Amrinone-associated thrombocytopenia: pharmacokinetic analysis.

Amrinone-associated thrombocytopenia is thought to result from nonimmune-mediated peripheral platelet destruction. Platelet destruction may be a concentration-dependent toxic effect of amrinone or its principal metabolite N-acetylamrinone. Eighteen children receiving amrinone after heart surgery were prospectively evaluated to correlate the pharmacokinetics of amrinone and N-acetylamrinone with thrombocytopenia. Amrinone and N-acetylamrinone plasma concentrations were determined by HPLC during loading, infusion, and terminal elimination, with concurrent monitoring of platelet counts. Thrombocytopenia developed in eight patients (platelet count, 66 +/- 17 x 10(9) platelets/L [mean +/- SD]). Peak and steady-state amrinone plasma concentration, amrinone total dose, duration of amrinone exposure, and amrinone area under curve (AUC) were similar between patients with and without thrombocytopenia. N-Acetylamrinone peak concentration, steady-state concentration, N-acetylamrinone AUC, and ratio of N-acetylamrinone to amrinone were greater in patients with thrombocytopenia. This association suggests that N-acetylamrinone, and not amrinone, may be the mediator of thrombocytopenia in children receiving amrinone.

Abnormal Doppler pulmonary venous flow patterns in children after repaired total anomalous pulmonary venous connection.

Doppler echocardiography was used to evaluate pulmonary venous flow patterns in 16 children with repaired total anomalous pulmonary venous connection and in 16 age-matched normal controls. Using right upper pulmonary venous pulsed Doppler tracings, peak velocities and velocity time integrals were determined for ventricular systole, ventricular diastole, and atrial systole. Mitral inflow indexes and cardiac outputs were obtained. Patients with repaired total anomalous pulmonary venous connection and controls were similar in weight, heart rate, mitral inflow indexes, and cardiac output. In normal children, peak velocities were greater during ventricular diastole than systole, but velocity time integrals were greater during ventricular systole than diastole. Compared with normals, repaired patients had unobstructed flow patterns with increased peak velocities during ventricular diastole (0.92 +/- 0.35 vs 0.62 +/- 0.12 m/s) and atrial systole (0.27 +/- 0.12 vs 0.17 +/- 0.04 m/s). Velocity time integrals of repaired patients were increased during atrial systole (0.02 +/- 0.01 vs 0.01 +/- 0.03 m) but decreased during ventricular systole (0.08 +/- 0.03 vs 0.12 +/- 0.03 m). Systolic-to-diastolic ratios were decreased in repaired patients for peak velocity (0.56 +/- 0.20 vs 0.79 +/- 0.12) and velocity time integral (0.6 +/- 0.18 vs 1.48 +/- 0.35). Thus, pulmonary venous flow in normal children is greater during ventricular systole than during ventricular diastole. Repaired patients show a shift in forward flow from ventricular systole to diastole, with greater reversed flow during atrial systole.

A novel approach to pediatric intraaortic balloon pump timing using M-mode echocardiography.

Timing balloon inflation and deflation is difficult in pediatric patients undergoing intraaortic balloon pumping, because the electrocardiogram and arterial pressure tracings are inadequate markers of the onset of diastole and systole. M-mode echocardiography provides a precise marker of aortic valve opening and closure, as well as balloon motion, and allows accurate timing by real-time adjustment of balloon inflation to diastole and deflation to systole.

Size of ventricular structures influences surgical outcome in Down syndrome infants with atrioventricular septal defect.

To evaluate the relation between ventricular structure size and surgical outcome in Down versus non-Down syndrome infants with an atrioventricular septal defect, we reviewed the charts and echocardiograms of 44 consecutive infants (34 with Down syndrome) who underwent atrioventricular septal defect repair. Children with Down syndrome had significantly greater aortic valve diameters, left ventricular valve areas, and left/right atrioventricular valve area ratios as well as fewer adverse outcomes than non-Down syndrome children.

Urokinase therapy for thrombosis of tricuspid prosthetic valve.

A 16-month-old child was born with pulmonic stenosis and a hypoplastic right ventricle. After palliative procedures, the patient began having signs of tricuspid insufficiency and stenosis necessitating a tricuspid valve replacement. A St. Jude Medical valve was implanted. While the child was on aspirin therapy, thrombus formation resulted in valve dysfunction. This thrombus was successfully dissolved with urokinase infusion, and normal valve function was restored.

Management of thoracic outlet syndrome.

Twelve hundred patients with thoracic outlet syndrome have been managed between 1973 and 1978. Diagnosis was based on a careful history and detailed physical examination designed to establish the presence of brachial plexus irritation. The cervical spine was evaluated and nerve conduction studies were obtained. All patients were initially treated with a comprehensive physical therapy program. One hundred thirteen patients had transaxillary first rib resections. Eighty percent of surgical patients had complete relief of symptoms and 13 percent were improved. Seven percent were unimproved and none was made worse by operation. There were no operative deaths. Complications occurred in 3 percent, and there were no recurrences requiring operation. This management plan reduced the number of patients requiring operation to 9.4 percent while maintaining satisfactory surgical results.

Right atrial ball-valve thrombus: a complication of central venous alimentation in an infant. Diagnosis and successful surgical management of a case.

The following is a case report of a 6-week-old premature infant in whom a ball-valve thrombus developed after prolonged central venous alimentation. Clinical presentation included facial edema, cyanotic episodes, and apnea. No murmur was present, but the diagnosis was suspected when a calcified right atrial mass became apparent on the plain chest film. The diagnosis was confirmed by echocardiography and then venous and cardiac angiography. The calcified thrombus was removed successfully from the right atrium by use of profound hypothermia with ether anesthesia and total circulatory arrest. Subsequently, the patient made an uneventful recovery and is healthy 3 years postoperatively.

Class I and class II anti-HLA antibodies after implantation of cryopreserved allograft material in pediatric patients.

OBJECTIVES: Very little is known regarding the immune response to cryopreserved allograft valves and patch material used in the surgical repair of congenital heart defects. METHODS: We prospectively measured the frequency of panel reactive antibodies directed against HLA class I (HLA-A, B, and C) and class II (HLA-DR/DQ) alloantigens in 24 children receiving cryopreserved allografts. We compared them with results in 11 previously reported control patients. Sixteen of the study patients underwent placement of a valved conduit (11 pulmonic, 5 aortic) between the right ventricle and pulmonary arteries, 6 underwent patch angioplasty of stenotic vessels with cryopreserved pulmonary artery, and 2 underwent placement of a pulmonary monocusp patch. Study patients had panel reactive antibodies measured before, 1 month, 3 months, and 1 year after the operation. RESULTS: With allograft implantation, panel reactive antibodies increased from 1.9% +/- 5% before the operation to 62% +/- 33% at 31 +/- 8 days after the operation, 92% +/- 15% at 3.3 +/- 0.6 months after the operation, and 85% +/- 18% at 1.1 +/- 0.2 years after the operation. The control group showed no change in panel reactive antibodies, with a level of 1.6% +/- 1% before the operation, 3.2% +/- 1% 28 +/- 5 days after the operation, and 1.7% +/- 1% 2.7 +/- 0.3 months after the operation. Class II antibodies (anti-HLA-DR/DQ) rose to 49% +/- 35% at 30 +/- 8 days and 70% +/- 26% at 3.3 +/- 0.6 months after the operation. CONCLUSIONS: Cryopreserved allograft material induces a marked response that involves both class I and class II anti-HLA antibodies within 3 months after operation in children. This alloantibody response may represent a form of "rejection," may have implications for those who require subsequent cardiac transplantation, and may play a role in early allograft failure.

Early and late results in pulmonary atresia and intact ventricular septum.

We examined the early and late results of operations in 29 consecutive neonates with pulmonary atresia and intact ventricular septum treated from 1980 to 1988. Transventricular pulmonary valvotomy and central aorta-pulmonary artery shunting were performed in 19 of 22 infants who had a patent infundibulum. Pulmonary valvotomy alone was performed in 3 of the 22 infants with a patent infundibulum, but 2 of these required subsequent systemic-pulmonary artery shunts. Primary shunting was used to palliate 7 infants who had absent infundibular portions of the right ventricle and a very diminutive right ventricular cavity. Tricuspid valve excision and atrial septectomy were also performed in 5 of these 7 infants to decompress large fistulous communications between the right ventricule and coronary artery. Two early deaths (2/29, 6.9%) occurred overall. Both were in infants who had a very small right ventricle. Definitive operation has been accomplished in 16 patients; 13 have had closure of residual interatrial communications and shunt ligation with no deaths, and 3 have undergone modified Fontan repair with 1 death. Actuarial survival rate for the entire group, including operative deaths, is 86% at 5 years. The technique of transventricular pulmonary valvotomy and systemic-pulmonary artery shunting offers a reliable means of palliating neonates with pulmonary atresia and intact ventricular septum and obtains good late right ventricular growth. Systemic-pulmonary shunting, tricuspid valvectomy, and atrial septectomy may offer a means of reducing or obliterating right ventricular-coronary artery fistulas.

Cost and efficacy of surgical ligation versus transcatheter coil occlusion of patent ductus arteriosus.

OBJECTIVE: The purpose of this study was to compare cost and efficacy of surgical closure of patent ductus arteriosus using new critical pathway methods with outpatient transcatheter coil occlusion of patent ductus arteriosus. METHODS: Surgical techniques included a transaxillary, muscle-sparing thoracotomy, triple ligation of the patent ductus arteriosus, no chest tube, and discharge from the hospital within 24 hours. Transcatheter coil occlusion of patent ductus arteriosus was done as an outpatient procedure. Costs were compared with inclusion of all hospital and professional charges. RESULTS: From July 1994 until March 1996, 20 patients underwent coil occlusion of patent ductus arteriosus and 20 patients underwent surgical closure of patent ductus arteriosus. Duration of hospitalization was significantly less for the patients receiving coil occlusion (11 +/- 6 hours) as compared with that for the patients having surgical ligation (28 +/- 7 hours, p < 0.05). Total charges were similar for surgical ligation ($7101 +/- $408) as compared with those for coil occlusion ($7104 +/- $886, p > 0.05). Morbidity in coil occlusion included inability to occlude the patent ductus arteriosus in two patients (2/20, 10%) and residual patency in two patients (2/18, 11%). Morbidity in the surgical group included nausea and vomiting necessitating hospitalization for more than 36 hours in one patient (1/20, 5%), transient left recurrent laryngeal nerve palsy in one (1/20, 5%), and pneumothorax in two patients (2/20, 10%). There were no instances of residual patency in the surgical group. CONCLUSIONS: Transaxillary thoracotomy without tube thoracostomy and with critical pathway methods allows safe and effective ligation of a patent ductus arteriosus with early hospital discharge. This surgical method has similar cost, higher efficacy rate, and applicability in all patients as compared with newer transcatheter coil occlusion techniques for closure of a patent ductus arteriosus.

Left heart hypoplasia and neonatal aortic arch obstruction: is the Rhodes left ventricular adequacy score applicable?

OBJECTIVE: Although the influence of small left heart structures on outcome of a biventricular repair in neonatal critical aortic stenosis is well documented, little is known about its effect in neonates with aortic arch obstruction and coarctation. The purpose of this study was to evaluate the influence of small left heart structures on early and late results of repair and the ability to achieve a biventricular repair in neonates with coarctation and aortic arch obstruction. PATIENTS: Neonates included in this study had a left ventricular adequacy score (as proposed by Rhodes and associates for critical aortic stenosis) that would have predicted a need for a univentricular (Norwood) repair. All were ductus dependent but had antegrade ascending aortic flow and a small but nonstenotic aortic valve (<30 mm Hg gradient). Twenty neonates aged 10 +/- 9 days were identified for the study with weights averaging 3. 1 +/- 0.6 kg. Selected left heart measurements obtained by preoperative echocardiography included the following: aortic anulus 5.3 +/- 0.3 mm, mitral anulus 8.4 +/- 1.0 mm, transverse aortic arch 3.4 +/- 0.6 mm, and left ventricular volume 25 +/- 4 mL/m2. All patients underwent coarctation repair by resection and extended end-to-end anastomosis to enlarge the transverse arch as needed. Three patients underwent simultaneous pulmonary artery banding because of a hemodynamically significant ventricular septal defect. These 3 patients have subsequently had their defects successfully closed without mortality. RESULTS: There were no early or late deaths at a follow-up of 38 +/- 16 months after the operation. Three patients (3/20, 15%) have had to undergo reintervention with balloon aortoplasty because of recurrent coarctation (gradient > 20 mm Hg) in 2 and resection of subaortic stenosis in 1. Late follow-up in the remaining patients reveals 1 with moderate subaortic stenosis (gradient = 43 mm Hg), 2 with mild aortic stenosis (gradient < 30 mm Hg), and 2 with mild to moderate mitral stenosis. At late follow-up, 16 patients (16/20, 80%) are completely free of symptoms and 4 (4/20, 20%) have mild residual symptoms. CONCLUSIONS: Biventricular physiology can be successfully achieved in neonates with small left heart structures and aortic arch obstruction with minimal mortality and excellent late functional results. Standard echocardiographic measurements used to predict the need for a univentricular repair in critical aortic stenosis are not valid for the neonate with aortic arch obstruction.

Congenital heart disease with ductal-dependent systemic perfusion: Doppler ultrasonography flow velocities are altered by changes in the fraction of inspired oxygen.

BACKGROUND: An unfavorable balance in systemic and pulmonary perfusion may occur in neonates with ductal-dependent systemic perfusion while being treated with prostaglandin E1 before surgical palliation or transplantation. At our institution, we adjust the fraction of inspired oxygen, with supplemental nitrogen if needed, to control pulmonary vascular tone and maintain systemic oxygen saturations near 75%. METHODS: We performed a noninvasive Doppler ultrasound study in 10 patients to determine whether velocity time integrals in the descending aorta and middle cerebral arteries and the peak velocity at the foramen ovale were acutely altered by changes in the fraction of inspired oxygen. Measurements were performed after 10- to 15-minute intervals of breathing 14% to 19%, 21%, and 35% oxygen. RESULTS: Antegrade descending aortic velocity time integrals did not change significantly when these patients breathed different amounts of oxygen; however, the retrograde velocity time integral in the descending aorta and the peak velocity of left-to-right shunt at the foramen ovale increased with increasing amounts of inspired oxygen. The ratio of antegrade to retrograde velocity time integrals in the descending aorta was greater with supplemental nitrogen than with supplemental oxygen. Middle cerebral arterial velocity time integrals were not significantly greater with supplemental nitrogen than with supplemental oxygen (p = 0.061). CONCLUSIONS: Systemic and interatrial Doppler velocities are acutely influenced by the fraction of inspired oxygen in neonates with ductal-dependent systemic perfusion.

Murine monoclonal CD3 antibody (OKT3)-based early rejection prophylaxis in pediatric heart transplantation.

The purpose of this study was to review our experience with the use of OKT3 (a murine monoclonal CD3 antibody) used as immune prophylaxis for pediatric heart transplant recipients. Orthotopic heart transplantation was performed in 18 pediatric patients, 8 girls and 10 boys, ranging in age from 17 days to 17 years. OKT3 therapy was initiated intraoperatively at a dose of approximately 0.2 mg/kg and was administered at a dose of approximately 0.1 to 0.2 mg/kg/day for a period of 11.5 +/- 2.5 days. Daily average OKT3 levels were 1132 +/- 469 ng/ml. Side effects that occurred during OKT3 therapy were fever (59%), diarrhea (24%), headaches (24%), vomiting (18%), encephalopathy (12%), pulmonary edema (6%), and rash (6%). Infections occurred in 24% of patients, all within 6 months of transplantation. In the first year after transplantation, patients experienced 3.4 +/- 2.4 episodes of mild rejection and 1.0 +/- 0.8 episodes of moderate rejection. No patient experienced severe rejection. Five of the surviving 14 patients (36%) have been weaned from chronic steroid therapy, and 42% are being maintained on alternate-day prednisone at a dose of 0.06 +/- 0.02 mg/kg/day. Coronary artery disease developed in three patients; two of whom died. Actuarial survival was 83% at 1 year and 73% at 2 years. This report shows that OKT3 prophylaxis in pediatric heart transplantation can be used with acceptable short-term adverse side effects and overall survival.

Methotrexate therapy in pediatric heart transplantation as treatment of recurrent mild to moderate acute cellular rejection.

We have used adjunctive therapy with methotrexate as treatment of recurrent mild-to-moderate acute cellular rejection and in an attempt to reduce rejection frequency and corticosteroid dosage. The purpose of this study was to review our experience with this treatment strategy. Eight patients, 13.1 +/- 1.1 years of age (mean +/- standard error of the mean) at the time of transplantation, were given methotrexate in addition to their standard triple therapy immunosuppression. Methotrexate was started at 6.2 +/- 2 months after transplantation after an average of 3.1 +/- 0.4 rejection episodes. Patients were given methotrexate weekly for 8 weeks at 2.5 or 5 mg orally every 12 hours for three doses (0.23 +/- 0.02 mg/kg/week). The time to resolution of rejection was 17.9 +/- 4 days after initiating methotrexate therapy. The number of rejections per month decreased significantly from the 2 months before methotrexate therapy (1.49 +/- 0.1) when compared with both the 2 months during methotrexate therapy (0.50 +/- 0.1) and the 2 months after methotrexate therapy was completed (0.44 +/- 0.3) (p < 0.005). Furthermore, when comparing total rejection frequency since transplantation and before methotrexate therapy to a follow-up period of 21.8 +/- 5 months after completion of methotrexate therapy, the rejection frequency was significantly less (0.81 +/- 0.2 versus 0.10 +/- 0.06 rejections/month) (p < 0.01). Prednisone dosage was also significantly less when comparing the time before methotrexate therapy to immediately after completion of methotrexate therapy (0.23 +/- 0.04 versus 0.15 +/- 0.03 mg/kg/day) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic input impedance in infants and children.

Flow and pressure measurements were performed in the ascending aortas of six pediatric patients ranging in age from 1 to 4 yr and in weight from 7.2 to 16.4 kg. From these measurements, input impedance was calculated. It was found that total vascular resistance decreased with increasing patient weight and was approximately one to three times higher than those of adults. Conductance per unit weight was relatively constant but was approximately three times higher than for adults. Strong inertial character was observed in the impedance of four of the six patients. Among a three-element and two four-element lumped-parameter models, the model with characteristic aortic resistor (R(c)) and inertance in series followed by parallel peripheral resistor (R(p)) and compliance fitted the data best. R(p) decreased with increasing patient weight and was one to three times higher than in adults, and R(c) decreased with increasing patient weight and was 2 to 15 times higher. The R(p)-to-R(c) ratio differed significantly between infants and children vs. adults. The results suggested that R(p) developed more rapidly with patient weight than did R(c). Compliance values increased with increasing patient weight and were 3 to 16 times lower than adult values.

Successful diagnosis and surgical treatment of single ventricle, truncus arteriosus.

The association of single ventricle and truncus arteriosus is rare. We present the successful surgical palliation of a patient who echocardiographically and angiographically has a truncus arteriosus type I and single left ventricle. At operation, the main pulmonary artery was dissected off the truncus arteriosus, and a 4-mm polytetrafluoroethylene graft was placed from the ascending aorta to the left pulmonary artery. The patient is currently 13 months old and growing well.

Bovine pericardium: a source of pulmonary venous obstruction in the Mustard procedure.

Following Mustard's popularization of the intraatrial baffle procedure for transposition of the great arteries, debate has persisted regarding the ideal materials to use. Reports of xenograft (i.e., bovine pericardium) as a suitable prosthetic material made it an appealing choice. We report our recent experience with 2 patients in whom bovine pericardium was used for atrial augmentation, with subsequent pulmonary venous obstruction. For this reason, we have abandoned this material as an acceptable prosthetic in the Mustard procedure.

Subclavian artery cannulation for infant extracorporeal membrane oxygenation.

A technique is presented for subclavian artery cannulation for extracorporeal membrane oxygenation. This method allows antegrade perfusion of the carotid artery to occur both during extracorporeal membrane oxygenation and after decannulation. This method may prevent neurologic sequelae associated with the more common techniques using the carotid artery.

Secondary sternal closure: a method of preventing cardiac compression.

A patient with severe congenital pulmonary stenosis who underwent pulmonary valvulectomy is reported. Acute cardiac compression and left ventricular failure developed in the immediate postoperative period. Because of extreme cardiac dilatation, the chest wall could not be closed. A technique of secondary sternal closure is described.

Randomized controlled study of inhaled nitric oxide after operation for congenital heart disease.

BACKGROUND: Inhaled nitric oxide selectively decreases pulmonary vascular resistance. This study was performed to determine whether inhaled nitric oxide decreases the incidence of pulmonary hypertensive crises after corrective procedures for congenital heart disease. METHODS: Patients with a systolic pulmonary arterial pressure of 50% or more of the systolic systemic arterial pressure during the early postoperative period were randomized to receive 20 parts per million inhaled nitric oxide (n = 20) or conventional therapy alone (n = 20). Acute hemodynamic and blood gas measurements were performed at the onset of therapy. The efficacy of sustained therapy was determined by comparing the number of patients in each group who experienced a pulmonary hypertensive crisis. RESULTS: In comparison to controls, there were no significant differences in the baseline and 1-hour measurements of patients who were treated with nitric oxide. Four patients in the control group and 3 patients in the nitric oxide group experienced a pulmonary hypertensive crisis. CONCLUSIONS: Nitric oxide did not substantially improve pulmonary hemodynamics and gas exchange immediately after operation for congenital heart disease. Nitric oxide also failed to significantly decrease the incidence of pulmonary hypertensive crises.