Roxane Carr

Octreotide for Sulfonylurea-Induced Hypoglycemia following Overdose

OBJECTIVE: To describe the use of octreotide in the management of 2 cases of sulfonylurea-induced hypoglycemia following overdose and to review the literature on the use of octreotide in the management of sulfonylurea overdose. CASE SUMMARY: Case 1 describes a 27-year-old woman who ingested 500 mg of glyburide; case 2 describes a 22-year-old woman following ingestion of glyburide 1000 mg. Despite administration of bolus doses of dextrose 50% and infusions of dextrose 10%, both patients demonstrated refractory hypoglycemia. Three doses of octreotide 50 μg were administered subcutaneously spaced 8 hours apart to both patients, resulting in a reduction of hypoglycemic episodes and a reduced need for dextrose administration. DISCUSSION: In addition to the 2 cases described, 8 citations involving 23 patients with sulfonylurea overdose in which octreotide was used were identified in the literature. As with our patients, episodes of hypoglycemia and the need for bolus doses of dextrose 50% were reduced following administration of octreotide. CONCLUSIONS: The use of octreotide appears to reduce the number of hypoglycemic episodes and glucose requirements, with no reported toxicities associated with its use for sulfonylurea-induced hypoglycemia following overdose.

A Systematic Review of the Pharmacokinetics of Antiepileptic Drugs in Neonates With Refractory Seizures

BACKGROUND Neonatal seizures are associated with neurological sequelae and an increased risk of epilepsy later in life. Phenobarbital and phenytoin remain the antiepileptic drugs (AEDs) most commonly used to treat neonatal seizures, despite their suboptimal effectiveness and safety. As a result, other AEDs, such as levetiracetam and topiramate, are often used in neonates with refractory seizures, despite limited data and off-label use. OBJECTIVES To systematically review published pharmacokinetic data for second-line AEDs used in neonates with seizures and to provide dosing recommendations for these agents in the neonatal population. METHODS A literature search was conducted in PubMed (1949-May 2012), Medline (1950-May 2012), and Embase (1980-May 2012). Each study was ranked according to the quality of evidence it provided, based on the classification system developed by the US Preventive Services Task Force. Information extracted from each study included study design, number of subjects, gestational and postnatal age, AED dosage regimen, pharmacokinetic parameters, pharmacokinetic model, AED serum concentrations, and sampling times. RESULTS Nineteen relevant pharmacokinetic studies involving a total of 8 different drugs were identified. No prospective, randomized, controlled studies (level I evidence) or nonrandomized controlled studies (level II-I evidence) were identified; 2 studies were prospective, nonrandomized, uncontrolled (cohort) studies (level II-2 evidence), 11 studies obtained evidence from multiple time series (level II-3 evidence), and 6 studies were case reports or descriptive studies (level III evidence). CONCLUSIONS There are limited pharmacokinetic data for the use of carbamazepine, levetiracetam, lidocaine, paraldehyde, topiramate, valproic acid, and vigabatrin for neonates with seizures refractory to treatment with first-line antiepileptic agents. Further research is needed to elucidate target AED serum concentrations (if any) required to optimize effectiveness and minimize dose-related adverse effects in neonates.

Pediatric Obesity: Pharmacokinetics and Implications for Drug Dosing

PURPOSE Clinicians are increasingly likely to have under their care obese children with diseases requiring pharmacotherapy. Optimal drug dosing for this population is unclear. Excess weight likely leads to alterations in pharmacokinetics. The purpose of this article was to describe the pharmacokinetics and pharmacodynamics in overweight and obese children and, where possible, provide recommendations for drug dosing. METHODS EMBASE (1980-May 2015), MEDLINE (1950-May 2015), and International Pharmaceutical Abstracts (1970-May 2015) databases were searched by using the following terms: obesity, morbid obesity, overweight, pharmacokinetics, pharmacodynamics, drug, dose, drug levels, pediatric, and child. The search was limited to English-language articles. References of relevant articles were searched to identify additional studies. FINDINGS Total body weight (TBW) is an appropriate size descriptor for dosing antineoplastic agents, succinylcholine, and cefazolin. Obese children seem to require less heparin, enoxaparin, and warfarin per kilogram TBW than normal-weight children; providing standard adult doses may be insufficient, however. Obese children may also require less vancomycin and aminoglycosides per kilogram TBW than normal-weight children. For these medications, an alternate size descriptor in children has not been described, and initial dosing based on TBW and monitoring serum concentrations (vancomycin and aminoglycosides) or coagulation parameters (heparin, enoxaparin, and warfarin) is warranted. Obese children require less propofol than normal-weight children; however, there is limited information about the dosing of other anesthetics or opioids. IMPLICATIONS Limitations to the available data include the inherent design constraints to case reports and retrospective cohort studies, as well as the small numbers of children in some of the studies. Use of normal-weight historical control subjects for obese children in the context of a pharmacokinetic study is not ideal. Although more information is becoming available, our understanding of the pharmacokinetics in obese children is still limited. When dosing information is not available for obese children, it may be necessary to extrapolate from available data in obese adults, but one should consider the effects of the childs age on pharmacokinetics.

Canadian Survey of Critical Care Pharmacists' Views and Involvement in Clinical Research

BACKGROUND: The involvement of Canadian critical care pharmacists in clinical research is not well documented. OBJECTIVE: To describe the clinical research experience of Canadian critical care pharmacists, describe their views about clinical research, and identify factors that facilitate their involvement in clinical research. METHODS: A cross-sectional electronic survey of Canadian critical care pharmacists was developed through an iterative process and conducted from July to October 2010. We invited 325 pharmacists from 129 hospitals across Canada to participate. Surveys with more than 30% of questions unanswered were discarded. RESULTS: Analyzable response rate was 66.2%. Overall, 33 pharmacists (15.7%) were highly involved in research, 54 (25.7%) were moderately involved, and 123 (58.6%) were minimally involved. Most respondents (97.2%) believed that critical care pharmacist involvement in research was desirable, and many (80.4%) expressed interest to be more involved in research. Nearly all respondents (99.5%) agreed that more support should be provided to pharmacists interested in conducting research. Pharmacists currently involved in research have obtained higher academic degrees (adjusted OR 11.23; p < 0.001), express a strong interest in research (adjusted OR 7.44; p < 0.001), report a higher level of training for involvement in research (adjusted OR 2.23; p = 0.047), and practice more often in a university hospital (adjusted OR 3.68; p = 0.004) within an intensive care unit where involvement in research is valued (adjusted OR 5.61; p < 0.001). Support from pharmacy departments is not related to involvement in research (adjusted OR 1.22; p = 0.633). CONCLUSIONS: Canadian critical care pharmacists are involved to varying degrees in clinical research and are very interested in initiating and supporting research activities. Opportunities are present but significant barriers exist. The value of pharmacist-initiated research needs recognition as a priority within hospital pharmacy administration.

A human factors and survey methodology-based design of a web-based adverse event reporting system for families

PURPOSE Adverse event reporting systems allow healthcare institutions to detect and prevent recurrence of avoidable patient harm. It is known that standard reporting systems, which are initiated by clinicians, detect only a minority of chart-documented adverse events. The objective of the study was to develop a web-based system, the Family Reporting System (FRS), to elicit adverse event reports from families of children admitted to hospital through survey methodology and human factors engineering techniques. MEASUREMENTS Face validity and usability were measured via standardized survey instruments. Utility was measured via the rate, typology, degree of harm, likelihood of recurrence, quality of information, and inter-rater agreement analysis of the reported events. RESULTS The FRS has good face validity, excellent usability, and good clinical utility. CONCLUSION The application of survey and human factors methodologies to the design of an electronic system is an effective means of developing an electronic adverse event reporting system for the use of families of pediatric patients.

Fluoxetine in the Treatment of Premenstrual Dysphoric Disorder

OBJECTIVE: To examine the role of fluoxetine in the treatment of premenstrual dysphoric disorder (PMDD). DATA SOURCES: Search strategy included MEDLINE (1966–February 2002), Embase (1988–February 2002), HealthStar (1975–December 2000), Current Contents (1996–November 2001), and Copernic (November 2001). Search terms included fluoxetine, premenstrual dysphoric disorder, PMDD, late luteal-phase dysphoric disorder, and severe premenstrual syndrome. STUDY SELECTION: English-language human studies were selected and evaluated based on quality of evidence. DATA SYNTHESIS: Eight prospective trials (3 double-blind, placebo-controlled, crossover; 3 double-blind, randomized, controlled; 2 open-label), 1 case series, and 1 meta-analysis were identified. Although 6 of the studies involved small sample sizes (n < 50), all found fluoxetine to be effective in the treatment of PMDD. CONCLUSIONS: Despite limited data, fluoxetine 20 mg/d appears to be effective in the treatment of PMDD. However, adverse effects, particularly headaches and sexual dysfunction, are possible. Given the long half-life of fluoxetine and the short duration of PMDD symptoms per cycle, larger, well-designed clinical trials evaluating intermittent dosing for only 1 week or a few doses need to be performed.

Drug Disposition and Therapy in Adolescence: The Effects of Puberty

Puberty, a part of adolescence, is a time of rapid physical, psychological, and psychosocial changes. Variability in drug absorption, distribution, metabolism and excretion occurs due to physical and hormonal changes, as well as those of body composition. Environmental factors affecting nutrition and compliance in the pubescent individual also affect success in achieving desired pharmacologic effects while minimizing toxicities. Based on available data, pharmacologic research has been relatively inadequate in providing information about drug disposition during puberty. The majority of available studies have neglected to provide staging for pubescent adolescents or have altogether excluded this population from their investigations. However, data are available that describe the effects of puberty on the pharmacokinetics of agents such as theophylline, digoxin, carbamazepine, lamotragine, vigabatrin and benzodiazepines.To date, few clinically significant changes in drug disposition have been noted during puberty. However, factors such as compliance, concomitant drug use, and the potentially rebellious nature of adolescents must be taken into consideration in the medical management of the adolescent.

Evaluating preferences for long term wheeze following RSV infection using TTO and best-worst scaling

Methods The objectives of this study were to explore preferences surrounding attributes of RSV using proxy- and selfperspectives. Time trade-off (TTO) and best-worst scaling were used to derive utilities for health states of RSV and determine relative preferences for different levels of disease attributes. Vignettes were constructed from focus group data and expert opinion. Respondents were randomized to either a child perspective (“imagine that your child has RSV”), or an adult perspective (“imagine that you have RSV”). Experimental design for the BWS was developed using Sawtooth Software. 1000 Canadians were recruited through a market research panel facilitating a societal perspective. Five attributes were used – hospitalization status, oxygen support, presence of tubes (IV/NG), breathing symptom severity, and risk of long term wheeze. Ethics approval was obtained from the UBC BREB. Respondents completed both TTO and BWS tasks. Results Disutility associated with the short term health state of RSV was significant. Disutility followed an expected gradient, with more time traded for more severe RSV, and less time traded for less severe RSV (mean range: 0.57 – 0.14). Utilities were lower in the child perspective than the adult perspective. 0% risk of long term risk of wheeze was most preferred over all other attributes, and respiratory failure was least preferred (-4.7). Strong negative preferences were similar for IV/NG (-3.3), ICU admission (-3.5), mechanical ventilation (-3.6), and severe breathing problems (-3.6). Utility associated with risk of wheeze became lower as risk increased, with a relative preference for 80% risk of wheeze (-2.8) between moderate (-1.5) and severe (-3.7) breathing problems. Conclusions Preferences indicate societal willingness to accept immediate, short term, potentially clinically significant consequences to avoid long term risk of wheeze. This study provides utilities that can be utilized for the evaluation of any potential or proposed treatment of RSV in children, and is important to understanding and applying priorities in health care.

The Medical Management of Pediatric Arrhythmias

Opinion statementArrhythmias are an important cause of morbidity and mortality in children. Despite recent technological advances in treatment, pharmacologic therapy remains the most common treatment modality for pediatric arrhythmias. The choice of antiarrhythmic agent, the duration of therapy, and the dosing schedule depend on multiple factors including the recurrence risk and the arrhythmia burden (the latter being determined by the hemodynamic effect of the arrhythmia), and the frequency and duration of episodes. As with all pediatric medications, consideration must be given to the drug formulation, palatability, adverse effects and adherence issues. There are very few randomized trials available to guide the choice of therapy for pediatric arrhythmias, and thus treatment options often reflect physician or institutional preferences. Although various classification schemes exist, we classify antiarrhythmic agents based on their primary site of action: atrial muscle/accessory pathway (class IA, IC, and III agents); the atrioventricular node (beta-blockers, calcium channel blockers, digoxin, and class III agents); or ventricular muscle (class I and III agents). This type of categorization assists in the approach to treatment required for each type of arrhythmia encountered.