Introduction

Advances in mechanical circulation have resulted in improvements in both survival and quality of life for an increasing number of patients with advanced heart failure.¹ Despite this, cardiogenic shock remains a condition with high mortality. Prompt identification and resuscitation of patients has a marked impact on improving outcomes.^2,3 Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an established strategy for cardiopulmonary support with increasing use in patients with cardiovascular collapse. However, this modality requires a higher level of care and traditionally has remained underutilized. This Expert Analysis article reviews indications, adverse effects, and management strategies for VA-ECMO.

In contrast to veno-venous ECMO, for which the primary focus is gas exchange, VA-ECMO allows for blood to be drained from a central vein and returned to the arterial system. This allows for both respiratory and circulatory support.³ Above all else, prompt recognition of clinical deterioration, pathology, and initiation of VA-ECMO in appropriate candidates portends the greatest chance for survival.⁴

The initiation of VA-ECMO is a high-risk intervention. Despite increasing indications and success with cardiac support, careful consideration should always be given before initiating an ECMO circuit. Contraindications for VA-ECMO in cardiac failure do exist and include the following: unrecoverable cardiac function, patients who are not candidates for transplantation or durable mechanical support, chronic organ dysfunction (emphysema, cirrhosis, renal failure), prolonged cardiopulmonary resuscitation (CPR) without adequate tissue perfusion, and those with compliance limitations (financial, cognitive, psychiatric, and social limitations). Physicians should consider patient prognosis, co-morbidities, and weaning strategies before undertaking the endeavor of supporting a patient on VA-ECMO. Guidelines and recommendations for use and maintenance are sparse. However, the Extracorporeal Life Support Organization (ELSO) is an international consortium focusing on all forms of ECMO, including published guidelines on VA-ECMO in cardiac failure.⁵

Indications for VA-ECMO

The classic indication for VA-ECMO is cardiogenic shock, defined by decreased cardiac output and myocardial contractility resulting in tissue hypoperfusion.³ This can result from either an acute event, such as a large myocardial infarction (MI), or worsening of a chronic ischemic or cardiomyopathic process. Though randomized data does not exist, non-randomized studies suggest that use of VA-ECMO in acute MI complicated by cardiogenic shock improves in-hospital survival and reduces 30-day mortality when used in conjunction with revascularization.^6,7

Cardiogenic shock can also occur as a result of a non-ischemic process. The most common non-ischemic etiologies include fulminant myocarditis and sepsis-associated cardiomyopathy. Patients with fulminant myocarditis bridged to recovery with VA-ECMO may have outcomes similar to myocarditis patients without shock.⁸ Data for VA-ECMO in mixed cardiogenic and septic shock is less robust, though a role may exist in patients for whom benefits of advanced cardiac support outweigh the risks of bleeding and thrombosis.⁹ Finally, VA-ECMO can also successfully be used in post-cardiotomy shock when it has successfully been used in patients who are unable to immediately be weaned from cardiopulmonary bypass.

With improved outcomes, indications have also expanded. More recently, patients with pulmonary hypertension and pulmonary embolism with right heart failure have also emerged as candidates for VA-ECMO. In these patients, VA-ECMO can be used as a bridge to more definitive treatment, such as thrombectomy, particularly when decompensation occurs acutely.

Assistance with CPR using VA-ECMO, known as extracorporeal CPR (E-CPR), is yet another use of VA-ECMO to assist in restoring circulation during cardiac arrest when used in conjunction with algorithmic life support strategies. Data show improved in-hospital survival and survival free of major neurologic impairment up to two years when VA-ECMO is used in conjunction with CPR in highly selected patients.^10,11

In addition to shock, VA-ECMO has an expanding role in Class IV/stage D heart failure. Similar to utilization in post-cardiotomy shock, VA-ECMO has also been used with success in patients post heart transplantation with primary graft dysfunction and myocardial rejection with hemodynamic instability. In these cases, early initiation of VA-ECMO has been shown to have more favorable patient outcomes.¹² While mortality for patients with primary graft dysfunction is high, patients supported early by VA-ECMO who survive past the initial event can have comparable survival rates to transplant recipients without primary graft dysfunction.¹³

Finally, VA-ECMO has also been used with success as a bridge to left ventricular assist device (LVAD) implantation or cardiac transplantation in patients with terminal heart failure. It can also be used as a bridge to decision in a rapidly decompensating patient in whom prognosis may be uncertain.^15,16 The use of VA-ECMO extends to postoperative management of LVAD patients, particularly in those with critical right heart failure. Here, the use of VA-ECMO can allow for cardiac support while the right ventricle adapts to hemodynamic changes after LVAD implantation.¹⁷

Adverse Events

As discussed, the greatest predictor of outcomes for VA-ECMO is prompt recognition and initiation of this technology. However, utilization of VA-ECMO must be carefully weighed against possible complications. The most common adverse events involve bleeding and thrombosis. Anticoagulation is a cornerstone of management for VA-ECMO to prevent circuit thrombosis. Though no standard targets for anticoagulation exist, a suggested activated partial thromboplastin time (aPTT) of 60-80 seconds is customary to prevent circuit thrombosis. In patients in whom the risk of bleeding may be higher, an aPTT goal of 40-60 seconds can be used. For patients with lower anticoagulation targets, the flow through the circuit should be maximized to reduce the chance of thrombosis.

Contributing to the bleeding and thrombotic risks are the hematologic consequences of maintaining an ECMO circuit, including hemolysis, acquired von Willebrand factor deficiency, and thrombocytopenia. These, along with an increased risk of disseminated intravascular coagulation and heparin-induced thrombocytopenia (with or without thrombosis) all add to the burden of hematologic complications for patients maintained on ECMO. Due to the high propensity for thrombus formation, knowledge of potential intra-atrial communication sites, such as atrial septal defects or a patent foramen ovale, is important for adjustment of anticoagulation to mitigate stroke risk and minimize consequences of thromboembolism.

After bleeding and thrombosis, infection remains the most significant complication related to the use of VA-ECMO. Sterile techniques and controlled implantation (operating room, cardiac catheterization suite) portend greater success in comparison to emergent initiation. Prolonged use of VA-ECMO also leads to a greater risk of infection. This is presumed to be from a greater duration of indwelling catheters; additionally, patients who require prolonged support with VA-ECMO also tend to suffer from critical illness and multi-organ dysfunction, putting them at a greater risk for infection.¹⁸ Continued antibiotic prophylaxis after initiation of VA-ECMO (with an intravenous first generation cephalosporin) remains an option to prevent catheter site-related infections, but its utility in the prevention of systemic infections remains controversial.

Limb ischemia is also a known complication of VA-ECMO. Cannula size and positioning in relation to the patient's vasculature plays a major role with this. In addition to limb ischemia, compartment syndrome resulting in muscle necrosis, acidosis and lower extremity amputation, can also occur. The use of a reperfusion catheter to perfuse distal to the entry site of ECMO cannulas increases the likelihood of limb preservation.¹⁹ This can be done either via a surgical end-to-side graft from the ECMO circuit into the superficial femoral artery, or through a catheter-based insertion of a reperfusion cannula via retrograde insertion from distal limb vessels.

As time on a VA-ECMO circuit increases, left ventricular distention is more likely to occur. VA-ECMO creates a large amount of afterload for the left ventricle (LV) to work against. This can commonly lead to LV distention and, subsequently, pulmonary edema. Various strategies have been used to assist in LV decompression for patients on ECMO. These can include intra-aortic balloon pumps, catheter-based pumps, creation of an atrial septostomy, or direct left ventricular decompression, the latter of which requires operating room placement and can be seen with the use of VA-ECMO in post-cardiotomy shock. Frequent echocardiograms, daily chest radiography, and close monitoring of hemodynamics can assist in identifying LV distention and worsening pulmonary edema to help in timing of LV decompression.

Management Strategies

There are no randomized controlled trials available for management strategies regarding VA-ECMO. However, there are management strategies that are accepted in the use of patients who require this therapy.^2,5 While initiation of VA-ECMO can occur at non-tertiary care sites, it is recommended that when possible, discussions between community providers and tertiary sites occur early when patients with impending cardiovascular collapse are identified. If possible, based on hemodynamic stability, early transfer of patients to tertiary care sites even prior to initiation of VA-ECMO is preferred. If unable, transfer to a higher care facility early after implantation is highly recommended for ongoing management and transition towards decannulation.

The continuous bedside presence of a cardiac perfusionist for oversight and management of the ECMO circuit is highly recommended because physician providers are not constantly at the bedside, and other care providers must focus on critical care tasks. Thus, the presence of a perfusionist to focus on ECMO-based parameters, including anticoagulation, gas exchange targets, cardiac outputs, and circuit temperatures, makes a profound impact on patient care with VA-ECMO.

Early after initiation of VA-ECMO, cardiac output should be targeted towards maintaining end organ perfusion. Ideally, this can be achieved solely with the VA-ECMO circuit by adjusting the revolutions per minute on the circuit in order to maximize perfusion to facilitate recovery from the circuit. At times, supplementation with inotropes based on other hemodynamic parameters (mean arterial pressure, systemic vascular resistance) may be necessary. Additionally, the majority of patients on VA-ECMO will be intubated and ventilated, particularly early after cannulation. Matching oxygenation with ventilation for ECMO requires meticulous and frequent analysis of hemodynamics and arterial blood gases. This is the cornerstone of management that a bedside perfusionist can oversee in concert with the ECMO physician and team.

As alluded to previously, anticoagulation is a cornerstone, and potential pitfall of any ECMO circuit. Though an aPTT in the 60-80 range is the starting target for anticoagulation, this can be adjusted, either higher or lower, based on patients' individualized needs and risk profile. In conjunction with this, hemolysis associated with ECMO circuits will, over time, cause anemia that may warrant blood product transfusion. Goals for transfusion, particularly of packed red blood cells, must be weighed against the overall individualized treatment plan for each patient.

In someone who may eventually be a transplant candidate, judicious use of transfusion products is recommended, such that allosensitization can be minimized to improve post-transplant related outcomes. This particularly applies to platelet transfusions. Routine platelet transfusions are from pooled or multi-donor sources. Each unit of multi-donor platelets has the potential for exposing a patient on VA-ECMO to many human leucocyte antigens, which may significantly increase the risk of allosensitization. In patients with a high likelihood of moving towards transplantation, single donor platelets may be considered to minimize allosensitization, though the option of single donor platelets comes at an additional expense and rarity and should be reserved for specific cases.

As with any technology used in critically ill patients, end-of-life discussions regarding resuscitation status, targets of therapy, and prognosis are essential. Daily updates and up-front discussions with family members are crucial when caring for a patient on VA-ECMO. A palliative care consultation, when available, should be initiated early in the process, ideally even prior to initiation of the ECMO circuit.²⁰

Conclusions

VA-ECMO is a proven strategy for supporting patients with cardiovascular collapse as a bridge to recovery or more definitive therapies. Initiation should be carefully considered in select patients. Early transfer and co-management with tertiary care sites with experience in caring for Class IV/stage D advanced heart failure patients is beneficial. Management strategies and targets must be carefully monitored as patients are transitioned to recovery or more definitive therapies to avoid complications.

Table 1: Indications for Veno-Arterial ECMO

• Cardiogenic shock: with or without MI
• Fulminant myocarditis
• Pulmonary hypertension and right heart failure
• Pulmonary embolus with hemodynamic compromise
• Cardiac arrest (assisted CPR)
• Medication overdose
• Non ischemic cardiomyopathy including sepsis induced cardiomyopathy
• Bridge to decision for transplant or VAD (LVAD/BiVAD)
• Support post cardiac surgery

Table 2: Common Complications of VA-ECMO (in Percent)

• Thrombosis: 1-22%
• Bleeding and coagulopathy, including hemolysis: 5-79%
• Limb ischemia: 13-25%
• Infection: 17-49%
• Neurologic events: 10-33%

TABLE 3: Targets for Initial Treatment (Adapted from Lafc, et al)²¹

• Flow: 60-80 cc/kg/min
• FiO₂: 100%
• SaO₂: 100%
• MvO₂: 60-75%
• SpO₂: 95-100%
• pCO₂: 35-45 mm Hg
• MAP: 60-90 mm Hg
• pH: 7.35-7.45
• Platelet count: greater than 80,000
• Hematocrit: greater than 28%

References

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Keywords: Acidosis, Amputation, Anemia, Antibiotic Prophylaxis, Arterial Pressure, Blood Platelets, Cardiac Catheterization, Cardiac Output, Cardiac Surgical Procedures, Cardiopulmonary Bypass, Cardiopulmonary Resuscitation, Catheterization, Catheters, Indwelling, Cephalosporins, Cognition, Compartment Syndromes, Critical Care, Critical Illness, Disseminated Intravascular Coagulation, Embolism, Emphysema, Erythrocytes, Extracorporeal Membrane Oxygenation, Femoral Artery, Foramen Ovale, Patent, Gases, Heart Arrest, Heart Failure, Heart Transplantation, Heart Ventricles, Heart-Assist Devices, Hematocrit, Hemolysis, Heparin, Hypertension, Pulmonary, Myocarditis, Palliative Care, Partial Thromboplastin Time, Platelet Count, Platelet Transfusion, Primary Graft Dysfunction, Prognosis, Pulmonary Edema, Pulmonary Embolism, Renal Insufficiency, Resuscitation, Shock, Cardiogenic, Shock, Septic, Stroke, Tertiary Healthcare, Thrombectomy, Thrombocytopenia, Thromboembolism, Thrombosis, Transplantation, Vascular Resistance, von Willebrand Factor

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