Clinical utility and tolerability of ketamine as adjunctive rescue therapy for refractory neonatal status epilepticus: a case report of a late preterm infant with multifocal hemorrhagic brain injury.

Background: Neonatal status epilepticus (NSE) is a life-threatening neurological emergency associated with high mortality and long-term neurodevelopmental morbidity. Although phenobarbital remains the recommended first-line antiseizure medication (ASM), followed by agents such as phenytoin or levetiracetam, seizure control is not always achieved. Ketamine, a non-competitive N methyl-D-aspartate (NMDA) receptor antagonist, has emerged as a potential rescue therapy for refractory status epilepticus because of its unique mechanism of action and favorable hemodynamic profile. However, evidence supporting its use in neonates remains scarce. Despite increasing recognition of refractory neonatal status epilepticus (RNSE), no universally accepted definition exists. Current recommendations suggest considering RNSE when electroclinical or electrographic seizures persist despite appropriate first- and second-line treatment, highlighting the importance of continuous EEG monitoring. Case presentation: We report a late preterm male infant with multifocal hemorrhagic brain injury who developed RNSE on the second day of life despite sequential treatment with phenobarbital, levetiracetam and midazolam. Ketamine was associated with disappearance of clinical seizures and persistence of shorter electrographic-only seizures. Complete electrographic seizure cessation occurred after continued ketamine and the subsequent addition of phenytoin. No acute hemodynamic or respiratory adverse events attributable to ketamine were observed. Conclusions: This case highlights both the potential and the limitations of ketamine in RNSE. Although seizure control cannot be attributed solely to ketamine because of concomitant multimodal therapy, its distinct pharmacological mechanism, favorable cardiovascular profile, and ease of administration make it a feasible and well-tolerated adjunctive treatment option. Continuous EEG monitoring remains essential for evaluating treatment response. Prospective neonatal studies are needed to define the optimal timing, dosing strategies, efficacy, and long-term safety of ketamine in RNSE.