What is the recommended emergency treatment protocol for status epilepticus, including airway management, benzodiazepine dosing, second‑line antiepileptic drugs, and steps for refractory seizures?

Emergency Treatment Protocol for Status Epilepticus

Administer IV lorazepam 4 mg at 2 mg/min immediately for any actively seizing patient, followed by a second-line agent (valproate, levetiracetam, or fosphenytoin) if seizures persist beyond 5 minutes, and escalate to continuous anesthetic infusions for refractory cases lasting beyond 20 minutes. 1

Immediate Stabilization (0–5 Minutes)

Airway Management

• Have airway rescue equipment (bag-valve-mask and intubation set) immediately available before administering any benzodiazepine, as respiratory depression requiring intervention is a predictable adverse effect 1
• Maintain continuous oxygen saturation monitoring throughout treatment, since apnea can develop up to 30 minutes after the final benzodiazepine dose 1
• Do not place objects in the patient's mouth or restrain the seizing patient 1

First-Line Benzodiazepine Therapy

• Lorazepam 4 mg IV at 2 mg/min is the preferred first-line agent, achieving 65% seizure termination and demonstrating superior efficacy over diazepam (59.1% vs 42.6%) with longer duration of action 1, 2
• If IV access is unavailable, administer IM midazolam 0.2 mg/kg (maximum 6 mg) or intranasal midazolam, both showing comparable efficacy to IV lorazepam 1
• May repeat lorazepam once after at least 1 minute if seizures continue 1

Simultaneous Critical Actions

• Check fingerstick glucose immediately and correct hypoglycemia with IV dextrose 1
• Establish IV access and begin fluid resuscitation to prevent hypotension 1
• Search for reversible causes: hyponatremia (most common electrolyte trigger), hypoxia, drug toxicity/withdrawal, CNS infection, stroke, or hemorrhage 1, 2, 3

Second-Line Treatment (5–20 Minutes)

If seizures persist after adequate benzodiazepine dosing, immediately escalate to one of the following second-line agents 1, 2:

Preferred Agent: Valproate

• Valproate 20–30 mg/kg IV (maximum 3000 mg) over 5–20 minutes achieves 88% seizure cessation with 0% hypotension risk, making it the safest second-line option 1, 3
• Absolutely contraindicated in women of childbearing potential due to fetal teratogenic risk 1
• Also contraindicated in liver disease; monitor for thrombocytopenia 2

Alternative: Levetiracetam

• Levetiracetam 30 mg/kg IV (maximum 2500–3000 mg) over 5 minutes produces 68–73% seizure cessation with minimal cardiovascular effects 1, 2, 3
• Life-threatening hypotension occurs in only 0.7% of patients, with a 20% intubation rate 2
• No cardiac monitoring required; excellent choice for elderly patients or those with cardiac disease 1
• The ESETT trial (Class I evidence) found 47% efficacy at 60 minutes, equivalent to fosphenytoin and valproate 2

Alternative: Fosphenytoin

• Fosphenytoin 20 mg PE/kg IV at maximum rate of 150 PE/min achieves 84% efficacy but carries 12% hypotension risk 1, 2
• Requires continuous ECG and blood pressure monitoring due to cardiovascular toxicity 1
• Can be administered IM if IV access is difficult 2
• Intubation rate of 26.4%, highest among second-line agents 2

Alternative: Phenobarbital

• Phenobarbital 20 mg/kg IV over 10 minutes yields 58.2% efficacy as initial second-line agent 1, 3
• Higher risk of respiratory depression and hypotension compared to other options 1, 3
• Reserve for cases where other agents are contraindicated or unavailable 1

Critical Pitfall to Avoid

• Never skip directly to third-line anesthetic agents (pentobarbital) until benzodiazepines and at least one second-line agent have been tried 3
• Never use neuromuscular blockers alone (e.g., rocuronium), as they only mask motor manifestations while electrical seizure activity continues causing brain injury 1, 3

Refractory Status Epilepticus (20+ Minutes)

Refractory SE is defined as seizures continuing despite benzodiazepines and one second-line agent; initiate continuous EEG monitoring and anesthetic agents at this stage 1, 3.

First-Choice Anesthetic: Midazolam Infusion

• Loading dose: 0.15–0.20 mg/kg IV, followed by continuous infusion starting at 1 mg/kg/min 1, 3
• Titrate up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min based on EEG response 1
• Achieves 80% seizure control with 30% hypotension risk, offering better hemodynamic stability than pentobarbital 1, 3
• Before tapering midazolam, load a long-acting anticonvulsant (phenytoin/fosphenytoin, valproate, levetiracetam, or phenobarbital) to ensure adequate coverage 1

Alternative: Propofol

• Bolus 2 mg/kg followed by infusion 3–7 mg/kg/hour achieves 73% seizure control 1, 3
• Hypotension occurs in 42% of patients (less than pentobarbital's 77%) 1
• Mandatory mechanical ventilation required, but shorter duration than barbiturates (4 days vs 14 days) 1, 3
• Useful in already-intubated patients without hypotension 1

Most Effective but Highest Risk: Pentobarbital

• Loading dose 13 mg/kg, then infusion 2–3 mg/kg/hour achieves 92% seizure control (highest efficacy) 1, 3
• Hypotension requiring vasopressors occurs in 77% of patients 1, 3
• Prolonged mechanical ventilation (mean 14 days) 1
• Reserve for cases refractory to midazolam and propofol 1

Emerging Option: Ketamine

• Ketamine 0.45–2.1 mg/kg/hour shows 64% efficacy when started early (within 3 days), but efficacy drops to 32% when delayed 1
• Acts on NMDA receptors, providing mechanistically distinct approach from GABA-ergic agents 1
• Use with caution in patients with depleted catecholamine reserves 1

Essential Monitoring Throughout Treatment

Continuous EEG Monitoring

• Initiate continuous EEG when refractory SE is declared to detect ongoing electrical seizure activity without motor manifestations 1, 3
• Approximately 25% of patients with convulsive SE have ongoing nonconvulsive electrical seizures after motor activity stops 1
• Continue EEG for at least 24–48 hours after complete anesthetic discontinuation, as late seizure recurrence is common and often nonconvulsive 1
• Titrate anesthetic agents to achieve EEG seizure suppression 1

Hemodynamic Monitoring

• Continuous blood pressure monitoring is mandatory for all anesthetic agents 1, 3
• Have vasopressors (norepinephrine or phenylephrine) immediately available, especially for barbiturates 1
• Monitor for cardiac dysrhythmias, particularly with fosphenytoin 1, 2

Respiratory Monitoring

• Prepare for mechanical ventilation before administering anesthetic agents 1, 3
• Continuous oxygen saturation monitoring throughout treatment 1

Special Considerations

Nonconvulsive Status Epilepticus

• Emergency EEG should be obtained promptly for patients with persistent altered consciousness to detect NCSE 1
• After initial benzodiazepine and second-line IV agents, balance aggressiveness considering risk of seizure-related brain injury versus medical complications from aggressive treatment 4
• Sequential IV antiepileptic drugs are usually the best approach rather than immediate anesthetic coma 4

Maintenance Dosing After Seizure Control

• Levetiracetam maintenance: 30 mg/kg IV every 12 hours (maximum 1500 mg) for convulsive SE; 15 mg/kg every 12 hours for nonconvulsive SE 1
• Phenytoin maintenance: 300–400 mg/day orally divided into multiple doses after IV loading 1
• Adjust all doses for renal dysfunction as needed 1

Pediatric Modifications

• Lorazepam 0.1 mg/kg IV (maximum 2 mg) for convulsive SE; 0.05 mg/kg (maximum 1 mg) for nonconvulsive SE 1
• Levetiracetam loading dose 40 mg/kg IV (maximum 2500 mg) in children 1
• Fosphenytoin rate should not exceed 1–3 mg/kg/min or 50 mg/min, whichever is slower 1

Prognosis and Outcome

• Overall mortality for status epilepticus ranges from 5–22%; in refractory cases mortality can reach 65% 1
• Time is brain: delayed treatment beyond 5 minutes increases morbidity and mortality due to progressive receptor changes favoring a proconvulsant state 1, 4