Dual Anti-glutamate Therapy in Super-refractory Status Epilepticus After Cardiac Arrest
SUPER-refractory Status Epilepticus After Cardiac Arrest: a Multicenter, Retrospective, Cohort Study of Dual Anti-glutamate Therapy With Ketamine and Perampanel
University of Milano Bicocca
80 participants
Jan 15, 2022
OBSERVATIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria6
- age ≥ 18 years
- patients in coma after cardio-circulatory arrest (CCA) admitted to the Intensive Care Unit and treated with target temperature management (TTM) for the first 24 hours
- initiation of continuous electroencephalographic (cEEG) monitoring within 24-36 hours of CCA
- diagnosis of super-refractory status epilepticus, relapsed after the first cycle of anesthetics (lasting \> 24 hours) and antiepileptic therapy, defined according to the international Salzburg criteria9
- presence of pupillary reflex present bilaterally
- presence of N20 cortical response present bilaterally
Exclusion Criteria3
- EEG with periodic pattern (generalized periodic discharges; GPDs)
- status epilepticus resolved after the first cycle of anesthetics + antiepileptics
- pregnant women
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Interventions
"Dual anti-glutamatergic therapy" (DUAL) intervention group: patients who received ketamine as a continuous i.v. for 3 days (induction dose 1.5-3 mg/kg, followed by maintenance dose 2-10 mg/kg/h; dose adjustment according to EEG target of "ketamine pattern") + oral perampanel via nasogastric tube for 5 days (12 mg if weight \> 60 kg; 9 mg if weight 50-60 kg; 6 mg if weight \< 50 kg), followed by gradual reduction according to clinical evolution.
Any antiseizure and anesthetic therapy according to usual clinical practice, excluding the two anti-glutamate drugs Ketamine and Perampanel
Locations(10)
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NCT05756621