Membrane oxygenators: current developments in design and application

Cardiopulmonary bypass (CPB) procedures require a blood-gas exchanger (oxygenator) to temporarily replace the respiratory function of the lungs. In the past the majority of CPB procedures have been carried out with bubble oxygenators which effect gas exchange by dispersion of bubbles into the blood. Membrane oxygenators, on the other hand, utilize a hydrophobic gas permeable membrane between the blood and gas phases.Bubble oxygenators are being superseded by membrane types for CPB due to improvements in membrane technology and mass transfer efficiency. These advances are reviewed in this paper and are illustrated by reference to the gas exchange and operating characteristics of a number of clinical oxygenators designed for adult CPB.Membrane oxygenatorsare also being used for long-term support in the treatment of acute respiratory failure. Operated in a partial bypass circuit, the oxygenator may have to function for several days or weeks. In one particular treatment method, the rate of spontaneous breathing is controlled by the partial or total removal of the metabolic CO₂ production by the membrane oxygenator. For this method, known as extracorporeal CO₂ removal (ECCO₂R), the oxygenator must be optimized for CO₂ transfer at low blood flow rates. The suitability of clinical oxygenators for ECCO₂R is discussed in terms of gas exchange and functionality over a prolonged operation.     

A respiratory venous chemoreceptor in the young puppy.

An extracorporeal venovenous shunt system utilizing a membrane oxygenator to alter venous blood gases was used to study the regulation of ventilation in 28 newborn and 4 adult dogs. There was no effect of the extracorporeal circuit per se (without the oxygenator in the system) on essential cardiovascular or respiratory function. When the puppies were placed on the extracorporeal circuit with the oxygenator in the system to effect changes in mixed venous blood gas composition there was a significant increase in venous P02 (Pv02), a decrease in venous Pco2 (Pvco2), a rise in venous pH (PHv), and a marked fall in minute ventilation (VE). There were no significant changes in cardiovascular function or arterial blood gases to account for the depression of ventilation. Acute changes in Pvo2 produced appropriate directional changes of VE under conditions where other arterial and venous blood gases were held constant. At a low Pvco2/Paco2 ratio, ventilation was depressed compared to those conditions with a high ratio. At any Pvc02/Paco2 ratio, ventilation could be depressed by raising the Pvo2. In adult animals ventilation could not be altered by changing venous blood gases. These experiments support the existence of a respiratory chemoreceptor sensitive to both PO2 and PCO2 in the prepulmonary or venous circulation of the newborn animal.     

Effect on breathing of acute pressure rise in pulmonary artery and right ventricle

We tested the hypothesis that breathing would be regulated in response to right ventricular and pulmonary arterial pressure changes when secondary events are controlled. Dogs were anesthetized, thoracotomies were performed, and cardiopulmonary bypass perfusion was established. Lungs were inflated to sustained pressures. The left diaphragmatic lobe was retrogradely cannulated and all other lobar arteries were ligated, forming a pulmonary arterial sac that drained to the oxygenator from the cannula and filled from systemic venous return by the beating right ventricle. Right atrial pressure was adjusted to produce sac flows of approximately 400 ml/min. We recorded systemic and pulmonary arterial pressures, sac flow, and the integrated diaphragm electromyogram (DEMG). Resistive loads were imposed on sac outflow by adjusting a clamp. Loaded mean pulmonary arterial pressures ranged from 27 to 70 Torr. Loading increased respiratory frequency without affecting peak DEMG amplitude. Responses did not occur after vagotomy. Effects were quantitatively modest: pressurization to approximately 50 Torr increased frequency approximately 3.4 breaths/min (22%). The magnitude of change was insufficient to explain in intact dogs the ventilatory responses that have been attributed to this reflexogenic unit.     

Alveolar slope and dead space of He and SF6 in dogs: comparison of airway and venous loading

Series (Fowler) dead space (VD) and slope of the alveolar plateau of two inert gases (He and SF6) with similar blood-gas partition coefficients (approximately 0.01) but different diffusivities were analyzed in 10 anesthetized paralyzed mechanically ventilated dogs (mean body wt 20 kg). Single-breath constant-flow expirograms were simultaneously recorded in two conditions: 1) after equilibration of lung gas with the inert gases at tracer concentrations [airway loading (AL)] and 2) during steady-state elimination of the inert gases continuously introduced into venous blood by a membrane oxygenator and partial arteriovenous bypass [venous loading (VL)]. VD was consistently larger for SF6 than for He, but there was no difference between AL and VL. The relative alveolar slope, defined as increment of partial pressure per increment of expired volume and normalized to mixed expired-inspired partial pressure difference, was larger by a factor of two in VL than in AL for both He and SF6. The He-to-SF6 ratio of relative alveolar slope was generally smaller than unity in both VL and AL. Whereas unequal ventilation-volume distribution combined with sequential emptying of parallel lung regions appears to be responsible for the sloping alveolar plateau during AL, the steeper slope during VL is attributed to the combined effects of continuing gas exchange and ventilation-perfusion inequality coupled with sequential emptying. The differences between He and SF6 point at the contributing role of diffusion-dependent mechanisms in intrapulmonary gas mixing.     

The effects of cardiopulmonary bypass with hollow fiber membrane oxygenator on blood clotting measured by thromboelastography

In cardiac surgical patients we investigated the effects of cardiopulmonary bypass (CPB) with a hollow fiber membrane oxygenator on blood clotting measured by thromboelastography (TEG). We found only a minimal change in the strength of blood clot described either by the TEG parameter MA (maximum amplitude) or by the shear modulus G calculated from MA. After CPB there was also a significant tendency towards hypercoagulation as defined by shortened parameters R, K and increased a-angle. After comparison with published data obtained in cardiac surgical patients using a bubble oxygenator we conclude that currently used extracorporeal technology exerts a less negative influence on blood clotting than had been conceived previously.     

Intrapulmonary Co2 receptors and ventilatory response to lung Co2 loading

The possible role of intrapulmonary CO2 receptors (IPC) in arterial CO2 partial pressure (PaCO2) homeostasis was investigated by comparing the arterial blood gas and ventilatory responses to CO2 loading via the inspired gas and via the venous blood. Adult male Pekin ducks were decerebrated 1 wk prior to an experiment. Venous CO2 loading was accomplished with a venovenous extracorporeal blood circuit that included a silicone-membrane blood oxygenator. The protocol randomized four states: control (no loading), venous CO2 loading, inspired CO2 loading, and venous CO2 unloading. Intravenous and inspired loading both resulted in hypercapnic hyperpnea. Comparison of the ventilatory sensitivity (delta VE/delta PaCO2) showed no significant difference between the two loading regimes. Likewise, venous CO2 unloading led to a significant hypocapnic hypopnea. Sensitivity to changes in PaCO2 could explain the response of ventilation under these conditions. The ventilatory pattern, however, was differentially sensitive to the route of CO2 loading; inspired CO2 resulted in slower deeper breathing than venous loading. It is concluded that IPC play a minor role in adjusting ventilation to match changes in pulmonary CO2 flux but rather are involved in pattern determination.     

Cardiogenic oscillations in He and SF6 expirograms during airway and venous loading

Cardiogenic oscillations in the expired partial pressure profiles of two inert gases (He and SF6) were monitored in seven anesthetized paralyzed mechanically ventilated dogs. He and SF6 were administered either intravenously by a membrane oxygenator and partial arteriovenous bypass [venous loading (VL)] or by washin into lung gas [airway loading (AL)]. The single-breath expirograms obtained during constant-flow expiration after inspiration of test gas-free air displayed distinct and regular cardiogenic oscillations. The relative oscillation amplitude (ROA), calculated as oscillation amplitude divided by mixed expired-inspired partial pressure difference, was in the range of 1-8%. The ROA for both He and SF6 was approximately 4.2 times higher in VL than in AL, which indicated that among lung units that emptied sequentially in the cardiac cycle, the effects of alveolar ventilation-perfusion (VA/Q) inequality were more pronounced than those of alveolar ventilation-alveolar volume (VA/VA) inequality. In AL, He and SF6 oscillations were 180 degrees out of phase compared with CO2 and O2 oscillations and with He and SF6 oscillations in VL, which suggests that regions with low VA/VA had high VA/Q and very low Q/VA. The ROA was practically unaffected by breath holding in both AL and VL, which indicates that there was little diffusive or convective (cardiogenic) mixing between the lung units that were responsible for cardiogenic oscillations. The ROA was consistently higher for He than for SF6, and the He-to-SF6 ratio was independent of route of test gas loading, averaging 1.6 in both AL and VL. This result may be explained by laminar Taylor dispersion, whereby oscillations generated in peripheral lung regions are dissipated in inverse proportion to diffusion coefficient during transit through the proximal (larger) airways.     

The accelerated atherogenesis of venous grafts might be attributed to aggravated concentration polarization of low density lipoproteins: A numerical study

We hypothesize that after implantation the much elevated water filtration rate of venous grafts may cause aggravated concentration polarization of low density lipoproteins (LDLs), in turn lead to the accelerated atherogenesis of the grafts. To verify the hypothesis, we numerically simulated the transport of LDLs in various models of arterial bypasses with different grafts (veins or arteries) and geometrical configurations. The results showed that the venous grafts might endure abnormally high lipid infiltration/accumulation within the vessel wall due to severely elevated luminal surface LDL concentration. When compared to the conventional bypass models, the S-type bypass had the lowest luminal surface LDL concentration along its host artery floor, but the highest degree of risk to develop atherosclerotic lesions in its venous graft. Among the three conventional bypass models, the one with 30° anastomosis had the lowest risk to develop atherosclerosis in the venous graft. In conclusion, when compared with the bypass models with arterial grafts, the venous bypass models had rather high levels of LDL concentration polarization (c_w) in the vein grafts, especially at the early stages of implantation. This might result in high infiltration/accumulation of LDLs within the walls of the venous grafts, leading to a fast genesis/development of atherosclerosis there.     

临床心脏病学之心肺转流技术的发展进程与述评

回顾了临床心脏病学的心肺机和心肺转流技术的诞生、改进、发展历程,以及其核心技术-人工氧合器的产生和进步,进而评述了生物医学工程技术进步对医学发展的推进作用。     

Development of a digital adaptive control system for PO2 regulation in a membrane oxygenator

Regulation of gas exchange in artificial lungs (oxygenators) during cardiopulmonary bypass is normally achieved by manual control of the gas composition and flow in response to intermittent sampling of the arterial partial pressures of oxygen (P_aO₂) and carbon dioxide (P_aCO₂). Manual control often results in abnormal blood gases which have been implicated in patient morbidity as well as influencing perfusion safety. Fine control of P_aO₂ and P_aCO₂ may be achieved by a combination of an in-line blood gas monitoring system and a membrane type oxygenator which is automatically regulated. The overall dynamics of the oxygenation process and control system components are complex and have nonlinear, multivariable and time-varying characteristics. Consequently, an adaptive control system approach is necessary. The implementation of a digital self-tuning control regime for P_aO₂ is described here. The controller is based on an explicit Linear Quadratic Gaussian (LQG) self-tuning control design which is presented using a polynomial equation approach. The controller performance was investigated in in vitro experiments. The self-tuner performed satisfactority with various sensor/oxygenator combinations for blood flow and temperature load disturbances. In contrast, a nonadaptive (proportional-integral, PI) type of control system was found to be unsuitable.     

Assisted circulation following myocardial infarction: a review of 25 patients treated before 1971

Twenty-five patients with impending death from myocardial infarction were treated with assisted circulation. Of these, 19 had suffered cardiac arrest from which they could not be resuscitated and six were in severe, intractable and expectedly terminal cardiogenic shock.All patients were treated by venoarterial bypass employing a bubble oxygenator. Assistance was continued for an average duration of one hour and 45 minutes at a flow rate between two and four litres per minute. The patients all showed improved cerebral, pulmonary and renal function and acid-base values returned to normal.Five patients survived for at least one month and two were improved; hence 28% of these otherwise terminal patients were helped by this technique of assisted circulation.     

Hypoxémies sévère en cours de CEC : démarches diagnostiques et conduite à tenir

The occurring of hypoxemia during CPB is a potentially serious event that requests emergency correction. Hypoxemia can be documented by repeated arterial blood gases, either systematic, or performed because of a dark red coloration of arterial blood or a drop in venous oxygen saturation, pulse oximetry or near infrared spectroscopy. The continuous surveillance of PaO₂, if available, will provide the earliest diagnosis. Except hypoxemia due to operating troubles (low flow on a canulation problem, acute haemorrhage, insufficient anaesthesia, etc.), hypoxemia during CPB is linked either to a defect in the administering of gases at the oxygenator, or to a deficient oxygenator. The analysis of the fraction of oxygen at the oxygenator exit (FeoO₂) will prove the defect in the administering of gases. The treatment consists in the use of a spare oxygen cylinder in case of hospital supply failure, the use of the accessory anaesthesia circuit in case of a flaw in the flow meter, or the identification and repair of leaks. In case of a deficient oxygenator, the measure of resistances will differentiate an obstruction associated to a shunt (caused by a lack in anticoagulation, or by platelet activation phenomenon, whether transitional or not) from a loss in the membrane transfer properties, which will most often request a replacement of the oxygenator.     

Cardiopulmonary response to extracorporeal venous CO2 removal in awake spontaneously breathing dogs

The ventilatory response to a reduction in mixed venous PCO2 has been reported to be a decrease in breathing even to the point of apnea with no change in arterial CO2 partial pressure (PaCO2), whereas a recent report in exercising dogs found a small but significant drop in PaCO2 (F. M. Bennett et al. J. Appl. Physiol. 56: 1335-1337, 1984). The purpose of the present study was to attempt to reconcile this discrepancy by carefully investigating the cardiopulmonary response to venous CO2 removal over the entire range from eupnea to the apneic threshold in awake, spontaneously breathing normoxic dogs. Six dogs with chronic tracheostomies were prepared with bilateral femoral arteriovenous shunts under general anesthesia. Following recovery, an extracorporeal venovenous bypass circuit, consisting of a roller pump and a silicone-membrane gas exchanger, was attached to the femoral venous cannulas. Cardiopulmonary responses were measured during removal of CO2 from the venous blood and during inhalation of low levels of CO2. Arterial PO2 was kept constant by adjusting inspired O2. The response to venous CO2 unloading was a reduction in PaCO2 and minute ventilation (VE). The slope of the response, delta VE/delta PaCO2, was the same as that observed during CO2 inhalation. This response continued linearly to the point of apnea without significant changes in cardiovascular function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Operating management of central venous hypertension complicating upper extremity dialysis access

Aim: To evaluate the importance of surgical bypass between the terminal part of functional arteriovenous shunt (av) for hemodialysis on upper extremity and inner jugular vein in axillosubclavian venous segment obstruction associated with central venous hypertension. Method: Retrospective assessment of surgical bypass between central segments of av fistula and ipsilateral/contralateral inner jugular vein using ePTFE graft in 17 patients over a 20 year period (1987-2006). Results: The surgical procedure was not associated with intra- or post-operative complications. Primary cumulative bypass and av fistula function persisted for 26 months on average. Conclusion: An accurate bypass to salvage the functional dialysis access associated with central venous hypertension requires careful decision based on clinical and radiological examination. The bypass procedure is beneficial where endovascular treatment is not indicated. Clinical and radiological bypass monitoring is crucial.     

The reality of a self-occluding pump head: Case report

A malfunction of an oxygenator pumphead during aortocoronary bypass surgery is described. Corrections were made and the operation proceeded without further incident. Although this malfunction is extremely rare, it is reviewed in detail to alert perfusionists to the possibility of such an occurrence.     

Renal preservation by hypothermic perfusion: 2. The influence of oxygenator design and oxygen tension

Rabbit kidneys have been perfused for 24 hr at 5 °C and tested by autotransplantation with immediate contralateral nephrectomy. The perfusate contained an extracellular balance of ions with dextran and bovine serum albumin. The circuit included a nonpulsatile pump, a 0.22-μm membrane filter, and an oxygenator.The efficiency of membrane, film, and bubble oxygenators was compared. Flat membrane oxygenators were found to be more efficient than tubing oxygenators, and although the bubble oxygenator was the most efficient it created problems with foaming. A simple film oxygenator provided the best compromise.Ten kidneys were perfused and transplanted in each of three experimental groups; a film oxygenator was used to provide partial pressures of oxygen of 676 mmHg, 137 mmHg, and 9 mmHg, respectively.There were no significant differences in behavior during perfusion, function after transplantation, or histology of transplanted kidneys in the three groups.The similarity of the results using a film oxygenator with those previously obtained with a membrane oxygenator indicates that complex membrane oxygenators are not necessary for preservation in our system. Moreover, the similarity of the results with oxygen tensions from 9 mmHg to 676 mmHg shows that deliberate oxygenation is also unnecessary.     

Contribution of continuing gas exchange to phase III exhaled PCO2 and PO2 profiles

Changes in PCO2 and PO2 during expiration have been ascribed to simultaneous gas exchange, but other factors such as ventilation-perfusion inhomogeneity in combination with sequential emptying may also contribute. An experimental and model approach was used to study the relationship between gas exchange and changes in expired PCO2 and PO2 in anesthetized dogs during prolonged high tidal volume expirations. Changes in PCO2 and PO2 were quantified by taking the area bounded by the sloping exhalation curve and a line drawn horizontally from a point where the Fowler dead space plus 250 ml had been expired. This procedure is similar to using the slope of the exhalation curve but it circumvents problems caused by nonlinearity of the PCO2 and PO2 curves. The gas exchange components of the CO2 and O2 areas were calculated using a single-alveolus lung model whose input parameters were measured in connection with each prolonged expiration. The relationship between changes in experimental CO2 areas caused by sudden reductions in mixed venous PCO2 (produced by right atrial infusions of NaOH) and those calculated by the model was also studied. In seven dogs, calculated CO2 and O2 areas were 13% higher and 25% lower than the respective experimental areas, but interindividual variations were large. Changes in experimental CO2 areas caused by step changes in mixed venous PCO2 were almost identical to changes in the calculated areas. We conclude that the changes in PCO2 and PO2 during expiration cannot be explained solely by gas exchange. However, the single-alveolus lung model accurately predicts changes in the CO2 exhalation curve caused by alterations in the alveolar CO2 flow.     

Changes in plasma atrial natriuretic peptide--immunoreactivity in patients undergoing coronary artery bypass graft placements

Plasma atrial natriuretic peptide immunoreactivity (IrANP) was measured before, during, and after cardiopulmonary bypass for coronary artery bypass graft placement. Eight subjects scheduled for elective operation had in the premedicated preoperative state slightly elevated IrANP compared to controls. Neither induction of anesthesia with a high dose narcotic/non-depolarising relaxant/diazepam technique nor cardiopulmonary bypass changed IrANP significantly. Mixed venous and arterial IrANP increased immediately after discontinuing bypass, and remained elevated 1 h later. Because ANPs affect peripheral resistance as well as urinary sodium loss, the post-bypass elevations in these peptides may contribute to cardiovascular and diuretic effects after cardiopulmonary bypass.     

Extracorporeal circulation in the isolated in situ lamb placenta: hemodynamic characteristics.

Decreased placental perfusion and respiratory gas exchange have been observed after experimental fetal cardiopulmonary bypass (CPB). To better characterize placental hemodynamics during CPB, seven isolated in situ lamb placentas were placed on a CPB circuit by use of umbilical arterial and venous cannulation. Measures were taken to simulate normal placental hemodynamics. Perfusion flow rates were varied from 15 to 300 ml.min-1.kg fetal wt-1 during normothermia and hypothermia. Placental vascular resistance (PVR) remained constant when perfusion pressure and flow were varied above 40 mmHg and 150 ml.min-1.kg-1, respectively. Below these values, PVR varied inversely. This increase in PVR was more marked when CPB was performed with hypothermia than with normothermia. The clinical implication is that decreased placental flow and pressure on CPB may lead to a vicious cycle, resulting in further impairment of placental perfusion and respiratory gas exchange. Hypothermia promotes this impairment.     

缩短体外循环管道对新生儿和小婴儿心脏手术输血量的影响

目的回顾分析了逐步缩短体外循环管道对新生儿和小婴儿心脏手术输血量的影响。方法将2000年至2010年体重10kg以下病人4822例,分为3组：组1（n=1265）Dedico901/902/Medtronic氧合器＋Stockert II/Jostra HL20人工心肺机;组2（n=2534）Rx-05氧合器＋Stockert II/Jostra HL20人工心肺机;组3（n=1023）Rx-05氧合器＋Jostra HL30人工心肺机。比较各组预充总量,红细胞悬液的使用量和血球压积。结果组3和组2的预充量显著低于组1预充量（组1,718±15ml;组2,458±15ml;组3,334±8ml,P〈0.001）。围术期各组血球压积无显著差异;然而各组在预充液中加入的红细胞悬液有显著差异（组1,313±5 ml;组2,205±5ml;组3,167±8ml,P〈0.001）,体外循环转流中加入的红细胞悬液组间也有显著性差异（组1,117±8ml;组2,88±7ml;组3,60±8ml,P〈0.001）。结论通过改进氧合器和缩短管道长度能减少预充量和总用血量,逐步向不用血心脏外科迈进。