scholarly journals Ex vivo models for research in extracorporeal membrane oxygenation: a systematic review of the literature

Perfusion ◽  
2020 ◽  
Vol 35 (1_suppl) ◽  
pp. 38-49
Author(s):  
Maximilian Valentin Malfertheiner ◽  
Lars Mikael Broman ◽  
Leen Vercaemst ◽  
Mirko Belliato ◽  
Anna Aliberti ◽  
...  

With ongoing progress of components of extracorporeal membrane oxygenation including improvements of oxygenators, pumps, and coating materials, extracorporeal membrane oxygenation became increasingly accepted in the clinical practice. A suitable testing in an adequate setup is essential for the development of new technical aspects. Relevant tests can be conducted in ex vivo models specifically designed to test certain aspects. Different setups have been used in the past for specific research questions. We conducted a systematic literature review of ex vivo models of extracorporeal membrane oxygenation components. MEDLINE and Embase were searched between January 1996 and October 2017. The inclusion criteria were ex vivo models including features of extracorporeal membrane oxygenation technology. The exclusion criteria were clinical studies, abstracts, studies in which the model of extracorporeal membrane oxygenation has been reported previously, and studies not reporting on extracorporeal membrane oxygenation components. A total of 50 studies reporting on different ex vivo extracorporeal membrane oxygenation models have been identified from the literature search. Models have been grouped according to the specific research question they were designed to test for. The groups are focused on oxygenator performance, pump performance, hemostasis, and pharmacokinetics. Pre-clinical testing including use of ex vivo models is an important step in the development and improvement of extracorporeal membrane oxygenation components and materials. Furthermore, ex vivo models offer valuable insights for clinicians to better understand the consequences of choice of components, setup, and management of an extracorporeal membrane oxygenation circuit in any given condition. There is a need to standardize the reporting of pre-clinical studies in this area and to develop best practice in their design.

2019 ◽  
Vol 24 (4) ◽  
pp. 290-295
Author(s):  
Catherine S. Heith ◽  
Lizbeth A. Hansen ◽  
Rhonda M. Bakken ◽  
Sharon L. Ritter ◽  
Breeanna R. Long ◽  
...  

OBJECTIVES With the expanding use of extracorporeal membrane oxygenation (ECMO), understanding drug pharmacokinetics has become increasingly important, particularly in pediatric patients. This ex vivo study examines the effect of a pediatric Quadrox-iD ECMO circuit on the sequestration and binding of mycophenolate mofetil (MMF), tacrolimus, and hydromorphone hydrochloride, which have not been extensively studied to date in pediatric ECMO circuits. Fentanyl, which has been well studied, was used as a comparator. METHODS ECMO circuits were set up using Quadrox-iD pediatric oxygenators and centrifugal pumps. The circuit was primed with whole blood and a reservoir was attached to represent a 5-kg patient. Fourteen French venous and 12 French arterial ECMO cannulas were inserted into the sealed reservoir. Temperature, pH, PO2, and PCO2 were monitored and corrected. MMF, tacrolimus, hydromorphone, and fentanyl were injected into the ECMO circuit. Serial blood samples were taken from a postoxygenator site at intervals over 12 hours, and levels were measured. RESULTS Hydromorphone hydrochloride was not as significantly sequestered by the ex vivo pediatric ECMO circuit when compared with fentanyl. Both mycophenolic acid and tacrolimus serum concentrations were stable in the circuit over 12 hours. CONCLUSIONS Hydromorphone may represent a useful medication for pain control for pediatric patients on ECMO due to its minimal sequestration. Mycophenolic acid and tacrolimus also did not show significant sequestration in the circuit, which was unexpected given their lipophilicity and protein-binding characteristics, but may provide insight into unexplored pharmacokinetics of particular medications in ECMO circuits.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Camille Mané ◽  
Clément Delmas ◽  
Jean Porterie ◽  
Géraldine Jourdan ◽  
Patrick Verwaerde ◽  
...  

2019 ◽  
Vol 43 (4) ◽  
pp. 268-276
Author(s):  
Mirko Belliato ◽  
Luca Caneva ◽  
Alessandro Aina ◽  
Antonella Degani ◽  
Silvia Mongodi ◽  
...  

Introduction: Veno-venous arterial extracorporeal membrane oxygenation is a hybrid-modality of extracorporeal membrane oxygenation combining veno-venous and veno-arterial extracorporeal membrane oxygenation. It may be applied to patients with both respiratory and cardio-circulatory failure. Aim: To describe a computational spreadsheet regarding an ex vivo experimental model of veno-venous arterial extracorporeal membrane oxygenation to determine the return of cannula pairs in a single pump–driven circuit. Methods: We developed an ex vivo model of veno-venous arterial extracorporeal membrane oxygenation with a single pump and two outflow cannulas, and a glucose solution was used to mimic the features of blood. We maintained a fixed aortic impedance and physiological pulmonary resistance. Both flow and pressure data were collected while testing different pairs of outflow cannulas. Six simulations of different cannula pairs were performed, and data were analysed by a custom-made spreadsheet, which was able to predict the flow partition at different flow levels. Results: In all simulations, the flow in the arterial cannula gradually increased differently depending on the cannula pair. The best cannula pair was a 19-Fr/18-cm arterial with a 17-Fr/50-cm venous cannula, where we observed an equal flow split and acceptable flow into the arterial cannula at a lower flow rate of 4 L/min. Conclusion: Our computational spreadsheet identifies the suitable cannula pairing set for correctly splitting the outlet blood flow into the arterial and venous return cannulas in a veno-venous arterial extracorporeal membrane oxygenation configuration without the use of external throttles. Several limitations were reported regarding fixed aortic impedance, central venous pressure and the types of cannulas tested; therefore, further studies are mandatory to confirm our findings


Author(s):  
Yair Levy

In this chapter, a general theoretical model is proposed that links learners’ satisfaction and learners’ value of e-learning systems in order to assess learners’ perceived effectiveness of such systems. The central research question in this study is: Is there a relationship between learners’ perceived satisfaction with e-learning systems and learners’ perceived value for learners’ perceived effectiveness of e-learning systems? The significance of the value construct in the context of e-learning systems has never been evaluated. How the value of e-learning systems relates to other constructs, such as satisfaction with e-learning systems and ultimately whether the value of e-learning systems can be used to indicate learners’ perceived IS effectiveness remains open. In this chapter, a general conceptual model or framework is proposed to address this phenomenon in the context of e-learning systems. The proposed model or framework will provide procedures to identify and measure the key constructs (satisfaction with e-learning systems, value of e-learning systems, and effectiveness of e-learning systems). This chapter also defines precisely the individual characteristics and four major dimensions (categories) for evaluating value of e-learning systems and satisfaction with e-learning systems based on comprehensive literature reviewed in Chapters II and III. Additionally, this chapter proposes five specific research questions that are addressed in Chapter VII. Two additional specific research questions are proposed in Chapters V and VI.


Author(s):  
David G. Platts ◽  
Charles McDonald ◽  
Kiran Shekar ◽  
Darryl J. Burstow ◽  
Daniel Mullany ◽  
...  

2020 ◽  
Vol 3 (5) ◽  
pp. 01-09
Author(s):  
AS Thiara

Background The main function of extracorporeal membrane oxygenation (ECMO) is to provide systemic perfusion and gas exchange for patients with severe, acute respiratory or cardiac illness. The ECMO system consists of blood pump and a membrane oxygenator. ECMO oxygenator fibers, blood pump and tubing may bind circulating compounds such as drugs and nutritional components during ECMO support. Any loss of vital nutrients due to adsorption to the ECMO circuits may lead to further nutritional debilitation in critical ill patients. Objective The purpose of study is to analyze the amount of nutritional supplements adsorbed to the ECMO circuit under controlled ex vivo conditions Methods Six identical ECMO circuits were primed with fresh human whole blood and maintained under physiological conditions at 36°C for 24 hours. A dose of nutritional supplement calculated for a 70 kg patient was added. 150 mL volume was drawn from priming bag for control samples and kept under similar conditions. Blood samples were obtained at predetermined time points and analyzed for concentrations of vitamins, minerals, lipids, and proteins. Statistical analyses were performed using mixed models with robust standard errors, which allows for repeated samples within each setup and incomplete data. Results No significant differences were found between the ECMO circuits and controls for any of the measured variables: cobalamin, folate, vitamin A, glucose, concentration of minerals, HDL cholesterol, LDL cholesterol, total cholesterol, triglycerides, and total proteins. There was an initial decrease and then and increase in the concentration of cobalamin and folate. Vitamin A concentrations decreased in both groups over time. There was a decrease in concentration of glucose and an increased concentration of lactate dehydrogenase over time in both groups. Conclusion There were no changes in the concentrations of nutritional supplements in an ex vivo ECMO circuit compared to control samples, indicating that parenteral nutrition can be given during ECMO support. However, the time span of this study was limited, and the design made it impossible to investigate any functional and structural changes over time in nutritional supplements which lead to diminished effects through the ECMO circuit.


Author(s):  
Gina M. Piscitello ◽  
Rene S. Bermea ◽  
John W. Stokes ◽  
Whitney D. Gannon ◽  
Anthony J. Kanelidis ◽  
...  

Purpose: Extracorporeal membrane oxygenation (ECMO) is an expensive and scarce life sustaining treatment provided to certain critically ill patients. Little is known about the informed consent process for ECMO or clinician viewpoints on ethical complexities related to ECMO in practice. Methods: We sent a cross-sectional survey to all departments providing ECMO within 7 United States hospitals in January 2021. One clinician from each department completed the 42-item survey representing their department. Results: Fourteen departments within 7 hospitals responded (response rate 78%, N = 14/18). The mean time spent consenting patients or surrogate decision-makers for ECMO varied, from 7.5 minutes (95% CI 5-10) for unstable patients to 20 minutes (95% CI 15-30) for stable patients (p = 0.0001). Few clinician respondents (29%) report patients or surrogate decision-makers always possess informed consent for ECMO. Most departments (92%) have absolute exclusion criteria for ECMO such as older age (43%, cutoffs ranging from 60-75 years), active malignancy (36%), and elevated body mass index (29%). A significant minority of departments (29%) do not always offer the option to withdraw ECMO to patients or surrogate decision-makers. For patients who cannot be liberated from ECMO and are ineligible for heart or lung transplant, 36% of departments would recommend the patient be removed from ECMO and 64% would continue ECMO support. Conclusion: Adequate informed consent for ECMO is a major ethical challenge, and the content of these discussions varies. Use of categorical exclusion criteria and withdrawal of ECMO if a patient cannot be liberated from it differ among departments and institutions.


Perfusion ◽  
2020 ◽  
Vol 35 (1_suppl) ◽  
pp. 29-33 ◽  
Author(s):  
Bishoy Zakhary ◽  
Jayne Sheldrake ◽  
Vincent Pellegrino

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.


Perfusion ◽  
2020 ◽  
Vol 35 (6) ◽  
pp. 529-533
Author(s):  
Jeffrey J Cies ◽  
Wayne S Moore ◽  
Nadji Giliam ◽  
Tracy Low ◽  
Daniel Marino ◽  
...  

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.


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