Strategies for Implementing Pediatric Dose Standardization: Considerations From the Vizient University Health System Consortium Pharmacy Network Pediatric Pharmacy Committee

Pediatric patients are at a heightened risk for medication errors due to variability in medication ordering and administration. Dose rounding and standardization have been 2 practices historically used to reduce variability and improve medication safety. This article will describe strategies for implementing pediatric dose standardization. Local practice often dictates the operational decisions made at an institutional level, leading to a lack of a standard methodology. Vizient survey results demonstrate there is wide variation in dose standardization and ready-to-use (RTU) practices although most responding institutions have attempted to limit bedside manipulation to reduce medication error. There are many barriers to consider before pursuing dose standardization at an institution. These include selecting medications to standardize, calculating appropriate standardized doses, preparing RTU products, and supplying the products to the patient. Strategies to overcome implementation issues are described as well as identification of knowledge gaps related to the preparation and use of RTU products in the pediatric population. There is opportunity to enhance an institution's ability to provide RTU medications. Although there are several barriers, those that have had successful implementation have leveraged their information technology systems, garnered multidisciplinary support, and customized their practice to meet their operational demands.

Cyclic Vomiting Syndrome in Pediatric Patients: A Review of Therapeutics

Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder that can present quite a challenge to clinicians caring for children with this complex disease. Different therapeutic interventions are recommended for prophylaxis and acute abortive therapy for a CVS attack. The aim of this review is to summarize therapeutic treatment recommendations from the 2008 North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHN) Consensus Statement on the Diagnosis and Management of Cyclic Vomiting Syndrome and discuss studies contemporary to this expert recommendation. After an extensive search of medical databases, 8 studies that evaluated therapeutic treatments for CVS were identified. Amitriptyline and cyproheptadine remain the standard of care for prophylaxis. Nutritional supplements such as carnitine and coenzyme Q10 have shown efficacy in decreasing episodes and severity in small studies with high tolerability among patients. The combination of ondansetron and sumatriptan are recommended for abortion of an acute vomiting episode, but other agents such as aprepitant and sedative agents can be considered when vomiting is refractory to initial treatments.

Antimicrobial Prophylaxis and Anticoagulation Therapy in Pediatric ECMO: A Survey Study

OBJECTIVE The purpose was to characterize antimicrobial and anticoagulation therapies used in health systems with children receiving extracorporeal membrane oxygenation (ECMO). METHODS An anonymous electronic survey assessing health system demographics and antimicrobial and anticoagulation therapies during ECMO was distributed to the American College of Clinical Pharmacy Pediatric Practice and Research Network and the Pediatric Pharmacy Association Critical Care Special Interest Group. The primary objective was to identify the number of respondents using antimicrobial prophylaxis for ECMO cannulation and ECMO runs. Secondary objectives included the first- and second-line anticoagulants and anticoagulation laboratory parameters. Additionally, the antimicrobial regimens and the dosing and administration of antithrombin III (AT III) with systemic anticoagulation were collected. Descriptive statistics were employed. RESULTS The questionnaire was completed by 38 respondents from 33 health systems; respondents practiced in the pediatric ICU (n = 20; 52.6%), cardiovascular ICU (n = 14; 36.8%), and neonatal ICU (n = 4; 10.5%). Twenty-eight (73.6%) respondents use antimicrobial prophylaxis during ECMO cannulation or ECMO runs, with most units using cefazolin monotherapy. Thirty-five (92.1%) respondents use heparin as the first-line anticoagulant and used a variety of laboratory tests including anti-factor Xa, activated clotting time, and activated partial thromboplastin time. The most common second-line anticoagulant was bivalirudin (n = 24; 63.2%). Thirty-six (94.7%) respondents use AT III with heparin, with most patients receiving AT III dosing calculated based on a formula for the desired AT III concentration. CONCLUSIONS The majority of respondents use antimicrobial prophylaxis, but variations in the regimens were noted. Heparin was the most common anticoagulant, but variations in laboratory monitoring and concomitant use of AT III were found.

Eculizumab Use in a Temporarily Dialysis-Dependent Patient With Shiga Toxin–Producing Escherichia Coli Hemolytic Uremic Syndrome With Neurological Complications

Shiga toxin–producing Escherichia coli hemolytic uremic syndrome (STEC-HUS) is the most common cause of acute renal failure in children, and it is associated with thrombocytopenia and hemolytic anemia. Although this disease primarily affects the kidney, it can also contribute to cellular damage in other organ systems, such as the CNS. Eculizumab is a monoclonal antibody that binds to complement proteins to prevent complement-mediated intravascular hemolysis in atypical HUS. In STEC-HUS, complement activation also occurs by Shiga toxin, and previous cases of eculizumab use in the setting of neurological involvement have been shown to be successful. We report the successful use of eculizumab in the setting of typical STEC-HUS–induced neurological symptoms including seizure, altered mental status, and left arm weakness. The patient also experienced concomitant renal failure requiring dose adjustment for hemodialysis. Following 2 doses of eculizumab, our patient was discharged to an inpatient rehabilitation facility with resolution of her renal injury, seizures, and altered mentation without adverse effects from eculizumab throughout the admission. Based on our case study, it appears that eculizumab may be given during or between hemodialysis without dose adjustment.

Teriparatide Therapy in a 4-Month-Old With Severe Hypoparathyroidism

Teriparatide is a human parathyroid hormone analog approved for the treatment of osteoporosis in adult patients. Its use for hypocalcemia and hypoparathyroidism in the pediatric population is described through case reports and small case series; however, larger studies that demonstrate long-term efficacy and safety are limited. At our institution, a 4-month-old premature (gestational age: 32 weeks) infant with multiple congenital anomalies, functional athymia, and severe hypoparathyroidism and receiving calcitriol, vitamin D, and calcium carbonate supplementation was initiated on subcutaneous injection of teriparatide. During the course of treatment, her calcium carbonate, vitamin D, and calcitriol supplementation requirements substantially decreased. Teriparatide effectively increased serum ionized calcium concentrations and decreased serum phosphorus concentrations in the present case-study over a 6-month period. Teriparatide was well tolerated, and no evidence of hypercalcemia was observed throughout treatment.

Trends and Costs Associated With the Diagnosis and Treatment of Infantile Spasms: A 10-Year Multicenter Retrospective Review

OBJECTIVE Early treatment of infantile spasms (IS) may be imperative for improvement of neurodevelopmental outcomes. Existing studies have led to inconclusive recommendations with variation in treatment. Our objective was to determine the national average cost, initial diagnostic workup, treatments, and hospital length of stay for patients with IS. METHODS This retrospective cohort study was designed to review data of patients < 2 years from 43 non-profit institutions. Data obtained included patient demographics, length of stay, admission cost, and treatments used from 2004 to 2014. Cost data were collected and adjusted to 2014 dollars, the year data were analyzed. RESULTS A total of 6183 patients met study criteria (n = 3382, 55% male). Three-quarters of patients (n = 4684, 76%) had an electroencephalogram, 56.4% had brain imaging (n = 3487), and 17% (n = 1050) underwent a lumbar puncture. Medication for IS was initiated during inpatient hospital stay in two-thirds of all patients (n = 4139, 67%). Most patients were initiated on corticotropin (n = 2066, 33%) or topiramate (n = 1804, 29%). Average length of stay was 5.8 days with an average adjusted cost of $18,348. Over time there was an 86.6% increase in cost from an average $12,534.54 (2004) to $23,391.20 (2014), a significant change (p < 0.01). This correlated with an increase in average length of stay. CONCLUSIONS Variability exists in diagnostic workup and pharmacotherapy initiated for IS, which may lead to differences in the cost of hospital stay. Further studies may help determine contributing factors to increased cost and improve health care utilization for IS patients.

Comparison of Timing to Develop Anti-Drug Antibodies to Infliximab and Adalimumab Between Adult and Pediatric Age Groups, Males and Females

OBJECTIVE To compare the timing of serum anti-drug antibodies in adult and pediatric age groups, males and females, treated for inflammatory bowel disease or arthritis with adalimumab or infliximab by retrospectively combining data collected during a 2-year therapeutic drug monitoring period. METHODS Four hundred thirty sera were divided in groups collected at 0, 3, 6, 12, and 24 months (T0, T3, T6, T12, and T24) after initiation of therapy and assayed for drug and relative anti-drug antibodies levels. At each time point, the percentage of sera presenting anti-drug antibodies, as well as the drug concentrations, were calculated and correlated with patient age and sex. RESULTS Anti-drug antibodies were present in 31.5% of sera and were significantly higher in the pediatric age group than in the adult age group, through all time points. The percentages of sera showing anti-drug antibodies were significantly different as early as 3 months and were sera from pediatric female group. The percentages of sera showing anti-drug antibodies reached the highest value at 6 months in the pediatric age group and at 12 months in the adult age group. CONCLUSIONS Sera from pediatric had an earlier presence of anti-drug antibodies than adults. In particular, pediatric females sera showed the fastest anti-drug antibodies development.

The Effect of Rapid Initiation Versus Delayed Initiation of Antibiotics in Pediatric Patients With Sepsis

OBJECTIVE The purpose of this study was to determine if administration of antibiotics within 1 hour of meeting sepsis criteria improved patient outcomes versus antibiotics administered greater than 1 hour after meeting sepsis criteria in pediatric patients. The Surviving Sepsis Campaign's international guidelines recommend appropriate antimicrobial therapy be administered within 1 hour of recognition of severe sepsis or septic shock. Data regarding outcomes in pediatric patients with sepsis regarding antibiotic timing are currently limited. METHODS This was a retrospective chart review of 69 pediatric patients admitted between July 1, 2013, and June 30, 2016, with a diagnosis of sepsis. RESULTS The primary outcome of in-hospital mortality was 7.1% in the within 1 hour group versus 14.6% in the greater than 1 hour group (p = 0.3399). Median hospital length of stay was significantly shorter in the within 1 hour group (15.4 versus 39.2 days, p = 0.0022). Median intensive care unit length of stay was also significantly shorter in the within 1 hour group (3.1 versus 33.6 days, p = 0.0191). There were no differences between groups for pediatric intensive care unit admission, end organ dysfunction, time to intubation, or time on the ventilator. CONCLUSIONS Pediatric patients who receive antimicrobial therapy within 1 hour of meeting sepsis criteria had improved hospital and intensive care unit length of stay. This study supports the Surviving Sepsis Guidelines recommendation to administer antibiotics within 1 hour in pediatric patients with sepsis or septic shock.

Antifungal Prophylaxis With Posaconazole in Immunocompromised Children Younger Than 13 Years

OBJECTIVE Prophylaxis with posaconazole (PP) is effective in the prevention of invasive fungal infections in immunocompromised adult patients. However, evaluation of its effectiveness and safety in children is limited. The aim of the study was to describe the use of posaconazole as antifungal prophylaxis in children. METHODS We reviewed the medical records of immunocompromised patients younger than 13 years with hematologic diseases and post hematopoietic stem cell transplant (HSCT) who received antifungal PP at the Instituto Nacional de Salud del Niño San Borja (INSN-SB) in Lima, Peru, from January 2014 to December 2018. RESULTS Fifty-six courses of PP were identified in 47 patients with a median age of 7.5 years (IQR, 4–10), 51.6% (n = 24) of whom were female. The main underlying medical conditions were aplastic anemia (n = 19, 33.9%), acute lymphoblastic leukemia (n = 18, 32.1%), acute myeloid leukemia (n = 14, 25.0%), and 34.1% had undergone HSCT. The median dose of posaconazole was 13.62 mg/kg/day (IQR, 12.0–16.8), and the median duration of PP was 24 days (IQR, 16–82). Gastrointestinal symptoms included abdominal pain (17.9%), nausea (16.1%), diarrhea (7.1%), and vomiting (3.6%). Elevated alanine aminotransferase and aspartate aminotransferase levels were observed in 9/35 patients (25.7%) and 10/51 (19.6%) patients, respectively. Five cases of breakthrough fungal infection were identified (8.9%). CONCLUSIONS Patients younger than 13 years who received PP showed an increase in transaminase values, and the development of breakthrough fungal infections.