**3. ECMO as a bridge-to-decision or bridge-to-transplant in patients with advance lung disease**

The most significant issue with lung transplantation is often long wait times. This problem seems more prominent in the Eurotransplant area than in the United Network for Organ Sharing area. Based on the OPTN/SRTR 2022 report, lung transplant candidates continued to be bridged-to-transplant; 3.6% on mechanical ventilation and ECMO, 1.8% on mechanical ventilation only, and 3.1% ECMO only and ECMO-BTT patients who survive to LTx have a post-transplant survival rate comparable to those who did not receive ECMO pre-transplant [1].

Traditionally, the concept of ECMO use in respiratory failure was to initiate it in conjunction with invasive mechanical ventilation and later by discontinuing ECMO support before ventilator weaning. However, with the ability of ECMO to take over the function of the gas exchange of the ventilator, this pattern is changing, and it will continue to evolve as further technological improvements are made. Some centers have reported successfully starting ECMO instead of invasive mechanical ventilation, bypassing the ventilator entirely [21, 22]. Abrams *et al*. [21] described an evolving paradigm of extracorporeal membrane oxygenation (ECMO) in respiratory failure as a temporary adjunct to invasive mechanical ventilation in severe respiratory failure and using ECMO to facilitate removal or avoidance of IMV while bridge-to-recovery or bridge-to-transplant, at their institution. The paradigm of bridge-to-transplant or bridge-to-decision from IMV and ECMO remains a consideration. However, it remains to be defined who are the specific patient populations for whom these strategies are most appropriate, including those with hypercapnic respiratory failure or awaiting lung transplantation.

Salna and Bacchetta [23] described a clinical decision-making algorithm used at their institution to optimize ECMO configurations and cannulation strategies based on patients' pathophysiology using a multidisciplinary ECMO team approach for BTT. Factors to decide whether patients will benefit from BTT were age, functional status

on admission, underlying disease, infection or other organ system dysfunction, and anticipated waitlist time. The primary goal of using ECMO as a BTT was to optimize transplant candidates before transplantation to improve lung transplant outcomes. Their goal was to help ambulation, which depends on optimal cannulation configurations and early physiotherapy, with patients being mobilized as early as ECMO day 1 [24]. They also aim to cannulate patients without intubation or general anesthesia whenever possible for accelerated recovery or optimization for transplantation.

Trudzinski *et al.* [25] published a retrospective analysis of patients with ILD and ARF treated with or without ECMO from March 2012 to August 2015. Forty patients with interstitial lung disease referred to their intensive care unit for acute respiratory failure were included in the analysis. Twenty-one were treated with ECMO. ECMO was initiated regardless of whether they could be a lung transplant candidate. From the total of 13 patients who were evaluated, eight were found adequate candidates for ECMO as a BTT. Six patients underwent lung transplantation, and 14 of the 15 patients who did not undergo lung transplantation (93.3%) died after 40.3 ± 27.8 days on ECMO. 83.3% of the patients who had a lung transplant were able to be discharged from the hospital. Their important finding was that those patients with ILD on ECMO who were not lung transplant candidates had a high mortality rate, comparable with the mortality rate of patients mechanically ventilated. Also, they demonstrated that ECMO had no value as a transplant-independent outcome improvement in ILD. On the other hand, patients who are candidates for lung transplantation benefit from ECMO therapy. The biggest reason for this benefit is the time gained on ECMO. They concluded that ECMO is a lifesaving option for patients with ILD and ARF provided they are candidates for lung transplantation. Unfortunately, ECMO cannot reverse the poor prognosis in patients who do not qualify for lung transplantation.

Decision supporting patients with acute or acute-on-chronic respiratory failure with ECMO is challenging, and there is no single guideline to help in decision-making. Even so, several high-volume lung transplants and ECMO centers have published their experience with ECMO as a bridge to transplant [22, 26, 27]. A typical decision tree of ECMO as a bridge-to-transplant algorithmic implementation, used only for those listed patients, as shown in **Figure 1** (adapted from Biscotti *et al*. [26]).

The timing of ECMO implementation is crucial. Therefore, they attempted to select patients in whom post-ECMO rehabilitation is likely, as best predicted by patients' pre-ECMO physical therapy performance. The aim was to liberate all patients from mechanical ventilation by using strategies such as early tracheostomy. The criteria for initiating physical therapy included hemodynamic stability, secure cannulas without active bleeding, and patient willingness to cooperate. Ambulation was implemented once the patients demonstrated physiologically adequate ECMO support is demonstrated during initial bedside physical therapy. Seventy-two patients received ECMO as a bridge to LTx. Of the 72 patients, 55.6% underwent the transplantation procedure, 92.5% survived to discharge, and 84% survived for 2 years. Patients with cystic fibrosis were more likely to have a BTT than patients with other lung diseases. Daily participation in physical therapy was achieved in 69.4% of patients. This study demonstrated favorable survival in patients receiving ECMO as a BTT, attaining high rates of physical therapy, and avoiding mechanical ventilation in patients awaiting lung transplantation. With more than half of these patients successfully BTT, we gained insight into the factors influencing patients' outcomes, including patient selection, the timing of ECMO, and patient management. However, clinical management decisions are highly center-specific, and these treatment algorithms must be adapted to fit the clinical setting appropriately.

*ECMO for Respiratory Failure in the Patient with Advance Lung Disease: A Bridge to Recovery… DOI: http://dx.doi.org/10.5772/intechopen.106824*

#### **Figure 1.**

*Bridge to transplantation decision algorithm. \* Pulmonary hypertension (PH). † Atrial septal defect (ASD). (ECLS = extracorporeal life support). Adapted from Biscotti et al. [26].*

The cannulation strategy was based on the patient's underlying disease, respiratory and hemodynamic status, and anticipated worsening of hypoxemia or progressive secondary pulmonary hypertension (PH). They also attempt to select patients in whom post-ECMO rehabilitation is likely, as best predicted by patients' pre-ECMO physical therapy performance. The form of 'awake ECMO' with spontaneously breathing patients is a safe and effective approach to BTT [26–29]. Several highvolume centers have shown that BTT has comparable outcomes with patients not requiring support [26, 27, 30–32].

Another meaningful discussion is the outcomes in the unique subset of patients requiring prolonged use of ECMO support before lung transplantation. In a 2016 review of the Extracorporeal Life Support Organization international multiinstitutional registry, of 974 patients who required prolonged (>14 days) ECMO support, 46% of these patients did not experience native lung recovery; among these, 40 patients (4.1%) underwent LTx with a 50% postoperative in-hospital mortality [33]. The longest reported successful bridge to transplant required ECMO support of 155 days [34]. Another case report describes a patient remaining on ECMO for as long as 403 days while waiting for a lung transplant. The authors conclude that it is at least technically feasible to maintain patients awaiting lung transplantation on ECMO for extended periods, albeit maintaining for more than 1-year may be difficult [35]. ECMO cannot reverse the poor prognosis in patients that do not qualify for lung transplantation. ARF in ILD is devastating in patients without the option of a lung transplant, despite ECMO.

The current biggest challenges for clinicians are when to consider ECMO as a BTD in patients with end-stage lung disease not yet listed for lung transplantation. The

decision is less about using ECMO-BTT and more about whether to extend ECMO-BTD to patients whose lung transplant candidate status is unknown and whether the patient clinically deteriorates while completing their lung transplant evaluation. Also, what if ECMO is needed to facilitate a remaining component of the transplant workup if a previously healthy patient has failed all interventions following an acute, irreversible pulmonary disease. Hoopes and colleagues [22] described a salvage transplant as a feasible approach in this cohort. Although the precise relationship between providing ECMO to patients before active listing and survival to transplant is unknown, their study examined 31 patients who successfully had ECMO-BTT, including seven patients not yet listed for transplant prior to ECMO initiation. The 1-year outcomes of the patients transplanted from an ECMO-BTT was greater than 90% [22]. In this context, rescue therapy denotes lung transplantation in patients not listed before ARF. In particular, salvage transplantation opens a window for clinically sick patients who are not yet listed for lung transplantation, allowing them to be transferred on ECMO to a facility and have an expedited evaluation for potential lung transplantation.

Patients with ILD that survived mechanical ventilation to discharge had a very limited prognosis without lung transplantation; 1-year survival rates were only 4% [36]. In some situations, such as acute exacerbation of ILD, it may be preferable to initiate ECMO-BTD, avoid intubation and mechanical ventilation, the use of sedation helping being awake, maintenance in the nutrition status, mobilization avoiding frailty, and provide emotional support for the patient and the family, and allowing patients who are otherwise considered good candidates to be able to complete the lung transplant evaluation.

Ideally, the bridge-to-decision patients have been already evaluated for a lung transplant and are hospitalized at an expertise lung transplant and ECMO center with adequate ICU resources to support these complex patients with the potential for long-term care, and the patient has completed part of the key initial lung transplant evaluation so that the remaining of the completed evaluation can be expedited, and that the patient does not have any obvious contraindications to be a candidate for lung transplantation.

In general, bridge-to-decision patients should have minimal or absent characteristics that have been associated with worse bridge-to-transplant survival. A multidisciplinary consensus among the lung transplant physicians, critical care intensivists, and ECMO team is essential for a successful transition from ECMO-BTD to ECMO-BTT. in addition, daily multidisciplinary rounds, including advanced care planning and early palliative care involvement are important. The patient and their family should be encouraged to reflect on these implications before deciding to accept ECMO bridge-to-decision. The decision to provide ECMO to patients with advanced lung disease not yet listed for lung transplant should apply existing data and expert opinion to the clinical circumstance. With tempered judgment and expert care, ECMO can provide a pathway to life for patients with end-stage lung disease who are not listed for a lung transplant at the time of their critical admission.

Another concern is when patients, who have started ECMO support, are not candidates for LTx. This situation is ethically challenging and emotionally charged, referred to as a 'bridge to nowhere", with obvious implications for the patient, their family, the caregivers, the hospital, and the healthcare system" [37]. Therefore, it is important to minimize this risk as much as possible through meticulous patient selection. Other concerns for decisions on considering patients who are candidates for ECMO BTD are those patients who are highly sensitized and have a higher risk for worsening sensitization due to ECMO-related needs for blood transfusion and

*ECMO for Respiratory Failure in the Patient with Advance Lung Disease: A Bridge to Recovery… DOI: http://dx.doi.org/10.5772/intechopen.106824*

concerns for increased waiting times, infections risk, and vascular complications. Other concerns for decisions on considering patients who are candidates for ECMO BTD are those patients who are highly sensitized and have higher risk for worsening sensitization due to ECMO related need for blood transfusion and concerns for increase waiting times, infections risk and vascular complications.

Even though ECMO as a BTD can benefit patients and families by giving them more time to share with each other and for discussions on collaborative decisionmaking. Courtwright *et al.* states the most common ethical issues involving disagreements among and between healthcare teams, patients, family, and other surrogates, particularly when confronted with decisions about the continuation or withdrawal of ECMO [38].

### **4. Conclusions**

ECMO is a lifesaving option for patients with advanced lung disease, and ARF provided they are suitable candidates for lung transplantation. Salvage transplantation opens a door for clinically sick patients who are not yet listed for lung transplantation, allowing them to be transferred on ECMO to a facility and have an expedited evaluation for potential lung transplantation. There is limited data and a lack of good guidelines on candidate selection.

The question regarding using ECMO as a BTD in patients with end-stage lung disease not yet listed for lung transplantation and if the patient clinically deteriorates while nearing completion of their transplant evaluation, or if ECMO support is needed to facilitate completing the lung transplant evaluation, is more challenged than whether using ECMO-BTT.

Daily interdisciplinary rounds, advanced care planning, and early palliative care involvement are essential. The patient and family should be encouraged to reflect on these implications before deciding to accept ECMO-BTD. It is important to have a protocol for ECMO withdrawal when not a candidate for LTx. Consensus guidelines on ECMO-BTD for patients, not jet listed for LTx as risk stratification to better assess those patients who will benefit the most and have the best outcomes post-transplant.
