**1. Introduction**

Lung transplantation has become an increasingly important modality for the treatment of severe lung disease. From its inception in 1985, the procedure has been refined so that it now represents the standard of care for end stage respiratory failure. As the efficacy of this treatment has been proven, we have seen the frequency of lung transplantation undergo an exponential rise. In 1993, for example, the International Society for Heart and Lung Transplantation (ISHLT) reports that a total of 1055 lung transplant procedures was performed. A decade later in 2003, that number had nearly doubled to 1934 and in 2013, the number of lung transplant procedures per year rose to 3892 [1]. In the same vein, a study in 2018 analyzing national trends of extracorporeal membrane oxygenation use in the National Inpatient Sample identified an over 360% increase in admissions for ECMO support from 2008 to 2014, among which mortality decreased among total admissions from over 60% down to 43% despite a trend toward an increased risk profile [2]. The widespread adoption of this treatment option, however, has brought into sharp relief the current organ donor

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shortage; there is currently a yearly potential lung transplant recipient mortality of up to 16% while awaiting organs to become available [3].

In tandem with the explosion in lung transplant procedures, a number of support modalities have seen an expanded role. Perhaps one of the most versatile tools in the armamentarium of the pulmonary transplant surgeon is extracorporeal membrane oxygenation (ECMO). This powerful tool is being increasingly implemented in all stages of lung transplantation—from supporting the failing native organ as a bridging tool to transplantation, to stabilizing the patient intraoperatively during the transplant procedure, to rescuing the patient with severe primary graft dysfunction immediately post-transplant. A number of advanced techniques for the application of ECMO in order to optimize the pulmonary transplant procedure are gaining traction—and with ECMO's expanded role in lung transplantation, so to have come a new set of technical and ethical challenges that must also be overcome.

The goal of this chapter is to discuss some of the recent advances in the application of ECMO in the setting of lung transplantation. We discuss the application of ECMO in the preoperative, perioperative, and postoperative period, and focus in particular on advances such as the use of awake ECMO and various cannulation strategies. We also briefly discuss some of the ethical issues surrounding ECMO for lung transplantation, including cost, quality of life, and the application of ECMO to marginal recipients.

### **2. VV- and VA-ECMO in lung transplantation**

In the setting of lung transplantation, ECMO may be utilized in either a venovenous (VV) or a veno-arterial (VA) configuration. The VV-ECMO modality is used strictly for respiratory support; this review will explore the current frontiers of usage in in the setting of either pre-operative bridge to transplant, as well as for bridging to graft recovery the subset of patients who develop severe post-transplant primary graft dysfunction (PGD). Alternatively, VA-ECMO may be utilized in the subset of patients with either pulmonary arterial hypertension requiring both cardiac and pulmonary support in the preoperative period, recently transplanted patients exhibiting hemodynamic instability, or in the intra-operative period for cardiopulmonary support [4].

Cannulation strategies for VA- and VV-ECMO are listed here. VV-ECMO is typically achieved via outflow and inflow cannulas in the femoral and internal jugular veins, with the tip of the drainage cannula placed to the level of the inferior vena cavaright atria junction and the tip of the return cannula at the right atrium. Alternatively, VV-ECMO may be achieved via a femoral-femoral cannulation strategy, with the tip of the drainage cannula in inferior vena cava and the tip of the outflow cannula is in the right atrium. Alternatively, a one-site cannulation strategy makes use of a dual lumen Avalon cannula (Avalon Elite, Maquet, Rastatt, Germany) percutaneously placed in the either internal jugular vein or in the subclavian vein [5].

VA-ECMO cannulation may be achieved using either a peripheral or central cannulation strategy. In a peripheral cannulation strategy, the femoral vein and artery are cannulated in a percutaneous fashion, with the tip of the arterial cannula placed in the common iliac artery. Alternatively, the arterial inflow cannula can be placed into the right subclavian artery. Because these peripheral strategies may in some cases only transmit arterial blood flow as far as the aortic arch (where blood oxygenated from the patient's native lungs and transmitted by the patient's heart) this may have the effect of poorly perfusing the heart and lungs (known as the Harlequin Syndrome). In this case, central cannulation of VA-ECMO is an option,

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bridging strategy [5, 8–17].

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placed in the ascending aorta through a median sternotomy incision [4].

with the venous cannula placed directly in the right atrium and the arterial cannula

A number of hybrid options also exist for selected scenarios; these include Veno-veno-arterial ECMO (VVA-ECMO) where an additional venous cannula is inserted to offload the left ventricle, typically into the right internal jugular vein. This may also describe the conversion of veno-venous (VV) ECMO to additionally supply cardiac support by the insertion of an arterial cannula. Other triple-catheter strategies include the insertion of a distal perfusion cannula to the cannulated lower extremity in peripheral VA-ECMO in order to decrease limb ischemia. This armamentarium provides the surgeon with a number of different techniques for providing either isolated pulmonary or cardiopulmonary support in the transplant

The first successful use of ECMO in the preoperative period prior to lung transplant may be traced back to 1975, when ECMO was described as being initiated to correct a profound hypercapnia in a 19-year-old boy prior to transplantation. While the patient was successfully removed from the oxygenator and weaned from mechanical ventilation, he ultimately died on the eighteenth postoperative day due to a bronchial dehiscence [6]. For the next 20 years, this modality was occasionally described in the literature in case studies; however, it was associated with dismal

In the past decade, however, there have been a number of advances in both the technology surrounding ECMO, and the management of the patient on ECMO, such that institutions are increasingly turning back to preoperative ECMO as an acceptable or even preferred modality for bridging patients with end stage respiratory disease to lung transplantation. This shift in management was preempted by a number of forces. First, the institution of the lung allocation score in 2005 allowed for more efficacious allocation of donor organs to those patients most emergently in need of a transplants rather than just the length of time on the waiting list. This meant that patients receiving continuous mechanical ventilation were listed with scores. ECMO was found to serve as a useful tool to stabilize ventilator-dependent patients approaching transplantation. Additionally, multicenter trials in the non-transplant population began to demonstrate the effectiveness of ECMO in ameliorating severe adult respiratory distress syndrome [7]. With the significant improvement in ECMO technologies, an increasing number retrospective and prospective studies have been conducted that show promising outcomes related to the use of ECMO as a

Some of those studies are reported here. Much of the initial research consisted of single-center retrospective studies. One of the first studies to demonstrate the efficacy of this therapy reported 17 bridged patients with a 78% 1-year survival after transplant, among whom allograft function did not differ between patients who did and did not receive ECMO bridging support [8]. A 2012 institutional study of 11 patients demonstrated shorter durations of mechanical support, and shorter post-transplant ICU and hospital stay in patients bridged with ECMO; a 1-year survival rate of over 85% after ECMO compared to 50% in patients with traditional mechanical ventilation was highlighted [15]. In 2013, a retrospective review of the medical records of 39 French patients bridged to lung transplantation on ECMO highlighted successful bridging to transplant in over 80% of the population,

*DOI: http://dx.doi.org/10.5772/intechopen.83833*

**3. ECMO in the preoperative period**

**3.1 ECMO as a bridge to lung transplantation**

outcomes and as a result did not gain widespread use.

patient.

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with the venous cannula placed directly in the right atrium and the arterial cannula placed in the ascending aorta through a median sternotomy incision [4].

A number of hybrid options also exist for selected scenarios; these include Veno-veno-arterial ECMO (VVA-ECMO) where an additional venous cannula is inserted to offload the left ventricle, typically into the right internal jugular vein. This may also describe the conversion of veno-venous (VV) ECMO to additionally supply cardiac support by the insertion of an arterial cannula. Other triple-catheter strategies include the insertion of a distal perfusion cannula to the cannulated lower extremity in peripheral VA-ECMO in order to decrease limb ischemia. This armamentarium provides the surgeon with a number of different techniques for providing either isolated pulmonary or cardiopulmonary support in the transplant patient.
