What is the treatment protocol for status epilepticus?

Status Epilepticus Treatment Protocol

Administer IV lorazepam 4 mg at 2 mg/min immediately as first-line treatment for any actively seizing patient, followed by a second-line antiseizure medication if seizures continue after 5-10 minutes. 1, 2

Immediate Actions (First 5 Minutes)

• Check fingerstick glucose immediately and correct hypoglycemia with IV dextrose—this is a rapidly reversible cause that must be addressed simultaneously with seizure treatment 1
• Establish IV access and prepare airway equipment (bag-valve-mask, intubation supplies) before administering any medications, as respiratory depression can occur 1, 2
• Administer oxygen and maintain continuous pulse oximetry monitoring throughout treatment 1
• Monitor vital signs continuously, particularly respiratory status and blood pressure 1

First-Line Treatment: Benzodiazepines (0-5 Minutes)

IV lorazepam 4 mg at 2 mg/min is the preferred first-line agent, with 65% efficacy in terminating status epilepticus—superior to diazepam (59.1% vs 42.6%) and longer duration of action than other benzodiazepines 3, 1, 2

• If seizures continue after 10-15 minutes, administer a second dose of lorazepam 4 mg IV 2
• Alternative if IV access unavailable: IM midazolam 0.2 mg/kg (maximum 6 mg) 1
• Critical pitfall: Have airway equipment immediately available, as respiratory depression requiring intervention can occur 1, 2

Second-Line Treatment: Non-Sedating Antiseizure Medications (5-20 Minutes)

If seizures persist after adequate benzodiazepine dosing (two doses of lorazepam), immediately escalate to one of the following second-line agents 1:

Preferred Second-Line Options (Choose One):

Valproate 20-30 mg/kg IV over 5-20 minutes 1

• 88% efficacy with 0% hypotension risk—superior safety profile compared to phenytoin 3, 1
• No cardiac monitoring required 1
• Contraindication: Avoid in women of childbearing potential without effective contraception due to teratogenic risks 1, 4

Levetiracetam 30 mg/kg IV over 5 minutes 1

• 68-73% efficacy with minimal cardiovascular effects—no hypotension risk 3, 1
• Excellent choice for elderly patients as no cardiac monitoring required 1
• Can be administered rapidly without ECG monitoring 1

Fosphenytoin 20 mg PE/kg IV at maximum rate of 50 mg/min 1

• 84% efficacy but 12% hypotension risk—requires continuous ECG and blood pressure monitoring 3, 1
• Most widely available second-line agent, with 95% of neurologists recommending phenytoin/fosphenytoin for benzodiazepine-refractory seizures 1
• Critical monitoring: Continuous cardiac monitoring mandatory due to cardiovascular toxicity 1

Phenobarbital 20 mg/kg IV over 10 minutes 1

• 58.2% efficacy but higher risk of respiratory depression 3, 1
• Reserve for cases where other agents contraindicated 1

Comparative Evidence for Second-Line Selection:

The highest quality evidence shows valproate has the best safety profile (0% hypotension) while maintaining high efficacy (88%), making it the optimal choice when not contraindicated 3, 1. Levetiracetam offers similar safety advantages with slightly lower efficacy (68-73%) but broader applicability across patient populations 1.

Refractory Status Epilepticus (>20 Minutes Despite Benzodiazepines + Second-Line Agent)

Refractory status epilepticus is defined as seizures continuing despite benzodiazepines and one second-line agent—at this stage, initiate continuous EEG monitoring and prepare for ICU admission 1, 5

Third-Line: Anesthetic Agents (Choose One):

Midazolam infusion (PREFERRED) 1

• Loading dose: 0.15-0.20 mg/kg IV 1
• Continuous infusion: 1 mg/kg/min, titrate up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min 1
• 80% efficacy with 30% hypotension risk—better safety profile than barbiturates 1
• Requires mechanical ventilation and continuous EEG monitoring 1

Propofol 1

• Loading dose: 2 mg/kg bolus 1
• Continuous infusion: 3-7 mg/kg/hour 1
• 73% efficacy with 42% hypotension risk 1
• Requires mechanical ventilation but shorter ventilation time (4 days vs 14 days with barbiturates) 1
• Advantage: Already commonly used for sedation in ventilated patients 1

Pentobarbital (Most Effective but Highest Risk) 1

• Loading dose: 13 mg/kg 1
• Continuous infusion: 2-3 mg/kg/hour 1
• 92% efficacy but 77% hypotension risk—highest seizure control rate but most severe adverse effects 1
• Requires vasopressor support in most cases and prolonged mechanical ventilation (mean 14 days) 1

Critical Monitoring for Anesthetic Agents:

• Continuous EEG monitoring mandatory to guide titration and detect ongoing electrical seizure activity 1, 5
• Continuous blood pressure monitoring with vasopressors immediately available 1
• Mechanical ventilation required for all anesthetic agents 1
• Titrate to EEG burst suppression pattern for seizure control 1

Super-Refractory Status Epilepticus

If seizures continue despite anesthetic agents or reemerge after weaning, consider 1, 5:

• Ketamine: 0.45-2.1 mg/kg/hour infusion—64% efficacy when administered early (within 3 days), but efficacy drops to 32% when delayed 1
• Alternative non-sedating ASMs: Lacosamide or brivaracetam 5
• Mortality rises dramatically: 10% in responsive cases, 25% in refractory, nearly 40% in super-refractory SE 5

Simultaneous Evaluation for Underlying Causes

While administering treatment, immediately search for and correct reversible causes 1:

• Metabolic: Hypoglycemia, hyponatremia, hypoxia 1, 6
• Toxic: Drug toxicity or withdrawal syndromes (alcohol, benzodiazepines) 1
• Structural: Ischemic stroke, intracerebral hemorrhage, trauma 1
• Infectious: CNS infection (meningitis, encephalitis) 1
• Autoimmune: Autoimmune encephalitis—treatment of underlying cause crucial for outcome 5

Critical Pitfalls to Avoid

• Never use neuromuscular blockers (e.g., rocuronium) alone—they only mask motor manifestations while allowing continued electrical seizure activity and brain injury 1
• Never skip to third-line agents (pentobarbital, propofol) until benzodiazepines and a second-line agent have been tried 1
• Do not delay anticonvulsant administration for neuroimaging—CT scanning can be performed after seizure control is achieved 1
• Do not use flumazenil routinely—it will reverse anticonvulsant effects and may precipitate seizure recurrence 1

Maintenance Therapy After Seizure Control

Once seizures are controlled, transition to maintenance dosing 1:

• Levetiracetam: 30 mg/kg IV every 12 hours OR increase prophylaxis dose by 10 mg/kg (to 20 mg/kg) IV every 12 hours (maximum 1,500 mg) 1
• Phenytoin/Fosphenytoin: Continue at maintenance dose of 5-7 mg/kg/day divided 1
• Valproate: Continue at maintenance dose based on clinical response 1

Outcome Considerations

Short-term mortality ranges from 10-15% after status epilepticus, primarily related to increasing age, underlying etiology, and medical comorbidities 5, 7. Refractoriness to treatment clearly correlates with worse outcomes, emphasizing the critical importance of rapid, aggressive early treatment 5, 7.