Guideline status: what currently applies
For adults, the S2k guideline Status epilepticus im Erwachsenenalter (DGN with ÖGN, 2020, AWMF 030-079) remains the reference for dosing. Its validity expired in 06/2025 and it is currently under revision. As of 10/2026, no new version had been published. ESETT, the ENLS protocol of the Neurocritical Care Society and NICE NG217 are used as supplementary sources.
For children beyond the neonatal period, the S1 guideline of the Society for Neuropaediatrics (GNP, AWMF 022-019, 2025) and the ERC Guidelines 2025 Paediatric Life Support apply. The recommendations differ on certain points. These differences are highlighted below where relevant.
Definition and timeline
Status epilepticus is present in a generalised tonic-clonic seizure lasting more than 5 minutes. It also includes ≥ 2 seizures between which the patient does not return to baseline (ILAE). From approximately 30 minutes onwards, there is a risk of permanent neuronal damage.
Benzodiazepines lose efficacy as seizure duration increases. The most common error in the treatment of status epilepticus is therefore underdosing.
| Time from seizure onset | Stage | Treatment |
|---|---|---|
| 0–5 min | Seizure | Protection, airway, O₂, monitoring, blood glucose, vascular access |
| from 5 min | Stage 1 – early status | Benzodiazepine, repeat 1× |
| approx. 20–40 min | Stage 2 – established, benzodiazepine-refractory status | Levetiracetam, valproate, (fos)phenytoin or phenobarbital IV |
| approx. 40–60 min | Stage 3 – refractory status | General anaesthesia, intubation, intensive care unit, EEG |
| ≥ 24 h despite anaesthesia | Super-refractory status | Neurocritical care |
Immediate measures
- Note the time
- Protect from injury
- Secure the airway, give O₂
- Check blood glucose
Investigate causes in parallel
Anticonvulsant treatment runs simultaneously with the search for the underlying cause:
- Hypoglycaemia: give glucose IV immediately
- Alcohol use disorder or malnutrition: thiamine 100 mg IV before or together with glucose
- Electrolyte disturbances (Na⁺, Ca²⁺, Mg²⁺): correct
- Eclampsia in pregnancy or the puerperium: magnesium according to the obstetric protocol
- Intoxication, withdrawal, discontinued antiseizure medication: take a history, measure drug levels, consider an antidote
- CNS infection, haemorrhage, stroke, trauma: CT and CSF analysis; in the presence of fever, consider meningitis or encephalitis
- Children with fever: a febrile seizure is treated in the same way, but the cause must still be investigated.
Emergency seizure management: benzodiazepine as stage 1 (adults)
If the seizure lasts longer than 5 minutes, a benzodiazepine is given at full dose. If the seizure persists, the dose is repeated once.
| Route | Drug | Dose | Note |
|---|---|---|---|
| IV | Lorazepam | 0.1 mg/kg, max. 4 mg per dose | Store ampoules refrigerated |
| IV | Midazolam | 0.2 mg/kg, max. 10 mg per dose | – |
| IV | Diazepam | 0.15–0.2 mg/kg, max. 10 mg per dose | – |
| IV | Clonazepam | 0.015 mg/kg, max. 1 mg per dose | – |
| IM | Midazolam | > 40 kg: 10 mg · 13–40 kg: 5 mg | First choice without vascular access |
| Intranasal / buccal | Midazolam | > 40 kg: 10 mg · 13–40 kg: 5 mg | Intranasal off-label; buccal prefilled syringe licensed only up to < 18 years |
All drugs may be repeated 1×.
Without vascular access, IM midazolam is the preferred option. In the RAMPART trial it was at least as effective as IV lorazepam. Establishing vascular access should not delay the first dose.
Respiratory depression may occur after benzodiazepines. Airway management and bag-mask ventilation must be available.
Stage 2: second-line therapy in adults
After two benzodiazepine doses, no third dose is given. Instead, treatment is escalated directly to stage 2. Benzodiazepines already administered in the prehospital setting count towards this total.
| Drug | IV dose | Infusion time | Caution |
|---|---|---|---|
| Levetiracetam | 60 mg/kg, max. 4500 mg | approx. 10 min | Off-label; few interactions, haemodynamically neutral |
| Valproate | 40 mg/kg, max. 3000 mg | approx. 10 min | Not in hepatic impairment, mitochondrial disease (e.g. POLG), urea cycle disorders; avoid where possible in people of childbearing potential (teratogenic) |
| Fosphenytoin | 20 mg PE/kg, max. 1500 mg PE | approx. 10 min | According to DGN (2020) not commercially available – check availability |
| Phenytoin | 20 mg/kg | max. 50 mg/min | Dedicated line, ECG and blood pressure monitoring (bradycardia, AV block, hypotension); extravasation → necrosis |
| Phenobarbital | 15–20 mg/kg | slowly | Reserve; respiratory depression and hypotension, especially after benzodiazepines |
In the ESETT trial, levetiracetam, valproate and fosphenytoin were equally effective. Seizures terminated in approximately half of cases with each drug. The choice is therefore guided by contraindications and availability.
In practical terms for levetiracetam: the concentrate (100 mg/ml) is diluted before administration, e.g. in 100 ml NaCl 0.9 %. In renal impairment, the maintenance dose must be adjusted. Importantly, levetiracetam does not replace an adequately dosed stage 1.
Stage 3: general anaesthesia in refractory status
If status persists despite stage 2, intubation and ventilation, transfer to the intensive care unit and continuous EEG follow. Suitable anaesthetic agents are midazolam or propofol (also in combination) or thiopental.
Anaesthesia is titrated under EEG guidance until seizure freedom or burst suppression is achieved. This target is maintained for approximately 24 hours, after which the agents are weaned gradually.
| Drug | Bolus | Maintenance | Note |
|---|---|---|---|
| Midazolam | 0.2 mg/kg | 0.1–0.5 mg/kg/h | Tachyphylaxis |
| Propofol | 2 mg/kg | 4–10 mg/kg/h | Propofol infusion syndrome at high doses and with prolonged use |
| Thiopental | 5 mg/kg | 0.5–5 mg/kg/h | Hypotension, accumulation |
Hypotension should be anticipated during induction of anaesthesia. A vasopressor should be prepared.
Super-refractory status is present when seizures persist for ≥ 24 hours despite anaesthesia or recur during weaning. In this situation, (es)ketamine, a haemodynamically sparing NMDA antagonist, is among the agents used. The evidence for this is derived from case series only. Dosing should follow the current specialist literature or neurocritical care protocols.
Status epilepticus in children: specific considerations
In children beyond the neonatal period, benzodiazepines are also the first choice. Body weight is estimated if necessary.
Stage 1 without vascular access
| Route | Drug | Dose |
|---|---|---|
| Buccal | Midazolam (prefilled syringe, licensed from 3 months) | 3 months to < 1 year: 2.5 mg (3–6 months in hospital only) · 1 to < 5 years: 5 mg · 5 to < 10 years: 7.5 mg · 10 to < 18 years: 10 mg |
| Intranasal | Midazolam (off-label) | GNP: 0.2 mg/kg, max. 10 mg · ERC 2025: 0.3 mg/kg intranasal/buccal, max. 10 mg |
| IM | Midazolam | 13–40 kg: 5 mg · > 40 kg: 10 mg |
| Rectal | Diazepam (according to GNP from 6 months) | ≤ 15 kg: 5 mg · > 15 kg: 10 mg |
Stage 1 with vascular access (IV/IO)
- Lorazepam: 0.1 mg/kg, max. 4 mg
- Diazepam: 0.15–0.2 mg/kg, max. 10 mg
- Midazolam: the recommendations differ here.
- ERC/RCUK 2025: 0.15 mg/kg, max. 10 mg
- GNP S1 guideline 2025: 0.1–0.2 mg/kg, max. 5 mg
- From approximately 33 kg, the two regimens result in different doses. Here too, avoid underdosing.
If the seizure persists, the dose is repeated once after 5 minutes. In total, no more than two benzodiazepine doses should be given. Emergency medication already administered by parents or emergency medical services counts towards this total.
Stage 2 in children
| Drug | IV/IO dose | Note |
|---|---|---|
| Levetiracetam | 40–60 mg/kg, max. 4500 mg, over 5–10 min | Off-label; first choice according to ERC 2025, preferred in hospital according to GNP |
| Phenobarbital | 15–20 mg/kg | Alternative (GNP: preferred in hospital); respiratory depression |
| Valproate | 40 mg/kg, max. 3000 mg | Avoid where possible in children < 2 years; not if metabolic, mitochondrial or hepatic disease is suspected |
| Phenytoin | 20 mg/kg over 20 min | ECG monitoring; alternative if levetiracetam is not available |
In EcLiPSE and ConSEPT, levetiracetam (40 mg/kg) and phenytoin were equally effective in children. However, levetiracetam is quicker to administer and better tolerated.
Refractory status is treated under general anaesthesia in the paediatric intensive care unit. The approach corresponds to that in adults, with weight-based dosing.
Practical summary
- Dose early and adequately: give benzodiazepines at full dose after 5 minutes of seizure activity. Without vascular access, use midazolam IM, buccal or intranasal.
- No more than two benzodiazepine doses: count prehospital doses, then escalate to stage 2 without delay.
- Choose second-line therapy according to the patient: levetiracetam, valproate and fosphenytoin were equally effective in ESETT. Contraindications (liver, mitochondrial disease, childbearing potential) and availability determine the choice.
- Prepare for anaesthesia: secure the airway, anticipate hypotension during induction, use EEG-guided therapy.
- Pay close attention in children: the midazolam regimens of GNP and ERC differ. The local protocol should specify which regimen applies.
References
- Rosenow F, Weber J et al. S2k-Leitlinie Status epilepticus im Erwachsenenalter. DGN gemeinsam mit der ÖGN, 2020; AWMF-Register 030-079, korrigierte Registerfassung 03/2022, gültig bis 29.06.2025 – laut AWMF-Register in Überarbeitung (Stand 10/2026 keine Neufassung). Publikation: Nervenarzt 2021.
- Trollmann R, Brandl U et al. (Gesellschaft für Neuropädiatrie). S1-Leitlinie Therapie des konvulsiven Status epilepticus im Kindes- und Jugendalter (jenseits der Neugeborenenperiode). AWMF-Register 022-019 (Fassung 2025).
- Djakow J, Turner NM, Skellett S et al. European Resuscitation Council Guidelines 2025 Paediatric Life Support. Resuscitation 2025;215 Suppl 1:110767.
- Resuscitation Council UK. Paediatric advanced life support algorithm – 2025 Resuscitation Guidelines sowie Paediatric Life Support Guideline 2025.
- Trinka E, Cock H, Hesdorffer D 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.
- Kapur J, Elm J, Chamberlain JM et al. Randomized trial of three anticonvulsant medications for status epilepticus (ESETT). N Engl J Med 2019;381:2103–2113.
- Silbergleit R, Durkalski V, Lowenstein D et al. Intramuscular versus intravenous therapy for prehospital status epilepticus (RAMPART). N Engl J Med 2012;366:591–600.
- Lyttle MD et al. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE). Lancet 2019;393:2125–2134.
- Dalziel SR et al. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT). Lancet 2019;393:2135–2145.
- National Institute for Health and Care Excellence (NICE). Epilepsies in children, young people and adults. NICE guideline NG217, 2022 (mit späteren Aktualisierungen).
- Neurocritical Care Society. Emergency Neurological Life Support (ENLS), Version 5.0 – Protokoll Status Epilepticus.
- Jünemann et al. Prähospitale Behandlung von Anfallsclustern und Status epilepticus. Clin Epileptol 2025.
- Fachinformation Midazolam 5 mg/ml Lösung zur Anwendung in der Mundhöhle, EMA-EPAR; deutsche Fassung Stand 07/2023.
- Fachinformation Diazepam Rektallösung 5 mg/10 mg – Dosierung bei Status epilepticus; Stand der Fassung ungeprüft.
This article does not replace clinical judgement in the individual case or the current summary of product characteristics and guidelines.
