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Dialoxygenation: A Preclinical Trial for Transforming the Artificial Kidney Into an oxygenator

ASAIO JOURNAL 2025年第1期71卷 92-98页

作者： Karacanoglu, Dilek Bedir, Esra Nakip, Ozlem Saritas Kesici, Selman Duran, Hatice Bayrakci, Benan Hacettepe Univ Ctr Life Support Practice & Res Dept Pediat Intens Care Med Ankara Turkiye TOBB Univ Econ & Technol Dept Mat Sci & Nanotechnol Engn Ankara Turkiye Bilkent Univ UNAM Natl Nanotechnol Res Ctr Ankara Turkiye Bilkent Univ Inst Mat Sci & Nanotechnol Ankara Turkiye Etlik City Hosp Dept Pediat Intens Care Unit Ankara Turkiye

Critically ill patients sometimes require tandem application of extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) which is easier and cheaper. We aimed to transform the kidney membrane into a lung membrane by adding hydrogen peroxide (H2O2) to the dialysate as the oxygen source. A solution containing H2O2 and a dialysate fluid mixture was used as the final dialysate. Starting with 100% H2O2 solution and gradually reducing the volume of H2O2, respectively: 50%, 10%, 5%, 4%, 3%, 2%, and 1%. PRISMAFLEX system, Prismaflex M60 set and a bag of packed red blood cells (pRBCs) were the prototype. blood flow rate was about 40 ml/minute and the dialysis rate was about 200 ml/m2/minute/1.73 m2. blood sampling times were;at the beginning (T0), at 15th (T1), 30th (T2), 60th (T3) minutes. Amongst eight attempts H2O2 concentration that increased the partial oxygen pressure (pO2) level significantly in a reasonable period, without any bubbles, was 3%. Methemoglobinemia was not observed in any trial. After the test with 3%, H2O2 in the dialysate fluid decreased progressively without any H2O2 detection at post-membrane blood. Three percent H2O2 solution is sufficient and safe for oxygenation in CRRT systems. With this new oxy-dialysate solution, both pulmonary and renal replacement can be possible via a single membrane in a simpler manner.

关键词： dialo-oxygenation extracorporeal membrane oxygenation continuous veno-venous hemodiafiltration artificial lung artificial kidney hydrogen peroxide biomembrane oxygenator

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oxygenator anatomy and function

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JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA 1997年第3期11卷 275-281页

作者： Wegner, JA University Medical Center Tucson AZUSA

The natural lung is the organ responsible for oxygen and carbon dioxide exchange between the blood and the outside environment. This function is accomplished by the large surface area and high permeability of the gas exchange interface, the alveolar-capillary membrane. These same features are fundamental to the design of an artificial lung, or oxygenator. Additional lung-like features essential to the design of an ideal oxygenator include the ability to achieve balanced oxygen and carbon dioxide exchange with minimal blood damage and blood activation. The purpose of this review is to present the past and current developments of the oxygenator designs in terms of the structural and functional features of the natural lung as well as the limitations in the ability to mimic the features of the lung because of the lack of appropriate technology. Copyright (C) 1997 by W.B. Saunders Company.

关键词： lung gas exchange oxygenator biocompatibility membrane oxygenator blood flow dynamics

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oxygenator impact on voriconazole in extracorporeal membrane oxygenation circuits

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PERFUSION-UK 2020年第6期35卷 529-533页

作者： Cies, Jeffrey J. Moore, Wayne S., II Giliam, Nadji Low, Tracy Marino, Daniel Deacon, Jillian Enache, Adela Chopra, Arun Ctr Pediat Pharmacotherapy LLC Pottstown PA USA St Christophers Hosp Children 160 East Erie Ave Philadelphia PA 19134 USA Drexel Univ Coll Med Philadelphia PA 19104 USA Atlantic Diagnost Labs Bensalem PA USA NYU Langone Med Ctr New York NY USA NYU Sch Med New York NY USA

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(R)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

关键词： extracorporeal membrane oxygenation pharmacokinetics pharmacodynamics drug sequestration voriconazole oxygenator Quadrox-i

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Contemporary oxygenator Design: Shear Stress-Related Oxygen and Carbon Dioxide Transfer

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ARTIFICIAL ORGANS 2018年第6期42卷 611-619页

作者： Hendrix, Rik H. J. Ganushchak, Yuri M. Weerwind, Patrick W. Maastricht Univ Med Ctr Dept Extra Corporeal Circulat P Debeyelaan 25POB 5800 NL-6202 AZ Maastricht Netherlands

Design of contemporary oxygenators requires better understanding of the influence of hydrodynamic patterns on gas exchange. A decrease in blood path width or an increase in intraoxygenator turbulence for instance, might increase gas transfer efficiency but it will increase shear stress as well. The aim of this clinical study was to examine the association between shear stress and oxygen and carbon dioxide transfer in different contemporary oxygenators during cardiopulmonary bypass (CPB). The effect of additional parameters related to gas transfer efficiency, that is, blood flow, gas flow, sweep gas oxygen fraction (FiO(2)), hemoglobin concentration, the amount of hemoglobin pumped through the oxygenator per minuteQhb, and shunt fraction were contemplated as well. Data from 50 adult patients who underwent elective CPB for coronary artery bypass grafting or aortic valve replacement were retrospectively analyzed. Data included five different oxygenator types with an integrated arterial filter. Relationships were determined using Pearson bivariate correlation analysis and scatterplots with LOESS curves. In the Capiox FX25, Fusion, Inspire 8F, Paragon, and Quadrox-i groups, mean blood flows were 4.8 +/- 0.9, 5.3 +/- 0.7, 4.9 +/- 0.7, 5.0 +/- 0.6, and 5.7 +/- 0.6 L/min, respectively. The mean O-2 transfer/m(2) membrane surface area was 44 +/- 14, 51 +/- 9, 60 +/- 10, 63 +/- 14, and 77 +/- 18, respectively, whereas the mean CO2 transfer/m(2) was 26 +/- 14, 60 +/- 22, 73 +/- 29, 74 +/- 19, and 96 +/- 20, respectively. Associations between oxygen transfer/m(2) and shear stress differed per oxygenator, depending on oxygenator design and the level of shear stress (r=0.249, r=0.562, r=0.402, r=0.465, and r=0.275 for Capiox FX25, Fusion, Inspire 8F, Paragon, and Quadrox-i, respectively, P<0.001 for all). Similar associations were noted between CO2 transfer/m(2) and shear stress (r=0.303, r=0.439, r=0.540, r=0.392, and r=0.538 for Capiox FX25, Fusion, Inspire 8F, Paragon, and Qua

关键词： Cardiopulmonary bypass oxygenator Shear stress Oxygen transfer Carbon dioxide transfer

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The Effects of Nitric Oxide in oxygenator Sweep Gas During Extracorporeal Circulation in a Neonatal Ovine Model

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ASAIO JOURNAL 2020年第6期66卷 671-676页

作者： Rossidis, Avery C. Lawrence, Kendall M. Mejaddam, Ali Y. Kim, Aimee G. Baumgarten, Heron D. Coons, Barbara E. Young, Kathleen Monos, Stylianos Hwang, Grace Flake, Alan W. Davey, Marcus G. Childrens Hosp Philadelphia Dept Surg Philadelphia PA 19104 USA

Extracorporeal membrane oxygenation is a life-saving intervention, but bleeding complications are frequent. Given that the combination of platelet loss and dysfunction is a major contributor to this acquired bleeding diathesis, efforts to combat these phenomena are of great clinical importance. In this study, we investigated the effects of nitric oxide (NO) added to the sweep gas of an extracorporeal circuit in a neonatal ovine model. Eight lambs (age 9.6 +/- 1.9 days) were cannulated via the neck vessels and maintained on a pumpless arteriovenous extracorporeal membrane oxygenation circuit with blood flow restricted to 100 ml/min for 72 hours. All animals were heparinized, and a subset (n = 4) also received NO in the sweep gas at a concentration of 200 ppm. We observed no adverse effects from NO administration, and methemoglobin levels remained unchanged. Platelet counts significantly declined in all animals over the course of the study;however, mean counts were higher in the NO-treated group, and this difference was statistically significant at 24 hours (62 +/- 3% vs. 32 +/- 7% of baseline, P < 0.01). Likewise, mean plasma levels of beta-thromboglobulin, a marker of platelet activation, were lower in the NO-treated group, and this difference was also significant at the 24 hour time point (9.5 +/- 2.2 vs. 19.7 +/- 6.5 pg/mL/10(3) platelets, P < 0.05). We conclude that 200 ppm NO can be safely blended into the oxygenator sweep gas of a low-flow extracorporeal circuit and that it may transiently attenuate platelet consumption and activation.

关键词： extracorporeal membrane oxygenation nitric oxide sweep gas platelet oxygenator

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Development and evaluation of a variable, miniaturized oxygenator for various test methods

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ARTIFICIAL ORGANS 2023年第4期47卷 695-704页

作者： Arens, Jutta Schraven, Lotte Kaesler, Andreas Flege, Christian Schmitz-Rode, Thomas Rossaint, Rolf Steinseifer, Ulrich Kopp, Ruedger Univ Twente Fac Engn Technol Dept Biomech Engn Engn Organ Support Technol Grp Enschede Netherlands Rhein Westfal TH Aachen Helmholtz Inst Inst Appl Med Engn Med FacDept Cardiovasc Engn Aachen Germany Rhein Westfal TH Aachen Med Fac Dept Intens Care Med Aachen Germany Rhein Westfal TH Aachen Helmholtz Inst Inst Appl Med Engn Med Fac Aachen Germany Rhein Westfal TH Aachen Med Fac Dept Anesthesiol Aachen Germany

BackgroundExtracorporeal 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. MethodsMain 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. ResultsNo 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. ConclusionTherefore, we consider this newly developed device as a valuable tool for basic experimental and numerical research on the optimization of oxygenators.

关键词： adaptable extracorporeal lung assist gas exchange hemocompatibility hemolysis oxygenator variable

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Poly2-methoxyethylacrylate (PMEA) coated oxygenator:: An ex vivo study

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INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS 2002年第3期25卷 223-229页

作者： Mueller, XM Jegger, D Augstburger, M Horisberger, J von Segesser, LK CHU Vaudois Dept Cardiovasc Surg CH-1011 Lausanne Switzerland

PMEA is a hydrophilic polymer coating with a unique design that minimizes the adsorption and denaturation of proteins and blood cells. This study compares thrombus resistance, blood path resistance, thrombocyte profile, and blood trauma of the PMEA coated Capiox membrane oxygenator (Terumo, Japan) vs. an uncoated version. Methods: Six calves (mean bodyweight: 75.3+/-4.5kg) were placed on cardiopulmonary bypass for 6 hours and randomly assigned to the coated or uncoated oxygenator, with a low heparinisation protocol (ACT>180s). Results: Macroscopically, red staining was observed in all uncoated oxygenators, and in none of the coated ones, Inlet pressure was significantly higher in the uncoated group (at 1h: 279+/-25 vs. 175+/-11mmHg, p<0.01 and at 6h: 217+/-10 vs. 171(8mmHg, p<0.01). Thrombocyte count values (corrected for hematocrit and normalized by prebypass values) were significantly higher in the coated group (at 1h: 76+/-6 vs. 53+/-13%, p<0.01 and at 6h: 70+/-6 vs. 44+/-26%, p<0.01). Plasma hemoglobin was below 100mg/L in both groups throughout the experiments. Conclusions: When compared with uncoated oxygenator, PMEA coated oxygenator exhibited increased thrombus resistance with lower inlet pressure and lower thrombocyte consumption. In both groups, trauma to red cells was minimal, emphasizing the efficient design of this type of oxygenator.

关键词： biocompatibility oxygenator cardio-pulmonary bypass

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Circuit oxygenator Contributes to Extracorporeal Membrane Oxygenation-Induced Hemolysis

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ASAIO JOURNAL 2015年第2期61卷 190-195页

作者： Williams, Duane C. Turi, Jennifer L. Hornik, Christoph P. Bonadonna, Desiree K. Williford, Walter L. Walczak, Richard J. Watt, Kevin M. Cheifetz, Ira M. Duke Childrens Hosp Dept Pediat Div Pediat Crit Care Durham NC USA Duke Univ Hosp Dept Perfus Durham NC USA Duke Univ Hosp Dept Resp Care Durham NC USA

Hemolysis can occur as a consequence of extracorporeal membrane oxygenation (ECMO) and is associated with increased mortality and morbidity. Shear stress generated by flow through the circuit and oxygenator is believed to cause ECMO-induced hemolysis. We hypothesize that either a smaller dimension oxygenator or an in-line hemofilter will increase ECMO-associated hemolysis. Circuits were configured with a Quadrox-D Adult oxygenator (surface area 1.8 m(2)), Quadrox-iD Pediatric oxygenator (surface area 0.8 m(2)), or Quadrox-D Adult oxygenator with an in-line hemofilter (N = 4) and ran for 6 hours. Samples were collected hourly from the ECMO circuit and a time-based hemolysis control. Plasma hemoglobin levels were assayed. Circuit-induced hemolysis at each time point was defined as the change in plasma hemoglobin standardized to the time-based hemolysis control. Plasma hemoglobin increased with the use of the smaller dimension pediatric oxygenator as compared with the adult oxygenator when controlling for ECMO run time (p = 0.02). Furthermore, there was a greater pressure gradient with the smaller dimension pediatric oxygenator (p < 0.05). Plasma hemoglobin did not change with the addition of the in-line hemofilter. The use of a smaller dimension pediatric oxygenator resulted in greater hemolysis and a higher pressure gradient. This may indicate that the increased shear forces augment ECMO-induced hemolysis.

关键词： pediatric oxygenator extracorporeal membrane oxygenation hemolysis

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The superiority of hollow fiber membrane over bubble oxygenator in a perfusion circuit for the evaluation of small caliber endothelialized arterial prostheses

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ARTIFICIAL ORGANS 1996年第1期20卷 30-36页

作者： Mazzucotelli, JP Lecouls, L Hamzaoui, A Philippon, C Bizouard, E Moczar, M Loisance, DY HOP HENRI MONDOR DEPT BIOCHIMF-94010 CRETEILFRANCE

A perfusion circuit was constructed from a pneumatic ventricular assist device, 2 compliance chambers, 4 small-diameter silicone tubes (ID 4 mm) simulating shear inducing vascular prostheses, and an oxygenator with a heat exchanger. A bubble oxygenator (in a BO circuit) and a hollow fiber membrane oxygenator (in an MO circuit) were studied. The circuits were perfused with 30% human serum containing culture medium for 7 days at 37 degrees C. The pH, Po-2, Pco(2), Na+, K+, Ca2+, Cl-, glucose, and total protein concentrations remained the same in BO and MO circuits during the 7 days of perfusion. The differences between the values measured in the perfusion medium and in the medium maintained in the static conditions of cell culture were not significant. In the BO circuit, the amount of cholesterol and triglyceride concentrations decreased whereas the relative amounts of albumin, alpha 1, alpha 2, beta, and gamma globulins remained stable in the perfusion medium. The medium from the BO circuit did not promote the proliferation of cultured human saphenous vein endothelial cells. In the medium from the MO circuit, the cholesterol and triglyceride concentrations did not change with perfusion time;the proliferation rate and anticoagulant function of endothelial cells were maintained. The hollow fiber membrane oxygenator preserves the biological characteristics of the cell culture medium in a perfusion circuit. The MO circuit permits the performance of relevant studies on shear stress resistance and functional activity of human endothelial cells seeded onto vascular prostheses.

关键词： vascular prosthesis perfusion circuit oxygenator endothelial cells

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Novel application of indocyanine green fluorescence imaging for real-time detection of thrombus in a membrane oxygenator

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ARTIFICIAL ORGANS 2021年第10期45卷 1173-1182页

作者： Sakurai, Hironobu Fujiwara, Tatsuki Ohuchi, Katsuhiro Hijikata, Wataru Inoue, Yusuke Seki, Haruna Tahara, Tomoki Yokota, Sachie Ogata, Asato Mizuno, Tomohiro Arai, Hirokuni Tokyo Med & Dent Univ Dept Cardiovasc Surg Grad Sch Med & Dent Sci Tokyo Japan Tokyo Med & Dent Univ Dept Adv Surg Technol Res & Dev Tokyo Japan Tokyo Inst Technol Sch Engn Tokyo Japan Asahikawa Med Univ Adv Med Engn Res Ctr Asahikawa Hokkaido Japan Tokyo Med & Dent Univ Fac Med Tokyo Japan

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.

关键词： acute animal experiment coronavirus disease 2019 extracorporeal membrane oxygenation indocyanine green fluorescence imaging indocyanine green oxygenator real-time thrombus detection thrombus

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