Red Flags
- Convulsive seizure ≥5 minutes — treat as status epilepticus immediately; do not wait for 30-minute classical definition[2]
- Persistent altered consciousness after convulsions stop — non-convulsive status; emergent EEG and continued anti-seizure therapy[2]
- Hypoglycaemia, hyponatraemia, hypoxia, hypotension, or hyperthermia during status — correct concurrent with anti-seizure therapy[2]
- Refractory CSE (continued seizure after benzodiazepine + adequate second-line ASM) — admit to ICU; anaesthetic agent and continuous EEG[2]
First-line treatment
Interventions
- Stabilisation pathway[2]ABC: airway, oxygen, IV access, monitor; check glucose; start timer; establish whether ≥5 min seizure; lateral position if airway clear
- Burst suppression on EEG for refractory CSE[2]Anaesthetic infusion (midazolam, propofol, or pentobarbital/thiopental) titrated to seizure suppression or burst-suppression for 24–48 hours, then graded weaning under EEG
First-line drug therapy
| Drug | Class | Adult | Paediatric | Notes |
|---|---|---|---|---|
| Lorazepam (first-line)[2] | Benzodiazepine | 4 mg IV bolus over 1–2 min; repeat once at 5–10 min if needed | 0.1 mg/kg IV (max 4 mg per dose) | First-line IV benzodiazepine; longer effective duration than diazepam; use IV diazepam 0.15 mg/kg or rectal 0.2 mg/kg if no IV access; intramuscular midazolam 10 mg if no IV |
| Midazolam (alternative first-line)[2] | Benzodiazepine | 10 mg IM, 10 mg buccal/intranasal, or 0.2 mg/kg IV | 0.2 mg/kg IM/IV (max 10 mg); buccal 0.5 mg/kg (max 10 mg) | Pre-hospital and out-of-hospital first-line where IV access not available; RAMPART trial showed equivalence to IV lorazepam |
| Levetiracetam (second-line)[2] | SV2A modulator | 60 mg/kg IV (max 4500 mg) over 10 min | 60 mg/kg IV (max 4500 mg) over 10 min | ESETT trial — equally effective as fosphenytoin and valproate; preferred for ease of administration, fewer cardiac concerns; renal dose adjustment |
| Sodium valproate (second-line)[2] | Multiple-mechanism ASM | 40 mg/kg IV (max 3000 mg) over 10 min | 40 mg/kg IV (max 3000 mg) | ESETT trial second-line option; avoid in women of childbearing potential without pregnancy prevention programme; hepatic injury and pancreatitis |
| Fosphenytoin (second-line)[2] | Sodium channel blocker | 20 mg PE/kg IV (max 1500 mg PE) at ≤150 mg PE/min | 20 mg PE/kg IV (max 1500 mg PE) at ≤2 mg PE/kg/min | Cardiac monitoring during infusion; hypotension and bradyarrhythmias; preferred over phenytoin where available (less infusion-site morbidity) |
| Midazolam infusion (refractory)[2] | Benzodiazepine continuous infusion | 0.2 mg/kg loading then 0.05–2.0 mg/kg/h titrated to EEG burst-suppression | Loading 0.15 mg/kg then 1–10 µg/kg/min titrated | First-choice anaesthetic agent for refractory CSE; tachyphylaxis common — cycle to propofol or pentobarbital if escalating doses |
| Propofol infusion (refractory)[2] | GABAA agonist anaesthetic | 1–2 mg/kg IV bolus then 1–10 mg/kg/h titrated to EEG | — | Avoid prolonged high-dose infusion (>4 mg/kg/h for >48 h) due to PRIS — propofol infusion syndrome (acidosis, rhabdomyolysis, cardiac failure) |
| Pentobarbital or thiopental (super-refractory)[2] | Barbiturate anaesthetic | Pentobarbital 5 mg/kg IV bolus then 0.5–5 mg/kg/h; thiopental 3–5 mg/kg IV bolus then 3–7 mg/kg/h | — | Super-refractory status; profound hypotension, immunosuppression, ileus; vasopressor support and MDT neuro-ICU care |
Lorazepam (first-line)[2]
Benzodiazepine
- Adult
- 4 mg IV bolus over 1–2 min; repeat once at 5–10 min if needed
- Paediatric
- 0.1 mg/kg IV (max 4 mg per dose)
First-line IV benzodiazepine; longer effective duration than diazepam; use IV diazepam 0.15 mg/kg or rectal 0.2 mg/kg if no IV access; intramuscular midazolam 10 mg if no IV
Midazolam (alternative first-line)[2]
Benzodiazepine
- Adult
- 10 mg IM, 10 mg buccal/intranasal, or 0.2 mg/kg IV
- Paediatric
- 0.2 mg/kg IM/IV (max 10 mg); buccal 0.5 mg/kg (max 10 mg)
Pre-hospital and out-of-hospital first-line where IV access not available; RAMPART trial showed equivalence to IV lorazepam
Levetiracetam (second-line)[2]
SV2A modulator
- Adult
- 60 mg/kg IV (max 4500 mg) over 10 min
- Paediatric
- 60 mg/kg IV (max 4500 mg) over 10 min
ESETT trial — equally effective as fosphenytoin and valproate; preferred for ease of administration, fewer cardiac concerns; renal dose adjustment
Sodium valproate (second-line)[2]
Multiple-mechanism ASM
- Adult
- 40 mg/kg IV (max 3000 mg) over 10 min
- Paediatric
- 40 mg/kg IV (max 3000 mg)
ESETT trial second-line option; avoid in women of childbearing potential without pregnancy prevention programme; hepatic injury and pancreatitis
Fosphenytoin (second-line)[2]
Sodium channel blocker
- Adult
- 20 mg PE/kg IV (max 1500 mg PE) at ≤150 mg PE/min
- Paediatric
- 20 mg PE/kg IV (max 1500 mg PE) at ≤2 mg PE/kg/min
Cardiac monitoring during infusion; hypotension and bradyarrhythmias; preferred over phenytoin where available (less infusion-site morbidity)
Midazolam infusion (refractory)[2]
Benzodiazepine continuous infusion
- Adult
- 0.2 mg/kg loading then 0.05–2.0 mg/kg/h titrated to EEG burst-suppression
- Paediatric
- Loading 0.15 mg/kg then 1–10 µg/kg/min titrated
First-choice anaesthetic agent for refractory CSE; tachyphylaxis common — cycle to propofol or pentobarbital if escalating doses
Propofol infusion (refractory)[2]
GABAA agonist anaesthetic
- Adult
- 1–2 mg/kg IV bolus then 1–10 mg/kg/h titrated to EEG
- Paediatric
- —
Avoid prolonged high-dose infusion (>4 mg/kg/h for >48 h) due to PRIS — propofol infusion syndrome (acidosis, rhabdomyolysis, cardiac failure)
Pentobarbital or thiopental (super-refractory)[2]
Barbiturate anaesthetic
- Adult
- Pentobarbital 5 mg/kg IV bolus then 0.5–5 mg/kg/h; thiopental 3–5 mg/kg IV bolus then 3–7 mg/kg/h
- Paediatric
- —
Super-refractory status; profound hypotension, immunosuppression, ileus; vasopressor support and MDT neuro-ICU care
Safety-net
- Family education — convulsive seizure lasting ≥5 minutes is a medical emergency; call ambulance and consider rescue benzodiazepine (buccal midazolam, rectal diazepam) at home if prescribed[2]
- After any episode of status epilepticus, see neurology within 1–2 weeks for triggers and ASM optimisation; never stop ASM abruptly[2]
- If patient has confusion or unusual behaviour after a seizure stops — non-convulsive status is possible; seek same-day medical review[2]
Referral criteria
- All convulsive status epilepticusEmergency department; HDU/ICU on persistence[2]
- Refractory or super-refractory statusNeurology and neurocritical care; consider tertiary transfer[2]
- New-onset refractory status epilepticus (NORSE) or febrile infection-related epileptic syndrome (FIRES)Tertiary epilepsy / encephalitis centre; immunomodulation (steroids, IVIg, plasma exchange, anakinra, tocilizumab)[2]
- All survivors of status — outpatient neurology within 1–2 weeksNeurology and ASM optimisation[2]
Clinical summary
Stepwise management of generalised convulsive status epilepticus from first-line benzodiazepine through anaesthetic-induced burst suppression in adults and children.
References
- 1.American Epilepsy Society Guideline: Evidence-Based Treatment of Convulsive Status Epilepticus (2016) and AES Treatments Committee Review on Refractory CSE (2020); ESETT trial (2020)
- 2.Treatment of Refractory Convulsive Status Epilepticus: A Comprehensive Review by the American Epilepsy Society Treatments Committee. Epilepsy Currents (2020)