Key Facts

Status epilepticus is a neurological emergency where rapid, protocolised treatment is essential. The longer the seizure continues, the harder it is to terminate and the greater the risk of permanent brain injury. The operational definition of 5 minutes allows earlier intervention.

Epidemiology

Incidence ~10-40 per 100,000 per year. Mortality 10-20% for convulsive SE (higher in elderly and those with underlying structural disease). ~60% of SE occurs in patients without a prior epilepsy diagnosis. Accounts for ~5-10% of epilepsy-related admissions.

Aetiology

• Known epilepsy: medication non-compliance (most common cause in known epileptics), intercurrent illness, sleep deprivation, alcohol
• Acute symptomatic: stroke, traumatic brain injury, CNS infection (meningitis, encephalitis), metabolic (hypoglycaemia, hyponatraemia, hypocalcaemia), drug toxicity/withdrawal (alcohol, benzodiazepines), autoimmune encephalitis
• Remote symptomatic: previous structural brain injury (stroke, TBI) with new trigger
• Febrile SE: in children (see febrile seizures)

Pathophysiology

Prolonged seizure activity causes: (1) progressive loss of GABA-A receptor inhibition (receptor internalisation) — explains why benzodiazepines become less effective with time, (2) upregulation of excitatory NMDA receptors, (3) excitotoxic neuronal death (glutamate-mediated calcium influx), (4) systemic complications: hyperthermia, rhabdomyolysis, lactic acidosis, aspiration, cardiac arrhythmias, cerebral oedema. After ~30 minutes of continuous seizure, irreversible neuronal damage begins.

Convulsive Status Epilepticus (CSE)

• Continuous or repetitive tonic-clonic seizure activity without recovery between episodes
• Patient unconscious between/during seizures
• May evolve from overt convulsions to subtle motor activity ("subtle SE" — twitching, nystagmoid eye movements) as the seizure continues

Non-convulsive Status Epilepticus (NCSE)

• Prolonged altered mental status/confusion without overt convulsions
• May present as unexplained prolonged confusion, behavioural change, or coma
• Diagnosed by EEG (continuous epileptiform discharges)
• Often under-recognised

Red Flags

• Seizure >5 minutes (do not wait for 30 minutes)
• No recovery between seizures
• Evolving to subtle SE (worsening prognosis)
• Hyperthermia (>40°C — poor prognosis)
• Refractory to initial treatment (requires escalation)
• Persistent unexplained confusion (consider NCSE)

Immediate (During Treatment)

• Blood glucose: MUST check immediately — treat hypoglycaemia with 50 mL 20% glucose IV
• ABG/VBG: lactate, pH (acidosis), oxygenation
• FBC, U&Es, calcium, magnesium, LFTs: metabolic causes
• AED levels: if known epileptic (phenytoin, carbamazepine, valproate levels)
• Toxicology screen: if drug overdose/withdrawal suspected
• Blood cultures: if infection suspected

After Stabilisation

• CT head: exclude structural cause (haemorrhage, tumour, abscess)
• MRI brain: more detailed structural assessment
• LP: if CNS infection or autoimmune encephalitis suspected (after CT excludes mass effect)
• EEG: as soon as possible; essential for:
  • Confirming SE if clinically uncertain
  • Diagnosing NCSE
  • Monitoring treatment response in RSE (continuous EEG — aim for burst suppression with anaesthesia)
• Autoimmune encephalitis panel: NMDA-R, LGI1, CASPR2 antibodies (if new-onset refractory SE without clear cause — NORSE)

Stage 1: Early Status (0-5 minutes)

• Secure airway, recovery position
• High-flow oxygen
• Check blood glucose: treat hypoglycaemia (IV glucose 10-20%)
• IV access: 2 large-bore cannulae

Stage 2: Established Status (5-15 minutes — First-line)

• IV lorazepam 4 mg (0.1 mg/kg); repeat once at 10 minutes if seizures continue
• If no IV access: buccal midazolam 10 mg or rectal diazepam 10-20 mg
• Thiamine 250 mg IV (Pabrinex) if alcohol-related or malnourished (BEFORE glucose)

Stage 3: Established Status (15-35 minutes — Second-line)

Choose ONE:

• IV phenytoin 20 mg/kg (max rate 50 mg/min); requires cardiac monitoring (risk of arrhythmia, hypotension); avoid if already on phenytoin
• IV levetiracetam 40-60 mg/kg (max 4.5 g) over 10 minutes; increasingly preferred (fewer cardiac risks)
• IV sodium valproate 40 mg/kg (max 3 g) over 5-10 minutes; avoid in liver disease, pregnancy, mitochondrial disease

Stage 4: Refractory Status Epilepticus (>35 minutes — Third-line)

• ITU admission
• Rapid sequence induction and intubation
• General anaesthesia: IV thiopental (3-5 mg/kg bolus then 3-5 mg/kg/hr), propofol (1-2 mg/kg bolus then 2-10 mg/kg/hr), or midazolam infusion (0.1-0.3 mg/kg bolus then 0.05-0.4 mg/kg/hr)
• Continuous EEG monitoring: target burst suppression for 24-48 hours
• Wean anaesthesia gradually after 24-48 hours: reintroduce if seizures recur

Super-refractory SE (>24 hours despite anaesthesia)

• Ketamine, immunotherapy (if autoimmune), ketogenic diet, hypothermia

Referral Criteria

• All status epilepticus: emergency management + neurology input
• RSE: ITU and neurology
• New-onset refractory SE (NORSE): investigate for autoimmune encephalitis

Mortality for convulsive SE: 10-20%. Mortality increases with: duration of SE, age, underlying aetiology (acute symptomatic worst), and need for anaesthesia. RSE mortality: ~30-50%. NCSE mortality: ~20-30%. Morbidity: ~10-20% of survivors develop new neurological deficit. Early treatment is key — mortality and morbidity increase sharply after 30 minutes of continuous seizure activity. Known epileptics with SE from medication non-compliance have better outcomes than acute symptomatic SE.

Status Epilepticus Treatment Protocol

Causes of Status Epilepticus