John McIntyre

Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial

BACKGROUND Rectal diazepam and buccal midazolam are used for emergency treatment of acute febrile and afebrile (epileptic) seizures in children. We aimed to compare the safety and efficacy of these drugs. METHODS A multicentre, randomised controlled trial was undertaken to compare buccal midazolam with rectal diazepam for emergency-room treatment of children aged 6 months and older presenting to hospital with active seizures and without intravenous access. The dose varied according to age from 2.5 to 10 mg. The primary endpoint was therapeutic success: cessation of seizures within 10 min and for at least 1 hour, without respiratory depression requiring intervention. Analysis was per protocol. FINDINGS Consent was obtained for 219 separate episodes involving 177 patients, who had a median age of 3 years (IQR 1-5) at initial episode. Therapeutic success was 56% (61 of 109) for buccal midazolam and 27% (30 of 110) for rectal diazepam (percentage difference 29%, 95% CI 16-41). Analysing only initial episodes revealed a similar result. The rate of respiratory depression did not differ between groups. When centre, age, known diagnosis of epilepsy, use of antiepileptic drugs, prior treatment, and length of seizure before treatment were adjusted for with logistic regression, buccal midazolam was more effective than rectal diazepam. INTERPRETATION Buccal midazolam was more effective than rectal diazepam for children presenting to hospital with acute seizures and was not associated with an increased incidence of respiratory depression.

Respiratory depression in children receiving diazepam for acute seizures: a prospective study

The aim of this study was to determine the incidence of respiratory depression following the use of diazepam in children presenting with seizures. All children presenting with seizures to a childrens A & E department over a period of 9 months were studied prospectively. Respiratory depression was defined as a fall in respiratory rate or oxygen saturation, or apnoea resulting in ventilation or resuscitation with bag‐and‐mask oxygen. There were 130 patient episodes involving 97 children who received treatment for their seizures before admission and/or in the A & E department. Administration of diazepam resulted in 122 patient episodes. The route of administration was rectal in 91 episodes, intravenous in 12 episodes, and both rectal and intravenous in 19 episodes. Eleven children had respiratory depression in relation to diazepam administration. Eight of these children required ventilation. The overall incidence of respiratory depression following the use of diazepam was 9%. The incidence of respiratory depression following diazepam given intravenously or rectally is high. The use of diazepam as first‐line therapy for children with acute seizures needs to be reviewed.

Drug Toxicity in the Neonate

The incidence of adverse drug reactions in neonates is thought to be at least 10%. The physiology of the newborn infant is different to that of both paediatric patients and adults. This therefore predisposes to certain types of drug toxicity, which are described below. Medication errors are also a significant problem in the neonatal period due to the lack of appropriate formulations designed for neonates.

Use of Over the Counter Medicines in Children

Objective To assess the reasons for over‐the‐counter (OTC) medicine use in children and the sociodemographic factors influencing this choice of self‐care rather than GP consultation.

Research in general paediatrics

Do district general hospitals have a role? The aim of this leading article is to explore the important topic of research in general paediatrics. The need for research in this field will be reviewed along with where and who should be carrying this out. The role of district general hospitals (DGHs) in research in general paediatrics is discussed. Decision making within medicine has correctly shifted towards evidence based practice. It is important to ensure that in the most common conditions seen in general paediatrics children receive the best treatment. There are still many situations, for example, treatment of acute seizures and sedation for procedures, which have outstanding therapeutic and management questions that need answering through research. The need to encourage research has been acknowledged by the inclusion of a general paediatric section in the Royal College of Paediatrics and Child Health Annual Meeting in York over the past few years. A review of randomised controlled trials (RCTs) published in Archives of Disease in Childhood from 1982 to 1996 found 249 RCTs, with only 28% being classified as being within the area of general paediatrics.1 This suggests that much of our research potential is concentrated on rare conditions and neglects the more common general paediatrics. Research is often thought of as non-clinical and clinical research. Non-clinical research, such as molecular and animal studies, is usually performed in academic laboratory based facilities and gives us the ideas and theories that are carried through into our clinical research. Clinical research, such as that into new drug therapies, is usually carried out initially in healthy adult volunteers and then tested in the paediatric patient population.2,3 Therefore wherever there is a paediatric population of patients there is the potential for research. General paediatricians in DGHs have participated in large multicentre trials, for …

Clinical trials: the viewpoint of children with a chronic illness compared with healthy children

The views of over 200 children (11–16 years old, who were either healthy or attending paediatric medical clinics with a chronic illness) on issues relating to paediatric clinical trials were determined by a questionnaire. Children with a chronic illness had a better understanding of the concept of dosing of medicines (40% vs 23%) and placebo (34% vs 20%). They were more likely to support childrens involvement in clinical trials (51% vs 37%). The altruistic nature of children in both groups was similar. It was of concern, however, that 57–63% children would participate as healthy volunteers in a cancer drug trial. Both groups were able to differentiate between the different types of illnesses where it is appropriate to study medicines in children (86–89% for illness where there is no treatment; 34–40% for ‘me-too’ drugs). Young people should be given more opportunities to be involved in decision-making regarding clinical trials of medicines.

Management of fever in children

Fever is a common symptom in children and probably the most common reason for a child to be taken to the doctor.1 It is a cause of anxiety for carers, bringing to the surface many fears, most of which are unfounded.2,–,5 The reaction of the health professional may reinforce these concerns, particularly if the nature of fever and its significance is not properly communicated and fever is managed as an illness rather than a symptom.3 Antipyretic use is widespread both in prehospital and hospital settings. When temperature reduction is seen as the end point, it is not surprising that various drugs and combinations of drugs have been used. The systematic review of studies comparing combined treatment of the commonly used antipyretics—paracetamol and ibuprofen—concludes that there is little benefit from a polypharmaceutical approach.6 It is also a reminder of how intensely research studies have pursued temperature reduction as the primary end point, perhaps at the expense of more important end points and of thinking of fever as a physiological response. All forms of life have a range of preferred environmental temperatures and seem to have thermoregulatory mechanisms. As homeotherms, humans regulate and maintain core temperature within very narrow limits, despite much larger variations in ambient temperature. Fever is not simply an elevated body temperature but a controlled elevation of body temperature above the normal range.7 8 The rise in body temperature results from an elevation of the hypothalamic …

The Caffeine Breath Test and CYP1A2 Activity in Children

The caffeine breath test is a non-invasive method of studying CYP1A2 activity that is suitable for children from the ages of 3 years upwards. It involves the oral administration of a stable isotope and the collection of breath samples for a period of 2 hours. Breath samples are analysed by continuous flow isotope ratio mass spectrometry. It has been used to study both drug interactions and the effect of disease on drug metabolism.