The levels of evidence (class I-IV) supporting the recommendations and ratings of recommendations (A-C, Good practice point [GPP]) are defined at the end of the "Major Recommendations" field.
General Initial Management
General management approaches in generalised convulsive, complex partial and subtle status epilepticus (SE) should include: assessment and control of the airways and of ventilation, arterial blood gas monitoring to see if there is metabolic acidosis and hypoxia requiring immediate treatment through airway management and supplemental oxygen, electrocardiogram (ECG) and blood pressure monitoring. Other measures include intravenous (i.v). glucose and thiamine as required, emergency measurement of antiepileptic drug levels, electrolytes and magnesium, a full haematological screen, and measures of hepatic and renal function. The cause of the status should be identified urgently and may require treatment in its own right (good practice point [GPP]).
Initial Pharmacological Treatment of Generalised Convulsive SE (GCSE) and Non-convulsive SE (NCSE)
The initial therapy of NCSE depends on the type and the cause. Subtle SE evolving from GCSE is refractory by nature and its further treatment is described below. Complex partial SE should be treated initially as GCSE. The preferred treatment pathway is i.v. administration of 4 mg of lorazepam; this dose is repeated if seizures continue for more than 10 min after first injection. If necessary, additional phenytoin (15 to 18 mg/kg) or equivalent fosphenytoin is recommended. Alternatively, 10 mg of diazepam directly followed by 15 to 18 mg/kg of phenytoin or equivalent fosphenytoin can be given; if seizures continue for more than 10 min after injection another 10 mg of diazepam is recommended. If necessary, additional lorazepam (4 to 8 mg) should be administered (Level A rating).
General Management of Refractory Status Epilepticus
GCSE that does not respond to initial anticonvulsant substances needs to be treated on an intensive care unit (GPP).
Pharmacological Treatment for Refractory GCSE and Subtle Status Epilepticus
In GCSE and subtle SE the task force members suggest proceeding immediately to the infusion of anaesthetic doses of midazolam, propofol or barbiturates because of the increasing risk of brain and systemic damage. Due to poor evidence the task force cannot recommend which of the anaesthetic substances should be administered first. They recommend the titration of the anaesthetic against an electroencephalogram (EEG) burst suppression pattern. This goal should be maintained for at least 24 hours. Simultaneously, the chronic antiepileptic medication the patient will be treated with in future should be initiated (GPP).
Barbiturates: To start with thiopental is administered as a 100 to 200 mg of bolus over 20 sec then further 50 mg of boluses every 2 to 3 min until seizures are controlled, infusion 3 to 5 mg/kg/hour. Pentobarbital (the first metabolite of thiopental) is marketed in the USA as the alternative to thiopental and is given as a bolus dose of 10 to 20 mg/kg followed by an infusion of 0.5 to 1 mg/kg/hour increasing to 1 to 3 mg/kg/hour.
Midazolam: Effective initial i.v. doses of midazolam are a 0.2 mg/kg bolus, followed by continuous infusion at rates of 0.1 to 0.4 mg/kg/hour.
Propofol: Bolus (i.v.) of 2 mg/kg is administered followed by a continuous infusion of 5 to 10 mg/kg/hour.
In cases of elderly patients in whom intubation and artificial ventilation would not be justified, non-anaesthetising anticonvulsants may be tried (see below) (GPP).
Pharmacological Treatment for Refractory NCSE
In complex partial SE, the time that has elapsed until termination of status is less critical compared to GCSE. Thus, general anaesthesia due to its possible severe complications should be postponed and non-anaesthetising anticonvulsants may be tried initially (GPP).
Phenobarbital: 20 mg/kg i.v., administration of additional boluses requires intensive care conditions.
Valproic acid: i.v. bolus of 25 to 45 mg/kg is administered followed by maximum rates up to 6 mg/kg/min.
If the treatment regimen includes the administration of anaesthetics then the same protocol applies as described for refractory GCSE.
Definitions:
Evidence Classification Scheme for a Therapeutic Intervention
Class I: An adequately powered prospective, randomized, controlled clinical trial with masked outcome assessment in a representative population or an adequately powered systematic review of prospective randomised controlled clinical trials with masked outcome assessment in representative populations. The following are required:
- Randomisation concealment
- Primary outcome(s) is/are clearly defined
- Exclusion/inclusion criteria are clearly defined
- Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias
- Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences
Class II: Prospective matched-group cohort study in a representative population with masked outcome assessment that meets a–e above or a randomised, controlled trial in a representative population that lacks one criteria a–e
Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment
Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion
Rating of Recommendations
Level A rating (established as effective, ineffective, or harmful) requires at least one convincing class I study or at least two consistent, convincing class II studies.
Level B rating (probably effective, ineffective, or harmful) requires at least one convincing class II study or overwhelming class III evidence.
Level C rating (possibly effective, ineffective, or harmful) requires at least two convincing class III studies.
Good Practice Point (GPP) Where there was lack of evidence but consensus was clear the Task Force members have stated their opinion as good practice points.
