• Fosphenytoin 20 mg/kg
• Valproic acid 40 mg/kg
• Levetiracetam 60mg/kg

A recent study suggested that levetiracetam may provide better hemodynamic outcome compared to fosphenytoin in certain situations.¹⁴ Second line agents do not work immediately, so they are considered adjunct therapy and not main stay of seizure therapy. They are, however, very effective in preventing seizure recurrence.¹⁵ 

While adult studies report cases of cardiac arrythmias and death from fosphenytoin due to its structural similarity to tricyclic antidepressants (blockade of fast acting sodium channels resulting in prolonged QRS duration and fatal wide complex ventricular tachyarrythmias), such reports in children are rare.¹⁶

Third-line agents: A variety of medications are considered as third-line agents. They are used for refractory seizures (lasting longer than 30 minutes). The majority of these agents require airway protection. Phenobarbital can be given without airway protection at the lower dose (5 mg/kg), but higher doses (10–20mg/kg) should be given only after the patient has their airway protected.¹⁷ Third-line agents include:¹⁷

• Phenobarbitol 5–20 mg/kg
• Propofol 1–5 mg/kg
• Pentobarbitol 5–20 mg/kg
• Ketamine 1–1.5 mg/kg
• Ketofol (ketamine 1 mg/kg with propofol 0.5 mg/kg)
• Lacosamide 6–10 mg/kg
• Topiramate (limited data on efficacy)

Burst suppression: If seizures require third-line agents, a burst suppression of 24–48 hours with a continuous infusion of pentobarbitol, midazolam, or propofol will be utilized and the patient will be placed on continuous EEG monitoring.^{18, 19}

Special considerations—neonates: First-line agent is midazolam 0.15 mg/kg, after which there is controversy. Phenobarbital 20 mg/kg (50 percent effective) has traditionally been use but other agents may be equally effective (fosphenytoin 20 mg/kg, lidocaine 2mg/kg, or leviteracetam 50 mg/kg).^20–23

Dr. Saidinejad is professor of clinical emergency medicine & pediatrics at the David Geffen School of Medicine at UCLA.

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