bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Age and Weight-Based Dosing of Enoxaparin on Anti-Factor Xa Levels In Pediatric Patients
Authors: Fung Lela S. , Klockau Christopher
Published: October 2020

OBJECTIVE

The objective of this dose range study is to expand on the relationship between age and weight-based doses of enoxaparin and resulting levels of anti-factor Xa (anti-Xa) in pediatric patients. The primary outcome of this study is to determine the average dose of enoxaparin required to produce a therapeutic effect. Secondary outcomes include the number of enoxaparin dose changes required to achieve a therapeutic level of anti-Xa in each age group, the success rates of achieving and maintaining therapeutic anti-Xa levels, and the effect of serum antithrombin concentrations on anti-Xa levels. The study will also determine whether different dispensed concentrations of enoxaparin play a role in achieving therapeutic levels of anti-Xa.

METHODS

Single center, retrospective chart review. Patients were excluded from the study if they were older than 18 years of age, were receiving enoxaparin for prophylactic purposes, had a creatinine clearance < 30 ml/min/1.73m2, and if no anti-factor Xa levels were drawn.

RESULTS

Average enoxaparin doses required for therapeutic levels of anti-factor Xa were 1.8 mg/kg for patients <1 month, 1.64 mg/kg (1 month to 1 year), 1.45 mg/kg (1 to 6 years), and 1.05 mg/kg (>6 years of age). An average of 3.24 dose changes was required for neonates to achieve therapeutic levels anti-factor Xa. The success rates for achieving and maintaining therapeutic levels were both 41%. Patients with low serum antithrombin levels were more likely to have low anti-Xa levels than those with normal or high values, 52% vs 40% vs 18%, respectively. Patients receiving diluted concentrations, 10 or 20 mg/mL, experienced lower anti-Xa levels than patients who received the standard manufactured concentration of 100 mg/mL, 61% vs 33%.

CONCLUSION

Based on this dose-range study, enoxaparin should be initiated at larger doses than recommended by the current guidelines to promptly achieve therapeutic anti-Xa levels. Doses should be divided into three age groups instead of two as currently suggested in the guidelines. To increase the likelihood of achieving therapeutic levels, the commercially available enoxaparin product should not be diluted if possible.
Pharmacists' Attitudes Towards Pediatric Cough and Cold Products and Behind the Counter Status
Authors: Huston Sally A. , Porter Kalen B. , Clements Tom , Shepherd Greene
Published: October 2020

BACKGROUND

Safety and efficacy issues regarding over-the-counter cough and cold (CAC) products for use in children have surfaced. Late in 2007 the FDA began reviewing CAC product status for use in children under 6 years old.

OBJECTIVE

In regards to CAC products for children < 6 years old, to determine pharmacists: 1) comfort level in recommending; 2) attitudes towards behind-the-counter (BTC) status; and 3) level of support for BTC status. An additional objective was to determine how frequently pharmacists were asked for CAC product recommendations for children

METHODS

Georgia Pharmacy Association members (2,045) were invited to anonymously participate in a self-administered online survey from January 3 – Feb 6, 2008. Topic areas included demographics, comfort in recommending CAC, and BTC status.

RESULTS

Most responding pharmacists (99.1%) feel pediatric CAC medicine safety problems are due to inappropriate use. More than 50% of chain and independent pharmacists were asked to recommend CAC medicines for children during cold/flu season once a day or less, and 79% reported counseling on less than 50% of total CAC sales. The majority of pharmacists felt comfortable recommending CAC medications when thinking of both safety and efficacy. Most pharmacists supported a BTC condition of sale for children under two for decongestants, antihistamines, and antitussives, and for decongestants and antitussives for children between 2 and 5 years old.

CONCLUSIONS

Most pharmacists indicate comfort in recommending CAC despite lack of evidence for safety or efficacy and support BTC status. Pharmacist education on this topic would be useful.
Stability of Ziprasidone Mesylate in an Extemporaneously Compounded Oral Solution
Authors: Green Kelsey , Parish Roy C.
Published: October 2020

OBJECTIVES

To formulate a liquid preparation of ziprasidone in a convenient concentration to allow dosing of less than 20 mg and of sufficient chemical and physical stability to enable an entire prescription or course of treatment to be prepared in a single batch.

METHODS

Geodon for injection (ziprasidone mesylate), 20 mg/mL, was diluted to 2.5 mg/mL in a commercially available sugar-free and alcohol-free, flavored syrup and stored at room temperature under ambient fluorescent light illumination, at room temperature in darkness, and under refrigeration. The ziprasidone content was measured in samples at various time intervals using a stability-indicating high-performance liquid chromatographic method.

RESULTS

When refrigerated, the ziprasidone syrup that was compounded in a commercially available, sugar-free and alcohol-free vehicle maintained at least 90% of stated potency for at least 6 weeks. Samples stored under other conditions were less stable, underscoring the manufacturer's labeling regarding refrigerated storage of the reconstituted injection.

CONCLUSIONS

The findings suggest that chemical and physical stability are maintained for 2 weeks under refrigeration, allowing the convenience of compounding for the long-term needs of a particular patient, rather than daily compounding. The only storage condition we recommend is refrigeration at 5°C.
Opioid Infusions in the Neonatal Intensive Care Unit
Authors: Suarez Amanda , Knoppert David C. , Lee David S. C. , Pletsch Donna , Seabrook Jamie A.
Published: October 2020

OBJECTIVES

The primary objective of this study was to compare the use of opioid infusions to that proposed in guidelines published in an in-house medication handbook. Secondary objectives were to assess the documented use of a standardized neonatal pain assessment tool and to describe the supplemental use of opioids concurrent with an opioid infusion.

METHODS

A retrospective chart review was performed for all patients in the NICU who received opioid infusions between November 1, 2005, and November 30, 2006. Data collected included patient characteristics, opioid infusion dosing and duration, supplemental opioid use, and pain assessment documentation.

RESULTS

Of the110 neonates who received morphine or fentanyl during the study period, 65 patients met inclusion criteria. Reasons for starting an opioid infusion included nonsurgical sedation and/or analgesia (51%), postoperative pain (17%), and procedural pain (1%). No reason was documented for 31% of patients. Thirtyeight percent of neonates received a loading dose of opioid before initiation of the infusion. The median dose was 100 mcg/kg (IQR=48.2) for morphine and and 1 mcg/kg (IQR=0.8) for fentanyl. The mean ± SD starting rates of morphine and fentanyl infusions were 12.3 ± 4.7 mcg/kg/hr and 1.5 ± 1.7 mcg/kg/hr, respectively. Supplemental opioid doses were given to 46% of neonates during the infusion period. Supplemental doses were given for procedures (69%) and pain/agitation/sedation (26%). No reason was documented for 5% of patients. The Neonatal Pain, Agitation and Sedation Scale scores were only documented 9% of the time for each day that the patient received an opioid infusion.

CONCLUSIONS

Dosing of opioids generally was within the recommendations that are described in the in-house medication handbook. A substantial percentage of neonates received supplemental opioid doses while on opioid infusions, mostly for procedural pain management. Documentation of the reason for using opioid infusions and the assessment of neonatal pain was poor.
Pharmacokinetics and Drug Dosing in Obese Children
Authors: Kendrick Jennifer G. , Carr Roxane R. , Ensom Mary H. H.
Published: October 2020

OBJECTIVES

To review pharmacokinetics in obese children and to provide medication dosing recommendations.

METHODS

EMBASE, MEDLINE, and International Pharmaceutical Abstracts databases were searched using the following terms: obesity, morbid obesity, overweight, pharmacokinetics, drug, dose, kidney function test, creatinine, pediatric, and child.

RESULTS

We identified 10 studies in which the authors examined drug dosing or pharmacokinetics for obese children. No information was found for drug absorption or metabolism. Obese children have a higher percent fat mass and a lower percent lean mass compared with normal-weight children. Therefore, in obese children, the volume of distribution of lipophilic drugs is most likely higher, and that of hydrophilic drugs is most likely lower, than in normal-weight children. Serum creatinine concentrations are higher in obese than normal-weight children. Total body weight is an appropriate size descriptor for calculating doses of antineoplastics, cefazolin, and succinylcholine in obese children. Initial tobramycin doses may be determined using an adjusted body weight, although using total body weight in the context of monitoring serum tobramycin concentrations would also be an appropriate strategy. We found no information for any of the opioids; antibiotics such as penicillins, carbapenems, vancomycin, and linezolid; antifungals; cardiac drugs such as digoxin and amiodarone; corticosteroids; benzodiazepines; and anticonvulsants. In particular, we found no information about medications that are widely distributed to adipose tissue or that can accumulate there.

CONCLUSIONS

The available data are limited because of the small numbers of participating children, study design, or both. The number and type of drugs that have been studied limit our understanding of the pharmacokinetics in obese children. In the absence of dosing information for obese children, it is important to consider the nature and severity of a child's illness, comorbidities, organ function, and side effects and physiochemical properties of the drug. Extrapolating from available adult data is possible, as long as practitioners consider the effects of growth and development on the pharmacokinetics relevant to the child's age.
Computerized Orders with Standardized Concentrations Decrease Dispensing Errors of Continuous Infusion Medications for Pediatrics
Authors: Sowan Azizeh K. , Vaidya Vinay U. , Soeken Karen L. , Hilmas Elora
Published: October 2020

OBJECTIVES

The use of continuous infusion medications with individualized concentrations may increase the risk for errors in pediatric patients. The objective of this study was to evaluate the effect of computerized prescriber order entry (CPOE) for continuous infusions with standardized concentrations on frequency of pharmacy processing errors. In addition, time to process handwritten versus computerized infusion orders was evaluated and user satisfaction with CPOE as compared to handwritten orders was measured.

METHODS

Using a crossover design, 10 pharmacists in the pediatric satellite within a university teaching hospital were given test scenarios of handwritten and CPOE order sheets and asked to process infusion orders using the pharmacy system in order to generate infusion labels. Participants were given three groups of orders: five correct handwritten orders, four handwritten orders written with deliberate errors, and five correct CPOE orders. Label errors were analyzed and time to complete the task was recorded.

RESULTS

Using CPOE orders, participants required less processing time per infusion order (2 min, 5 sec ± 58 sec) compared with time per infusion order in the first handwritten order sheet group (3 min, 7 sec ± 1 min, 20 sec) and the second handwritten order sheet group (3 min, 26 sec ± 1 min, 8 sec), (p<0.01). CPOE eliminated all error types except wrong concentration. With CPOE, 4% of infusions processed contained errors, compared with 26% of the first group of handwritten orders and 45% of the second group of handwritten orders (p<0.03). Pharmacists were more satisfied with CPOE orders when compared with the handwritten method (p=0.0001).

CONCLUSIONS

CPOE orders saved pharmacists' time and greatly improved the safety of processing continuous infusions, although not all errors were eliminated. pharmacists were overwhelmingly satisfied with the CPOE orders
Once-Daily Amoxicillin for Pharyngitis
Authors: Andrews Megan , Condren Michelle
Published: October 2020

A once-daily antibiotic regimen for group A β-hemolytic streptococcal pharyngitis (GABHS) could improve compliance and be effective in the prevention of rheumatic fever, a dangerous complication of untreated or poorly treated GABHS. Amoxicillin is ideal for once-daily dosing due to its low cost. Azithromycin, cefadroxil, ceftibuten, cefixime and extended release amoxicillin are also FDA approved to treat GABHS once daily; however, even when taken for short courses, these antibiotics are more expensive compared with a oncedaily dosing of conventional amoxicillin for 10 days. The American Heart Association recently recommended once-daily amoxicillin dosing when treating GABHS, and amoxicillin has been proven to be effective when dosed once daily, with no obvious disadvantage compared with twice-daily dosing or with conventional penicillin treatment 3 to 4 times daily.
The Use of Daptomycin and Linezolid to Treat Vancomycin-Intermediate Staphylococcus haemolyticus Infection in a Premature Infant
Authors: Porter Kalen B. , Lynch Bethany , Mani Chitra S.
Published: October 2020

Infections with staphylococcal species, especially coagulase-negative staphylococci are common after neurosurgical procedures. We report a case of a coagulase-negative staphylococci infection of a ventricular shunt site in a 105-day-old, premature infant born at 25 weeks gestation with multiple medical problems. The patient was successfully treated with a combination of daptomycin and linezolid for the persistent infection, which was increasingly resistant to vancomycin. The patient was initially treated with a combination of vancomycin and rifampin; however, the course of therapy had to be changed when the bacteria was identified as having intermediate resistance to vancomycin. Therapy was initially changed to linezolid monotherapy, but culture results continued to be positive for the bacteria, necessitating removal of an external ventricular drain and combination therapy of daptomycin and linezolid for 2 weeks before insertion of a new ventricular shunt. The patient received 4 weeks of therapy with no further positive results of the culture analysis. To our knowledge, this is the first published case report of the use of daptomycin to successfully treat a central nervous system infection in a premature infant.
Nebulized Furosemide in the Treatment of Bronchopulmonary Dysplasia in Preterm Infants
Authors: Sahni Jasmine , Phelps Stephanie J.
Published: October 2020

Bronchopulmonary dysplasia (BPD) is a chronic pulmonary disease commonly seen in preterm infants who require supplemental oxygen and/or assisted mechanical ventilation. BPD, a major cause of morbidity and mortality among premature infants, occurs in 5,000 to 10,000 premature infants in the United States each year. Despite numerous medical advances, no single intervention will prevent or treat BPD; hence, premature infants have an increased risk for developing significant sequelae that affect both cognitive and motor function. This article provides a brief overview of BPD and reviews the available literature regarding the safe and effective use of nebulized furosemide in the treatment of this disorder.
Dosing Evaluation of Continuous Intravenous Fentanyl Infusions in Overweight Children: A Pilot Study
Authors: Gish Emily C. , Harrison Donald , Gormley Andrew K. , Johnson Peter N.
Published: October 2020

OBJECTIVES

The purpose of this study was to assess the appropriateness of weight-based dosing of continuous intravenous infusion of fentanyl in overweight/obese versus normal-weight children admitted to the pediatric intensive care unit (PICU).

METHODS

This retrospective, pilot study included 5- to 12-year-old children admitted to the PICU over a 2-year period who received continuous intravenous infusion fentanyl for ≥ 4 days. The overweight/obese group included children with a body mass index (BMI) ≥ 85th percentile, while the control group included children with BMI < 85th percentile. The primary objective was to compare the number of fentanyl continuous intravenous infusion dosage changes required per day to achieve adequate sedation between groups. Secondarily, opioid withdrawal symptoms following the discontinuation of fentanyl and concomitant sedative/analgesic regimens were analyzed between groups. Student t tests and chi-square analyses were performed as appropriate, with an a priori alpha of p≤0.05.

RESULTS

Sixteen normal-weight and 15 overweight/obese patients with 18 and 16 individual infusions were identified, respectively. No statistical difference was found between groups for the number of dosage changes per day, 0.92 versus 0.69 (p=0.16). Five patients in each group experienced withdrawal (p=0.71). The total number of concomitant bolus doses received was greater in the overweight/obese group but did not reach statistical significance.

CONCLUSIONS

There was a numerical, but statistically nonsignificant difference in the number of sedative/analgesic bolus doses and dosing changes per day between groups. Larger studies are warranted to determine the optimal dosing strategy for continuous intravenous infusion fentanyl in overweight/obese children.
Dexmedetomidine as Part of Balanced Anesthesia Care in Children With Malignant Hyperthermia Risk and Egg Allergy
Authors: Dewhirst Elisabeth , Naguib Aymen , Tobias Joseph D.
Published: October 2020

Malignant hyperthermia is an acute hypermetabolic crisis triggered in susceptible patients by the administration of succinylcholine or a volatile anesthetic agent. When anesthesia care is provided to malignant hyperthermia-susceptible patients, a total intravenous anesthesia technique with propofol is frequently chosen. However, coexisting allergies to egg and soybeans may contraindicate the use of propofol. We present our experience with the use of dexmedetomidine as part of the anesthesia regimen in 3 patients with family histories of malignant hyperthermia and personal histories of egg or soybean allergies. In 2 patients, dexmedetomidine was used as part of a general anesthesia regimen and for sedation during spinal anesthesia in the third patient. Previous reports of the use of dexmedetomidine in patients susceptible to malignant hyperthermia are reviewed, and its benefits in such patients are discussed.
Using a Trigger Tool to Assess Adverse Drug Events in a Children's Rehabilitation Hospital
Authors: Burch Kelly J.
Published: October 2020

INTRODUCTION

Some of the most common actions after an adverse drug event (ADE) have been carefully listed, studied, and described as “triggers.” Trigger-based tools for finding and evaluating ADEs have been validated in varied patient populations. A recent article described the frequency and severity of ADEs in hospitalized children in tertiary care children's hospitals. Our objective was to discover whether children in a pediatric rehabilitation setting are at higher risk for ADEs because of polypharmacy, or at a lower risk because of relative overall clinical stability.

METHODS

A pediatric inpatient trigger tool was used in 3 groups of children hospitalized in a pediatric rehabilitation setting. ADE frequencies and patient characteristics were compared with values from a multicenter study using the same tools in pediatric tertiary care hospitals. Changes in ADE frequency over time were assessed (2005, n=20; 2006, n=20; 2008, n=19).

RESULTS

No serious ADEs were newly discovered using the trigger tool. Nearly all of the ADEs (16 of 17) discovered by the trigger tool had not been voluntarily reported to the hospital's event reporting program. ADE frequencies expressed per patient were higher than those seen in tertiary care children's hospitals. Longer lengths of stay resulted in lower ADE frequencies when expressed per day. ADE frequency increased in the institution over time, reflecting increases in the acuity and complexity of patients cared for at this facility. Many ADEs affected bowel frequency.

CONCLUSIONS

Systematic chart review using a trigger tool discovered ADEs that had not been voluntarily reported or evaluated. ADEs in pediatric rehabilitation patients occurred less often than those in tertiary pediatric care when expressed as rates per day, but were more frequent when expressed per patient or per medication. Types and severity of ADEs in pediatric rehabilitation can guide monitoring and attention to specific areas of care.
Safety and Population Pharmacokinetic Analysis of Intravenous Acetaminophen in Neonates, Infants, Children, and Adolescents With Pain or Fever
Authors: Zuppa Athena F. , Hammer Gregory B. , Barrett Jeffrey S. , Kenney Brian F. , Kassir Nastya , Mouksassi Samer , Royal Mike A.
Published: October 2020

OBJECTIVES

The administration of acetaminophen via the oral and rectal routes may be contraindicated in specific clinical settings. Intravenous administration provides an alternative route for fever reduction and analgesia. This phase 1 study of intravenous acetaminophen (Ofirmev, Cadence Pharmaceuticals, Inc., San Diego, CA) in inpatient pediatric patients with pain or fever requiring intravenous therapy was designed to assess the safety and pharmacokinetics of repeated doses over 48 hours.

METHODS

Neonates (full-term to 28 days) received either 12.5 mg/kg every 6 hours or 15 mg/kg every 8 hours. Infants (29 days to <2 years), children (2 to <12 years) and adolescents (≥12 years) received either 12.5 mg/kg every 4 hours or 15 mg/kg every 6 hours. Both noncompartmental and population nonlinear mixed-effects modeling approaches were used. Urinary metabolite data were analyzed, and safety and tolerability were assessed.

RESULTS

Pharmacokinetic parameters of acetaminophen were estimated using a two-compartment disposition model with weight allometrically expressed on clearances and central and peripheral volumes of distribution (Vds). Postnatal age, with a maturation function, was a significant covariate on clearance. Total systemic normalized clearance was 18.4 L/hr per 70 kg, with a plateau reached at approximately 2 years. Total central and peripheral Vds of acetaminophen were 16 and 59.5 L/70 kg, respectively. The drug was well tolerated based on the incidence of adverse events. The primary and minor pathways of elimination were acetaminophen glucuronidation, sulfation, and glutathione conjugate metabolites across all age groups.

CONCLUSIONS

Intravenous acetaminophen in infants, children, and adolescents was well tolerated and achieved plasma concentrations similar to those achieved with labeled 15 mg/kg body weight doses by oral or rectal administration.
Heparin-Induced Thrombocytopenia in the Pediatric Population: A Review of Current Literature
Authors: Vakil Niyati H , Kanaan Abir O , Donovan Jennifer L
Published: October 2020

Heparin-induced thrombocytopenia is a rare and serious reaction to unfractionated heparin and low-molecular-weight heparins in children. Quick recognition, discontinuation of heparin, and subsequent treatment with an alternative anticoagulant are essential steps to prevent serious complications such as thrombus and limb amputation. The purpose of this review is to describe the clinical features of heparin-induced thrombocytopenia in children and to summarize the data available for its management. This paper summarizes data and relates the use of direct thrombin inhibitors with clinical outcomes. A literature search was conducted with Ovid, using the key terms argatroban, bivalirudin, hirulog, danaparoid, lepirudin, direct thrombin inhibitor, heparin-induced thrombocytopenia, thrombosis, warfarin, and fondaparinux. Articles were excluded if they were classified as editorials, review articles, or conference abstracts or if they involved patients 18 years of age or older or described disease states not related to thrombosis. Nineteen articles containing 33 case reports were identified and evaluated for this review. Of the 33 cases, 14, 10, 4, and 2 cases described the use of lepirudin, danaparoid, argatroban, and bivalirudin, respectively. Two cases did not report the type of anticoagulant used, and 1 case used aspirin. The most commonly reported complication was bleeding.
Decrease in Therapeutic Errors Involving Prescription Cough and Cold Medications in Young Children
Authors: Doyon Suzanne , Tra Yolande , Klein-Schwartz Wendy
Published: October 2020

OBJECTIVES

This study sought to determine whether an increase in therapeutic errors involving prescription cough and cold medications (CCM) reported to poison centers was observed following the October 2007 voluntary withdrawal of over-the-counter CCM.

METHODS

Analysis of therapeutic errors involving prescription CCM in children under 2 years of age for the 33 months before and the 27 months after the October 2007 withdrawal.

RESULTS

Total counts of therapeutic errors involving prescription CCM in children under 2 years of age decreased from 452 to 337 per year. Rates of therapeutic errors decreased from 0.43 cases/100,000 person-month prewithdrawal to 0.32 postwithdrawal, a 25.6% decrease (p<0.0001).

CONCLUSIONS

An increase in harm as measured by the number of poison center calls for therapeutic errors involving prescription CCM was not observed in the 27-month time period after the withdrawal. A significant decrease in therapeutic errors involving these products is reported.
Management of Patients With Cystic Fibrosis and Allergic Bronchopulmonary Aspergillosis Using Anti-Immunoglobulin E Therapy (Omalizumab)
Authors: ElMallah Mai K , Hendeles Leslie , Hamilton Robert G , Capen Cindy , Schuler Pamela M
Published: October 2020

Omalizumab is a recombinant DNA-derived humanized immunoglobulin G (IgG) anti-IgE monoclonal antibody approved for use in patients with allergic asthma. However, it is not approved for allergic bronchopulmonary aspergillosis (ABPA). Conflicting reports exist about the effects of omalizumab on ABPA in patients with cystic fibrosis (CF). We report 2 patients with CF treated with omalizumab, in whom frequency of ABPA exacerbations was markedly reduced with treatment. Additionally, hospitalizations were reduced from 5 per year to once in 18 months in the first patient and from twice to once per year in the second patient. Free IgE decreased by 87.9% after 6 months of therapy in the first patient and by 95.6% after 7 months of therapy in the second patient. Neither of the two patients had evidence of asthma. Omalizumab may be useful in treating ABPA in patients with CF, and including free IgE in monitoring the response to therapy will be helpful.
Medication Preparation in Pediatric Emergencies: Comparison of a Web-Based, Standard-Dose, Bar Code–Enabled System and a Traditional Approach
Authors: Damhoff Heather N. , Kuhn Robert J. , Baker-Justice Stephanie N.
Published: October 2020

OBJECTIVES: Increased acuity within the pediatric emergency department increases the risk of medication-related adverse events, despite the availability of validated dosing references. The eBroselow system is a standardized, web-based, bar code–enabled dosing system that eliminates the need for mathematic calculations. This study was designed to assess the accuracy of the eBroselow system and the time needed to prepare medications during pediatric simulated resuscitations compared with standard dosing references.

METHODS: This is a two-treatment, two-period crossover trial in which 13 nurses from the adult emergency department who had had pediatric advanced life support training within the previous 3 years, carried out medication dosing during pediatric code simulations. Nurses were randomized to the eBroselow system or to traditional dosing references during period one and transitioned to the opposite treatment group during period two.

RESULTS: Use of the eBroselow system resulted in a 24.6% increase in the accuracy of prepared medications, with a complete elimination of clinically significant errors (those ≥20% deviation from the recommended dose). In addition, on average, medications were prepared 8 minutes faster with the eBroselow system versus standard dosing references.

CONCLUSIONS: Use of the eBroselow system, a standardized, bar code–based, electronic medication dosing reference, increased the accuracy of medication doses prepared during pediatric code simulations by nearly 25%, with no errors being considered clinically significant.
Hypersensitivity Reaction After Inhalation of a Lactose-Containing Dry Powder Inhaler
Authors: Robles Janie , Motheral Lesley
Published: October 2020

Milk protein allergy–induced reactions from lactose-containing dry powder inhalers (DPIs) have not been widely described in the literature. Lactose is a common inactive ingredient in many pharmaceutical products that is used to enhance the stability of active substances in medicinal products, including asthma medications. Contamination of lactose with milk proteins has been identified in reports of inhaled corticosteroid product lot testing. Serious respiratory sequelae may follow after the inhalation of a DPI corticosteroid in a patient with milk protein allergy because DPIs that contain lactose may be contaminated with milk proteins. Lactose-containing DPIs are contraindicated in patients with milk protein allergy. Although manufacturers identify this contraindication in product package inserts, some drug references may not include this information and health care professionals may lack awareness. Clinicians should consider reviewing multiple medication resources for warnings and contraindications of medications to prevent complications. We describe a refractory asthma exacerbation secondary to a hypersensitivity reaction following administration of a lactose-containing DPI corticosteroid and long-acting β2 agonist combination in a child with a milk protein allergy.
Propylene Glycol Toxicity in Children
Authors: Lim Terri Y. , Poole Robert L. , Pageler Natalie M.
Published: October 2020

Propylene glycol (PG) is a commonly used solvent for oral, intravenous, and topical pharmaceutical agents. Although PG is generally considered safe, when used in high doses or for prolonged periods, PG toxicity can occur. Reported adverse effects from PG include central nervous system (CNS) toxicity, hyperosmolarity, hemolysis, cardiac arrhythmia, seizures, agitation, and lactic acidosis. Patients at risk for toxicity include infants, those with renal or hepatic insuficiency, epilepsy, and burn patients receiving extensive dermal applications of PG containing products. Laboratory monitoring of PG levels, osmolarity, lactate, pyruvate, bicarbonate, creatinine, and anion gap can assist practitioners in making the diagnosis of PG toxicity. Numerous studies and case reports have been published on PG toxicity in adults. However, very few have been reported in pediatric patient populations. A review of the literature is presented.
Medication Adsorption into Contemporary Extracorporeal Membrane Oxygenator Circuits
Authors: Harthan Aaron A. , Buckley Klayton W. , Heger Margaret L. , Fortuna Randall S. , Mays Kyle
Published: October 2020

OBJECTIVE: This study was conducted to evaluate the amount of medication adsorbed into extracorporeal membrane oxygenation (ECMO) circuits with a polymethylpentane membrane oxygenator and heparin-coated polyvinyl chloride tubing.

METHODS: An ECMO circuit with the aforementioned components was set up ex vivo and primed with expired blood. Midazolam, lorazepam, morphine, and fentanyl were administered to the circuit. Fifteen minutes after medication administration, 60 mL of blood were removed and stored in a 60-mL syringe to serve as a control. Medication levels were drawn from the ECMO circuit (test) and control syringe (control) 15 minutes, 24 hours, and 48 hours after the medications were administered. ECMO circuit medication levels were compared to their corresponding syringe control medication levels. Descriptive statistics were used to determine the percentage of medication remaining in the blood and compare it to the control value.

RESULTS: Except for morphine, there was a large decline in medication levels over the 48-hour period. Compared to control values, 17.2% of midazolam, 41.3% of lorazepam, 32.6% of fentanyl, and 102% of morphine remained in the ECMO circuit.

CONCLUSION: Despite the use of newer components in ECMO circuits, a large quantity of medication is adsorbed into the ECMO circuit. Midazolam, lorazepam, and fentanyl all showed reductions in medication levels greater than 50%. Morphine may have advantages for patients on ECMO, as its concentration does not appear to be affected.
Evaluation of Off-label Prescribing at a Children's Rehabilitation Center
Authors: Luedtke Kyle E. , Buck Marcia L.
Published: October 2020

OBJECTIVE: This study was developed to evaluate the incidence of off-label prescribing at a pediatric rehabilitation center. Secondary objectives were to describe the medications, patient age groups, and diagnoses most often associated with off-label prescribing.

METHODS: This was a prospective observational study conducted at an academic, inpatient children's rehabilitation center from November 11, 2011, to April 1, 2012. Patients younger than 16 years of age who received at least 1 prescription medication were included. Data were collected from the patients' electronic medical records.

RESULTS: A total of 240 medications orders were placed during the study, with 57% written off-label. Thirty-five patients (88%) received at least 1 off-label medication. Forty-nine percent of the orders were for patients younger than the approved range, with 48% written for an unapproved indication, 2% for an alternative route of administration, and 1% for an unapproved age and indication. Children 2 to 12 years of age received 40% of the off-label orders, followed by adolescents with 37%. The therapeutic classes most often prescribed off-label were central nervous system agents and anti-infectives.

CONCLUSION: Off-label prescribing was found in the majority of children receiving rehabilitative services, a rate as high or higher than that reported in pediatric acute care or clinic settings. The medications prescribed off-label most often were central nervous system agents, reflecting the need to study medications in the chronic rehabilitation population to optimize function in children with brain or spinal cord injury.
Hemolytic Anemia Following Rasburicase Administration: A Review of Published Reports
Authors: Nguyen Annhien P. , Ness Genevieve L.
Published: October 2020

Tumor lysis syndrome (TLS) is a potentially lethal complication of anticancer treatment. It is caused by the rapid death of malignant cells after initiation of cytotoxic therapy and is typically observed in patients with bulky or highly proliferative malignancies. Currently, rasburicase is one of the recommended therapies for this oncologic emergency. Although this drug is generally well tolerated among patients, there have been several reports of hemolytic anemia following rasburicase infusions. With drug-induced hemolytic anemia, the condition usually resolves shortly after the offending agent is discontinued. However, anemia that is prolonged or severe can lead to problems such as splenomegaly and rapid heart rate. This paper will review primary literature identified through PubMed, International Pharmaceutical Abstracts, and Embase concerning the incidence of hemolytic anemia with rasburicase use. From the available data, the occurrence of hemolytic anemia will be discussed.
Enteral Topiramate in a Pediatric Patient with Refractory Status Epilepticus: A Case Report and Review of the Literature
Authors: Shelton Chasity M. , Alford Elizabeth L. , Storgion Stephanie , Wheless James , Phelps Stephanie J.
Published: October 2020

We describe the use of topiramate in a healthy 12-year-old (88-kg) male who developed refractory generalized convulsive status epilepticus. Seizures persisted despite aggressive use of benzodiazepines (intravenous lorazepam; oral clorazepate), barbiturates (i.e., phenobarbital, pentobarbital), and hydantoins. The child's seizures were controlled with nasogastrically administered topiramate in doses up to 500 mg twice daily (11.4 mg/kg/day). The patient did not display any clinical or laboratory signs of metabolic acidosis while receiving topiramate. Topiramate should be considered as a treatment option in refractory status epilepticus.
Severe Malaria Complicated by G6PD Deficiency in a Pediatric Tanzanian Immigrant
Authors: Damhoff Heather N. , Kuhn Robert J. , Stadler Laura P.
Published: October 2020

Approximately 1,500 cases of malaria are diagnosed in the United States each year. Most cases are travelers and immigrants returning from parts of the world where malaria transmission occurs. Malaria is the most frequent cause of systemic febrile illness without localizing symptoms in travelers returning from the developing world, so vigilance by providers is needed when evaluating patients returning from areas in which malaria is endemic. Despite the availability of effective treatment, malaria still accounts for more than 1 million deaths per year worldwide, with rates being disproportionately high in young children under the age of 5. We present the case of a 4-year-old refugee who emigrated from Tanzania with severe malaria due to dual infections of Plasmodium falciparum and P. ovale, whose treatment course was complicated by quinidine gluconate cardiotoxicity and glucose-6-phosphate dehydrogenase deficiency.
Voriconazole Monitoring in Children with Invasive Fungal Infections
Authors: Tucker Lyn , Higgins Tara , Egelund Eric F. , Zou Baiming , Vijayan Vini , Peloquin Charles A.
Published: October 2020

OBJECTIVES: The primary objective of this study was to determine the optimal daily dose of voriconazole required to achieve therapeutic trough concentrations in children 1 month to 18 years of age. The secondary objective was to analyze the association between voriconazole trough concentrations and clinical and microbiological outcomes, toxicity, and mortality.

METHODS: This study was a retrospective chart review (October 2009 to August 2012) of pediatric oncology/bone marrow transplant patients with proven or probable invasive fungal infections treated with intravenous or oral voriconazole. Patients were excluded if they were older than 18 years of age, had no voriconazole concentrations drawn during the study period, or received voriconazole prior to the study period.

RESULTS: Thirty-four patients were reviewed; 11 patients met all criteria for inclusion. There were 6 males and 5 females, with a median age of 8 years (range: 0.8–14.8) and a median weight of 27 kg (range: 9–74). Doses were adjusted to a median 6 mg/kg/dose (range: 3–8.7 mg/kg/dose) given every 8 (n = 5) to 12 (n = 6) hours; dose regimens varied greatly. All but 1 child achieved a voriconazole trough concentration above 1 mg/L; 7 children had a trough concentration above 2 mg/L. The median time to achieve a therapeutic trough concentration was 11 days (range: 6–37 days). Therapy failed for 4 of 11 patients, including 3 of the 4 youngest patients (p=0.022). Three of the 4 for whom therapy failed also had voriconazole trough concentrations less than 2 mg/L; this did not reach statistical significance. Voriconazole therapy was discontinued in 2 patients due to toxicity.

CONCLUSIONS: This study confirmed that voriconazole pharmacokinetics vary greatly in pediatric oncology/bone marrow transplant patients. “Optimal” doses varied over nearly a 3-fold range. Younger patients may be at greater risk of poor outcomes and may require additional monitoring and dose adjustment.
Time to First Antimicrobial Administration After Onset of Sepsis in Critically Ill Children
Authors: Fusco Nicholas M. , Parbuoni Kristine A. , Morgan Jill A.
Published: October 2020

OBJECTIVES: Delay of antimicrobial administration in adult patients with severe sepsis and septic shock has been associated with a decrease in survival to hospital discharge. The primary objective of this investigation was to determine the time to first antimicrobial administration after the onset of sepsis in critically ill children. Secondary objectives included appropriateness of empiric antimicrobials and microbiological testing, fluid resuscitation during the first 24 hours after onset of sepsis, intensive care unit and hospital length of stay, and mortality.

METHODS: Retrospective, chart review of all subjects less than or equal to 18 years of age admitted to the pediatric intensive care unit (PICU) with a diagnosis of sepsis between January 1, 2011, and December 31, 2012.

RESULTS: A total of 72 subjects met the inclusion criteria during the study period. Median time to first antimicrobial administration by a nurse after the onset of sepsis was 2.7 (0.5–5.1) hours. Cultures were drawn prior to administration of antimicrobials in 91.7% of subjects and were repeated within 48 hours in 72.2% of subjects. Empiric antimicrobial regimens were appropriate in 91.7% of cases. The most common empiric antimicrobial regimens included piperacillin/tazobactam plus vancomycin in 19 subjects (26.4%) and ceftriaxone plus vancomycin in 15 subjects (20.8%). Median PICU length of stay was 129 (64.6–370.9) hours, approximately 5 days, and median hospital length of stay was 289 (162.5–597.1) hours, approximately 12 days. There were 4 deaths during the study period.

CONCLUSIONS: Time to first antimicrobial administration after onset of sepsis was not optimal and exceeded the recommendations set forth in international guidelines. At our institution, the process for treating pediatric patients with severe sepsis and septic shock should be modified to increase compliance with national guidelines.
A Review of the Treatment of Type 2 Diabetes in Children
Authors: Onge Erin St. , Miller Shannon A. , Motycka Carol , DeBerry Adrienne
Published: October 2020

The incidence of type 2 diabetes and obesity in children and adolescents has risen at staggering rates. Studies have shown that treating type 2 diabetes with oral medications in children may be more difficult than treating in adults. Compounding this problem is the fact that most of the medications available for treating type 2 diabetes have not been studied in children. Recently, the American Diabetes Association and the Pediatric Endocrine Society have collaborated to create a guideline for the treatment of type 2 diabetes in children. Similar to the treatment of adults with type 2 diabetes, metformin remains the mainstay of therapy along with diet and exercise. Adjunctive therapy should be based on the limited clinical evidence available as well as on patient preference. In order to avoid detrimental microvascular and macrovascular complications, patients, clinicians, and family members should work together to ensure adequate treatment of type 2 diabetes in children.
Characterization of Dexmedetomidine Dosing and Safety in Neonates and Infants
Authors: Estkowski Lauren M. , Morris Jennifer L. , Sinclair Elizabeth A.
Published: October 2020

OBJECTIVES: To describe and compare off-label use and cardiovascular (CV) adverse effects of dexmedetomidine in neonates and infants in the pediatric intensive care unit (PICU).

METHODS: Patients younger than 12 months with corrected gestational ages of at least 37 weeks who were receiving continuous infusion of dexmedetomidine at a tertiary pediatric referral center between October 2007 and August 2012 were assessed retrospectively. Patients were excluded if dexmedetomidine was used for procedural sedation, postoperative CV surgery, or if postanesthesia infusion weaning orders existed at the time of PICU admission.

RESULTS: The median minimum dexmedetomidine dose was similar between infants and neonates at 0.2 mcg/kg/hr (IQR, 0.17–0.3) versus 0.29 mcg/kg/hr (IQR, 0.2–0.31), p = 0.35. The median maximum dose was higher for infants than neonates (0.6 mcg/kg/hr [IQR, 0.4–0.8] vs. 0.4 mcg/kg/hr [IQR, 0.26–0.6], p < 0.01). Additional sedative use was more common in infants than neonates (75/99 [76%] vs. 15/28 [54%], p = 0.02). At least 1 episode of hypotension was noted in 34/127 (27%) patients and was similar between groups. An episode of bradycardia was identified more frequently in infants than neonates (55/99 [56%] vs. 2/28 [7%], p < 0.01). Significant reduction in heart rate and systolic blood pressure was noted when comparing baseline vital signs to lowest heart rate and systolic blood pressure during infusion (p < 0.01).

CONCLUSIONS: Dexmedetomidine dose ranges were similar to US Food and Drug Administration–labeled dosages for intensive care unit sedation in adults. More infants than neonates experienced a bradycardia episode, but infants were also more likely to receive higher dosages of dexmedetomidine and additional sedatives.
Metabolic and Hormonal Effects of Antenatal Betamethasone after 35 Weeks of Gestation
Authors: Sifianou Popi , Thanou Voula , Karga Helen
Published: October 2020

BACKGROUND: Antenatal corticosteroid therapy recently has been considered for term and near-term infants, in addition to preterm infants, delivered by elective cesarean section, with the aim of preventing an adverse respiratory outcome.

OBJECTIVES: The objective of this study was to investigate hormonal and metabolic effects of antenatal betamethasone when administered to term fetuses.

METHODS: Cord blood levels of cortisol, C-peptide, insulin-like growth factor I and its binding protein 3, and 5 more analytes including glucose were measured in singleton newborns of over 35 weeks of gestational age. In anticipation of a cesarean delivery, the mother was either treated or not treated with 12 mg of intramuscularly administered antenatal betamethasone approximately 24 hours prior to birth. Babies of comparable gestational age, sex, and nutritional status who were not treated antenatally served as controls.

RESULTS: Cord serum cortisol levels of the betamethasone-treated fetuses were suppressed to <10% of that of untreated controls (median levels of 11.6 nmol/L vs. 138.2 nmol/L, respectively), and their C-peptide and glucose levels were significantly higher (2.85 mcg/L vs. 1.19 mcg/L, respectively, p < 0.0001; and 62.5 mg/dL vs. 56.0 mg/dL, respectively, p = 0.01).

CONCLUSIONS: Prophylactic betamethasone therapy causes immediate hormonal alterations, which might interfere with the metabolic adaptation of the newborn. This issue deserves thorough investigation.
Stability of Hydrocortisone Preservative-Free Oral Solutions
Authors: Chappe Julie , Osman Névine , Cisternino Salvatore , Fontan Jean-Eudes , Schlatter Joël
Published: October 2020

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.