Authors' objectives: Convulsive status epilepticus is defined as ≥ 5 minutes of either continuous seizure activity or repetitive seizures without regaining consciousness. It is regarded as an emergency condition that requires prompt treatment to avoid hospitalisation and to reduce morbidity and mortality. Rapid pre-hospital first-line treatment of convulsive status epilepticus is currently benzodiazepines, administered either by trained caregivers in the community (e.g. buccal midazolam, rectal diazepam) or by trained health professionals via intramuscular or intravenous routes (e.g. midazolam, lorazepam). There is a lack of clarity about the optimal treatment for convulsive status epilepticus in the pre-hospital setting. To assess the current evidence on the clinical effectiveness and cost-effectiveness of treatments for adults with convulsive status epilepticus in the pre-hospital setting.

Authors' results and conclusions: Four trials (1345 randomised participants, of whom 1234 were adults) assessed the intravenous or intramuscular use of benzodiazepines or other antiepileptic drugs for the pre-hospital treatment of convulsive status epilepticus in adults. Three trials at a low risk of bias showed that benzodiazepines were effective in stopping seizures. In particular, intramuscular midazolam was non-inferior to intravenous lorazepam. The addition of levetiracetam to clonazepam did not show clear advantages over clonazepam alone. One trial at a high risk of bias showed that phenobarbital plus optional phenytoin was more effective in terminating seizures than diazepam plus phenytoin. The median time to seizure cessation from drug administration varied from 1.6 minutes to 15 minutes. The proportion of people with recurrence of seizures ranged from 10.4% to 19.1% in two trials reporting this outcome. Across trials, the rates of respiratory depression among participants receiving active treatments were generally low (from 6.4% to 10.6%). The mortality rate ranged from 2% to 7.6% in active treatment groups and from 6.2% to 15.5% in control groups. Only one study based on retrospective observational data met the criteria for economic evaluation; therefore, it was not possible to draw any robust conclusions on cost-effectiveness. Both intravenous lorazepam and intravenous diazepam administered by paramedics are more effective than a placebo in the treatments of adults with convulsive status epilepticus, and intramuscular midazolam is non-inferior to intravenous lorazepam. Large well-designed clinical trials are needed to establish which benzodiazepines are more effective and preferable in the pre-hospital setting.

Authors' methods: We searched major electronic databases, including MEDLINE, EMBASE, PsycInfo®, CINAHL, CENTRAL, NHS Economic Evaluation Database, Health Technology Assessment Database, Research Papers in Economics, and the ISPOR Scientific Presentations Database, with no restrictions on publication date or language of publication. Final searches were carried out on 21 July 2020. Systematic review of randomised controlled trials assessing adults with convulsive status epilepticus who received treatment before or on arrival at the emergency department. Eligible treatments were any antiepileptic drugs offered as first-line treatments, regardless of their route of administration. Primary outcomes were seizure cessation, seizure recurrence and adverse events. Two reviewers independently screened all citations identified by the search strategy, retrieved full-text articles, extracted data and assessed the risk of bias of the included trials. Results were described narratively. The limited number of identified trials and their differences in terms of treatment comparisons and outcomes hindered any meaningful pooling of data. None of the included trials was conducted in the UK and none assessed the use of buccal midazolam or rectal diazepam. The review of economic evaluations was hampered by lack of suitable data.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/NIHR132153#/

Year Published: 2022

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/RSVK2062#/abstract

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/RSVK2062

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk