1. Cyanosis
Cyanosis is a physical sign characterized by bluish discoloration of the skin or mucous membranes due to the presence of excessive amount (not a ratio) of reduced hemoglobin in the capillary bed. Clinically, cyanosis can be noticed when the concentration of reduced hemoglobin is more than 3-5 g/dL.
Various neonatal clinical conditions may present with cyanosis. Some healthy neonates look blue (nonpathologic cyanosis) due to facial plethora, neonatal polycythemia, circum oral venous congestion, or just a dark lip. However, because neonates with pathologic cyanosis are usually critically ill and most of the cyanotic CHDs are potentially life-threatening, early assessment and decision-making, and timely interventions are very important to improve their outcomes.
There are two mechanisms (or types) of pathologic cyanosis. One mechanism involves excessive oxygen uptake (or consumption) by the tissues (peripheral cyanosis). In patients with peripheral cyanosis, the extremities are cyanotic, pale and cool, but the tongue and conjunctiva are pinkish, that is, systemic arterial oxygen saturation is usually normal. Sepsis, cold exposure, shock or low cardiac output state, hypoplycemia, or metabolic disorders are differential diagnoses of peripheral cyanosis. The other mechanism of cyanosis involves decreased oxygen saturation (increased reduced hemoglobin) in the systemic arterial blood (central cyanosis); this form of cyanosis is usually found in cardiovascular, pulmonary, central nervous system or neuromuscular abnormalities, or methemoglobinemia. Patients with central cyanosis show cyanosis on the extremity as well as on the lip, tongue, and conjunctiva. Since peripheral circulation is usually normal, the patient's extremities are warm and capillary filling is rapid. Arterial blood gas analysis will show decreased oxygen tension and saturation in patients with central cyanosis.
The most common noncardiac causes of cyanosis in the newborn are pulmonary disorders such as primary lung disease, airway obstruction and extrinsic compression of the lungs
5). Therefore, differentiating the cardiovascular and pulmonary causes of cyanosis in the neonates is an important issue in clinical practice. In the majority of patient, high index of suspicion and a thorough history taking and physical examination with blood pressure measurements at the four extremities, measurements of oxygen saturation with a hyperoxia test, EKG, and chest radiography may differentiate cyanosis of different origins.
Because some cases of neonatal undiagnosed cyanotic CHD may show rapid deterioration or result in the death of the patient, immediate medical interventions are mandatory in critically ill neonates with suspected congenital heart disease even before an accurate cardiac diagnosis is made.
Some useful clues can be employed to differentiate cyanosis of cardiac and pulmonary origins (
Table 1). In patients with cardiac cause of cyanosis, respiration is relatively comfortable despite cyanosis, which may worsen on crying. A heart murmur and abnormal cardiac silhouette indicate cardiac defects. While cyanotic CHDs with ductal-dependant pulmonary circulation (right-sided obstructive lesions) usually show normal or decreased pulmonary vascular markings (darker lung field) in chest radiographs, ductal-independent mixing lesions such as TGA, truncus arteriosus, and total anomalous pulmonary venous return (TAPVR) may be frequently associated with pulmonary vascular congestion or edema. An abnormal QRS axis or rhythm disturbances suggest heart defects. Arterial blood CO
2 tension is normal or low. Response to 100% O
2 supply is blunted because of right-to-left shunts in the cardiac level. A neonate with oxygen saturation less than 85% (O
2 tension less than 50 mmHg) in both room air and 100% oxygen is very likely to have a cyanotic CHD with an intracardiac right-to-left shunt, and immediate presumptive therapy with prostaglandin infusion should be initiated in such patients
5).
Patients with pulmonary causes of cyanosis usually show apparent tachypnea, distress, and retraction. Cyanosis may improve on crying because of increased ventilation. Rale, crackle, or wheezing may be heard in such patients. In chest radiography, the cardiac shape and size are usually normal, but the lung fields may show abnormal findings such as a ground-glass appearance, pneumonic infiltration, atelectasis, or pneumothorax. In these patients, arterial blood CO
2 tension is usually high because of airway problems and alveolar hypoventilation. These patients show a profound response to 100% O
2 supply and hyperventilation, although this response is transient in some severe cases. In cyanotic patients with lung problems, arterial blood O
2 saturation may easily increase up to 100% (arterial blood O
2 tension >150 mmHg) in 100% oxygen supply ("hyperoxia" test), but this value hardly reach 100% in patients with cyanotic CHDs
5).
Certain CHDs may present with a "differential cyanosis", in which the preductal part of the body (upper part of the body) is pinkish but the postductal part of the body (lower part of the body) is cyanotic, or vice versa ("reverse differential cyanosis"). The prerequisite for this unique situation is the presence of a right-to-left shunt through the PDA and severe coarctation of the aorta or aortic arch interruption or severe pulmonary hypertension. In patients with severe coarctation of the aorta or interruption of the aortic arch with normally related great arteries, the preductal part of the body is supplied by highly oxygenated pulmonary venous blood via the LA and LV, whereas the postductal part is supplied by deoxygenated systemic venous blood via the RA, RV, main pulmonary artery (MPA) and the PDA. In the newborn with structurally normal heart, a differential cyanosis may be associated with persistent pulmonary hypertension of the newborn. In the cases of TGA with coarctation of the aorta or aortic arch interruption, the upper body is mostly supplied by systemic venous blood via the RA, RV, and ascending aorta, whereas the lower body is supplied by highly oxygenated pulmonary venous blood via the LA, LV, MPA, and then the PDA. For accurate detection of differential cyanosis, oxygen saturation should be measured in both preductal (right finger) and postductal (feet) parts of the body.
2. Respiratory distress and/or pulmonary edema
Severe respiratory distress or pulmonary edema develops in cases of CHDs with excessive and nonrestrictive pulmonary blood flow or lesions associated with pulmonary venous obstruction, which result in tachypnea, chest wall retraction and increased work of breathing.
The common lesions responsible for these symptoms include most left-sided obstructive lesions (present with systemic hypotension or collapse), TGA with restrictive interatrial communication (presents with severe cyanosis), an obstructive type of TAPVR (presents with severe cyanosis) and truncus arteriosus (present with mild cyanosis). Simple left-to-right shunt lesions including VSD, ASD, AVSD, and PDA rarely present with severe pulmonary edema or distress during the neonatal period because of the relatively high pulmonary vascular resistance, which may restrict pulmonary blood flow. Preterm PDA may present with pulmonary edema and respiratory distress.
3. Systemic hypotension, shock, or collapse
In the newborn, various clinical conditions may present with systemic hypotension, shock, or collapse. The most common cardiac causes of these symptoms are the left-sided obstructive lesions, such as HLHS, critical AS, severe coarctation, and interruption of the aortic arch. A typical example is HLHS, in which the left ventricle cannot support the systemic circulation. The RV supports the pulmonary and systemic circulation that is maintained by the flow from the MPA to the aorta through the PDA. The upper part of the body and coronary arteries are supplied by the retrograde flow to the aortic arch and ascending aorta in this situation. Constriction and closure of the PDA result in sudden systemic hypotension and shock. In such situations, the only way to rescue the patient is to open the PDA immediately and perform other supportive managements including fluid therapy, respiratory care (usually involving mechanical ventilation with sedation, paralysis, and controlled ventilation), and inotropic support. The other causes of cardiogenic shock in the newborn are neonatal dilated cardiomyopathy or myocarditis and myocardial dysfunction due to tachyarrhythmias such as atrial flutter or paroxysmal supraventricular tachycardia.
Other significant conditions that may be suspected in the differential diagnosis of neonatal shock are neonatal sepsis or meningitis, hypoglycemia, and inborn errors of metabolism. In addition to careful history-taking and physical examination, chest radiography and electrocardiography are very useful to differentiate CHDs from other causes in emergent situations. One study in the neonates presenting with either bacterial sepsis or meningitis, or left-sided obstructive lesions showed that the presence of cardiomegaly predicted heart defects with 85% sensitivity and 95% specificity with a positive predictive value of 95% for CHDs
6). If a neonate presenting with shock is suspected to have a CHD, the initial management should involve the basics of advanced life support along with immediate prostaglandin infusion to maintain the PDA even before an accurate diagnosis is made by a cardiologist
5).