Extracorporeal Membrane Oxygenation

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Chapter 6

Extracorporeal Membrane Oxygenation

Alejandro V. Garcia, Arul S. Thirumoorthi and Charles J.H. Stolar

Extracorporeal membrane oxygenation (ECMO) is a life-saving technology that employs partial heart/lung bypass for extended periods. It provides gas exchange and perfusion for patients with acute, reversible cardiac or respiratory failure. This affords the patient’s cardiopulmonary system a time to ‘rest,’ during which the patient is spared the deleterious effects of high airway pressure, high FiO₂, traumatic mechanical ventilation, and impaired perfusion. As of 2011, the Extracorporeal Life Support Organization (ELSO) has registered approximately 40,000 neonates and children treated with ECMO for a variety of cardiopulmonary disorders. The number of centers providing extracorporeal support and reporting to ELSO continues to increase along with the total number of cases.¹

History

The initial effort to develop extracorporeal bypass came from cardiac surgeons. Their goal was to correct intracardiac lesions and, therefore, they needed to arrest the heart, divert and oxygenate the blood, and perfuse the patient so that repair could be performed. The first cardiopulmonary bypass circuits involved cross circulation between the patient and another subject (usually the patient’s mother or father) acting as both the pump and the oxygenator.²

The first attempts at establishing cardiopulmonary bypass and oxygenation by complete artificial circuitry were constructed with disk-and-bubble oxygenators, and were limited because of hemolysis encountered by direct mixing of oxygen and blood. The discovery of heparin and the development of semipermeable membranes (silicone rubber) capable of supporting gas exchange by diffusion were major advancements toward the development of ECMO.³ During the 1960s and early 1970s, this silicone membrane was configured into a number of oxygenator models.^4–7

In 1972, the first successful use of prolonged cardiopulmonary bypass was reported.⁸ The patient had sustained a ruptured aorta following a motorcycle accident. Venoarterial extracorporeal bypass support was maintained for three days. A multicenter prospective randomized trial sponsored by the National Heart, Lung, and Blood Institute (a branch of the National Institutes of Health) studied the efficacy of ECMO for adult respiratory distress syndrome. In 1979, they concluded that the use of ECMO had no advantage over conventional mechanical ventilation, and the trial was stopped before completion.⁹ However, Bartlett and colleagues noted that all of the patients in the study had irreversible pulmonary fibrosis before the initiation of ECMO. In 1976, they reported the first series of infants with ECMO.¹⁰ Six (43%) of 14 babies with respiratory distress syndrome survived. Many of these infants were premature and weighed less than 2 kg. In addition, 22 patients with meconium aspiration syndrome had a 70% survival rate, although these neonates tended to be larger.

Since then, despite study design issues, three randomized controlled trials and a number of retrospective published reports have confirmed the efficacy of ECMO over conventional mechanical ventilation.11–18 By 1996, 113 centers had ECMO programs registered with ELSO.¹ Over the next two decades, improvements in technology, a better understanding of the pathophysiology of pulmonary failure, and a greater experience using ECMO have contributed to improved outcomes for infants with respiratory failure. In 2003, the University of Michigan reported an association between ECMO volume and an observed reduction in neonatal mortality seen in that state between 1980 and 1999.¹⁹

ELSO, formed in 1989, is a collaboration of health care professionals and scientists with an interest in ECMO. The organization provides the medical community with guidelines, training manuals and courses, and a forum in which interested individuals can meet and discuss the future of extracorporeal life support. The group also provides a registry to investigators for the collection of data from most centers with an ECMO program throughout the world. This database provides valuable information for analysis of this life-saving biotechnology.20,21

Clinical Applications

Neonates are the patients who benefit most from ECMO. Cardiopulmonary failure in this population secondary to meconium aspiration syndrome (MAS), congenital diaphragmatic hernia (CDH), persistent pulmonary hypertension of the newborn (PPHN), and congenital cardiac disease are the most common pathophysiologic processes requiring ECMO. In children, the most common disorders treated with ECMO are viral and bacterial pneumonia, acute respiratory distress syndrome (ARDS), acute respiratory failure (non-ARDS), sepsis, and cardiac disease. Treatment of patients who cannot be weaned from bypass after cardiac surgery and patients with end-stage ventricular failure needing a bridge to heart transplantation are areas where ECMO use is increasing.1,22,23 Some less frequently used indications for ECMO include respiratory failure secondary to smoke inhalation,²⁴ severe asthma,²⁵ rewarming of hypercoagulopathic/hypothermic trauma patients,²⁶ and maintenance of an organ donor pending liver allograft harvest and transplantation.²⁷

Pathophysiology of Newborn Pulmonary Hypertension

Pulmonary vascular resistance (PVR) is the hallmark and driving force of the fetal circulation. Normal fetal circulation is characterized by PVR that exceeds systemic pressures, resulting in higher right-sided heart pressures and, therefore, preferential right-to-left blood flow. The fetal umbilical vein carries oxygenated blood from the placenta to the inferior vena cava via the ductus venosus. Because of the high PVR, the majority of the blood that reaches the right atrium from the inferior vena cava is directed to the left atrium through the foramen ovale. The superior vena cava delivers deoxygenated blood to the right atrium that is preferentially directed to the right ventricle and pulmonary artery. This blood then takes the path of least resistance and shunts from the main pulmonary artery directly to the descending aorta via the ductus arteriosus, bypassing the pulmonary vascular bed and the left side of the heart. Therefore, as a consequence of these anatomic right-to-left shunts, the lungs are almost completely bypassed during fetal circulation.

At birth, with the infant’s initial breath, the alveoli distend and begin to fill with air. This is paralleled by relaxation of the muscular arterioles of the pulmonary circulation and the expansion of the pulmonary vascular bed. This leads to a rapid drop in PVR to below systemic levels that causes the left atrial pressure to become higher than the right atrial pressure. The result is closure of the foramen ovale, and all venous blood flows from the right atrium to the right ventricle and into the pulmonary artery. The ductus arteriosus also closes at this time. Therefore, all fetal right-to-left circulation ceases, completing separation of the pulmonary and systemic circulations. Anatomic closure of these structures takes several days to weeks. Thus, maintaining systemic pressure greater than the pulmonary circulation is vital to sustaining normal circulation.

Failure of the transition from fetal circulation to newborn circulation is described as PPHN or persistent fetal circulation (PFC).²⁸ Clinically, PPHN is characterized by hypoxemia out of proportion to pulmonary parenchymal or anatomic disease. In hypoxic fetuses and infants, the proliferation of smooth muscle in the arterioles may extend far beyond the terminal bronchioles, resulting in thickened and more reactive vessels. In response to hypoxia, these vessels undergo significant self-perpetuating vasoconstriction. Although sometimes idiopathic, PPHN can occur secondary to a number of disease processes such as MAS, CDH, polycythemia, and sepsis.

Treatment for PPHN is directed at decreasing right-to-left shunting and increasing pulmonary blood flow. Previously, most newborns were treated with hyperventilation, induction of alkalosis, neuromuscular blockade, and sedation. Unfortunately, these therapies have not reduced morbidity, mortality, or the need for ECMO. ECMO allows for the interruption of the hypoxia-induced negative cycle of increased smooth muscle tone and vasoconstriction. ECMO provides richly oxygenated blood and allows the pulmonary blood pressure to return to normal subsystemic values without the iatrogenic complications encumbered by overly aggressive ‘conventional’ therapy.

Data recommending permissive hypercapnia and spontaneous respirations as principles of treatment for these children have been reported.²⁹ Hyperventilation and neuromuscular blockade are not part of the treatment strategy. This strategy has decreased morbidity, mortality, and the need for ECMO in several centers.

Patient Selection Criteria

The selection of patients as potential ECMO candidates continues to remain controversial. The selection criteria are based on data from multiple institutions, patient safety, and mechanical limitations related to the equipment. The risk of performing an invasive procedure that requires heparinization of a critically ill infant or child must be weighed against the predicted mortality of the patient with conventional therapy alone. A predictive mortality of greater than 80% after exhausting all conventional therapies is the criterion most institutions follow to select patients for ECMO. These criteria are subjective and will vary between facilities based on local clinical experience and available technologies. All ECMO centers must develop their own criteria and continually evaluate their patient selection based on ongoing outcomes data.

Recommended pre-ECMO studies are listed in Box 6-1. The definition of ‘conventional therapy’ is not consistent for each indication. Nevertheless, ECMO is indicated when (1) there is a reversible disease process; (2) the ventilator treatment is causing more harm than good; and (3) tissue oxygenation requirements are not being met. A discussion of generally accepted selection criteria for using neonatal ECMO follows.

Reversible Cardiopulmonary Disorders

The underlying principle of ECMO relies on the premise that the patient has a reversible disease process that can be corrected with either therapy (including the possibility of organ transplantation) or ‘rest’, and that this reversal will occur in a relatively short period of time. Prolonged exposure to high-pressure mechanical ventilation with high concentrations of oxygen can have a traumatic effect on the newborn’s lungs and frequently leads to the development of bronchopulmonary dysplasia (BPD).³⁰ It has been suggested that BPD can result from high levels of ventilatory support for as little as four days or less.³¹ The pulmonary dysfunction that follows barotrauma and oxygen toxicity associated with mechanical ventilation typically requires weeks to months to resolve. Therefore, patients who have been ventilated for a long time and in whom lung injury has developed are not amenable to a short course of therapy with ECMO. Most ECMO centers will not accept patients who have had more than ten to 14 days of mechanical ventilation, owing to the high probability of established, irreversible pulmonary dysfunction.

Echocardiography should be performed on every patient being considered for ECMO to determine cardiac anatomy and function. Treatable conditions such as total anomalous pulmonary venous return and transposition of the great vessels, which may masquerade initially as pulmonary failure, can be surgically corrected but may require ECMO resuscitation initially. Infants with correctable cardiac disease should be considered on an individual basis. Also, ECMO is an excellent bridge to cardiac and lung transplantation.

Coexisting Anomalies

Every effort should be made to establish a clear diagnosis before the initiation of ECMO. Infants with anomalies incompatible with life do not benefit from ECMO (i.e., trisomy 13 or 18). ECMO is not a resource that is intended to delay an inevitable death. Many lethal pulmonary conditions, such as overwhelming pulmonary hypoplasia, congenital alveolar proteinosis, and alveolar capillary dysplasia, may present as reversible conditions but are considered lethal.³²

Gestational Age

The gestational age of an ECMO patient should be at least 34 to 35 weeks. In the early experience with ECMO, significant morbidity and mortality related to intracranial hemorrhage (ICH) was associated with premature infants (<34 weeks’ gestation).³³ Despite modifications in the ECMO technique over the past two decades, premature infants continue to be at risk for ICH. In preterm infants, ependymal cells within the brain are not fully developed, thus making these infants susceptible to hemorrhage. Systemic heparinization necessary to maintain a thrombus-free circuit adds to this risk.

Birth Weight

Technical considerations and limitation of cannula size restrict ECMO candidates to infants weighing at least 2000 g. The smallest single-lumen ECMO cannula is 8 French, and flow through a tube is proportional to the fourth power of the radius. Small veins permit only small cannulas, resulting in flow that will be reduced by a power of four. Neonates who weigh less than 2 kg provide technical challenges in cannulation and in maintaining adequate blood flow through the small catheters.

Bleeding Complications

Infants with ongoing, uncontrollable bleeding or an uncorrectable bleeding diathesis pose a relative contraindication to ECMO.²⁰ Any coagulopathy should be corrected before initiating ECMO because the need for continuous systemic heparinization adds an unacceptable risk of bleeding.

where P_atm is the atmospheric pressure and FiO₂ is the inspired concentration of oxygen.

where MAP is the mean airway pressure.

Although criteria for ECMO varies from institution and by diagnosis, it is generally accepted that, in the setting of optimal management, an (A–a)DO₂ greater than 625 mmHg for more than four hours, or an (A–a)DO₂ greater than 600 mmHg for more than 12 hours, or an OI of greater than 40 establishes both a relatively sensitive and specific predictor of mortality. Other criteria used by many institutions include a preductal PaO₂ less than 35–50 mmHg for two to 12 hours or a pH of less than 7.25 for at least two hours along with intractable hypotension. These are sustained values measured over a period of time and are not accurate predictors of mortality.14,20,35–37 Patients with CDH are in their own category, and criteria for this disease are discussed later in this chapter.

Older infants and children do not have as well-defined criteria for high mortality risk. The ventilation index is determined by the following:

The combination of a ventilation index greater than 40 and an OI more than 40 correlates with a 77% mortality.³⁸ A mortality of 81% is associated with an (A–a)DO₂ greater than 580 mmHg and a peak inspiratory pressure of 40 cmH₂O.³⁸ Indications for support in patients with cardiac pathology are based on clinical signs such as hypotension despite the administration of inotropes or volume resuscitation, oliguria (urine output < 0.5 mL/kg/h), and decreased peripheral perfusion.

Congenital Diaphragmatic Hernia

Of most interest to pediatric surgeons are neonates with abdominal viscera in the thoracic cavity due to a CDH. These patients are plagued with pulmonary hypertension and have pulmonary hypoplasia, both on the ipsilateral and contralateral sides. Often, pulmonary insufficiency ensues and a vicious cycle of hypoxia, hypercarbia, and acidosis is very detrimental. This process must be interrupted by medical management, which has vastly improved over the past two decades with the use of permissive hypercapnia/spontaneous respiration, pharmacologic therapy, and delayed elective repair.

Various other strategies have been tried to manage critically ill newborns with CDH.³⁹ High-frequency oscillation may have its major role in forestalling respiratory failure when used as a ‘front end’ strategy rather than as a ‘rescue therapy’.⁴⁰ Surfactant plays no more than an anecdotal role. Nitric oxide may be helpful as a vasodilator in the treatment of pulmonary hypertension in these patients. Other pulmonary vasculature vasodilators such as epoprostenol, sildenafil, and iloprost are starting to demonstrate significant efficacy in babies with CDH. The primary indicator for ECMO in the CDH patient occurs when tissue oxygen requirements are not being met, as evidenced by progressive metabolic acidosis, mixed venous oxygen desaturation, and multiple organ failure. The other major indicator is mounting iatrogenic pulmonary injury.

The goal is to maintain preductal oxygen saturations between 90–95%. Spontaneous breathing is preserved by rigorously avoiding muscle relaxants.41,42 Sedation is used only as needed. Meticulous attention to maintaining a clear airway and the well-being of the infant is obvious, but critical. Permissive hypercapnia with spontaneous respiration is initiated with intermittent mandatory ventilation (IMV), 30–40 breaths per minute, equal I/E time, inspiratory gas flow of 5–7 L/min, peak inspiratory pressure (PIP) of 20–22 cmH₂O, and positive end-expiratory pressure (PEEP) of 5 cmH₂O. The FiO₂ is selected to maintain preductal SaO₂ greater than 90%. If this method of ventilation is not effective, as demonstrated by severe paradoxical chest movement, severe retractions, tachypnea, inadequate or labile oxygenation (preductal O₂ saturations <80%), or PaCO₂ greater than 60 mmHg, then a new mode of ventilation is needed.