Veno-Veno-Arterial ECMO (VVA ECMO), also known as Veno-venous and Arterial ECMO, combines the principles of both veno-venous (VV ECMO) and veno-arterial (VA ECMO) to provide cardiopulmonary support. This hybrid ECMO modality is used in post-transplant patients who experience both respiratory and circulatory failure, or those with severe cardiac and respiratory dysfunction simultaneously. It is a more complex form of ECMO, typically used for patients who are critically ill following lung transplantation and experiencing complications such as primary graft dysfunction (PGD), severe right heart failure, or multisystem organ failure.

Indications for VVA ECMO Post-Lung Transplant

VVA ECMO may be required for post-lung transplant patients who experience both respiratory failure and cardiovascular collapse. These patients are often in acute distress and need both oxygenation support and circulatory assistance. Specific indications include:

1. Primary Graft Dysfunction (PGD) and Right Heart Failure:
• Primary graft dysfunction (PGD) is one of the most common causes of respiratory failure following lung transplantation. PGD can lead to severe hypoxemia, pulmonary edema, and impaired gas exchange. In some cases, PGD may also cause right heart failure due to pulmonary hypertension, especially if the graft does not function properly, or the pulmonary vasculature is unable to accommodate the new lung.
• VVA ECMO can provide both respiratory support (via the venous circuit) and cardiovascular support (via the arterial circuit), helping the heart and lungs to rest while therapies for PGD are initiated.
2. Severe Right Heart Dysfunction:
• After lung transplantation, right heart failure may occur as a result of increased pulmonary vascular resistance or pulmonary embolism. This condition is often difficult to manage with mechanical ventilation alone and may require right ventricular support in addition to lung support. The arterial component of VVA ECMO supports the right heart by improving cardiac output and reducing right ventricular afterload, while the venous component assists with oxygenation and carbon dioxide removal.
3. Severe Respiratory Failure with Hypoxia:
• For patients who are unable to maintain adequate oxygenation despite optimal mechanical ventilation or high-flow oxygen therapy, VVA ECMO can be used as a bridge to recovery or to lung re-transplantation. In cases of severe PGD or acute rejection, VVA ECMO provides oxygenation and CO2 removal while protecting the transplanted lung from the detrimental effects of high ventilation pressures.
4. Rejection and Infection:
• Acute rejection or severe infection can compromise the function of the transplanted lung, leading to severe respiratory and circulatory failure. In such cases, VVA ECMO is used to provide combined respiratory and circulatory support while the medical team addresses the underlying cause, such as immunosuppressive therapy adjustments or antibiotic treatment.
5. Multi-Organ Failure:
• Lung transplant patients may develop multi-organ failure due to a variety of factors, including infection, ischemic injury, or severe rejection. VVA ECMO may be employed when the patient is facing both respiratory failure and hemodynamic instability, especially if the lungs are unable to sustain life and cardiovascular function is also deteriorating.
6. Failure to Wean from Ventilator:
• Some transplant patients struggle with weaning from the ventilator despite minimal lung damage or good graft function. This may occur due to cardiac dysfunction or other complications that make it difficult for the patient to tolerate extubation. VVA ECMO may support both the cardiac and respiratory systems, allowing the patient to recover or bridge them to re-transplantation.

How VVA ECMO Works

In a VVA ECMO setup, there are both venous and arterial cannulas used to provide both respiratory and circulatory support. Here’s how it works:

1. Venous Cannulation (for Oxygenation):
• Blood is drained from a large vein, typically the femoral vein, internal jugular vein, or subclavian vein. The venous cannula is inserted into the vein to direct the blood into the ECMO circuit.
• The oxygenator in the ECMO circuit oxygenates the blood and removes carbon dioxide. This process provides respiratory support to the patient’s lungs by oxygenating the blood and removing excess CO2.
2. Arterial Cannulation (for Circulatory Support):
• Oxygenated blood is returned to the body through an arterial cannula, which is typically inserted into a femoral artery or subclavian artery. The arterial return helps to support cardiac output, providing circulatory support and assisting the right heart in cases of right ventricular failure or low cardiac output.
3. Cardiac and Pulmonary Support:
• The venous circuit of VVA ECMO ensures respiratory gas exchange, while the arterial circuit provides cardiovascular support, increasing cardiac output and reducing the afterload on the right heart in particular.
• In this hybrid ECMO configuration, the right heart can be supported even if right ventricular function is severely compromised due to pulmonary vascular disease or ischemic injury from the transplant procedure.
4. Ventilator Settings:
• While VVA ECMO provides oxygenation and CO2 removal, the patient is still typically on a mechanical ventilator with lung-protective settings. This means the ventilator is set to deliver low tidal volumes and low airway pressures to minimize ventilator-induced lung injury (VILI), especially since the transplanted lung may still be recovering or in a state of acute rejection or inflammation.
5. Continuous Monitoring and Adjustment:
• The ECMO circuit requires constant monitoring to ensure that blood flow rates, oxygen levels, and ventilation settings are optimal. Adjustments may be necessary based on the patient’s condition, and regular assessments of the patient’s hemodynamics and oxygenation are critical to determine if further interventions, such as weaning from ECMO or re-transplantation, are required.

Benefits of VVA ECMO for Post-Transplant Patients

1. Combined Respiratory and Circulatory Support:
• One of the key benefits of VVA ECMO is its ability to provide both respiratory support (via the venous component) and cardiovascular support (via the arterial component). This is essential for post-lung transplant patients who may have both respiratory failure and cardiovascular instability, especially those with primary graft dysfunction, right heart failure, or severe rejection.
2. Lung Protection:
• By offloading both the lungs and the heart, VVA ECMO allows the new lung to rest and recover, particularly in cases of PGD or ischemic injury. It helps avoid ventilator-induced lung injury (VILI) and reduces high ventilator pressures, which is crucial for protecting the transplanted lung.
3. Right Heart Support:
• VVA ECMO provides right ventricular support, which is critical in cases of right heart failure after lung transplantation. It helps to reduce pulmonary vascular resistance and improve right heart afterload, aiding in circulatory recovery.
4. Bridge to Recovery or Re-transplantation:
• VVA ECMO can serve as a bridge to recovery, allowing time for acute rejection or infection to be treated, or it can be a bridge to lung re-transplantation for patients with failed grafts.
5. Improved Survival Rates:
• Early initiation of VVA ECMO can improve the likelihood of survival in post-lung transplant patients, especially in severe cases of PGD or acute rejection, where conventional treatment alone might be insufficient.

Risks and Challenges of VVA ECMO in Post-Transplant Patients

1. Bleeding Complications:
• Like all forms of ECMO, VVA ECMO requires anticoagulation to prevent clotting in the circuit. This increases the risk of bleeding, including intracranial hemorrhage, gastrointestinal bleeding, and hemorrhage at the cannulation sites. Post-transplant patients are already at higher risk due to the use of immunosuppressive therapies.
2. Infections:
• The use of ECMO increases the risk of infection, particularly in post-transplant patients who are immunocompromised due to medications. This includes hospital-acquired infections or ECMO circuit infections.
3. Vascular Complications:
• The placement of large-bore cannulas for both venous and arterial access can result in vascular injury, thrombosis, or limb ischemia. These complications are particularly concerning for critically ill post-transplant patients, who may have weakened blood vessels.
4. Multi-Organ Failure:
• Prolonged ECMO use can contribute to multi-organ dysfunction, including renal failure or liver dysfunction. Some post-transplant patients may already have compromised organ function due to prolonged ICU stays or pre-existing comorbidities.
5. Weaning Challenges:
• Weaning from ECMO can be difficult, especially in patients with right heart dysfunction or severe lung injury. The weaning process must be carefully managed, as premature attempts to wean can lead to recurrent respiratory failure or cardiovascular collapse.

Outcomes and Prognosis

The prognosis for post-lung transplant patients on VVA ECMO depends on several factors, including:

• Early initiation of ECMO and timely intervention can improve outcomes.
• The severity and cause of the respiratory and circulatory failure.
• Whether the patient responds to treatment for acute rejection, infection, or PGD.
• The patient’s overall health and the presence of other comorbidities.

For patients with severe PGD, right heart failure, or acute rejection, VVA ECMO can provide critical support, but long-term survival is contingent upon successful treatment of the underlying issue and weaning from ECMO.

Conclusion

VVA ECMO offers combined respiratory and circulatory support for post-lung transplant patients who experience severe respiratory failure and cardiovascular compromise. It provides temporary support to allow for recovery, treatment of underlying conditions such as rejection, or a bridge to re-transplantation. However, the technique comes with significant risks, including bleeding, infection, and vascular complications, necessitating careful management and monitoring. When used appropriately, VVA ECMO can be a life-saving intervention for critically ill post-transplant patients.