Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomised controlled trial.

BACKGROUND: Phenytoin is the current standard of care for second-line treatment of paediatric convulsive status epilepticus after failure of first-line benzodiazepines, but is only effective in 60% of cases and is associated with considerable adverse effects. A newer anticonvulsant, levetiracetam, can be given more quickly, is potentially more efficacious, and has a more tolerable adverse effect profile. We aimed to determine whether phenytoin or levetiracetam is the superior second-line treatment for paediatric convulsive status epilepticus. METHODS: ConSEPT was an open-label, multicentre, randomised controlled trial conducted in 13 emergency departments in Australia and New Zealand. Children aged between 3 months and 16 years, with convulsive status epilepticus that failed first-line benzodiazepine treatment, were randomly assigned (1:1) using a computer-generated permuted block (block sizes 2 and 4) randomisation sequence, stratified by site and age (≤5 years, >5 years), to receive 20 mg/kg phenytoin (intravenous or intraosseous infusion over 20 min) or 40 mg/kg levetiracetam (intravenous or intraosseous infusion over 5 min). The primary outcome was clinical cessation of seizure activity 5 min after the completion of infusion of the study drug. Analysis was by intention to treat. This trial is registered with the Australian and New Zealand Clinical Trials Registry, number ACTRN12615000129583. FINDINGS: Between March 19, 2015, and Nov 29, 2017, 639 children presented to participating emergency departments with convulsive status epilepticus; 127 were missed, and 278 did not meet eligibility criteria. The parents of one child declined to give consent, leaving 233 children (114 assigned to phenytoin and 119 assigned to levetiracetam) in the intention-to-treat population. Clinical cessation of seizure activity 5 min after completion of infusion of study drug occurred in 68 (60%) patients in the phenytoin group and 60 (50%) patients in the levetiracetam group (risk difference -9·2% [95% CI -21·9 to 3·5]; p=0·16). One participant in the phenytoin group died at 27 days because of haemorrhagic encephalitis; this death was not thought to be due to the study drug. There were no other serious adverse events. INTERPRETATION: Levetiracetam is not superior to phenytoin for second-line management of paediatric convulsive status epilepticus. FUNDING: Health Research Council of New Zealand, A+ Trust, Emergency Medicine Foundation, Townsville Hospital Private Practice Fund, Eric Ormond Baker Charitable Fund, and Princess Margaret Hospital Foundation.

Variation in CT use for paediatric head injuries across different types of emergency departments in Australia and New Zealand.

OBJECTIVES: CT of the brain (CTB) for paediatric head injury is used less frequently at tertiary paediatric emergency departments (EDs) in Australia and New Zealand than in North America. In preparation for release of a national head injury guideline and given the high variation in CTB use found in North America, we aimed to assess variation in CTB use for paediatric head injury across hospitals types. METHODS: Multicentre retrospective review of presentations to tertiary, urban/suburban and regional/rural EDs in Australia and New Zealand in 2016. Children aged <16 years, with a primary ED diagnosis of head injury were included and data extracted from 100 eligible cases per site. Primary outcome was CTB use adjusted for severity (Glasgow Coma Scale) with 95% CIs; secondary outcomes included hospital length of stay and admission rate. RESULTS: There were 3072 head injury presentations at 31 EDs: 9 tertiary (n=900), 11 urban/suburban (n=1072) and 11 regional/rural EDs (n=1100). The proportion of children with Glasgow Coma Score ≤13 was 1.3% in each type of hospital. Among all presentations, CTB was performed for 8.2% (95% CI 6.4 to 10.0) in tertiary hospitals, 6.6% (95% CI 5.1 to 8.1) in urban/suburban hospitals and 6.1% (95% CI 4.7 to 7.5) in regional/rural. Intragroup variation of CTB use ranged from 0% to 14%. The regional/rural hospitals admitted fewer patients (14.6%, 95% CI 12.6% to 16.9%, p<0.001) than tertiary and urban/suburban hospitals (28.1%, 95% CI 25.2% to 31.2%; 27.3%, 95% CI 24.7% to 30.1%). CONCLUSIONS: In Australia and New Zealand, there was no difference in CTB use for paediatric patients with head injuries across tertiary, urban/suburban and regional/rural EDs with similar intragroup variation. This information can inform a binational head injury guideline.

Australasian bronchiolitis guideline.

AIM: Bronchiolitis is the most common lower respiratory tract disorder in infants aged less than 12 months, and research has demonstrated that there is substantial variation in practice patterns despite treatment being well defined. In order to align and improve the consistency of the management of bronchiolitis, an evidence-based guideline was developed for the Australasian population. METHODS: The guideline development committee included representation from emergency and paediatric specialty medical and nursing personnel in addition to geographical representation across Australia and New Zealand - rural, remote and metropolitan. Formulation of the guideline included identification of population, intervention, comparator, outcomes and time questions and was associated with an extensive literature search from 2000 to 2015. Evidence was summarised and graded using the National Health and Medical Research Council and Grading of Recommendations Assessment, Development and Evaluation methodology, and consensus within the guideline group was sought using nominal group technique principles to formulate the clinical practice recommendations. The guideline was reviewed and endorsed by key paediatric health bodies. RESULTS: The guideline consists of a usable clinical interface for bedside functionality supported by evidence summary and tables. The Grading of Recommendations Assessment, Development and Evaluation and National Health and Medical Research Council processes provided a systematic and transparent process to review and assess the literature, resulting in a guideline that is relevant to the management of bronchiolitis in the Australasian setting. CONCLUSION: This is the first robust Australasian acute paediatric guideline and provides clear guidance for the management of the vast majority of patients seen in Australasian emergency departments and general paediatric wards with bronchiolitis.

A multicentre randomised controlled trial of levetiracetam versus phenytoin for convulsive status epilepticus in children (protocol): Convulsive Status Epilepticus Paediatric Trial (ConSEPT) - a PREDICT study.

BACKGROUND: Convulsive status epilepticus (CSE) is the most common life-threatening childhood neurological emergency. Despite this, there is a lack of high quality evidence supporting medication use after first line benzodiazepines, with current treatment protocols based solely on non-experimental evidence and expert opinion. The current standard of care, phenytoin, is only 60% effective, and associated with considerable adverse effects. A newer anti-convulsant, levetiracetam, can be given faster, is potentially more efficacious, with a more tolerable side effect profile. The primary aim of the study presented in this protocol is to determine whether intravenous (IV) levetiracetam or IV phenytoin is the better second line treatment for the emergency management of CSE in children. METHODS/DESIGN: 200 children aged between 3 months and 16 years presenting to 13 emergency departments in Australia and New Zealand with CSE, that has failed to stop with first line benzodiazepines, will be enrolled into this multicentre open randomised controlled trial. Participants will be randomised to 40 mg/kg IV levetiracetam infusion over 5 min or 20 mg/kg IV phenytoin infusion over 20 min. The primary outcome for the study is clinical cessation of seizure activity five minutes following the completion of the infusion of the study medication. Blinded confirmation of the primary outcome will occur with the primary outcome assessment being video recorded and assessed by a primary outcome assessment team blinded to treatment allocation. Secondary outcomes include: Clinical cessation of seizure activity at two hours; Time to clinical seizure cessation; Need for rapid sequence induction; Intensive care unit (ICU) admission; Serious adverse events; Length of Hospital/ICU stay; Health care costs; Seizure status/death at one-month post discharge. DISCUSSION: This paper presents the background, rationale, and design for a randomised controlled trial comparing levetiracetam to phenytoin in children presenting with CSE in whom benzodiazepines have failed. This study will provide the first high quality evidence for management of paediatric CSE post first-line benzodiazepines. TRIAL REGISTRATION: Prospectively registered with the Australian and New Zealand Clinical Trial Registry (ANZCTR): ACTRN12615000129583 (11/2/2015). UTN U1111-1144-5272. ConSEPT protocol version 4 (12/12/2014).

Fever phobia in caregivers presenting to New Zealand emergency departments.

OBJECTIVE: To determine the prevalence of fever phobia among caregivers of children presenting to New Zealand EDs. METHODS: A cross-sectional survey was administered to caregivers of children <5 years of age presenting to three New Zealand EDs. We defined fever phobia as caregivers having a high level of concern regarding fever or having incorrect beliefs regarding the consequences of fever. RESULTS: A total of 502 caregivers completed the survey. Fever phobia was present in 365 (74.3% [95% confidence interval, CI 70.3-78.0%]) respondents, with 242 (49.3% [95% CI 44.9-53.7%]) caregivers reporting a high level of concern regarding fever, and 288 (61.8% [95% CI 57.3-66.1%]) caregivers reporting at least one incorrect belief regarding the consequences of fever. Majority of caregivers (n = 383, 87.6% [95% CI 84.2-90.4%]) knew the correct dosing interval for paracetamol, compared to less than half of caregivers (n = 179, 42.5% [95% CI 37.9-47.3%]) for ibuprofen. Caregivers reported non-evidence-based fever management practices such as sponging, always giving paracetamol and/or ibuprofen for fever, and waking children from sleep to give antipyretics. Over one-third of caregivers identified ED doctors (n = 195, 40.2% [95% CI 34.7-43.2%]) and ED nurses (n = 173, 35.7% [95% CI 31.5-40.0%]) as sources of information regarding fever management. A higher level of education was associated with fever phobia (odds ratio 1.68 [95% CI 1.04-2.72], P = 0.04). CONCLUSIONS: Fever phobia is prevalent among caregivers of children presenting to New Zealand EDs. Opportunistic caregiver education in the ED in conjunction with public health strategies are needed to dispel undue fears and misconceptions about fever.

Impact of oral corticosteroids on respiratory outcomes in acute preschool wheeze: a randomised clinical trial.

OBJECTIVE: To determine if administration of oral prednisolone to preschool children with acute wheeze alters respiratory outcomes. DESIGN: Double-blind, randomised, placebo-controlled equivalence trial. SETTING: Three hospitals in New Zealand. PATIENTS: 477 children aged 24-59 months with acute wheeze associated with respiratory illness. INTERVENTIONS: 2 mg/kg (maximum 40 mg) oral prednisolone or similar placebo, once daily for 3 days. MAIN OUTCOME MEASURES: Primary outcome was change in Preschool Respiratory Assessment Measure (PRAM) score 24 hours after intervention. Secondary outcomes included PRAM score at 4 hours, length of emergency department and inpatient stays, admission and representation rates, time to return to normal activities and use of additional oral prednisolone or intravenous medications. Analysis was by intention-to-treat. RESULTS: There was no difference between groups for change in PRAM score at 24 hours (difference between means -0.39, 95% CI -0.84 to 0.06, p=0.09). Absolute PRAM score was lower in the prednisolone group at 4 hours (median (IQR) 1 (0-2) vs 2 (0-3), p=0.01) and 24 hours (0 (0-1) vs 0 (0-1), p=0.01), when symptoms had resolved for most children regardless of initial treatment. Admission rate, requirement for additional oral prednisolone and use of intravenous medication were lower in the prednisolone group, although there were no differences between groups for time taken to return to normal activities or rates of representation within 7 days. CONCLUSION: Oral prednisolone does not alter respiratory outcomes at 24 hours or beyond in preschool children presenting with acute wheeze.

Fetal heart rate variability and brain stem injury after asphyxia in preterm fetal sheep.

This study was undertaken to determine the mechanisms mediating changes in fetal heart rate variability (FHRV) during and after exposure to asphyxia in the premature fetus. Preterm fetal sheep at 0.6 of gestation (91 +/- 1 days, term is 147 days) were exposed to either sham occlusion (n = 10) or to complete umbilical cord occlusion for either 20 (n = 7) or 30 min (n = 10). Cord occlusion led to a transient increase in FHRV with abrupt body movements that resolved after 5 min. In the 30 min group there was a marked increase in FHRV in the final 10 min of occlusion related to abnormal atrial activity. After reperfusion, FHRV in both study groups was initially suppressed and progressively increased to baseline levels over the first 4 h of recovery. In the 20 min group this improvement was associated with return of normal EEG activity and movements. In contrast, in the 30 min group the EEG was abnormal with epileptiform activity superimposed on a suppressed background, which was associated with abnormal fetal movements. As the epileptiform activity resolved, FHRV fell and became suppressed for the remainder of the study. Histological assessment after 72 h demonstrated severe brain stem injury in the 30 min group but not in the 20 min group. In conclusion, during early recovery from asphyxia, epileptiform activity and associated abnormal fetal movements related to evolving neural injury can cause a confounding transient increase in FHRV, which mimics the normal pattern of recovery. However, chronic suppression of FHRV was a strong predictor of severe brain stem injury.