Consultation with the Specialist: Nonrespiratory Cyanosis: Table 1.

Cyanosis is a physical finding of multiple etiologies that can occur at any age, but most often poses the greatest diagnostic and management challenges when it involves the neonate, especially the newborn infant. Nonrespiratory causes of cyanosis include congenital defects of the heart and great vessels, erythrocyte abnormalities, central nervous system disorders, hypoglycemia, and sepsis (TableT1). Examples are: the 4-hour-old infant who is increasingly cyanotic but is breathing peacefully; the 6-hour-old infant who is increasingly cyanotic and has rapid and labored respirations; the meconium-stained newborn, who becomes increasingly cyanotic with labored respirations despite undergoing tracheal intubation and suctioning; and the mildly cyanotic,hypotonic 8-hour-old infant whose respirations are shallow and irregular and who has periods of apnea. Although the common feature in each of these patients is cyanosis,the etiologies differ.The recognition of cyanosis depends on a number of factors,including the amount of reduced hemoglobin in the circulation (about 0.78 mmol/L of [5 g/dL] of reduced hemoglobin must be present for cyanosis to be clinically evident). Oxidation of hemoglobin by exogenous chemicals and certain specific hemoglobin abnormalities result in methemoglobinemia in which the hemoglobin molecule is incapable of carrying oxygen. The total hemoglobin concentration is another significant factor in that the newborn who has polycythemia may appear cyanotic and the patient who has severe anemia may not have sufficient unsaturated hemoglobin to exhibit clinical cyanosis.Determining the cause of cyanosis in the newborn may be relatively simple or it may be the ultimate challenge to the physician’s knowledge, experience, and ingenuity. Acrocyanosis or cyanosis of the extremities is a relatively common finding in the newborn whose limbs are exposed or cold. Central cyanosis characteristically involves the lips, tongue, mucous membranes,and nail beds (except in the neonate). Differential cyanosis may be seen with certain cardiovascular defects in the presence of a patent ductus arteriosus. Cyanotic lower extremities and acyanotic upper extremities, most often the right arm, occur with right-to-left shunting through a patent ductus arteriosus in association with coarctation of the aorta or interruption of the aortic arch.The availability of technologically advanced diagnostic procedures does not preclude the absolutely essential need to obtain an accurate and complete history and perform a careful physical examination. When was the cyanosis first noted? Is it increasing or remaining stable? Which areas of the body does it involve? What is the mother’s health status? What medications was the mother given prior to the delivery? What was the route of delivery? Was the delivery easy or difficult? What was the Apgar score? What was the birthweight?What are the infant’s pulse and respiratory rates? What is the temperature? Is the muscle tone normal or diminished? How does the cry sound? What is the character of the respirations? Are there retractions?Are rales present? Is there a heart murmur? Does examination of the abdomen demonstrate organomegaly? Are the peripheral pulses present and equal? Answering these questions will provide the examining physician with important information needed to make the correct diagnosis.The cyanosis associated with congenital heart defects most often is central, and little or no improvement in the patient’s color or arterial Po2is noted following the breathing of 100% oxygen. Respirations often are unlabored unless there is pulmonary congestion or the patient’s status has been complicated by the development of heart failure or acidosis,which will affect the respiratory pattern. The presence or absence of a heart murmur is of little assistance because several of the most serious anatomic abnormalities, such as transposition of the great arteries,produce only a very soft murmur or no murmur at all. The character of the second heart sound (S2) may be helpful; a very loud S2 suggests pulmonary or systemic hypertension or malposition of the aorta.Three primary categories of congenital heart defects cause cyanosis. The first are those that result in decreased pulmonary blood flow and are basically a combination of obstruction to pulmonary blood flow and right-to-left shunting at the atrial and/or ventricular levels. Such defects include tetralogy of Fallot,transposition of the great arteries with ventricular septal defect and pulmonary stenosis, pulmonary atresia with intact ventricular septum,and severe pulmonary stenosis with intact ventricular septum. The second category are those defects that result in normal or increased pulmonary blood flow. These include admixture lesions in which mixing of systemic and pulmonary venous blood results in systemic arterial unsaturation. Examples of this category are uncomplicated transposition of the great arteries, total anomalous pulmonary venous return, and truncus arteriosus. The third category includes those defects that cause pulmonary vascular congestion. Cardiac malformations causing left-sided outflow tract obstruction may diminish systemic perfusion and cause respiratory distress because of pulmonary venous obstruction. Also,large left-to-right shunts may produce respiratory distress from pulmonary vascular overload. Cyanosis can be present in each of these subgroups of the third category, but it occurs for quite different reasons.Primary pulmonary hypertension of the newborn or right-to-left shunting through the patent ductus arteriosus and/or foramen ovale with or without primary pulmonary disease may be difficult to differentiate from a cyanotic congenital heart defect. Such right-to-left shunting in the absence of a cardiac structural defect may occur with polycythemia,hypoglycemia, asphyxia, meconium aspiration, group B streptococcal pneumonia, diaphragmatic hernia,and pulmonary hypoplasia.Central nervous system depression causes shallow, irregular respirations; cyanosis; and periods of apnea. Affected infants typically appear hypotonic and lethargic. The findings most often are due to intracranial hemorrhage, but they also could be related to certain sedative medications administered to the mother during her labor, central nervous system infections, or metabolic or electrolyte disturbances.Methemoglobin, an oxidized form of hemoglobin, cannot carry oxygen and, when present in significant quantities, will cause cyanosis. Methemoglobinemia may be acquired following exposure to aniline dyes,nitrobenzene, nitrites, and nitrates. It also occurs as a congenital disorder due to nicotinamide adenine dinucleotide (NADH) cytochrome b5 reductase deficiency and hemoglobin M disorder.Cyanosis may be present in the hypoglycemic newborn and in the septic neonate whose systemic perfusion is markedly compromised.Once the presence of cyanosis is determined from the physical examination of the infant, its degree of severity should be documented immediately by oximetry and confirmed by arterial blood gas and pH determinations. The accuracy of oximetry is influenced by alterations in pH, Pco2, hemoglobin, and peripheral perfusion. It also is affected by the integrity of the application of the electrode to the digit and by movement artifact. Valid arterial blood gas and pH values are obtained best by sampling from the right radial artery.Arterial blood gases and pH should be determined with the patient breathing room air (if clinically stable) and following the breathing of 100% oxygen for 5 to 10 minutes. If the oxygen tension rises to exceed 150 mm Hg,cyanotic congenital heart disease can be excluded, although little or no change in oxygen tension strongly suggests that such a defect is the cause of the cyanosis.The gold standard for immediately ruling out noncardiac causes of cyanosis and establishing the diagnosis of cyanotic congenital heart disease remains echocardiography. When performed by qualified personnel, the exact anatomic diagnosis can be determined with speed and precision.The laboratory evaluation of most infants who have cyanosis should include hematocrit and hemoglobin determinations, white blood cell counts, differential counts, blood glucose determinations, and chest radiographs. If a cardiac etiology is likely, echocardiography is essential;in selected cases, cardiac catheterization and angiocardiography may be necessary to define the cardiac anatomy more precisely. Electrocardiography should be performed if clinical findings suggest a tachyarrhythmia. If a central nervous system etiology is suspected,appropriate scans and drug levels should be considered. The presence of methemoglobin may be detected by placing a few drops of the patient’s blood on filter paper and comparing it with normal blood. Methemoglobin will produce a chocolate brown color.The cyanosis that results from pulmonary disease usually resolves partially, if not completely,following the administration of oxygen. Such treatment will not produce similar results in patients who have nonrespiratory cyanosis, and the cause must be determined and addressed to achieve a successful outcome.Of all of these etiologies, the most common cause of cyanosis in the neonate is a cyanotic congenital heart defect. In many such infants,pulmonary blood flow depends primarily or entirely upon the patency of the ductus arteriosus. If such an entity is suspected, the patient’s primary care physician can provide very essential treatment. This patency must be preserved for the patient to survive, and this may be accomplished by infusing prostaglandin E1 at a dose of 0.05 to 0.1 mcg/kg per minute intravenously, remembering that the most serious side effects of the drug are hypoventilation and apnea.