Journal of Pediatric Pharmacology and Therapeutics最新文献

Spironolactone is a mineralocorticoid receptor antagonist with potassium-sparing effects used in the management of heart failure to minimize morbidity and mortality. It is typically given in combination with an angiotensin-converting enzyme inhibitor (ACEI) as part of standard management of pediatric heart failure but has limited literature regarding safety and efficacy in this population. We report a case of probable concomitant enalapril and spironolactone-induced hyperkalemia in a 2-month old female. The patient presented with Class III congestive heart failure and was initiated on enalapril and spironolactone. New hyperkalemia (serum potassium concentration 8.9 mEq/L) developed on day 7 after initiation and persisted despite decreases in the spironolactone dose. Persistent hyperkalemia and hyponatremia with a metabolic acidosis led to the discontinuation of spironolactone by day 12 of admission. The hyperkalemia resolved within 72 hours of discontinuation without further interventions. Based on our patient's course, hyperkalemia in a pediatric patient may occur when spironolactone and an ACEI are given concomitantly and resolve upon discontinuation of spironolactone.

Objective: The use of clopidogrel for postprocedural primary thromboprophylaxis in pediatric cardiac patients is becoming more common. This study aimed to explore, using P2Y12 reaction unit (PRU) values, whether the currently recommended static low clopidogrel dose of 0.2 mg/kg/day for patients under 24 months is optimal, or if a gradual dosage escalation would be more appropriate; and to propose a hypothetical dosing scheme for clopidogrel thromboprophylaxis in these patients.

Methods: Exploratory, retrospective cohort study in cardiac patients 0-24 months old receiving clopidogrel for thromboprophylaxis between 2018 and 2021. Data collected from medical records included patient demographics and diagnoses, clopidogrel dosing and duration, PRU values, concomitant anticoagulant and antiplatelet therapies, adverse events, and outcomes. Exponential and linear regression analyses were employed to model dosage as a function of time using therapeutic PRU values and to identify the best-fit dosing scheme for clopidogrel.

Results: Forty-four cardiac patients on clopidogrel for thromboprophylaxis were included. No statistically significant difference was observed between the predicted dosing from the fitted and the referent regressions, indicating that the observed clopidogrel doses that achieved a therapeutic PRU followed a dosing gradient inconsistent with the static low dose (0.2 mg/kg/day) recommended by the Platelet Inhibition in Children On cLOpidogrel (PICOLO) trial during the first 24 months of age.

Conclusions: Pediatric cardiac patients may require a gradual escalation of clopidogrel dosing with age, in contrast to the static low dose recommended by the PICOLO trial during the first 24 months of life. An age-based dosing scheme may prove beneficial for this age group. Prospective studies evaluating age-based clopidogrel dosing in this patient population could offer further insight into this relationship.

Metabolic alkalosis, characterized by an increase in serum bicarbonate (>28 mEq/L) and serum pH (>7.45), is associated with clinical complications including arrhythmias, mental confusion, and seizures. Non-pharmacologic measures are recommended first-line for treatment of hypochloremic metabolic alkalosis, but pharmacologic treatment may be needed. This review of the literature provides detailed descriptions of dosage regimens, efficacy, safety, and other considerations for use of pharmacologic agents. The literature search included published human studies in the English language from EMBASE and Ovid MEDLINE from 1946 to January 2025. A total of 11 studies representing 736 pediatric patients were included. Use of acetazolamide, hydrochloric acid, ammonium chloride, and arginine hydrochloride have been reported in the literature for pharmacologic management of hypochloremic metabolic alkalosis. Of these agents, acetazolamide and arginine hydrochloride are the only two available for use in the United States. Acetazolamide monotherapy was evaluated in 5 studies, representing 270 patients (36.6%). Arginine chloride monotherapy was evaluated in 2 studies, representing 427 critically ill patients (58.0%). Only 1 study compared the safety and efficacy of acetazolamide and arginine hydrochloride but was limited by variable dosing and undocumented routes of administration and duration of therapy. Adverse effects were reported in 7 patients (0.95%) in the studies included, all of which occurred with acetazolamide. Given that acetazolamide is a US Food and Drug Administration (FDA)-labeled commercially available medication for enteral and intravenous administration, it is the authors' opinion that it should be administered as a first-line pharmacologic agent for pediatric patients refractory to other interventions for hypochloremic metabolic alkalosis.

Objective: Parenteral nutrition (PN) is initiated as early as possible in very-low-birth-weight (VLBW) neonates to prevent protein catabolism. Each institution takes a different approach to ensure that appropriate nutrition is administered as soon as possible after birth. This study aimed to describe the initial nutritional management for VLBW infants in various neonatal intensive care units.

Methods: A 16-question electronic survey was distributed to Pediatric Pharmacy Association (PPA) members through PPA listservs. The primary outcome was to identify the most common macronutrients and micronutrients in starter PN and their concentrations. Secondary outcomes were starting concentrations of electrolytes in the VLBW starter PN, maximum osmolarity, dextrose and calcium concentration permitted in peripheral PN, and use of fat emulsion, including starting dose, start time, and type of fat emulsion.

Results: Of 70 individual institutions included, 64 institutions (91%) stocked standardized starter PN, and 6 institutions (9%) stocked custom-compounded starter PN. The most common contents were amino acids (100%), dextrose (100%), calcium gluconate (73%), and heparin (74%), with mean (range) reported concentrations of 3.5% (1.8%-6%), 8.9% (5%-12.5%), 14 mEq/L (0.2-38 mEq/L), and 0.5 units/mL (0.2-1 units/mL), respectively. Among 66 institutions, the mean initial fat emulsion dose was 1.2 g/kg/day (0.5-3 g/kg/day). Mean maximum osmolarity for peripheral PN was 1016 mOsm/L (900-1250 mOsm/L).

Conclusions: This study found that although there are common contents reported in VLBW starter PNs, there is wide variation in their concentrations. Future research on the nutritional needs of VLBW neonates may provide an opportunity to develop more widely accepted standardized starter PNs.

Objective: The objective was to assess the pharmacoepidemiology of ganciclovir and valganciclovir for treatment of congenital cytomegalovirus (cCMV), adverse events, and hearing screen outcomes in infants treated with antiviral therapy.

Methods: We included infants discharged from Pediatrix Medical Group neonatal intensive care units (NICUs) between 2010 and 2020. We calculated the number of infants with cCMV and the proportion treated per year. We identified infants with cCMV treated with antivirals and used logistic regression models to compare adverse events (neutropenia, thrombocytopenia, and hepatic dysfunction) before and during treatment. Hearing screen outcomes were assessed using a logistic regression model as our primary analysis, with further sensitivity analyses to allow for the possibility of endogenous treatment.

Results: A total of 465 infants from 144 sites met our inclusion criteria, of whom 262 received antiviral treatment. From 2010 to 2020, the annual number of infants with cCMV fell by one-third and the proportion of infants receiving antiviral treatment more than doubled. Neutropenia (absolute neutrophil count ANC <1000 μL) was significantly more common among infants receiving antiviral treatment after adjustment for gestational age and postnatal age (OR 3.2, 95% CI: 1.4-7.3). Neither thrombocytopenia nor hepatic dysfunction was associated with treatment. The primary logistic regression analysis and sensitivity analyses indicated that antiviral exposure was associated with elevated risk of hearing screen failure.

Conclusions: Our data support previous studies identifying neutropenia as an adverse effect of antiviral treatment. In our cohort of infants with cCMV, treatment was associated with increased likelihood of failed hearing screen; this finding could be a result of unmeasured confounding variables or other limitations of retrospective analysis. Further studies should focus on identifying which infants with cCMV will most likely benefit from treatment, the optimal duration of treatment, and long-term outcomes.

Objective: The link between maternal diabetes and congenital heart defects is well-established; however, few studies have investigated subclinical cardiovascular dysfunction at birth, which may serve as an early indicator of future risk.

Methods: We analyzed cardiovascular metrics, including heart rate and blood pressure during the postnatal hospital stay, in 1927 maternal-infant dyads at Nebraska Medicine (2012-2023), including 226 with gestational diabetes mellitus (GDM), 27 with type 1 DM (T1DM), 67 with type 2 DM (T2DM), and 1607 with no DM. Relationships between maternal diabetes subtype and neonatal cardiovascular metrics were examined using treatment effects modeling. Correlations between maternal glycemic burden, as assessed by average HbA1c and 1-hour oral glucose tolerance test (OGTT) during pregnancy, and newborn cardiovascular metrics were also evaluated.

Results: Compared with no DM, T1DM was associated with higher newborn systolic blood pressure (SBP) (+4.6 mm Hg, p = 0.002), pulse pressure (PP) (+3.1 mm Hg, p = 0.006), and SBP variability (+1.2 mm Hg, p = 0.048). T2DM was associated with higher newborn SBP (+2.9 mm Hg, p = 0.03) and PP (+2.0 mm Hg, p = 0.02) and lower SBP variability (-1.3 mm Hg, p = 0.049). There were sigsnificant positive correlations between maternal HbA1c and newborn heart rate (p = 0.009, R ² = 0.27), mean arterial pressure (p = 0.004, R ² = 0.20), SBP (p < 0.001, R ² = 0.22), diastolic BP (p = 0.03, R ² = 0.17), and PP (p = 0.001, R ² = 0.17). No correlations were observed between maternal 1-hour OGTT and newborn cardiovascular metrics.

Conclusions: These findings indicate early subclinical changes in cardiovascular physiology in offspring of women with DM. The differential impacts of diabetes subtypes on newborn BP and strong link to maternal glycemic burden suggest severity and timing of maternal diabetes influence neonatal cardiovascular physiology.