Evaluation of the Closure of Patent Ductus Arteriosus With Ibuprofen Compared to Indomethacin.

OBJECTIVE: Limited data exist comparing indomethacin and ibuprofen for the treatment of patent ductus arteriosus (PDA). The objective was to compare the safety and efficacy of indomethacin and ibuprofen for treatment of PDA closure. METHODS: This single-center, pre-test/post-test quasi-experiment included preterm infants admitted to the neonatal intensive care unit who received indomethacin (July 1, 2013-September 30, 2015) or ibuprofen (December 1, 2015-July 31, 2019) for PDA. Patients were excluded if they were thrombocytopenic, had existing kidney injury, unresolved intraventricular hemorrhage (IVH) or necrotizing enterocolitis (NEC) at treatment initiation. Data were obtained from the electronic health record. Study outcomes were complete PDA closure, degree of PDA closure, resolution of symptoms, and new-onset acute kidney injury (AKI), IVH, or NEC. RESULTS: A total of 114 patients were included: 44 (39%) received indomethacin and 70 (61%) received -ibuprofen. Twenty-one (21%) patients experienced successful PDA closure within 1 week: 13 (32%) indomethacin patients and 8 (13%) ibuprofen patients (p = 0.023). PDA size reduction occurred in 43 (46%) patients with 29 (25%) experiencing complete symptom resolution. Significantly more indomethacin patients compared with ibuprofen patients experienced new-onset AKI (48% vs 17%; p < 0.001) and received concomitant nephrotoxins (68% vs 39%; p = 0.002). There were no significant differences in new-onset IVH or NEC. CONCLUSIONS: Indomethacin administration successfully closed the PDA in more neonates than ibuprofen but resulted in higher rates of AKI. However, this was confounded by more frequent administration of concomitant nephrotoxins. Larger trials are needed to help elucidate the optimal drug for closure of the PDA in neonates.

Change in Student Pharmacists' Perceptions and Confidence of Pediatric Related Topics After Participation in Pediatric Pharmacy-Focused Skills Laboratory.

OBJECTIVE: The objective of this study was to assess the impact of a pediatric pharmacy-focused skills laboratory on student pharmacist confidence and comfort with pediatric topics. METHODS: This study compared student responses on a questionnaire completed both pre- and post-lab. The lab activities included pre-readings, a pre-lab lecture, and a 2-hour laboratory session. The questionnaire assessed perceptions related to counseling pediatric patients and confidence in communicating with children and caregivers. Wilcoxon rank sum tests compared the differences in the preand post-lab questionnaire results. The McNemar test was used to test for conversion. RESULTS: A total of 187 of 221 pharmacy students completed the pre-lab questionnaire (85% response rate) and 116 completed the post-lab questionnaire (52% response rate). Significantly higher confidence levels were reported in the post-lab questionnaire for 5 of the 7 questionnaire items. Specifically, concerning level of confidence in measuring oral solutions, 17.5% of students' pre-lab, compared with 42.6% post-lab felt completely confident in being able to determine the appropriate measuring devices for liquid medications. No statistically significant differences were noted regarding comfort level or knowledge. CONCLUSIONS: Although an increase in confidence was seen in several areas, some students still lacked confidence after the lab session, suggesting that more pediatric-focused activities may be needed in the curriculum to reinforce pediatric concepts.

Epidemiology and Risk Factors for Bacteremia in Pediatric and Adolescent Patients.

BACKGROUND: Epidemiology and risk factors for bacteremia in pediatric and adolescent patients have not been fully elucidated. OBJECTIVE: The purpose of this study was to identify primary causative agents of bacteremia in pediatric and adolescent patients and associated risk factors. We hypothesized that these would be different than those seen in adults. PATIENTS AND METHODS: This retrospective cohort, epidemiologic evaluation included patients admitted to a tertiary referral center from January 01, 2013, to December 31, 2015. Patients <18 years old with a confirmed positive blood culture were included; the first positive culture per organism per patient was analyzed. The primary outcome was to determine the most frequent causative organisms of bacteremia; the secondary outcome was an evaluation of risk factors for acquiring staphylococcal bacteremia. RESULTS: A total of 913 isolates were evaluated, including 92 unique organisms. The most frequently identified were Staphylococcus epidermidis (238/913, 26.1%), followed by Staphylococcus aureus (136/913, 14.9%). Methicillin resistance was observed in 60.3% of S aureus. Two hundred thirty-six patients were included in the risk factor analysis. Prematurity, previous antibiotics, and intubation/ventilation were more likely associated with S epidermidis (P < .001, P < .001, and P = .032, respectively). Patients with a recent or previous hospitalization and those with dermatitis/eczema were statistically more likely to grow S aureus (P < .001, P = .029, respectively). CONCLUSIONS: Although epidemiology of organisms associated with pediatric and adolescent bacteremia was similar to adults, risk factors were different than seen in that population. Further understanding of these risk factors may be helpful in developing preemptive infection control strategies in patients at risk.

Antipsychotic Use in the Prevention and Treatment of Intensive Care Unit Delirium in Pediatric Patients.

OBJECTIVES: To describe the antipsychotics, route of administration, dosage regimen, and outcomes reported to prevent or treat delirium in hospitalized children. METHODS: Medline, Embase, and International Pharmaceutical Abstracts were searched using the keywords "haloperidol," "olanzapine," "quetiapine," "risperidone," "ziprasidone," and "delirium." Articles evaluating the use of these agents to manage delirium in hospitalized children that were published between 1946 and August 2019 were included. Two authors independently screened each article for inclusion. Reports were excluded if they were published abstracts or included fewer than 3 patients in the report. RESULTS: Thirteen reports that included 370 children receiving haloperidol, quetiapine, olanzapine, and/or risperidone for delirium treatment were reviewed. Most children received haloperidol (n = 131) or olanzapine (n = 125). Significant variability in dosing was noted. A total of 23 patients (6.2%) had an adverse drug event, including 13 (56.5%) who experienced dystonia and 3 (13.0%) with a prolonged corrected QT interval. Most reports described improvement in delirium symptoms; however, only 5 reports used a validated screening tool for PICU delirium to evaluate antipsychotic response. CONCLUSIONS: Most reports noted efficacy with antipsychotics, but these reports were limited by sample size and lacked a validated PICU delirium tool. Future research is needed to determine the optimal agent and dosage regimen to treat PICU delirium.

Pilot Study Comparing Modified Finnegan Scoring Versus Adjusted Scoring System for Infants With Iatrogenic Opioid Abstinence Syndrome After Cardiothoracic Surgery.

OBJECTIVES: To compare the modified Finnegan Scoring System (modified Finnegan) with an Adjusted Scoring System Criteria (adjusted Finnegan) for infants after cardiothoracic surgery with iatrogenic opioid abstinence syndrome (IOAS). METHODS: This was a retrospective, observational pilot study. This study was conducted in a tertiary care academic hospital. Infants after cardiothoracic surgery with IOAS transferred between the pediatric intensive care unit and neonatal intensive care unit between January 1, 2014, and January 31, 2016, were included retrospectively. The main outcome variable was to compare the area under the curve for the mean modified Finnegan versus adjusted Finnegan. RESULTS: Twenty-five patients were included in the study. Twenty patients with at least 30 scores were included in the final analysis. Overall, the modified Finnegan scores were at least 2 points higher than the adjusted Finnegan. The difference in area under the curve was 34.6 (p < 0.001). CONCLUSIONS: Use of the modified Finnegan tool for older infants with IOAS could overestimate withdrawal, leading to unnecessary interventions.

Sedation and Analgesia Using Medications Delivered via the Extravascular Route in Children Undergoing Laceration Repair.

OBJECTIVES: To describe the method of delivery, dosage regimens, and outcomes of sedatives and analgesics administered via the extravascular route for laceration repair in children. METHODS: Medline, Embase, and International Pharmaceutical Abstracts were searched using the keywords "child," "midazolam," "ketamine," dexmedetomidine," "fentanyl," "nitrous oxide" (N2O), and "laceration repair." Articles evaluating the use of extravascular sedation in children for laceration repair published in the English language between 1946 and June 2017 were included. Two authors independently screened each article for inclusion. Reports were excluded if they did not contain sufficient details on dosage regimen and outcomes. RESULTS: A total of 16 reports representing 953 children receiving sedatives and analgesics via the extravascular route were included for analyses. A statistical analysis was not performed because of heterogeneity in dosing and types of analyses conducted. Midazolam and N2O were the most common agents, with oral (PO) midazolam being the most common agent. Other agents that have supporting data were intranasal (IN) dexmedetomidine, IN ketamine, IN midazolam, PO diazepam, PO ketamine, transmucosal (TM) midazolam, and TM fentanyl. CONCLUSIONS: Most of the agents administered through the extravascular route were efficacious. Selection of the agents should be based on perceived need for analgesia versus sedation, patient accessibility, and adverse drug events. Future research is needed to determine the optimal agent and route for laceration repair.

Medication Dosage in Overweight and Obese Children.

Approximately 31.8% of U.S. children ages 2 to 19 years are considered overweight or 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 for lipophilic medications. Conversely, the Vd of hydrophilic medications may be increased or decreased due to increased lean body mass, blood volume, and decrease 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 Advocacy Group recommends that weight-based dosing should be used in patients ages < 18 years who are < 40 kg; weight-based dosing should be used in patients ≥ 40 kg, unless, unless the recommended adult dose for the specific indication is exceeded; clinicians should use pharmacokinetic analysis for adjusting medications in overweight/obese children; and research efforts continue to evaluate dosing of medications in obese/overweight children.

Clonidine for Sedation and Analgesia and Withdrawal in Critically Ill Infants and Children.

The need for sedation and analgesia and treatment of iatrogenic drug withdrawal is common in critically ill children. First-line therapy typically includes opioid agonists. However, clonidine, a central α2 agonist, has been suggested as a treatment option for sedation and analgesia and iatrogenic drug withdrawal. Therefore, we conducted a literature search to identify articles evaluating the use of enteral (PO) and transdermal clonidine in critically ill infants and children for sedation and analgesia and treatment of iatrogenic drug withdrawal. The literature search was limited to English-language articles in Medline (1946-May 2016), Embase (1988-May 2016), and International Pharmaceutical Abstracts (1970-May 2016). Reference citations from relevant articles were also reviewed. Ten case reports and studies, representing a total of 114 children receiving clonidine, were included. Fifty patients (43.9%) received clonidine for sedation and analgesia while mechanically ventilated, and 33 (29.0%) received clonidine for treatment or prevention of drug withdrawal. The remaining 31 patients (27.1%) were included in a pharmacokinetic study that did not evaluate clinical outcomes. Seventy-nine patients (69.3%) received PO clonidine, with a dosage range of 2-15 µg/kg/day divided every 6-8 hours. Thirty-five patients (30.7%) received transdermal clonidine, with a dosage range of 2.3-20 µg/kg/day. Whole, cut, and occluded transdermal patches were used in the reports. Patients receiving cut patches had more variable and significantly higher serum clonidine concentrations than those receiving whole patches. Only three studies reported that the PO clonidine dose was tapered at the end of therapy; however, no report specifically described the process. The two most common adverse events reported with PO and transdermal clonidine were bradycardia and hypotension. PO and transdermal clonidine have a potential role for sedation and analgesia and drug withdrawal in critically ill infants and children. The use of cut transdermal patches should be avoided. Future prospective studies are needed to further define clonidine's role as adjunct therapy or monotherapy.

Metabolic Acidosis with Ophthalmic Dorzolamide in a Neonate.

Carbonic anhydrase inhibitors are a common cause of normal anion gap metabolic acidosis; however, development is less commonly associated with ophthalmic administration of these agents. We report a case of a premature neonate who was being treated at our institution with betaxolol, dorzolamide, and latanoprost ophthalmic products for suspected bilateral congenital glaucoma. In addition, the patient was also receiving caffeine, ursodiol, and acidified liquid human milk fortifier. The patient developed a normal anion gap metabolic acidosis, and both dorzolamide ophthalmic solution and the acidified human milk fortifier were considered potential causes. Upon discontinuation of the dorzolamide ophthalmic solution and the switching of liquid human milk fortifiers, the normal anion gap metabolic acidosis gradually resolved. As a result of the pH and acidity, the acidified liquid human milk fortifier is thought to be associated with an anion gap acidosis; therefore, dorzolamide is suspected to be the primary cause of a normal gap acidosis. This case demonstrates that systemic effects can occur with ophthalmic administration of dorzolamide in a premature neonate. Ophthalmic agents should not be overlooked as a potential cause of systemic toxicity.

Caregiver Perception, Self-efficacy, and Knowledge of Methadone Tapers for Children With Iatrogenic Opioid Abstinence Syndrome.

Background: There are no definitive guidelines regarding the management of iatrogenic opioid abstinence syndrome (IOAS), but methadone tapers are one common approach. Methadone tapers can be complex for caregivers to manage, and there is a paucity of data about caregiver experiences administering medication tapers postdischarge. Objective: The primary objective was to describe caregiver perception, self-efficacy, and knowledge of administering methadone tapers. Secondary objectives included an assessment of the change in self-efficacy and knowledge of methadone and IOAS before and after discharge as well as clinical outcomes occurring postdischarge. Methods: This was an exploratory, descriptive, institutional review board-approved study surveying caregivers of children receiving methadone tapers for IOAS. Caregivers were included if they had a child ≤12 years of age discharged to home on a methadone taper. The study consisted of 2 phases: a questionnaire and observation/counseling session predischarge and a telephone interview after taper completion. Univariate descriptive statistics were utilized for data analysis. Results: Phase 1 of the study was completed by 12 caregivers, and only 5 completed phase 2. The majority of caregivers were completely confident predischarge (83.3%) and postdischarge (80%) in administering methadone as prescribed. However, some caregivers were confused about the purpose of the taper and experienced difficulty in measuring oral solutions. Conclusions: Despite high self-efficacy, caregivers experienced difficulties in understanding taper management and during the observation session. The results of this study suggest presenting information to caregivers utilizing minimal medical jargon, conducting a counseling/observation session predischarge, and utilizing the teach-back method with caregivers to assess for understanding.