Ravindra Arya1, Harsh Kothari2, Zongjun Zhang2, Baoguang Han2, Paul S Horn2, Tracy A Glauser2. 1. From the Comprehensive Epilepsy Center, Division of Neurology (R.A., P.S.H., T.A.G.), and the Division of Epidemiology and Biostatistics (P.S.H.), Cincinnati Children's Hospital Medical Center, OH; the Department of Pediatrics (H.K.), The Unterberg Children's Hospital at Monmouth Medical Center, Long Branch, NJ; the Department of Mathematical Sciences (Z.Z.), University of Cincinnati, OH; and Biogen (B.H.), Cambridge, MA. Ravindra.Arya@cchmc.org. 2. From the Comprehensive Epilepsy Center, Division of Neurology (R.A., P.S.H., T.A.G.), and the Division of Epidemiology and Biostatistics (P.S.H.), Cincinnati Children's Hospital Medical Center, OH; the Department of Pediatrics (H.K.), The Unterberg Children's Hospital at Monmouth Medical Center, Long Branch, NJ; the Department of Mathematical Sciences (Z.Z.), University of Cincinnati, OH; and Biogen (B.H.), Cambridge, MA.
Abstract
OBJECTIVE: This is a network meta-analysis of nonvenous drugs used in randomized controlled trials (RCTs) for treatment of acute convulsive seizures and convulsive status epilepticus. METHODS: Literature was searched according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines for RCTs examining treatment of acute convulsive seizures or status epilepticus with at least one of the study arms being a nonvenous medication. After demographic and outcome data extraction, a Bayesian network meta-analysis was performed and efficacy results were summarized using treatment effects and their credible intervals (CrI). We also calculated the probability of each route-drug combination being the most clinically effective for a given outcome, and provided their Bayesian hierarchical ranking. RESULTS: This meta-analysis of 16 studies found that intramuscular midazolam (IM-MDZ) is superior to other nonvenous medications regarding time to seizure termination after administration (2.145 minutes, 95% CrI 1.308-3.489), time to seizure cessation after arrival in the hospital (3.841 minutes, 95% CrI 2.697-5.416), and time to initiate treatment (0.779 minutes, 95% CrI 0.495-1.221). Additionally, intranasal midazolam (IN-MDZ) was adjudged most efficacious for seizure cessation within 10 minutes of administration (90.4% of participants, 95% CrI 79.4%-96.9%), and persistent seizure cessation for ≥1 hour (78.5% of participants, 95% CrI 59.5%-92.1%). Paucity of RCTs produced evidence gaps resulting in small networks, routes/drugs included in some networks but not others, and some trials not being connected to any network. CONCLUSIONS: Despite the evidence gaps, IM-MDZ and IN-MDZ exhibit the best efficacy data for the nonvenous treatment of acute convulsive seizures or status epilepticus.
OBJECTIVE: This is a network meta-analysis of nonvenous drugs used in randomized controlled trials (RCTs) for treatment of acute convulsive seizures and convulsive status epilepticus. METHODS: Literature was searched according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines for RCTs examining treatment of acute convulsive seizures or status epilepticus with at least one of the study arms being a nonvenous medication. After demographic and outcome data extraction, a Bayesian network meta-analysis was performed and efficacy results were summarized using treatment effects and their credible intervals (CrI). We also calculated the probability of each route-drug combination being the most clinically effective for a given outcome, and provided their Bayesian hierarchical ranking. RESULTS: This meta-analysis of 16 studies found that intramuscular midazolam (IM-MDZ) is superior to other nonvenous medications regarding time to seizure termination after administration (2.145 minutes, 95% CrI 1.308-3.489), time to seizure cessation after arrival in the hospital (3.841 minutes, 95% CrI 2.697-5.416), and time to initiate treatment (0.779 minutes, 95% CrI 0.495-1.221). Additionally, intranasal midazolam (IN-MDZ) was adjudged most efficacious for seizure cessation within 10 minutes of administration (90.4% of participants, 95% CrI 79.4%-96.9%), and persistent seizure cessation for ≥1 hour (78.5% of participants, 95% CrI 59.5%-92.1%). Paucity of RCTs produced evidence gaps resulting in small networks, routes/drugs included in some networks but not others, and some trials not being connected to any network. CONCLUSIONS: Despite the evidence gaps, IM-MDZ and IN-MDZ exhibit the best efficacy data for the nonvenous treatment of acute convulsive seizures or status epilepticus.
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