Diagnosis and rescue of malignant hyperthermia induced by anesthesia during radical surgery in a cervical cancer patient using the National Remote Emergency System: A case report.

RATIONALE: Malignant hyperthermia (MH) is a rare yet serious medical complication that typically arises following general anesthesia or the administration of specific anesthetics. Due to the infrequency of MH, anesthesiologists often lack sufficient expertise in identifying and managing it, leading to misdiagnosis and inappropriate treatment. There is an urgent need to enhance the diagnosis and management of MH through the utilization of relevant tools. PATIENT CONCERNS: In this case, a 52-year-old woman underwent radical cervical cancer surgery under general anesthesia, with no family or significant medical history. She experienced a gradual increase in end-tidal carbon dioxide (ETCO2) to a maximum of 75 mm Hg and a rise in body temperature from 36.5 to 37.5 °C in a very short period, as well as a blood gas analysis showing a pH of 7.217. DIAGNOSIS: The anesthesiologist immediately used The WeChat applet-based National Remote Emergency System for Malignant Hyperthermia (MH-NRES), and the score was 40, which indicated that the patient was very likely to have MH. INTERVENTIONS: We immediately discontinued sevoflurane and switched total intravenous anesthesia to maintain general anesthesia, with a rapid intravenous infusion of dantrolene sodium. OUTCOMES: The ETCO2 and the temperature quickly dropped to normal, followed by successful completion of the surgery, and the patient was discharged 8 days after surgery. LESSONS: The experience can provide a basis use of MH-NRES and improve the ability of anesthesiologists to deal with intraoperative MH as well as increase the survival probability of patients.

Endotracheal tube cuff rupture during anesthesia in 2 dogs.

A 15-year-old intact male dachshund dog weighing 4.3 kg and a 5-year-old intact male mixed-breed dog weighing 13.6 kg were referred for examination because of paraparesis and facial paralysis, respectively. Magnetic resonance imaging (MRI) of the thoracolumbar region and brain was performed. The dogs were premedicated with IV butorphanol, 0.2 mg/kg body weight (BW) and midazolam, 0.2 mg/kg BW. Anesthesia was induced with IV propofol, 4 to 5 mg/kg BW and maintained with sevoflurane in oxygen. The dachshund was orotracheally intubated with a 5.0-millimeter internal diameter endotracheal (ET) tube. During positioning in the MRI room, intermittent positive pressure ventilation (IPPV) was applied. The mixed-breed dog was orotracheally intubated with a 6.0-millimeter internal diameter ET tube. After inflation of the ET tube cuff, a leaking test was done by applying positive pressure ventilation. In both dogs, a distinct "popping" sound was heard when positive pressure was applied, after which air leakage from the cuff was evident. Failure to inflate the pilot balloon led to suspicion of a ruptured cuff. Reintubation was completed, both dogs remained stable during anesthesia, and no postanesthetic complications were observed. Rupture of both cuffs, which was visually confirmed, was thought to be caused by overinflation of the cuff, repeated sterilization of the ET tubes, and positive pressure ventilation. Repeated sterilization of ET tubes with ethylene oxide can alter the physical integrity of cuffs. Care should be taken not to overinflate ET tube cuffs, especially when they have been repeatedly sterilized, as cuff rupture may result in failure to provide adequate IPPV. Key clinical message: This report describes 2 cases in which ET tube cuff rupture was noted during anesthesia for MRI.

Rupture du ballonnet du tube endotrachéal pendant l'anesthésie chez 2 chiens. Un chien teckel mâle intact de 15 ans pesant 4,3 kg et un chien croisé mâle intact de 5 ans pesant 13,6 kg ont été référés pour examen en raison de paraparésie et de paralysie faciale, respectivement. Une imagerie par résonance magnétique (IRM) de la région thoraco-lombaire et du cerveau a été réalisée. Les chiens ont reçu une prémédication avec du butorphanol IV, 0,2 mg/kg de poids corporel (PC), et du midazolam, 0,2 mg/kg PC. L'anesthésie a été induite avec du propofol IV, 4 à 5 mg/kg de PC et maintenue avec du sévoflurane dans de l'oxygène. Le teckel a été intubé par voie orotrachéale avec un tube endotrachéal (TE) de diamètre interne de 5,0 millimètres. Lors du positionnement dans la salle d'IRM, une ventilation intermittente à pression positive (VIPP) a été appliquée. Le chien de race mixte a été intubé par voie orotrachéale avec un TE de 6,0 millimètres de diamètre interne. Après le gonflage du ballonnet du TE, un test d'étanchéité a été effectué en appliquant une ventilation à pression positive. Chez les deux chiens, un son distinct de « claquement ¼ a été entendu lorsqu'une pression positive a été appliquée, après quoi une fuite d'air du ballonnet est devenue évidente. Le fait de ne pas gonfler le ballon pilote a fait soupçonner une rupture du ballonnet. Une ré-intubation a été effectuée, les deux chiens sont restés stables pendant l'anesthésie et aucune complication post-anesthésique n'a été observée. La rupture des deux ballonnets, confirmée visuellement, aurait été causée par un surgonflage du ballonnet, une stérilisation répétée des TE et une ventilation à pression positive. La stérilisation répétée des TE avec de l'oxyde d'éthylène peut altérer l'intégrité physique des ballonnets. Il convient de veiller à ne pas surgonfler les ballonnets des TE, en particulier lorsqu'ils ont été stérilisés à plusieurs reprises, car la rupture du ballonnet peut entraîner l'incapacité de fournir une VIPP adéquate.Message clinique clé:Ce rapport décrit 2 cas dans lesquels une rupture du ballonnet du TE a été constatée lors d'une anesthésie pour IRM.(Traduit par Dr Serge Messier).

Effects of sevoflurane and fullerenol C60 on lower limb ischemia-reperfusion injury in streptozocin-induced diabetic mice.

BACKGROUND: Ischemia-reperfusion injury (IRI) poses a significant challenge for physicians, necessitating the management of cell damage and the preservation of organ functions. Various surgical procedures, such as vascular surgery on extremities, temporary cross-clamping of the abdominal aorta in aortic surgery, and the use of a tourniquet in extremity surgeries, may induce lower limb IRI. The susceptibility to IRI is heightened in individuals with diabetes. This study aimed to investigate the effects of fullerenol C60 and sevoflurane on mouse muscle tissue in a lower limb IRI model and to assess their potential in preventing complications arising from ischemia-reperfusion in mice with streptozocin-induced diabetes. METHODS: A total of 36 adult Swiss albino mice were randomly divided into six groups, each consisting of six mice: control group (group C), diabetes group (group D), diabetes-ischemia/reperfusion group (group DIR), diabetes-ischemia/reperfusion-fullerenol C60 group (group DIR-FC60), diabetes-ischemia/reperfusion-sevoflurane group (group DIR-S), and diabetes-ischemia/reperfusion-sevoflurane-fullerenol C60 group (DIR-S-FC60). Streptozocin (55 mg/kg) was intraperitoneally administered to induce diabetes in the relevant groups, with mice displaying blood glucose levels of 250 mg/dL or higher at 72 h were considered diabetic. After 4 weeks, all groups underwent laparotomy under anesthesia. In DIR-FC60 and DIR-S-FC60 groups, fullerenol C60 (100 mg/kg) was intraperitoneally administrated 30 min before the ischemia period. Sevoflurane, delivered in 100% oxygen at a rate of 2.3% and 4 L/min, was administered during the ischemia period in DIR-S and DIR-S-FC60 groups. In the IR groups, a microvascular clamp was placed on the infrarenal abdominal aorta for 120 min during the ischemia period, followed by the removal of the clamp and a 120-min reperfusion period. At the end of the reperfusion, gastrocnemius muscle tissues were removed for histopathological and biochemical parameter examinations. RESULTS: Histopathological examination revealed a significant reduction in the disorganization and degeneration of muscle cells in the DIR-S-FC60 group compared to the DIR group (p = 0.041). Inflammatory cell infiltration was notably lower in the DIR-S, DIR-FC60, and DIR-S-FC60 groups than in the DIR group (p = 0.031, p = 0.011, and p = 0.013, respectively). The total damage scores in the DIR-FC60 and DIR-S-FC60 groups were significantly lower than in the DIR group (p = 0.018 and p = 0.008, respectively). Furthermore, the levels of malondialdehyde (MDA) in the DIR-S, DIR-FC60, and DIR-S-FC60 groups were significantly lower than in the DIR group (p < 0.001, p < 0.001, and p < 0.001, respectively). Catalase (CAT) enzyme activity in the DIR-S, DIR-FC60, and DIR-S-FC60 groups was higher than in the DIR group (p = 0.001, p = 0.014, and p < 0.001, respectively). Superoxide dismutase (SOD) enzyme activity in the DIR-FC60 and DIR-S-FC60 groups was also higher than in the DIR group (p < 0.001 and p = 0.001, respectively). CONCLUSION: Our findings indicate that administering fullerenol C60 30 min prior to ischemia in diabetic mice, in combination with sevoflurane, led to a reduction in oxidative stress and the correction of IR-related damage in muscle tissue histopathology. We believe that the administration of fullerenol C60 before IR, coupled with sevoflurane administration during IR, exerts a protective effect in mice.

Influencing Factors of Delirium during Recovery in Urological Postoperative Patients Undergoing Sevoflurane Anaesthesia.

OBJECTIVE: To analyse the incidence and influencing factors of delirium during recovery in urological postoperative patients undergoing sevoflurane anaesthesia. METHODS: The clinical data of patients undergoing sevoflurane anaesthesia in the urology surgery department in our hospital from January 2022 to December 2022 were retrospectively analysed. The incidence of delirium during the recovery period was recorded by using the Chinese version of the Confusion Assessment Method (CAM) for Severity of Delirium after surgery, and the patients were divided into occurrence and non-occurrence groups. Whether delirium occurred during recovery was determined through univariate analysis. In binary logistic regression analysis, the occurrence of emergence delirium was the dependent variable, and the variables with statistical differences in the univariate analysis were the independent variables. The influencing factors of emergence delirium in post-urological surgery patients who underwent sevoflurane anaesthesia were determined. RESULTS: Delirium during recovery occurred in 10 of 100 patients (10.00%). Odds ratio (OR) of age (OR = 1.445, p = 0.022), history of diabetes (OR = 1.798, p = 0.010), operation time (OR = 1.670, p = 0.008), American Society of Anesthesiologists (ASA) classification (OR = 1.740, p = 0.006) and sevoflurane inhalation concentration (OR = 1.890, p = 0.001) are the influencing factors of postoperative delirium in urologic patients undergoing sevoflurane anaesthesia. CONCLUSIONS: Age, history of diabetes, operation time, ASA classification and sevoflurane inhalation concentration are the influencing factors.

Impact of various anesthetic regimens on motor-evoked potentials in infants undergoing spinal surgery: A case series.

Motor-evoked potential (MEP) monitoring is commonly used in children. MEP monitoring in infants is difficult due to smaller signals requiring higher stimulation voltages. There is limited information on the effect of different anesthetics on MEP monitoring in this age group. This case series describes the effect of different anesthetic regimens on MEP monitoring in infants. Patients <1 year of age who underwent spinal surgery with MEP monitoring between February 2022 and July 2023 at a single tertiary care children hospital were reviewed. The motor-evoked potential amplitudes were classified into 4 levels based on the voltage in the upper and lower limbs (none, responded, acceptable, sufficient). "Acceptable" or "sufficient" levels were defined as successful monitoring. A total of 19 infants were identified, involving 3 anesthesia regimens: 4/19 (21.1%) cases were anesthetized with propofol/remifentanil total intravenous anesthesia (TIVA), 3/19 (15.8%) with propofol/remifentanil/low-dose sevoflurane and another 12/19 (63.2%) cases who initially received propofol/remifentanil/sevoflurane and were converted to propofol/remifentanil anesthesia intraoperatively. The 4 cases with propofol/remifentanil showed 20/32 (62.5%) successful monitoring points. In contrast, 6/24 (25%) successful points were achieved with propofol/remifentanil intravenous anesthesia/0.5 age-adjusted minimum alveolar concentration sevoflurane. In 12 cases converted from propofol/remifentanil/low-dose inhalational anesthetics to TIVA alone, successful MEP monitoring points increased from 46/96 (47.9%) to 81/96 (84.4%). Adding low-dose inhalation anesthetic to propofol-based TIVA suppresses MEP amplitudes in infants. The optimal anesthetic regimen for infants requires further investigation.

Minimal alveolar concentration of sevoflurane in combination with remimazolam in adults during laryngeal mask insertion: an up-down sequential allocation study.

BACKGROUND: Remimazolam is a novel ultrashort-acting intravenous benzodiazepine sedative-hypnotic. The combination of remimazolam and sevoflurane does not increase respiratory sensitivity, produce bronchospasm, or cause other adverse conditions. We aimed to observe the effects of different remimazolam doses on the minimum alveolar concentration (MAC) of sevoflurane at end-expiration during laryngeal mask insertion and evaluate the effect of sex on the efficacy of the combination of remimazolam on the suppression of laryngeal mask insertion in adult patients. METHODS: We included 240 patients undergoing laparoscopic surgery under general anesthesia with elective placement of a laryngeal mask (120 males and 120 females). The patients were randomly divided into four groups according to sex: a control group (randomization for female patients, RF0; randomization for male patients, RM0) and three remimazolam groups (RF1, RM1 / RM2, RF2 / RM3, RF3), with 30 patients in each group. Induction was established by vital capacity rapid inhalation induction (VCRII), using 8% sevoflurane and 100% oxygen (6 L/min) in all patients. The (RF1, RM1), (RM2, RF2), and (RM3, RF3) groups were continuously injected with remimazolam at doses of 1, 1.5, and 2.0 mg/kg/h, respectively, while the (RM0, RF0) group was injected with an equal volume of normal saline. The end-expiratory concentration of sevoflurane was adjusted to a preset value after the patient's eyelash reflex disappeared. After the end-expiratory concentration of sevoflurane was kept stable for at least 15 min, the laryngeal mask was placed, and the patient's physical response to the mask placement was observed immediately and within 30 s of placement. The MAC of sevoflurane was measured using the up-and-down sequential method of Dixon. RESULTS: The calculated MAC of end-expiratory sevoflurane during laryngeal mask insertion in adult females was (2.94 ± 0.18)%, (2.69 ± 0.16)%, (2.32 ± 0.16)% and (1.83 ± 0.15)% in groups RF0, RF1, RF2 and RF3; (2.98 ± 0.18)%, (2.80 ± 0.19)%, (2.54 ± 0.15)% and (2.15 ± 0.15)% in male groups RM0, RM1, RM2 and RM3, respectively. The MAC values were significantly lower in the (RF1-RF3, RM1-RM3) group when compared to the (RF0, RM0) group. There was no significant difference between (RF0, RF1) and (RM0, RM1), but the MAC value of the RF2-RF3 group was significantly lower than that of the RM2-RM3 group. CONCLUSIONS: Remimazolam can effectively reduce end-expiratory sevoflurane MAC values during laryngeal mask placement in adults. When remimazolam was measured above 1.5 mg/kg/h, the effect of inhibiting laryngeal mask implantation in female patients was stronger than that in male patients. Remimazolam at a dose of 1-2 mg/kg/h combined with sevoflurane induction can be safely and effectively used in these patients.

Sirtuin 3 (SIRT3) improves sevoflurane-induced postoperative cognitive impairment by regulating mitochondrial oxidative stress.

One of the most prevalent co-operative disorders is postoperative cognitive dysfunction (POCD), however, its pathogenesis remains unclear. Thus, the aim of this work was to evaluate SIRT3's impact on cognitive decline in aged mice under anesthesia. Adeno-associated virus SIRT3 vector (AAV-SIRT3) or empty vector (AAV-VEH) was injected into the hippocampal region of aged mice after sevoflurane induction in order to upregulate the expression of SIRT3. The expression levels of SIRT3, pro-inflammatory cytokines, and apoptotic factors in hippocampus tissues were identified by PCR, Western blotting, TUNEL staining, and enzyme-linked immunosorbent assay (ELISA), and the cognitive function of mice was assessed. The SIRT3 expression was down-regulated in the hippocampal tissue of anesthetized mice. SIRT3 overexpression can improve the learning and memory ability, reduce the escape latency, and increase the residence time in the platform and platform crossing ability of mice. The overexpression of SIRT3 in hippocampus can reduce the oxidative stress response and inflammatory response induced by anesthesia in mice, increase the superoxide dismutase (SOD) expression level, and decrease the expression level of MDA and inflammatory factors in hippocampus. In addition, SIRT3 overexpression can also reduce anesthetic-induced hippocampal cell apoptosis. By reducing the hippocampus mitochondrial oxidative stress response, SIRT3 plays a significant role in the pathophysiology of POCD in mice and is a potential target for POCD treatment and diagnosis.

The role of astrocytic γ-aminobutyric acid in the action of inhalational anesthetics.

BACKGROUND: Inhalational anesthetics target the inhibitory extrasynaptic γ-aminobutyric acid type A (GABAA) receptors. Both neuronal and glial GABA mediate tonic inhibition of the extrasynaptic GABAA receptors. However, the role of glial GABA during inhalational anesthesia remains unclear. This study aimed to evaluate whether astrocytic GABA contributes to the action of different inhalational anesthetics. METHODS: Gene knockout of monoamine oxidase B (MAOB) was used to reduce astrocytic GABA levels in mice. The hypnotic and immobilizing effects of isoflurane, sevoflurane, and desflurane were assessed by evaluating the loss of righting reflex (LORR) and tail-pinch withdrawal response (LTWR) in MAOB knockout and wild-type mice. Minimum alveolar concentration (MAC) for LORR, time to LORR, MAC for LTWR and time to LTWR of isoflurane, sevoflurane, and desflurane were assessed. RESULTS: Time to LORR and time to LTWR with isoflurane were significantly longer in MAOB knockout mice than in wild-type mice (P < 0.001 and P = 0.032, respectively). Time to LORR with 0.8 MAC of sevoflurane was significantly longer in MAOB knockout mice than in wild-type mice (P < 0.001), but not with 1.0 MAC of sevoflurane (P=0.217). MAC for LTWR was significantly higher in MAOB knockout mice exposed to sevoflurane (P < 0.001). With desflurane, MAOB knockout mice had a significantly higher MAC for LORR (P = 0.003) and higher MAC for LTWR (P < 0.001) than wild-type mice. CONCLUSIONS: MAOB knockout mice showed reduced sensitivity to the hypnotic and immobilizing effects of isoflurane, sevoflurane, and desflurane. Behavioral tests revealed that the hypnotic and immobilizing effects of inhalational anesthetics would be mediated by astrocytic GABA.

Echinatin mitigates sevoflurane-induced neurotoxicity through regulation of ferroptosis and iron homeostasis.

Surgery and anesthesia are vital medical interventions, but concerns over their potential cognitive side effects, particularly with the use of inhalational anesthetics like sevoflurane, have surfaced. This study delves into the neuroprotective potential of Echinatin against sevoflurane-induced neurotoxicity and the underlying mechanisms. Echinatin, a natural compound, has exhibited anti-inflammatory, antioxidant, and anticancer properties. Sevoflurane, while a popular anesthetic, is associated with perioperative neurocognitive disorders (PND) and neurotoxicity. Our investigation began with cellular models, where Echinatin demonstrated a significant reduction in sevoflurane-induced apoptosis. Mechanistically, we identified ferroptosis, a novel form of programmed cell death characterized by iron accumulation and lipid peroxidation, as a key player in sevoflurane-induced neuronal injury. Echinatin notably suppressed ferroptosis in sevoflurane-exposed cells, suggesting a pivotal role in neuroprotection. Expanding our research to a murine model, we observed perturbations in iron homeostasis, inflammatory cytokines, and antioxidants due to sevoflurane exposure. Echinatin treatment effectively restored iron balance, mitigated inflammation, and preserved antioxidant levels in vivo. Behavioral assessments using the Morris water maze further confirmed Echinatin's neuroprotective potential, as it ameliorated sevoflurane-induced spatial learning and memory impairments. In conclusion, our study unveils Echinatin as a promising candidate for mitigating sevoflurane-induced neurotoxicity. Through the regulation of ferroptosis, iron homeostasis, and inflammation, Echinatin demonstrates significant neuroprotection both in vitro and in vivo. These findings illuminate the potential for Echinatin to enhance the safety of surgical procedures involving sevoflurane anesthesia, minimizing the risk of cognitive deficits and neurotoxicity.

Similarity and dissimilarity in alterations of the gene expression profile associated with inhalational anesthesia between sevoflurane and desflurane.

Although sevoflurane is one of the most commonly used inhalational anesthetic agents, the popularity of desflurane is increasing to a level similar to that of sevoflurane. Inhalational anesthesia generally activates and represses the expression of genes related to xenobiotic metabolism and immune response, respectively. However, there has been no comprehensive comparison of the effects of sevoflurane and desflurane on the expression of these genes. Thus, we used a next-generation sequencing method to compare alterations in the global gene expression profiles in the livers of rats subjected to inhalational anesthesia by sevoflurane or desflurane. Our bioinformatics analyses revealed that sevoflurane and, to a greater extent, desflurane significantly activated genes related to xenobiotic metabolism. Our analyses also revealed that both anesthetic agents, especially sevoflurane, downregulated many genes related to immune response.

The role of perioperative sedative anesthetics in preventing postoperative delirium: a systematic review and network-meta analysis including 6679 patients.

OBJECTIVE: Postoperative delirium is a common and debilitating complication that significantly affects patients and their families. The purpose of this study is to investigate whether there is an effective sedative that can prevent postoperative delirium while also examining the safety of using sedatives during the perioperative period. METHODS: The net-meta analysis was used to compare the incidence of postoperative delirium among four sedatives: sevoflurane, propofol, dexmedetomidine, and midazolam. Interventions were ranked according to their surface under the cumulative ranking curve (SUCRA). RESULTS: A total of 41 RCT studies involving 6679 patients were analyzed. Dexmedetomidine can effectively reduce the incidence of postoperative delirium than propofol (OR 0.47 95% CI 0.25-0.90), midazolam (OR 0.42 95% CI 0.17-1.00), normal saline (OR 0.42 95% CI 0.33-0.54) and sevoflurane (OR 0.39 95% CI 0.18-0.82). The saline group showed a significantly lower incidence of bradycardia compared to the group receiving dexmedetomidine (OR 0.55 95% CI 0.37-0.80). In cardiac surgery, midazolam (OR 3.34 95%CI 2.04-5.48) and normal saline (OR 2.27 95%CI 1.17-4.39) had a higher rate of postoperative delirium than dexmedetomidine, while in non-cardiac surgery, normal saline (OR 1.98 95%CI 1.44-2.71) was more susceptible to postoperative delirium than dexmedetomidine. CONCLUSION: Our analysis suggests that dexmedetomidine is an effective sedative in preventing postoperative delirium whether in cardiac surgery or non-cardiac surgery. The preventive effect of dexmedetomidine on postoperative delirium becomes more apparent with longer surgical and extubation times. However, it should be administered with caution as it was found to be associated with bradycardia.

Involvement of Fgf2-mediated tau protein phosphorylation in cognitive deficits induced by sevoflurane in aged rats.

OBJECTIVE: Anesthetics have been linked to cognitive alterations, particularly in the elderly. The current research delineates how Fibroblast Growth Factor 2 (Fgf2) modulates tau protein phosphorylation, contributing to cognitive impairments in aged rats upon sevoflurane administration. METHODS: Rats aged 3, 12, and 18 months were subjected to a 2.5% sevoflurane exposure to form a neurotoxicity model. Cognitive performance was gauged, and the GEO database was employed to identify differentially expressed genes (DEGs) in the 18-month-old cohort post sevoflurane exposure. Bioinformatics tools, inclusive of STRING and GeneCards, facilitated detailed analysis. Experimental validations, both in vivo and in vitro, examined Fgf2's effect on tau phosphorylation. RESULTS: Sevoflurane notably altered cognitive behavior in older rats. Out of 128 DEGs discerned, Fgf2 stood out as instrumental in regulating tau protein phosphorylation. Sevoflurane exposure spiked Fgf2 expression in cortical neurons, intensifying tau phosphorylation via the PI3K/AKT/Gsk3b trajectory. Diminishing Fgf2 expression correspondingly curtailed tau phosphorylation, neurofibrillary tangles, and enhanced cognitive capacities in aged rats. CONCLUSION: Sevoflurane elicits a surge in Fgf2 expression in aging rats, directing tau protein phosphorylation through the PI3K/AKT/Gsk3b route, instigating cognitive aberrations.

Prelimbic cortical pyramidal neurons to ventral tegmental area projections promotes arousal from sevoflurane anesthesia.

AIMS: General anesthesia has been used in surgical procedures for approximately 180 years, yet the precise mechanism of anesthetic drugs remains elusive. There is significant anatomical connectivity between the ventral tegmental area (VTA) and the prelimbic cortex (PrL). Projections from VTA dopaminergic neurons (VTADA ) to the PrL play a role in the transition from sevoflurane anesthesia to arousal. It is still uncertain whether the prelimbic cortex pyramidal neuron (PrLPyr ) and its projections to VTA (PrLPyr -VTA) are involved in anesthesia-arousal regulation. METHODS: We employed chemogenetics and optogenetics to selectively manipulate neuronal activity in the PrLPyr -VTA pathway. Electroencephalography spectra and burst-suppression ratios (BSR) were used to assess the depth of anesthesia. Furthermore, the loss or recovery of the righting reflex was monitored to indicate the induction or emergence time of general anesthesia. To elucidate the receptor mechanisms in the PrLPyr -VTA projection's impact on anesthesia and arousal, we microinjected NMDA receptor antagonists (MK-801) or AMPA receptor antagonists (NBQX) into the VTA. RESULTS: Our findings show that chemogenetic or optogenetic activation of PrLPyr neurons prolonged anesthesia induction and promoted emergence. Additionally, chemogenetic activation of the PrLPyr -VTA neural pathway delayed anesthesia induction and promoted anesthesia emergence. Likewise, optogenetic activation of the PrLPyr -VTA projections extended the induction time and facilitated emergence from sevoflurane anesthesia. Moreover, antagonizing NMDA receptors in the VTA attenuates the delayed anesthesia induction and promotes emergence caused by activating the PrLPyr -VTA projections. CONCLUSION: This study demonstrates that PrLPyr neurons and their projections to the VTA are involved in facilitating emergence from sevoflurane anesthesia, with the PrLPyr -VTA pathway exerting its effects through the activation of NMDA receptors within the VTA.

Influencing Factors of Delirium during Recovery in Urological Postoperative Patients Undergoing Sevoflurane Anaesthesia

Objective: To analyse the incidence and influencing factors of delirium during recovery in urological postoperative patients undergoing sevoflurane anaesthesia. Methods: The clinical data of patients undergoing sevoflurane anaesthesia in the urology surgery department in our hospital from January 2022 to December 2022 were retrospectively analysed. The incidence of delirium during the recovery period was recorded by using the Chinese version of the Confusion Assessment Method (CAM) for Severity of Delirium after surgery, and the patients were divided into occurrence and non-occurrence groups. Whether delirium occurred during recovery was determined through univariate analysis. In binary logistic regression analysis, the occurrence of emergence delirium was the dependent variable, and the variables with statistical differences in the univariate analysis were the independent variables. The influencing factors of emergence delirium in post-urological surgery patients who underwent sevoflurane anaesthesia were determined. Results: Delirium during recovery occurred in 10 of 100 patients (10.00%). Odds ratio (OR) of age (OR = 1.445, p = 0.022), history of diabetes (OR = 1.798, p = 0.010), operation time (OR = 1.670, p = 0.008), American Society of Anesthesiologists (ASA) classification (OR = 1.740, p = 0.006) and sevoflurane inhalation concentration (OR = 1.890, p = 0.001) are the influencing factors of postoperative delirium in urologic patients undergoing sevoflurane anaesthesia. Conclusions: Age, history of diabetes, operation time, ASA classification and sevoflurane inhalation concentration are the influencing factors. (AU)

mtDNA-cGAS-STING axis-dependent NLRP3 inflammasome activation contributes to postoperative cognitive dysfunction induced by sevoflurane in mice.

The activation of NLRP3 inflammasome in microglia is critical for neuroinflammation during postoperative cognitive dysfunction (POCD) induced by sevoflurane. However, the molecular mechanism by which sevoflurane activates the NLRP3 inflammasome in microglia remains unclear. The cGAS-STING pathway is an evolutionarily conserved inflammatory defense mechanism. The role of the cGAS-STING pathway in sevoflurane-induced NLRP3 inflammasome-dependent neuroinflammation and the underlying mechanisms require further investigation. We found that prolonged anesthesia with sevoflurane induced cognitive dysfunction and triggered the neuroinflammation characterized by the activation of NLRP3 inflammasome in vivo. Interestingly, the cGAS-STING pathway was activated in the hippocampus of mice receiving sevoflurane. While the blockade of cGAS with RU.521 attenuated cognitive dysfunction and NLRP3 inflammasome activation in mice. In vitro, we found that sevoflurane treatment significantly activated the cGAS-STING pathway in microglia, while RU.521 pre-treatment robustly inhibited sevoflurane-induced NLRP3 inflammasome activation. Mechanistically, sevoflurane-induced mitochondrial fission in microglia and released mitochondrial DNA (mtDNA) into the cytoplasm, which could be abolished with Mdivi-1. Blocking the mtDNA release via the mPTP-VDAC channel inhibitor attenuated sevoflurane-induced mtDNA cytosolic escape and reduced cGAS-STING pathway activation in microglia, finally inhibiting the NLRP3 inflammasome activation. Therefore, regulating neuroinflammation by targeting the cGAS-STING pathway may provide a novel therapeutic target for POCD.

Uso tópico de sevoflurano en heridas complejas de miembro inferior / Topical use of sevoflurane in complex lower limb wounds

El dolor crónico asociado a heridas de larga evolución en miembros inferiores constituye una situación de conflicto con características angustiantes que compromete seriamente la calidad de vida e interfiere en el proceso de reparación tisular, estableciendo un cuadro propio en el cual la herida se transforma en un componente más de esta compleja condición y no el motivo en sí de la consulta. Dadas las limitaciones y efectos negativos de las terapias usuales para el alivio del dolor crónico en heridas, se establece una apertura a nuevas propuestas adyuvantes. Motivo de ello es el propósito del presente trabajo, a través del uso de sevoflurano tópico para evaluar el incremento de la analgesia en una población con úlceras en miembro inferior de diverso origen etiológico.

Sevoflurane exerts antidepressant-like effects via the BDNF-TrkB pathway.

Depression has emerged as the predominant psychiatric affliction affecting individuals. Prior research has substantiated the antidepressant properties exhibited by numerous anesthetics. Sevoflurane, a widely utilized inhalant anesthetic in clinical practice, remains relatively uncharted in terms of its specific antidepressant effects. In this study, we used open field test, forced swimming test and novelty-suppressed feeding test to investigate the anxiety and depression-like behaviors in C57BL/6 mice following the inhalation of sevoflurane. We then used western blotting to scrutinized the expression levels of proteins associated with the brain-derived neurotrophic factor (BDNF)-tryosine receptor kinase B (TrkB) pathway in the hippocampus and prefrontal cortex. To further investigate whether sevoflurane exerts antidepressant-like effects via the BDNF-TrkB pathway, we downregulated TrkB expression by administering siRNA into the lateral ventricle. We found that the inhalation of 2.5 % sevoflurane exerted a significant antidepressant-like effect, accompanied by an elevation in p-TrkB expression levels in the hippocampus and prefrontal cortex. Intriguingly, this antidepressant-like effect was abrogated following the downregulation of TrkB expression through the microinjection of siRNA into the lateral ventricle. In conclusion, this study provides evidence supporting the notion that sevoflurane exerts its antidepressant-like effect via the BDNF-TrkB signaling pathway.

Liraglutide improves sevoflurane-induced postoperative cognitive dysfunction via activating autophagy and inhibiting apoptosis.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients. Liraglutide (LRG) has high homology (97%) with natural glucagon like peptide-1, and it has been proved to be effective in some nervous system diseases. Whether LRG could regulate POCD has not been reported. METHODS: Sevoflurane (Sev) was used to simulate postoperative cognitive dysfunction (POCD) model. Morris water maze test was performed to evaluate the memory ability and neurological function of rats. Escape latency, swim distance, crossing platform times, average velocity, and targeting quadrant time were analyzed. The cell apoptosis, mRNA and protein expression were measured through flow cytometry, PCR, and western blotting, respectively. RESULTS: LRG significantly improved the memory ability and neurological function of Sev-treated rats, but 3-MA reversed the effects of LRG. LRG remarkably inhibited apoptosis but up-regulated autophagy related proteins both in vivo and in vitro levels. However, knocking down AMPK could markedly reverse the influence of LRG on apoptosis, autophagy, and cell apoptosis. CONCLUSIONS: LRG induced autophagy activation can maintain cell homeostasis and promote cell survival by blocking the apoptotic pathway. LRG could improve Sev-induced POCD via activating autophagy, inhibiting apoptosis, and regulating AMPK/mTOR signaling pathway. This study provides a novel therapeutic strategy for the prevention and treatment of POCD.

Effect of propofol and sevoflurane on postoperative fatigue after laparoscopic hysterectomy.

BACKGROUND: Postoperative fatigue syndrome (POFS) is an important factor in postoperative recovery. However, the effect of anesthetic drugs on postoperative fatigue in female patients has been rarely studied. This study compared the effects of maintaining general anesthesia with propofol or sevoflurane on the incidence of POFS in patients undergoing laparoscopic hysterectomy. METHODS: This prospective, single-blind, randomized controlled trial enrolled patients scheduled for laparoscopic hysterectomy. Eligible patients were randomized into the propofol and sevoflurane groups. The primary outcome was the incidence of POFS within 30 Days, defined by a simplified identity consequence fatigue scale (ICFS-10) scores≥24 or Visual Analogue Scale (VAS) scores of fatigues>6. Secondary outcomes were perioperative grip strength, early ambulation and anal exhaust after surgery, and inpatient days. RESULTS: 32 participants were assigned to the propofol group (P) and 33 to the sevoflurane group (S). Incidence of POFS on postoperative D1 was P (8/32) vs. S (10/33) (p = 0.66, 95% confidence interval [CI]: 16.4-27.00); D3 P (2/32) vs. S (5/33) (p = 0.45,95% CI:5.96-23.76). POFS were not found on postoperative D5 and D30. There were no differences in perioperative grip strength, early ambulation and anal exhaust after surgery, and inpatient days between the two groups. CONCLUSIONS: POFS after scheduled laparoscopic hysterectomy was unaffected by anesthesia with propofol vs. sevoflurane. The incidence of POFS was highest on the first postoperative day, at 27.7%, and declined progressively over the postoperative 30 days. Trial registration Chinese Clinical Trial Registry (No. ChiCTR 2,000,033,861), registered on 14/06/2020).

Effect of fullerenol C60 on lung and renal tissue in lower extremity ischemia­reperfusion injury in sevoflurane­treated rats.

The aim of the present study was to examine the effect of fullerenol C60 on lung and kidney tissue in sevoflurane­treated rats with lower extremity ischemia­reperfusion (IR) injury. A total of 30 Wistar albino rats weighing 225­275 g were used and were equally divided into five groups (n=6/group): i) Sham; ii) IR; iii) IR­fullerenol C60 (IR­FUL); iv) IR­sevoflurane; and v) IR­fullerenol C60­sevoflurane (IR­FUL­SEVO). Fullerenol C60 was administered intraperitoneally prior to lower extremity IR induction and sevoflurane was administered during the IR injury. Subsequently, lung and kidney histopathological examinations, and serum biochemical analyses were performed. Lung tissue showed markedly increased congestion and neutrophil infiltration in the IR group compared with in the sham group, and notable decreases in congestion and neutrophil infiltration were observed in the treatment groups compared with in the IR group. In the histopathological evaluation of the kidney samples, vacuolization, loss of brush border in tubular epithelial cells, tubular epithelial loss and varying degrees of tubular damage were observed in all groups that underwent IR. There was a significant increase in the mean renal tubule injury score in all IR groups compared with that in the sham group. In addition, the mean kidney injury score was significantly lower in the IR­FUL and IR­FUL­SEVO groups than that in the IR group. It was observed that the expression levels of tumor necrosis factor­α, interleukin 1ß and intercellular adhesion molecule 1 in the lung and kidney tissues were increased following IR, and were decreased in the groups treated with fullerenol C60 and sevoflurane. Notably, it was determined that the reduction in cytokine expression was greatest in the IR­FUL group. When the oxidant status parameters in the lungs and kidneys were examined, thiobarbituric acid reactive substances levels, and catalase and glutathione S­transferase enzyme activities were significantly different in the groups receiving sevoflurane or fullerenol C60 treatment compared with those in the IR group. The present study demonstrated the protective effects of fullerenol C60 on the lung and kidney tissues of rats under sevoflurane anesthesia after establishment of lower extremity IR. The results of the present study showed that fullerenol C60 can reduce oxidative and histopathological damage in the lungs and kidneys following IR of the lower extremities.