Laura W. Lund

Ex vivo testing of the intravenous membrane oxygenator.

Intravenous oxygenation represents a potential respiratory support modality for patients with acute respiratory failure or with acute exacerbations of chronic respiratory conditions. Our group has been developing an intravenous oxygenator, the IMO, which uses a constrained fiber bundle and a rapidly pulsating balloon within the fiber bundle. Balloon pulsation drives blood flow past the fibers at greater relative velocities than would otherwise exist within the host vessel, and gas exchange rates are enhanced. The purpose of this study was twofold: (1) to characterize the gas exchange performance of the current IMO in an extracorporeal mock vena cava vessel under conditions of known fixed vessel geometry and controlled blood flow rates; and (2) to compare the IMO gas exchange performance to that reported for the clinically tested IVOX device within a comparable ex vivo set-up. The ex vivo flow loop consisted of a 1 inch ID tube as a mock vena cava that was perfused directly from an anesthetized calf at blood flow rates ranging from 1 to 4 1/2 L/min. O2 and CO2 exchange rates were measured for balloon pulsation rates, which ranged from 0 to 180 bpm. Balloon pulsation significantly increased gas exchange, by 200-300% at the lowest blood flow rate and 50-100% at the highest blood flow rate. Balloon pulsation eliminated much if not all of the dependence of the gas exchange rate on blood flow rate as seen in passive oxygenators. This suggests that in clinical application the IMO may exhibit less gas transfer variability due to differences in cardiac output Over the entire flow rate range studied, the CO2 and O2 gas exchange rates of the IMO at maximal balloon pulsation varied from approximately 250 to 350 ml/min/m2. At maximum balloon pulsation the IMO exchanged CO2 and O2 at rates from 50-500% greater, depending upon the blood flow rate, than the exchange rates reported for the IVOX device in ex vivo tests.

Development of a low flow resistance intravenous oxygenator.

A potentially attractive support device for patients with acute respiratory failure is an intravenous membrane oxygenator. One problem, however, is that the membrane surface area required for sufficient gas exchange can unduly increase vena cavai pressure drop and impede venous return. The purpose of this study was to design and develop an intravenous oxygenator that would offer minimal venous flow resistance in situ. The device uses a constrained fiber bundle of smaller cross sectional size than the vena cava so as to effect an intentional shunt flow of venous blood around the fiber bundle and reduce the venous pressure drop caused by the device. A pulsating balloon within the fiber bundle redirects part of this shunt flow into reciprocating flow in and out of the fiber bundle. This offers dual advantages: 1) Blood flow through the fiber bundle is mainly perpendicular to the fibers; and 2) the requisite energy for driving flow comes largely

Recent progress in engineering the Pittsburgh intravenous membrane oxygenator.

The University of Pittsburgh intravenous membrane oxygenator (IMO) is undergoing additional engineering development and characterization. The focus of these efforts is an IMO device that can supply as much as one-half basal O2 consumption and CO2 elimination rates while residing within the inferior and superior vena cavae after peripheral venous insertion. The current IMO design consists of a bundle of hollow fiber membranes potted to manifolds at each end, with an intra-aortic type balloon integrally situated within the fiber bundle. Pulsation of the balloon using helium gas and a balloon pump console promotes fluid and fiber motion and enhances gas exchange. During the past year, more than 15 IMO prototypes have been fabricated and extensively bench tested to characterize O2 gas exchange capacity, balloon inflation/deflation over relevant frequency ranges, and the pneumatics of the sweep gas pathway through the device. The testing has led to several engineering changes, including redesign of the helium and sweep gas pathways within the IMO device. As a result, the maximum rate of balloon pulsation has increased substantially above the previous 70 bpm to 160 bpm, and the vacuum pressure required for sufficient sweep gas flow has been reduced. The recent IMO prototypes have demonstrated an O2 exchange capacity of as much as 90 ml/min/m2 in water, which appears within 70% of our design goal when extrapolated to scaled up devices in blood.

Respiratory dialysis. A new concept in pulmonary support.

Use of a new intravenous oxygenator made of hollow fiber membranes arranged around a centrally positioned balloon is reported. In vitro studies using fluorescent image tracking velocimetry and gas exchange analysis demonstrated enhanced convective mixing with balloon pulsations and augmented gas flux (100% increase in pO2) compared with the device in its static configuration. In vivo observations confirmed a greater than 50% increase in O2 flux with balloon activation. Those parameters that produce radial flow and convective mixing in vitro enhance gas flux in vivo, thus confirming the efforts to exceed the fluid limit translate into improved gas exchange.

Removing extra CO2 in COPD patients

For patients experiencing acute respiratory failure due to a severe exacerbation of chronic obstructive pulmonary disease (COPD), noninvasive positive pressure ventilation has been shown to significantly reduce mortality and hospital length of stay compared to respiratory support with invasive mechanical ventilation. Despite continued improvements in the administration of noninvasive ventilation (NIV), refractory hypercapnia and hypercapnic acidosis continue to prevent its successful use in many patients. Recent advances in extracorporeal gas exchange technology have led to the development of systems designed to be safer and simpler by focusing on the clinical benefits of partial extracorporeal carbon dioxide removal (ECCO2R), as opposed to full cardiopulmonary support. While the use of ECCO2R has been studied in the treatment of acute respiratory distress syndrome (ARDS), its use for acute hypercapnic respiratory during COPD exacerbations has not been evaluated until recently. This review will focus on literature published over the last year on the use of ECCO2R for removing extra CO2 in patients experiencing an acute exacerbation of COPD.

Avoidance of intubation during acute exacerbation of chronic obstructive pulmonary disease for a lung transplant candidate using extracorporeal carbon dioxide removal with the Hemolung

For patients with severe chronic obstructive pulmonary disease (COPD) experiencing an acute exacerbation, the necessity for invasive mechanical ventilation (IMV) not only is associated with high mortality but also can be particularly disadvantageous to a patient also awaiting lung transplantation. In this case report, we describe our use of a novel extracorporeal carbon dioxide removal (ECCO2R) device for partial respiratory support in such a patient whowas failing support with noninvasive ventilation (NIV). The Hemolung Respiratory Assist System (ALung Technologies, Pittsburgh, Pa) provided ECCO2R at a blood flow of approximately 500 mL/min through a single 15.5F venovenous cannula inserted percutaneously through the left femoral vein. This casewas conducted as part of the first human clinical feasibility study of theHemolung device andwas the first time the device was used at our facility.

Gas permeability of hollow fiber membranes in a gas-liquid system

Abstract Designing an effective intravenous membrane oxygenator requires selecting hollow fiber membranes (HFMs) which present minimal resistance to gas exchange over extended periods of time. To evaluate HFMs, we developed a simple apparatus and methodology for measuring HFM permeability in a gas-liquid environment which has the capability of studying a variety of fiber types in any liquid of interest, such as blood. Using this system, we measured the O2 and CO2 exchange permeabilities of Mitsubishi MHF 200L composite HFMs and KPF 280E microporous HFMs in water at 37°C. The membrane permeability measured for the MHF 200L composite fiber was 7.9 × 10−6 ml/s/cm2/cmHg for O2 and 8.4 × 10−5 ml/s/cm2/cmHg for CO2, and for the KPF 280E microporous fiber, 1.4 × 10−5 ml/s/cm2/cmHg for O2 and 3.2 × 10−4 ml/s/cm2/cmHg for CO2. The permeabilities of the microporous HFMs were over two orders of magnitude less than what would be measured in a gas-gas system due to liquid infiltration of the pores, emphasizing the importance of measuring permeability in a gas-liquid system for relevant applications such as intravenous oxygenation. Furthermore, both O2 and CO2 permeabilities of the microporous fiber were consistent with a liquid infiltration depth of only 1%. The O2 permeability of the MHF fiber was found to be less than the overall exchange permeability ultimately required of our intravenous oxygenation device (K ≈ 1 × 10−5 ml(STP)/s/cm2/cmHg). Consequently, the MHF 200L composite fiber appears unsuitable for intravenous oxygenation devices such as ours.

Respiratory dialysis for avoidance of intubation in acute exacerbation of COPD.

Noninvasive ventilatory support has become the standard of care for patients with chronic obstructive pulmonary disease (COPD) experiencing exacerbations leading to acute hypercapnic respiratory failure. Despite advances in the use of noninvasive ventilation and the associated improvement in survival, as many as 26% of these patients fail noninvasive support and have a higher subsequent risk of mortality than patients treated initially with invasive mechanical ventilation. We report the use of a novel device to avoid invasive mechanical ventilation in two patients who were experiencing acute hypercapnic respiratory failure because of an exacerbation of COPD and were deteriorating, despite support with noninvasive ventilation. This device provided partial extracorporeal carbon dioxide removal at dialysis-like settings through a single 15.5 Fr venovenous cannula inserted percutaneously through the right femoral vein. The primary results were rapid reduction in arterial carbon dioxide and correction of pH. Neither patient required intubation, despite imminent failure of noninvasive ventilation before initiation of extracorporeal support. Both patients were weaned from noninvasive and extracorporeal support within 3 days. We concluded that low-flow extracorporeal carbon dioxide removal, or respiratory dialysis, is a viable option for avoiding intubation and invasive mechanical ventilation in patients with COPD experiencing an exacerbation who are failing noninvasive ventilatory support.

Acute in vivo studies of the Pittsburgh intravenous membrane oxygenator.

The efficacy of an innovative intravenous membrane oxygenator (IMO) was tested acutely (6-8 hrs) in seven calves. The IMO prototypes consisted of a central polyurethane balloon within a bundle of hollow fibers with a membrane surface area of 0.14 m2. The IMO devices were inserted through the external jugular vein into the inferior vena cava of anesthetized calves (68.9 +/- 2.3 kg). Rhythmic balloon pulsation (60-120 bpm) was controlled with an intra-aortic balloon pump console. Oxygen sweep gas was delivered through the device at 3.0 L/min. Gas concentrations were monitored continuously by mass spectroscopy. The principal results were as follows: 1) oxygen and carbon dioxide exchange ranged from 125 to 150 ml/min/m2 and 150 to 200 ml/min/m2, respectively; 2) there was at least a 30-50% augmentation of gas exchange with balloon pulsation; 3) maximum exchange occurred with 60-90 bpm balloon pulsations; and 4) hemodynamic parameters remained unchanged. There were no device related complications, and the feasibility of insertion of the device by a cervical cut-down was established. These acute in vivo experiments show that the Pittsburgh IMO device can exchange oxygen and carbon dioxide gases in vivo at levels consistent with this current prototype design, and that intravenous balloon pulsation significantly enhances gas exchange without causing any end-organ damage.

Is condensation the cause of plasma leakage in microporous hollow fiber membrane oxygenators

Extracorporeal membrane oxygenators are comprised of large bundles of microporous hollow fiber membranes (HFMs) across which oxygen and carbon dioxide are transferred to and from blood. Long term use of extracorporeal oxygenators is limited by plasma leakage through the pores of the HFM walls, requiring replacement of the oxygenator. Condensation of water vapor on the pore walls is thought to be a possible precursor to plasma leakage. To explore this mechanism, a simple theoretical analysis is used to examine the temperature of the gas flow through the HFMs. For conditions representative of two commercially available oxygenators, the analysis predicts that the gas heats up to the temperature of blood flow outside of the fibers after passing through less than 0.5% of the fiber lengths. Once the gas temperature and hence the fiber wall temperature equilibrates with the blood, condensation of water vapor is no longer possible. In vitro testing of microporous HFMs under gas flow rates and temperature conditions similar to those of extracorporeal oxygenators but with the fibers submerged in water is also presented. The fibers showed negligible degradation in carbon dioxide transfer over a four-day period. These results of both the theoretical and experimental analyses indicate that the condensation of water vapor within the pores of the HFMs is unlikely to be the cause of plasma leakage in clinically used extracorporeal oxygenators.