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.     

A clinical evaluation of the Terumo Capiox SX18R hollow fiber oxygenator

The Terumo Capiox SX18R is a commercially available, low prime, reverse phase, hollow fiber membrane oxygenator. The oxygenator consists of a 1.8 m2 microporous polypropylene hollow fiber bundle, a 2200 cm2 tubular stainless steel heat exchanger, and an open hard shell venous reservoir with integral cardiotomy filter. The Terumo Capiox SX18R oxygenator was evaluated to determine its clinical oxygenating performance. Blood samples were drawn from 25 patients yielding 114 data points. The following parameters were recorded: blood flow, cardiac index, gas flow, gas to blood flow ratio, and oxygen fraction. Samples were assayed for hematocrit, hemoglobin, arterial and venous blood gas values, and venous oxygen saturation. The data and assay results were used to calculate arterial, venous, and membrane gas oxygen content, oxygen transfer, shunt fraction, and oxygen diffusion capacity. The Terumo Capiox SX18R oxygenator performed adequately with sufficient oxygen transfer reserve and carbon dioxide clearance under a variety of clinical conditions for the tested population.     

Functional and Biocompatibility Performances of an Integrated Maglev Pump-Oxygenator

To provide respiratory support for patients with lung failure, a novel compact integrated pump-oxygenator is being developed. The functional and biocompatibility performances of this device are presented. The pump-oxygenator is designed by combining a magnetically levitated pump/rotor with a uniquely configured hollow fiber membrane bundle to create an assembly free, ultracompact, all-in-one system. The hemodynamics, gas transfer and biocompatibility performances of this novel device were investigated both in vitro in a circulatory flow loop and in vivo in an ovine animal model. The in vitro results showed that the device was able to pump blood flow from 2 to 8 L/min against a wide range of pressures and to deliver an oxygen transfer rate more than 300 mL/min at a blood flow of 6 L/min. Blood damage tests demonstrated low hemolysis (normalized index of hemolysis [NIH]∼0.04) at a flow rate of 5 L/min against a 100-mm Hg afterload. The data from five animal experiments (4 h to 7 days) demonstrated that the device could bring the venous blood to near fully oxygen-saturated condition (98.6% ± 1.3%). The highest oxygen transfer rate reached 386 mL/min. The gas transfer performance was stable over the study duration for three 7-day animals. There was no indication of blood damage. The plasma free hemoglobin and platelet count were within the normal ranges. No gross thrombus is found on the explanted pump components and fiber surfaces. Both in vitro and in vivo results demonstrated that the newly developed pump-oxygenator can achieve sufficient blood flow and oxygen transfer with excellent biocompatibility.     

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.     

A new type of fluorocarbon liquid oxygenator.

A new oxygenator based on gas transfer across liquid-liquid interfaces (liquid oxygenator) is introduced. Perfluorinated chemicals are used as gas carriers. This liquid oxygenator differs from others in its concept basing on the dispersion of the blood droplets in an inert liquid by means of shear forces. This method allows high efficiency both with respect to saturation and to required blood flow. The results of gas transfer experiments in vitro and in vivo are satisfactory.     

Respiration: gas transfer

The principles of gas transfer between the atmosphere and cell mitochondria can be considered in a number of steps: inspired gases are humidified in the upper airways and mix with expired gases in the alveoli. In perfused alveoli, gases then diffuse passively down a partial pressure gradient into pulmonary capillary blood. Gases are transported by the blood, in a dissolved state or by specific transport systems, to the systemic capillaries from where they diffuse into cells. Efficient gas exchange between the atmosphere and mitochondria requires the transfer of large volumes of gas with minimal reduction in partial pressure. The nature of oxygen binding to haemoglobin and the transport of carbon dioxide as bicarbonate in the blood improve the body’s ability to transfer these gases. An understanding of how anaesthetic gases are transferred to their site of action and why side effects occur is important to the safe conduct of anaesthesia.     

An in vitro comparison of gas transfer and pressure drop of the Bentley Duraflo Coated Spiral Gold and the Medtronic Carmeda Coated Maxima hollow fiber membrane oxygenators

Two models of heparin coated, hollow fiber membrane oxygenators were tested in vitro to compare gas transfer and transoxygenator pressure drop using an established protocol. Oxygen and carbon dioxide transfer rates were measured at blood flows of 2.5 and 5.0 liters per minute with gas flow: blood flow ratios of 1:1 and 2:1 at both blood flows. All testing was performed under normothermic conditions. The data shows that oxygen transfer increases as blood flow is increased in both oxygenators. Similarly, carbon dioxide transfer is increased by both increased blood and gas flows. Finally, the pressure drop was dependent on blood flow rate alone. This study demonstrated these two oxygenators to be comparable in both oxygen and carbon dioxide transfer and also in transoxygenator pressure drop.     

Computational model-based design of a wearable artificial pump-lung for cardiopulmonary/respiratory support

Mechanical ventilation and extracorporeal membrane oxygenation are the only immediate options available for patients with respiratory failure. However, these options present significant shortcomings. To address this unmet need for respiratory support, innovative respiratory assist devices are being developed. In this study, we present the computational model-based design, and analysis of functional characteristics and hemocompatibility performance, of an innovative wearable artificial pump-lung (APL) for ambulatory respiratory support. Computer-aided design and computational fluid dynamics (CFD)-based modeling were utilized to generate the geometrical model and to acquire the fluid flow field, gas transfer, and blood damage potential. With the knowledge of flow field, gas transfer, and blood damage potential through the whole device, design parameters were adjusted to achieve the desired specifications based on the concept of virtual prototyping using the computational modeling in conjunction with consideration of the constraints on fabrication processes and materials. Based on the results of the CFD design and analysis, the physical model of the wearable APL was fabricated. Computationally predicted hydrodynamic pumping function, gas transfer, and blood damage potential were compared with experimental data from in vitro evaluation of the wearable APL. The hydrodynamic performance, oxygen transfer, and blood damage potential predicted with computational modeling, along with the in vitro experimental data, indicated that this APL meets the design specifications for respiratory support with excellent biocompatibility at the targeted operating condition.     

Control of body temperature: use of the respiratory tract as a heat exchanger

The theoretical potential of the respiratory tract as a heat exchanger is enormous because the large alveolor surface area is in intimate contact with pulmonary blood flow. However, this potential is severely limited by some powerful physiologic mechanisms that ensure thermal isolation of alveolar gas, by the detrimental effects of dry gas and extremes of temperature on respiratory epithelium, and by the unfavorable thermal properties of respiratory gases in general. Optimal respiratory cooling using hyperventilation with cold helium-oxygen-CO₂ through a double lumen tube increased the rate of body heat loss by only 1.1°C/hr. Although respiratory cooling alone cannot effect heat transfer of sufficient magnitude to produce rapid cooling far induced hypothermia, it may find use as an adjunct in treating hyperthermic conditions and in induced hypothermia. Respiratory warming does not suffer the limitations of respiratory cooling and should find use in inhalation warming of hypothermic patients and in maintaining the body temperature of patients, especially small babies under anesthesia, who are unable to defend their own central temperature.     

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.     

Intra-arterial and extra-arterial pH, PCO2 and PO2 monitors

In vitro blood gas analysers inherently limit the frequency of serial blood gas measurements because of blood loss and cost. In vivo blood gas monitors eliminate an inherent cost and blood loss associated with measurement. Optode microsensing is a technology that can be readily adapted to in vivo measurement of pH, PCO₂ and PO₂. Optode-based intra-arterial devices that display continuous values have been developed that are practical for routine use but consistent performance remains a problem; an extra-arterial device that provides intermittent values has been shown to be consistent but is not yet available for routine use. The transfer of blood gas measurements from laboratory analysers to the combination of point-of-care analysers and monitors should have as profound an impact on acute respiratory care as did the introduction of laboratory-based blood gas analysers over 30 years ago. However, we must be sure these devices are reliable, consistent and cost beneficial in order to avoid widespread adoption of yet another technology that provides more data, more cost, and questionable patient benefit.     

Performance of Baffled Bubble Blood Oxygenators

Bubble blood oxygenators equipped with baffles of various types in the oxygenating column were studied. The rate of hemolysis, the volumetric coefficient for oxygen absorption into blood, and the fractional gas holdup were found to be affected mainly by the superficial gas velocity. When compared with the conventional bubble blood oxygenator without baffles, the bubble oxygenators equipped with various types of baffles (i.e., horizontal perforated baffles, radial vertical baffles, and a concentric hollow cylinder with and without horizontal perforated baffles) showed less hemolysis, larger gas holdup and higher values of the coefficient for oxygen absorption. Values of the heat transfer coefficient on the surface of the cylindrical baffle, which is useful as a built-in heat exchanger, were several times greater than those for single-phase heat transfer in conventional blood heat exchangers.     

Benefits and limitation of extracorporeal circulation with autologous blood using low priming membrane oxygenator

The high incidence of hepatitis following cardiopulmonary bypass has stimulated attempts to develop a technique of perfusion without homologous blood. Between October, 1987 and March, 1988, 36 patients underwent open heart surgery without homologous blood transfusion were investigated. Patients with infective endocarditis and urgent surgical cases were excluded from this study. Out of 36 patients using hemoconcentrator, autologous blood and the Variable Prime Cobe Membrane Lung (VPCML), 28 patients (78%) could avoid homologous blood transfusion during the operation and 24 patients (67%) received no homologous blood throughout their hospital stay. Thus, the application of lower volume extracorporeal oxygenator system, reinfusion of residual pump volume using hemoconcentrator and predonated autologous blood could achieved cardiac surgery without homologous blood transfusions in the majority of patients. Moreover, the VPCML had sufficient gas transfer in adult patients with body weight ranging from 37 kg to 70 kg. In renal function, serum creatinine levels in patients without homologous blood were within normal limits throughout 1 month after surgery. However, creatinine level was significantly elevated at the third postoperative day in the homologous blood transfusion group. Thus, these results suggest that application of VPCML and hemoconcentrator combined with predonated autologous blood is useful to achieve open heart surgery without donor blood.     

Technical Indicators to Evaluate the Degree of Large Clot Formation Inside the Membrane Fiber Bundle of an Oxygenator in an In Vitro Setup

The most common technical complication during ECMO is clot formation. A large clot inside a membrane oxygenator reduces effective membrane surface area and therefore gas transfer capabilities, and restricts blood flow through the device, resulting in an increased membrane oxygenator pressure drop (dpMO). The reasons for thrombotic events are manifold and highly patient specific. Thrombus formation inside the oxygenator during ECMO is usually unpredictable and remains an unsolved problem. Clot sizes and positions are well documented in literature for the Maquet Quadrox‐i Adult oxygenator based on CT data extracted from devices after patient treatment. Based on this data, the present study was designed to investigate the effects of large clots on purely technical parameters, for example, dpMO and gas transfer. Therefore, medical grade silicone was injected into the fiber bundle of the devices to replicate large clot positions and sizes. A total of six devices were tested in vitro with silicone clot volumes of 0, 30, 40, 50, 65, and 85 mL in accordance with ISO 7199. Gas transfer was measured by sampling blood pre and post device, as well as by sampling the exhaust gas at the devices’ outlet at blood flow rates of 0.5, 2.5, and 5.0 L/min. Pre and post device pressure was monitored to calculate the dpMO at the different blood flow rates. The dpMO was found to be a reliable parameter to indicate a large clot only in already advanced “clotting stages.” The CO₂ concentration in the exhaust gas, however, was found to be sensitive to even small clot sizes and at low blood flows. Exhaust gas CO₂ concentration can be monitored continuously and without any risks for the patient during ECMO therapy to provide additional information on the endurance of the oxygenator. This may help detect a clot formation and growth inside a membrane oxygenator during ECMO even if the increase in dpMO remains moderate.     

Effect of CO2 and blood media on laser probe temperature

Blood may limit laser ablation of arterial plaque by decreasing thermal energy transfer from metal-capped probes to arterial occlusions. Since a gas is a good insulator of heat, CO2 may be a better medium for laser recanalization. To study this possibility, a metal-capped fiber was positioned in a segment of blood-filled polyethylene tubing and activated with an argon laser. Probe temperatures were measured in blood and as the blood was displaced by flowing CO2 gas. Probe temperatures were higher at all powers studied in CO2 gas than in blood. Maximum probe temperatures averaged 518 +/- 24 degrees C after CO2 infusion versus 320 +/- 7 degrees C in blood, (P less than 0.0001). Blood aggregate formation was noted on the probe surface in blood but not in CO2 medium. Thus CO2 gas may be a preferable medium for laser recanalization, since higher probe temperatures are achieved, and the probe surface remains free of insulating blood coagulate.     

Afterword: Bottom–Line Status Report: CAN Current Trends in Membrane Gas Transfer Technology Lead to an Implantable Intrathoracic Artificial Lung?

Abstract: For at least 170 years, attempts have been made to alleviate inadequate gas exchange of patients with respiratory failure. Major milestones in the struggle to assist failing natural lungs to achieve adequate blood gas exchange include utilization of oxygen inhalation therapy, mechanical ventilatory assistance, and development of both extracorporeal and intracorporeal mechanical blood gas exchangers. Current state–of–the–art technology related to mechanical membrane blood gas exchangers has produced highly efficient gas transfer membranes and designs capable of replacing all the gas transfer functions of the natural lungs by a mechanical oxygenator–CO₂ remover that can fit into a unilateral thoracic cavity. The possibility thus exists of moving extracorporeal mechanical blood oxygenators into the body as an implantable intracorporeal artificial lung. Problems impeding the development of an implantable, intrathoracic artificial lung have been identified, and at least partially successful attempts to solve them have been reported. The conclusion drawn is that the appropriate answer to the question posed in the title of this communication is affirmative. Reasons for this conclusion include the persistent widespread major need for better relief from respiratory failure, the advanced state–of–the–art of mechanical blood gas exchanger technology, and the incompletely tapped ingenuity of the human mind.     

Application of ultrastructural morphometry to lung biopsy specimens in pulmonary histiocytosis X.

Stereological techniques were applied to an electron microscopic study of biopsy samples from nine human lungs with diffuse pulmonary histiocytosis X, and the results were compared with values for normal lungs. This made possible a morphometric analysis of the tissue changes associated with the measurable abnormalities in gas transfer present in this disease. The small increases in arithmetic mean thickness of the alveolar-capillary membranes appeared insufficient to account for the reduction in gas transfer present. When compared with normal lung, a threefold increase in volumetric fraction of septal intercapillary tissue was found along with a corresponding decrease in septal capillaries. While uniformity of distribution cannot be determined by this method, it appears that abnormalities of blood gas transfer in this disease result primarily from a decrease in the available diffusing surface and the ventilation-perfusion distrubances with which these tissue changes are associated.     

Intravascular Oxygenator: A New Alternative Method for Augmenting Blood Gas Transfer in Patients With Acute Respiratory Failure

A unique hollow fiber membrane oxygenator (IVOX) has been developed, which is inserted into the vena caval blood stream to transfer O2/CO2 to/from circulating blood in an intact subject without involving the natural lungs. Extensive laboratory testing has demonstrated that the device can transfer significant quantities of O2 and CO2 for up to 3 weeks without significant harmful sequelae or complications. Clinical trials are in progress under FDA supervision, in which IVOX has been utilized to date in 56 patients with ARDS. Preliminary findings indicate that risks and hazards from IVOX are nil, and evidence of benefit to the patient has been demonstrated in 86% of the patients. At this time, clinical utilization of IVOX is in the experimental, data collecting mode to determine its proper role or niche as a method for temporary augmentation of blood gas transfer in patients with advanced acute respiratory failure.     

The pumping oxygenator: design criteria and first in vitro results

A new project is presented, the pumping oxygenator, functionally integrating pulsatile pumping and blood oxygenation in a single device. Solid, semipermeable silicone membranes allow gas exchange and simultaneously transfer energy from pressurized gas to blood thanks to their distensibility and to inlet and outlet 1-way valves. Two small-sized (1 m2 exchange surface area) prototypes were designed, constructed, hydraulically characterized, and subjected to gas transfer evaluation tests. Blood flow rates (Q(b)) up to 1,250 ml/min were obtained with 30 mm Hg static preload and 130 mm Hg afterload with 0.7 m upstream and 2.1 m downstream 3/8 inch pipes. Physiological oxygen transfer (VO2 = 5 ml/dl, ml of transferred O2/dl of treated blood) was delivered at Q(b) < 900 ml/min, about 4 ml/dl at Q(b) = 1,250 ml/min. VO2 also was significantly increased by increasing percent systolic time. CO2 transfer decreased regularly with increasing Q(b) from VCO2 = 4.8 ml/dl at Q(b) = 400 ml/min to VCO 2 = 2.1 ml/dl at Q(b) = 1,250 ml/min. The results confirm the possibility of integrating oxygenation and pulsatile pumping. The pumping oxygenator represents a promising project deserving further improvements.     

Impact of hollow-fiber membrane surface area on oxygenator performance: Dideco D903 Avant versus a prototype with larger surface area

This study compares the gas transfer capacity, the blood trauma, and the blood path resistance of the hollow-fiber membrane oxygenator Dideco D 903 with a surface area of 1.7 m2 (oxygenator 1.7) versus a prototype built on the same principles but with a surface area of 2 m2 (oxygenator 2). Six calves (mean body weight: 68.2 +/- 3.2 kg) were connected to cardiopulmonary bypass (CPB) by jugular venous and carotid arterial cannulation, with a mean flow rate of 4 l/min for 6 h. They were randomly assigned to oxygenator 1.7 (N = 3) or 2 (N = 3). After 7 days, the animals were sacrificed. A standard battery of blood samples was taken before the bypass, throughout the bypass, and 24 h, 48 h, and 7 days after the bypass. The oxygenator 2 group showed significantly better total oxygen and carbon dioxide transfer values throughout the perfusion (p < .001 for both comparison). Hemolytic parameters (lactate dehydrogenase and free plasma hemoglobin) exhibited a slight but significant increase after 5 h of bypass in the oxygenator 1.7 group. The pressure drop through the oxygenator was low in both groups (range, 43-74 mmHg). With this type of hollow-fiber membrane oxygenator, an increased surface of gas exchange from 1.7 m2 to 2 m2 improves gas transfer, with a limited impact on blood trauma and no increase of blood path resistance.