Perspective

Cyanosis is a clinical sign caused by the presence of deoxygenated blood in the capillary beds, most readily observed in the mucous membranes, conjunctiva, nail beds, and skin. The presence of cyanosis usually means that there are at least 4 to 5 g/dL of deoxyhemoglobin in the blood, which correlates with an oxygen saturation of about 80 to 85%.³ Central cyanosis results from a decrease in pulmonary ventilation and oxygenation, a decrease in pulmonary perfusion, the shunting of deoxygenated blood directly into the systemic circulation, or the presence of abnormal hemoglobin. Cyanosis in the neonate can be due to a variety of cardiac, pulmonary, or hematologic causes. Cardiac causes of cyanosis include congenital lesions with right-to-left shunts and cardiac lesions with decreased or increased pulmonary blood flow. Common pulmonary causes of cyanosis include bronchiolitis, pneumonia, and pulmonary edema. Methemoglobinemia can be one of the hematologic causes of cyanosis.

Clinical Features of Cyanosis

The region of the body that is cyanotic can provide important clinical clues to the cause of the cyanosis. Central cyanosis involves the lips, tongue, and mucous membranes, whereas peripheral cyanosis (acrocyanosis) involves the hands and feet. Acrocyanosis is a common phenomenon in neonates caused by cold stress and peripheral vasoconstriction. Central cyanosis reflects a pathologic origin and is an ominous sign. Infants with cyanosis secondary to a congenital heart defect may not exhibit as much respiratory distress compared with the infant with cyanosis due to a pulmonary cause. Thus a cardiac cause of central cyanosis may be more likely than a purely pulmonary cause in the child who appears “comfortably blue.” Another important clinical clue to the cause of central cyanosis is that cyanosis of cardiac origin usually worsens with crying, whereas cyanosis due to a pulmonary cause may improve when the infant cries.⁴ Cyanotic congenital heart defects with right-to-left shunting will demonstrate a minimal improvement with supplemental oxygen, whereas cyanosis of a purely pulmonary origin typically exhibits a significant improvement with supplemental oxygen (Table 171-1).

General Appearance and Pulses

All four extremities should be palpated for the presence and quality of pulses. The brachial and femoral pulses are the easiest to feel in infants. Bounding pulses are typically present in infants with a patent ductus arteriosus. Coarctation of the aorta should be suspected in any child with strong or unequal pulses in the upper extremities and weak pulses in the lower extremities. The pulse may be weak and thready in all extremities in a child who presents with CHF and shock.

Vital Signs and Blood Pressures

A mild resting tachypnea or tachycardia may be the only clinical clue to an underlying cardiovascular disorder. Age-related variables in heart rates, respiratory rates, and blood pressures can be a source of frustration and confusion to those clinicians who do not manage pediatric patients on a routine basis. Although there are numerous tables of pediatric vital signs with variations based on sleep or awake states, one can easily recall a rough estimate of the normal pediatric heart rates and respiratory rates by a simplified table of pediatric vital signs (Table 171-2).⁷ The methods to calculate the normal expected blood pressures and hypotensive blood pressures are also listed in Table 171-2.⁸

An accurate blood pressure reading is accomplished by use of a cuff that covers two thirds of the upper arm or thigh. A cuff that is too narrow will overestimate the patient’s true blood pressure, and a cuff that is too large will underestimate the true blood pressure. Any child with a suspected cardiac disorder should have blood pressures measured in both arms. If the blood pressure in the left arm is significantly lower than the blood pressure in the right arm, a coarctation of the aorta proximal to the origin of the left subclavian artery should be suspected. Blood pressures should be measured in the thighs in any child with a suspected aortic coarctation or documented hypertensive blood pressures in the upper extremities. The mere presence of femoral pulses does not rule out clinically the possibility of a coarctation of the aorta. Even with an appropriately sized cuff, the blood pressures in the thighs can be 10 to 20 mm Hg higher than the blood pressures in the upper extremities because of the lack of well-designed blood pressure cuffs for the legs. Therefore, if the measured blood pressure in the lower extremities is lower than the blood pressure in the upper extremities, coarctation of the aorta should be suspected. Pulse oximetry readings that are lower in the legs than in the upper extremities are also suggestive of either a coarctation of the aorta or a right-to-left-shunt across a patent ductus arteriosus.⁹

Cardiac Auscultation

The intensity and degree of splitting of the S₂ heart sound (which reflects closure of the pulmonic and aortic valves) are extremely important in a pediatric cardiologic evaluation. In normal children, both components (aortic closure and pulmonic closure) of S₂ should be heard along the left upper sternal border (the pulmonic area). A widely split and fixed S₂ suggests a physiologic problem resulting from either a constant volume overload to the right side of the heart (e.g., atrial septal defect) or a pressure overload to the right side of the heart (e.g., pulmonic stenosis). The classic congenital heart defect that is associated with a widely split and fixed S₂ is the atrial septal defect. The intensity of the S₂ component may be louder than normal in the child with pulmonary hypertension.

The third heart sound (S₃), which is best heard along the lower left sternal border or the apex, can be a normal finding in children and young adults. S₃ is produced by a rapid filling of the ventricles and is heard during early diastole, just after the S₂ sound. A loud S₃, however, is pathologic and due to dilated ventricles from volume overload (e.g., CHF and large ventricular septal defects). The fourth heart sound (S₄) occurs late in diastole, just before the S₁ sound. The finding of an S₄ is due to a decrease in compliance of a stiff, hypertrophic ventricle, best heard at the apex with the patient in the left lateral decubitus position.

Cardiac murmurs are produced by turbulent blood flow through the heart. The presence of a cardiac murmur may not be associated with an underlying cardiac defect, however. The location, intensity, quality, timing, and radiation of the murmur determine whether the murmur is suggestive of an underlying cardiac pathologic condition. Although systolic murmurs can be present without any underlying anatomic abnormalities, diastolic murmurs are always considered pathologic in nature. Some of the other criteria that would suggest an underlying anatomic cardiac abnormality are listed in Box 171-4. Murmurs may be difficult to appreciate in the noisy emergency department setting and given the degree of tachycardia that is often present even in normal infants. However, the location of the murmur may be a valuable clinical tool in determining the underlying anatomic origin of the murmur (Box 171-5).

Murmurs without any underlying anatomic abnormalities or hemodynamic significance are termed innocent or functional murmurs. All innocent murmurs are associated with normal ECGs and normal chest radiographs. Two of the most common innocent murmurs encountered in the pediatric population are the neonatal pulmonic flow murmur (also known as the peripheral pulmonic stenosis murmur) and Still’s murmur. The pulmonic flow murmur of the neonate is due to the relatively thin walls and angulation of the right and left pulmonary arteries at birth. This systolic murmur is best heard at the left upper sternal border with radiation throughout the entire chest, axilla, and back. It usually disappears by 3 to 6 months of age. Persistence of a systolic murmur in the pulmonic area beyond this period should raise the possibility of a pathologic pulmonary arterial stenosis.

Another common innocent murmur in children is Still’s murmur, which is a systolic murmur that typically occurs in children between 2 and 6 years of age. This systolic murmur is best heard along the left midsternal border. The distinctive quality of this murmur has been described as being vibratory, musical, and twanging and results from turbulent flow. The distinct quality of this murmur helps distinguish Still’s murmur from a ventricular septal defect murmur, which has a harsher quality. The intensity of Still’s murmur can be increased with fever, excitement, exercise, or anemia.

Hyperoxia Test

The hyperoxia test is an important bedside diagnostic tool to help differentiate between cardiac and pulmonary causes of central cyanosis. This test consists of assessment of the rise in arterial oxygenation with the administration of 100% oxygen. An arterial blood gas is measured on room air (if tolerated) and repeated after several minutes on high-flow oxygen (100% oxygen); the two blood gas analyses are then compared. When the child is breathing high-flow oxygen, an arterial oxygen partial pressure (PaO₂) of more than 250 mm Hg virtually excludes hypoxia due to CHD—a “passed” hyperoxia test.¹⁰ An arterial oxygen reading of less than 100 mm Hg (in a child without obvious pulmonary disease) is consistent with a right-to-left shunt and is highly predictive of CHD—a “failed” hyperoxia test.¹⁰ Values between 100 and 250 mm Hg may indicate lesions with intracardiac mixing. Pulse oximetry is not an appropriate substitute for an arterial blood gas analysis; it is not sensitive enough to determine “pass or fail” of the test because a child breathing high-flow oxygen and registering 100% on pulse oximetry may actually have a PaO₂ anywhere between 80 and 680 mm Hg.¹ Prolonged administration of 100% oxygen may cause some theoretic problems, such as closure of the ductus arteriosus in those infants with critical left-sided heart obstructions or pulmonary vasodilation (which would potentially worsen pulmonary vascular congestion).³ However, oxygen should not be withheld initially in critically ill infants; continuous reassessment is crucial in the evaluation and management of children with suspected CHD.¹

Arterial Blood Gas Analysis

Patients with CHF exacerbation can exhibit respiratory acidosis (low pH and high PaCO₂) in addition to a low PaO₂. In contrast, children with compensated cyanotic congenital heart defects may have a normal pH despite a (chronically) low PaO₂. Patients with congenital heart defects who are not experiencing respiratory failure are unlikely to exhibit elevation in PaCO₂. Any cardiac condition that results in inadequate tissue perfusion (i.e., any of the acyanotic congenital heart defects that are manifested in CHF) will exhibit a metabolic acidosis with or without respiratory compensation.

Hemoglobin and Hematocrit Levels and Serum Electrolyte Values

The hemoglobin and hematocrit levels may reveal a compensatory physiologic elevation (i.e., polycythemia) in children with cyanotic congenital heart defects. Any concurrent medical illness or blood loss that produces an acute anemia could potentially precipitate an acute deterioration by compromising the oxygen-carrying capacity in these children with an underlying congenital heart defect. Hemoglobin and hematocrit levels are also helpful in evaluating whether a child’s pallor is due to CHF or anemia. Serum electrolyte values may be helpful in the evaluation of children with acute dysrhythmias or suspected metabolic acidosis and those children who are receiving chronic diuretic therapy.

Chest Radiography

Three features of the chest radiograph (Fig. 171-2) that deserve special attention are the cardiac size (cardiothoracic ratio), the cardiac shape (silhouette), and the degree of pulmonary vascular markings. The easiest method to determine the heart size in children is to determine the cardiothoracic ratio, which is obtained by comparing the largest transverse diameter of the cardiac shadow on the posteroanterior view of the chest radiograph with the widest internal diameter (measured from the inside rib margin to the widest point above the costophrenic angles) of the chest. The films should be obtained during maximal inspiration whenever possible.

The normal cardiothoracic ratio in children is approximately 50%. The cardiothoracic ratio is not very accurate in newborns and small infants, in whom a good inspiratory view is rarely obtained.¹¹ A cardiac silhouette that is larger than normal may be due to a shunt lesion, cardiomegaly, or pericardial effusion.¹¹ An enlarged heart shadow on a chest radiograph more reliably reflects a problem with volume overload rather than pressure overload. Problems with pressure overload are better represented on the ECG.

The cardiac size can be falsely increased in infants by the presence of the thymus, which can be seen in the mediastinum on the chest radiograph from birth until about 5 years of age. The thymic borders are typically wavy in appearance and sometimes can be seen as the classic “sail sign” along the superior right border of the heart (Fig. 171-3). The thymic shadow may not be visible radiographically in infants during times of physiologic stress but should reappear when the infant recovers.

The three classic cardiac silhouettes seen in patients with congenital heart defects are the boot-shaped heart of tetralogy of Fallot (Fig. 171-4), the egg-on-a-string silhouette of transposition of the great vessels, and the snowman-shaped or figure-of-eight heart of total anomalous pulmonary venous return.

The degree of pulmonary vascular markings is one of the key factors to consider in working through the differential diagnosis of congenital heart defects. Increased pulmonary vascularity is present when the pulmonary arteries appear enlarged and are visible in the lateral third of the lung fields or the lung apices. Another marker of increased pulmonary vascularity is when the diameter of the right pulmonary artery in the right hilum on the posteroanterior view of the chest is wider than the internal diameter of the trachea. The differential diagnosis of a cyanotic infant with decreased vascular markings includes tetralogy of Fallot, pulmonary atresia, and tricuspid atresia. The cyanotic infant with increased vascular markings may have transposition of the great vessels, total anomalous pulmonary venous return, or truncus arteriosus. Increased vascular markings in an acyanotic infant are suggestive of an endocardial cushion defect, ventricular septal defect, atrial septal defect, or patent ductus arteriosus.

In a normal left-sided aortic arch, the aorta descends to the left of the midline and displaces the tracheal air shadow slightly toward the right of midline above the level of the carina. In contrast to this, the tracheal air shadow may be midline or deviated toward the left in the presence of a right-sided aortic arch.³ It is important to note this finding because a right-sided aortic arch is found in up to 25% of the children with tetralogy of Fallot.⁹ Rib notching secondary to increased collateral blood flow along the intercostal vessels can sometimes be appreciated between the fourth and eighth ribs in older children with undiagnosed coarctation of the aorta but is rarely visualized in children with coarctation of the aorta who are younger than 5 years.¹¹

Electrocardiography

The electrocardiographic findings in infants and children can sometimes be problematic because various components of the ECGs change according to the child’s age (Table 171-3).⁸ At birth, the muscle mass of the right ventricle is greater than that of the left ventricle; this is demonstrated by right axis deviation on the neonatal ECG. By the end of the first month of life, the left ventricle assumes dominance. By 6 months of age, the left ventricular to right ventricular mass ratio is 2:1, which then reaches the adult ratio of 2.5:1 by adolescence. The durations of the PR interval, QRS complex, and QT intervals increase with age.

Left axis deviation is present when the QRS axis is less than the lower limit of normal for the child’s age; it occurs with left ventricular hypertrophy and left bundle branch block. Right axis deviation is present when the QRS axis is greater than the upper limit of normal for the child’s age; it occurs with right ventricular hypertrophy and right bundle branch block. A “superior” QRS axis (0 to −180 degrees with an S wave in aVF greater than the R wave) may be suggestive of an endocardial cushion defect or tricuspid atresia.

Some of the more common indications to obtain an ECG in a pediatric patient include chest pain, dyspnea, syncope, palpitations, and suspected dysrhythmias. Another indication to obtain an ECG is in those children with known cardiac disorders who present with signs and symptoms that could reflect an acute decompensation of their underlying disorder. A rare but potentially fatal congenital cardiac abnormality that will demonstrate electrocardiographic abnormalities (i.e., ischemic changes) is the condition of the anomalous origin of the left coronary artery. These infants have a history of poor feeding, irritability, and failure to thrive, then suddenly present with cardiogenic shock secondary to myocardial ischemia.

Biochemical Markers

As in adults, cardiac troponin T (cTnT) and cardiac troponin I (cTnI) are highly sensitive and specific in children for myocardial damage.¹¹ Reference values are slightly higher for neonates younger than 3 months; normal and indeterminate values will depend on the bioassay used.¹¹ The indications for troponin testing in children include suspected cardiac ischemia (of any etiology), myocarditis, and myocardial dysfunction in sepsis syndrome.^11,12 Several studies have evaluated the use of plasma B-type natriuretic peptide (BNP) levels in the assessment and management of CHF in adults.¹³ Studies of BNP levels in children have demonstrated a similar correlation of elevated levels in children with CHF, and these also correlated with the clinical symptoms of heart failure and the ejection fraction as measured by echocardiography.¹⁴ The clinician is urged to refer to the particular range of age-specific values from the laboratory kit used at his or her institution.

Perspective

The incidence of CHD in the United States has remained fairly constant at approximately 1%, or 8 to 10 cases per 1000 live births. This equates to approximately 32,000 infants born each year with some form of CHD¹⁵ (Table 171-4). Although a large percentage of CHD is now detected with prenatal ultrasonograms, one study also recommended routine pulse oximeter readings in all newborns before discharge from the nursery as an additional inexpensive screening tool for CHD.¹⁶

Clinical Features

The age, severity of symptoms, and time of presentation of a child with CHD vary by the specific defect, complexity and severity of the defect, and timing of the normal physiologic changes that occur as the fetal circulation transitions to that of a neonate (Table 171-5). The more severe or complex CHD lesions may not be clinically apparent immediately after birth. However, as the ductus arteriosus begins to close in the first several weeks of life, cardiac defects with obstructive lesions of the pulmonary or systemic circulations will be unmasked, and these infants will present clinically with acute cyanosis, shock, or both. Even the harsh systolic murmur of a large, isolated ventricular septal defect may not be heard until about the fourth to sixth week of life when the left-to-right shunt across the ventricular septal defect increases because of the decrease in the PVR. In general, the more severe the anatomic defect is (i.e., lack of pulmonary blood flow or lack of systemic blood flow), the earlier in life these conditions will be manifested with cyanosis and shock.

Although CHD has been subdivided traditionally into cyanotic and acyanotic conditions, not all CHD lesions will fit neatly into a single category; some of the more complex defects have mixed pathophysiologic effects. The exact anatomic diagnosis of a CHD is dependent on echocardiography or cardiac catheterization; establishment of the exact anatomic diagnosis seldom is possible in the emergency department setting.

Diagnostic Strategies

The emergency physician must rely on several key elements of the clinical examination in addition to findings on the chest radiograph and ECG to narrow the diagnostic possibilities. For example, with use of the data in Box 171-6, the presence of cyanosis, a grade 3/6 systolic ejection murmur best heard at the midleft sternal border, a boot-shaped heart, and a decreased pulmonary blood flow on the chest radiograph with evidence of right ventricular hypertrophy on the ECG suggest tetralogy of Fallot. Only a brief discussion of some of the more common CHDs is presented in this chapter.

Management

The majority of children who present to the emergency department with shock due to dehydration and hypovolemia are typically given intravenous fluids in boluses of 20 mL/kg. However, if a child with a suspected CHD presents to the emergency department in possible cardiogenic shock, one should consider use of smaller boluses of 10 mL/kg to prevent an iatrogenic complication of fluid overload. Frequent reassessment should be performed and the child’s response after each bolus of 10 mL/kg monitored to determine whether additional fluid boluses or inotropic agents are necessary.

One unique pharmacologic intervention that can be lifesaving in infants involves the use of prostaglandin E₁ (PGE₁) to maintain the patency of the ductus arteriosus. CHD that is manifested within the first 2 to 3 weeks of life with a sudden onset of cyanosis or cardiovascular collapse is typically due to duct-dependent cardiac lesions (Box 171-7).⁴

Closure of the ductus arteriosus in patients with these specific cardiac lesions causes life-threatening situations by either an interruption of blood flow to the lungs, producing cyanosis (i.e., tricuspid atresia), or a disruption of blood flow to the systemic circulation, producing shock (i.e., hypoplastic left heart syndrome).⁴ Box 171-8 details one suggested method to prepare this potentially lifesaving PGE₁ infusion. The PGE₁ infusion is typically started at 0.05 to 0.1 µg/kg/min (the method of preparation described in Box 171-8). A known adverse reaction to a PGE₁ infusion is apnea; one should perform endotracheal intubation on these infants before the initiation of the PGE₁ infusion. Not only will intubation provide a secure airway, but controlled ventilation will also help decrease the infant’s work of breathing, shunting much needed cardiac output and metabolic demands from the overtaxed respiratory apparatus. Other adverse reactions to a PGE₁ infusion include fever, seizures, bradycardia, hypotension, flushing, and decreased platelet aggregation.

Acyanotic Congenital Heart Defect

Acyanotic CHD can be further subdivided (Fig. 171-5) into obstructive lesions (i.e., pulmonic stenosis, aortic stenosis, and coarctation of the aorta) and lesions characterized by left-to-right shunts with an associated increase in pulmonary blood flow (i.e., ventricular septal defects, atrial septal defects, patent ductus arteriosus, and endocardial cushion defects). These acyanotic lesions usually are manifested within the first 6 months of life with symptoms of CHF; however, atrial septal defects can remain asymptomatic until adulthood.

Cyanotic Congenital Heart Diseases

Cyanotic CHDs are a result of either decreased pulmonary blood flow to the lungs or right-to-left shunting of desaturated blood directly into the systemic circulation. They can be further subdivided into those conditions with an increased pulmonary blood flow and those lesions with decreased pulmonary blood flow (Fig. 171-6). The classic cyanotic CHD can be remembered by the five t‘s: truncus arteriosus, transposition of the great vessels, tricuspid atresia, tetralogy of Fallot, and total anomalous pulmonary venous return. Other forms of cyanotic CHD include Ebstein’s anomaly, pulmonary atresia, severe pulmonary stenosis, hypoplastic left heart syndrome, and hypoplastic right heart syndrome. Many of these cyanotic heart lesions are routinely detected either on prenatal ultrasonographic examinations or in the nursery; only tetralogy of Fallot is covered in this section.

Postoperative Complications of Congenital Heart Defects

A variety of postoperative complications can be seen in patients who present to the emergency department weeks to months after cardiac surgery. The types of complications that could occur in each case depend on the original underlying cardiac defect and the surgical procedure that was used to correct that defect. Some of the complications that may be seen in the emergency department include thrombosis of a shunt-conduit with decreased flow, increased shunt-conduit flow with resultant CHF, atrial and ventricular dysrhythmias, heart blocks, myocardial ischemia, and endocarditis. The size of the cardiac silhouette and the degree of pulmonary blood flow visualized on the chest radiograph may provide valuable clues as to whether there is an increased or decreased blood flow through a surgical conduit that was created to provide an improvement in blood flow to the pulmonary system.²⁹ Comparison of the child’s other postoperative chest radiographs can help determine whether there has been a change in the heart size and pulmonary vascularity.

The postpericardiotomy syndrome is an inflammatory pericarditis that can occur 1 to 6 weeks after any surgical procedure that involved a pericardiotomy. This immunologic phenomenon is believed to occur as a sequela of blood in the pericardial sac. This syndrome is characterized by fever, chest pain, and pericardial effusion. A pericardial friction rub may be heard, depending on the amount of fluid that accumulates in the pericardial sac. The chest radiograph may reveal an enlarged cardiac silhouette, and the echocardiogram will confirm the diagnosis. Pericardiocentesis is rarely required but may be necessary if the amount of pericardial effusion is significant enough to cause a pericardial tamponade. The majority of cases will resolve within 2 to 3 weeks with bed rest and nonsteroidal anti-inflammatory medication.

Many of these postoperative complications, including the postpericardiotomy syndrome, can be avoided in children who undergo closure of patent ductus arteriosus, atrial septal defects, and ventricular septal defects by the transcatheter placement of various occluder devices.

Respiratory Syncytial Virus Infections in Infants and Children with Congenital Heart Defects

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections in infants and children worldwide, with the majority of children being infected at least once by 2 years of age. Reinfection occurs commonly throughout life.²⁹ RSV lower respiratory tract infections account for more than 125,000 pediatric admissions annually in the United States, with a fatality rate of 6.3 deaths per 100,000 patients up to 4 years of age (Box 171-10).^30,31 Children with CHD who have RSV infections tend to have a higher rate of intensive care unit admissions and require mechanical ventilation more frequently than those children who do not have CHD. Children with CHD who require hospitalization for RSV infection have a fatality rate that is two to six times greater than that of children without CHD.^30,31 RSV is responsible for a mortality rate of 40% in infants with CHD and up to 70% in infants with CHD and associated pulmonary hypertension.

Two products can be used to prevent RSV infections. Both of these preparations require monthly administration before the onset of the peak RSV season, which typically runs from November through March in most of the United States. The two currently available preparations are palivizumab (Synagis, a humanized monoclonal antibody) and RSV immune globulin (RespiGam).³² The use of palivizumab in the prevention of RSV infections in high-risk infants and children has largely replaced RSV immune globulin because palivizumab can be given intramuscularly, requires a 100-fold lesser volume, and has a 50-fold smaller protein load than RSV immune globulin.³³

In 1998 the Food and Drug Administration gave approval for the use of palivizumab in prevention of RSV lower respiratory tract infections in selected infants and children who were deemed to have a higher risk of severe infections. During the 4-year period from 1998 to 2002, several multicenter studies involving more than 24,000 subjects (including data from the Palivizumab Outcomes Registry) have demonstrated the efficacy of palivizumab in preventing hospitalizations of high-risk infants and children.³⁴ During this same 4-year period, another multicenter study involving six countries demonstrated a 45% relative reduction in hospitalization of 1287 high-risk children younger than 2 years with CHD who were given monthly intramuscular injections of palivizumab during a 5-month period.³³ This study also demonstrated a significant reduction in the total number of hospital days, supplemental oxygen requirement, total number of days in the intensive care unit, and total number of days requiring intubation in the group that received the monthly palivizumab intramuscular injections. On the basis of these results, the Food and Drug Administration in September 2003 gave approval for the use of palivizumab in infants and children with hemodynamically significant CHD (Box 171-11). The American Academy of Pediatrics emphasizes that prophylaxis with palivizumab should be initiated before the onset of the RSV season. RSV can persist on environmental surfaces for several hours; the best method to prevent the spread of RSV-contaminated secretions within the emergency department setting is meticulous handwashing and wearing of a mask in caring for children with a documented or suspected RSV infection.

Perspective

CHF is defined as a clinical syndrome in which the cardiac output is unable to meet the hemodynamic and metabolic demands of the body. Although there is a wide array of causes of CHF, the primary cause in infants and children is CHD, which results in volume or pressure overload. Other causes of CHF include the anomalous left coronary artery in infants, myocarditis, endocarditis, rheumatic heart disease, pericardial effusions, anemia, cardiomyopathies, systemic hypertension, hypothyroidism, electrolyte imbalances, endocrine disorders, cardiac toxins, and dysrhythmias that compromise cardiac output.

CHF can result from a derangement in any of the four primary determinants of normal cardiac function: (1) excessive preload (e.g., large left-to-right shunts and severe chronic anemia); (2) decreased cardiac contractility (e.g., myocarditis); (3) excessive afterload (i.e., left-sided obstructive lesions); and (4) rhythm abnormalities that compromise cardiac output or stroke volume (e.g., paroxysmal supraventricular tachycardia and severe forms of heart block). The treatment of CHF depends on which of these four primary determinants of normal cardiac function are compromised. For example, inotropic agents and diuretics may be required in a child with volume overload and decreased cardiac contractility, whereas vasodilatory agents may be required in a child with CHF due to an increased afterload.

Clinical Features

Although the clinical manifestations of CHF depend on the exact pathophysiologic cause of the CHF, common presenting signs and symptoms include tachycardia, gallop rhythm (especially an S₃), tachypnea with rales, hepatomegaly, peripheral edema, and decreased peripheral perfusion of the extremities. Wheezing and a chronic cough may also be the presenting symptoms of CHF.

Diagnostic Strategies

The chest radiograph typically reveals an enlargement of the cardiac silhouette and varying degrees of pulmonary congestion. An echocardiogram will be able to assess the ejection fraction as well as to identify underlying anatomic defects. Plasma BNP has been reported to be helpful in differentiating cardiac from pulmonary causes of dyspnea in children.³⁵ Other diagnostic studies to consider are case specific and depend on the suspected cause of the child’s CHF.

Management

Acute stabilization of any child who presents with CHF includes administration of supplemental oxygen and agents to augment cardiac contractility and to improve cardiac output. Children who present in severe respiratory distress secondary to pulmonary edema may require intubation to support oxygenation and ventilation. Children with respiratory distress due to pulmonary congestion may also benefit from elevation of the head and upper torso. Continuous positive airway pressure or biphasic positive airway pressure ventilation may be useful initially to avert the need for endotracheal intubation. Plasma BNP levels have been used also to monitor the response to treatment regimens in patients with CHF.¹⁴

Diuretics and inotropic agents are the mainstay for treatment of the majority of children with CHF. Furosemide (Lasix) in a dose of 1 mg/kg is the most common loop diuretic used to increase renal perfusion and to improve urine output. With the proper use of furosemide and digoxin (Table 171-6), most children with CHF will demonstrate a favorable response. The narrow therapeutic index of digoxin requires that levels be monitored closely to prevent iatrogenic digoxin toxicity, which could cause a worsening of the preexisting CHF.

Other inotropic agents that are used for the treatment of CHF in infants and children are dopamine, dobutamine, and epinephrine (Table 171-7). Standardized drips have been established and have replaced the dated “rule of six.”³⁶ Dopamine is an endogenous catecholamine with complex cardiovascular effects. Dopamine can increase renal blood flow in low doses (2-5 µg/kg/min) and will increase the cardiac contractility and heart rate in moderate doses (5-10 µg/kg/min). Dopamine stimulates cardiac beta₁-adrenergic receptors both directly and indirectly through the release of endogenous norepinephrine stored in the cardiac sympathetic nerves. Because of this, some of the inotropic effects of dopamine may be reduced in those patients with decreased endogenous myocardial norepinephrine stores (i.e., patients with chronic CHF and neonates). At higher doses (10-20 µg/kg/min), dopamine will also increase the SVR, but excessive vasoconstriction may compromise end-organ perfusion at infusion rates of more than 20 µg/kg/min. If additional inotropic effects are required, the addition of either dobutamine or epinephrine infusions may be preferable to an increase in the dopamine infusion to more than 20 µg/kg/min. The major toxicities of dopamine are tachycardia, vasoconstriction, and ventricular ectopy.

Dobutamine is a synthetic catecholamine with more selective cardiac inotropic effects and some beta₂-adrenergic vasodilatory effects. It is not a vasopressor, but it could be a good adjunct in the treatment of low cardiac output states that are secondary to poor myocardial function. Dobutamine may have an advantage over dopamine in that it has fewer arrhythmogenic effects than dopamine and may also have a more direct effect on the enhancement of coronary blood flow. The main toxicities of dobutamine are tachycardia, ventricular ectopy, and hypotension.

Epinephrine is a potent inotrope and chronotrope and also increases the SVR. Epinephrine is useful in scenarios in which poor cardiac output is also associated with diminished systemic vascular tone. Toxicities associated with epinephrine include tachydysrhythmias, severe hypertension, hyperglycemia, lactic acidosis, and hypokalemia.

Amrinone and milrinone are newer inotropic agents that also have peripheral vasodilatory effects. These agents have been used to improve cardiac index in septic shock and to prevent low cardiac output states for children with CHD. Side effects of these medications include profound hypotension, dysrhythmias, hypersensitivity reactions, fever, hepatotoxicity, and thrombocytopenia.

Another vasodilating medication that has been used for arterial and venous dilatory effects is nitroprusside. Nitroprusside has potent vasodilatory effects on both the systemic and pulmonary circulatory systems. This medication has a prompt onset of action and a short duration of action. Nitroprusside should be used cautiously in patients with either hepatic or renal impairment or both to avoid cyanide toxicity (severe metabolic acidosis and coma) or thiocyanate toxicity (irritability, seizures, abdominal pain, and vomiting).

Perspective

Dysrhythmias are not as common in children as they are in adults. The most common cause of cardiopulmonary arrest in infants and children is the untreated progression of respiratory failure or shock rather than a primary cardiac dysrhythmia.³⁷ Accordingly, the most common arrest rhythm that will confront the emergency physician will be asystole or bradycardia rather than ventricular fibrillation or ventricular tachycardia. When confronted with a child with a primary cardiac dysrhythmia, the physician must identify and treat the underlying cause quickly and systematically. The conditions in children who are at risk for development of dysrhythmias are listed in Box 171-12. Various medications, drugs, and toxins can also precipitate dysrhythmias in children. Even those medications that are used to treat underlying cardiac problems, such as digoxin, amiodarone, and procainamide, can themselves precipitate dysrhythmias. Drugs of abuse (e.g., cocaine and crystal methamphetamine, among others) and overdose of prescription medications (e.g., cyclic antidepressants) should be considered in the evaluation of any previously healthy adolescent patient who presents with an acute dysrhythmia.

Pediatric dysrhythmias can be divided into three broad categories of rhythms by their effect on the child’s pulse: slow (sinus bradycardia and heart blocks), fast (supraventricular tachycardia or ventricular tachycardia with a pulse), or absent (ventricular tachycardia without a pulse, ventricular fibrillation, pulseless electrical activity, or asystole).³⁸ The most common dysrhythmia in children is supraventricular tachycardia, which occurs most commonly in infants and young children. Although supraventricular tachycardia can spontaneously occur in infants without any underlying structural cardiac defects, ventricular tachycardias typically are due to an underlying myocardial abnormality.

Clinical Features

Rhythm disturbances in infants can be manifested with symptoms such as fussiness, lethargy, poor feeding, pallor, respiratory distress, or cardiogenic shock. Older children present with chest pain, palpitations, difficulty in breathing, or syncope. The type and degree of severity of the presenting signs and symptoms must be taken into account in the evaluation and management of the specific dysrhythmia in each case.

Management

Not every child who exhibits a rhythm disturbance requires emergency intervention. Emergency treatment and stabilization of any dysrhythmia depend on two key clinical questions: (1) Does the child have a pulse? and (2) If a pulse is present, is it slow or fast, and is the child hemodynamically stable or unstable? Children who have a pulse with good perfusion parameters (i.e., an alert child with strong distal pulses, warm extremities, and brisk capillary refill times) do not require emergency intervention unless they exhibit a rhythm that has the potential to rapidly degenerate into a more serious condition. Children who exhibit electrocardiographic evidence of conduction abnormalities (e.g., Mobitz type II second-degree heart blocks, complete heart blocks, prolonged QT intervals, or aberrant conduction such as the Wolff-Parkinson-White syndrome) may also warrant more emergency treatment.

A summary of the treatment algorithms for pediatric dysrhythmias and the most commonly used medications in treatment of these dysrhythmias are listed in Box 171-13. Although some medications can be used to treat only atrial tachycardias (e.g., the use of adenosine for supraventricular tachycardia) or ventricular tachycardias (e.g., the use of lidocaine for ventricular tachycardia), amiodarone and procainamide can be used for a wide array of both atrial and ventricular dysrhythmias, including supraventricular tachycardia and ventricular tachycardia.^38–40

Bradydysrhythmias

Tachydysrhythmias

Pulseless Rhythms

Special Resuscitation Situations in Children

Children with single-ventricle physiology (e.g., hypoplastic left heart syndrome, double-outlet right ventricle physiology, among others) after a palliative shunting procedure should be given standard resuscitation care.⁵² Heparin may be used in the pre-arrest or arrest of infants with a systemic–to–pulmonary artery shunt or right ventricle–to–pulmonary artery shunt to halt thrombus propagation in this low circulatory flow state.⁵² A target oxyhemoglobin saturation (SpO₂) of approximately 80% is preferred in these children. End-tidal carbon dioxide readings after resuscitation may lag behind because of varying pulmonary blood flow changes that do not necessarily reflect cardiac output. The goal is to provide adequate preload with judicious fluids to balance systemic and pulmonary blood flow.⁵² If it is available, extracorporeal membrane oxygenation may be considered in these patients.^52,53

Children with a history of pulmonary hypertension should also receive standard PALS care. Preload should be optimized with isotonic saline boluses. Inhaled nitric oxide in the intensive care unit may be given to reduce PVR.52,54 Intravenous prostacyclin is also used to decrease PVR and may be an option in the emergency department. Early contact with the child’s cardiologist and cardiothoracic surgeon is instrumental in the postresuscitative care of children with CHD.

Perspective

Bacterial endocarditis involves an infection of the endothelial surfaces of the heart with a propensity for the valves. The incidence of bacterial endocarditis in children may be increasing slightly because of the many advances in surgical technology that are now allowing many children with very complex congenital heart lesions to survive. Children with indwelling intravenous lines with or without underlying CHD are also at risk for development of bacterial endocarditis. Although bacterial endocarditis most commonly occurs in children with an underlying CHD or an acquired cardiac lesion (e.g., acute rheumatic valvular heart disease), it can also occur in patients with no underlying anatomic defects of the valves or endocardium.⁶³

Factors that predispose children with underlying anatomic cardiac defects to bacterial endocarditis include dental procedures and other surgical procedures involving the respiratory, gastrointestinal, or genitourinary tracts. Those cardiac lesions with a more turbulent blood flow or a higher flow velocity are more prone to development of bacterial endocarditis secondary to a greater risk of endothelial surface damage, which then increases the risk of platelet deposition and vegetation formation. Cardiac lesions that carry this higher risk include ventricular septal defects, aortic valvular stenosis, tetralogy of Fallot, single-ventricle states, prosthetic valves, and postoperative systemic-to-pulmonary shunts. Isolated secundum atrial septal defects carry a much lower risk for bacterial endocarditis because the shunt flow through the atrial septal defect is typically of a much lower velocity.

Clinical Features and Diagnostic Strategies

The early clinical manifestations of bacterial endocarditis may be nonspecific. The child may simply present with only fever and tachycardia. However, bacterial endocarditis should be suspected in any child with an anatomic cardiac defect who presents with an unexplained fever. This diagnosis should always be considered in any child with a known CHD or an acquired cardiac lesion who presents with any of the conditions listed in Box 171-14. A new heart murmur is present in less than 50% of the bacterial endocarditis cases.⁶⁴ The largest study of pediatric infective endocarditis to date⁶⁵ found common presenting signs to be fever (99%), petechiae (21%), changing murmur (21%), dental caries (14%), and hepatosplenomegaly (14%); less common signs were CHF (9%), splinter hemorrhages (5%), Roth’s spots (5%), and Osler’s nodes (4%).

In addition to vigilance for the diagnosis of infective endocarditis, especially in children with CHD, the emergency physician should be aware of the indications for prophylaxis. In 2007 the AHA in conjunction with the American Academy of Pediatrics and the Infectious Diseases Society of America published revised guidelines for the prevention of infective endocarditis.⁶⁶ The changes simplify and greatly narrow the recommendations to provide prophylaxis for only the higher risk patients and procedures (Box 171-15). For those children for whom prophylaxis is recommended, the indications are (1) all dental procedures and (2) any manipulation or perforation of the gingival or oral mucosa.⁶⁶ Antibiotic prophylaxis for infective endocarditis is no longer recommended for gastrointestinal and genitourinary procedures (Box 171-16). The committee found that it is still reasonable to give prophylaxis for procedures on the respiratory tract, infected skin, or musculoskeletal tissue only for high-risk patients (Table 171-9).⁶⁶

Diagnostic studies for a child with suspected bacterial endocarditis include a complete blood cell count, C-reactive protein (CRP) assessment, measurement of erythrocyte sedimentation rate (ESR), three blood cultures,⁶⁷ chest radiography, and electrocardiography. Cultures from scrapings of cutaneous emboli can also aid in the diagnosis. Although the definitive diagnostic study is the echocardiogram, it is only 80% sensitive in detecting the nidus of infection on the endocardium or valves.⁶⁸ Streptococcus viridans and Staphylococcus aureus are the two most common offending organisms recovered from the blood cultures of children with bacterial endocarditis. Studies have shown that in children with CHD, 60% of the cases caused by staphylococcal species are methicillin resistant and associated with increased risk of mortality.⁶⁹

Management

Antibiotics should be started immediately after blood culture samples have been obtained. Although the choice of intravenous antibiotics depends on the suspected source of seeding and the child’s immune status, a common recommended regimen includes an aminoglycoside plus a penicillinase-resistant penicillin such as oxacillin. If methicillin-resistant staphylococci are suspected, vancomycin should also be included in the initial empirical antibiotic regimen.⁷⁰

A surge of antibiotic resistance to the three major causes of bacterial endocarditis—streptococci, staphylococci, and enterococci—has increased the mortality rate of bacterial endocarditis, now at 25 to 40%.⁷¹ Complications of bacterial endocarditis include systemic septic emboli, pulmonary emboli, central nervous system emboli with resultant neurologic deficits, dysrhythmias, CHF, myocarditis, myocardial abscesses, and valvular obstruction and destruction. Despite appropriate antibiotic treatment, surgical intervention to remove septic vegetations or valve replacement is sometimes necessary.

Perspective

Myocarditis is an inflammatory condition of the myocardium with various infectious and noninfectious origins. In the United States, the most common cause is viral; Coxsackievirus B and enteroviruses account for the majority of cases. Other viral causes include echoviruses, influenza A and B viruses, adenovirus, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, and hepatitis B virus. Bacterial causes include Corynebacterium diphtheriae, Streptococcus pyogenes, S. aureus, Mycoplasma pneumoniae, Borrelia burgdorferi, and meningococcus. Noninfectious causes include Kawasaki disease, acute rheumatic fever (ARF), collagen vascular disorders (e.g., systemic lupus erythematosus), toxins (e.g., cocaine and doxorubicin), endocrine disorders (e.g., hyperthyroidism), and drug-induced hypersensitivity (e.g., penicillins, sulfonamides, phenytoin, carbamazepine).

Clinical Features

Myocarditis usually has a gradual onset with preceding upper respiratory tract infection symptoms. The presenting signs and symptoms of a child with myocarditis depend on the cause of the myocarditis, the age of the patient, and the degree of myocardial inflammation. The key to diagnosis of myocarditis in infants and children is to include it in the differential diagnosis of a child with symptoms disparate from the presentation. In mild cases, the only sign of myocarditis may be tachycardia. Tachycardia that is disproportionate to the degree of fever should alert the clinician to the possibility of myocarditis.⁷² Other presenting signs and symptoms include fever, myalgias, fatigue, tachypnea, wheezing, abdominal pain, and chest pain. More severe cases of myocarditis can even have signs and symptoms of acute CHF and various dysrhythmias. The physical examination may reveal a new murmur, a gallop rhythm, or a pericardial friction rub with muffled heart tones (if the myocarditis is also accompanied by pericarditis and subsequent pericardial effusion). In general, these are sick children with vague symptoms.

Diagnostic Strategies and Management

The evaluation and management of the child with myocarditis depend on the suspected cause and the presenting signs and symptoms. Blood cultures and viral titers should be considered in infectious and postinfectious cases. Appropriate antibiotics should be initiated immediately in cases with suspected bacterial origin. The chest radiograph may be normal in very mild cases, but cardiomegaly will be evident in more advanced cases. The electrocardiographic findings are usually nonspecific and can include low-voltage, nonspecific ST segment abnormalities, T wave inversions, atrioventricular blocks, and various other dysrhythmias. Creatine kinase-MB, cTnT, cTnI, CRP, and ESR may be elevated.

The echocardiogram is an essential component of the workup of any child with suspected myocarditis. The echocardiogram will not only be useful to assess the degree of left ventricular function, but it will also be able to detect associated pericardial effusion that may accompany the myocarditis. Although an endomyocardial biopsy is rarely required, it is the definitive method to confirm the diagnosis and origin of myocarditis. If the endomyocardial biopsy is performed, it will typically demonstrate a myocardial inflammation with lymphocytic and monocytic infiltrates. The goal of treatment is to maintain adequate cardiac output and to control any associated dysrhythmias. Children who present in CHF may require inotropic support and diuretics. Digoxin and the various pressors must be used very cautiously in children with myocarditis because the inflamed myocardium is sensitive to the dysrhythmogenesis of these medications. The use of beta-blockers is contraindicated,⁷² and the routine use of immunosuppressive agents remains controversial.⁷³ Although the majority of children with acute viral myocarditis make a full recovery, a few patients will progress to dilated cardiomyopathy, which is characterized by dilated ventricles and impaired systolic contractility.

Perspective

Pericarditis is an inflammatory process within the pericardial sac that may not be associated with a pericardial effusion. In the majority of cases, pericarditis in children is self-limited and follows a benign clinical course. In children, there are normally about 10 to 15 mL of fluid within the pericardial sac. A sudden increase or a large amount of fluid within this pericardial sac can cause a tamponade-induced decrease in stroke volume, which will cause a diminished cardiac output and hypotension.

Although the most common causes of pericarditis include bacterial and viral infections, other causes are ARF, systemic lupus erythematosus, uremia, postpericardiotomy syndrome, leukemia, lymphoma, and tuberculosis. Approximately 30% of pericarditis cases are due to bacteria such as pneumococcus, S. aureus, meningococcus, and Haemophilus influenzae.² Approximately 30% of the purulent bacterial pericarditis cases occur in children younger than 6 years.²⁸ Viral causes are common, but a specific viral pathogen is recovered in only 20 to 30% of the cases.²⁸ Common viral causes include Coxsackieviruses, echoviruses, adenovirus, Epstein-Barr virus, and influenza viruses.

Clinical Features

The presenting signs and symptoms of pericarditis depend on the cause of the pericarditis as well as on the amount of fluid that has accumulated within the pericardial sac. Chest pain that varies with position is a common complaint with pericarditis. The chest pain that is classically associated with pericarditis is exacerbated with inspiration and the supine position but relieved when the patient sits up or leans forward. Tachycardia is also a common finding in patients with pericarditis and may be the only clue to the diagnosis. Other physical examination findings that have been associated with pericarditis include fatigue, tachypnea, neck vein distention, pulsus paradoxus, hepatomegaly, lower extremity edema, and thready distal pulses if heart failure is present. The cardiac auscultatory findings in a patient with pericarditis can include a harsh-sounding friction rub or diminished or muffled heart tones, if there is a significant amount of fluid within the pericardial sac. The pericardial friction rub, if present, is best heard when the patient sits up or leans forward. This friction rub of pericarditis can be distinguished from a pleural friction rub by having the patient hold his or her breath during auscultation. The friction rub of pericarditis will remain present during breath-holding; the pleural friction rub will no longer be heard while the patient holds the breath.

The chest radiograph in a child with pericarditis may not reveal an enlarged cardiac silhouette, depending on the amount of fluid that has accumulated within the pericardial sac. If there is a large collection of fluid within the pericardial sac, the heart shadow on the chest radiograph will resemble a “water bottle” silhouette. Approximately 50% of pericarditis cases also have an associated pleural effusion.²

The classic electrocardiographic findings of pericarditis include diffuse ST segment elevation and diffuse T wave inversions in all leads. The classic electrocardiographic changes associated with pericarditis evolve through four phases (Fig. 171-13). During the initial phase, there is diffuse ST segment elevation in all leads secondary to subepicardial inflammation; PR segment depression may also be seen. During the second phase, the previously elevated ST segments begin to return to isoelectric baseline, and the T wave amplitudes begin to decrease with flattening of the T waves. During the third phase, although the ST segments are now back to isoelectric baseline, the T waves are now inverted. The fourth and final phase demonstrates complete resolution of the ST segment and T wave abnormalities. Diminished electrocardiographic voltages in all leads can also occur if there is a significant amount of fluid accumulated within the pericardial sac.

The diagnostic procedure of choice in any patient with suspected pericarditis is the echocardiogram; this study will confirm both the presence and the amount of accumulated fluid within the pericardial sac. Although echocardiography cannot accurately quantify the exact amount of fluid that has accumulated within the pericardial space, the presence of an anterior and posterior fluid collection is suggestive of a large collection.

Management

The management of a child with pericarditis depends on both the suspected cause and the amount of fluid that has accumulated within the pericardial space. These children require admission for observation and analgesia with nonsteroidal anti-inflammatory drugs. Certainly those patients with fever, respiratory distress, or signs of CHF should be admitted and an echocardiogram performed emergently. An emergency pericardiocentesis will be required in those patients who have signs of acute cardiac tamponade. Any fluid that is aspirated from the pericardial space should be sent for routine cell counts, Gram’s stain, and cultures. Anti-inflammatory agents and appropriate antibiotics should also be initiated on the basis of the suspected cause. Steroids are reserved for refractory cases that are not responsive to these agents and would be considered only after an infectious etiology is ruled out.⁷⁴

Perspective

Kawasaki disease, originally described as mucocutaneous lymph node syndrome by Dr. Tomisaku Kawasaki in 1967, has emerged as a significant cause of acquired cardiac disease in children in the United States. An estimated 3000 to 5000 cases of Kawasaki disease are diagnosed annually in the United States. Up to 20% of untreated children have some degree of coronary artery abnormalities.⁷⁵ This febrile, exanthematous, multisystem vasculitis is seen most commonly in children younger than 5 years with a male-to-female ratio of 1.5:1. The incidence is higher in Asian children and in certain geographic locations, such as Hawaii. Although the exact cause of this vasculitis of small and medium-sized vessels remains unknown, early clinical recognition and initiation of high-dose aspirin and intravenous immune globulin (IVIG) therapies have improved the morbidity and mortality rates of Kawasaki disease in children.

Clinical Features

The key to prevention of the coronary artery complications of Kawasaki disease is first to recognize the clinical signs and symptoms of this disease. In addition to fever, the physical examination of a child with Kawasaki disease may reveal the typical findings as listed in Box 171-17 and illustrated in Figure 171-14. The classic features of Kawasaki disease may be manifested simultaneously or in series of days; a careful history and physical examination may elucidate the need for further testing. In addition, very young children may not have a classic presentation and require further investigation. All children with suspected Kawasaki disease, with either classic or incomplete features, should undergo echocardiography for detection of the presence and degree of coronary aneurysm.⁷⁶

Incomplete Kawasaki Disease.

The classic presentation of Kawasaki disease is a clinical diagnosis of four or more of the five criteria in a child who is febrile 5 days or more. However, these strict criteria may miss a substantial number of children who present with incomplete Kawasaki disease. Any child may have an incomplete presentation, but this is mostly seen in infants younger than 6 months.⁷⁶

The AHA’s Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease has published consensus guidelines on the approach to incomplete Kawasaki disease.⁷¹ The more inclusive criteria recommend that in a child who is febrile 5 days or more, the presence of two or three criteria should prompt further testing. A CRP of 3 mg/dL or more or an ESR of 40 mm/hr or more or both necessitate further laboratory investigations, such as those listed in Box 171-18. All of these children will also need echocardiography to assess for coronary aneurysm, and the recommendation is to treat empirically those whose supplementary laboratory values (see Box 171-18) are positive for systemic inflammation while echocardiographic confirmation is awaited.⁷⁶

Children with a CRP of less than 3 mg/dL and an ESR of less than 40 mm/hr may be observed daily and reassessed. The committee also added a stipulation that the infant 6 months or younger with fever of 7 days or more should also undergo supplemental laboratory testing and, if any signs of systemic inflammation are found, should have an echocardiogram. This underscores the current limits of diagnosis of Kawasaki disease as well as the obligation to prevent the disastrous sequelae of aneurysmal development.

Differential Considerations

Measles can mimic Kawasaki disease but is rare in vaccinated children (i.e., a febrile illness with red eyes, a rash, and erythema of the oropharynx). The measles rash classically begins on the head and face and progresses caudally. The rash of Kawasaki disease typically begins on the trunk and then spreads to the face and extremities. In contrast, Kawasaki disease can exhibit a polymorphous rash that is nonbullous and nonvesicular.

The palmar lesions of measles are discrete macular lesions (Fig. 171-14F), whereas the palmar finding in children with Kawasaki disease is diffuse erythema, which may later lead to desquamation (Fig. 171-14C).

Streptococcal disease, including pharyngitis and scarlet fever, can be confused with Kawasaki disease, but conjunctivitis and swelling of the hands and feet are unusual for streptococcal disease. Other infectious or autoimmune causes that may mimic Kawasaki disease include Rocky Mountain spotted fever, leptospirosis, Stevens-Johnson syndrome, and juvenile rheumatoid arthritis.⁷⁶

There are many imitators of Kawasaki disease. Conversely, this systemic vasculitis can affect any organ system and thus mislead the clinician in diagnosis. For example, Kawasaki disease can be manifested with nausea, vomiting, and abdominal pain in a febrile child, which may be mistaken for a surgical abdomen. In addition, a febrile, irritable child with Kawasaki disease may exhibit a cerebrospinal fluid pleocytosis and be misdiagnosed with viral meningitis. For this reason, Kawasaki disease should be included in the differential diagnosis of any child with several days of fever, rash, and nonpurulent conjunctivitis to avoid the pitfall of early diagnostic closure.

Clinical Course

Kawasaki disease is postulated to be caused by an infectious agent that enters the respiratory tract and initiates an oligoclonal immunoglobulin A response, which activates lymphocytes, cytokines, and proteinases that weaken vessel walls and predispose the entire circulation to aneurysms.⁷⁷ The main reason to recognize this disease entity in children is to initiate prompt therapies to prevent the cardiac complications of Kawasaki disease, which occur in two phases. Approximately 25% of patients have mild diffuse myocardial inflammation. This occurs during the acute febrile period and is characterized by tachycardia, a gallop rhythm, and nonspecific ST-T wave changes. Up to 5% of the children also exhibit some degree of CHF during this acute phase of their illness. This carditis usually resolves when the fever resolves. Pericardial effusions also occur in up to 20 to 40% of cases. Mild mitral and aortic regurgitation is also seen in 1 to 2% of untreated cases on echocardiographic examinations. This phase of the disease is mild and self-resolving. Therapy during this phase of the illness is primarily supportive.

The second phase of the disease involves coronary artery dilation, which usually peaks 2 to 4 weeks from the onset of the illness and is seen in 15 to 25% of the untreated patients with Kawasaki disease.⁷⁸ Without the appropriate treatment, 15 to 20% of children with Kawasaki disease go on to have coronary aneurysms within 1 to 3 weeks from the onset of their illness.² These coronary aneurysms can then lead to myocardial infarction, thrombosis, rupture, and a variety of ischemia-induced dysrhythmias. Significant risk factors for coronary aneurysmal formation include male gender, age younger than 1 year or older than 8 years, prolonged febrile period longer than 10 to 14 days, early myocarditis, anemia (hemoglobin <10 g/dL), white blood cell count greater than 30,000, increased band count, elevated ESR, elevated CRP level, low serum albumin levels, aneurysms involving other arteries (renal, axillary, or iliac), and giant coronary aneurysms (>8 mm in diameter). Death from Kawasaki disease is primarily due to myocardial infarction secondary to coronary artery occlusion. Giant coronary artery aneurysmal rupture is rare. Although most of the fatalities of Kawasaki disease occur within 6 weeks from the onset of the illness, sudden death can also occur many years after the illness. Prompt recognition and treatment have decreased this mortality rate from 2% to less than 0.01%.⁷⁵

Management

The main goal of treatment during the acute febrile phase of Kawasaki disease is to provide supportive care and to decrease the inflammation of the myocardium and coronary arteries. The two major components of treatment include IVIG infusion and high-dose aspirin therapy, which together have an additive effect. This combination of IVIG and high-dose aspirin, when it is initiated within 10 days from the onset of the illness, can substantially decrease the progression to coronary artery dilation and aneurysm formation compared with aspirin therapy alone and results in a more rapid resolution of fever and the other indicators of acute inflammation.⁷⁶ However, despite prompt treatment with IVIG and high-dose aspirin, 2 to 4% of the children still have coronary artery abnormalities.⁷⁶

The current IVIG regimen involves an infusion of 2 g/kg during 10 to 12 hours. Side effects of IVIG include hypotension, nausea, vomiting, headache, and seizures. Close cardiac monitoring during the IVIG infusion is recommended. The 5 to 10% of children who receive IVIG and experience a persistent or recurrent fever after the initial dose of IVIG may be given a second infusion at the same dose. Approximately two thirds of those children who fail to respond to the initial dose of IVIG will improve with the second infusion.

Aspirin is initiated at 80 to 100 mg/kg/day orally divided into an every-6-hour dosing regimen until the child is afebrile for 48 to 72 hours (or longer). This dose is then decreased to 3 to 5 mg/kg orally each day until the laboratory study results return to normal, which typically occurs 6 to 8 weeks after the onset of the disease. Aspirin therapy is continued beyond this period only in those children in whom coronary artery abnormalities are present. Ibuprofen can antagonize the antiplatelet effects of aspirin and should be avoided during treatment.⁷⁶

The use of corticosteroids as primary treatment has not been well established. A multicenter, randomized, double-blind study to determine the efficacy of the addition of methylprednisolone to initial conventional therapy showed no difference in clinical outcome, including dimensions of coronary artery aneurysms, length of hospital stay, and rate of re-treatment with IVIG.⁷⁹ The current recommendations include corticosteroids for refractory cases of Kawasaki disease, in which high-dose aspirin is continued, a second dose of IVIG is administered, and corticosteroids are added to decrease the risk of coronary artery aneurysm.^76,80 Other complications, such as coronary aneurysmal thrombosis, likewise have limited data to guide management. Therapeutic options include streptokinase, tissue-type plasminogen activator, and interventional cardiac catheterization.⁷⁶

The follow-up of children with Kawasaki disease depends on the degree and presence of carditis and coronary artery abnormalities detected on the initial echocardiogram. Other imaging modalities used to follow aneurysmal parameters include electron-beam computed tomography, coronary magnetic resonance angiography, and multislice spiral computed tomography.⁷⁶ Those children with more severe cardiac abnormalities require close follow-up by a cardiologist who is experienced in managing the cardiac complications of Kawasaki disease. Overall, prompt diagnosis and appropriate therapies can prevent coronary aneurysm formation in up to 95% of the cases as well as result in rapid symptomatic improvement in up to 90% of the cases.⁸¹

Perspective

ARF is the result of a delayed immune reaction to a group A streptococcal infection. ARF is one of the most common causes of acquired heart disease in children. In the United States, ARF most commonly occurs in children 5 to 15 years of age and has an attack rate of 0.3% in children with an untreated streptococcal infection. Although this disease affects multiple organ systems, carditis is the most serious complication.

Clinical Features and Diagnostic Considerations

The diagnosis of ARF is based on the Jones criteria (Box 171-19). In addition to the Jones criteria, there must also be evidence of an antecedent streptococcal infection, which can be documented by a positive throat culture, a positive rapid streptococcal antigen test finding, or an elevated antistreptolysin O (ASO) titer. The ASO titer begins to rise 1 to 3 weeks after streptococcal infection, peaks at 3 to 5 weeks, and reliably falls to baseline after 6 months.⁸² The streptozyme test is not as reliable and therefore should not be used as a definitive test for evidence of an antecedent group A streptococcal infection.⁸³ The diagnosis of ARF is made in a patient with a documented antecedent streptococcal infection who exhibits either two major criteria or one major plus two minor criteria. The most common presenting major criterion is the migratory polyarthritis, which commonly involves the larger joints of the extremities as well as the smaller tarsal joints in the foot and the smaller carpal joints in the hand. The carditis of ARF most commonly involves valvulitis of the mitral and aortic valves, which clinically is manifested as occult mitral or aortic insufficiency. The murmur of mitral insufficiency is characterized as a holosystolic murmur best heard over the apex with radiation to the axilla. The murmur of aortic insufficiency is characterized as a diastolic murmur that is best heard over the base of the heart. Innocent murmurs that are normally exacerbated with fever can be mistaken for the murmurs of mitral or aortic insufficiency. The other cardiac manifestations of ARF include CHF, pericarditis, and various degrees of heart block. The two dermatologic major criteria (erythema marginatum and subcutaneous nodules) and chorea occur less commonly than the migratory polyarthritis and carditis. Chorea may occur as the only manifestation of ARF. If arthritis is used as a major component, arthralgia cannot be used as a minor component to make the diagnosis. Likewise, if carditis is used as a major component, a prolonged PR interval cannot be used as a minor component.⁸³

In addition to the ECG, CRP level, ESR, and documentation of an antecedent streptococcal infection, the diagnostic workup of ARF should also include a chest radiograph as well as an echocardiogram to evaluate the degree of cardiac involvement.

Differential Considerations

The differential diagnosis of ARF includes myocarditis, bacterial endocarditis, Lyme disease, systemic lupus erythematosus, juvenile rheumatoid arthritis, serum sickness, and septic arthritis.

Management

The acute management of ARF should first focus on stabilization and treatment of any of the symptomatic cardiac manifestations of the illness, such as CHF or tamponade due to a pericardial effusion. Additional goals in ARF management include appropriate antibiotic therapy to eradicate the streptococcal infection, bed rest, and anti-inflammatory agents for the arthritis. Steroids should be used in the treatment of carditis only under direction of a cardiologist. Another important aspect in the management of ARF is the prevention of recurrent attacks through the prophylactic use of penicillin, which can be given as monthly injections of 1.2 million units of benzathine penicillin G. Alternative prophylactic regimens include oral penicillin administered twice daily and, for penicillin-allergic patients, twice daily oral erythromycin. This prophylaxis with penicillin or erythromycin is required until 18 years of age at the minimum but can be continued for life, depending on the degree of cardiac involvement and the risk for recurrence.

Perspective

In a large registry study of 1866 sudden deaths in young athletes, 1048 (56%) were found to be due to cardiovascular disease, and 416 (22%) were due to direct blunt trauma.⁸⁴ The most common cardiovascular cause of sudden death in the athlete is hypertrophic cardiomyopathy, which accounts for up to 36% of the cardiovascular-related cases (Box 171-20).⁷⁰

Specific Disorders