What is the definition and management of status epilepticus?

Status Epilepticus: Definition and Management

Definition

Status epilepticus is defined as continuous seizure activity lasting more than 5 minutes or recurrent seizures without return to baseline consciousness between episodes. 1, 2

While the traditional definition specified 30 minutes of seizure activity, the operational definition has been reduced to 5 minutes to emphasize the urgency of treatment initiation. 3 This change reflects the understanding that prolonged seizures can cause permanent neurological damage, and early intervention reduces morbidity and mortality. 4

Immediate Management Algorithm

Step 1: First-Line Treatment (0-5 minutes)

Administer intravenous lorazepam 4 mg at 2 mg/min immediately for any actively seizing patient. 5

• Lorazepam demonstrates 65% efficacy in terminating status epilepticus and is superior to diazepam (59.1% vs 42.6%). 5
• Alternative benzodiazepine options include IM midazolam (if IV access is delayed) or intranasal midazolam. 5
• Critical action: Check fingerstick glucose immediately and correct hypoglycemia while administering benzodiazepines. 5
• Have airway equipment immediately available before administering lorazepam, as respiratory depression can occur. 5, 6
• If seizures continue after the first dose, repeat lorazepam 4 mg after a 10-15 minute observation period. 6

Step 2: Second-Line Treatment (5-20 minutes)

If seizures persist after adequate benzodiazepine dosing, immediately administer one of the following second-line agents—all three have equivalent efficacy of approximately 45-47% in benzodiazepine-refractory status epilepticus. 4

Recommended second-line options (choose one):

• Valproate 30 mg/kg IV over 5-20 minutes: 88% efficacy with 0% hypotension risk—the safest cardiovascular profile. 5, 2
• Levetiracetam 30 mg/kg IV (maximum 3000 mg) over 5 minutes: 68-73% efficacy with minimal cardiovascular effects and no cardiac monitoring required. 4, 5, 2
• Fosphenytoin 20 mg PE/kg IV at maximum rate of 150 mg/min: 84% efficacy but 12% hypotension risk requiring continuous ECG and blood pressure monitoring. 5, 1, 2
• Phenobarbital 20 mg/kg IV over 10 minutes: 58.2% efficacy but higher risk of respiratory depression. 5

Key clinical decision point: Valproate offers the best safety profile with no hypotension risk, making it preferable in hemodynamically unstable patients or elderly patients. 5, 2 Avoid valproate in women of childbearing potential due to teratogenicity. 5

Step 3: Refractory Status Epilepticus (20-60 minutes)

Refractory status epilepticus is defined as seizures continuing despite benzodiazepines and one second-line agent. 5

At this stage, initiate continuous EEG monitoring and prepare for ICU admission with mechanical ventilation capability. 5, 7

Third-line anesthetic agents (choose one):

• Midazolam infusion (preferred first choice): 0.15-0.20 mg/kg IV loading dose, then continuous infusion at 1 mg/kg/min, titrate up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min. 5

  • 80% overall success rate with 30% hypotension risk—the best balance of efficacy and safety. 5

• Propofol: 2 mg/kg bolus, then 3-7 mg/kg/hour infusion. 5, 2

  • 73% efficacy with 42% hypotension risk. 5
  • Requires mechanical ventilation but shorter ventilation time than barbiturates (4 days vs 14 days). 5, 2

• Pentobarbital: 13 mg/kg bolus, then 2-3 mg/kg/hour infusion. 5

  • Highest efficacy at 92% but 77% hypotension risk requiring vasopressors and prolonged mechanical ventilation (mean 14 days). 5

During anesthetic infusion, load with a long-acting anticonvulsant (phenytoin/fosphenytoin, valproate, levetiracetam, or phenobarbital) to ensure adequate levels are established before tapering the anesthetic. 5

Step 4: Super-Refractory Status Epilepticus (>24 hours)

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

• Consider ketamine infusion: 0.45-2.1 mg/kg/hour, with 64% efficacy when administered early (within 3 days) but only 32% efficacy when delayed. 5
• Ketamine acts on NMDA receptors, providing a mechanistically distinct approach from GABA-ergic agents. 5
• Alternative options include barbiturates (thiopentone or pentobarbital) or isoflurane. 8, 7

Simultaneous Critical Actions

Throughout all treatment stages, simultaneously search for and correct underlying causes: 5, 1

• Metabolic: Hypoglycemia, hyponatremia, hypoxia 5, 1, 6
• Toxic: Drug toxicity, alcohol withdrawal 4, 5
• Structural: Ischemic stroke, intracerebral hemorrhage, CNS infection 5, 1
• Establish IV access and start fluid resuscitation to maintain euvolemia and prevent hypotension. 5
• Maintain continuous vital sign monitoring, particularly respiratory status and blood pressure. 5

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. 5
• Do not skip to third-line agents until benzodiazepines and a second-line agent have been tried. 5
• Do not delay anticonvulsant administration for neuroimaging—CT scanning can be performed after seizure control is achieved. 5
• Avoid using flumazenil routinely, as it will reverse anticonvulsant effects and may precipitate seizure recurrence. 5

Monitoring Requirements by Treatment Stage

First-line (benzodiazepines):

• Continuous oxygen saturation monitoring with supplemental oxygen available 5
• Respiratory depression monitoring 6

Second-line (fosphenytoin/phenytoin):

• Continuous ECG and blood pressure monitoring 5, 2

Third-line (anesthetics):

• Continuous EEG monitoring to guide titration 5
• Continuous blood pressure monitoring 5
• Mechanical ventilation capability 5, 2
• Vasopressor availability for hypotension management 5

Prognosis and Outcomes

Early treatment and cessation of status epilepticus reduces morbidity and mortality. 4 Short-term mortality ranges from 10-15% overall, rising to 25% in refractory cases and nearly 40% in super-refractory status epilepticus. 7 Mortality is primarily related to increasing age, underlying etiology, and medical comorbidities rather than the seizures themselves. 7