What is the management approach for status epilepticus?

Status Epilepticus Management

Administer IV lorazepam 4 mg at 2 mg/min immediately as first-line treatment, followed by a second-line agent (valproate, levetiracetam, or fosphenytoin) if seizures persist after 5-10 minutes, and escalate to continuous anesthetic infusions for refractory cases. 1, 2

Immediate Stabilization and First-Line Treatment

Benzodiazepines are the mandatory first-line treatment with Level A evidence. 3, 1

• Administer IV lorazepam 4 mg at 2 mg/min for any actively seizing patient, with demonstrated 65% efficacy in terminating status epilepticus 1, 2
• If seizures continue after 10-15 minutes, give a second dose of lorazepam 4 mg IV slowly 2
• Have airway equipment immediately available before administering lorazepam, as respiratory depression is the most important risk 1, 2
• Check fingerstick glucose immediately and correct hypoglycemia while administering treatment 1, 4
• Establish IV access, monitor vital signs continuously, maintain unobstructed airway, and have artificial ventilation equipment ready 2

Alternative benzodiazepine routes include IM midazolam or intranasal midazolam if IV access is unavailable, though IV lorazepam remains preferred due to longer duration of action. 1, 5

Second-Line Treatment (If Seizures Persist After Benzodiazepines)

Emergency physicians must administer an additional antiepileptic medication for refractory status epilepticus that has failed benzodiazepine treatment (Level A recommendation). 3

Preferred Second-Line Agents (Choose One):

Valproate is the optimal second-line choice with 88% efficacy and 0% hypotension risk, superior safety profile compared to alternatives. 1, 6, 4

• Valproate: 20-30 mg/kg IV over 5-20 minutes (Level B recommendation) 3, 1, 4

  • 88% seizure control rate with no hypotension risk 1, 6
  • Significantly safer cardiovascular profile than phenytoin 1, 6

• Levetiracetam: 30 mg/kg IV over 5 minutes (maximum 2,500-3,000 mg) (Level C recommendation) 3, 1, 4

  • 68-73% efficacy with minimal cardiovascular effects 1, 6
  • No cardiac monitoring required, making it ideal for elderly patients 1
  • Can be administered rapidly without ECG monitoring 1

• Fosphenytoin: 20 mg PE/kg IV at maximum rate of 150 PE/min (Level B recommendation) 3, 1, 4

  • 84% efficacy but 12% hypotension risk 1, 6
  • Requires continuous ECG and blood pressure monitoring due to cardiovascular toxicity 1, 6
  • Traditional agent with 95% of neurologists recommending it, but inferior safety profile to valproate 1

• Phenobarbital: 20 mg/kg IV over 10 minutes (Level C recommendation) 3, 1

  • 58.2% efficacy with higher risk of respiratory depression 1
  • Reserve for cases where other agents are contraindicated 1

Critical pitfall: Never skip directly to third-line anesthetic agents until benzodiazepines and at least one second-line agent have been tried. 1

Simultaneous Evaluation for Underlying Causes

While administering anticonvulsants, immediately search for and correct reversible causes: 3, 4, 2

• Hypoglycemia (check fingerstick glucose immediately) 1, 4
• Hyponatremia 3, 4
• Hypoxia 3, 4
• Drug toxicity or withdrawal syndromes 3, 1, 4
• CNS infections (meningitis, encephalitis) 3, 4
• Ischemic stroke or intracerebral hemorrhage 3, 4
• Systemic infections 3

Do not delay anticonvulsant administration to obtain neuroimaging—CT scanning can be performed after seizure control is achieved. 1

Refractory Status Epilepticus (Seizures Continuing Despite Benzodiazepines + One Second-Line Agent)

Refractory status epilepticus is defined as seizures persisting after adequate benzodiazepine dosing and one second-line agent. 1, 4

Initiate continuous EEG monitoring at this stage, as 25% of patients with apparent seizure cessation have continuing electrical seizures on EEG. 4

Third-Line Anesthetic Agents (Choose One):

Midazolam infusion is the preferred first-choice anesthetic agent with 80% efficacy and lower hypotension risk than barbiturates. 1

• Midazolam: 0.15-0.20 mg/kg IV loading dose, then continuous infusion at 1 mg/kg/min 1, 4

  • 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 with phenytoin/fosphenytoin, valproate, levetiracetam, or phenobarbital during the midazolam infusion to ensure adequate long-acting anticonvulsant levels before tapering 1

• Propofol: 2 mg/kg bolus, then 3-7 mg/kg/hour infusion (Level C recommendation) 3, 1, 4

  • 73% seizure control rate 1
  • Requires mechanical ventilation but shorter ventilation time than barbiturates (4 days vs 14 days) 1, 6
  • 42% hypotension risk (less than barbiturates at 77%) 1
  • Continuous blood pressure monitoring mandatory 1
  • EEG should guide titration to achieve seizure suppression 1

• Pentobarbital: 13 mg/kg bolus, then 2-3 mg/kg/hour infusion (Level C recommendation) 3, 1

  • Highest efficacy at 92% seizure control 1
  • Highest hypotension risk at 77% requiring aggressive vasopressor support 1
  • Longest mechanical ventilation time (14 days average) 1, 6
  • Reserve for super-refractory cases unresponsive to midazolam or propofol 1, 6

Critical monitoring for all anesthetic agents: 1, 4

• Continuous EEG to guide titration and detect ongoing electrical seizures 1, 4
• Continuous vital sign monitoring, especially blood pressure and respiratory status 1, 4
• Prepare for mechanical ventilation regardless of agent chosen 1, 4

Super-Refractory Status Epilepticus

Super-refractory SE is defined as seizures that reemerge after weaning anesthetics or continue despite propofol/midazolam. 7

• Consider additional non-sedating ASM (lacosamide, brivaracetam) 7
• Ketamine is increasingly used with growing evidence supporting its use 5, 7
• Barbiturate coma with pentobarbital if not already tried 1, 8, 9
• Evaluate for autoimmune encephalitis and consider immunotherapy if suspected 7
• Consult neurology if patient fails to respond or regain consciousness 2

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
• Do not delay progression to second-line agents—move to the next treatment step if seizures continue after 5-10 minutes 4
• Do not skip second-line agents and jump directly to anesthetics 1
• Monitor for respiratory depression with all benzodiazepines and barbiturates 4
• Avoid excessive sedation, especially with multiple doses of lorazepam, as sedative effects may add to post-ictal impairment of consciousness 2

Outcome Considerations

Short-term mortality ranges from 10-15% after status epilepticus, rising to 25% in refractory cases and nearly 40% in super-refractory SE. 7 Mortality and morbidity are primarily related to underlying etiology (highest with CNS infections), age, rapidity of treatment, and adequacy of care. 10, 7 Time is brain—rapid administration of appropriate antiseizure medications is vital for halting seizure activity and preventing permanent neurological impairment. 5, 7