Effects of general anesthetics on seizure termination, mortality, and neurological prognosis in a rat model of pediatric refractory status epilepticus: A comparative randomized controlled study.

Abstract

<h4>Introduction</h4>Refractory status epilepticus (RSE) is a serious neurological emergency in children associated with significant mortality and morbidity. General anesthetics (GAs) are routinely used to treat RSE. However, the optimal selection of GAs for pediatric RSE remains unknown.<h4>Objective</h4>We aimed to identify the optimal agent by comparing the efficacy and safety of different GAs in a rat model of RSE.<h4>Methods</h4>Sprague-Dawley rats at postnatal day 20 were subjected to lithium-pilocarpine-induced SE. Animals that developed RSE (pharmacoresistant to the first- and second-line therapies) were randomized to receive one of five GAs (midazolam, propofol, dexmedetomidine, esketamine, or sevoflurane) as the third-line therapy or vehicles. The latency to SE termination (time from the initiation of GAs to SE termination) and 24-hour mortality were assessed. On Day 5 following SE, a series of behavioral tests were performed to evaluate the behavior and cognition.<h4>Results</h4>All five GAs effectively terminated the RSE, with propofol and sevoflurane having the shortest latencies to SE termination. GAs significantly improved survival after the complete termination of SE. Additionally, GAs reduced the cognitive deficits caused by SE, especially episodic memory, without affecting the behavioral abnormalities. Finally, we proposed a multi-dimensional model that integrated the efficacy, safety, and effect of GAs on neurological prognosis, suggesting that sevoflurane might be the optimal treatment.<h4>Conclusion</h4>Our study showed that treatment with GAs effectively terminated RSE and improved survival and short-term cognition. Our proposed model suggests that volatile anesthetics may be the optimal choice for treating RSE. These results may be used to inform the design of comparative clinical trials of GAs for RSE in children.

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