What is the stepwise management of status epilepticus in adults?

Stepwise Management of Status Epilepticus in Adults

Administer IV lorazepam 4 mg at 2 mg/min immediately as first-line treatment for any actively seizing patient, followed by a second-line anticonvulsant (valproate, levetiracetam, or fosphenytoin) if seizures persist beyond 5 minutes, and escalate to continuous anesthetic infusions for refractory cases.

Stage 1: Immediate First-Line Treatment (0-5 minutes)

Benzodiazepines are the cornerstone of initial therapy. Administer IV lorazepam 4 mg at 2 mg/min as the immediate first-line treatment for any patient actively seizing 1, 2, 3. Lorazepam demonstrates 65% efficacy in terminating status epilepticus and is superior to diazepam (59.1% vs 42.6% seizure cessation) with a longer duration of action 1, 2. If IV access is unavailable, IM midazolam 10 mg or intranasal midazolam are acceptable alternatives 1.

Critical simultaneous actions:

• Have airway equipment immediately available before administering any benzodiazepine due to respiratory depression risk 1, 3
• Check fingerstick glucose immediately and correct hypoglycemia 1
• Establish IV access and begin fluid resuscitation 1
• Prepare continuous cardiac and respiratory monitoring 4

If seizures continue after the first dose, give a second 4 mg dose of lorazepam after 10-15 minutes 2. Status epilepticus is now operationally defined as seizures lasting ≥5 minutes, shortened from the traditional 30 minutes because delayed treatment significantly increases morbidity and mortality to 5-22% (and up to 65% in refractory cases) 1, 2.

Stage 2: Second-Line Anticonvulsants (5-20 minutes)

If seizures persist after adequate benzodiazepine dosing, immediately escalate to a second-line agent—do not delay. The 2024 American College of Emergency Physicians guidelines establish that valproate, levetiracetam, and fosphenytoin have equivalent efficacy (45-47% seizure cessation) as second-line agents 5. However, their safety profiles differ substantially.

Recommended second-line agents in order of safety profile:

Valproate (Preferred for Safety)

• Dose: 20-30 mg/kg IV (maximum 3000 mg) over 5-20 minutes 1, 2
• Efficacy: 88% seizure control 1
• Hypotension risk: 0% 1
• Advantage: Superior safety profile with no cardiac monitoring required 1
• Contraindication: Absolutely contraindicated in women of childbearing potential due to teratogenic risk 1

Levetiracetam (Excellent Alternative)

• Dose: 30 mg/kg IV (maximum 2500-3000 mg) over 5 minutes 1, 5
• Efficacy: 68-73% 1, 5
• Hypotension risk: 0.7% 5
• Intubation rate: 20% 1
• Advantage: Minimal cardiovascular effects, no cardiac monitoring required, safe in elderly and pregnancy 1

Fosphenytoin (Traditional Agent)

• Dose: 20 mg PE/kg IV at maximum rate of 150 PE/min 1, 2, 4
• Efficacy: 84% 1
• Hypotension risk: 12% 1, 5
• Intubation rate: 26.4% 1
• Requirement: Continuous ECG and blood pressure monitoring mandatory 1, 4
• Note: 95% of neurologists recommend phenytoin/fosphenytoin for benzodiazepine-refractory seizures, making it the most widely available option 1

Phenobarbital (Last Resort)

• Dose: 20 mg/kg IV over 10 minutes 1, 2
• Efficacy: 58.2% as initial second-line agent 6, 1
• Disadvantage: Higher risk of respiratory depression and hypotension 6, 1

The evidence strongly favors valproate or levetiracetam over fosphenytoin due to superior safety profiles 1, 5. Valproate appears to have a slight efficacy advantage (88% vs 84%) with dramatically lower hypotension risk (0% vs 12%) compared to fosphenytoin 1.

While administering anticonvulsants, simultaneously search for reversible causes:

• Hypoglycemia, hyponatremia, hypoxia 1, 5, 2
• Drug toxicity or withdrawal syndromes (especially alcohol) 1, 2
• CNS infection, ischemic stroke, intracerebral hemorrhage 1, 5, 2
• Do not delay anticonvulsant therapy to obtain neuroimaging 1

Stage 3: Refractory Status Epilepticus (20+ minutes)

Refractory status epilepticus is defined as seizures continuing despite benzodiazepines and one second-line agent 1. At this stage, initiate continuous EEG monitoring immediately, as approximately 25% of patients have ongoing nonconvulsive electrical seizures without motor activity 2, 7.

Anesthetic agents for refractory SE (in order of preference):

Midazolam Infusion (First Choice)

• Loading dose: 0.15-0.20 mg/kg IV 1, 2
• Maintenance: 1 mg/kg/min continuous infusion, titrate up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min 1
• Efficacy: 80% overall success rate 1, 2
• Hypotension risk: 30% 1, 2
• Critical action: Load with a long-acting anticonvulsant (phenytoin/fosphenytoin, valproate, levetiracetam, or phenobarbital) during the midazolam infusion before tapering to ensure adequate anticonvulsant coverage 1

Propofol (Alternative)

• Dose: 2 mg/kg bolus, then 3-7 mg/kg/hour infusion 1, 2
• Efficacy: 73% seizure control 1, 2
• Hypotension risk: 42% 1, 2
• Advantage: Requires mechanical ventilation but shorter duration than barbiturates (4 days vs 14 days) 1, 2
• Requirement: Mechanical ventilation mandatory 1

Pentobarbital (Most Effective but Highest Risk)

• Dose: 13 mg/kg bolus, then 2-3 mg/kg/hour infusion 1, 2
• Efficacy: 92% seizure control (highest of all agents) 1, 2
• Hypotension risk: 77% requiring vasopressors 1, 2
• Disadvantage: Prolonged mechanical ventilation (mean 14 days) 1, 2

Continuous EEG monitoring is essential throughout refractory SE treatment to guide titration to achieve seizure suppression and detect nonconvulsive seizures 1, 2, 7. Continue EEG monitoring for at least 24-48 hours after complete anesthetic discontinuation, as late seizure recurrence is common and often nonconvulsive 1.

Stage 4: Super-Refractory Status Epilepticus

Super-refractory SE is defined as seizures that reemerge after weaning or continue despite propofol or midazolam 7. At this stage, consider:

• Ketamine: 0.45-2.1 mg/kg/hour infusion, with 64% efficacy when administered early (within 3 days) but only 32% when delayed 1
• Additional non-sedating ASMs: Lacosamide or brivaracetam 7
• Barbiturates: Thiopental or pentobarbital if not already used 1

Critical 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 persistent altered mental status solely to post-ictal state—obtain urgent EEG to rule out nonconvulsive status epilepticus, which occurs in >50% of cases 1
• Avoid delaying treatment for neuroimaging in active status epilepticus—CT can be performed after seizure control is achieved 1

Monitoring Requirements Throughout Treatment

• Continuous vital sign monitoring, particularly respiratory status and blood pressure 1, 4
• Continuous ECG monitoring during fosphenytoin administration 1, 4
• Prepare for respiratory support regardless of administration route 1
• Monitor throughout the period where maximal serum phenytoin concentrations occur (approximately 10-20 minutes after end of infusion) 4

Maintenance Therapy After Seizure Control

After achieving seizure control, transition to maintenance dosing:

• Levetiracetam: 30 mg/kg IV every 12 hours (maximum 1500 mg) for convulsive SE, or 15 mg/kg every 12 hours for non-convulsive SE 1
• Phenytoin: 300-400 mg per day orally divided into multiple doses 1
• Valproate or phenobarbital: Continue at appropriate maintenance doses 1

The key to successful management is rapid recognition, immediate benzodiazepine administration, prompt escalation to second-line agents within 5 minutes, and aggressive treatment of refractory cases with continuous EEG guidance 1, 5, 2, 7.