Journal of Pediatric Pharmacology and Therapeutics最新文献

Objective: Determine whether early administration (EA) of long-acting insulin in pediatric diabetic -ketoacidosis (DKA) reduces time to acidosis resolution while maintaining safety when compared with late administration (LA).

Methods: This retrospective review compared EA (within 4 hours) to LA (4 to 24 hours) of long-acting insulin in DKA management in the pediatric intensive care unit between 2015 and 2022. Admissions were excluded for patients ≥18 years of age, without type 1 diabetes, with insufficient laboratory data, or who did not receive insulin glargine within 24 hours of starting treatment. Primary outcome was resolution of acidosis, measured as time to normalization of serum sodium bicarbonate concentration (>15 mEq/L). Secondary outcomes included hospital and intensive care lengths of stay, and insulin infusion duration. Safety outcomes were hypokalemia, hypoglycemia, and cerebral edema.

Results: Of the 233 admissions evaluated, 51 met inclusion for each group. The median patient age was 11 years, 42% female, and 59% had new-onset diabetes. No difference was found in the median time to acidosis resolution (8.13 hours [EA] and 8.02 hours [LA]; p = 0.4161). Median insulin infusion durations were 16.2 and 17.6 hours for EA and LA, respectively (p = 0.8750). Median hospital stay was 2 days for both groups (p = 0.9068). Hypoglycemia and hypokalemia rates were not significantly different but occurred more often than previously reported.

Conclusions: Early administration of long-acting insulin in pediatric DKA did not affect acidosis duration or treatment length when compared with late administration. Incidence of hypoglycemia and hypokalemia were similar between groups.

Objective: Clonidine has been widely used in the pediatric population to treat neonatal abstinence syndrome (NAS), attention deficit hyperactivity disorder (ADHD), sedation, and Tourette's syndrome; however, there is no consensus on dosing. This research aims to recommend optimal dosing of clonidine in the pediatric population using physiologically based pharmacokinetic (PBPK) modeling.

Methods: The pediatric PBPK model was developed from an adult model by scaling the clearance processes from adults to pediatrics using ontogeny equations. The adult and pediatric models were verified using clinical PK data, and the model performance was evaluated based on visual predictive checks and absolute fold error (AFE). The final pediatric PBPK model was used to simulate clonidine PK in the virtual pediatric population. The optimal dose was recommended based on a target concentration representing clonidine's α-2 central agonist activity (EC₅₀ = 40.5 nM).

Results: The adult and pediatric models predicted well, with more than 90% of observed data captured within the 95% prediction interval of simulated data. The AFE values were within 2-fold for clonidine plasma concentrations from observed and predicted data. The pediatric simulations showed that 30 µg/kg dose orally for neonates and 0.9 mg/day orally for children (6-17 years) are optimal for achieving target concentrations for maximal α-2 adrenergic activity.

Conclusions: The pediatric PBPK model of clonidine scaled from the adult PBPK model provided optimal dosing recommendations for clonidine in different pediatric age groups. The pediatric PBPK model described in this study can be extended to other pediatric age groups and routes of administration.

Objective: The primary objective of this study was to determine pediatric prescribers' knowledge and confidence in identifying bad tasting liquid medications. The secondary objective examined the techniques used to mask the taste of liquid medications and whether any of the masking techniques recommended by prescribers were reported to be effective in children.

Methods: Nationally, health care prescribers were invited to participate in an online survey about medication tastes and masking practices. Participants included physicians, physician assistants, and nurse practitioners who prescribe oral liquid medications. They were asked to complete a 17-question survey consisting of 4 demographic questions, 6 about their practice; 1 on confidence identifying bad tasting medications; 1 on knowledge of Ew Meds^TM; 4 on taste masking; and 1 on potential taste tools.

Results: Seventy-five prescribers completed the survey. Prescribers correctly identified Ew Meds^TM 27.9% of the time (median score 3.35/12) and 34.7% (26/75) of prescribers felt confident with their knowledge of bad tasting medications. Thirty percent (21/71) of prescribers reported educating patients about masking bad tasting medications "most of the time" or "always" and 12.7% (9/71) never educate patients. Almost all prescribers who responded about masking indicated they recommend mixing the medication in food or drink (55/58, 95%). In general, taste masking techniques reported by pediatric prescribers had mixed effectiveness.

Conclusion: Based on prescribers' limited confidence and knowledge regarding medication taste, education about bad tasting liquid medications and appropriate taste masking should be readily available, including the dangers of altering medication efficacy when mixing in food and drink.

Introduction: Pediatric patients often receive vasoactive agents following cardiothoracic surgery or when in shock. The use of vasoactive agents varies between different settings and has largely changed because of anecdotal observations or small observational studies. Although vasoactive agents are frequently used, there are limited studies in pediatric populations comparing them to one another. The purpose of this systematic review is to quantify the comparative effects of epinephrine and dopamine while identifying gaps in knowledge.

Methods: A systematic review of published manuscripts was completed to identify full-text manuscripts in English using PubMed, Embase, and Cochrane databases. Studies were included if they included clinical data using dopamine and epinephrine in different patients and included data for the same end points for patients receiving epinephrine or dopamine.

Results: A total of 5 studies with 397 patients were included. Of the included patients, 187 received epinephrine and 210 received dopamine. The mean age for all the patients was 45 months. When all patient data were pooled, a significantly lower mortality was associated with epinephrine compared with dopamine (risk ratio, 0.74; 95% CI, 0.55-0.99). When only neonatal data were pooled, epinephrine was associated with a significantly higher average heart rate (10 bpm; 95% CI, 2.0-18.7) and a significantly lower average mean arterial blood pressure (-2.5 mm Hg; 95% CI, -4.6 to -0.4).

Conclusion: Limited data are available comparing dopamine to epinephrine in pediatric patients. The -available data demonstrate an apparent mortality benefit associated with the use of epinephrine.

Objectives: The primary aim of this study was to determine continuation rates of stress ulcer prophylaxis (SUP) upon transfer from a pediatric intensive care unit (PICU) to a general medicine unit and upon hospital discharge. The secondary aim was to identify patient characteristics or concomitant medications that were associated with continuation of SUP at transfer from the PICU.

Methods: This retrospective chart review included patients who were initiated on acid suppression for SUP in the PICU between June 2021 and May 2022 and subsequently transferred to a general medicine unit prior to discharge. Patients were excluded if they were receiving acid suppressant therapy prior to admission or were started on acid suppressants for an indication other than SUP.

Results: Two hundred three patients (median age, 3.3 years) were included. The rates of SUP continuation at the time of transfer from the PICU to a general medicine unit and at hospital discharge were 61.6% and 9.9%, respectively. Patients continued on SUP at the time of transfer from the PICU were more likely to be prescribed concomitant corticosteroids (p < 0.01), anticoagulants or antiplatelet medications (p < 0.01).

Conclusions: The continuation of SUP from the PICU to the general medicine unit is common at our institution and calls into question the appropriateness of this practice. Future research is warranted to investigate the appropriateness of the continuation of SUP at transitions of care. Additionally, implementation of institutional protocols standardizing review of SUP may help reduce unnecessary prescribing of acid suppressants in general medicine units and at discharge.

Objective: Seizures are one of the most common neurologic complications seen in a neonate. Historically, phenobarbital has been the agent of choice, but can lead to adverse neurologic outcomes, which has contributed to the use of other agents. Levetiracetam has proven great efficacy with an excellent safety profile in older patients, causing interest of its use in neonates. The objective of this study was to determine if levetiracetam would provide similar neonatal seizure resolution rates as phenobarbital.

Methods: The study was a single-center, retrospective, cohort study from August 1, 2020 to August 31, 2022 investigating the efficacy and safety of using levetiracetam compared with phenobarbital as a first line treatment for neonatal seizures. The primary outcome was to assess overall seizure resolution after administration of levetiracetam or phenobarbital, without addition of a second antiseizure medication.

Results: There were 87 patients included in the study. Fifteen neonates (27.78%) achieved seizure resolution with phenobarbital compared with 9 neonates (27.27%) who received levetiracetam first line (p = 0.959). Neonates who received phenobarbital had higher rates of adverse effects. Neonates who received a benzodiazepine prior to administration of levetiracetam had lower seizure resolution rates (p = 0.021).

Conclusions: These findings suggest there is no difference in using phenobarbital over levetiracetam to achieve complete seizure resolution in a neonate. Higher rates of adverse events were seen in the phenobarbital group. The use of a benzodiazepine prior to administration of levetiracetam may reduce the efficacy of levetiracetam.