status epilepticus

**Definition:** Generalized convulsive SE = continuous seizure ≥5 min (operational definition for treatment, per ILAE/Neurocritical Care Society) or recurrent seizures without recovery of consciousness between them. Neuronal injury begins at about 30 min.

**Pathophysiology:** Failure of the mechanisms that normally terminate seizures. GABA-A receptors are internalized, so inhibition falls and benzodiazepines become less effective over time (the reason to treat early). NMDA/glutamate receptors are upregulated, so excitation rises. Result: self-sustaining seizure activity, excitotoxicity (Ca2+ influx), and neuronal death.

**Common causes:** - Antiseizure drug noncompliance or withdrawal (most common in known epileptics) - Alcohol withdrawal; benzodiazepine or barbiturate withdrawal - Stroke (ischemic or hemorrhagic), CNS infection (meningitis, encephalitis), tumor, trauma - Metabolic: hypoglycemia, hyponatremia, hypocalcemia, uremia, hepatic failure - Toxins/drugs: isoniazid (give pyridoxine/B6), bupropion, tricyclic antidepressants, theophylline, cocaine, other sympathomimetics - Eclampsia (treat with magnesium sulfate) - Hypoxic brain injury, autoimmune encephalitis (e.g., anti-NMDA receptor)

**Complications:** Hypoxia, lactic acidosis, hyperthermia, rhabdomyolysis with acute kidney injury (myoglobinuria), aspiration, hypoglycemia or hyperglycemia, cardiac arrhythmias, cerebral edema, permanent neurologic deficits, and death.

**Management (stepwise):** 1. **Stabilize:** ABCs, oxygen, IV access, monitor vitals and ECG. **Check fingerstick glucose** immediately. Give thiamine and then dextrose if hypoglycemic or if alcohol use is suspected. Draw labs (BMP, Ca, Mg, CBC, tox screen, antiseizure drug levels, CK, pregnancy test). 2. **Emergent (0–5 min) first-line: benzodiazepine.** IV lorazepam 0.1 mg/kg (max 4 mg/dose, may repeat once). If there is no IV access, use IM midazolam (the RAMPART trial showed it is at least as good as IV lorazepam) or rectal diazepam. 3. **Urgent (5–20 min) second-line:** IV levetiracetam, fosphenytoin, or valproate (ESETT trial showed equivalent efficacy). Avoid valproate in pregnancy, liver disease, and mitochondrial disease. Phenytoin and fosphenytoin carry a risk of arrhythmia and hypotension, so use cardiac monitoring. 4. **Refractory SE (persists despite 1st- and 2nd-line drugs):** Intubate and give continuous IV anesthetic infusion (midazolam, propofol, or pentobarbital), with continuous EEG monitoring. Watch for propofol infusion syndrome with prolonged high-dose use. 5. **Find and treat the underlying cause** (CT/MRI, LP if infection is suspected, correct metabolic problems, antibiotics/acyclovir, pyridoxine for INH toxicity).

**Nonconvulsive SE:** Altered mental status without prominent motor activity. It requires EEG for diagnosis. Consider it in any patient who fails to wake after seizures.

**Board pearls:** - The first step in any seizing patient is ABCs and glucose, then a benzodiazepine. - Benzodiazepines enhance GABA-A by increasing the *frequency* of Cl⁻ channel opening. Barbiturates increase the *duration*. - Phenytoin: Na⁺ channel blocker (zero-order kinetics at high doses; side effects include gingival hyperplasia, hirsutism, and drug-induced lupus). - Febrile seizures are usually brief and benign. Prolonged febrile seizures (≥5 min) are treated like SE. - EEG shows continuous epileptiform discharges. - Prognosis depends mostly on the underlying etiology, patient age, and duration of SE.