Progressive withdrawal versus intermittent interruption of sedation during electroconvulsive therapy in super-refractory status epilepticus: a multicenter randomized clinical trial

Abstract

Status epilepticus (SE) is a neurological emergency associated with high mortality and numerous sequelae, requiring early identification and intervention. Despite epileptic seizures usually cease with benzodiazepines or other antiepileptic drugs, when cases exhibit refractoriness, the management becomes more challenging. Within the realm of refractoriness, we encounter refractory and super-refractory status epilepticus (RSE and SRSE respectively). RSE is defined when the seizure persists despite treatment with benzodiazepines and at least one antiepileptic drug. SRSE is characterized by the persistence of seizures after 24 hours of sedation. The therapeutic strategies available to treat SRSE are currently limited. Electroconvulsive therapy (ECT) has been recommended as a nonpharmacological option for treatment after other alternatives are unsuccessful. However, only case series have been published on their use in ceasing SRSE, which provides scarce evidence on their effectiveness and safety. Given the limited therapeutic options and considering the outcomes observed in published cases, it becomes apparent that assessing the efficacy of ECT to treat SRSE could be crucial in the future not only for the early control of the SE but also for the reduction of mortality and associated sequelae. The main goal of our study is to analyze the efficacy of ECT in terminating super-refractory status epilepticus and to compare it based on the sedation protocol employed. We propose two sedation options: one involving interruption several hours before the ECT session, resuming once the session is completed, and another where sedation is progressively reduced as the patient undergoes ECT sessions, without abrupt interruption at any point. Our secondary objectives include analyzing and comparing the time required to achieve the termination of SE, assessing the degree of seizure control if termination is not achieved and evaluating the adverse effects and neurological sequelae of ECT with both sedation protocols. For these purposes, we have designed a multicenter randomized clinical trial in which 408 patients will be consecutively and non-probabilistically recruited. The participants must be adults with SRSE scheduled to undergo ECT, with a one-year follow-up capability and without pre-existing cognitive impairment or memory loss. They will be randomized 1:1 into two intervention groups, with each group receiving ECT under either one of the mentioned sedation protocols. We will analyze clinical and electroencephalographic changes after each ECT session. In the favorable scenario of achieving the termination of SRSE, follow-up visits will be conducted to identify the presence or absence of long-term neurological sequelae and compare them according to the received sedation protocol