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.     

Development of a new hollow fiber silicone membrane oxygenator for ECMO: the recent progress.

Throughout the last 50 years, many improvements have been made for a more effective oxygenator. A large plate type membrane oxygenator, used by Clowes, and a coil type, used by Kolff, has evolved into the small hollow fiber oxygenator. The complex bubble oxygenator, or rotating disk oxygenator, has become a small disposable bubble oxygenator. The currently available oxygenators are extremely small, efficient, and can be used for extended periods of time. However, there are some problems with extracorporeal membrane oxygenation (ECMO). Currently in the United States, there are no clinically applicable hollow fiber ECMO oxygenators available, in spite of the extended ECMO application. Therefore, the development of a small, yet efficient, silicone hollow fiber membrane oxygenator for long-term ECMO usage was attempted. Based on the results of many experimental models, preclinical oxygenator models for long-term ECMO were developed in our laboratory using an ultra-thin silicone rubber hollow fiber membrane.     

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.     

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.     

Clinical evaluation of the microporous hollow fiber oxygenator

This report concerns a clinical evaluation for a newly devised hollow fiber oxygenator, Capiox II. It functions on a one-pump system, and is simple to set up and operate. This equipment was used for 118 patients undergoing cardiac surgery at Tokyo University Hospital from February 1982 through February 1983. The gas transfer capacity proved to be satisfactory. The employment of an air-oxygen blender prevented overoxygenation, and reasonable levels of PaO₂ and PaCO₂ were demonstrated with a FiO₂ 0.7, ratio 0.7 at normothermia. The destruction of platelets was much less with the use of this oxygenator, as compared to findings with the BOS-10. Hemolysis by Capiox II appeared to be lower than that by BOS-10, but the difference was not statistically significant. Differences were distinct in the amount of microbubbles; strikingly, no bubble was evidenced in Capiox II by the ultrasound bubble detector, during general procedures. We conclude that Capiox II is of excellent clinical value, and should be used especially for infants as well as adult patients with possible long perfusions. The merits and demerits of this equipment are given attention.     

Use of roller pump in venovenous extracorporeal membrane oxygenation as an emergency rescue procedure

A 41 years old male patient, having acute respiratory distress syndrome (ARDS) due to viral pneumonia, was put on venovenous (VV) extracorporeal membrane oxygenation (ECMO). After 3 h of initiation, the ECMO pump malfunctioned. The patient was initially managed on a hand crank for 5 h. However, as another machine would be available after 12–24 h, we decided to use a roller pump with a conventional cardiopulmonary bypass (CPB) circuit. We successfully manage this crisis with this technique without any complications. This technique can be lifesaving in catastrophic situations such as ECMO console or pump failures when there are neither backup machines nor service engineers available.     

新型软组织置入材料β磷酸三钙/硅橡胶的微观形貌和细胞相容性

目的 制备新型软组织置入材料β磷酸三钙/硅橡胶,并进行微观形貌观察分析和细胞相容性评价.方法 将粉末状β磷酸三钙(β-TCP-1)和颗粒状β磷酸三钙(β-TCP-2)分别与硅橡胶(silicone rubbcr,SR)基胶交联复合,经模压成型制备出2种复合材料(β-TCP-1/SR)和(β-TCP-2/SR)并进行扫描电镜微观形貌分析,直接接触法和共培养法进行细胞相容性评价,将所得数据行统计学分析.结果 β磷酸三钙立体分布于复合材料中,形成了孔隙状结构;直接接触实验中在复合材料作用下细胞的生长受到轻度影响;细胞与材料共培养后同一时间点细胞计数:多聚赖氨酸包被的玻片＞复合材料＞硅橡胶(P＜0.05),2种复合材料间差异无统计学意义(P＞0.05);复合材料上的细胞呈多角形,SR上的细胞呈梭形,数目少.结论 β磷酸三钙与硅橡胶复合后,形成了有利于与机体结合的孔隙状结构,改善了细胞相容性.     

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.     

Clinical Results of Extracorporeal Membrane Oxygenation (ECMO) Support for Acute Respiratory Failure: A Comparison of a Centrifugal Pump ECMO with a Roller Pump ECMO

Purpose The purpose of this study was to compare the clinical results of extracorporeal membrane oxygenation (ECMO) using a centrifugal pump (CP group) and that using a roller pump (RP group) for the treatment of acute respiratory failure (ARF).Methods From November 1990 to July 2001, the ECMO system was introduced for the treatment of 15 patients with ARF; 10 cases of pneumonia or adult respiratory distress syndrome (ARDS), 4 cases of pulmonary hemorrhage, and 1 case of hypoxemia following cardiac surgery. Five patients were included in the RP group, and 10 were included in the CP group.Results The mean PaO₂/FIO₂ ratio, PaCO₂ prior to ECMO induction, and the mean duration of ECMO support were 59.8, 38.8mmHg, and 125h, respectively, in the RP group, and 65.6, 82.0mmHg, and 107h, respectively, in the CP group. The mean PaCO₂ value was significantly (P 0.05) higher in the CP group than in the RP group due to the ventilation with permissive hypercapnia. In the RP group, all patients died of either complications or recurrence due to ARF. In the CP group, 3 patients including 2 with pulmonary hemorrhaging were discharged.Conclusions Although the centrifugal pump ECMO improved the clinical results of ARF, the overall prognosis nevertheless depended on the original disease.This study was reported at the 102nd Annual Congress of the Japan Surgical Society, Kyoto, April 11–13, 2002     

Development of a novel polyimide hollow-fiber oxygenator

We have developed a membrane oxygenator using a novel asymmetric polyimide hollow fiber. The hollow fibers are prepared using a dry/wet phase-inversion process. The gas transfer rates of O(2) and CO(2) through the hollow fibers are investigated in gas-gas and gas-liquid systems. The polyimide hollow fiber has an asymmetric structure characterized by the presence of macrovoids, and the outer diameter of the hollow fiber is 330 microm. It is found that the polyimide hollow-fiber oxygenator can enhance the gas transfer rates of O(2) and CO(2), and that the hollow fiber provides excellent blood compatibility in vitro and in vivo.     

Experimental use of a compact centrifugal pump and membrane oxygenator as a cardiopulmonary support system

Compactness and high performance are the most important requirements for a cardiopulmonary support system. The Nikkiso (HPM-15) centrifugal pump is the smallest (priming volume; 25 ml, impeller diameter; 50 mm) in clinically available centrifugal pumps. The Kuraray Menox (AL-2000) membrane oxygenator, made of double-layer polyolefin hollow fiber, has a minimum priming volume (80 ml) and a low pressure loss (65 mm Hg at 2.0 L/min of blood flow) compared with other oxygenators. The aim of this study was to evaluate the performance of the most compact cardiopulmonary support system (total priming volume: 125 ml) in animal experiments. The cardiopulmonary bypass was constructed in a canine model with the Nikkiso pump and Menox oxygenator in comparison with a conventional cardiopulmonary support system. The partial cardiopulmonary bypass was performed for 4 h to evaluate the gas exchange ability, blood trauma, serum leakage, hemodynamics, and blood coagulative parameters. The postoperative plasma free hemoglobin level of the compact cardiopulmonary system was 29.5 +/- 10.21 mg/dl (mean +/- SD), which was lower than that of the conventional cardiopulmonary system, 48.75 +/- 27.39 mg/dl (mean +/- SD). This compact cardiopulmonary system provided the advantage in terms of reduction of the priming volume and less blood damage. These results suggested the possibility of miniaturization for the cardiopulmonary bypass support system in open-heart surgery in the near future.     

Development of an Intravascular Pumping Oxygenator Using a New Silicone Membrane

Abstract: A new intravascular pumping oxygenator (IVPO) was developed for intravascular gas exchange and circulatory assistance in critically ill patients with respiratory and circulatory failure. The IVPO utilizes new silicone hollow fibers (diameter. 1 mm: membrane width, 50 μm) and consists of two driving tubes for the oxygenation and pumping of circulating blood. The performance characteristics of the IVPO were studied using an experimental ex vivo model. With a mean hemoglobin concentration of 10.5 ± 2.3 g/dl, total oxygen transfer was 5.6 ± 1.5 ml/min at a blood flow of 200 ml/min and 6.3 ± 2.2 ml/min at a blood flow of 250 ml/min. Total CO₂ transfer was 3.8 ± 1.4 ml/min at a blood flow of 200 ml/min and 4.2 ± 1.6 ml/min at a blood flow of 250 ml/min during IVPO pumping. This preliminary experiment demonstrated that the IVPO has the capacity to function both as a circulatory assist pump and as an intravascular hollow fiber oxygenator.     

Development of an Atraumatic Small Centrifugal Pump for Second-Generation Cardiopulmonary Bypass

A small and light direct-drive centrifugal pump has been developed for cardiopulmonary bypass. In the development process, blood compatibility studies including a hemolysis study, an in vitro fluid dynamic performance study, and in vivo durability and feasibility studies were performed. The centrifugal pump with a 50 mm diameter impeller resulted in almost the same index of hemolysis value as did a Bio-Medicus centrifugal pump. Heat dissipation from the motor was prevented by using a flexible drive cable. Forty-eight-hour sealing durability around the driving axis was accomplished by using a fluoro-rubber V-ring that connected to the hard chrome-plated stainless steel. In vitro and in vivo performances of the pump were satisfactory. Thrombus formation behind the impeller was prevented by using a holed impeller that generated blood flow from the back to the surface of the impeller. Elimination of air during priming procedures was also easier with this modification. This centrifugal pump has one-quarter of the priming volume, size, and weight of magnetically coupled centrifugal pump systems.     

Intravasal injection of formed-in-place medical grade silicone rubber for vas occlusion

This paper describes two consecutive studies: a volume study and an efficacy study. The volume study determined the appropriate volume of Medical Grade Silicone Rubber (MSR) needed to achieve complete occlusion of the vas deferens. This was done by in-vitro testing of 130 human vas specimens containing plugs of MSR formed in vivo . The volume of MSR needed to occlude the vas was 0.1531 ± 0.0059 ml injected by five to six turns of the applicator handwheel. There was a correlation between MSR volume, weight, and the number of turns of the applicator handwheel. An influence of body height upon the volume and weight of the MSR was also observed. An oval shaped clamp (15 mm long) was more effective in producing secure vas occlusion than was a round clamp (10 mm long). The mean outer diameter of the vas specimens was 1.80 ± 0.15 mm, and the mean maximum dilated inner diameter was 0.93 ± 0.11 mm.
The efficacy study was a clinical trial to compare MSR vas occlusion (using an oval 15 mm clamp and the appropriate volume derived from the volume study, n =58) with no-scalpel vasectomy as the standard procedure ( n =64). The azoospermia rate following MSR vas occlusion was not significantly different from that following no-scalpel vasectomy, and was achieved in 3–6 months.     

Evaluation of Hemolysis in a Pulsatile Assist Device for Centrifugal Pump

Abstract: To evaluate the blood trauma caused by a new device for producing a pulsatile flow of the centrifugal pump, the pulsatile assist device for the centrifugal pump (PAD-CP) that we have developed, a hemolysis study was performed in vitro and in animal experimentation. For the in vitro testing, 2 identical sets of hemolysis test circuits were prepared with 2,400 ml of bovine blood. The 2 circuits were pumped simultaneously. Plasma total hemoglobin levels were less than 40 mg/dl after 3 h, under a pump flow of 2 L/min. Hemolysis increased to a severe level after 4 h of 4 L/min pump flow. The cause of this hemolysis was thought to be a vibration of the circuit because of incomplete compression of the polyurethane tube in the PADCP. Five adult sheep (average body weight, 47 kg) were used for in vivo evaluation of hemolysis. Hemolysis was less than 30 mg/dl of plasma hemoglobin after 4 h of open chest extracorporeal circulation with 3.0–3.6 Limin of flow rate using the PAD-CP. Other hematologic changes after PAD-CP driving were within normal limits. We conclude that the PAD-CP has proven to have possible clinical applications.     

Development of an Autoflow Cruise Control System for a Centrifugal Pump

Abstract: To improve the ease of driving a centrifugal pump that is afterload dependent, we have developed an automatic flow control system for the Terumo Capiox centrifugal pump system. This system consists of an autoflow cruise control system with a safety cutoff. The Capiox Pump Console 3000 was controlled by a personal computer through a serial communication line. In the usual manual mode, the motor speed knob works as a pump speed control, and in the autoflow mode, the same knob works as a blood flow rate control. After selecting and obtaining the desired flow rate, the mode was changed from manual to autoflow mode. In the autoflow mode, the computer compares the desired flow rate with the actual flow measured by an ultrasonic Doppler flow-meter and adjusts the motor rotational speed accordingly. During both in vivo and in vitro testing, this autoflow mode was able to return the changed flow that was disrupted by either clamping and declamping of the tubing or by the bolus injection of a vasomotor drug to the selected flow rate within 10 s without any significant fluctuation. In conclusion, the newly developed computer controlled autoflow system was able to produce a reliable and effective flow regulation for a centrifugal pump.     

Development of the Baylor-Nikkiso Centrifugal Pump with a Purging System for Circulatory Support

Abstract: The Baylor-Nikkiso centrifugal pump is a magnetically coupled system with a V-ring seal separating the pump and the actuator chamber. To prevent thrombus formation behind the impeller and to extend the life of the pump to 2 weeks of continuous operation, we incorporated a purging chamber behind the V-ring seal. An external pump connected to this purging chamber infused fluid at a constant rate to wash the shaft-seal area. To evaluate the effectiveness of the purging system, we have carried out biventricular bypass experiments using calves. The purging system was successful in reducing the level of thrombus formation after 2 weeks of operation. The results of these studies confirmed that the Baylor-Nikkiso centrifugal pump with this purging system is suitable for at least 2 weeks of continuous operation as a circulatory support system.     

Antithrombogenicity of polyacrylonitrile-polyethyleneoxide hollow fiber membrane developed for designing an antithrombogenic continuous ultrafiltration system

To develop a continuous arteriovenous hemofiltration (CAVH) system, which does not need systemic anticoagulation, for patients of acute renal failure having bleeding tendencies, a totally antithrombogenic continuous ultrafiltration system (ACUS) was designed, which consists of an antithrombogenic polyacrylonitrile-polyethyleneoxide (PAN-PEO) hollow fiber membrane and ionically heparin-bound catheter, tubing, and module header. Antithrombogenicity of PAN-PEO membrane, which occupies more than 90% of total inner surface area of ACUS, was considered to be due to highly concentrated PEO near the inner surface of the membrane and the finely dispersed (less than 500 A) microstructure of the inner surface. ACUS was applied to 24 patients without systemic anticoagulation, and one filter worked for an average of 32 h without deteriorating their bleeding tendencies. Any significant changes in major parameters of biocompatibility during those treatments were not observed. More than 200 ml/h of ultrafiltrate was obtained even under very low mean blood pressure, less than 70 mm Hg. Based upon these results, ACUS was concluded to be suitable for mild and sustained treatment to control fluid and electrolyte balance in patients of acute renal failure with bleeding complications.     

Development of a flow-transformed pulsatile total artificial heart for total implantation

To realize a totally implantable total artificial heart (TAH), a new pulsatile TAH, the flow-transformed pulsatile TAH (FTPTAH), was developed. The system was composed of a single centrifugal pump (CFP) and two three-way valves. One port of each three-way valve was connected to the inlet and outlet of a CFP. The other two ports of each valve were connected to the right and left atrium, and the pulmonary artery and aorta. The CFP can perfuse the pulmonary and systemic circulation alternately with pulsatile flow by switching the two three-way valves. A prototype and the secondary model in which the solenoid valves and a spool valve were included, respectively, were connected to a mock circulatory unit with the results that a pulsatile TAH with physiological flow wave form could be obtained from a single CFP, about 5 L/min of pulsatile output could be obtained alternately on the right and left side by switching the solenoid valves or a spool valve, and flow balance between the right and left could be easily controlled by the switching duration. The system is feasible for a totally implantable TAH because it does not need a compliance chamber and can be miniaturized.     

Development of a disposable magnetically levitated centrifugal blood pump (MedTech Dispo) intended for bridge-to-bridge applications--two-week in vivo evaluation

Last year, we reported in vitro pump performance, low hemolytic characteristics, and initial in vivo evaluation of a disposable, magnetically levitated centrifugal blood pump, MedTech Dispo. As the first phase of the two-stage in vivo studies, in this study we have carried out a 2-week in vivo evaluation in calves. Male Holstein calves with body weight of 62.4–92.2 kg were used. Under general anesthesia, a left heart bypass with a MedTech Dispo pump was instituted between the left atrium and the descending aorta via left thoracotomy. Blood-contacting surface of the pump was coated with a 2-methacryloyloxyethyl phosphorylcholine polymer. Post-operatively, with activated clotting time controlled at 180–220 s using heparin and bypass flow rate maintained at 50 mL/kg/min, plasma-free hemoglobin (Hb), coagulation, and major organ functions were analyzed for evaluation of biocompatibility. The animals were electively sacrificed at the completion of the 2-week study to evaluate presence of thrombus inside the pump,together with an examination of major organs. To date, we have done 13 MedTech Dispo implantations, of which three went successfully for a 2-week duration. In these three cases, the pump produced a fairly constant flow of 50 mL/Kg/min. Neurological disorders and any symptoms of thromboembolism were not seen. Levels of plasma-free Hb were maintained very low. Major organ functions remained within normal ranges. Autopsy results revealed no thrombus formation inside the pump. In the last six cases, calves suffered from severe pneumonia and they were excluded from the analysis. The MedTech Dispo pump demonstrated sufficient pump performance and biocompatibility to meet requirements for 1-week circulatory support. The second phase (2-month in vivo study) is under way to prove the safety and efficacy of MedTech Dispo for 1-month applications.