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Biomedical subjects

E C McGough

Publications and source records attributed to E C McGough.

At least 19 recordsLinked to original sources
PubMed2000

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.

Administration, Inhalation↗
PubMed2000

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.

Adolescent↗
PubMed2000

Spectrum and influence of hypoplasia of the left heart in neonatal aortic coarctation.

Obstruction of the left ventricular outflow tract may be associated with hypoplasia of the left heart, which importantly influences the options for treatment. Although the influence of the size of the left heart on the outcome for critical aortic stenosis has been described, less is known about the spectrum of such hypoplasia seen with neonatal aortic coarctation, and how this influences outcome. To determine, first, the spectrum and influence of hypoplasia of the left heart in neonatal coarctation, second, if the previously described critical values for adequacy of the left heart in neonates with critical aortic stenosis are applicable to neonates with coarctation, and, third, if any of the variables or associated abnormalities are risk factors for recoarctation, we studied 63 neonates who underwent repair of coarctation. From the initial echocardiogram, we measured multiple structures in the left heart, and calculated a score for adequacy as has been done for critical aortic stenosis. The sizes were compared to previously reported minimal values. We then analyzed the influence of the variables and the associated anomalies on outcome. There were no deaths. There was a broad spectrum of sizes that did not correlate with the need for re-intervention. The calculated score for adequacy would have predicted survival in only 56% of the patients, and 73% of the neonates had at least one parameter measured in the left heart below the previously reported minimal values. There is, therefore, a broad spectrum of sizes for the left heart in neonates with aortic coarctation that is not predictive of outcome. Minimal sizes, and the score for adequacy used for critical aortic stenosis, are not applicable to neonates with coarctation.

Aortic Coarctation↗
PubMed2000

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.

Aorta↗
PubMed1999

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.

Abnormalities, Multiple↗
PubMed1999

Echocardiographic diagnosis of thrombus originating from the ductus arteriosus.

Initial functional closure of the ductus arteriosus normally occurs within hours after birth, with permanent closure taking several weeks. The mechanism for ductal closure has been well studied and has not been shown to include thrombus formation. We describe a normal infant found to have a thrombus originating in the ductus arteriosus that occluded the ductus and subsequently extended into the left pulmonary artery, threatening to occlude it as well. This case illustrates the importance of echocardiography in making this rare diagnosis. It also emphasizes the role of echocardiography as an effective means of following the progression or regression of such a thrombus.

Anticoagulants↗
PubMed1999

Critical pathways for postoperative care after simple congenital heart surgery.

OBJECTIVE: To evaluate the clinical, financial, and parent/patient satisfaction impact of critical pathways on the postoperative care of pediatric cardiothoracic patients with simple congenital heart lesions. STUDY DESIGN: Critical pathways were developed by pediatric intensive care nurses and implemented under the direction of pediatric cardiothoracic surgeons. PATIENTS AND METHODS: Critical pathways were used during a 12-month study on 46 postoperative patients with simple repair of atrial septal defect (ASD), coarctation of the aorta (CoA), and patent ductus arteriosus (PDA). Using the study criteria, a control group of 58 patients was chosen from 1993. Prospective and control group data collected included postoperative intubation time, total laboratory tests, arterial blood gas utilization, morphine utilization, time in the pediatric intensive care unit, total hospital stay, total hospital charges, total hospital cost, and complications. Variances from the critical pathway and satisfaction data were also recorded for study patients. RESULTS: Resource utilization was reduced after implementation of critical pathways. Significant reductions were seen in total hours in the pediatric intensive care unit, total number of laboratory tests, postoperative intubation times, arterial blood gas utilization, morphine utilization, length of hospitalization (ASD, 4.9 to 3.1 days; CoA, 5.2 to 3.2 days; and PDA, 4.1 to 1.4 days; all P < 0.05), total hospital charges (ASD, $16,633 to $13,627; CoA, $14,292 to $8319; and PDA, $8249 to $4216; all P < 0.05), and total hospital costs. There was no increase in respiratory complications or other complications. Patients and families were generally satisfied with their hospital experience, including analgesia and length of hospitalization. CONCLUSIONS: Implementation of critical pathways reduced resource utilization and costs after repair of three simple congenital heart lesions, without obvious complications or patient dissatisfaction.

Aortic Coarctation↗
PubMed1998

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.

Aortic Valve↗
PubMed1998

Late results and reintervention after aortic valvotomy for critical aortic stenosis in neonates and infants.

BACKGROUND: Many centers have adopted balloon valvuloplasty for treatment of infants with critical aortic stenosis because of historically poor early results and a lack of long-term results with surgical valvotomy. We evaluated our results with open aortic valvotomy over the past decade, specifically examining factors influencing survival and reintervention in the current era. METHODS: From 1986 to 1996, 37 infants in the first 3 months of life underwent open aortic valvotomy for critical aortic stenosis. All patients underwent cardiopulmonary bypass, valvotomy, and valve debridement under direct vision with standard techniques. RESULTS: Early mortality was 11% (4 of 37, 70% confidence limit 7% to 20%) and all early deaths were in neonates less than 2 weeks of age. Late death occurred in 6 patients a mean of 10 +/- 12 months (range, 2 to 36 months) after valvotomy. Actuarial survival, including operative deaths was 92% +/- 6% at 1 month, 78% +/- 9% at 1 year, and 73.4% +/- 10% at 10 years. In a multifactorial regression analysis, the best predictors of death were the presence of endocardial fibroelastosis and small body surface area and the best predictor of the need for late reintervention was preoperative aortic annular size. Thirteen patients required reintervention: repeat operation in 7 patients, balloon valvuloplasty in 3 patients, and both balloon valvuloplasty and reoperation in 3 patients. Actuarial freedom from reintervention postoperatively is 97% +/- 3% at 1 month, 73% +/- 9% at 1 year, and 55% +/- 11% at 10 years. Reintervention was for recurrent left ventricular outflow obstruction in 9 patients and mixed aortic stenosis and aortic insufficiency in 4. Echocardiography 4.3 +/- 2.5 years after aortic valvotomy in survivors who have not required reintervention (n = 20) revealed a Doppler peak instantaneous systolic gradient of 37 +/- 14 mm Hg and mild or less aortic regurgitation in 16 patients and moderate aortic regurgitation in 4 patients. CONCLUSIONS: Current surgical results with critical aortic stenosis in the neonate and young infant are acceptable in terms of both late survival, reintervention, and functional results in the majority of patients. Newer interventions, such as balloon valvuloplasty, should be carefully evaluated for long-term results and should be compared more appropriately to current surgical results to determine the best treatment modality for the neonate and infant with critical aortic stenosis.

Actuarial Analysis↗
PubMed1997

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.

Adolescent↗
PubMed1996

Prospective analysis of HLA immunogenicity of cryopreserved valved allografts used in pediatric heart surgery.

BACKGROUND: The HLA immunogenicity of cryopreserved valved allografts used in the surgical repair of congenital heart defects is unknown. METHODS AND RESULTS: To determine the immunogenicity of these allografts, we measured prospectively the frequency of panel-reactive HLA class I alloantibodies (PRA) before, 1 month after, and 3 months after allograft implantation in 9 children (age, 5.4 +/- 2.1 years) and after open-heart surgery without allograft implantation in 11 age-matched control children (age, 4.0 +/- 1.5 years). PRA was determined against an HLA-select frozen T-lymphocyte panel using the antiglobulin cytotoxicity technique. After allograft implantation, PRA increased from 3.2 +/- 2.7% before surgery to 63.3 +/- 12% at 25 +/- 2 days after surgery and 99.7 +/- 0.3% at 3.4 +/- 0.3 months after surgery. The use of dithiothreitol to remove IgM alloantibodies resulted in a modest decrease in PRA at 1 month (33.2 +/- 13%) but no change at 3 months (93.0 +/- 3.4%), suggesting the initial humoral response is an IgM alloantibody that switches almost exclusively to IgG by 3 months. Control patients showed no increase in PRA over time: 1.6 +/- 1% before surgery, 3.2 +/- 1% at 28 +/- 5 days after surgery, and 1.7 +/- 1% at 2.7 +/- 0.3 months after surgery. CONCLUSIONS: Cryopreserved valved allografts in children induce a marked HLA alloantibody response that increases to broad panel reactivity within 3 months after surgery. This HLA sensitization has potential not only for causing deleterious effects on allograft function but also for limiting the future opportunity of heart transplantation in patients who receive cryopreserved valved allografts.

Adolescent↗
PubMed1996

Aortic valve repair and replacement after balloon aortic valvuloplasty in children.

BACKGROUND: Little is known about the incidence, indications, and results of surgical repair or replacement of the aortic valve after balloon aortic valvuloplasty (BAV) for congenital aortic stenosis in children. This study was designed to evaluate patterns of failure requiring operation after BAV for congenital aortic stenosis and to review our experience with successful repair, rather than replacement, of selected aortic valves after BAV. METHODS: From March 1986 to June 1995, 60 patients with congenital aortic stenosis aged 1 day to 27 years (mean +/- standard deviation, 7.3 +/- 6 years) underwent BAV. Twenty-three patients (38%) required operation a mean of 44 +/- 37 months (range, 1 to 110 months) after BAV, because of severe aortic insufficiency in 13 patients and recurrent or residual aortic stenosis in 10 patients. Severe aortic insufficiency was invariably due to avulsion of a cusp from the annulus, with resulting cusp prolapse and insufficiency. Operative intervention consisted of valve replacement in 14 patients and valve repair in 9 patients. Repair techniques included reattachment of an avulsed cusp to the aortic annulus, relief of commissural fusion, and debridement of thickened cusps. RESULTS: Actuarial freedom from surgical intervention after BAV was 88% +/- 4% at 1 year, 70% +/- 6% at 5 years, and 51% +/- 12% at 9 years. The need for aortic valve operation was unrelated to age at the time of BAV, indication for operation (aortic insufficiency versus aortic stenosis), age of operation, or preoperative gradient. All patients survived aortic valve operation; there was one late death at an average follow-up of 27 +/- 20 months (range, 2 to 61 months) after aortic valve operation. Stenosis was well relieved in all patients undergoing valve replacement. The 9 valve repair patients have been followed for 22 +/- 14 months (range, 1 to 47 months). Echocardiographic follow-up of the valve repair patients revealed a mean residual aortic stenosis peak instantaneous gradient of 32 mm Hg and mild aortic insufficiency or less in all patients. CONCLUSIONS: Aortic valve operation is required in 5% to 7% of patients yearly after BAV. The need for operation appears to be unrelated to age at the time of BAV; aortic insufficiency predominates over aortic stenosis as an indication for operative intervention. Valve repair can be applied in some patients after BAV with good intermediate-term results and may delay the need for aortic valve replacement.

Adolescent↗
PubMed1996

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.

Adolescent↗
PubMed1995

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.

Case-Control Studies↗
PubMed1995

Absorbable polydioxanone suture and results in total anomalous pulmonary venous connection.

BACKGROUND: Despite theoretical advantages of absorbable suture in the growing vascular anastomosis, there has not been a documented advantage over nonabsorbable suture in preventing late anastomotic stenosis in total anomalous pulmonary venous connection (TAPVC). METHODS: We reviewed our experience from 1982 to 1994 with 65 hospital survivors of total TAPVC repair to examine the influence of suture type on survival and incidence of late pulmonary venous obstruction. From 1982 until 1988, we used continuous nonabsorbable polypropylene suture for the pulmonary venous-left atrial anastomosis in supracardiac, infracardiac, and mixed types of TAPVC: In 1989, we adopted a running absorbable polydioxanone suture technique. Cardiac catheterization and echocardiography were used to evaluate late pulmonary venous obstruction. RESULTS: Late pulmonary venous obstruction occurred in 17% (4/23) of survivors after repair with polypropylene suture compared with 3.2% (1/32) after repair with polydioxanone suture (p < 0.05). There were no instances of late pulmonary venous obstruction in the intracardiac TAPVC group (0/10). All late pulmonary venous obstructions occurred within 16 months after operation. The actuarial 3-year and 5-year freedom from late pulmonary venous obstruction was 100% for intracardiac TAPVC, 96% for the polydioxanone group, and 81% for the polypropylene group. Five patients died late (5/65, 7.7%), 3 in the polypropylene suture group (3/23, 13%) and 2 in the polydioxanone group (2/32, 6%). CONCLUSIONS: Continuous absorbable polydioxanone suture for the repair of TAPVC results in a low incidence of late pulmonary venous obstruction and death and appears to offer advantages over a continuous nonabsorbable suture. A continuous nonabsorbable suture may limit growth of a vascular anastomosis, particularly one involving a "low-pressure" anastomosis such as in the repair of TAPVC:

Absorption↗
PubMed1994

Early and intermediate results of the Fontan procedure at moderately high altitude.

At higher elevations, alveolar hypoxia increases pulmonary vascular resistance and may limit the cardiac output of individuals without a subpulmonary ventricle. Thus, we reviewed the outcome of definitive palliation for tricuspid atresia and other forms of single ventricle in 60 consecutive Fontan patients living at a mean elevation of 1,370 m (range, 910 to 2,130 m). There were four early deaths (6.7%; 70% confidence limits, 4.1% to 10.7%) and six late deaths. Kaplan-Meier actuarial survival (+/- standard error) is 79.6% +/- 8.2% at 5 years. Survival was significantly decreased in patients with a preoperative mean pulmonary arterial pressure greater than or equal to 15 mm Hg unless the Fontan procedure was performed with a residual fenestration. Exercise tolerance was significantly worse at higher elevations in a subgroup of patients who have traveled to altitudes of 1,680 to 3,350 m. We conclude that the early and intermediate results of the Fontan procedure at moderately high altitude are similar to results reported at sea level. However, exercise tolerance may be impaired at higher elevations in many patients.

Adolescent↗
PubMed1994

Age-related amrinone pharmacokinetics in a pediatric population.

OBJECTIVES: To measure the plasma concentrations of amrinone and N-acetyl-amrinone achieved using current pediatric dosing recommendations. To examine the pharmacokinetics of amrinone in an extended age range of pediatric patients. To examine any age-related differences in the relative contribution of hepatic metabolism vs. renal elimination of amrinone. DESIGN: Prospective study. SETTING: A pediatric intensive care unit in a tertiary care teaching hospital. PATIENTS: Thirty-one patients aged 4 days to 15 yrs who required a constant infusion of amrinone. INTERVENTIONS: Blood samples were obtained 15 mins after each 0.75 mg/kg loading dose, and every 6 hrs during a constant infusion of amrinone to measure plasma amrinone, N-acetyl-amrinone and N-glycolyl-amrinone concentrations by high-performance liquid chromatography. Blood samples to measure amrinone, N-acetyl-amrinone, and N-glycolyl-amrinone concentrations during elimination were also obtained at regular intervals after discontinuation of the infusion. Six-hour urine collections were obtained to measure amrinone renal clearance. MEASUREMENTS AND MAIN RESULTS: Plasma amrinone concentrations > or = 2 micrograms/mL were obtained in 13 of 14 patients after a 3-mg/kg loading dose. There was a six-fold variability in steady-state plasma amrinone concentrations in patients receiving the same ordered infusion rate. There was a significant (p = .001) difference between the ordered and measured amrinone infusion rates. Six (19.4%) of 31 patients had steady-state plasma amrinone concentrations of < or = 2 micrograms/mL. There was a large variability in the volume of distribution, clearance, and elimination half-life which did not appear to be age-related. Renal clearance of amrinone ranged between 0.4 and 2.18 mL/kg/min, and did not increase with age. There was no increase in the proportion of children with a high plasma steady-state N-acetyl-amrinone/amrinone ratio over time from 1 to 24 months of life. CONCLUSIONS: Administering a 3-mg/kg amrinone loading dose in four divided doses over 1 hr resulted in relatively rapid therapeutic plasma concentrations without excessively high concentrations and good clinical tolerance. The wide interindividual variation in clearance and volume of distribution resulted in a variable dose-concentration relationship; children receiving lower amrinone infusion rates may-have subtherapeutic plasma steady-state concentrations. There did not appear to be any age-related change in renal clearance or hepatic metabolism of amrinone in children aged 1 to 24 months.

Adolescent↗