Efficacy of IV Ketamine in Refractory/Super-Refractory Status Epilepticus: A Systematic Review and Meta-Analysis.

Abstract

Background and objectives: Intravenous ketamine is increasingly used for refractory and super-refractory status epilepticus (RSE/SRSE), yet its efficacy and optimal use remain uncertain. We therefore aimed to synthesize the available evidence to quantify the effectiveness of ketamine in achieving seizure cessation and to explore differences in treatment characteristics between patients who respond and those who do not.

Methods: We conducted a systematic review and meta-analysis to estimate the pooled seizure cessation rate associated with intravenous ketamine. Secondary analyses compared ketamine initiation timing, dosing, and infusion duration between patients who achieved seizure cessation (responders) and those who did not (nonresponders).

Results: Fourteen studies comprising 388 adult patients (249 responders, 139 nonresponders) were included. The pooled seizure cessation rate with ketamine was 64% (95% CI 49%-76%) with moderate heterogeneity (I ² = 54.1%). Sensitivity analysis showed no single study substantially influenced results, supporting robustness. Responders received ketamine earlier (3.2 ± 2.6 days) than non-responders (4.3 ± 2.6 days), mean difference of -0.90 days (95% CI: -1.31 to -0.49; p < 0.0001). The mean maintenance dose was 2.5 ± 1.4 mg/kg/hr (responders: 2.5 ± 1.3; nonresponders: 2.6 ± 1.4), with no significant difference between groups (mean difference -0.14 mg/kg/hr; 95% CI -0.45 to 0.18; p = 0.39). Infusion duration averaged 5.0 ± 4.2 days in both groups, with no significant difference (mean difference -0.07 days; 95% CI -1.02 to 0.88; p = 0.88). Ketamine discontinuation due to adverse events was rare (0.7%, 3/55 patients).

Discussion: Intravenous ketamine demonstrates consistent effectiveness and safety as an adjunctive therapy in RSE/SRSE. However, the timing of initiation cannot be reliably linked to improved clinical outcomes given current methodological limitations and heterogeneity across studies. Future prospective research using standardized definitions and rigorous temporal data collection is needed to clarify whether the timing of ketamine initiation independently influences therapeutic success and to define its optimal integration within established status epilepticus (SE) treatment algorithms.

Registration: The systematic review was registered (June 7, 2024) with the International Prospective Register of Systematic Reviews (PROSPERO, CRD42024549523).