Extracorporeal Life Support

ECLS is primarily utilized for short-term support of patients with decompensated heart failure who are unresponsive to medical therapy. Adaptations to the traditional cardiopulmonary bypass circuit have resulted in the standard ECLS circuit (Figure 27-2). The ECLS cannulation is initiated by placement of vascular cannulas within the patient’s circulatory system.

Figure 27–2 Extracorporeal membrane oxygenation circuit.

Venoarterial (V-A) ECLS provides both biventricular and typically pulmonary support. It is important to note that complete cardiac support cannot be provided by V-A ECLS because of incomplete drainage of the right heart. Routine cannulation for V-A ECLS occurs via one of three arterial and venous access points: (1) The transcervical approach places the venous cannula in the right atrium via the right internal jugular vein and the arterial cannula in the ascending aorta via the right carotid artery; (2) the transthoracic approach with direct cannulation of the right atrium and aorta through a median sternotomy is utilized for postoperative cardiac patients who either cannot be weaned from cardiopulmonary bypass or require mechanical circulatory assistance in the immediate post-operative period; and (3) femoral artery and vein cannulation is an option for older/larger children via the femoral artery and vein. The transcervical and transthoracic approaches are the preferred methods for small children. Figure 27-3 demonstrates a chest radiograph evaluation of cannula placement in a patient supported by V-A ECLS.

Figure 27–3 Chest radiograph showing extracorporeal membrane oxygenation cannulas.

Venovenous (V-V) ECLS provides pulmonary support without cardiac support. In V-V ECLS a single cannula is placed in the right atrium through a transcervical approach. This cannula provides both inflow and outflow for the circuit. V-V ECLS can improve RV dysfunction as a result of oxygenated, pH-balanced blood flowing to the lungs, thus decreasing pulmonary vascular resistance and right heart afterload. In addition, improved filling of the LV can occur through decreasing RV overdistension. Likewise, the absence of an aortic cannula prevents the increase in LV afterload seen with venoarterial ECLS. However, at times the indirect cardiac effects of V-V ECLS do not adequately improve ventricular dysfunction and conversion from V-V ECLS to V-A ECLS is required. See Table 27-1 for a comparison of V-A versus V-V ECLS.

Table 27–1 Venoarterial vs. Venovenous ECMO

The no membrane oxygenator VAD is an adaptive technique to traditional ECLS that several centers have utilized. This form of ECLS eliminates the oxygenator from the standard circuit configuration. This technique allows for mechanical circulatory support while limiting both the harmful inflammatory effects of the oxygenator and reducing the initial need for anticoagulation.⁵⁷ It allows the ECLS device to be utilized as either an RV assist device, LV assist device, or a biventricular assist device.

Extracorporeal Life Support Circuit

Through either extrathoracic or transthoracic placement, the most common configuration involves placement of a venous drainage cannula in the right atrium where blood is passively drained from the patient to the venous reservoir. Blood then passes through a servoregulated roller-head or centrifugal pump that pumps blood through the remainder of the system. Gas exchange (O₂ addition and CO₂ removal) is provided through an artificial lung (oxygenator) where a sweep gas passes in counter current to the blood, allowing diffusion to occur. Blood temperature is controlled by a countercurrent heat exchanger. Finally, blood is pumped to the body into the aorta at systemic pressure. Additional components include ports for infusion of medications, a hemofilter for fluid control or dialysis, and monitoring systems that regulate gas exchange, flow, and pressure.

Extracorporeal Life Support Physiology

Patient circulatory physiology is altered by the initiation of mechanical circulatory support, and it is important to understand how ECLS affects these patients. Mechanical circulatory support affords recovery of myocardial function through a variety of mechanisms. Alteration of both RV and LV preload and afterload occurs to varying degrees based on which device is utilized and how it is utilized. Some of these alterations can be deleterious. Adequate decompression of the left heart decreases left atrial hypertension and reduces cardiac wall stress, cardiac work, and myocardial oxygen consumption, allowing for improved coronary perfusion. Mechanical circulatory support of the LV allows for reverse molecular remodeling with normalization of heart failure and apoptosis markers, normalized expression of genes involved in calcium homeostasis, cell growth, and differentiation, and up-regulation of structural proteins.⁵⁸ With adequate venous drainage, both right atrial and left atrial pressures are lowered. This effect is important to prevent complications such as pulmonary edema or hemorrhage, pleural effusions, ascites, superior vena cava syndrome, or stroke. Likewise, a low to normal central venous pressure is important for patients who have experienced cardiac arrest and are at risk for ongoing cerebral ischemia as a result of cerebral edema and increased intracranial pressure.

Myocarditis

The clinical course of patients with myocarditis is variable. Some patients present with subclinical disease, others have an indolent course that progresses to dilated cardiomyopathy, and a subset of patients demonstrate fulminant disease. Those with fulminant acute myocarditis often experience a rapidly progressive course leading to death. Without mechanical circulatory support, patients with a fulminant course had expected survival rates of only 25% to 50%.^59–61 With the aggressive utilization of ECLS as a bridge to transplantation or recovery (or VAD if a longer recovery time is anticipated), survival rates for patients with any form of myocarditis are now reported to be as high as 90% to 93%.^62–64 It has been suggested that the institution of ECLS may aid in the normalization of ventricular geometry, a phenomenon that is referred to as reversible remodeling. This process is thought to improve ventricular dysfunction because of favorable influences on the neurohormonal cardiovascular milieu and unloading of the LV.⁶⁵ For patients with the most severe disease, that is, end-stage dilated cardiomyopathy resulting from fulminant myocarditis, the use of mechanical circulatory support without transplantation has resulted in survival rates as high as 67% to 80%.^66–68

Postcardiopulmonary Bypass

Failure to wean from cardiopulmonary bypass occurs in approximately 1% to 3.2% of pediatric congenital cardiac surgery cases.^69–71 Individual institutions have reported survival rates to hospital discharge between 32% and 54% for pediatric patients who require ECLS after cardiac surgery.^70–77 One small series has reported a survival rate as high as 80%.⁶⁹ However, the July 2009 ELSO registry report for postoperative cardiac surgery patients younger than 16 years reported an overall survival rate of only 40%.⁵⁰ All of these patients demonstrate LCOS refractory to medical management as detailed in prior sections. It has been demonstrated that in patients with decompensated heart failure, a rising blood lactate level >0.75 mmol/L/hour on serial measurements despite escalating inotropic support may accurately predict a poor outcome.¹⁰ For this patient population, it is anticipated that cardiac arrest or end-organ dysfunction will occur. The use of mechanical circulatory support is a widely accepted tool to support the vital organs while allowing for myocardial recovery.^78–80 It is imperative that this group of postoperative cardiac patients be evaluated for residual cardiac defects before considering mechanical circulatory support. Diagnostic or interventional cardiac catheterization may guide treatment pathways or be therapeutic. On occasion a patient’s condition may warrant immediate mechanical support in order to safely proceed with cardiac catheterization. In these instances it is feasible to obtain hemodynamic and angiographic data or to perform therapeutic interventions in the cardiac catheterization laboratory. Balloon valvuloplasty or angioplasty of aortic arch obstructions, device closure of residual atrial or ventricular septal defects, coiling of aortopulmonary collateral vessels, and/or balloon or blade atrial septostomy all may be crucial interventions to improve cardiac output and allow for separation from mechanical circulatory support. If these defects cannot be managed in the catheterization laboratory, prompt return to the operating suite will be required. Residual cardiac defects, if left untreated, have been shown to be nearly universally fatal for patients requiring mechanical circulatory support.⁸⁰

The use of ECLS for postcardiotomy support in neonates and infants with single-ventricle physiology remains controversial and continues to be considered a relative contraindication in some centers. The 2009 ELSO report lists a 34% survival rate for ECLS use in patients following the stage I Norwood procedure,⁵⁰ which is lower than for other postcardiotomy patients.^50,81

Extracorporeal Cardiopulmonary Resuscitation

In-hospital cardiac arrest in children continues to be associated with dismal outcomes despite advances in cardiopulmonary resuscitation (CPR). A prospective multicenter observational study from the National Registry of Cardiopulmonary Resuscitation reported a good neurologic outcome for 73% of survivors of an in-hospital cardiac arrest, yet the rate of survival to hospital discharge was only 27%.⁸² Another multicenter observational study from the Pediatric Emergency Care Applied Research Network reviewed in-hospital cardiac arrests that occurred during an 18-month period between 2003 and 2004. It also reported a good neurologic outcome for 76% for survivors and an improved (49%) rate of survival to hospital discharge with the utilization of extracorporeal CPR. Both reviews excluded out-of-hospital, do-not-resuscitate, or neonatal ICU patients.⁸³ However, while neurocognitive outcome has improved for survivors of cardiac arrest, the duration of CPR has been inversely proportional to survival. One center demonstrated that a witnessed in-hospital cardiac arrest of >30-minute duration was universally fatal without the utilization of ECLS.⁸⁴ This knowledge has led to an emerging interest in the use of ECLS for patients who have failed to reestablish a perfusing rhythm and adequate circulation with conventional CPR rescue techniques. The American Heart Association guidelines for in-hospital pediatric cardiac arrest now recommend consideration of ECLS during CPR if the conditions leading to the arrest are likely to be reversible or amenable to heart transplantation.⁸⁵ However, wide variability in patient selection and the ability to institute ECLS in a timely fashion (5 to 176 minutes) has led to variable success reports ranging from 0% to 100%.^86–95 Table 27-3 presents a summary of the current literature on ECPR. Thus large centers have increasingly dedicated resources for the rapid deployment of ECLS, utilizing a team that is immediately available to cannulate with a pre-primed circuit. The 2009 ELSO Registry for neonatal and pediatric patients supported with ECLS following cardiac arrest reported a survival to hospital discharge rate of 38%.⁵⁰

Table 27–3 Summary of Literature for Extracorporeal Cardiopulmonary Resuscitation

Myocardial Failure: Bridge to Transplantation

While heart transplantation is the treatment of choice for patients with end-stage myocardial failure, many children die every year waiting for a suitable organ to become available. As a result, mechanical circulatory support is now increasingly utilized as a bridge to heart transplantation. The most common indications for ECLS as a bridge to transplant include end-stage congenital heart disease, cardiomyopathy, and graft rejection after heart transplantation. To date, no randomized controlled trials have been performed in the pediatric age group to determine if mechanical circulatory support as a bridge to cardiac transplantation confers improved survival for patients with myocarditis. Children with myocardial failure resulting from myocarditis demonstrate increased short-term survival when treated with ECLS and transplantation,⁶⁷ however; long-term survival reports suggest that bridge to transplantation may only be indicated for patients with giant cell or the acute form of myocarditis but not those with the fulminant form.^62–6396

Factors that dictate which mechanical circulatory support device is used include patient size, the need for pulmonary support, and duration of wait time. Complications associated with ECLS generally limit the duration of support with this device to approximately 2 weeks, although support that lasts >4 weeks has been rarely reported. As long as complications precluding transplant have not developed, there should be no arbitrary cutoff for duration of support. A recent review of the United Network for Organ Sharing Database from 1995 to 2005 evaluated both clinical status at transplantation and risk factors for short- and long-term mortality of patients supported with various mechanical circulatory support devices. This study revealed that 30-day survival was significantly decreased for patients who received a bridge to transplant with ECLS versus VAD; long-term (10-year) survival was not affected. Not surprisingly, preoperative severity of illness also predicted early survival following cardiac transplantation. The overall 10-year survival rate was 56.8%.⁹⁷

ECLS has been the mainstay of therapy for small children and neonates in the United States for short-term support (~2 weeks) because of a paucity of devices for this age group. The use of paracorporeal pulsatile assist devices (Berlin Heart and Medos HIA) for neonates in European countries has demonstrated early promising results.^98–100 The utilization of this technology is in its nascent stage in the United States. However, a retrospective review that compared survival outcomes of children supported with ECLS versus Berlin Heart to heart transplantation or recovery at Arkansas Children’s Hospital favored the use of the Berlin Heart (57% vs. 86%).¹⁰¹

Malignant Dysrhythmias

Mechanical circulatory support is an essential therapy for patients with malignant dysrhythmia that is unresponsive to pharmacotherapy. A subset of patients with acute fulminant myocarditis presents with refractory LCOS and dysrhythmia that further compromises end-organ perfusion. If these patients do not rapidly respond to antiarrhythmic agents, many progress to cardiac arrest and death. In this scenario, mechanical circulatory support may be beneficial as a bridge to recovery or transplantation.⁶³ Several potentially lethal tachyarrhythmias, such as supraventricular tachycardia, junctional ectopic tachycardia, or ventricular tachycardia, can occur congenitally or are acquired in the postoperative period as a result of the ingestion of toxic substances or medications.^102–104 Again, ECLS can allow time for resolution of dysrhythmia, for medical treatment to take effect, and/or for recovery of cardiac function.

Refractory Respiratory Failure

Severe neonatal respiratory failure refractory to maximal medical therapy that requires ECLS is the most common indication for ECLS. Diagnoses include meconium aspiration syndrome, congenital diaphragmatic hernia, persistent pulmonary hypertension of the newborn, sepsis, respiratory distress syndrome, or other congenital lung abnormalities. Three randomized controlled trials involving neonates have been conducted and all reported that ECLS improved the survival rate.^53,105–107 It has been reported that of infants treated with ECLS, the proportion of infants with congenital diaphragmatic hernia has been increasing, whereas the proportion with respiratory distress syndrome, meconium aspiration syndrome, and sepsis has been decreasing.¹⁰⁸ However, the overall patient survival for this group remains at 75%.¹ A recent report, the first to perform a systematic comparison of neonatal ECLS practice patterns and respiratory failure deaths between countries, demonstrated distinct differences between the United States and the United Kingdom. It concluded that U.S. clinicians seem more willing to utilize ECLS for persistent pulmonary hypertension of the newborn and congenital diaphragmatic hernia. This difference in practice pattern was correlated with a decrease in the U.S. neonatal death rate from congenital diaphragmatic hernia in comparison with the United Kingdom.¹⁰⁹

During the past 2 decades, successful treatment of pediatric patients with ECLS is increasingly being described in patient groups that would have been excluded in the past. ECLS is now considered for patients with trauma, immunosuppression, underlying bleeding disorders, sickle cell disease, status asthmaticus, pulmonary embolism, established multiple organ system failure, and more. However, reported survival rates are variable. For example, whereas a survival rate of 94% is reported in patients treated with ECLS for refractory status asthmaticus,¹¹⁰ that of immunocompromised patient populations is only 31% to 36%.^111–112 Even of greater concern is that although case reports of survival with good neurologic outcome exist for the hematopoietic stem cell transplant population, review of the ELSO database demonstrates an almost universal fatal outcome for these patients.^113–114 The duration of ECLS required until successful decannulation is often longer for respiratory indications of use. This finding is likely due to the fact that parenchymal lung disease often requires a longer period of recovery than does myocardial dysfunction. The most common diagnosis in the pediatric respiratory ECLS group of patients is acute respiratory distress syndrome. Overall survival for this group of patients remains at 56%.⁵⁰ Although no randomized controlled trials for pediatric patients with refractory respiratory failure have been performed, a prospective, observational study with matched control subjects demonstrated improved survival of ECLS patients when compared with conventional support.¹¹⁵

Contraindications

If a patient has been selected as an appropriate candidate for consideration of mechanical circulatory support, then few absolute contraindications exist. While each institution may have slight variations of this list of contraindications, it is generally accepted that weight <2 kg, irreversible cardiac failure without the option for transplantation, severe neurologic dysfunction, severe intracranial or intraabdominal bleeding, and lethal congenital abnormalities are all absolute contraindications. Technical limitations would include an inability to obtain vascular access as a result of thrombosis, abnormal anatomy, or prior surgery. As previously discussed, when considering a postoperative cardiac patient for mechanical circulatory support, it is prudent to rule out the possibility of a residual cardiac defect. Furthermore, cardiac arrest is not an absolute contraindication if rapid resuscitation is available and the underlying etiology is deemed to be reversible.

Critical Care Management During Extracorporeal Life Support

Patients who require mechanical circulatory support are critically ill, often with loss of multiple end-organ function. It is not surprising that complications occur with a greater frequency for this group of patients than for other critically ill pediatric patients. The basic management principles are discussed in this section. Table 27-4 will be referred to frequently throughout this section because it summarizes the most common reported complications for pediatric patients supported by ECLS as of July 2009.

Table 27–4 Complications of ECMO, ELSO Registry, July 2009

Cardiac Output

When assessing the hemodynamic state of a patient, one must consider to what degree the patient is contributing to cardiac and or pulmonary circulation versus the ECLS device. The amount of flow provided by the ECLS device is easily obtained from circuit monitors, although least accurately from revolutions per minute (rpm)/circuit diameter calculations. For most cardiac ECLS patients, flow is initiated at 120 to 150 mL/kg/min. However, it is important to note that flow should be adjusted to fit the physiologic needs of each patient. Patients with single-ventricle physiology or sepsis may require higher flows approaching 200 mL/kg/min to support their metabolic needs. Assessment of the patient’s intrinsic cardiac output is often unobtainable. However, indirect evaluation of the patient’s cardiac output is possible through assessment of arterial systolic blood pressure, pulse pressure, heart rate, organ perfusion, mixed venous oxygen saturation, and lactic acid levels on a given flow rate. Comparisons of these variables over time allow the clinician to make decisions regarding the adequacy of circulatory support or the readiness to wean from support. An echocardiogram also can provide valuable information and help guide therapy. Mixed venous saturation is measured in the venous return portion of the circuit, with a goal of 65% to 80% in acyanotic patients. However, if a “left-to-right” shunt exists, such as a left atrial vent, the mixed venous saturation will be falsely elevated. In cyanotic patients an arterial venous oxygen saturation difference (Sa-VO₂) of 20% to 25% is typically targeted. Serial lactate measurements often are a helpful aid in the assessment of total end-organ perfusion. A delay in clearance may occur in patients with ongoing hepatic dysfunction, sepsis, low CO, and end-organ hypoperfusion. An approximation of the relative contributions of the patient and circuit pulmonary parameters is possible. This assessment is permitted through analysis of serial patient and circuit blood gas assays such as pH, PCO₂, and PaO₂, with consideration of the mechanical ventilation settings (includes fraction of inspired oxygen [FIO₂] and PEEP), circuit flow rate, CO₂ sweep rate, and circuit oxygen concentration.

Finally, “shunts” within the patient or the circuit must be taken into consideration. An example of a “right-to-left” patient shunt includes a patient with a patent ductus arteriosus and pulmonary artery hypertension, or an atrial septal defect or ventricular septal defect with pulmonary artery hypertension or RV outflow tract obstruction. Circuit “left-to-right” shunts are generally limited to a left atrial vent, the hemodialysis filter, and continuous arterial blood gas devices. Patient shunts that have the potential to be bidirectional, such as a patent ductus arteriosus or an intracardiac shunt, typically confound analysis. For these reasons an optimal cardiac repair with closure of residual “defects” should be performed prior to institution of mechanical circulatory support or early within the course of treatment. Therefore total blood flow for the patient on mechanical circulatory support requires the addition of ECLS circuit flow with the patient’s native cardiac output minus any “shunt” within the system as a whole.