Abstract
BackgroundConvulsive 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.MethodsWe conducted a systematic review of randomised controlled trials (RCTs) assessing antiepileptic drugs offered to adults as first-line treatments. Major electronic databases were searched.ResultsFour 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.ConclusionsIntravenous 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.
Highlights
Convulsive status epilepticus is the most severe form of epileptic attack and a life-threatening neurological emergency, which is associated with substantial mortality and morbidity [1,2,3,4]
Definition of seizure cessation and of convulsive status epilepticus varied across the four included trials, our findings showed that, in general, benzodiazepines were effective at stopping seizures in adults treated in the pre-hospital setting
In the only trial with an untreated placebo arm by Alldredge et al, convulsive status epilepticus was successfully terminated before arrival at the emergency department in 59.1%, of adults treated with 2 mg IV lorazepam, in 42.6% of those treated with 5 mg IV diazepam and in 21.1% of those who received placebo, with no significant difference between the two benzodiazepine treatments [15]
Summary
Convulsive status epilepticus is the most severe form of epileptic attack and a life-threatening neurological emergency, which is associated with substantial mortality and morbidity [1,2,3,4]. 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. 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. 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 be considered
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