How should status epilepticus be managed emergently, including airway support, benzodiazepine dosing, second‑line antiepileptic choices, and refractory treatment for adults and children?

Emergency Management of 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. 1

Immediate Airway and Stabilization (0-2 minutes)

• Have airway equipment (bag-valve-mask, intubation set) immediately available before administering any benzodiazepine, as respiratory depression requiring intervention is predictable and may occur up to 30 minutes after the last dose. 1
• Continuously monitor oxygen saturation and maintain supplemental oxygen throughout treatment. 1
• Check fingerstick glucose immediately and correct hypoglycemia—a rapidly reversible cause that occurs in 1-2% of post-seizure patients even with normal mental status. 1
• Establish IV access and begin fluid resuscitation simultaneously with benzodiazepine administration to prevent hypotension. 1

First-Line Treatment: Benzodiazepines (0-5 minutes)

Adults:

• Lorazepam 4 mg IV at 2 mg/min is the preferred first-line agent, with 65% efficacy in terminating status epilepticus and superior performance over diazepam (59.1% vs 42.6% seizure cessation). 1
• May repeat lorazepam 4 mg once after 5 minutes if seizures continue. 1
• Alternative if lorazepam unavailable: Midazolam 10 mg IM (97% relative efficacy to IV lorazepam) or diazepam 10 mg IV. 1

Pediatrics:

• Lorazepam 0.1 mg/kg IV (maximum 2 mg) for convulsive status epilepticus, may repeat once after ≥1 minute. 1
• Lorazepam 0.05 mg/kg IV (maximum 1 mg) for non-convulsive status epilepticus, may repeat every 5 minutes up to 4 doses. 1
• Midazolam 0.2 mg/kg IM (maximum 6 mg) if IV access is delayed, may repeat every 10-15 minutes. 1

Critical Pitfall: Benzodiazepine Underdosing

• 76-81% of patients receive inadequate benzodiazepine doses, and inadequate dosing is associated with progression to refractory status epilepticus in 75.4% of cases and non-convulsive status epilepticus with coma in 80.6%. 2, 3
• Do not give subtherapeutic doses—ensure full 4 mg lorazepam or equivalent is administered. 1, 2

Second-Line Treatment (5-20 minutes)

If seizures persist after adequate benzodiazepine dosing, immediately escalate to one of the following second-line agents. The ESETT trial demonstrated equivalent efficacy (~46-47% seizure cessation) among all three options, so selection should be based on safety profile and contraindications. 4

Recommended Second-Line Agents (in order of safety profile):

1. Valproate (Preferred for safety profile):

• Dose: 20-30 mg/kg IV (maximum 3000 mg) over 5-20 minutes. 1, 4
• Efficacy: 88% seizure control with 0% hypotension risk—superior safety profile compared to phenytoin. 1
• Advantages: Rapid administration, minimal cardiorespiratory effects, no cardiac monitoring required. 1, 4
• Contraindications: Absolutely contraindicated in women of childbearing potential (teratogenic risk), liver disease, thrombocytopenia risk. 1, 4

2. Levetiracetam (Best for elderly/cardiac patients):

• Dose: 30 mg/kg IV (maximum 2500-3000 mg) over 5 minutes. 1, 4
• Efficacy: 68-73% seizure control with 0.7% hypotension risk and 20% intubation rate. 1, 4
• Advantages: No cardiac monitoring required, minimal cardiovascular effects, favorable side-effect profile, fewer drug interactions. 1, 4
• Disadvantages: Potential nausea and rash. 4

3. Fosphenytoin (Traditional choice, higher risk):

• Dose: 20 mg PE/kg IV (maximum rate 150 PE/min). 1, 4
• Efficacy: 84% seizure control but 12% hypotension risk and 26.4% intubation rate. 1, 4
• Advantages: Most widely available, 95% of neurologists recommend for benzodiazepine-refractory seizures, can be given IM if needed. 1, 4
• Disadvantages: Requires continuous ECG and blood pressure monitoring due to cardiovascular risks. 1, 4
• Pediatric rate: Do not exceed 1-3 mg/kg/min or 50 mg/min, whichever is slower. 1

4. Phenobarbital (Reserve for other failures):

• Dose: 20 mg/kg IV over 10 minutes (maximum 1000 mg). 1
• Efficacy: 58.2% seizure control as initial second-line agent. 1
• Disadvantages: Higher risk of respiratory depression and hypotension compared to alternatives. 1

Maintenance Dosing After Second-Line Agent:

Levetiracetam maintenance:

• Adults: 30 mg/kg IV every 12 hours (maximum 1500 mg) for convulsive SE; 15 mg/kg every 12 hours for non-convulsive SE. 1
• Pediatrics: 30 mg/kg IV every 12 hours (maximum 1500 mg) for convulsive SE; 15 mg/kg every 12 hours for non-convulsive SE. 1
• Renal adjustment required: Reduce dose by 50% if CrCl 30-50 mL/min; by 75% if CrCl <30 mL/min. 1

Phenytoin/Fosphenytoin maintenance:

• Transition to oral phenytoin 300-400 mg daily divided into multiple doses. 1

Refractory Status Epilepticus (20+ minutes)

Definition: Seizures continuing despite benzodiazepines and one second-line agent. 1

Initiate continuous EEG monitoring at this stage, as >50% of patients have ongoing electrical seizures without clinical manifestations. 1, 5

Third-Line Anesthetic Agents:

1. Midazolam Infusion (First choice for refractory SE):

• Loading dose: 0.15-0.20 mg/kg IV. 1
• Maintenance: 1 mg/kg/min continuous infusion, titrate up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min. 1
• Efficacy: 80% seizure control with 30% hypotension risk. 1
• Critical step: Load with a long-acting anticonvulsant (phenytoin/fosphenytoin, valproate, levetiracetam, or phenobarbital) during the midazolam infusion before tapering to ensure adequate anticonvulsant coverage. 1

2. Propofol (Alternative for intubated patients):

• Loading dose: 2 mg/kg IV bolus. 1
• Maintenance: 3-7 mg/kg/hour infusion. 1
• Efficacy: 73% seizure control with 42% hypotension risk. 1
• Advantages: Shorter ventilation time than barbiturates (4 days vs 14 days), already commonly used for sedation in ventilated patients. 1
• Disadvantages: Requires mechanical ventilation, continuous blood pressure monitoring essential. 1

3. Pentobarbital (Most effective but highest risk):

• Loading dose: 13 mg/kg IV. 1
• Maintenance: 2-3 mg/kg/hour infusion. 1
• Efficacy: 92% seizure control—highest among all agents. 1
• Disadvantages: 77% hypotension risk requiring vasopressors, prolonged mechanical ventilation (mean 14 days). 1

EEG Monitoring Requirements:

• Continuous EEG throughout anesthetic infusion to guide titration and achieve seizure suppression. 1
• Continue EEG for minimum 48 hours after complete anesthetic discontinuation, as late seizure recurrence is common and often non-convulsive. 1
• Do not attribute altered mental status solely to post-ictal state—obtain urgent EEG if patient does not awaken within expected timeframe, as non-convulsive status epilepticus occurs in >50% of cases. 1

Simultaneous Management of Underlying Causes

While administering anticonvulsants, immediately search for and treat reversible causes:

• Hypoglycemia: Check fingerstick glucose and correct immediately. 1
• Hyponatremia: Most common electrolyte disturbance precipitating seizures. 1
• Hypoxia: Ensure adequate oxygenation. 1
• Drug toxicity or withdrawal syndromes: Consider toxicology screen. 1, 4
• CNS infection: Evaluate for meningitis/encephalitis if fever present. 1, 4
• Acute cerebrovascular events: Ischemic stroke or intracerebral hemorrhage, especially in patients >40 years. 1, 4

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

Special Populations

Alcohol Withdrawal Seizures:

• Follow standard benzodiazepine protocol first. 1
• If benzodiazepine-refractory, administer levetiracetam 30 mg/kg IV over 5 minutes as second-line agent (68-73% efficacy). 1
• Evidence strength is low (expert opinion/limited observational data) for alcohol-withdrawal-specific protocols. 1

Pregnancy:

• Activate EMS immediately for any seizure during pregnancy to secure maternal and fetal safety. 1
• Avoid valproate due to teratogenic risk—use levetiracetam as preferred second-line agent. 1

Pediatric Febrile Seizures:

• Antipyretics (acetaminophen, ibuprofen) do not terminate ongoing febrile seizures nor prevent future febrile seizures—do not use as acute seizure therapy. 1
• Febrile seizures affect 2-4% of children, most commonly between 6 months and 2 years of age. 1

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 skip to third-line agents (pentobarbital, propofol) until benzodiazepines and a second-line agent have been tried. 1
• Do not overlook non-convulsive status epilepticus—requires EEG monitoring, especially in patients with persistent altered consciousness. 4, 5
• Ensure adequate benzodiazepine dosing—underdosing is pervasive (76-81% of patients) and leads to progression to refractory SE. 2, 3

Prognosis

• Overall mortality for status epilepticus ranges from 5-22%; in refractory cases mortality can reach 65%. 1
• Time is brain—delayed treatment raises morbidity and mortality significantly. 1, 6, 7