Kevin K. Graner

The Effect of Age and Weight on Vancomycin Serum Trough Concentrations in Pediatric Patients

Vancomycin treatment failure has been associated with low serum vancomycin trough concentrations, prompting recommendations to increase the daily doses in adults and children. Despite more aggressive vancomycin dosing, there continues to be significant variability in vancomycin trough concentrations in pediatric patients.

Implementation of patient-centered bedside rounds in the pediatric intensive care unit.

Implementation of effective family-centered rounds in an intensive care unit environment is fraught with challenges. We describe the application of PDSA (Plan, Do, Study, Act) cycles in a quality improvement project to improve the process of rounds and increase family participation and provider satisfaction. We conducted pre-/postintervention surveys and used 5 process measures for a total of 1296 daily patient rounds over 7 months. We were successful in conducting family-centered rounds for 90% of patients, with 40% family participation and a 64.6% satisfactory rating by pediatric intensive care unit providers.

Stability of fentanyl 5 μg/mL diluted with 0.9% sodium chloride injection and stored in polypropylene syringes

PURPOSE The stability of fentanyl 5 microg/mL in 0.9% sodium chloride solution packaged in polypropylene syringes was studied. METHODS Samples of fentanyl 5 microg (as the citrate) per milliliter in 0.9% sodium chloride injection were prepared and assessed for chemical stability using a validated, stability-indicating high- performance liquid chromatographic (HPLC) assay. A total of 12 syringe samples were submitted for chemical stability testing by HPLC. The syringes were protected from light and stored in controlled ambient conditions (23-27 degrees C and 55-65% relative humidity) in an environmental chamber. Three samples were tested initially and at each 30-day interval. Each syringe sample was tested with two determinations, using the average of the determinations for the assay result. Samples were assessed for pH and inspected for color and visible particulate matter. Stability was defined as the retention of 90-110% of the initial drug concentration at 30, 60, and 90 days. RESULTS Fentanyl citrate injection maintained the appearance of a clear, colorless solution, with mean +/- S.D. pH values ranging from 4.13 +/- 0.01 to 4.52 +/- 0.02 throughout the study period. Recovery of fentanyl ranged from 99.86% +/- 0.29% to 102.74% +/- 1.60% of the initial concentration, with no detectable changes in the chromatographic profiles of all tested samples. CONCLUSION Fentanyl 5 microg (as the citrate) per milliliter in 0.9% sodium chloride injection, packaged in polypropylene syringes and stored protected from light, was stable for at least 90 days in controlled ambient conditions.

A Retrospective Analysis of Outcomes of Dalteparin Use in Pediatric Patients: A Single Institution Experience

BACKGROUND Dalteparin is a commonly used low molecular weight heparin (LMWH) with extensive safety data in adults. With distinct advantages of once daily dosing and relative safety in renal impairment, it has been used off-label in pediatric practice; however, age-based dosing guidelines, safety and efficacy data in children are evolving. OBJECTIVES To report our institutional experience with the use of dalteparin in the treatment and prophylaxis of venous thromboembolism (VTE) in pediatric patients. PATIENTS/METHODS Retrospective chart review of all children (0-18years) that received dalteparin from December 1, 2000 through December 31, 2011. Doses per unit body weight per day (units/kg/day) were calculated for age-based group comparisons. RESULTS Of 166 patients identified, 116 (70%) received prophylactic doses while 50 (30%) received therapeutic doses of dalteparin. Infants (<1year) required significantly higher weight-based dosing to achieve therapeutic anti-Xa levels compared to children (1-10years) or adolescents (>10-18years) (mean dose units/kg/day; 396.6 versus 236.7 and 178.8 respectively, p<0.0001). Overall response rate, including complete and partial thrombus resolution, was 83%. Bleeding complications were minor and the rates were similar in therapeutic and prophylaxis patients. No significant differences in dosing or bleeding events were noted based on obesity or malignancy. CONCLUSIONS In our experience, dalteparin is effective for prophylaxis and therapy of VTE in pediatric patients. Dosing should be customized in an age-based manner with close monitoring of anti-Xa activity in order to achieve optimal levels, prevent bleeding complications, and to allow full benefit of prevention or therapy of thrombotic complications.

Optimization of vancomycin dosing in very low-birth-weight preterm neonates.

OBJECTIVE To compare vancomycin serum trough concentrations and 24-hour area under the serum concentration-versus-time curve (AUC24) among very low-birth-weight (VLBW) premature infants before and after implementation of an institution-wide increase in neonatal vancomycin dosing. STUDY DESIGN We performed a retrospective analysis of vancomycin concentrations among preterm VLBW neonates before (2007-2010) and after (2010-2013) implementation of a new vancomycin dosing protocol consisting of increased vancomycin daily dose and frequency of administration. RESULTS Neonates weighing < 1,500 g and receiving the new vancomycin dosing regimen had lower rates of undetectable trough concentrations (24 vs. 50%, p = 0.04), higher median trough concentrations (10.8 vs. 5.9 µg/mL, p = 0.003), a higher proportion of goal trough concentrations of 10 to 20 µg/mL (35 vs. 4%, p = 0.005), and a significantly higher vancomycin AUC24 (438 vs. 320 mg·h/L, p = 0.004) compared with historical controls. CONCLUSION Increasing the vancomycin daily dose and dosing frequency led to an increase in vancomycin trough concentrations and AUC24, and a decrease in the proportion of undetectable (< 5.0 µg/mL) troughs, without an increase in toxicity among VLBW premature neonates.

Stability of chlorothiazide sodium in polypropylene syringes

PURPOSE The stability of a solution of chlorothiazide injection diluted with sterile water and stored in polypropylene syringes under refrigerated conditions was investigated. METHODS Chlorothiazide solutions were compounded by adding 20 mL of sterile water for injection to a 500-mg vial of chlorothiazide sodium for injection. Six batches of chlorothiazide solution (25 mg/mL) were compounded; 0.5-mL portions were transferred to 1-mL polypropylene syringes, which were sealed with a Luer tip cap and stored at refrigeration temperatures (2-8 °C) protected from light. Three batches were potency tested by stability-indicating high-performance liquid chromatography (HPLC) assay using a 0.5-mL sample from each batch at designated time points. Visual and pH testing were performed using the three remaining batches; the contents of two syringes per batch were combined and visually inspected for container integrity and solution color and clarity, with duplicate pH testing performed at each time point. RESULTS HPLC analyses showed that the remaining percentage of the initial chlorothiazide content declined at an average daily rate of 1.4%, decreasing to 93% by day 6. All samples remained intact, clear, and colorless, with no visible particulate matter or precipitation observed throughout the study period. For all samples of chlorothiazide solution, pH values remained within the range of 9.2-10.0 throughout the 10-day study period. CONCLUSION When packaged in 1-mL polypropylene syringes and stored protected from light at refrigerated conditions, a solution of chlorothiazide sodium injection in water was stable for six days.