**4. Pulseless electrical activity**

Pulseless electrical activity (PEA) is a form of cardiac arrest characterized by cardiac electrical activity, detected by ECG, but with the absence of a detectable pulse [13]. Although PEA is a commonly seen cardiac rhythm in adult and pediatric resuscitations (referred to as a "nonshockable rhythm"), occurring in approximately 32 and 24% of cardiac arrests, respectively [14], its occurrence in neonatal resuscitation is unusual and not widely recognized. In response to the inclusion of ECG in the 2015 neonatal resuscitation guidelines, there has been a rise in awareness of PEA in neonatal resuscitation. ECG displaying PEA could falsely mislead health care providers into overestimating the HR and delay necessary resuscitation techniques. It is possible that PEA may be common in asphyxiated newborns but has been undetected in the clinical setting prior to the recent use of ECG in the delivery room. Recent case reports have raised concerns over the reliability of ECG use during neonatal resuscitation, and the detection of PEA has been cited as a potential limitation of ECG use to guide delivery room resuscitation [15, 16]. Data from studies in the pediatric population indicate decreased survival following resuscitation with PEA events [17, 18], however this is inconsistent throughout the literature. Recent case studies in newborn infants presenting with cardiac arrest with PEA rhythm, as indicated on ECG [15, 16], suggest dire outcomes. Further studies (animal and prospective clinical) are needed to determine the cause and actual incidence of PEA in order to improve the survival of newborns experiencing PEA in the delivery room.

*Animal Models in Medicine and Biology*

newborn infants.

**2. Asphyxia at birth**

blood circulation [10].

**3. Current neonatal resuscitation guidelines**

which entails chest compressions (CC) and 100% oxygen with or without administration of epinephrine [5–9]. Despite receiving CPR, approximately 1 million newborns die annually worldwide. Even with successful resuscitation, infants receiving extensive CPR in the delivery room have a high incidence of mortality (40–80%) and neurologic morbidity (e.g. 57% hypoxic–ischemic encephalopathy and seizures) [5, 6, 9]. Therefore, resuscitation techniques require further refinement to provide better outcomes. The guidelines for neonatal resuscitation recommended by the American Academy of Pediatrics/American Heart Association Neonatal Resuscitation Program [2–4] are based, in part, on the recognition that the cause of cardiovascular collapse in most newborns is asphyxia. However, in many cases the guidelines rely on data from studies in the adult population and extrapolate it to the neonatal population. Such data may not be entirely applicable to the neonatal population, because the most common cause of cardiovascular collapse in the adult population is primary cardiac compromise/ventricular fibrillation, not asphyxia. Therefore it is imperative that pre-clinical studies with

appropriate animal models are carried out to determine the optimal

resuscitation techniques before they are translated into the delivery room for

that newborn infants fail to make a successful transition to ex-utero life [10]. Asphyxia may occur from several perinatal events, such as failure of placental gas exchange prior to delivery (e.g. placental abruption, uterine rupture, umbilical cord prolapse, chorioamnionitis), or deficient pulmonary gas exchange immediately after birth (e.g. apnea, airway obstruction, respiratory distress syndrome) [10]. Asphyxia is a condition of impaired gas exchange with simultaneous hypoxia and hypercapnia, leading to a mixed metabolic and respiratory acidosis [10]; it depresses myocardial function leading to cardiogenic shock, pulmonary hypertension, mesenteric reperfusion, acute renal failure, and ultimately cardiac arrest. The cascade of hypoxic–ischemic insults results in dysfunction of one or more organ systems in over 80% of asphyxiated newborn infants [11], leading to significant mortality and long-term morbidity. Newborns affected by perinatal asphyxia often present with an inadequate heart rate that does not respond to positive pressure ventilation (PPV). This is due to depressed myocardial function, vasodilation, and very low diastolic blood pressures through which the heart is unable to efficiently contract. Ineffective pumping of enough blood to the lungs inhibits the exchange and consumption of oxygen that is being delivered via PPV [10]. This inevitably leads to the need for CC to mechanically pump the blood through the heart until the myocardium is adequately oxygenated to resume spontaneous contraction and

Asphyxia at birth, also known as perinatal asphyxia, is the most common reason

Heart rate (HR) is the most important clinical indicator to evaluate the status of compromised newborns and to guide resuscitation efforts in the delivery room [3]. An increase in the newborn's HR remains the most reliable indicator of adequate ventilation [3]. Until recently, HR assessment in the newborn was achieved via (i) palpation of the umbilical cord, (ii) auscultation of the precordium, and/or

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