Application effects of remimazolam and propofol on elderly patients undergoing hip replacement.

OBJECTIVE: To explore the anesthetic and analgesic effects of remimazolam and propofol in elderly patients undergoing hip replacement and their effects on respiratory and circulatory systems, stress and cognitive function. METHODS: Sixty elderly patients undergoing elective hip replacement in the hospital were selected as the research subjects, and they were divided into the remimazolam group and the propofol group according to the admission sequence of patients. The remimazolam group was anesthetized with remimazolam, and the propofol group was anesthetized with propofol. The anesthesia-related indicators, perioperative pain degree [Visual Analogue Scale (VAS)], circulatory indicators [heart rate, mean arterial pressure (MAP)] before anesthesia (T0), immediately before laryngeal mask insertion (T1), at 5 min after laryngeal mask insertion (T2), at 30 min after laryngeal mask insertion (T3) and at 5 min after laryngeal mask removal (T4), stress response indicators (plasma epinephrine, norepinephrine, cortisol) before anesthesia induction and at 24 h and 72 h after surgery, cognitive function [Mini-Mental State Examination (MMSE)] and adverse reactions were compared between the two groups. RESULTS: Among the 60 enrolled patients, only 1 case was excluded due to withdrawal, thus 30 cases in the remimazolam group and 29 cases in the propofol group were included. There were statistically significant differences in the heart rate, MAP, plasma epinephrine, norepinephrine, cortisol and VAS score in the two groups from the aspects of interaction effect and time-point effect (P < 0.05). The heart rate and MAP at T1, T2 and T3 in the two groups were significantly decreased compared with those at T0, but the heart rate and MAP in the remimazolam group at T1, T2 and T3 were significantly higher than those in the propofol group (P < 0.05). There were no statistical differences in the anesthesia time, awakening time and extubation time between the remimazolam group and the propofol group (P > 0.05). The levels of plasma epinephrine, norepinephrine and cortisol in the two groups were significantly higher at 24 h and 72 h after surgery than those before anesthesia induction, and the above levels were significantly lower in the remimazolam group than those in the propofol group (P < 0.05). The VAS scores at each time point in the two groups were significantly reduced compared to before surgery, but there was no statistically significant difference between the two groups after surgery (P > 0.05). The MMSE scores of the two groups were significantly lower at 1 d and 3 d after surgery compared with those before anesthesia induction, but the score in the remimazolam group was significantly higher than that in the propofol group (P < 0.05). In addition, the incidence rates of adverse reactions were significantly lower in the remimazolam group compared to the propofol group (P < 0.05). CONCLUSION: Compared with propofol, remimazolam can achieve equivalent anesthetic and analgesic effects in elderly patients undergoing hip replacement. However, the latter one can significantly relieve respiratory and circulatory suppression, stress response and cognitive dysfunction, with good safety. TRIAL REGISTRATION: This single-center, prospective, RCT has completed the registration of the Chinese Clinical Trial Center at 31/12/2021 with the registration number ChiCTR2100055039 .

Varenicline improved laparotomy-induced cognitive impairment by restoring mitophagy in aged mice.

Growing incidence of postoperative cognitive dysfunction (POCD) in the elderly populations after major surgery challenges us to provide stable and effective treatments. Mitochondria dysfunction is essential in the pathogenesis of aging and neurodegenerative diseases. It is hypothesized that varenicline improves cognitive impairment through restoring mitophagy and tau phosphorylation. Wild type C57BL/6 mice (male, 18-month-old) were subjected to laparotomy with or without chronic varenicline administration. Postoperative cognition and anxiety were determined by Morris water maze and elevated plus maze tests. Meanwhile, oxidative stress, mitochondria function, mitophagy and tau phosphorylation, as well as the correlation of PKR and STAT3 were characterized. In aged mice following laparotomy, persistent cognitive dysfunction in spatial learning and memory were indicated by longer escape latency and less crossing frequency in the target quadrant. Laparotomy also induced anxiety responses deficits. After postoperative 14 days, significant ROS accumulation and smaller mitochondria with impaired function were presented in the hippocampus. Simultaneously, there were abundant of neuronal apoptosis and translocation of tau phosphorylation in the mitochondria. Enhanced mitophagy and down regulated ChAT activity were distributed in the mice subjected to laparotomy. PKR signaling was activated and required for subcellular activation of STAT3 in the brain. After chronic varenicline administration (1 mg/kg/day), cognitive dysfunction, hippocampal oxidative stress, as well as fragile mitophagy were improved. Our results highlight that laparotomy caused cognitive impairment with persistent oxidative stress, mitochondria dysfunction and autophagy dysregulation. PKR/STAT3 maybe the potential mechanism, and perioperative varenicline treatment could be an efficient therapeutic strategy for POCD.

Abnormal phosphorylation of tau protein and neuroinflammation induced by laparotomy in an animal model of postoperative delirium.

Postoperative delirium (POD) is an acute neuropsychological disturbance after surgery, whose prevalence is related with advancing age. Neuroinflammation and abnormal tau phosphorylation that commonly presenting in Alzheimer's disease (AD) may contribute to the progression and duration of POD. To study the acute influence of surgery on cognitive function, wild type male C57BL/6 N mice were randomly divided into three groups: Control (CON), Laparotomy at 4 h and 24 h (LAP-4 h, LAP-24 h), then subjected to laparotomy under sevoflurane anaesthesia. The cognitive performance, peripheral and central inflammatory responses and tau phosphorylation levels were evaluated at 4 h and 24 h postoperatively. When LAP4-hrs displayed anxiety behaviors with high mRNA levels of inflammatory cytokines, such as interleukin-1ß (IL-1ß), IL-6, IL-8, TNF-α and MCP-1 in the liver, and IL-8 in the hippocampus, results at 24 h were different. In the liver, only IL-10 protein was obviously elevated, but in the hippocampus, both pro- and anti-inflammatory cytokines were significantly decreased whilst the elimination of anxiety. The activity of major related kinases and phosphatases was remarkably changed which may contribute to the dephosphorylated tau protein. With tremendous neuropathological changes and significant numbers of activated microglias and astrocytes observed in the sub-regions of hippocampus, the memory impairment existed at both 4 h and 24 h. Since the association of dephosphorylated tau with POD, these findings may supply novel implications for the understanding of tauopathies and as a theoretical basis for preventions from the postoperative cognitive dysfunction (POCD).

Differential effects of propofol and dexmedetomidine on neuroinflammation induced by systemic endotoxin lipopolysaccharides in adult mice.

Propofol and dexmedetomidine are commonly used in clinical situations where neuroinflammation may be imminent or even established but comparative data on their effects on neuroinflammatory and cognitive parameters are lacking. Using a murine model of neuroinflammation induced by systemic lipopolysaccharide (LPS), this study compared the effects of these two agents on cognitive function, neuroinflammatory parameters, oxidative stress and neurotransmission. Male adult C57BL/6 N mice were anaesthetised with propofol or dexmedetomidine prior to intraperitoneal injection of LPS. Cognitive and motor function were assessed by the Y-maze and Rotarod tests respectively. Inflammatory responses were evaluated by relative levels of cytokine mRNA and immunoreactivity of glia cells. LPS caused a marked elevation in IL-1ß and TNF-α levels both peripherally and in the brain, together with microglia activation (p < 0.05) and cognitive impairment. These changes were accompanied by an increase in 8-hydroxy-2'-deoxyguanosine (8-OHdG) (p < 0.05). Dexmedetomidine attenuated microglia activation (p < 0.05) and the elevation in 8-OHdG level (p < 0.05). Propofol did not affect cognition. However, both drugs lowered the number of vesicular glutamate transporter 1 (VGLUT 1), but was associated with higher levels of apoptosis and 8-OHdG (p < 0.05). Data from this study suggest dexmedetomidine and propofol have different anti-neuroinflammatory and neuroprotective profiles. However, neither drug can fully attenuate the effects of LPS induced cognitive impairment.

Synthesis and photocatalytic activity of Pt-ZnO hybrid nanocomposite by solution plasma technology.

In this paper, Pt-ZnO hybrid nanocomposites were prepared by solution plasma technology. X-ray diffraction (XRD) and energy dispersive x-ray analysis (EDX) were used to verify their chemical composition. The size and morphology of the Pt-ZnO hybrid nanocomposites were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). These results indicate that about 2-3 nm Pt nanoparticles (NPs) were synthesized and dispersed on the pyramid-like ZnO (20-60 nm) surface. Photodegradation of Rhodamine B (RhB) demonstrates that the Pt (5 wt%)-ZnO hybrid nanocomposite has better photocatalytic activity than commercial P25 because Pt NPs restrain the photogenerated electron/hole recombination and increase the catalyst activity.