What is the management of seizures?

Management of Seizures

Immediately administer intravenous lorazepam 4 mg at 2 mg/min as first-line treatment for any actively seizing patient, followed by a second-line agent (fosphenytoin, levetiracetam, or valproate) if seizures persist beyond 5 minutes. 1, 2

Immediate Stabilization and First-Line Treatment

Benzodiazepines are the definitive first-line therapy for active seizures, with Level A evidence supporting their use. 3, 1

• Lorazepam 4 mg IV at 2 mg/min is the preferred benzodiazepine, demonstrating 65% efficacy in terminating status epilepticus and superior performance compared to diazepam (59.1% vs 42.6%). 1, 4, 5
• If seizures continue after 10-15 minutes, administer a second dose of lorazepam 4 mg IV. 4
• Have airway equipment immediately available before administering any benzodiazepine, as respiratory depression can occur. 1, 4
• Check fingerstick glucose immediately and correct hypoglycemia while administering treatment—this is a rapidly reversible cause. 1, 2

Alternative Benzodiazepine Routes

• IM midazolam 0.2 mg/kg (maximum 6 mg) if IV access is unavailable or delayed, which can be repeated every 10-15 minutes. 1
• Intranasal midazolam is another option when IV access is challenging. 1

Second-Line Treatment (If Seizures Persist After Benzodiazepines)

Status epilepticus is operationally defined as seizures lasting ≥5 minutes, requiring immediate escalation to second-line agents. 1, 2

All three second-line agents have equivalent efficacy (45-47% seizure cessation at 60 minutes), so selection should be based on safety profile and patient-specific contraindications. 2, 6

Recommended Second-Line Agents (Choose One):

• Levetiracetam 60 mg/kg IV (maximum 4500 mg) over 10 minutes

  • Hypotension risk: 0.7%
  • Intubation rate: 20%
  • Preferred in elderly patients due to minimal cardiovascular effects and no cardiac monitoring requirements. 1, 2

• Valproate 40 mg/kg IV (maximum 3000 mg) over 10 minutes

  • Hypotension risk: 1.6%
  • Intubation rate: 16.8%
  • Superior safety profile with 88% efficacy in some studies and significantly lower hypotension rates than phenytoin. 1, 2
  • Avoid in women of childbearing potential due to teratogenicity and neurodevelopmental risks. 1

• Fosphenytoin 20 mg PE/kg IV at maximum rate of 150 mg/min

  • Hypotension risk: 3.2%
  • Intubation rate: 26.4%
  • Requires continuous ECG and blood pressure monitoring due to cardiovascular risks. 1, 2
  • Traditional agent with 95% of neurologists recommending it for benzodiazepine-refractory seizures. 1

Third-Line Treatment for Refractory Status Epilepticus

Refractory status epilepticus is defined as seizures continuing despite benzodiazepines and one second-line agent. 1

Initiate continuous EEG monitoring at this stage to guide therapy and detect non-convulsive seizure activity. 1, 2

Anesthetic Agents (Choose One):

• Midazolam infusion (first-choice anesthetic agent)

  • Loading dose: 0.15-0.20 mg/kg IV
  • Continuous infusion: 1 mg/kg/min, titrate up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min
  • Efficacy: 80%
  • Hypotension risk: 30%
  • Preferred due to lower hypotension risk compared to barbiturates. 1

• Propofol

  • Loading dose: 2 mg/kg bolus
  • Continuous infusion: 3-7 mg/kg/hour
  • Efficacy: 73%
  • Hypotension risk: 42%
  • Requires mechanical ventilation but shorter ventilation time (4 days vs 14 days with pentobarbital). 1

• Pentobarbital

  • Loading dose: 13 mg/kg
  • Continuous infusion: 2-3 mg/kg/hour
  • Efficacy: 92% (highest)
  • Hypotension risk: 77% (requires vasopressor support)
  • Reserved for cases failing other anesthetic agents due to severe hypotension and prolonged sedation. 1

• Ketamine (emerging fourth-line agent)

  • Dose: 0.45-2.1 mg/kg/hour
  • Efficacy: 64% when used early (within 3 days), drops to 32% when delayed
  • Mechanistically distinct (NMDA receptor antagonist vs GABA-ergic agents). 1

Critical Simultaneous Actions

Search for and treat underlying causes while administering anticonvulsants: 3, 2, 6

• Metabolic: Hypoglycemia, hyponatremia, hypoxia, hypocalcemia
• Structural: Ischemic stroke, intracerebral hemorrhage, CNS infection (meningitis/encephalitis)
• Toxic: Drug toxicity (tramadol, cocaine, theophylline, isoniazid), alcohol withdrawal
• Medication: Non-compliance with antiseizure medications (most common precipitant in known epilepsy patients) 2

Obtain neuroimaging (CT head) after seizure control is achieved—do not delay anticonvulsant administration for imaging. 1

Common 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
• Failing to recognize non-convulsive status epilepticus in patients with persistent altered mental status—obtain EEG if consciousness does not return. 2, 6
• Phenytoin is ineffective for seizures secondary to alcohol withdrawal, theophylline toxicity, or isoniazid toxicity. 7

Special Populations

• Elderly patients: Use lower benzodiazepine doses (2-5 mg) and prefer levetiracetam as second-line agent due to minimal cardiovascular effects. 4, 1
• Pregnant patients: Avoid valproate; consider levetiracetam or fosphenytoin. 1
• Renal dysfunction: Adjust levetiracetam and valproate doses. 1

Prognosis and Monitoring

• Mortality from status epilepticus ranges from 5-22%, reaching 65% in refractory cases. 3
• Approximately 16-26% of patients with status epilepticus require endotracheal intubation. 2, 6
• Continuous vital sign monitoring is essential, particularly respiratory status and blood pressure, regardless of administration route. 1
• Most patients with acute symptomatic seizures do not have epilepsy and do not require long-term anticonvulsant therapy—only those with recurrent seizures and uncorrectable predisposing factors need maintenance treatment. 7