Pathophysiology Of Cyanosis

Cyanosis results from deoxygenated blood entering the arterial circulation. This can result from either abnormal alignment of anatomic segments, resulting in venous drainage being directed to the systemic arterial circulation with limited systemic–pulmonary mixing (e.g., D-transposition) or abundant systemic–pulmonary mixing (e.g., tetralogy of Fallot, single ventricle, total anomalous pulmonary venous connection). The concentration of deoxygenated hemoglobin must exceed 5 g/dL in systemic arterial blood for cyanosis to be manifest, so patients who are anemic may have low oxygen saturations but may not appear cyanotic. Furthermore, clinical cyanosis is often not recognized by parents and even by clinicians, especially in patients who have deeply pigmented skin.

The magnitude of cyanosis depends on which of the two physiologic types mentioned above is present. In the first, the transposition type, cyanosis is independent of the amount of pulmonary blood flow but instead is related to the amount of mixing between the systemic and pulmonary circulations—with more mixing, there is less cyanosis, and with less mixing, there is more cyanosis. In normal physiology, the aorta is fully saturated, and the aortic saturation is higher than the pulmonary saturation. The pulmonary and systemic circulations are in series, and oxygenated blood returns from the lungs and exits to the body via the aorta. In transposition physiology, the pulmonary artery saturation is higher than the aortic saturation. There are two parallel circulations where the oxygenated blood returns mostly to the lungs and deoxygenated blood mostly to the body. The presence of an atrial septal defect (ASD) (or creating one with a balloon atrial septostomy) allows for some mixing between the two circulations, which results in improved systemic saturation (although still lower than pulmonary saturation). Most of these patients have high pulmonary blood flow.

In the second type of cyanotic heart disease, tetralogy physiology, cyanosis depends on the amount of pulmonary blood flow. With much systemic–pulmonary mixing at some level, the greater the amount of pulmonary blood flow, the lesser the degree of cyanosis; the less pulmonary flow, the more cyanosis.

In differential cyanosis, the preductal oxygen saturation (right arm) is higher than the postductal (lower extremity). This occurs when one ventricle delivers the blood to the upper half of the body, and the other ventricle provides some of the blood to the lower half of the body via a patent ductus arteriosus in the absence of complete systemic–pulmonary mixing. This occurs in coarctation of the aorta and interrupted aortic arch and with persistent pulmonary hypertension of the newborn. Reverse differential cyanosis (postductal saturation > preductal saturation) occurs with transposition of the great arteries in addition to the above conditions.

Other factors affecting the oxygen content in both the pulmonary venous and systemic venous blood can worsen cyanosis in these lesions. Pulmonary edema, pulmonary parenchymal disease, or increased metabolic demands can result in a greater than expected degree of cyanosis.

Clinical Presentation And Evaluation

Cyanosis is the most common presenting sign in these newborns when cyanosis is severe. In lesions with abundant mixing and with pulmonary overcirculation, such as truncus arteriosus, total anomalous pulmonary venous connection, and single ventricle without pulmonary stenosis, the cyanosis is less obvious, but tachypnea and respiratory distress may bring the patient to medical attention. Some lesions such as tetralogy of Fallot have a variable presentation depending on the severity of the obstruction to right ventricular outflow. Despite their variability of presentation, these lesions are discussed together because they present at the same age and should all be considered in the differential of a neonate with suspected severe congenital heart disease. It should also be noted that cyanotic congenital heart disease is increasingly diagnosed prenatally via echocardiography, allowing for delivery of infants with the most severe cases in tertiary care hospitals equipped to care for cyanotic heart disease, reducing end-organ damage and complications, and potentially improving overall survival rates.

The differential diagnosis of cyanosis in an infant or young child includes the congenital cardiac lesions described below but also includes acrocyanosis (blue discoloration of extremities caused by peripheral vasoconstriction), pulmonary disease, and methemoglobinemia.

Evaluation of these patients includes a thorough physical examination and pre- and postductal saturations, chest radiography, electrocardiography, and hyperoxia test. Transthoracic echocardiography confirms the anatomy of the lesions and may provide important information regarding cardiac physiology.

The hyperoxia test can be a useful tool for differentiating cardiac and noncardiac cyanosis. It relies on the principle that hypoxemia caused by cardiac abnormalities is not corrected by increasing the inspired fraction of inspired oxygen (FiO₂). Therefore, in a child with FiO₂ of 100%, a right radial (i.e., preductal) arterial pAO₂ less than 150 mm Hg suggests cyanotic congenital heart disease. Higher pAO₂s suggest pulmonary disease with rare exceptions. Furthermore, pulmonary disease usually permits a much larger increase in pAO₂ than does structural heart disease.

Transposition of the Great Arteries

Transposition of the great arteries means that the pulmonary artery arises above the left ventricle and the aorta above the right ventricle (Figure 44-1). It is the most common cardiac cause of cyanosis in the neonatal period (0.2-0.4 in 1000 live births), accounting for 7% of congenital heart defects. Its incidence is increased in infants of diabetic mothers. It is not seen in patients with DiGeorge syndrome. Cyanosis results because the pulmonary and systemic circulations flow parallel to one another with minimal mixing: deoxygenated systemic venous blood returns to the right atrium and right ventricle and out the aorta, and oxygenated pulmonary venous blood returns to the left atrium and left ventricle and exits into the pulmonary arteries. These two parallel circuits are compatible with survival only because there is some point of mixing, usually at the foramen ovale.

Figure 44-1 Transposition of the great arteries.

Immediate intervention is usually necessary to augment the interatrial shunt. This is accomplished through a Rashkind balloon atrial septostomy (see Figure 44-1). This procedure allows for increased mixing, resulting in tolerable aortic saturations. Surgery remains the definitive therapy. Historically, this was accomplished through an atrial switch operation—Mustard (see Figure 44-1) or Senning procedures—redirecting inflow from the pulmonary veins to the right ventricle and from the venae cavae to the left ventricle. Perioperative mortality was low, but concerns regarding arrhythmia and the durability of the right ventricle (which remains the systemic ventricle) led to a different surgical approach, with a higher degree of technical difficulty but improved physiology. Currently, the preferred method is the arterial switch operation in which (1) the aorta is bisected and the distal aorta is brought beneath the bifurcation of the pulmonary trunk while the pulmonary trunk is displaced anteriorly (the Lecompte maneuver) where the aorta is anastomosed to the former pulmonary trunk and the main pulmonary artery is anastomosed to the former aortic trunk, (2) the coronary arteries are detached from the former aortic trunk and reimplanted on the pulmonary trunk (the new aortic root) with pericardial patches placed on the sites where the coronary arteries were harvested, and (3) the ASD is repaired (see Figure 44-1).