Dual Anti-glutamate Therapy in Super-refractory Status Epilepticus After Cardiac Arrest

Status epilepticus (SE) is found in 20-30% of patients in coma after cardiac arrest, is often refractory to medical therapy and is considered a negative prognostic factor. Intensity and duration of treatment of refractory and super-refractory post-anoxic SE pose the ethical dilemma between futility of treatments and, conversely, their premature suspension. A recent study by the Epilepsy Center of the San Gerardo Hospital has shown that patients with super-refractory post-anoxic SE and favorable prognostic indicators can achieve a good functional outcome in more than 40% of cases, if treated with intensive and protracted therapy.However, there is profound uncertainty about the best combination of antiseizure medications and anesthetics to use in this condition. A combined anti-glutamatergic therapy with ketamine (anti-NMDA receptor) and perampanel (anti-AMPA receptor), aimed at counteracting the excitotoxicity linked to global cerebral ischemia, could be particularly effective in the treatment of super-refractory SE with post-anoxic etiology. Preliminary results in the first 26 patients treated in the Coordinating Center of the project indicate that this therapy appears safe and highly effective (80% SE resolution, 40% good neurological outcome).The aim of the SUPER-CAT study is to investigate the efficacy and safety of combined therapy with ketamine and perampanel (dual anti-glutamatergic therapy) in patients with post-anoxic super-refractory status epilepticus, compared to other therapies, using a multi-centre, retrospective, cohort study design.

Inclusion Criteria:age ≥ 18 yearspatients in coma after cardio-circulatory arrest (CCA) admitted to the Intensive Care Unit and treated with target temperature management (TTM) for the first 24 hoursinitiation of continuous electroencephalographic (cEEG) monitoring within 24-36 hours of CCAdiagnosis of super-refractory status epilepticus, relapsed after the first cycle of anesthetics (lasting > 24 hours) and antiepileptic therapy, defined according to the international Salzburg criteria9presence of pupillary reflex present bilaterallypresence of N20 cortical response present bilaterallyExclusion Criteria:EEG with periodic pattern (generalized periodic discharges; GPDs)status epilepticus resolved after the first cycle of anesthetics + antiepilepticspregnant women