Levetiracetam for pediatric convulsive status epilepticus in emergency settings: A systematic review and meta‐analysis comparing levetiracetam, phenytoin, and valproate

Convulsive status epilepticus (CSE) is a life‐threatening neurological emergency in children. When first‐line benzodiazepines fail, the optimal second‐line antiseizure medication remains debated. This systematic review and meta‐analysis compared the efficacy and safety of intravenous levetiracetam (LEV) versus phenytoin/fosphenytoin (PHT/FOS) and versus valproate (VPA) as second‐line treatments for pediatric CSE. We systematically searched PubMed, Embase, Cochrane Library, and Web of Science from inception to May 2026 for randomized controlled trials (RCTs) comparing LEV with PHT/FOS or VPA in children aged 3 months to 18 years with benzodiazepine‐refractory CSE. The primary outcome was clinical cessation of CSE. Secondary outcomes included seizure recurrence within 24 h, need for intubation, and serious adverse events (SAEs). Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random‐effects model. Risk of bias was assessed using Cochrane RoB 2. Nine RCTs (1714 patients) were included. For LEV vs. PHT/FOS, no significant difference was found in seizure cessation (RR = 1.05, 95% CI .99 to 1.13; I 2 = 38%; 9 studies, n = 1610). LEV showed a trend toward lower seizure recurrence within 24 h (RR = .77, 95% CI .55 to 1.09, p = .14; I 2 = 0%; seven studies, n = 765). Need for intubation (RR = .69, 95% CI .40 to 1.21; I 2 = 68%; six studies, n = 899) and SAEs (RR = 1.18, 95% CI .88 to 1.60; I 2 = 0%; five studies, n = 834) did not differ significantly between groups. For LEV vs. VPA, no differences were observed in seizure cessation (RR = 1.05, 95% CI .87 to 1.27; I 2 = 0%; two studies, n = 221), seizure recurrence (RR = 1.04, 95% CI .47 to 2.30; I 2 = 0%; two studies, n = 213), intubation (RR = .69, 95% CI .32 to 1.51; I 2 = 0%; two studies, n = 221), or SAEs (RR = .20, 95% CI .02 to 1.71; I 2 = 0%; two studies, n = 221). No statistically significant differences in efficacy were found among levetiracetam, phenytoin/fosphenytoin, and valproate as second‐line treatments for pediatric convulsive status epilepticus. Levetiracetam offers practical advantages in administration and safety, supporting its use as an appropriate first‐choice second‐line agent. Further well‐designed comparative studies with standardized outcome assessments are needed.