Washington Manual Summary
"Status epilepticus is defined as continuous seizure activity lasting more than 5 minutes, or two or more seizures without return to baseline consciousness between them. It is a neurological emergency requiring immediate treatment, as neuronal injury begins within minutes and increases with duration."
Washington Manual of Critical Care, 4th Ed. Wolters Kluwer 2023. Chapter: Neurological Emergencies.Clinical Synopsis
- Definition (NCS 2024): Seizure ≥5 minutes OR ≥2 seizures without full recovery between them. The old 30-minute definition is obsolete.
- Types: GCSE (generalised convulsive — most common, most dangerous), NCSE (non-convulsive — needs EEG), RSE (refractory — 2 adequate ASMs failed), SRSE (>24h despite anaesthetic agents)
- Incidence in India: NCC (neurocysticercosis) most common cause of new-onset seizures. OP poisoning = major cause of SE in Indian ICUs.
- Time critical: GABA receptors internalise within 30 min of SE → BZD resistance develops → treat immediately and adequately
- NCSE: Present in 16–37% of comatose ICU patients on EEG — routinely missed without EEG monitoring
Marino Physiology — Seizure Mechanisms
"Seizures are classified by the presence or absence of abnormal movements (convulsive versus nonconvulsive seizures), the type of abnormal movement (e.g., tonic–clonic, myoclonic), and the extent of involvement (generalized versus focal seizures)."
Marino PL. The ICU Book, 5th Ed. Ch.46: Disorders of Movement. Wolters Kluwer; 2025. p.749NCSE clinical manifestations (from 105 reported cases) — Marino Table 46.2: Confusion (49%), Coma (22%), Lethargy (21%), Speech disturbances (15%), Myoclonus (13%), Bizarre behaviour (11%), Agitation/delirium (8%), Hallucinations (6%).
Key insight: Impaired consciousness (confusion, coma, or lethargy) was present in ~80% of NCSE. In ICU patients with unexplained coma: nonconvulsive seizures detected in 16% on continuous EEG monitoring. This is why continuous EEG is mandatory in all comatose ICU patients not awakening within 60 min of apparent seizure cessation.
BZD (Step 1): IM midazolam 0.15 mg/kg (or 10 mg) — as effective as IV lorazepam (RAMPART trial). Recommended when IV access unavailable.
Levetiracetam (Step 2): 60 mg/kg IV over 5–15 min; max single dose 4,500 mg. No hypotension or respiratory depression; no drug interactions.
Fosphenytoin (Step 2): 20 mg PE/kg IV at ≤150 mg PE/min; max 1,500 mg PE. Water-soluble; less cardiac depression than phenytoin.
Valproic Acid (Step 2): 40 mg/kg IV over 5–10 min; max 3,000 mg. Equivalent to levetiracetam/fosphenytoin; 40% risk of hyperammonaemia.
NCS 2024 Treatment Algorithm
IM: Midazolam 0.2 mg/kg IM (max 10 mg) — RAMPART trial: IM midazolam = IV lorazepam; faster when no IV access
Buccal/IN: Midazolam 0.2 mg/kg per nostril; useful prehospital
Levetiracetam: 60 mg/kg IV over 10 min (max 4500 mg) — preferred (no interactions, no cardiac effects)
Valproate: 40 mg/kg IV over 10 min (max 3000 mg) — avoid in pregnancy, liver disease
Fosphenytoin: 20 mg PE/kg IV at ≤150 mg PE/min — needs cardiac monitoring
SE Drug Reference (Marino Ch.46 + NCS 2024)
| Drug | Route | Dose | Onset | Key Points |
|---|---|---|---|---|
| Lorazepam | IV only | 0.1 mg/kg IV (max 4 mg); repeat × 1 after 5 min | 2–3 min | Gold standard IV BZD; longer duration than diazepam |
| Midazolam | IM / Buccal / IN | 0.2 mg/kg IM (max 10 mg) | 0.2 mg/kg buccal | 0.2 mg/kg each nostril | 5–10 min | RAMPART: IM midazolam = IV lorazepam. Preferred prehospital |
| Diazepam | IV / PR | 0.15–0.2 mg/kg IV (max 10 mg) | 0.5 mg/kg PR | 1–3 min (IV) | Short brain duration — always follow with 2nd-line ASM |
| Levetiracetam | IV | 60 mg/kg IV over 10 min (max 4500 mg) | 15–20 min | No drug interactions; no cardiac effects; safe in liver disease; ESETT = best choice |
| Sodium Valproate | IV | 40 mg/kg IV over 10 min (max 3000 mg) | 15–20 min | Avoid: pregnancy, liver disease, valproate-sensitive mitochondrial disease. 40% hyperammonaemia |
| Fosphenytoin | IV | 20 mg PE/kg IV at ≤150 mg PE/min (max 1500 mg PE) | 15–30 min | Cardiac monitoring mandatory; avoid in cardiac disease; less cardiac depression than phenytoin (no propylene glycol) |
| Phenobarbitone | IV | 20 mg/kg IV at 50–100 mg/min (max 1000 mg) | 15–30 min | Widely available in India; sedating; useful when LEV/VPA unavailable |
Status Epilepticus Treatment Algorithm
0–5 min: Stabilise + Emergency Bloods
ABCDE. Check glucose (MANDATORY — hypoglycaemia = most common reversible cause). If <60 mg/dL: Thiamine 200 mg IV first → then 25g Dextrose IV. IV access × 2. SpO₂, ECG, BP, temp. Draw: glucose, Na, Ca, Mg, drug levels, toxicology, cultures.
5–20 min: FIRST-LINE — Benzodiazepine
IV access: Lorazepam 0.1 mg/kg IV (max 4 mg) → repeat once at 5 min if no response.
No IV: Midazolam 10 mg IM into anterolateral thigh — RAMPART trial: equivalent to IV lorazepam AND faster in practice.
20–40 min: SECOND-LINE — Non-sedating ASM
BZD failed → give ONE: Levetiracetam 60 mg/kg IV over 10 min (preferred) OR Valproate 40 mg/kg IV over 10 min OR Fosphenytoin 20 mg PE/kg IV at ≤150 mg PE/min. ESETT: all three equally effective (~48% each).
40–60 min: REFRACTORY SE — Anaesthesia + EEG
Intubate. Continuous EEG monitoring (mandatory). Start: Propofol 1–2 mg/kg bolus → 1–10 mg/kg/hr TITRATED TO BURST SUPPRESSION on EEG. Maintain 24–48h, then attempt slow wean.
Find the Cause — Always
CT head (urgent: exclude structural, haemorrhage, herniation). LP (if CNS infection possible — give Ceftriaxone 2g IV immediately if meningitis suspected). MRI (encephalitis, PRES, cortical dysplasia). Autoimmune panel: anti-NMDA-R, anti-LGI1, anti-CASPR2. OP toxidrome: organophosphate screen.
Common Mistakes in Status Epilepticus
RAMPART trial: IM midazolam 10 mg = IV lorazepam. Don't delay 5–10 minutes getting IV access while the patient seizes. Give IM midazolam NOW; get IV access concurrently.
Most common reason BZDs fail is INADEQUATE DOSING. Give full weight-based dose: Lorazepam 4 mg (not 1–2 mg), Diazepam 10–20 mg (not 5 mg), Midazolam 10 mg IM. Underdosing → BZD resistance → harder-to-treat SE.
BZD terminates the seizure but has short brain duration. Always follow with a 2nd-line ASM (levetiracetam, valproate, or fosphenytoin) even if BZD worked — prevents recurrence.
Marino (p.751): NCSE present in 16–37% of ICU patients with impaired consciousness. If not waking up 60 min after apparent seizure cessation → NCSE until proven otherwise. Get EEG — you cannot diagnose NCSE clinically.
Hypoglycaemia causes seizures AND prevents BZD response. Check glucose BEFORE or SIMULTANEOUSLY with first BZD dose. Give 25g Dextrose IV if <60 mg/dL. Give thiamine 200 mg IV FIRST if alcoholic/malnourished (prevents Wernicke's).
Exam Pearls
Q: Current definition of status epilepticus (NCS 2024)?
Seizure ≥5 minutes OR ≥2 seizures without full recovery between them. The old 30-minute definition is obsolete. At 5 minutes, seizures are unlikely to self-terminate and GABA receptors begin to internalise (→ BZD resistance). Treat immediately at 5 min.
Q: RAMPART trial — what did it show?
IM midazolam 10 mg was equivalent to IV lorazepam for prehospital status epilepticus, AND resulted in faster treatment (no IV access needed). IM midazolam is now the preferred route when IV access is unavailable. (NEJM 2012)
Q: ESETT trial — what did it show about 2nd-line agents?
Levetiracetam 60 mg/kg, Valproate 40 mg/kg, and Fosphenytoin 20 mg PE/kg are ALL equally effective for established SE (~47–50% success each). No agent was superior. Levetiracetam preferred due to better safety profile (no drug interactions, no cardiac effects). (NEJM 2019)
Q: EEG target in refractory SE on anaesthetic agents?
Burst suppression — brief bursts of electrical activity separated by periods of suppression. Maintain for 24–48h, then wean slowly with EEG monitoring. Continuous EEG mandatory in all refractory SE patients.
Q: Marino's insight on NCSE in ICU?
Marino Ch.46 (p.751): NCSE is commonly missed — most common presentation is confusion/coma (present in ~80% of NCSE). Detected in 16% of ICU patients with impaired consciousness on continuous EEG. Lesson: get EEG in any unexplained altered consciousness, especially if not improving after apparent seizure cessation.
References
- Marino PL. Marino's The ICU Book, 5th edition. Chapter 46: Disorders of Movement (pp.749–764). Philadelphia, PA: Wolters Kluwer; 2025.
- Glauser T, Shinnar S, Gloss D, et al. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults (Neurocritical Care Society 2016, updated 2024). Epilepsy Currents. 2016;16(1):48–61.
- Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus Intravenous Therapy for Prehospital Status Epilepticus (RAMPART). N Engl J Med. 2012;366(7):591–600.
- Kapur J, Elm J, Chamberlain JM, et al. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus (ESETT). N Engl J Med. 2019;381(22):2103–2113.
- Betjemann JP, Lowenstein DH. Status Epilepticus in Adults. Lancet Neurol. 2015;14(6):615–624.
- Washington Manual of Critical Care, 4th Ed. Kollef MH, Witt CA (eds). Wolters Kluwer; 2023.
- Oh TE (ed). Oh's Intensive Care Manual, 8th edition. Chapter 51: Status Epilepticus. Elsevier; 2018.