Abstract
AimThe aim of this study was to estimate the comparative efficacy and safety of antiepileptic drugs (AEDs) in adults with benzodiazepine-resistant convulsive status epilepticus (SE). MethodsMEDLINE, CENTRAL, ClinicalTrials.gov, and Opengrey.eu were searched (from inception to 3rd April, 2018) for randomized controlled trials (RCTs) of AEDs used intravenously to treat benzodiazepine-resistant SE in adults. Efficacy outcomes were SE cessation within 1 h from drug administration and seizure freedom at 24 h. Safety outcomes were respiratory depression and hypotension. Effect sizes were estimated by network meta-analyses within a frequentist framework. The hierarchy of competing interventions was established using the surface under the cumulative ranking curve (SUCRA) and mean ranks. ResultsFive RCTs were considered, involving 349 patients. Included interventions were valproate (VPA; 20–30 mg/kg), phenytoin (PHT; 20 mg/kg), diazepam (DZP; 0.2 mg/kg, then 4 mg/h), phenobarbital (PHB; 20 mg/kg, then 100 mg every 6 h), lacosamide (LCM; 400 mg), and levetiracetam (LEV; 20 mg/kg); PHB was superior to PHT, VPA, DZP, LEV, and LCM with respect to SE cessation and performed better than VPA, DZP, and LCM in the achievement of seizure freedom at 24 h. No differences were noted between drugs in the occurrence of respiratory depression and hypotension. According to SUCRA, PHB had the greatest probabilities of being best in the achievement of SE control and seizure freedom, whereas VPA and LCM ranked best for the safety outcomes. ConclusionsOur study suggests that high-dose PHB is effective in controlling SE and preventing seizure recurrence, and LCM and VPA could be better tolerated options. Further head-to-head comparative studies are strongly required to provide more definitive evidence.This article is part of the Special Issue “Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".
Highlights
Status epilepticus (SE) is as a condition “resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally, prolonged seizures” [1]
Both VPA and LEV were used at dosages much lower than those reported by the American Epilepsy Society, which recommends to administer VPA at 40 mg/kg and LEV at 60 mg/kg [23]
No clear-cut differences were found across treatments in the safety outcomes, VPA and LCM were associated with the lowest likelihood to develop respiratory depression and hypotension and suggested to be among the better tolerated options
Summary
Status epilepticus (SE) is as a condition “resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally, prolonged seizures” [1]. It is a medical and neurological emergency, with longterm consequences including “neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures” [1]. The aim of this study was, to systematically and critically appraise the extant RCTs of AEDs used to treat benzodiazepine-resistant convulsive SE in adults, and estimate their comparative efficacy and safety by means of a network meta-analysis
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