bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACT

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 &lt; 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

ABSTRACT
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

OBJECTIVESThe 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.METHODSNeonates (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 &lt;2 years), children (2 to &lt;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.RESULTSPharmacokinetic 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.CONCLUSIONSIntravenous 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.
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&lt;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.
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.
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.
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.
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 &lt; 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 &lt; 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 &lt; 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 &lt;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 &lt; 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.