Remimazolam Protects Against LPS-Induced Endotoxicity Improving Survival of Endotoxemia Mice

Abstract

Remimazolam is a new benzodiazepine of sedative drugs with an ultra-short-acting anesthetic effect, commonly used for critically ill patients (especially septic patients) in intensive care units (ICUs). Although some anesthetics have been reported to show certain anti-inflammatory effects, the role of remimazolam in inflammation is still remained unknown. Here, we studied the effects of remimazolam on macrophage in response to LPS both in vivo and in vitro. Interestingly, compared with LPS treatment group, remimazolam remarkably improved survival rate of endotoxemia mice and decreased the release of LPS-induced inflammatory mediators (such as TNF-α, IL-6, and IL-1β). We further found that remimazolam not only inhibited the activation of MAPK signal pathway at 15 min after LPS treatment but also disturbed Rab5a related TLR4 expression at cell surface in response to LPS at a later time. Such evidence suggests that remimazolam might be beneficial to septic patients who are suffering from uncontrolled inflammatory responses.

Novel anesthetics in pediatric practice: is it time?

“…Currently, the preclinical literature involving remimazolam administration is scarce. Through TLR4 receptor downregulation, remimazolam was shown to interfere with lipopolysaccharide (LPS)-induced endotoxemia via blockade of NF-kB signaling pathway and reversal of LPS-induced phosphorylation of Akt and Erk protein kinases essential for neuronal survival [32 ▪▪ ]. The interaction with NF-kB was also beneficial in promoting glioma cell apoptosis in vitro [33] and in alleviating neuropathic pain in adult rats [34].…”

Remimazolam Supplemented to General Anesthesia Alleviates Stress and Cognitive Impairment in Elder Patients After Hip Surgery

“…Additionally, upregulated pro-inflammatory cytokine expression may lead to hyperalgesia and further cause sensitization of the central and peripheral nervous system, affecting cognitive capabilities [ 20 ]. In previous studies, remimazolam has been shown to decrease the inflammatory response in LPS-induced endotoxicity [ 21 ], reduce neuropathic pain by regulating autophagy and bradykinin receptor B1. The ameliorating effects of remimazolam on hemodynamic stability are also well recognized [ 22 ].…”

Postoperative delirium, neuroinflammation, and influencing factors of postoperative delirium: A review

“…[50] Remimazolam, an ultrashort-acting benzodiazepine, ameliorated the LPS-induced peripheral blood septic response in mice, reduced the number of LPS-induced deaths, and decreased the production of inflammatory factors in cultured macrophages in vitro. [51] In contrast, animal studies have shown that remimazolam can cause behavioral abnormalities and neuronal degeneration in mice. [52]…”