Extracorporeal gas exchange

The high mortality associated with acute respiratory failure and further exacerbation of the lung injury by mechanical ventilation continues to pose a challenge in the management of critically ill patients. By providing total gas exchange and complete lung rest, extracorporeal membrane oxygenation (ECMO) has improved the survival rate of selected neonatal, pediatric, and adult patients. Arteriovenous carbon dioxide removal (AVCO2R) was developed as a less labor intensive, less costly, and less complex technique of extracorporeal gas exchange, allowing near total CO2 removal.     

High flow/low resistance cannulas for percutaneous arteriovenous carbon dioxide removal

Percutaneous cannulas with low resistance are necessary for arteriovenous carbon dioxide removal (AVCO2R) to allow highest flow at lowest pressure to maximize CO2 removal. Commercially available arterial (A) and venous (V) percutaneous cannulas (8-18 Fr) were tested for pressure/flow characteristics under conditions that simulated percutaneous AVCO2R at clinically pertinent flow rates between 200-1000 ml/min to obtain the M number previously described by Delius, et al. The Bio-Medicus (Bio-Medicus, Grand Rapids, MI) 17F A, Research Medical, Inc (RMI) (Model FEM II, Research Medical, Inc., Midvale, UT) 16F A, and RMI 18F V cannulas exhibited the lowest M numbers that correlated with low resistance to flow. The four most clinically favorable arterial cannulas (8, 10, 12, and 14 Fr), coupled with a venous cannula four French sizes larger, were used in an AVCO2R circuit in adult sheep (n = 3) at varying mean arterial pressures (MAP) between 65-105 mmHg. The 8, 10, 12, and 14 Fr arterial cannulas allowed an arteriovenous flow of 208 +/- 72, 530 +/- 37, 848 +/- 66, and 944 +/- 96 ml/min, respectively, at a MAP of 65 mmHg. An increase in MAP to 105 mmHg was associated with approximately a 41, 30, 32, and 27% increment in blood flow, respectively. In summary, an arterial percutaneous cannula of 10 Fr or larger will allow AVCO2R blood flow greater than 500 ml/min, as previously shown by Brunston et al. to achieve total CO2 removal without incurring hypercapnia.     

Assay of DNA content and estrogen receptor status in human breast cancer

IVOX was named as an acronym for intravascular oxygenator. The device does not need a blood pomp like an extracorporeal membrane oxygenator (ECMO), and performs intracorporeal gas exchange to be a small elongated, hollow fiber membrane oxygenator designed to lie within the subject's venae cavae so that circulating venous blood can flow freely over and around the external surfaces of the hollow fibers. The amount of gas exchange in IVOX is less than ECMO, however, the equipment is simple and there is no effect to hemodynamics and body temperature. IVOX has been utilized in the management of 165 clinical trials patients in 31 international critical care centers. Currently the gas transfer rate by means of the IVOX device constitutes 1/4 to 1/3 the total metabolic requirement of adult acute respiratory failure patients. Therefore, intentional hypoventilation to limit airway pressures (mild permissive hypercapnia) is recommended to improve CO2 removal with increasing mixed venous CO2 concentrations. In the future, improvements of design, function, and methods of utilization of IVOX device are expected to increase the amount of gas exchange and to enlarge the indications for its use.     

Theory of gas exchange in the avian parabronchus

To understand the distribution of oxygen and carbon dioxide in the avian lung, a theoretical treatment of gas exchange in the parabronchus of the avian lung is described. The model is modified after Zeuthen (1942). In addition to bulk flow through the parabronchial lumen, diffusion through the air spaces of both the parabronchial lumen and air capillaries is treated. The relationship of PO2 and PCO2 within the blood capillaries, air capillaries, and parabronchial lumen to parabronchial blood flow and ventilation is graphically shown. The results indicate that the variations of PO2 and PCO2 along an air capillary are less than one torr under resting conditions. Removal of diffusion resistance within the air space of the air capillaries increases calculated parabronchial gas exchange by less than 0.1% at rest. At high or resting ventilation rates the partial pressure profile along the parabronchial lumen calculated considering bulk flow only agrees well with the profile calculated considering bulk flow and axial diffusion, but as the ventilation rate decreases there is increasingly large disagreement. Forward diffusion of O2 toward the parabronchus reduces pre-parabronchial PO2 and backward diffusion of CO2 from the parabronchus increases PCO2. Neglecting diffusion within the air spaces of both the lumen and the air capillaries increases calculated parabronchial gas exchange by less than 2% (CO2) or 6% (O2) at rest.     

Intravascular gas transfer. Membrane surface area and sweeping gas flows are of prime importance

Single and double hollow fiber intravascular gas exchangers were evaluated in an extracorporeal veno-venous bypass circuit (right atrium to pulmonary artery) including a tubular blood chamber (mimicking caval veins with an inner diameter of 26 mm) for evaluation of the membrane surface area/host vessel diameter gas transfer relationships. Six bovine experiments (body wt: 68 +/- 4 kg) with staged ex vivo blood flows of 1, 2, 3, and 4 L/min and a device oxygen inflow of 0, 3, and 6 L/min (0 or 3 L/min/device) were performed. Total oxygen transfer at a blood flow of 1 L/min was 33 +/- 4 ml/ min for a gas flow of 3 L/min (one device) vs 60 +/- 25 ml/ min for a gas flow of 6 L/min (two devices); at a blood flow of 2 L/min, the corresponding oxygen transfer was 46 +/- 16 ml/min for a gas flow of 3 L/min vs 95 +/- 44 ml/min for a gas flow of 6 L/min; at a blood flow of 3 L/min, the corresponding oxygen transfer was 48 +/- 24 ml/min for a gas flow of 3 L/ min vs 92 +/- 37 ml/min for a gas flow of 6 L/min (p < 0.01 for comparison of areas under the curves). Total carbon dioxide transfer at a blood flow of 1 L/min was 47 +/- 18 ml/min for a gas flow of 3 L/min vs 104 +/- 26 ml/min for a gas flow of 6 L/min; at a blood flow of 2 L/min, the corresponding carbon dioxide transfer was 59 +/- 19 ml/min for a gas flow of 3 L/ min vs 129 +/- 39 ml/min for a gas flow of 6 L/min; at a blood flow of 3 L/min, the corresponding carbon dioxide transfer was 60 +/- 22 ml/min for a gas flow of 3 L/min vs 116 +/- 49 ml/min for a gas flow of 6 L/min (p < 0.01). For the given setup, the blood flow/gas transfer relationship is non linear, and a plateau is achieved at a blood flow of 2.5 L/min for O2 and CO2. Doubling membrane surface area and consecutively sweeping gas flows result in doubling of gas transfers at all tested blood flows. However, increased membrane surface area and blood flow produce a higher pressure drop that in turn limits the fiber density that can be used clinically.     

Airway mechanics, gas exchange, and blood flow in a nonlinear model of the normal human lung

A model integrating airway/lung mechanics, pulmonary blood flow, and gas exchange for a normal human subject executing the forced vital capacity (FVC) maneuver is presented. It requires as input the intrapleural pressure measured during the maneuver. Selected model-generated output variables are compared against measured data (flow at the mouth, change in lung volume, and expired O2 and CO2 concentrations at the mouth). A nonlinear parameter-estimation algorithm is employed to vary selected sensitive model parameters to obtain reasonable least squares fits to the data. This study indicates that 1) all three components of the respiratory model are necessary to characterize the FVC maneuver; 2) changes in pulmonary blood flow rate are associated with changes in alveolar and intrapleural pressures and affect gas exchange and the time course of expired gas concentrations; and 3) a collapsible midairway segment must be included to match airflow during a forced expiration. Model simulations suggest that the resistances to airflow offered by the collapsible segment and the small airways are significant throughout forced expiration; their combined effect is needed to adequately match the inspiratory and expiratory flow-volume loops. Despite the limitations of this lumped single-compartment model, a remarkable agreement with airflow and expired gas concentration measurements is obtained for normal subjects. Furthermore, the model provides insight into the important dynamic interactions between ventilation and perfusion during the FVC maneuver.     

The content of electrolytes (Na, K, Ca, Mg) in vertebrate otoliths and otoconia

IVOX (intravenous oxygenator and CO2 removal device) augments venous gas exchange in patients with severe respiratory failure. Controlled hypoventilation with permissive hypercapnia reduces airway pressures during mechanical ventilation and augments CO2 exchange through the IVOX. To quantify the additive effects of gradual permissive hypercapnia and IVOX on gas exchange and reduction of airway pressures, 13 adult sheep underwent tracheostomy and severe smoke inhalation injury. Seven were mechanically ventilated alone (control), and six had mechanical ventilation, systemic anticoagulation, and implantation of IVOX (size 7 with 0.21-m2 surface area) (IVOX group). Both groups were anesthetized and paralyzed for 24 hr. In the IVOX group, minute ventilation was decreased in a stepwise fashion to produce a gradual increase in PaCO2, from 30 to 95 mm Hg, over 12 hr, and then sustained for an additional 12 hr. Sodium bicarbonate was given intravenously as necessary to keep arterial pH above 7.25. There were no significant differences in mean arterial pressure, cardiac output, or pulmonary artery pressure between the two groups. In the IVOX/permissive hypercapnia group, IVOX CO2 removal increased as a linear function of PaCO2 (y = 0.87x + 8.99, R2 = 0.80). IVOX CO2 removal was only 40 ml/min at normocapnia (40 mm Hg) but increased to 91 ml/min when PaCO2 was 95 mm Hg. Both peak inspiratory pressure and minute ventilation of the IVOX/permissive hypercapnia group were significantly lower than the control group, 30 +/- 4 mm Hg vs 51 +/- 3 mm Hg and 3.9 +/- 0.3 liters vs 8.4 +/- 0.5 liters (P < 0.05) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of reaction resistance in limiting carbon monoxide uptake in rabbit lungs

The contribution of reaction resistance to overall resistance to pulmonary carbon monoxide (CO) uptake [DLCO/(ThetaCO . Vc), where DLCO is lung CO diffusing capacity, ThetaCO is CO uptake conductance of erythrocytes, and Vc is pulmonary capillary blood volume] was determined in 10 anesthetized, paralyzed, and artificially ventilated rabbits. On the basis of the classical double-reciprocal equation of F. G. W. Roughton and R. E. Forster (J. Appl. Physiol. 11: 290-302, 1957), DLCO/(ThetaCO . Vc) was obtained by solving the relation DLCO/(ThetaCO . Vc) = 1 - 2/(DLNO/DLCO), where DLNO/DLCO represents the ratio between the respective single-breath diffusing capacities (DL) of nitric oxide (NO) and CO pulmonary capillary blood. The lungs of eight rabbits were inflated, starting from residual volume, by using 55 ml of indicator gas mixture (0.2% CO and 0.05% NO in nitrogen). DL values were calculated by taking the end-tidal partial pressures of CO and NO as analyzed by using a respiratory mass spectrometer. The overall value was DLCO/(ThetaCO . Vc) = 0.4 +/- 0.025 (mean +/- SD). Because of the use of O2-free indicator gas mixtures, the end-tidal O2 partial pressures were approximately 21 Torr. In one other rabbit, the application of 0.2% CO and 0.001% NO yielded DLCO/(ThetaCO . Vc) = 0.39; in the tenth rabbit, however, inspiratory volume was varied, and an identical value was found at functional residual capacity. We conclude that the contribution of reaction resistance to overall resistance to pulmonary CO uptake is independent of the inspiratory NO concentration used, including, with respect to the pertinent literature, the conclusion that in rabbits, dogs, and humans this contribution amounts to 40% when determined at functional residual capacity.     

Elective stenting of a de novo ostial lesion of the right internal mammary artery

Left single lung transplantation was performed under perioperative extracorporeal membrane oxygenation (ECMO) support for a patient of primary pulmonary hypertension. Continuous ECMO in this patient for one day after the transplantation decreased the pulmonary blood flow and probably served to minimize the potential complication of reperfusion edema of the graft. During this period, the ECMO was gradually weaned so that the grafted lung could adapt itself to the gradually increased blood flow through it. The patient was extubated without difficulty 2 days alter the removal of ECMO and made a smooth recovery.     

Red cell distortion and conceptual basis of diffusing capacity estimates: finite element analysis

To understand the effects of dynamic shape distortion of red blood cells (RBCs) as it develops under high-flow conditions on the standard physiological and morphometric methods of estimating pulmonary diffusing capacity, we computed the uptake of CO across a two-dimensional geometric capillary model containing a variable number of equally spaced RBCs. RBCs are circular or parachute shaped, with the same perimeter length. Total CO diffusing capacity (DLCO) and membrane diffusing capacity (DMCO) were calculated by a finite element method. DLCO calculated at two levels of alveolar PO2 were used to estimate DMCO by the Roughton-Forster (RF) technique. The same capillary model was subjected to morphometric analysis by the random linear intercept method to obtain morphometric estimates of DMCO. Results show that shape distortion of RBCs significantly reduces capillary diffusive gas uptake. Shape distortion exaggerates the conceptual errors inherent in the RF technique (J. Appl. Physiol. 79: 1039-1047, 1995); errors are exaggerated at a high capillary hematocrit. Shape distortion also introduces additional error in morphometric estimates of DMCO caused by a biased sampling distribution of random linear intercepts; errors are exaggerated at a low capillary hematocrit.     

A coupled diffusion model for the reduction of agglomerates of iron oxide granules

A coupled diffusion model is presented to describe the reduction of agglomerates of ferrous oxide grains. The reducing gas (CO) is imagined as diffusing first through the boundary layer created by gas flow at the pellet surface, then through, the agglomerate and finally diffusing into individual grains toward a moving boundary where the reduction occurs. The model is a general one applicable to packed beds of ore particles, briqueties or with some simplication to spherical pellets. Analytic solutions are obtained for platelet grains in slabs and the reduction of spherical pellets of spherical grains is computed for a range of values of the ratio of diffusivities of CO in the grains and pellet.     

Effects of blood flow pulse frequency on mass transfer efficiency of a commercial hollow fibre oxygenator

The clinical advantages achievable through pulsatile blood perfusion during cardio-pulmonary bypass have recently suggested the design of new pulsatile systems for extracorporeal circulation. Still it is not clear whether current commercial membrane oxygenators could be adopted with such systems, since their behaviour with pulsatile perfusion has not been satisfactorily documented yet. In a previous paper, we assessed that pulsatile perfusion of a widely used hollow fibre oxygenator (Sorin Monolyth) at 60 bpm provides more time-consistent oxygen transfer than steady perfusion. The present work is aimed to evaluate how the pulse frequency influences the gas transfer performance of the same device. The oxygenator was subjected to in vitro trials using a roller pump with pulsatile module (Stockert Instrumente) to generate pulsed flow. Four different pulse frequencies (45, 60, 75 and 90 bpm) were investigated at a fixed blood flow rate (4.0 l/min). The experiments lasting six hours were carried out using bovine blood with inlet conditions according to AAMI standards requirements. Blood samples were withdrawn every hour and O2 and CO2 transfer rates were evaluated. The experimental findings confirm that with pulsatile blood flow no time decay take place during prolonged perfusion. Moreover, when pulse frequency increases, transition levels occur for both O2 and CO2. Over these thresholds gas transfer rates display significant increases (p < 0.05), though of little magnitude (up to 2.5% for oxygen over 60 bpm; up to 3.7% for carbon dioxide over 75 bpm).     

Mechanical circulatory support for post cardiotomy cardiogenic shock in infants

Eleven infants weighing 2.3 to 7.8 kg underwent mechanical circulatory support for post cardiotomy cardiogenic shock. Initiated pre-operatively in two patients, extracorporeal membrane oxygenation was used in a total of eight patients aged 6 days to 3 months in association with repair of cyanotic congenital heart disease with increased pulmonary blood flow or with a right sided obstructive lesion. Ventricular assist devices were used in three other patients: a centrifugal left ventricular assist device in Patient 1 (10 months, 5.7 kg) after repair of the anomalous left coronary artery, and a pneumatic biventricular assist device (stroke volume 12 ml) in Patient 2 (6 months, 7.0 kg) for cardiac arrest after closure of ventricular septal defect and in Patient 3 (10 months, 7.8 kg) for post transplant graft failure. Duration of extracorporeal membrane oxygenation duration ranged from 26 to 192 hr (mean, 88 hr). Three patients were weaned from extracorporeal membrane oxygenation and two survived. Two others were separated from extracorporeal membrane oxygenation because of bleeding, but both subsequently died. Patient 1 was weaned from the left ventricular assist device after 192 hr and discharged from the hospital. Support was discontinued after 45 hr in Patient 2 who exhibited irreversible brain damage. Patient 3 was weaned from a biventricular assist device after 174 hr, but suffered recurrent graft failure. Our results show that an appropriate circulatory support system should be selected according to the cardiac anatomy in infants.     

Rate of nitric oxide production by lower alveolar airways of human lungs

This report describes methods for measuring nitric oxide production by the lungs' lower alveolar airways (VNO), defined as those alveoli and bronchioles well perfused by the pulmonary circulation. Breath holding or vigorous rebreathing for 15-20 s minimizes removal of NO from the lower airways and results in a constant partial pressure of NO in the lower airways (PL). Then the amount of NO diffusing into the perfusing blood will be the pulmonary diffusing capacity for NO (DNO) multiplied by PL and by mass balance equals VNO, or VNO = DNO(PL). To measure PL, 10 normal subjects breath held for 20 s followed by exhalation at a constant flow rate of 0.83 +/- 0.14 (SD) l/s or rebreathed at 59 +/- 15 l/min for 20 s while NO was continuously measured at the mouth. DNO was estimated to equal five times the single-breath carbon monoxide diffusing capacity. By using breath holding, PL equaled 2.9 +/- 0.8 mmHg x 10(-6) and VNO equaled 0.39 +/- 0.12 microl/min. During rebreathing PL equaled 2.3 +/- 0.6 mmHg x 10(-6) and VNO equaled 0.29 +/- 0.11 microl/min. Measurements of NO at the mouth during rapid, constant exhalation after breath holding for 20 s or during rebreathing provide reproducible methods for measuring VNO in humans.     

Adjuncts to mechanical ventilation

Adjunctive ventilatory strategies have been developed to improve oxygenation and carbon dioxide (CO2) removal during mechanical ventilation of critically ill patients. These techniques allow clinicians to attain their clinical goals at lower levels of ventilatory support. In this article, the authors discuss extracorporeal CO2 removal, venovenous intravena caval oxygenator, and tracheal gas insufflation as adjuncts to CO2 removal and nitric oxide, surfactant replacement therapy, perfluorocarbon-associated gas exchange, and prone positioning as adjuncts to oxygenation.     

Pulsatile augmentation device for extracorporeal circulation

A device has been designed, constructed, and tested to provide pulsatile pressure/flow to a standard extracorporeal bypass circuit. The pulsatile augmentation device is pneumatically driven similar to an artificial heart ventricle except that there are no valves. It is constructed of polyurethane by vacuum forming and high frequency welding. Drivers used are a modified Arrow-Kontron intraaortic balloon pump or the Utah artificial heart driver. In vitro testing with fresh bovine blood demonstrated acceptable blood compatibility and hemodynamic function. In vivo testing for 4 h in a right and left heart extracorporeal bypass circuit showed good pulse augmentation in pulmonary and systemic bypass circuits. The device shows promise for adding pulse to standard cardiopulmonary bypass and to extracorporeal right heart circulatory assist circuits.     

Cardiopulmonary adaptations to pneumonectomy in dogs. IV. Membrane diffusing capacity and capillary blood volume

Lung diffusing capacity for carbon monoxide (DLco) and its components, membrane diffusing capacity (Dmco) and capillary blood volume (Vc), as well as pulmonary blood flow (Qc), were measured at rest at several lung volumes and during treadmill exercise by a rebreathing technique in four adult dogs after right pneumonectomy (R-PNX) and in six matched control dogs (Sham) 6-12 mo after surgery. In both groups, lung inflation at rest was associated with a small increase in DLco and Dmco but not in Vc. After R-PNX, total DLco was lower by 30% at peak exercise compared with control values. When compared with DLco in a normal left lung, DLco in the remaining lung continued to increase along the normal relationship with respect to Qc up to a cardiac output equivalent to 34 l/min through both lungs of the Sham dog. There was no evidence of an upper limit of DLco being reached. The augmentation of DLco from rest to exercise was associated with corresponding increases in Dmco and Vc; after R-PNX, both Dmco and Vc continued to increase with respect to Qc along similar relationships as in control dogs without reaching an upper limit, suggesting a much larger alveolar-capillary reserve for gas exchange by diffusion than previously recognized. At higher levels of blood flow through the remaining lung, DLco was greater in adult dogs after R-PNX than after left pneumonectomy (Carlin et al. J. Appl. Physiol. 70: 135-142, 1991), suggesting that additional sources of compensation, e.g., lung growth, exist after removal of > 50% of lung.     

Transfer of carbon monoxide during an inspiratory pause procedure in mechanically ventilated pigs

We studied the effect of forced inflation at different alveolar volumes (VA) on carbon monoxide diffusing capacity (DLCO) in anaesthetized, paralysed and mechanically ventilated healthy pigs. An inspiratory pause procedure (equivalent of the single-breath technique) consisting of a pause between an inflation and expiration, both at a constant flow rate, was used. The procedure was computer-controlled and could easily be standardized. In five pigs, VA was varied at constant inflation volume by increasing positive end-expiratory pressure (PEEP) from 2 to 10 cmH2O. Inspiratory pause time was varied from 1 to 8 s to verify whether the decay of CO was exponential. In nine pigs, DLCO was estimated at four different VA values by inflating with 15-30 ml kg-1 at 2 cmH2O PEEP. An exponential decay of CO was always obtained. With increasing VA by either an increase in PEEP or inflation volume, DLCO remained constant. Since the diffusing capacity of the pulmonary membrane is expected to increase with increasing VA, the constant DLCO may be attributed to a decrease in capillary blood volume.     

Development of a silicone hollow fiber membrane oxygenator for ECMO application

A new silicone hollow fiber membrane oxygenator for extracorporeal membrane oxygenation (ECMO) was developed using an ultrathin silicone hollow fiber, with a 300 microm outer diameter and a wall thickness of 50 microm. The hollow fibers were mechanically cross-wound on the flow distributor to achieve equal distribution of blood flow without changing the fiber shape. The housing, made of silicone coated acryl, was 236 mm long with an inner diameter of 60 mm. The surface area was 1.0 m2 for prototype 211, and 1.1 m2 for prototype 209. The silicone fiber length was 150 mm, and the silicone membrane packing density was 43% for prototype 211 and 36% for prototype 209. Prototype 211 has a priming volume of 208 ml, and prototype 209 has a priming volume of 228 ml. The prototype 211 oxygenator demonstrates a gas transfer rate of 120 +/- 5 ml/min (mean +/- SD) for O2 and 67 +/- 12 ml/min for CO2 under 2 L of blood flow and 4 L of O2 gas flow. Prototype 209 produced the same values. The blood side pressure drop was low compared with the silicone sheet oxygenator (Avecor, 1500ECMO). These results showed that this new oxygenator for ECMO had efficiency similar to the silicone sheet oxygenator that has a 50% larger surface area. These results suggest that the new generation oxygenator using an ultrathin silicone hollow fiber possesses sufficient gas transfer performance for long-term extracorporeal lung support.     

Continued development of the Nimbus/University of Pittsburgh (UOP) axial flow left ventricular assist system

Nimbus and the University of Pittsburgh (UOP) have continued the development of a totally implanted axial flow blood pump under the National Institutes of Health (NIH) Innovative Ventricular Assist System (IVAS) program. This 62 cc device has an overall length of 84 mm and an outer diameter of 34.5 mm. The inner diameter of the blood pump is 12 mm. It is being designed to be a totally implanted permanent device. A key achievement during the past year was the completion of the Model 2 pump design. Ten of these pumps have been fabricated and are being used to conduct in vitro and in vivo experiments to evaluate the performance of different materials and hydraulic components. Efforts for optimizing the closed loop speed control have continued using mathematical modeling, computer simulations, and in vitro and in vivo testing. New hydraulic blade designs have been tested using computational fluid dynamics (CFD) and flow visualization. A second generation motor was designed with improved efficiency. To support the new motor, a new motor controller fabricated as a surface mount PC board has been completed. The program is now operating under a formal QA system.