Hanna Phan

Clinical Uses of Dexmedetomidine in Pediatric Patients

Dexmedetomidine is being used off-label as an adjunctive agent for sedation and analgesia in pediatric patients in the critical care unit and for sedation during non-invasive procedures in radiology. It also has a potential role as part of anesthesia care to prevent emergence delirium and postanesthesia shivering. Dexmedetomidine is currently approved by the US FDA for sedation only in adults undergoing mechanical ventilation for <24 hours.Pediatric experiences in the literature are in the form of small studies and case reports. In patients sedated for mechanical ventilation and/or opioid/benzodiazepine withdrawal, the loading dose ranged from 0.5 to 1 μg/kg and was usually administered over 10 minutes, although not all patients received loading doses. This patient group also received a continuous infusion at rates ranging from 0.2 to 2 μg/kg/h, with higher rates used in burn patients and those with withdrawal following ≥24 hours of opioid/benzodiazepine infusion. The dexmedetomidine dosage used for anesthesia and sedation during non-invasive procedures, such as radiologic studies, ranged from a loading dose of 1–2 μg/kg followed by a continuous infusion at 0.5–1.14 μg/kg/h, with most patients spontaneously breathing. For invasive procedures, such as awake craniotomy or cardiac catheterization, dosage ranged from a loading dose of 0.15 to 1 μg/kg followed by a continuous infusion at 0.1–2 μg/kg/h. Adverse hemodynamic and respiratory effects were minimal; the agent was well tolerated in most patients. The efficacy of dexmedetomidine varied depending on the clinical situation: efficacy was greatest during non-invasive procedures, such as magnetic resonance imaging (MRI), and lowest during invasive procedures, such as cardiac catheterization.Dexmedetomidine may be useful in pediatric patients for sedation in a variety of clinical situations. The literature suggests potential use of dexmedetomidine as an adjunctive agent to other sedatives during mechanical ventilation and opioid/benzodiazepine withdrawal. In addition, because of its minimal respiratory effects, dexmedetomidine has also been used as a single agent for sedation during non-invasive procedures such as MRI. However, additional studies in pediatric patients are warranted to further evaluate its safety and efficacy in all age ranges.

Off-label and unlicensed medication use and associated adverse drug events in a pediatric emergency department.

Objectives: The study objectives were to (1) determine the types and frequency of off-label (OL) or unlicensed (UL) medications used in a pediatric emergency department (PED) and before admission, (2) describe OL/UL-associated adverse drug events (ADEs) resulting in admission to the PED and those occurring during patient care in PED, and (3) determine the outcomes of these ADEs. Methods: Medical records of patients 18 years or younger admitted to the PED over a 5-month period were reviewed. Off-label/UL use of medications was determined based on Food and Drug Administration-approved labeling. The Adverse Drug Reaction Probability Scale was used to determine ADE causality. Data were analyzed using descriptive statistics. Results: A total of 2191 patients with 6675 medication orders were evaluated. About 26.2% (n = 1712) of medication orders were considered as OL/ UL use; 70.5% (n = 1208) of these medications were ordered as part of treatment in the PED, and the remaining 29.5% (n = 504) were home medications before their PED evaluation. Inhaled bronchodilators (30.4%), antimicrobials (14.8%), and antihistamines/antiemetics (9.1%) were the most common OL/UL medication classes. The frequency of ADEs among licensed medication use was greater compared with OL/UL use by 2-fold. Reported overall rate of ADEs was 0.6% (n = 40). Of these 40 ADEs, 5 resulted from the use of an OL/UL medication, 3 from home medication use, and 2 from PED-prescribed medications. Conclusions: The frequency of reported ADEs associated with OL/UL medications was less than the frequency of ADEs from licensed medication use, with overall ADE frequency of less than 1%.

Treatment of Allergic Rhinitis in Infants and Children: Efficacy and Safety of Second-Generation Antihistamines and the Leukotriene Receptor Antagonist Montelukast

Allergic rhinitis (AR) affects a large percentage of paediatric patients. With the wide array of available agents, it has become a challenge to choose the most appropriate treatment for patients. Second-generation anti-histamines have become increasingly popular because of their comparable efficacy and lower incidence of adverse effects relative to their first-generation counterparts, and the safety and efficacy of this drug class are established in the adult population. Data on the use of the second-generation anti-histamines oral cetirizine, levocetirizine, loratadine, desloratadine and fexofenadine, and the leukotriene receptor antagonist montelukast as well as azelastine nasal spray in infants and children are evaluated in this review.These agents have been found to be relatively safe and effective in reducing symptoms associated with AR in children. Alternative dosage forms such as liquids or oral disintegrating tablets are available for most agents, allowing ease of administration to most young children and infants; however, limited data are available regarding use in infants for most agents, except desloratadine, cetirizine and montelukast. Unlike their predecessors, such as astemizole and terfenadine, the newer second-generation antihistamines and montelukast appear to be well tolerated, with absence of cardiotoxicities. Comparative studies are limited to cetirizine versus ketotifen, oxatomide and/or montelukast. Although second-generation antihistamines and montelukast are deemed relatively safe for use in paediatric patients, there are some noteworthy drug interactions to consider when selecting an agent. Given the wide variety of available agents for treatment of AR in paediatric patients, the safety and efficacy data available for specific age groups, type of AR, dosage form availability and cost should be considered when selecting treatment for AR in infants and children.

Serotonin syndrome following a single 50 mg dose of sertraline in a child

Objective. To report a case of serotonin syndrome associated with a single, 50 mg dose of sertraline in a child and discuss the findings in context with previous relevant literature involving other selective serotonin reuptake inhibitors used in children. Case Summary. A nine-year old male with chronic behavioral problems was prescribed oral sertraline 50 mg daily. After the first dose, the patient presented with abdominal pain, seizure-like activity, and change in mental status. He was admitted to a tertiary-care pediatric hospital and was treated for serotonin syndrome. Laboratory findings of elevated creatine kinase and serum creatinine were consistent with rhabdomyolysis as result of continued hypertonicity. Sertraline was discontinued and treatment with lorazepam and cyproheptadine was initiated. Clinical status, creatine kinase, and serum creatinine improved over 5 days of hospitalization. The Adverse Drug Reaction Probability Scale by Naranjo et al was applied to assess causality. The scale indicated the association of a single dose of sertraline and serotonin syndrome as “probable.” Conclusion. To our knowledge this is the first reported case of serotonin syndrome associated with a single dose of sertraline in a child using a validated causality scale. The sertraline 50 mg dose given to the child was higher than usual recommended initial doses (25 mg). This potential adverse reaction should be considered when selecting antidepressant therapy for children.

Medication Error Identification Rates by Pharmacy, Medical, and Nursing Students

Objective. To assess and compare prescribing error-identification rates by health professional students. Methods. Medical, pharmacy, and nursing students were asked to complete a questionnaire on which they evaluated the accuracy of 3 prescriptions and indicated the type of error found, if any. The number of correctly identified prescribing errors and the number of correct types of errors identified were compared and error identification rates for each group were calculated. Results. One hundred seventy-five questionnaires were returned (87% response rate). Pharmacy students had a significantly higher error-identification rate than medical and nursing students (p < 0.001). No significant differences were found between medical and nursing students (p = 0.88). Compared to medical students, pharmacy students more often were able to identify correctly the error type for each prescription (p < 0.001; p = 0.023; p = 0.001). Conclusions. Of the 3 student groups, pharmacy students demonstrated a significantly higher error-identification rate, which may be associated with the greater number of pharmacology and pharmacotherapeutics course hours that pharmacy students complete.

Recommendations for meeting the pediatric patient's need for a clinical pharmacist: A joint opinion of the pediatrics practice and research network of the american college of clinical pharmacy and the pediatric pharmacy advocacy group

Children warrant access to care from clinical pharmacists trained in pediatrics. The American College of Clinical Pharmacy Pediatrics Practice and Research Network (ACCP Pediatrics PRN) released an opinion paper in 2005 with recommendations for improving the quality and quantity of pediatric pharmacy education in colleges of pharmacy, residency programs, and fellowships. Although progress has been made in increasing the availability of pediatric residencies, there is still much to be done to meet the direct care needs of pediatric patients. The purpose of this joint opinion paper is to outline strategies and recommendations for expanding the quality and capacity of pediatric clinical pharmacy practitioners by elevating the minimum expectations for pharmacists entering pediatric practice, standardizing pediatric pharmacy education, expanding the current number of pediatric clinical pharmacists, and creating an infrastructure for development of pediatric clinical pharmacists and clinical scientists. These recommendations may be used to provide both a conceptual framework and action items for schools of pharmacy, health care systems, and policymakers to work together to increase the quality and quantity of pediatric training, practice, and research initiatives.

Induction dose of propofol for pediatric patients undergoing procedural sedation in the emergency department.

Objective This study aimed to determine if patient age is an independent predictor of the propofol dose required for the induction of sedation in pediatric patients for procedures performed in the emergency department (ED). Methods This is a retrospective study conducted in an academic, tertiary ED between May 2005 and October 2009. Medical records of patients younger than 18 years who received propofol for procedural sedation were evaluated. Data collected included patient demographics, procedure type, propofol doses administered, time to sedation induction, pain scores before procedure, opioid administration, and adverse effects. Factors predictive of propofol induction dose were analyzed using linear regression analyses. Results Eighty-eight patients were included in the final analyses. The mean age was 11 years (range, 1–17 years), and 75% were male. The mean induction dose required was 2.1 ± 1.3 mg/kg using a median of 3 boluses (interquartile range, 2–4). The mean time to induction was 3.9 ± 4.2 minutes. In the linear regression analyses (R2 = 0.07), patient age was inversely predictive of the induction dose (in milligram per kilogram) of propofol (coefficient = −0.074; P = 0.013). Sex, race, procedure type, pain score before procedure, and opioid administration were not predictive of induction dose. Transient respiratory depression occurred in 13.6% and hypotension occurred in 8% of patients, without further complications. Conclusions In pediatric patients undergoing procedural sedation in the ED, age is an independent predictor of the dose of propofol required for induction of sedation. Therefore, younger patients may require higher doses by body weight (in milligram per kilogram).

Research fellowship programs as a pathway for training independent clinical pharmacy scientists.

The American College of Clinical Pharmacy (ACCP) Research Affairs Committee published a commentary in 2013 on training clinical pharmacy scientists in the context of changes in economic, professional, political, and research environments. The commentary centered on the opportunities for pharmacists in clinical/translational research including strategies for ACCP, colleges of pharmacy, and the profession to increase the number and impact of clinical pharmacy scientists. A postdoctoral fellowship is cited as a current training pathway, capable of producing independent and productive pharmacy researchers. However, a decline in the number of programs, decreased funding availability, and variability in fellowship program activities and research focus have brought into question the relevance of this research training pathway to meet demand and opportunities. In response to these points, this commentary examines the state of research fellowship training including the current ACCP research fellowship review process, the need for standardization of research fellowship programs, and strategies to strengthen and promote research fellowships as relevant researcher training pathways.

The role of the pediatric pharmacist in personalized medicine and clinical pharmacogenomics for children: pediatric pharmacogenomics working group.

With the initiatives by the National Institutes of Health and the Food and Drug Administration, pharmacogenomics has now moved from the laboratory to the patient bedside. Over 100 drug-products now contain pharmacogenomic information as part of their labeling. Many of these are commonly used in the pediatric population. Direct-to-consumer genetic test kits also require intervention and guidance from healthcare professionals. This increased trend towards personalized medicine mandates that healthcare professionals develop a working knowledge about pharmacogenomics and its application towards patient care. Because pharmacogenomic testing can provide patient-specific predictors for response to and safety of medications, pharmacists are positioned to play an active role in pharmacogenomic testing, clinical interpretation of results, and recommendations for individualization of drug therapy. Opportunities for pharmacists exist in both inpatient and outpatient settings, such as pharmacist-managed clinical pharmacogenomics consultation services and educating patients and families about pharmacogenomic testing. In addition to clinical roles, pharmacists may also be involved in genetically-influenced drug discovery and development. Given the potential for genetic and age-dependent factors to influence drug selection and dosing, pediatric pharmacists should be involved in the development of dosing recommendations and interprofessional practice guidelines regarding pharmacogenomic testing in pediatric patients. Opportunities to become knowledgeable and competent in pharmacogenomics span from coursework as part of the pharmacy curriculum to postgraduate education (e.g., residencies, fellowships, continuing education). However, there exists a need for additional postgraduate learning opportunities for practicing pharmacists. As a result, the Pediatric Pharmacy Advocacy Group (PPAG) acknowledges a need for increased education of both student and practicing pharmacists, with consideration of special patient populations, such as infants and children. PPAG endorses and advocates for the involvement of pediatric pharmacists in pharmacogenomic testing and in using those results to provide safe and effective medication use in pediatric patients of all ages. Additionally, PPAG strongly encourages pediatric pharmacists to take responsibility for educating patients and their families about the importance of pharmacogenomic testing and its role in the safe and effective use of medications.

Exhaled Breath Condensate Detects Baseline Reductions in Chloride and Increases in Response to Albuterol in Cystic Fibrosis Patients

Impaired ion regulation and dehydration is the primary pathophysiology in cystic fibrosis (CF) lung disease. A potential application of exhaled breath condensate (EBC) collection is to assess airway surface liquid ionic composition at baseline and in response to pharmacological therapy in CF. Our aims were to determine if EBC could detect differences in ion regulation between CF and healthy and measure the effect of the albuterol on EBC ions in these populations. Baseline EBC Cl−, DLCO and SpO2 were lower in CF (n = 16) compared to healthy participants (n = 16). EBC Cl− increased in CF subjects, while there was no change in DLCO or membrane conductance, but a decrease in pulmonary-capillary blood volume in both groups following albuterol. This resulted in an improvement in diffusion at the alveolar-capillary unit, and removal of the baseline difference in SpO2 by 90-minutes in CF subjects. These results demonstrate that EBC detects differences in ion regulation between healthy and CF individuals, and that albuterol mediates increases in Cl− in CF, suggesting that the benefits of albuterol extend beyond simple bronchodilation.