Pharmacotherapy considerations for pediatric acute agitation management in the emergency department.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: To review the current literature regarding the pharmacological management of acute agitation in pediatric patients and practical considerations when comparing agents for empiric use in the emergency department (ED). SUMMARY: ED providers play an integral role in the management of acute agitation in pediatric patients. The development of acute agitation is multifactorial, and patients may quickly escalate upon arrival or while boarding in the ED. Nonpharmacological de-escalation strategies should be prioritized. If a patient poses a safety risk to themself or staff members, the administration of pharmacological treatment may be necessary to target the underlying cause and allow for the patient to safely engage in assessment and treatment. There is limited guidance regarding medication selection and dosing for acute agitation in pediatrics despite being a key facet of multimodal management. CONCLUSION: The literature regarding pharmacotherapy for acute agitation management in pediatric patients remains scarce. Medications utilized vary depending on institutional practice as well as provider preference. Evidence suggests that implementing an institutional protocol for pediatric acute agitation in the ED may improve patient outcomes. Additional studies are needed optimize the pharmacological management of acute pediatric agitation and patient outcomes in the ED.

Successful Use of Intravenous Methylnaltrexone for Opioid-Induced Constipation in Critically Ill Pediatric Patients.

Objectives Methylnaltrexone is U.S. Food and Drug Administration (FDA) approved as a subcutaneous injection for adults with opioid-induced constipation (OIC). Case series have described the use of methylnaltrexone for OIC in the pediatric oncology population. There are limited data describing its intravenous use in critically ill pediatric patients. Methods We conducted a retrospective observational study at St. Louis Children's Hospital. Patients less than 18 years old who received at least one dose of intravenous methylnaltrexone while admitted to an intensive care unit between January 2016 and August 2019 were included. The primary outcome was documented laxation within 24 hours of methylnaltrexone administration. Results Sixteen patients received a total of 34 doses of intravenous methylnaltrexone. Patients received a median of 1.69 (interquartile range [IQR], 0.9-4.86) morphine milligram equivalents per kilogram per 24 hours, over a median of 14 days (IQR, 11-30), before methylnaltrexone administration. The median dose of methylnaltrexone was 0.15 mg/kg (IQR, 0.15-0.16). Ten patients (63%) responded to the first dose of methylnaltrexone, and 14 patients (88%) responded to at least one dose. Overall, 26 doses (76%) led to patient response. Four patients (25%) experienced adverse events (emesis, abdominal pain) after methylnaltrexone administration. No signs or symptoms of opioid withdrawal were documented. Conclusions Intravenous methylnaltrexone appears to be safe and effective in treating OIC in critically ill pediatric patients. No serious adverse events or signs of opioid withdrawal were observed after single and repeat dosing. Patients responded to methylnaltrexone with varying opioid dosing and durations prior to administration.

Fentanyl Exposure in Preterm Infants: Five-Year Neurodevelopmental and Socioemotional Assessment.

Objective: To evaluate the association between cumulative fentanyl dose during neonatal intensive care and 5-year neurodevelopmental and socioemotional outcomes in very preterm infants. Materials and Methods: Patient demographics and clinical factors during the perinatal and neonatal course were collected in 84 patients born between 23- and 30-weeks gestational age (GA). Cumulative fentanyl dose during neonatal intensive care was calculated. Developmental testing at age 5 years included the Wechsler Preschool and Primary Scale of Intelligence Full-Scale Intelligence Quotient, Third Edition, Clinical Evaluation of Language Fundamentals-Preschool, Second Edition, Movement Assessment Battery for Children, Second Edition (MABC-2), and Shape School Assessment. Socioemotional outcomes were assessed via caregiver's responses on the Child Behavior Checklist/1.5-5 (CBCL/1.5-5.5) and Social Responsiveness Scale, Second Edition (SRS-2). Covariates were identified on bivariate analysis (p < 0.1). Linear regression models related outcome measures to the log of cumulative fentanyl dose adjusted for covariates. Results: Higher cumulative fentanyl dose was associated with lower composite motor scores on bivariate analysis (p < 0.01). Cumulative fentanyl dose did not correlate with composite intelligence quotient, language, or executive function. The Clinical Risk Index for Babies score, log of mechanical ventilation, inotrope, and anesthesia duration, and log of cumulative midazolam and hydrocortisone dose were also associated with MABC-2 scores (p < 0.1). Cumulative fentanyl dose was not associated with composite MABC-2 scores on multiple linear regression. Higher cumulative fentanyl dose was associated with decreased socioemotional problems based on caregiver's response on CBCL/1.5-5.5 t-scores driven by fewer symptoms of depression. The McMaster Family Assessment Device general functioning scale score, maternal age, GA, log of total parenteral nutrition days, patent ductus arteriosus requiring treatment, and log of inotrope hours were also associated with CBCL/1.5-5.5 t-scores (p < 0.1). Cumulative fentanyl dose (p = 0.039) and family dysfunction score (p = 0.002) remained significant after controlling for covariates on multiple linear regression. Conclusion: Cumulative fentanyl dose during neonatal intensive care did not correlate with 5-year motor, cognitive, or language outcomes after controlling for other variables. Fentanyl dose was associated with caregiver reported total socioemotional problems on the CBCL/1.5-5.5 on multivariate modeling. Additional long-term studies are needed to fully elucidate the safety of fentanyl in very preterm neonates.