What is the role of Keppra (levetiracetam) in treating status epilepticus in pediatric patients?

Levetiracetam as Second-Line Treatment for Pediatric Status Epilepticus

Levetiracetam is an effective and safe second-line agent for pediatric status epilepticus, with comparable efficacy to phenytoin and valproate but with superior safety profile and ease of administration. 1, 2

Recommended Dosing Protocol

Loading dose: 40 mg/kg IV over 5 minutes (maximum 2,500-3,000 mg) 1, 2, 3

• This higher pediatric dose (40 mg/kg) is specifically recommended for children and demonstrates superior efficacy compared to lower doses 2, 3
• The 30 mg/kg dose used in adults shows reduced efficacy (38-67%) in pediatric populations 2
• Administer rapidly over 5 minutes without cardiac monitoring requirements 1, 2

Maintenance dosing: 1

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

Efficacy Evidence in Pediatric Populations

Levetiracetam demonstrates 62.8-94% seizure control rates as second-line therapy 3, 4, 5

• The EcLiPSE trial (largest pediatric study, n=286) showed 70% seizure termination with levetiracetam versus 64% with phenytoin, though this difference was not statistically significant 4
• A multicenter study demonstrated 62.8% seizure freedom with levetiracetam compared to only 37.2% with fosphenytoin 3
• A randomized controlled trial found equivalent efficacy: levetiracetam 94%, phenytoin 89%, valproate 83% (p=0.38) 5
• Particularly effective in children under 2 years, with 57% seizure termination in this age group 6

Superior Safety Profile Compared to Alternatives

Levetiracetam causes significantly fewer adverse effects than phenytoin or fosphenytoin 1, 3, 4

• No hypotension risk (0%) versus 12% with phenytoin/fosphenytoin 1
• Reduced ICU admissions by 18.1% compared to fosphenytoin 3
• Shorter hospital stays by 1.9 days compared to fosphenytoin 3
• Minimal adverse effects: fatigue, dizziness, rarely nausea or transient transaminitis 2
• No cardiovascular monitoring required during administration 1, 2

In contrast, phenytoin/fosphenytoin requires continuous ECG and blood pressure monitoring due to cardiovascular risks 1

Treatment Algorithm for Pediatric Status Epilepticus

First-line (0-5 minutes): 1

• IV lorazepam 0.1 mg/kg (maximum 2 mg), may repeat once after at least 1 minute
• Maximum 2 doses total

Second-line (5-20 minutes after benzodiazepine failure): 1, 2

• Levetiracetam 40 mg/kg IV over 5 minutes (preferred option)
• Alternative: Valproate 20-30 mg/kg IV over 5-20 minutes (88% efficacy, 0% hypotension)
• Alternative: Fosphenytoin 20 mg PE/kg IV (84% efficacy, 12% hypotension risk, requires slower infusion at maximum 1-3 mg/kg/min)

Third-line (refractory status epilepticus): 1

• Midazolam infusion: 0.15-0.20 mg/kg IV load, then 1 mg/kg/min continuous infusion
• Propofol: 2 mg/kg bolus, then 3-7 mg/kg/hour infusion
• Pentobarbital: 13 mg/kg bolus, then 2-3 mg/kg/hour infusion

Critical Monitoring Requirements

Prepare for respiratory support before administration 1, 2

• Continuous oxygen saturation monitoring throughout treatment 1
• Have bag-valve-mask ventilation and intubation equipment immediately available 2
• Risk of apnea increases when combined with other sedatives 2

Post-administration monitoring protocol: 2

• Vital signs and neurological assessments every 15 minutes during infusion and for 2 hours post-infusion
• Then every 30 minutes for hours 2-8
• Then hourly from 8-24 hours

Practical Advantages Over Phenytoin

Levetiracetam offers significant logistical benefits 1, 3, 4

• Faster administration: 5 minutes versus minimum 20 minutes for phenytoin 3, 4
• No cardiac monitoring required during infusion 1, 2
• No need for third-line treatment: 16.3% reduction in need for additional anticonvulsants compared to fosphenytoin 3
• Can be administered through peripheral IV without risk of purple glove syndrome 4

Special Considerations

Prior levetiracetam exposure does not preclude use 3

• In one study, 21.3% of patients were already on oral levetiracetam at time of status epilepticus 3
• An additional 9.4% had previous levetiracetam exposure 3
• Efficacy remained high despite prior exposure 3

Renal dose adjustments required: 1

• CrCl 50-80 mL/min: 500-1,000 mg every 12 hours
• CrCl 30-50 mL/min: 250-750 mg every 12 hours
• CrCl <30 mL/min: 250-500 mg every 12 hours

Common Pitfalls to Avoid

Do not use inadequate loading doses 2

• The 20 mg/kg dose shows significantly reduced efficacy (38% within 30 minutes) 2
• Always use 40 mg/kg in pediatric patients for optimal seizure control 2, 3

Do not skip to third-line agents prematurely 1

• Ensure adequate trial of benzodiazepines and one second-line agent before escalating 1
• Levetiracetam should be given full opportunity to work (assess at 15 minutes post-infusion) 5

Do not use neuromuscular blockers alone 1

• They only mask motor manifestations while allowing continued electrical seizure activity and brain injury 1