Development of a new silicone membrane oxygenator for ECMO.

Two types small and efficient ECMO oxygenators were developed utilizing the most up to date hollow fiber technology. Newly silicone hollow fibers possess sufficient mechanical strength while maintaining ultra thin walls of 50 micro meter. Two types of oxygenators were made with this fiber. The fiber length for the type 1 module is 150mm with a priming volume 194 cc (surface area 1.3 m(2)) and type 2 has a fiber length of 100 mm with a 144 cc priming volume (the surface area 0.8 m(2)). The studies were performed at 0.5, 1.0 and 2.0 L/min of blood flow and these oxygenators demonstrated. O(2) gas transfer rate of 69+/-4 ml/min/L for type 1 and 68+/-6 ml/min/L for type 2. The CO(2) gas transfer rate was 25+/-2 ml/min/L for type 1 and 32+/-2 ml/min/L for type 2. These results demonstrate type 2 oxygenator has similar gas exchange capabilities to those of Kolobows' oxygenator which has about 2.0 times larger surface area. Additionally, comparative hemolysis tests were preformed with this new oxygenator and the Kolbow. The NIH value was 0.006 (g/100 L) for the type 1 oxygenator and 0.01 (g/100 L) for the Kolbow oxygenator. These results suggested that this ECMO oxygenator had sufficient gas exchange performance in spite of being smaller and induced minimal blood damage.     

North American neonatal extracorporeal membrane oxygenation (ECMO) devices and team roles: 2008 survey results of Extracorporeal Life Support Organization (ELSO) centers

In early 2008, surveys of active extracorporeal membrane oxygenation (ECMO) centers in North America were conducted by electronic mail regarding neonatal ECMO equipment and professional staff. Eighty of 103 (78%) North American ECMO centers listed in the Extracorporeal Life Support Organization directory as neonatal centers responded to the survey. Of the responding centers, 82.5% routinely used roller pumps for neonatal ECMO, and the remaining 17.5% used centrifugal pumps. Silicone membrane oxygenators were used by 67% of the respondents, whereas 19% used micro-porous hollow fiber oxygenators, and 14% used polymethylpentene hollow fiber oxygenators. Of the silicone membrane oxygenator users, 86% used the Medtronic Ecmotherm heat exchanger, 10% used the Gish HE-4 heat exchanger, and 4% used the Terumo Conducer device. Sixty-four percent of the responding centers used some form of in-line blood gas monitoring. Six percent of the centers used a bubble trap in the arterial line, and 5% used an arterial line filter. A bladder was used by 85% of the centers, and 4% of these used a mechanical bladder box for servo regulation; the remaining 96% used pressure servo regulation. An air bubble detector was used by 88% of the responding centers. A surface coating was used by 44% of the centers on all their neonatal ECMO patients. Thirty-one percent of the centers use an activated clotting time of 180-220 seconds. At 54% of the responding centers, perfusionists were involved with the ECMO program, registered nurses were involved at 70% of the centers, and respiratory therapists were involved at 46% of the centers. Compared with a 2002 survey, silicone membrane use is declining, and the use of centrifugal blood pumps and coated ECMO circuits is becoming more apparent. ECMO teams are still multidisciplinary, made up of combinations of registered nurses, respiratory therapists, and perfusionists.     

Retrospective analysis comparing hollow fiber and silicone membrane oxygenators for neonates on ECMO

There is little information showing the use of microporous polypropylene hollow fiber oxygenators during extra-corporeal life support (ECLS). Recent surveys have shown increasing use of these hollow fibers amongst ECLS centers in the United States. We performed a retrospective analysis comparing the Terumo BabyRx hollow fiber oxygenator to the Medtronic 800 silicone membrane oxygenator on 14 neonatal patients on extracorporeal membrane oxygenation (ECMO). The aim of this study was to investigate the similarities and differences when comparing pressure drops, prime volumes, oxygenator endurance, and gas transfer capabilities between the two groups.     

Gas Transfer Performance of a Hollow Fiber Silicone Membrane Oxygenator: Ex Vivo Study

Based on the results of in vitro studies of many experimental models, a silicone hollow fiber membrane oxygenator for pediatric cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO) was developed using an ultrathin silicone hollow fiber with a 300 microm outer diameter and a wall thickness of 50 microm. In this study, we evaluated the gas transfer performance of this oxygenator simulating pediatric CPB and ECMO conditions. Two ex vivo studies in a pediatric CPB condition for 6 h and 5 ex vivo studies in an ECMO condition for 1 week were performed with venoarterial bypass using healthy calves. At a blood flow rate of 2 L/min and V/Q = 4 (V = gas flow rate, Q = blood flow rate) (pediatric CPB condition), the O2 and CO2 gas transfer rates were maintained at 97.44 +/- 8.88 (mean +/- SD) and 43.59 +/- 15.75 ml/min/m2, respectively. At a blood flow rate of 1 L/min and V/Q = 4 (ECMO condition), the O2 and CO2 gas transfer rates were maintained at 56.15 +/- 8.49 and 42.47 +/- 9.22 ml/min/m2, respectively. These data suggest that this preclinical silicone membrane hollow fiber oxygenator may be acceptable for both pediatric CPB and long-term ECMO use.     

Development of silicone rubber hollow fiber membrane oxygenator for ECMO

Silicone rubber hollow fiber membrane produces an ideal gas exchange for long-term ECMO due to nonporous characteristics. The extracapillary type silicone rubber ECMO oxygenator having an ultrathin hollow fiber membrane was developed for pediatric application. The test modules were compared to conventional silicone coil-type ECMO modules. In vitro experiments demonstrated a higher O2 and CO2 transfer rate, lower blood flow resistance, and less hemolysis than the conventional silicone coil-type modules. This oxygenator was combined with the Gyro C1E3 centrifugal pump, and three ex vivo experiments were conducted to simulate pediatric V-A ECMO condition. Four day and 6 day experiments were conducted in cases 1 and 2, respectively. Case 3 was a long-term experiment up to 2 weeks. No plasma leakage and stable gas performances were achieved. The plasma free hemoglobin was maintained within a normal range. This compact pump-oxygenator system in conjunction with the Gyro C1E3 centrifugal pump has potential for a hybrid total ECMO system.     

Extracorporeal membrane oxygenator compatible with centrifugal blood pumps

Coil-type silicone membrane oxygenators can only be used with roller blood pumps due to the resistance from the high blood flow. Therefore, during extracorporeal membrane oxygenation (ECMO) treatment, the combination of a roller pump and an oxygenator with a high blood flow resistance will induce severe hemolysis, which is a serious problem. A silicone rubber, hollow fiber membrane oxygenator that has a low blood flow resistance was developed and evaluated with centrifugal pumps. During in vitro tests, sufficient gas transfer was demonstrated with a blood flow less than 3 L/min. Blood flow resistance was 18 mm Hg at 1 L/min blood flow. This oxygenator module was combined with the Gyro C1E3 (Kyocera, Japan), and veno-arterial ECMO was established on a Dexter strain calf. An ex vivo experiment was performed for 3 days with stable gas performance and low blood flow resistance. The combination of this oxygenator and centrifugal pump may be advantageous to enhance biocompatibility and have less blood trauma characteristics.     

North American neonatal extracorporeal membrane oxygenation (ECMO) devices: 2002 survey results

In mid 2002, surveys of active extracorporeal membrane oxygenation (ECMO) centers in the United States and Canada were conducted via E-mail regarding neonatal equipment and personnel. Seventy-four out of 99 (75%) North American ECMO centers listed in the Extracorporeal Life Support Organization (ELSO) directory responded to the survey. Of the responding centers, 95% use roller pumps, and the remaining 5% use centrifugal pumps. Silicone membrane oxygenators were used by 97% of the respondents, while 3% used hollow fiber oxygenators. Of the silicone membrane oxygenator users, 82% used the Medtronic ECMOtherm heat exchanger, 15% used a Gish heat exchanger, and 3% used the Dideco D720 heat exchanger. Sixty-one percent of the responding centers used some form of in-line blood gas monitoring. Five percent of the centers used a bubble trap in the arterial line, and 12% used an arterial line filter. A bladder was used by 92% of the centers, and 29% used a mechanical bladder box for servo regulation, the remaining 71% used pressure servo regulation. An air bubble detector was used by 65% of the responding centers, although 81% had the device available. Heparin coating was used by 5% of the centers on all their neonatal ECMO patients. The average low range ACT was 183 seconds, and the average high range ACT was 216 seconds. At 49% of the responding centers, perfusionists were involved with the ECMO program, registered nurses were involved at 84% of the centers, and respiratory therapists were involved at 61% of the centers, perfusion assistants were involved at one center (1%), and biomedical engineers were involved at one of the centers. When compared to a 1990 survey, a shift away from using bladder boxes and toward using air bubble detectors is apparent. But other than those two shifts, ECMO is done in much the same manner as it was done 12 years ago.     

Preclinical evaluation of a new hollow fiber silicone membrane oxygenator for pediatric cardiopulmonary bypass: ex-vivo study.

Based on the results of many experimental models, a hollow fiber silicone membrane oxygenator applicable for long-term extracorporeal membrane oxygenation (ECMO) was developed. For further high performance and antithrombogenicity, this preclinical model was modified, and a new improved oxygenator was successfully developed. In addition to ECMO application, the superior biocompatibility of silicone must be advantageous for pediatric cardiopulmonary bypass (CPB). An ex vivo short-term durability test for pediatric CPB was performed using a healthy miniature calf for six hours. Venous blood was drained from the left jugular vein of a calf, passed through the oxygenator and infused into the left carotid artery using a Gyro C1E3 centrifugal pump. For six hours, the O2 and CO2 gas transfer rates were maintained around 90 and 80 ml/min at a blood flow rate of 2 L/min and V/Q=3, respectively. The plasma free hemoglobin was maintained around 5 mg/dl. These data suggest that this newly improved oxygenator has superior efficiency, less blood trauma, and may be suitable for not only long-term ECMO but also pediatric CPB usage.     

Pressure drop, shear stress, and activation of leukocytes during cardiopulmonary bypass: a comparison between hollow fiber and flat sheet membrane oxygenators

The membrane oxygenator is known to be superior to the bubble oxygenator, but little information is available about the difference between the hollow fiber and flat sheet membrane oxygenators with regard to pressure drop, shear stress, and leukocyte activation. In this study, we compared these 2 types of membrane oxygenators in patients undergoing cardiopulmonary bypass (CPB) surgery with special focus on leukocyte activation and pressure drop across the oxygenators. Plasma concentration of elastase, a marker indicating leukocyte activation, increased to 593+/-68% in the flat sheet oxygenator group versus 197+/-42% in the hollow fiber oxygenator group (p<0.01) at the end of CPB compared to their respective baseline concentrations before CPB. Pressure drop across the oxygenator was significantly higher in the flat sheet group than in the hollow fiber group throughout the entire period of CPB (p<0.01). High pressure drop across the oxygenator as well as the calculated shear stress was positively correlated with the release of elastase at the end of CPB (r = 0.760, p<0.01, r = 0.692, p<0.01). However, this positive correlation existed in the flat sheet oxygenator but not in the hollow fiber oxygenator. Clinically, both membrane oxygenators have satisfactory performance in O2 and CO2 transfer. These results suggest that a higher pressure drop across the flat sheet oxygenator is associated with more pronounced activation of leukocytes in patients undergoing cardiopulmonary bypass.     

From the spinning disc to the membrane oxygenator for open-heart surgery

Gibbon's rotating cylinder could not be enlarged to oxygenate an animal larger than a cat. The spinning disc oxygenator, introduced in 1947, had the capacity to perfuse a dog and the potential to increase oxygenation capacity by addition of more discs. When centers began to do three to four open-heart operations per day, the disposable bubble oxygenator was more practical. Bubble size was optimized to decrease the flow of oxygen relative to the blood flow and reduce trauma to blood. The bubble oxygenator is the type most commonly used today. Use of deep hypothermia with whole blood at an esophageal temperature of 10 degrees C was initially complicated by brain damage due to aggregation of white blood corpuscles and platelets. The introduction of hemodilution permitted safe utilization of hypothermic perfusion. Perfusion of infants should not be carried out at hematocrit below 25 ml/100 m. Early membrane oxygenators used nonporous silicone, or modified silicone membranes. High priming volumes, high pressure drop and marginal gas transfer efficiency characterized these devices. Recent advances in membrane technology have spawned a new generation of membrane oxygenators utilizing microporous polypropylene. In these new oxygenators, with either microporous hollow fibers or sheet membrane, the gas transfer characteristics are far superior to those of types produced in the past. The hollow-fiber devices typically have larger surface areas and higher pressure drop than in the new state-of-the-art flat plate models. An evaluation of one of these new-generation membrane oxygenators gave optimal oxygen and carbon dioxide exchange at a gas flow of 1 l/min of 60% oxygen in air at 30 degrees C and 2 l/min of 80% oxygen in air at normal temperature and rewarming for an adult. Today, after almost 40 years of oxygenator development, these new membrane device can offer better platelet preservation and reduced blood trauma as compared with types developed in the past. The new membrane oxygenators are fast becoming the preferred choice for use in infants and in protracted perfusion.     

Description of a flow optimized oxygenator with integrated pulsatile pump

Extracorporeal membrane oxygenation (ECMO) is a well-established therapy for several lung and heart diseases in the field of neonatal and pediatric medicine (e.g., acute respiratory distress syndrome, congenital heart failure, cardiomyopathy). Current ECMO systems are typically composed of an oxygenator and a separate nonpulsatile blood pump. An oxygenator with an integrated pulsatile blood pump for small infant ECMO was developed, and this novel concept was tested regarding functionality and gas exchange rate. Pulsating silicone tubes (STs) were driven by air pressure and placed inside the cylindrical fiber bundle of an oxygenator to be used as a pump module. The findings of this study confirm that pumping blood with STs is a viable option for the future. The maximum gas exchange rate for oxygen is 48mL/min/L(blood) at a medium blood flow rate of about 300mL/min. Future design steps were identified to optimize the flow field through the fiber bundle to achieve a higher gas exchange rate. First, the packing density of the hollow-fiber bundle was lower than commercial oxygenators due to the manual manufacturing. By increasing this packing density, the gas exchange rate would increase accordingly. Second, distribution plates for a more uniform blood flow can be placed at the inlet and outlet of the oxygenator. Third, the hollow-fiber membranes can be individually placed to ensure equal distances between the surrounding hollow fibers.     

A description of a prototype miniature extracorporeal membrane oxygenation circuit using current technologies in a sheep model

In the United States, standardization of neonatal extracorporeal membrane oxygenation (ECMO) circuit was achieved during the 1980s. Since that time, the consoles and components of the ECMO circuit have remained fundamentally unchanged (bladder, rollerpump, silicone membrane oxygenator). Extracorporeal technology, however, has witnessed many significant advancements in components during the past two decades. These new technologies have characteristics that may improve outcomes when applied in the ECMO arena. Understanding how these technologies perform in long-term applications is necessary. Therefore, the purpose of this project is to evaluate the performance of a miniature ECMO circuit consisting of current generation technologies in an animal model. An ECMO circuit (prime volume 145 mL) was designed that included a hollow fiber oxygenator and a remote mounted centrifugal pump. All circuit tubing and components were surface coated. Three sheep (approx 13 kg) were placed on ECMO using standard neck cannulation techniques and maintained according to clinical protocols. Technical implementation, oxygenator function, and hematological parameters were accessed. Duration of ECMO was 20, 48, and 58 hours. There was no evidence of oxygenator failure, as measured by pressure drop and oxygen transfer, in any of the procedures. No plasma leak was observed in any oxygenators. Platelet count trended downward after 24 hours. Visual inspection after ECMO showed very little evidence of gross thrombosis. This ECMO circuit design departs dramatically from the typical North American systems. The use of this console and components facilitated a 70% reduction in priming volume over a traditional ECMO circuit. Further investigations should be conducted to determine if circuit miniaturization can reduce the morbidity associated with blood product consumption and the bloods contact with the artificial surfaces of the ECMO circuitry.     

Studies on ECMO. (III)--Study on pumpless A-V ECMO

Silicon hollow fiber membrane oxygenator is considered to be useful for long term extracorporeal membrane oxygenation (ECMO) and blood usually flows inside of the fiber (inside flow type). But if it flows outside of the fiber (outside flow type), the pressure drop is supposed to be less than that of inside flow type. In this study the oxygenator of an outside flow type was used. At first, the pilot study was done to evaluate the capability of this oxygenator as an outside flow type. The pressure drop was 50 mmHg at the blood flow of 400 ml.min-1. At this blood flow and same gas flow, CO2 transfer rate was 22.3 ml.min-1. In the second study, the effects of pumpless arterio-venous ECMO (pumpless A-V ECMO) were studied in 8 dogs under mechanical hypoventilation. During ECMO, there were no significant changes in hemodynamics when the blood flow rate was 15% of cardiac output. PaO2 and PaCO2 recovered considerably. In conclusion, pumpless A-V ECMO using this membrane oxygenator of outside flow type is effective for CO2 removal and considered to be clinically useful.     

Similarity of Clinical and Laboratory Results Obtained with Microporous Teflon Membrane Oxygenator and Bubble-Film Hybrid Oxygenator

For 80 elective clinical cardiopulmonary bypasses we alternately used either a commercial microporous Teflon membrane oxygenator or a commercial hybrid bubble-film oxygenator. Setup time was a little longer with the membrane unit (20 minutes), but priming volume (2,250 ml) was the same. No problems were encountered with the hybrid oxygenator. However, despite our monitoring of additional variables, including shim and inlet pressure and recirculation flow, gas exchange abnormalities were encountered in 5 patients on whom the membrane oxygenator was used; in 4 of these cases the abnormalities were encountered prior to our recognition of the potential for occasional internal shunting with this device.There were no hospital deaths. When the two groups, matched except for oxygenator selection, were compared, there were no significant differences clinically or hematologically. For cardiopulmonary bypass of 2 hours or less, both oxygenators studied are definite improvements over previous silicone membrane and high-gas-flow bubble oxygenators. However, lower cost and reduced complexity favor the hybrid oxygenator.     

Development of a New Hollow Fiber Silicone Membrane Oxygenator: In Vitro Study

An experimental silicone hollow fiber membrane oxygenator for long-term extracorporeal membrane oxygenation (ECMO) was developed in our laboratory using an ultrathin silicone hollow fiber. However, the marginal gas transfer performances and a high-pressure drop in some cases were demonstrated in the initial models. In order to improve performance the following features were incorporated in the most recent oxygenator model: increasing the fiber length and total surface area, decreasing the packing density, and modifying the flow distributor. The aim of this study was to evaluate the gas transfer performances and biocompatibility of this newly improved model with in vitro experiments. According to the established method in our laboratory, in vitro studies were performed using fresh bovine blood. Gas transfer performance tests were performed at a blood flow rate of 0.5 to 6 L/min and a V/Q ratio (V = gas flow rate, Q = blood flow rate) of 2 and 3. Hemolysis tests were performed at a blood flow rate of 1 and 5 L/min. Blood pressure drop was also measured. At a blood flow rate of 1 L/min and V/Q = 3, the O2 and CO2 gas transfer rates were 72.45 +/- 1.24 and 39.87 +/- 2.92 ml/min, respectively. At a blood flow rate of 2 L/min and V/Q = 3, the O2 and CO2 gas transfer rates were 128.83 +/- 1.09 and 47.49 +/- 5.11 ml/min. Clearly, these data were superior to those obtained with previous models. As for the pressure drop and hemolytic performance, remarkable improvements were also demonstrated. These data indicate that this newly improved oxygenator is superior to the previous model and may be clinically acceptable for long-term ECMO application.     

Different oxygenators for cardiopulmonary bypass lead to varying degrees of human complement activation in vitro

Complement activation was studied in vitro with six different membrane and bubble oxygenators for cardiopulmonary bypass. There was a similar increase in terminal (C5 to C9) activation with all oxygenators (p less than 0.001), ranging from 281% (117% to 444%) to 453% (225% to 680%) after 60 minutes (median and 95% confidence intervals). C3 activation was not observed with a hollow fiber membrane and a soft shell bubble oxygenator. On the other hand, a capillary membrane, a sheet membrane, a nonporous membrane, and a hard shell bubble oxygenator all induced a similar increase in C3 activation (p less than 0.01), ranging from 107% (23% to 346%) to 272% (88% to 395%) after 60 minutes. The differences in C3 activation could not be explained by the blood contact materials or any other single factor known to induce activation, which suggests that overall complement activation during cardiopulmonary bypass is a multifactorial effect. The tubing set per se induced only minor C3 activation but contributed to the overall formation of terminal complement complex. The study further indicates that an arterial line blood filter prevents activated neutrophils from being reinfused to the patient and should be used regardless of type of oxygenator.     

Recent progress and future prospect of the prolonged extracorporeal lung assist for respiratory failure

Extracorporeal membrane oxygenation (ECMO) is becoming an accepted therapeutic option for acute respiratory failure in both infants and adults. ECMO has been applied for relatively short-term support and numerous centers have reported satisfactory results with emphasis on patient selection, techniques of cannulation and perfusion, and prevention of complications. To use ECMO for a prolonged support, however, new type of artificial lung and system need to be developed. Most of the membrane oxygenators have the possibility of serum leakage through micropores. To prevent this problem, several dense membrane oxygenators have been developed and clinically used with good gas exchange. A low heparin dosage during ECMO results in reduced bleeding complication. Full systemic heparinization can be avoided during ECMO by using heparin-coated perfusion equipment. Respiratory support by means of pumpless PA-LA extracorporeal membrane oxygenation driven by pulmonary arterial pressure is attractive because of its simplicity and might be suitable for prolonged use. Further studies are necessary to develop an oxygenator for long-term ECMO.     

Haematological characteristics of a new membrane oxygenator: the Cobe CML

The new Cobe CML membrane oxygenator is more compact than other membrane oxygenators and has a combined venous and cardiotomy suction reservoir. Its size makes it as easy to use as a bubble oxygenator. The studies reported here were designed to show whether the excellent haemocompatibility found with other types of membrane oxygenators had ben compromised by the changes introduced in the Cobe CML oxygenator. Platelet number and function (ADP induced aggregation) plasma betathromboglobulin concentration and plasma haemoglobulin concentration were studied in nine patients where the Cobe CML oxygenator had been used and these were compared with ten patients managed with a Shiley S-100 bubble oxygenator. We conclude that the constructional changes of the Cobe CML oxygenator do not affect the haemocompatibility of this type of membrane oxygenator and that it remains significantly better than the Shiley S-100 bubble oxygenator.     

Numerical modeling of anisotropic fiber bundle behavior in oxygenators

Prediction of flow patterns through oxygenator fiber bundles can allow shape optimization so that efficient gas exchange occurs with minimal thrombus formation and hemolysis. Computational fluid dynamics (CFD) simulations can be used to predict three-dimensional flow velocities and flow distribution from spatially dependent variables and they allow estimations of erythrocyte residence time within the fiber bundle. This study builds upon previous work to develop an accurate numerical model for oxygenators, which would allow for accelerated iterations in oxygenator shape and diffuser plate design optimization. Hollow fiber flow channels were developed to permit experimental calculation of fluid permeability in two directions: main flow along the hollow fiber and perpendicular to the hollow fibers. Commercial software was used to develop three-dimensional CFD models of the experimental flow channels and an anisotropic porous media model for oxygenators from these experimental results. The oxygenator model was used to predict pressure loss throughout the device, visualize blood distribution within the fiber bundle, and estimate erythrocyte residence time within the bundle. Experimental flow channels measurements produced a streamwise permeability of 1.143e(-8) m(2) and transverse permeability of 2.385e(-9) m(2) . These permeabilities, coupled with previous work with volume porosity, were used to develop the numerical model of anisotropic behavior through porous fiber bundles, which indicated a more uniform flow field throughout the oxygenator. Incorporation of known anisotropic fiber bundle behavior in previous numerical models more accurately represents fluid behavior through an oxygenator fiber bundle. CFD coupled with experimental validation can produce a powerful tool for oxygenator design and development.     

The development of the modern oxygenator

From 1953 when Gibbon first successfully supported a patient with extracorporeal circulation to about 1980 many different types of oxygenators were developed. Since their introduction in the early 1980s, microporous hollow fiber oxygenators with blood flow outside the fiber have become the dominant type of oxygenator in use. Their success has been due to both the ability to specify the required properties for a good oxygenator and the application of modern design tools, especially computational fluid dynamics, to the design process. The result has been the availability of many oxygenators from different manufacturers that differ to some extent in their performance but all of which provide adequate performance for successful and safe clinical use.