**2. Indications and outcomes**

respiratory failure, where venoarterial ECMO provided 75 h of life-sustaining support in 1972 [1]. Despite initial barriers to widespread adoption, by the 1990s, a growing body of literature demonstrated a clinical benefit to ECMO in certain patients. Advances in ECMO technology, critical care, rehabilitation, and comorbidity management have resulted in increased adoption of ECMO, with ever-increasing duration of ECMO runs. In 2003, there were 1606 patients supported with ECMO [2], with this number increasing to 2895 by 2011 [3] and more than 6600 cases in 2015 [4]. Although the mean duration of ECMO support is approximately 1 week, reports of over 7 months exist in the literature. Long-term ECMO, defined as 3 weeks or longer of ECMO support, has become increasingly prevalent, with many centers reporting

In general, the initial indications for long-term ECMO support are the same as short-term ECMO support, and it is the patient's recovery which dictates the duration of use. **Table 1** lists respiratory indications for ECMO support, with diagnosis, average run duration, and percent survival stratified by age group. Despite the ability of ECMO to treat both respiratory and circulatory conditions, it is the patients with severe respiratory failure who are most commonly supported on long-term ECMO. In contrast, patients with cardiogenic shock are typically transitioned to ventricular assist device (VAD) therapy or heart transplant prior to 3 weeks of ECMO support. The most prevalent respiratory indications for long-term ECMO include bacterial and viral pneumonia, acute respiratory distress syndrome (ARDS), and acute respiratory failure in the adult and pediatric populations. In the neonatal patient

**Age group Diagnosis Average run duration (h) % survival**

Persistent pulmonary hypertension of newborn 155 77 Sepsis 144 72 Respiratory distress syndrome of newborn 136 84 Meconium aspiration syndrome 133 94

Bacterial pneumonia 283 60 Aspiration pneumonia 242 69 Acute respiratory failure, non-ARDS 226 52

ARDS, non-post-op/trauma 313 54 Acute respiratory failure, non-ARDS 275 55 Bacterial pneumonia 261 61 ARDS, postop/trauma 256 57

Neonatal Congenital diaphragmatic hernia 257 51

Pediatric Viral pneumonia 317 66

Adult Viral pneumonia 325 65

**Table 1.** Average ECMO run duration and % survival by age group and diagnosis, 2016 data [4].

success in long-term support.

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The decision to support a patient with ECMO is based on the severity of cardiopulmonary dysfunction, the response to conventional therapy, as well as patient and family preferences for the aggressiveness of treatment. The duration of ECMO use, in contrast, is dependent on patient recovery and the patient's ability to transition to alternative therapies. Indeed, patient and family preferences for the duration of aggressive critical care must be considered, and honest explanations of ECMO outcomes must be provided.

Unfortunately, the data necessary to predict patient outcomes on long-term ECMO support remain limited. Instead, case series and case reports guide much of the decision-making, and key examples are described later.

### **2.1. Respiratory failure**

Respiratory failure remains the condition most commonly supported with long-term ECMO, with ARDS the inciting respiratory insult in many cases. When supporting a patient with severe respiratory failure with ECMO, clinicians must consider strategies for decannulation, which currently include patient recovery and lung transplantation. Despite increased acceptance of ECMO as a long-term therapy, it is currently unable to support patients outside of the intensive care unit (ICU), and does not allow for patients to return to activities of daily living. The ideal scenario for these patients is a full recovery, and there are increasing reports of patients recovering from long-term ECMO support for severe respiratory failure. The longest reported ECMO run with recovery is in a 26-year-old drowning victim, who was supported for 117 days on ECMO [5].

In patients unlikely to recover their native pulmonary function, or in patients with progressive underlying respiratory failure, ECMO may be utilized as a bridge to lung transplantation. The longest reported successful bridge to transplant required ECMO support of 155 days [6]. In these cases, ECMO provides the needed gas-exchange function, allowing for reduced reliance on mechanical ventilation. The principle advantage of this strategy lies in the ability to liberate patients from mechanical ventilation, allowing some patients to talk, eat, and ambulate, which serve to prevent pre-transplant deconditioning. There are two patient populations who receive ECMO as a bridge to lung transplantation: patients with chronic respiratory failure who are listed for transplantation prior to ECMO initiation and those patients without history of respiratory failure, who are only listed for transplantation after ECMO therapy has begun.

In the setting of acute respiratory decompensation, it is unlikely for a patient's transplant candidacy to improve beyond their baseline—instead, the role of ECMO in these patients is to prevent their deconditioning and to avoid transplant-precluding complications. As such, the contemporary management of patients with respiratory failure exceeding the abilities of conventional support measures involves ECMO support followed by urgent lung transplantation, as the prolonged ECMO use continuously exposes patients to the risk of complication.

Acute respiratory decompensation occurs not infrequently in patients who are listed for lung transplantation. For these patients, the use of ECMO provides necessary gas-exchange function in the setting of inadequate native lung function. The use of ECMO in these patients has been widely reported, and the algorithms guiding this management strategy are maturing. One single-center experience reports the use of ECMO as a bridge to lung transplant over a 9-year period, in which the median duration of ECMO use was 12 days (interquartile range—IQR 6.25 to 18.75) [7]. In the series of 72 patients, 56% of patients were successfully bridged to transplant, with 38% surviving for up to 2 years. Notably, the patients were free from mechanical ventilation for a mean time of 10.2 days (SD 18.8 days), and 69% of patients were ambulatory while on ECMO. A similar experience was reported on 31 patients who were bridged to lung transplantation using ECMO over a 5-year period at two institutions [8]. They report ambulation while on ECMO in 18 patients, liberation from the ventilator in 3 patients, and a median duration of ECMO use of 11 days (IQR 3.5–17). Five patients were on ECMO for over 21 days, with one patient requiring 53 days of support. Of note, 7 of the 31 patients were not listed for transplantation prior to ECMO cannulation.

The decision to support patients with acute or acute-on-chronic respiratory failure with ECMO is a challenging one, and no single guideline exists to aid in decision-making. Even so, multiple high-volume pulmonary transplant and ECMO centers have published their experience with ECMO as a bridge to transplant. A typical decision tree is shown in **Figure 1** (adapted from Biscotti et al. [7] and Hoopes et al. [8]). Note that the clinical management decisions are highly center specific, and these treatment algorithms must be adapted to appropriately fit the clinical setting.

Continuous advancement in the technology of ECMO as well as improvements in critical care and rehabilitation have improved the outcomes of all ECMO patients, including those requiring long-term support. A study describing the course of 127 patients placed on ECMO for respiratory failure between 2006 and 2010 found an overall survival to decannulation of 64%. In the stratified analysis, they found that 59, 31, and 52% of patients survived after being placed on ECMO for 10 days or less, 11–20 days, or more than 21 days, respectively. They found no statistically significant difference in survival between the 45 patients who were supported on ECMO for 10 days or less, and the 10 patients who were supported long term (*p* = 0.39) [9]. Similarly, a study of 55 patients placed on ECMO for severe ARDS demonstrated no significant difference in hospital or 30-day mortality, with 27% of patients supported for 3 or more weeks expiring versus 43% of patients supported less than 3 weeks [10]. These data, albeit limited, provide evidence for cautious optimism in the care of patients with severe respiratory failure.

**2.2. Circulatory collapse**

highly dependent on clinical setting.

The use of long-term ECMO for the treatment of cardiogenic shock is less common than for respiratory failure, as many are transitioned to VAD therapy before their tenure on ECMO

**Figure 1.** General treatment algorithm for ECMO as a bridge to lung transplant. Note that implementation details are

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**Figure 1.** General treatment algorithm for ECMO as a bridge to lung transplant. Note that implementation details are highly dependent on clinical setting.

#### **2.2. Circulatory collapse**

to prevent their deconditioning and to avoid transplant-precluding complications. As such, the contemporary management of patients with respiratory failure exceeding the abilities of conventional support measures involves ECMO support followed by urgent lung transplantation, as the prolonged ECMO use continuously exposes patients to the risk of

Acute respiratory decompensation occurs not infrequently in patients who are listed for lung transplantation. For these patients, the use of ECMO provides necessary gas-exchange function in the setting of inadequate native lung function. The use of ECMO in these patients has been widely reported, and the algorithms guiding this management strategy are maturing. One single-center experience reports the use of ECMO as a bridge to lung transplant over a 9-year period, in which the median duration of ECMO use was 12 days (interquartile range—IQR 6.25 to 18.75) [7]. In the series of 72 patients, 56% of patients were successfully bridged to transplant, with 38% surviving for up to 2 years. Notably, the patients were free from mechanical ventilation for a mean time of 10.2 days (SD 18.8 days), and 69% of patients were ambulatory while on ECMO. A similar experience was reported on 31 patients who were bridged to lung transplantation using ECMO over a 5-year period at two institutions [8]. They report ambulation while on ECMO in 18 patients, liberation from the ventilator in 3 patients, and a median duration of ECMO use of 11 days (IQR 3.5–17). Five patients were on ECMO for over 21 days, with one patient requiring 53 days of support. Of note, 7 of the 31 patients were not listed for transplantation prior to ECMO

The decision to support patients with acute or acute-on-chronic respiratory failure with ECMO is a challenging one, and no single guideline exists to aid in decision-making. Even so, multiple high-volume pulmonary transplant and ECMO centers have published their experience with ECMO as a bridge to transplant. A typical decision tree is shown in **Figure 1** (adapted from Biscotti et al. [7] and Hoopes et al. [8]). Note that the clinical management decisions are highly center specific, and these treatment algorithms must be adapted to appropri-

Continuous advancement in the technology of ECMO as well as improvements in critical care and rehabilitation have improved the outcomes of all ECMO patients, including those requiring long-term support. A study describing the course of 127 patients placed on ECMO for respiratory failure between 2006 and 2010 found an overall survival to decannulation of 64%. In the stratified analysis, they found that 59, 31, and 52% of patients survived after being placed on ECMO for 10 days or less, 11–20 days, or more than 21 days, respectively. They found no statistically significant difference in survival between the 45 patients who were supported on ECMO for 10 days or less, and the 10 patients who were supported long term (*p* = 0.39) [9]. Similarly, a study of 55 patients placed on ECMO for severe ARDS demonstrated no significant difference in hospital or 30-day mortality, with 27% of patients supported for 3 or more weeks expiring versus 43% of patients supported less than 3 weeks [10]. These data, albeit limited, provide evidence for cautious optimism in the care of patients with severe

complication.

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cannulation.

ately fit the clinical setting.

respiratory failure.

The use of long-term ECMO for the treatment of cardiogenic shock is less common than for respiratory failure, as many are transitioned to VAD therapy before their tenure on ECMO would be considered long term (21 days). Reports of patients being supported on venoarterial ECMO for prolonged durations do exist in the literature, however. In one study, a patient unable to wean from cardiopulmonary bypass following re-do sternotomy and aortic valve replacement was supported with venoarterial ECMO for 33 days postoperatively before being successfully weaned and decannulated [11]. Unfortunately, this patient ultimately suffered a cerebrovascular accident and died in a high-dependency unit. In a cohort of 98 patients receiving ECMO for refractory cardiogenic shock, Rousse et al. reported a median duration of ECMO use of 8 days, with the maximum duration of 81 days [12]. This cohort suffered 50% mortality, with 30% of patients recovering to normal cardiac function, 13% of patients receiving a heart transplant, and 7% of patients transitioned to VAD therapy.

For patients with cardiogenic shock or pulmonary hypertension, the cannulation options are more limited. In principle, the cannulae must provide venous drainage as well as return of oxygenated blood to the arterial system with adequate return pressure to provide end-organ perfusion. In the acute cannulation of patients with cardiopulmonary collapse, the common femoral artery is the preferred vessel for arterial cannulation in adults. Of note, the presence of the arterial cannula in the common femoral artery can compromise distal limb perfusion, and insertion of a distal perfusion catheter is often required. Unfortunately, the groin access required for cannulation of the common femoral artery limits mobility and may be deleteri-

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Although there is no commonly accepted cannulation site for long-term venoarterial access, one reported technique is cannulation of subclavian vessels [13]. This technique is reported to provide adequate flows and improved ambulation options. Technically, this cannulation method requires a small infraclavicular incision, anastomosis of a synthetic arterial graft with the subclavian artery in an end-to-side fashion, and direct insertion of the cannula into the arterial graft. Naturally, decannulation from this arrangement requires a surgical procedure

In cases where there is right heart dysfunction or severe pulmonary hypertension, venoarterial ECMO through femoral vein and femoral artery is the traditional means of decompressing the right ventricle. In patients with a congenital atrial septal defect, a less invasive technique can be employed, in which a dual-lumen cannula is placed under fluoroscopic or echocardiographic guidance [14]. This goal of this configuration is to direct the oxygenated blood returned from the ECMO circuit through the atrial septal defect and into the left atrium, thus reducing the blood delivered through the right ventricle. This configuration promotes ambulation, as the dual-lumen venovenous cannula is inserted through the internal jugular vein. Both animal and human studies have shown success with creation of an atrial septostomy in conjunction with venovenous ECMO for the treatment of pulmonary hypertension [15]. If this technique cannot provide adequate right ventricular unloading, central cannula-

The first central cannulation technique involves venous drainage from the right atrium and return of oxygenated blood into the pulmonary artery. Technically, this is accomplished through a median sternotomy or thoracotomy, with insertion of the venous drainage cannula into the right atrial appendage, and a synthetic arterial graft is anastomosed to the main pulmonary artery in an end-to-side fashion. The arterial cannula is inserted into this graft. In the patient with pulmonary hypertension, this configuration requires that the ECMO circuit pumps against this high-resistance pulmonary vasculature. This is rarely an issue, however, as even the vasculature of severe pulmonary hypertension has a lower driving pressure than systemic arterial pressure, and modern ECMO circuits have little difficulty driving blood through the systemic circulation. One major advantage of this configuration is that it places the arterial return in the main pulmonary artery, benefiting from the systemic-embolus protection afforded by the pulmonary vasculature. Additionally, cannulae can be tunneled out of the subcutaneous tissues and skin without access to upper or lower limbs, promoting

ous to rehabilitation.

mobility.

with either explant or close ligation of the arterial graft.

tion is required, with two primary configurations.

The decision to provide long-term ECMO support for these patients is largely dependent on their presumed recovery path, and it is the patients who are poor candidates for VAD support who are typically supported on venoarterial ECMO in the long term. These patients must be aggressively medically optimized, as the goal of the ECMO therapy is in recovery of native cardiac function prior to decannulation. Indeed, some patients will not recover native cardiac function, will never become transplant candidates, and are unsuitable for VAD as a destination therapy. Management of these patients is a significant challenge both medically and ethically, and the family must frequently be updated in the plan of care.
