Gentamicin in Neonates with Hemodynamically Significant Patent Ductus Arteriosus.

Background: Gentamicin has been shown to cause vasodilation in preclinical studies. Hemodynamically significant patent ductus arteriosus (hsPDA) is a commonly observed congenital heart disorder in preterm neonates. Concomitant gentamicin theoretically shall delay the closure/result in nonclosure of ductus arteriosus (DA). Similarly, hsPDA can alter the pharmacokinetics of gentamicin and so trough gentamicin concentrations. We carried out the present study to evaluate the association between gentamicin use and closure of hsPDA (treated with acetaminophen) as well as the effect of hsPDA on trough concentrations. Methods: This study was a prospective, observational study that included 60 neonates diagnosed with hsPDA by echocardiography and 102 neonates without hsPDA. Demographic details, size of DA as per echocardiography at the end of treatment with acetaminophen, gentamicin-dosing regimen, and trough concentrations were collected. Standard definitions were adhered in classifying the gestational age, birth weights, and size of DA. The numerical values are reported in median (range). Results: Neonates with hsPDA had significantly lower daily doses of gentamicin [4.5 (2.5-10), 7 (3.2-13) mg; P < 0.001] but longer duration of therapy [8 (3-14), 5 (3-7) days; P < 0.001] than those without hsPDA in very preterm neonates. No significant differences were observed in the trough concentrations of gentamicin between the groups. No association was observed between gentamicin use and closure of DA. However, those with successful closure of DA received gentamicin for a longer duration [6 (3-10), 4 (3-14) days; P < 0.05] that was independent of acetaminophen duration and had received higher cumulative doses of gentamicin. Conclusion: In conclusion, we observed a significantly longer duration of gentamicin therapy in neonates with hsPDA compared to those without hsPDA. No significant differences were observed in the rates of closure of DA with concomitant gentamicin administration and gentamicin trough concentrations.

Population pharmacokinetic-pharmacodynamic modeling of acetaminophen in preterm neonates with hemodynamically significant patent ductus arteriosus.

BACKGROUND: Pharmacokinetics (PK) of intravenous acetaminophen has not been assessed in preterm neonates with hemodynamically significant patent ductus arteriosus (PDA). Moreover, there is a lack of data evaluating the association between PK and pharmacodynamics (PD) of acetaminophen in hemodynamically significant PDA. Hence, we performed a population PK-PD modeling of acetaminophen in preterm neonates with hemodynamically significant PDA. METHODS: A prospective, observational study was carried out in preterm neonates with hemodynamically significant PDA receiving intravenous acetaminophen (15 mg/kg six hourly) for maximum of nine days. The diameter of the ductus arteriosus was measured using General Electric Vivid 7® (echocardiography) and was the PD measure. The PK-PD modeling was performed using Monolix 2019R2. We performed Monte Carlo (MC) simulations to determine the probability of ductus arteriosus closure from first to the ninth day of acetaminophen treatment. RESULTS: Fifty-five neonates were recruited. A one-compartment model with first-order elimination described well the PK of acetaminophen. Clearance (CL) and volume of distribution (Vd) for typical neonate weighing 0.98 kg was 0.0452 L/h and 1.18 L, respectively. A combination of an Imax model with effect compartment and an exponential disease progression model described well the PD of acetaminophen. The average baseline diameter of the ductus arteriosus (E0) was 2.53 mm while IC50 was 0.477 µg/mL. The disease progression rate constant (Kprog) and effect compartment transfer rate constant (ke0) were 0.00425 h-1 and 0.000103 h-1, respectively. MC simulations of the current dosing regimen revealed a probability of 73.7% ductus arteriosus closure compared to 83.8% with 20 mg/kg six hourly dose. CONCLUSION: The PK-PD model developed can be used for dosing acetaminophen in premature neonates with hemodynamically significant PDA. Intravenous dose of 20 mg/kg intravenously every six hours is likely to provide a better therapeutic effect than the existing dosing regimen.

Intravenous acetaminophen (at 15 mg/kg/dose every 6 hours) in critically ill preterm neonates with patent ductus arteriosus: A prospective study.

WHAT IS KNOWN AND OBJECTIVES: Acetaminophen has been increasingly used in treating patent ductus arteriosus (PDA) in preterm neonates. Variations were observed in the dosing regimen of acetaminophen across the studies. There is hardly any data available for a relatively higher dose of intravenous acetaminophen (15 mg/kg/dose every 6 hours) in the preterm population. We present here the results of a prospective study with this dose of intravenous acetaminophen for treating PDA in critically ill preterm neonates. METHODS: Preterm neonates (≤37 weeks of gestational age) with haemodynamically significant PDA were enrolled. Intravenous acetaminophen at 15 mg/kg/dose every 6 hours was administered. Echocardiographic monitoring, liver and renal function tests were carried out. Standard definitions were adhered for defining acute kidney injury (AKI) and hepatotoxicity. RESULTS: Fifty-five neonates were recruited. Following the first dose, less than half had their serum acetaminophen concentrations in the therapeutic range. Extreme preterm neonates were less likely to have a sustained therapeutic acetaminophen concentration after the first dose. Following multiple doses and at steady state, 97.2% and 98.8% respectively were in the therapeutic range. Forty-three (78.2%) neonates had successful closure of the ductus arteriosus of which 22 were extreme preterm, 17 were very preterm and 4 were late preterm neonates; and considering their birthweights, 21 were extremely low, 16 were very low and 6 were low birthweight categories. Ten neonates had elevated alanine aminotransferase levels with three in the low-to-moderate risk of hepatotoxicity category. Eight neonates had altered renal function tests indicating AKI. WHAT IS NEW AND CONCLUSION: Intravenous acetaminophen at 15 mg/kg/dose every 6 hours was efficacious in 78.2% of the preterm neonates with PDA. We observed a lower incidence of hepatotoxicity, and AKI in the study population. No association was observed between the serum acetaminophen concentrations and PDA closure.

Advanced heart block in acute rheumatic fever.

First degree heart block is considered a minor criterion for the diagnosis of this condition. The cases presented here demonstrate that higher degrees of heart block do occur in rheumatic fever. Children presenting with acquired heart block should be worked-up for rheumatic fever. Likewise, it is imperative to serially follow the electrocardiogram in patients already diagnosed with acute rheumatic fever, as the conduction abnormalities can change during the course of the disease.

Fetal supraventricular tachycardia, treating the baby by targeting the mother.

Fetal supraventricular tachycardia (SVT) is the most common form of fetal tachycardia. If started early in pregnancy, it can cause non-immune fetal hydrops. Echocardiography is the preferred method for the diagnosis with simultaneous pulsed Doppler recording from the superior vena cava and ascending aorta. Transplacental therapy with digoxin is the most common way of treatment. We present a case of fetal SVT detected at 26 weeks of pregnancy. Digoxin therapy restored the rhythm initially, but later paroxysms of fetal SVT persisted necessitating the addition of second antiarrhythmic medication which was discussed with the parents. The couple chose to proceed for premature delivery at 32 weeks.

Diagnosing a patent foramen ovale in children: is transesophageal echocardiography necessary?

BACKGROUND AND PURPOSE: transesophageal echocardiography (TEE) is the gold standard for the diagnosis of a patent foramen ovale in adults. In children, acoustic windows on transthoracic echocardiography (TTE) are better than in adults; thus, an invasive TEE may not be necessary. Our goal was to assess the validity of TTE with agitated saline injection for the diagnosis of a patent foramen ovale in children using TEE as the gold standard. METHODS: fifty consecutive pediatric patients >1 year of age referred for TEE were prospectively enrolled. Imaging included 2-dimensional, color Doppler, and agitated saline contrast injections with and without Valsalva by TTE followed by TEE. Interpreters of the TTE were blinded to TEE results. Studies were categorized as "inconclusive" if the TTE images were inadequate for definitive diagnosis by the blinded interpreter. RESULTS: TTE results were considered conclusive in 43 of 50 (86%) patients. Among the 43 conclusive studies, the 2 modalities disagreed in 1 patient. TTE had a positive predictive value of 100%, negative predictive value 97%, sensitivity of 88%, and specificity of 100% for detecting a patent foramen ovale. CONCLUSIONS: TTE with agitated saline injection is diagnostic for the assessment of atrial septal integrity in the majority of children.

Spatial relationship between the ventricular septal defect and the anomalous muscle bundle in a double-chambered right ventricle.

BACKGROUND: The hemodynamic profile and surgical approach to a double-chambered right ventricle (RV) are influenced by the position of a ventricular septal defect (VSD) in relation to the obstructing muscle bundle. This relationship, however, has not been systematically evaluated, with available literature yielding conflicting results. The objective of this study was to describe this relationship in a series of consecutive patients. DESIGN: This is a retrospective study of patients with double-chambered RV at a single institution between 1999 and 2005. The location of the VSD in relation to the obstructing muscle bundle was established by a review of echocardiograms, cardiac catheterizations, and surgical notes. RESULTS: Twenty-seven patients were identified, and 4 excluded because of inadequate data. There was no disagreement among the methods to determine the relationship between the VSD and the muscle bundle(s). The median age was 65 months (8-204 months). An associated VSD was seen in 21 patients (91%); 18 perimembranous (86%), 2 muscular (9%), and 1 supracristal (5%). The VSD was proximal to the obstructing muscle bundle in 13 (62%), and distal to the bundle in 9 (38%); the supracristal defect was distal, the 2 muscular were proximal, and 11 (61%) of the perimembranous defect were proximal to the muscle bundle. CONCLUSION: The position of the VSD in relation to the anomalous muscle bundle in a double-chambered RV is heterogeneous. The majority of defects communicate with the high-pressure chamber proximal to the muscle bundle(s).

Anomalous systemic arterial supply to the lungs: an unusual etiology for cardiomegaly.

Anomalous systemic arterial blood supply to the lungs is a rare anomaly of lung development. It may present with various manifestations that are shared with more commonly encountered congenital and acquired heart diseases. Thus, it may evade early diagnosis or even lead to a wrong diagnosis and treatment. This lesion should be suspected in left ventricular overload conditions in the absence of a clear explanation.