Journal of Pediatric Pharmacology and Therapeutics最新文献

Congenital muscular dystrophy type 1A (MDC1A), an autosomal recessive disorder, is one of the most prevalent forms of congenital muscular dystrophy, characterized by the loss of Laminin-α₂ subunit (Merosin). Approximately one-third of affected patients experience epileptic seizures, typically manifesting around 8 years of age, with focal onset and secondary generalization, often with tonic-clonic semiology. Most reported cases show limited or no response to conventional treatment, though a subset responds to valproate or lamotrigine. The efficacy of levetiracetam in these patients remains insufficiently studied. Metabolic acidosis is not listed as a known adverse effect of levetiracetam in the medication's technical information. In this case, an 11-year-old male with MDC1A presented with nocturnal seizure equivalents and was started on levetiracetam therapy. Approximately 24 hours after receiving the loading dose, the patient's condition deteriorated significantly, and severe metabolic acidosis with an elevated anion gap was observed. The patient required transfer to the pediatric intensive care unit and received intensive intravenous hydration and potassium supplementation. Upon discontinuation of levetiracetam, the patient stabilized, and metabolic normalization was achieved within approximately 24 hours. There are very few reports in the literature that also point to the development of a high anion gap metabolic acidosis after levetiracetam administration. The underlying mechanism is hypothesized but not experimentally verified, and a causal relationship remains unproven. Nevertheless, this observation represents a potentially serious adverse event associated with a commonly used medication, warranting heightened clinical awareness. We therefore recommend actively highlighting this and considering safety monitoring based on the individual risk of the patients being treated.

Objectives: Primary objective: to quantify tocilizumab (TCZ) use in pediatric inpatients. Secondary objectives: to explore safety and clinical outcomes.

Methods: This retrospective cohort study took place in a free-standing, 564-bed children's hospital. Pediatric inpatients who received intravenous TCZ from January 2016 to May 2021 were included. Data collected included demographics, indication, dose, number of administrations, safety events on days 0 to 7 after TCZ, use of extracorporeal support (ES), presence of concurrent infection, and survival to discharge. Exploratory analyses assessed characteristics associated with mortality.

Results: A total of 103 TCZ courses (n = 87 patients) were analyzed. Median age was 14 years. Tocilizumab indications included cytokine release syndrome (CRS; 56%), autoimmune disease (27%), graft-versus-host disease (GVHD; 5%), and COVID-19 (4%). The median TCZ dose was 8 mg/kg (IQR, 7.9-11.9), 18% of courses were administered during active infection, and ES was used in 15% of courses. New-onset alanine transaminase (ALT) or aspartate transaminase (AST) levels >3 times upper limit of normal (ULN) occurred in 53% and 60% of courses, respectively. Of 29 courses with evaluable hematologic data, 10% resulted in new-onset neutropenia and 3% in severe thrombocytopenia. Overall survival to discharge was 83%. In multivariable analyses, independent associations with mortality were found for the use of ES (OR, 8.68; 95% CI, 1.85-4.87), oncologic diagnosis (OR, 7.07; 95% CI, 1.14-89.29), and post-TCZ infection (OR, 11.17; 95% CI, 1.50-138.13).

Conclusions: Tocilizumab is used for many pediatric inpatient indications, most commonly CRS. Newly identified transaminitis was common following TCZ administration. Risk factors for mortality are likely confounded by illness severity. Administration during active infection was not independently associated with increased mortality.

Objective: This study aimed to assess parents' knowledge, attitudes, and practices regarding the use of paracetamol in children.

Methods: A cross-sectional study was conducted in the in Al-Baha region. A self-administered electronic questionnaire was constructed and distributed by the research team using a simple random sampling method. The questionnaire included sections regarding the sociodemographic data, knowledge, practices and attitudes regarding pediatrics' paracetamol use. Parents or children's caregivers were targeted by the study.

Results: 41.9% of 1000 survey respondents reported administering paracetamol to their children. Parents reported administering paracetamol based on experience with similar symptoms in their children (27.2%). One-third of the respondents (33.3%) believes that the maximum amount to be administered in 1 time is a single dose, 58.8% are aware that overdose of paracetamol can harm the child, 60.8% had never administered adults' paracetamol to their children, 26% measure doses using a graded cup or a teaspoon, 61.3% preferred paracetamol syrup, and 56.9% store the drugs in the refrigerator. Re-administration of pediatric paracetamol, as per instructions of the manufacturer, is practiced by 40%. Physicians are the source of drug information in 48.1% of cases. Physician's prescriptions are the source of obtaining paracetamol in 51.1% of cases.

Conclusion: A parental knowledge gap exists regarding the correct use of paracetamol for children in Al-Baha region. Educational programs should focus on the risks of overdose and the importance of following recommended dosages. Educational programs should also recommend limiting OTC dispensing of pediatric medications. Health care professionals should educate parents during clinical visits. Social media can be utilized to disseminate correct drug information. Narrowing of these gaps in parents' knowledge and practices improves safety and efficacy of paracetamol yielding better health outcomes.

Objective: This study aimed to evaluate the success and safety of an institution-specific strategy for converting dexmedetomidine to clonidine in the cardiac intensive care unit at a tertiary care pediatric hospital.

Methods: This retrospective descriptive study included pediatric patients under 18 years of age receiving at least 7 days of dexmedetomidine infusion before conversion to clonidine between January 1, 2018, and October 1, 2023. A successful conversion was defined as dexmedetomidine infusion discontinuation in the absence of therapy reinitiation within 36 hours after the initial enteral clonidine dose; no dose increases greater than 15% within 36 hours of initial clonidine dose, and no requirement for supplemental doses. Patients with dexmedetomidine discontinuation before completing stepwise conversion were evaluated for adverse drug events (ADEs). Descriptive statistics were used to analyze the data.

Results: A total of 148 episodes of conversion from dexmedetomidine to clonidine were evaluated for 134 patients. Patient demographics and treatment characteristics included a median age at conversion of 4.6 months (IQR, 1.5-7.1), a median duration of dexmedetomidine exposure of 19 days (IQR, 12-34), a median initial clonidine dose of 9.3 mcg/kg/day (IQR, 7.2-10), and a median time to discontinuation of 19 hours (IQR, 17-36) after the first dose of clonidine. Successful conversion occurred in 99 (67%) of episodes evaluated, and no ADEs were identified.

Conclusion: The conversion allowed for most patients to tolerate the conversion to clonidine, and no ADEs were identified.

Objective: Lorazepam is a benzodiazepine drug that hospital pharmacies commonly dispense to treat patients with severe anxiety and seizure disorders. Lorazepam oral concentrate, a marketed oral formulation of lorazepam, contains polyethylene glycol and propylene glycol in a solution (2 mg/mL). At Strong Memorial Hospital nurses draw patient-specific doses from a 30mL bulk bottle of lorazepam oral concentrate for administration. This study aims to investigate the stability of lorazepam when stored in repackaged amber-colored ENFit Oral syringes under typical hospital pharmacy conditions (stored at ambient temperature), to reduce waste.

Methods: Stability indicating HPLC assay was established to investigate the degradation profile of lorazepam treated at ambient temperature (∼25°C) and hot conditions (60°C) under acidic (1N HCL), basic (1N NaOH), and oxidative (H₂O₂) stress conditions. This HPLC assay established a robust calibration curve to check the stability of the repackaged lorazepam ENFit Oral Syringes. The repackaged syringes were stored at Strong Memorial Hospital's Inpatient Pharmacy at ambient temperature (72 ± 4°F) for 182 days and samples were taken to investigate the stability of the repackaged formulation.

Results: After 182 days, both volumes (0.25 mL and 0.5 mL) of lorazepam repackaged formulation in the ENFit oral syringes, exhibited no visible changes and remained within the acceptable concentration range (100 ± 10%) when stored at ambient temperature (72 ± 4°F). The stability data demonstrated that lorazepam repackaged in amber-colored ENFit Oral Syringes remained stable at room temperature for up to 90 days.

Conclusion: This study represents a 30-day extension in the stability compared with the previously reported 60-day stability period for the repackaged lorazepam oral syringes.

Cannabidiol (CBD) is a naturally occurring cannabinoid isolated from Cannabis sativa. CBD has therapeutic benefit for the treatment of seizures associated with various epilepsy syndromes in children; however, data are lacking related to the use of CBD for other indications in pediatric patients. Despite this lack of clinical data, the use of CBD products as a complementary treatment for various conditions in children continues to increase. Thus, it is imperative that those involved in the care of children and adolescents are well informed with current information related to CBD use in pediatrics. This review will address the pharmacology of CBD, legal and regulatory factors, usage patterns, current efficacy data, and safety concerns related to the use of CBD in children and adolescents. Recommendations for clinicians, public health officials, and researchers are also provided to effectively manage the use of unapproved CBD products in the pediatric population.

Objective: The objective of this study was to assess first through third year pediatric medical residents' confidence levels surrounding first-line pharmacotherapy for common mental health conditions in the pediatric patient population and identify areas of need in resident education initiatives.

Methods: From April 2024 through June 2024, 68 pediatric medical residents participating in a pediatric residency program at an academic tertiary medical center were invited to complete a self-assessment questionnaire. Residents rated their confidence in developing a treatment plan, prescribing, and counseling on medications for pediatric mental health conditions, general physical health conditions, and pharmacotherapy using a 5-point Likert scale.

Results: A total of 28 pediatric medical residents (41% response rate), ranging from postgraduate year 1 to year 3, completed the survey. Compared with physical health conditions, pediatric mental health conditions were associated with lower confidence scores in medical residents in the areas of developing a treatment plan (mean 3.31 vs 4.28, p < 0.001), prescribing medication (mean 2.77 vs 4.02, p<0.001), and counseling on medication side effects (mean 2.94 vs 4.01, p < 0.001).

Conclusions: This study highlights significant gaps in medical residents' confidence in managing pediatric mental health pharmacotherapy compared with physical health conditions within a single institution's residency program.

Objective: Bumetanide is commonly used to achieve diuresis and alleviate fluid overload in pediatric cardiac intensive care unit (PCICU) patients. This study aims to describe the dosing, efficacy, and safety of bumetanide continuous infusion (CI) regimens used in PCICU patients.

Methods: This single center, retrospective study included patients <6 years of age, admitted to the PCICU who received a bumetanide CI for at least 6 hours. The primary outcome was identifying doses and the total duration of bumetanide CI regimens. Secondary efficacy outcomes were determined by the ability to achieve negative fluid balance within 24 hours and the time to reach negative fluid balance. Secondary safety outcomes were based on the prevalence of electrolyte imbalances and renal impairment.

Results: Data from 90 pediatric patients represented 106 hospital encounters in this study. The median age of our study population was 137 days, with a median weight of 4.3 kg. The dose ranged from 0.005 mg/kg/hr to 0.3 mg/kg/hr, with a median dose of bumetanide of 0.046 mg/kg/hr and a median duration of 5.8 days. The change in serum electrolytes and creatinine during baseline and peak infusion rates was not clinically significant.

Conclusion: This study remains the largest pediatric study to date describing the dosing, efficacy, and safety concerns of bumetanide CI in the PCICU population. However, using a high-dose bumetanide drip >0.1 mg/kg/hr may not improve the overall outcome, and future studies can explore specific advantages of its use in neonates undergoing cardiac surgery.