These findings support the hypothesis that the poor PDA closure rates with INDO for neonates >10 days postnatal age are the result of pharmacokinetic differences only and that weight does not impact response rates. Individualized pharmacokinetic/pharmacodynamic dosing of INDO continues to achieve higher closure rate than current dosing standards. Patients historically known as poor responders significantly benefit from this dosing approach.
The population pharmacokinetics of intravenous indomethacin were investigated with 665 indomethacin serum concentrations from 83 neonates (mean +/- SD: gestational age, 28.8 +/- 2.5 weeks; postnatal age, 5.7 +/- 4.7 days; birth weight, 1.13 +/- 0.40 kg) receiving indomethacin for symptomatic patent ductus arteriosus. A one-compartment open model was used for pharmacokinetic analysis. Hypotheses were tested to determine which developmental and demographic data influenced clearance (CL) and volume of distribution (V(area)). In the final regression equation CL and V(area) were modeled as a function of body weight and postnatal age (PNA) from 0 to 20 days. Final estimates were as follows: CL (ml/hr) = 2.63.weight (kg) + 0.244.PNA (days) and V(area) (L) = 0.28.weight (kg) + 0.0041.PNA (days). The coefficients of variation for interindividual variability in CL and V(area) were 77% and 28%, respectively. Intraindividual variability was 19%. These mean population parameter estimates should prove useful in designing dosage regimens to achieve desired indomethacin concentrations for neonates from 0 to 20 days of age with symptomatic patent ductus arteriosus.
Two infants with cerebral arteriovenous malformation (CAVM), both initially seen with persistent fetal circulation, were studied with cross-sectional echo. The descending aorta, which is dilated in infants with CAVM, was identified in the subxiphoid four-chamber and short-axis views in both infants. In both infants the arteriovenous malformation was readily identified by cross-sectional echo as a lucency within the brain. Pulsation of the cranial lucency was noted in one infant, but only still frames from the head echo were preserved in the other infant, and pulsation was not commented on in that case.
We report a case of an 18-month-old male, born to a woman with third trimester febrile illness, who had a history of congestive heart failure and respiratory distress, cardiomegaly, and electrocardiographic (ECG) findings suggestive of cardiomyopathy and myocarditis. After gradual improvement in heart size and function with pharmacologic therapy, he developed a terminal episode of respiratory distress and cardiogenic shock, with ECG findings of an anterolateral infarct. At autopsy it was found that endocardial fibroelastosis with mural thrombi in the left ventricle had been complicated by thromboembolism to the left anterior descending coronary artery, resulting in transmural infarction of the anteroseptal region of the left ventricle. Myocardial infarction is a potential but unusual thromboembolic complication of endocardial fibroelastosis. A high index of suspicion for coronary artery thromboemboli should be maintained in pediatric patients with cardiomyopathy and suspected myocardial infarction.
A sixteen-month-old child presented with cyanosis of the right arm. Investigation revealed bilateral persistent ductus arteriosus with isolation of the right subclavian artery from the aorta. Pulmonary vascular resistance and pulmonary arterial pressure were elevated so that the right subclavian artery received desaturated blood from the right pulmonary artery via the persistent right ductus arteriosus.
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