Capillary Membrane Oxygenator Research Articles

Insights into Gradient and Anisotropic Pore Structures of Capiox® Gas Exchange Membranes for ECMO: Theoretically Verifying SARS-CoV-2 Permeability.

When using the extracorporeal capillary membrane oxygenator (sample A) for ECMO treatments of COVID-19 severely ill patients, which is dominantly used in Japan and worldwide, there is a concern about the risk of SARS-CoV-2 scattering from the gas outlet port of the membrane oxygenator. Terumo has launched two types of membranes (sample A and sample B), both of which are produced by the microphase separation processes using polymethylpentene (PMP) and polypropylene (PP), respectively. However, the pore structures of these membranes and the SARS-CoV-2 permeability through the membrane wall have not been clarified. In this study, we analyzed the pore structures of these gas exchange membranes using our previous approach and verified the SARS-CoV-2 permeation through the membrane wall. Both have the unique gradient and anisotropic pore structure which gradually become denser from the inside to the outside of the membrane wall, and the inner and outer surfaces of the membrane have completely different pore structures. The pore structure of sample A is also completely different from the other membrane made by the melt-extruded stretch process. From this, the pore structure of the ECMO membrane is controlled by designing various membrane-forming processes using the appropriate materials. In sample A, water vapor permeates through the coating layer on the outer surface, but no pores that allow SARS-CoV-2 to penetrate are observed. Therefore, it is unlikely that SARS-CoV-2 permeates through the membrane wall and scatter from sample A, raising the possibility of secondary ECMO infection. These results provide new insights into the evolution of a next-generation ECMO membrane.

Simulation of blood oxygenation in capillary membrane oxygenators using modified sulfite solution

Blood oxygenation is the main performance characteristic of capillary membrane oxygenators (CMOs). Handling of natural blood in in vitro investigations of CMOs is quite complex and time-consuming. Since the conventional blood analog fluids (e.g. water/glycerol) lack a substance with an affinity to capture oxygen comparable to hemoglobin's affinity, in this study a novel approach using modified sulfite solution is proposed to address this challenge. The solution comprises sodium sulfite as a component, simulating the role of hemoglobin in blood oxygenation. This approach is validated by OTR (oxygen transfer rate) measured using native porcine blood, in two types of commercially available CMOs. Consequently, the number of complicated natural blood investigations in the evolution procedure of newly developed oxygenators would considerably decrease. Moreover, the reassessing of failed devices, in clinics, would be performed more precisely using a modified sulfite solution than simple water/glycerol testing.

Novel Concept for Pure Diffusive Capillary Membrane Oxygenators

The preeminent limitation of silicone membrane oxygenators is the poor gas permeability compared with microporous hollow fiber oxygenators (MHFO). However, the imponderability of plasma leakage, foam formation, and brittleness are all hazards that result in blood trauma formation, hereby limiting the application of MHFO during long-term oxygenation therapies. Here, we introduce a novel type of pure diffusive capillary-form silicone membrane called silicone hollow sphere. Silicone hollow sphere walls embed hollow microspheres into the core. The lodging of such microspheres promotes a higher gas exchange performance (as a result of the reduction of dense material) without altering the total thickness of capillary walls; thereby the demanded mechanical strength for handling is nevertheless conserved. Out of the same silicone material, seven SiHSp fibers with six different design specifications and a control were constructed to define experimentally the appropriate configuration for subsequent production. Each fiber was used in a miniaturized module oxygenator of a constant effective membrane surface area (Amem = 0.02 m) and length (L =183 mm) for a fair evaluation. Modules were investigated in vitro with porcine blood. O2 and CO2 transfer rates weighed 12.6 mlO2/min and 10.4 mlCO2/min, respectively, for one type of SiHSp, comparable with microporous polypropylene (OXYPHAN) exhibiting 14.1 mlO2/min and 13.2 mlCO2/min, respectively, at a maximum blood flow rate (Qmax = 200 ml/min). Silicone hollow sphere fibers show a promising competency to MHFs. They also show an evident dominancy over the conventional silicone fibers, evaluated by the control module, which emphasizes the advantage of this design.

Comparison of Two Different Minimized Extracorporeal Circulation Systems: Hematological Effects after Coronary Surgery

Cardiopulmonary bypass induces hemolysis and activation of inflammatory and coagulation systems as a result of a combination of mechanical trauma and biological mechanisms. The aim of our study was to evaluate the performance of two different minimized extracorporeal circulation (ECC) systems and to compare their influence on blood components. From January 2003 to December 2008, 1,218 patients underwent coronary artery bypass grafting with minimized ECC. The PRECiSe system (41%) consists of a microporous capillary membrane oxygenator (MO) and a diagonal pump (DeltaStream DP2). The MECC system (59%) is composed of a polymethylpentene MO with a plasma-tight diffusion membrane and a centrifugal pump (RotaFlow). Serial blood samples were taken preoperatively (T0), on arrival to intensive care unit (T1), 6 hours postoperatively (T2), and at discharge (T3). Demographic data, intraoperative, and technical parameters were similar in both groups. At T1 and T2, the platelet count in the PRECiSe group was significantly lower than that in the MECC group (p < 0.01). Furthermore, at T1, levels of lactate dehydrogenase were significantly higher in the PRECiSe group (p < 0.05). In addition, postoperative blood loss was significantly higher using the PRECiSe system (p < 0.05). In conclusion, cardiac surgery with the MECC system is associated with less postoperative bleeding and improved blood cell preservation.

Enhanced oxygen delivery induced by perfluorocarbon emulsions in capillary tube oxygenators.

Previous studies showed that a new generation of perfluorocarbon (PFC) emulsions increased tissue PO2 in the cat retina to a degree that could not be explained by the small increase in arterial O2 content seen after the infusion of low doses of 1 g PFC/kg body weight. It seems that increased O2 delivery at the tissue level after PFC infusion is caused by a local effect in the microcirculation. The authors studies this effect in vitro at steady state in a closed loop circuit, consisting of one of two types of capillary tube oxygenators, deoxygenator(s), a reservoir bag filled with anticoagulated bovine blood or saline (control), and a roller pump, to see if the addition of PFC would have an effect on the PO2 difference (delta PO2) across the capillary tube membrane oxygenator at a blood flow rate of 3 l/min. Perfluorocarbon was added in three incremental doses, each giving about 0.7 vol% of PFC. The delta PO2 across the oxygenator was measured before and after each dose. The mean percent increases in delta PO2 in blood for two types of oxygenators were 19.2 +/- 8% (mean +/- SD, n = 6, P = 0.002) and 9.9 +/- 4% (n = 3, P = 0.05), respectively, whereas the mean percent change in delta PO2 in saline was -4.9 +/- 2% (n = 2, P = 0.2). Inlet PO2s to the oxygenator were only minimally increased. The authors conclude that O2 delivery was significantly enhanced after injection of PFC in blood in this capillary tube model. A near wall excess of PFC particles may account for the augmentation of O2 diffusion in this model.

Heparin-Coated versus Non-Coated Surfaces for Extracorporeal Circulation

Studies were made to compare completely heparin-bonded (HBS) and conventional extracorporeal circulation surfaces using capillary membrane oxygenators (CMO) in sheep and dogs for up to five days. The aims were: to investigate the need for systemic heparinization in the case of heparin-coated surfaces, to assess blood compatibility and gas exchange performance of both systems and the extent of complement activation, and to find solutions for plasma leakage by the use of CMO. All studies were performed under standardized conditions, such as drugs, surgery, priming, blood flow rate etc. For heparin-coated surface studies all blood interfaces (CMO, catheters, tubes, etc) were coated. It was possible to eliminate systemic heparinization totally when HBS were used. During the five-day non-heparin application period blood coagulation parameters were almost unchanged and in the physiological range, platelets did not drop below 80%, hemolysis was negligible and gas exchange performance was unaffected. Less complement activation occurred with HBS than with non-coated surfaces.

Technical Aspects of Plasma Leakage Prevention in Microporous Capillary Membrane Oxygenators

A limiting factor in using microporous capillary membrane oxygenators (CMO) for long-term extracorporeal lung support is leakage. Application of heparin-coated CMO requires additional examination because leakage is probably caused by the temperature conditions of the gas, the blood and the circuit environment, and the surface tension phenomenon at the micropores. The authors designed a thermostatized box in which the temperature of flowing gas (Tg) and blood (Tb), and the interior temperature of the box (Ti) could be regulated independently. Tb was adjusted to the animal's body temperature, and Tg was kept about 2 degrees C higher to prevent condensation of the evaporated fluid from the blood side, through the micropores, into the gas phase. Ti was maintained between Tg and Tb. The saturated outlet gas could therefore condense only outside the box. This system was used during 5 days of venovenous bypass using a covalently heparin-bonded (Carmeda) CMO (Maxima, Medtronic) in four adult sheep. No plasma leakage occurred, the surface tension of condensate water remained constant, and the gas exchange capacity of CMO was unchanged.

Heparin Free Long-term Extracorporeal Circulation Using Bioactive Surfaces

As already shown, a single bolus injection of heparin is sufficient to perform extracorporeal circulation (ECC) for long-term lung support if bioactive surfaces (HBS) are used. In the present study whether complete avoidance of systemic heparinization using HBS is possible was studied. Seven conscious sheep (50-60 kg) underwent venovenous bypass under standardized conditions using a Maxima capillary membrane oxygenator. Drug administration, surgery, and other conditions, such as priming volume and blood flow rates, were identical in all experiments. All blood contacting surfaces (oxygenator, catheters, etc.) were HBS. The ECC periods were set for 24 hr (n = 3) and 5 days (n = 4). At no time was heparin administered. No complications occurred in any experiment. Partial thromboplastin time, activated clotting time, and other coagulation parameters remained within physiologic ranges. Platelets did not drop below 80% of baseline values, and hemolysis rates were negligible. Blood gas data and other vital parameters were normal during the entire ECC period. Results show that HBS can be applied to long-term ECC, without the necessity for heparin administration.

Technical Aspects of Plasma Leakage Prevention in Microporous Capillary Membrane Oxygenators

Technical Aspects of Plasma Leakage Prevention in Microporous Capillary Membrane Oxygenators

The effect of two-phase nature of blood on the gas exchange in capillary membrane oxygenators

The effect of two-phase nature of blood on the gas exchange in capillary membrane oxygenators

The Detection of Microemboli in the Middle Cerebral Artery during Cardiopulmonary Bypass: A Transcranial Doppler Ultrasound Investigation Using Membrane and Bubble Oxygenators

Twenty-seven patients were examined who were undergoing cardiopulmonary bypass (CPB) surgery with either a bubble oxygenator or a capillary membrane oxygenator. The latter incorporated an arterial filter and bubble trap. A noninvasive Doppler ultrasound technique is described for monitoring irregularities in the Doppler flow signals attributable to gaseous microemboli detected in the middle cerebral artery during CPB. The ultrasound index for detecting gaseous microemboli (MEI) indicated the presence of such microemboli in 22 of the 27 patients during insertion of the aortic cannula. Measurements during CPB showed the MEI ranged from 4 to 39 in the 17 patients with a bubble oxygenator. However, all 10 patients with a membrane oxygenator had an MEI of 0. Varying the gas flow rates in 3 patients with bubble oxygenators showed a change in MEI from 4 ± 4 (SD) at a flow rate of 2 L/min to 17 ± 9 at a flow rate of 5 L/min. This observation supports the assumption that the MEI is providing quantitative information regarding the presence of gaseous emboli in the middle cerebral artery.

Utilization of the Bentley BOS-CM50 Capillary Fiber Membrane Oxygenator with a Bio-Medicus Pump for Long-Term Right Ventricular Assist: A Case Report

Following six vessel coronary artery bypass surgery, a 67-year-old man developed acute hypoxia and severe pulmonary hypertension secondary to a protamine reaction. Right ventricular bypass with oxygenation was required using a Bio-Medicus pump and Bentley BOS-CM50 capillary fiber membrane oxygenator. This helped to lower the pulmonary artery pressure from 36 mmHg to 9 mmHg. Arterial blood gases were maintained with a pH of 7.35-7.50, pCO2 30-40 mmHg, and PO2 60-200 mmHg, and activated clotting times (ACT) were kept above 480 seconds. The oxygenator was used for 14 hours without complications and removed from the circuit when the patient's mean pulmonary artery pressures were kept below 20 mmHg, and pO2s above 60 mmHg with the patient supported on the ventilator. The patient was subsequently weaned off right ventricular bypass after 66 hours of support. The Bentley CM50 capillary fiber membrane oxygenator was safely used for 14 hours, which was associated with a reduction in pulmonary hypertension in a patient recovering from a protamine reaction.

Clinical Evaluation of a Microporous Hollow-fiber Membrane Oxygenator with Large Gas Transfer Capability

A capillary tube membrane oxygenator composed of microporous hollow fibers has been evaluated in 400 cases of cardiac surgery. The available membrane area in this device is 5.4 M2. The priming volume of the oxygenator and an integral heat exchanger is 700 ml. The perfusions were conducted with moderate hypothermia and hemodilution. Arterial pO2 was controlled by appropriate adjustment of the FiO2. The pCO2 was controlled by changing the gas flow. The duration of perfusion was up to 476 minutes at blood flow rates of 2.0 to 6.7 L/min. Oxygen transfer was as high as 352 ml/min. The mean arterial pO2 was 281 mm Hg and the pCO2 38 mm Hg. Platelet count did not change significantly during perfusion. This device has proven to provide good gas exchange for nearly eight hours in this series. Two units developed small leaks of blood into the gas phase of the device. These leaks did not affect gas exchange. This oxygenator-heat exchanger unit has proven to be simple to prime, easy to operate, provide adequate gas exchange for all adults and safe for cardiac surgery.

Novel method for fabricating capillary membrane oxygenators

Operating problems associated with existing capillary membrane oxygenators have been impaired CO2 removal, nonuniform tube perfusion, thrombus formation in the blood manifolds (headers) and fall-off in performance with scale-up of small units. These faults are primarily due to poor tube ventilation, inadequate control of tube lengths, and ineffective header design. A novel semiautomatic fabrication technique is described that minimises or eliminates these deficiencies. The technique produces a well ventilated tube bundle by accurately spacing the tubes within the potted end-sections (tube sheet). The tube sheet is 10–12 mm thick, about one half of that in previously described units. To give uniform tube perfusion and eliminate stagnant regions over the tube sheet, blood is introduced normal to the tube axis through headers of hemitoroidal configuration. Three oxygenators with different dimensions and flow capacities were testedin vitro andin vivo. Good agreement was obtained between the theoretically predicted and experimentally measured oxygen-transfer rates for all units, no loss in performance being shown with oxygenator scale-up. After canine partial-bypass of six hours duration, thrombus formation was minimal in the headers with only 1 per cent of the tubes being occluded. Further optimisation is possible with smaller-diameter capillaries.

Thrombus formation in a staged capillary membrane oxygenator associated with a microaggregate blood filter: a scanning electron microscope study.

Blood contact at interfaces in extracorporeal devices is a source of traumas. Proteins are very rapidly adsorbed; then, depending on which proteins are left various degrees of platelet aggregation follow and thrombi develop. The scanning electron microscope reveals very instructive information on the morphology of the blood deposits which adhere to foreign surfaces. Oxygenators such as the Awad D, which is a staged one made of silicone rubber, become "thrombus invaded" after prolonged extracorporeal circulation in spite of adequate heparinization of the blood. In most cases, evaluation of membranes and devices is assessed with respect to transfer of blood gases. Careful examination of the morphology of deposits should be developed. This study shows the importance of blood flow rate, design, and materials.

Implantable artificial lung: Preliminary report

The ultimate treatment of chronic respiratory insufficiency is pulmonary replacement by an artificial organ, homologous lung transplantation, or chronic paracorporeal respiratory supplementation. The woven capillary membrane oxygenator appears to be a major development toward implantable artificial organs. The four units tested are made up of screens 3.5 by 4.0 cm. of capillary tubing 0.3 mm. I.D. by 0.64 mm. O.D. assembled into rectangular blocks. Units made up by five, ten, twenty, and forty screens have been assembled and tested according to the protocol suggested by Galletti. The maximum oxygen transfer rate with blood was 48 ml. per minute per square meter. Water carbon dioxide transfer rate was 23.1 ml. per minute per square meter. The pressure drops in the liquid phase were 8.5, 15.3, 13.8, 17.6 mm. Hg at 1 L. per minute flow. These results indicate that the woven capillary membrane lung is an acceptably efficient oxygenator. The characteristics of design and performance suggest that this oxygenator can be made to be implanted into the chest or used as a paracorporeal respiratory assistance device.

Thrombus formation and microaggregate removal during prolonged extracorporeal circulation using a capillary membrane oxygenator. A scanning electron microscope study.

Despite adequate heparinization, thrombus formation occurs at the blood/foreign material interface. Depending on the part of the device, the material and the blood flow, the amount and the components of thrombi vary greatly. This is not dangerous by itself but clots can be expelled downstream and damage the lungs, brain, kidney and retina. Interposition of a filter may prevent risks of embolization. The present paper reports the scanning electron microscope study carried out on the Awad oxygenator after use during prolonged extracorporeal circulation on 13 dogs. No filter has been inserted in the circuit for the first six experiments. A screen filter (4) or a polyurethane foam filter (3) was employed in the following ones.

Nature of deposits in a tubular membrane oxygenator after prolonged extracorporeal circulation: A scanning electron microscope study

Although silicone fibers are among the most compatible with tissue and blood, numerous deposits are observed after their prolonged usage in a capillary membrane oxygenator, even when the blood has been properly heparinized. The scanning electron microscope (SEM) study shows that the morphology of these deposits varies greatly, depending upon the part of the unit from which the sample is taken. The area close to the inlet is the most severely affected. The outlet zone is affected to a lesser degree, and the areas in between are only slightly affected.

A compact perfusion system for studies on the control of metabolic processes in isolated organs from small animals.

A compact apparatus for perfusion of isolated organs from small animals is described. The system is based on a module principle making it useable both in low and high pressure perfusions. 40-80 ml of heparinized, diluted rat blood used as liver-perfusion medium, is recirculated in the system, which is temperature controlled by means of a water jacket. A new type of capillary membrane oxygenator is used for oxygenation. The system permits rapid measurements of perfusate flow, vascular resistance, bile production (when the isolated liver is used), urinary production (when the isolated kidney is used), gas tensions, oxygen consumption, pH and perfusion pressure. Descriptions of the techniques used for operation and perfusion of isolated livers and kidneys from rats are given. By the generally accepted criteria of viability the isolated rat liver remains almost normal for the test period of 3 h. Liver functions were normal as judged by formation of glucose, respiratory rate, urea and bile production and gross morphology. There was very little leakage of liver enzymes into the perfusate. The transformation and elimination of labelled corticosterone were studied to test the steroid metabolizing activity of the isolated rat liver preparation.

Use of a capillary membrane oxygenator for total cardiopulmonary bypass in calves

IN RECENT YEARS, SEVERAL TYPES OF oxygenators which eliminate a direct blood-oxygen interface have been designed, tested, and in some instances brought to clinical use. [l, 2, 4-6, 81. More recently, the design and functional concept of a hollow fiber capillary membrane oxygenator has been reported [3]. Although this oxygenator has been demonstrated to perform satisfactorily during vein-to-vein perfusion in dogs, no information exists concerning the efficacy of its use in procedures requiring total cardiopulmonary bypass for periods approaching 4 hr. ‘I’he followmg study was designed to evaluate the operational characteristics of a hollow fiber membrane oxygenator and to determine the effects of this device on various hematological and biochemical parameters.