Status Epilepticus: When a Seizure Does Not Stop — and Why the Clock Is the Most Important Factor in Whether the Brain Survives Intact

CNS infections — the dominant Indian cause

Bacterial meningitis: Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, and in newborns, Group B Streptococcus. Bacterial meningitis causes SE through direct cortical irritation by the inflammatory exudate. In any patient with SE and fever — particularly with neck stiffness or photophobia — bacterial meningitis must be considered and empirical antibiotics started before lumbar puncture, not after. At KIMS, this principle is followed absolutely.

Viral encephalitis: Herpes simplex encephalitis (HSE) is the most important treatable viral encephalitis — SE may be the presenting feature. IV acyclovir must be started empirically in any patient with SE and encephalitic features (fever, altered behaviour, temporal lobe changes on MRI). Japanese encephalitis and other arboviral encephalitides are significant in parts of India.

Neurocysticercosis: Taenia solium cysts in the brain — the most common identifiable cause of new-onset seizures in Indian adults — can trigger SE, particularly as cysts begin to die and provoke an inflammatory response. CT brain showing ring-enhancing lesions or calcifications with SE should prompt consideration of NCC.

Drug default — the preventable cause

A person with established epilepsy stops taking their antiepileptic medication — because they ran out, because the medication was unavailable at the pharmacy, because they felt well and decided they no longer needed it, or because a family member advised stopping. Within days to weeks, seizures break through — and in some patients, this breakthrough takes the form of SE.

Drug default is directly preventable. At KIMS, every epilepsy patient is counselled at every appointment: never stop your medication without discussing it with your neurologist. The medication is keeping the seizures controlled. The epilepsy has not gone away because the seizures have stopped — the seizures have stopped because the medication is working. Every family of a KIMS epilepsy patient receives written instructions on what to do if they are running low on medication.

Metabolic causes — acute and treatable

• Hypoglycaemia: The most immediately correctable cause of SE. Blood glucose is checked and glucose given in every SE patient before anything else, without exception. At KIMS, IV dextrose is given empirically to any SE patient whose glucose cannot be checked immediately.

• Hyponatraemia: Low sodium — from any cause — lowers the seizure threshold. Common in: prolonged vomiting, excessive free water intake, SIADH from CNS infection or injury. Careful, controlled sodium correction is required — too rapid correction risks osmotic demyelination syndrome.

• Hypocalcaemia: Particularly relevant in neonates and young infants. Checked and corrected promptly.

• Uraemia: Kidney failure produces accumulation of compounds that lower seizure threshold and can cause SE. Treatable with dialysis.

• Hepatic encephalopathy: Liver failure produces hyperammonaemia and other metabolic disturbances causing SE.

Autoimmune encephalitis — the diagnosis not to miss

Anti-NMDA receptor encephalitis and other antibody-mediated encephalitides can present as new-onset SE — often in a previously healthy young person, with accompanying psychiatric symptoms, movement abnormalities, and autonomic instability. This is not a diagnosis that will be made without specifically testing for it. At KIMS, the autoimmune encephalitis panel (anti-NMDA, anti-LGI1, anti-CASPR2, anti-GABA-B, anti-AMPA, and others) is sent in any patient with new-onset refractory SE without an obvious cause — because the treatment (immunotherapy: corticosteroids, IVIG, plasma exchange, rituximab) is specific, effective, and entirely different from standard SE management.

Acute brain injury

Stroke — ischaemic or haemorrhagic — can precipitate SE, particularly in elderly patients. Traumatic brain injury. Brain tumour with seizure breakthrough. SE following neurosurgery.

Sub-therapeutic antiepileptic drug levels in established epilepsy

When an antiepileptic drug level falls below the therapeutic range — due to non-adherence, drug interaction, illness reducing absorption, or a change in metabolism — breakthrough seizures can proceed to SE. Drug levels are checked as a priority in every known epilepsy patient presenting with SE at KIMS.

Phase 0 — Pre-hospital (0–5 minutes from seizure start)

If the family has been prescribed rescue medication (buccal midazolam or rectal diazepam) for a patient with known epilepsy and prolonged seizure history — this is the moment to use it. Buccal midazolam (0.3–0.5 mg/kg, max 10 mg) is administered by a trained family member between the gum and cheek if the seizure reaches 5 minutes. This pre-hospital benzodiazepine — if given promptly — may terminate SE before hospital arrival. Training and prescription of buccal midazolam is provided at KIMS for every epilepsy patient with a history of prolonged seizures.

Phase 1 — Immediate (0–5 minutes from hospital arrival): Stabilise and first-line treatment

All of the following happen simultaneously — not sequentially:
• Airway: position on side (recovery position), suction if needed, oxygen
• IV access — two large-bore IV lines
• Blood glucose — check immediately; give IV dextrose if low or unmeasurable
• Blood samples: electrolytes, glucose, full blood count, liver and kidney function, calcium, magnesium, AED levels (if known epileptic), blood cultures (if febrile), lactate
• Continuous pulse oximetry and cardiac monitoring

First-line benzodiazepines — given immediately, before imaging:
• IV lorazepam: 0.1 mg/kg (maximum 4 mg), given over 2 minutes. Can be repeated once after 5 minutes if seizure continues. The preferred first-line agent when IV access is established.
• IM midazolam: 0.2 mg/kg (maximum 10 mg, adult). Equally effective to IV lorazepam in clinical trials — and faster when IV access has not yet been established. The preferred pre-hospital and paramedic route in many situations. At KIMS, IM midazolam is used when IV access is delayed.
• Intranasal midazolam: 0.2 mg/kg via atomiser into both nostrils. Effective, non-invasive, can be administered by family members. Particularly useful in children in community settings.
• Rectal diazepam: 0.3–0.5 mg/kg. The classic community rescue medication — less commonly used now that buccal and intranasal midazolam have been shown to be more effective and more acceptable.

First-line benzodiazepines terminate SE in approximately 60–70% of patients when given promptly. The failure to give adequate doses of benzodiazepines is one of the most common errors in SE management — under-dosing due to concern about respiratory depression. At KIMS, the dose is given in full, with respiratory support standing by.

Phase 2 — If seizure continues at 20–30 minutes: Second-line antiepileptics

If SE continues despite two doses of benzodiazepine, second-line IV antiepileptics are started. At KIMS, the following are used as second-line:

IV Levetiracetam: 60 mg/kg (maximum 4,500 mg) over 10 minutes. Now the preferred second-line agent at KIMS, based on trial evidence and its favourable safety profile — no cardiac monitoring required, no respiratory depression, no sedation, no drug interactions, safe in pregnancy and renal disease. The ESETT and ESTABLISHED trials confirm levetiracetam as equally effective to fosphenytoin and valproate.

IV Sodium Valproate: 40 mg/kg (maximum 3,000 mg) over 15 minutes. Highly effective second-line agent. Contraindicated in pregnancy (teratogenicity), liver disease, and known mitochondrial disease. Not recommended in girls and women of childbearing age unless other options have failed. At KIMS, valproate is the second-line choice in patients with known valproate-responsive epilepsy syndromes.

IV Fosphenytoin: 20 mg PE/kg over 15 minutes with cardiac monitoring (risk of cardiac arrhythmia and hypotension). Less commonly used at KIMS as first-choice second-line agent since the ESETT trial data, but available and effective. Not appropriate for patients with generalised epilepsy syndromes (JME, CAE) — can worsen these.

If the first second-line agent fails, a second second-line agent can be given.

Phase 3 — Refractory SE (30–60 minutes and beyond): Neuro ICU and anaesthetic agents

Refractory SE — SE continuing despite benzodiazepines and two second-line agents — requires admission to KIMS Neuro ICU, intubation and ventilation, and continuous infusion of anaesthetic agents:

IV Midazolam infusion: 0.1–2 mg/kg/hour — the most commonly used first anaesthetic agent for RSE at KIMS. Titrated to EEG burst suppression pattern — confirming seizure activity is suppressed, not just the convulsions.

IV Propofol infusion: 1–15 mg/kg/hour. Rapid onset and offset — useful for rapid titration. Risk of propofol infusion syndrome (PRIS) with doses above 5 mg/kg/hour for more than 48 hours — manifesting as metabolic acidosis, rhabdomyolysis, and cardiac failure. Triglyceride monitoring is essential. Not recommended in children under 16 for SE.

IV Thiopentone infusion: The deepest level of barbiturate anaesthesia for truly refractory SE. Prolonged half-life means slow emergence after discontinuation. Used at KIMS when midazolam and propofol have both failed.

IV Ketamine: An NMDA antagonist — increasingly used as an adjunct in RSE, particularly in autoimmune encephalitis-related SE. Has the advantage of supporting rather than depressing blood pressure, unlike other anaesthetic agents.

Continuous EEG monitoring in Neuro ICU: All RSE patients at KIMS Neuro ICU have continuous EEG monitoring. This is essential because:
1. anaesthetic agents may suppress the visible convulsions while electrical SE continues — EEG is the only way to know the seizures have actually stopped;
2. NCSE must be detected after convulsions are controlled;
3. EEG guides titration of anaesthetic agents to burst suppression;
4. EEG detects seizure recurrence when anaesthetics are being weaned.

Phase 4 — Treating the underlying cause simultaneously

Seizure control is necessary but not sufficient. Finding and treating the cause is what prevents recurrence. At KIMS, simultaneously with seizure control:

• Empirical IV antibiotics (ceftriaxone + ampicillin in children; ceftriaxone + vancomycin in adults) — started before lumbar puncture if clinical meningitis is suspected. The risk of delaying antibiotics to wait for LP far exceeds any diagnostic benefit of a pre-antibiotic LP in the acute setting.

• Empirical IV acyclovir — started if encephalitic features are present, pending HSV PCR results. Started before LP results in any patient where viral encephalitis cannot be excluded.

• Glucose, sodium, calcium correction — as indicated by blood results

• AED dose correction for patients with sub-therapeutic levels

• Autoimmune panel sent for unexplained refractory SE in young patients

• CT brain — to exclude haemorrhage, identify structural cause, assess for neurocysticercosis

• MRI brain with DWI and FLAIR — preferred over CT when the patient is stabilised; more sensitive for encephalitis, cortical injury from SE itself, and subtle structural causes

Option 1 — Multiple anaesthetic agent trials

Sequential or combination use of midazolam, propofol, ketamine, and thiopentone — titrated to EEG burst suppression. The goal is to achieve and maintain burst suppression on continuous EEG while the underlying cause is treated.

Option 2 — Immunotherapy where autoimmune encephalitis is suspected

High-dose IV methylprednisolone, IVIG, and plasma exchange — started empirically in young patients with SRSE without identified infectious cause, since autoimmune encephalitis requires specific immunotherapy, not just seizure suppression.

Option 3 — Ketogenic diet in SRSE

The ketogenic diet — very high fat, very low carbohydrate — has been used as adjunctive treatment in SRSE with documented efficacy in case series. It can be administered through nasogastric tube in intubated patients.

Option 4 — Adjunctive agents and hypothermia

Magnesium sulphate infusion: Used as adjunctive agent, particularly in pregnancy-associated SE (eclampsia).

Hypothermia protocol: Therapeutic cooling (35°C) has been used in selected SRSE cases based on emerging evidence.

The goal in SRSE is to maintain burst suppression on continuous EEG while identifying and treating the underlying cause — and to attempt careful anaesthetic weaning every 24–48 hours once the cause is treated.