Toward ambulatory arteriovenous CO2 removal: initial studies and prototype development

Extracorporeal arteriovenous carbon dioxide removal (AVCO2R) using percutaneous cannulae and a low resistance gas exchanger achieves near total CO2 removal, allowing lung rest and potentially improving survival. AVCO2R, redesigned to allow ambulation, has potential as treatment for severe chronic obstructive pulmonary disease or rehabilitation before lung transplant. The purposes of this study were to 1) determine the optimal ambulatory access for AVCO2 removal and 2) develop a prototype Ambulatory-AVCO2R gas exchanger. Initially, reinforced Gore-Tex 6 mm (two) and 8 mm (four) grafts were anastomosed to sheep carotid arteries and jugular veins as a loop in parallel to the cranial circulation to determine blood flow capabilities. Blood flow was 100-150 ml/min with a 14 gauge dialysis needle, and transected 6 mm Gore-Tex grafts achieved 500-900 ml blood flow, whereas transected 8 mm grafts achieved up to 2000 ml/min flow. The polytetrafluoroethylene (PTFE) loops were then connected to our newly developed ultra low resistance pumpless gas exchanger for ambulatory AVCO2R. The average pressure gradient across the prototype Ambulatory-AVCO2R gas exchangers (n = 5) was 2.8 +/- 0.8 mm Hg, and mean CO2 removal was 104.8 +/- 14.0 ml/min, with an average blood flow of 900 ml/min. We conclude that an 8 mm Gore-Tex reinforced graft arteriovenous loop supplies ample blood flow for our new ultra low resistance Ambulatory-AVCO2R to achieve near total CO2 removal.     

Short term performance evaluation of a perfluorocopolymer coated gas exchanger for arteriovenous CO2 removal

A new perfluorocopolymer coating for micropore hollow fiber gas exchangers was developed to improve gas exchange, reduce plasma leakage, and reduce blood-surface interactions. The present authors evaluated gas exchanger performance using this new coating in a prospective, randomized, controlled, unblinded, large animal model of CO2 retention. Adult sheep (30-40 kg), under general anesthesia, underwent cannulation of the carotid artery (12 F) and jugular vein (14 F). The perfluorocopolymer coated (n = 5) and uncoated (n = 5) gas exchangers were attached to an arteriovenous CO2 removal (AVCO2R) circuit. Blood gases, CO2 removal, and hemodynamics were monitored throughout the 6 hour study. Average CO2 removal was 107.6 +/- 15.6 ml/min (coated) vs. 93.0 +/- 13.9 ml/min (uncoated; p < 0.01). PaCO2 and CO2 removal for both coated and uncoated did not deteriorate significantly over the study. Average AVCO2R blood flow was 1,130 +/- 25 ml/min (coated) versus 1,101 +/- 79 ml/min (uncoated; p = not significant). Likewise, cardiac output and AVCO2R blood flow did not change over the duration of the study. No significant differences in the pressure gradient or resistance between devices (coated, 6.89 +/- 1.14 mm Hg/L/min; uncoated, 6.42 +/- 0.23 mm Hg/L/min) was noted. The authors concluded that the new perfluorocopolymer coated gas exchanger improved CO2 removal without compromising hemodynamics in an acute performance evaluation.     

Hemodynamic stability during arteriovenous carbon dioxide removal for adult respiratory distress syndrome: a prospective randomized outcomes study in adult sheep

To evaluate the ability of arteriovenous carbon dioxide removal (AVCO2R) to maintain hemodynamic stability during treatment of adult respiratory distress syndrome (ARDS), we used our smoke/burn, LD40 sheep model of ARDS. With onset of ARDS (PaO2/FiO2 < 200) animals were randomized to AVCO2R (n = 20) or SHAM (n = 8). With AVCO2R, the carotid artery (10-14 F) and jugular vein (14-16 F) were cannulated; SHAM received identical management, sparing the vessels. AVCO2R maintained stable hemodynamics compared to SHAM at 48 hours; heart rate (114.8+/-6.1 vs. 110.1+/-11.0 beats/min.), mean arterial pressure (112+/-5.1 vs. 107.0+/-8.5 mm Hg), cardiac output (7.4+/-0.5 vs. 7.5+/-0.9 L/min.), pulmonary arterial pressure (26+/-2.4 vs. 21+/-1.3 mm Hg), pulmonary arterial wedge pressure (14.1+/-1.8 vs. 14.0+/-1.2 mm Hg), and central venous pressure (7+/-1.6 vs. 8+/-0.9 mm Hg). At 48 hours, AVCO2R allowed significant reductions (p<0.05) in minute ventilation (13.6+/-2.5 to 7.6+/-0.8 L/min); tidal volume (TV) (389.4+/-24.1 to 295.0+/-10.1 ml); peak inspiratory pressure (PIP) (25.4+/-9.2 to 18.8+/-2.5 cm H2O); RR (27.5+/-0.7 to 21.6+/-1.8 breaths/min); and FiO2 (0.96+/-0.00 to 0.48+/-0.2) while normocapnia was maintained. AVCO2R is an effective method of CO2 removal during severe respiratory failure that is hemodynamically well tolerated.     

The effect of augmented hemodynamics on blood flow during arteriovenous carbon dioxide removal

Arteriovenous carbon dioxide removal (AVCO2R) as an alternative treatment for acute respiratory distress syndrome uses a low resistance gas exchanger in a simple arteriovenous shunt to achieve total CO2 removal and allow lung rest. We have previously shown in our clinically relevant LD40 ovine model of smoke/burn induced acute respiratory distress syndrome that AVCO2R allows significant decreases in respiratory rate, tidal volume, peak airway pressure, and FiO2, as compared with standard mechanical ventilation. In addition, we have shown in a prospective randomized outcomes study that AVCO2R increases ventilator free days, decreases ventilator dependent days, and significantly improves survival. The purpose of this study is to further define the limits of AVCO2R through hemodynamic augmentation and evaluation of peak end expiratory pressure (PEEP). Administration of an alpha agonist (phenylephrine) and a beta agonist (isoproterenol) increased mean arterial pressure (MAP) and cardiac output (CO), respectively. MAP increases ranged from 2.4% to 94.4% and CO increases ranged from 33% to 146%. Phenylephrine caused elevations in MAP (2.4-94.4%) and AVCO2R flow (9-67%), and CO never decreased more than 10%. Isoproterenol administration increased CO (33-146%), decreased MAP (9-54%), and decreased AVCO2R flow (11-42%). In a second group, PEEP was increased stepwise from 0 (baseline) to 20 cm H2O. Increasing PEEP did not result in significant hemodynamic changes (< 10% change from baseline PEEP) for MAP, CO, or AVCO2R flow. In conclusion, alpha agonist administration increased AVCO2R blood flow, whereas beta agonist administration decreased MAP and AVCO2R blood flow, despite CO elevation. Various levels of PEEP are well tolerated and thus allow a range of options during AVCO2R.     

Complete respiratory support with AVCO2R and CPAP-mimic ventilation for total gas exchange in sheep

The altered respiratory mechanics in patients with chronic obstructive pulmonary disease (COPD) present unique challenges with regard to treatment during an acute exacerbation that often leads to respiratory support with mechanical ventilation. Alternative therapies are badly needed to reduce morbidity and mortality associated with mechanical ventilator use. We hypothesized that arteriovenous carbon dioxide removal (AVCO(2)R) coupled with continuous positive airway pressure (CPAP) would achieve total gas exchange eliminating the need for intubation/mechanical ventilation, thus reducing baro/volutrauma. This hypothesis was tested in six adult sedated apneic sheep with AVCO(2)R administered through a simple arteriovenous (AV) shunt for CO(2) removal. Because it is impractical to apply a CPAP mask to conscious sheep, the CPAP was mimicked in intubated/sedated sheep by positive end-expiratory pressure (PEEP) of 5-10 mmH(2)O with negligible ventilation. The AVCO(2)R and CPAP-mimic maintained Pa(o)(2) and Pa(co)(2) in the normal physiological ranges. The CO(2) removal was 120-150 ml/min through AVCO(2)R with AV blood flow of 1.1-1.5 L/min. A high fraction of inspired oxygen percentage (Fi(o)(2)) level (89 ± 3%) was required to achieve 40 ± 7% O(2) in the small bronchus. Thus, AVCO(2)R and CPAP-mimic achieved total gas exchange in anesthetized sheep and may be a potential option for acute COPD exacerbation in humans.     

Interleukin-8, aquaporin-1, and inducible nitric oxide synthase in smoke and burn injured sheep treated with percutaneous carbon dioxide removal

We previously showed that a percutaneous arteriovenous gas exchanger was effective in removing CO2 and reversing respiratory failure in an ovine model of adult respiratory distress syndrome (ARDS) produced by smoke inhalation and burn injury (Alpard et al., Ann Surg 230:215-224, 1999). In this study, we tested the hypothesis that arteriovenous CO2 removal (AVCO2R) lessened endogenous inflammation in the lung. Myeloperoxidase activity, aquaporin-1 (AQP-1), interleukin-8 (IL-8), and inducible nitric oxide synthase mRNAs as well as aquaporin-1, and IL-8 protein were measured in ovine lung tissue. Lung tissue was taken at 96 h (time of sacrifice) from animals with combined smoke inhalation and 40% third degree dermal burn and subsequently treated with AVCO2R or sham (ventilator alone) after onset of ARDS (PaO2:FiO2 ratio of < 200). Myeloperoxidase activity was 1.862 +/- 0.302 U/mg protein in the ventilator group and 0.830 +/- 0.141 in the AVCO2R plus ventilator group. AQP-1 mRNA was 140,482 +/- 31,702 copies/microg total RNA in the ventilator group and 61,854 +/- 22,433 copies/microg total RNA in the AVCO2R plus ventilator group (p = 0.076). mRNA for IL-8 mRNA in the ventilator alone treated animals was 74,000 +/- 3,300 copies/microg total RNA compared to < 1,000 copies/microg total RNA in the ventilator plus AVCO2R group. This result was highly significant (p < 0.001) Inducible nitric oxide synthase mRNA was 7,853 +/- 2,229 copies/microg total RNA for the AVCO2R group and 5,854 +/- 2,070 copies/microg total RNA for the ventilator managed animals. These differences were not statistically significant (p = 0.54). Percutaneous AVCO2R produced a specific decrease in IL-8 in the smoke and burn injured animals. Furthermore, this effect was consistent with cell signaling mechanisms that increase the expression of IL-8 by cyclic stretching and the observed reduction in the number of neutrophils in the lung parenchyma. Therefore, we speculate that the mechanism by which CO2 removal exerts a beneficial effect may be due to both decreases in ventilatory requirements, with an accompanying reduction in alveolar stretching, and reduction of neutrophil numbers in lung tissue.     

Hemodynamic and gas transfer properties of a compliant thoracic artificial lung

A compliant thoracic artificial lung (TAL) has been developed for acute respiratory failure or as a bridge to transplantation. The development goal was to increase TAL compliance, lower TAL impedance, and improve right ventricular function during use. Prototypes were tested in vitro and in vivo in eight pigs between 67 and 79 kg to determine hemodynamic and gas transfer properties. The in vitro compliance was 16.2 +/- 4.4 ml/mm Hg at pressures < 7.8 mm Hg and 4.3 +/- 1.1 ml/mm Hg above 7.8 mm Hg. In vivo, this compliance significantly reduced blood flow pulsatility from 1.7 at the inlet to 0.36 at the outlet. Device resistance was 1.9 and 1.8 mm Hg/(L/min) at a flow rate of 4 L/min in vitro and in vivo, respectively. Approximately 75% of the resistance was at the inlet and outlet. In vivo TAL O2 and CO2 transfer rates were 188 and 186 ml/min, respectively, at 4 L/min of blood and gas flow, and average outlet O2 saturations exceeded 98% for average flow rates up to and including the maximum tested, 5.3 L/min. The new design has a markedly improved compliance and excellent gas transfer but also possesses inlet and outlet resistances that must be reduced in future designs.     

Percutaneous venovenous CO2 removal with regional anticoagulation in an ovine model

Extracorporeal CO2 removal may reduce minute ventilation requirements and allow for better tolerance of low tidal volume ventilating strategies in patients with severe respiratory insufficiency. Conventional extracorporeal gas exchange is labor-intensive, expensive, and usually requires systemic anticoagulation. In this study, a simplified venovenous circuit was developed by using regional citrate anticoagulation to avoid potential complications associated with systemic heparin. Five healthy adult sheep underwent percutaneous placement of a double-lumen 18F catheter into the internal jugular vein. The extracorporeal circuit consisted of a hollow fiber oxygenator and a variable speed roller pump. Regional anticoagulation consisted of a continuous citrate infusion to the inflow limb of the circuit. Systemic calcium levels were maintained by calcium chloride infusion through a central line. CO2 transfer was measured at varying levels of blood and gas flow. CO2 transfer ranged from 31 ml/min (500 ml/min blood flow; 2 l/min gas flow) to 150 ml/min (1000 ml/min blood flow; 15 l/min gas flow) and was directly proportional to blood flow and gas flow (p < 0.05). Normocapnia was maintained despite a 75% reduction in minute ventilation. At 24 hours, there was no significant clot formation in the circuit.     

Preclinical evaluation of a hollow fiber silicone membrane oxygenator for extracorporeal membrane oxygenator application

A silicone membrane hollow fiber oxygenator applicable for use as an extracorporeal membrane oxygenator (ECMO) has been developed in our laboratory. This silicone hollow fiber displays astonishing mechanical stability, is barely compressible or stretchable, and assembles easily while maintaining good gas permeability. The priming volume is 140 cc with a surface area of 0.8 m2. This study evaluated the gas transfer performances and biocompatibility of the oxygenator under ECMO and CPB conditions. In vitro studies that were performed at a blood flow rate of 2 L/min, and revealed O2 and CO2 gas transfer rates of 82.35 +/- 0.56 ml/m2/L/min and 38.72 +/- 2.88 ml/m2/L/min, respectively. The commercially available Kolobow (Avecor 1500) oxygenator was used as the control, and had O2 and CO2 gas transfer rates of 53.8 +/- 0.5 ml/m2/L/min and 24.7 +/- 2.0 ml/m2/L/min. To evaluate blood trauma, Normalized Index of Hemolysis (NIH) was measured according to American Society of Testing and Materials (ASTM) standards. The NIH findings were 0.0112 g/100L at a blood flow of 1 L/min, and 0.0152 g/100L at 5 L/min. Three ex vivo experiments, using a blood flow rate of 1 L/min, were performed with venoarterial bypass, and O2 transfer rate and CO2 transfer rate of the oxygenators were well maintained. This indicates that this preclinical silicone membrane hollow fiber oxygenator has superior efficiency, less blood trauma, and is smaller when compared with the only clinically available Kolobow oxygenator.     

EC CO2R: oxygenator or hemodialyzer? An in vitro study.

In respiratory support of patients with acute respiratory distress syndrome (ARDS), the extracorporeal CO2 removal (EC CO2R) technique should be the earliest and easiest procedure so as to have the lowest blood flow rate. Extracorporeal circulation (ECC) can be achieved using an oxygenator for CO2 removal under the dry form (dissolved CO2) or a hemodialyser for CO2 removal under the wet form (bicarbonates). This study investigated different methods allowing an increase in CO2 transfer, using liquid flow rates up to 0.330 l/min. The experimental set-up employed heated (38 degrees C) aqueous polyelectrolytic solutions mimicking the venous blood (pH 7.20, PCO2 53 mmHg). Four in vitro methods were tested: Series I: a DIDECO D702 oxygenator without blood (= liquid) acidification, Series II: D702 oxygenator with inlet HCl acidification, Series III: a HOSPAL H10-10 hemodialyzer without dialysate alkalinisation, Series IV: H10-10 hemodialyzer with NaOH dialysate alkalinisation. Maximum gas flow in the oxygenator and dialysate rate in hemodialyzer were 5 and 0.55 l/min respectively. For the four series the CO2 transfer (TCO2) (mean +/- S.E. ml/min) and pH out were: [table: see text] The difference between the four series was statistically significant (t-test). Acidification using the oxygenator increased CO2 transfer by 80%, but CO2 elimination was better with hemodialysis.     

Evaluation of local gas exchange in a pulsating respiratory support catheter

An intravenous respiratory support catheter, the next generation of artificial lungs, is being developed in our laboratory to potentially support acute respiratory failure or patients with chronic obstructive pulmonary disease with acute exacerbations. A rapidly pulsating 25 ml balloon inside a bundle of hollow fiber membranes facilitates supplemental oxygenation and CO2 removal. In this study, we hypothesized that non-uniform gas exchange in different regions of this fiber bundle was present because of asymmetric balloon collapse and the interaction of longitudinal flow. Four quarter regions and two rings around the central balloon were selectively perfused to evaluate local gas exchange in a 3.18 cm test section using helium as the sweep gas. Quarter region CO2 exchange rates at 400 beats per minute were 156.8 +/- 0.8, 162.5 +/- 1.8, 157.2 +/- 0.2, and 196.6 +/- 0.8 ml/min/m2 (top, front, bottom, and back, respectively). The back section, adjacent to convex balloon collapse, had 17-20% higher exchange than the other sections caused by higher relative velocities past its stationary fibers. Inner and outer ring maximum pulsation gas exchange rates were 174.4 +/- 1.8 and 174.6 +/- 0.9 ml/min/m2, respectively, showing that fluid flow was equally distributed throughout the fiber bundle.     

Development of an artificial placenta IV: 24 hour venovenous extracorporeal life support in premature lambs

An extracorporeal artificial placenta would change the paradigm of treating extremely premature infants. We hypothesized that a venovenous extracorporeal life support (VV-ECLS) artificial placenta would maintain fetal circulation, hemodynamic stability, and adequate gas exchange for 24 hours. A near-term neonatal lamb model (130 days; term = 145 days) was used (n = 9). The right jugular vein was cannulated for VV-ECLS outflow, and an umbilical vein was used for inflow. The circuit included a peristaltic roller pump and a 0.5 m(2) hollow fiber oxygenator. Lambs were maintained on VV-ECLS in an "amniotic bath" for up to 24 hours. Five of nine fetuses survived for 24 hours. In the survivors, average mean arterial pressure was 69 ± 10 mm Hg for the first 4 hours and 36 ± 8 mm Hg for the remaining 20 hours. The mean fetal heart rate was 202 ± 30. Mean VV-ECLS flow was 94 ± 20 ml/kg/min. Using a gas mixture of 50% O(2)/3% CO(2) and sweep flow of 1-2 L/min, the mean pH was 7.27 ± 0.09, with Po(2) of 35 ± 12 mm Hg and Pco(2) of 48 ± 12 mm Hg. Necropsy revealed a patent ductus arteriosus in all cases, and there was no gross or microscopic intracranial hemorrhage. Complications in failed attempts included technically difficult cannulation and multisystem organ failure. Future studies will enhance stability and address the factors necessary for long-term support.     

Effects of systemic hemodynamics on flow within vascular accesses used for hemodialysis

Absolute value of access flow (QA) and change in flow (deltaQA) over time are major determinants of access patency. However, QA may change in response to variation in systemic hemodynamics among dialysis sessions. We examined the effect of mean arterial pressure (MAP), cardiac output (CO), and segmental resistances (R) on QA. Access flow and CO (L/min) were determined by Transonic ultrasound dilution. Static intra-access pressures (mm Hg) at the arterial segment (AS) and venous segment (VS) were determined with the access unoccluded. During access occlusion (O), the AS pressure was equated to arterial pressure (MAPo), whereas the VS pressure reflected venous pressure (VP). Total and segmental vascular resistances (mm Hg-min/L) were calculated as deltaP/Q. We studied 58 arteriovenous (AV) grafts and 35 autologous AV fistulae (AVF) with measurements on two or more occasions in 43 grafts and 25 AVF. MAPC differed from MAPo by >20 mm Hg in 22% of patients. AS (58 +/- 2 vs. 31 +/- 2) and VS (40 +/- 1 vs. 25 +/- 2) were greater in grafts than in AVF, whereas VP was equal. Access flow (0.91 +/- 0.03 vs. 0.91 +/- 0.05 L/min), cardiac output (5.1 +/- 0.1 vs. 5.5 +/- 0.2 L/min), and total access resistance (115 +/- 5 vs. 11 +/- 6) were equal in grafts and AVF, but non-access systemic R was lower in patients with AVF that those with grafts (26 +/- 1 vs. 30 +/- 1). AS and VS resistances were greater in AVF than grafts (87 +/- 6 vs. 54 +/- 3 and 37 +/- 3 vs. 16 +/- 3). Multivariate analysis indicated that CO and ipsilateral MAPo affected flow in both access types. In grafts, all three access resistance elements, AS, VS, and total independently influenced flow, whereas in AVF, the VS did not. Unexpectedly, the ratio of systemic to access resistance also influenced access flow. The pressure in the venous system draining the access affected access flow in AVF but not grafts. We conclude that the hemodynamics of grafts and AVF differ. Cardiac output, MAP, and the arterial segment resistance influence QA in both access types and need to be considered when evaluating QA as part of the trend analysis for detecting access dysfunction.     

Insensible water loss from the medtronic minimax oxygenator: an In Vitro study

The purposes of this study were to quantify the insensible water loss that occurs across the Medtronic Minimax oxygenator and to estimate the resultant rise in fluid sodium concentration.A Carmeda-coated extracorporeal membrane oxygenation circuit connected to a Medtronic Minimax Plus oxygenator was primed with normal saline and attached to a closed reservoir. The gas sweep was randomly assigned to one of three rates: 2, 5, or 10 LPM (liters per minute). Each sweep rate was run in triplicate. The sodium concentration of the circuit was assessed after 12 and 24 hours of each trial. At the end of each 24-hour run, the evaporative loss was calculated.The average insensible water losses were 6.9+/-0.4 ml/h, 16.6+/-1.5 ml/h, and 34.4+/-0.3 ml/h at gas sweep rates of 2, 5, and 10 LPM, respectively (p<0.0001). Daily evaporative water losses for the membrane can be estimated to be 82.7+/-2.2 ml for each 1 LPM of sweep gas flow for a normal saline pump flow of 300 ml/min. In a closed circuit, a faster sweep gas rate is associated with a more rapid rise in sodium concentration (p<0.0001).     

Early experience with a polymethyl pentene oxygenator for adult extracorporeal life support

Silicone oxygenators are the standard devices used for Extracorporeal Life Support (ECLS), but they have some limitations. Microporous polypropylene hollow fiber oxygenators overcome many of these problems but, unfortunately, develop plasma leak. Polymethyl-pentene (PMP) is a novel oxygenator material. We report our initial experience with the Medos Hilite 7000LT, a PMP hollow fiber oxygenator, in six adult respiratory ECLS patients with these characteristics: age, mean 32.2 (+/-13) years; weight, mean 81.2 (+/-17) kg; PaO2/FIO2, mean 62.8 [+/-33] mm Hg; Murray Score, mean 3.4 [+/-0.3]; and sepsis related organ failure assessment score, mean 9.6 [+/-2.3]. One patient was cannulated within 10 hours of multiple trauma and 1 hour after thoracolaparotomy; another patient was cannulated 12 hours after a thoracotomy. All six patients survived. Heparin was infused (7.8-32.5 u/kg/hr) to maintain activated clotting time at 162 to 238 seconds; international normalized ratio was 0.9 to 3.4. Two of the six patients required transfusions of fresh frozen plasma, receiving one and five units, respectively. Fibrinogen was 1.4 to 6 g/dl; no cryoprecipitate was needed. Platelet counts were between 65 and 306, and very little platelet transfusion (mean 2.33; +/-3.03 units per patient) was required to maintain these levels. Two patients did not require any platelet transfusion. Maximum blood flow was 5.3 L/min, sweep was 3 to 10 L/min, and resistance was 11 to 43 Paul Wood Units. There were no oxygenator failures. Mean duration of ECLS was 151.7 hours (+/-75.6). Our initial experience with PMP oxygenators in adults was satisfactory, and platelet consumption and resistance to blood flow seem to be greatly reduced with PMP.     

Ex vivo evaluation of a new extracorporeal lung assist device: NovaLung membrane oxygenator

When lung function is compromised,alternative devices need to be deployed in order to maintain blood oxygenation. A new device, NovaLung, has been designed for acute lung failure. We went about evaluating its gas exchange capability. Three calves (79.5 +/- 7.8 kg) were connected to the NovaLung System with a priming volume of 240 mL, gas exchange surface area of 1.3 m2 and exhibiting a biologically coated surface. A standard battery of blood samples were taken before implantation and over a six hour period. Hematocrit remained stable ranging from 27 +/- 4% (baseline) to 29 +/- 5% (6 hrs). Platelets were preserved ranging from 882 +/- 27.4 U/L (baseline) to 734 +/- 147 (6 hrs). LDH remained stable at 719 +/- 85 U/L (baseline) vs 686 +/- 190 U/L (6 hrs) and the pressure drop was maintained below 20 mmHg. Minimal hemolysis was observed. Oxygen transfer peaked at two hours acute extracorporeal lung support (ECLS)with a mean value of 130 +/- 50 ml/min. In conclusion, the device is easy to use,provides adequate O2 and CO2 transfer for partial lung support in an acute setting. Shows minimal signs of hemolysis and platelets levels are maintained throughout the six hour ECLS period.     

In vitro evaluation of a newly developed implantable artificial lung

A prototype of an implantable artificial lung without a pump (Prototype II) has been tested. A commercially available membrane oxygenator, MENOX AL6000alpha (Dainippon Ink and Chemicals, Inc., Tokyo, Japan), was used as a basic model. The packing density of the hollow fiber was decreased in order to achieve low resistance through the blood pathway. The configuration of its housing was also re-designed using computational fluid dynamics (CFD). The first prototype, known as Prototype I, was already tested in a 15 kg pig, which showed excellent gas exchange with normal hemodynamics. A second prototype, Prototype II, has a larger membrane surface area than Prototype I. The device was evaluated for resistance through the blood path and gas transfer rate in an in vitro setting by the single pass method using fresh bovine blood. The resistance through the blood path of Prototype II was 2.7+- 0.7 mmHg/(L/min) at Q = 5L/min. The oxygen (O2) transfer rate was 178 +- 5.3 ml/min at Q = 5 L/min, V/Q = 3, and the carbon dioxide (CO2) transfer rate was 149 +- 28 ml/min at Q = 5 L/min, V/Q = 2 (Q: blood flow rate, V: sweep oxygen flow rate through the artificial lung). For the purpose of implantation, this prototype showed sufficiently low resistance in the pulmonary circulation with reasonable gas exchange.     

Apneic oxygenation combined with extracorporeal arteriovenous carbon dioxide removal provides sufficient gas exchange in experimental lung injury

We hypothesized that apneic oxygenation, using an open lung approach, combined with extracorporeal CO2 removal, would provide adequate gas exchange in acute lung injury. We tested this hypothesis in nine anesthetized and mechanically ventilated pigs (85-95 kg), in which surfactant was depleted from the lungs by repeated lung lavage. After a lung recruitment maneuver, the tracheal tube was connected to 20 cm H2O continuous pressure (100% O2) for oxygenation of the blood. A pumpless membrane ventilator (interventional lung assist by Novalung) was connected in an arteriovenous shunt for CO2 removal. PaO2 and PaCO2 were recorded for 3.5 hours. PaO2 was 464 (403, 502) mm Hg (median and interquartile range) throughout the experiment. The O2 uptake through the lungs was 185 (164, 212) ml/min. PaCO2 increased asymptotic towards 60 mm Hg. The CO2 removal through the membrane ventilator was 180 (150, 180) ml/min. Thus, the method provided adequate gas exchange in this experimental model, suggesting that it might have potential as an alternative treatment modality in acute lung injury.     

Evaluation of a pumping assist lung that uses a rotating fiber bundle

A paracorporeal respiratory assist lung (PRAL) is being developed for supplemental gas exchange to allow the native lungs of acute lung failure patients to heal. The device consists of a rotating annular microporous hollow fiber membrane bundle. The rotation augments the gas exchange efficiency of the device at constant flow-rate thereby uncoupling gas exchange and flow rate. The rotating fibers also enable the PRAL to pump the blood without the need for an additional pump or arterial cannulation. Blood flow rates will be between 500 and 750 ml/min with CO(2) removal rates of 100-130 ml/min. A prototype was manufactured with an overall surface area of 0.25 m. When rotated at 1500 rpm, CO(2) removal increased by 133% and O(2) transfer increased by 157% during an in vitro bovine blood study. The pumping of the rotating fiber bundle was assessed in a glycerol/water solution. At 1500 rpm, the PRAL generated 750 ml/min against 52 mm Hg pressure. Hemolysis of the device was assessed using in vitro bovine blood from a slaughterhouse. Plasma free hemoglobin levels were similar regardless of whether the rotating fibers were present in the PRAL, indicating that a rotating fiber bundle can be used to increase gas exchange without causing blood trauma.     

Online conductivity monitoring: validation and usefulness in a clinical trial of reduced dialysate conductivity

Relatively low dialysate conductivity (Cndi) may improve outcomes by reducing the overall sodium burden in dialysis patients. Excess sodium removal, however, could lead to hemodynamic instability. We performed a randomized controlled trial of reduction of Cndi. For the study, 28 patients were randomized to maintenance of Cndi at 13.6 mS/cm (equivalent to 135 mmol/L of Na+) or serial reduction of Cndi in steps of 0.2 mS/cm, guided by symptoms and blood pressure. Sodium removal estimated from pre- and postplasma concentrations correlated well with removal measured by conductivity monitoring as ionic mass balance (R2 0.66, p < 0.0001). Of the 16 patients randomized to reduction of Cndi, 6 achieved Cndi 13.4 mS/cm, 6 achieved 13.2 mS/cm, and 4 achieved 13.0 mS/cm. No episodes of disequilibrium occurred. Interdialytic weight gain was reduced from 2.34 +/- 0.10 kg to 1.57 +/- 0.11 kg (p < 0.0001). Predialysis systolic blood pressure fell from 144 +/- 3 mm Hg to 137 +/- 4 mm Hg (p < 0.05). The reduction in convective sodium removal was balanced by an increase in diffusive sodium removal (95 +/- 9 mmol cf. 175 +/- 14 mmol, p < 0.0001). Reduction in Cndi monitored by IMB is safe and practical and leads to improved interdialytic weight gains and blood pressure control, while avoiding excessive sodium removal.