Dual Antiglutamate Therapy in Super-Refractory Status Epilepticus After Cardiac Arrest (SUPER-CAT Study).
18 affiliations
- 1Epilepsy Center, Department of Neurology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
- 2Department of Medicine and Surgery, University of Milano-Bicocca, Italy.
- 3Department of Emergency and Intensive Care, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
- 4Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy.
- 5Epilepsy Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
- 6PhD Program in Neuroscience, University of Milano-Bicocca, Milano, Italy.
- 7Neurophysiology Unit and Epilepsy Centre, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, Italy.
- 8Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Italy.
- 9Department of Neurology and Intensive Care, Santa Chiara Hospital, Azienda sanitaria universitaria integrata del Trentino (Asuit), Trento, Italy.
- 10Epilepsy Unit, IRCCS Mondino Foundation, Pavia, Italy.
- 11S.C. Neurologia, Ospedale Centrale di Bolzano, Italy.
- 12S.C. Neurologia, Ospedale Brotzu Cagliari, Italy.
- 13Neurology Unit, Department of Neurosciences, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
- 14Division of Anesthesia and Intensive Care, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
- 15Unit of Neurology, University Hospital of Parma, Italy.
- 16S.C. Neurologia, Ospedale M. Bufalini Cesena, Italy.
- 17CRUISE Research Center, Dipartimento di Scienze della Salute, Università Magna Graecia di Catanzaro, Italy; and.
- 18S.C. Neurofisiologia, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy.
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.
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BibTeX
@article{beretta2026dual,
title = {{Dual Antiglutamate Therapy in Super-Refractory Status Epilepticus After Cardiac Arrest (SUPER-CAT Study).}},
author = {Simone Beretta and Matteo Pozzi and Simone Tagliabue and Elisa Bianchi and Emanuela Rossi and Francesco Pasini and Angela Giglio and Giulia Sofia Cereda and Carlo Morotti Colleoni and Giulia Pederzoli and Giada Giovannini and Niccolò Orlandi and Stefano Meletti and Alessandra Gaiani and Stefania Filipponi and Alberto Cucino and Marco Normanno and Ilaria Mariani and Margherita Scanziani and Marco Giani and Susanna Diamanti and Anna Coppo and Jacopo C DiFrancesco and Andrea Stabile and Lorenzo Tinti and Igor Florio and Chiara Sist and Marta Corona and Beatrice Pinna and Francesco Orlandini and Giovanni Cossu and Monica Ferlisi and Marilena Casartelli-Liviero and Francesco Misirocchi and Irene Florindo and Lucia Zinno and Yerma Bartolini and Marco Longoni and Emilio Russo and Antonello Grippo and Carlo Ferrarese and Giuseppe Foti and Leonello Avalli},
journal = {Neurology},
year = {2026},
month = oct,
doi = {10.1212/wnl.0000000000218565},
url = {https://europepmc.org/article/MED/42837646},
note = {CC BY},
}
RIS
TY - JOUR
TI - Dual Antiglutamate Therapy in Super-Refractory Status Epilepticus After Cardiac Arrest (SUPER-CAT Study).
AU - Simone Beretta
AU - Matteo Pozzi
AU - Simone Tagliabue
AU - Elisa Bianchi
AU - Emanuela Rossi
AU - Francesco Pasini
AU - Angela Giglio
AU - Giulia Sofia Cereda
AU - Carlo Morotti Colleoni
AU - Giulia Pederzoli
AU - Giada Giovannini
AU - Niccolò Orlandi
AU - Stefano Meletti
AU - Alessandra Gaiani
AU - Stefania Filipponi
AU - Alberto Cucino
AU - Marco Normanno
AU - Ilaria Mariani
AU - Margherita Scanziani
AU - Marco Giani
AU - Susanna Diamanti
AU - Anna Coppo
AU - Jacopo C DiFrancesco
AU - Andrea Stabile
AU - Lorenzo Tinti
AU - Igor Florio
AU - Chiara Sist
AU - Marta Corona
AU - Beatrice Pinna
AU - Francesco Orlandini
AU - Giovanni Cossu
AU - Monica Ferlisi
AU - Marilena Casartelli-Liviero
AU - Francesco Misirocchi
AU - Irene Florindo
AU - Lucia Zinno
AU - Yerma Bartolini
AU - Marco Longoni
AU - Emilio Russo
AU - Antonello Grippo
AU - Carlo Ferrarese
AU - Giuseppe Foti
AU - Leonello Avalli
PY - 2026
DA - 2026/10/05
JO - Neurology
DO - 10.1212/wnl.0000000000218565
UR - https://europepmc.org/article/MED/42837646
AB - 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.
SN - 0028-3878
SN - 1526-632X
ER -