title: Pharmacologic treatment of status epilepticus.
abstract: BACKGROUND
  Status epilepticus (SE) requires rapid identification of its cause and urgent pharmacological treatment. Despite an estimated incidence of up to 61 per 100,000 per year, evidence from high-class clinical trials is only available for the early stages of SE.
  
  
  METHODS
  Following a four-stage approach of SE (early, established, refractory and super-refractory), we present pharmacological treatment options and their clinical utility.
  
  
  CONCLUSIONS
  Intravenous lorazepam and intramuscular midazolam appear as most effective treatments for early SE. In children, buccal midazolam has emerged as first-line non-intravenous drug with similar efficacy and safety to other intravenous or rectal benzodiazepines. In established SE intravenous antiepileptic drugs are in use. There are no double-blind, but six randomized open studies with valproate and two with levetiracetam. A meta-analysis found higher rates of seizure cessation with valproate 75.7% (95% CI 63.7-84.8) and phenobarbital 73.6%, (95% CI 58.3-84.8) than with levetiracetam (68.5%, 95% CI 56.2-78.7) or phenytoin (50.2%, 95% CI 34.2-66.1). Based on the favourable tolerability profile of levetiracetam and valproate, the authors prefer these drugs in established SE over phenytoin. Treatment options in refractory SE are intravenous anaesthetics. In super-refractory SE ketamine, magnesium, steroids and other drugs have been used with variable outcomes. At this stage therapeutic decisions are based on doctors' preferences, patient factors such as age and comorbidity, and cause of SE, if identified.
authors.affiliation: a Department of Neurology, Christian Doppler Medical Centre , Paracelsus Medical University Salzburg, and Centre for Cognitive Neurosciences Salzburg , Salzburg , Austria.|b Institute of Public Health, Medical Decision Making and HTA , University for Medical Informatics and Health Technology, UMIT , Hall in Tirol , Austria.
authors.forename: Eugen
authors.initials: E
authors.lastname: Trinka
authors.affiliation: a Department of Neurology, Christian Doppler Medical Centre , Paracelsus Medical University Salzburg, and Centre for Cognitive Neurosciences Salzburg , Salzburg , Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Höfler
authors.affiliation: a Department of Neurology, Christian Doppler Medical Centre , Paracelsus Medical University Salzburg, and Centre for Cognitive Neurosciences Salzburg , Salzburg , Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Leitinger
authors.affiliation: a Department of Neurology, Christian Doppler Medical Centre , Paracelsus Medical University Salzburg, and Centre for Cognitive Neurosciences Salzburg , Salzburg , Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rohracher
authors.affiliation: a Department of Neurology, Christian Doppler Medical Centre , Paracelsus Medical University Salzburg, and Centre for Cognitive Neurosciences Salzburg , Salzburg , Austria.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Kalss
authors.affiliation: c Department of Neurological, Biomedical, and Movement Sciences , University of Verona , Verona , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Brigo
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D006801:Humans; D007649:Ketamine / Q000627:therapeutic use; D000077287:Levetiracetam; D010889:Piracetam / Q000031:analogs & derivatives / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012640:Seizures / Q000188:drug therapy; D013226:Status Epilepticus / Q000188:drug therapy* / Q000503:physiopathology; D017211:Treatment Failure; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D001569:Benzodiazepines; D000077287:Levetiracetam; D014635:Valproic Acid; D007649:Ketamine; D010889:Piracetam
keywords: Status epilepticus; anaesthetics; antiepileptic drugs; benzodiazepines; outcome