Management of the first stage of convulsive status epilepticus in adults: a systematic review of current randomised evidence

Moira Cruickshank, Mari Imamura, Carl Counsell, Lorna Aucott, Paul Manson, Corinne Booth, Graham Scotland, Miriam Brazzelli* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

6 Citations (Scopus)
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Background: Convulsive status epilepticus is the most severe form of epilepsy and requires urgent treatment. We synthesised the current evidence on first-line treatments for controlling seizures in adults with convulsive status epilepticus before, or at, arrival at hospital. Methods: We conducted a systematic review of randomised controlled trials (RCTs) assessing antiepileptic drugs offered to adults as first-line treatments. Major electronic databases were searched. Results: Four RCTs (1234 adults) were included. None were conducted in the UK and none assessed the use of buccal or intranasal midazolam. Both intravenous lorazepam and intravenous diazepam administered by paramedics were more effective than placebo and, notably, intramuscular midazolam was non-inferior to intravenous lorazepam. Overall, median time to seizure cessation from drug administration varied from 2 to 15 min. Rates of respiratory depression among participants receiving active treatments ranged from 6.4 to 10.6%. Mortality ranged from 2 to 7.6% in active treatment groups and 6.2 to 15.5% in control groups. Conclusions: Intravenous and intramuscular benzodiazepines are safe and effective in this clinical context. Further research is needed to establish the most clinically and cost-effective first-line treatment and preferable mode of administration. Head-to-head trials comparing buccal versus intranasal midazolam versus rectal diazepam would provide useful information to inform the management of the first stage of convulsive status epilepticus in adults, especially when intravenous or intramuscular access is not feasible. Approaches to improve adherence to clinical guidelines on the use of currently available benzodiazepines for the first-line treatment of convulsive status epilepticus should also be considered.

Original languageEnglish
Pages (from-to)3420-3429
Number of pages10
JournalJournal of Neurology
Issue number7
Early online date30 Jan 2022
Publication statusPublished - 1 Jul 2022

Bibliographical note

Funding Information:
This work is funded by the National Institute for Health Research, Project No. 132153.


  • Convulsive status epilepticus
  • benzodiazepines
  • antiepileptic drugs
  • first-line treatment
  • review
  • First-line treatment
  • Review
  • Antiepileptic drugs
  • Benzodiazepines
  • Midazolam/therapeutic use
  • Humans
  • Status Epilepticus/drug therapy
  • Anticonvulsants/therapeutic use
  • Seizures/drug therapy
  • Adult
  • Diazepam/therapeutic use
  • Lorazepam/therapeutic use


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