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.

Evaluation of Intravenous Ranitidine on Gastric pH in Critically Ill Pediatric Patients.

OBJECTIVE: To determine the dosing regimen of intravenous ranitidine (IVR) most likely to achieve a gastric pH of ≥4 in critically ill pediatric patients. METHODS: A retrospective cohort study was designed and included patients younger than 19 years with gastric pH samples taken from a nasogastric tube within 24 hours after a dose of IVR in an intensive care unit. Data collection included patient demographics, clinical variables, IVR dosing, and gastric pH samples. Descriptive statistical analysis and multivariable logistic regression analysis with clustering of patients was performed to determine variables associated with odds of obtaining a pH of ≥4. RESULTS: A total of 628 patients (1356 nasogastric samples) met study criteria (median age 1.3 years [IQR, 0.33, 5.7 years]; 53% male). The IVR dose was 0.90 ± 0.30 mg/kg per dose every 8.1 ± 2.9 hours, and 60.9% of patients (n = 383) had a pH ≥4. Patients with a pH value ≥4 had gastric pH samples taken earlier after a dose of IVR (6.7 ± 5.0 vs. 5.9 ± 4.7 hours, p < 0.001) but had no difference in IVR dose per kilogram (0.88 ± 0.31 vs. 0.88 ± 0.26, p = 0.86) or frequency of dosing (7.9 ± 3.2 vs. 7.9 ± 3.2 hours, p = 0.89). A multivariable logistic regression model identified increasing age, decreased kidney function, and decreased time to pH sample after an IVR dose with significantly greater odds of pH ≥4. CONCLUSIONS: The IVR dosing to maintain a gastric pH ≥4 in critically ill pediatric patients should occur more frequently than every 8 hours. Gastric pH evaluation may be necessary to assess IVR efficacy.

Cefepime Pharmacokinetics in Critically Ill Pediatric Patients Receiving Continuous Renal Replacement Therapy.

This retrospective study included pediatric intensive care unit patients receiving continuous veno-venous hemodiafiltration (CVVHDF) being treated with cefepime. The free drug concentration above one time the MIC (fT>1×MIC) and four times a presumed MIC (fT>4×MIC) of 8 µg/ml were calculated. Four patients received doses ranging from 48 to 64 mg/kg of body weight every 6 to 12 h. Three patients achieved 100% fT>1×MIC, with the fourth patient achieving 98% fT>1×MIC. Therapeutic drug monitoring should be considered for critically ill patients receiving cefepime on CVVHDF.

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.

The "Ideal" Body Weight for Pediatric Gentamicin Dosing in the Era of Obesity: A Population Pharmacokinetic Analysis.

BACKGROUND: Obese pediatric patients often require dose reductions when initiating gentamicin therapy. An appropriate method for calculating ideal body weight for dosing gentamicin in pediatric patients has not been validated. METHODS: A retrospective population pharmacokinetic study was designed and included non-intensive care pediatric patients who received gentamicin and had serum gentamicin concentrations sampled. Actual body weight (ABW), adjusted body weight, and fat-free mass (FFM) were used to describe the pharmacokinetic variables. Descriptive statistical methods were used for the population, and pharmacokinetic analysis occurred with NONMEM (ICON Plc, Dublin, Ireland). Simulation was performed to estimate dosing based on adjustments in body weight. RESULTS: A total of 520 patients met inclusion criteria (male 57.3%, mean age 9.6 ± 4.9 years, ABW 38.0 ± 24.3 kg). Obesity was present in 21.3% of the patients and overweight in 15.8%. Gentamicin was administered at 2.17 ± 0.86 mg/kg per dose. A median of 2 (interquartile range, 1-3) gentamicin serum concentrations were sampled at a median 1.8 (interquartile range, 1.1-7.8) hours after a dose. Population pharmacokinetic analysis demonstrated a 2-compartment model with allometrically scaled FFM providing the best fit. Other significant covariates included serum creatinine and age. Simulation demonstrated increased doses per body weight for traditional and once-daily dosing when using FFM for gentamicin dosing. CONCLUSIONS: FFM should be used to adjust ABW for empirically dosing gentamicin in pediatric patients aged 2-18 years.