Abstracts

Rapid termination of status epilepticus (SE) significantly impacts SE outcome. Despite several recent large trials for SE treatment, there are no evidence based guidelines using a systematic analysis for best initial SE therapy. This is important because medical practitioners are often unaware as to which initial AED is best for terminating SE in adults and children. Medline, Index Medicus, CINAHL, EMBASE databases were searched along with hand searching for published abstracts in both English language and non-English journals for trials involving randomization of patients with newly diagnosed SE into various medication regimens as initial treatment. Refractory SE (RSE) Trials were excluded and trials were divided by age so that separate analyses could be performed for adults and children. Three reviewers independently extracted data and assessed trial quality. Relative risk (RR) with 95% confidence intervals (CI) were calculated for each trial. Summary RR and 95% CI for dichotomous data were tabulated using a random effects model. A test of statistical heterogeneity was conducted for each pooled RR calculation. Three analyses were performed: use of any benzodiazepine (BZD) versus no BZD; lorazepam versus diazepam; and diazepam and phenytoin versus phenobarbital as initial treatment. A number needed to treat (NNT) analysis with 95% CI were performed as a subanalysis for adult patients. Of 2024 articles found in the initial search, 13 papers were identified as studies. 8 trials met inclusion criteria; 4 in adults and 4 in children. The four trials in adults represented 758 patients with newly diagnosed SE and randomization to lorazepam, diazepam, diazepam and phenytoin or phenobarbital. Not surprisingly, the use of any BZD resulted in greater success than not using a BZD (RR=0.78; 95% CI, 0.66 to 0.92). The NNT was 8 for BZD. Lorazepam is better at terminating SE than diazepam (RR=0.68; 95% CI, 0.49 to 0.96) The NNT was 7 favoring lorazepam suggesting that for every 7 SE patients in which lorazepam is used, one case of failing to stop SE by diazepam is prevented. There was no significant difference between diazepam and phenytoin versus phenobarbital. ( RR = 1.02; 95% CI, 0.81 to 1.28)
The 4 pediatric trials represented 237 patients randomized to rectal or IV diazepam, IM midazolam or buccal midazolam; however there was significant heterogeneity between the studies (p=0.01). Therefore combining data from these trials is inappropriate. However, there were no reported significant differences between any of the benzodiazepines in terminating SE. Lorazepam followed by either phenytoin or phenobarbital are the best initial choice for SE management in adults. Any choice of rectal, IV diazepam or buccal, IM midazolam is useful initially in children with SE. A trial for RSE is needed to complete an evidence based protocol for SE. Guidelines need to be disseminated to all medical practitioners who manage SE initially. (Supported by Mayo School of Continuing Medical Education)