Refractory Status Epilepticus (adult)
Seizures continue after a benzodiazepine and a loaded second-line ASM
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NeurologyEmergency
Refractory Status Epilepticus Management (Adult ICU)
Refractory Status Epilepticus Management (Adult ICU): Refractory Status Epilepticus (adult) → Confirm Refractory SE (RSE) → Focal SE with awareness, or ...
Pathway Overview
18 steps
Algorithm Steps
18 total
01Start 02Action Confirm Refractory SE (RSE)
Clinical or EEG seizures continue after adequate treatment. Do not wait: treat now.
- Seizures continue after an adequate benzodiazepine dose
- AND after a loaded second-line ASM (levetiracetam, valproate or phenytoin/fosphenytoin)
- Not waking after convulsions stop: suspect non-convulsive SE and get EEG now
- Get neurology and ICU input now
03Warning Focal SE with awareness, or NCSE without coma: no anaesthetic coma yet
Anaesthetic coma is for convulsive SE, or non-convulsive SE (NCSE) with coma. In other types its harms may outweigh benefit.
- Convulsive SE, or NCSE with coma: go on to the anaesthetic steps below
- Focal SE with preserved awareness, or NCSE without coma: give another IV ASM not yet used; do not intubate for coma at this stage
- Get epilepsy specialist and EEG review. Use the anaesthetic steps only if seizures become convulsive or consciousness falls
04Warning Child, pregnant or postpartum: different care
Check before you choose drugs. Do not delay seizure control for these checks.
- Child: use a paediatric SE protocol. Avoid prolonged propofol.
- Pregnant or recently postpartum: treat eclampsia with IV magnesium sulfate; urgent obstetric input
- Pregnancy: avoid valproate; pentobarbital is contraindicated; avoid ketamine in third trimester
05Action Find and treat the cause now (at the same time)
Anaesthetics alone often fail if the cause is not treated. Do not delay the anaesthetic infusion.
- Low glucose: give IV glucose now; give IV thiamine with it if alcohol use or malnutrition
- Seizures with low sodium (adult): 3% saline 150 mL IV over 20 min; recheck and repeat until sodium rises 5 mmol/L. Max rise 10 mmol/L in the first 24 h
- Correct low calcium or magnesium
- Suspected CNS infection: blood cultures and empirical IV antimicrobials now; LP when safe
- Isoniazid overdose: IV pyridoxine (Poisons Information Centre 13 11 26)
- Other drugs or toxins, withdrawal (alcohol, benzodiazepine, ASM non-adherence)
- Stroke, bleed, tumour, trauma: urgent CT, then MRI
- New onset with no cause (NORSE): suspect autoimmune encephalitis; neurology for early immunotherapy
06Action Convulsive or comatose: secure airway, prepare for anaesthetic infusion
ICU care. Hypotension is common with every anaesthetic agent.
- Intubate and ventilate. Hyperkalaemia or rhabdomyolysis: avoid suxamethonium
- Continuous EEG as soon as possible. Paralysis hides convulsions but not seizures
- Arterial line, central venous access, vasopressor ready
- Continue maintenance ASMs at therapeutic doses; check levels
- Valproate: not in liver disease, POLG mitochondrial disease, urea cycle disorder, porphyria or pregnancy. Avoid with carbapenems (e.g. meropenem): valproate levels fall fast
07Action Start continuous IV anaesthetic now: midazolam or propofol
For convulsive SE or NCSE with coma. First choice is midazolam or propofol (next 2 steps). Choose by blood pressure, age and local protocol.
- Midazolam: less hypotension than barbiturates; accumulates in renal impairment
- Propofol: fast on and off; risk of propofol infusion syndrome (PRIS)
- Ketamine (add-on) and barbiturate: usually for super-refractory SE (later steps)
- No trial shows one agent is better
08Action Option 1: Midazolam infusion (adult)
Midazolam 5 mg/mL or 1 mg/mL. Titrate to the EEG target.
- Load: 0.2 mg/kg IV; repeat if needed, max 0.5 mg/kg total
- Infusion: 0.05-2 mg/kg/h; max 2 mg/kg/h
- Breakthrough seizures: repeat bolus and increase the rate
- Severe renal impairment: active metabolite accumulates; prolonged sedation
- Tolerance develops; rate may need to increase over time
09Action Option 2: Propofol infusion (adult)
Propofol 1% (10 mg/mL). Not for children (see warning above). Titrate to the EEG target.
- Load: 1-2 mg/kg IV; repeat every 3-5 min if needed (max 10 mg/kg total)
- Infusion: 30-200 mcg/kg/min (about 2-12 mg/kg/h)
- Avoid more than 5 mg/kg/h beyond 48 h: high PRIS risk
- PRIS signs: acidosis, rising lactate, CK or potassium, ECG change, heart failure
- Monitor triglycerides, CK, lactate and potassium
- Do not combine with a ketogenic diet (fatal PRIS reported)
10Action Titrate to EEG target, hold 24-48 h, then wean
Target: stop electrographic seizures, or burst suppression. No proof one target is better.
- Titrate on continuous EEG, not on clinical signs
- Seizures continue at maximum dose: add or switch to a second agent
- Hold 24-48 h of EEG seizure control before the first wean
- Treat hypotension with fluids and vasopressors; do not stop at an inadequate dose
- No continuous EEG on site: repeated EEG, and discuss transfer to a centre with continuous EEG
11Action Wean the anaesthetic slowly under continuous EEG
After 24-48 h of EEG seizure control
- Wean gradually; there is no agreed wean rate
- Continue continuous EEG during and after the wean
- Maintenance ASMs at therapeutic doses before the wean
- Watch for EEG and clinical seizure recurrence
12Decision Seizures recur during or after the wean?
EEG or clinical seizures
- If Yes
13Warning Seizures recur: super-refractory SE (SRSE)
SE persists or recurs 24 h or more after anaesthetic start, including on wean. Restart the anaesthetic that worked; re-wean after 24-48 h control.
- Restart or increase anaesthetic; add a second agent. Get epilepsy specialist input
- Look again for the cause: autoimmune, infection, toxic, structural
- Optimise maintenance ASMs; check levels
14Action SRSE: add ketamine infusion (adult)
Add to midazolam or propofol. Titrate to the EEG target.
- Load: 1-2.5 mg/kg IV
- Infusion: 1-10 mg/kg/h; max 10 mg/kg/h
- Caution in severe cardiovascular disease: hypertension, tachycardia, arrhythmia
- Avoid in third trimester of pregnancy
15Action SRSE not controlled: barbiturate infusion (thiopentone in Australia)
Specialist ICU only. Target burst suppression on EEG. Expect hypotension and long recovery (days).
- Australia: thiopentone load 2-7 mg/kg IV (expect hypotension); infusion 2-5 mg/kg/h (max 5 mg/kg/h)
- Where available: pentobarbital load 5-15 mg/kg IV at max 50 mg/min; infusion 0.5-5 mg/kg/h
- Harms: hypotension, cardiac depression, ileus, infection
- Pentobarbital is contraindicated in pregnancy. Barbiturates: not in acute porphyria
16Action SRSE: other specialist therapies
Epilepsy specialist and neuro-ICU decision. Evidence is low quality.
- Suspected autoimmune cause or NORSE: early immunotherapy
- Phenobarbital IV: an option under specialist advice (NICE third line). Dose: see phenobarbitone PI
- Ketogenic diet: not with propofol, liver failure, pancreatitis or metabolic acidosis
- Focal lesion: consider epilepsy surgery (tertiary centre)
- Hypothermia: no outcome benefit in a convulsive SE trial; not routine
17Outcome Goals of care: SRSE duration alone does not predict outcome
Recovery to or near baseline is possible, even after prolonged SRSE. Get specialist input before limiting treatment.
- Set goals with the family early; update them as the cause becomes clear
- Tell the family: coma and life support can last days to months
- Do not judge prognosis while sedation or encephalopathy persists, or before the cause is known
- Base prognosis on the cause, not on age or SE duration alone
If No18Outcome No recurrence: seizure-free off anaesthetic
Continue maintenance ASMs and EEG monitoring. Complete the cause work-up.
- Continue maintenance ASMs
- Continue EEG monitoring after the wean
- Complete the cause work-up if not done: MRI, LP, autoimmune antibodies
- Slow waking is common: do not judge prognosis while sedation or encephalopathy persists
Guideline Source
Guidelines for the Evaluation and Management of Status Epilepticus - Neurocritical Care Society (Brophy et al., 2012)
Clinical Safety Information
Clinical Decision Support — Not a Substitute for Clinical Judgment
Individual patient factors may require deviation from these recommendations.
Known Limitations
- Adults only: children need a paediatric SE protocol (avoid prolonged propofol)
- Evidence for anaesthetic choice, EEG target and wean rate is low quality; follow local ICU protocol
- Anaesthetic coma is for convulsive SE or NCSE with coma; focal SE with awareness needs specialist advice first
- Pentobarbital and fosphenytoin are not registered in Australia; thiopentone and IV phenytoin are used
- Requires ICU care with continuous EEG
Contraindicated Populations
Children: use a paediatric SE protocol; avoid prolonged propofolPregnancy or postpartum: treat eclampsia with magnesium sulfate; obstetric input; avoid valproate and pentobarbitalAcute porphyria: avoid barbiturates and valproateFocal SE with preserved awareness or NCSE without coma: not anaesthetic coma first; another IV ASM and specialist advice
Applicable Regions
AUUSEUglobal
AU: Pentobarbital and fosphenytoin are not on the ARTG. Thiopentone is the barbiturate used; IV phenytoin is the usual phenytoin product. Poisons Information Centre 13 11 26.
EU: Thiopental is more often used than pentobarbital. UK NICE NG217 (2022) lists general anaesthesia or phenobarbital as third-line options under expert guidance.
US: NCS 2012 and AES guidance primarily followed; pentobarbital is the barbiturate used.
Version 2Next review: 2027-09-30
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Frequently Asked Questions
What is the Refractory Status Epilepticus Management (Adult ICU)?
The Refractory Status Epilepticus Management (Adult ICU) is a emergency clinical algorithm for Neurology. It provides a structured decision tree to guide clinical decision-making, based on Guidelines for the Evaluation and Management of Status Epilepticus - Neurocritical Care Society (Brophy et al., 2012).
What guideline is the Refractory Status Epilepticus Management (Adult ICU) based on?
This algorithm is based on Guidelines for the Evaluation and Management of Status Epilepticus - Neurocritical Care Society (Brophy et al., 2012) (DOI: 10.1007/s12028-012-9695-z).
What are the limitations of the Refractory Status Epilepticus Management (Adult ICU)?
Known limitations include: Adults only: children need a paediatric SE protocol (avoid prolonged propofol); Evidence for anaesthetic choice, EEG target and wean rate is low quality; follow local ICU protocol; Anaesthetic coma is for convulsive SE or NCSE with coma; focal SE with awareness needs specialist advice first; Pentobarbital and fosphenytoin are not registered in Australia; thiopentone and IV phenytoin are used; Requires ICU care with continuous EEG. Individual patient factors may require deviation from these recommendations.
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