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.     

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.     

New membrane oxygenator (LPM 50): influence on extravascular lung water and pulmonary function in comparison to bubble oxygenator

A prospective, randomized, clinical study involving 30 patients undergoing aorta-coronary bypass grafting was designed to compare the influence of a new membrane oxygenator and a commonly used bubble oxygenator on extravascular lung water and pulmonary function after extracorporeal circulation. Although membrane oxygenators might have some advantages from the biochemical and biophysical points of view, in this clinical study no differences in lung water accumulation and pulmonary gas exchange could be detected between bubble and membrane oxygenators after extracorporeal circulation.     

Effects of Ultrathin Silicone Coating of Porous Membrane on Gas Transfer and Hemolytic Performance

Abstract: To assess the effect of an ultrathin (0.2 μm) silicone-coated microporous membrane oxygenator on gas transfer and hemolytic performance, a silicone-coated capillary membrane oxygenator (Mera HP Excelung-prime, HPO-20H-C, Senko Medical Instrument Mfg. Co., Ltd. Tokyo, Japan) was compared with a noncoated polypropylene microporous membrane oxygenator of the same model and manufacturer using an in vitro test circuit. The 2 oxygenators showed little difference in the oxygen (O₂) transfer rate over a wide range of blood flow rates (1 L/min to 8 L/min). The carbon dioxide (CO₂) transfer rate was almost the same in both devices at low blood flow rates. but the silicone-coated oxygenator showed a decrease of more than 20% in the CO₂ transfer rate at higher blood flow rates. This loss in performance could be partly attenuated by increasing the gas/blood flow ratio from 0.5 or 1.0 to 2.0. In the hemolysis study, the silicone-coated membrane oxygenator showed a smaller increase in plasma free hemoglobin than the noncoated oxygenator. The pressure drop across both oxygenators was the same. These results suggest that the ultrathin silicone-coated porous membrane oxygenator may be a useful tool for long-term extracorporeal lung support while maintaining a sufficient gas transfer rate and causing less blood component damage.     

Comparative evaluation of a new disposable rotating membrane oxygenator with bubble oxygenator.

The comparative in vivo performance of adult-size bubble and rotating membrane oxygenators was evaluated during closed-chest cardiopulmonary bypass for six hours in two groups of dogs. The results show that the rotating membrane oxygenator is efficient in oxygen and carbon dioxide transfer with minimal trauma to blood, while platelet destruction and hemolysis were marked with the bubble oxygenator. Cerebral, cardiac, and respiratory complications were frequent with the bubble oxygenator and absent with the membrane oxygenator.     

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.     

中国体外循环8年动态分析

目的 了解近8年来中国体外循环的发展动态,对我国未来体外循环的发展提出预测和建议.方法 2003年至2010年,逐年对全国开展心脏手术的医院进行问卷调查,内容涉及开展体外循环(on-pump)心脏手术和非体外循环(off-pump)心脏手术例数、氧合器使用情况及体外膜肺氧合(extracorporeal membrane oxygenation,ECMO)例数.收集并计算各年度各类氧合器的使用构成比;按手术例数对医院进行分级,计算不同级别医院所占比例.结果 2010年全国心脏手术170 547例,其中体外循环136753例.2010年进口膜式氧合器使用比例较2003年升高(59.75％对43.22％),鼓泡式氧合器比例显著降低(43.78％对14.59％),国产膜式氧合器使用比例也有所升高(13.00％对25.66％).2010年全国开展ECMO的医院共44家,总例数206例;年手术量＞1000例的医院32家,占43％;手术量＜50例的医院255家,占3％.结论 中国体外循环近年来发展速度较快,膜式氧合器使用率逐年上升,鼓泡式氧合器使用率逐年下降;未来需进一步集中体外循环医疗资源.     

In Vivo Uptake and Elimination of Isoflurane by Different Membrane Oxygenators during Cardiopulmonary Bypass

Background: Volatile anesthetics are frequently used during cardiopulmonary bypass (CPB) to maintain anesthesia. Uptake and elimination of the volatile agent are dependent on the composition of the oxygenator. This study was designed to evaluate whether the in vivo uptake and elimination of isoflurane differs between microporous membrane oxygenators containing a conventional polypropylene (PPL) membrane and oxygenators with a new poly-(4-methyl-1-pentene) (PMP) membrane measuring isoflurane concentrations in blood.

Methods: Twenty-four patients undergoing elective coronary bypass surgery with the aid of CPB were randomly allocated to one of four groups, using either one of two different PPL-membrane oxygenators for CPB or one of two different PMP-membrane oxygenators. During hypothermic CPB, 1% isoflurane in an oxygen-air mixture was added to the oxygenator gas inflow line (gas flow, 3 l/min) for 15 min. Isoflurane concentration was measured in blood and in exhaust gas at the outflow port of the oxygenator. Between-group comparisons were performed for the area under the curve (AUC) during uptake and elimination of the isoflurane blood concentrations, the maximum isoflurane blood concentration (Cmax), and the exhausted isoflurane concentration (FE).

Results: The uptake of isoflurane, expressed as AUC of isoflurane blood concentration and a function of FE, was significantly reduced in PMP oxygenators compared to PPL oxygenators (P < 0.01). Cmax was between 8.5 and 13 times lower in the PMP-membrane oxygenator groups compared to the conventional PPL-membrane oxygenator groups (P < 0.01).     

In vivo uptake and elimination of isoflurane by different membrane oxygenators during cardiopulmonary bypass

BACKGROUND: Volatile anesthetics are frequently used during cardiopulmonary bypass (CPB) to maintain anesthesia. Uptake and elimination of the volatile agent are dependent on the composition of the oxygenator. This study was designed to evaluate whether the in vivo uptake and elimination of isoflurane differs between microporous membrane oxygenators containing a conventional polypropylene (PPL) membrane and oxygenators with a new poly-(4-methyl-1-pentene) (PMP) membrane measuring isoflurane concentrations in blood. METHODS: Twenty-four patients undergoing elective coronary bypass surgery with the aid of CPB were randomly allocated to one of four groups, using either one of two different PPL-membrane oxygenators for CPB or one of two different PMP-membrane oxygenators. During hypothermic CPB, 1% isoflurane in an oxygen-air mixture was added to the oxygenator gas inflow line (gas flow, 3 l/min) for 15 min. Isoflurane concentration was measured in blood and in exhaust gas at the outflow port of the oxygenator. Between-group comparisons were performed for the area under the curve (AUC) during uptake and elimination of the isoflurane blood concentrations, the maximum isoflurane blood concentration (C(max)), and the exhausted isoflurane concentration (F(E)). RESULTS: The uptake of isoflurane, expressed as AUC of isoflurane blood concentration and a function of F(E), was significantly reduced in PMP oxygenators compared to PPL oxygenators (P < 0.01). C(max) was between 8.5 and 13 times lower in the PMP-membrane oxygenator groups compared to the conventional PPL-membrane oxygenator groups (P < 0.01). CONCLUSIONS: The uptake of isoflurane into blood via PMP oxygenators during CPB is severely limited. This should be taken into consideration in cases using such devices.     

Oxygenation strategy and neurologic damage after deep hypothermic circulatory arrest. I. Gaseous microemboli.

OBJECTIVES: Recent studies suggest that myocardial reperfusion injury is exacerbated by free radicals when pure oxygen is used during cardiopulmonary bypass. Partial replacement of the oxygenator gas mixture with nitrogen, however, such as has already been adopted clinically in many centers, could increase the risk of gaseous nitrogen microembolus formation and therefore of brain damage because of the low solubility of nitrogen, particularly under conditions of hypothermia. METHODS: Ten 7- to 10-kg piglets were cooled for 30 minutes to 15 degrees C on cardiopulmonary bypass and then rewarmed for 40 minutes to 37 degrees C. In 5 piglets cardiopulmonary bypass was normoxic and in 5 it was hyperoxic. In each group 3 bubble oxygenators without arterial filters and 2 membrane oxygenators with filters were used. Cerebral microemboli were monitored continuously by carotid Doppler ultrasonography (8 MHz) and intermittently by fluorescence retinography. RESULTS: Embolus count was greater with lower rectal temperature (P <.001), use of a bubble oxygenator (P <.001), and lower oxygen concentration (P =.021) but was not affected by the temperature gradient between blood and body during cooling or rewarming. CONCLUSIONS: Gaseous microemboli are increased with normoxic perfusion, but this is only important if a bubble oxygenator without a filter is used.     

Modeling flow effects on thrombotic deposition in a membrane oxygenator

The hypothesis that regions of low blood velocity in a membrane oxygenator, as predicted by computational fluid dynamics (CFD), would correspond with regions of clinical thrombotic deposition was investigated. Twenty heparin-coated oxygenators were sectioned following use in adult extracorporeal membrane oxygenation. The activated clotting time (ACT) was maintained at approximately 180 s via heparin infusion throughout the support period. Cross-sections were systematically photographed, and slides made to allow image projection upon a digitizing pad. Thrombotic deposition was traced to allow creation of a device cross-section image with an overlaid color scale representing thrombotic deposition frequency. A two-dimensional CFD model was developed to predict blood velocities throughout the oxygenator cross-section. Direct spatial comparisons were made between maps of CFD modeled blood speed and thrombotic deposition. Theoretical oxygenator design modification was performed within the CFD model to investigate flow paths which might minimize regions of low blood velocity. CFD results demonstrated that low velocity regions qualitatively matched regions with a high incidence of thrombotic deposition. Thrombotic deposition was also correlated to longer perfusion periods. This technique of coupling clinical data and CFD offers the potential to relate flow characteristics to thrombotic deposition and represents a potentially powerful new methodology for the optimization of oxygenator flow-related biocompatibility.     

Miniaturization: The Clue to Clinical Application of the Artificial Placenta

The artificial placenta as a fascinating treatment alternative for neonatal lung failure has been the subject of clinical research for over 50 years. Pumpless systems have been in use since 1986. However, inappropriate dimensioning of commercially available oxygenators has wasted some of the theoretical advantages of this concept. Disproportional shunt fractions can cause congestive heart failure. Blood priming of large oxygenators and circuits dilutes fetal hemoglobin (as the superior oxygen carrier), is potentially infectious, and causes inflammatory reactions. Flow demands of large extracorporeal circuits require cannula sizes that are not appropriate for use in preterm infants. NeonatOx, a tailored low‐volume oxygenator for this purpose, has proven the feasibility of this principle before. We now report the advances in biological performance of a refined version of this specialized oxygenator.     

Ultrasound detection of micro-emboli in the middle cerebral artery during cardiopulmonary bypass surgery

The occurrence of neurological sequelae following cardiopulmonary bypass (CBP) surgery has stimulated interest in refining the techniques of extracorporeal circulation. Air micro-emboli originating from the oxygenator have been postulated as one source of cerebral damage. Since controversy still exists regarding the merits of bubble versus membrane oxygenators, this has prompted investigators to devise methods to determine the amount of micro-emboli produced during CPB. In this study, 27 patients undergoing CPB surgery for coronary artery disease (21) or valve replacement (6) were examined. The surgical and anaesthetic techniques were standardised in all patients except for the type of oxygenator used. A bubble oxygenator was used in 17 patients (Bentley Bio-10, William Harvey or Dideco) and a membrane oxygenator with a 25 microns filter in the remaining 10 patients (Bentley BOS CM50). Transcranial pulsed Doppler ultrasound was used to obtain blood velocity signals from the middle cerebral artery throughout CPB. A flow disturbance index (FDI) was defined which provided a representative index of the number of micro-emboli passing the ultrasound transducer. The FDI indicated the presence of gaseous micro-emboli during insertion of the aortic cannula in 22 of the 27 patients. In the 17 patients with a bubble oxygenator, the FDI ranged from 4-39. In the 10 patients with a membrane oxygenator, the FDI was always 0. Variation of gas flow rates in 3 patients with bubble oxygenators showed a change in the FDI from 4 +/- 4 at a flow rate of 2 l/min to 17 +/- 9 at 5 l/min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of extracorporeal lung assist in the treatment of acute respiratory failure

For patients with most severe acute respiratory distress syndrome (ARDS) conservative treatment with lung protective ventilation is often not sufficient to prevent life-threatening hypoxemia and additional strategies are necessary. Extracorporeal lung assist (ECLA) or extracorporeal membrane oxygenation (ECMO) using capillary membrane oxygenators can provide sufficient gas exchange and lung rest. In 2 randomized trials mortality was unchanged for ECMO. Today an technically enhanced ECMO is used for most severe ARDS using clinical algorithm and different case studies demonstrated a survival rate about 56%. Today miniaturized ECMO with optimized blood pumps and oxygenators are available and could enhance safety and clinical management. Another approach is an arterio-venous pumpless interventional lung assist (ILA) with a low resistance oxygenator. Advantages seem a simplified clinical management and less blood trauma. At present new devices are developed for chronic respiratory failure or bridge to lung transplant. Oxygenators with even less flow resistance could be implanted paracorporeal using the right ventricle as driving force. An intravascular oxygenator has been developed using the combination of a miniaturized blood pump and an oxygenator for implantation in the vena cava. Well designed clinical trials are necessary to demonstrate a clinical benefit for these experimental devices.     

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.     

Risk factors for intracranial hemorrhage in adults on extracorporeal membrane oxygenation.

OBJECTIVE: Intracranial hemorrhage is a recognized complication in neonates and infants on extracorporeal membrane oxygenator support and various risk factors associated with this have been defined. The prevalence and risk factors associated with intracranial hemorrhage in adults on extracorporeal membrane oxygenator support are unknown and this study was performed to define these factors. METHODS: A retrospective study of adults supported with extracorporeal membrane oxygenators at a single institution between January 1992 and December 1996 was performed. Age, gender, weight, body surface area, renal function, anticoagulation, coagulation variables, blood flow, arterial pressure, arterial cannulation sites, duration of support, extracranial bleeding, native cardiac function and presence of intracranial microemboli were analyzed to determine the risk factors for intracranial hemorrhage. RESULTS: Fourteen out of 74 adults on extracorporeal membrane oxygenator support had intracranial hemorrhage (18.9%). An increased risk of intracranial hemorrhage showed a positive correlation with female gender (P = 0.02, odds ratio 6.5), use of heparin (P = 0.05, odds ratio 8.5), creatinine greater than 2.6 mg/ dl (P = 0.009, odds ratio 6.5), need for dialysis (P = 0.03, odds ratio 4.3) and thrombocytopenia (P = 0.007, odds ratio 18.3). Diminishing renal function and the need for dialysis were associated with increasing duration of support. Multivariable logistic regression showed female gender and thrombocytopenia, especially with platelet counts less than 50000 cells/mm3 to be the most important predictors of intracranial hemorrhage. Intracranial hemorrhage was associated with a mortality of 92.3% compared with a mortality of 61% in those without intracranial hemorrhage (P = 0.027). CONCLUSION: Intracranial hemorrhage is a significant complication in adults on extracorporeal membrane oxygenator support. Judicious management of anticoagulation, prevention of renal failure and aggressive correction of thrombocytopenia may help to lower the risk of intracranial hemorrhage in adults on extracorporeal membrane oxygenator support.     

Hypothermia: its possible role in cardiac surgery

The current safety of operations on the heart requiring cardiopulmonary bypass occurred because of a series of step-by-step laboratory and clinical investigations that were compromises between the time needed for heart repair and the brain's requirement for oxygen. The first step, so clearly shown in a paper by Bigelow and associates in 1950, was the reduction of the brain's need for oxygen by surface cooling to 28 degrees to 32 degrees C, limited to this level by cardiac and pulmonary failure at levels lower than this. The six to eight minutes of circulatory arrest permitted time for repair of simple defects. This method was rapidly adopted by many surgeons. As low-flow pump oxygenators became available, blood cooling to 10 degrees to 20 degrees C was introduced. This increased the periods of circulatory arrest to 30 to 60 minutes, and also made still longer periods of bypass with the pump oxygenator possible. Hypothermia to reduce oxygen and metabolic requirements is still an important adjunct to bypass, even with the currently used efficient pump oxygenators. It remains the most important component of myocardial preservation, and has made possible the delay needed for transportation between the harvesting and the transplantation of organs.     

Blood-Gas Interface Oxygenators Versus Membrane Oxygenators: What Are the Proved Differences?

Membrane oxygenators are said to be less traumatic to blood than the liquid-gas interface types. A review of the literature frequently cited on protein chemistry shows that the conditions of these early experiments were far removed from those of the liquid-gas interface blood oxygenators in use today. The assumption that blood trauma, particularly protein denaturation, is significantly reduced by elimination of the blood-gas interface cannot be supported by these early reports. A review of papers comparing blood-gas interface oxygenators with membrane oxygenators reveals only one in which physiological gas tensions were maintained. It is concluded that: (1) the theoretical superiority of the membrane oxygenator is based on data which may or may not be pertinent, and (2) the experimental and clinical superiority of the membrane oxygenator is as yet unproved.     

Clinical Results and Pump Analysis of the Gyro Pump for Long‐Term Extracorporeal Life Support

Rescuing patients in severe cardiac failure with extracorporeal support remains challenging. The Gyro pump is a centrifugal blood pump and was now used for cardiopulmonary bypass, although it was originally developed for long‐term cardiac assist. Little is known about clinical experiences using this pump. Here, we report on the clinical results of long‐term extracorporeal life support for over 4 days using the Gyro pump with Excelung, a hollow fiber oxygenator coated with silicone and heparin. Seven patients underwent extracorporeal life support with 15 pump and oxygenator combinations. Gyro and Excelung were used for venoarterial extracorporeal support in six patients and for right ventricular support in one patient. Patient characteristics, pump driving conditions, and blood chemistry were obtained retrospectively. All pumps were subsequently disassembled and examined macroscopically, with 6 of 15 pumps also examined by scanning electron microscopy (SEM). The patient mortality rate was 57.1%. Mean duration of support was 10.5 ± 7.2 days per pump and oxygenator combination. Lactate dehydrogenase and aspartate aminotransferase were generally maintained below 1000 and 100 IU/L, respectively, after the first 4 days of pump driving. Thrombi were found in two pumps, one used without anticoagulation and the other driven at a very slow rotational speed. SEM revealed no wear in the male bearings and very low wear and deformation (0.02 ± 0.03 mm) in the female bearings. The combination of Gyro and Excelung may be applicable for long‐term biventricular and right ventricular support, although proper anticoagulation should be administrated to avoid thrombus formation inside the pump.     

In vitro drug adsorption and plasma free hemoglobin levels associated with hollow fiber oxygenators in the extracorporeal life support (ECLS) circuit

The purpose of this study was to identify the percentage of fentanyl or morphine sulfate lost from adhesion to either the polyvinylchloride (PVC) tubing or the surface of two different hollow fiber oxygenators used in current extracorporeal life support circuits and to identify any difference in the plasma free hemoglobin (PFH) levels generated when using these oxygenator and/or drug combinations. For each drug examined, six simple circuits were assembled; for each drug, two circuits contained tubing without an oxygenator (control), two circuits contained the Jostra Quadrox D (Maquet Cardiopulmonary, AG Hirrlingen, Germany), and two circuits contained the Terumo Baby Rx (Terumo Cardiovascular Systems Corp., Ann Arbor, MI). Fentanyl or morphine sulfate was added to yield initial circuit concentrations equal to 1430 ng/mL, respectively. Throughout the 6-hour in vitro testing, samples to evaluate the drug and PFH levels were drawn at various time intervals. Significance in this study is defined as p < .05. Fentanyl's initial adsorption seems to be 80% in circuits without oxygenators, 86% in the circuits containing the Quadrox D oxygenator, and 83% in the circuits with the Baby Rx oxygenator. Morphine sulfate seems to be initially adsorbed at a rate of 40% in all circuits and does not seem to be adsorbed by either of the tested oxygenators. The PFH levels were significantly (p < .05) elevated in the fentanyl circuits. The type of oxygenator does not seem to play a significant role in drug adsorption. During this in vitro study, the majority of both drugs were lost to the PVC tubing. The type of oxygenator did not seem to significantly affect PFH. However, fentanyl in any combination or alone was associated with increased PFH levels.