Refractory status epilepticus: anaesthetic coma, midazolam, propofol, ketamine

Also known as Refractory status epilepticus · Super-refractory status epilepticus · RSE · SRSE · Anaesthetic coma · Propofol infusion syndrome

Refractory status epilepticus (RSE) = SE continuing despite first-line (benzodiazepine) AND second-line (anti-seizure medication — levetiracetam, fosphenytoin, valproate) therapy. SUPER-refractory (SRSE) = RSE persisting or recurring ≥24h after anaesthetic onset (or recurrence on taper). MORTALITY: death in about one-third to one-half of reported RSE/SRSE cases. MANAGEMENT: (1) INTUBATE + ventilate (anaesthetics suppress respiration). (2) ANAESTHETIC INFUSION: midazolam, propofol, thiopental/pentobarbital, ketamine — titrate to BURST SUPPRESSION on EEG (or seizure cessation). (3) CONTINUOUS EEG (cEEG — mandatory — titrate to EEG target, detect non-convulsive seizures). (4) MAINTENANCE ASMs (continue + add new — lacosamide, brivaracetam, perampanel). (5) ADDRESS CAUSE (autoimmune — antibodies +…

high34 referencesUpdated 19 Aug 202625 min readSource-verified · Sept 2026

Checked against its sources on 23 Sept 2026

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8 MCQs

In one line

Refractory status epilepticus (RSE) = SE despite benzo + second-line ASM — about one-third of established cases. Management: (1) INTUBATE + ventilate. (2) ANAESTHETIC INFUSION — midazolam (loading about 0.2 mg/kg, infusion titrated on cEEG; mean maximal 0.22 mg/kg/h in a refractory-NCSE series) or propofol (median 4.8 mg/kg/h, range 2.1-13) or thiopental/pentobarbital — titrated to BURST SUPPRESSION or seizure cessation on cEEG. (3) CONTINUOUS EEG MANDATORY (diagnose NCSE, detect relapse, titrate anaesthetic). (4) MAINTENANCE ASMs in parallel. (5) ADDRESS CAUSE. Super-refractory (SRSE): persists or recurs 24 h or more after anaesthetic onset → add KETAMINE (adults: 0.5 mg/kg bolus, 0.2-15 mg/kg/h maintenance). Watch PROPofol INFUSION SYNDROME (association with over 4 mg/kg/h for over 48 h — bradycardia, metabolic acidosis, rhabdomyolysis, hyperlipidaemia).

^[17] ^[4] ^[26] ^[20] ^[18] ^[19]

Meet the patient

A 45-year-old with known idiopathic generalised epilepsy has been seizing for two hours despite 0.1 mg/kg IV lorazepam, loading doses of levetiracetam and fosphenytoin, and a titrated midazolam infusion. He is intubated. The continuous EEG shows ongoing ictal rhythms over both fronto-temporal regions. BP is 95 over 60 on low-dose noradrenaline. The consultant asks you to add a ketamine infusion.^[24]^[26]^[17]

This is patient entire RSE staircase exists for. Three questions decide the next move: has the seizure outgrown the GABA drugs? (yes — time-dependent pharmacoresistance), what is the EEG target? (burst suppression on the cEEG), and what is the next mechanism? (NMDA blockade — ketamine). Hold those three and the rest of the algorithm slots into place.^[34]^[18]^[4]

References34Show

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