Adiponectin deficiency is a critical factor contributing to cognitive dysfunction in obese mice after sevoflurane exposure.

BACKGROUND: The number of major operations performed in obese patients is expected to increase given the growing prevalence of obesity. Obesity is a risk factor for a range of postoperative complications including perioperative neurocognitive disorders. However, the mechanisms underlying this vulnerability are not well defined. We hypothesize that obese subjects are more vulnerable to general anaesthesia induced neurotoxicity due to reduced levels of adiponectin. This hypothesis was tested using a murine surgical model in obese and adiponectin knockout mice exposed to the volatile anaesthetic agent sevoflurane. METHODS: Obese mice were bred by subjecting C57BL/6 mice to a high fat diet. Cognitive function, neuroinflammatory responses and neuronal degeneration were assessed in both obese and lean mice following exposure to 2 h of sevoflurane to confirm sevoflurane-induced neurotoxicity. Thereafter, to confirm the role of adiponectin deficiency in, adiponectin knockout mice were established and exposed to the sevoflurane. Finally, the neuroprotective effects of adiponectin receptor agonist (AdipoRon) were examined. RESULTS: Sevoflurane triggered significant cognitive dysfunction, neuroinflammatory responses and neuronal degeneration in the obese mice while no significant impact was observed in the lean mice. Similar cognitive dysfunction and neuronal degeneration were also observed in the adiponectin knockout mice after sevoflurane exposure. Administration of AdipoRon partially prevented the deleterious effects of sevoflurane in both obese and adiponectin knockout mice. CONCLUSIONS: Our findings demonstrate that obese mice are more susceptible to sevoflurane-induced neurotoxicity and cognitive impairment in which adiponectin deficiency is one of the underlying mechanisms. Treatment with adiponectin receptor agonist ameliorates this vulnerability. These findings may have therapeutic implications in reducing the incidence of anaesthesia related neurotoxicity in obese subjects.

Berberine Alleviates Sevoflurane Anesthesia-Induced Cognitive Dysfunction in Neonatal Mice via Regulating CREB1.

BACKGROUND: Sevoflurane has been shown to stimulate neurotoxicity and lead to cognitive impairment. Berberine is known for its role in regulating nervous system diseases, including cognitive dysfunction. This study aimed to investigate the effects of berberine on cognitive dysfunction induced by sevoflurane anesthesia and its potential mechanisms. METHODS: In the in vivo study, neonatal mice were subjected to sevoflurane anesthesia to induce cognitive dysfunction. The cognitive function of the neonatal mice was evaluated using the Morris water maze test, open field test, and tail suspension test. Enzyme-linked immunosorbent assay (ELISA) was utilized to assess the levels of inflammatory factors. Immunohistochemistry (IHC) was conducted to detect ionized calcium-binding adaptor molecule 1 (IBA-1)-positive cells and cleaved caspase-3-positive cells in the hippocampus of the neonatal mice. Western blotting was used to measure the levels of cyclic adenosine monophosphate (cAMP) response element-binding protein 1 (CREB1) in hippocampal tissues and neurons. Hippocampal neurons were isolated from the hippocampus of neonatal mice. These neurons were treated with berberine or subjected to cell transfection. The cell counting kit-8 (CCK-8) assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay were conducted to measure cell viability and apoptosis of hippocampal neurons in vitro. RESULTS: Berberine significantly attenuated sevoflurane-induced cognitive impairment and inflammation in neonatal mice (p < 0.05 or p < 0.01). Additionally, berberine reduced sevoflurane-triggered neuronal apoptosis in the hippocampus of neonatal mice (p < 0.01). Sevoflurane markedly decreased CREB1 expression in the hippocampus of neonatal mice (p < 0.01), which was elevated by berberine treatment (p < 0.01). Mechanistically, sevoflurane significantly suppressed cell viability and promoted cell apoptosis of hippocampal neurons (p < 0.0001 or p < 0.01), which were mitigated by berberine (p < 0.05, p < 0.01, or p < 0.001). Furthermore, berberine significantly elevated CREB1 expression in sevoflurane-treated hippocampal neurons (p < 0.01). The beneficial effects of berberine on cell viability and apoptosis in sevoflurane-treated hippocampal neurons were blocked by CREB1 depletion (p < 0.001). CONCLUSION: Our results demonstrated that CREB1 was significantly decreased in the hippocampus of sevoflurane-treated neonatal mice in vivo and in sevoflurane-treated hippocampal neurons in vitro. This decrease was mitigated by berberine treatment. Moreover, berberine improved sevoflurane anesthesia-induced cognitive impairment in neonatal mice by attenuating neuronal inflammation and apoptosis in vivo. The inhibitory effects of berberine on sevoflurane-induced cell apoptosis were reversed by CREB1 downregulation. These findings indicate that berberine protects against sevoflurane anesthesia-induced cognitive impairment by reducing apoptosis of hippocampal neurons, partially through increasing CREB1 expression.

Novel insights into sevoflurane-induced developmental neurotoxicity mechanisms.

Aim: This study explores Sevoflurane (Sevo)-induced neurotoxicity mechanisms in neonates through transcriptome sequencing and models.Methods: Seven-day-old mice were exposed to 3% Sevo, and hippocampal tissue was collected for analysis of differentially expressed lncRNAs and mRNAs compared with normal mice. MiR-152-3p was selected, and the interaction between H19, USP30, and miR-152-3p was explored in BV2 microglial cells and mouse hippocampal neurons.Results: Sevo disrupts mitochondrial autophagy via USP30 upregulation, exacerbating neurotoxicity and activating NLRP1 inflammasome-mediated inflammation.Conclusion: Sevo neurotoxicity is mediated through the H19/miR-152-3p/USP30 axis, implicating microglial regulation of neuronal pyroptosis.

[Box: see text].

An analysis of the safety of Sevoflurane drugs: A disproportionality analysis based on Food and Drug Administration Adverse Event Reporting System.

Sevoflurane is a volatile anesthetic that can tolerate inhalation induction and is widely used for inducing anesthesia due to its pleasant odor. As a drug that has been on the market for nearly 30 years, the vast majority of adverse reactions have been documented. This study aims to improve the adverse reactions related to Sevoflurane through the mining, organizing and analysis of Food and Drug Administration Adverse Event Reporting System database data. We collected, organized, and analyzed reports from the first quarter of 2004 to the fourth quarter of 2022. We performed disproportionality analysis algorithms, including reporting odds ratio, the proportional reporting ratio values, to quantify the signal values of different adverse events (AEs). A total of 1126 AEs and 27 system organ classes were identified by performing statistics analysis system software. By combining algorithm calculations, we create a forest map of the top 30 AEs of the reporting odds ratio signal. Based on the reviewing relevant literature, we found that the vast majority of AEs have been reported in relevant studies. However, there is currently no study revealing the correlation between atrial fibrillation and Sevoflurane, which means that atrial fibrillation may be an unreported AE of Sevoflurane. In the present study, we found that atrial fibrillation may be a new adverse reaction of Sevoflurane through the Food and Drug Administration Adverse Event Reporting System database, which can function as a novel guideline to guide us in the more standardized use of Sevoflurane in clinical practice.

Early Cognitive Function after Deep Sedation Using Different Anesthetic Agents in Pediatric Patients: A Prospective, Randomized Controlled Trial.

Background and Objectives: The impact of anesthetic agents on memory and cognitive function following general anesthesia is of great interest, particularly regarding their effects on the developing pediatric brain. While numerous studies have examined the relationship between anesthetic drugs and brain function, research focusing on early cognitive function following sedation remains limited. Materials and Methods: This study was a prospective, randomized controlled trial involving 148 pediatric patients scheduled for hematological procedures, specifically bone marrow aspiration (BMA) and intrathecal chemotherapy (ITC). Patients were divided into two groups based on the primary anesthetic used: the inhalational sedation group (IHG), in which sevoflurane was used, and the intravenous sedation group (IVG), which received propofol infusion. Apart from the main anesthetic agent, all sedation methods were consistent across both groups. A cognitive function test administered before sedation involved memorizing four distinct images, each associated with a different number. Then, the patients were asked to identify the omitted image upon awakening in the recovery room. Herein, this pre- vs. post-sedation test is called the early recognition assessment (ERA) tool. The primary outcome was the correct response rate after sedation for the two groups. Secondary outcomes included the sedation score, the behavior response score, and the correct response rates according to the number of sedation procedures. Results: This study included 130 patients in the final analysis, with 74 originally assigned to each group. The initial cognitive assessment revealed no significant difference in performance between the anesthetic agents. In addition, no differences were observed in the rates of correct responses or post-sedation scores after repeated procedures. However, the IVG demonstrated higher behavior response scores compared to the IHG. Conclusions: There were no significant differences in the rates of correct responses using the ERA tool between the two groups, irrespective of the number of sedation procedures performed. While some differences were noted in preoperative, intraoperative, and post-anesthesia care, these did not significantly impact the cognitive outcomes measured.

Effect of remimazolam versus propofol on hypotension after anesthetic induction in patients undergoing coronary artery bypass grafting: A randomized controlled trial.

STUDY OBJECTIVE: There is scarce evidence on the hemodynamic stability of remimazolam during anesthetic induction in patients with significant coronary artery disease. This study aims to compare the effects of remimazolam and propofol on post-induction hypotension in patients undergoing coronary artery bypass grafting (CABG). DESIGN: Randomized controlled trial. SETTING: Tertiary teaching hospital. PATIENTS: Adult patients undergoing isolated CABG. INTERVENTIONS: Patients were randomly allocated to received either remimazolam (n = 50) or propofol (n = 50) for anesthetic induction. The remimazolam group received an initial infusion at 6 mg/kg/h, which was later adjusted to 1-2 mg/kg/h to maintain a bispectral index of 40-60 after loss of consciousness. In the propofol group, a 1.5 mg/kg bolus of propofol was administered, followed by 1-1.5% sevoflurane inhalation as needed to achieve the target bispectral index. MEASUREMENTS: The primary outcome was the area under the curve (AUC) below the baseline mean arterial pressure (MAP) during the first 10 min after anesthetic induction. Secondary outcomes included the AUC for MAP <65 mmHg and the requirement for vasopressors. MAIN RESULTS: The remimazolam group demonstrated a significantly lower AUC under the baseline MAP compared to the propofol group (mean [SD], 169.8 [101.0] mmHg·min vs. 220.6 [102.4] mmHg·min; mean difference [95% confidence interval], 50.8 [10.4-91.2] mmHg·min; P = 0.014). Additionally, the remimazolam group had a reduced AUC for MAP <65 mmHg (7.3 [10.3] mmHg·min vs. 13.9 [14.9] mmHg·min; P = 0.007) and a lower frequency of vasopressor use compared to the propofol group (60% vs. 88%, P = 0.001). CONCLUSIONS: Remimazolam may offer improved hemodynamic stability during anesthetic induction in patients undergoing CABG, suggesting its potential advantage over propofol for patients with significant coronary artery disease in terms of hemodynamic stability.

Desflurane versus sevoflurane anesthesia and postoperative recovery in older adults undergoing minor- to moderate-risk noncardiac surgery - A prospective, randomized, observer-blinded, clinical trial.

STUDY OBJECTIVE: The effect of volatile anesthetics on postoperative recovery in older adults is still not entirely clear. Thus, we evaluated the effect of desflurane versus sevoflurane anesthesia on speed of postoperative recovery in older adults eligible for same-day discharge. We further evaluated the incidence of postoperative nausea and vomiting (PONV), bispectral index (BIS) values, and S100B concentrations. DESIGN: Single-center, prospective, observer-blinded, randomized clinical trial. SETTING: Operating room. PATIENTS: 190 patients ≥65 years of age and scheduled for minor- to moderate-risk noncardiac surgeries. INTERVENTIONS: Goal-directed administration of desflurane versus sevoflurane for maintenance of anesthesia with an intraoperative goal of BIS 50 ± 5. MEASUREMENTS: The primary outcome was the time to anesthesia recovery, which was defined as the time between arrival at the post-anesthesia care unit (PACU) and reaching criteria for discharge from PACU, based on modified Aldrete score ≥ 12 points. Modified Aldrete scores were assessed at PACU arrival and thereafter in five-minute intervals. PONV was evaluated during PACU stay and the first three postoperative days, BIS values were recorded during PACU stay, and S100B values were measured before and after surgery, and on the second postoperative day. MAIN RESULTS: 95 patients were randomized to receive desflurane, and 95 patients to receive sevoflurane. We did not observe a significant difference in median duration of postoperative recovery between the groups (desflurane: 0 min [0;0]; sevoflurane: 0 min [0;0]; p = 0.245). 77 patients (81.1%) in the desflurane group and 84 patients (88.4%) in the sevoflurane group already had Aldrete scores ≥12 points upon arrival at PACU (p = 0.277). There was also no significant difference in the incidences of PONV (p = 0.606), postoperative BIS values (p = 0.197), and postoperative maximum S100B concentrations (p = 0.821) between the groups. CONCLUSIONS: Despite previous reports, we did not observe significant faster recovery times after desflurane anesthesia. Both volatile anesthetics may be appropriate for same-day discharge in older adults.

Possible role of high calcium concentrations in rat neocortical neurons in inducing hyper excitatory behavior during emergence from sevoflurane: a proposed pathophysiology.

Sevoflurane has been shown to increase the incidence of emergence delirium in children; however, the mechanism remains unclear. Sevoflurane increases cytoplasmic calcium concentration which in turn may play a role in emergence delirium. This study aimed to investigate the level of intracellular calcium in rats experiencing hyperexcitatory behavior after exposure to sevoflurane, as well as the role of magnesium in preventing this phenomenon. After ethical approval, 2-5-week-old Sprague-Dawley rats (n = 34) were insufflated with sevoflurane in a modified anesthesia chamber. One group received magnesium sulphate intraperitoneally. After termination of sevoflurane exposure, the occurrence of hyperexcitation was observed. Brain tissue samples from the rats were studied for intracellular calcium levels under a two-channel laser scanning confocal microscope and were quantitatively calculated using ratiometric calculation. The presence of inflammation or oxidative stress reaction was assessed using nuclear factor κB and malondialdehyde. The incidence of hyperexcitatory behavior post sevoflurane exposure was 9 in 16 rats in the observation group and none in the magnesium group. Tests for inflammation and oxidative stress were within normal limits in both groups. The rats showing hyperexcitation had a higher level of cytosol calcium concentration compared to the other groups. To conclude, the calcium concentration of neocortical neurons in Sprague-Dawley rats with hyperexcitatory behavior is increased after exposure to sevoflurane. Administration of magnesium sulphate can prevent the occurrence of hyperexcitation in experimental animals.

Do all sedatives promote biological sleep electroencephalogram patterns? A machine learning framework to identify biological sleep promoting sedatives using electroencephalogram.

BACKGROUND: Sedatives are commonly used to promote sleep in intensive care unit patients. However, it is not clear whether sedation-induced states are similar to the biological sleep. We explored if sedative-induced states resemble biological sleep using multichannel electroencephalogram (EEG) recordings. METHODS: Multichannel EEG datasets from two different sources were used in this study: (1) sedation dataset consisting of 102 healthy volunteers receiving propofol (N = 36), sevoflurane (N = 36), or dexmedetomidine (N = 30), and (2) publicly available sleep EEG dataset (N = 994). Forty-four quantitative time, frequency and entropy features were extracted from EEG recordings and were used to train the machine learning algorithms on sleep dataset to predict sleep stages in the sedation dataset. The predicted sleep states were then compared with the Modified Observer's Assessment of Alertness/ Sedation (MOAA/S) scores. RESULTS: The performance of the model was poor (AUC = 0.55-0.58) in differentiating sleep stages during propofol and sevoflurane sedation. In the case of dexmedetomidine, the AUC of the model increased in a sedation-dependent manner with NREM stages 2 and 3 highly correlating with deep sedation state reaching an AUC of 0.80. CONCLUSIONS: We addressed an important clinical question to identify biological sleep promoting sedatives using EEG signals. We demonstrate that propofol and sevoflurane do not promote EEG patterns resembling natural sleep while dexmedetomidine promotes states resembling NREM stages 2 and 3 sleep, based on current sleep staging standards.

Impact of varied anesthesia maintenance strategies on postoperative respiratory complications in pediatric patients undergoing tonsillectomy and adenoidectomy (AmPRAEC study): study protocol for a multicenter randomized, double-blind clinical trial.

BACKGROUND: Postoperative respiratory adverse events are the most common perioperative complications in pediatric anesthesia, particularly prevalent in children undergoing tonsillectomy and adenoidectomy, with an incidence rate as high as 50%. The choice of anesthetic induction regimen directly influences the incidence of respiratory adverse events during the induction period. However, this effect seems to have minimal impact on postoperative outcomes. The occurrence rate of postoperative respiratory adverse events is likely more closely associated with the anesthetic maintenance phase, yet this relationship remains uncertain at present. METHODS: The objective of this study was to assess the impact of different anesthetic maintenance regimens on postoperative respiratory adverse events in pediatric patients undergoing tonsillectomy and adenoidectomy. The AmPRAEC study is a multicenter, randomized, double-blind controlled trial. A total of 717 pediatric patients were recruited from 12 medical centers and randomly assigned to three groups: group A (intravenous maintenance group, receiving propofol infusion); group B (intravenous-inhalational combination group, maintained with 1% sevoflurane combined with propofol); and group C (inhalational maintenance group, maintained with 2-3% sevoflurane inhalation). The primary outcome measure was the incidence rate of postoperative respiratory adverse events. DISCUSSION: This clinical trial aims to elucidate the impact of various anesthetic maintenance regimens on postoperative respiratory adverse events in pediatric patients. The outcomes of this study are anticipated to facilitate anesthesiologists in devising more comprehensive perioperative management strategies, enhancing comfort, and improving the clinical outcomes for this patient population. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) ChiCTR2300074803. Registered on August 16, 2023.

Comparison of the Influence of Intraoperative Use of Sevoflurane and Isoflurane on Postoperative Nausea, Vomiting, and Cough.

INTRODUCTION: Postoperative nausea, vomiting, and cough are the most common adverse effects of general anesthesia resulting in high discomfort to the patient resulting in uneasiness during the recovery period. This study aimed to compare the influence of intraoperative use of sevoflurane and isoflurane on postoperative nausea, vomiting, and cough. MATERIALS AND METHODS: After approval from the institutional ethical committee, this quantitative observational institutional study was conducted on all patients aged between 18 and 65 years undergoing surgery under general anesthesia at KMC Hospital, Mangalore. Patients were allocated into the sevoflurane group or isoflurane group. RESULTS: All demographic parameters such as age, sex, American Society of Anesthesiologists physical status, and duration were comparable (P > 0.05). The sevoflurane group had higher number of patients (11 [14.86%]) with postoperative nausea at 0 h as compared isoflurane group (7 [9.45%]). Two patients in the isoflurane group reported postoperative vomiting at 0 h, whereas no patient in the sevoflurane group reported vomiting. For cough, a statistically significant correlation was seen between the two groups (P = 0.000) with majority of patients in the isoflurane group, i.e., 50 (67.6%) patients reporting cough at 0 h while only 15 (20.3%) reported cough in the sevoflurane group. CONCLUSION: Sevoflurane was found to be better than isoflurane in terms of postoperative nausea vomiting and cough immediately after emergence in our study. Isoflurane cause the emergence of cough whereas no significant difference in nausea and vomiting was observed in both groups.

Résumé Introduction:Les nausées, vomissements et toux postopératoires sont les effets indésirables les plus courants de l'anesthésie générale, entraînant un inconfort élevé pour le patient, entraînant un malaise pendant la période de récupération. Cette étude visait à comparer l'influence del'utilisation peropératoire du sévoflurane et de l'isoflurane sur les nausées, vomissements et toux postopératoires.Méthode:Après approbation du comité d'éthique institutionnel, cette étude institutionnelle observationnelle quantitative a été menée sur tous les patients âgés de 18 à 65 ans subissant une intervention chirurgicale sous anesthésie générale à l'hôpital KMC de Mangalore. Les patients ont été répartis dans le groupe sévoflurane ou le groupe isoflurane.Résultats:Tous les paramètres démographiques comme l'âge, le sexe, l'ASA PS et la durée étaient comparables. ( P > 0,05) Le groupe sévoflurane avait un nombre plus élevé de patients [11 (14,86 %)] présentant des nausées postopératoires à 0 heure par rapport au groupe isoflurane [7 (9,45 %)]. 2 patients du groupe Isoflurane ont signalé des vomissements postopératoires à 0 heure alors qu'aucun patient du groupe Sévoflurane n'a signalé de vomissements. Pour la toux, une corrélation statistiquement significative a été observée entre les deux groupes ( P = 0,000) avec une majorité de patients dansle groupe isoflurane, c'est-à-dire 50 (67,6 %) patients signalant une toux à 0 heure, alors que seulement 15 (20,3 %) ont signalé une toux dans le groupe sévoflurane.Conclusion:Le sévoflurane s'est révélé meilleur que l'isoflurane en termes de nausées, vomissements et toux postopératoires immédiatement après l'émergence dans notre étude. L'isoflurane provoque une toux d'émergence alors qu'aucune différence significative en termes de nausées et de vomissements n'a été observée dans les deux groupes.

Comparison of Propofol-Based Total Intravenous Anesthesia versus Volatile Anesthesia with Sevoflurane for Postoperative Delirium in Adult Coronary Artery Bypass Grafting Surgery: A Prospective Randomized Single-Blinded Study.

OBJECTIVES: To compare the incidence of delirium and early (at 1 week) postoperative cognitive dysfunction (POCD) between propofol-based total intravenous anesthesia (TIVA) and volatile anesthesia with sevoflurane in adult patients undergoing elective coronary artery bypass graft surgery (CABG) with cardiopulmonary bypass (CPB). DESIGN: This was a prospective randomized single-blinded study. SETTING: The study was conducted at a single institution, the Sree Chitra Tirunal Institute for Medical Sciences and Technology, a tertiary care institution and university-level teaching hospital. PARTICIPANTS: Seventy-two patients undergoing elective CABG under CPB participated in this study. INTERVENTIONS: This study was conducted on 72 adult patients (>18 years) undergoing elective CABG under CPB who were randomized to receive propofol or sevoflurane. Anesthetic depth was monitored to maintain the bispectral index between 40 and 60. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit. Early POCD was diagnosed when there was a reduction of >2 points in the Montreal Cognitive Assessment score compared to baseline. Cerebral oximetry changes using near-infrared spectroscopy (NIRS), atheroma grades, and intraoperative variables were compared between the 2 groups. MEASUREMENTS & MAIN RESULTS: Seventy-two patients were randomized to receive propofol (n = 36) or sevoflurane (n = 36). The mean patient age was 59.4 ± 8.6 years. The baseline and intraoperative variables, including atheroma grades, NIRS values, hemoglobin, glycemic control, and oxygenation, were comparable in the 2 groups. Fifteen patients (21.7%) patients developed delirium, and 31 patients (44.9%) had early POCD. The incidence of delirium was higher with sevoflurane (n = 12; 34.2%) compared to propofol (n = 3; 8.8%) (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.13-2.62; p = 0.027)*. POCD was higher with sevoflurane (n = 20; 57.1%) compared to propofol (n = 11; 32.3%) (OR, 1.63; 95% CI, 1.01-2.62; p = 0.038)*. In patients aged >65 years, delirium was higher with sevoflurane (7/11; 63.6%) compared to propofol (1/7; 14.2%) (p = 0.03)*. CONCLUSIONS: Propofol-based TIVA was associated with a lower incidence of delirium and POCD compared to sevoflurane in this cohort of patients undergoing CABG under CPB. Large-scale, multicenter randomized trials with longer follow-up are needed to substantiate the clinical relevance of this observation.

The miR-182-5p/GPX4 Pathway Contributes to Sevoflurane-Induced Ototoxicity via Ferroptosis.

Our study aimed to investigate the role of ferroptosis in sevoflurane-induced hearing impairment and explore the mechanism of the microRNA-182-5p (miR-182-5p)/Glutathione Peroxidase 4 (GPX4) pathway in sevoflurane-induced ototoxicity. Immunofluorescence staining was performed using myosin 7a and CtBP2. Cell viability was assessed using the CCK-8 kit. Fe2+ concentration was measured using FerroOrange and Mi-to-FerroGreen fluorescent probes. The lipid peroxide level was assessed using BODIPY 581/591 C11 and MitoSOX fluorescent probes. The auditory brainstem response (ABR) test was conducted to evaluate the hearing status. Bioinformatics tools and dual luciferase gene reporter analysis were used to confirm the direct targeting of miR-182-5p on GPX4 mRNA. GPX4 and miR-182-5p expression in cells was assessed by qRT-PCR and Western blot. Ferrostatin-1 (Fer-1) pretreatment significantly improved hearing impairment and damage to ribbon synapses in mice caused by sevoflurane exposure. Immunofluorescence staining revealed that Fer-1 pretreatment reduced intracellular and mitochondrial iron overload, as well as lipid peroxide accumulation. Our findings indicated that miR-182-5p was upregulated in sevoflurane-exposed HEI-OC1 cells, and miR-182-5p regulated GPX4 expression by binding to the 3'UTR of GPX4 mRNA. The inhibition of miR-182-5p attenuated sevoflurane-induced iron overload and lipid peroxide accumulation. Our study elucidated that the miR-182-5p/GPX4 pathway was implicated in sevoflurane-induced ototoxicity by promoting ferroptosis.

Different narcotic gases and concentrations for immobilization of ostrich embryos for in-ovo imaging.

In-ovo imaging using avian eggs has been described as a potential alternative to animal testing using rodents. However, imaging studies are hampered by embryonal motion producing artifacts. This study aims at systematically comparing isoflurane, desflurane and sevoflurane in three different concentrations in ostrich embryos. Biomagnetic signals of ostrich embryos were recorded analyzing cardiac action and motion. Ten groups comprising eight ostrich embryos each were investigated: Control, isoflurane (2%, 4%, and 6%), desflurane (6%, 12%, and 18%) and sevoflurane (3%, 5%, and 8%). Each ostrich egg was exposed to the same narcotic gas and concentration on development day (DD) 31 and 34. Narcotic gas exposure was upheld for 90 min and embryos were monitored for additional 75 min. Toxicity was evaluated by verifying embryo viability 24 h after the experiments. Initial heart rate of mean 148 beats/min (DD 31) and 136 beats/min (DD 34) decreased over time by 44-48 beats/minute. No significant differences were observed between groups. All narcotic gases led to distinct movement reduction after mean 8 min. Embryos exposed to desflurane 6% showed residual movements. Isoflurane 6% and sevoflurane 8% produced motion-free time intervals of mean 70 min after discontinuation of narcotic gas exposure. Only one embryo death occurred after narcotic gas exposure with desflurane 6%. This study shows that isoflurane, desflurane and sevoflurane are suitable for ostrich embryo immobilization, which is a prerequisite for motion-artifact free imaging. Application of isoflurane 6% and sevoflurane 8% is a) safe as no embryonal deaths occurred after exposure and b) effective as immobilization was observed for approx. 70 min after the end of narcotic gas exposure. These results should be interpreted with caution regarding transferability to other avian species as differences in embryo size and incubation duration exist.

Effects of different anesthetic regimens on postoperative cognitive function of elderly patients undergoing thoracic surgery: a double-blinded randomized controlled trial.

OBJECTIVE: Postoperative cognitive dysfunction (POCD) is a serious surgical complication. We assessed the different POCD incidences between anesthesia using sevoflurane and sevoflurane combined with dexmedetomidine, with propofol-based sedation in elderly patients who underwent a thoracic surgical procedure. METHODS: A total of 90 patients aged 65 to 80 years old who underwent a thoracic surgical procedure at our hospital and 15 nonsurgical participants as controls, were enrolled in this study. Patients were divided in a randomized 1:1:1 ratio into 3 groups. All participants were randomized into a trial with three anesthesia groups (P, PS, PSD) or a control group (C) of healthy matches. All trial groups received distinct anesthetic combinations during surgery, while controls mirrored patient criteria.Group P (propofol and remifentanil were maintained during the surgery), Group PS (propofol, remifentanil, and sevoflurane were maintained during the surgery), and Group PSD (propofol, remifentanil, sevoflurane, and dexmedetomidine were maintained during the surgery).All participants were rated using a series of cognitive assessment scales before and three days after surgery. All participants were interviewed over the telephone, 7 days, 30 days, and 90 days postoperatively. RESULTS: POCD incidences in the PSD (combined anesthetization with propofol, sevoflurane, and dexmedetomidine) group was significantly lower than that in the PS (combined anesthetization with propofol and sevoflurane) group, 1 day post-surgery (10.0% vs. 40.0%, P = 0.008), and the results were consistent at 3 days post-surgery. When the patients were assessed 7 days, 30 days, and 90 days postoperatively, there was no significant difference in POCD incidence among the three groups. Multivariate logistic regression analysis of POCD one day after surgery showed that education level was negatively correlated with incidence of POCD (P = 0.018) and single lung ventilation time was positively correlated with incidence of POCD (P = 0.001). CONCLUSION: For elderly patients who underwent a thoracic surgical procedure, dexmedetomidine sedation shows an obvious advantage on improving short-term POCD incidence, which is caused by sevoflurane.

Effect of volatile versus propofol anaesthesia on major complications and mortality after cardiac surgery: a multicentre randomised trial.

BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).

Autophagic degradation of DHCR7 activates AKT3 and promotes sevoflurane-induced hippocampal neuroinflammation in neonatal mice.

Repeated sevoflurane exposure in neonatal mice triggers neuroinflammation with detrimental effects on cognitive function. Yet, the mechanism of the sevoflurane-induced cytokine response is largely unknown. In this study, we reveal that 3-MA, an autophagy inhibitor, attenuated the sevoflurane-induced neuroinflammation and cognitive dysfunction, including the decreased freezing time and fewer platform crossings, in the neonate mice. 3-Methyladenine (3-MA) suppressed sevoflurane-induced expression of interleukin-6 and tumor necrosis factor-alpha in vitro. Moreover, sevoflurane activates IRF3, facilitating cytokine transcription in an AKT3-dependent manner. Mechanistically, sevoflurane-induced autophagic degradation of dehydrocholesterol-reductase-7 (DHCR7) resulted in accumulations of its substrate 7-dehydrocholesterol (7-DHC), mimicking the effect of sevoflurane on AKT3 activation and IRF3-driven cytokine expression. 3-MA significantly reversed sevoflurane-induced DHCR7 degradation, AKT phosphorylation, IRF3 activation, and the accumulation of 7-DHC in the hippocampal CA1 region. These findings pave the way for additional investigations aimed at developing novel strategies to mitigate postoperative cognitive impairment in pediatric patients.

Dexmedetomidine improves the circulatory dysfunction of the glymphatic system induced by sevoflurane through the PI3K/AKT/ΔFosB/AQP4 pathway in young mice.

Multiple sevoflurane exposures may damage the developing brain. The neuroprotective function of dexmedetomidine has been widely confirmed in animal experiments and human studies. However, the effect of dexmedetomidine on the glymphatic system has not been clearly studied. We hypothesized that dexmedetomidine could alleviate sevoflurane-induced circulatory dysfunction of the glymphatic system in young mice. Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 2 h daily, continuously for 3 days. Intraperitoneal injection of either normal saline or dexmedetomidine was administered before every anaesthesia. Meanwhile the circulatory function of glymphatic system was detected by tracer injection at P8 and P32. On P30-P32, behavior tests including open field test, novel object recognition test, and Y-maze test were conducted. Primary astrocyte cultures were established and treated with the PI3K activator 740Y-P, dexmedetomidine, and small interfering RNA (siRNA) to silence ΔFosB. We propose for the first time that multiple exposure to sevoflurane induces circulatory dysfunction of the glymphatic system in young mice. Dexmedetomidine improves the circulatory capacity of the glymphatic system in young mice following repeated exposure to sevoflurane through the PI3K/AKT/ΔFosB/AQP4 signaling pathway, and enhances their long-term learning and working memory abilities.