Extracorporeal Membrane Oxygenation for Neonatal Respiratory Failure
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Recent medical advances, such as permissive hypercapnia, inhaled nitric oxide, and the use of oscillatory ventilation, have spared numerous patients from ECMO, yet many children still benefit from this modality. Patients with reversible cardiopulmonary disease, who meet criteria, should be considered ECMO candidates. As of January 2015, 27,728 neonates (74% survival) and 6,569 pediatric patients (57% survival) have been treated with ECMO for respiratory failure and 13,124 neonatal and pediatric patients for cardiac failure. ECMO provides an excellent opportunity to provide “rest” to the cardiopulmonary systems thus avoiding the additional lung or cardiac injury which otherwise would be necessary to maintain life support. This chapter outlines the indications, contraindications, management approach, and complications associated with ECMO as well as the various bypass configurations and cannulation strategies which may be employed.
KeywordsExtracorporeal membrane oxygenation Extracorporeal support Respiratory failure Cardiac failure ECMO Cannulation
Extracorporeal membrane oxygenation (ECMO) is a lifesaving technology that affords partial heart/lung bypass for extended periods. ECMO is a supportive rather than a therapeutic modality as it provides sufficient gas exchange and perfusion in patients with acute, reversible cardiac or respiratory failure. It provides a finite period to “rest” the cardiopulmonary systems at which time they are spared insults from traumatic mechanical ventilation and perfusion impairment. ECMO was first implemented in newborns in 1974. Most information on the use of ECMO comes from the Extracorporenal Life Support Organization (ELSO). International registering ELSO has recorded 50,903 neonatal and pediatric patients treated with ECMO for a wide range of cardiorespiratory disorders. Several randomized trials in the United States and the United Kingdom found that ECMO support improved survival outcomes when compared with conventional care and it has become accepted practice in neonatal care (Bartlett et al. 1985; Jenks et al. 2017). In the neonatal period the most common disorders treated with ECMO are meconium aspiration syndrome (MAS), congenital diaphragmatic hernia (CDH), persistent pulmonary hypertension of the neonate (PPHN), sepsis, respiratory distress syndrome (RDS), and cardiac support. For the pediatric population, viral and bacterial pneumonia, acute respiratory failure (non-ARDS), acute respiratory distress syndrome (ARDS), and cardiac disease are the most common pathophysiologic processes requiring ECMO intervention (Butler et al. 2017; Frenckner 2015; Campbell et al. 2003).
Candidates for ECMO are expected to have a reversible cardiopulmonary disease process, with a predictive mortality greater than 80–90%, and exhaustion of ventilatory and other therapies. Obviously, these criteria are subjective and vary between institutions. Criteria for mortality risk in neonatal respiratory failure have been suggested to identify infants with a >80% mortality (Bailly et al. 2017; Barbaro et al. 2016). These include (a) the oxygenation index (OI), calculated as FiO2* mean airway pressure * 100/PaO2(OI >25 is predictive of a 50% mortality rate and is a relative indication for ECMO while OI >40 equates with 80% mortality and mandates implementation of ECMO), and (b) an alveolar-arterial oxygen gradient (A-aDO2) >625 mmHg for more than 4 h, or an A-aDO2 >600 mmHg for more than 12 h. Older infants and children do not have as well-defined criteria for high mortality risk. The combination of a ventilation index (respiratory rate* PaCO2* peak inspiratory pressure/1,000) >40 and an OI >40 correlates with a 77% mortality, whereas a mortality of 81% is associated with an A-aDO2 >580 mmHg and a peak inspiratory pressure of ≥40 cmH2O. In general, ECMO is indicated in pediatric patients with respiratory failure when the A-aDO2 is >600 mmHg on FiO2 1.0 despite optimal treatment. Indications for support in patients with cardiac pathology are based on clinical signs of cardiovascular failure such as hypotension despite the administration of inotropes or volume resuscitation, metabolic acidosis, oliguria (urine output <0.5 cc/kg per h), and decreased peripheral perfusion.
In addition, the gestational age should be at least 34–35 weeks due to the increased risk for intracranial hemorrhage (ICH) and the birth weight at least 2 kg secondary to cannula size limitations. The length of mechanical ventilation, and its associated toxicity from prolonged exposure to high concentrations of oxygen and elevated positive pressure ventilation prior to ECMO should be preferably no longer than 10–14 days due to the development of bronchopulmonary dysplasia. Babies with lethal congenital anomalies should not be considered for ECMO support. Treatable conditions such as total anomalous pulmonary venous return and transposition of the great vessels, which may masquerade initially as pulmonary failure, can be corrected with surgery but may require ECMO resuscitation initially. Therefore, echocardiogram should be rapidly obtained to determine cardiac anatomy. There should be no evidence of significant neurologic injury such as seizures. Patients with suggestion of a small ICH (grades I–II) should be considered candidates for ECMO on an individual basis and monitored closely for worsening of the hemorrhage. In fact, all patients with gross active bleeding or major coagulopathy should be corrected prior to initiating ECMO.
Types of Extracorporeal Membrane Oxygenation
Most reports have suggested that there is no overall advantage with either the VA or VV technique (McHoney and Hammond 2018). VA ECMO seem to be the more popular of the two modes according to the ECMO registries, presumably as the VA ECMO may give the additional benefit in the presence of severe cardiac dysfunction (McHoney and Hammond 2018). Size and vascular anatomy may sometimes dictate the mode use.
For VV and DLVV bypass, the procedure is exactly as described above including dissection of the artery, which is marked with a vessel loop, so that a future switch from VV to VA ECMO can be accomplished, if necessary. The catheter tip should be in the mid-right atrium (6 cm in the neonate) with the arterial portion of the catheter pointed toward the ear. This directs the oxygenated blood flow toward the tricuspid valve.
Cannula position is confirmed by chest X-ray and by transthoracic echocardiogram when necessary. The venous catheter should be located in the inferior aspect of the right atrium and the arterial catheter at the ostium of the innominate artery and the aorta. With a double-lumen venous catheter, the tip should be in the mid-right atrium with reinfusion of oxygenated blood flow toward the tricuspid valve (Hirschl and Bartlett 2012; Kim and Stolar 2003; Kim and Stolar 2000).
Patient Management in ECMO
Once the cannulas are connected to the circuit, bypass is initiated, and flow is slowly increased to100–150 ml/kg per min so that the patient is stabilized. Continuous inline monitoring of the venous (pre-pump) SvO2 and arterial (post-pump) PaO2 as well as pulse oximetry is vital. The goal of VA ECMO is to maintain a mixed venous PO2 (SvO2) of 37–40-mmHg and saturation of 65–70%. VV ECMO is more difficult to monitor due to variation in the degree of recirculation, which may produce a falsely elevated SvO2 assessment. Inadequate oxygenation and perfusion are indicated by metabolic acidosis, oliguria, and hypotension. Arterial blood gasses should be monitored hourly with PaO2 and PaCO2 maintained as close to normal level as possible. As soon as these parameters are met, all vasoactive drugs are weaned, and ventilator levels are adjusted to “rest” settings. Gastrointestinal prophylaxis is initiated, and mild sedation and analgesia is provided usually with fentanyl and midazolam, but the use of a paralyzing agent is avoided. A cephalosporin is often administered for prophylaxis. Routine blood, urine, and tracheal cultures should be taken.
Heparin is administered (typically 30–60 mg/kg per h) throughout the ECMO course in order to preserve a circuit free of thrombus. ACTs should be monitored hourly and maintained at 180–220 s. A complete blood count should be obtained every 6 h and coagulation profiles daily. In order to prevent hemorrhage, platelets are transfused to maintain a platelet count above 100,000/mm3, and some authors sustain fibrinogen levels above 150 mg/dl. The hematocrit should remain above 40% using red blood cell transfusions so that oxygen delivery is optimized.
Volume management of patients on ECMO is extremely important. It is imperative that all inputs and outputs be diligently recorded and electrolytes monitored every 6 h. All fluid losses should be repleted and electrolyte abnormalities corrected. All patients should receive maintenance fluids as well as adequate nutrition using hyperalimentation. The first 48–72 h of ECMO typically involves fluid extravasation into the soft tissues. The patient becomes edematous and may require volume replacement (crystalloid, colloid, or blood products) in order to maintain adequate intravascular and bypass flows, hemodynamics, and urine output greater than 1 cc/kg per h. By the third day of bypass, diuresis of the excess extracellular fluid begins and can be facilitated with the use of furosemide if necessary.
Surgical procedures, such as CDH repair, may be performed while the child remains on bypass. Hemorrhagic complications are a frequent morbidity associated with this situation and increases mortality. To avoid these complications, prior to the procedure, the platelet count should be greater than 100,000/mm3, a fibrinogen level above 150 mg/dl, an ACT reduced to 180–200 s, and ECMO flow increased to full support, and it is imperative that meticulous hemostasis be obtained throughout the surgery. Fibrinolysis inhibitor aminocaproic acid (100 mg/kg) just prior to incision followed by a continuous infusion (30 mg/kg per h) until all evidence of bleeding ceases is a useful adjunct.
As the patient improves, the flow of the circuit may be weaned at a rate of 10–20 ml/h as long as the patient maintains good oxygenation and perfusion. Flows should be decreased to 30–50 ml/kg per min, and the ACT should be at a higher level (200–220 s) to prevent thrombosis. Moderate conventional ventilator settings are used, but higher settings can be used if the patient needs to be weaned from ECMO urgently. If the child tolerates the low flow, all medications and fluids should be switched to vascular access on the patient, and the cannulas may be clamped with the circuit bypassing the patient via the bridge. The patient is then observed for 2–4 h, and if this is tolerated, decannulation should be performed. This should be executed under sterile conditions with muscle relaxant onboard to prevent air aspiration into the vein. The catheters are removed and the vessels are ligated. The wound should be irrigated and closed over a small drain, which is removed 24 h later.
Extracranial bleeding is a common complication of the heparinized ECMO patient either at the site of cannulation or at other sites and is noted in 21% of neonatal cases, 44% of pediatric respiratory cases, and 40% of all cardiac cases. Bleeding at the site of cannulation can often be treated with local pressure or the placement of topical hemostatic agents such as Gelfoam, Surgicel, or topical thrombin. For all sites of bleeding, the platelet count should be increased to >100,000 mm3 and the ACT lowered to 180–200 s. Sometimes the temporary discontinuation of heparin and normalization of the coagulation status is warranted to help stop the hemorrhage with availability of a second circuit should acute clotting of the circuit occur. Aggressive surgical intervention is warranted if bleeding persists.
Neurological sequelae are a serious morbidity of the ECMO population and include learning disorders, motor dysfunction, and cerebral palsy (Schiller et al. 2016; Madderom et al. 2013). These outcomes appear to be as much due to hypoxia and acidosis prior to the ECMO course as due to the time on ECMO itself. ICH is the most devastating complication, occurring in 7.4% of newborn patients with an associated 57% mortality among newborns who have ICH on ECMO. Frequent comprehensive neurologic exams should be performed, and cranial ultrasounds obtained daily for the first days of ECMO and then based on local protocols. Blood pressure should be carefully monitored and maintained within normal parameters to help decrease the risk of ICH. If necessary, electroencephalograms may be helpful in the neurologic evaluation.
Oliguria and increasing blood urea nitrogen and creatinine levels, may be seen in the ECMO patient during the initial 48 h, at which time renal function is expected to improve. If this does not occur, consideration must be toward poor tissue perfusion. This may be due to low cardiac output, insufficient intravascular volume, or inadequate pump flow, all of which should be corrected. In the event of continued renal failure, hemofiltration or hemodialysis can be performed to maintain proper fluid balance and electrolyte levels and are reported to be required in 14% of cases.
Conclusion and Future Directions
ELSO registry neonatal respiratory failure cases (January 2015)
Number of patients
Percent survived to DC
Congenital diaphragmatic hernia
Meconium aspiration syndrome
Persistent pulmonary hypertension of the newborn/persistent fetal circulation
Respiratory distress syndrome/hyaline membrane disease
ELSO registry pediatric respiratory failure cases (January 2015)
Number of patients
Acute respiratory failure
ELSO registry cardiac failure cases (as of January 2015)
Number of ECLS runs
Recent medical advances, such as permissive hypercapnia, inhaled nitric oxide, and the use of oscillatory ventilation, have spared numerous babies from ECMO, yet many children still benefit from this modality.
In summary, any patient with reversible cardiopulmonary disease, who meets criteria, should be considered an ECMO candidate. ECMO provides an excellent opportunity to provide “rest” to the cardiopulmonary systems thus avoiding the additional lung or cardiac injury which otherwise would be necessary to maintain life support.
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