Fosphenytoin Population Pharmacokinetics in the Acutely Ill Pediatric Population.

OBJECTIVE: The purpose of this study is to describe the pharmacokinetics of phenytoin in pediatric patients receiving fosphenytoin. DESIGN: Retrospective, population pharmacokinetic analysis. SETTING: Emergency department or PICU of a large tertiary care children's hospital. PATIENTS: Patients less than 19 years old who received fosphenytoin in the PICU or emergency center for treatment of seizures from January 2011 to June 2017 were included. INTERVENTIONS: Population pharmacokinetic analysis was performed with NONMEM v7.3 (Icon Plc, Dublin, Ireland). Simulation was performed to determine optimal loading dose and maintenance dosing regimens. MEASUREMENTS AND MAIN RESULTS: A total of 536 patients (55.4% male; median age, 3.4 yr [interquartile range, 0.92-8.5 yr]) met study criteria. Fosphenytoin was administered at median 15.1 mg/kg/dose (interquartile range, 6.3-20.7 mg/kg/dose). Mean serum concentrations of 17.5 ± 7.8 mg/L were at a median 4.2 hours (interquartile range, 2.5-7.8 hr) after a dose. A pharmacokinetic model with two compartments, allometrically scaled fat-free mass on all parameters, and serum creatinine and concomitant phenobarbital use on clearance had the best fit. Simulation demonstrated that a 20 mg/kg loading dose followed by 6 mg/kg/dose every 8 hours had the greatest percentage of concentrations in the 10-20 mg/L range, with reduced doses to achieve therapeutic in patients with reduced kidney function. CONCLUSIONS: A loading dose of 20 mg/kg followed by 6 mg/kg/dose every 8 hours based on fat-free mass is a reasonable empiric strategy for attainment and maintenance of therapeutic trough concentrations. Concomitant phenobarbital use may increase clearance of phenytoin and fosphenytoin dose reductions should occur in patients with reduced kidney function.

Inhaled Tranexamic Acid As a Novel Treatment for Pulmonary Hemorrhage in Critically Ill Pediatric Patients: An Observational Study.

OBJECTIVES: To describe the use of inhaled or endotracheally instilled tranexamic acid in critically ill pediatric patients for the treatment of pulmonary hemorrhage, which can be severe, life-threatening, and include potentially high-risk management procedures. DESIGN: Retrospective observational study from 2011-2018 with patients followed until hospital discharge. SETTING: Free-standing children's hospital with an annual ICU volume of more than 3,500 yearly admissions. PATIENTS: Pediatric patients, ages 0 to 18 years, admitted to an ICU and who received at least one dose of inhaled or endotracheally instilled tranexamic acid were included. INTERVENTIONS: Inhaled or endotracheally instilled tranexamic acid. MEASUREMENTS AND MAIN RESULTS: This study described the efficacy and adverse effects of patients who received inhaled or endotracheally instilled tranexamic acid. A total of 19 patients met inclusion criteria; median age was 72 months (11-187 mo), most patients were female (11, 58%), and almost half our patients (8, 42%) had congenital heart disease. Nine of 19 encounters (47%) had diffuse alveolar hemorrhage, four (21%) had pulmonary hemorrhage related to major aortopulmonary collateral arteries, two (11%) had mucosal airway bleeding, two (11%) were iatrogenic, one had a pulmonary embolism, and one patient did not have their etiology of pulmonary hemorrhage determined. Cessation of pulmonary hemorrhage was achieved in 18 of 19 patients (95%) with inhaled tranexamic acid with no major adverse events recorded. CONCLUSIONS AND RELEVANCE: We demonstrate that inhaled tranexamic acid may be safely used to treat pulmonary hemorrhage from varied etiologies in critically ill pediatric patients. Prospective studies are required in this vulnerable population to determine optimal dosing and delivery strategies, as well as to define any differential effect according to etiology.