| Summary: | Convulsive status epilepticus (CSE) is an emergency condition associated with mortality and morbidity. It is commonly treated with antiepileptic drugs (AEDs), but these may cause serious adverse events and even death in children. Research on their effectiveness for CSE, and related adverse events in children remains limited. The primary aim of this research was thus to evaluate the effectiveness and safety of AEDs in treating acute tonic-clonic seizure including convulsive status epilepticus (CSE). Two systematic reviews and meta-analyses were conducted to address these aims. The first evaluated the effectiveness of AEDs in children with acute tonic-clonic seizures including (CSE). The second evaluated the safety of AEDs in this population. The systematic review of AED effectiveness identified 20 studies published between 1946 and April 2015. It showed that buccal midazolam was more effective than rectal diazepam for treating acute tonic-clonic seizures including CSE in children, and was associated with a lower recurrence rate. Lorazepam and diazepam were equally effective in terminating seizures, but for lorazepam, intravenous administration was more effective than the buccal, sublingual or intranasal routes. Intravenous valproate appeared to be more effective than intravenous phenytoin and phenobarbital; however, the difference was not significant. The systematic review of AED safety for children with acute tonic-clonic seizures identified 25 studies, published between 1946 and April 2015. These studies were predominantly randomised controlled trials and of these 19 studies reported more than one adverse event, while 6 reported none. A total of 203 adverse events were documented, most commonly respiratory depression (101 children), mainly after treatment with diazepam (46 children). The rates of respiratory depression with buccal midazolam and rectal diazepam were similar (3.0% and 3.3%, respectively). Compared to intravenous diazepam, intravenous lorazepam was associated with less respiratory depression. No child suffered respiratory depression associated with intravenous valproate treatment, compared to one child with intravenous phenobarbital. When looking at all adverse events, intravenous valproate was significantly safer than intravenous phenobarbital. Respiratory depression was not noted in children who received intravenous levetiracetam; however, all levetiracetam studies identified in this review were cohort and non-comparative. In conclusion, in the treatment of acute tonic-clonic seizures (including CSE), buccal was the best administration route for children admitted to the emergency department. Intravenous lorazepam treatment was associated with less respiratory depression than intravenous diazepam. Where IV access was practicable, intravenous lorazepam was the drug of choice. More randomised control trials are needed to evaluate the effectiveness and safety of AEDs as a second-line treatment.
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