Overview
Status Epilepticus
Topic Overview
Summary
Status epilepticus (SE) is defined as continuous seizure activity lasting over 5 minutes or recurrent seizures without regaining consciousness between episodes. It is a medical emergency with mortality of 10-20% and requires rapid, stepwise treatment. First-line is benzodiazepines (lorazepam IV or buccal midazolam); escalate through second-line (levetiracetam/phenytoin/valproate) to third-line (anaesthetic agents) if seizures persist.
Key Facts
- Definition: Seizure over 5 minutes OR ≥2 seizures without recovery
- Mortality: 10-20%; higher in refractory SE and elderly
- First-line: Lorazepam 4mg IV or midazolam 10mg IM/buccal
- Second-line: Levetiracetam, phenytoin, or valproate IV
- Third-line: RSI + propofol/thiopentone/midazolam infusion (ICU)
- Causes: Medication non-compliance, alcohol withdrawal, stroke, metabolic, infection, tumour
Clinical Pearls
"Time is brain" — neuronal damage increases with seizure duration; aim for seizure termination within 30 minutes
If no IV access: buccal/IM midazolam or rectal diazepam are effective first-line alternatives
Always consider non-convulsive status epilepticus in prolonged altered consciousness
Why This Matters Clinically
Status epilepticus causes progressive neuronal injury, systemic complications (aspiration, rhabdomyolysis, hyperthermia), and death. Rapid escalation through treatment stages is essential. Every clinician must know the stepwise protocol.
Visual Summary
Visual assets to be added:
- Status epilepticus treatment algorithm (timed protocol)
- Benzodiazepine dosing chart
- ECG/EEG during status
- Causes of status epilepticus infographic
Epidemiology
Incidence
- Overall: 10-40 per 100,000/year
- Mortality: 10-20% (higher in refractory SE, elderly, anoxic)
- Morbidity: 10-20% develop new neurological deficits
Demographics
- Bimodal age distribution: Children under 1 year and elderly
- More common in males
Aetiology
| Cause | Notes |
|---|---|
| Known epilepsy | AED non-compliance (most common in known epileptics), breakthrough |
| Alcohol withdrawal | Common in acute hospitals |
| Stroke/haemorrhage | Especially acute phase |
| CNS infection | Meningitis, encephalitis |
| Metabolic | Hypoglycaemia, hyponatraemia, hypocalcaemia, uraemia |
| Drug toxicity | Theophylline, tramadol, antipsychotics |
| Tumour | New or known |
| Head injury | Acute or late |
| Anoxic brain injury | Post-cardiac arrest |
Pathophysiology
Progressive Seizure Pathophysiology
Phase 1 (0-30 min):
- GABA-A receptor internalisation → reduced inhibitory control
- Glutamate release → excitotoxicity
- Initial compensation (catecholamine surge)
Phase 2 (30-60 min):
- NMDA receptor activation → calcium influx → neuronal injury
- Metabolic demand exceeds supply
- Lactate accumulation, acidosis
Phase 3 (over 60 min):
- Failure of homeostatic mechanisms
- Hyperthermia, rhabdomyolysis, multi-organ failure
- Irreversible neuronal death
Why Benzodiazepines Become Less Effective
- GABA-A receptor internalisation during prolonged seizures
- Explains need for early treatment and escalation
Clinical Presentation
Convulsive Status Epilepticus (Most Common)
Non-Convulsive Status Epilepticus (NCSE)
Focal Motor Status
Red Flags
| Feature | Significance |
|---|---|
| Not responding to 1st-line benzodiazepines | Proceed to 2nd-line immediately |
| Hyperthermia | Suggests prolonged seizure; poor prognosis |
| New-onset in non-epileptic | Search for underlying cause (stroke, infection, metabolic) |
| Post-arrest | Anoxic injury — prognosis guarded |
Continuous tonic-clonic movements
Common presentation.
Unresponsive GCS
Common presentation.
May evolve from discrete tonic-clonic movements to subtle myoclonus
Common presentation.
Clinical Examination
Initial Assessment
- Airway: Patent? Secretions? Recovery position
- Breathing: SpO₂, give O₂
- Circulation: HR, BP, IV access
- Disability: Nature of seizure activity, pupil response
- Exposure: Temperature, signs of trauma
During Seizure
- Protect from injury
- Do NOT restrain
- Do NOT insert anything in mouth
- Time the seizure
Post-Ictal
- GCS
- Focal signs (Todd's paresis suggests focal onset)
- Fever (infection as cause)
- Signs of trauma (tongue bite, injuries)
Investigations
Immediate (Bedside)
| Test | Purpose |
|---|---|
| Blood glucose | Hypoglycaemia — treat immediately |
| SpO₂ | Hypoxia |
| Temperature | Hyperthermia |
| ECG | Arrhythmias, QTc (drug-induced) |
Laboratory
| Test | Purpose |
|---|---|
| U&E | Sodium, potassium, calcium, renal function |
| Glucose | Confirm fingerprick |
| Calcium, magnesium | Metabolic causes |
| AED levels | Compliance, toxicity |
| FBC | Infection |
| ABG/VBG | Acidosis, lactate |
| CK | Rhabdomyolysis |
| Toxicology screen | If cause unclear |
Imaging
- CT Head: If new-onset, focal onset, trauma, or cause unclear
- Urgent if suspected structural cause
EEG
- If NCSE suspected
- Continuous EEG monitoring in ICU for refractory SE
Classification & Staging
By Timing
| Stage | Duration | Term |
|---|---|---|
| Early SE | 5-30 min | Impending SE |
| Established SE | 30-60 min | Established SE |
| Refractory SE | Over 60 min or persists despite 2 AEDs | Refractory SE |
| Super-refractory SE | Over 24h despite anaesthesia OR recurs on weaning | Super-refractory SE |
By Type
- Convulsive (generalised tonic-clonic)
- Non-convulsive (absence, focal aware/impaired awareness)
- Focal motor (epilepsia partialis continua)
Management
Time-Based Protocol (UK Modified)
0-5 MINUTES: STABILISE
- Airway, O₂, recovery position
- Check glucose — treat hypoglycaemia
- IV access
5-10 MINUTES: FIRST-LINE (BENZODIAZEPINES)
| Drug | Dose | Route |
|---|---|---|
| Lorazepam | 4mg (0.1mg/kg) | IV — repeat once in 5-10 min if needed |
| Midazolam | 10mg | IM or buccal (if no IV access) |
| Diazepam | 10mg | IV or rectal |
10-20 MINUTES: SECOND-LINE (IF SEIZURES PERSIST) Choose ONE:
| Drug | Dose | Notes |
|---|---|---|
| Levetiracetam | 60mg/kg (max 4.5g) IV over 10 min | Fewer interactions; safe in liver disease |
| Phenytoin | 20mg/kg IV (max 50mg/min) | ECG monitoring; avoid if hypotension |
| Valproate | 40mg/kg IV (max 3g) over 10 min | Avoid in pregnancy, liver disease |
20-40 MINUTES: THIRD-LINE (GENERAL ANAESTHESIA)
- Rapid sequence induction (RSI)
- Propofol infusion (2-5 mg/kg/hr) OR
- Midazolam infusion (0.05-0.4 mg/kg/hr) OR
- Thiopentone (3-5 mg/kg bolus, infusion)
- ICU admission, continuous EEG monitoring
- Burst suppression target
Treat Underlying Cause
- Glucose if hypoglycaemia
- Thiamine if alcohol-related/malnourished
- Antibiotics if infection
- Correct electrolyte abnormalities
Pyridoxine
- Consider IV pyridoxine (100-300mg) in:
- Isoniazid overdose
- Refractory SE of unknown cause
Complications
From Prolonged Seizure
- Neuronal injury (hippocampal sclerosis)
- New epilepsy
- Cognitive impairment
- Aspiration pneumonia
- Rhabdomyolysis → AKI
- Hyperthermia
- Fractures, dislocations (vertebral, shoulder)
- Death
From Treatment
- Respiratory depression (benzodiazepines)
- Hypotension (propofol, phenytoin)
- Purple glove syndrome (phenytoin extravasation)
- Propofol infusion syndrome (rare, prolonged use)
Prognosis & Outcomes
Mortality
- Overall: 10-20%
- Anoxic SE: Very high mortality and poor neurological outcomes
- Drug-induced/alcohol SE: Generally better outcomes
Prognostic Factors
| Factor | Impact |
|---|---|
| Duration | Longer = worse |
| Cause | Anoxic and CNS infection = worst |
| Age | Elderly = higher mortality |
| Refractory SE | Higher mortality |
| Comorbidities | Higher mortality |
Evidence & Guidelines
Key Guidelines
- NICE CG137: Epilepsies — updated 2022
- Advanced Life Support (Resus Council UK) — Seizure Algorithm
- American Epilepsy Society Guidelines for Status Epilepticus
Key Trials
- RAMPART Trial: IM midazolam as effective as IV lorazepam for pre-hospital SE
- ESETT Trial: Levetiracetam, fosphenytoin, and valproate equally effective as second-line
Patient & Family Information
What is Status Epilepticus?
Status epilepticus is a seizure that lasts too long (more than 5 minutes) or seizures that happen one after another without the person waking up. It is a medical emergency.
What to Do If Someone Has a Prolonged Seizure
- Call 999 immediately
- Keep them safe from injury
- Do NOT put anything in their mouth
- Time the seizure
- If prescribed emergency medication (buccal midazolam or rectal diazepam), give it
After Treatment
- Investigation to find the cause
- Adjustment of regular epilepsy medication if needed
- Follow-up with neurology
Resources
References
Primary Guidelines
- NICE. Epilepsies: Diagnosis and Management (CG137/NG217). 2022. nice.org.uk
- Resuscitation Council UK. Adult Advanced Life Support: Seizure Algorithm. resus.org.uk
Key Trials
- Silbergleit R, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus (RAMPART). N Engl J Med. 2012;366(7):591-600. PMID: 22335736
- Kapur J, et al. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus (ESETT). N Engl J Med. 2019;381(22):2103-2113. PMID: 31774955