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Surgical resection is the best-known approach for breast cancer treatment. However, post-operative metastases increase the rate of death. The potential effect of anesthetic drugs on long-term tumor growth, risk of metastasis, and recurrence after surgery has been investigated in cancer patients. However, the underlying mechanisms remain unclear. Therefore, we aimed to elucidate the anti-metastatic effect of lidocaine combined with common anesthetics and its mechanisms of action on lung metastasis in breast cancer models. The combination of lidocaine with propofol or sevoflurane inhibited the growth of TNBC cells compared to treatment alone. In addition, the combination effectively inhibited cancer cell migration and invasion. It suppressed tumor growth and increased the survival rate in breast 4 T1 orthotopic models. More importantly, it inhibited lung metastasis and recurrence compared with groups treated with a single anesthetic. In co-culture with TAMs and TNBC cells, lidocaine not only reduced M2-tumor-associated macrophages (TAM) that were increased by sevoflurane or propofol but also increased M1 macrophage polarization, impeding tumor growth in TNBC. Also, we found that the transforming growth factor-β (TGF-β) derived from TAMs increased EMT signaling in TNBC cells, and that lidocaine affected cancer cells as well as M2-TAMs, inducing M2 to M1 reprogramming and decreasing TGF-β/Smads-mediated EMT signaling in TNBC cells, leading to inhibition of cancer metastasis and recurrence. These findings suggest lidocaine combined with general anesthetics as a potential therapeutic approach for the inhibition of recurrence and metastasis of breast cancer patients undergoing curative resection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: To conduct a systematic review looking into the use of sevoflurane in the management of status asthmaticus (SA) in adults., Methods: We performed a systematic search on PubMed, EMBASE, and The Cochrane Library - CENTRAL through 23rd August 2023, restricting to studies reported in English. We included studies reporting use of sevoflurane in asthmatics beyond its use as an anaesthetic agent in surgeries i.e. in the emergency department (ED) and critical care setting, and focused on patient's clinical parameters, ventilation pressures and weaning of invasive ventilation., Results: A total of 13 publications fulfilled the inclusion criteria, comprising of 18 cases. All publications were of case reports/ series and conference abstracts, and no randomised trials were available. Most patients required intubation despite best medical management before sevoflurane administration, and high airway pressures and respiratory acidosis were apparent. There was significant heterogeneity regarding severity of asthma, treatment instituted, and the delivery, duration and concentration of sevoflurane administered. Many of the studies also did not quantify the changes in parameters pre- and post-sevoflurane. Sixteen patients experienced improvements in clinical status with sevoflurane administration-one required escalation to extracorporeal membrane oxygenation (ECMO), and another did not survive., Conclusion: The systematic review suggests sevoflurane can be a valuable treatment option in SA. As these cases are rare and heterogenous, further prospective case series are needed to support this., (© 2024. The Author(s).)

Background: Remimazolam is manifested by rapid action, hemodynamic stability, and fast recovery. Our study aimed to investigate whether the quality of recovery (QoR) after remimazolam anesthesia in patients undergoing transurethral resection of bladder tumor, which is predominantly performed in the elderly population, is not inferior to that after conventional anesthesia using sevoflurane., Methods: Thirty-four patients were randomly allocated into either of group S (n = 17, receiving sevoflurane anesthesia), or group R (n = 17, receiving remimazolam anesthesia). The QoR was assessed by Korean version of QoR-15 questionnaire, on the day before and after the surgery. Scores acquired for each individual item, QoR-15 scores categorized into 5 dimensions (physical comfort, physical independence, psychological support, emotional state, and pain), and overall global score were subjected to comparative analysis. The primary outcome was postoperative global QoR-15, and a noninferiority delta value of 8.0 was employed., Results: The postoperative global QoR-15 in the group S was 141 (134-146), and in the groups R was 133 (128-142) (P = .152). The mean difference of global QoR-15 (group S-group R) was 1.471 (95% confidence interval of -10.204 to 13.146), and the lower 95% confidence interval margin was lower than the noninferiority margin of -8.0. When comparing the QoR-15 sorted by 5 dimensions, pain scored higher in the group S (20 [18-20]) compared to the group R (15 [15-20], P = .032)., Conclusion: The postoperative QoR following transurethral resection of bladder tumor was found to be lower in patients anesthetized with remimazolam in comparison to those anesthetized with sevoflurane., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Laparoscopy represented one of the most innovative surgical techniques approached in the surgery field. Dexmedetomidine association with general anesthesia promotes the response control to trauma by altering the neuroinflammatory reflex, provides better clinical outcomes in the postoperative period and reduces the excessive use of drugs with risk for addiction. This trial aims to evaluate the potential drug treatment of dexmedetomidine on organic function, with the targets in neuroinflammation, perioperative pain control and blood pressure measurements in a medium-sized surgical model., Methods: Fifty-two patients were randomized in two groups: Sevoflurane and Dexmedetomidine - A (dexmedetomidine infusion [1 μg/kg loading, .2-.5 μg/kg/h thereafter]) vs Sevoflurane and Saline .9% - B. Three blood samples were collected at three times: before surgery, 4 to 6 hours after surgery and 24 hours postoperatively. The primary outcome was inflammatory and endocrine mediators dosage analisys. Finally, we evaluated pain and opioid use as secondary outcomes, also the hemodynamic values., Results: In Dexmedetomidine group A, a reduction of Interleukin 6 was found during 4-6 hours after surgery. A reduction of IL-10 was noted in the measurement of its values 24 hours after the procedure, with statistical significance. Also, systolic and diastolic blood pressure, as well heart rate were attenuated, and there was a lower incidence of pain and opioid consumption in the first postoperative hour ( P < .0001) in the anesthetic recovery room., Conclusions: Dexmedetomidine provided anti-inflammatory activity, sympatholytic effect and analgesia with cardiovascular safety. It reinforces the therapeutic nature of highly selective α2-adrenergic agonists when combined within anesthetic interventions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Intraoperative opioid use has a positive relationship with postoperative nausea and vomiting (PONV), and opioid-free anaesthesia (OFA) might reduce PONV. We investigated whether OFA compared with opioid-based anaesthesia would reduce PONV during the first 2 postoperative days among patients undergoing thoracoscopic lung resection., Methods: In this randomised controlled trial, 120 adult patients were randomly assigned (1:1, stratified by sex) to receive either OFA with esketamine, dexmedetomidine, and sevoflurane, or opioid-based anaesthesia with sufentanil and sevoflurane. A surgical pleth index (SPI) of 20-50 was applied for intraoperative analgesia provision. All subjects received PONV prophylaxis (dexamethasone and ondansetron) and multimodal analgesia (flurbiprofen axetil, ropivacaine wound infiltration, and patient-controlled sufentanil). The primary outcome was the occurrence of PONV during the first 48 h after surgery., Results: The median age was 53 yr and 66.7% were female. Compared with opioid-based anaesthesia, OFA significantly reduced the incidence of PONV (15% vs 31.7%; odds ratio [OR]=0.38, 95% confidence interval [CI], 0.16-0.91; number needed to treat, 6; P=0.031). Secondary and safety outcomes were comparable between groups, except that OFA led to a lower rate of vomiting (OR=0.23, 95% CI, 0.08-0.77) and a longer length of PACU stay (median difference=15.5 min, 95% CI, 10-20 min). The effects of OFA on PONV did not differ in the prespecified subgroups of sex, smoking status, and PONV risk scores., Conclusions: In the context of PONV prophylaxis and multimodal analgesia, SPI-guided opioid-free anaesthesia halved the incidence of PONV after thoracoscopic lung resection, although it was associated with a longer stay in the PACU., Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200059710)., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Sevoflurane (SEV), a commonly used inhalational anesthetic, reportedly inhibits colorectal cancer (CRC) malignancy, but whether SEV can inhibit the malignancy of CRC by regulating circular RNAs (circRNAs) remains unclear. Therefore, we aimed to identify specific circRNAs that may be affected by SEV and to investigate their functional roles in CRC., Methods: RT-qPCR was employed to detect the expression of circRNAs and mRNAs in CRC cells and tissues. Fluorescence in situ hybridization (FISH) was used to determine the location of circSKA3. Protein expression was assessed by western blot analysis. Function-based in vitro and in vivo experiments, including CCK-8, colony formation, transwell, and apoptosis assays and mouse xenograft tumor models, were conducted using circSKA3-knockdown and circSKA3-overexpression cell lines. RNA immunoprecipitation, RNA pull-down and mass spectrometry analyses were performed to explore the related mechanism., Results: Our findings revealed that SEV could inhibit CRC cell activity, proliferation and migration and promote apoptosis in CRC cells. We found that circSKA3 was upregulated in CRC and associated with poorer survival and that its expression could be reduced by SEV. The overexpression of circSKA3 reversed the effects of SEV on inhibiting cell activity, proliferation and migration and promoting apoptosis. The mechanistic analysis revealed that circSKA3 could bind to the ARM structural domain of β-catenin and thereby disrupt its interaction with the CK1/GSK3β/β-TrCP1 destruction complex, resulting in the ubiquitinated degradation of β-catenin and the activation of Wnt/β-catenin signaling. In addition, SEV downregulated circSKA3 in vivo to inhibit tumor growth., Conclusions: All the results showed that SEV could inhibit CRC progression via circSKA3 by increasing β-catenin ubiquitination degradation., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: Intravenous anesthetics have excellent analgesic activity without inducing the side effect in the respiratory system. The aim and objective of the current experimental study was to access the neuroprotective effect of sevoflurane against isoflurane induced cognitive dysfunction in rats., Methods: Isoflurane was used for induction the neurodysfunction in the rats, and rats received the oral administration of sevoflurane (2.5, 5 and 10 mg/kg). Morris water test was carried out for the estimation of cognitive function. Neurochemical parameters, antioxidant parameters and pro-inflammatory cytokines were also estimated., Results: Sevoflurane significantly (P < 0.001) altered the neurochemical parameters such as anti-choline acetyltransferase, acetylcholine esterase, acetylcholine, protein carbonyl, choline brain-derived neurotrophic factor, and amyloid β; antioxidant parameters such as glutathione, superoxide dismutase, and malondialdehyde; pro-inflammatory cytokines include interleukin (IL-2, IL-10, IL-4, IL-6, IL-10, IL-1β), and tumor necrosis factor-α. Sevoflurane significantly reduced the activity of caspase-3., Conclusions: Sevoflurane exhibited the neuroprotection against the cognitive dysfunction in rats via anti-inflammatory and antioxidant mechanism.

Sevoflurane, commonly administered to children as anesthesia, often leads to emergence delirium (ED). Currently, a consensus is lacking among clinicians regarding pharmacological interventions to improve recovery. To determine an effective approach, we compared the effects of several drugs in lowering the incidence of ED after sevoflurane anesthesia in children.We searched online databases for relevant randomized controlled trials (59 studies selected; 5199 NMA-eligible participants) and performed a frequentist network meta-analysis (NMA). This study was registered on PROSPERO (number CRD: 42022329939).All included studies had a low to moderate risk of overall bias. The incidence of ED after sevoflurane anesthesia in children differed according to other drugs administered, and were ranked from high to low according to the surface under the cumulative ranking curve (SUCRA).Sufentanil (91.2%) and dexmedetomidine (77.6%) were more likely to reduce the incidence (SUCRA value) of ED, whereas the placebo (6.5%), ramelteon (11.1%), and magnesium (18%) were less likely to reduce the incidence of ED. Remifentanil (89.3%) ranked first in shortening emergence time, followed by placebo (82.4%) and ketamine (69.7%). Placebo shortened extubation time, followed by remifentanil (66.5%) and alfentanil (61.4%).Sufentanil and remifentanil lowered sevoflurane-induced ED incidences among children and shortened the emergence time more effectively than other drugs. Most adjuvant drugs that are combined with sevoflurane either do not change or may even prolong extubation time. Further research and clinical trials are required to support and update these conclusions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Sevoflurane is suggested to exert protective functions against myocardial ischemia-reperfusion injury (MIRI). However, the particular mechanism remains elusive. Therefore, this research explored the mechanism of sevoflurane in MIRI-induced damage and pyroptosis., Methods: Subsequent to gain-or loss-of-function assays or/and sevoflurane treatment, the MIRI model was developed in rats. Cardiac function and body and heart weight of rats were evaluated, followed by measurement of apoptosis and creatine kinase MB (CK-MB), lactate dehydrogenase (LDH), and pyroptosis-related protein levels. After loss-of-function assays or/and sevoflurane treatment in human cardiomyocytes (HCMs), the hypoxia/reoxygenation (H/R) model was constructed. In HCMs, cell viability, apoptosis, and pyroptosis-related proteins were detected. Circular RNA PAN3 (circPAN3), microRNA (miR)-29b-3p, and stromal cell-derived factor 4 (SDF4) expression was determined in rat myocardial tissues and HCMs. Mechanistically, interactions among circPAN3, miR-29b-3p, and SDF4 were analyzed., Results: MIRI modeling increased miR-29b-3p expression and diminished circPAN3 and SDF4 expression in H/R-treated HCMs and MIRI rats, which was nullified by sevoflurane preconditioning. Mechanistically, circPAN3 negatively targeted miR-29b-3p to upregulate SDF4. Moreover, sevoflurane preconditioning reduced heart weight/body weight ratio, LDH, CK-MB, myocardial infarct size, left ventricular end-diastolic pressure, apoptosis, and pyroptosis, while elevating the increase and decrease of left ventricular pressure (±dp/dt max ) and left ventricular systolic pressure in MIRI rats. In addition, sevoflurane preconditioning augmented viability while diminishing apoptosis and pyroptosis in H/R-treated HCMs. Moreover, circPAN3 silencing or miR-29b-3p overexpression abrogated alleviatory effects of sevoflurane on myocardial injury and pyroptosis in vitro., Conclusion: Sevoflurane treatment ameliorated myocardial injury and pyroptosis in MIRI via circPAN3/miR-29b-3p/SDF4 axis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Preclinical studies in acute respiratory distress syndrome (ARDS) have suggested that inhaled sevoflurane may have lung-protective effects and clinical trials are ongoing to assess its impact on major clinical outcomes in patients with ARDS. However, the underlying mechanisms of these potential benefits are largely unknown. This investigation focused on the effects of sevoflurane on lung permeability changes after sterile injury and the possible associated mechanisms., Methods: To investigate whether sevoflurane could decrease lung alveolar epithelial permeability through the Ras homolog family member A (RhoA)/phospho-Myosin Light Chain 2 (Ser19) (pMLC)/filamentous (F)-actin pathway and whether the receptor for advanced glycation end-products (RAGE) may mediate these effects. Lung permeability was assessed in RAGE -/- and littermate wild-type C57BL/6JRj mice on days 0, 1, 2, and 4 after acid injury, alone or followed by exposure at 1% sevoflurane. Cell permeability of mouse lung epithelial cells was assessed after treatment with cytomix (a mixture of TNFɑ, IL-1β, and IFNγ) and/or RAGE antagonist peptide (RAP), alone or followed by exposure at 1% sevoflurane. Levels of zonula occludens-1, E-cadherin, and pMLC were quantified, along with F-actin immunostaining, in both models. RhoA activity was assessed in vitro., Results: In mice after acid injury, sevoflurane was associated with better arterial oxygenation, decreased alveolar inflammation and histological damage, and non-significantly attenuated the increase in lung permeability. Preserved protein expression of zonula occludens-1 and less increase of pMLC and actin cytoskeletal rearrangement were observed in injured mice treated with sevoflurane. In vitro, sevoflurane markedly decreased electrical resistance and cytokine release of MLE-12 cells, which was associated with higher protein expression of zonula occludens-1. Improved oxygenation levels and attenuated increase in lung permeability and inflammatory response were observed in RAGE -/- mice compared to wild-type mice, but RAGE deletion did not influence the effects of sevoflurane on permeability indices after injury. However, the beneficial effect of sevoflurane previously observed in wild-type mice on day 1 after injury in terms of higher PaO 2 /FiO 2 and decreased alveolar levels of cytokines was not found in RAGE -/- mice. In vitro, RAP alleviated some of the beneficial effects of sevoflurane on electrical resistance and cytoskeletal rearrangement, which was associated with decreased cytomix-induced RhoA activity., Conclusions: Sevoflurane decreased injury and restored epithelial barrier function in two in vivo and in vitro models of sterile lung injury, which was associated with increased expression of junction proteins and decreased actin cytoskeletal rearrangement. In vitro findings suggest that sevoflurane may decrease lung epithelial permeability through the RhoA/pMLC/F-actin pathway., (© 2023. The Author(s).)

Background: The recommended dose of ephedrine in adults (0.1 mg kg -1 ) frequently fails to treat hypotension after induction of general anaesthesia in neonates and infants less than 6 months of age. The aim of this study was to determine the optimal dose of ephedrine in this population for the treatment of hypotension after induction of general anaesthesia with sevoflurane., Methods: We conducted a multicentre, prospective, randomised, open-label, controlled, dose-escalation trial. Subjects were randomised if presenting a >20% change from baseline in MAP. Six cohorts of 20 subjects each were enrolled. Ten subjects in the first cohort received 0.1 mg kg -1 i. v. (reference dose). For each subsequent cohort, 10 subjects were assigned to the next higher dose (consecutively 0.6, 0.8, 1, 1.2, and 1.4 mg kg -1 i. v.), and the other subjects were assigned to one or more doses already investigated in previous cohorts. The primary outcome was the return of MAP to >80% of baseline at least once within 10 min after ephedrine administration., Results: A total of 119 infants (25% females), with a mean age (standard deviation) of 2.7 (1.3) months, received their allocated dose of ephedrine. The optimal dose of ephedrine was 1.2 mg kg -1 , with a percentage of success of 65.5% (95% confidence interval, 35.6-86.4). The doses of ephedrine investigated did not induce adverse events., Conclusions: Doses of ephedrine much higher (∼10-fold) than those used in adults are necessary in neonates and infants for the treatment of hypotension after induction of general anaesthesia with sevoflurane., Clinical Trial Registration: NCT02384876., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Intrathecal nusinersen administration, a fundamental step in the treatment of spinal muscular atrophy, is challenging in children., Aims: This retrospective monocentric analysis of prospectively collected data evaluated the feasibility of needleless general anesthesia exclusively with sevoflurane, without imaging guidance, for children undergoing nusinersen administration in a 24-month period., Methods: Clinical data included demographics, type of spinal muscular atrophy, presence and severity of scoliosis. Primary outcome was defined by the number of predefined sentinel adverse events related to anesthesia. Secondary outcomes were assessed by duration of the procedure, number of lumbar puncture attempts, and number of failures. Other measures included number and type of moderate, minor and minimal adverse events, as well as number and type of puncture-related adverse events., Results: 116 patients (mean age: 8.7 (SD 6.9) years; with scoliosis: 49.1%) underwent 250 lumbar punctures; two cases of prolonged desaturation, considered as sentinel adverse events, (0.8%) were recorded during anesthesia (primary outcome). None of the patients underwent orotracheal intubation nor required an unplanned admission in the Pediatric Intensive Care Unit. No patient required an unplanned or prolonged hospitalization after the procedure. Mean number of puncture attempts was 1.6 (SD 1.3), and mean duration of the procedure was 14.1 (SD 8.3) minutes. No failure in the drug administration occurred (secondary outcomes)., Conclusion: In this single-center experience, needleless general anesthesia with inhaled sevoflurane without imaging guidance has been shown to be feasible for children with spinal muscular atrophy undergoing lumbar puncture for nusinersen administration., (© 2023 John Wiley & Sons Ltd.)

Background: This prospective randomized controlled study was designed to evaluate the effect of S-ketamine with sufentanil given intraoperatively and postoperatively on recovery of gastrointestinal (GI) function and postoperative pain in gynecological patients undergoing open abdomen surgery., Methods: One hundred gynecological patients undergoing open abdomen surgery were randomized into an S-ketamine group (group S) or placebo group (0.9% saline; group C). Anesthesia was maintained with S-ketamine, sevoflurane, and remifentanil-propofol target-controlled infusion in group S and with sevoflurane and remifentanil-propofol target-controlled infusion in group C. All patients were connected to patient-controlled intravenous analgesia (PCIA) pump at the end of the surgery with sufentanil, ketorolac tromethamine, and tropisetron in group C and additional S-ketamine in group S. The primary outcome was the time of first postoperative flatus, and the secondary outcome was postoperative pain score of patients. Postoperative sufentanil consumption within the first postoperative 24 h and adverse events such as nausea and vomiting were recorded., Results: The time of first postoperative flatus in group S was significantly shorter (mean ± SD, 50.3 ± 13.5 h) than that in group C (mean ± SD, 56.5 ± 14.3 h, p = 0.042). The patient's visual analog scale (VAS) pain score 24 h after surgery at rest was significantly lower in group S than in group C (p = 0.032). There were no differences in sufentanil consumption within the first postoperative 24 h, postoperative complications related to PCIA between the two groups., Conclusions: S-ketamine accelerated postoperative GI recovery and reduced 24 h postoperative pain in patients undergoing open gynecological surgery., Trial Registration: ChiCTR2200055180. Registered on 02/01/2022. It is a secondary analysis of the same trial., (© 2023. The Author(s).)

Ischemia-reperfusion injury (IRI) is an inflammatory process inherent in organ transplantation procedures. It is associated with tissue damage and, depending on its intensity, can impact early graft function. In liver transplantation (LT), strategies to alleviate IRI are essential in order to increase the use of extended criteria donor (ECD) grafts, which are more susceptible to IRI, as well as to improve postoperative graft and patient outcomes. Sevoflurane, a commonly used volatile anesthetic, has been shown to reduce IRI. This scoping review aims to give a comprehensive overview of the existing experimental and clinical data regarding the potential benefits of sevoflurane for hepatic IRI (HIRI) and to identify any gaps in knowledge to guide further research. We searched Medline and Embase for relevant articles. A total of 380 articles were identified, 45 of which were included in this review. In most experimental studies, the use of sevoflurane was associated with a significant decrease in biomarkers of acute liver damage and oxidative stress. Administration of sevoflurane before hepatic ischemia (preconditioning) or after reperfusion (postconditioning) appears to be protective. However, in the clinical setting, results are conflicting. While some studies showed a reduction of postoperative markers of liver injury, the benefit of sevoflurane on clinical outcomes and graft survival remains unclear. Further prospective clinical trials remain necessary to assess the clinical relevance of the use of sevoflurane as a protective factor against HIRI.

Objective: Malignant hyperthermia (MH) is characterized by a state of hypermetabolism after exposure to halogenated inhalational anesthetics or succinylcholine. The aims of this study were to carry out an updated review on the subject and report an illustrative case of MH in urgent maxillofacial surgery., Material and Methods: A search of the PubMed/MEDLINE database using the keyword "malignant hyperthermia" was performed including articles published over the last 11 years in English, Spanish or Portuguese. Exclusion criteria were similar presentations but not associated with MH and cases not related to the use of anesthetic drugs as a trigger of the condition., Case Report: A 45-year-old man (75 kg, ASA status IE) with a negative family history for neuromuscular diseases, victim of a car accident with a facial fracture, underwent surgery under balanced general anesthesia and developed signs of MH 4 h after anesthesia induction. In our patient, the causative agent was sevoflurane and the diagnosis of MH was confirmed, subsequently, by muscle biopsy., Results/discussion: Overall, 44 cases of MH were found. According to the recent literature, MH shows a male predilection (3:1) and the mean age of patients is 32.2 ± 22.2 years. The most frequently cited causative agents were sevoflurane (30.5%), isoflurane (22.2%), and sevoflurane + succinylcholine (13.8%). The most common clinical indicators included hypercarbia (88.8%), hyperthermia (86.1%), and tachycardia (63.8%). Dantrolene was administered in 24 cases. The outcome was favorable in 31 cases (86.1%). The in vitro muscle contracture test (IVCT) was performed in only 15 patients and all of them tested positive. In our patient, the causative agent was sevoflurane and the diagnosis of MH was confirmed by muscle biopsy., Conclusion: The mortality from MH is still high and an early clinical diagnosis and specific treatment with dantrolene are necessary for a favorable outcome. A complete understanding will allow better management of patients with MH. At present, the best management is to identify susceptible patients and to avoid triggering agents, combined with vigilant monitoring., (© 2022 Special Care Dentistry Association and Wiley Periodicals LLC.)

Objective: The repercussions of ischemia-reperfusion and inflammatory response to surgical injury may compromise the return of physiologic processes in video-laparoscopic surgeries. Dexmedetomidine, as an adjuvant drug in general anesthesia, alters the neuroinflammatory reaction, provides better clinical outcomes in the perioperative period, and may reduce the excessive use of chronic medication in patients with a history of addiction. This study evaluated the immunomodulatory potential of dexmedetomidine on perioperative organ function in video-laparoscopic cholecystectomy patients., Methods: There were two groups: Sevoflurane and Dexmedetomidine A (26 patients) vs. Sevoflurane and Saline 0.9% B (26 patients). Three blood samples were collected three times: 1) before surgery, 2) 4-6h after surgery, and 3) 24h postoperatively. Inflammatory and endocrine mediators were protocolized for analysis. Finally, hemodynamic outcomes, quality upon awakening, pain, postoperative nausea and vomiting, and opioid use were compared between groups., Results: We have demonstrated a reduction of Interleukin 6 six hours after surgery in group A: 34.10 (IQR 13.88-56.15) vs. 65.79 (IQR 23.13-104.97; p = 0.0425) in group B. Systolic blood pressure, diastolic blood pressure, and mean arterial pressure was attenuated in group A in their measurement intervals ( p < 0.0001). There was a lower incidence of pain and opioid consumption in the first postoperative hour favoring this group ( p < 0.0001). We noticed better quality upon awakening after the intervention when comparing the values of peripheral oxygen saturation and respiratory rate., Conclusions: Dexmedetomidine provided anti-inflammatory benefits and contributed to postoperative analgesia without the depressive side effects on the respiratory and cardiovascular systems commonly observed with opioids., Trial Registration: Immunomodulatory Effect of Dexmedetomidine as an Adjuvant Drug in Laparoscopic Cholecystectomies, NCT05489900, Registered 5 August 2022-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05489900?term=NCT05489900&draw=2&rank=1.

The application of Sevoflurane (Sev) in neurological diseases has been documented. We herein clarified the role of Sev in intracerebral hemorrhage (ICH). Through bioinformatics analysis, ICH-related microRNA (miRNA) was collected with microRNA-133b (miR-133b) chosen for the study subject. Then, the related downstream gene Forkhead box O4 (FOXO4) was identified. For in vivo assays, an ICH mouse model was established by autologous blood injection. For in vitro assays, hippocampal neurons were extracted from mouse brain tissues, and erythrocyte lysates were employed to simulate in vitro hemorrhage. Interaction between miR-133b and FOXO4 as well as between FOXO4 and BCL2 were assayed. We found decreased miR-133b in the brain tissue of ICH mice and erythrocyte lysate-treated hippocampal neurons. Sev treatment attenuated ICH and hippocampal neuronal apoptosis in mice by upregulating miR-133b. miR-133b targeted FOXO4 expression, and inhibition of FOXO4 attenuated hippocampal neuronal apoptosis by increasing BCL2 expression. Sev attenuated ICH in mice by increasing BCL2 expression through regulation of miR-133b-mediated FOXO4 expression. The findings highlighted the protective effect of Sev on ICH mice through the regulation of miR-133b-mediated FOXO4 expression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Sevoflurane is the most commonly used anesthetic in clinical practice and exerts a protective effect on cerebral ischemia-reperfusion (I/R) injury. This study aims to elucidate the molecular mechanism by which sevoflurane postconditioning protects against cerebral I/R injury. Oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro and the middle cerebral artery occlusion (MCAO) model in vivo were established to simulate cerebral I/R injury. Sevoflurane postconditioning reduced neurological deficits, cerebral infarction, and ferroptosis after I/R injury. Interestingly, sevoflurane significantly inhibited specificity protein 1 (SP1) expression in MACO rats and HT22 cells exposed to OGD/R. SP1 overexpression attenuated the neuroprotective effects of sevoflurane on OGD/R-treated HT22 cells, evidenced by reduced cell viability, increased apoptosis, and cleaved caspase-3 expression. Furthermore, chromatin immunoprecipitation and luciferase experiments verified that SP1 bound directly to the ACSL4 promoter region to increase its expression. In addition, sevoflurane inhibited ferroptosis via SP1/ACSL4 axis. Generally, our study describes an anti-ferroptosis effect of sevoflurane against cerebral I/R injury via downregulating the SP1/ASCL4 axis. These findings suggest a novel sight for cerebral protection against cerebral I/R injury and indicate a potential therapeutic approach for a variety of cerebral diseases.

Objective: The authors aimed to compare the anti-inflammatory and antioxidant effects of propofol and sevoflurane in children with cyanotic congenital heart disease (CCHD) undergoing cardiac surgery with cardiopulmonary bypass., Design: Prospective, randomized, double-blind study., Setting: Single center, university hospital., Participants: Children ages 1-10 years with CCHD undergoing elective cardiac surgery with cardiopulmonary bypass., Interventions: Children were randomized to receive general anesthesia with either sevoflurane (group S) or propofol (group P). Systemic inflammatory response syndrome (SIRS) occurrence was assessed at the end of the surgery and at the sixth, 12th, and 24th postoperative hours. Blood samples were obtained at 4 times: after anesthesia induction (T0), after release of the aortic cross-clamp (T1), at the end of the surgery (T2), and at the postoperative 24th hour (T3). The serum levels of interleukin 6 and tumor necrosis factor alpha, and the total antioxidant status (TAS) and total oxidant status, were analyzed., Results: SIRS was more common in group S than in group P at all times (p = 0.020, p = 0.036, p = 0.004, p = 0.008). There were no significant differences between the groups in the mean tumor necrosis factor alpha and interleukin 6 levels at any time. The TAS level at T2 was higher in group P than group S (p = 0.036). The serum TAS level increased at T2 compared with T0 in group P, but it decreased in group S (p = 0.041)., Conclusion: The results showed that propofol provided a greater antioxidant effect and reduced SIRS postoperatively more than sevoflurane in children with CCHD undergoing cardiac surgery., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Sevoflurane is identified as an effective candidate drug for acute lung injury (ALI) treatment, but its curing effects and detailed mechanisms have not been fully disclosed. The present study was designed to resolve this academic issue., Methods: The ALI mice models were established, and Hematoxylin-eosin staining assay was performed to examine tissue morphologies. Cell viability was determined by CCK-8 assay, and Annexin V-FITC/PI double staining assay was used to examine cell apoptosis. The expression levels of proteins were determined by performing Western Blot analysis and immunofluorescence staining assay. ROS levels were examined by using DCFH-DA staining assay., Results: In this study, we investigated this issue and the ALI models were respectively established by treating the BALB/c mice and the murine macrophage cell line RAW264.7 with different concentrations of lipopolysaccharide (LPS) in vivo and in vitro, which were subsequently subjected to sevoflurane co-treatment. The results showed that sevoflurane reduced LPS-induced ALI in mice and suppressed LPS-triggered oxidative stress and apoptotic cell death in the RAW264.7 cells. Interestingly, we evidenced that the elimination of reactive oxygen species (ROS) by N-acetyl-L-cysteine (NAC) reversed LPS-induced cell apoptosis in RAW264.7 cells. Then, we verified that sevoflurane suppressed oxidative damages to restrain LPS-induced apoptotic cell death in the RAW264.7 cells through activating the anti-oxidant Keap1/Nrf2 pathway. Mechanistically, sevoflurane down-regulated Keap1 and upregulated Nrf2 in nucleus to activate the downstream anti-oxidant signaling cascades, which further ameliorated LPS-induced cell apoptosis and lung injury by eliminating oxidative damages., Discussion: Taken together, our study illustrated that the sevoflurane attenuates LPS-induced ALI by inhibiting oxidative stress-mediated apoptotic cell death and inflammation, and the Keap1/Nrf2 pathway played an important role in this process.

Introduction: Opioid-free anaesthesia (OFA) may reduce opioid-related side effects such as postoperative nausea and vomiting (PONV) and hyperalgesia. This study aims to investigate the effects of balanced OFA on PONV and pain outcomes in patients undergoing video-assisted thoracoscopic surgery (VATS)., Methods and Analysis: This randomised controlled trial will be conducted at the First Affiliated Hospital of Soochow University in Suzhou, China. A total of 120 adults scheduled for VATS lung resection will be randomly assigned with a 1:1 ratio to either an OFA group or a control group, stratified by sex (n=60 in each group). Patients will receive balanced anaesthesia with esketamine, dexmedetomidine and sevoflurane (the OFA group), or sufentanil and sevoflurane (the control group). All patients will receive PONV prophylaxis with intraoperative dexamethasone and ondansetron. Multimodal analgesia consists of intraoperative flurbiprofen axetil, ropivacaine infiltration at the end of surgery and postoperative patient-controlled sufentanil. The primary outcome is the incidence of PONV within 48 hours after surgery. Secondary outcomes are nausea, vomiting, need for antiemetic therapy, pain scores at rest and while coughing, postoperative sufentanil consumption, need for rescue analgesia, length of post-anaesthesia care unit stay, length of postoperative hospital stay, and 30-day and 90-day post-surgical pain and mortality. Safety outcomes are hypotension, bradycardia, hypertension, tachycardia, interventions for haemodynamic events, level of sedation, headache, dizziness, nightmare and hallucination. All analyses will be performed in the modified intention-to-treat population., Ethics and Dissemination: Ethics approval was obtained from the Ethics Committee of the First Affiliated Hospital of Soochow University (2022-042). All patients will provide written informed consent. The results of this study will be published in a peer-reviewed journal., Trial Registration Number: Chinese Clinical Trial Registry (ChiCTR2200059710)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Information on the effectiveness of a new long-lasting buprenorphine formulation, extended-release buprenorphine, in the neonatal rat is very limited. This study compares whether a high dose of extended-release buprenorphine (XR-Hi) attenuates thermal hypersensitivity for a longer period than a low dose of extended-release buprenorphine (XR-Lo) in a neonatal rat incisional pain model. Two experiments were performed. Experiment one: Male and female postnatal day-5 rat pups (n = 38) were randomly assigned to 1 of 4 treatment groups and received a subcutaneous administration of one of the following: 1) 0.9%NaCl (Saline), 0.1 mL; 2) sustained release buprenorphine (Bup-SR), 1 mg/kg; 3) XR-Lo, 0.65 mg/kg; and 4) XR-Hi, 1.3 mg/kg. Pups were anesthetized with sevoflurane in 100% O2 and a 5 mm long skin incision was made over the left lateral thigh and underlying muscle dissected. The skin was closed with surgical tissue glue. Thermal hypersensitivity testing (using a laser diode) and clinical observations were conducted 1 hour (h) prior to surgery and subsequently after 1, 4, 8, 24, 48, 72 h of treatment. Experiment two: The plasma buprenorphine concentration level was evaluated at 1, 4, 8, 24, 48, 72 h on five-day-old rat pups. Plasma buprenorphine concentration for all treatment groups remained above the clinically effective concentration of 1 ng/mL for at least 4 h in the Bup-SR group, 8 h in XR-Lo and 24 h in XR-Hi group with no abnormal clinical observations. This study demonstrates that XR-Hi did not attenuate postoperative thermal hypersensitivity for a longer period than XR-Lo in 5-day-old rats; XR-Hi attenuated postoperative thermal hypersensitivity for up to 4 h while Bup-SR and XR-Lo for at least 8 h in this model., Competing Interests: The authors have declared that no competing interests exist.

Despite extensive evidence on the organ protective effects of sevoflurane, its effect on disturbed sleep remains unclear. We hypothesised that sevoflurane preconditioning positively impacts disturbed sleep caused by systemic inflammation. A prospective, randomised laboratory investigation was conducted in C57BL/6J mice. A mouse model of lipopolysaccharide (LPS)-induced systemic inflammation was employed to investigate the effects of sevoflurane on sleep recovery. Symptom recovery was evaluated through electroencephalography/electromyography (EEG/EMG) and histological studies. The mice were exposed to 2% sevoflurane before and after peritoneal injection of LPS. The EEG and EMG were recorded for 24 h after the procedure. Brain tissue was harvested after the sevoflurane/LPS procedure and was immunostained using individual antibodies against choline acetyltransferase (ChAT) and Fos. The ChAT-positive and ChAT/Fos double-positive cells were analysed quantitatively in the pedunculopontine tegmental nucleus and laterodorsal tegmental nucleus (PPTg/LDTg). Compared with control mice, mice preconditioned with sevoflurane but not post-conditioned showed a significant increase in rapid eye movement (REM) sleep during EEG recording following the LPS challenge. They also demonstrated a shorter REM latency, indicating an early recovery from LPS-altered sleep. The bouts of REM episodes were retained with sevoflurane preconditioning. More ChAT/Fos double-positive cells were observed in the PPTg/LDTg in the sevoflurane preconditioning plus LPS group than in the LPS-only group. Sevoflurane preconditioning promotes recovery from altered sleep induced by systemic inflammation. Activation of PPTg/LDTg is considered a mechanism underlying sleep reintegration. The recovery phenomenon shows potential for clinical application in cases of sleep disturbances induced by systemic inflammation., (© 2022 European Sleep Research Society.)

Background and Objectives: End-stage renal disease (ESRD) is associated with increased anesthetic risks such as cardiovascular events resulting in higher perioperative mortality rates. This study investigated the perioperative and postoperative outcomes in ESRD patients receiving propofol target-controlled infusion with brachial plexus block during arteriovenous (AV) access surgery. Materials and Methods: We recruited fifty consecutive patients scheduled to receive AV access surgery. While all patients received general anesthesia combined with ultrasound-guided brachial plexus block, the patients were randomly assigned to one of two general anesthesia maintenance groups, with 23 receiving propofol target-controlled infusion (TCI) and 24 receiving sevoflurane inhalation. We measured perioperative mean arterial pressure (MAP), heart rate, and cardiac output and recorded postoperative pain status and adverse events in both groups. Results: ESRD patients receiving propofol TCI had significantly less reduction in blood pressure than those receiving sevoflurane inhalation (p < 0.05) during AV access surgery. Perioperative cardiac output and heart rate were similar in both groups. Both groups reported relatively low postoperative pain score and a low incidence of adverse events. Conclusions: Propofol TCI with brachial plexus block can be used as an effective anesthesia regimen for ESRD patients receiving AV access surgery. It can be used with less blood pressure fluctuation than inhalational anesthesia.

Pyroptosis is a type of programmed cell death, and pyroptosis-associated inflammatory response is closely associated with the pathogenesis of acute lung injury (ALI). Sevoflurane, a common clinical anesthetic, has been reported as therapeutic drug for ALI. However, the detailed mechanisms by which sevoflurane ameliorates ALI have not been fully delineated. In this study, we found that sevoflurane phosphorylated and activated the GSK-3β to suppress LPS-induced pyroptotic cell death, inflammation and ALI. Specifically, in the LPS-induced ALI mice models, sevoflurane attenuated lung damages and fibrosis, and restrained the production of the pro-inflammatory cytokines. Also, LPS increased the expression levels of pyroptosis-related proteins to promote pyroptotic cell death in ALI mice lung tissues, and LPS-induced pyroptotic cell death was reduced by sevoflurane co-treatment. Moreover, the potential underlying mechanisms were uncovered, and we illustrated that sevoflurane promoted GSK-3β activation in LPS-treated ALI mice lung tissues, and re-activation of GSK-3β by the PI3K/Akt pathway inhibitor LY294002 suppressed LPS-induced pyroptotic cell death in vivo. Consistently, in the in vitro macrophages, our data hinted that LPS-induced pyroptotic cell death were also reversed by sevoflurane. Collectively, the above results suggest that sevoflurane re-activated GSK-3β to suppress LPS-induced pyroptotic cell death, inflammation and ALI., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Proper symptom management to improve quality of dying is mandatory in palliative care patients. Home-based control of pain caused by leg ulcers is challenging, especially when the pain is severe and refractory to conventional analgesics, the patient is intolerant to opioids and refuses invasive measures. This was the case for an 87-year-old woman under oncological palliative care who suffered from a leg ulcer causing refractory pain, which produced suicidal ideation. Leg amputation was indicated, but she had signed a living will refusing any invasive measures. After obtaining written informed consent, sevoflurane was applied topically on the ulcer, which resulted in a rapid and long-lasting reduction of pain. Daily self-administration of sevoflurane successfully controlled the wound pain and the patient abandoned her suicidal ideation, the wound healed 35 days later, and her quality of dying improved remarkably. Topical sevoflurane deserves further research on ulcers of vascular and also neoplastic aetiology., Competing Interests: Competing interests: MG-P has acted as a consultant for Vapogenix Inc and owns stock options., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Sevoflurane anesthesia is deemed as potential therapeutic drug for lipopolysaccharide (LPS)-induced acute lung injury (ALI), but the molecular mechanisms have not been fully delineated., Aim: The present study explored the specific molecular mechanism of sevoflurane regulating autophagy to reduce LPS induced ALI., Methods: Male C57BL/6J mice and mouse pulmonary microvascular endothelial cells (MPVECs) were treated with LPS to construct ALI models, and the levels of inflammation, apoptosis and autophagy were detected after treatment with sevoflurane. Meanwhile, cells were treated with autophagy inhibitor or AMP-activated protein kinase (AMPK)/unc-51 like autophagy activating kinase 1 (ULK1) pathway inhibitor in vitro to detect their effects on cell survival., Results: Sevoflurane reduced inflammation, recovered cell division so as to suppress cell apoptosis and maintain cell survival, and activated autophagic flux in LPS-induced ALI models in vivo and in vitro. Of note, the suppressing effects of sevoflurane on LPS-induced cell death were abrogated by inhibiting autophagy. Moreover, we evidenced that sevoflurane promoted activation of the AMPK/ULK1 pathway in LPS-induced ALI models. Blockage of this pathway abrogated the promoting effects of sevoflurane on cell autophagy and cell viability in LPS-treated cells., Conclusion: Collectively, sevoflurane suppresses apoptosis and inflammation via activating protective autophagy, thereby ameliorating LPS-induced ALI, and the AMPK/ULK1/ PIKFYVE pathway is responsible for the process., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: It was to investigate the mechanism of atrial fibrillation after mitral valve replacement under extracorporeal circulation in patients with rheumatic heart disease under sevoflurane anesthesia maintenance and to provide scientific and effective basis for clinical treatment., Methods: Forty patients with rheumatic heart disease who underwent mitral valve replacement were randomly rolled into group I (sinus rhythm of propofol anesthesia, n = 10), group II (atrial fibrillation rhythm of propofol anesthesia, n = 10), group III (sinus rhythm of sevoflurane anesthesia, n = 10), and group IV (atrial fibrillation rhythm of sevoflurane anesthesia, n = 10). Inflammatory factors, free tissue of right atrium, and incidence of postoperative atrial fibrillation were compared among all groups., Results: (i) The serum levels of NT-proBNP, CRP, sST-2, IL-6, TNF- α , and TGF- β 1 in group II were higher than those in group I, group III, and group IV, and the indexes in group III were higher than those in group IV ( P < 0.05). (ii) The relative expression levels of PLB, CaMK II, Bax, and TP53 in the free tissue of right atrium in group II were higher than those in group I, III, and IV, and the index levels in group IV were higher than those in group III ( P < 0.05). (iii) The incidence of postoperative atrial fibrillation in group III (0.00%) was significantly lower than that in group I (30%), group II (50%), and group IV (40.0%), and group II (50%) was the highest ( P < 0.05)., Conclusion: The maintenance of sevoflurane anesthesia can improve the inflammatory response and myocardial tissue autophagy in patients with sinus rhythm and atrial fibrillation rhythm and can reduce the incidence of postoperative atrial fibrillation in patients., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Hao Che et al.)

Purpose: Sevoflurane is a common used inhaled anesthetic that was reported to regulate the progression of multiple cancers. Here, we aimed to investigate the function and regulatory mechanism underlying sevoflurane in glioma cells., Methods: A172 and U251 cells were treated with different concentrations of sevoflurane. Colony formation, EdU satining and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry, and transwell assays were performed to evaluate cell proliferation, apoptosis, migration and invasion, respectively. Circ&#95;VCAN, microRNA-146b-5p (miR-146b-5p) and nuclear factor I B (NFIB) expression levels were assessed by real-time quantitative PCR (RT-qPCR) or western blot. Bioinformatics analysis and dual-luciferase reporter assay were applied to evaluate the correlation between miR-146b-5p and circ&#95;VCAN or NFIB. A xenograft glioma mice model was established to verify the effect of sevoflurane on tumor growth in vivo., Results: Sevoflurane (Sev) inhibited proliferation, migration, invasion, and elevated apoptosis of A172 and U251 cells. Sevoflurane treatment inhibited the expression of circ&#95;VCAN and NFIB, but elevated the expression of miR-146b-5p in glioma cells. Overexpression of circ&#95;VCAN alleviated the inhibition effects of sevoflurane on the malignant phenotypes of glioma in vitro and in vivo. Besides, miR-146b-5p is a target of circ&#95;VCAN and negatively regulated NFIB expression. Overexpression of miR-146b-5p partly reversed the effects of circ&#95;VCAN in Sev-treated glioma cells. Furthermore, miR-146b-5p deletion enhanced glioma progression in sevoflurane treated glioma cells by targeting NFIB. Moreover, circ&#95;VCAN could upregulate NFIB expression by sponging miR-146b-5p in Sev-treated glioma cells., Conclusion: Sevoflurane alleviated proliferation, migration and invasion, but enhanced apoptosis of glioma cells through regulating circ&#95;VCAN/miR-146b-5p/NFIB axis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Postoperative cognitive dysfunction (POCD) in elderly patients undergoing general anesthesia is a major problem in the aging society. Sevoflurane is the most widely applied anesthetic in clinical practice. In this study, we investigated the effects of the GLP-1 analogue liraglutide on cognitive function in aged rats anesthetized by sevoflurane. Specifically, 48 Sprague-Dawley rats were divided into the control (C) group, the liraglutide (L) group, the sevoflurane (S) group, and the sevoflurane+liraglutide (SL) group, each group with 12 rats. In the S group and the SL group, the rats were injected subcutaneously with normal saline and liraglutide after inhalation of a mixture of 3% sevoflurane and pure oxygen. In the C group and the L group, normal saline and liraglutide were injected subcutaneously into the rats after inhalation of pure oxygen. Morris Water Maze Task was applied for the detection of spatial learning and memory in rats; HE and TUNEL for staining; and western blot for quantifying Bax, Bcl-2 expression, and examining caspase-3 activity in hippocampal tissues as well as for revealing the antiapoptotic mechanism. Besides, the accumulation of inflammatory factors NF- κ B and IL-1 β in the hippocampal tissue was quantitatively studied to reveal the anti-inflammatory mechanism. The protective effect of liraglutide on sevoflurane toxicity was the first to be confirmed in this study. Additionally, this study elucidated the mechanism of the above effect. The results of this study might be helpful to find an effective medical solution for the treatment of POCD caused by sevoflurane anesthesia., Competing Interests: The authors declare that they have no competing interest., (Copyright © 2022 Qin Zhang et al.)

Background: Percutaneous nephrolithotomy (PCNL) is the first-line and guideline-recommended treatment for large renal calculi. Multimodal analgesia (MMA) comprising a combination of different analgesics is an increasingly popular method for pain control as it has been shown to reduce postoperative pain and reduce opioid use and the risk of opioid misuse, with a shorter recovery time in various procedures and patient populations., Objective: In this study, we tested the hypothesis that MMA with propofol and sevoflurane (PS) can decrease pain intensity during surgery and used IoC2 as a real-time index of the analgesic effect of sevoflurane., Study Design: Prospective, single-center, double-blind, randomized controlled clinical trial., Setting: Xuanwu Hospital of Capital Medical University., Methods: Patients scheduled for elective percutaneous nephrolithotomy from January 2020 to July 2020 were randomized into 2 groups, standard multimodal analgesia (propofol + sevoflurane group) and control (propofol [P] group). The PS group received propofol 2.5 mg/kg/h along with 1% sevoflurane after induction for 30 minutes during the main anesthetic procedure, and the P group received propofol 5 mg/kg/h by intravenous infusion during the operation. Index of consciousness 2 (IoC2), namely nociception index, intraoperative hemodynamic fluctuation, bispectral index (BIS), electromyography, postanesthesia care unit (PACU) length of stay, visual analog scale (VAS) score, and Aldrete and Steward scores were recorded., Results: A total of 153 patients undergoing PCNL were enrolled. The demographic and clinical characteristics were similar between the 2 groups. IoC2 was reduced in the PS group compared to the P group at T10, T11, T12, T13, T14, and T15 time points, indicating that analgesia was more effective in the former. The BIS of the PS group did not differ significantly from that of the P group except at T12, T13, T14, and T15. PACU length of stay was shorter in the PS group than in the P group (mean [SD]: 54.35 [16.61] vs 47.39 [13.15], P = 0.04). VAS pain scores did not differ significantly between the 2 groups., Conclusion: MMA with propofol and sevoflurane provided better analgesia than propofol alone and may be an effective method to reduce stress and the intraoperative nociceptive stimulus response in patients undergoing PCNL, thereby promoting rapid postoperative recovery.

Background: Traumatic brain injury (TBI) is a kind of acquired brain injury, which is caused by external mechanical forces. Moreover, the neuroprotective role of sevoflurane (Sevo) has been identified in TBI. Therefore, this research was conducted to figure out the mechanism of Sevo in TBI via FGF2., Methods: The key factors of neuroprotective effects of Sevo in TBI rats were predicted by bioinformatics analysis. A TBI model was induced on rats that then inhaled Sevo for 1 h and grouped via lentivirus injection. Modified Neurological Severity Score was adopted to evaluate neuronal damage in rats, followed by motor function and brain water content measurement. FGF2, EZH2, and HES1 expression in brain tissues was evaluated by immunofluorescence staining, and expression of related genes and autophagy factors by RT-qPCR and Western blot analysis. Methylation-specific PCR was performed to assess HES1 promoter methylation level, and ChIP assay to detect the enrichment of EZH2 in the HES1 promoter. Neuronal damage was assessed by cell immunofluorescence staining, and neuronal apoptosis by Nissl staining, TUNEL staining, and flow cytometry., Results: Sevo diminished brain edema, improved neurological scores, and decreased neuronal apoptosis and autophagy in TBI rats. Sevo preconditioning could upregulate FGF2 that elevated EZH2 expression, and EZH2 bound to the HES1 promoter to downregulate HES1 in TBI rats. Also, FGF2 or EZH2 overexpression or HES silencing decreased brain edema, neurological deficits, and neuronal autophagy and apoptosis in Sevo-treated TBI rats., Conclusions: Our results provided a novel insight to the neuroprotective mechanism of Sevo in TBI rats by downregulating HES1 via FGF2/EZH2 axis activation., (© 2022. The Author(s).)

Sevoflurane was first synthesized independently by Richard Wallin and Bernard Regan at Travenol Laboratories Incorporated and Ross Terrell and Louise Croix at Airco, Inc in the late 1960s, and subsequent animal studies and a phase-1 human trial of the agent published in 1981 showed promising results. Further research in the United States was halted, however, because of concerns regarding potential nephrotoxicity and the introduction of less degradable alternatives. Interest in sevoflurane resumed in Japan when Maruishi Pharmaceutical Company, Limited (Ltd) (Maruishi) decided to continue its development in 1982. They secured approval by the Japanese Ministry of Health, Labor and Welfare for its clinical use in January 1990. Because of its low blood:gas partition coefficient and resulting rapid action, sevoflurane quickly became the anesthetic of choice of Japanese anesthesiologists. In 1992 Abbott Laboratories, now AbbVie, Inc (Abbott, North Chicago, IL) finalized a licensing agreement with Maruishi to seek the US Food and Drug Administration approval for sevoflurane sales in the United States. Approved in June 1995, sevoflurane is now marketed by Abbott in 120 countries and has been administered >120 million times. This report details the Japanese contribution to the development of sevoflurane., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

Background: The perioperative inflammatory response may be implicated in adverse outcomes including neurocognitive dysfunction and cancer recurrence after oncological surgery. The immunomodulatory role of anesthetic agents has been demonstrated in vitro; however, its clinical relevance is unclear. The purpose of this meta-analysis was to compare propofol and sevoflurane with respect to biomarkers of perioperative inflammation. The secondary aim was to correlate markers of inflammation with clinical measures of perioperative cognition., Methods: Databases were searched for randomized controlled trials examining perioperative inflammation after general anesthesia using propofol compared to sevoflurane. Inflammatory biomarkers investigated were interleukin (IL)-6, IL-10, tissue necrosis factor alpha (TNF-α), and C-reactive protein (CRP). The secondary outcome was incidence of perioperative neurocognitive disorders. Meta-analysis with metaregression was performed to determine the difference between propofol and sevoflurane., Results: Twenty-three studies were included with 1611 participants. Studies varied by surgery type, duration, and participant age. There was an increase in the mean inflammatory biomarker levels following surgery, with meta-analysis revealing no difference in effect between propofol and sevoflurane. Heterogeneity between studies was high, with surgery type, duration, and patient age contributing to the variance across studies. Only 5 studies examined postoperative cognitive outcomes; thus, a meta-analysis could not be performed. Nonetheless, of these 5 studies, 4 reported a reduced incidence of cognitive decline associated with propofol use., Conclusions: Surgery induces an inflammatory response; however, the inflammatory response did not differ as a function of anesthetic technique. This absence of an effect suggests that patient and surgical variables may have a far more significant impact on the postoperative inflammatory responses than anesthetic technique. The majority of studies assessing perioperative cognition in older patients reported a benefit associated with the use of propofol; however, larger trials using homogenous outcomes are needed to demonstrate such an effect., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

Background: Recent studies have shown that propofol and sevoflurane, two common anesthetics, can prevent tumor development. The prevalence of lung adenocarcinoma in China is highest in Yunnan Xuanwei, and many patients with lung cancer in this area are often resistant to platinum-based treatments., Objective: The objective of the study was to investigate the effects of propofol and sevoflurane on malignant biological behavior and cisplatin resistance of Xuanwei lung adenocarcinoma., Methods: Herein, XWLC-05/R, a cisplatin-resistant cell line of XWLC-05 cells from Xuanwei lung adenocarcinoma, was constructed. The XWLC-05 cells and XWLC-05/R cells were treated with propofol and sevoflurane singly or as a combination and subjected to CCK-8 assay, clone formation tests, and flow cytometry analysis to assess the proliferation level of cells. The morphology and number of apoptotic bodies in XWLC-05 cells and XWLC-05/R were examined with a transmission electron microscope. The ANNEXIN V-FITC/PI and transwell assays were performed to evaluate apoptosis, invasion, and migration of the cells. Subsequently, we constructed a Xuanwei lung adenocarcinoma xenograft model to investigate the effects of propofol and sevoflurane on the tumorigenicity of XWLC-05 cells in vivo., Results: Treatment with propofol and sevoflurane significantly inhibited proliferation, invasion, migration, and induced apoptosis of XWLC-05 and XWLC-05/R cells. These effects were more pronounced when propofol and sevoflurane were co-incubated with the cells. Moreover, both propofol and sevoflurane significantly inhibited Wnt/β- catenin and PI3K/AKT pathways. Moreover, the two drugs effects suppressed the malignant biological behavior of XWLC-05 cells and XWLC-05/R cells, and this effect was counteracted by 740Y-P (PI3K/AKT pathway activator) and Wnt pathway activator 1 (Wnt/β-catenin pathway activator). In vivo experiments confirmed that propofol and sevoflurane alleviated the tumorigenicity of XWLC-05 cells., Conclusions: In summary, this study shows, for the first time, that propofol and sevoflurane decrease the proliferation, invasion, migration and induce apoptosis of XWLC-05 cells and XWLC-05/R cells by impeding the Wnt/β-catenin and PI3K/AKT signaling pathways, thereby alleviating the development of Xuanwei lung adenocarcinoma in vivo. Moreover, these effects are more pronounced when the two drugs are combined., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Remifentanil reduces cough during extubation. Ramosetron, a 5-HT 3 receptor antagonist, is a potent antiemetic. Regarding the antitussive property of 5-HT receptor agonists, ramosetron can mediate the cough reflex by increasing the remifentanil requirement. This study evaluated the effect of ramosetron on the optimal effect-site concentration (Ce) of remifentanil for preventing emergence cough from sevoflurane anesthesia in female patients., Methods: Forty-seven randomly selected female patients undergoing laparoscopic cholecystectomy received either ramosetron 0.3 mg (n = 23) or the same volume of normal saline (n = 24) intravenously at the end of surgery. The remifentanil Ce using target-controlled infusion in 50% of patients (EC 50 ) and 95% of patients (EC 95 ) were assessed using Dixon's up-and-down or isotonic regression method with a bootstrapping approach., Results: Using Dixon's up-and-down method, the EC 50 of remifentanil in the control group (1.33 ± 0.38 ng/mL) was comparable to that of ramosetron group (1.50 ± 0.69 ng/mL) (P = 0.615). Using isotonic regression analysis, the EC 50 (83% confidence interval) did not differ between the two groups (1.17 [0.86-1.43] ng/mL and 1.13 [0.68-1.56] ng/mL in control and ramosetron groups). However, the EC 95 (95% confidence interval) was significantly lower in the control group than in the ramosetron group (1.90 [1.45-1.96] ng/mL and 2.92 [2.35-2.97] ng/mL)., Conclusion: Remifentanil Ce for preventing emergence cough was higher in the ramosetron group than in the control group. It may indicate the lowering effect of ramosetron on the antitussive activity of remifentanil., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The purpose of this study was to evaluate the efficacy and safety of sevoflurane-remifentanil (SR) vs propofol-remifentanil (PR) as inhalation anesthesia or total intravenous anesthesia in patients undergoing craniotomy, respectively., Methods: Electronic databases included PubMed, ScienceDirect, Embase, Cochrane library, CNKI, and Wanfang data were searched using suitable search items. Randomized clinical controlled trials comparing the combination of SR and PR as anesthetics for neurosurgery were included. The outcomes included wake-up time, spontaneous respiration time, extubation time, and safety., Results: Seventeen studies were included in this meta-analysis. There were no statistically significant differences in wake-up time (P = .25, standardized mean difference (SMD) = 0.29, 95% CI -0.20 to 0.77), extubation time (P = .1, SMD = 0.52, 95% CI -0.11 to 1.14) and spontaneous respiration time (P = .58, SMD = 0.43, 95% CI -1.07 to 1.93) when patients with SF and PF for anesthesia maintenance. Moreover, the changes of hemodynamic parameters are similar between the 2 groups. During anesthesia maintenance, SF could significantly increase the incidence of hypotension and brain edema than PF (P = .02, SMD = 1.68, 95% CI 1.07 to 2.62; P < .0001, SMD = 3.37, 95% CI 1.86 to 6.12), PF markedly promoted the incidence of hypertension (P = .001, SMD = 0.55, 95% CI 0.39 to 0.79). The postoperative adverse reactions were similar between the 2 groups (P > .05), but the incidence of postoperative nausea and vomiting proved to be higher in SF group (P < .0001, SMD = 2.12, 95% CI 1.47 to 3.07)., Conclusions: SR and PR as anesthetics in patients underwent craniotomy had similar effects, but PR was superior to SR in terms of safety of intraoperation and postoperation., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To uncover the protective role of sevoflurane on hypoxia/reoxygenation-induced cardiomyocyte apoptosis through the protein kinase B (Akt) pathway., Methods: An in vitro hypoxia/reoxygenation (H/R) model was established in cardiomyocyte cell line H9c2. Sevoflurane (SEV) was administrated in H9c2 cells during the reoxygenation period. Viability, layered double hydroxide (LDH) release, and apoptosis in H9c2 cells were determined to assess H/R-induced cell damage. Relative levels of apoptosis-associated genes were examined. Moreover, phosphorylation of Akt was determined., Results: H/R injury declined viability and enhanced LDH release and apoptotic rate in H9c2 cells. Cyclooxygenase-2 (Cox-2) was upregulated following H/R injury, which was partially reversed by SEV treatment. In addition, SEV treatment reversed changes in viability and LDH release owing to H/R injury in H9c2 cells, which were further aggravated by overexpression of Cox-2. The Akt pathway was inhibited in H9c2 cells overexpressing Cox-2., Conclusions: Sevoflurane protects cardiomyocyte damage following H/R via the Akt pathway, and its protective effect was abolished by overexpression of Cox-2., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Chunyan Guo et al.)

Objective: The electroencephalographic derived indices have been developed for adult patients, however these monitors have not been validated for infants., Methods: Frontal EEGs were recorded in 115 infants aged <1 year [0-3-months (N = 27), 4-6-months (N = 30), 7-9-months (N = 29) and 10-12-months (N = 29)] who received general anaesthesia with sevoflurane. Total power (µV 2 ) and relative β-, α-, θ-, δ-power (%) were analyzed. Additionally, in 20 EEGs event marker were added (baseline, loss of consciousness, intraoperative situation, extubation) to assess perioperative EEG dynamics., Results: Newborns show a mean relative δ-power at 80% in intraoperative EEG compared to infants (10-12 months) showing 47.5%. Relative β-power and α-power are low in newborns (mean 3.2% and 4.6%; respectively), with a marked increase in the older infants (4-6 months) (mean 10.9% and 14.4%; respectively). EEG dynamic in newborns from baseline (relative δ-power of 88%) to the intraoperative situation (80.5%) are discrete. In contrast infants >6-months have a strong reduction of relative δ-power from baseline to the intraoperative situation, which corresponds to an increase of faster frequencies., Conclusions: Age dependent perioperative EEG signatures can be demonstrated in infants younger than one year., Significance: We demonstrate significant differences in EEG readouts between newborns and infants which questions our monitoring systems in paediatric anaesthesia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Aims: Sevoflurane preconditioning (SPC) results in cerebral ischemic tolerance; however, the mechanism remains unclear. Promoting microglia/macrophages polarization from pro-inflammatory state to anti-inflammatory phenotype has been indicated as a potential treatment target against ischemic stroke. In this study, we aimed to assess the effect of SPC on microglia polarization after stroke and which signaling pathway was involved in this transition., Methods: Mouse primary microglia with SPC were challenged by oxygen-glucose deprivation (OGD) or lipopolysaccharide (LPS), and mice with SPC were subjected to middle cerebral artery occlusion (MCAO). Then, the mRNA and protein levels of pro-inflammatory/anti-inflammatory factors were analyzed. GSK-3β phosphorylation and Nrf2 nuclear translocation were measured. The mRNA and protein expression of pro-inflammatory/anti-inflammatory factors, neurological scores, infarct volume, cellular apoptosis, the proportion of pro-inflammatory/anti-inflammatory microglia/macrophages, and the generation of super-oxidants were examined after SPC or GSK-3β inhibitor TDZD treatment with or without Nrf2 deficiency., Results: Sevoflurane preconditioning promoted anti-inflammatory and inhibited pro-inflammatory microglia/macrophages phenotype both in vitro and in vivo. GSK-3β phosphorylation at Ser9 was increased after SPC. Both SPC and TDZD administration enhanced Nrf2 nuclear translocation, reduced pro-inflammatory microglia/macrophages markers expression, promoted anti-inflammatory markers level, and elicited a neuroprotective effect. Nrf2 deficiency abolished the promoted anti-inflammatory microglia/macrophages polarization and ischemic tolerance induced by TDZD treatment. The reduced percentage of pro-inflammatory positive cells and super-oxidants generation induced by SFC or TDZD was also reversed by Nrf2 knockdown., Conclusions: Our results indicated that SPC exerts brain ischemic tolerance and promotes anti-inflammatory microglia/macrophages polarization by GSK-3β-dependent Nrf2 activation, which provides a novel mechanism for SPC-induced neuroprotection., (© 2021 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Ischemia/reperfusion (I/R) injury is a phenomenon that the reperfusion of ischemic organs or tissues aggravates their damage, which poses a serious health threat and economic burden to the world. I/R gives rise to a series of physiological and pathological world, including inflammatory response, oxidative stress, brain edema, blood-brain barrier destruction, and neuronal death. Therefore, finding effective treatment measures is extremely important to the recovery of I/R patients and the improvement of long-term quality of life. Sevoflurane is an important volatile anesthetic which has been reported to reduce myocardial I/R damage and infarct size. Sevoflurane also has anti-inflammatory and neuroprotective effects. As reported sevoflurane treatment could reduce nerve function injury, cerebral infarction volume and the level of inflammatory factors. At the same time, there is evidence that sevoflurane can reduce neuron apoptosis and antioxidant stress. The protective effect of sevoflurane in brain injury has been proved to be existed in several aspects, so that a comprehensive understanding of its neuroprotective effect is helpful to exploit new treatment paths for I/R, provide clinicians with new clinical treatment decisions, contribute to the effective treatment of I/R patients and the improvement of quality of life after I/R healing., Competing Interests: None

Sevoflurane has been reported to have anti-tumorigenic effects in glioma. Circ&#95;0000215 was found to play vital functions in the pathological progressions of glioma. However, whether circ&#95;0000215 mediates the inhibitory effects of sevoflurane on glioma cells remains unclear. In vitro assays were performed using cell counting kit-8, flow cytometry, transwell and Western blot assays. The expression levels of circ&#95;0000215, microRNA (miR)-1200 and NCR3LG1 (Natural Killer Cell Cytotoxicity Receptor 3 Ligand 1) were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and/or Western blot. The dual-luciferase reporter assay and pull-down assay were used to investigate the relationship between miR-1200 and circ&#95;0000215 or NCR3LG1. In vivo assay was conducted using xenograft nude mice model. In vitro assays suggested that sevoflurane repressed glioma cell proliferation, metastasis and induced apoptosis as well as hindered tumor growth in vivo, which were reversed by circ&#95;0000215 overexpression. Mechanically, circ&#95;0000215 was confirmed to directly target miR-1200, and NCR3LG1 was a target of miR-1200 in glioma cells. Importantly, circ&#95;0000215 could regulate NCR3LG1 expression via miR-1200. Besides that, rescue assay suggested that circ&#95;0000215 attenuated the inhibitory effects of sevoflurane on glioma cell growth and metastasis, which were reversed by miR-1200 overexpression or NCR3LG1 knockdown. Our study revealed that sevoflurane could suppress glioma tumorigenesis by regulating circ&#95;0000215/miR-1200/NCR3LG1 axis, suggesting a new insight into the therapeutic potential of sevoflurane in glioma treatment., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Reducing intra-operative opioid consumption benefits patients by decreasing postoperative opioid-related adverse events. We assessed whether opioid-free anesthesia would provide effective analgesia-antinociception monitored by analgesia index in video-assisted thoracoscopic surgery., Methods: Patients (ASA Ⅰ-Ⅱ, 18-65 years old, BMI <30 kg m-2) scheduled to undergo video-assisted thoracoscopic surgery under general anesthesia were randomly allocated into two groups to receive opioid-free anesthesia (group OFA) with dexmedetomidine, sevoflurane plus thoracic paravertebral blockade or opioid-based anesthesia (group OA) with remifentanil, sevoflurane, and thoracic paravertebral blockade. The primary outcome variable was pain intensity during the operation, assessed by the depth of analgesia using the pain threshold index with the multifunction combination monitor HXD‑I. Secondary outcomes included depth of sedation monitoring by wavelet index and blood glucose concentration achieved from blood gas., Results: One hundred patients were randomized; 3 patients were excluded due to discontinued intervention and 97 included in the final analysis. Intraoperative pain threshold index readings were not significantly different between group OFA and group OA from arriving operation room to extubation (P = 0.86), while the brain wavelet index readings in group OFA were notably lower than those in group OA from before general anesthesia induction to recovery of double lungs ventilation (P <0.001). After beginning of operation, the blood glucose levels in group OFA increased compared with baseline blood glucose values (P < 0.001). The recovery time and extubation time in group OFA were significantly longer than those in group OA (P <0.007)., Conclusions: This study suggested that our OFA regimen achieved equally effective intraoperative pain threshold index compared to OA in video-assisted thoracoscopic surgery. Depth of sedation was significantly deeper and blood glucose levels were higher with OFA. Study's limitations and strict inclusion criteria may limit the external validity of the study, suggesting the need of further randomized trials on the topic. Trial registration: ChiCTR1800019479, Title: "Opioid-free anesthesia in video-assisted thoracoscopic surgery lobectomy"., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The general anesthetic sevoflurane is being repurposed as a topical analgesic for painful chronic wounds. We conducted a Bayesian cost-effectiveness analysis (CEA) comparing the addition of domiciliary topical sevoflurane to conventional analgesics (SEVOFLURANE, n = 38) versus conventional analgesics alone (CONVENTIONAL, n = 26) for the treatment of nonrevascularizable painful leg ulcers in an outpatient Pain Clinic of a Spanish tertiary hospital., Methods: We used real-world data collected from charts to conduct this CEA from a public healthcare perspective and with a one-year time horizon. Costs of analgesics, visits and admissions were considered, expressed in €2016. Analgesic effectiveness was measured with SPID (Sum of Pain Intensity Difference). A Bayesian regression model was constructed, including "treatment" and baseline characteristics for patients ("arterial hypertension") and ulcers ("duration", "number", "depth", "pain") as covariates. The findings were summarized as a cost-effectiveness plane and a cost-effectiveness acceptability curve. One-way sensitivity analyses, a re-analysis excluding those patients who died or suffered from leg amputation, and an extreme scenario analysis were conducted to reduce uncertainty., Results: Compared to CONVENTIONAL, SEVOFLURANE was associated with a 46% reduction in costs, and the mean incremental effectiveness (28.15±3.70 effectiveness units) was favorable to SEVOFLURANE. The estimated probability for SEVOFLURANE being dominant was 99%. The regression model showed that costs were barely influenced by any covariate, whereas effectiveness was noticeably influenced by "treatment". All sensitivity analyses showed the robustness of the model, even in the extreme scenario analysis against SEVOFLURANE., Conclusions: SEVOFLURANE was dominant over CONVENTIONAL as it was less expensive and much more effective., Competing Interests: Dr. Selva-Sevilla and Dr. Cortiñas-Sáenz have nothing to disclose. Dr. Fernández-Ginés has a patent “Analgetic microspheres comprising a volatile halogenated anaesthetic” issued to Dámaso Fernández-Ginés. Dr. Gerónimo-Pardo owned stock options from Vapogenix Inc, and he had a personal interest in the issue since he started the repurposing process for the inhalation general anesthetic sevoflurane to be used as a topical analgesic. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Isoflurane is the only volatile anaesthetic agent licensed for equine use in the United Kingdom, but sevoflurane is also commonly used. The two agents have rarely been compared for use in clinical elective surgery., Methods: This single centre, prospective, randomised, blinded clinical investigation recruited 101 healthy client owned horses undergoing elective surgery. Anaesthesia was standardised and horses randomly assigned to receive isoflurane (I) or sevoflurane (S) for maintenance of anaesthesia in 100% oxygen. Horses were ventilated to normocapnia and received intravenous fluid therapy and haemodynamic support with dobutamine to maintain mean arterial blood pressure above 60 mm Hg. Recovery was timed and video-recorded to allow offline evaluation by two experienced clinicians unaware of the volatile agent used. No post-anaesthetic sedation was administered., Results: There was no significant difference between groups in terms of haemodynamic support required during anaesthesia nor in quality or duration of recovery. Inotropic support to maintain MAP above 60 mm Hg was required by 67 of 101 (67%) of horses. Five horses in the I group required additional ketamine or thiopentone to improve the plane of anaesthesia., Conclusions: Haemodynamic support needed during anaesthesia as well as the duration and quality of recovery were similar with isoflurane and sevoflurane., (© 2021 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Sevoflurane is a volatile liquid from the family of ether-derived alogenated hydrocarbons that is approved for the induction and  maintenance of inhalational general anesthesia in the hospital setting. This review describes the pioneering experience of a Spanish Pain Unit in the  home treatment of complicated painful wounds using topical sevoflurane  instillations according to a protocol approved for off-label use. Aspects of  safety and efficacy, both analgesic, antimicrobial and pro-healing are  addressed, and some future lines of research are discussed in terms of  new formulations for topical use. After more than seven years of use of the protocol, an experience of over 70,000 applications of topical sevoflurane  has been gained. In general terms, the analgesic effect appears quickly, is  highly intense and persists for several hours. As a result, patients can  reduce their consumption of systemic analgesics and benefit from an  improvement in their quality of life. In addition, there are signs that  suggest sevoflurane also possesses antimicrobial and pro-healing  properties. Regarding safety, pruritus at the level of the periulcerous skin  is the most frequently reported adverse effect, although it is usually  transient and well-tolerated, and no systemic toxicity has been reported.  Overall, the risk-benefit balance of the drug has so far been very  favorable. To avoid manipulation of this volatile liquid, we have developed  a new formulation of sevoflurane in gel form, which has made it possible  to successfully apply sevoflurane in the context of painful pathologies  where the skin remains intact. Furthermore, these types of new  formulations, including sevoflurane microspheres, which we have also  developed, could improve the efficacy and safety of topical sevoflurane  while reducing the occupational exposure of healthcare staff. This means  that the development of new formulations is a field with a very promising  future., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Sevoflurane (Sev) has protective effects in acute lung injury (ALI), but the relevant mechanisms are still not fully understood. The present study aimed to determine whether Sev exerts a protective effect on lipopolysaccharide (LPS)-induced ALI by regulating ferroptosis. In this study, we found that Sev could protect mice from lung injury caused by LPS stimulation, including extenuating lung histological damage, pulmonary edema and pulmonary vascular permeability, and the content of inflammatory factors in Bronchoalveolar lavage fluid (BALF), as well as improving the survival rate of ALI mice, which was in line with the effects of ferroptosis inhibitor ferrostatin-1. Simultaneously, Sev could eliminate the worsening effects of ferroptosis inducer Fe-citrate on LPS-induced ALI to a certain extent. Additionally, the administration of Sev could inhibit ferroptosis caused by LPS, which was manifested by reducing the accumulation of MDA and Fe 2+ , and increasing the levels of GSH and GPX4 in the lung tissues of ALI mice. It was also observed in BEAS-2B cells that the increased MDA and Fe 2+ levels and the decreased GSH and GPX4 levels caused by LPS could be rescued by ferrostatin-1 and Sev. LPS stimulation compensatory up-regulated heme oxygenase-1 (HO-1) expression in mouse lung tissues and BEAS-2B cells, which could be enhanced by Sev. Moreover, HO-1 depletion could offset the inhibitory effect of Sev on LPS-induced ferroptosis and inflammation in BEAS-2B cells. Taken together, Sev inhibited ferroptosis by up-regulating HO-1 expression to reduce LPS-induced ALI, which may provide a possible mechanism for the application of Sev in clinical anesthesia., (Copyright © 2021 Elsevier Inc. All rights reserved.)