Intravenous antiepileptic drugs in adults with benzodiazepine-resistant convulsive status epilepticus: A systematic review and network meta-analysis

AIM: The 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). METHODS: MEDLINE, 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. RESULTS: Five 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. CONCLUSIONS: Our 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.