Ketamine Biomarkers May Predict SRSE Response
KETAMINE showed moderate efficacy in super-refractory status epilepticus, with EEG patterns and inflammatory biomarkers linked to treatment response.
Ketamine in Super-Refractory Status Epilepticus
Intravenous ketamine may offer a useful treatment option for some adults with super-refractory status epilepticus, while early biologic and electroencephalographic patterns could help identify who is most likely to respond. In a single-center retrospective observational study, 12 adults treated with intravenous ketamine for super-refractory status epilepticus between August 2020 and September 2025 were evaluated for clinical outcomes, laboratory findings, and EEG characteristics.
The sustained response rate was 58%, defined as seizure cessation without recurrence after complete withdrawal of anesthetic therapy. This suggests that ketamine delivered meaningful seizure control in more than half of this highly complex cohort. Safety findings were also reassuring overall, with adverse effects described as mild. The most common issue was transient elevation of liver enzymes, reported in 42% of patients.
EEG Features and Inflammatory Biomarkers
The clearest differences emerged when responders and non-responders were compared. Patients who did not respond to ketamine showed evidence of a markedly hyperinflammatory state at status epilepticus onset. Composite inflammatory indices including the neutrophil-to-lymphocyte ratio, Systemic Inflammation Response Index, and Systemic Immune-Inflammation Index were all significantly higher in non-responders, pointing to a possible relationship between systemic inflammation and reduced ketamine effectiveness.
EEG findings also separated the groups. A beta background pattern was significantly more common among responders, whereas discontinuous and burst-suppression backgrounds were linked to poorer outcomes. These observations suggest that ketamine response in super-refractory status epilepticus may not be random, but instead tied to identifiable physiologic signatures visible on EEG and in routine inflammatory markers.
A New Predictive Score for Ketamine Response
To further explore this signal, the investigators developed an exploratory Ketamine EEG Outcome Score, or KEOS. The score demonstrated excellent discriminatory performance, with an area under the curve of 0.97, along with 100% sensitivity and 85.7% specificity. Although preliminary, this finding raises the possibility that structured EEG assessment could support treatment monitoring and decision-making during prolonged refractory seizures.
The findings should be interpreted cautiously because of the small sample size and retrospective design. Still, the study adds an important biologic dimension to the use of ketamine in super-refractory status epilepticus and supports future prospective multicenter validation.
Reference
Pavan S et al. Ketamine in super-refractory status epilepticus: Combined value of inflammatory biomarkers and EEG features. Epilepsia. 2026;doi:10.1002/epi.70242.
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