Remimazolam Improves the Markers of Postresuscitation Cerebral Injury in a Swine Model of Cardiac Arrest

Abstract

Introduction Previous studies have manifested that those sedatives acting on γ-aminobutyric acid A (GABAa) receptor could produce effective brain protection against regional and global ischemic stimulation. The present study was designed to investigate the effect of a novel GABAa receptor agonist, remimazolam post-conditioning (RP) on cerebral outcome after global ischemic stimulation induced by cardiac arrest and resuscitation in swine. Methods A total of 24 swine were utilized in this study, in which the animals were randomly divided into the following three groups: Sham group (n = 6), CPR group (n = 9), and CPR + RP group (n = 9). The experimental model was established by the procedure of 10 min of cardiac arrest and 5 min of cardiopulmonary resuscitation (CPR). Those resuscitated swine in the CPR + RP group received an intravenous infusion of 2.5 mg/kg of remimazolam within 60 min. Post-resuscitation cerebral injury biomarkers and neurological function were evaluated for a total of 24 h. At 24 h post-resuscitation, brain cortex was harvested to evaluate the severity of pathologic damage including tissue inflammation, oxidative stress, apoptosis, and necroptosis. Results Baseline characteristics and CPR outcomes were not significantly different between the CPR and CPR + RP groups. After resuscitation, significantly greater cerebral injury and neurological dysfunction were observed in the CPR and CPR + RP groups than in the Sham group. However, remimazolam post-conditioning significantly alleviated cerebral injury and improved neurological dysfunction after resuscitation when compared with the CPR group. At 24 h post-resuscitation, tissue inflammation, oxidative stress, and cell apoptosis and necroptosis were significantly increased in the CPR and CPR + RP groups when compared with the Sham group. Nevertheless, the severity of pathologic damage mentioned above were significantly milder in those swine treated with the remimazolam when compared to the CPR group. Conclusions In a swine model of cardiac arrest and resuscitation, the remimazolam administered after resuscitation significantly improved the markers of post-resuscitation cerebral injury and therefore protected the brain against global ischemic stimulation.