Extracorporeal Blood Oxygenation Research Articles

PULM5: Hyperbaric Blood Oxygenation – Basic Considerations and First Results

Hyperbaric oxygen therapy is beneficial in several applications, but hyperbaric chambers are scarce. We are developing a novel technology for extracorporeal hyperbaric blood oxygenation (HBOX). This extracorporeal procedure uses pressure to increase the oxygen (O2) concentration in blood. The technology can provide support when large amounts of oxygen are needed: In the treatment of CO poisoning the dissolved oxygen displaces the CO from the blood, removing it from the organism. This way, the oxygen deficiency can be ended rapidly, reducing or preventing secondary damage that frequently occurs. In acute respiratory failure (ARF) the HBOX technology can support lung function, by significantly increasing oxygen transport across a specific membrane area, while maintaining adequate CO2-removal. The prototype of the HBOX consists of 2 roller pumps with a hollow-fiber membrane oxygenator (HFMO) placed in between, a control unit for gas and blood flow and a double lumen catheter. By varying the flow rates of the roller pumps, excess pressure is generated in the HFMO without causing significant blood damage. Simultaneously, the oxygen pressure in the HFMO is increased, allowing for hyperbaric oxygenation. To avoid bubble formation, either O2 increase is limited, or excess O2 is removed in second HFMO before reinfusion. The prototype was tested in-vitro using porcine blood that was either CO poisoned or conditioned to mimic ARF. In acute in-vivo experiments for CO poisoning, we used CO-poisoned pigs (ca. 75 kg, COHb = 43 %, n = 3). For in-vivo experiments for ARF, 70 kg sheep were used with ventilator settings simulating respiratory failure, resulting in SaO2 = 69 %, paCO2 = 72 mmHg (n = 2). In-vitro test results show that the HBOX can fully oxygenate hypoxic blood (sO2 ca. 40 %) with a hilite 800 LT at a flow rate of 2 L/min, which is twice the amount of oxygen transferred, compared to conventional mode, Fig. 1. In in-vivo trials, the CO elimination rate from the animals’ blood doubled when using HBOX + oxygen mask compared to oxygen mask alone, see Fig. 2. In the ARF trials, the HBOX approach resulted in SaO2 of 89, 95, and 99 % and paCO2 was 49, 46, and 39 mmHg at blood flows of 0.5, 1.0, and 1.5 L/min, respectively, see Fig. 3. The HBOX is a promising approach to increase oxygen transport across a specific membrane area. The increased oxygen levels can be used for efficient extracorporeal CO removal. For respiratory support, the hyperbaric technology adds a new dimension to ECMO treatment, allowing the use of smaller oxygenators, potentially reducing the need for anticoagulation, as well as inflammatory responses and thus invasiveness. The hyperbaric technology can be used gradually, so that the membrane efficiency can be increased during intervention. This allows us to build an oxygenator with an ideal flow distribution over a wide range of blood flows, which avoids thrombus formation in the device at lower blood flows.Figure 1. Laboratory results oxygenation performanceFigure 2. Elimination rate COHb in in-vivo trialsFigure 3. Arterial blood gases during in-vivo trial for ARF

Fabrication of anti-leakage Hyflon AD/Poly(4-methyl-1-pentene) hollow fiber composite membrane for an extra-corporeal membrane oxygenation (ECMO) system

Extra-corporeal membrane oxygenation (ECMO) systems can perform the roles of the human heart and lungs to realize extra-corporeal oxygenation of blood. This system mainly depends on the gas-blood exchange membrane, the quality of which impacts the oxygenation performance. Currently, the most widely used gas-blood exchange membrane is made of poly(4-methyl-1-pentene) (PMP) hollow fibers. However, plasma leakage often occurs during clinical applications, which decreases the oxygenation performance and the service life and may endanger the patient's life in serious cases. In this work, Hyflon AD/PMP hollow fiber composite membranes were prepared by coating Hyflon AD on the surfaces of PMP hollow fibers to form ultra-thin, dense layers. Compared the plasma leakage time of the composite membrane with that of the pristine PMP membrane, the Hyflon AD60 layer showed great improvement in anti-leakage performance. The Hyflon AD60/PMP hollow fiber composite membrane possessed lower platelet adhesion and protein adhesion than that of the PMP membrane, indicating better blood compatibility of the Hyflon AD60 membrane. Cytotoxicity experiments were conducted to further confirm the biosafety of Hyflon AD60 as a blood contact medical membrane material. Gas permeance and oxygenation performance of the Hyflon AD60/PMP hollow fiber composite membrane were tested to ensure gas exchange efficiency during the gas separation process. Therefore, the optimized Hyflon AD60/PMP hollow fiber composite membrane has potential for clinical use.

Membrane Contactors and Their Application Potential

Nowadays, due to the scarcity of natural resources, there is more pressure on the reuse of materials and the application of circular economy principles. For this purpose, increasingly efficient and energy-saving technologies capable of extracting valuable raw materials from waste streams are needed, thus reducing energy and material dependence on primary resources. One such innovative technology is represented by membrane contactors, which enable mass sharing without the need for phase dispersion within each other, thus achieving lower operational and space requirements, as compared to conventional mass sharing devices (e.g. packed bed, tower column or stirred bed reactors). In addition, membrane contactors are very versatile and can be used not only for the recovery of valuable materials from waste streams in waste management processes (in particular recycling of metals or organics), but also as life-saving devices in biomedical applications (e.g. as extracorporeal blood oxygenation devices).

Membrane Oxygenator for Extracorporeal Blood Oxygenation

Extracorporeal blood oxygenation has become an alternative to supply O2 and remove CO2 from the bloodstream, especially when mechanical ventilation provides insufficient oxygenation. The use of a membrane oxygenator offers the advantage of lower airway pressure than a mechanical ventilator to deliver oxygen to the patient’s blood. However, research and development are still needed to find appropriate membrane materials, module configuration, and to optimize hydrodynamic conditions for achieving high efficient gas transfer and excellent biocompatibility of the membrane oxygenator. This review aims to provide a comprehensive description of the basic principle of the membrane oxygenator and its development. It also discusses the role and challenges in the use of membrane oxygenators for extracorporeal oxygenation on respiratory and cardiac failure patients.

Coronavirus infection: principles of ethyotropic chemotherapy

In the development of the infectious process caused by coronaviruses, two stages can be distinguished: early (ethiotropic) and late (pathogenetic). Therapeutic principles depend on these stages. At the first stage, when the virus accumulates, ethiotropic chemotherapeutic drugs suppressing virus reproduction are predominantly used. The article considers 7 major chemotherapeutic approaches aimed at specific targets in the replication of coronaviruses: viral RNA polymerase inhibitors, inhibitors of viral protease Mpro, inhibitors of proteolytic activation of viral protein S, which carries out the virus entry into the target cell, inhibitors of virus uncoating in the intracellular endosomes, exogenous interferon compounds, preparations of natural and recombinant virus neutralizing antibodies, as well as combinations of the above drugs. At the second stage, when the virus multiplication drops down and threatening pathological processes of excessive inflammation, acute respiratory distress syndrome, pulmonary edema, hypoxia and threatening sepsis develop, it is reasonable to realize antipathogenetic approaches, such as extracorporeal blood oxygenation, detoxication, anti-inflammatory and antibacterial therapeutic drugs and measures.

COVID-19: etiology, clinical picture, treatment

Whereas the XX century marked the history of acute respiratory disease investigation as a period for generating in-depth system of combating influenza viruses (Articulavirales: Orthomyxoviridae, Alpha-/Betainfluenzavirus) (based on environmental and virological monitoring of influenza A virus in its natural reservoir — aquatic and semi-aquatic birds — to supervising epidemic influenza), a similar system is necessary to build up in the XXI century with regard to especially dangerous betacoronaviruses (Nidovirales: Coronaviridae, Betacoronavirus): Severe acute respiratory syndrome-related coronavirus (SARS-CoV) (subgenus Sarbecovirus), Severe acute respiratory syndrome-related coronavirus 2 (SARSCoV-2) (Sarbecovirus), Middle East respiratory syndrome-related coronavirus (MERS-CoV) (Merbecovirus). This became particularly evident after pandemic potential has been revealed in 2020 by the SARS-CoV-2. This review provides an insight into the historic timeline of discovering this virus, its current taxonomy, ecology, virion morphology, life cycle, molecular biology, pathogenesis and clinical picture of the etiologically related COVID-19 (Coronavirus disease 2019) as well as data available in the scientific literature on the anti-SARS-CoV-2-effectiveness of passive immunotherapy and most debated drugs used to treat COVID-19: Chloroquine, Hydroxychloroquine, Nitazoxanide, Ivermectin, Lopinavir and Ritonavir, Camostat mesilate, Remdesivir, Ribavirin, Tocilizumab, Anakinra, corticosteroids, and type I interferons. The pathogenesis of SARS-CoV-2 infection implicates decreased efficacy of artificial respiration, which, in this case might be replaced by more efficient extracorporeal membrane blood oxygenation supplemented with nitrogen oxide and/or Heliox inhalations.

Molecular Targets in the Chemotherapy of Coronavirus Infection.

In the pathogenesis of the infectious process in the respiratory tract by SARS, MERS, and COVID-19 coronaviruses, two stages can be distinguished: early (etiotropic) and late (pathogenetic) ones. In the first stage, when the virus multiplication and accumulation are prevalent under insufficient host immune response, the use of chemotherapeutic agents blocking the reproduction of the virus is reasonable to suppress the development of the disease. This article considers six major chemotherapeutic classes aimed at certain viral targets: inhibitors of viral RNA polymerase, inhibitors of viral protease Mpro, inhibitors of proteolytic activation of viral protein S allowing virus entry into the target cell, inhibitors of virus uncoating in cellular endosomes, compounds of exogenous interferons, and compounds of natural and recombinant virus-neutralizing antibodies. In the second stage, when the multiplication of the virus decreases and threatening pathological processes of excessive inflammation, acute respiratory distress syndrome, pulmonary edema, hypoxia, and secondary bacterial pneumonia and sepsis events develop, a pathogenetic therapeutic approach including extracorporeal blood oxygenation, detoxification, and anti-inflammatory and anti-bacterial therapy seems to be the most effective way for the patient’s recovery.

Respiratory Support During Pulmonary Artery Thromboembolia (Review)

Pulmonary artery thromboembolia (PATE) is not a clinical entity as such, but a complication of different diseases and conditions leading to deep thrombosis in the low tension circulation system, right cardiac chambers or causing local thrombosis in the pulmonary artery system. PATE is characterized by complex pathogenesis of respiratory failure of varying severity, which makes it difficult to choose a respiratory support technique.Purpose of the overview: to show advantages of different respiratory support techniques and prospects of high-flux oxygen therapy with regard to PATE pathophysiology.82 sources were selected based on the principle of combining clinical and experimental data from papers published over the recent 5 years and earlier that are still relevant for medical practice.The overview presents the structure of main causes and prevalence of PATE and considers thrombogenesis stages and predominant manifestations of respiratory failure during PATE occurring due to inconsistency between pulmonary ventilation and perfusion. Review discusses five methods of respiratory therapy in PATE patients: low-flux and high-flux oxygen therapy, non-invasive and invasive artificial lung ventilation, extracorporeal blood oxygenation. Finally, the paper shows the efficacy and limitations of these methods.Conclusion. High-flux oxygen therapy seems to be the most effective and promising technique in PATE patients thanks to absence of adverse cardiohemodynamic consequences, subjective comfort for patients, and relation to minimal risks of secondary infectious complications.Nevertheless, the clinical experience accumulated is insufficient to make an absolute choice of one particular technique for respiratory support during PATE. It is necessary to continue investigating the clinical efficacy of high-flux oxygen therapy in the specific population of patients who experienced PATE.

The Maximal Pore Size of Hydrophobic Microporous Membranes Does Not Fully Characterize the Resistance to Plasma Breakthrough of Membrane Devices for Extracorporeal Blood Oxygenation.

Extracorporeal membrane oxygenation (ECMO) in blood-outside devices equipped with hydrophobic membranes has become routine treatment of respiratory or cardiac failure. In spite of membrane hydrophobicity, significant amounts of plasma water may form in the gas compartment during treatment, an event termed plasma water breakthrough. When this occurs, plasma water occludes some gas pathways and ultimately cripples the oxygenator gas exchange capacity requiring its substitution. This causes patient hemodilution and increases the activation of the patient's immune system. On these grounds, the resistance to plasma water breakthrough is regarded as an important feature of ECMO devices. Many possible events may explain the occurrence of plasma breakthrough. In spite of this, the resistance to plasma breakthrough of ECMO devices is commercially characterized only with respect to the membrane maximal pore size, evaluated by the bubble pressure method or by SEM analysis of membrane surfaces. The discrepancy between the complexity of the events causing plasma breakthrough in ECMO devices (hence determining their resistance to plasma breakthrough), and that claimed commercially has caused legal suits on the occasion of the purchase of large stocks of ECMO devices by large hospitals or regional institutions. The main aim of this study was to identify some factors that contribute to determining the resistance to plasma breakthrough of ECMO devices, as a means to minimize litigations triggered by an improper definition of the requirements of a clinically efficient ECMO device. The results obtained show that: membrane resistance to breakthrough should be related to the size of the pores inside the membrane wall rather than at its surface; membranes with similar nominal maximal pore size may exhibit pores with significantly different size distribution; membrane pore size distribution rather than the maximal pore size determines membrane resistance to breakthrough; the presence of surfactants in the patient's blood (e.g., lipids, alcohol, etc.) may significantly modify the intrinsic membrane resistance to breakthrough, more so the higher the surfactant concentration. We conclude that the requirements of ECMO devices in terms of resistance to plasma breakthrough ought to account for all these factors and not rely only on membrane maximal pore size.

The effect of hemicylindrical disruptors on the cell free layer thickness in animal blood flows inside microchannels

AbstractBlood-side resistance to oxygen transport in extracorporeal membrane blood oxygenators (MBO) depends on fluid mechanics governing the laminar flow in very narrow channels, particularly the hemodynamics controlling the cell free layer (CFL) built-up at solid/blood interfaces. The CFL thickness constitutes a barrier to oxygen transport from the membrane towards the erythrocytes. Interposing hemicylindrical CFL disruptors in animal blood flows inside rectangular microchannels, surrogate systems of MBO mimicking their hemodynamics, proved to be effective in reducing (ca. 20%) such thickness (desirable for MBO to increase oxygen transport rates to the erythrocytes). The blockage ratio (non-dimensional measure of the disruptor penetration into the flow) increase is also effective in reducing CFL thickness (ca. 10–20%), but at the cost of risking clot formation (undesirable for MBO) for disruptors with penetration lengths larger than their radius, due to large residence times of erythrocytes inside a low-velocity CFL formed at the disruptor/wall edge.

The development of oxygenators in extra corporeal circulation

The objective of this paper is to present one of the most important components of the extracorporeal circulation circuit, the oxygenator. In addition, the manufacture materials, the function and superiority of modern oxygenators are presented in order to stress their advantages over the older types. The future of oxygenators and the tendency to develop small intravascular artificial lungs are also discussed. A bibliographic study of the history and first reports of extracorporeal blood oxygenation has been performed in an attempt to describe the function of these initial oxygenators and to analyze the disadvantages which led to the development and to the exclusive of the membrane oxygenators. Since the establishment of the current knowledge that the artificial membrane of the modern oxygenators is the best material to oxygenate blood and remove carbon dioxide during extracorporeal circulation, further research concerning the oxygenator’s membrane was necessary to solve particular problems, such as plasma leak. Technologic advantages in the oxygenator’s membrane made possible the safe use of the oxygenator for 28 days in the extracorporeal membrane oxygenation (ECMO) circuits. The different materials used for the construction of the oxygenators are discussed with details. The incorporation in the oxygenator of additional devices, such as the heat exchanger, the arterial filter and blood reservoir to develop one compact construction is considered to be one more upgrade of the oxygenator’s technology. Accidents and safety precautions of the oxygenators are also discussed especially that of the thrombosis of the device. The necessity for more detailed and accurate monitoring of the oxygenator in real time during cardiac surgery is discussed. The latter holistic approach to the operation of the oxygenator and of the components which incorporate in the device offers specific advantages, while modification of the surface in contact with the blood ameliorates the inflammatory response.

Development of a self-pumping extracorporeal blood oxygenation device characterized by a rotating shaft with embedded fiber packages.

To offer respiratory support for patients with lung disease, a novel technological solution for blood pumping and oxygenation is being developed. The pump-lung system was designed to integrate fiber membranes into six packages radially embedded in a rotating hollow shaft placed along the longitudinal axis of the device. Fiber packages are inclined with respect to the rotation axis so that the rotational motion of the rotating shaft allows a self-pumping system to be obtained. Both hemodynamic and gas transfer performances were investigated using both in vitro experiments and in silico flow analyses. The predicted flow velocity in the pump chamber was smooth and characterized by high peripheral velocities near the housing wall. As the blood flow enters the inlet, the static pressure increased with the angular momentum imparted to the fiber packages. Experiments confirmed that the proposed pump-lung system can provide adequate blood flow and oxygen transfer over the range of intended operating conditions (0.5-5 L/min and 500-1500 r/min). Although the study did not include animal testing, the novel pump-oxygenator solution is feasible for respiratory support in patients with lung diseases.

Extracorporeal membrane oxygenation as a method to manage acute cardiopulmonary failure after emergency coronary artery bypass grafting

Acute cardiopulmonary failure after emergency coronary artery bypass grafting (CABG) is a complex thera­peutic problem due to its high mortality rate. This paper reports the safety and effectiveness of extracorpor­eal membrane oxygenation (ECMO) in treating acute cardiopulmonary failure following emergency CABG. A 37-day period of mechanical circulation support and extracorporeal blood oxygenation with the ECMO method served as a bridge to recovery. At day 34 following the disconnection of ECMO, a patient with EF > 35% was transferred to a rehabilitation ward. The procedure can be successful only when the physi­cians, nurses and perfusionists of the intensive care team cooperate closely.

Continuous gas transfer monitoring during extracorporeal membrane oxygenation

Abstract Extracorporeal membrane oxygenation therapy can prevent hypoxia, and the related inherent danger of death, if mechanical ventilation does not maintain sufficient physiological gas exchange. This form of therapy provides supplemental extracorporeal blood oxygenation and decarboxylation. The most important values to be monitored for the supervision of extracorporeal gas exchange are blood gas measurements, which are normally obtained only intermittently. Continuous measurement during this therapy is rarely implemented because the devices used are costly, and the amount of supervision and maintenance required is complex and expensive (even on the relatively short term of several hours). We present an alternative approach to supervise extracorporeal gas exchange that avoids the use of blood gas analyzers. This is achieved using venous oxygen saturation and additional sensors within the gas phase of the extracorporeal setup. Finally, carbon dioxide gas transfer is measured directly and oxygen gas transfer is estimated using an extended Kalman filter based on an evaluated gray-box model. The proposed method is characterized in silico and evaluated using in vivo data (accuracy of oxygen gas transfer estimation 9.1 ± 49 mL/min). Results suggest that monitoring of gas transfer with adequate performance is possible and that clinical application using this measurement value in closed-loop control is also feasible.

Extracorporeal membrane blood oxygenators: effect of membrane wetting on gas transfer and device performance

ABSTRACTHollow fiber contactors are successfully used as blood oxygenators in extracorporeal membrane oxygenation (ECMO); the optimization of these devices relies on a full comprehension of transport mechanisms involving respiratory gasses. This phenomenon is not clearly understood although it strongly affects blood oxygenators' performance.This work presents a model for countercorrent ECMO oxygenators, accounting for both membrane wetting and chemical reactions occurring in these systems. In the first part of the paper, the theoretical framework is presented; later, membrane wetting is analyzed and it is shown its effect on the overall mass transfer coefficients. Namely, it comes to light that membrane wetting strongly reduces membrane performances in terms of gasses transport and of respiratory quotient. Copyright © 2012 Curtin University of Technology and John Wiley & Sons, Ltd.

Extracorporeal Blood Oxygenation and Ozonation (EBOO): A Controlled Trial in Patients with Peripheral Artery Disease

Since 1990 our group has been using extracorporeal circulation to ozonate blood by an original method, known as extracorporeal blood oxygenation and ozonation (EBOO), with the aim of amplifying the results observed with ozone autohemotherapy. To verify the hypothesis that EBOO improves the skin lesions typical of peripheral artery disease (PAD) patients. Twenty-eight patients with PAD were randomized to receive EBOO or intravenous prostacyclin in a controlled clinical trial. The primary efficacy parameters were regression of skin lesions and pain,and improvement in quality of life and vascularisation. Patients treated with EBOO showed highly significant regression of skin lesions with respect to patients treated with prostacyclin. Other parameters that were significantly different in the two groups of patients were pain,pruritus, heavy legs and well-being. No significant differences in vascularisation of the lower limbs before and after treatment were found in either group. No side effects or complications were recorded during the 210 EBOO treatments. EBOO was much more effective than prostacyclin for treating skin lesions in PAD patients and also had a positive effect on patient general condition without any apparent change in arterial circulation. This suggests other mechanisms of action of EBOO.

Designing Microporous Hollow Fibre Blood Oxygenators

Extracorporeal blood oxygenators are used to oxygenate the blood during open-heart surgery. Today the vast majority of these blood oxygenators use hydrophobic microporous hollow fibre membranes to separate the blood and gas phases. Oxygen diffuses from the gas phase through the gas-filled membrane pores into the blood. Oxygen in the blood plasma binds to haemoglobin present in the red blood cells. Consequently the rate of oxygen transfer is enhanced compared to the oxygenation of water where the oxygen does not react in the liquid phase. Here mass transfer and friction factor correlations developed for nonreactive Newtonian and non-Newtonian fluids are used to predict results for blood. Characteristic parameters such as the Reynolds and Schmidt numbers and the friction factor have been modified to account for the shear-thinning behaviour of blood. A mass transfer enhancement factor has been developed based on film theory which accounts for the reaction between oxygen and haemoglobin. These equations may be used to predict the performance of a blood oxygenator based on results for simple systems such as the oxygenation of water. Consequently in the initial stages of new blood oxygenator designs, experiments may be conducted using water rather than blood to save time and money.

New Fiber Configuration for Intravenous Gas Exchange

Implantation of a membrane oxygenator (IO) into the vena cava for blood oxygenation in patients with acute lung failure has been researched for the last 25 years. Compared to the extra corporeal blood oxygenation, where blood is handled outside the body, IO doesn't present tubes, housings or heat exchangers, thus reducing considerably blood contact surface and setting priming volume to zero. Otherwise, restricted space in the vena cava and unadvantageous blood flow conditions represent so far a limitation for sufficient gas exchange. A new fiber configuration for intravenous use is being developed, which increases the implantable fiber surface and enhances gas exchange due to the increased blood convection. This is made possible by new fiber bundles, which are free to slide on a catheter and after implantation assume a twisted shape characterized by high homogeneity and fiber density.

Designing Blood Oxygenators

Extracorporeal blood oxygenators are used to provide cardiopulmonary support during open heart surgery. In the study reported here, mass transfer correlations were determined for commercially available blood oxygenators. Two configurations used commercially, flow outside and across bundles of hollow fibers and flow in thin channels between parallel flat sheet membranes, were investigated. Water and glycerol/water mixtures were used as a substitute for blood. Diffusion of oxygen into and out of these solutions was studied. For flow across bundles of hollow fibers, the mass transfer correlations derived here are in agreement with analogous correlations for crossflow heat exchangers. However, for flow in thin channels, the rate of mass transfer is often less than predicted from theory. This compromised mass transfer can be explained by considering slight variations in the thickness of the blood flow channels. The mass transfer correlations developed here could be used to design better blood oxygenators.

EXTRACTION OF MINUTE GAS BUBBLES FROM LIQUIDS FLOWING IN A SIMULATED CARDIOPULMONARY BYPASS SYSTEM BY A VENTURI-ASPIRATOR UNIT

An experimental study is performed to extract minute gas bubbles from liquids flowing in a simulated cardiopulmonary bypass system using a Venturi-aspirator unit. In other words, oxygen bubbles in oxygenated blood are simulated by air bubbles in water with AP30 (about same viscosity as whole blood). This study is intended to determine the feasibility of using a Venturi aspirator unit to extract minute gas bubbles from a simulated cardiopulmonary bypass system. Testing of the Venturi-type bubble extraction is carried out using three different test sections. Two Venturis are used, and a straight tube configuration is used as a control. The two Venturis are similar, with the exception that one has a longer inlet cone which causes the entering liquid to accelerate at a slower rate. Results are obtained for effectiveness of the aspirator unit as functions of total flow rate, extraction suction, suction pressure difference, and hydraulic head. It is concluded from the study that:(i) The effectiveness of the Venturis is typically between 90 and 100 percent. It increases with an increase in suction or suction pressure difference but decreases with an increase in total flow rate.(ii) The Venturi is most suitable for extraction of minute gas bubbles, especially for use with AP30 (whole blood), which yields substantially higher effectiveness than water.(iii) It is anticipated that a Venturi-aspirator unit can be superior to other bubble separation device as the cardiopulmonary bypass system for applications in extra corporeal blood oxygenation.