Ketamine in super‐refractory status epilepticus: Combined value of inflammatory biomarkers and EEG features

Abstract Objective This study aimed to evaluate the efficacy and safety of intravenous ketamine in a cohort of patients with super‐refractory status epilepticus (SRSE) and to explore whether specific clinical, laboratory, and EEG patterns could predict treatment response. Methods This single‐center retrospective observational study included all adult patients treated with intravenous ketamine for SRSE between August 2020 and September 2025, at the University Hospital of Trieste. Demographic, clinical, laboratory, and EEG data were collected from medical records. EEG recordings obtained during and after ketamine infusion were analyzed according to American Clinical Neurophysiology Society (ACNS) terminology. Associations between baseline characteristics, clinical outcomes, and laboratory and EEG patterns were examined using univariate statistics, and an exploratory EEG severity score, the KEOS (Ketamine EEG Outcome Score), was constructed to assess predictive accuracy. Results Twelve patients met the inclusion criteria. The sustained response rate, defined as seizure cessation without recurrence after complete anesthetic withdrawal, was 58%. Non‐responders exhibited a profound hyperinflammatory state at the onset of status epilepticus, with significantly higher levels of composite indices such as the neutrophil‐to‐lymphocyte ratio (NLR), Systemic Inflammation Response Index (SIRI), and Systemic Immune‐Inflammation Index (SII). Moreover, a “beta background” pattern was significantly more frequent among responders, whereas discontinuous or burst‐suppression backgrounds were associated with poor outcomes. The KEOS demonstrated excellent discrimination (area under the curve AUC = .97, sensitivity = 100%, specificity = 85.7%). Adverse events were mild, with transient liver enzyme elevation in 42% of patients. Significance Intravenous ketamine showed moderate efficacy and a favorable safety profile in this SRSE cohort. The identification of specific EEG signatures together with systemic inflammatory biomarkers suggests the potential for a more biologically informed approach to ketamine monitoring and treatment optimization. However, given the limited sample size, these findings should be interpreted as hypothesis‐generating and warrant validation in larger, prospective multicenter studies.