Although the use of acetylcysteine by oral or intravenous administration for the treatment of acetaminophen overdose is generally effective and safe,1–3 there are aspects of its administration that may be “gray” and less than optimal for several reasons. The paper by Pauley et al4 in the current issue of The Journal describes an off-label regimen for the intravenous administration of acetylcysteine for treating acetaminophen overdose in pediatric patients. The authors' experience complements those of several other recent reports of alternative intravenous (IV) regimens administered to adult5–7 and pediatric8 patients.
Kawasaki disease is an autoimmune disease found predominantly in children under the age of 5 years. Its incidence is higher in those who live in Asian countries or are of Asian descent. Kawasaki disease is characterized as an acute inflammation of the vasculature bed affecting mainly the skin, eyes, lymph nodes, and mucosal layers. Although the disease is usually self-limiting, patients may develop cardiac abnormalities that can lead to death. The exact cause of the disease is unknown; however, researchers hypothesize that an infectious agent is responsible for causing Kawasaki disease. Initial treatment options with intravenous immune globulin and aspirin are sufficient to cure most patients who acquire this disease. Unfortunately, in up to one-quarter of patients, the disease will be refractory to initial therapy and will require further management with corticosteroid, immunomodulatory, or cytotoxic agents. The lack of randomized, controlled trials makes treatment of refractory disease difficult to manage. Until larger randomized, controlled trials are published to give more guidance on therapy for this stage of disease, clinicians should use the data available from observational studies and case reports in conjunction with their clinical expertise to make treatment decisions.
OBJECTIVE: Conventionally, intravenous N-acetylcysteine (IV-NAC) administration is a 3-bag regimen administered over the course of 21 hours, which increases the risk of reconstitution and administration errors. To minimize errors, an alternative IV-NAC regimen consists of a loading dose (150 mg/kg) followed by a maintenance infusion (15 mg/kg/hr) until termination criteria are met. The aim was to determine the clinical outcomes of an alternative IV-NAC regimen in pediatric patients.
METHODS: A retrospective review of pharmacy dispensing records and diagnostic codes at a pediatric hospital identified patients who received alternative IV-NAC dosing from March 1, 2008, to September 10, 2012, for acetaminophen overdoses. Exclusion criteria included chronic liver disease, initiation of oral or other IV-NAC regimens, and initiation of standard IV-NAC infusion prior to facility transfer. Clinical and laboratory data were abstracted from the electronic medical record. Descriptive statistics were utilized. Clinical outcomes and adverse drug reaction incidences were compared between the alternative and Food and Drug Administration (FDA)–approved IV-NAC regimens.
RESULTS: Fifty-nine patients (mean age 13.4 ± 4.3 years; range: 2 months-18 years) with acetaminophen overdoses were identified. Upon IV-NAC discontinuation, 45 patients had normal alanine transaminase (ALT) concentrations, while 14 patients' ALT concentrations remained elevated (median 140 units/L) but were trending downward. Two patients (3.4%) developed hepatotoxicity (aspartate transaminase/ALT > 1000 units/L). No patients developed hepatic failure, were listed for a liver transplant, were intubated, underwent hemodialysis, or died. Two patients (3.4%) developed anaphylactoid reactions. No known medication or administration errors occurred. Clinical outcome incidences of the studied endpoints with the alternative IV-NAC regimen are at the lower end of published incidence ranges compared to the FDA IV-NAC regimen for acetaminophen overdoses.
CONCLUSIONS: This alternative IV-NAC regimen appears to be effective and well tolerated among pediatric patients when compared to the FDA-approved regimen. It may also result in fewer reconstitution and administration errors, leading to improved patient safety.
OBJECTIVES: To characterize off-label prescribing among US pediatric intensive care units (PICUs), determine characteristics associated with off-label use, and identify medications in highest need for additional study.
METHODS: Medications prescribed for ≥1% PICU patients (age < 18 years) in 2010 were identified from 39 children's hospitals. Use in a patient younger than the Food and Drug Administration (FDA)-approved age for any indication was considered off-label. Hierarchical multivariable modeling was used to identify characteristics associated with off-label use, accounting for center effects. Highest-impact drugs were defined by: 1) high off-label use (off-label use in at least 5% of the PICU cohort), 2) high risk medication, and 3) high priority status by the FDA or Best Pharmaceuticals for Children Act (BPCA).
RESULTS: A total of 66,896 patients received ≥1 medication of interest (n = 162) during their PICU stay. A median of 3 (interquartile range, 2–6) unique drugs per patient were used off-label. Those who received ≥1 drug off-label (85% of the cohort) had longer median PICU (2 days vs 1 day) and hospital (6 days vs 3 days) lengths of stay and higher mortality (3.6% vs 0.7%), p < 0.001. Factors independently associated with off-label drug use included: age 1 to 5 years, chronic conditions, acute organ failures, mechanical ventilation, arterial or venous catheters, dialysis, and blood products. Half of prescribed medications (n = 84) had been used off-label: 26 with significant off-label use, 30 high-risk medications, and 47 with high FDA/BPCA priority. The highest impact medications identified were: dexmedetomidine, dopamine, hydromorphone, ketamine, lorazepam, methadone, milrinone, and oxycodone.
CONCLUSIONS: Most PICU patients are exposed to off-label medication use, with uncertain evidence. Future medication research in this population should focus on medications with high impact potential.
OBJECTIVES: The physical and chemical stability of a preservative-free oral solution of hydrocortisone succinate was studied at different pH values and storage temperatures.
METHODS: Oral solutions of hydrocortisone 1 mg/mL were prepared by dissolving hydrocortisone succinate powder in citrate buffers at pH 4.0, 5.5, and 6.5, or with sterile water (pH 7.4) stored in amber glass vials. Three identical samples of the formulations were prepared and stored under refrigeration (3–7°C), ambient temperature (20–22°C) and high temperature (29–31°C). A 200-μL sample was withdrawn from each of the 3 samples immediately after preparation and at 1, 7, 14, 21, and 35 days. Samples were assayed in duplicate using stability-indicating liquid chromatography. Stability was determined by evaluating the percentage of the initial concentration remaining at each time point; stability was defined as the retention of at least 90% of the initial concentration of hydrocortisone succinate.
RESULTS: At least 92% of the initial hydrocortisone succinate concentration in solutions pH 5.5, 6.5, and 7.4 remained throughout the 14-day study period under refrigeration. There were no detectable changes in color, odor, or pH and no visible microbial growth in these samples. In other storage conditions, hydrocortisone succinate was rapidly degraded.
CONCLUSIONS: The hydrocortisone succinate preservative-free oral solutions at pH 5.5, 6.5, or 7.4 are chemically stable when stored under refrigeration for at least 14 days. They provide flexible and convenient dosage forms without any preservatives for pediatric patients.
OBJECTIVES: Evaluate the incidence of postcatheter removal clinical sepsis when antibiotics were infused prior to the removal of percutaneously inserted central venous catheters (PICCs).
METHODS: A retrospective chart review of premature neonates (n = 196) weighing ≤1250 g at birth with 218 PICC line removals in the presence or absence of antibiotics at a tertiary level neonatal intensive care unit (NICU) between January 1, 2010, and May 31, 2012. Charts were reviewed looking for the presence of clinical sepsis defined as a sepsis workup including white blood cell count, differential, C-reactive protein, blood and/or cerebral spinal fluid (CSF), and urine cultures along with at least 48 hours of antibiotic therapy given within 72 hours after removal of a PICC line. Antibiotics were considered present at line removal if given within 12 hours before catheter removal either electively or at completion of a planned course.
RESULTS: When antibiotics were given within 12 hours before PICC line removal, only 2% of the line removal episodes (1/48) resulted in a neonate developing clinical sepsis versus 13% (21/165) when no antibiotics were given prior to removal (p = 0.03, Fisher's exact test). Despite the increased use of elective antibiotics with line removal, there was no increase in total antibiotic usage due to the overall decrease in episodes of clinical sepsis or changes in antibiogram susceptibility patterns.
CONCLUSIONS: There was an 11% absolute decrease and a 6-fold relative decrease in postcatheter removal clinical sepsis events in premature neonates who received antibiotics prior to PICC line removal.
OBJECTIVES: The objective of this study was to evaluate the safety and efficacy of polyethylene glycol-electrolyte solution vs polyethylene glycol-3350 for the treatment of fecal impaction in pediatric patients.
METHODS: A retrospective, observational, institutional review board–approved study was conducted over a 1-year time period. Patients were included in the study if they were admitted to the hospital with a diagnosis of fecal impaction or constipation and were treated with either polyethylene glycol-electrolyte solution (PEG-ES) or polyethylene glycol-3350 (PEG-3350). Patients were excluded if they were discharged prior to resolution of treatment and/or did not receive PEG-ES or PEG-3350.
RESULTS: Fifty-one patients (ranging in age from 1 month to 15 years) were evaluated: 23 patients received PEG-ES and 28 patients received PEG-3350. Sex, race, age, and weight were not statistically different between the 2 groups. Resolution of fecal impaction was not significantly different between PEG-ES vs PEG-3350 (87% and 86%, respectively; p = 0.87). There was only 1 reported side effect with PEG-3350, vs 11 reported side effects with PEG-ES (p < 0.01).
CONCLUSIONS: Theses results suggest that PEG-3350 is as effective as PEG-ES for the treatment of fecal impaction in pediatric patients and is associated with fewer side effects.
A syndrome of hepatosplenomegaly, thrombocytopenia, and anemia and the presence of sea-blue histiocytes in bone marrow has been associated with parenteral soybean oil administration in patients receiving long-term total parenteral nutrition (TPN). A case is described here where this syndrome was observed in a pediatric patient who received long-term parenteral fish oil nutrition.
Background: As the responsibility of a pediatric pharmacist expands intoEVALUATION OF A PHARMACIST ON-CALL PROGRAM IN A GENERAL PEDIATRIC CLINIC