**3. Indications and contraindications for VA-ECMO**

The major indication for VA-ECMO is cardiogenic shock as defined in the ELSO guidelines [14]. This includes inadequate tissue perfusion due to hypotension and low cardiac output despite volume repletion, inotropes, vasopressors, and intraaortic balloon counterpulsation use. Common causes for cardiogenic shock are acute myocardial infarction (AMI), myocarditis, peripartum cardiomyopathy, acute decompensation of chronic heart failure, and postcardiotomy shock.

Septic shock is an indication in some centers. The guidelines on prognostication of survival without ECMO are based on the IABP score in postcardiotomy patients [15] and the Samuels score also in postcardiotomy patients [16]. In a retrospective analysis, Samuels et al. [16] showed that early insertion of mechanical support reduces multi-organ failure in these patients. In hospital mortality, correlates with increasing inotropic support needed to get patients off cardiopulmonary bypass following cardiac surgery. The combination of pharmacological criteria together with hemodynamic presentation should be used for mechanical support initiation in cardiogenic shock. Earlier institution of mechanical support devices tends to lower incidence of postoperative multi-organ failure and improve discharge rates [16].

The advantage of VA-ECMO is that it provides quick biventricular support and can be achieved at the bedside for poor oxygenation, biventricular failure, refractory malignant arrhythmias, and heart failure with severe pulmonary failure. VA-ECMO can be used as a bridge to recovery, AMI after revascularization, myocarditis, postcardiotomy shock, chronic heart failure, and non-revascularizable AMI.

*Advances in Extracorporeal Membrane Oxygenation - Volume 3*

failure cardiologists.

**2. The ECMO circuit**

influenza patients [7]. Anselmi et al. recently reported the use of ECMO in pregnant patients [8]. Increasing utilization of ECMO in adults has revealed some of the common complications such as bleeding and coagulopathy which impact survival in this patient population. The delicate balance between adequate anticoagulation and bleeding complications presents one of the greatest challenges of ECMO therapy today. The ELSO (Extracorporeal Life Support Organization) was established in 1989. The ELSO was formed as an offshoot of a study group that began in 1984 discussing cases. The ELSO focuses on collection and sharing of data and has fostered a rich collaboration among the majority of centers performing ECMO. The ELSO has hence remained a good resource for surgeons, neonatologists, nurses, perfusionists, respiratory therapists, biomedical engineers, critical care physicians, and heart

A total of 73,000 ECMO procedures were recorded by the ELSO as of early 2016 of which greater than 25% were performed in adult patients [9]. From 2006 to 2011, adult ECMO volumes increased greater than four times in the United States [10]. Adult ECMO has increased in volume due to its usefulness in improving survival in ARDS (acute respiratory distress syndrome) patients [11]. Additionally, with the improvement in technology, highly specialized hospitals have evolved the capabilities to transport critically ill patients from rural areas to their critical care units making it possible for rural populations to be able to receive advanced care [12, 13]. This review will focus on the venoarterial ECMO system and its use as a bridge

The ECMO circuit (**Figure 1**) in its most basic form consists of a pump that is capable of pumping blood it receives from the drainage cannula to the membrane oxygenator which then leads to a heat exchanger. The oxygenated temperatureoptimized blood is then returned to the patient by the return cannula. ECMO cannulation can be done centrally through the right atrium and ascending aorta or peripherally via the femoral artery and vein. The type of cannulation used whether central or peripheral influences the outcomes as the complications differ. When central cannulation is used, bleeding requiring transfusions is higher. In central cannulation higher rates of reoperation are also noted. Increased complications will decrease survival and increase resource utilization. On the other hand, peripheral cannulation has been noted to produce fewer bleeding complications. It can be

to other long-term durable devices and/or cardiac transplantation.

**144**

**Figure 1.** *VA-ECMO circuit.*

ECMO can be used as a bridge to cardiac transplant as well as durable mechanical circulatory support: ventricular assist device (VAD) and the total artificial heart (TAH).

The absolute contraindications for VA-ECMO would be unrecoverable heart and the patient not being a candidate for cardiac transplant or VAD. Chronic organ dysfunctions such as emphysema, cirrhosis, and end-stage renal failure are all considered absolute contraindications. Compliance in terms of financial and medical strategies and cognitive, psychiatric, or social limitations are considered contraindications. Prolonged CPR without adequate tissue perfusion is also an absolute contraindication.

The relative contraindications for ECMO would be inability to tolerate anticoagulation, advanced age, and obesity. Advanced age is a gray area as there are no defined cutoffs due to lack of existing data in older patients.

## **4. Complications during VA-ECMO support**

Complications encountered during ECMO support include lack of a fine balance between anticoagulation and bleeding, limb ischemia, disseminated intravascular coagulation (DIC), heparin-induced thrombocytopenia (HIT), bleeding from a preexisting surgical site requiring reexploration, and progression of preexisting renal failure.

#### **4.1 Anticoagulation and bleeding**

Interaction of blood with non-endothelial surfaces leads to inflammation and prothrombosis. ECMO therefore leads to consumptive coagulopathy as well as a dilution of coagulation factors resulting in decreased fibrinogen levels. The inflammatory response secondary to ECMO gives rise to a hypercoagulable state, requiring anticoagulation to prevent thrombosis of the circuit. The delicate balance between adequate anticoagulation and bleeding complications presents one of the greatest challenges of ECMO therapy today. Different anticoagulation protocols are used across the centers. Uniformity in these protocols is lacking [17].

ECMO has historically been the mainstay of resuscitation in pediatric care. Adult ECMO protocols have hence evolved from the pediatric practice of anticoagulation in ECMO. Higher flow and larger cannula sizes in adult ECMO contribute less to turbulence, stasis, and thrombogenicity. Simple circuits with minimum number of connectors create less turbulence, while larger cannulas especially on the venous side reduce stasis and thrombogenicity, therefore requiring lower levels of anticoagulation. This suggests that anticoagulation protocols used in the pediatric population may not be optimal in adults.

Survival on ECMO appears to be more favorable in the younger population, and bleeding and coagulopathy appear to be the most common complications which raise the question if the coagulation system changes in its character and dimensions with advancing age. Interestingly, aging is accompanied by increases in plasma concentrations of factors VII and VIII and fibrinogen progressively [18, 19]. Coagulation cascade upregulation with age may increase thrombosis in pathological states demanding special attention when designing anticoagulation therapy for adult and especially older patients on ECMO.

Genetic polymorphisms and ethnic variations further complicate and influence drug metabolism and efficacy which need to be accounted for while developing anticoagulation protocols and selecting anticoagulants [20]. Clinical significance

**147**

*Extracorporeal Membrane Oxygenation as a Bridge to Cardiac Transplantation*

but needs further research for specific delineation of inciting factors.

and predictive value of hypercoagulability markers need to be defined in different age groups in prospective studies in order to be able to define optimal anticoagulation regimens. Research is needed in areas of optimizing anticoagulation protocols in adults with respect to age, gender, race, ethnicity, and technical aspects. If tailored appropriately adult ECMO therapy could probably achieve better success with far less aggressive anticoagulation than that used in the pediatric population.

Though centrifugal pumps are increasingly used, they are not without disadvantages. Centrifugal pumps are continuous flow pumps (CF pumps) and produce shear stress leading to acquired von Willebrand factor deficiency and bleeding complications. A recent retrospective analysis demonstrated an increased risk for nonsurgical bleeding (gastrointestinal, pulmonary, and neurological) with centrifugal pumps despite lower levels of heparin anticoagulation [21]. This study used patients supported on ECMO for 5 days for comparison of bleeding complications using centrifugal and roller pumps. The underlying etiology can be multifactorial

Femoral arterial cannulation carries an increased risk of profound distal limb ischemia. Some of the causes that lead to lower limb ischemia during ECMO support are acute embolism, dissection/perforation or rupture of the common femoral artery (CFA) or the iliac artery, thrombosis, pseudoaneurysm, hyperperfusion, and ischemia after decannulation usually due to distal embolization [22]. This problem has been solved to a large extent by prophylactically placing an ipsilateral perfusion catheter [22]. In a small study using 43 patients who underwent femoral artery cannulation, placement of a prophylactic superficial femoral artery [SFA] catheter in ten patients produced no limb ischemia. Of the rest of the patients (n = 33) who did not receive prophylactic SFA cannulation, seven patients had limb ischemia. Four of these patients underwent fasciotomy and decannulation leading to amputation in one patient. The three patients who received SFA cannulation for limb ischemia did not need amputation [23]. Foley et al. also showed that age was a predictor for limb ischemia [23]. Patients who developed limb ischemia were significantly younger than those patients without limb ischemia. This has been attributed to the size of the arterial cannula with respect to the femoral artery size in younger patients. CFA diameter was noted to increase with age. It was considered to be related to BSA and gender with increasing diameters found in males and those who have a larger BSA [24]. However, the data presented by Foley et al. found no correlation between the rate of limb ischemia and BSA, BMI, or size of the cannula as compared to the

Accurate insertion of the arterial cannula in the CFA is of paramount importance to minimize risk of ipsilateral limb ischemia. One of the important aspects is to avoid improper retrograde SFA cannulation leading to significant flow limitation and in extreme cases to complete occlusion. Additionally, measurement of pressure in the SFA after placing the patient on ECMO support will identify the patients who actually need a catheter for antegrade perfusion [25]. Such an approach may reduce the extra effort and insertion of an additional catheter in all patients

Considering the limited data in the current literature, the use of prophylactic SFA cannulation in younger individuals may be a reasonable approach with or

*DOI: http://dx.doi.org/10.5772/intechopen.84935*

**4.2 Roller versus centrifugal pumps**

**4.3 Limb ischemia**

earlier literature [23, 24].

prophylactically.

*Extracorporeal Membrane Oxygenation as a Bridge to Cardiac Transplantation DOI: http://dx.doi.org/10.5772/intechopen.84935*

and predictive value of hypercoagulability markers need to be defined in different age groups in prospective studies in order to be able to define optimal anticoagulation regimens. Research is needed in areas of optimizing anticoagulation protocols in adults with respect to age, gender, race, ethnicity, and technical aspects. If tailored appropriately adult ECMO therapy could probably achieve better success with far less aggressive anticoagulation than that used in the pediatric population.

#### **4.2 Roller versus centrifugal pumps**

Though centrifugal pumps are increasingly used, they are not without disadvantages. Centrifugal pumps are continuous flow pumps (CF pumps) and produce shear stress leading to acquired von Willebrand factor deficiency and bleeding complications. A recent retrospective analysis demonstrated an increased risk for nonsurgical bleeding (gastrointestinal, pulmonary, and neurological) with centrifugal pumps despite lower levels of heparin anticoagulation [21]. This study used patients supported on ECMO for 5 days for comparison of bleeding complications using centrifugal and roller pumps. The underlying etiology can be multifactorial but needs further research for specific delineation of inciting factors.

#### **4.3 Limb ischemia**

*Advances in Extracorporeal Membrane Oxygenation - Volume 3*

defined cutoffs due to lack of existing data in older patients.

across the centers. Uniformity in these protocols is lacking [17].

**4. Complications during VA-ECMO support**

(TAH).

contraindication.

renal failure.

**4.1 Anticoagulation and bleeding**

population may not be optimal in adults.

adult and especially older patients on ECMO.

ECMO can be used as a bridge to cardiac transplant as well as durable mechanical circulatory support: ventricular assist device (VAD) and the total artificial heart

The absolute contraindications for VA-ECMO would be unrecoverable heart and the patient not being a candidate for cardiac transplant or VAD. Chronic organ dysfunctions such as emphysema, cirrhosis, and end-stage renal failure are all considered absolute contraindications. Compliance in terms of financial and medical strategies and cognitive, psychiatric, or social limitations are considered contraindications. Prolonged CPR without adequate tissue perfusion is also an absolute

The relative contraindications for ECMO would be inability to tolerate anticoagulation, advanced age, and obesity. Advanced age is a gray area as there are no

Complications encountered during ECMO support include lack of a fine balance between anticoagulation and bleeding, limb ischemia, disseminated intravascular coagulation (DIC), heparin-induced thrombocytopenia (HIT), bleeding from a preexisting surgical site requiring reexploration, and progression of preexisting

Interaction of blood with non-endothelial surfaces leads to inflammation and prothrombosis. ECMO therefore leads to consumptive coagulopathy as well as a dilution of coagulation factors resulting in decreased fibrinogen levels. The inflammatory response secondary to ECMO gives rise to a hypercoagulable state, requiring anticoagulation to prevent thrombosis of the circuit. The delicate balance between adequate anticoagulation and bleeding complications presents one of the greatest challenges of ECMO therapy today. Different anticoagulation protocols are used

ECMO has historically been the mainstay of resuscitation in pediatric care. Adult ECMO protocols have hence evolved from the pediatric practice of anticoagulation in ECMO. Higher flow and larger cannula sizes in adult ECMO contribute less to turbulence, stasis, and thrombogenicity. Simple circuits with minimum number of connectors create less turbulence, while larger cannulas especially on the venous side reduce stasis and thrombogenicity, therefore requiring lower levels of anticoagulation. This suggests that anticoagulation protocols used in the pediatric

Survival on ECMO appears to be more favorable in the younger population, and bleeding and coagulopathy appear to be the most common complications which raise the question if the coagulation system changes in its character and dimensions with advancing age. Interestingly, aging is accompanied by increases in plasma concentrations of factors VII and VIII and fibrinogen progressively [18, 19]. Coagulation cascade upregulation with age may increase thrombosis in pathological states demanding special attention when designing anticoagulation therapy for

Genetic polymorphisms and ethnic variations further complicate and influence drug metabolism and efficacy which need to be accounted for while developing anticoagulation protocols and selecting anticoagulants [20]. Clinical significance

**146**

Femoral arterial cannulation carries an increased risk of profound distal limb ischemia. Some of the causes that lead to lower limb ischemia during ECMO support are acute embolism, dissection/perforation or rupture of the common femoral artery (CFA) or the iliac artery, thrombosis, pseudoaneurysm, hyperperfusion, and ischemia after decannulation usually due to distal embolization [22]. This problem has been solved to a large extent by prophylactically placing an ipsilateral perfusion catheter [22]. In a small study using 43 patients who underwent femoral artery cannulation, placement of a prophylactic superficial femoral artery [SFA] catheter in ten patients produced no limb ischemia. Of the rest of the patients (n = 33) who did not receive prophylactic SFA cannulation, seven patients had limb ischemia. Four of these patients underwent fasciotomy and decannulation leading to amputation in one patient. The three patients who received SFA cannulation for limb ischemia did not need amputation [23]. Foley et al. also showed that age was a predictor for limb ischemia [23]. Patients who developed limb ischemia were significantly younger than those patients without limb ischemia. This has been attributed to the size of the arterial cannula with respect to the femoral artery size in younger patients. CFA diameter was noted to increase with age. It was considered to be related to BSA and gender with increasing diameters found in males and those who have a larger BSA [24]. However, the data presented by Foley et al. found no correlation between the rate of limb ischemia and BSA, BMI, or size of the cannula as compared to the earlier literature [23, 24].

Accurate insertion of the arterial cannula in the CFA is of paramount importance to minimize risk of ipsilateral limb ischemia. One of the important aspects is to avoid improper retrograde SFA cannulation leading to significant flow limitation and in extreme cases to complete occlusion. Additionally, measurement of pressure in the SFA after placing the patient on ECMO support will identify the patients who actually need a catheter for antegrade perfusion [25]. Such an approach may reduce the extra effort and insertion of an additional catheter in all patients prophylactically.

Considering the limited data in the current literature, the use of prophylactic SFA cannulation in younger individuals may be a reasonable approach with or

without direct SFA pressure measurements especially if it can be done at the bedside. Duplex ultrasonography or direct SFA pressure measurements done at the time of ECMO placement may be an alternative to an early decision on which patients need the SFA cannulation. The existing literature does not seem to report a direct correlation with mortality in these patients which is another area of investigation that needs future attention.
