**1. Introduction**

Neonatal encephalopathy secondary to perinatal asphyxia is a common condition, with a global incidence varying between 1.3 and 6.6‰ depending on birth location [1]. It is associated with significant mortality (i.e., 23% of all neonatal deaths worldwide) and long-term morbidity, including cerebral palsy and global developmental delay [2–4]. In developed countries, therapeutic hypothermia has become the standard treatment for newborns born at 36 or more weeks of gestational age who have suffered from birth asphyxia and who present with moderate to severe encephalopathy in the first hours of life [5]. Hypothermia treatment has been shown to reduce the risk of death and long-term disability in these newborns [6, 7].

primary diagnosis was persistent pulmonary hypertension, meconium aspiration, congenital diaphragmatic hernia, sepsis, and idiopathic respiratory distress. The results suggested significant survival benefits for the newborns, who received ECMO, with a relative risk reduction of 0.55 (95% CI 0.39–0.77) (*p = 0.0005*). These results translate into four newborns, who needed to be treated with ECMO for one newborn to benefit from a reduction in mortality.

Extracorporeal Membrane Oxygenation Use in Asphyxiated Newborns…

http://dx.doi.org/10.5772/intechopen.78761

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As of mid-2017, the international extracorporeal life support organization (ELSO) registry reported a total of 35,598 neonatal runs of ECMO worldwide in active centers [21]. The majority of these neonatal ECMO runs were for pulmonary indications (75%) and a smaller proportion for cardiac indications (20%); extracorporeal cardiopulmonary resuscitation (ECPR)

Several studies have reported on the short- and long-term outcomes of newborns treated with ECMO (22, 23). Some of these studies have found that newborns treated with ECMO are at an increased risk of death and neurodevelopmental impairments [22, 23]. However, a population-based study, which reported the outcomes of 224 newborns treated with ECMO for various indications between 1993 and 2000, showed that 86% of these newborns survived, and 49% had a normal development in the motor, cognitive, and behavioral domains at 5 years of age. The survival and long-term outcomes of newborns, who received ECMO, have been shown to depend significantly on the underlying disease and the indication for ECMO [24, 25]. For example, newborns with congenital diaphragmatic hernia had lower survival rates and a higher incidence of long-term neurodevelopmental impairments, compared to newborns treated with ECMO for other indications, such as

ECMO-related brain injury is a multifactorial process in which factors related to the pre-ECMO illness and events during the ECMO course (including cannulation) play a role [26–30]. During cannulation, a period occurs of decreased blood flow and potential hypoxia when the neck vessels need to be ligated. In veno-arterial (VA) ECMO, the lack of pulsatile blood flow may lead to endothelial dysfunction, which could contribute to the lack of brain autoregulation [29, 30]. In veno-venous (VV) ECMO, even if the carotid artery is spared, a concern exists about venous congestion due to the obstructive nature of the cannula, which can lead to systemic venous congestion and a higher incidence of posterior fossa hemorrhage, compared to patients who are treated with VA ECMO [27, 28]. Thus, although neonatal ECMO has significantly improved the prognosis of some critically ill newborns, it still is associated with a

Clinicians raise concern about increased bleeding risk when providing therapeutic hypothermia during ECMO support. However, several studies have reported the short- and long-term outcomes of newborns treated with ECMO and hypothermia without bleeding complications. Hichiba et al. [31] found that newborns with a body weight between 2 and 5 kg, who were treated with ECMO for severe respiratory failure, could receive hypothermia

constituted only 5% of the total neonatal ECMO runs [21].

non-negligible risk for brain injury in the treated newborns.

**3. ECMO and therapeutic hypothermia**

meconium aspiration syndrome [25].

Hemodynamic instability can develop after birth asphyxia and during hypothermia [8], and may be so severe that some of these asphyxiated newborns treated with hypothermia require support with extracorporeal membrane oxygenation (ECMO) [9–11]. First, transient myocardial ischemia and papillary muscle dysfunction due to subendocardial ischemia occur in one-third of asphyxiated newborns [12, 13]. Second, pulmonary vascular resistances in these newborns are high due to hypoxia-induced pulmonary vasoconstriction, and thus pulmonary hypertension frequently co-exists along with the cardiac dysfunction. Acute pulmonary hypertension may lead to a reduction in the right ventricular function, which, if left untreated, subsequently can impair the left ventricular filling, and hence explain a lower cardiac output [14]. In addition, therapeutic hypothermia results in a lower heart rate in these newborns and a reduction of cardiac output, which reflect the adaptation to the decreased tissue demand during hypothermia treatment [15]. Evidence is accumulating that this hemodynamic instability (including hypotension and persistent pulmonary hypertension) and associated metabolic acidosis and hypoxemia have the potential to worsen brain injury in these newborns [16–18], and thus deserve early and optimal management. Therefore, optimizing the hemodynamic profile of these newborns as early as possible is of the utmost importance for decreasing their risk of further brain injury, even if this requires initiation of ECMO.

## **2. General aspects of neonatal ECMO**

The first reported successful use of neonatal ECMO was in 1975 with a newborn who had meconium aspiration syndrome [19]. Since then, the neonatal ECMO field has evolved rapidly along with the indications and contraindications for this therapy. Broadly, ECMO usually is indicated in newborns for disease processes—believed to be reversible—associated with high mortality.

One of the largest randomized clinical trials of ECMO with newborns was undertaken by the United Kingdom collaborative ECMO trial group [20]. This study enrolled a total of 185 newborns with gestational age ≥35 weeks and birth weight ≥2 kg. The main indication for ECMO in this study was severe respiratory failure with an oxygenation index ≥40. The primary diagnosis was persistent pulmonary hypertension, meconium aspiration, congenital diaphragmatic hernia, sepsis, and idiopathic respiratory distress. The results suggested significant survival benefits for the newborns, who received ECMO, with a relative risk reduction of 0.55 (95% CI 0.39–0.77) (*p = 0.0005*). These results translate into four newborns, who needed to be treated with ECMO for one newborn to benefit from a reduction in mortality.

As of mid-2017, the international extracorporeal life support organization (ELSO) registry reported a total of 35,598 neonatal runs of ECMO worldwide in active centers [21]. The majority of these neonatal ECMO runs were for pulmonary indications (75%) and a smaller proportion for cardiac indications (20%); extracorporeal cardiopulmonary resuscitation (ECPR) constituted only 5% of the total neonatal ECMO runs [21].

Several studies have reported on the short- and long-term outcomes of newborns treated with ECMO (22, 23). Some of these studies have found that newborns treated with ECMO are at an increased risk of death and neurodevelopmental impairments [22, 23]. However, a population-based study, which reported the outcomes of 224 newborns treated with ECMO for various indications between 1993 and 2000, showed that 86% of these newborns survived, and 49% had a normal development in the motor, cognitive, and behavioral domains at 5 years of age. The survival and long-term outcomes of newborns, who received ECMO, have been shown to depend significantly on the underlying disease and the indication for ECMO [24, 25]. For example, newborns with congenital diaphragmatic hernia had lower survival rates and a higher incidence of long-term neurodevelopmental impairments, compared to newborns treated with ECMO for other indications, such as meconium aspiration syndrome [25].

ECMO-related brain injury is a multifactorial process in which factors related to the pre-ECMO illness and events during the ECMO course (including cannulation) play a role [26–30]. During cannulation, a period occurs of decreased blood flow and potential hypoxia when the neck vessels need to be ligated. In veno-arterial (VA) ECMO, the lack of pulsatile blood flow may lead to endothelial dysfunction, which could contribute to the lack of brain autoregulation [29, 30]. In veno-venous (VV) ECMO, even if the carotid artery is spared, a concern exists about venous congestion due to the obstructive nature of the cannula, which can lead to systemic venous congestion and a higher incidence of posterior fossa hemorrhage, compared to patients who are treated with VA ECMO [27, 28]. Thus, although neonatal ECMO has significantly improved the prognosis of some critically ill newborns, it still is associated with a non-negligible risk for brain injury in the treated newborns.
