Status Epilepticus Treatment Protocol
Administer IV lorazepam 4 mg at 2 mg/min immediately for any actively seizing patient, then escalate directly to valproate 20–30 mg/kg IV if seizures persist after adequate benzodiazepine dosing, and proceed to midazolam infusion for refractory cases. 1
Stage 1: Immediate Stabilization (0–5 minutes)
First-Line Benzodiazepine Therapy
Administer IV lorazepam 4 mg at 2 mg/min as the immediate first-line treatment for any patient actively seizing, with demonstrated 65% efficacy in terminating status epilepticus and superior performance compared to diazepam (59.1% vs 42.6% seizure cessation). 1, 2, 3
Lorazepam is preferred over diazepam because it has a longer duration of action (several hours vs 20–30 minutes) due to a much smaller volume of distribution of unbound drug, allowing orderly administration of long-acting anticonvulsants without seizure recurrence. 1, 2, 4
Have airway equipment immediately available before administering lorazepam, as respiratory depression requiring intervention can occur; maintain continuous oxygen saturation monitoring throughout treatment. 1
If IV access is unavailable, administer IM midazolam 10 mg, which provides efficacy equivalent to IV lorazepam. 1
Critical Simultaneous Actions
Check fingerstick glucose immediately and correct hypoglycemia while administering benzodiazepines, as this is a rapidly reversible cause. 1
Search for and treat underlying causes concurrently: hypoglycemia, hyponatremia, hypoxia, drug toxicity or withdrawal (especially alcohol, benzodiazepines, barbiturates), CNS infection, ischemic stroke, intracerebral hemorrhage. 1
Do not delay anticonvulsant administration for neuroimaging—CT scanning can be performed after seizure control is achieved. 1
Stage 2: Second-Line Anticonvulsants (5–20 minutes)
If seizures persist after adequate benzodiazepine dosing (typically two doses of lorazepam 4 mg), immediately escalate to a second-line agent without delay. 1
Preferred Agent: Valproate
Administer valproate 20–30 mg/kg IV (maximum 3000 mg) over 5–20 minutes, which achieves 88% seizure control with 0% hypotension risk—the best safety profile among second-line agents. 1
Valproate is superior to phenytoin in head-to-head trials (88% vs 84% efficacy; 0% vs 12% hypotension risk). 1
Absolute contraindication: Do not use valproate in women of childbearing potential due to significant teratogenic risk and neurodevelopmental delay. 1
Alternative Second-Line Agents
Levetiracetam (preferred alternative):
- 30 mg/kg IV (maximum 2500–3000 mg) over 5 minutes achieves 68–73% seizure control with minimal cardiovascular effects (≈0.7% hypotension) and 20% intubation rate. 1, 5
- Does not require continuous cardiac monitoring and has the best safety profile after valproate. 1
- Particularly suitable for elderly patients and those with cardiovascular comorbidities. 1
Fosphenytoin (traditional option):
- 20 mg PE/kg IV at maximum rate of 150 PE/min (not to exceed 50 mg/min in practice) achieves 84% seizure control but carries 12% hypotension risk. 1
- Requires continuous ECG and blood pressure monitoring due to cardiovascular risks. 1
- Intubation rate approximately 26%. 1
Phenobarbital (reserve option):
- 20 mg/kg IV over 10 minutes achieves 58.2% seizure control as initial second-line agent. 1, 5
- Higher risk of respiratory depression and hypotension compared to other agents—use only when alternatives are unavailable or contraindicated. 1
Evidence Context: ESETT Trial
The 2019 Established Status Epilepticus Treatment Trial demonstrated no statistically significant difference in efficacy among levetiracetam, fosphenytoin, and valproate (seizure cessation rates 47%, 45%, and 46% respectively). 1 Therefore, agent selection should prioritize safety profile and contraindications rather than efficacy alone. 1
Stage 3: Refractory Status Epilepticus (20+ minutes)
Refractory status epilepticus is defined as ongoing seizures despite adequate benzodiazepines AND failure of one second-line agent. 1
Critical Actions at This Stage
Initiate continuous EEG monitoring immediately, as approximately 25% of patients have ongoing non-convulsive electrical seizures without motor manifestations. 1
Prepare for mechanical ventilation and ICU-level care, as all anesthetic agents require respiratory support. 1
Load a long-acting anticonvulsant (phenytoin/fosphenytoin, valproate, levetiracetam, or phenobarbital) during the anesthetic infusion to ensure adequate levels are established before tapering. 1
First-Choice Anesthetic: Midazolam Infusion
Loading dose: 0.15–0.20 mg/kg IV
Continuous infusion: Start at 1 mg/kg/min, titrate up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min 1
Achieves 80% seizure control with 30% hypotension risk—the best balance of efficacy and safety among anesthetic agents. 1
EEG should guide titration to achieve seizure suppression. 1
Alternative Anesthetic Agents
Propofol (for intubated patients without hypotension):
Loading dose: 2 mg/kg IV bolus
Infusion: 3–7 mg/kg/hour 1
Achieves 73% seizure control with 42% hypotension risk. 1
Requires mechanical ventilation but shorter duration than barbiturates (mean 4 days vs 14 days). 1
Continuous blood pressure monitoring essential, as propofol causes hypotension in 42% of patients. 1
Pentobarbital (highest efficacy, highest complication rate):
Loading dose: 13 mg/kg IV
Infusion: 2–3 mg/kg/hour 1
Achieves 92% seizure control—the highest efficacy among all agents—but carries 77% hypotension risk requiring vasopressor support. 1
Associated with prolonged mechanical ventilation (mean 14 days) and should be reserved for cases refractory to midazolam and propofol. 1
Post-Seizure Care and Monitoring
Continuous EEG Monitoring
Maintain continuous EEG throughout the entire tapering process and for at least 24–48 hours after discontinuation, as breakthrough seizures occur in more than 50% of patients and are often only detectable by EEG without clinical manifestations. 1
Do not attribute altered mental status solely to post-ictal state—obtain urgent EEG if the patient does not awaken within expected timeframe, as nonconvulsive status epilepticus occurs in >50% of cases. 1
Transition to Maintenance Therapy
Switch to oral phenytoin 300–400 mg per day divided into multiple doses after seizure control with IV fosphenytoin/phenytoin. 1
For levetiracetam, continue 30 mg/kg IV every 12 hours (maximum 1500 mg per dose) for convulsive status epilepticus, or 15 mg/kg IV every 12 hours for non-convulsive status epilepticus. 1
Renal Dose Adjustments for Levetiracetam
| Creatinine Clearance | Dosage | Frequency |
|---|---|---|
| >80 mL/min (Normal) | 500–1,500 mg | Every 12 hours |
| 50–80 mL/min (Mild) | 500–1,000 mg | Every 12 hours |
| 30–50 mL/min (Moderate) | 250–750 mg | Every 12 hours |
| <30 mL/min (Severe) | 250–500 mg | Every 12 hours |
| ESRD on dialysis | 500–1,000 mg | Every 24 hours* |
Critical Pitfalls to Avoid
Never use neuromuscular blockers alone (e.g., rocuronium), as they only mask motor manifestations while allowing continued electrical seizure activity and brain injury. 1
Do not skip to third-line agents (pentobarbital) until benzodiazepines AND a second-line agent have been tried. 1
Do not use intramuscular diazepam due to erratic absorption—use rectal route instead if IM administration is being considered. 1
Benzodiazepines are frequently underdosed throughout the United States—ensure full 4 mg doses of lorazepam are administered rather than partial doses. 6
Prognosis
- Overall mortality for status epilepticus ranges from 5% to 22%, increasing dramatically to approximately 65% in refractory cases, underscoring the importance of rapid, aggressive treatment. 1