What is the treatment protocol for status epilepticus in the Emergency Department (ED)?

Emergency Department Treatment Protocol for Status Epilepticus

For benzodiazepine-refractory status epilepticus in the ED, administer levetiracetam, fosphenytoin, or valproate as second-line agents—all three are equally effective, stopping seizures in approximately 50% of patients, with valproate having the advantage of causing less hypotension than fosphenytoin. 1

Initial Stabilization and First-Line Treatment

Immediate Actions (0-5 minutes):

• Assess and secure airway, breathing, and circulation—have equipment for airway management immediately available before administering any medications 2, 3
• Establish IV access and administer high-flow oxygen to prevent hypoxia 2
• Check fingerstick glucose immediately to rule out hypoglycemia 2
• Obtain vital signs including temperature to identify infectious causes 2

First-Line Benzodiazepine Treatment:

• Administer lorazepam 0.1 mg/kg IV (maximum 4 mg) at 2 mg/min 2, 3
• May repeat once after 5-10 minutes if seizures continue 2
• Alternative: midazolam 10 mg IM if IV access unavailable 4

Second-Line Treatment for Benzodiazepine-Refractory Status Epilepticus

If seizures persist after adequate benzodiazepine dosing, immediately administer ONE of the following three equally effective options 1:

Option 1: Levetiracetam

• Dose: 40-60 mg/kg IV (maximum 2,500-4,500 mg) at 5 mg/kg/min 5, 2
• Advantages: Minimal cardiovascular effects, no drug interactions, broad-spectrum efficacy 4
• Success rate: 68-73% 5, 6

Option 2: Fosphenytoin

• Dose: 20 mg/kg PE (phenytoin equivalents) IV at 150 mg/min 5, 2
• Requires continuous ECG and blood pressure monitoring 6
• Disadvantages: Hypotension in 12% of cases, potential arrhythmias, drug interactions 1, 5
• Success rate: 56-84% 5

Option 3: Valproate

• Dose: 30 mg/kg IV at 6 mg/kg/hour (or 20-30 mg/kg over 5-20 minutes) 5, 2, 6
• Preferred advantage: 0% hypotension versus 12% with fosphenytoin while maintaining similar efficacy 1, 6
• Success rate: 68-88% 5, 6

Critical Evidence: The 2024 ACEP guidelines, based on the ESETT trial, demonstrate that all three second-line agents result in seizure cessation in approximately 50% of patients, with no difference based on age or home medications 1. The choice should be based on patient-specific contraindications and side effect profiles rather than efficacy differences.

Simultaneous Evaluation for Underlying Causes

While administering anticonvulsants, immediately investigate and treat reversible causes 1, 5:

• Hypoglycemia (administer dextrose if glucose <60 mg/dL)
• Hyponatremia and other electrolyte abnormalities
• Hypoxia
• Drug toxicity or withdrawal (alcohol, benzodiazepines)
• CNS infection (meningitis, encephalitis)
• Ischemic stroke or intracerebral hemorrhage
• Systemic infection with fever

Obtain laboratory studies: electrolytes, complete blood count, toxicology screen, anticonvulsant drug levels 2

Refractory Status Epilepticus (Third-Line Treatment)

If seizures persist after second-line agent, escalate to anesthetic medications and transfer to ICU 2, 6:

Option 1: Midazolam

• Loading dose: 0.15-0.20 mg/kg IV bolus
• Continuous infusion: 1 mg/kg/min 6

Option 2: Propofol

• Loading dose: 1-2 mg/kg IV bolus
• Continuous infusion: 2-10 mg/kg/hour 5, 2, 6
• Requires intubation and mechanical ventilation 6

Option 3: Phenobarbital

• Dose: 20 mg/kg IV at 50-100 mg/min (maximum 1,000 mg) 5, 2
• Success rate: 58.2% as initial agent 6
• Higher success than propofol but more hypotension 6

Option 4: Pentobarbital

• Bolus: 13 mg/kg, then infusion 2-3 mg/kg/hour 6

Initiate continuous EEG monitoring to detect ongoing seizure activity and guide treatment 2

Critical Pitfalls to Avoid

• Do not delay second-line treatment waiting for benzodiazepines to work—early treatment reduces morbidity and mortality 1
• Do not underdose anticonvulsants—use full weight-based loading doses 5
• Do not assume seizures have stopped based on cessation of motor activity alone—nonconvulsive status epilepticus occurs frequently, requiring EEG confirmation 1, 5
• Phenytoin/fosphenytoin may be ineffective in toxin-related or alcohol withdrawal seizures—consider alternative agents 1
• Monitor respiratory status continuously regardless of medication route, as respiratory depression can occur with all agents 6, 3

Special Considerations

For patients already on home anticonvulsants: The use of the patient's home medication as a second-line agent does not affect the probability of stopping seizures—choose based on side effect profile 1

Elderly patients (>50 years): Use standard dosing for second-line agents; no adjustment needed 3

Nonconvulsive status epilepticus: Consider emergent EEG in patients with persistent altered consciousness after apparent seizure cessation, those who received paralytics, or patients in drug-induced coma 5