What are the ILAE (International League Against Epilepsy) guidelines for managing status epilepticus?

ILAE Guidelines for Status Epilepticus Management

Status epilepticus is defined by the ILAE as seizures lasting ≥5 minutes or recurrent seizures without return to baseline consciousness, requiring immediate benzodiazepine treatment followed by second-line antiseizure medications if seizures persist. 1, 2

Definition and Time-Critical Thresholds

The ILAE 2015 definition establishes two critical timepoints: t1 when seizures are unlikely to self-terminate (5 minutes for convulsive SE), and t2 when long-term neuronal injury becomes likely (30 minutes for convulsive SE). 1, 2 This operational definition emphasizes that time is brain—prolonged seizures cause progressive changes in synaptic receptors, creating a more proconvulsant state with increased risk of permanent brain damage. 1

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

Administer IV lorazepam 4 mg at 2 mg/min immediately for any actively seizing patient, with demonstrated 65% efficacy in terminating status epilepticus. 3, 4 Lorazepam is preferred over diazepam due to longer duration of action and superior efficacy (59.1% vs 42.6% seizure termination). 3

Alternative routes when IV access unavailable:

• IM midazolam (preferred prehospital option) 3
• Intranasal midazolam 3
• Rectal diazepam (though IM diazepam should be avoided due to erratic absorption) 5, 4

Critical simultaneous actions:

• Check fingerstick glucose immediately and correct hypoglycemia 3
• Assess airway, breathing, circulation and provide high-flow oxygen 6
• Have airway equipment immediately available before administering benzodiazepines due to respiratory depression risk 3

Second-Line Treatment: Non-Sedating Antiseizure Medications (5-20 minutes)

If seizures continue after adequate benzodiazepine dosing, immediately escalate to one of the following second-line agents (do not delay—failure to progress rapidly is a common pitfall): 3, 6

Valproate (Preferred for most patients)

• Dose: 20-30 mg/kg IV over 5-20 minutes 3, 6
• Efficacy: 88% seizure control with 0% hypotension risk 3, 6
• Advantages: Superior safety profile compared to phenytoin, no cardiac monitoring required 3
• Contraindications: Women of childbearing potential (teratogenicity risk), hepatic dysfunction 4

Levetiracetam (Best cardiovascular safety profile)

• Dose: 30 mg/kg IV over 5 minutes (approximately 2000-3000 mg for average adults) 3, 6
• Efficacy: 68-73% seizure control 3, 6
• Advantages: Minimal cardiovascular effects, no cardiac monitoring required, safe in elderly patients 3
• Considerations: Requires dose adjustment in renal dysfunction 4

Fosphenytoin (Traditional option, requires monitoring)

• Dose: 20 mg PE/kg IV at maximum rate of 150 PE/min 3, 6
• Efficacy: 84% seizure control but 12% hypotension risk 3, 6
• Requirements: Continuous ECG and blood pressure monitoring mandatory 3, 6
• Advantages: Most widely available, 95% of neurologists recommend for benzodiazepine-refractory seizures 3

Phenobarbital (Reserve for specific situations)

• Dose: 20 mg/kg IV over 10 minutes 3
• Efficacy: 58.2% but higher respiratory depression risk 3
• Use when: Other options unavailable or contraindicated 5

Third-Line Treatment: Refractory Status Epilepticus (>20 minutes)

Refractory SE is defined as seizures continuing despite benzodiazepines and one second-line agent. 3 At this stage, initiate continuous EEG monitoring immediately as 25% of patients with apparent clinical seizure cessation have continuing electrical seizures. 6

Midazolam Infusion (First choice for refractory SE)

• Loading dose: 0.15-0.20 mg/kg IV 3, 4
• Continuous infusion: 1 mg/kg/min, titrate up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min 3, 4
• Efficacy: 80% overall success rate 3
• Hypotension risk: 30% (lower than pentobarbital at 77%) 3
• Critical action: Load with phenytoin/fosphenytoin, valproate, or levetiracetam during infusion to ensure adequate long-acting anticonvulsant levels before tapering 3

Propofol (Alternative for intubated patients)

• Loading dose: 2 mg/kg bolus 3, 6
• Continuous infusion: 3-7 mg/kg/hour, titrate to EEG burst suppression 3, 4
• Efficacy: 73% seizure control 3
• Advantages: Shorter mechanical ventilation time (4 days vs 14 days with pentobarbital), already commonly used for sedation 3
• Hypotension risk: 42% 3
• Requirements: Mechanical ventilation mandatory, continuous blood pressure monitoring 3

Pentobarbital (Most effective but highest risk)

• Loading dose: 13 mg/kg 3
• Continuous infusion: 2-3 mg/kg/hour 3
• Efficacy: 92% seizure control (highest of all agents) 3
• Hypotension risk: 77% (highest of all agents) 3
• Reserve for: Super-refractory cases when midazolam and propofol have failed 6

Fourth-Line: Super-Refractory Status Epilepticus

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

• Ketamine: 0.45-2.1 mg/kg/hour infusion, acts on NMDA receptors providing mechanistically distinct approach from GABA-ergic agents, 64% efficacy when administered early (within 3 days) 3
• Phenobarbital: 10-20 mg/kg IV loading dose for super-refractory cases 6
• Consider immunotherapy if autoimmune encephalitis suspected 7

Simultaneous Evaluation and Management

While administering treatment, immediately search for and treat underlying causes: 3, 6

• Hypoglycemia (check fingerstick glucose first) 3
• Hyponatremia 3, 6
• Hypoxia 3, 6
• Drug toxicity or withdrawal syndromes 3, 6
• CNS infections (meningitis, encephalitis) 3, 6
• Ischemic stroke 3
• Intracerebral hemorrhage 3, 6
• Traumatic brain injury 7

Nonconvulsive Status Epilepticus

EEG is required for reliable diagnosis of nonconvulsive SE. 7 Initial approach mirrors convulsive SE with benzodiazepines and second-line IV agents, but aggressiveness should be balanced considering risk of seizure-related injury versus medical complications from aggressive treatment. 1 Usually, sequential IV antiseizure drugs are preferred over anesthetic agents (oral/tube options acceptable if IV unavailable). 1

Critical Pitfalls to Avoid

• Never use neuromuscular blockers alone—they only mask motor manifestations while allowing continued electrical seizure activity and brain injury 3, 4
• Do not skip to third-line agents until benzodiazepines and a second-line agent have been tried 3, 4
• Do not delay progression to next treatment step—if seizures continue after 5-10 minutes, escalate immediately 6
• Do not delay anticonvulsant administration for neuroimaging—CT scanning can be performed after seizure control 3
• Monitor for respiratory depression with all benzodiazepines and barbiturates 6
• Prepare for mechanical ventilation regardless of administration route when using anesthetic agents 3, 4

Monitoring Requirements

• Continuous vital sign monitoring (especially respiratory status and blood pressure) throughout treatment 3, 4
• Continuous video EEG monitoring mandatory for refractory and super-refractory SE management 6, 7
• EEG should guide titration to achieve seizure suppression in refractory cases 3, 4

Special Populations

Pediatric patients: Lorazepam 0.1 mg/kg (maximum 2 mg) IV, may repeat once after at least 1 minute 6

Pregnant patients: Activate EMS for any seizure in pregnancy 5

Febrile seizures in children: Follow local standards for fever management, observe for 24 hours; complex febrile seizures require inpatient observation and investigation for underlying etiology 5