What is the first-line treatment for status epilepticus in pediatric patients?

Management of Status Epilepticus in Pediatrics

First-Line Treatment: Benzodiazepines

Administer IV lorazepam 0.1 mg/kg (maximum 4 mg) immediately as first-line treatment for pediatric convulsive status epilepticus, which can be repeated once after at least 1 minute if seizures persist. 1

Lorazepam Administration Details

• Lorazepam demonstrates 65% efficacy in terminating status epilepticus and is superior to diazepam (59.1% vs 42.6%) 1
• The dose can be repeated once if seizures continue, with a maximum of 2 doses for convulsive status epilepticus 2
• For non-convulsive status epilepticus, use 0.05 mg/kg IV (maximum 1 mg), repeatable every 5 minutes up to 4 doses 2
• Continuous oxygen saturation monitoring and preparation for respiratory support are essential before administration 1, 3

Alternative Route When IV Access Unavailable

• Administer midazolam 0.2 mg/kg IM (maximum 6 mg) if IV access is challenging or delayed 1, 4
• IM midazolam is superior to IV lorazepam in prehospital settings, with 73.4% seizure cessation vs 63.4% for IV lorazepam 1
• IM midazolam may be repeated every 10-15 minutes as needed 4

Critical Monitoring During Benzodiazepine Administration

• Have airway equipment, bag-valve-mask ventilation, and intubation equipment immediately available 2
• Respiratory depression requiring intervention occurs in a significant minority, with increased risk when combined with other sedatives or opioids 2
• Younger children (under 6 years) may require higher mg/kg doses than older children and adults 2

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Second-Line Treatment: After Benzodiazepine Failure (5-20 Minutes)

Administer levetiracetam 40 mg/kg IV (maximum 2,500 mg) as a bolus over 5 minutes immediately after benzodiazepine failure. 1

Why Levetiracetam as Preferred Second-Line Agent

• Levetiracetam has 68-73% efficacy in seizure control with minimal cardiovascular effects 1, 2
• No hypotension risk and no requirement for cardiac monitoring, making it safer than phenytoin/fosphenytoin 1
• Can be administered rapidly over 5 minutes without cardiovascular complications 2

Alternative Second-Line Agents

If levetiracetam is unavailable or contraindicated, consider these alternatives in order of preference:

Valproate 20-30 mg/kg IV over 5-20 minutes:

• 88% efficacy with 0% hypotension risk, superior safety profile compared to phenytoin 2, 5
• Particularly effective in preventing seizure recurrence within 24 hours 6
• Avoid in women of childbearing potential due to teratogenicity risk 2

Fosphenytoin 15-20 PE/kg IV:

• Administer at rate not exceeding 1-3 PE/kg/min (maximum rate: 150 PE/min) in pediatric patients 1, 7
• 84% efficacy but 12% hypotension risk requiring continuous cardiac monitoring 2
• Monitor heart rate via ECG and reduce infusion rate if heart rate decreases by 10 beats per minute 1, 4
• Must be diluted in normal saline; incompatible with glucose-containing solutions 4

Phenobarbital 20 mg/kg IV over 10 minutes:

• 58.2% efficacy as initial second-line agent, but higher risk of respiratory depression and hypotension 2, 6
• May be preferred in neonates over phenytoin due to altered phenytoin pharmacokinetics in young infants 4

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Refractory Status Epilepticus: After Second-Line Failure (20-40 Minutes)

Transfer immediately to pediatric intensive care unit (PICU) and initiate continuous EEG monitoring if seizures persist after second-line treatment. 1

First-Choice Third-Line Agent: Midazolam Infusion

• Loading dose: 0.15-0.20 mg/kg IV 1, 2
• Continuous infusion: Start at 1 mg/kg/min, increasing by 1 mg/kg/min every 15 minutes until seizures stop (maximum 5 mg/kg/min) 1, 2
• 80% overall success rate with 30% hypotension risk, lower than pentobarbital (77%) 2
• Requires mechanical ventilation and continuous blood pressure monitoring 2

Alternative Third-Line Anesthetic Agents

Propofol:

• 2 mg/kg bolus, then 3-7 mg/kg/hour infusion 2
• 73% efficacy with 42% hypotension risk 2
• Requires mechanical ventilation but shorter ventilation time than barbiturates (4 days vs 14 days) 2
• Continuous blood pressure monitoring essential 2

Pentobarbital:

• 13 mg/kg bolus, then 2-3 mg/kg/hour infusion 2
• Highest efficacy at 92% but 77% hypotension risk requiring vasopressors 2
• Associated with prolonged mechanical ventilation (mean 14 days) 2
• Reserved for cases where midazolam and propofol have failed 2

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Maintenance Dosing After Seizure Control

Levetiracetam Maintenance

• Convulsive status epilepticus: 30 mg/kg IV every 12 hours (maximum 1,500 mg) 1, 2
• Non-convulsive status epilepticus: 15 mg/kg IV every 12 hours (maximum 1,500 mg) 1, 2

Phenobarbital Maintenance

• 1-3 mg/kg IV every 12 hours 2

Lorazepam Maintenance

• Increase prophylaxis dose by 10 mg/kg (to 20 mg/kg) IV every 12 hours (maximum 1,500 mg) for convulsive status epilepticus 2

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Concurrent Essential Management

Simultaneously search for and treat underlying causes while administering anticonvulsants:

• Check fingerstick glucose immediately and correct hypoglycemia with appropriate dextrose dose based on age and weight 1, 2
• Assess for hyponatremia, hypoxia, drug toxicity or withdrawal syndromes 1, 2
• Evaluate for CNS infection, ischemic stroke, intracerebral hemorrhage, and electrolyte abnormalities 1, 2
• Ensure airway, breathing, and circulation (CAB) with high-flow oxygen 1
• Establish IV or intraosseous access for medication administration 1

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Critical Pitfalls to Avoid

• Never use neuromuscular blockers alone (e.g., rocuronium), as they only mask motor manifestations while allowing continued electrical seizure activity and brain injury 2
• Do not skip to third-line agents until benzodiazepines and a second-line agent have been tried 2
• Avoid using phenytoin with glucose-containing solutions, which causes precipitation 4
• Do not administer benzodiazepines too rapidly, which increases respiratory depression risk 4
• Never use flumazenil in patients receiving benzodiazepines for seizure control, as it reverses anticonvulsant effects and may precipitate seizures 4
• Avoid valproate in women of childbearing potential due to significantly increased risks of fetal malformations and neurodevelopmental delay 2

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Special Pediatric Considerations

Neonates and Young Infants

• Phenobarbital is preferred over phenytoin in neonates due to altered phenytoin pharmacokinetics, including decreased protein binding leading to higher free phenytoin levels 4
• Benzyl alcohol (preservative in lorazepam) has been associated with "gasping syndrome" in neonates at dosages >99 mg/kg/day 3

Weight-Based Dosing Verification

• Always verify infant's actual weight and recalculate dose as mg PE/kg before administering fosphenytoin 4
• For a 7-8 kg infant, ensure fosphenytoin dose does not exceed 20 mg PE/kg to avoid toxicity 4

Age-Related Pharmacokinetics

• Younger age is associated with slightly higher weight-normalized clearance of lorazepam 8
• Paradoxical excitation occurs in 10-30% of pediatric patients under 8 years, characterized by tremors, agitation, euphoria, and brief visual hallucinations 3