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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.

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.

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.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.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.FFM should be used to adjust ABW for empirically dosing gentamicin in pediatric patients aged 2-18 years.