Neurology. 2026 Oct 27;107(8):e218565. doi: 10.1212/WNL.0000000000218565. Epub 2026 Oct 5.
ABSTRACT
BACKGROUND AND OBJECTIVES: The SUPER-refractory status epilepticus (SE) after Cardiac Arrest Treatment (SUPER-CAT) study evaluated the efficacy and safety of dual antiglutamate therapy (combined AMPA and NMDA receptor blockade) in patients with super-refractory SE (SRSE) after cardiac arrest and without unfavorable prognostic indicators.
METHODS: Multicenter cohort study including patients with postanoxic SRSE meeting the following criteria: bilaterally preserved N20 cortical responses, intact pupillary reflexes, and absence of generalized periodic discharges. Patients treated with dual antiglutamate therapy (DUAL; ketamine 1.5-7.5 mg/kg/h for 3 days plus perampanel 6-12 mg/d for 5 days with tapering) were compared with patients receiving other combinations of antiseizure and anesthetic agents (OTHERS). The primary outcome was resolution of SE. Secondary outcomes included awakening to follow commands and good neurologic outcome at 6 months (modified Rankin Scale 0-3) in patients with fewer than 2 unfavorable multimodal prognostic indicators and 6-month mortality for the entire cohort. Safety analysis included in-hospital mortality and potentially treatment-related adverse events. Patients treated with single antiglutamate agents were described separately.
RESULTS: Between May 2012 and May 2025, 95 of 1,352 consecutive post-cardiac arrest intensive care unit patients met inclusion criteria (mean age 66, interquartile range 55-73; 41% female; DUAL = 43; OTHERS = 41; single antiglutamate = 11). Compared with OTHERS, DUAL was associated with a higher rate of SE resolution (84% vs 49%; OR 5.4; 95% CI 1.9-14.9; p = 0.001), a greater likelihood of awakening before discharge (56% vs 32%; OR 2.7; 95% CI 1.0-7.3; p = 0.053) and lower 6-month mortality (52% vs 74%; OR 0.37; 95% CI 0.15-0.97; p = 0.043). A trend toward better 6-month neurologic outcome was observed in the DUAL group (39% vs 25%; OR 1.89; 95% CI 0.64-5.56; p = 0.245). Reversible cholestatic liver injury occurred more frequently in DUAL group, compared with OTHERS (77% vs 27%; OR 9.00; 95% CI 3.34-24.19; p < 0.001).
DISCUSSION: In patients with postanoxic SRSE without unfavorable prognostic indicators, dual antiglutamate therapy was highly effective in resolving SE and was associated with improved short-term clinical outcomes.
TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT05756621.
PMID:42837646 | DOI:10.1212/WNL.0000000000218565