Status Epilepticus Drug Dosages
Administer IV lorazepam 4 mg at 2 mg/min immediately as first-line treatment, followed by valproate 20-30 mg/kg IV (maximum 3000 mg) over 5-20 minutes as the preferred second-line agent if seizures persist. 1
First-Line Treatment (0-5 minutes)
Benzodiazepines – Immediate Administration
Adults:
- Lorazepam 4 mg IV at 2 mg/min (65% efficacy; superior to diazepam) 1
- Midazolam 10 mg IM if IV access unavailable (equivalent efficacy to IV lorazepam) 1
- May repeat lorazepam once after adequate time if seizures continue 1
Pediatrics:
- Lorazepam 0.05-0.10 mg/kg IV/IM (maximum 4 mg per dose), may repeat every 10-15 minutes 2
- Midazolam 0.2 mg/kg IM (maximum 6 mg per dose) if IV access unavailable, may repeat every 10-15 minutes 2
Critical Safety Measure: Have airway equipment immediately available before administering any benzodiazepine—respiratory depression requiring intervention is predictable 1
Second-Line Treatment (5-20 minutes)
If Seizures Persist After Adequate Benzodiazepine Dosing
The 2019 ESETT trial demonstrated equivalent efficacy (45-47% seizure cessation) among valproate, levetiracetam, and fosphenytoin, so selection should prioritize safety profile rather than efficacy 1
Preferred Agent – Valproate:
- Adults: 20-30 mg/kg IV (maximum 3000 mg) over 5-20 minutes 1
- Pediatrics: 30 mg/kg IV over 5-20 minutes 2
- Efficacy: 88% with 0% hypotension risk 1
- Contraindication: Absolutely avoid in women of childbearing potential due to teratogenicity 1
Alternative Second-Line Agents:
Levetiracetam:
Fosphenytoin:
- Adults: 20 mg PE/kg IV at maximum rate 150 PE/min 1
- Pediatrics: 20 mg PE/kg IV over 10-20 minutes at rate not exceeding 1 mg PE/kg/min 2
- Efficacy: 84% but 12% hypotension risk requiring continuous ECG and blood pressure monitoring 1
- Must dilute in normal saline only—incompatible with glucose-containing solutions 2
Phenobarbital:
- Adults: 20 mg/kg IV over 10 minutes 1
- Pediatrics: 20 mg/kg IV (maximum 1000 mg) over 10 minutes, may repeat after 15 minutes (maximum total 40 mg/kg) 2
- Efficacy: 58.2% as initial second-line agent 1
- Higher risk of respiratory depression and hypotension due to vasodilatory and cardiodepressant effects 2
Refractory Status Epilepticus (20+ minutes)
Definition & Escalation
Refractory status epilepticus is defined as ongoing seizures despite adequate benzodiazepine therapy AND failure of one second-line anticonvulsant 1. At this stage, initiate continuous EEG monitoring and escalate to anesthetic agents 1.
Third-Line Anesthetic Agents
Midazolam Infusion (First Choice):
- Loading dose: 0.15-0.20 mg/kg IV 1, 2
- Continuous infusion: 1 mg/kg/min, titrate up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min 1, 2
- Efficacy: 80% with 30% hypotension risk 1
- Critical: Load with a long-acting anticonvulsant (phenytoin/fosphenytoin, valproate, levetiracetam, or phenobarbital) during the midazolam infusion before tapering 1
Propofol (Alternative for Intubated Patients):
- Loading dose: 2 mg/kg IV bolus 1
- Continuous infusion: 3-7 mg/kg/hour 1
- Efficacy: 73% with 42% hypotension risk 1
- Requires mechanical ventilation but shorter duration than barbiturates (4 days vs 14 days) 1
Pentobarbital (Highest Efficacy, Highest Complication Rate):
- Loading dose: 13 mg/kg IV 1
- Continuous infusion: 2-3 mg/kg/hour 1
- Efficacy: 92% but 77% hypotension risk requiring vasopressor support 1
- Mean mechanical ventilation duration: 14 days 1
Maintenance Dosing After Seizure Control
Levetiracetam Maintenance:
- Adults (convulsive SE): 30 mg/kg IV every 12 hours OR increase prophylaxis dose by 10 mg/kg (to 20 mg/kg) IV every 12 hours (maximum 1500 mg) 1
- Adults (non-convulsive SE): 15 mg/kg IV every 12 hours (maximum 1500 mg) 1
- Pediatrics (convulsive SE): 30 mg/kg IV every 12 hours (maximum 1500 mg) 1
- Pediatrics (non-convulsive SE): 15 mg/kg IV every 12 hours (maximum 1500 mg) 1
Phenobarbital Maintenance:
- Pediatrics: 1-3 mg/kg IV every 12 hours 1
Phenytoin/Fosphenytoin Maintenance:
- Adults: 300-400 mg oral daily divided into multiple doses after IV loading 1
Critical Monitoring & Concurrent Actions
Simultaneous Evaluation for Reversible Causes:
- Check fingerstick glucose immediately and correct hypoglycemia 1
- Search for hyponatremia, hypoxia, drug toxicity or withdrawal (alcohol, benzodiazepines, barbiturates), CNS infection, ischemic stroke, intracerebral hemorrhage 1
- Do NOT delay anticonvulsant administration to obtain neuroimaging 1
Continuous Monitoring Requirements:
- Oxygen saturation with supplemental oxygen available 2
- Continuous vital sign monitoring, particularly respiratory status and blood pressure 1
- Continuous EEG monitoring in refractory cases to guide anesthetic titration and detect ongoing electrical seizure activity 1
- EEG should continue for at least 24-48 hours after anesthetic discontinuation, as breakthrough seizures occur in >50% of patients and are often only detectable by EEG 1
Common Pitfalls to Avoid
- Never use neuromuscular blockers alone (e.g., rocuronium)—they only mask motor manifestations while allowing continued electrical seizure activity and brain injury 1
- Do not skip to third-line agents (e.g., pentobarbital) until benzodiazepines and a second-line agent have been tried 1
- Avoid intramuscular diazepam due to erratic absorption—use rectal route instead 3
- Do not infuse phenytoin/fosphenytoin with glucose-containing solutions—causes precipitation 2
- Do not administer benzodiazepines too rapidly—increases respiratory depression risk 2
- Do not use flumazenil in patients receiving benzodiazepines for seizure control—it reverses anticonvulsant effects and may precipitate seizures 2
Prognosis Context
Overall mortality for status epilepticus ranges from 5-22%, increasing dramatically to ≈65% in refractory cases 1. Every minute of delay in seizure control increases morbidity and mortality risk 2. This underscores the critical importance of rapid, aggressive treatment following the algorithm above.