Emergency Management of Status Epilepticus
Administer IV lorazepam 4 mg at 2 mg/min immediately for any actively seizing patient, followed by a second-line agent (valproate, levetiracetam, or fosphenytoin) if seizures persist beyond 5 minutes, and escalate to continuous anesthetic infusions (midazolam, propofol, or pentobarbital) for refractory cases. 1
Immediate First-Line Treatment (0-5 minutes)
Benzodiazepines are the cornerstone of initial therapy and must be given without delay. 1
- IV lorazepam 4 mg at 2 mg/min is the preferred first-line agent, achieving seizure termination in 65% of cases and demonstrating superior efficacy to diazepam (59.1% vs 42.6%) 1
- Lorazepam has a longer duration of action than other benzodiazepines, reducing seizure recurrence 1
- Have airway equipment immediately available before administration due to respiratory depression risk 1
- If IV access is unavailable, use IM midazolam 0.2 mg/kg (maximum 6 mg) or intranasal midazolam, both showing comparable efficacy 1
- Check fingerstick glucose immediately and correct hypoglycemia while administering benzodiazepines 1
Status epilepticus is operationally defined as seizures lasting ≥5 minutes or recurrent seizures without return to baseline, requiring immediate treatment at this threshold rather than waiting 20-30 minutes 1
Second-Line Treatment (5-20 minutes)
If seizures persist after adequate benzodiazepine dosing, immediately escalate to one of the following second-line agents—do not delay. 2, 1
Preferred Second-Line Options (in order of safety profile):
1. Valproate: 20-30 mg/kg IV (maximum 3000 mg) over 5-20 minutes
- 88% efficacy with 0% hypotension risk, making it the safest second-line option 1
- Superior safety profile compared to fosphenytoin (88% vs 84% efficacy; 0% vs 12% hypotension) 1
- Absolutely contraindicated in women of childbearing potential due to teratogenic risk 1
2. Levetiracetam: 30 mg/kg IV (maximum 2500-3000 mg) over 5 minutes
- 68-73% efficacy with minimal cardiovascular effects (≈0.7% hypotension risk) 1
- Does not require continuous cardiac monitoring 1
- 20% intubation rate 1
- Requires renal dose adjustment: reduce dose by 50% if CrCl <50 mL/min 1
3. Fosphenytoin: 20 mg PE/kg IV at maximum rate of 150 PE/min
- 84% efficacy but 12% hypotension risk requiring continuous ECG and blood pressure monitoring 1
- 26.4% intubation rate 1
- Most widely available second-line agent, with 95% of neurologists recommending it for benzodiazepine-refractory seizures 1
4. Phenobarbital: 20 mg/kg IV over 10 minutes
- 58.2% efficacy as initial second-line agent 1
- Higher risk of respiratory depression and hypotension compared to alternatives 1
The ESETT trial (2019) demonstrated no significant difference in efficacy between levetiracetam, fosphenytoin, and valproate (47%, 45%, and 46% respectively), so selection should be based on safety profile and contraindications 2
Critical Simultaneous Actions:
- Search for and treat reversible causes: hypoglycemia, hyponatremia, hypoxia, drug toxicity/withdrawal, CNS infection, stroke, intracerebral hemorrhage 1
- Establish IV access and begin fluid resuscitation to prevent hypotension 1
- Do not delay anticonvulsant administration to obtain neuroimaging—CT can be performed after seizure control 1
Refractory Status Epilepticus (20+ minutes)
Refractory SE is defined as seizures continuing despite benzodiazepines and one second-line agent. 1
Initiate continuous EEG monitoring at this stage, as >50% of refractory cases have ongoing nonconvulsive electrical seizures without motor manifestations 1, 3
Third-Line Anesthetic Agents:
1. Midazolam infusion (preferred first-choice anesthetic):
- Loading dose: 0.15-0.20 mg/kg IV
- Maintenance: 1 mg/kg/min continuous infusion, titrate up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min 1
- 80% overall success rate with 30% hypotension risk 1
- Load a long-acting anticonvulsant (phenytoin/fosphenytoin, valproate, levetiracetam, or phenobarbital) during the midazolam infusion before tapering 1
2. Propofol:
- Loading dose: 2 mg/kg bolus
- Maintenance: 3-7 mg/kg/hour infusion 1
- 73% efficacy with 42% hypotension risk 1
- Requires mechanical ventilation but shorter duration than barbiturates (4 days vs 14 days) 1
- Useful in intubated patients without hypotension 1
3. Pentobarbital (highest efficacy but most adverse effects):
- Loading dose: 13 mg/kg
- Maintenance: 2-3 mg/kg/hour infusion 1
- 92% efficacy but 77% hypotension risk requiring vasopressors 1
- Prolonged mechanical ventilation (mean 14 days) 1
Critical Monitoring Requirements:
- Continuous EEG monitoring to guide titration and detect nonconvulsive seizures 1
- Continuous blood pressure monitoring and vasopressor availability 1
- Prepare for mechanical ventilation regardless of agent chosen 1
- Continue EEG for minimum 48 hours after complete anesthetic discontinuation, as late seizure recurrence is common and often nonconvulsive 1
Super-Refractory Status Epilepticus
SE that continues despite propofol or midazolam, or reemerges after weaning. 3
- Ketamine may be considered as a fourth-line agent, with 64% efficacy when given early (within 3 days) but only 32% when delayed 1
- Dosing: 0.45-2.1 mg/kg/hour continuous infusion 1
- Acts on NMDA receptors, providing mechanistically distinct approach from GABA-ergic agents 1
- Use with caution in patients with depleted catecholamine reserves, as ketamine can suppress myocardial contractility 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 until benzodiazepines and a second-line agent have been tried 1
- Do not attribute altered mental status solely to post-ictal state—obtain urgent EEG if patient does not awaken within expected timeframe, as nonconvulsive SE occurs in >50% of cases 1
- Avoid intramuscular diazepam due to erratic absorption—use rectal route instead if IM administration is being considered 1