Status Epilepticus Pharmacotherapy

Status epilepticus is a seizure lasting 5 minutes or longer, or repeated seizures without recovery between them. It is a medical emergency with mortality of up to 20 percent. Pharmacotherapy combines rapid benzodiazepines, then a second-line antiseizure drug, then anaesthesia if seizures continue.

Pharmacology. Benzodiazepines act within minutes. Second-line drugs build up over 10 to 20 minutes. Refractory status needs deep sedation with EEG monitoring.

• Lorazepam 4 mg intravenously (0.1 mg/kg, maximum 4 mg), repeated once after 5 to 10 minutes.
• Diazepam 10 mg intravenously (0.15 to 0.2 mg/kg, maximum 10 mg), repeated once; rectal 10 mg in adults, 0.5 mg/kg in children aged 2 to 12 (maximum 10 mg).
• Midazolam 10 mg intramuscularly (over 40 kg), 5 mg intramuscularly (13 to 40 kg); buccal 10 mg; intranasal 0.2 mg/kg (maximum 10 mg).
• Levetiracetam 60 mg/kg intravenously (maximum 4,500 mg) over 10 minutes.
• Phenytoin 20 mg/kg intravenously (maximum rate 50 mg/min, or 25 mg/min in older adults and cardiac disease) with ECG and blood pressure monitoring.
• Valproate 40 mg/kg intravenously (maximum 3,000 mg) over 10 minutes.
• Phenobarbital 15 to 20 mg/kg intravenously at up to 100 mg/min.
• Anaesthetics: propofol 1 to 2 mg/kg then 2 to 10 mg/kg/h; midazolam 0.2 mg/kg then 0.1 to 0.4 mg/kg/h; thiopental 3 to 5 mg/kg then 3 to 5 mg/kg/h.

Differences. Lorazepam, diazepam and midazolam are similar in efficacy. Levetiracetam, valproate and phenytoin have similar second-line success.

• 0 to 5 minutes: airway, oxygen, bedside glucose, intravenous access, time recorded. Treat hypoglycaemia with 50 mL of 50% dextrose intravenously in adults (2 mL/kg of 10% dextrose in children), with thiamine 100 mg first in alcohol use or malnutrition.
• 5 to 20 minutes: first-line benzodiazepine; where intravenous access is not available, intramuscular or buccal midazolam or rectal diazepam.
• 20 to 40 minutes: one second-line drug if seizures persist. Choose levetiracetam or valproate in older adults and cardiac disease, and avoid valproate in women of childbearing potential and in liver disease. Avoid phenytoin in heart block.
• Over 40 minutes (refractory): intensive care, intubation, anaesthetic infusion titrated on EEG to burst suppression.
• Treat the cause: severe malaria with artesunate; bacterial meningitis with ceftriaxone and dexamethasone; eclampsia with magnesium sulphate 4 g intravenously over 5 to 15 minutes then 1 g/h for 24 hours; isoniazid overdose with pyridoxine; symptomatic hyponatraemia with 3% sodium chloride 100 to 150 mL over 10 minutes; neurocysticercosis, central nervous system infection in HIV, stroke, and drug withdrawal.
• Infants: pyridoxine 100 mg intravenously for refractory seizures.

Selection. Do not delay the second-line drug beyond 20 minutes.

Contraindications. Phenytoin: second or third degree heart block, sinus bradycardia. Valproate: liver failure, mitochondrial disease, pregnancy. Phenobarbital: porphyria.

Adverse effects. Respiratory depression and hypotension (benzodiazepines, phenobarbital, anaesthetics). Phenytoin: hypotension, arrhythmia, purple glove syndrome and tissue necrosis on extravasation. Valproate: hyperammonaemia, thrombocytopenia.

Interactions. Benzodiazepines with opioids or alcohol deepen respiratory depression. Propofol infusion syndrome with prolonged high doses.

Special groups.

• Pregnancy: lorazepam and levetiracetam first; magnesium sulphate for eclampsia; avoid valproate.
• Children: lorazepam 0.1 mg/kg, buccal midazolam by age (5 mg at 1 to 4 years, 7.5 mg at 5 to 9 years, 10 mg from 10 years), levetiracetam 40 to 60 mg/kg, phenobarbital 20 mg/kg.
• Older adults: lower doses and slower phenytoin rates.
• Kidney and liver impairment: avoid valproate in liver disease.

Monitoring. Oxygen saturation, blood pressure, heart rate, ECG with phenytoin, glucose, sodium, calcium, acid-base balance, EEG in refractory cases.

Referral and escalation. Refractory status, or no return to baseline after 30 minutes of seizure control (consider non-convulsive status), needs intensive care and neurology.