General Anesthetic Research Articles

Head and neck cancers: epidemiology, diagnosis and treatments

Introduction: Head and neck cancers (HNC) affect many subsites in the upper aero-digestive tract. The risk factors include tobacco smoking, chewing betel nut/paan, excessive alcohol consumption, hereditary factors and viruses such as human papillomavirus (HPV) and Epstein–Barr virus (EBV). Early diagnosis, lifestyle changes and HPV vaccination will improve survival. Epidemiology: Globally, recent estimates from GLOBOCAN shows there are 890,000 cases of head and neck cancers annually and 450,000 deaths annually (1). There is an increasing incidence of oral cavity, lip, buccal cancers in the developing world due to higher consumption of tobacco, alcohol and chewing areca nut. There has been an increasing incidence of some HNC due to high-risk strains of human papillomavirus (HPV) (2). Cancers caused by HPV include tonsil cancer, tongue base cancer and unknown primary cancers. The EBV causes nasopharyngeal cancers especially in the Far East. There is a decreasing incidence of some cancers caused by smoking such as laryngeal and hypopharyngeal cancers mainly due to the reduction in smoking rates in some developed countries. Overall, there is a predicted increase in HNC of up to 30% annually by 2030 (2). The HPV-associated cancers affect mainly younger males, who do not necessarily smoke or drink alcohol. The HPV is a strong prognostic factor so patients with HPV positive cancers respond better to treatment as there are less genetic mutations when compared to cancers driven by tobacco smoking. These trends are alarming with socioeconomic impacts. Diagnosis: Symptoms of HNC include difficulty swallowing, persistent sore throat, difficulty breathing, hoarseness, neck lumps, referred pain to the ear, weight loss, and systemic symptoms in advanced disease. A full ENT examination is performed of the oral cavity, oropharynx, neck and ideally flexible nasendoscopy. Ultrasound-guided FNAC or core biopsy of neck lumps are performed. Cross-sectional imaging with CT or MRI scans followed by tumour biopsies either under local or general anaesthetic. Tumour biopsies are assessed using H&E stains, and tests for HPV detection (p. 16 immunohistochemistry, in situ hybridisation or polymerase chain reaction). A PETCT scan is useful for staging cancers, identifying the origin of unknown primary cancers and for surveillance. Treatments: The head and neck cancer multidisciplinary team reviews all investigations and recommends either curative or palliative treatment options that are in every patient’s best interests. Surgery can be open, endoscopic or with the use of a robot. Microvascular reconstruction with flaps is performed as necessary to improve function and quality of life. Oncologic treatments include intensity-modulated radiotherapy (IMRT), which can be combined with chemotherapy. Immunotherapy is a second-line treatment for recurrent HNC currently. Advanced cancers can be treated with palliative intent or best supportive care especially if the patients are frail and have significant comorbidities. There are ongoing clinical trials and research studies exploring better, less-toxic treatments. Multiomics approach and artificial intelligence are exciting developments. Conclusion: There is an increasing incidence of some HNC especially cancers driven by tobacco smoking, alcohol consumption and high-risk human papillomaviruses. Smoking cessation, HPV vaccination, early diagnosis and improvements in treatments are important factors in ensuring good outcomes.

Comparing Similarity And Difference between Two Local Anesthetics, Lidocaine And Procaine

Amide type lidocaine and lipid type procaine are important anesthetics. In fact, they not only solve the problem of overused opioids, but also stimulate the invention of local anesthetic operations, which both declines the time of surgery and limits the possible damage of general anesthetics to patients’ bodies. But these two anesthetics also have their different target diseases, mechanisms, and side effects. For example, lidocaine is not only used for analgesic in dental and skin surgery operations, but also maintain the welfare of patients, who stay in the hospital waiting for recovery, by limiting the pain they could feel from their chronic illness. Actually, procaine has antiatherogenic effects, also multiple target sites which could provide some protection for the old while using. Besides, based on the fact that these chemicals come from different groups, amide type and lipid type, their mechanisms causing anesthetic effects could also be different, which would be introduced in the following context.

Cognitive function mediates the relationship between age and anaesthesia-induced oscillatory-specific alpha power.

Cognitive decline is common among older individuals, and although the underlying brain mechanisms are not entirely understood, researchers have suggested using EEG frontal alpha activity during general anaesthesia as a potential biomarker for cognitive decline. This is because frontal alpha activity associated with GABAergic general anaesthetics has been linked to cognitive function. However, oscillatory-specific alpha power has also been linked with chronological age. We hypothesize that cognitive function mediates the association between chronological age and (oscillatory-specific) alpha power. We analysed data from 380 participants (aged over 60) with baseline screening assessments and intraoperative EEG. We utilized the telephonic Montreal Cognitive Assessment to assess cognitive function. We computed total band power, oscillatory-specific alpha power, and aperiodics to measure anaesthesia-induced alpha activity. To test our mediation hypotheses, we employed structural equation modelling. Pairwise correlations between age, cognitive function and alpha activity were significant. Cognitive function mediated the association between age and classical alpha power [age → cognitive function → classical alpha; β = -0.0168 (95% confidence interval: -0.0313 to -0.00521); P = 0.0016] as well as the association between age and oscillatory-specific alpha power [age → cognitive function → oscillatory-specific alpha power; β = -0.00711 (95% confidence interval: -0.0154 to -0.000842); P = 0.028]. However, cognitive function did not mediate the association between age and aperiodic activity (1/f slope, P = 0.43; offset, P = 0.0996). This study is expected to provide valuable insights for anaesthesiologists, enabling them to make informed inferences about a patient's age and cognitive function from an analysis of anaesthetic-induced EEG signals in the operating room. To ensure generalizability, further studies across different populations are needed.

Gastric Ultrasound for Gastric Content Evaluation.

Gastric content aspiration occurs once every 2000-3000 general anaesthetics. It is associated with a 20% incidence of in-hospital mortality. The incidence of pulmonary aspiration in patients undergoing surgery is at least three times more, up to 1 in 895 general anaesthetics. Pulmonary aspiration indeed is associated with half of our airway-related mortality linked with anaesthesia. The pulmonary aspiration causes significant morbidity including respiratory failure, acute lung injury, and multi-organ failure in adults. This review study aims to compare the stomach volume and contents in patients following standard fasting guidelines by Point of care gastric ultrasound measurements. Perioperative gastric ultrasound is a developing diagnostic modality that is modest, easy, non-invasive and efficient. It is very helpful to determine gastric contents in adult, obese, paediatric, and obstetric patients. It is a dependable and replicable tool that can be used for effective anaesthetic management. Gastric ultrasound is an irreplaceable procedure to complement the use of fasting guidelines, particularly when these guidelines have not been followed, or may not be relevant. Further series of research with metanalysis is required to understand the influence of point-of-care gastric ultrasound assessment on perioperative outcomes.

Microglia facilitate and stabilize the response to general anesthesia via modulating the neuronal network in a brain region-specific manner

General anesthesia leads to a loss of consciousness and an unrousable state in patients. Although general anesthetics are widely used in clinical practice, their underlying mechanisms remain elusive. The potential involvement of nonneuronal cells is unknown. Microglia are important immune cells in the central nervous system (CNS) that play critical roles in CNS function and dysfunction. We unintentionally observed delayed anesthesia induction and early anesthesia emergence in microglia-depleted mice. We found that microglial depletion differentially regulates neuronal activities by suppressing the neuronal network of anesthesia-activated brain regions and activating emergence-activated brain regions. Thus, microglia facilitate and stabilize the anesthesia status. This influence is not mediated by dendritic spine plasticity. Instead, it relies on the activation of microglial P2Y12 and subsequent calcium influx, which facilitates the general anesthesia response. Together, we elucidate the regulatory role of microglia in general anesthesia, extending our knowledge of how nonneuronal cells modulate neuronal activities.

Microglia facilitate and stabilize the response to general anesthesia via modulating the neuronal network in a brain region-specific manner.

General anesthesia leads to a loss of consciousness and an unrousable state in patients. Although general anesthetics are widely used in clinical practice, their underlying mechanisms remain elusive. The potential involvement of nonneuronal cells is unknown. Microglia are important immune cells in the central nervous system (CNS) that play critical roles in CNS function and dysfunction. We unintentionally observed delayed anesthesia induction and early anesthesia emergence in microglia-depleted mice. We found that microglial depletion differentially regulates neuronal activities by suppressing the neuronal network of anesthesia-activated brain regions and activating emergence-activated brain regions. Thus, microglia facilitate and stabilize the anesthesia status. This influence is not mediated by dendritic spine plasticity. Instead, it relies on the activation of microglial P2Y12 and subsequent calcium influx, which facilitates the general anesthesia response. Together, we elucidate the regulatory role of microglia in general anesthesia, extending our knowledge of how nonneuronal cells modulate neuronal activities.

Anesthetic protocol using propofol and isoflurane in spectacled bear (Tremarctos ornatus)

The management of wild animals generally requires chemical containment with the use of sedatives, tranquilizers, general anesthetics or dissociative drugs. The spectacled bear (Tremarctos ornatus) is the only member of the family Ursidae characteristic of South America. There are few reports on the main anesthetic protocols used in this specie. The aim of the present study was to report the use of propofol and isoflurane in a captive spectacled bear, after sedation with tiletamine-zolazepam. A male bear approximately 15 years old and 264 lb (scale weight) underwent anesthesia for treatment of a recurrent ulcerated wound on the neck. A combination of tiletamine and zolazepam injected intramuscularly was initially used. Due to the need to prolong the anesthetic time, the decision was made to administer propofol 1% (4.0 mg/kg/IV), which proved satisfactory regarding the inhibition of eyelid and laryngotracheal reflexes, thereby facilitating tracheal intubation. The subsequent use of isoflurane provided adequate maintenance of anesthesia, with vital signs within the normal range for the species, but there was hyperthermia. Based on the present findings, the use of tiletamine/zolazepam, propofol and isoflurane proved satisfactory and the doses employed were safe for the spectacled bear (Tremarctos ornatus). Inhalation anesthesia was essential to prolonging the time and maintaining safety throughout the procedure.

Spinal Versus General Anesthesia for Outpatient Total Hip and Knee Arthroplasty in the Ambulatory Surgery Center: A Matched-Cohort Study

BackgroundSpinal anesthesia is the predominant regimen in outpatient total joint arthroplasty (TJA), but induction often is unsuccessful, unobtainable, or against patient preference. We compared outcomes of same-day discharge (SDD) TJA with spinal versus general anesthesia in a free-standing ambulatory surgery center (ASC). MethodsWe took 105 general anesthesia TJA and one-to-one nearest-neighbor matched them to 105 spinal anesthesia TJA over 7 years at 1 ASC. The rate of successful SDD, minutes to discharge, postoperative pain and nausea, and 90-day complications were compared. Postanesthesia care unit outcomes were additionally stratified by spinal anesthetic (mepivacaine versus bupivacaine). ResultsAll spinal anesthetic patients underwent SDD compared with 103 (98%) general anesthetic patients (P = .498). Mepivacaine spinal anesthesia patients spent the fewest minutes in postanesthesia care unit prior to discharge from the facility (206), followed by general anesthesia (227), and bupivacaine spinal anesthesia (291; P < .001). General anesthesia patients had the highest levels of pain at 1 hour (5.2 versus 1.5 versus 1.5) and 2 hours (3.2 versus 2.0 versus 1.3) postoperatively, and rates of nausea (48 versus 22 versus 28%) compared with mepivacaine and bupivacaine spinal anesthesia, respectively. The 90-day complications (6 versus 7), admissions (1 versus 3), and reoperations (5 versus 2) were similar among spinal and general anesthesia, respectively (P ≥ .445). ConclusionsBoth spinal and general anesthesia led to reliable SDD with similar 90-day complication rates. General anesthesia facilitated faster discharge from the ASC compared with bupivacaine spinal anesthesia but led to higher levels of pain and incidence of nausea postoperatively. Level of EvidenceLevel 3, Retrospective Cohort Comparison.

Apoptotic mechanism of development inhibition in zebrafish induced by esketamine

Esketamine, a widely used intravenous general anesthetic, is also employed for obstetric and pediatric anesthesia, and depression treatment. However, concerns regarding esketamine abuse have emerged. Moreover, the potential in vivo toxicity of esketamine on growth and development remains unclear. To address these concerns, we investigated the effects of esketamine exposure on developmental parameters, cell apoptosis, and gene expression in zebrafish. Esketamine exposure concentration-dependently decreased the heart rate and body length of zebrafish embryos/larvae while increasing the hatching rate and spontaneous movement frequency. Developmental retardation of zebrafish larvae, including shallow pigmentation, small eyes, and delayed yolk sac absorption, was also observed following esketamine treatment. Esketamine exposure altered the expression of apoptosis-related genes in zebrafish heads, primarily downregulating bax, caspase9, caspase3, caspase6, and caspase7. Intriguingly, BTSA1, a Bax agonist, reversed the anti-apoptotic and decelerated body growth effects of esketamine in zebrafish. Collectively, our findings suggest that esketamine may hinder embryonic development by inhibiting embryonic apoptosis via the Bax/Caspase9/Caspase3 pathway. To the best of our knowledge, this is the first study to report the lethal toxicity of esketamine in zebrafish. We have elucidated the developmental toxic effects of esketamine on zebrafish larvae and its potential apoptotic mechanisms. Further studies are warranted to evaluate the safety of esketamine in animals and humans.

Patient Satisfaction With, and Outcomes of, Ultrasound-Guided Regional Anesthesia at a Referral Hospital in Tanzania: A Cross-Sectional Study.

Regional anesthesia techniques are increasingly used in high-income countries (HICs) for both surgical anesthesia and postoperative analgesia. However, regional anesthesia has not been utilized to the same degree in low- to middle-income countries (LMICs) due to a lack of resources and trained personnel. This study evaluates patient satisfaction with, and outcomes of, ultrasound-guided regional anesthesia for extremity surgery at Kilimanjaro Christian Medical Center (KCMC) in the Northeastern zone of Tanzania. Study patients were ≥18 years of age; American Society of Anesthesiologists (ASA) physical status I, II, or III; and underwent extremity surgery under peripheral nerve block with ultrasound guidance at KCMC. After placement, blocks were assessed for effectiveness intraoperatively, as demonstrated by the need for supplemental analgesic or sedative medication or conversion to a general anesthetic. Postoperatively, patients were assessed for satisfaction with their nerve block and pain at 12 and 24 hours. Adverse events related to regional anesthesia were assessed immediately, 45 minutes after block placement, and at 12 and 24 hours postoperatively. The primary outcome was patient satisfaction at 12 hours. Secondary outcomes were block success rate and analgesia at 12 and 24 hours postoperatively. A convenience sample of 170 patients was included in the study, of whom 156 (95% confidence interval [CI], 87-95) were either satisfied or very satisfied with their block. Block placement was highly successful with only 8 of 170 participants (95% CI, 2.4-8.3), requiring conversion to a general anesthetic. Analgesia continued in the postoperative period, with 164 of 170 (95% CI, 93-98) patients and 145 of 170 (95% CI, 80-90) patients reporting acceptable analgesia at 12 and 24 hours, respectively. No major adverse events, such as local anesthetic toxicity, infection, bleeding, nerve injury, or pneumothorax, were observed. Our study found that ultrasound-guided regional anesthesia in a resource-constrained setting was effective for extremity surgery and resulted in high patient satisfaction. No complications occurred. The use of ultrasound-guided regional anesthesia shows promise for the safe and effective care of patients undergoing extremity surgery in LMICs.

Crosstalk between GABAA receptors in astrocytes and neurons triggered by general anesthetic drugs

General anesthetic drugs cause cognitive deficits that persist after the drugs have been eliminated. Astrocytes may contribute to such cognition-impairing effects through the release of one or more paracrine factors that increase a tonic inhibitory conductance generated by extrasynaptic γ-aminobutyric acid type A (GABAA) receptors in hippocampal neurons. The mechanisms underlying this astrocyte-to-neuron crosstalk remain unknown. Interestingly, astrocytes express anesthetic-sensitive GABAA receptors. Here, we tested the hypothesis that anesthetic drugs activate astrocytic GABAA receptors to initiate crosstalk leading to a persistent increase in extrasynaptic GABAA receptor function in neurons. We also investigated the signaling pathways in neurons and aimed to identify the paracrine factors released from astrocytes. Astrocytes and neurons from mice were grown in primary cell cultures and studied using in vitro electrophysiological and biochemical assays. We discovered that the commonly used anesthetics etomidate (injectable) and sevoflurane (inhaled) stimulated astrocytic GABAA receptors, which in turn promoted the release paracrine factors, that increased the tonic current in neurons via a p38 MAPK-dependent signaling pathway. The increase in tonic current was mimicked by exogenous IL-1β and abolished by blocking IL-1 receptors; however, unexpectedly, IL-1β and other cytokines were not detected in astrocyte-conditioned media. In summary, we have identified a novel form of crosstalk between GABAA receptors in astrocytes and neurons that engages a p38 MAPK-dependent pathway.Brief commentary BackgroundMany older patients experience cognitive deficits after surgery. Anesthetic drugs may be a contributing factor as they cause a sustained increase in the function of “memory blocking” extrasynaptic GABAA receptors in neurons. Interestingly, astrocytes are required for this increase; however, the mechanisms underlying the astrocyte-to-neuron crosstalk remain unknown. Translational significanceWe discovered that commonly used general anesthetic drugs stimulate GABAA receptors in astrocytes, which in turn release paracrine factors that trigger a persistent increase in extrasynaptic GABAA receptor function in neurons via p38 MAPK. This novel form of crosstalk may contribute to persistent cognitive deficits after general anesthesia and surgery.

Effect of Regional Anesthesia on Oncological Outcomes (Meta-Analysis)

Metastatic processes remain the main cause of deaths in oncology. Methods of anesthesia, in particular regional anesthesia, are considered as potential modulators of the immune response and metastatic spread. The ambiguity of the available data on the effect of regional and general anesthesia on metastatic spread is partly due to the fact that general anesthetic in combined anesthesia is quite often not taken into account, and this, in turn, masks the possible influence of regional anesthesia.The purpose of this meta-analysis was to make a comparative assessment of the effect of general anesthesia and general anesthesia in combination with regional anesthesia on the relapse-free and overall survival of cancer patients after surgery.Materials and methods. We analyzed 8 randomized controlled trials involving 1822 patients and comparing the groups of cancer patients who were operated either under general anesthesia (total intravenous (TIVA) or inhalation (IA)), or general anesthesia in combination with regional anesthesia (TIVA+RA or IA+RA, respectively). Trial using combinations of inhaled and intravenous anesthetics was excluded from the analysis for a more accurate assessment of the effect of regional anesthesia. The study complies with the recommendations of the Cochrane Community and PRISMA standards. The protocol was registered on the INPLASY platform. We used PubMed, Google Scholar and CENTRAL databases. We used a subgroup analysis and GRADE tool to assess the quality of evidence.Results. There were no statistically significant differences in relapse-free and overall survival when comparing different anesthesia methods. For a relapse-free survival, comparing TIVA vs TIVA+RA resulted in no significant difference : OR=1.20 [95% CI 0.92-1.55]; when IA vs IA+RA were compared, OR=1.10 [95% CI 0.94-1.29]. Similar results were obtained for overall survival.Conclusion. Based on the meta-analysis results, regional anesthesia had no effect on relapse-free and overall survival in oncosurgery patients.

Seeing is Believing: Chasing Sevoflurane Vapor Trails

PurposeSevoflurane is an inhalational general anesthetic that has been used recently to treat chronic, painful lesions, reportedly supporting analgesia and wound healing. The potential for repeated exposure to off-gassed sevoflurane vapor, especially outside the air-conditioned operating theatre environment, is of some concern. DesignThis paper explores the qualitative and quantitative pathing of off-gassed sevoflurane from a topically applied liquid source. MethodsUsing a small, unventilated test-box (total volume 0.5 m3) with infra-red imaging and gas-analysing, we investigated the spatial distribution of sevoflurane vapor following complete vaporization of a 20 mL liquid sample. Utilizing the infra-red absorption of sevoflurane, it was possible to visualize (as an apparent reduction in temperature) the streaming path of the sevoflurane vapor. Sevoflurane levels (%) in the test-box were measured using an infra-red gas analyzer. FindingsIn keeping with its higher density than air, sevoflurane vapor was seen to “waterfall” from the liquid source and accumulate in the bottom of the test-box. Sevoflurane vapor concentration was minimal above the liquid source. When extrapolated to a larger (unventilated) room, we estimate that the sevoflurane concentration would be less than 10 ppm one centimetre above the liquid pool. With vacuum extraction, these levels would be even lower. ConclusionsDue to sevoflurane’s tendency to accumulate on the floor, it is concluded that topical application of liquid sevoflurane posses virtually no risk to off-gas exposure in unventilated spaces.

Novel treatment system using endoscopic ultrasound-guided high-intensity focused ultrasound: A proof-of-concept study

AimHigh-intensity focused ultrasound (HIFU) is a novel minimally invasive local treatment of solid tumors. Endoscopic ultrasound-guided HIFU (EUS-HIFU) using mechanical effects would have potential benefits, including precise detection of target lesions and enhance drug delivery. The aim of this study is to develop EUS-HIFU device and to prove our concept in porcine model using a locally injected phase change nano droplet (PCND) as the sensitizer. MethodA phospholipid PCND contained volatile perfluoro-carbon liquids. The prototype HIFU apparatus comprised a small (20 × 20 mm) transducer with center frequency of 2.1 MHz, attachable to a linear EUS transducer. Under general anesthetic, a single porcine received EUS-guided injection of PCND. The HIFU transducer was placed laparotomically in the stomach, and the liver was ablated through the gastric wall. ResultsPCND was injected successfully and a distinct lesion was generated at the HIFU transducer focus only in injected areas that received HIFU exposure at 4.7 kW/cm2 at a duty cycle of 5 % (mean temporal intensity, 0.245 kW/cm2) for 30 s. The generated lesions were mechanically fractionated in macroscopic view. ConclusionThe concept of transluminal HIFU ablation using novel EUS-HIFU system was proved in a porcine animal model. This novel treatment system has great potential for future cancer treatment although further investigation in more animals and different organs are warranted.

A retrospective analysis of the patient journey for children with an unerupted maxillary central incisor.

Maxillary central incisors (MCI) are the third most impacted teeth. Timely multidisciplinary management is indicated as unerupted incisors can cause functional- and appearance-related distress. To assess the patient journey for children with unerupted MCI, including referral, clinical assessment, surgical management and follow-up treatment, and highlight areas for improvement, as well as identify factors impacting orthodontic treatment burden (OTB). A retrospective service evaluation of children aged 6-16 years who had surgical management of unerupted MCI under general anaesthetic (GA) between 2018 and 2021. Fifty-two children with 62 unerupted MCI were identified. Mean age at referral was 8.8 years. Most children (82.7%) had supernumerary teeth in the anterior maxilla. Mean time between listing for GA and surgery increased from 4.3 to 15.2 months following the COVID-19 lockdown. Mean age at surgery was 10.4 years. Supernumerary removal and incisor exposure and bond was the most common treatment (56.6%). Most patients required hospital orthodontic treatment post-surgery (65.4%). Most children referred were below 9 years (60.1%); these children had reduced OTB compared to those who had been referred at an older age. Stage of root development was also a significant predictor in OTB. An unexpected finding was that conical supernumeraries were found to prevent MCI eruption.

The Use of Isoflurane and Adjunctive Magnesium Chloride Provides Fast, Effective Anaesthetization of Octopus vulgaris.

A wide variety of substances have been used to anaesthetise invertebrates, but many are not anaesthetics and merely incapacitate animals rather than preventing pain. In essence, the role of an ideal general anaesthetic is to act as a muscle relaxant, an analgesic, an anaesthetic, and an amnesic. To achieve all these properties with a single substance is difficult, and various adjuvants usually need to be administered, resulting in a cocktail of drugs. In a clinical setting, the vast majority of patients are unaware of surgery being carried out and have no memory of it, so they can claim to have felt no pain, but this is much more difficult to demonstrate in invertebrates. Here, we show that 1% MgCl2, a muscle relaxant, is a useful adjuvant for the clinical anaesthetic isoflurane on Octopus vulgaris when applied alone in seawater for 10 min before the clinical anaesthetic. After this, full anaesthesia can be achieved in 5 min using 1% isoflurane insufflated into the saline still containing MgCl2. Full recovery takes place rapidly in about 10 to 15 min. The depth of anaesthesia was monitored using changes in respiratory rate, chromatophore pattern, and withdrawal movements of the arms and siphon. This methodology reduces stress on the animal and minimises the quantity of anaesthetic used.

7,8-Dihydroxyflavone ameliorates cognitive impairment induced by repeated neonatal sevoflurane exposures in mice through increasing tau O-GlcNAcylation

BackgroundSevoflurane, one of the most commonly used general anesthetics for pediatric anesthesia, has recently gained significant attention in both preclinical and clinical settings due to its potential neurotoxicity in the developing brain. Tau phosphorylation, induced by sevoflurane, is recognized as one of the major causes of neurotoxicity. 7,8-dihydroxyflavone (DHF), a TrkB receptor agonist, has been reported to exhibit potential neuroprotective effects against tauopathies. In this study, our objective was to investigate whether DHF could provide neuroprotective effects against sevoflurane-induced neurotoxicity and explore the underlying molecular mechanisms. MethodsSix-day-old mice were subjected to 2 h of anesthesia with 3 % sevoflurane, with or without pretreatment of DHF (5 mg/kg/day, i.p.) for 3 consecutive days. Autonomic motor ability was assessed by open-field test, while learning and memory abilities were evaluated by the fear conditioning test. Western blotting was conducted to measure the levels of t-TrkB, p-TrkB, tau, and phosphorylated tau. Additionally, a co-immunoprecipitation assay was performed to investigate the interaction between O-GlcNAcylation and tau. ResultsRepeated neonatal sevoflurane exposures resulted in reduced freezing time during the context and cued fear conditioning tests in adulthood. However, pretreatment with DHF restored the freezing time to the level of the control group, indicating that DHF effectively alleviated cognitive impairments induced by neonatal sevoflurane exposure. We also observed that repeated neonatal sevoflurane exposures increased tau phosphorylation while decreasing tau O-GlcNAcylation. However, DHF pretreatment rebalanced the tau O-GlcNAcylation/phosphorylation ratio by enhancing the interaction between tau and O-GlcNAcylation. ConclusionOur findings demonstrate that DHF effectively ameliorates sevoflurane-induced cognitive impairment in developing mice by restoring the balance between tau O-GlcNAcylation and phosphorylation. Therefore, this study suggests that DHF has the potential to be a therapeutic agent for treating cognitive impairment associated with anesthetics, such as sevoflurane.

Risk of attention deficit hyperactivity disorder diagnosis following multiple exposures to general anesthesia in the paediatric population: A systematic review and meta-analysis

Abstract Objectives The risk of attention deficit hyperactivity disorder (ADHD) following multiple exposures to anesthesia has been debated. Our objective was to systematically review the literature to examine the association between multiple exposures to general anesthesia before age 5 and subsequent diagnosis of ADHD. Methods A systematic search of EMBASE, PubMed, and SCOPUS was performed using key search terms in February 2022. We included studies that: were published after 1980, included only otherwise healthy children who experienced two or more exposures to general anesthetic before age 5, diagnosed ADHD by a medical professional before age 19 years after exposure to general anesthetic, were cross-sectional, case–control, or cohort study, and were published in English. The results (expressed as hazard ratios [HR] and associated 95% confidence intervals [CI]) were pooled using meta-analytic techniques. Studies which did not present their results as HR and 95% CI were analyzed separately. GRADE was used to determine the certainty of the findings. PRISMA guidelines were followed at each stage of the review. Results Eight studies (196,749 children) were included. Five reported HR and 95% CI and were subsequently pooled for meta-analysis. Multiple exposures to anesthesia were associated with diagnosis of ADHD before the 19th year of life (HR: 1.71; 95% CI: 1.59, 1.84). Two of the three studies not used in the meta-analysis also found an increased risk of ADHD diagnosis following multiple anesthetic exposures. Conclusions There was an association between multiple early exposures to general anesthesia and later diagnosis of ADHD.

The Role of Neuroactive Steroids in Analgesia and Anesthesia: An Interesting Comeback?

Published evidence over the past few decades suggests that general anesthetics could be neurotoxins especially when administered at the extremes of age. The reported pathology is not only at the morphological level when examined in very young and aged brains, given that, importantly, newly developing evidence suggests a variety of behavioral impairments. Since anesthesia is unavoidable in certain clinical settings, we should consider the development of new anesthetics. A promising and safe solution could be a new family of anesthetics referred to as neuroactive steroids. In this review, we summarize the currently available evidence regarding their anesthetic and analgesic properties.

Management for Patient with Asthma in Lumbal Canal Stenosis Using General Anesthetic and Epidural Analgetic: A Case Report

Background: Lumbar canal stenosis, which often occurs concurrently with degenerative spondylolisthesis (DS), is characterized by low back and leg pain. The treatment of high-degree spondylolisthesis is by surgery, which is a combination procedure of decompression and fusion. Surgical patients with a history of uncontrolled asthma three months before surgery had nearly double the risk of postoperative mortality. Case presentation: A 53-year-old male patient was diagnosed with Lumbal Canal Stenosis ec HNP at levels L2-l3, L3-l4, L4-l5, L5-s1 Spondylolisthesis at level L4-l5 Meyerding grade 1 Spondylosis Lumbalis. The patient has a history of mild intermittent bronchial asthma, which was diagnosed 2 years ago. The patient was planned for Decompression-Stabilization-Fusion surgery, with the anesthesia plan being general anesthesia prone position with epidural analgesia. Conclusion: Combined general anesthesia (GA) and epidural analgesia (EA) for major surgery due to excellent pain control, reduced perioperative morbidity, and even reduced mortality compared with systemic analgesia. For surgical patients who have a history of asthma, determining whether a patient's asthma is well-controlled or poorly controlled is key to mitigating perioperative complications.