(SRSE), new research suggests.
In a retrospective cohort study of survivors of cardiac arrest with postanoxic sustained SRSE, resolution of the condition was achieved by 81% of those who received intensive treatment of ketamine plus perampanel, versus 41% of those who received standard care.
The novelty of the new treatment approach is the duration of therapy as well as the dual antiglutamate drugs, researchers note.
“So the logic is to continue treatment until resolution of refractory status epilepticus under continuous EEG [electroencephalographic] monitoring,” reported lead investigator Simone Beretta, MD, San Gerardo University Hospital, Monza, Italy.
Therapy was guided by data on brainstem reflexes, N20 cortical responses, neuronal serum enolase levels, and neuroimaging.
If all or most of these indicators are favorable, “we continue to treat without any time limit,” Dr. Beretta said. However, if the indicators become unfavorable, clinicians should consider lowering the intensity of care, he added.
The findings were presented at the 2021 World Congress of Neurology (WCN).
SUPER-CAT trial
In SRSE, epileptic seizures occur one after another without patients recovering consciousness in between. Standard aggressive therapy for the condition does not include antiglutamatergic drugs, the researchers noted.
In the Super-Refractory Status Epilepticus After Cardiac Arrest: Aggressive Treatment Guided by Multimodal Prognostic Indicators (SUPER-CAT) study, researchers assessed the combination of two such medications.
The first was the anti-NMDA receptor drug ketamine, which was given by intravenous bolus and then continuous infusion for 3 days guided by continuous EEG to reach a ketamine EEG pattern, as evidenced by alpha and beta waves. It was combined with the anti-AMPA receptor antiepileptic perampanel via nasogastric tube for 5 days, followed by slow tapering.
Dr. Beretta noted that in the ongoing TELSTAR trial, which involved a similar patient population, a different drug combination is being used. A major difference between the two trials is that in the TELSTAR trial, aggressive therapy continues for only 2 days if there is no response.
“In the SUPER-CAT study, we continue far beyond 2 days in the majority of patients,” he said. In addition, ketamine and perampanel were not assessed in TELSTAR.
In SUPER-CAT, 489 survivors of cardiac arrest were recruited over 10 years. Of these, 101 had refractory status epilepticus. After excluding those with more than two indicators of poor prognosis (n = 31) or whose status epilepticus resolved (n = 14), 56 patients were determined to have SRSE. All had experienced relapse after undergoing one cycle of anesthetic.
The 56 participants received one of three treatment regimens: double antiglutamate (DAG) therapy of ketamine and perampanel (n = 26), single antiglutamate therapy with either agent (n = 8), or aggressive nonantiglutamate (NAG) therapy with antiepilepsy drugs and anesthetics other than ketamine or perampanel (n = 22).
The single-antiglutamate group was not included in the analysis of patient outcomes.
The DAG and NAG groups were well balanced at baseline. There were no significant differences in median age (60 years vs. 66 years), gender, low cerebral blood flow, presence of bilateral pupillary or corneal reflexes, neuron-specific enolase levels, cortical N20 somatosenory evoked potentials, moderate to severe postanoxic brain injury, and hypothermia/targeted temperature management.