Healthcare in India

Healthcare in India

Approach and Management of Cyanotic Newborn: Guidance for Primary Caretakers

Cyanotic congenital heart disease can be categorized based on duct dependent lesions, duct dependent mixing lesions, lesions presenting as severe pulmonary arterial hypertension, cyanosis associated with increased pulmonary blood flow and non-duct dependent reduced pulmonary blood flow. Their presentation is dramatic and the progress is catastrophic unless properly intervened. To reach complete correct diagnosis and to plan timely intervention, multidisciplinary approach is necessary.

Cyanotic Congenital heart disease (CHD) remains an important cause of morbidity and mortality in neonates. Usually their presentation is dramatic and the progress is catastrophic unless properly intervened. Cyanotic CHD presenting in neonatal period requires an aggressive and systematic approach to reach complete correct diagnosis and to plan timely intervention whether corrective or palliative. This involves teamwork of obstetrician, neonatologist, pediatric cardiologist, pediatric cardiac surgeon and pediatric cardiac intesivist. In current era usually diagnostic work up is done with detail echocardiographic evaluation supplemented by CT / MRI / cardiac catheterization in some cases if required.

Initial Evaluation of Neonate with Cyanosis

Cyanosis (from the Greek word meaning “dark blue”) in the newborn is defined as an arterial saturation less than 90% and a PO2 less than 60 mmHg. The most common mechanisms causing arterial desaturation are-

Differentiating among these causes is the first step toward diagnosis and treatment of these sick neonates. A careful history should be obtained from the parents with particular attention to any problems with feeding, breathing, or diaphoresis. A thorough physical examination should then be performed. Dysmorphic features may suggest a genetic syndrome with associated congenital heart lesions. The character of the infant's respirations should be noted. Carefully performed auscultation and systemic examination gives important clues towards the diagnosis.
Pulse oximetry and an arterial blood gas determinationshould beperformed immediately if cyanosis is present or suspected. These measurements should be performed initially on room air to serve as a baseline. Subsequent measurements obtained on 100% oxygen (Hyperoxia Test – 100 % inspired oxygen for at least 10 minutes) may help to differentiate between cardiogenic and non-cardiogenic causes of neonatal cyanosis1. Infants with neurological or primary pulmonary causes of cyanosis will demonstrate substantial increases in arterial PO2 (usually >200 mmHg) on 100% oxygen while infants with cyanotic CHD show minimal elevation (PO2 < 70 mmHg). Some neonates with cyanotic CHD with increased pulmonary blood flow (like Truncus Arteriosus) may show substantial increase in arterial PO2 level (up to 100-200 mmHg) with Hyperoxia Test.
A chest radiograph should always be performed in initial evaluation of cyanotic CHD. Apart from ruling out abnormalities of the lung fields and extra-thoracic structures, chest radiograph gives important information regarding cardiac silhouette and degree of pulmonary blood flow. Pulmonary vascular markings may be decreased in cyanotic CHD with duct dependent pulmonary circulation (e.g. pulmonary Atresia) and obstructed pulmonary blood flow (e.g. critical pulmonary stenosis). In contrast, pulmonary vascular markings may be increased in admixture lesions like transposition of the great arteries (TGA), total anomalous pulmonary venous connection (TAPVC) and truncus arteriosus.
The cyanotic heart diseases presenting in neonatal period can be discussed under following groups:
(I) Duct dependent lesions - Cyanosis is dependent on right to left shunt due to pulmonary stenosis (PS) or atresia
(II) Duct dependent mixing lesions – Transposition of great arteries
(III) Lesions presenting as severe pulmonary arterial hypertension – Obstructed TAPVC
(IV) Cyanosis associated with increased pulmonary blood flow – Admixture lesions.
(V) Non-duct dependent reduced pulmonary blood flow

Group I
1. Pulmonary atresia with intact ventricular septum
They are group of very sick patients and present in neonatal life with cyanosis as the ductus constricts. Classical presentation includes severe cyanosis associated with tachypnea in early neonatal period. Clinical features include deep cyanosis, single second heart sound and a continuous murmur may or may not be heard. Chest radiograph will show absence of cardiomegaly which reduces pulmonary blood flow. Congestive heart failure (CHF) may be part of this complex if there is associated significant tricuspid regurgitation (TR).
As soon as the diagnosis is suspected, these patients should be started on prostaglandin E1 (PGE1) infusion2. PGE1 serves to reopen the ductus arteriosus or prevent it from closing. This allows partially desaturated systemic arterial blood to enter the pulmonary artery and be oxygenated. Timely use of this agent has profoundly decreased early morbidity and mortality in patients with cyanotic heart defects. Patients can be stabilized more easily, allowing for safe transport to a tertiary care center.  The initial dose of PGE1 is 0.05 mcg/kg/min (maximum up to 0.4 mcg/kg/min), which can be reduced to 0.01 - 0.02 mcg/kg/min when the patient is stable. Adverse effects are relatively uncommon and include apnea, hypotension, edema, and fever.
Subsequently a detailed echocardiographic evaluation to assess the atrial communication, right ventricular size, inflow, cavity, outflow, type of atresia - membranous/muscular, dependency of coronary circulation should be done.
The goals of intervention (catheter/surgical) in this group of patients are to enhance pulmonary blood flow and promote right ventricular growth in cases of relative hypoplasia3.
Patients in whom the right ventricle is severely hypoplastic and coronary circulation is dependant on right ventricle will be candidates for early Blalock Taussig (BT) shunt or ductal stenting. If there is associated restrictive PFO, they need balloon atrial septostomy (BAS).
Those who do not have RV dependant coronary circulation usually have better right ventricular cavity. If they have membranous pulmonary atresia, they will be benefited by performing radio frequency guided pulmonary valvar perforation and balloon dilation of the pulmonary valve. Patients with non-dependant coronary circulation and muscular pulmonary atresia, if have associated mild right ventricular hypoplasia, are taken up for surgical right ventriculotomy. They may or may not need additional BT shunt.

2. Pulmonary atresia with ventricular septal defect (VSD)
The clinical presentation and initial management is almost similar to patients with pulmonary atresia with intact ventricular septum. However, CHF is relatively rare is this group of patients presenting with cyanosis in neonatal period.
These patients usually have adequate right ventricle size and initial intervention would be 
BT shunt or ductal stenting provided that the branch pulmonary arteries are confluent.
Patients with more complex heart diseases associated with pulmonary atresia like tricuspid atresia, double inlet ventricle will also have similar presentation and initial management strategies as discussed above.
3. Critical PS with TR
Some patients of isolated critical valvular PS present with cyanosis due to right to left atrial shunt in newborn period. They are usually associated with TR and CHF. The initial management in these patients will be supportive care (including decongestive and ionotropic support) and PGE1 infusion if required. These patients need urgent balloon dilation of the pulmonary valve with good results4. However some cases may need repeat balloon dilation later in the life for restenosis/residual obstruction.
4. Ebstein’s anomaly of the tricuspid valve
Severe Ebstein's anomaly of the tricuspid valve may present in neonatal period with CHF, tricuspid regurgitation and right to left atrial shunt. These patients will have functional pulmonary atresia due to severely incompetent tricuspid valve associated with elevated pulmonary vascular resistance leading to poor antegrade flow through pulmonary valve. These patients can usually be stabilized with medical treatment, as they tend to improve with fall of pulmonary vascular resistance. Corrective or palliative surgery is planned according to the degree of tricuspid valve displacement electively.

Group II
D Transposition of Great Arteries (dTGA) with intact ventricular septum
dTGA is the most common cyanotic CHD present in early neonatal period. These babies present with severe cyanosis, CHF and hypoxia due to inadequate intra-circulatory mixing as ductus constricts in early neonatal period. Clinical examination is usually unrewarding expect presence of deep cyanosis and CHF. These babies are very sick and deteriorate rapidly unless intervened timely. They should be started on PGE1 infusion as soon as diagnosis is suspected. Other supportive measures should be started and the baby should be transported to a centre where balloon atrial septostomy (BAS) can be done to allow adequate mixing. BAS can even be done under echocar­diographic guidance also. After stabilization they should undergo arterial switch operation before 4 weeks of life5.
Group III
Obstructed TAPVC
These are another group of patients who became critically ill in early neonatal period. In these patients pulmonary veins are not attached to the left atrium, but converge in a common confluence just posterior to left atrium. This confluence drains into a systemic venous structure which may be obstructed. Usual sites of obstruction are hepatic sinusoids in case of infradiaphragmatic TAPVC or at interatrial communication (patent foramen ovale or atrial septal defect). The obstruction to pulmonary venous flow causes pulmonary venous hypertension and subsequent pulmonary edema. These babies are often extremely ill, with profound desaturation and acidosis. The clinical examination shows evidence of pulmonary arterial hypertension and CHF with or without cardiomegaly. The PGE1 administration does not improve oxygenation in this case because elevated pulmonary pressures in the right side of the heart (due to obstructed pulmonary outflow) will result in right to left shunting across an open ductus further decreasing arterial saturation1. The only treatment for this condition is emergency surgery6. Those with restrictive interatrial communication may get benefited with BAS which should be used as temporary measure for initial stabilization.
Group IV
Admixture Lesions:
These patients will have increased pulmonary blood flow with pulmonary arterial hypertension. The cardinal clinical features are presence of mild cyanosis, CHF, cardiomegaly, loud P2 if second heart sound is splitted and flow murmurs. After initial diagnostic work up, these patients should be treated with aggressive decongestive therapy and nutrition interventions to control CHF and optimize the weight gain. The type of surgical intervention will depends upon individual lesion:
1. dTGA with VSD:
Babies with dTGA and VSD may need balloon atrial septostomy to decompress the left atrium and improve CHF. The arterial switch operation and VSD closure are usually done between 4-8 weeks of life.
2. Truncus Arteriosus:
These patients should have surgical correction i.e. closure of the VSD and right ventricle to pulmonary artery conduit at 4-6 weeks of life7. The first appearance of CHF in the form of tachypnea can be taken as an indication of fall in pulmonary vascular resistance and optimal time for corrective surgery.
3. Single ventricle physiology:
This group includes patients with tricuspid atresia, double inlet ventricle or straddling AV valves with no PS physiology.  They should be offered pulmonary artery banding at 4-8 weeks of life, the time when CHF starts appearing to prevent the effects of excessive pulmonary blood flow i.e. pulmonary hypertension, ventricular dilation or ventricular outlet obstruction.
Group V
Cardiac lesions in this group are collectively know as ‘TOF physiology’, which is combination of a large interventricular communication with pulmonary outflow tract obstruction. Namely these lesions are tetralogy of Fallot, double outlet right ventricle with PS, tricuspid atresia with PS, dTGA with VSD and PS, atrioventricular canal defect with PS and other complex cyanotic heart disease associated with PS (Univentricular physiology). The degree of cyanosis is variable and is directly proportionate to severity of pulmonary outflow tract obstruction. Salient clinical features include variable cyanosis, absence of CHF or cardiomegaly, single second heart sound and ejection systolic murmur at pulmonary area (intensity of murmur is inversely proportionate to degree of cyanosis). These neonates are usually managed conservatively. However, if they develop repeated spells, not adequately controlled with the treatment of precipitating factors and beta-blockers, or if the saturation is below 70%, they are palliated with BT shunt. 
Mimicker of cyanotic CHD in the Newborn
Primary Pulmonary Arterial Hypertension of Newborn
Some infants present with cyanosis due to right to left shunt at atrial level with persistent pulmonary hypertension. The most important role of the pediatric cardiologist in this condition is to rule out any treatable cause for PAH. They are best managed by neonatologist with ventilatory and other supportive measures.

Conclusion

Cyanotic heart disease presenting in the neonatal period requires rapid diagnosis and early referral to an equipped centre because these patients can become unstable very quickly. Prostaglandin E1 plays a key role in preoperative stabilization in many, but not all, of these conditions. Echocardiography is the diagnostic tool of choice in most of cases. A timely planned intervention; either surgical or catheter based, palliative or corrective can salvage most of cyanotic newborns