With the use of risk-adapted chemotherapy based treatments, outcomes for children and adolescents with hematological malignancies have significantly improved in industrialized countries. For example, in acute lymphoblastic leukemia (ALL), the most common pediatric cancer, with a peak incidence in preschool-children, long-term survival steadily improved in US Children’s Oncology Group (COG) clinical trials; 499 patients treated from 1970–1972 had a survival rate at 10 years of ∼20% versus >90% in 11,806 patients treated from 2010–2015.1 Similar or better results have been achieved in major single-institution clinical trials including the Total Therapy protocols at St. Jude Children’s Research Hospital (SJCRH).
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EDUCATION
PharmD,
PharmD,
PharmD,
PharmD,
PharmD,
PharmD, and
PharmD
Postural orthostatic tachycardia syndrome (POTS) is a chronic illness with unknown mortality and high morbidity, often diagnosed in the adolescent years. Published literature regarding POTS primarily focuses on the adult population, and guidance on treatment in pediatrics is sparse. The purpose of this clinical review is to evaluate the current literature on the management of POTS in pediatric patients. A search was conducted using the Cochrane database, Google Scholar, and PubMed. Studies were included if they evaluated the management of POTS, primarily in pediatric patients. Case reports and series were excluded. Eight published studies met the inclusion and exclusion criteria. To date, there are no US Food and Drug Administration-approved agents for the treatment of POTS. However, select pharmacological therapies have shown positive outcomes by addressing symptom origins, such as providing heart rate control, peripheral autonomic modulation, and targeting hypovolemia. Targeted pharmacological therapies studied in children and young adults include ivabradine, metoprolol, midodrine, pyridostigmine, intravenous crystalloid fluids, and fludrocortisone. Before adding pharmacotherapeutic interventions, non-pharmacologic interventions such as patient education, avoidance of symptom-triggering environments and medications, dietary fluid and sodium supplementation, exercise, and use of compression garments should be first attempted. Although the body of evidence for the management of POTS is expanding, additional research is needed to determine safe and efficacious dosing and establish clear guidelines for POTS in the pediatric population.
PA-S,
PA-S,
MS, MSPAS, PA-C,
PharmD, MEHP, and
MS, PhD
Chylous effusion and chylous ascites are rare but serious conditions that affect both fetuses and neonates. Previous studies have documented chylous effusions or chylous ascites treatment with medications as an adjunct to respiratory support and dietary modifications, but no formal recommendations have been made. New literature suggests propranolol as an effective and safe treatment option, though no randomized clinical studies have been published to date. This review aims to assess the efficacy and safety of propranolol in the treatment of chylous effusion and chylous ascites in fetuses and newborns from case reports. A comprehensive search of 10 databases and grey literature was completed. The inclusion criteria for articles were age at diagnosis less than 40 days old and case report/series. Articles were excluded if they were animal studies or not published in English. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 4 articles were ultimately included in the study for a total of 10 reported cases. Propranolol administered to mother and neonates was effective in 100% of cases. The most common oral dose for mothers was 20 mg, 4 times daily, titrated to 40 mg, 4 times daily. The maximum dosage varied for administration orally to neonates, with the median being 3 mg/kg/day. Side effects, including bradycardia and transient hypoglycemia, were seen in 20% of the cases and resolved with dose adjustment. Propranolol is a relatively effective and safe treatment option for chylous effusion and chylous ascites that can be administered prenatally or to neonates.OBJECTIVE
METHODS
RESULTS
CONCLUSION
RESEARCH
PharmD,
MD, MSCE,
MD,
DO, MPH,
PharmD, and
MD, MS
Anthracycline chemotherapy agents have significant dose-dependent cardiotoxic effects. Carnitine, a non-essential amino acid, is involved in long chain fatty acid oxidation, and carnitine deficiency can result in cardiomyopathy and cardiac arrhythmias. If administered concurrently with chemotherapy, carnitine supplementation could be a potential strategy to prevent cardiotoxicity. However, the association between serum carnitine concentrations and anthracycline cardiotoxicity during cancer treatment in the childhood, adolescent, and young adult (CAYA) age range has not been established. This prospective pilot cohort study characterized changes in serum carnitine concentrations and cardiac function before, during, and approximately 1 year after large-dose anthracycline therapy in newly diagnosed CAYA cancer patients. Among 21 patients with a mean cumulative anthracycline dose exposure of 409 mg/m2 of doxorubicin equivalents, left ventricular ejection fraction and relative wall thickness decreased, indicating an overall decline in cardiac function. A reversible decrease in serum carnitine concentrations was also observed. A non-statistically significant positive correlation was observed; for every 1 mmol/L decrease in serum carnitine concentration, there was a 0.09% decrease in LVEF (p = 0.2). These findings from this small pilot study suggest that there may be a relationship between serum carnitine concentrations and cardiac function after anthracycline therapy that should be evaluated in larger studies.OBJECTIVE
METHODS
RESULTS
CONCLUSIONS
PharmD,
PharmD, and
PharmD
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. 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. 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). 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.OBJECTIVE
METHODS
RESULTS
CONCLUSIONS
PharmD,
PharmD,
PharmD,
PharmD,
MPH,
MD,
MD, and
PharmD
A protocol was developed for neonatal intensive care unit (NICU) delirium: Step 1, gabapentin for pain or melatonin for sleep; Step 2, add on other Step 1 agent; Step 3, antipsychotics. The purpose of this study was to describe the utility and dosing of gabapentin for NICU delirium. Retrospective evaluation of NICU patients from January 1, 2021–December 31, 2022 who received >1 dose of gabapentin based on the delirium protocol. Data collection included demographics, gabapentin regimen, and concomitant sedatives and analgesics. The primary objective was to identify the number of patients receiving gabapentin for Step 1 or Step 2. Secondary objectives included identifying the number of patients requiring antipsychotics (Step 3), the gabapentin regimen, comparison of Échelle de Douleur et d'Inconfort du Nouveau-né (EDIN), Cornell Assessment of Pediatric Delirium (CAPD), and Withdrawal Assessment Tool-1 (WAT-1) scores 72 hours pre- and post-gabapentin initiation, and comparison of opioids, clonidine, and melatonin 24 hours pre- and 72 hours post-gabapentin initiation. Wilcoxon signed rank tests were employed with significance defined at p < 0.05. Twenty-nine patients were studied. The majority (n = 22; 75.9%) received gabapentin for Step 1; no patients required Step 3. The median initial dose was 14.4 mg/kg/day divided every 8 hours. Twelve (41.4%) required increase to a median of 16.9 mg/kg/day. A significant decrease in EDIN and WAT-1 scores was noted, but there was no change in CAPD scores or opioid, clonidine, or melatonin doses pre- versus post-gabapentin. The majority received gabapentin at a median dose of 14 mg/kg/day as Step 1 for delirium. Gabapentin was associated with a significant decrease in pain and withdrawal scores.OBJECTIVE
METHODS
RESULTS
CONCLUSION
MD, MPH,
PharmD,
PhD,
MD, and
PharmD
This study sought to demonstrate a non-inferiority analgesic ceiling effect previously demonstrated within adults for pediatric patients receiving a maximum ketorolac dose of 15 mg. We conducted a retrospective cohort study of pediatric ED patients weighing at least 60 kg treated with 30 mg (pre-intervention) or 15 mg (post-intervention) intravenous (IV) ketorolac for headache. The primary outcome included patient-reported pain scores. Additional outcomes included demographic variables, adjunct medication use and adverse effects. Categorical data were evaluated using a χ2 test, and numerical data were evaluated using an ANOVA F test and Welch 2-sample t test. The pre- and post-intervention groups included 216 and 62 patients, respectively. Overall demographics were similar between the groups (72.3% female, 49.3% White/Caucasian, mean age 15.5 years, mean weight 79.2 kg, and mean baseline 10-point pain score 7.5). Twelve (5.6%) in the pre-intervention group required rescue analgesic compared with 2 patients (3.2%) in the post-intervention group (p = 0.416). In the pre-intervention group, 198 patients (91.7%) received nausea medication compared with 52 patients (83.9%) in the post-intervention group (p = 0.087). Mean 10-point pain scores following ketorolac administration decreased by 3.9 in the pre-intervention group compared with 5.1 in the post-intervention group (p = < 0.001). Common (0.9%) or rare (0.9%) side effects were infrequent and only seen in the pre-intervention group patients. Truncating the maximum intravenous ketorolac dose in pediatric patients at least 60 kg in weight to 15 mg compared with 30 mg results in effective analgesia in pediatric patients with headache. Future research could explore differences in admission rates, treatment of other indications, or treatment with multiple-dose regimens.OBJECTIVE
METHODS
RESULTS
CONCLUSIONS
MD,
PharmD,
MS,
PhD, and
MD
A risk stratified sedation weaning protocol improved patient outcomes in a pediatric intensive care unit (PICU). We sought to determine the protocol effect on medication costs. This was a retrospective observational cohort study in an academic tertiary care children’s hospital PICU (2018–2020) comparing the cost when weaning benzodiazepine, alpha agonist, and/or opioid infusions in intubated children <18 years of age. There were 84 total sedation weaning instances (pre-protocol n = 41 and post-protocol n = 41); 2 patients had 2 encounters, 1 in each phase. The total cost (in 2022 United States Dollars) of sedation weaning was $400,328.87 ($15,994.44/kg) pre-protocol compared with $170,458.85 ($11,227.52/kg) post-protocol. The median cost of sedation wean per patient for pre-protocol patients was $3197.42 (IQR: $322.66–$12,643.29) and post-protocol patients was $1851.44 (IQR: $425.05–$5355.85; p = 0.275). A linear regression model estimated the expected cost of sedation wean for post-protocol patients to be $5173.20 lower than for pre-protocol patients of the same weight and overall drug risk (p = 0.036). The proportion of withdrawal symptoms in the pre-protocol patients (16%) was not significantly different from the proportion in the post-protocol patients (14%; p = 0.435). Implementation of a PICU sedation weaning protocol in a single-center conferred cost benefit without negatively impacting patient outcomes. A larger multicenter study would provide insight to the applicability to PICUs in varied settings with differing patient populations.OBJECTIVE
METHODS
RESULTS
CONCLUSIONS
PharmD,
MD,
PharmD,
MD,
MD, and
PharmD
Previous studies have shown an association between alteplase for line clearance and central line–associated bloodstream infections (CLABSIs). The objective of this study was to evaluate the use of post-alteplase antibiotics as a CLABSI reduction strategy in pediatric intensive care unit (PICU) patients. This was a single center, retrospective, observational study evaluating PICU patients from January 1, 2014, through August 1, 2021, conducted at a tertiary academic PICU. Included in this study were critically ill patients who had 1 or more central venous lines (CVLs) requiring alteplase for line clearance. The primary objective was incidence of CLABSI occurrence post alteplase administration for CVL clearance, with or without targeted single-dose antibiotics (piperacillin-tazobactam or vancomycin) post alteplase. Secondary outcomes included evaluation of total alteplase administrations and risk factors associated with CLABSI occurrence. Two hundred fifty patients were included, with 156 receiving alteplase only, 82 piperacillin-tazobactam, and 12 vancomycin, and with median ages of 2.8, 3.8, and 3.8 years, respectively. Seven CLABSIs occurred in the alteplase-only group, with 0 incidences in both the piperacillin-tazobactam (exact OR, 0.12; exact 95% CI, <0.01–0.59; p < 0.01) and vancomycin (exact OR, 1.20; exact 95% CI, 0.03–9.80; p = 1.00) groups. Patients in the piperacillin-tazobactam group achieved statistical significance for CLABSI risk factors that may benefit by decreasing CLABSI incidence (p values <0.01–0.02). Alteplase use has been associated with CLABSIs. Providing a single dose of post-alteplase antibiotics targeting the most likely site-specific pathogens may reduce the incidence of CLABSIs.OBJECTIVE
METHODS
RESULTS
CONCLUSIONS
PharmD,
BScPharm, PharmD,
PharmD,
PhD, and
BScPharm, MD
To evaluate age, adjunctive antiseizure medication (ASM), and specific ASMs on lacosamide (LCM) weight normalized dose-to-concentration ratio (DCR) and US Food and Drug Administration (FDA) dosing guidelines in pediatric patients. Patients 1 mo to ≤18 years with a LCM serum concentration between October 2009 and June 2017 were considered. Demographics, LCM DCR, and adjunctive ASM were recorded. LCM DCR/hr was used as a surrogate for clearance. Data were stratified by age (1 mo-< 2 yr; ≥ 2–6 yr; ≥ 6–12 yr; and ≥12–≤18 yr), FDA dosing weights, and ASM potential to interaction with LCM. There were 646 sera (380 patients) with median dose 8.36 mg/kg/day (IQR, 5.92–11.16). 50.2% of doses were within FDA-weight guidelines; however, 40.4% exceeded recommendations. Most (81.3%) LCM concentrations were between 2 and 12 mg/L. A difference existed in DCR between ages, with those <2 years having the highest DCR (p < 0.001). Moving across age groups, the DCR decreases by 30.7%, 50.5%, and 63.4%. There was a weak (r2 = 0.073) but significant (p < 0.001) negative correlation between DCR and age. 84.8% received adjunctive ASM consisting of at least one of 31 different ASMs. DCR was higher with adjunctive ASMs compared with monotherapy [0.061 (0.039–0.095) vs 0.043 (0.030–0.062)], respectively (p < 0.001) and was greatest with inducers. Phenobarbital increased DCR by 2.6-fold, topiramate by 72.1%, and clobazam by 32.6%. Inhibitors had no effect. The correlation between age and DCR was weak, accounting for 6% of variability. Strong inducers significantly increased DCR. Synergy may exist when multiple inducers are given. Weak inhibitors did not affect DCR. Those ≥6 to 11 kg, ≥30 to 50 kg, and those given strong inducers may require larger initial LCM doses. Serum concentrations should be used to individualize dosing, especially in those receiving strong inducers.OBJECTIVE
METHODS
RESULTS
CONCLUSIONS
BRIEF PRACTICE REPORT
DO,
MD, PhD,
MD,
PharmD,
PharmD, and
MB, BCh, BAO
Inhaled nitric oxide (iNO) is a mainstay of treatment for infants with persistent pulmonary hypertension. However, abrupt discontinuation of inhaled nitric oxide can result in rebound pulmonary hypertension. The objective of this analysis is to describe the use of sildenafil to facilitate the weaning from iNO in preterm neonates. This retrospective chart review identified all infants who were receiving iNO and subsequently received sildenafil between 2017 and 2021. Neonates were included if they met the following criteria: gestational age at birth less than 34 weeks, receiving iNO, and started on sildenafil with the indication to facilitate weaning or discontinuation of iNO. Patients were excluded if they had major congenital anomalies, including congenital heart disease or congenital diaphragmatic hernia. We identified 7 neonates with a gestational age range of 22 5/7 weeks to 31 0/7 weeks and birth weight range of 545 to 910 g with previously failed attempts at iNO weaning. The most common starting dose for sildenafil was 0.125 mg/kg intravenously every 8 hours or 0.25 mg/kg enterally every 8 hours. Four infants were able to discontinue iNO within 48 hours of sildenafil initiation, 1 patient discontinued iNO within 5 days, and 1 patient within 10 days of sildenafil initiation. One patient experienced weaning failure from iNO despite initiation of sildenafil. No adverse events, such as hypotension or deaths, were reported in any of the 7 infants. Sildenafil facilitated weaning off iNO in most preterm neonates evaluated without adverse side effects.OBJECTIVE
METHODS
RESULTS
CONCLUSIONS
PharmD,
PharmD,
PharmD, and
PharmD
The purpose of this study was to evaluate the feasibility of a pharmacist-driven discharge medication reconciliation (DMR) service at our children’s hospital by completing a 2-week pilot on a general pediatrics unit. This was a prospective study and included patients discharged during pilot hours whose DMR was completed by the pharmacist. The primary outcome was evaluation of time required for a pharmacist to complete the DMR. Secondary outcomes included classification of pharmacist interventions made and their associated cost-avoidance, medication-related problems reported within 14 days of discharge, hospital readmission due to medication problems within 30 days of discharge, and medical resident satisfaction assessed via prepilot and postpilot surveys. A total of 67 patients had their DMR completed by a pharmacist during the pilot. The pharmacist spent an average of 30 minutes completing each DMR, although this was variable, as evidenced by an SD of 36.4 minutes. Pharmacists documented 89 total interventions during the study period. The most common intervention types were therapeutic optimization (32.6%) and modification of directions (29.2%). Total estimated cost-avoidance during the study pilot was $84,048.01. For the pilot population, 1 medication-related problem was identified within 14 days of discharge. There were no medication-related readmissions identified. Medical residents reported increased confidence that the DMR was completed accurately and satisfaction with the DMR process during the pilot compared with before the pilot. Implementing a pharmacist discharge medication service requires consideration of pharmacist time and salary, which may be offset by cost-avoidance.OBJECTIVE
METHODS
RESULTS
CONCLUSIONS
CLINICAL VIGNETTE
MD,
MD,
MD,
MD, and
MD
Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was given US Food and Drug Administration approval based on its therapeutic benefits to treat patients with cystic fibrosis (CF) who had at least 1 allele of the CF transmembrane conductance regulator (CFTR) with phenylalanine deleted at position 508 (F508del). The increase in genotyping studies has increased the frequency of use of CFTR modulators; however, severe allergic reactions to CFTR modulators have also been described. It is critical to avoid the offending medication and select alternative treatments while dealing with drug allergies. Drug desensitization may be taken into consideration in situations where there is no other option. This article describes home desensitization treatment for a patient with CF who developed a maculopapular rash following CFTR modulator medication. There are currently no alternative drugs for CFTR modulators, which are crucial for patients with CF, and limited experience is available with allergic reactions to these drugs. It is important to establish desensitization protocols in order to control drug reactions to CFTR modulators, which are vital for individuals with CF.
MD,
MD, MS, and
PharmD
Lead poisoning in children has the potential for devastating neurodevelopmental consequences. There is significant socioeconomic disparity in children with lead poisoning. Specific lead chelation regimens have been approved for children by the US Food and Drug Administration, however in the United States, there has been a recent national shortage of the primary therapy, edetate calcium disodium (CaNa2 EDTA). This case report presents a 23-month-old child with severe symptomatic lead poisoning during a national shortage of CaNa2 EDTA to highlight the need for advocacy regarding critical medication shortages, especially for antidote therapy. The infant’s initial blood lead level was 364 mcg/dL and he received a continuous infusion of CaNa2 EDTA (1000 mg/m2/day), as well as dimercaprol (4 mg/kg intramuscularly every 4 hours). The supply of CaNa2 EDTA was exhausted on day 3 of therapy so he was transitioned to enteral succimer monotherapy. Initial parenteral therapy of 72 hours achieved a lead level of 72 mcg/dL; he then completed his enteral course of succimer along with environmental mitigation. However, elevated blood lead levels persisted and he subsequently required 3 more courses of enteral succimer, and he continues to have detectable blood lead levels 2 years after initial presentation. In the face of medication shortages including CaNa2 EDTA, and now also dimercaprol, clinicians must create and study alternative chelation therapy regimens for pediatric lead toxicity. Furthermore, public policy initiatives, including the development of a national supply stockpile of chelation agents, must be created in order to minimize supply chain disruption and ensure adequate and equitable antidote therapy for lead poisoning outbreaks.
OPINION
PharmD,
PharmD, and
PharmD on behalf of the Advocacy Committee of the Pediatric Pharmacy Association
Approximately 14.7 million US children aged 2 to 19 years are obese. This creates significant challenges to dosing medications that are primarily weight based (mg/kg) and in predicting pharmacokinetics parameters in pediatric patients. Obese individuals generally have a larger volume of distribution (Vd) for lipophilic medications. Conversely, the Vd of hydrophilic medications may be increased or decreased owing to increased lean body mass, blood volume, and decreased percentage of total body water. They may also experience decreased hepatic clearance secondary to fatty infiltrates of the liver. Hence, obesity may affect loading dose, dosage interval, plasma half-life, and time to reach steady-state concentration for various medications. Weight-based dosing is also a cause for potential medication errors. This position statement of the Pediatric Pharmacy Association recommends that weight-based dosing should be used in patients ages <18 years who weigh <40 kg; weight-based dosing should be used in patients ≥40 kg, unless the recommended adult dose for the specific indication is exceeded; clinicians should use pharmacokinetic analysis for adjusting medications in children diagnosed with overweight and obesity; and research efforts continue to evaluate dosing of medications in children diagnosed with overweight and obesity.
PharmD
ChatGPT (chat generative pre-trained transformer) is a chatbot, which is a program designed to simulate written or spoken human conversation.1 The simulation of written human conversation by ChatGPT is done using a pre-trained deep-learning artificial neural network.2 When you ask ChatGPT a question, it tokenizes your query into individual words or parts of words, assigning a unique numerical value to each token. These numerical representations are fed into the model, which processes the input to generate a response. The quality of ChatGPT’s simulated conversation relies on the complexity of the artificial neural network, determined by factors
Meropenem/Vaborbactam in Pediatrics: 2 Cases of CRE Intraabdominal Infection
Ugene SanoPharmD,
Rachel MeyersPharmD,
Uzma HasanMD, and
Steven SmokePharmD
Systematic Review of Adverse Events of IL-1 and IL-6 Inhibitor Use in Pediatrics
Amandi PereraBMSc,
Nikita ChughBMSc, and
Facundo Garcia-BournissenMD, PhD
Diphenhydramine: A Review of Its Clinical Applications and Potential Adverse Effect Profile
Wajahat Nazir KhanMBBS and
Joseph D. TobiasMD
Opportunities for Pharmacogenomics in Pediatrics: Prescribing Trends of Psychiatric Medications With Pharmacogenomic Implications at a Multistate Pediatric Health System
Megan L. MillerPharmD,
Nathan D. SeligsonPharmD,
Benjamin Q. DuongPharmD,
Josephine EliaMD,
Shirin HasanMD,
Thomas LacyMD,
Kathryn V. BlakePharmD, and
Kelsey J. CookPharmD
eISSN: 2331-348X ISSN: 1551-6776
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