No previous study has specifically evaluated the incidence, clinical features, management and prognosis of patients presenting to the emergency department (ED) with status epilepticus (SE). We therefore performed a 12-month retrospective multicentre population survey on the management of SE in the ED.
Materials and results
We conducted an observational retrospective study from 1 January 2016 to 31 December 2016 in four centres, one University and three Community Hospital EDs, in Florence (Italy). All together, these facilities cover an urban area of 600 118 inhabitants (mean age 47 years).
Over the 12-month period, from a total of 246 635 patients presenting to the ED, we selected 15 715 patients with a primary complaint of loss of consciousness, neurological disorder and altered mental status and 7530 patients with specific words in their ED medical records including ‘seizure’, ‘convulsion’, ‘epilepsy’, ‘focal’, ‘absence’ and ‘status epilepticus’. Within these two main groups of eligible patients, a team of medical researchers identified 1537 patients with apparent or suspected seizures. Of these, 101 patients with SE were identified by two senior physicians according to the recent definition released by the League Against Epilepsy task force . Five cases of dispute amongst the two reviewers were evaluated by a third experienced physician, and 99 adult patients with SE were finally enrolled in the study. Clinical features of the patients, aetiology and semiology of SE, treatment performed in ED and 30-day mortality were reported by reviewing hospital records and performing phone interviews.
Incidence, aetiology and semiology of status epilepticus
Among the 99 patients with SE, 49 were women with a mean age of 64 ± 23 years (range: 18–100 years). The incidence of SE was 16 cases (95% confidence interval: 8–23) for every 100 000 inhabitants and SE cases were 40 (95% confidence interval: 27–52) for every 100 000 ED presentations. Forty-six patients presented with convulsive SE, 29 with focal onset evolving into bilateral convulsive SE, 18 with focal SE and six with absence SE. Fifty-seven patients had a known history of epilepsy. Six patients had recurrent SE. Ninety-three patients had a symptomatic SE, and no cause was found in six patients (cryptogenic SE). Acute or precipitating disorders were identified in 68 patients, and remote and progressive pathologies were present in 37 and 27 cases, respectively (Table 1).
Treatment in emergency department and 30-day mortality
Benzodiazepines were used in 82 patients, whereas intravenous non-benzodiazepine antiepileptic drugs (second-line treatment) were used in 76 patients. Levetiracetam was administered in 59 patients, phenytoin in 12, lacosamide in 11 and valproic acid in 9. Intravenous infusion of midazolam and propofol (third-line treatment) was used in 6 and 12 patients, respectively.
The average hospital length of stay was 8.4 ± 8.3 days. A total of 13 patients died within 30 days from ED presentation. In two patients, death was caused by refractory SE whereas in the other 11, it was related to the underlying disorders that triggered SE.
Our survey data suggest that an ED with an annual census of 50 000 patients can expect an average of two cases of SE every month. SE accounted for 6% of all apparent or suspected seizures presented to the ED. Acute or precipitating disorder was present in 68.7% of the affected patients. Acute disorders initially presenting with SE are very heterogeneous, with sepsis and ischemic stroke being the most common.
The optimal treatment of SE in the acute setting is still not standardised. Benzodiazepines are administered as soon as SE is recognised, and phenytoin, valproic acid, levetiracetam and lacosamide are considered second-line treatments . There is no current evidence that recommends the best second-line drug in case of SE . However, in our study, levetiracetam was the most frequently used.
The 30-day mortality was 13%, and SE per se was the cause of death in only 15% of cases, whereas all other deaths were owing to underlying pathologies.
Owing to the retrospective design of our study, some cases of SE may have been missed, whereas others may have been inappropriately included, and clinical pictures may have been different if collected prospectively.
In summary, this survey suggests that patients rarely present to ED with SE. SE occurs most frequently as convulsive SE triggered by underlying pathology that needs to be identified and promptly treated to reduce the risk of death. Benzodiazepines are the first drugs administrated in SE. Non-benzodiazepine antiepileptic drugs are also frequently used, with levetiracetam being the most used.
The authors thank Serena Rovida (MD) from Linköping University Hospital (Sweden) for the collaboration in writing the manuscript.
Conflicts of interest
Dr Gaetano Zaccara has received speaker’s or consultancy fees from EISAI, Jansen-Cilag, Sanofi-Aventis, and UCB Pharma. For the remaining authors there are no conflicts of interest.
1. Trinka E, Cock H, Hesdorfferet D, Rossetti AO, Sheffer IE, Shinnar S, et al. A definition and classification of status epilepticus – Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia 2015; 56:1515–1523.
2. Zaccara G, Giorgi FS, Amantini A, Giannasi G, Campostrini R, Giovannelli F, et al. Why we prefer levetiracetam over phenytoin for treatment of status epilepticus. Acta Neurol Scand. 2018; 137:618–622.
3. Trinka E, Hofler J, Leitinger M. Pharmacologic treatment of status epilepticus. Expert Opin Phamacother 2016, 17: 513–534.
4. Yasiry Z, Shorvon SD. The relative effectiveness of five antiepileptic drugs in treatment of benzodiazepine-resistant convulsive status epilepticus: a meta-analysis of published studies. Seizure 2014; 23:167–174.