Ketamine use in the refractory and super refractory status epilepticus: a systematic review
TL;DR
Ketamine-containing regimens were associated with clinically relevant seizure reduction or cessation in RSE/SRSE, without a consistent signal of acute haemodynamic harm, but the independent effect of ketamine on sustained seizure control, survival, and functional recovery remains uncertain.
Abstract
Background Refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) are associated with substantial morbidity, mortality, and intensive care requirements. Ketamine has emerged as a potential adjunct because of its N-methyl-D-aspartate receptor antagonism and relatively favourable haemodynamic profile. Objective To evaluate the effectiveness and safety of ketamine in RSE and SRSE resolution. Methods This systematic review followed PRISMA 2020 and was registered in PROSPERO (CRD42024625516). PubMed, Scopus, Web of Science, and Biblioteca Virtual en Salud were searched from inception to 20 November 2025. Two independent reviewers screened studies, extracted clinical, therapeutic, electroencephalographic, haemodynamic, and survival data, and assessed risk of bias using National Institutes of Health quality assessment tools. Meta-analysis was not performed because of substantial heterogeneity. Results Twelve studies comprising 491 patients were included. Ketamine was generally administered as part of multimodal therapy after failure of several antiseizure medications and intravenous anaesthetics. Infusion rates ranged from 0.05 mg/kg/h to 10.5 mg/kg/h, and treatment duration ranged from 6 h to 29 days. Study-defined response rates following ketamine initiation ranged from 43.3% for complete electrographic seizure cessation to 100% for overall RSE/SRSE resolution; however, the highest estimates often reflected combined treatment rather than ketamine alone. Short-term or hospital survival ranged from 45.8% to 81.8%. Immediate haemodynamic deterioration appeared uncommon, although attribution was limited by baseline instability and concomitant therapy. Conclusion Ketamine-containing regimens were associated with clinically relevant seizure reduction or cessation in RSE/SRSE, without a consistent signal of acute haemodynamic harm. However, the independent effect of ketamine on sustained seizure control, survival, and functional recovery remains uncertain. Prospective comparative studies using standardised dosing, timing, and outcome definitions are required. Systematic Review Registration PROSPERO identifier CRD42024625516.