Ketamine in Refractory Status Epilepticus: Clinical Evidence and Therapeutic Implications

Refractory status epilepticus remains one of the most challenging neurological emergencies in clinical practice, carrying high rates of morbidity and mortality and posing a significant risk of permanent neurological damage. Despite the widespread use of conventional antiepileptic drugs and anesthetic agents, a substantial proportion of patients fail to achieve adequate seizure control, highlighting the need for alternative therapeutic approaches that target different pathophysiological mechanisms. In this context, ketamine has gained increasing attention as a potential treatment option for refractory and superrefractory status epilepticus. The aim of this study was to review and synthesize the available evidence regarding the use of ketamine in the management of refractory status epilepticus, with particular focus on its mechanism of action, clinical effectiveness, and practical implications for neurological care. A systematic review of the literature was conducted, including studies that evaluated the administration of ketamine in adult patients with refractory or superrefractory status epilepticus. The selected studies comprised a variety of designs, including retrospective analyses, prospective registries, case series, and narrative reviews. The evidence indicates that ketamine has been associated with partial or complete seizure control in a considerable proportion of patients, especially when introduced early during the course of refractory status epilepticus. Its non-competitive antagonism of N-methyl-D-aspartate (NMDA) receptors allows modulation of sustained glutamatergic hyperexcitability, a key mechanism underlying seizure persistence when GABAergic therapies become less effective. In addition, ketamine demonstrated a favorable hemodynamic profile and a low incidence of severe adverse effects in critically ill neurological patients. Overall, the findings suggest that ketamine represents a valuable therapeutic option in refractory status epilepticus and support its consideration within individualized treatment strategies, while further prospective studies are needed to better define optimal dosing, timing, and patient selection.