Seizure Treatment in Children Transported to Tertiary Care: Recommendation Adherence and Outcomes.

Convulsive seizures account for 15% of pediatric air transports. We evaluated seizure treatment received in community hospital emergency departments among transported patients for adherence to recommended management. This study was a retrospective cohort study of children transported for an acute seizure to a tertiary pediatric hospital from 2010 to 2013. Seizure treatment was evaluated for adherence to recommended management. The primary outcome was intubation. Among 126 events, 61% did not receive recommended acute treatment. The most common deviation from recommended care was administration of >2 benzodiazepine doses. Lack of adherence to recommended care was associated with a greater than twofold increased risk of intubation (relative risk 2.4; 95% confidence interval, 1.4-4.13) and 1.5-fold increased risk of admission to the ICU (relative risk 1.65; 95% confidence interval, 1.24-2.16). Duration of ventilation was commonly <24 hours (87%) for patients who did or did not receive recommended acute seizure care. Among events treated initially with a benzodiazepine, only 32% received a recommended weight-based dosage, and underdosing was most common. Adherence to evidence-based recommended acute seizure treatment during initial care of pediatric patients using medical air transportation was poor. Intubation was more common when patients did not receive recommended acute seizure care. Educational efforts with a sustained quality focus should be directed to increase adherence to appropriate pediatric seizure treatment of children in community emergency departments

Variation of community consultation and public disclosure for a pediatric multi-centered Exception from Informed Consent trial

BACKGROUND: The U.S. federal regulation “Exception from Informed Consent (EFIC) for Emergency Research,” 21 Code of Federal Regulations 50.24, permits emergency research without informed consent under limited conditions. Additional safeguards to protect human subjects include requirements for community consultation and public disclosure prior to starting the research. Because the regulations are vague about these requirements, Institutional Review Boards (IRBs) determine the adequacy of these activities at a local level. Thus there is potential for broad interpretation and practice variation. AIM: To describe the variation of community consultation and public disclosure activities approved by IRBs, and the effectiveness of this process for a multi-center, EFIC, pediatric status epilepticus clinical research trial. Methods: Community consultation and public disclosure activities were analyzed for each of 15 participating sites. Surveys were conducted with participants enrolled in the status epilepticus trial to assess the effectiveness of public disclosure dissemination prior to study enrollment. RESULTS: Every IRB, among the 15 participating sites, had a varied interpretation of EFIC regulations for community consultation and public disclosure activities. IRBs required various combinations of focus groups, interviews, surveys, and meetings for community consultation; news releases, mailings, and public service announcements for public disclosure. At least 4,335 patients received information about the study from these efforts. 158 chose to be included in the “Opt Out” list. Of the 304 participants who were enrolled under EFIC, 12 (5%) had heard about the study through community consultation or public disclosure activities. The activities reaching the highest number of participants were surveys and focus groups associated with existing meetings. Public disclosure activities were more efficient and cost-effective if they were part of an in-hospital resource for patients and families. CONCLUSION: There is substantial variation in IRBs' interpretations of the federal regulations for community consultation and public disclosure. One of the goals of community consultation and public disclosure efforts for emergency research is to provide community members an opportunity to opt-out of EFIC research; however, rarely do patients or their legally authorized representatives report having learned about a study prior to enrollment

Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group (ESETT): a double-blind, responsive-adaptive, randomised controlled trial

BackgroundBenzodiazepine-refractory, or established, status epilepticus is thought to be of similar pathophysiology in children and adults, but differences in underlying aetiology and pharmacodynamics might differentially affect response to therapy. In the Established Status Epilepticus Treatment Trial (ESETT) we compared the efficacy and safety of levetiracetam, fosphenytoin, and valproate in established status epilepticus, and here we describe our results after extending enrolment in children to compare outcomes in three age groups.MethodsIn this multicentre, double-blind, response-adaptive, randomised controlled trial, we recruited patients from 58 hospital emergency departments across the USA. Patients were eligible for inclusion if they were aged 2 years or older, had been treated for a generalised convulsive seizure of longer than 5 min duration with adequate doses of benzodiazepines, and continued to have persistent or recurrent convulsions in the emergency department for at least 5 min and no more than 30 min after the last dose of benzodiazepine. Patients were randomly assigned in a response-adaptive manner, using Bayesian methods and stratified by age group (<18 years, 18-65 years, and >65 years), to levetiracetam, fosphenytoin, or valproate. All patients, investigators, study staff, and pharmacists were masked to treatment allocation. The primary outcome was absence of clinically apparent seizures with improved consciousness and without additional antiseizure medication at 1 h from start of drug infusion. The primary safety outcome was life-threatening hypotension or cardiac arrhythmia. The efficacy and safety outcomes were analysed by intention to treat. This study is registered in ClinicalTrials.gov, NCT01960075.FindingsBetween Nov 3, 2015, and Dec 29, 2018, we enrolled 478 patients and 462 unique patients were included: 225 children (aged <18 years), 186 adults (18-65 years), and 51 older adults (>65 years). 175 (38%) patients were randomly assigned to levetiracetam, 142 (31%) to fosphenyltoin, and 145 (31%) were to valproate. Baseline characteristics were balanced across treatments within age groups. The primary efficacy outcome was met in those treated with levetiracetam for 52% (95% credible interval 41-62) of children, 44% (33-55) of adults, and 37% (19-59) of older adults; with fosphenytoin in 49% (38-61) of children, 46% (34-59) of adults, and 35% (17-59) of older adults; and with valproate in 52% (41-63) of children, 46% (34-58) of adults, and 47% (25-70) of older adults. No differences were detected in efficacy or primary safety outcome by drug within each age group. With the exception of endotracheal intubation in children, secondary safety outcomes did not significantly differ by drug within each age group.InterpretationChildren, adults, and older adults with established status epilepticus respond similarly to levetiracetam, fosphenytoin, and valproate, with treatment success in approximately half of patients. Any of the three drugs can be considered as a potential first-choice, second-line drug for benzodiazepine-refractory status epilepticus.FundingNational Institute of Neurological Disorders and Stroke, National Institutes of Health