Refractory and Super-Refractory Status Epilepticus in Nerve Agent-Poisoned Rats Following Application of Standard Clinical Treatment Guidelines.
Autor: | Morgan JE; Neuroscience Department, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, United States., Wilson SC; Neuroscience Department, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, United States., Travis BJ; Neuroscience Department, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, United States., Bagri KH; Neuroscience Department, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, United States., Pagarigan KT; Neuroscience Department, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, United States., Belski HM; Neuroscience Department, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, United States., Jackson C; Neuroscience Department, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, United States., Bounader KM; Neuroscience Department, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, United States., Coppola JM; Neuroscience Department, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, United States., Hornung EN; Neuroscience Department, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, United States., Johnson JE; Comparative Pathology Department, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, United States., McCarren HS; Neuroscience Department, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, United States. |
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Jazyk: | angličtina |
Zdroj: | Frontiers in neuroscience [Front Neurosci] 2021 Sep 10; Vol. 15, pp. 732213. Date of Electronic Publication: 2021 Sep 10 (Print Publication: 2021). |
DOI: | 10.3389/fnins.2021.732213 |
Abstrakt: | Nerve agents (NAs) induce a severe cholinergic crisis that can lead to status epilepticus (SE). Current guidelines for treatment of NA-induced SE only include prehospital benzodiazepines, which may not fully resolve this life-threatening condition. This study examined the efficacy of general clinical protocols for treatment of SE in the specific context of NA poisoning in adult male rats. Treatment with both intramuscular and intravenous benzodiazepines was entirely insufficient to control SE. Second line intervention with valproate (VPA) initially terminated SE in 35% of rats, but seizures always returned. Phenobarbital (PHB) was more effective, with SE terminating in 56% of rats and 19% of rats remaining seizure-free for at least 24 h. The majority of rats demonstrated refractory SE (RSE) and required treatment with a continuous third-line anesthetic. Both ketamine (KET) and propofol (PRO) led to high levels of mortality, and nearly all rats on these therapies had breakthrough seizure activity, demonstrating super-refractory SE (SRSE). For the small subset of rats in which SE was fully resolved, significant improvements over controls were observed in recovery metrics, behavioral assays, and brain pathology. Together these data suggest that NA-induced SE is particularly severe, but aggressive treatment in the intensive care setting can lead to positive functional outcomes for casualties. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Morgan, Wilson, Travis, Bagri, Pagarigan, Belski, Jackson, Bounader, Coppola, Hornung, Johnson and McCarren.) |
Databáze: | MEDLINE |
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