Macro- and micronutrient disposition in an ex vivo model of extracorporeal membrane oxygenation

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

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Effect of ex vivo extracorporeal membrane oxygenation flow dynamics on immune response

Perfusion ◽

10.1177/0267659119830012 ◽

2019 ◽

Vol 34 (1_suppl) ◽

pp. 5-14 ◽

Cited By ~ 4

Author(s):

Katrina K Ki ◽

Margaret R Passmore ◽

Chris Hoi Houng Chan ◽

Maximillian V Malfertheiner ◽

Mahe Bouquet ◽

...

Keyword(s):

Inflammatory Response ◽

Extracorporeal Membrane Oxygenation ◽

Ex Vivo ◽

Antigen Expression ◽

High Flow ◽

Flow Dynamics ◽

Low Flow ◽

Technological Advancement ◽

Ex Vivo Model ◽

Membrane Oxygenation

Background: Extracorporeal membrane oxygenation is a life-saving support for heart and/or lung failure patients. Despite technological advancement, abnormal physiology persists and has been associated with subsequent adverse events. These include thrombosis, bleeding, systemic inflammatory response syndrome and infection. However, the underlying mechanisms are yet to be elucidated. We aimed to investigate whether the different flow dynamics of extracorporeal membrane oxygenation would alter immune responses, specifically the overall inflammatory response, leukocyte numbers and activation/adhesion surface antigen expression. Methods: An ex vivo model was used with human whole blood circulating at 37°C for 6 hours at high (4 L/minute) or low (1.5 L/minute) flow dynamics, with serial blood samples taken for analysis. Results: During high flow, production of interleukin-1β (p < 0.0001), interleukin-6 (p = 0.0075), tumour necrosis factor-α (p = 0.0013), myeloperoxidase (p < 0.0001) and neutrophil elastase (p < 0.0001) were significantly elevated over time compared to low flow, in particular at 6 hours. While the remaining assessments exhibited minute changes between flow dynamics, a consistent trend of modulation in leukocyte subset numbers and phenotype was observed at 6 hours. Conclusion: We conclude that prolonged circulation at high flow triggers a prominent pro-inflammatory cytokine response and activates neutrophil granule release, but further research is needed to better characterize the effect of flow during extracorporeal membrane oxygenation.

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Ex Vivo Model to Decipher the Impact of Extracorporeal Membrane Oxygenation on Beta-lactam Degradation Kinetics

Therapeutic Drug Monitoring ◽

10.1097/ftd.0000000000000369 ◽

2017 ◽

Vol 39 (2) ◽

pp. 180-184 ◽

Cited By ~ 12

Author(s):

Cyril Leven ◽

Pierre Fillâtre ◽

Antoine Petitcollin ◽

Marie-Clémence Verdier ◽

Jérôme Laurent ◽

...

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Ex Vivo ◽

Degradation Kinetics ◽

Beta Lactam ◽

Ex Vivo Model ◽

Membrane Oxygenation ◽

The Impact

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Effects of an Ex Vivo Pediatric Extracorporeal Membrane Oxygenation Circuit on the Sequestration of Mycophenolate Mofetil, Tacrolimus, Hydromorphone, and Fentanyl

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-24.4.290 ◽

2019 ◽

Vol 24 (4) ◽

pp. 290-295

Author(s):

Catherine S. Heith ◽

Lizbeth A. Hansen ◽

Rhonda M. Bakken ◽

Sharon L. Ritter ◽

Breeanna R. Long ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Extracorporeal Membrane Oxygenation ◽

Mycophenolic Acid ◽

Pediatric Patients ◽

Ex Vivo ◽

Centrifugal Pumps ◽

Ecmo Circuit ◽

Binding Characteristics ◽

Membrane Oxygenation ◽

Set Up

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.

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Influence of extracorporeal membrane oxygenation on the pharmacokinetics of ceftolozane/tazobactam: an ex vivo and in vivo study

Journal of Translational Medicine ◽

10.1186/s12967-020-02381-1 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Camille Mané ◽

Clément Delmas ◽

Jean Porterie ◽

Géraldine Jourdan ◽

Patrick Verwaerde ◽

...

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Ex Vivo ◽

In Vivo Study ◽

Membrane Oxygenation

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Quantification of perflutren microsphere contrast destruction during transit through an ex vivo extracorporeal membrane oxygenation circuit

Intensive Care Medicine Experimental ◽

10.1186/s40635-016-0079-0 ◽

2016 ◽

Vol 4 (1) ◽

Cited By ~ 7

Author(s):

David G. Platts ◽

Charles McDonald ◽

Kiran Shekar ◽

Darryl J. Burstow ◽

Daniel Mullany ◽

...

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Ex Vivo ◽

Membrane Oxygenation

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Influence of Extracorporeal Membrane Oxygenation Circuit on Nutritional Supplements

Journal of Clinical Research and Reports ◽

10.31579/2690-1919/057 ◽

2020 ◽

Vol 3 (5) ◽

pp. 01-09

Author(s):

AS Thiara

Keyword(s):

Vitamin A ◽

Extracorporeal Membrane Oxygenation ◽

Ex Vivo ◽

Nutritional Supplements ◽

Ecmo Support ◽

Blood Pump ◽

Ecmo Circuit ◽

Membrane Oxygenation ◽

Over Time ◽

Control Samples

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.

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

Perfusion ◽

10.1177/0267659120907439 ◽

2020 ◽

Vol 35 (1_suppl) ◽

pp. 38-49

Author(s):

Maximilian Valentin Malfertheiner ◽

Lars Mikael Broman ◽

Leen Vercaemst ◽

Mirko Belliato ◽

Anna Aliberti ◽

...

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Clinical Studies ◽

Best Practice ◽

Ex Vivo ◽

Research Question ◽

Exclusion Criteria ◽

Coating Materials ◽

Specific Research ◽

Membrane Oxygenation ◽

Research Questions

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.

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Extracorporeal membrane oxygenation and V/Q ratios: an ex vivo analysis of CO2 clearance within the Maquet Quadrox-iD oxygenator

Perfusion ◽

10.1177/0267659120906767 ◽

2020 ◽

Vol 35 (1_suppl) ◽

pp. 29-33 ◽

Cited By ~ 4

Author(s):

Bishoy Zakhary ◽

Jayne Sheldrake ◽

Vincent Pellegrino

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Dead Space ◽

Gas Flow ◽

Ex Vivo ◽

Respiratory Acidosis ◽

Gas Flows ◽

Membrane Oxygenation ◽

In Series ◽

Membrane Oxygenators ◽

Different Levels

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.

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Oxygenator impact on voriconazole in extracorporeal membrane oxygenation circuits

Perfusion ◽

10.1177/0267659120937906 ◽

2020 ◽

Vol 35 (6) ◽

pp. 529-533

Author(s):

Jeffrey J Cies ◽

Wayne S Moore ◽

Nadji Giliam ◽

Tracy Low ◽

Daniel Marino ◽

...

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Closed Loop ◽

Ex Vivo ◽

Entire Study ◽

Drug Degradation ◽

Membrane Oxygenation ◽

Drug Loss ◽

In Series

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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