113: Artificial Lung

Extracorporeal membrane oxygenation (ECMO) has continued to evolve since the pioneers of cardiac surgery, Gibbon and Lillehei, developed cardiopulmonary bypass in the 1950s. The term ECMO applies to the use of an extracorporeal circuit, consisting of tubing, oxygenator and blood pump, in the setting of cardiopulmonary failure. The original ECMO was veno-arterial (VA) as popularized by Bartlett in the early 1980s. Over the last three decades ECMO has evolved into several forms including VA, veno-venous (VV), arterio-venous (AV), right atrium to aorta (RA–Ao), and pulmonary artery to left atrium (PA–LA). ECMO in some form may be indicated for acute cardiac failure, respiratory failure, or a mixed presentation; the specific application of the therapy will depend on the presentation of the patient. Likewise, several programs have developed ambulatory capability of most forms of ECMO to aid recovery or suitability for transplant. Ambulatory ECMO is often referred to as the “artificial lung.”

Historically, ECMO in the adult was considered “salvage” therapy for patients “dying” from severe respiratory failure despite maximal medical therapy. Some of the oft-quoted trials in the 1980s compared ECMO with conventional medical therapy and failed to show survival advantage. However, there have been significant advances in ECMO, and evidence now favors earlier utilization of the technology to minimize end-organ damage that might occur during prolonged maximal ventilatory and medical support. This is particularly apparent in the case of respiratory failure associated with H1N1 influenza. Survival is approximately 72% for patients placed on ECMO within 6 days of intubation compared with only 30% for patients on ECMO 7 or more days after intubation.¹

ECMO is indicated for the short-to-medium-term management of respiratory failure, cardiac failure, or both. Specifically, patients are evaluated when the native disease process is thought to have an estimated mortality of 50% or greater, is reversible, and/or requires a bridge to transplant. The Extracorporeal Life Support Organization (ELSO) publishes guidelines which cover application of ECMO in the adult. In the case of acute respiratory distress syndrome (ARDS), this would include a PaO₂/FiO₂ ratio of less than 100 despite optimization of ventilator settings.

Special scenarios include H1N1 infection, where early deployment of ECMO is associated with better outcomes, and delay may adversely affect the risk/benefit ratio. In addition, use of ECMO as a bridge-to-transplant for lung recipients should be considered when maximal medical therapy is insufficient. Many programs utilize ambulatory ECMO to improve the respiratory status and conditioning prior to transplant.

ECMO as a bridge to lung transplantation has significantly increased during the last 10 years. A recent analysis of the UNOS database showed that the use of ECMO at the time of lung transplantation has grown 150% in the last 24 months compared to all previous decades (1970–2010). This increase in utilization is reflected in the growing success reported with the use of different ECMO modalities in patients awaiting lung transplantation. We recently submitted our experience with the use of ambulatory ECMO as a bridge to lung transplantation, reporting the use of ECMO in 31 patients with end-stage lung disease. In our series, all of the patients were awake and the vast majority followed an “algorithm-directed” ECMO management program that involved the use of physical therapy and ambulation in preparation for lung transplant. In our series, the 30-day, 1-year, 3-year and 5-year survival was 97%, 92%, 83%, and 66%, respectively.² A summary of a modern series of patients bridged to lung transplant while on ECMO is presented in Table 113-1.

ECMO use is now being considered in awake, nonintubated patients to improve oxygenation, to facilitate ambulation, and to improve physical conditioning prior to transplant.

Indications for ECMO

1. Patients with irreversible end-stage lung disease presenting with clinical deterioration (refractory hypoxia or hypercapnia) or lack of response despite the use of invasive or noninvasive mechanical ventilation.

2. Patients with severe pulmonary hypertension refractory to pulmonary vasodilators and/or hemodynamic deterioration caused by right ventricular failure.

3. Patients with severe exercise-induced pulmonary hypertension associated with advanced lung disease, presenting with clinical deterioration and progressive physical decline, and unable to maintain ambulation and good functional status.

Contraindications to the Use of ECMO

1. Active bloodstream infection

2. Acute renal failure not responsive to medical therapy (need for dialysis)

3. Hereditary or acquired coagulation disorders (i.e., blood dyscrasia, heparin-induced thrombocytopenia)

4. Evidence of end-organ failure other than the lung

5. Underlying irreversible neurological or neuromuscular disease

Several studies have shown that the use of mechanical ventilation in patients with idiopathic pulmonary fibrosis is not effective and is associated with high mortality rates. Delaying initiation of ECMO in an attempt to maximize alternative medical treatments may result in worsening physical condition, secondary organ dysfunction, and jeopardize their candidacy for possible lung transplantation.

Areas of Controversy

Advanced age (>65 years) is considered by some a relative contraindication for lung transplantation. Nevertheless, several reports have demonstrated good outcomes in patients >65 years of age. A recent report of the use of ambulatory VV ECMO in patients with cystic fibrosis and hypercapneic respiratory failure suggests that patients with severe bronchiectasis or cystic fibrosis can be successfully bridged to lung transplantation without an increased risk for infectious complications.

There are four categories for ECMO cannulation in the adult:

1. VV ECMO is indicated for management of isolated respiratory failure. The success of this strategy relies on the patient's own hemodynamics and only assists with gas exchange. Blood is withdrawn from the right atrium/inferior vena cava (IVC) via a long peripheral cannula inserted via a central vein. Oxygenated blood is returned via a superior vena cava (SVC) cannula into the right atrium with flow directed at the tricuspid valve. The oxygenated blood is then pumped out the pulmonary artery, through the dysfunctional lungs, and then returned to the left heart where it is pumped to the systemic circulation. The Avalon Elite^TM dual lumen cannula (DLC) (Maquet Cardiovascular, San Jose, CA), designed by Wang and Zwischenberger, is a significant advance in the arena of VV ECMO.³ Single percutaneous access of the right internal jugular vein yields several advantages: single-site cannulation, reduced risk for complications associated with femoral or central cannulation, and the ability to allow ambulation by avoiding the use of the femoral site. Placement of the Avalon cannula may be performed bedside in the intensive care unit (ICU); however, it requires either fluoroscopic or echocardiographic guidance for optimal placement of the return and infusion ports.⁴

2. VA ECMO is indicated in the setting of acute cardiogenic shock or in the setting of a primary respiratory process complicated by diminished cardiac function. Cannulation is performed with venous drainage from the right femoral vein through a long cannula placed such that optimal drainage from the right atrium is achieved. Oxygenated blood is returned via femoral arterial cannula. Cannulas may be placed percutaneously in the ICU or a direct cut-down for access to the femoral vasculature. Blood via the axillary artery by direct anastomosis of a conduit facilitates ambulation. This strategy may be an important consideration in the conversion of ambulatory VV ECMO to VA ECMO as this configuration continues to allow ambulation.⁵

3. AV ECMO/AVCO₂ removal. AV ECMO utilizes the patient's native hemodynamics to drive flow through a low resistance gas exchange device, the goal being CO₂ removal. This configuration is most suited to those patients awaiting lung transplantation whose primary issue is severe CO₂ retention. Sometimes described as pumpless extracorporeal lung assist (pECLA), flow through the circuit is usually 15% to 20% of cardiac output, which limits its use for oxygenation. Central cannulation has also been described.^6,7

4. Central cannulation refers to placement of ECMO cannulas via thoracotomy or sternotomy. This most commonly refers to placement of ECMO for failure to wean from cardiopulmonary bypass. The disadvantage is the need for full operating room support; however, the full array of ECMO options are available via the great vessels, and complications of peripheral cannulation are avoided.

Significant advances in commercially available oxygenator membranes have resulted in improved durability, including patients bridged to lung transplantation. Currently, most ECMO systems have replaced polypropylene with polymethylpentene (PMP) fibers. PMP membrane oxygenators are smaller, provide efficient gas exchange without plasma leak, and are associated with faster priming (saving blood and valuable time and making CO₂ flushing unnecessary). In addition, the PMP oxygenators are associated with less circuit resistance, are less prone to malfunctioning due to blood trauma or blood clots, and can be functional for several weeks to months. Modern ECMO components, including PMP oxygenators, can be heparin coated, reducing excessive use of heparin, minimizing risk of over-anticoagulation, and reducing the use of blood products. Heparin-coated tubing is also associated with a reduction in the rates of leukocytes, platelets, and complement activation. New centrifugal pumps have been created offering a nonocclusive, demand-regulated pump flow that eliminates the risk of raceway tubing wear and circuit rupture, facilitating patient mobilization and ambulation.

Interventional Lung Assist (Novalung)

The interventional lung assist (iLA), or Novalung, consists of a low resistance PMP membrane designed to allow gas exchange by simple diffusion. The iLA has been successfully used to bridge patients to lung transplantation using a “pumpless” AV mode (pECLA), in which the device is attached to the systemic circulation via femoral artery, although central cannulation has also been reported in patients bridged to lung transplantation (PA–LA or PA–PV). The device is effective for CO₂ removal but is less effective for O₂ augmentation as it only receives approximately 15% to 20% of the cardiac output for extracorporeal gas exchange. Novalung has been compared to other CO₂ removal devices in patients awaiting lung transplantation and all provided similar CO₂ clearance.

Dual Lumen Cannula (Avalon Elite)

A new type of DLC (Fig. 113-1), the Avalon Elite, is placed percutaneously through the internal jugular vein; the drainage lumen is open to both the SVC and IVC, while the infusion lumen is open to the right atrium. The blood from systemic circulation flows through the SVC and IVC into the drainage lumen to the artificial lung device. The blood is oxygenated and returned via the infusion lumen into the right atrium. Compared to traditional ECMO approaches, this device offers important advantages in patients awaiting lung transplantation: it requires single-site cannulation, reduces the risk for complications associated with femoral or central cannulation, and facilitates ambulation by avoiding the use of the femoral site. The DLC has a unique design with improved flexibility (reducing kinking problems associated with rigid cannulas). The infusion lumen of the cannula is an ultra-thin membrane that collapses during insertion to allow space for an atraumatic introducer that facilitates placement. The Avalon DLC has shown recirculation fractions of 2% when fluoroscopy or transthoracic echocardiography guidance is used.

The DLC has been used to facilitate ambulation during ECMO in awake and nonintubated patients. Garcia et al.⁸ first reported the use of ambulatory VV ECMO using a DLC in a patient with COPD with refractory hypercapnia. The patient was able to exercise using a treadmill and a stationary bike while on ECMO and was successfully bridged to lung transplantation approximately 19 days later. Subsequent to this report, many other centers have reported similar results and have confirmed the feasibility and safety of the DLC as a bridge to lung transplantation. For VV ECMO, a single-site approach using a DLC was preferred in patients with hypercapnia and preserved oxygenation, whereas a two-site approach was chosen for patients with severe hypoxemia. Bermudez et al.⁹ presented their single-center experience with 17 patients that were bridged to lung transplantation. The 30-day, 1-year, and 3-year survival rates were not different when compared to nonsupported patients, and the survival was not affected by ECMO type at 2 years. Hayes et al.¹⁰ reported the use of a DLC to facilitate ambulation and transplant in four patients with cystic fibrosis and hypercapneic respiratory failure. More recently, Lang et al.¹¹ reported their experience with ECMO as a bridge to lung transplantation in 34 patients, and reported the use of a DLC in two patients.

The cannulation strategy is frequently chosen based on: ability to facilitate ambulation (DLC via internal jugular vein is the preferred route, although central VA ECMO and iLA [PA–LA] can also allow ambulation); hemodynamic instability; and presence of severe pulmonary hypertension and/or right heart failure (central or femoral cannulation for VA ECMO is preferred). Cannulation approaches performed for bridging patients to lung transplantation include femoral vein to internal jugular vein (traditional VV), femoral vein to femoral artery (traditional VA), RA–Ao (central VA), PA–LA, and right internal jugular with DLC (ambulatory VV).

Fig. 113-2 shows our preferred cannulation strategy for ambulatory ECMO as a bridge to lung transplantation.

Hoopes et al.¹² recently reported the use of a DLC in a patient with severe right ventricular failure secondary to pulmonary hypertension associated with pulmonary veno-occlusive disease. An atrial septostomy was created concomitant to the insertion of the DLC, to unload the right heart pressures and to facilitate forward flow. The patient was able to ambulate and was successfully bridged to lung transplantation. Bonacchi et al.¹³ reported the use of VV ECMO in 30 patients with severe acute respiratory failure and described their experience with the use of a customized arterial cannula to reduce the amount of blood recirculation fraction (BRF) when high ECMO flows were needed to improve systemic oxygenation. In their “χ” configuration, a traditional inflow cannula is modified by making a 60º angle in its distal third to allow tip orientation toward the tricuspid valve. In their series, the authors report a significant improvement in oxygenation indices and a reduction of >20% in the BRF. Importantly, the study showed that the modified cannula can be safely used without mechanical complications.

DLC and Axillary Artery (“Walking Hybrid”)

Bacchetta et al.⁵ reported that for patients on VV ECMO using a DLC, a conversion VA ECMO can be accomplished by adapting the existing catheter: the two lumens are connected using a Y-connector and the end of the Y-connector is then joined to the venous drainage of the extracorporeal or CPB circuit. The arterial cannula can then be placed intrathoracically or peripherally. The authors suggest that using a combined axillary artery cannulation and the DLC venous cannulation could facilitate ambulation while awaiting lung transplantation.

Once ECMO has been established, attention must be directed toward optimizing recovery, minimizing complications, and minimizing end-organ damage.

1. Ventilator: Minimal settings should be employed to minimize barotrauma. FiO₂ should be reduced to 30% or less if possible and P_plateau should be maintained below 25.

2. Anticoagulation: Modern ECMO circuits feature heparin-bonded tubing, which will help minimize thrombotic complications; however, the oxygenator requires some level of anticoagulation to be maintained. An activated clotting time (ACT) level of 1.5 times normal should be maintained. Direct monitoring of heparin and other coagulation factors may also be employed.

3. Blood Transfusion: Oxygen carrying capacity must be optimized to make best use of the ECMO circuit, particularly in the VV setting.

4. Hemodynamics: Normal hemodynamics are critical to the performance of VV ECMO. It may be necessary to utilize pressors and occasionally may be necessary to convert to VA ECMO. In the setting of VA ECMO, native cardiac function must be monitored with regular echocardiography to avoid complications. Fluid overload should be aggressively managed with either diuresis or ultrafiltration, which can be accomplished in series with the ECMO circuit if necessary.

5. ECMO circuit: In more prolonged periods of ECMO support it may be necessary to exchange the oxygenator at intervals. Modern oxygenators have demonstrated the ability to be used for several weeks.

Ideally, a gas mixer in line with the oxygenator will allow for decrease in the concentration of oxygen provided, independent of gas flow, thereby allowing for very fine monitoring of whether the patient has recovered oxygenation or ventilation capability. Recruitment maneuvers should be performed prior to the weaning trial to optimize lung function. Once the patient demonstrates good performance with no support from the oxygenator, the cannulas may be removed. VA ECMO weaning is likewise performed by reducing support. However, this now requires decreasing the pump flow rate. Again, after the patient demonstrates satisfactory performance after a period of no support, the cannulas may be removed.

As ECMO continues to evolve so too does its safety profile. Nevertheless, it remains an invasive therapy with requirement for extracorporeal circulation of the patient's blood volume. Caregivers must be particularly vigilant to prevent or minimize the complications that may arise. Cannulas can become dislodged during patient positioning and transport. Pump and oxygenator may fail, and backups should be readily available. In the case of the commonly used centrifugal pump, a battery backup and hand-crank system should be available at the bedside at all times.

Meticulous hemostasis is a first step to avoid bleeding. ACT may be allowed to run closer to normal for a period to assist with hemostasis. The use of factor transfusion has been described in refractory cases; however, it carries the risk of circuit thrombosis. Cerebral/coronary ischemia is particular to VA ECMO and is most likely to manifest in patients with femoral-only cannulation. Arterial blood is returned from the circuit via the femoral artery and flows retrograde up the descending aorta. In the case of increased native cardiac output, which may occur due to insufficient unloading due to low flow or cannula position, deoxygenated blood may be ejected from the heart to counter the retrograde flow of oxygenated blood from the circuit. If the native ejection is such that the “meeting point” of these two competing blood streams is distal to the left carotid artery, cerebral ischemia will ensue despite excellent distal organ perfusion. It should also be apparent that coronary ischemia is a particular concern. To monitor for this requires right upper extremity pulse oximetry at a minimum, and arterial blood gases should be checked, preferably from the right upper extremity, in addition to echocardiographic monitoring of cardiac function. In some cases it may be necessary to resort to central or peripheral right axillary cannulation.

The recent success of ECMO is a consequence of both significant advances in technology of the components of the circuit as well as available changes in ECMO configuration that allows the use of ECMO in awake and ambulatory patients. The objectives are to improve the preoperative condition of the patient by enhancing physical strength, cardiovascular fitness, and reducing the risk for posttransplant complications.

A 27-year-old Caucasian male with no significant past medical history was admitted to the ICU after an episode of nonresolving pneumonia complicated by the development of ARDS (Fig. 113-3). The patient deteriorated requiring use of mechanical ventilation. The patient's high airway pressures and decreased lung compliance were treated with continuous sedation and neuromuscular blocking agents. After the patient failed to respond to conventional medical therapy and protective lung ventilation (including use of newer modes of mechanical ventilation such as airway pressure release ventilation [APRV]), he was referred to our institution for consideration of lung transplantation approximately 3 weeks later. As a result of severe deconditioning and profound neuromuscular weakness, the patient was not considered an appropriate candidate for lung transplantation. His poor lung compliance and high oxygen requirements precluded the possibility of achieving ambulation and physical reconditioning. Therefore, ambulatory ECMO as a bridge to lung transplantation was initiated. A 31 French Avalon cannula was inserted in the right internal jugular vein under fluoroscopy and echocardiography guidance (as previously described in the literature).⁴ The patient was started on VV ECMO and was weaned from mechanical ventilation within 24 hours. All sedative medications were discontinued and the patient started a program of physical rehabilitation including daily ambulation while on ECMO with a goal of a walk distance of >400 feet (Fig. 113-4). The patient remained on VV ECMO for approximately 49 days and was successfully bridged to a bilateral lung transplant. The patient was discharged home within 2 weeks of transplant with good physical performance and without the use of supplemental oxygen. This case illustrates the value of ECMO for patients with severe end-stage lung failure who are unable to recover from catastrophic lung injury and who are unable to bridge to lung transplantation with the use of conventional mechanical ventilation.