18: Extracorporeal Life Support in the Neonate

Extracorporeal life support (ECLS) provides oxygen (O₂) delivery, carbon dioxide (CO₂) removal, and cardiac support in patients who have cardiac and/or respiratory failure by draining blood from the right atrium through a cannula with the aid of a pump and then propelling blood through an oxygenator, where gas exchange occurs. From there, it is returned to the patient into the aorta (venoarterial [VA]) or right atrium (venovenous [VV]) (Figures 18–1, 18–2, and 18–3). Uniform guidelines have been established to describe essential equipment, procedures, personnel, and training required for ECLS and can be found in the ECMO Specialist Training Manual published by the Extracorporeal Life Support Organization. (Note: The term extracorporeal membrane oxygenation [ECMO] has generally been replaced by ECLS, reflecting an expanded role beyond oxygenation for this technology.)

ECLS is used primarily for critically ill term and late preterm newborns with reversible respiratory and/or cardiac failure who have failed appropriate maximal medical management with ventilator support (conventional or high frequency), inhaled nitric oxide, volume expansion, or inotropic/vasopressor support. Neonatal conditions treated with ECLS support include meconium aspiration syndrome, congenital diaphragmatic hernia, persistent pulmonary hypertension of the newborn, respiratory distress syndrome, sepsis, and pneumonia. ECLS can be used to support patients with cardiac failure owing to congenital heart disease, postcardiotomy heart failure, cardiomyopathy, or severe rhythm disturbances and may be used as a bridge to cardiac transplantation.

1. Weight ≥1.6–1.8 kg; gestational age ≥32–34 weeks. The cannula size is determined by the infant's weight; the lower limit in weight is based on the limitation of cannula sizes available.

2. Respiratory criteria

   1. Oxygenation index (OI). Historically, an OI >30–40 for 0.5–4 hours was routinely used to determine the severity of illness and establish when a neonate was felt to be at high risk for death if not treated with ECLS. Although OI levels can be helpful in establishing a trend, most centers rely on additional parameters to guide their decisions to initiate ECLS, including the inability to wean from 100% oxygen within a period of time and/or ongoing hypotension or metabolic acidosis.

      

      (Fio₂, fraction of inspired O₂; MAP, mean airway pressure; Pao₂, partial pressure of oxygen, arterial)

   2. Acute deterioration with intractable hypoxemia. Patients who have a Pao₂ <30–40 mm Hg or a preductal SaO₂ <80% for greater than an hour and are not responding to conventional therapies should be considered for ECLS support.

   3. Barotrauma. Severe air leak from pneumothoraces that are not responsive to low tidal volume conventional ventilation or high-frequency oscillatory or jet ventilation may benefit from lung rest on ECLS.

3. Cardiovascular/oxygen delivery criteria

   1. Plasma lactate levels >5 mmol/L (45 mg/dL). Patients with a metabolic acidosis not improving, or escalating, despite volume expansion and inotropic/vasopressor support can be supported with ECLS.

   2. Mixed venous oxygen saturations (SvO₂) <55–60% for 0.5–1 hour. Low SvO₂ levels indicate a critical level of O₂ extraction and suggest an increased metabolic stress. With further decreases in SvO₂ levels, there is impending risk of cellular death if not reversed.

   3. Cardiac arrest. ECLS during cardiopulmonary resuscitation (extracorporeal cardiopulmonary resuscitation [ECPR]) is available in many centers for patients with or without primary heart disease in situations in which the cardiac arrest is witnessed.

Decisions for determining contraindications to ECLS are institution based.

1. Gestational age <32–34 weeks and/or a birthweight <1600–1800 g due to the risk of intracranial hemorrhage and surgical difficulties with vessel cannulation. Lower birthweight and gestational age infants are at risk for increased mortality and morbidity. With current technology requiring the use of systemic heparinization during ECLS, there is concern for a higher risk of intracranial hemorrhage in patients <32 weeks. Despite size limitations in preterm infants, newer technologies and smaller cannulae sizes are being developed, which may allow ECLS support at younger gestational ages and in smaller weight categories.

2. Mechanical ventilation >14 days due to the likelihood of irreversible lung disease.

3. Intracranial hemorrhage >grade II due to a higher risk of extending the hemorrhage. Those with an intracranial hemorrhage >grade II may be considered candidates for ECLS on an individual basis.

4. Severe congenital anomalies incompatible with long-term survival.

5. Cardiac lesions that cannot be corrected or palliated.

6. Congenital diaphragmatic hernia patients with best OI >45 or who have never had a preductal saturation >85% or Paco 2 <70. See references that follow.

7. Marked perinatal asphyxia

   1. Severe neurologic syndrome persisting after respiratory and metabolic resuscitation (stuporous, flaccid, and absent primitive reflexes).

   2. High plasma lactate levels

      1. Lactate levels >25 mmol/L (225 mg/dL) are highly predictive of death.

      2. Lactate levels >15 mmol/L (135 mg/dL) are highly predictive of adverse neurologic outcome.

   3. Base deficit >30 on 2 ABGs.

8. Multiple organ dysfunction syndrome in neonates can develop when there has been an acute sepsis, hypoperfusion, or hypoxia and may be preceded by a systemic inflammatory response. Neonates can often have respiratory failure, metabolic acidosis, a coagulopathy that doesn't resolve with transfusion therapy, and cardiac, renal, and gastrointestinal dysfunction. If a neonate has such significant multiple organ dysfunction that they are not likely to survive, ECLS may not provide any benefit.

Patients should optimally be transferred early in their course. An OI of >25 suggests significant hypoxic respiratory failure, equating to a patient with a mean airway pressure of 15 with an Fio₂ of 1.0 who achieves a Pao₂ of only 60 mm Hg. Any patient requiring 100% oxygen without signs of improvement on high-frequency and/or inhaled nitric oxide within 2–3 hours or those who have persistent hypotension, acidosis, and/or lactic acidosis despite vasopressor/inotropic therapy should be considered a candidate for transport on their current therapy to an ECLS center.

Before ECLS initiation, parents should be made aware of the potential complications. It is important to emphasize that ECLS is a supportive therapy rather than curative and that there are some circumstances where neonates may not survive. Potential complications:

1. Difficulties may arise during cannulation, including the inability to achieve adequate venous drainage or infusion secondary to a venous web, valve, or vessel spasm. Perforation of the right atrium leading to pericardial tamponade can occur suddenly and be life-threatening, requiring immediate surgical evacuation.

2. Hemorrhage may develop in any organ, most significantly the brain. Blood accumulation in the pericardium, abdomen, retroperitoneum, or chest can result in decreased pulse pressure, low SvO₂ levels, hypotension, and inability to maintain ECLS flows.

3. Thrombosis or emboli in the circuit may lead to an infarction in the brain, and is usually associated more commonly with VA ECLS.

4. Infections, hemolysis, renal failure, accidental decannulation, arrhythmias (due to the venous catheter being positioned in the atrium), and mechanical problems (ie, oxygenator failure, fracture of the tubing or connector sites) are other possible ECLS complications.

5. ECLS survivors are at risk for significant neurologic sequelae resulting from the underlying disease process and/or their treatment (see Section XXI). Decreased tone and poor feeding may lengthen hospital stay and necessitate ongoing rehabilitative services. Chronic lung disease may lead to future hospitalizations. Other long-term complications, including blindness, hearing loss, and cognitive problems requiring special support in school, can also occur. Despite these stated complications, most infants have excellent morbidity-free outcomes.

1. Before initiating ECLS, patients require evaluation for structural heart disease and intracranial hemorrhage with an echocardiogram and head ultrasound.

2. Screening labs should include electrolytes, ionized calcium, blood urea nitrogen, creatinine, glucose, complete blood count, differential, platelet count, coagulation studies including international normalized ratio (INR), fibrin breakdown products, total and direct bilirubin, arterial blood gas (ABG), lactate, activating clotting time (ACT), antithrombin III level, blood culture, and a blood type and screen. Labs should be followed daily to twice daily.

3. Bladder catheter, enteral feeding tube or tube for low intermittent suction, and a rectal temperature probe should be inserted as needed. It is extremely important to place these tubes before the initiation of anticoagulation and ECLS given the risks of bleeding.

4. For VV ECLS, a percutaneously placed internal jugular central line can serve as a guide for placement of the VV cannula. Other access for IV infusions, blood draws and arterial blood gases, and central blood pressure monitoring via percutaneously inserted central lines, umbilical arterial, and/or venous catheters or femoral arterial and/or venous catheters should preferably be placed before the initiation of ECLS as well.

During ECLS, the patient's blood is exposed to plastic, silicone, polymethylpentene, and other circuit compounds, which can cause activation of the immune system with the release of inflammatory mediators (complement, leukotrienes, cytokines, and leukocytes). The coagulation cascade and fibrinolytic system are also activated. Consumption of platelets by the hollow fiber or membrane oxygenator or filter used for continuous renal replacement can exacerbate the coagulopathy and the additive responses can result in massive capillary leak. This process may be mitigated somewhat by pretreating neonates with a glucocorticoid, but the evidence for this has not been established.

Gas exchange through the oxygenator mimics pulmonary respiration (see Figure 18–1). Some oxygenators house hollow fibers. Blood flows around the fibers, in constant contact with the fiber surface. Oxygen flow, however, occurs through the fibers. The microporous nature of the fibers allows gas exchange by diffusion across the membrane based on concentration gradients, allowing O₂ delivery and CO₂ removal. The Fio₂ delivered to the oxygenator influences the oxygen delivered to the blood.

Membrane oxygenators are designed to allow blood to flow on one side of the membrane, whereas gas flows on the other side. Again, concentration gradients are the driving force for diffusion. Membrane oxygenators are more likely to have complications with plasma leaks, air emboli, water vapor condensation, and thrombus formation.

To provide varying oxygen concentrations for both types of oxygenators, the gas blender is used to dial in an appropriate O₂ concentration. To remove CO₂, the flow meter is adjusted, which provides gas flow or “sweep gas” through the oxygenator and serves to wash out CO₂ from the oxygenator system.

1. In patients on ECLS, O₂ delivery is influenced by the following:

   1. O₂ content of the blood after it passes through the oxygenator

   2. Rate of blood flow through the ECLS circuit, particularly in membrane oxygenators

   3. O₂ uptake through the patient's lung

   4. Native cardiac output

   5. Patient's hemoglobin

2. Oxygenation through the circuit depends on the following:

   1. The amount of O₂ in the gas phase (the driving concentration gradient).

   2. The ease with which O₂ crosses the hollow fiber or membrane (permeability).

   3. The ability of O₂ to diffuse through the blood layer (its solubility in plasma). Because there is more O₂ in the sweep gas than in the blood, there is always a large concentration gradient that never achieves equilibrium throughout the oxygenator. Sweep gas flow has little influence on oxygen exchange. Blood flow, however, may influence oxygenation. If the blood flows faster than the time it takes to achieve complete saturation of the hemoglobin with oxygen, blood will leave the oxygenator incompletely saturated. The “rated flow” is the pump blood flow rate at which maximal O₂ delivery is achieved. Oxygenation decreases at flows that exceed that rate. Additionally, the likelihood of hemolysis increases. Devices have a flow rated graph on their web site.

3. For patients on ECLS, CO₂ exchange is affected by 3 main factors:

   1. The relative concentration of CO₂ on either side of the oxygenator hollow fibers or membrane (which is usually at least 45–50 mm Hg in the venous blood and zero in the sweep gas of the oxygenator, allowing very efficient transfer of CO₂).

   2. The movement of gas through the oxygenator or sweep gas flow-rate (which constantly refreshes the concentration gradient by moving air through the oxygenator).

   3. The surface area of the hollow fibers or membrane. Because the diffusion of CO₂ through blood and the hollow fibers or membrane occurs rapidly (6 times faster than O₂), it remains independent of blood flow rate through the oxygenator. Factors that decrease the functional surface area, however, will limit CO₂ transfer before affecting oxygenation.

1. Advantages and disadvantages of VA and VV ECLS

   1. VA ECLS. Provides cardiopulmonary bypass that runs in parallel to the native cardiac output. Blood from the right atrium serves as the source for ECLS pump preload, which is oxygenated and then infused into the brachiocephalic artery/aortic circulation.

      1. VA ECLS advantages

         1. May provide full cardiac and respiratory support for the nonfunctioning heart and lungs.

         2. May decrease the load on the heart, allowing for recovery. However, if left ventricular (LV) failure is severe, the flow through the arterial cannula may exceed the ability of the LV to eject. Under such conditions, acute pulmonary edema may occur, leading to dire outcomes if the left atrium (LA) is not decompressed.

      2. VA ECLS disadvantages

         1. Results in ligation of the carotid artery; reconstruction may or may not be possible. VA ECLS also causes temporary interruption of isohemispheric cerebral blood flow when carotid cannulation is used.

         2. Causes a higher incidence of central nervous system (CNS) hemorrhage.

         3. Potentially may allow emboli to enter the arterial circulation, which could cause a stroke.

         4. May compromise organ tolerance to hypoxia (especially in the brain and kidneys) because of the lack of pulsatility in the blood flow.

   2. VV ECLS. Provides respiratory support (and indirectly circulatory support) that runs in series with the native cardiac output.

      1. VV ECLS advantages

         1. Maintains function of the carotid artery because it is not used for cannulation

         2. Preserves pulsatile flow, which may better preserve organ function

         3. Allows the lungs to serve as filters for emboli so embolic strokes are less likely

         4. Increases the availability of oxygen to the coronary circulation as blood is ejected from the left ventricle due to the arterial admixture of the mixed venous blood

      2. VV ECLS disadvantages

         1. Provides only indirect circulatory support by improving myocardial oxygenation; patients may continue to require inotrope/vasopressor support, but many patients experience improvement in cardiac function after cannulation for VV ECLS.

         2. May not provide full oxygen delivery. In this case, some native lung function may be necessary to sustain appropriate gas exchange.

         3. More prone to difficulties with cannula position. Provides less support due to recirculation. (See Section XVIII.B.4).

1. Circuit preparation. Occurs once a patient is felt to need ECLS. The circuit tubing is connected and then primed with packed red blood cells, fresh-frozen plasma (FFP), sodium bicarbonate, calcium gluconate, and heparin. Some institutional preferences may include albumin or tris-hydroxymethyl amino-methane.

2. Neonatal vascular access. Usually through the right internal jugular vein and right common carotid artery for VA ECLS, each using a single lumen cannula for access, and the right internal jugular vein for VV ECLS with a dual lumen cannula for access.

3. Patient positioning. Patients should be positioned with the head turned to the left and the neck extended using a neck roll.

4. Medications. To provide analgesia/anesthesia and surgical preparedness, patients should receive a narcotic and neuromuscular blocking agent before the procedure. Sedatives and narcotics are usually provided throughout the ECLS course; however, most patients do not require ongoing therapy with neuromuscular blocking agents. For patients receiving muscle relaxants, the ventilator settings should be adjusted and the end tidal CO₂ followed.

5. X-ray placement. An x-ray cassette should be placed under the patient before initiation of surgical placement of the cannula(e).

6. Heparin for anticoagulation. Patients not already receiving anticoagulation should have an ACT drawn and be given a heparin bolus of 50–100 U/kg immediately before the insertion of the cannula(e) to prevent clot formation. After the ACT level falls to 250–300 seconds, a continuous heparin infusion is started. The typical starting dose is 10–20 U/kg/h, and the typical steady-state infusion rate is 20–40 U/kg/h. If ongoing bleeding and coagulopathy are a concern or the patient has recently had surgery, the heparin drip may be held until an appropriate coagulation status is achieved.

7. Appropriate cannula positions/sizes. See Figures 18–2 and 18–3. Cannula size choices should be determined based on the patient size. The size of the venous cannula is critical because restricted flow due to high resistance may cause blood-shearing resulting in hemolysis.

   1. For VA cannulation. The arterial cannula tip should be in the brachiocephalic artery, at or just above the junction of the aortic arch. Optimal positioning is achieved when the cannula tip is at T3–4 (just above the carina) after the neck roll is removed. The tip of the venous cannula should be in the right atrium near the junction of the inferior vena cava. If the arterial cannula is positioned high in the right common carotid artery, streaming of blood can occur into the right subclavian artery, causing the right arm to appear more oxygenated than the rest of the body, invalidating any arterial blood gas sampling from a right radial artery. The catheter generally needs to be adjusted in these situations.

   2. For VV cannulation. The cannula chosen should have the largest internal diameter to minimize resistance to blood flow. The cannula tip should be well into the right atrium at T7–8 or about 1–2 cm above the diaphragm for most cannulae. Removal of the neck roll may advance the catheter as much as 1 cm. Proper cannula position helps maintain appropriate flows, a critical feature of VV ECLS. Flows of 120 mL/kg/min should be achievable after intravascular volume expansion and removal of the neck roll. It is imperative to assess for signs of significant recirculation after VV cannulation. In this situation, venous saturations may be >85–90% and arterial saturations lower than their baseline levels. (See recirculation in Section XVIII.B.4.)

8. Intravascular volume. Before connecting the ECLS cannula(e) to the circuit, surgeons may allow backflow of the patient's blood in the cannula(e) to assure that there is no air in the circuit. During these times, blood pressures may drift downward momentarily, and intravascular volume may be needed.

9. Ongoing heparin therapy. The ACT range depends on the type of monitoring equipment and institution-specific standards. ACT levels are monitored regularly and kept in a range between 200 to 220 seconds. When disseminated intravascular coagulation (DIC) or bleeding occurs, clinicians may target a lower ACT goal, typically between 180 to 200 seconds. A heparin bolus may be necessary if the ACT falls below 180 seconds and the ECLS flow is interrupted for a circuit change or modification. Because the circuit flow rate also has an impact on thrombus formation, an attempt should be made to maintain ECLS flows >80 mL/kg/min whenever the ACT levels drop to <180 seconds.

   The ACT assays whole blood clotting. As such, factors that affect ACT include heparin dosing, coagulation and anticoagulation factor levels, and antithrombin III (ATIII) levels, as well as the platelet count and function. If the ACT is at the lower end of the target range, a bolus of heparin (5–10 U/kg) may be needed when platelets are transfused. ACT levels may overestimate heparin effect and therefore lead to inadequate anticoagulation.

   Furosemide often prompts a brisk diuresis. Diuresis increases heparin clearance, often necessitating an increase in the heparin infusion rate. Likewise, a spontaneous increase in urine output, continuous renal replacement therapy, or platelet transfusions often require an increase in the heparin rate to maintain the target ACT level.

10. Management of coagulopathy and anemia. Coagulopathies should be corrected at the earliest possible opportunity.

    1. Fibrinogen levels. Should be kept >150 mg/dL using cryoprecipitate.

    2. INR levels. Should be kept ≤1.4 by treating with FFP and/or cryoprecipitate.

    3. Platelet counts. Generally maintained >80,000 μL or >100,000 if there is bleeding.

    4. Antithrombin III antigen levels. Normally kept >60–100%, especially with excessive clot buildup in the circuit and/or a high heparin infusion rate (eg, >40 U/kg/h). Infants demonstrate physiologically low ATIII levels until 6–9 months of age depending on their gestational age and other illnesses. Furthermore, low ATIII levels may result from DIC, endothelial injury, ongoing protein losses from a chylothorax or nephrotic syndrome, dilutional effects of cardiac bypass, liver disease with synthetic failure, or from congenital deficiencies (rare).

       ATIII, a serine protease inhibitor produced by the liver, is essential to endogenous anticoagulation by inhibiting the activity of thrombin and Xa. It also inactivates plasmin, IXa, XIa, and XIIa. ATIII is necessary for an adequate response to heparin. Heparin, a glycosaminoglycan produced by basophils and mast cells, works by binding to ATIII and upregulating the catalytic activity of ATIII a 1000-fold.

       FFP has approximately 1 U of antithrombin/mL. ATIII concentrate, however, increases the serum level with a much smaller administration volume and so may be appropriate to use if a goal ATIII level is preferred. Larger protein losses, with the loss of other coagulation factors, may be more efficiently treated with FFP.

    5. Unfractionated heparin levels (anti-Xa). Help to determine whether a prolonged ACT level is due to a heparin effect or coagulopathy. Normal goals are 0.25–0.5 IU/mL.

    6. Hematocrit levels. Maintained at >35% for VA ECLS and >40% for VV ECLS.

    7. Thromboelastography. Assays whole blood to provide information about intrinsic factor, platelet function, anticoagulation, and fibrinolytic function. As such, it may be used for further assessment in particularly challenging cases.

1. Thrombus in the oxygenator. Suspected when an increase in the preoxygenator pressure and a fall in the postoxygenator pressure occurs (see Figure 18–1). Trends in the change in pressures (Δ pressure) should be followed. If the Δ pressure is increasing to above acceptable parameters, the oxygenator or circuit should be changed. In addition, consumption of clotting factors and platelets suggests the presence of thrombi in the circuit, so called “circuit DIC.” This often requires a change of the entire circuit.

2. Gas pressure. Monitored and controlled in the sweep gas line.

3. SvO₂ levels. During ECLS, SvO₂ levels reflect the degree of O₂ extraction and should normally be in the 75–80% range. SvO₂ levels <50% indicate a critical level of O₂ extraction and suggest that the rate of tissue metabolism dangerously exceeds the rate of O₂ delivery. Once this occurs, cells use the markedly less efficient anaerobic metabolism producing lactic acid. SvO₂ levels present a useful parameter to follow in VA ECLS, but due to the recirculation phenomenon in VV ECLS, they may sometimes be more difficult to interpret. (See Tables 18–1 and 18–2.)

Neonates who receive ECLS already have substantial ventilator-associated lung inflammation and injury. An extremely important benefit of ECLS is to provide “resting” ventilator settings. Although centers vary in the level of rest ventilator settings, for VA ECLS patients, a low rate of 10 breaths/min (10–20), a modest to high positive end-expiratory pressure (PEEP) of 5–14 cm H₂O, a low peak inspiratory pressure (PIP) in the 12–20 cm H₂O range, with a low Fio₂ of ∽40% is used. In VA ECLS, the ventilator Fio₂ of ∽ 40% may improve oxygenation of coronary blood.

Higher ventilator settings may be necessary if appropriate gas exchange cannot be achieved on VV ECLS (ie, a rate of 20–30 breaths/min, PIP of 15–25 cm H 2 O, PEEP of 5–10 cm H 2 O, and Fio₂ from 30 to 50%). Some centers use high-frequency oscillatory ventilation for lung rest, usually with a mean airway pressure of 10–14 cm H₂O and low amplitudes.

ECLS patients frequently need their urine output augmented with a diuretic. Particularly with VA ECLS, the kidneys may be sensitive to the nonpulsatile nature of the flow, resulting in a decrease in renal function. For patients with preexisting or developing renal failure and/or those with anasarca, hemofiltration may be added in parallel to the ECLS circuit via a small shunt. This system allows for removal of excess fluid and stabilizes electrolyte abnormalities. (See Figure 18–1.)

Antibiotics, sedatives, antianxiety medications, proton pump inhibitors, and total parenteral nutrition should be delivered to the patient if possible, but with limited access can be delivered into the ECLS circuit at patient venous access locations. Because the volume of distribution is higher due to the ECLS circuit volume, higher doses may be needed. If renal failure is present, doses may need to be decreased. Discussion with the pharmacist will help with correct dosing.

Myocardial stun may occur after an ischemic insult to the heart and after the initiation of VA or VV ECLS. In patients on VA ECLS, left ventricular (LV) stun can occur when the LV is not properly ejecting blood, becomes overdistended, and impedes cardiac ejection, potentially resulting in cardiac damage and pulmonary edema. Cardiac stun should be suspected any time there is a loss in pressure on ECLS that is not secondary to the recent initiation of VA ECLS, hypovolemia, pneumothorax, pneumopericardium, hemothorax, or hemopericardium. An echo showing minimal LV wall motion can confirm the diagnosis.

Management of cardiac stun is challenging. Increasing ECLS flow in an attempt to try to improve oxygenation may cause further LV dilation, increasing the LV afterload and increasing myocardial oxygen consumption. Additional volume to improve right heart filling, inotropic agents to improve left heart ejection, maximizing postmembrane oxygen content and total oxygen delivery, and reducing afterload with vasodilators may allow for recovery of the stunned ventricle.

Cardiac stun failing to improve within 4–5 days represents an ominous sign and suggests myocarditis or myocardial infarction. Decompression may be necessary by balloon septostomy with or without a stent in place. Alternatively, a transthoracic LV catheter may be connected to the venous drainage side of the ECLS circuit.

Right ventricular (RV) dysfunction can occur, particularly in neonates with severe pulmonary hypertension before the initiation of ECLS. In some cases, even while on VV ECLS, the RV becomes further dilated and dysfunctional, causing it to bow into the LV, compromising LV filling and cardiac output. Cardiac echo assessment is necessary, and the use of agents to reduce RV afterload, such as inhaled nitric oxide, milrinone, and/or sildenafil, are warranted. If medical management is not effective, patients may need to be converted to VA ECLS.

Thrombosis in the circuitry may necessitate the need for a circuit change. During circuit changes, a large percentage of blood volume is exchanged, and there can be electrolyte imbalances and arrhythmias. Blood drug levels may need to be adjusted as well. Clots in the cannula(e) can be challenging to manage because removal of these thrombi requires temporary discontinuation of ECLS.

1. VA ECLS

   1. VA ECLS blood flows. After cannulation, bypass flow is slowly increased. Typically, VA ECLS flow is maintained at ∽60–80% of total blood flow (100–150 mL/kg/min), and the pulse pressure is generally around 10–20 mm Hg if the heart has effective contractility.

      The goal of VA ECLS is to provide adequate oxygen delivery to all tissues. As more blood is routed through the circuit with a high flow rate, the systemic arterial pulse contour may become dampened and then flatten if total bypass is achieved. In this situation, more blood drains into the circuit, decreasing both right and left heart preload and resulting in a decrease in the left ventricular stroke volume. Despite the lack of pulsatility, the mean blood pressure remains fairly constant and is the best gauge of blood pressure dynamics.

   2. SvO₂ levels. SvO₂ levels of 75–80% usually reflect adequate tissue oxygen supply.

   3. Oxygen delivery/CO₂ removal. In VA ECLS, part of the blood from the right atrium also circulates through the native lung into the left heart and out the aorta, returning again to the right heart. This blood will be exposed to variable ventilation, depending on lung function and status of the disease process. With improvement in native lung function and cardiac output, the oxygen content of the blood returning will be higher.

      A major strategy to improve oxygen delivery includes maintaining a higher hemoglobin level. Increasing the ECLS blender O₂ or ventilator Fio₂ will also improve the arterial saturations if they are low. A failing oxygenator (because of reduced functional surface area) may decrease oxygen delivery as well.

      Increasing the sweep gas flow rate will lower the CO₂. An increasing CO₂ level may be the first sign that the oxygenator is developing excessive clot formation.

   4. Trialing off VA ECLS. After the initial disease processes and inflammatory responses have subsided and pulmonary function has improved (demonstrated by improvement in chest radiographs and lung compliance), patients are ready to be weaned off VA ECLS. Before the trial, all infusions should be moved from the ECLS circuit to the patient if not done previously. Heparin may continue to run through the circuit or be split so that one-half is transfused to the patient and one-half to the circuit. The surgical team should be notified of the estimated time of possible decannulation.

      1. Starting 12 hours before the anticipated trial off, the ECLS blood flows are decreased slowly and ventilator settings adjusted as needed based on blood gases. The pump flow can be weaned hourly by 10–20 mL/min while gradually increasing ventilatory support. ECLS blood flows are weaned to a target “idling” flow of 50–100 mL/kg/min. Once this is accomplished, the cannulae are clamped and the bridge clamp is removed. To maintain integrity of the cannulae and circuit while trialing off, the cannulae are flushed every 5 minutes by opening the venous cannula, clamping the bridge or shunt, then opening the arterial cannula for 5–10 seconds, followed by reversing the sequence. Patient blood gases should be obtained with a frequency that assures adequate lung function throughout the trial. The low flow state of the trial increases the possibility of thrombosis formation in the circuit; the length of time for the trial may depend on cannulae and circuit integrity. If the patient does not appear ready for decannulation, infusions may continue in the patient's vascular catheters or moved to the circuit. All heparin infusions will be moved back to the circuit. If parameters remain within the acceptable ranges, patients may be decannulated.

2. VV ECLS

   1. VV ECLS blood flows. As with VA ECLS, flow is gradually increased to 100–120 mL/kg/min. With the use of a double-lumen VV ECLS catheter, blood is withdrawn simultaneously from the right atrium via one side of the cannula, oxygenated in the extracorporeal lung or oxygenator, then reinfused continuously back into the right atrium via the other side of the cannula; consequently, there is no net effect on the right atrial volume, intracardiac flow, or aortic blood flow. Ideally the output from the return port is directed toward the tricuspid valve. The native cardiac output propels oxygenated blood forward to the systemic arterial system and tissues. O₂ delivery can be augmented by increasing the O₂ content of the venous blood in the right atrium or by maneuvers that decrease recirculation (eg, increasing native cardiac output, repositioning the cannula). Because oxygenator blood mixes continuously with desaturated venous blood entering the right atrium, the final O₂ content of the blood reaching the aorta and tissues is limited by the amount of blood that can be drained into the ECLS circuit, oxygenated, and returned to the venous system. The optimal pump flow rate is one that provides the highest effective pump flow at the lowest revolutions per minute of the pump, resulting in the highest O₂ delivery and causing the least degree of tubing wear and/or hemolysis.

   2. Pao₂ levels. Patients usually have arterial saturation levels of 80–95%, with Pao₂ levels of 50–80 mm Hg. During VV ECLS, only indirect circulatory support is achieved, and lower oxygen saturations often need to be tolerated. Pao₂ levels may rise as native pulmonary function improves.

   3. Ventilator strategies. When the size of the venous cannula limits ECLS flow, maintenance of some native pulmonary gas exchange may be necessary to achieve adequate patient oxygenation. In this situation, using higher PEEP levels may facilitate O₂ delivery.

   4. Recirculation. Occurs when oxygenated blood from the ECLS circuit delivered to the reinfusion lumen is siphoned back to the venous drainage lumen instead of flowing across the tricuspid valve. The recirculation fraction depends on the type of cannula, native cardiac output, and right atrial volume. When pump flow rises above optimal flow, recirculation increases and effective flow decreases. Clinically significant recirculation is recognized by a decrease in patient arterial saturations and a rise in SvO₂ levels with increasing pump flow. Higher degrees of recirculation decrease the effective O₂ delivery from the circuit, possibly contributing to increased hemolysis as well. Other factors that increase recirculation include the following:

      1. Decreased right atrial volume causes a higher percentage of returned oxygenated blood to be drained back to the pump.

      2. A catheter malpositioned too high in the superior vena cava or too low in the inferior vena cava increases recirculation. Furthermore, inappropriate positioning of the outflow ports may result in blood being directed away from the tricuspid valve, thus increasing the recirculation fraction. Catheters may migrate with changes in lung volume, increasing edema of the neck, a change in the patient's position or with the patient's movements, necessitating adjustment of the cannula to maintain adequate flows and minimize recirculation. Maintaining the catheter position is critical in VV ECLS.

      3. Poor cardiac output leads to greater recirculation because a smaller fraction of the oxygenated pump blood is propelled forward out of the right atrium.

   5. Oxygen delivery/CO₂ removal. Major strategies to improve oxygen delivery in VV ECLS include increasing the hemoglobin, increasing ECLS flow, and improving the native cardiac output. Recirculation issues may not be amenable to changes in ECLS flow, forcing acceptance of suboptimal gas exchange. Increasing the sweep gas flow rate will lower the CO₂.

   6. Trialing off VV ECLS. Given the dynamics of VV ECLS, circuit flow rates do not require weaning. Blood flow may remain constant (usually 60–100 mL/kg/min) followed by weaning the Fio₂ sweep gas flow rate to room air. During this time, the ventilator settings are increased to levels expected to achieve normal gas exchange. Then the sweep gas tubing is disconnected from the blender source, which functionally removes the patient from ECLS. ACT levels, blood gases, and SvO₂ levels are followed, and once assured of success after 1–2 hours, the patient may be decannulated and the heparin drip discontinued. If a percutaneous technique was used for VV cannula insertion, simply cutting the sutures and removing them and then the cannula is all that is required. Pressure at the site for 15–20 minutes should achieve adequate hemostasis.

1. Patient complications of ECLS. Patient complications per the Extracorporeal Life Support Organization (ELSO) International Summary data as of July 2011 for neonatal respiratory patients are as follows: acute renal failure (continuous renal replacement required, 16.5%; dialysis required, 3.2%); hypertension requiring vasodilators, 12.3%; hypotension requiring inotropics, 20.1%; CNS infarction, 7.5%; intracranial hemorrhage, 7.0%; culture-proven infection, 6.0%; surgical bleeding, 6.3%; pulmonary hemorrhage, 4.5%; pneumothorax requiring treatment 6.1%; DIC, 2.5%; hemolysis,10.9%; seizures, 10.5%; brain death, 0.9%.

2. Mechanical problems. Include oxygenator clots, 17.2%; cannula problems, 11.7%; oxygenator failure, 6%; air in the circuit, 5.9%; pump failure, 1.7%; raceway rupture, 0.3%.

The Neonatal ECLS Registry (established in 1985), as of July 2011, lists 29,839 neonatal patients. Currently, the overall cumulative neonatal survival rate is 75% for respiratory, 39% for cardiac, and 39% for extracorporeal cardiopulmonary resuscitation use of ECLS for patients with refractory cardiopulmonary arrest. The cumulative drop in survival over the years reflects a larger proportion of patients treated with high-mortality diagnoses. The registry also tracks cumulative survival rates for specific diseases: meconium aspiration syndrome, 94%; pulmonary hypertension, 78%; hyaline membrane disease, 84%; sepsis, 75%; pneumonia, 57%; airleak syndrome 74%; congenital diaphragmatic hernia, 51%; congenital heart defect 38%; cardiac arrest, 22%; cardiogenic shock, 39%; cardiomyopathy, 63%; myocarditis, 49%; cardiac transplant, 30%. Congenital diaphragmatic hernia and lower birthweight status in those patients treated for respiratory failure are variables associated with increased mortality and morbidity.

Results of a randomized study comparing patients treated with ECLS versus conventional support suggest that the underlying disease processes appear to be the major influence on morbidity at 7 years of age in former newborns with severe respiratory failure. When comparing the ECLS group with the conventionally treated group, a higher respiratory morbidity and increased risk of behavioral problems was noted in the group of children treated conventionally. There were no cognitive differences between the 2 trial groups (76% of the children available for follow-up testing in both groups were within the normal range, although they fell below population norms). Overall, 40% of the children had normal neuromotor development (43% of the children in the ECLS group and 35% in the conventionally treated group). Behavioral problems, particularly hyperactivity, were more common in the conventionally treated children. Progressive sensorineural hearing loss was found in both groups and could be late in onset and progressive. Inciting causes for certain neurologic sequelae were difficult to discern. However, it was felt that cannulation itself, causing disruption of the cerebral circulation, was not responsible for subsequent neurologic or behavioral consequences. The increased survival among children randomized to ECLS (67% compared with conventional survival at 41%) was not offset by disability among survivors.