**10. Persistent pulmonary hypertension of the newborn**

### **(Persistent Fetal Circulation)**

PPHN occurs in term and post-term infants. Predisposing factors include birth asphyxia, meconium aspiration pneumonia, early-onset sepsis, hypoglycemia, polycythemia, maternal use of nonsteroidal anti-inflammatory drugs with in utero constriction of the ductus arterious, and pulmonary hypoplasia as a result of diaphragmatic hernia, amniotic fluid leak, oligohydramnions, or pleural effusions. PPHN is often idiopathic. Some patients with PPHN have low plasma arginine and nitric oxide metabolite concentrationsand polymorphisms of the carbamoyl phosphate synthase gene, findings suggestive of a possible subtle defect in nitric oxide production. The incidence is 1/500-1,500 live births with a wide variation between different clinical centers.


PPHN occurs in term and post-term infants. Predisposing factors include birth asphyxia, meconium aspiration pneumonia, early-onset sepsis, hypoglycemia, polycythemia, maternal use of nonsteroidal anti-inflammatory drugs with in utero constriction of the ductus arterious, and pulmonary hypoplasia as a result of diaphragmatic hernia, amniotic fluid leak, oligohydramnions, or pleural effusions. PPHN is often idiopathic. Some patients with PPHN have low plasma arginine and nitric oxide metabolite concentrationsand polymorphisms of the carbamoyl phosphate synthase gene, findings suggestive of a possible subtle defect in nitric oxide production. The incidence is 1/500-1,500 live births with a wide

a. Pathophysiology: Persistence of the fetal circulatory pattern of right-to-left shunting through the PDA and foramen ovale after birth is due to excessively high pulmonary vascular resistance. Fetal pulmonary vascular resistance is usually elevated relative to fetal systemic or postnatal pulmonary pressure. This fetal state permits shunting of oxygenated umbilical venous blood to the left atrium ( and brain) through the foramen ovale and bypasses the lungs through the ductus arterious to the descending aorta. After birth, pulmonary vascular resistance normally declines rapidly as a consequence of vasodilation secondary to gas filling the lungs, a rise in postnatal Pao2, a reduction in Pco2, increased pH, and release of vasoactive substances. Increased neonatal pulmonary vascular resistance may (1) be maladaptive from an acute injury (e.g., not demonstrating normal vasodilation in response to increased oxygen and other changes after birth); (2) be the result of increased pulmonary artery medial muscle thickness and extension of smooth muscle layers into the usually nonmuscular, more peripheral pulmonary arterioles in response to chronic fetal hypoxia; (3) be due to pulmonary hypoplasia ( diaphragmatic hernia, Potter syndrome); (4) be obstructive as a result of polycythemia or total anomalous pulmonary venous return; or (5) be due to alveolar capillary dysplasia, a lethal, possibly familial disorder characterized by a thickened alveolar septum and a reduced number of small pulmonary arteries and capillaries. Apart from the etiology, profound hypoxia from right-to-left shunting and normal or

b. Clinical Manifestations: Infants become ill in the delivery room or within the first 12 hr of life. PPHN related to polycythemia, idiopathic causes, hypoglycemia, or asphyxia may result in severe cyanosis with tachypnea, although initially, signs of respiratory distress may be minimal. Infants who have PPHN associated with meconium aspiration, group B streptococcal pneumonia, diagphragmatic hernia, or pulmonary hypoplasia usually exhibit cyanosis, grunting, flaring, retractions, tachycardia, and

wall deformity.

variation between different clinical centers.

elevated Pco2 are present.

**(Persistent Fetal Circulation)** 

**10. Persistent pulmonary hypertension of the newborn** 

3. If the medical treatment is unsuccessful or if the use of indomethacin is contraindicated, a surgical ligation of the ductus is indicated. The standard operative approach to the PDA has been through a posterolateral thoracotomy. The safety, effectiveness, and minimally invasive nature of video-assisted thoracoscopic surgery (VATS) have been reported for premature PDA. Advantages of the technique may include no need to cut the muscle and to spread ribs, thus a reduced compromise of respiratory mechanics and of chest shock. Multiorgan involvement may be present. Myocardial ischemia, papillary muscle dysfunction with mitral and tricuspid regurgitation, and cardiac stunning produce cardiogenic shock with decreased pulmonary blood flow, tissue perfusion, and oxygen delivery. The hypoxia is quite labile and often out of proportion to the findings on chest roentgenograms.


Treatment with inhaled nitric oxide (iNO) is indicated for newborns with an oxygen index (OI) of less than 25. Nitric oxide (NO) is an endothelially derived gas signaling molecule that relaxes vascular smooth muscle and that can be delivered to the lung by means of an inhalation device **.** In 2 large, randomized trials, NO reduced the need for extracorporeal membrane oxygenation (ECMO) by approximately 40%. Although these trials led to the US Food and Drug Administration (FDA) approving iNO as a therapy for persistent pulmonary hypertension of the newborn (PPHN), iNO did not reduce mortality, the length of hospitalization, or the risk of neurodevelopmental impairment. A randomized study confirmed that beginning iNO at a milder or earlier point in the disease course (for an oxygenation index of 15-25) did not decrease the incidence of ECMO and/or death or improve other patient outcomes, including the incidence of neurodevelopmental impairment.The use of iNO has not been demonstrated to reduce the need for ECMO in newborns with congenital

Evaluation and Emergency Treatment of

b. Pathology and pathophysiology

fraction).

cyanosis may also be present.

severely affected neonates.

c. Clinical manifestations

(MR).

normal).

indicated.

d. Management

demonstrable by echocardiography. 2. Three levels of severity have been recognized.

compliance producing tachypnea.

dysfunction seen in the newborn infant.

rhythm, hypotension, and vascular collapse result.

with severe acidosis, CNS damages, or advanced sepsis.

**12. Emergency treatment if cyanotic CHD is suspected** 

treatment of hypogycemia are all that are required for mild cases.

Criticlly Ill Neonate with Cyanosis and Respiratory Distress 249

1. Subendocardial ischemia or necrosis ( possibly secondary to hypoxic pulmonary vasoconstriction) occurs in the papillary muscles and other areas of the ventricles in the newborn infant who had prenatal or perinatal hypoxia and distress. Evidence of pulmonary hypertension, bidirectional shunts at the atrial and/or ductal levels, and TR are usually present. Variable degrees of LV dysfunction are

a. Transient tachypnea of the newborn is the mildest form of the condition. Mild LV dysfunction leads to fluid retention, pulmonary edema, and reduced lung

b. Transient tricuspid ( or mitral) regurgitation results from papillary muscle infarction ( evidenced by elevated serum levels of creatine phosphokinase MB

c. Severe CHF with cardiogenic shock is the most severe form of myocardial

1. Tachypnea develops usually in full-term neonates with a low Apgar score. Mild

2. A systolic murmur of TR or MR is commonly present. Rarely, CHF with gallop

3. The ECG may show generalized flat T waves and minor ST segment depression. Abnormal Q waves suggestive of anterior or inferior infarction may be seen. 4. CXR films show varying degrees, sometimes marked, of cardiomegaly. PVMs may be increased due to pulmonary venous congestion ( described as wet lung) in

5. Echo study reveals varying degrees of myocardial dysfunction, including an enlarged LA and /or LV, decreased contractility of the LV, and mitral regurgitation

6. Laboratory studies may reveal mild reduction of Po2 and pH ( but usually without CO2 retention), hypoglycemia, and elevated CPK MB fraction in patients with significant TR. A myocardial perfusion scan may show a diffuse impairment of thallium-201 uptake (different from myocarditis, in which myocardial perfusion is

7. Infants with transient myocardial ischemia usually recover unless it is associated

1. Supportive measures with administration of oxygen, correction of acidosis, and

2. For severely affected infants, ventilatory assistance, short-acting inotropic agents ( such as dopamine), a vasodilator agent, and fluid restriction and diuretic(s) may be

If a cyanotic CHD is suspected, PGE1 should be started or made available. The starting dose is 0.05 to 0.1 µg/kg/min, administered in a continuous IV drip. When the desired effects

diaphragmatic hernia. In these newborns, iNO should be used in non-ECMO centers to allow for acute stabilization, followed by immediate transfer to a center that can provide extracorporeal membrane oxygenation (ECMO).Contraindications to iNO include congenital heart disease characterized by left ventricular outflow tract obstruction (eg, interrupted aortic arch, critical aortic stenosis, hypoplastic left heart syndrome) and severe left ventricular dysfunction.The appropriate starting dose is 20 ppm. Doses higher than this have not been shown to be more effective and have been associated with adverse effects, including methemoglobinemia and increased levels of nitrogen dioxide (NO2).Appropriate lung recruitment and expansion are essential to achieve the best response. If a newborn has severe parenchymal lung disease and PPHN, strategies such as HFV may be required.Most newborns require iNO for less than 5 days. In general, the dose can be weaned to 5 ppm after 6-24 hours of therapy. The dose is then slowly weaned and discontinued when the FiO2 is less than 0.4-0.6 and the iNO dose is 1 ppm. Abrupt discontinuation at higher doses should be avoided because it may cause abrupt rebound pulmonary hypertension. In centers that do not have immediate availability of ECMO support, use of iNO must be approached with caution. Because iNO cannot be abruptly discontinued, transport with iNO is usually needed if a subsequent referral for ECMO is necessary. This capability should be determined in collaboration with the ECMO center before treatment is started. The use of iNO with high frequency ventilation (HFV) creates particular problems for transport, and this should be considered before these therapies are combined in a non-ECMO center.

ECMO, an adaptation of cardiopulmonary bypass, is used when optimal support fails to maintain acceptable oxygenation and perfusion . The introduction of ECMO and other new therapies has had a major effect on reducing the mortality rate associated with PPHN. ECMO support can now be provided using a double-lumen catheter in the internal jugular vein; thus, ligation of the right common carotid artery can be avoided. Although iNO is an effective pulmonary vasodilator, ECMO remains the only therapy that has been proven to be life-saving for PPHN. Therefore, timely transfer to an ECMO center is vital for newborns with severe PPHN.However, it is often difficult to determine the proper timing of a referral to an ECMO center. Referral and transfer should occur before refractory hypoxemia develops. Early consultation and discussion with clinicians at the ECMO center is strongly recommended. Continuous delivery of NO is required during transport. Baseline criteria for newborns considered for ECMO are generally as follows:


#### **11. Transient myocardial ischemia**

#### a. Prevalence

Transient myocardial ischemia is a rarely recognized condition; the prevalence is unknown.

b. Pathology and pathophysiology

248 Congenital Heart Disease – Selected Aspects

therapies are combined in a non-ECMO center.

are generally as follows:

hemorrhage)

a. Prevalence

unknown.

 Gestation of more than 34 week Weight more than 2000 g

**11. Transient myocardial ischemia** 

diaphragmatic hernia. In these newborns, iNO should be used in non-ECMO centers to allow for acute stabilization, followed by immediate transfer to a center that can provide extracorporeal membrane oxygenation (ECMO).Contraindications to iNO include congenital heart disease characterized by left ventricular outflow tract obstruction (eg, interrupted aortic arch, critical aortic stenosis, hypoplastic left heart syndrome) and severe left ventricular dysfunction.The appropriate starting dose is 20 ppm. Doses higher than this have not been shown to be more effective and have been associated with adverse effects, including methemoglobinemia and increased levels of nitrogen dioxide (NO2).Appropriate lung recruitment and expansion are essential to achieve the best response. If a newborn has severe parenchymal lung disease and PPHN, strategies such as HFV may be required.Most newborns require iNO for less than 5 days. In general, the dose can be weaned to 5 ppm after 6-24 hours of therapy. The dose is then slowly weaned and discontinued when the FiO2 is less than 0.4-0.6 and the iNO dose is 1 ppm. Abrupt discontinuation at higher doses should be avoided because it may cause abrupt rebound pulmonary hypertension. In centers that do not have immediate availability of ECMO support, use of iNO must be approached with caution. Because iNO cannot be abruptly discontinued, transport with iNO is usually needed if a subsequent referral for ECMO is necessary. This capability should be determined in collaboration with the ECMO center before treatment is started. The use of iNO with high frequency ventilation (HFV) creates particular problems for transport, and this should be considered before these

ECMO, an adaptation of cardiopulmonary bypass, is used when optimal support fails to maintain acceptable oxygenation and perfusion . The introduction of ECMO and other new therapies has had a major effect on reducing the mortality rate associated with PPHN. ECMO support can now be provided using a double-lumen catheter in the internal jugular vein; thus, ligation of the right common carotid artery can be avoided. Although iNO is an effective pulmonary vasodilator, ECMO remains the only therapy that has been proven to be life-saving for PPHN. Therefore, timely transfer to an ECMO center is vital for newborns with severe PPHN.However, it is often difficult to determine the proper timing of a referral to an ECMO center. Referral and transfer should occur before refractory hypoxemia develops. Early consultation and discussion with clinicians at the ECMO center is strongly recommended. Continuous delivery of NO is required during transport. Baseline criteria for newborns considered for ECMO

No major intracranial hemorrhage on cranial sonograms (ie, larger than a grade II

Transient myocardial ischemia is a rarely recognized condition; the prevalence is

Reversible lung disease or mechanical ventilation for 7-14 days

No evidence of lethal congenital anomalies or inoperable cardiac disease

	- a. Transient tachypnea of the newborn is the mildest form of the condition. Mild LV dysfunction leads to fluid retention, pulmonary edema, and reduced lung compliance producing tachypnea.
	- b. Transient tricuspid ( or mitral) regurgitation results from papillary muscle infarction ( evidenced by elevated serum levels of creatine phosphokinase MB fraction).
	- c. Severe CHF with cardiogenic shock is the most severe form of myocardial dysfunction seen in the newborn infant.
	- 1. Tachypnea develops usually in full-term neonates with a low Apgar score. Mild cyanosis may also be present.
	- 2. A systolic murmur of TR or MR is commonly present. Rarely, CHF with gallop rhythm, hypotension, and vascular collapse result.
	- 3. The ECG may show generalized flat T waves and minor ST segment depression. Abnormal Q waves suggestive of anterior or inferior infarction may be seen.
	- 4. CXR films show varying degrees, sometimes marked, of cardiomegaly. PVMs may be increased due to pulmonary venous congestion ( described as wet lung) in severely affected neonates.
	- 5. Echo study reveals varying degrees of myocardial dysfunction, including an enlarged LA and /or LV, decreased contractility of the LV, and mitral regurgitation (MR).
	- 6. Laboratory studies may reveal mild reduction of Po2 and pH ( but usually without CO2 retention), hypoglycemia, and elevated CPK MB fraction in patients with significant TR. A myocardial perfusion scan may show a diffuse impairment of thallium-201 uptake (different from myocarditis, in which myocardial perfusion is normal).
	- 7. Infants with transient myocardial ischemia usually recover unless it is associated with severe acidosis, CNS damages, or advanced sepsis.
	- 1. Supportive measures with administration of oxygen, correction of acidosis, and treatment of hypogycemia are all that are required for mild cases.
	- 2. For severely affected infants, ventilatory assistance, short-acting inotropic agents ( such as dopamine), a vasodilator agent, and fluid restriction and diuretic(s) may be indicated.
