had adverse effects on prognosis. Patient selection and procedures from ECMO implantation to weaning need to be closely monitored and performed in a timely manner to improve outcome. [ABSTRACT FROM AUTHOR]

Having physiological correct flow waveforms is a key feature for experimental studies of blood flow, especially in the process of developing and testing a new medical device such as stent, mechanical heart valve, or any implantable medical device that involves circulation of blood through the device. It is also a critical part of a perfusion system for cardiopulmonary bypass and extracorporeal membrane oxygenation procedures. This study investigated the feasibility of a novel roller pump for use in experimental flow phantoms. Flow rates of carotid flow profile measured directly with the ultrasonic flow meter matched well with the reference flow rates programmed into the machine with similarity index of 0.97 and measured versus programmed flow rates at specific time‐points of peak systolic velocity (PSV): 0.894 vs 0.880, end systolic velocity (ESV): 0.333 vs 0.319, and peak diastolic velocity (PDV): 0.514 vs 0.520 L/min. Flow rates derived from video analysis of the pump motion for carotid, suprarenal, and infrarenal flows also matched well with references with similarity indices of 0.99, 0.99, and 0.96, respectively. Measured flow rates (mean/standard deviation) at PSV, ESV, and PDV time‐points for carotid: 0.883/0.016 vs 0.880, 0.342/0.007 vs 0.319, and 0.485/0.009 vs 0.520; suprarenal: 3.497/0.014 vs 3.500, 0.004/0.003 vs 0, and 1.656/0.073 vs 1.453; infrarenal: 4.179/0.024 vs 4.250, −1.147/0.015 vs −1.213, and 0.339/0.017 vs 0.391 L/min, respectively. The novel roller pump is suitable for benchtop testing of physiological flow. [ABSTRACT FROM AUTHOR]

Occurrence of microbubbles (MB) is a major problem during venoarterial extracorporeal life support (ECLS) with partially severe clinical complications. The aim of this study was to establish an in vitro ECLS setup for the generation and detection of MB. Furthermore, we assessed different MB elimination strategies. Patient and ECLS circuit were simulated using reservoirs, a centrifugal pump, a membrane oxygenator, and an occluder (modified roller pump). The system was primed with a glycerin solution of 44%. Three different revolution speeds (2500, 3000, and 3400 rpm) were applied. For MB generation, the inflow line of the pump was either statically or dynamically (15 rpm) occluded. A bubble counter was used for MB detection. The effectiveness of the oxygenator and dynamic bubble traps (DBTs) was evaluated in regard to MB elimination capacities. MB generation was highly dependent on negative pressure at the inflow line. Increasing revolution speeds and restriction of the inflow led to increased MB activity. The significant difference between inflow and outflow MB volume identified the centrifugal pump as a main source. We could show that the oxygenator's ability to withhold larger MB is limited. The application of one or multiple DBTs leads to a significant reduction in MB count and overall gas volume. The application of DBT can significantly reduce the overall gas volume, especially at high flow rates. Moreover, large MB can effectively be broken down for faster absorption. In general, the incidence of MBs is significantly dependent on pump speed and restriction of the inflow. The centrifugal pump was identified as a major source of MB generation. [ABSTRACT FROM AUTHOR]

Clot formation within membrane oxygenators (MOs) remains a critical problem during extracorporeal membrane oxygenation (ECMO). The composition of the clots—in particular, the presence of von Willebrand factor (vWF)—may be an indicator for prevalent nonphysiological flow conditions, foreign body reactions, or coagulation abnormalities in critically ill patients. Mats of interwoven gas exchange fibers from randomly collected MOs (PLS, Maquet, Rastatt, Germany) of 21 patients were stained with antibodies (anti‐vWF and anti‐P‐selectin) and counterstained with 4′,6‐diamidino‐2‐phenylindole. The extent of vWF‐loading was correlated with patient and technical data. While 12 MOs showed low vWF‐loadings, 9 MOs showed high vWF‐loading with highest accumulations close to crossing points of adjacent gas fibers. The presence and the extent of vWF‐fibers/"cobwebs," leukocytes, platelet–leukocyte aggregates (PLAs), and P‐selectin‐positive platelet aggregates were independent of the extent of vWF‐loading. However, the highly loaded MOs were obtained from patients with a significantly elevated SOFA score, severe thrombocytopenia, and persistent liver dysfunction. The coagulation abnormalities of these critically ill patients may cause an accumulation of the highly thrombogenic and elongated high‐molecular‐weight vWF multimers in the plasma which will be trapped in the MOs during the ECMO therapy. [ABSTRACT FROM AUTHOR]

Nowadays, an increasing number of neonatal and pediatric patients with severe heart failure benefits from extracorporeal membrane oxygenation (ECMO) support. A total of 39 pediatric patients needed venoarterial ECMO (vaECMO) support in our department between January 2008 and December 2016. Patients were retrospectively divided in two groups: 30‐day survivor group (17 patients) and 30‐day nonsurvivor group (22 patients). Outcome and factors predictive for 30‐day mortality and mid‐ as well as long‐term survival up to 7‐year follow‐up were analyzed by univariate analysis and Kaplan‐Meier survival estimation. Basic demographics and preoperative characteristics did not differ between groups (P > 0.05). 67% of patients were successfully weaned off ECMO and 44% survived 30‐day after ECMO application. After 7‐year follow‐up 28% of pediatric patients were alive. Thirty‐day survivors were significantly more likely to undergo elective cardiac surgery (P = 0.001), whereas significantly more 30‐day nonsurvivors underwent urgent surgery (P = 0.004). Odds of incidence of catecholamine refractory circulatory failure, failed myocardial recovery, and cerebral edema was significantly higher in 30‐day nonsurvivor group (41.6‐fold, 16‐fold, and 2.5‐fold, respectively). Kaplan‐Meier survival estimation analysis revealed significant differences in terms of mid‐ and long‐term survival among neonates, infants, toddlers, and preadolescents (Breslow P = 0.037 and Log‐Rank P = 0.028, respectively). vaECMO provides an efficient therapy option for life‐threatening heart disorders in neonates and pediatric patients being at high risk for myocardial failure leading to circulatory arrest. Urgency of surgery effected on higher mortality, but there was no difference in terms of mortality in 30‐day survivor group in comparison to 30‐day nonsurvivor group among neonates, infants, toddlers, and preadolescents. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) provides cardiorespiratory support during cardiopulmonary resuscitation unresponsive to conventional methods. Here, we analyzed the extracorporeal cardiopulmonary resuscitation (ECPR) results of children in a cardiac arrest setting after cardiac surgery. Of 3119 cases of pediatric open‐heart surgery, 31 required postoperative ECMO. Among the 31 patients, 11 experienced cardiac arrest and ECPR in the early postoperative period. These 11 patients' median age is 1.5 [range, 0.1‐19] months and median weight is 3.9 [range, 2.9‐10.3] kg. The medical records of ECPR cases were analyzed. The median ECMO‐assisted time was 68 (range, 13‐456) hours and 4 cases (36.4%) survived. The ECMO‐assisted times were ≤2 days in 4 patients (all eventually died), ≥6 days in 3 patients (all also died), and all 4 cases supported for 2‐6 days were discharged successfully (P = 0.006). In the survivors and nonsurvivors, peak lactate levels were 10.8 ± 7.04 and 22.8 ± 6.98 mmol/L (P = 0.023) and peak creatinine levels were 47.50 ± 25.9 and 153.7 ± 73.9 mg/dL (P = 0.035), respectively. In these 11 ECPR cases, the most common complications were bleeding requiring re‐exploration (n = 6, 54.5%) and renal failure (n = 6, 54.5%). The incidence of renal failure was significantly correlated with hypoperfusion time (P = 0.015). ECPR is valuable in children with postoperative cardiac arrest. The higher peak lactate level, higher peak creatinine level, and prolonged ECMO duration were associated with higher mortality. Early diagnosis and intervention of residual anatomical problems could improve survival. Bleeding and renal failure were the most common complications and the incidence of renal failure may be correlated with longer hypoperfusion duration. [ABSTRACT FROM AUTHOR]

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

The ProtekDuo is a single site, dual lumen cannula that may be used in a multitude of configurations.1 It was initially designed as right ventricular assist device (RVAD) cannula that comes in conjunction with the TandemHeart pump (LivaNova PLC, London, UK). As such it is a game changer in the setting of ECMO in COVID-19 patients suffering from ARDS and may be recommended for initial use in these patients. This method still provides reduced RV blood flow by about 40% and was sufficient offloading the RV in this patient.7 At the present time, ECMO management with the ProtekDuo cannula appears to reduce mortality, AKI and length of the ECMO run. [Extracted from the article]

The objective of this study was to evaluate the hemodynamic performance and gaseous microemboli (GME) handling ability of a simulated neonatal extracorporeal life support (ECLS) circuit with an in‐line continuous renal replacement therapy (CRRT) device. The circuit consisted of a Maquet RotaFlow centrifugal pump or HL20 roller pump, Quadrox‐iD Pediatric diffusion membrane oxygenator, 8‐Fr arterial cannula, 10‐Fr venous cannula, and Better‐Bladder (BB) with “Y” connector. A second Quadrox‐I Adult oxygenator was added postarterial cannula for GME experiments. The circuit and pseudo‐patient were primed with lactated Ringer's solution and packed human red blood cells (hematocrit 40%). All hemodynamic trials were conducted at ECLS flow rates ranging from 200 to 600 mL/min and CRRT flow rate of 75 mL/min at 36°C. Real‐time pressure and flow data were recorded with a data acquisition system and GME were detected and characterized using the Emboli Detection and Classification Quantifier System. CRRT was added at distinct locations such that blood entered CRRT between the pump and oxygenator (A), recirculated through the pump (B), or bypassed the pump (C). With the centrifugal pump, all CRRT positions had similar flow rates, mean arterial pressure (MAP), and total hemodynamic energy (THE) loss. With the roller pump, C demonstrated increased flow rates (293.2–686.4 mL/min) and increased MAP (59.4–75.5 mm Hg) (P < 0.01); B had decreased flow rates (129.7–529.7 mL/min), and MAP (34.2–45.0 mm Hg) (P < 0.01); A maintained the same when compared to without CRRT. At 600 mL/min C lost more THE (81.4%) (P < 0.01) with a larger pressure drop across the oxygenator (95.6 mm Hg) (P < 0.01) than without CRRT (78.3%; 49.1 mm Hg) (P < 0.01). C also demonstrated a poorer GME handling ability using the roller pump, with 87.1% volume and 17.8% count reduction across the circuit, compared to A and B with 99.9% volume and 65.8–72.3% count reduction. These findings suggest that, in contrast to A and B, adding CRRT at position C is unsafe and not advised for clinical use. [ABSTRACT FROM AUTHOR]

A continuous flow extracorporeal ventricular assist device (VAD) was modified to support functionally univentricular infants and children awaiting heart transplantation. A centrifugal VAD, designed to flow from 1.5 to 8 L/min, was used as a bridge-to-transplant in four patients with functionally univentricular circulation. A variable restrictive recirculation shunt permitted lower flow ranges in small patients. In hypoxic patients, an oxygenator was incorporated into the circuit. From 2012 to 2015, the modified VAD was placed in four patients with Glenn physiology. Age ranged from 0.97 to 6.98 years (median = 2.2 yrs). Body surface area ranged from 0.41 to 0.84 m2 (median = 0.54 m2). One patient was on extracorporeal membrane oxygenation prior to VAD. A recirculation shunt was used in three patients. Three patients required temporary use of an oxygenator for 4, 10, and 27 days. Median time on the VAD was 32.3 days (range = 23-43 days). A decrease in the cavopulmonary pressure was noted in all patients, as was a fall in the B-type natriuretic peptide. Three patients survived transplant and were discharged at 28-82 days post-transplantation. One patient died after 35 days of support. Two patients experienced major bleeding events. Two patients experienced cerebrovascular accidents, one major and one minor. The centrifugal VAD successfully supported palliated functionally univentricular patients awaiting heart transplantation. The modified recirculation shunt facilitated the successful support of patients in whom optimal flows were substantially lower than that recommended by the manufacturer. The continuous-flow VAD effectively decompressed the cavopulmonary system. The design allowed placement of an in-line oxygenator in hypoxic patients. Further investigation is required to decrease the thromboembolic events, and associated morbidity, in patients supported with this device. [ABSTRACT FROM AUTHOR]

Acute renal failure ( ARF) is associated with increased mortality in pediatric extracorporeal membrane oxygenation ( ECMO). The aim of this study was to identify predictors of ARF during ECMO in pediatric patients after cardiac surgery. A retrospective study analyzed 42 children (≤15 years) after cardiac surgery requiring venous-arterial ECMO between December 2008 and December 2014 at Fuwai Hospital. ARF was defined as ≥300% rise in serum creatinine ( SCr) concentration from baseline or application of dialysis. Multivariate logistic regression was performed to identify the predictors of ARF during ECMO. A total of 42 children (age, interquartile range [ IQR], 13.0 [7.2-29.8] months; weight, IQR, 8.5 [6.7-11.0] kg) after cardiac surgery requiring ECMO were included in this study. The total survival rate was 52.4%, and the incidence of ARF was 40.5%. As the result of univariate analysis, ECMO duration, cardiopulmonary resuscitation, maximum free hemoglobin ( FHB) during ECMO, lactate level, and mean blood pressure before initiation of ECMO were entered in multiple logistic regression analysis. In multiple logistic regression analysis, FHB during ECMO ( OR 1.136, 95% CI 1.023-1.261) and lactate level before initiation of ECMO ( OR 1.602, 95% CI 1.025-2.502) were risk factors for ARF during ECMO after pediatric cardiac surgery. There was a linear correlation between maximum SCr and maximum FHB ( Pearson's r = 0.535, P = 0.001). Maximum SCr during ECMO has also a linear correlation with lactate level before initiation of ECMO ( Pearson's r = 0.342, P = 0.044). Increased FHB during ECMO and high lactate level before initiation of ECMO were risk factors for ARF during ECMO in pediatric patients after cardiac surgery. [ABSTRACT FROM AUTHOR]

We already developed an ex vivo liver-kidney model perfused for 6 h in which the kidney acted as a homeostatic organ to improve the circuit milieu compared to liver alone. In the current study, we extended the multiorgan perfusions to 24 h to evaluate the results and eventual pitfalls manifesting with longer durations. Five livers and kidneys were harvested from female pigs and perfused over 24 h. The extracorporeal circuit included a centrifugal pump, heat exchanger, and oxygenator. The primary end point of the study was the evaluation of the organ functions as gathered from biochemical and acid-base parameters. In the combined liver-kidney circuit, the organs survived and maintained an acceptable homeostasis for different lengths of time, longer for the liver (up to 19-23 h of perfusions) than the kidney (9-13 h of perfusions). Furthermore, glucose and creatinine values decreased significantly over time (from the 5th and 9th hour of perfusion onward). The addition of a kidney to the perfusion circuit improved the biochemical environment by removing excess products from ongoing metabolic processes. The consequence is a more physiological milieu that could improve results from future experimental studies. However, it is likely that long perfusions require some nutritional support over the hours to maintain the organ's vitality and functionality throughout the experiments. [ABSTRACT FROM AUTHOR]

Refinements in extracorporeal membrane oxygenation (ECMO) equipment, including heparin-coated surfaces, centrifugal pump, membrane oxygenator, and more biocompatible pump-oxygenator circuits, have reduced procedure-related complications and have made ECMO a safe and effective therapy for critical patients.The aim of this study was to evaluate the performance of two different ECMO circuit systems in a clinical setting and compare their outcomes. From December 2004 to December 2009, 121 patients requiredECMO for primary or postcardiotomy cardiogenic shock at our heart center.We used the Medtronic circuit system in our earlier series (Group M, n = 64), and from July 2007, ECMO was carried out mainly with the Quadrox D PLS circuit system (Group Q, n = 56). We retrospectively summarized and analyzed the data of these patients. The evaluation was based on the comparison between properties of the membrane oxygenators and pumps, anticoagulation therapy, circuit-related complications, and clinical outcomes. Support pump flow rates, platelet counts, and trans-membrane pressure drops (TMPDs) of preoxygenator and postoxygenator pressures were compared between two groups at the time of support established (T1) and support established for 24 h (T2). There were no significant differences between the two groups with regard to patient characteristics and pre- ECMO data. The support pump flow rates and platelet counts at different times were comparable in the two groups. The cannulation technique, ECMO duration, and mean heparin dosage were similar in both groups. There were also no significant differences between the groups in mortality or complications related to bleeding and organ dysfunction. Compared with the M group, the Q group experienced less mechanical failure of the ECMO circuit. The Quadrox PLS circuit system showed less circuit thrombus formation (P < 0.045), less plasma leakage (P < 0.001), and less need for replacement of oxygenators (P < 0.001). Furthermore, frequency of hemolysis during ECMO was significantly lower (P < 0.045). In addition, at T1 and T2, TMPDs were significantly lower in theQgroup.Our results suggest that both ECMO circuit systems provide similar effects for safe clinical application, but the Quadrox PLS ECMO circuit system demonstrated partially improved biocompatibility in terms of improved cell preservation, lower TMPDs, less plasma leakage, and thrombus formation. [ABSTRACT FROM AUTHOR]