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Taking Your ECMO With You: Continued Progress Toward an Ambulatory Goal

Jenkins, Christina S.; van Berkel, Victor

doi: 10.1097/MAT.0000000000000647
Invited Commentaries

From the Department of Cardiovascular and Thoracic Surgery, University of Louisville School of Medicine, Louisville, Kentucky.

Submitted for consideration July 2017; accepted for publication in revised form July 2017.

The authors have no conflicts of interest to report.

Correspondence: Victor van Berkel, Department of Cardiovascular and Thoracic Surgery, University of Louisville School of Medicine, 201 Abraham Flexner Way, Suite 1200, Louisville, KY 40202. E-mail:

Continued advances in the design of ventricular assist devices have transformed the treatment and management of adults and children with end-stage heart failure, allowing for outpatient therapy while awaiting heart transplantation or as destination therapy in end-stage heart failure. However, patients diagnosed with acute and chronic end-stage lung disease do not yet have similar ambulatory support options. Critically ill patients with end-stage lung disease are limited to prolonged mechanical ventilation or extracorporeal membrane oxygenation (ECMO) for lung support before transplantation. These options are not ideal for these patients pretransplant, as mobility and the ability to participate in rehabilitation are limited with these methods of lung support. Studies have demonstrated that patients able to ambulate on ECMO have acceptable survival post-lung transplantation1,2; however, ambulatory ECMO, although feasible, requires significant multidisciplinary support and coordination to ensure patient safety and safe transport of the ECMO circuit around the intensive care unit. In addition, regular physical therapy to prevent deconditioning in critically ill patients has been shown to be beneficial3 but is a challenge in these patients.

In 2016, according to the united network for organ sharing (UNOS) database, 2,327 lung transplants were performed in the United States; however, between 2011 and 2014, only approximately 65–70% of individuals listed for transplant had been transplanted at 1 year, leaving many individuals without a meaningful treatment option in the interim period before transplantation. The current wait-list mortality for lung transplant is 10–15 deaths per 100 patient years of waiting.4 In addition, the registry of the International Society for Heart and Lung Transplantation reported in 2016 that increased severity of recipient illness, including those patients requiring preoperative mechanical ventilation at the time of transplantation, was one risk factor contributing to mortality posttransplant at 1 year.4 Presumably, development of an artificial lung support device could promote partial lung recovery or allow for ambulatory support of patients with more severe lung disease and may lessen the mortality risk of severe pretransplant end-stage lung disease.

For these reasons, multiple centers have been working to develop ambulatory mechanical lung support devices, which are in various stages of testing and validation. Initial efforts to develop and test implantable artificial lung support devices were reported as early as the 1970s with research on ECMO, and since that time, device design has been refined in size, shape, and materials to minimize complications and broaden applications.5–10 Each device has its own set of strengths and weaknesses but the similar long-term goal of providing an ambulatory mechanical support option for patients with both acute and chronic end-stage lung disease awaiting transplantation. The ideal ambulatory artificial lung would maximize oxygenation and carbon dioxide removal, with the lowest possible risk of morbidity (including a low risk of hemolysis and thrombogenicity), and have long-term durability. In addition, the device would need to be of a size allowing patients to easily ambulate and transport the device, freeing them from mandatory intensive care unit or hospital stays. Questions remain as to the ideal design to maximize oxygenation and ventilation, and debate continues on the optimal technique for implantation and the most desirable and feasible pump for the artificial lung.

In this edition of the ASAIO Journal, three papers highlight some of the recent progress and challenges regarding development of ambulatory artificial lung support and preparations for in vivo trials of durability in treatment of end-stage lung disease. Each of these devices, the M-Lung, Pittsburgh ambulatory assist lung (PAAL), and compliant thoracic artificial lung (cTAL), provides a different design to achieve efficient oxygenation and ventilation while maintaining a size conducive to an ambulatory device.

Authors from the University of Michigan report their experience with the development of the M-Lung, which is a hollow fiber membrane lung with concentric circular blood flow paths.11 The M-Lung was designed to be used in their end-stage lung disease model, without a pump. Researchers theorize that circular blood flow chambers minimize thrombosis and that a membrane lung with concentric circular blood flow paths connected by gates should have high oxygen transfer efficiency because of secondary mixing. In vitro testing of their design demonstrated an oxygen transfer efficiency of 357 ml/min/m2 and CO2 clearance of 200 ml/min at 2 l/min of flow, with a fiber surface area of 0.28 m2. In comparison to similar devices, the in vitro studies of the M-Lung demonstrated higher oxygen transfer efficiency. The M-Lung also required low priming volumes, limiting complications related to hemodilution. However, these tests did not evaluate the amounts of hemolysis, thrombogenicity, or long-term durability of the M-Lung model in vivo. In addition, they recommend modifications to the size and permeability of the prototype M-lung to limit pressure drops across the device depending on the clinical condition for which the M-lung will be used. While results of the in vitro studies of the M-Lung are promising, additional studies are needed to delineate potential complications related to hemolysis and thrombogenicity and to address feasibility of the M-Lung for partial or complete long-term mechanical support in end-stage lung disease as a bridge to transplantation.

In comparison, the University of Pittsburgh describes in vitro studies of the PAAL, a hollow fiber membrane bundle for gas exchange designed with a centrifugal pump.12 The PAAL provides 180 ml/min oxygenation at 3.5 l/min of flow and oxygen efficiency of 278 ml/min/m2 using 0.68 m2 of surface area. The goal of the PAAL design was to create a device with a small, compact profile. This design would not only allow ambulatory support but would also theoretically decrease adverse events, like hemolysis, by reducing the interaction of the blood with the device material surface. To compensate for the smaller design, oxygen efficiency had to be maximized by increasing the velocity of flow through the fiber bundle. PAAL is compatible with the Avalon Elite double lumen cannula (Maquet, Rastatt, Germany) and is currently using a centrifugal pump. Design modifications of the PAAL will integrate the fiber bundle with a new centrifugal pump into one unit to create a compact, ambulatory lung. In addition, one advantage of the PAAL is that it has low levels of hemolysis in the system. Decreasing the fiber bundle diameter and increasing the fiber bundle length appear to accomplish this goal of low levels of hemolysis.

An advantage of the increase in oxygenation efficiency in both the M-Lung and the PAAL is the reduction in the required surface area for gas exchange, allowing the design of smaller devices. Plans for in vivo testing of PAAL are planned to validate the performance of initial design and test durability of the device in an animal model.7 Previous studies by Zwischenberger with a paracorporeal artificial lung using the Avalon cannula and Centrimag pump, with a different hollow fiber membrane oxygenator, demonstrated a progressive decline in oxygen transfer and carbon dioxide removal more than a 24 day period in sheep.9

In their most recent article, Skoog et al. report outcomes from a 14 day in vivo trial in sheep of the cTAL.13 The cTAL relies on the patient right ventricular function to pump blood through the device using pulmonary artery and left atrial cannulas. Previous studies have demonstrated success in bridging patients to transplant using a pulmonary artery to left atrial conduit, with a paracorporeal device in parallel to the native pulmonary system.8 These current experiments were used to determine whether the current model cTAL could be used for at least 2 weeks without affecting normal physiology or having major complications. Researchers found that resistance remained low in the device over the study period, and in general, the experimental animals tolerated the cTAL during the study period and demonstrated adequate oxygenation and ventilation. However, the in vivo studies did discover several areas for design improvement, including changes in function and resistance based on pump location placement on the animal, hemodilution from the priming volume because of the size of the device, and plasma leakage with longer term use.

The progress in end-stage lung disease management via mechanical support devices and outcomes from in vitro and in vivo studies continues to be encouraging. As data from continued mechanical lung design modifications and results of short-term and long-term in vivo experimentation is collected, continued innovation and critical analysis are likely to further improve outcomes of artificial lung support. The research presented in this edition of ASAIO Journal suggest that we are approaching the development of a sustainable mechanical lung support device to successfully bridge patients to transplant or recovery in acute and chronic end-stage lung disease.

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Copyright © 2017 by the American Society for Artificial Internal Organs