bluuebunny/crossref_metadata_2025 huggingface dataset:
Clevidipine for Perioperative Blood Pressure Control in Infants and Children Undergoing Cardiac Surgery for Congenital Heart Disease
Authors: Tobias Joseph D. , Schechter William S. , Phillips Alistair , Weinstein Samuel , Michler Robert , Berkenbosch John W. , Montoya Carlos
Published: October 2020

OBJECTIVE

To determine the efficacy and adverse effect profile of clevidipine when used for perioperative blood pressure (BP) control during surgery for congenital heart disease (CHD).

METHODS

We retrospectively reviewed our experience with the perioperative use of clevidipine in pediatric-aged patients undergoing surgery for CHD.

RESULTS

The study cohort included 14 patients ranging from 11 months to 15 years (7.4 ± 4.6 years) and weighing from 5 to 41 kg (21.8 ± 11.1 kg). Clevidipine was administered as a continuous infusion for control of either postoperative BP or intraoperative mean arterial pressure (MAP) during cooling and cardiopulmonary bypass (CPB). It was administered as a bolus for BP control during emergence from anesthesia following cardiac surgery. The continuous infusion was started at 1 mcg/kg/min and increased in increments of 0.5 to 1 mcg/kg/min as needed. For postoperative BP control, dosing requirements varied from 1 to 7 mcg/kg/min (mean = 2.0 ± 1.2 mcg/kg/min). The target BP was achieved within 5 minutes in all patients. Two patients were treated with intravenous or oral propranolol for an increase in heart rate (HR) while receiving clevidipine. Despite doses up to 10 mcg/kg/min, effective control of MAP could not be achieved during CPB and cooling (core body temperature 28°C to 32°C). Bolus doses of clevidipine (10 to 15 mcg/kg) controlled BP during emergence from anesthesia with a decrease of the MAP from 97 ± 6 mm Hg to 71 ± 5 mm Hg (p<0.01).

CONCLUSIONS

Clevidipine is effective for perioperative BP control in infants and children with CHD; however, it does not appear effective in controlling MAP during cooling and CPB.
Use of Intravesicular Amikacin Irrigations for the Treatment and Prophylaxis of Urinary Tract Infections in a Patient with Spina Bifida and Neurogenic Bladder: A Case Report
Authors: Huynh Donna , Morgan Jill A.
Published: October 2020

This case report describes the use of intravesicular amikacin irrigations to treat and prevent urinary tract infections (UTIs) in a pediatric patient with spina bifida and neurogenic bladder. A 15 year old Hispanic female was admitted for a UTI caused by Enterobacter cloacae and multiple-drug resistant Pseudomonas aeruginosa. A 7 day course of daily intravenous amikacin and ceftazidime was initiated along with twice daily intravesicular amikacin irrigations (15 mg/30 mL) with a dwell time of 2 hours. The patient improved and was discharged on prophylactic Bactrim SS (sulfamethoxazole/trimethoprim) 1 tablet daily and intravesicular amikacin irrigations (15 mg/30 mL) once every other day. Approximately 2 months after discharge, the patient developed another UTI from multidrug resistant Escherichia coli and was treated with a 14 day course of daily intravenous ciprofloxacin accompanied by daily intravesicular amikacin irrigations. Adjunctive therapy with either once daily or twice daily intravesicular amikacin irrigations successfully treated the patient's UTI. However, prophylactic treatment with intravesicular amikacin failed to prevent future UTIs in this patient.
Arthritis Associated With Antithyroid Therapy in a 15-Year-Old Girl
Authors: Ploegstra Wieteke M. , Boontje Ronald P. , Kamps Arvid W.A.
Published: October 2020

A 15-year-old white girl with autoimmune thyroiditis developed arthritis 3 weeks after starting therapy with the antithyroid drug thiamazole. Because an adverse drug reaction of thionamide therapy was suspected, thiamazole was withdrawn, and symptoms disappeared rapidly. Thionamide therapy is indicated for hyperthyroidism and has been widely used since 1948. Reported adverse drug reactions range from mild to potentially life threatening. Arthritis is an uncommon but serious side effect and can develop as a part of the antithyroid arthritis syndrome or as a part of antineutrophil cytoplasmic antibody-associated vasculitis that is induced by antithyroid drugs. Little is known about the exact pathogenesis. Therapy consists of prompt discontinuation of the drug, where upon symptoms rapidly disappear. Because of possible cross-reactivity with alternative thionamides, another form of treatment for hyperthyroidism is recommended. Clinical awareness is important, and prompt withdrawal of the antithyroid drug is necessary when serious side effects occur.
Neonatal Pharmacology: Extensive Interindividual Variability Despite Limited Size
Authors: Tayman Cuneyt , Rayyan Maisa , Allegaert Karel
Published: October 2020

Providing safe and effective drug therapy to neonates requires knowledge of the impact of development on the pharmacokinetics and pharmacodynamics of drugs. Although maturational changes are observed throughout childhood, they are most prominent during the first year of life. Several of these processes overlap, making development an extremely dynamic system in the newborn compared with that in infants, children, or adults. Changes in body composition and porportions, liver mass, metabolic activity, and renal function collectively affect the pharmacokinetic behavior of medications. Instead of simply adapting doses by scaling adult or pediatric doses on the basis of a patient's weight and/or body surface area, integrated knowledge of clinical maturation and developmental pharmacology is critical to the safe and effective use of medications in neonates. Unfortunately, the effects of human ontogeny on both pharmacokinetics and pharmacodynamics have not been well established in these early stages of life, and information regarding the influence of developmental changes on the pharmacodynamics of medications is even more limited. Theoretically, age-dependent variations in receptor number and affinity for drugs have significant potential to influence an individual's response to drug therapy. In this review, some of the relevant covariates of pharmacokinetics and pharmacodynamics in neonates are reviewed and illustrated based on the published literature.
Worsening Bradycardia Following Antithymocyte Globulin Treatment of Severe Aplastic Anemia
Authors: Godown Justin , Deal Allison M. , Riley Kathy , Bailliard Frederique , Blatt Julie
Published: October 2020

Immunosuppressive regimens, which include antithymocyte globulin (ATG), are widely used for the treatment of severe aplastic anemia (SAA). However, bradycardia has been reported only as a rare side effect of ATG therapy in the manufacturer's product information and, in rare cases, in the adult literature. We present an adolescent with SAA and preexisting bradycardia who underwent immunosuppression therapy with ATG, methylprednisolone, and tacrolimus and developed profound sinus bradycardia with successive doses of ATG.
Antipsychotic Treatment of Adolescent Dual Diagnosis Patients
Authors: Price Scott A. , Brahm Nancy C.
Published: October 2020

BACKGROUND

A diagnosis of schizophrenia requires development of a pharmacotherapy regimen that balances many factors in the therapeutic decision-making process. Patient age and the presence or absence of comorbid chemical dependency represent two factors. Comorbid chemical dependency can have a profound impact on the successful treatment of schizophrenia, making patients with dual diagnoses of schizophrenia and chemical dependence a uniquely challenging population. There is little information regarding treatment of schizophrenia and chemical dependence in the pediatric population. Existing data from pediatric and adult populations may facilitate a well-guided and knowledgeable approach to treating pediatric dual diagnosis patients.

METHODS

A review of the literature for medication trials evaluating antipsychotic medication used to treat schizophrenia in childhood and adolescence as well as antipsychotic use in the treatment of the dual diagnoses of schizophrenia and chemical dependence was done. Databases for Ovid MEDLINE, PubMed, and PsycInfo were searched using the terms “addiction,” “adolescence,” “childhood,” “dual diagnosis,” “schizophrenia,” and “substance abuse.” Results were limited to English-language articles.

RESULTS

Seven articles were identified related to psychotic disorders and substance abuse in pediatric populations. Psychosis measurement instruments included the Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale, and Clinical Global Impression. Mean improvements were insignificant in most cases. Medication trials included clozapine, olanzapine, risperidone, and molindone. Trial safety concerns included metabolic effects, increased prolactin levels, and akathisia. One study with random assignment to olanzapine was discontinued early because of substantial weight gain without evidence of superior efficacy. Clozapine treatment was associated with more adverse drug events.

CONCLUSION

There is a great need for more research and use of available data to develop safe and effective treatment guidelines for childhood and adolescent dual diagnosis patients. When appropriate decisions are made regarding treatment of patients with comorbid schizophrenia and chemical dependence, both conditions may benefit with increased remission.
A Review of Candida Prophylaxis in the Neonatal Intensive Care Population
Authors: Chicella Michael F. , Woodruff Eloise D. , Desai Mital M.
Published: October 2020

OBJECTIVE

To review the efficacy and safety of antifungal prophylaxis in the neonatal intensive care setting.

DATA SOURCES

English-language literature was accessed using MEDLINE (January 1988– December 2010). The following Medical Subject Heading (MeSH) search terms were used: “amphotericin B,” “fluconazole,” “nystatin,” “itraconazole,” “caspofungin,” “voriconazole,” “Candida,” “prevention and control,” and “critically ill.” Literature was further limited to studies focusing on patient birth to 6 months of age. Abstracts and original research articles were included. Preference was given to published controlled trials. Articles providing descriptions of the safety and effectiveness of antifungal prophylaxis in neonatal intensive care patients were also used in this review.

RESULTS

Twenty-two studies have evaluated the impact of antifungal prophylaxis on Candida colonization or invasive infections in the Neonatal Intensive Care Unit (NICU). The two antifungal agents most commonly studied were nystatin and fluconazole. All of the nystatin studies demonstrated that nystatin is effective at reducing fungal colonization and invasive fungal infections. All of the studies designed to evaluate the impact of fluconazole prophylaxis on fungal colonization demonstrated a reduction in the incidence of fungal colonization with fluconazole prophylaxis. A total of 12 of 16 studies that evaluated the impact of fluconazole prophylaxis on the incidence of invasive fungal infections demonstrated a reduction in invasive fungal infections with fluconazole prophylaxis. Two studies found no difference between fluconazole and nystatin when used for prophylaxis.

CONCLUSION

Antifungal prophylaxis appears to be effective in reducing the incidence of Candida colonization and invasive Candida infections in the NICU. Antifungal prophylaxis also appears to be safe in the NICU population. The impact of antifungal prophylaxis on resistance patterns could be significant and needs to be evaluated long term before widespread prophylaxis can be recommended.
National Survey of Extended-Interval Aminoglycoside Dosing in Pediatric Cystic Fibrosis Pulmonary Exacerbations
Authors: Prescott William A
Published: October 2020

OBJECTIVES

The Cystic Fibrosis Foundation recently deemed the use of extended-interval dosing (EID) of aminoglycosides acceptable for the treatment of cystic fibrosis (CF) pulmonary exacerbations, but current practices across United States (US) pediatric CF accredited care centers and affiliate programs are unknown. The objectives of this research are to characterize the practice trends, dosing strategies, therapeutic drug monitoring practices, and adverse drug reaction monitoring of EID of aminoglycosides in the treatment of pulmonary exacerbations across US pediatric CF programs.

METHODS

A 38-question online survey was distributed on behalf of the author by the CF Foundation to all US pediatric CF accredited care centers and affiliate programs.

RESULTS

Of the 70 participating CF programs (42.2% survey response rate), 94.3% reported using EID of aminoglycosides (as once-daily or twice-daily dosing), whereas 84.3% reported using once-daily EID in their pediatric CF population. The frequency of EID use increased with patient age. Tobramycin dosed 10 mg/kg per day every 24 hours, infused over the course of 30 minutes, in combination with an antipseudomonal beta-lactam, was the most commonly cited regimen. Monitoring of aminoglycoside serum concentrations was reported by 98.5% of programs, with a tobramycin peak of 25 to 30 mg/L and trough of less than 1 mg/L targeted most frequently. Nephrotoxicity was commonly monitored through serum creatinine measurements, whereas ototoxicity was monitored by audiometry in approximately one-half of programs.

CONCLUSIONS

This study indicates that the use of EID of aminoglycosides across US pediatric CF accredited care centers and affiliate programs is common, particularly among adolescents, with tobramycin being the preferred agent.
Approach to the Pediatric Prescription in a Community Pharmacy
Authors: Benavides Sandra , Huynh Donna , Morgan Jill , Briars Leslie
Published: October 2020

Pediatric patients are more susceptible to medication errors for a variety of reasons including physical and social differences and the necessity for patient-specific dosing. As such, community pharmacists may feel uncomfortable in verifying or dispensing a prescription for a pediatric patient. However, the use of a systematic approach to the pediatric prescription can provide confidence to pharmacists and minimize the possibility of a medication error. The objective of this article is to provide the community pharmacist with an overview of the potential areas of medication errors in a prescription for a pediatric patient. Additionally, the article guides the community pharmacist through a pediatric prescription, highlighting common areas of medication errors.
Probable Association of Tachyarrhythmia With Nebulized Albuterol in a Child With Previously Subclinical Wolff Parkinson White Syndrome
Authors: Kroesen Michiel , Maseland Machiel , Smal Jaime , Reimer Annet , van Setten Petra
Published: October 2020

We present the case of a 2-year-old asthmatic boy with atrioventricular (AV)-reentry tachycardia following albuterol inhalation, who was later diagnosed with Wolff-Parkinson-White (WPW) syndrome. The Naranjo adverse drug reaction probability scale score for this adverse event was 7, indicating that the association between his AV-reentry tachycardia and inhalation of albuterol is probable. To our knowledge, this is the first case report that shows the potential arrhythmogenic effects of albuterol in a child with WPW syndrome. We urge clinicians to be aware of this potentially life-threatening adverse effect and to closely monitor these patients when they need beta-adrenergic drugs in case of emergency. Furthermore, this report highlights the dilemma regarding the safe treatment of pediatric patients with both asthma and WPW syndrome.
Neonatal Abstinence Syndrome: Essentials for the Practitioner
Authors: Siu Anita , Robinson Christine A.
Published: October 2020

The incidence of neonatal abstinence syndrome (NAS) has increased dramatically during the past 15 years, likely due to an increase in antepartum maternal opiate use. Optimal care of these patients is still controversial because of the available published literature lacking sufficient sample size, placebo control, and comparative pharmacologic trials. Primary treatment for NAS consists of opioid replacement therapy with either morphine or methadone. Paregoric and tincture of opium have been abandoned because of relative safety concerns. Buprenorphine is emerging as a treatment option with promising initial experience. Adjunctive agents should be considered for infants failing treatment with opioid monotherapy. Traditionally, phenobarbital has been used as adjunctive therapy; however, results of clonidine as adjunctive therapy for NAS appear to be beneficial. Future directions for research in NAS should include validating a simplified scoring tool, conducting comparative studies, exploring home management options, and optimizing management through pharmacogenomics.
Development and Implementation of a Pharmacist-Managed, Neonatal and Pediatric, Opioid-Weaning Protocol
Authors: Johnson Melissa R. , Nash David R. , Laird Mary R. , Kiley Robert C. , Martinez Michael A.
Published: October 2020

OBJECTIVES: To compare the length of wean and abstinence severity in neonatal and pediatric patients with neonatal abstinence syndrome or iatrogenic opioid dependence treated with a pharmacist-managed, methadone-based protocol compared with physician-managed patients treated with either methadone or dilute tincture of opium (DTO).

METHODS: This was a prospective, single-centered, interventional evaluation of 54 pharmacist-managed patients versus 53 retrospective, physician-managed patients. Wean duration and severity of neonatal abstinence syndrome were compared between groups using the Student t test.

RESULTS: Significantly shorter wean duration in in utero-exposed pharmacist-managed patients compared with patients on physician-managed DTO (11.7 days vs 24.2 days, p < 0.001), but not compared with patients on physician-managed methadone (11.7 days vs 47 days, p = 0.101). No statistically significant difference was seen in wean duration in iatrogenic-exposed pharmacist-managed patients compared with patients on either physician-managed DTO or methadone (8.69 days vs 14 days, p = 0.096) and (8.69 days vs 9.82 days, p = 0.34), respectively. There were significantly fewer abstinence scores >12 in pharmacist-managed patients versus physician-managed DTO, but not physician-managed methadone (2.05 vs 17.3, p = 0.008 and 2.05 vs 74.3, p = 0.119, respectively). Significantly fewer abstinence scores ≥8 × 3 consecutively were seen in pharmacist-managed patients compared with patients on either physician-managed DTO or methadone (2.89 vs 11.9, p = 0.01 and 2.89 vs 24, p < 0.001, respectively).

CONCLUSIONS: Use of a pharmacist-managed, methadone-based weaning protocol standardizes patient care and has the potential to decrease abstinence severity and shorten duration of wean versus physician-managed patients exposed to opioids in utero. Additionally, a methadone wean of 10% to 20% per day was well tolerated in both neonatal and pediatric patients.
Vancomycin Dosing in Healthy-Weight, Overweight, and Obese Pediatric Patients
Authors: Eiland Lea S. , Sonawane Kalyani B.
Published: October 2020

OBJECTIVES: With an increase in vancomycin resistance and the prevalence of obesity in children, alterations of vancomycin dosing regimens may be necessary to achieve target serum concentrations. The primary objective of this study was to describe initial vancomycin dosing with resulting serum concentrations in healthy-weight and overweight/obese children. Secondary objectives include comparing vancomycin dosing regimens of healthy-weight and overweight/obese patients that produced target trough serum concentrations and evaluating the likelihood of attaining target concentrations by patient characteristics.

METHODS: This retrospective review evaluated healthy-weight and overweight/obese patients, aged 2 to 18 years, who had vancomycin trough serum concentrations obtained between 2005 and 2010. Vancomycin dosing, initial trough serum concentrations, pharmacokinetic parameters, and patient demographics were collected for analysis. Target trough serum concentrations were defined as 10 to 20 mg/L.

RESULTS: The study included 98 patients (48 healthy weight, 50 overweight/obese) of which only 14 patients (14.2%, 6 healthy weight, 8 obese) reached a target trough serum concentration with empiric dosing. No difference was found between the mean daily dosing of vancomycin that produced target trough serum concentrations in healthy-weight or overweight/obese patients (53.63 mg/kg/day vs 51.6 mg/kg/day, respectively). Demographic or clinical characteristics were not found to be associated with the likelihood of target trough serum concentration attainment.

CONCLUSIONS: Vancomycin dosing in healthy-weight and overweight/obese pediatric patients did not reach target trough serum concentrations most of the time. In obtaining initial target serum concentrations, no dosing difference was identified for overweight/obese patients compared with healthy-weight patients. Alternate dosing strategies, therapeutic monitoring, and clinical outcomes should continue to be evaluated in this population.
A Filtration System That Greatly Reduces Aluminum in Calcium Gluconate Injection, USP Used to Prepare Parenteral Nutrition Solutions
Authors: Yokel Robert A. , Harris Wesley R. , Spilling Christopher D. , Abramov Vasiliy P. , Lone Jason M. , Kuhn Robert J.
Published: October 2020

OBJECTIVE: The study objective was to reduce aluminum (Al) in Calcium Gluconate Injection, US Pharmacopeia (USP) used in the preparation of parenteral nutrition (PN) solutions.

METHODS: A flow-through filter containing an immobilized chelator that complexes Al from Calcium Gluconate Injection, USP as it flows through the filter was designed, refined by design modifications, and extensively tested. When a small-volume parenteral vial containing 100 mL of Calcium Gluconate Injection, USP is connected on the inlet side of the filter, and the outlet side is connected to an evacuated receiving vial, the filtered solution is drawn into the receiving vial. This constitutes a complete system to remove Al from Calcium Gluconate Injection, USP.

RESULTS: The extent of Al removal is flow rate dependent. At a flow rate of 1 mL/min approximately 85% of the Al was removed from calcium gluconate solution. PN solutions have been reported to deliver 15 to 23 mcg/kg/day Al to neonates. Given that Calcium Gluconate Injection, USP provides 85% of the Al in neonatal PN solutions, removal of 85% of the Al from this source was calculated to reduce Al delivered to most neonates to <5 mcg/kg/day.

CONCLUSIONS: A point-of-use, self-contained, single-use, disposable, Al-complexing filter has been created. It was calculated to reduce Al delivered in PN solutions by 72%, resulting in daily Al delivery below the level that results in Al accumulation associated with central nervous system and bone toxicity to all but the smallest (<1 kg) infants.
Proton Pump Inhibitor Prescribing Patterns in Newborns and Infants
Authors: Illueca Marta , Alemayehu Berhanu , Shoetan Nze , Yang Huiying
Published: October 2020

OBJECTIVES: In 2011, the Food and Drug Administration (FDA) approved intravenous esomeprazole 0.5 mg/day for children aged >1 month and oral esomeprazole for infants aged 1 month to <1 year at doses of 2.5, 5, and 10 mg based on weight. Prior to 2011, proton pump inhibitors (PPIs) were not approved for use in infants aged <1 year. This study determined PPI usage rates prior to the FDA approval among newborns and infants in both the inpatient and outpatient settings and compared PPI and histamine-2 receptor antagonist (H2RA) usage in the inpatient setting.

METHODS: We conducted a retrospective analysis of PPI prescribing patterns for newborns and infants from 2003 to 2008 using data from the Premier Perspective Inpatient Hospital Database and the PharMetrics Patient-Centric Database for inpatient and outpatient data, respectively. PPI use and diagnoses were determined from clinical and charge records from more than 500 hospitals. Descriptive statistics were used to summarize the findings.

RESULTS: Our analysis showed that PPIs were prescribed for approximately 5000 newborns (0.13%) and 15,000 infants (2.65%) each year in the hospital setting and 1.6% of newborns and infants, as a group, in the outpatient setting. Newborns and infants receiving PPIs most often had diagnoses of gastroesophageal reflux disease (GERD) and were generally prescribed an adult PPI dose, although the actual dose administered could not be substantiated.

CONCLUSIONS: Although no PPI was approved by the FDA for patients aged <1 year at the time of this study, results of this analysis indicate that PPIs were commonly prescribed for newborns and infants, mostly in hospital, but also in outpatient settings. Most PPIs were prescribed for infants with a diagnosis of GERD.
Optimizing Pediatric Esmolol Dosing Using Computerized Practitioner Order Entry
Authors: Chao Tihua , Perry James C. , Romanowski Gale L. , Tremoulet Adriana H. , Capparelli Edmund V.
Published: October 2020

OBJECTIVES: The aims of this study were to 1) describe the cardiovascular dose-response of esmolol and dose-limiting adverse effects in pediatric patients; 2) assess an institutional guideline for protocol adherence, efficacy, and achievement of therapeutic targets for pediatric patients with tachyarrhythmias or systemic hypertension; and 3) revise the protocol accordingly.

METHODS: In this prospective study, pediatric/neonatal subjects were identified using a medication utilization report in the electronic medical record and treated with esmolol for blood pressure or rhythm control at Rady Children's Hospital San Diego between November 1, 2012, and February 28, 2013. Inclusion criteria required subjects to be under intensive care and have bedside telemetry monitoring. Data collection consisted of patient demographic information, administration history of esmolol, concurrent administration of other cardiovascular medications, patient cardiovascular goals, and vital signs.

RESULTS: A total of 8 subjects representing 10 administrations of esmolol were included in the study. Whereas esmolol was found to be safe and effective overall for control of hypertension and tachyarrhythmia, protocol adherence was poor, leading to subtherapeutic dosing schemes, dose changes prior to achievement of presumed steady-state pharmacokinetics, and erratic dosing to target effect.

CONCLUSIONS: After the review, the data were revealed at a program-wide conference and consensus was reached on a new, data-driven protocol. As a result of this quality improvement initiative, the new protocol provides more precise dosing and clearly delineated therapeutic targets and is designed to reflect specific esmolol pharmacokinetics. The effort emphasizes the need to construct foundations for follow-up quality improvement efforts in intensive care pharmacology.
Successful Use of Daptomycin in a Preterm Neonate With Persistent Methicillin-Resistant Staphylococcus epidermidis Bacteremia
Authors: Gawronski Kristen M.
Published: October 2020

There is limited information regarding the use of daptomycin in the neonatal population, and dosage adjustments for neonates with renal dysfunction. We report on the successful use of daptomycin in a 1-month-old, former 24-week gestation neonate with persistent methicillin-resistant Staphylococcus epidermidis (MRSE) bacteremia and impaired renal function. We also review the available literature supporting daptomycin use in the neonatal period. Daptomycin peak and trough serum levels were obtained immediately prior to and 60 minutes after the fifth dose. While vancomycin remains the drug of choice for methicillin-resistant Staphylococcal infections, due to increasing reports of treatment failures, alternative therapies are recommended. Based on mounting evidence, daptomycin may be considered an option in persistently bacteremic neonates who fail vancomycin therapy, although further investigation is warranted.
Continuous Inhalation of Ipratropium Bromide for Acute Asthma Refractory to β2-agonist Treatment
Authors: Koumbourlis Anastassios C. , Mastropietro Christopher
Published: October 2020

To present the case of a patient with persistent bronchospasm, refractory to treatment with β2-agonists, that resolved promptly with continuous inhalation of large dose (1000 mcg/hr) ipratropium bromide, and to discuss the possibility of tolerance to β2-agonists as the cause for his failure to respond to adrenergic medications. The patient had received multiple doses of albuterol, as well as subcutaneous terbutaline (0.3 mg), intravenous magnesium sulfate (1 g) and intravenous dexamethasone (10 mg) prior to his admission to the intensive care unit. He remained symptomatic despite systemic intravenous steroids, continuous intravenous terbutaline (up to 0.6 mcg/kg/min), and continuous nebulized albuterol (up to 20 mg/hr for 57 hr) followed by 49 hours of continuous levalbuterol (7 mg/hr). Due to the lack of response, all β2-agonists were discontinued at 106 hours post-admission, and he was started on large dose ipratropium bromide (1000 mcg/hr) by continuous nebulization. Clinical improvement was evident within 1 hour and complete resolution of his symptoms within 4 hours. Continuous inhalation of large dose ipratropium bromide may be an effective regimen for the treatment of patients hospitalized with acute asthma who are deemed to be nonresponsive and/or tolerant to β2-agonist therapy.
Retrospective Analysis of Large-Dose Intrapleural Alteplase for Complicated Pediatric Parapneumonic Effusion and Empyema
Authors: Taylor Jessica L. , Liu Meixia , Hoff David S.
Published: October 2020

OBJECTIVES: Medical treatment of complicated parapneumonic effusion or empyema in pediatric patients includes antibiotics and pleural space drainage. Intrapleural fibrinolysis may facilitate pleural drainage; however, there is a lack of consensus regarding the optimal dosing regimen. The primary purpose of this study was to evaluate the efficacy and safety of a large-dose intrapleural alteplase regimen in pediatric patients. Secondarily, this investigation sought to differentiate the clinical characteristics of responders and non-responders to intrapleural alteplase therapy.

METHODS: All patients with parapneumonic effusions treated with intrapleural alteplase between June 2003 and December 2011 were reviewed retrospectively. Efficacy was assessed by comparing chest tube output, in mL/hr and mL/kg/hr, for 24 hours before and after the first dose of alteplase. Additional efficacy outcomes included duration of in situ chest tubes, a need for surgical intervention for pleural effusion, and length of hospital stay. Safety was assessed by frequency and severity of adverse events. Non-responders and responders were compared based on demographic and disease characteristics. Responders were defined as patients who did not require surgical intervention after intrapleural alteplase therapy.

RESULTS: Seventy-three patients, aged 0.5 to 22.5 years, received intrapleural alteplase to facilitate pleural drainage. Median alteplase dose was 7 mg (range, 3 to 10 mg; median 0.38 mg/kg). Chest tube output increased from 10.7 to 24.2 mL/hr (p = 0.006), and median length of hospital stay was 9 days. Eighty-four percent of patients were responders. The most common adverse events were pain (20.5%) and oxygen desaturation greater than 10% from baseline (16.4%). High-flow nasal cannula was the most common intervention for oxygen desaturation to 80% to 90%. Nine patients (12%) required a blood transfusion during the study.

CONCLUSION: Large-dose intrapleural alteplase is effective in facilitating pleural drainage in pediatric patients with complicated parapneumonic effusion or empyema. Common adverse effects include pain and oxygen desaturation. The potential for bleeding warrants clinical monitoring.
MMR Vaccine: When Is the Right Time for the Second Dose?
Authors: Herrera Oscar R. , Thornton Terrika A. , Helms Richard A. , Foster Stephan L.
Published: October 2020

Outbreaks of measles have been reported over the past 5 years, particularly affecting children between the ages of 1 and 5 years. Most of these children are younger than the age recommended by the Advisory Committee on Immunization Practices for the second dose of measles-mumps-rubella (MMR) vaccine. Question may arise as to whether strict adherence to the scheduled second dose is required or whether there is opportunity for earlier immunization under special circumstances (e.g., traveling abroad, poor response as evidenced by titer levels). The history of measles, its characteristics, and its evolving past and current immunization policies will be reviewed, focusing on the original intent of the recommended schedule and presenting a case in which deviating from current practice could be justified.
Drug Shortages and Implications for Pediatric Patients
Authors: Butterfield Lindsay , Cash Jared , Pham Kathy ,   on Behalf of the Advocacy Committee for the Pediatric Pharmacy Advocacy Group
Published: October 2020

Drug shortages in the United States continue to be a significant problem that negatively impacts pediatric patients of all ages. These shortages have been associated with a higher rate of relapse among children with cancer, substitution of less effective agents, and greater risk for short- and long-term toxicity. Effective prevention and management of any drug shortage must include considerations for issues specific to pediatric patients; hence, the Pediatric Pharmacy Advocacy Group (PPAG) strongly supports the effective management of shortages by institutions caring for pediatric patients. Recommendations published by groups such as the American Society of Health-System Pharmacists and the American Society for Parenteral and Enteral Nutrition should be incorporated into drug shortage management policies. PPAG also supports the efforts of the Food and Drug Administration (FDA) to not only address but prevent drug shortages caused by manufacturing and quality problems, delays in production, and discontinuations. Prevention, mitigation, and effective management of drug shortages pose significant challenges that require effective communication; hence, PPAG encourages enhanced and early dialogue between the FDA, pharmaceutical manufacturers, professional organizations, and health care institutions.
Overview of Pharmacological Treatment Options for Pediatric Patients with Refractory Kawasaki Disease
Authors: Saneeymehri Seyyedeh , Baker Katherine , So Tsz-Yin
Published: October 2020

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.
Evaluation of an Alternative Intravenous N-Acetylcysteine Regimen in Pediatric Patients
Authors: Pauley Kathryn A. , Sandritter Tracy L. , Lowry Jennifer A. , Algren D. Adam
Published: October 2020

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.
Treatment of Generalized Convulsive Status Epilepticus in Pediatric Patients
Authors: Alford Elizabeth L. , Wheless James W. , Phelps Stephanie J.
Published: October 2020

Generalized convulsive status epilepticus (GCSE) is one of the most common neurologic emergencies and can be associated with significant morbidity and mortality if not treated promptly and aggressively. Management of GCSE is staged and generally involves the use of life support measures, identification and management of underlying causes, and rapid initiation of anticonvulsants. The purpose of this article is to review and evaluate published reports regarding the treatment of impending, established, refractory, and super-refractory GCSE in pediatric patients.
Impact of Clinical Pharmacist on the Pediatric Intensive Care Practice: An 11-Year Tertiary Center Experience
Authors: Tripathi Sandeep , Crabtree Heidi M. , Fryer Karen R. , Graner Kevin K. , Arteaga Grace M.
Published: October 2020

OBJECTIVES: With increasing complexity of critical care medicine comes an increasing need for multidisciplinary involvement in care. In many institutions, pharmacists are an integral part of this team, but long-term data on the interventions performed by pharmacists and their effects on patient care and outcomes are limited. We aimed to describe the role of pediatric clinical pharmacists in pediatric intensive care unit (PICU) practice.

METHODS: We retrospectively reviewed the records of pharmacy interventions in the PICU at the Mayo Clinic in Rochester, Minnesota, from 2003-2013, with a distinct period of increased pharmacist presence in the PICU from 2008 onward. We compared demographic and outcome data on patients who did and who did not have pharmacy interventions during 2 periods (2003–2007 and 2008–2013).

RESULTS: We identified 27,773 total interventions by pharmacists during the 11-year period, of which 79.8% were accepted by the clinical team. These interventions were made on 10,963 unique PICU admissions and prevented 5867 order entry errors. Pharmacists' interventions increased year over year, including a significant change in 2008. Patients who required pharmacy involvement were younger, sicker, and had longer intensive care unit, hospital, and ventilator duration. Average central line infections and central line entry rates decreased significantly over the study period.

CONCLUSIONS: Increased pharmacist presence in the PICU is associated with increased interventions and prevention of adverse drug events. Pharmacist participation during rounds and order entry substantially improved the care of critically sick children and should be encouraged.
Dexmedetomidine Infusion to Control Agitation due to Anticholinergic Toxidromes in Adolescents, a Case Series
Authors: Gee Samantha W. , Lin Ada , Tobias Joseph D.
Published: October 2020

Dexmedetomidine is an α2-adrenergic agonist approved by the US Food and Drug Administration for the sedation of adults who are intubated on mechanical ventilation and in non-intubated adults who are undergoing surgical procedures. However, it has also recently become a commonly used sedative agent in varied clinical settings for the pediatric patient as well. We present the use of dexmedetomidine for sedation in a unique clinical scenario, the severely agitated and combative patient following the intentional misuse of anticholinergic drugs. Its applications in this situation are discussed, and previous reports in the literature are reviewed.
Morphine: An Effective Abortive Therapy for Pediatric Paroxysmal Sympathetic Hyperactivity After Hypoxic Brain Injury
Authors: Raithel Deborah S. , Ohler Kirsten H. , Porto Isabel , Bicknese Alma R. , Kraus Donna M.
Published: October 2020

Paroxysmal sympathetic hyperactivity (PSH) is a life-threatening condition characterized by hyperadrenergic activity and autonomic dysfunction. Also termed autonomic storms, PSH can occur after a variety of cerebral insults, most commonly traumatic brain injury. Limited pediatric literature is available, especially in patients with brain injury from hypoxia. No consensus exists for the terminology, diagnostic criteria, or treatment algorithm for PSH. Thus, the optimal management, including medication selection and dosing, remains unclear. We present the detailed treatment of a 9-year-old, African American male with hypoxic brain injury after pulseless arrest following status asthmaticus, who subsequently developed PSH. The patient began to experience episodes of tachycardia, hypertension, tachypnea, diaphoresis, rigidity, and dystonic posturing on hospital day 5. After ruling out other potential causes, a diagnosis of PSH was made. Episodes of PSH failed to respond to lorazepam or labetalol but were aborted successfully with morphine. Management of PSH after hypoxic brain injury required medications for acute treatment as well as for prevention of PSH. Morphine was found to be highly effective and safe for aborting the autonomic crises. Other agents more commonly described in the literature did not result in an adequate response and were associated with significant adverse effects. A combination of clonazepam, baclofen, and either propranolol or clonidine aided in reducing the frequency of episodes of PSH. We suggest using morphine for aborting severe episodes of PSH that do not respond to antihypertensive agents or benzodiazepines.
Outpatient Management of Pediatric Type 1 Diabetes
Authors: Beck Joni K. , Cogen Fran R.
Published: October 2020

The incidence of both type 1 and type 2 diabetes (T1DM and T2DM) continues to rise within the pediatric population. However, T1DM remains the most prevalent form diagnosed in children. It is critical that health-care professionals understand the types of diabetes diagnosed in pediatrics, especially the distinguishing features between T1DM and T2DM, to ensure proper treatment. Similar to all individuals with T1DM, lifelong administration of exogenous insulin is necessary for survival. However, children have very distinct needs and challenges compared to those in the adult diabetes population. Accordingly, treatment, goals, and age-appropriate requirements must be individually addressed. The main objectives for the treatment of pediatric T1DM include maintaining glucose levels as close to normal as possible, avoiding acute complications, and preventing long-term complications. In addition, unique to pediatrics, facilitating normal growth and development is important to comprehensive care. To achieve these goals, a careful balance of insulin therapy, medical nutrition therapy, and exercise or activity is necessary. Pharmacological treatment options consist of various insulin products aimed at mimicking prior endogenous insulin secretion while minimizing adverse effects. This review focuses on the management of pediatric T1DM in the outpatient environment, highlighting pharmacotherapy management strategies.
Characterizing the Risk Factors Associated With Venous Thromboembolism in Pediatric Patients After Central Venous Line Placement
Authors: Wisecup Sarah , Eades Shannan , Turiy Yuliya
Published: October 2020

OBJECTIVES: With the apparent increase in venous thromboembolism noted in the pediatric population, it is important to define which children are at risk for clots and to determine optimal preventative therapy. The purpose of this study was to determine the risk factors for venous thromboembolism in pediatric patients with central venous line placement.

METHODS: This was an observational, retrospective, case-control study. Control subjects were patients aged 0 to 18 years who had a central venous line placed. Case subjects had a central line and a radiographically confirmed diagnosis of venous thromboembolism.

RESULTS: A total of 150 patients were included in the study. Presence of multiple comorbidities, particularly the presence of a congenital heart defect (34.7% case vs. 14.7% control; p < 0.005), was found to put pediatric patients at increased risk for thrombosis. Additionally, the administration of parenteral nutrition through the central line (34.7% case vs. 18.7% control; p = 0.03) and location of the line increased the risk for clot formation.

CONCLUSIONS: With increased awareness of central venous line–related thromboembolism, measures should be taken to reduce the number and duration of central line placements, and further studies addressing the need for thromboprophylaxis should be conducted.
Successful Daptomycin Use in a Pediatric Patient With Acute, Bilateral Osteomyelitis Caused by Methicillin-Resistant Staphylococcus aureus
Authors: Billups Kelsey L. , Stultz Jeremy S.
Published: October 2020

Staphylococcus aureus is the most common bacteria associated with the development of osteomyelitis in pediatric patients. Osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) can be difficult to safely and effectively treat. Vancomycin, linezolid, and clindamycin are commonly used to treat osteomyelitis caused by MRSA. While adult studies suggest intravenous (IV) daptomycin may by beneficial for the treatment of MRSA osteomyelitis, it is not Food and Drug Administration approved for use in pediatrics, and minimal data are available related to its use in this population. This case report describes the successful use of daptomycin (8 mg/kg/dose IV daily) combined with rifampin for 5 weeks, followed by 5 weeks of oral sulfamethoxazole/trimethoprim, for treatment of acute bilateral osteomyelitis caused by MRSA in an 8-year-old male. The patient did not initially respond to the combination of vancomycin plus rifampin and gentamicin, nor did he respond to ceftaroline treatment. After initiation of daptomycin, his fevers quickly subsided, his pain rapidly improved, and his inflammatory markers significantly decreased. While daptomycin was effective in this patient, additional research is needed to determine the true safety and efficacy of this drug for treatment of osteomyelitis caused by MRSA in pediatric patients.