Status Epilepticus

What You'll Learn

Definition: continuous seizure ≥5 min (t₁) or recurrent seizures without recovery; neuronal injury risk at 30 min (t₂)
First-line: BZDs — IM midazolam 10 mg (RAMPART: noninferior to IV lorazepam, numerically favored 73.4% vs 63.4% because it can be delivered faster without IV access); underdosing in >75%
Second-line: ESETT — fosphenytoin 20 mg PE/kg, VPA 40 mg/kg, LEV 60 mg/kg — ALL equivalent (~46–47%)
VA Cooperative: stepwise efficacy decline 55.5% → 7.0% → 2.3%
Refractory SE: failed 2 agents → anesthetic infusion with cEEG. Titrate to electrographic seizure suppression; burst suppression is commonly used in deeper coma but is not the only evidence-based endpoint.
NCSE: Salzburg criteria — EDs >2.5 Hz = NCSE; ≤2.5 Hz needs secondary criteria; sensitivity 97.7%
NORSE/FIRES: immunotherapy ≤72 h; ketogenic diet ≤7 days; anakinra: SE cessation 50–60%; mortality 16–22%

HighYield Pearls

t₁ = 5 min (CSE) / 10 min (focal & absence): operational diagnosis — start treatment; t₂ = 30 min for neuronal injury
RAMPART: IM midazolam 10 mg noninferior to IV lorazepam for prehospital convulsive SE and numerically favored (73.4% vs 63.4%) because it can be delivered faster without IV access
ESETT: levetiracetam 60 mg/kg, fosphenytoin 20 mg PE/kg, and valproate 40 mg/kg are all EQUIVALENT (~46–47%) for benzo-refractory SE
>75% of SE patients are underdosed on benzos — "refractory" SE may be iatrogenic; give the FULL weight-based dose before escalating
Always check cEEG after CSE termination: ~40% have ongoing non-convulsive SE; altered MS post-arrest / post-stroke = cEEG
Salzburg criteria for NCSE: EDs >2.5 Hz = NCSE; ≤2.5 Hz needs secondary criteria (evolution, clinical response to IV ASM)
NORSE/FIRES workup: autoimmune panel (NMDAR, GABA_B, LGI1, AMPAR, GAD), HSV/EBV PCR, paraneoplastic; start IV steroids + IVIG/PLEX ≤72 h, then rituximab ± anakinra/tocilizumab
Ketogenic diet ≤7 days in SRSE/FIRES; AVOID propofol in mitochondrial / POLG disease (PRIS risk)
Neonatal SE: always trial pyridoxine 100 mg IV; check ammonia, lactate, AA/OA screen
Top SE etiologies: subtherapeutic AED levels, acute stroke / TBI / tumor / abscess, CNS infection, metabolic, alcohol/BZD withdrawal, autoimmune encephalitis

🔍 Quick ReferenceClinical / classification · EEG · Treatment algorithm

Clinical / classification

Seizure ≥5 min or recurrent without recovery → convulsive SE (t₁)
Altered mental status without overt motor activity + epileptiform EEG → nonconvulsive SE (NCSE)
Subtle eye twitching / nystagmoid jerks / autonomic surges after CSE control → subtle (electrographic) SE
Previously healthy adult with febrile prodrome → refractory SE, cryptogenic → NORSE
Child with febrile illness → explosive refractory SE + devastating cognitive sequelae → FIRES
SE persisting ≥24 h on continuous IV anesthetic → super-refractory SE (SRSE)

EEG patterns

Generalized periodic discharges (GPDs) >2.5 Hz with clinical correlate → NCSE (Salzburg)
Lateralized periodic discharges (LPDs/PLEDs) with focal twitching → focal NCSE (often HSV / acute stroke)
Ictal-interictal continuum (IIC) → treat as NCSE if clinical change with IV BZD
Anesthetic infusion in RSE → titrate to electrographic seizure suppression on cEEG; burst suppression is commonly used in deeper coma but not the only evidence-based endpoint
Extreme delta brushes → anti-NMDAR encephalitis
PLEDs over temporal lobe + RBCs in CSF → HSV encephalitis → SE

Treatment algorithm / drugs

IM midazolam 10 mg (no IV) → RAMPART first-line (prehospital)
IV lorazepam 0.1 mg/kg (max 4 mg) → in-hospital first-line BZD
Levetiracetam 60 mg/kg / fosphenytoin 20 mg PE/kg / valproate 40 mg/kg → ESETT second-line (all equivalent)
Midazolam 0.2–2 mg/kg/h, propofol, pentobarbital infusions → refractory SE (intubate, titrate to electrographic seizure suppression; burst suppression in deeper coma is one acceptable endpoint, not the only one)
Ketamine, ketogenic diet, hypothermia, ECT, intrathecal anesthetics → super-refractory SE adjuncts
Steroids + IVIG/PLEX ≤72 h, then rituximab ± anakinra / tocilizumab → NORSE / FIRES
Pyridoxine 100 mg IV → neonatal refractory SE
Avoid propofol → POLG / mitochondrial disease (PRIS)

Definition & Stages

ILAE 2015 Operational Time Points

t₁ = 5 min: seizure regarded as continuous → initiate treatment
t₂ = 30 min: risk of long-term neuronal injury, hippocampal damage, network alteration
Most self-terminating tonic-clonic seizures end within 2–3 min

Stages of Status Epilepticus

Stage	Time Frame	Definition	Treatment Phase
Developing SE	0–5 min	Not yet meeting SE; most seizures self-terminate	Stabilization (ABCs, glucose, IV access)
Established SE	5–30 min	Ongoing ≥5 min or recurrent without recovery	1st line: BZDs; 2nd line: IV ASMs
Refractory SE	No strict time cutoff (typically 30–60+ min)	Failure of one adequate BZD + one adequate non-BZD ASM	Anesthetics or additional non-sedating ASM
Super-Refractory SE	≥24 h on anesthetics	Persists/recurs despite ≥24 h continuous anesthetic	Multimodal ICU; immunotherapy if NORSE

Epidemiology

Incidence: 10–41 per 100,000/year; bimodal: highest in children (<1 yr) and elderly (>60 yr)
~20% of patients present with SE as their first-ever seizure
30-day mortality: ~10% adults, ~2% children
RSE develops in 23–55% of SE patients; SRSE in ~10–15% of all SE
Etiology is the strongest predictor of outcome (acute symptomatic = worst prognosis)

💎 Board Pearl

>75% of SE patients receive subtherapeutic BZDs — apparent refractoriness may be iatrogenic underdosing; confirm doses before escalating

Convulsive SE Treatment Algorithm

0–5 min: Stabilization

Recovery position; suction; O₂ via non-rebreather; do NOT place objects in mouth
2 large-bore IVs; POC glucose, BMP, CBC, ASM levels, toxicology
D50W 25–50 mL if hypoglycemia; thiamine 100 mg IV first if malnourished/alcohol
Continuous cardiac telemetry + pulse oximetry; note exact seizure onset time
Prepare for cEEG as soon as available

5–20 min: First-Line — Benzodiazepines

Agent	Route	Adult Dose (>40 kg)	Onset	Repeat
Midazolam	IM	10 mg (>40 kg) or 5 mg (13–40 kg)	3–5 min	Single dose
Midazolam	Buccal	10 mg (first-line when IV/IM access unavailable)	3–5 min	Single dose
Midazolam	Intranasal	0.2 mg/kg (commonly 5–10 mg; first-line when IV/IM access unavailable)	3–5 min	Single dose
Lorazepam	IV	0.1 mg/kg IV (max 4 mg per dose); may repeat ×1 in 5–10 min	2–3 min	Yes, ×1
Diazepam	IV / PR	IV: 0.15–0.2 mg/kg (max 10 mg per dose); PR: 0.2 mg/kg	1–2 min	Yes, ×1

RAMPART Trial (2012)

893 prehospital SE patients: IM midazolam 10 mg vs. IV lorazepam 4 mg
Non-inferior to IV lorazepam (primary endpoint met); IM midazolam achieved higher seizure cessation rate (73.4% vs. 63.4%) with faster overall time to drug administration
Advantage = faster drug delivery — IM avoids IV access delays in seizing patients
IM midazolam = preferred first-line when IV access not immediately available

BZD Underdosing — The #1 Treatment Error

Subtherapeutic BZD dosing in >75% of SE patients (ESETT cohort, SENSE registry)
Underdosing → higher rates of refractory SE, intubation, and death
PHTSE trial: placebo group had >2× respiratory dysfunction vs. lorazepam/diazepam
Uncontrolled SE is more dangerous than BZDs — use full guideline-recommended doses

20–40 min: Second-Line — Non-BZD ASMs

Agent	Loading Dose	Max	Key Considerations
Fosphenytoin	20 mg PE/kg	1500 mg PE	Cardiac monitor; hypotension/arrhythmia; avoid in conduction disorders
Valproic acid	40 mg/kg	3000 mg	Avoid in pregnancy, mito disease, hepatic failure; best hemodynamics
Levetiracetam	60 mg/kg	4500 mg	Safest profile; no cardiac/hepatic toxicity; no drug interactions

ESETT Trial (2019)

384 patients aged 2–95 with BZD-resistant CSE
Seizure cessation + improved consciousness at 60 min: LEV 47%, fosphenytoin 45%, VPA 46%
No significant difference — all three equivalent; choose based on patient factors

VA Cooperative Trial (1998)

Stepwise efficacy decline: 1st ASM 55.5% → 2nd ASM 7.0% → 3rd ASM 2.3%
Fundamental rationale for aggressive, protocol-driven, early treatment

>40 min: Third-Line Options

Option A: additional non-sedating ASM (lacosamide, brivaracetam) — may terminate RSE in ~50%
Option B: anesthetic infusion (midazolam, propofol, pentobarbital) — requires intubation + cEEG
No Class I evidence for either strategy; individualize based on clinical severity

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