Pharmacologic Management of Pediatric Burns.

Many pediatric patients with burn injuries may be initially treated in a hospital where pediatric specialized care, including resources and trained personnel may be limited. This includes resuscitation in adult emergency departments and inpatient care in mixed adult-pediatric burn units. The intent of this review is to provide a compilation of topics for the adult trained pharmacist or another healthcare practitioner on the management of pediatric patients with burn injuries. This article focuses on several key areas of pharmacologic burn management in the pediatric patient that may differ from the adult patient, including pain and sedation, fluid resuscitation, nutrition support, antimicrobial selection, anticoagulation, and inhalation injury. It is important that all clinicians have resources to help optimize the management of burn injuries in the pediatric population as, in addition to burn injury itself, pediatric patients have different pharmacokinetics and pharmacodynamics affecting which medications are used and how they are dosed. This article highlights several key differences between pediatric and adult patients, providing an additional resource to assist adult-trained pharmacists or other healthcare practitioners with making clinical decisions in the pediatric burn population.

Comparison of Amikacin Pharmacokinetics in Neonates With and Without Congenital Heart Disease.

OBJECTIVES: The primary objective was to compare the volume of distribution (Vd), clearance (CL), elimination rate (Ke), and half-life (t½) of amikacin in neonates with cyanotic defects, acyanotic defects, and controls, adjusted for gestational and postnatal age. Secondary objectives were to compare the incidence of acute kidney injury (AKI) between controls and the congenital heart disease (CHD) group and to identify potential risk factors. METHODS: This retrospective cohort study included neonates receiving amikacin from January 1, 2013 to August 31, 2016. Patients were excluded if concentrations were not appropriately obtained or if AKI or renal anomalies were identified prior to amikacin initiation. Congenital heart disease was classified as acyanotic or cyanotic. Patients with CHD were matched 1:1 with non-CHD controls according to postmenstrual age. Bivariate analyses were performed using Wilcoxon-Mann-Whitney test, Pearson χ2 tests, or Fisher exact as appropriate with a p value <0.05. Regression analyses included logistic and analysis of covariance. RESULTS: Fifty-four patients with CHD were matched with 54 controls. Median (IQR) postnatal age (days) at amikacin initiation significantly differed between CHD and controls, 3.0 (1.0-16.0) versus 1.0 (1.0-3.0), p = 0.016. After adjusting for gestational and postnatal age, there was no difference in the mean (95% CI) Vd (L/kg) and CL (L/kg/hr) between CHD and controls, 0.47 (0.44-0.50) versus 0.46 (0.43-0.49), p = 0.548 and 0.05 (0.05-0.05) versus 0.05 (0.05-0.05), p = 0.481, respectively. There was no difference in Ke or t½ between groups. There was no difference in AKI between the CHD and controls, 18.5% versus 9.3%, p = 0.16. CONCLUSIONS: Clinicians should consider using standard amikacin dosing for neonates with CHD and monitor renal function, since they may have greater AKI risk factors.

Incidence of Corrected QT Prolongation With Concomitant Methadone and Atypical Antipsychotics in Critically Ill Children.

OBJECTIVE: To evaluate the safety of the combination of methadone and an atypical antipsychotic in PICU patients. METHODS: This was a retrospective observational cohort pilot study in a single-center PICU in an academic children's hospital. Children 1 month to 18 years of age were included if they received methadone, were then initiated on an atypical antipsychotic (i.e., quetiapine or risperidone), and had EKG monitoring before and after medication initiation. RESULTS: Prolongation of the corrected QT (QTc) interval occurred in 5 of the 34 included patients when an atypical antipsychotic was added to methadone. Of the 5 patients who had a prolonged QTc interval, 4 (80%) were older than 12 years and had a median weight of 91.3 kg. There were statistical differences between age and weight when comparing patients who experienced QTc prolongation, but no differences in sex, ethnicity, electrolyte deficiencies, number of additional QTc-prolonging medications, and number of additional drug-drug interactions were identified. When comparing atypical antipsychotics, 9.5% of patients receiving risperidone had a prolonged QTc interval, versus 23% of patients receiving quetiapine (p = 0.04). The net change in QTc interval after initiation of methadone was 0.19 milliseconds (IQR: -3, 15), which increased after atypical antipsychotic initiation to 4 milliseconds (IQR: -16, 15). CONCLUSIONS: Our pilot trial suggests there is no clinically significant difference in incidence of QTc prolongation with addition of atypical antipsychotics to methadone.

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.

Tobramycin Serum Concentrations in Tracheostomy-Dependent Children Receiving Inhaled Tobramycin.

Introduction: In recent years, administration of inhaled aminoglycosides has gained popularity in tracheostomy-dependent pediatric patients because of medication delivery to the target site of action while minimizing systemic absorption and adverse effects. A recent report of detectable serum tobramycin concentrations in critically ill children receiving inhaled tobramycin 300 mg every 12 h prompted our investigation in tracheostomy-dependent pediatric patients receiving inhaled tobramycin 80 mg every 8 h. Methods: Serum tobramycin trough concentrations were obtained from tracheostomy-dependent pediatric patients receiving treatment with inhaled tobramycin 80 mg every 8 h for the treatment of tracheitis. Patient data, including demographic data, medical history, renal function, and serum concentrations, were collected. Results: Twelve patients with a median age of 0.5 (0.3-6.1) years had serum tobramycin concentrations evaluated. Eleven of the 12 patients had undetectable trough concentrations (<0.6 mcg/mL). All of these patients had normal blood urea nitrogen (BUN) and serum creatinine (SCr) for age and no history of kidney disease. One patient had a detectable trough concentration of 2.1 mcg/mL. This patient was 11 months old and had polycystic kidney disease with an elevated BUN and SCr for age. Conclusions: Detectable serum concentration from systemic absorption of inhaled tobramycin 80 mg every 8 h is unlikely in tracheostomy-dependent pediatric patients with normal renal function. However, in tracheostomy-dependent pediatric patients with a history of renal dysfunction or elevations in BUN or SCr, inhaled tobramycin should be used with caution. Monitoring serum concentrations to guide dose modification should be considered in these patients.

Comparison of Amikacin Pharmacokinetics in Neonates Following Implementation of a New Dosage Protocol.

OBJECTIVES: The primary aim was to compare attainment of goal serum amikacin concentrations using two dosage regimens in patients admitted to a neonatal intensive care unit. Secondary objectives included comparison of percentages of supratherapeutic trough concentrations, and subtherapeutic and supratherapeutic peak concentrations. METHODS: This was an Institutional Review Board-approved, retrospective study of neonates receiving amikacin during January-December 2013 (group 1) and January-December 2014 (group 2). Group 1 received amikacin dosage consistent with published recommendations, whereas group 2 was dosed using a modified protocol that was based on postmenstrual and postnatal age. Goal serum amikacin peak concentration was defined as 20 to 35 mg/L; hence, subtherapeutic and supratherapeutic peak concentrations were defined as <20 mg/L and >35 mg/L, respectively. Supratherapeutic trough concentrations were >8 mg/L. Between-group analysis was performed using Wilcoxon-Mann-Whitney test, Student t-test or χ2, or Fisher exact analysis as appropriate with a p value <0.05. RESULTS: A total of 278 neonates were included (group 1: n = 144; group 2: n = 134). Most patients were male (60%) and were admitted for prematurity or respiratory distress (77%). The median gestational age in group 1 was 34.4 weeks (range, 30.0-37.9 weeks) versus group 2 at 36.9 weeks (range, 31.4-38.9 weeks), whereas the postnatal age was similar between both groups at 4 days. There was a significant increase in attaining goal peak amikacin concentrations between groups 1 and 2, 34% versus 84%, p < 0.001, and decrease in supratherapeutic peak concentrations, 65% versus 12%, p < 0.001. There was no significant difference in subtherapeutic peak or supratherapeutic trough concentrations. CONCLUSIONS: A modified neonatal amikacin dosage protocol resulted in increased peak amikacin serum concentration compared with published dosage recommendations. Future research should focus on determination of the optimal dosage regimen in neonates.

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.

Impact of a Drug Shortage on Medication Errors and Clinical Outcomes in the Pediatric Intensive Care Unit.

OBJECTIVES: The purpose of this study was to assess the rate of prescribing errors, resulting adverse events, and patient outcomes associated with sedation and analgesia in the pediatric intensive care unit (PICU) before and during a national shortage of fentanyl and injectable benzodiazepines. METHODS: A retrospective chart review was performed of patients admitted to the PICU with at least 1 prescribed order for a sedative or analgesic agent during the time periods of January to February of 2011 and 2012. Initial orders for sedative and analgesic agents were identified and investigated for appropriateness of dose and were assessed for error-associated adverse events. Orders were stratified by timing in regard to clinical pharmacist on-site availability. Demographic and outcome information, including unintended extubations, ventilator days, and PICU length of stay, were gathered. RESULTS: One hundred sixty-nine orders representing 72 patients and 179 orders representing 75 patients in 2011 and 2012, respectively, were included in analysis. No differences were found in the rate of prescribing errors in 2011 and 2012 (33 errors in 169 orders vs. 39 errors in 179 orders, respectively, p=0.603). No differences were found in rates of prescribing errors in regard to clinical pharmacist on-site availability. A significant increase was seen in unintended extubations per 100 ventilator days, with 0.15 in 2011 vs. 1.13 in 2012, respectively (p<0.001). A significant decrease was seen in ventilator days per patient (p<0.001) and PICU length of stay per patient (p=0.019). CONCLUSIONS: There were no differences in rates of prescribing errors before versus during the fentanyl and benzodiazepine shortage.