James W. Wiggins

The Treatment of Kawasaki Syndrome with Intravenous Gamma Globulin

We compared the efficacy of intravenous gamma globulin plus aspirin with that of aspirin alone in reducing the frequency of coronary-artery abnormalities in children with acute Kawasaki syndrome in a multicenter, randomized trial. Children randomly assigned to the gamma globulin group received intravenous gamma globulin, 400 mg per kilogram of body weight per day, for four consecutive days; both treatment groups received aspirin, 100 mg per kilogram per day, through the 14th day of illness, then 3 to 5 mg per kilogram per day. Two-dimensional echocardiograms were interpreted blindly and independently by two or more readers. Two weeks after enrollment, coronary-artery abnormalities were present in 18 of 78 children (23 percent) in the aspirin group, as compared with 6 of 75 (8 percent) in the gamma globulin group (P = 0.01). Seven weeks after enrollment, abnormalities were present in 14 of 79 children (18 percent) in the aspirin group and in 3 of 79 (4 percent) in the gamma globulin group (P = 0.005). No child had serious adverse effects from receiving gamma globulin. We conclude that high-dose intravenous gamma globulin is safe and effective in reducing the prevalence of coronary-artery abnormalities when administered early in the course of Kawasaki syndrome.

A Single Intravenous Infusion of Gamma Globulin as Compared with Four Infusions in the Treatment of Acute Kawasaki Syndrome

BACKGROUND Treatment of acute Kawasaki syndrome with a four-day course of intravenous gamma globulin, together with aspirin, has been demonstrated to be safe and effective in preventing coronary-artery lesions and reducing systemic inflammation. We hypothesized that therapy with a single, very high dose of gamma globulin would be at least as effective as the standard regimen. METHODS We conducted a multicenter, randomized, controlled trial involving 549 children with acute Kawasaki syndrome. The children were assigned to receive gamma globulin either as a single infusion of 2 g per kilogram of body weight over 10 hours or as daily infusions of 400 mg per kilogram for four consecutive days. Both treatment groups received aspirin (100 mg per kilogram per day through the 14th day of illness, then 3 to 5 mg per kilogram per day). RESULTS The relative prevalence of coronary abnormalities, adjusted for age and sex, among patients treated with the four-day regimen, as compared with those treated with the single-infusion regimen, was 1.94 (95 percent confidence limits, 1.01 and 3.71) two weeks after enrollment and 1.84 (95 percent confidence limits, 0.89 and 3.82) seven weeks after enrollment. Children treated with the single-infusion regimen had lower mean temperatures while hospitalized (day 2, P less than 0.001; day 3, P = 0.004), as well as a shorter mean duration of fever (P = 0.028). Furthermore, in the single-infusion group the laboratory indexes of acute inflammation moved more rapidly toward normal, including the adjusted serum albumin level (P = 0.004), alpha 1-antitrypsin level (P = 0.007), and C-reactive protein level (P = 0.017). Lower IgG levels on day 4 were associated with a higher prevalence of coronary lesions (P = 0.005) and with a greater degree of systemic inflammation. The two groups had a similar incidence of adverse effects (including new or worsening congestive heart failure in nine children), which occurred in 2.7 percent of the children overall. All the adverse effects were transient. CONCLUSIONS In children with acute Kawasaki disease, a single large dose of intravenous gamma globulin is more effective than the conventional regimen of four smaller daily doses and is equally safe.

Clinical spectrum of Kawasaki disease in infants younger than 6 months of age

We report an unselected series of eight patients younger than 6 months of age with Kawasaki disease evaluated between January 1982 and May 1984. The incidence of coronary artery aneurysms (six patients) and the mortality (two patients) were unusually high in this small series. Because of the confusing clinical presentation in three patients, diagnosis was delayed until pathologic or echocardiographic evidence of coronary vasculitis or aneurysm was discovered. The currently accepted clinical criteria for Kawasaki disease may not always identify patients with the pathologic findings of the syndrome who are younger than 6 months of age. The diagnosis of Kawasaki disease and echocardiographic evaluation of the coronary arteries should be considered in young infants with prolonged fever of unknown origin.

Autoantibodies to SS-A/Ro in infants with congenital heart block

Antibodies to SS-A/Ro have been proposed to be a serologic marker for the neonatal lupus syndrome, which is characterized by congenital heart block or cutaneous lupus or both. The antibodies occur in the mother and are transiently found in the childs serum. We examined an unselected series of 12 children with idiopathic CHB, isolated in 10 children and with cutaneous lupus lesions in two. Six of these children and their mothers were studied during the childs neonatal period, and six were studied retrospectively. All six neonates had SS-A/Ro autoantibodies. Nine of 12 mothers had SS-A/Ro autoantibodies. Of the seropositive mothers, one had systemic lupus erythematosus, two had sicca syndrome, one had photosensitivity, one had arthralgias, and four were asymptomatic. We propose that congenital heart block may be related to transplacental passage of maternal SS-A/Ro antibodies and that neonatal lupus may be the most common cause.

Coagulopathy and platelet activation in Kawasaki syndrome: Identification of patients at high risk for development of coronary artery aneurysms

Prospective evaluation of platelet activation and hypercoagulability was performed in 31 patients with Kawasaki syndrome. Most patients had elevated acute-phase reactants when studied during the first 3 weeks of their illness; 17 of 25 (68%) patients had factor VIII activity greater than 150%, 18 of 24 (75%) had fibrinogen greater than 400 mg/dl, and 17 of 31 (55%) had a platelet count greater than 450,000/mm3. Antithrombin III was depressed initially in 17 of 25 (68%) patients. Depleted fibrinolytic activity, as measured by a euglobulin lysis time greater than 300 minutes, was documented in nine of 20 (45%) patients. Plasma beta-thromboglobulin (BTG) measured at 0 to 3 weeks was elevated (greater than 43 ng/ml) in seven of 24 (29%) patients. All patients with coronary artery aneurysms had elevated BTG values. The mean BTG in the group with aneurysms was 72.3 ng/ml when measured during the first 3 weeks after onset of fever, and 87.7 ng/ml at 4 to 7 weeks. The group without aneurysms had mean BTG values of 29.4 and 28.3 ng/ml at 0 to 3 and 4 to 7 weeks, respectively. The difference between the two groups was significant (P less than 0.002) for both the initial and later values. An elevated BTG during the first 3 weeks after onset of fever was highly associated with aneurysm formation in our patients (P less than 0.007). No aneurysms occurred in patients with a normal BTG value.

The St. Jude medical cardiac valve in infants and children: Role of anticoagulant therapy

The experience at the University of Colorado with the St. Jude Medical cardiac valve was reviewed to determine the feasibility of placing this prosthesis in children and the role of anticoagulation. A St. Jude Medical cardiac valve was placed in 33 patients ranging in age from 2.5 months to 17 years. Seven patients were less than 1 year of age. Nineteen valves were placed in the aortic position in patients aged 5 months to 17 years (mean 9.5 years). Five patients had valve replacement only, 13 had concomitant aortoventriculoplasty and 1 a Manouguian procedure. Indications for anulus enlarging procedures were recurrent subaortic stenosis or inability to place an adult-sized valve in the native aortic anulus, or both. There were no early or late deaths. Fourteen valves were placed in the mitral position. They were anular positioned in 6 patients aged 6 months to 16 years and supraanular positioned in 8 patients aged 2.5 months to 2 years. There were no deaths with the anular positioned replacements and seven deaths (two early and five late) with the supraanular positioned replacements. Four of the five late deaths were associated with marked pre- and postoperative left ventricular dysfunction. The follow-up time was 784 patient-months in 31 long-term survivors. Anticoagulation was achieved with warfarin, usually in combination with sulfinpyrazone, dipyridamole or aspirin. There were four episodes of thromboembolism, three occurring in patients with suboptimal anticoagulation, and one in a patient lost to follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Pediatric Myocardial Infarction After Racemic Epinephrine Administration

Myocardial infarction is a previously unreported complication of treatment with racemic epinephrine that is used commonly in the emergency department for severe respiratory distress in bronchiolitis or croup syndrome. We describe a pediatric patient who presented with the croup syndrome and severe respiratory distress that required multiple doses of nebulized racemic epinephrine in the emergency department. The patient developed ventricular tachycardia and mild chest discomfort during one treatment, which resolved spontaneously on discontinuation of the nebulization. Persistently abnormal electrocardiograms and elevated creatine phosphokinase MB isoenzyme (CPK–MB) levels suggested a myocardial infarction had occurred. Subsequent echocardiography, cardiac catheterization, and angiography revealed an anatomically normal heart with normal coronary circulation; however, a stress nuclear study showed a small myocardial infarct. The significance of this previously unreported complication of racemic epinephrine is discussed, along with recommendations for proper use in the emergency department.

Hemodynamic effects of ketamine, hypoxia and hyperoxia in children with surgically treated congenital heart disease residing ≥ 1,200 meters above sea level

Little data are available on the hemodynamic effects of premedications and anesthetic agents on infants and children. Ketamine is the most frequently used anesthetic agent for cardiac catheterization procedures in pediatric patients with congenital heart disease. Previous reports both suggest and deny ketamines pulmonary vasoreactive effects. Since the advent of sophisticated noninvasive equipment, one of the few indications for cardiac catheterization is to obtain accurate pressure data. If ketamine alters pulmonary vascular resistance, it would negate the primary reason for the procedure. Because the patient population studied herein resides greater than or equal to 1,200 meters above sea level, concerns about pharmacologic effects on pulmonary vascular resistance are enhanced. Simultaneous pulmonary artery and aortic pressures, thermodilution cardiac outputs, and blood gases were measured in room air (16% oxygen) and with ketamine infusion in 14 patients at cardiac catheterization. Reaction to hypoxia identified 3 groups: normal, intermediate and hyperresponders. The normal responders had normal resistance ratios (0.11) in room air and had little resistance ratio response to hypoxia (+0.02), hyperoxia (-0.03) or ketamine (+0.01). The intermediate responders had a slightly higher but normal resistance ratio (0.20) in room air, and a moderate reaction to hypoxia (+0.13), hyperoxia (-0.08) and ketamine (+0.11). The hyperresponders had an elevated resistance ratio (0.42) in room air and a striking reaction to hypoxia (+0.65), hyperoxia (-0.17) and ketamine (+0.49). Hypoxia and ketamine have a greater effect on resistance ratio than hypoxia alone in patients with reactive pulmonary vascular beds. Ketamine should not be used in children undergoing procedures to establish operability based on pulmonary vascular resistance or pulmonary vascular reactivity.

Nitric oxide and prostacyclin treatment of an infant with primary pulmonary hypertension

Abstract Primary pulmonary hypertension is a progressive disease with high mortality. The etiology of primary pulmonary hypertension in pediatric patients is unknown; some cases are thought to be familial, 1 but most are sporadic. Mortality is high if the disease is present in infants 2,3 Younger children with primary pulmonary hypertension have a larger decrease in pulmonary vascular resistance (PVR) with vasodilators than older patients, suggesting vasoconstriction is more important than structural changes in the development of pediatric primary pulmonary hypertension. 4 Therefore, vasodilator therapy may be more successful in younger patients because of increased pulmonary vasoreactivity. Prostacyclin is often effective as an acute vasodilator in pediatric primary pulmonary hypertension. 4 Therapy with prostacyclin and other vasodilators is frequently limited because of systemic hypotension. Brief inhalation of nitric oxide selectively dilates the pulmonary vascular bed of adults with primary pulmonary hypertension 5 and children with primary pulmonary hypertension 6 and congenital heart disease, 7,8 but has not been used as prolonged therapy without assisted ventilation. We describe a case of primary pulmonary hypertension in which inhalation of nitric oxide successfully aided the transition to chronic prostacyclin infusion (therapy with oxygen and calcium antagonists was not effective and prostacyclin was not immediately available).

Variant angina in an adolescent

SummaryWe describe a case of variant angina associated with acute myocardial ischemia in an adolescent presenting with severe chest pain and transient ST elevation. Subsequent cardiac catheterization revealed normal coronary anatomy, and the patient has been asymptomatic since discharge on calcium channel blockers. Variant angina is a rare cause of chest pain in adolescents.