John Hayden

Efficacy of α2-Agonists for Sedation in Pediatric Critical Care: A Systematic Review.

Objective: Children in PICUs normally require analgesics and sedatives to maintain comfort, safety, and cooperation with interventions. &agr;2-agonists (clonidine and dexmedetomidine) have been described as adjunctive (or alternative) sedative agents alongside opioids and benzodiazepines. This systematic review aimed to determine whether &agr;2-agonists were effective in maintaining patients at a target sedation score over time compared with a comparator group. We also aimed to determine whether concurrent use of &agr;2-agonists provided opioid-sparing effects. Data Sources: A systematic search was performed using the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, CINAHL, and LILACS. Study Selection: We included randomized controlled trials of children in PICU treated with clonidine or dexmedetomidine for the indication of sedation. Data Extraction: Two authors independently screened articles for inclusion. Data Synthesis: Six randomized controlled trials with sufficient data were identified and critically appraised. Three clonidine trials (two vs placebo and one vs midazolam) and three dexmedetomidine trials (two vs fentanyl, one vs midazolam) were included. Due to study heterogeneity it was not possible to pool studies. A narrative synthesis is provided. Conclusions: Reporting of study results using the outcome “time maintained at target sedation score’ for clonidine or dexmedetomidine was poor. Only one trial compared clonidine with midazolam using a sedation score outcome. This study was underpowered to demonstrate equivalence to midazolam as a sedative. The adjunctive use of clonidine demonstrated significant decreases in opioid use in neonates but not in older groups. Clonidine dose was inconsistent between studies. Dexmedetomidine demonstrated an opioid-sparing effect in two small trials. Further studies, including dose-finding studies and studies with sedation score–based outcomes, are needed.

Intranasal fentanyl versus intravenous morphine in the emergency department treatment of severe painful sickle cell crises in children: Study protocol for a randomised controlled trial

BackgroundChildren with sickle cell disease (SCD) frequently and unpredictably present to the emergency department (ED) with pain. The painful event is the hallmark acute clinical manifestation of SCD, characterised by sudden onset and is usually bony in origin. This study aims to establish if 1.5mcg/kg of intranasal fentanyl (INF; administered via a Mucosal Atomiser Device, MAD™) is non-inferior to intravenous morphine 0.1 mg/kg in severe SCD-associated pain.Methods/designThis study is a randomised,double-blind, double-dummy active control trial of children (weighing more than 10 kg) between 1 year and 21 years of age with severe painful sickle cell crisis. Severe pain is defined as rated seven or greater on a 0 to 10 age-appropriate numeric pain scale or equivalent. The trial will be conducted in a single tertiary urban paediatric ED in Dublin, Ireland. Each patient will receive a single active agent and a single placebo via the intravenous and intranasal routes. All clinical and research staff, patients and parents will be blinded to the treatment allocation. The primary endpoint is severity of pain scored at 10 min from administration of the study medications. Secondary endpoints include pain severity measured at 0, 5, 15, 20, 30, 60 and 120 min after the administration of analgesia, proportion of patients requiring rescue analgesia and incidence of adverse events. The trial ends at 120 min after the administration of the study drugs. A clinically meaningful difference in validated pain scores has been defined as 13 mm. Setting the permitted threshold to 50% of this limit (6 mm) and assuming both treatments are on average equal, a sample size of 30 patients (15 per group) will provide at least 80% power to demonstrate that INF is non-inferior to IV morphine with a level of significance of 0.05.DiscussionThis clinical trial will inform of the role of INF 1.5mcg/kg via MAD in the acute treatment of severe painful sickle cell crisis in children in the ED setting.Trial registrationCurrent Controlled Trials ISRCTN67469672 and EudraCT no. 2011-005161-20

Single dose oral dexamethasone versus multi-dose prednisolone in the treatment of acute exacerbations of asthma in children who attend the emergency department: study protocol for a randomized controlled trial

BackgroundAsthma is a major cause of pediatric morbidity and mortality. In acute exacerbations of asthma, corticosteroids reduce relapses, subsequent hospital admission and the need for ß2-agonist therapy. Prednisolone is relatively short-acting with a half-life of 12 to 36 hours, thereby requiring daily dosing. Prolonged treatment course, vomiting and a bitter taste may reduce patient compliance with prednisolone. Dexamethasone is a long-acting corticosteroid with a half-life of 36 to 72 hours. It is used frequently in children with croup and bacterial meningitis, and is well absorbed orally. The purpose of this trial is to examine whether a single dose of oral dexamethasone (0.3 mg/kg) is clinically non-inferior to prednisolone (1 mg/kg/day for three days) in the treatment of exacerbations of asthma in children who attend the Emergency Department.Methods/designThis is a randomized, non-inferiority, open-label clinical trial. After informed consent with or without assent, patients will be randomized to either oral dexamethasone 0.3 mg/kg stat or prednisolone 1 mg/kg/day for three days. The primary outcome measure is the comparison between the Pediatric Respiratory Assessment Measure (PRAM) across both groups on Day 4. The PRAM score, a validated, responsive and reliable tool to determine asthma severity in children aged 2 to 16 years, will be performed by a clinician blinded to treatment allocation. Secondary outcomes include relapse, hospital admission and requirement for further steroid therapy. Data will be analyzed on an intention-to-treat and a per protocol basis. With a sample size of 232 subjects (105 in each group with an estimated 10% loss to follow-up), we will be able to reject the null hypothesis - that the population means of the experimental and control groups are equal with a probability (power) of 0.9. The Type I error probability associated with this test (of the null hypothesis) is 0.05.DiscussionThis clinical trial may provide evidence that a shorter steroid course using dexamethasone can be used in the treatment of acute pediatric asthma, thus eliminating the issue of compliance to treatment.RegistrationISRCTN26944158 and EudraCT Number 2010-022001-18

Design and Evaluation of Video Podcasts for Providing Online Feedback on Formative Pharmaceutical Calculations Assessments

Objective. To evaluate worked example video podcasts as a method of providing feedback to pharmacy interns for an online and formative pharmaceutical calculations assessment. Methods. A theory-informed approach based on multimedia learning theory was used to design video podcasts as feedback on a calculations examination. A mixed-methods evaluation completed by pharmacy interns enrolled in Ireland’s National Pharmacy Internship Programme was used to establish cognitive and affective attitudes toward video podcasts compared with conventional written solutions. Results. The majority of students found video podcasts were clear, helpful for learning, easy to understand, and useful as a method of feedback. Majority reported that they felt positively about standard written solutions. The evaluation suggested distinct benefits for each kind of feedback, something that has not been previously reported. Thematic analysis of qualitative data indicated useful features of video podcasts, including clear explanation, step-by-step approach, and synchronization of audio and visual information. Conclusion. Respondents reported positive cognitive and affective attitudes toward video podcasts as online feedback. Video podcasts are a helpful and novel way of providing feedback on pharmaceutical calculations. A similar opinion of traditional written solutions suggests that students may benefit from both forms of feedback. Further study is required to identify the particular benefits associated with both kinds.

Medication accessibility after diagnosis of ADHD in Croatia – Authors' reply

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Abstract P-480: α2 AGONISTS IN PAEDIATRIC CRITICAL CARE SEDATION

A national survey was conducted in two parts, the initial stage involved contacting all paediatric intensive care units in the UK by the telephone to ascertain whether there was a nursing protocol for paralysed patients. The second stage, an online survey, was sent to all paediatric intensive care units agreeing to participate, distributed locally by email, amongst all nursing staff to evaluate individual understanding. The survey contained 5 basic questions aiming to gauge the differentiation between sedation and paralysis, then the monitoring of paralysis.

Effectiveness of α2agonists for sedation in paediatric critical care: study protocol for a retrospective cohort observational study

Introduction Mechanically ventilated children in paediatric intensive care units are commonly administered analgesics and sedative agents to minimise pain and distress and facilitate cooperation with medical interventions. Opioids and benzodiazepines are the most common analgesic and sedative agents but have safety concerns. The α2 agonists clonidine and dexmedetomidine are alternative sedatives in use despite neither having robust evidence to support their use. Studies evaluating effectiveness of α2 agonists to date have not focused on sedation-based outcomes instead focusing on opioid-sparing properties and ventilation outcomes. The aim of this study is to evaluate if an opioid-based sedation regimen, with an α2 agonist adjunct (clonidine or dexmedetomidine), produces a non-inferior proportion of time adequately sedated compared with a control group without an α2 agonist adjunct, while conferring potential additional benefits such as reduced opioid administration and less exposure to potential additional agents such as benzodiazepines. Methods and analysis We will conduct a retrospective cohort study in two Irish paediatric intensive care units using clinical information on patient characteristics, sedation scores and drug use. Eligible children admitted between January 2014 and June 2016 who were mechanically ventilated and received an opioid infusion will be included. Patients will be categorised into two exposure categories (received an α2 agonist or did not receive an α2 agonist) and the time adequately sedated (measured using the COMFORT Behaviour Score) will be calculated using interpolation of nursing sedation scores at each recorded time point. At least 150 per group is planned for inclusion to ensure adequate study power. Propensity score matching will be used in analysis to account for potential confounding by indication. Ethics and dissemination The study has been approved by the ethics committees of both hospitals. Dissemination will occur via local, national and international presentations for academic and healthcare audiences as well as through peer reviewed publications.