OBJECTIVE:To determine the incidence of cytomegalovirus (CMV) DNAemia and disease, identify potential risk factors, and assess the safety and efficacy of weight-based valganciclovir dosing in pediatric post-renal transplant patients.METHODS:This single-center, retrospective study included patients ≤21 years who received a kidney transplant between January 1, 2011, and November 1, 2019, with 3 to 24 months of follow-up data. Demographics and clinical characteristics were collected to assess for potential risk factors. Descriptive statistics and logistic regressions were used to determine rates of CMV DNAemia considering clinical characteristics and chemoprophylaxis.RESULTS:Fifty-seven patients were included. The incidence of CMV DNAemia was 43.9%. Cytomegalovirus seropositive status was associated with increased risk of CMV DNAemia. Patients receiving valganciclovir for <150 days had 8.33 (95% CI, 1.68-41.29) greater odds of developing CMV DNAemia than patients receiving valganciclovir for 180 ± 30 days, p = 0.01. The median time to detectable CMV PCR after transplant was 140 days (range, 12-511 days). Cytomegalovirus DNAemia was not statistically different between those receiving weight-based vs FDA-approved valganciclovir dosing; however, patients receiving the FDA-approved dosing were more likely to develop neutropenia. Among the intermediate-risk group, the adjusted relative risk of CMV DNAemia was 0.62 (95% CI, 0.36-1.09) for those not receiving chemoprophylaxis compared with those who did.CONCLUSIONS:Risk of CMV DNAemia is higher among patients receiving valganciclovir for <150 days. Further exploration of weight-based valganciclovir dosing for CMV chemoprophylaxis in high- and intermediate-risk post-renal transplant patients is needed to minimize adverse drug effects while maintaining efficacy.

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.

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.

PURPOSE The relationship between initial fentanyl infusion dosage and time to goal sedation in nonobese and obese critically ill children was examined. METHODS A retrospective cohort study of 75 fentanyl infusions initiated in mechanically ventilated children age 2-17 years with an inpatient admission between January 1, 2012, and May 31, 2014, who subsequently received a fentanyl infusion was conducted. The primary outcomes of the study included the time to goal sedation and fentanyl dosage characteristics (i.e., underdosage, optimal dosage, or overdosage). Sedation scores were assessed by the State Behavioral Scale, a validated instrument to assess sedation in children. Key independent (predictor) variables were collected, including baseline demographics and admission diagnoses. Multivariable regression models were used to examine the association between initial fentanyl infusion dosage and time to goal sedation or dosing characteristics while controlling for obesity status and other modifying or confounding factors. RESULTS A total of 75 infusions met the study's inclusion criteria, representing 74 patients. The majority of patients (52%) were boys, and the median age was 8.1 years. Eighteen children (24%) were obese. The median time to goal sedation was 10.9 hours. Among nonobese children, every 10-μg/hr increase in initial fentanyl dosage was associated with a 19% lower probability of achieving goal sedation at any point in time. Initial fentanyl dosage was not associated with time to goal sedation in obese children. CONCLUSION Fentanyl infusion rates in obese and nonobese children varied widely in the time needed to achieve goal sedation. At any given time, initial fentanyl infusion rates were less likely to result in goal sedation in nonobese than in obese children.

OBJECTIVES:The purpose of this study was to describe the method of delivery, dosage regimens, and outcomes of sedatives administered by extravascular route for imaging procedures in children.METHODS:Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Database of Systematic Reviews were searched using keywords "child", "midazolam", "ketamine", dexmedetomidine", "fentanyl", "nitrous oxide", and "imaging." Articles evaluating the use of extravascular sedation in children for imaging procedures published in English between 1946 and March 2015 were included. Two authors independently screened each article for inclusion. Reports were excluded if they did not contain sufficient details on dosage regimens and outcomes.RESULTS:Twenty reports representing 1,412 patients ranging in age from 0.33 to 19 years of age were included for analysis. Due to discrepancies in doses and types of analyses, statistical analyses were not performed. Oral midazolam was the most common agent evaluated; other agents included intranasal (IN) ketamine, IN midazolam, IN fentanyl, IN and transmucosal dexmedetomidine, and N2O. Most agents were considered efficacious compared with placebo.CONCLUSIONS:Most agents showed efficacy for sedation during imaging when delivered through an extra-vascular route. Selection of agents should be based on onset time, duration, patient acceptability, recovery time, and adverse events. More robust studies are necessary to determine the optimal agent and route to utilize for imaging procedures when sedation is needed.

Loop diuretics are commonly used in critically ill children to achieve appropriate fluid balance. They are often administered as a continuous intravenous infusion ( CI ) in hemodynamically unstable children because of fewer alterations in central venous pressure, oxygen saturation, and heart rate compared with scheduled intermittent dosing. During the past few years, however, drug shortages have been reported for bumetanide, torsemide, and furosemide. Therefore, to explore the use of alternative agents for CI , we performed a literature search to identify articles evaluating the use of furosemide, bumetanide, ethacrynic acid, and torsemide CI in critically ill children. The search was limited to English‐language articles in the MEDLINE (1946–December 2013), EMBASE (1980–December 2013), and International Pharmaceutical Abstracts (1970–December 2013) databases and the Cochrane Database of Systematic Reviews (2005–December 2013). Reference citations from relevant articles were also reviewed. A total of 10 reports representing 173 pediatric patients were included in the analysis. Most of the reports provided evidence for furosemide, and no reports with torsemide were identified. Wide variability in CI dosing was reported in these studies. When selecting the loop diuretic CI for critically ill patients, clinicians should consider their adverse‐event profiles, compatibility with other concomitant intravenous infusions, and pharmacoeconomics. Fluid balance and urine output should be monitored routinely to ensure appropriate response. The lowest initial dose should be used to achieve an appropriate fluid balance and target urine output of 1–3 ml/kg/hour while limiting the likelihood of toxicity.