Sevoflurane blocks KLF5-mediated transcriptional activation of ITGB2 to inhibit macrophage infiltration in hepatic ischemia/reperfusion injury.

BACKGROUND: Sevoflurane (Sevo) preconditioning and postconditioning play a protective role against injury induced by hepatic ischemia/reperfusion (I/R). At the same time, the involvement of macrophage infiltration in this process and the precise mechanisms are unclear. Here, we designed this research to elucidate the protective effects of Sevo against hepatic I/R injury and the molecules involved. METHODS: The alleviating effect of Sevo on the liver injury was analyzed by liver function analysis, hematoxylin and eosin staining, Masson trichrome staining, terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling, western blot analysis and an enzyme-linked immunosorbent assay. An in vitro cell model was developed using alpha mouse liver 12 (AML12) cells, and the cell model was treated with oxygen-glucose deprivation and reoxygenation and Sevo. Multiple bioinformatics databases were used to screen transcriptional regulators related to hepatic I/R injury and the targets of Krueppel-like factor 5 (KLF5). KLF5 expression was artificially upregulated alone or with integrin beta-2 (ITGB2) knockdown to substantiate their involvement in Sevo-mediated hepatoprotection. RESULTS: Sevo protected the liver against I/R injury by reducing cell apoptosis and inflammatory response. KLF5 was upregulated in liver tissues following I/R injury, whereas KLF5 overexpression aggravated macrophage infiltration and liver injury induced by I/R injury. KLF5 bound to the promoter of ITGB2 to enhance ITGB2 transcription. Knockdown of ITGB2 reversed the aggravation of injury caused by KLF5 overexpression in mice and AML12 cells. CONCLUSIONS: Sevo blocked KLF5-mediated transcriptional activation of ITGB2, thereby inhibiting macrophage infiltration in hepatic I/R injury.

The changing of α5-GABAA receptors expression and distribution participate in sevoflurane-induced learning and memory impairment in young mice.

BACKGROUND: Sevoflurane is a superior agent for maintaining anesthesia during surgical procedures. However, the neurotoxic mechanisms of clinical concentration remain poorly understood. Sevoflurane can interfere with the normal function of neurons and synapses and impair cognitive function by acting on α5-GABAAR. METHODS: Using MWM test, we evaluated cognitive abilities in mice following 1 h of anesthesia with 2.7%-3% sevoflurane. Based on hippocampal transcriptome analysis, we analyzed the differential genes and IL-6 24 h post-anesthesia. Western blot and RT-PCR were performed to measure the levels of α5-GABAAR, Radixin, P-ERM, P-Radixin, Gephyrin, IL-6, and ROCK. The spatial distribution and expression of α5-GABAAR on neuronal somata were analyzed using histological and three-dimensional imaging techniques. RESULTS: MWM test indicated that partial long-term learning and memory impairment. Combining molecular biology and histological analysis, our studies have demonstrated that sevoflurane induces immunosuppression, characterized by reduced IL-6 expression levels, and that enhanced Radixin dephosphorylation undermines the microstructural stability of α5-GABAAR, leading to its dissociation from synaptic exterior and resulting in a disordered distribution in α5-GABAAR expression within neuronal cell bodies. On the synaptic cleft, the expression level of α5-GABAAR remained unchanged, the spatial distribution became more compact, with an increased fluorescence intensity per voxel. On the extra-synaptic space, the expression level of α5-GABAAR decreased within unchanged spatial distribution, accompanied by an increased fluorescence intensity per voxel. CONCLUSION: Dysregulated α5-GABAAR expression and distribution contributes to sevoflurane-induced partial long-term learning and memory impairment, which lays the foundation for elucidating the underlying mechanisms in future studies.

Substance specific EEG patterns in mice undergoing slow anesthesia induction.

The exact mechanisms and the neural circuits involved in anesthesia induced unconsciousness are still not fully understood. To elucidate them valid animal models are necessary. Since the most commonly used species in neuroscience are mice, we established a murine model for commonly used anesthetics/sedatives and evaluated the epidural electroencephalographic (EEG) patterns during slow anesthesia induction and emergence. Forty-four mice underwent surgery in which we inserted a central venous catheter and implanted nine intracranial electrodes above the prefrontal, motor, sensory, and visual cortex. After at least one week of recovery, mice were anesthetized either by inhalational sevoflurane or intravenous propofol, ketamine, or dexmedetomidine. We evaluated the loss and return of righting reflex (LORR/RORR) and recorded the electrocorticogram. For spectral analysis we focused on the prefrontal and visual cortex. In addition to analyzing the power spectral density at specific time points we evaluated the changes in the spectral power distribution longitudinally. The median time to LORR after start anesthesia ranged from 1080 [1st quartile: 960; 3rd quartile: 1080]s under sevoflurane anesthesia to 1541 [1455; 1890]s with ketamine. Around LORR sevoflurane as well as propofol induced a decrease in the theta/alpha band and an increase in the beta/gamma band. Dexmedetomidine infusion resulted in a shift towards lower frequencies with an increase in the delta range. Ketamine induced stronger activity in the higher frequencies. Our results showed substance-specific changes in EEG patterns during slow anesthesia induction. These patterns were partially identical to previous observations in humans, but also included significant differences, especially in the low frequencies. Our study emphasizes strengths and limitations of murine models in neuroscience and provides an important basis for future studies investigating complex neurophysiological mechanisms.

Postoperative liver injury after sevoflurane or propofol anesthesia in patients undergoing non-cardiac surgery: a retrospective cohort study.

Although sevoflurane is generally considered safe, reports suggest that sevoflurane may cause postoperative liver injury more frequently than previously believed. Therefore, we aimed to compare the incidence of clinically significant postoperative liver injury following non-cardiac surgery between patients who underwent sevoflurane anesthesia and propofol-based total intravenous anesthesia. We retrospectively reviewed adult surgical patients from January 2010 to September 2022 who underwent general anesthesia in our center using sevoflurane or propofol over 3 h. After 1:1 propensity score matching, the incidence of postoperative liver injury was compared between the two groups. Out of 58,300 patients reviewed, 44,345 patients were included in the analysis. After propensity score matching, 7767 patients were included in each group. The incidence of postoperative liver injury was 1.4% in the sevoflurane group, which was similar to that in the propofol group (1.6%; p = 0.432). Comparison of the severity of postoperative alanine aminotransferase elevation showed that the incidence of borderline and mild elevation was higher in the sevoflurane group, but there was no difference in the incidence of moderate and severe elevation. In conclusion, sevoflurane anesthesia over 3 h was not associated with a higher incidence of clinically significant postoperative liver injury compared to propofol anesthesia.

Integrated ribosome and proteome analyses reveal insights into sevoflurane-induced long-term social behavior and cognitive dysfunctions through ADNP inhibition in neonatal mice.

A growing number of studies have demonstrated that repeated exposure to sevoflurane during development results in persistent social abnormalities and cognitive impairment. Davunetide, an active fragment of the activity-dependent neuroprotective protein (ADNP), has been implicated in social and cognitive protection. However, the potential of davunetide to attenuate social deficits following sevoflurane exposure and the underlying developmental mechanisms remain poorly understood. In this study, ribosome and proteome profiles were analyzed to investigate the molecular basis of sevoflurane-induced social deficits in neonatal mice. The neuropathological basis was also explored using Golgi staining, morphological analysis, western blotting, electrophysiological analysis, and behavioral analysis. Results indicated that ADNP was significantly down-regulated following developmental exposure to sevoflurane. In adulthood, anterior cingulate cortex (ACC) neurons exposed to sevoflurane exhibited a decrease in dendrite number, total dendrite length, and spine density. Furthermore, the expression levels of Homer, PSD95, synaptophysin, and vglut2 were significantly reduced in the sevoflurane group. Patch-clamp recordings indicated reductions in both the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs). Notably, davunetide significantly ameliorated the synaptic defects, social behavior deficits, and cognitive impairments induced by sevoflurane. Mechanistic analysis revealed that loss of ADNP led to dysregulation of Ca 2+ activity via the Wnt/ß-catenin signaling, resulting in decreased expression of synaptic proteins. Suppression of Wnt signaling was restored in the davunetide-treated group. Thus, ADNP was identified as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general anesthetics. This study provides important insights into the mechanisms underlying social and cognitive disturbances caused by sevoflurane exposure in neonatal mice and elucidates the regulatory pathways involved.

In vivo imaging reveals a synchronized correlation among neurotransmitter dynamics during propofol and sevoflurane anesthesia.

General anesthesia is widely applied in clinical practice. However, the precise mechanism of loss of consciousness induced by general anesthetics remains unknown. Here, we measured the dynamics of five neurotransmitters, including γ-aminobutyric acid, glutamate, norepinephrine, acetylcholine, and dopamine, in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective. Results revealed that the concentrations of γ-aminobutyric acid, glutamate, norepinephrine, and acetylcholine increased in the cortex during propofol-induced loss of consciousness. Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia. Notably, the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness. Furthermore, the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups. These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.

The cGAS/STING signaling pathway is involved in sevoflurane induced neuronal necroptosis via regulating microglia M1 polarization.

OBJECTIVE: The specific mechanisms of sevoflurane-induced neurotoxicity are still undetermined. The aim of the current study was to investigate the role of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway in sevoflurane-induced neuronal necroptosis. METHODS: BV2 microglial cells were divided into a control group and a 4% sevoflurane exposure group. Western blotting was used to detect expression of the M1 polarization marker inducible nitric oxide synthase (iNOS). RNA was collected for RNA sequencing analysis. After STING knockdown in microglia, western blotting was performed to examine expression of the pro-inflammatory markers CD16 and CD32. The tumor necrosis factor-α (TNF-α) level in media was detected using an enzyme-linked immunosorbent assay. BV2 microglia conditioned media was collected to incubate HT22 neuronal cells, and their cell activity was measured using a CCK8 assay. Calcium was observed by fluorescence. Western blotting was performed to evaluate receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like (MLKL) expression. Neuronal necroptosis rate were detected using flow cytometry. RESULTS: Sevoflurane exposure promoted microglial M1 polarization. The cGAS/STING pathway was screened and identified by RNA sequencing analysis of sevoflurane-exposed microglia and the control group. Compared with the control group, STING knockdown in microglia rescued the amoeboid morphology, inhibited TNF-α release, and significantly decreased iNOS, CD16, and CD32 expression. Moreover, calcium ions and necroptosis within neurons were decreased, and RIPK1, RIPK3, and p-MLKL expression was markedly decreased in microglia media culture with STING knockdown. CONCLUSION: These results suggest that sevoflurane can regulate microglial M1 polarization by activating the cGAS/STING signaling pathway and increasing immune factor release, thus accelerating the neuronal necroptosis induced by calcium overload.

Comparison between inhalational anesthetics in terms of DNA damage and immunological markers.

This study compared genetic damage and immunological markers between surgical patients who underwent inhalational anesthesia with isoflurane or sevoflurane. Blood samples were collected from surgical patients (n = 18 in the isoflurane group and n = 17 in the sevoflurane group) at baseline (before the anesthesia procedure) and the day after anesthesia. DNA damage was detected using an alkaline comet assay; proinflammatory interleukin (IL)-6 was detected by flow cytometry, and white blood cells were detected via an automatic hematology analyzer. The characteristics of both groups were similar, and neither of the two anesthetics induced DNA damage. Similarly, mild neutrophilia was observed after anesthesia in both groups. Increased IL-6 levels were observed 1 day after anesthesia regardless of the type of anesthetic, but this increase was greater in the isoflurane group. Our study suggested that isoflurane and sevoflurane administration may contribute to changes in the immune parameters measured, though no genotoxic hazard was identified, in healthy adult patients who undergo low-stress surgery.

Effects of sevoflurane on lung alveolar epithelial wound healing and survival in a sterile in vitro model of acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a serious lung condition that often leads to hospitalization in intensive care units and a high mortality rate. Sevoflurane is a volatile anesthetic with growing interest for sedation in ventilated patients with ARDS. It has been shown to have potential lung-protective effects, such as reduced inflammation and lung edema, or improved arterial oxygenation. In this study, we investigated the effects of sevoflurane on lung injury in cultured human carcinoma-derived lung alveolar epithelial (A549) cells. We found that sevoflurane was associated with improved wound healing after exposure to inflammatory cytokines, with preserved cell proliferation but no effect on cell migration properties. Sevoflurane exposure was also associated with enhanced cell viability and active autophagy in A549 cells exposed to cytokines. These findings suggest that sevoflurane may have beneficial effects on lung epithelial injury by promoting alveolar epithelial wound healing and by influencing the survival and proliferation of A549 epithelial cells in vitro. Further research is needed to confirm these findings and to investigate the key cellular mechanisms explaining sevoflurane's potential effects on lung epithelial injury.

Nicardipine constant rate infusion alleviates the cardiovascular effects of dexmedetomidine infusions without affecting the minimal alveolar concentration in sevoflurane-anesthetized dogs.

Two randomized crossover trials evaluated the effects of nicardipine constant rate infusion (CRI) on 1) the anesthetic potency of sevoflurane and 2) the ability to attenuate dexmedetomidine-induced cardiovascular depression in anesthetized dogs. First, six healthy Beagle dogs weighing 11.7 ± 0.9 kg were allocated to one of three treatments that administered a CRI of carrier (saline) or dexmedetomidine 0.5 or 3.0 µg/kg/h following a loading dose. The minimum alveolar concentration (MAC) of sevoflurane was determined utilizing electric stimuli before and after the loading dose of nicardipine (20 µg/kg intravenously for 10 min), followed by CRI at 40 µg/kg/h with 60 min of equilibration. Subsequently, cardiovascular and blood gas variables were evaluated in another trial under sevoflurane anesthesia at the individual 1.5 MAC. After baseline measurements, the dogs were assigned to two treatments (dexmedetomidine CRI at 0.5 or 3.0 µg/kg/h following a loading dose) with sevoflurane doses adjusted to 1.5 times of MAC equivalent, and the measurements were repeated every 15 min for 120 min. After 60 min, nicardipine CRI at 40 µg/kg/h with a loading dose was added to the dexmedetomidine CRI. Dexmedetomidine infusions significantly decreased the sevoflurane MAC but nicardipine did not significantly alter the MAC either with or without dexmedetomidine CRI in dogs. Dexmedetomidine dose-dependently decreased the cardiac index and increased the systemic vascular resistance index; these effects were fully counteracted by concomitant nicardipine CRI. Nicardipine CRI can be useful for controlling the cardiovascular depression elicited by dexmedetomidine in anesthetized dogs without affecting the anesthetic potency of sevoflurane.

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.

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.

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.

Lidocaine effects on neutrophil extracellular trapping and angiogenesis biomarkers in postoperative breast cancer patients with different anesthesia methods: a prospective, randomized trial.

BACKGROUND: Anesthesia techniques and drug selection may influence tumor recurrence and metastasis. Neutrophil extracellular trapping (NETosis), an immunological process, has been linked to an increased susceptibility to metastasis in individuals with tumors. Furthermore, recurrence may be associated with vascular endothelial growth factor A (VEGF-A), a mediator of angiogenesis. This study investigates the impact of lidocaine (combined with sevoflurane or propofol anesthesia ) during breast cancer surgery inhibits the expression of biomarkers associated with metastasis and recurrence (specifically H3Cit, NE, MPO, MMP-9 and VEGF-A). METHODS: We randomly assigned 120 women undergoing primary or invasive breast tumor resection to receive one of four anesthetics: sevoflurane (S), sevoflurane plus i.v. lidocaine (SL), propofol (P), and propofol plus i.v. lidocaine (PL). Blood samples were collected before induction and 3 h after the operation. Biomarkers associated with NETosis (citrullinated histone H3 [H3Cit], myeloperoxidase [MPO], and neutrophil elastase [NE]) and angiogenesis were quantified using enzyme-linked immunosorbent assays. RESULTS: Patient and breast tumor characteristics, along with perioperative management, did not differ between study groups. In intra-group comparisons, S and P groups demonstrated a statistically significant increase in post-operative MPO (S group: 10.39[6.89-17.22] vs. 14.31[8.55-20.87] ng ml-1, P = 0.032; P group: 9.45[6.73-17.37] vs. 14.34[9.87-19.75] ng ml-1, P = 0.035)and NE(S group: 182.70[85.66-285.85] vs. 226.20[91.85-391.65] ng ml-1, P = 0.045; P group: 154.22[97.31-325.30] vs. 308.66[132.36-483.57] ng ml-1, P = 0.037) concentrations compared to pre-operative measurements, whereas SL and PL groups did not display a similar increase. H3Cit, MMP-9, and VEGF-A concentrations were not significantly influenced by the anesthesia techniques and drugs. CONCLUSIONS: Regardless of the specific technique employed for general anesthesia, there was no increase in the postoperative serum concentrations of MPO and NE after perioperative lidocaine infusion compared to preoperative serum concentrations. This supports the hypothesis that intravenous lidocaine during cancer surgery aimed at achieving a cure may potentially decrease the likelihood of recurrence. Further interpretation and discussion of clinical implications are warranted, emphasizing the significance of these findings in the context of cancer surgery and recurrence prevention. CLINICAL TRIAL REGISTRATION: ChiCTR2300068563.

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).

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.

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.

Epigenetic Mechanism of SETD1B-mediated Histone Methylation in Cognitive Impairment Induced by Sevoflurane Anesthesia in Neonatal Mice.

Sevoflurane (Sev) anesthesia is associated with cognitive deficits and neurotoxicity. This study explores the epigenetic mechanism of SET domain containing 1B (SETD1B) in Sev-induced cognitive impairment in neonatal mice. Neonatal mice (C57BL/6, n = 72) were exposed to 3% Sev for 2 h per day at P6, 7, and 8, and the control neonatal mice were only separated from the mother for 2 h. The mice were divided into groups of 12 individuals, with an equal number of male and female mice in each group. Mice were intraperitoneally injected with adenovirus-packaged SETD1B overexpression vector. Behavioral tests (Morris water maze, open field test, T-maze, novel object recognition, etc.) were performed at P30. Mouse hippocampal neuronal cells were cultured in vitro. SETD1B, C-X-C motif chemokine receptor 4 (CXCR4), NLR family pyrin domain containing 1 (NLRP1), Cleaved Caspase1, and GSDMD-N expressions in hippocampal tissues or cells were determined by quantitative real-time polymerase chain reaction and Western blot. SETD1B and histone H3 lysine 4 methylation (H3K4me1, H3K4me2, and H3K4me3) enrichment on the CXCR4 promoter was analyzed by ChIP. Sev insulted cognitive impairment and diminished SETD1B expression in mouse hippocampal tissues. SETD1B overexpression mitigated cognitive impairment, enhanced H3K4me3 levels in hippocampal tissues, and restrained hippocampal neuronal pyroptosis. SETD1B increased CXCR4 expression by elevating the H3K4me3 level on the CXCR4 promoter, thereby curbing NLRP1/Caspase1-mediated hippocampal neuronal pyroptosis. To conclude, SETD1B enhances CXCR4 expression by elevating the H3K4me3 level on the CXCR4 promoter, thereby suppressing NLRP1/Caspase1-triggered hippocampal neuronal pyroptosis and alleviating Sev-induced cognitive impairment in neonatal mice.

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.

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.