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ABSTRACT Objective: Intravenous non-volatile anaesthetics like propofol are commonly used in cardiac surgeries across several countries. Volatile anaesthetics like isoflurane may help in protecting the myocardium and minimize ischaemia-reperfusion injury. Hence, we did this review to compare the cardioprotective effect of isoflurane and propofol among patients undergoing coronary artery bypass grafting (CABG). Methods: We conducted a search in the databases Medical Literature Analysis and Retrieval System Online (or MEDLINE), Embase, PubMed Central®, ScienceDirect, Google Scholar, and Cochrane Library from inception until April 2021. We carried out a meta-analysis with random-effects model and reported pooled risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI) depending on the type of outcome. Results: We analysed 13 studies including 808 participants. Almost all were low-quality studies. For cardiac index, the pooled SMD was 0.14 (95% CI: -0.22 to 0.50); for cardiac troponin I, pooled SMD was 0.10 (95% CI: -0.28 to 0.48). For mortality, the RR was 3.00 (95% CI: 0.32 to 28.43); for MI, pooled RR was 1.58 (95% CI: 0.59 to 4.20); and for inotropic drug use, pooled RR was 1.04 (95% CI: 0.90 to 1.21). For length of intensive care unit stay, the pooled SMD was 0.13 (95% CI: -0.29 to 0.55), while pooled SMD for mechanical ventilation time was -0.02 (95% CI: -0.54 to 0.51). Conclusion: Isoflurane did not have significant cardioprotective effect compared to propofol following CABG. Hence, the anaesthetists need to check some viable alternatives to manage these patients and reduce the rate of postoperative complications.
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Objective:To evaluate the effect of sleep fragmentation on postoperative cognitive dysfunction (POCD) and hippocampal glutaminergic metabolism in aged mice anesthetized with isoflurane.Methods:Forty healthy SPF-grade male C57BL/6J mice, aged 18 months, weighing 20-30 g, were divided into 4 groups ( n= 10 each) by the random number table method: normal control group (group C), sleep fragmentation group (group SF), isoflurane anesthesia/surgery group (group I/S), and sleep fragmentation plus isoflurane anesthesia/surgery group (group SF+ I/S). Group C did not received any treatment. Group SF received sleep fragmentation for 24 h. The right carotid artery exposure was performed under isoflurane anesthesia in group I/S. Group SF+ I/S received isoflurane anesthesia/right carotid artery exposure at 24 h after sleep fragmentation. The metabolic levels of glutamate (Glu), glutamine (Gln), Glu/Gln complex (Glx), and N-acetylaspartate (NAA) and their ratio to creatine (Cr) were measured by in vivo 9.4T hydrogen proton magnetic resonance spectroscopy at 2 h after anaesthesia. Y maze and Morris water maze tests were used to evaluate the cognitive function at 1-7 days after surgery. The mice were sacrificed after the behavioral testing, brain tissues were immediately obtained, and the number of Nissl bodies and density of dendritic spines in the hippocampal CA1 region were measured by Nissl staining and Golgi staining, respectively. Results:Compared with group C, the percentage of exploration time and shuttle times at the novel arm were significantly decreased, the number of crossing the original platform was decreased, the time of stay at the target quadrant was shortened, the ratios of Glu/Cr, Gln/Cr and Glx/Cr in the hippocampal CA1 region were increased, and the ratio of NAA/Cr was decreased, and the number of Nissl bodies and density of dendritic spines were decreased in SF, I/S and SF+ I/S groups ( P<0.05). Compared with group SF and group I/S, the percentage of exploration time and shuttle times at the novel arm were significantly decreased, the number of crossing the original platform was decreased, the time of stay at the target quadrant was shortened, the ratios of Glu/Cr and Glx/Cr in hippocampal CA1 region was increased, the ratio of NAA/Cr was decreased, and the number of Nissl bodies and density of dendritic spines were decreased in group SF+ I/S ( P<0.05). Conclusions:Sleep fragmentation exacerbates POCD in aged mice anesthetized with isoflurane, and the mechanism is related to nerve injury induced by abnormality in hippocampal glutaminergic metabolism excitability.
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Abstract Objectives: Isoflurane (ISO) is widely used in the clinic and research. The authors aimed to explore whether Neobaicalein (Neob) could protect neonatal mice from ISO-induced cognitive damage. Method: The open field test, Morris water maze test, and tail suspension test was performed to assess the cognitive function in mice. Enzyme-linked immunosorbent assay was used to evaluate inflammatory-related protein concentrations. Immunohistochemistry was used to assess Ionized calcium-Binding Adapter molecule-1 (IBA-1) expression. Hippocampal neuron viability was detected using the Cell Counting Kit-8 assay. Double immunofluorescence staining was employed to confirm the interaction between proteins. Western blotting was used to assess protein expression levels. Results: Neob notably improved cognitive function and exhibited anti-inflammatory effects; moreover, under isotreatment, it exhibited neuroprotective effects. Furthermore, Neob suppressed interleukin-1β, tumor necrosis factor-α, and interleukin-6 levels and upregulated interleukin-10 levels in ISO-treated mice. Neob significantly mitigated iso-induced increases in IBA-1 - positive cell numbers of the hippocampus in neonatal mice. Furthermore, it inhibited ISO-induced neuronal apoptosis. Mechanistically, Neob was observed to upregulate cAMP Response Element Binding protein (CREB1) phosphorylation and protected hippocampal neurons from ISO-mediated apoptosis. Moreover, it rescued ISO-induced abnormalities of synaptic protein. Conclusions: Neob prevented ISO anesthesia-induced cognitive impairment by suppressing apoptosis and inflammation through upregulating CREB1.
Subject(s)
Animals , Rats , Transcranial Direct Current Stimulation , Isoflurane/pharmacology , Anesthesia , Neuralgia/therapy , AnalgesicsABSTRACT
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 ß; 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-1ß), 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.
Subject(s)
Animals , Rats , Oxidative Stress , Neuroprotective Agents , Cognitive Dysfunction , Sevoflurane , IsofluraneABSTRACT
Resumen: Introducción: los sedantes de uso no convencional y aquéllos fuera de recomendación como los anestésicos inhalados se usaron ante la escasez de medicamentos durante la pandemia por SARS-CoV-2. Objetivos: comparar el costo y resultados obtenidos con el uso de anestésicos inhalados versus sedantes intravenosos en COVID-19. Material y métodos: estudio retrospectivo en una unidad de terapia intensiva (UTI) de un hospital público de referencia. Se hizo un cálculo de costos de sedación de los dos primeros días de estancia en la UTI. Las dosis de fármacos fueron tomadas del expediente clínico y los costos de adquisición directamente de CompraNet. Se comparan medias de costos por medicamento y por grupo. Resultados: de 151 pacientes, 81 recibieron sedación intravenosa y 70 anestesia inhalada con o sin sedantes intravenosos. No hubo diferencia en mortalidad, días de ventilación mecánica, estancia en la UTI y estancia hospitalaria entre grupos. Se observó una reducción significativa de costos derivados del menor uso de midazolam, propofol y dexmedetomidina (p < 0.0001) cuando se usó anestesia inhalada y una diferencia entre medias de costos totales de sedación de $4,108.42 M.N. por día por paciente. Conclusiones: la anestesia inhalada durante la pandemia por COVID-19 permitió una reducción de costos comparada con sedación intravenosa en los primeros dos días de estancia en la UTI.
Abstract: Introduction: non-conventional sedatives and those off-label, such as inhaled anesthetics, were used due to the shortage of medicines during the SARS-CoV-2 pandemic. Objectives: to compare the cost and results obtained with the use of inhaled anesthetics versus intravenous sedatives in COVID-19. Material and methods: retrospective study in a public reference hospital ICU. A calculation of sedation costs was made of the first two days of ICU stay. Drug doses were taken from the clinical records and acquisition costs directly from CompraNet. Mean costs per medication and per group are compared. Results: of 151 patients, 81 received intravenous sedation and 70 received inhaled anesthesia with or without intravenous sedatives. There was no difference in mortality, days of mechanical ventilation, ICU stay, and hospital stay between groups. A significant reduction in costs derived from the less use of midazolam, propofol and dexmedetomidine (p < 0.0001), and a difference between means of total sedation costs of $4,108.42 Mexican pesos per patient per day was observed with inhaled anesthesia. Conclusions: inhaled anesthesia during the COVID-19 pandemic compared to intravenous sedation allowed a cost reduction in the first two days of ICU stay.
Resumo: Introdução: sedativos de uso não convencional e não recomendados, como anestésicos inalatórios, foram utilizados devido à escassez de medicamentos durante a pandemia de SARS-CoV-2. Objetivos: comparar o custo e os resultados obtidos com o uso de anestésicos inalatórios versus sedativos intravenosos na COVID-19. Material e métodos: estudo retrospectivo em uma UTI de um hospital público de referência. Foi feito um cálculo dos custos de sedação para os dois primeiros dias de internação na UTI. As doses dos medicamentos foram retiradas do prontuário clínico e os custos de aquisição diretamente do CompraNet. Os custos médios por medicamento e por grupo são comparados. Resultados: dos 151 pacientes, 81 receberam sedação intravenosa e 70 anestesia inalatória com ou sem sedativos intravenosos. Não houve diferença na mortalidade, dias em ventilação mecânica, permanência na UTI e internação entre os grupos. Uma redução significativa nos custos derivados do menor uso de midazolam, propofol e dexmedetomidina (p < 0.0001) foi observada quando a anestesia inalatória foi usada e uma diferença entre as médias dos custos totais de sedação de $4,108.42 M.N. por dia por paciente. Conclusões: a anestesia inalatória durante a pandemia de COVID-19 permitiu redução de custos em comparação com a sedação endovenosa nos primeiros dois dias de internação na UTI.
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Objective:To observe and analyze the changes in activity of layer 2/3 cortical neurons in isoflurane-anesthetized mice by Real-time Ultra-large-Scale High-resolution (RUSH) imaging platform.Methods:Clean-grade healthy male Rasgrf2-Cre/Ai148d mice, aged 8-12 weeks, weighing 18-25 g, were studied.The mice recovered ten days after the skull replacement surgery and proceeded to the next experiment.Imaging data of calcium fluorescence signals from layer 2/3 cortical neurons were acquired by RUSH imaging platform after fixing the head of mice.The time of imaging data acquisition in the awake state, during anesthesia with 1.2% isoflurane, and after the end of anesthesia was 100, 600 and 600 s, respectively.Imaging data were analyzed using Image J and MATLAB softwares.Results:The overall trend of activity of layer 2/3 cortical neurons decreased first and then stabilized with the inhalation of 1.2% isoflurane.The cortical neural activity were gradually increased when isoflurane inhalation was stopped.The recovery rate of neural activity was different in different brain regions after isoflurane inhalation was stopped.The recovery of neural activity in the primary motor cortex was delayed obviously.During the maintenance of anesthesia, the activities of most layer 2/3 cortical neurons in the retrosplenial cortex were weakened, however, some of the neurons became more active.Conclusions:The neural activity in the 2/3 layer of cortex in isoflurane anesthetized mice is inconsistent in observation region, brain region and single cell, suggesting that different neural pathways are involved in the process of anesthesia induction and recovery from anesthesia.
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AIM: To examine the effects of three commonly used general anesthetics on the proliferation and activation of glial cells in neonatal rats. METHODS: Neonatal rats were exposed to either isoflurane, sevoflurane or desflurane for 2 h on postnatal day 2 (P2). The animals were euthanatihed and the brain were harvested on P7 and P14, respectively. The immunohistochemical localihation of glial markers (vimentin, GFAP, Iba1) were examined. RESULTS: Activation of astrocyte in granular layer and molecular layer of dentate gyrus of hippocampus was significantly enhanced on P7 and P14 after desflurane exposure, while that in isoflurane group the change was only significantly different on P14. The activation of microglia in the granular layer of dentate gyrus but not in the pyramidal cell layer of CA1 region was significantly enhanced in the desflurane group on P7 and P14, while the isoflurane group only showed significant difference on P14. CONCLUSION: Short time exposure of different inhalation anesthetics has different effects on the activation of glial cells in different subregions of hippocampus in neonatal rats on postnatal day 2, and sevoflurane may have the least effect on it.
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Previous studies have demonstrated that isoflurane inhale anesthesia can effectively attenuate the ischemia-reperfusion-induced pulmonary hypertension (PAH), indicating a protective effect of isoflurane on pulmonary circulation. Pulmonary artery smooth muscle cells (PASMCs) play an important role in pulmonary vascular remodeling and PAH. The abnormality of PASMC structure and function may greatly contribute to the development of PAH. This study aims to explore the effects of isoflurane on hypoxia-induced PASMC pyroptosis and the underlying mechanisms, and to find potential therapeutic target for the treatment of PAH. PASMCs were cultured at 37 ℃, 5%CO
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Objective:To investigate the effects of isoflurane anesthesia on the transcription levels of clock genes RORα and Rev-erbα and their circadian rhythm changes in the hippocampus and cerebral cortex of mice. Methods:Thirty-six 7-week-old male C57BL/6J mice were divided into control group and isoflurane anesthesia group ( n=18) according to random number table method. They were subjected to 12 h light/12 h dark environment for 1 week. Mice in the isoflurane anesthesia group were anesthetised with 1.2% isoflurane at 22:00 pm on the night before the experiment for 6 h; 4 h after anesthesia, the light time of 8:00 am was taken as the zeitgeber time (ZT0), and then, every 8 h was taken as the recorded time (ZT8, ZT16, ZT24, ZT32 and ZT40). The RORα and Rev-erbα mRNA expressions were measured by real-time fluorescent quantitative PCR (RT-qPCR) at each time point in the cerebral cortex and hippocampus of the two groups. The cosine curves of RORα and Rev-erbα mRNA expressions were analyzed by Chronos-Fit software. Results:As compared with the control group, the isoflurane anesthesia group had significantly down-regulated RORα mRNA expression in the hippocampus, significantly up-regulated RORα mRNA expression in the cerebral cortex, and significantly down-regulated Rev-erbα mRNA expression in the cerebral cortex ( P<0.05). The RORα and Rev-erbα mRNA expressions in the hippocampus and cerebral cortex of the control group showed a rhythmic cycle of about 24 h; while the circadian rhythm of RORα mRNA shifted to the right by 5.41 h, and the circadian rhythm of Rev-erbα mRNA shifted to the left by 0.89 h in the hippocampus of the isoflurane anesthesia group. The peak circadian rhythm of RORα mRNA shifted to the right by 0.35 h, and the peak circadian rhythm of Rev-erbα mRNA shifted to the left by 0.56 h in the cerebral cortex of the isoflurane anesthesia group. Conclusion:Isoflurane anesthesia can induce the changes of RORα and Rev-erbα transcription levels and circadian rhythm changes in the hippocampus and cerebral cortex of mice.
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The lateral hypothalamic area (LHA) plays a pivotal role in regulating consciousness transition, in which orexinergic neurons, GABAergic neurons, and melanin-concentrating hormone neurons are involved. Glutamatergic neurons have a large population in the LHA, but their anesthesia-related effect has not been explored. Here, we found that genetic ablation of LHA glutamatergic neurons shortened the induction time and prolonged the recovery time of isoflurane anesthesia in mice. In contrast, chemogenetic activation of LHA glutamatergic neurons increased the time to anesthesia and decreased the time to recovery. Optogenetic activation of LHA glutamatergic neurons during the maintenance of anesthesia reduced the burst suppression pattern of the electroencephalogram (EEG) and shifted EEG features to an arousal pattern. Photostimulation of LHA glutamatergic projections to the lateral habenula (LHb) also facilitated the emergence from anesthesia and the transition of anesthesia depth to a lighter level. Collectively, LHA glutamatergic neurons and their projections to the LHb regulate anesthetic potency and EEG features.
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Off pump CABG is the most commonly performed cardiac surgical procedure involving multi vessel grafting through median sternotomy. Approach of lateral and posterior walls of heart for grafting, necessitates need for lifting or tilting heart producing elevated atrial pressures, fall in cardiac output and thus profound hypotension. Maintaining delicate balance between myocardial oxygen demand and supply is crucial to prevent myocardial insults and associated sequelae for which the mean arterial pressure is maintained >70 mmHg to facilitate adequate coronary perfusion pressure achieved by infusion of vasopressors like dobutamine and increased preload. Another strategy adopted by anaesthesiologist to limit this hypotension is by reducing isoflurane and thus cardiac surgical patients are prone for awareness. Awareness is the explicit recall of sensory perceptions during anaesthesia.METHODSWe studied 40 patients with ASA physical status II & III, between age group of 18 to 65 years scheduled for elective off pump CABG after institutional ethical committee clearance and written informed consent. Patients were randomly allocated into two groups of 20 each. Group 1 (isoflurane in oxygen given with BIS maintained at 55+/-5) and Group 2 (isoflurane in oxygen given without BIS).Comparison of the two groups was done in terms of gender, age, height, weight, heart rate, hemodynamics, dial concentration, minimum alveolar concentration, drugs consumed, time to extubation and intraoperative awareness. Results were statistically analyzed using independent t test, chi square test and Fischer exact test. Data was presented in terms of mean, median and standard deviation. The 'p' value of <0.05 was considered significant.RESULTSHeart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure were higher in Group 1 compared to Group 2. The dial concentration and minimum alveolar concentration were found to be statistically significant 5 minutes after intubation upto 4.5 hours of the cardiac surgical procedure with 'p' value <0.05. Amount of midazolam and propofol used in Group 1 was higher when compared to Group 2 while there was no statistical significance with use of opioid (fentanyl) or muscle relaxant (pancuronium). Time to extubation and intraoperative awareness were comparable between both the groups.CONCLUSIONSBIS monitoring reduces amount of isoflurane used along with the prevention of awareness in cardiac surgical patients. It helps not only the anaesthesiologist but also the other operation theatre personnel by preventing environmental pollution.
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Introduction: Sevoflurane is a volatile anesthetic agent, which is non-irritant with low solubility and lack of arrhythmogenicity, which makes it an ideal agent for ambulatory anesthesia. The aim of our study is to compare the cardiovascular effects at equivalent minimum alveolar concentration (MAC) doses and the recovery profile of sevoflurane and isoflurane, in patients undergoing valvular replacement surgery. Materials and Methods: This is a hospital-based, randomized, interventional, comparative study with sample size of seventy participants divided into two groups. Group A (35) received sevoflurane (1MAC) and Group B (35) received isoflurane (1MAC). Patients were of the American Society of Anesthesiologists Grade 2–4. The age group was 20–25 years with body weight of 30–65 kg, undergoing valvular heart surgery. The primary outcomes are to compare the changes in heart rate, systolic and diastolic blood pressures, mean arterial pressure, cardiac output (CO), cardiac index, systemic vascular resistance index (SVRI), and stroke volume variable, during maintenance of anesthesia. The secondary outcomes are the time taken for eye opening on verbal commands and extubation. Results: There was a decrease in blood pressure, CO, and SVRI with both agents (statistically insignificant, P > 0.05), but comparatively hemodynamics was more stable along with early recovery with sevoflurane (statistically insignificant). Conclusions: Sevoflurane and isoflurane can safely be used for fast-track anesthesia in patients undergoing valvular heart surgery. Sevoflurane provided a better hemodynamic profile, early awakening, and extubation as compared with isoflurane, even though the difference was insignificant. Thus, sevoflurane with opioids may be preferred in patients undergoing valvular heart surgery
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OBJECTIVE@#To study the protective effect of isoflurane preconditioning on hepatic ischemia-reperfusion (I/R) injury mediated by the noncanonical pyroptosis pathway.@*METHODS@#Thirty C57BL/6 mice were randomly divided into sham-operated group, isoflurane group and I/R group, and in the latter two groups, hepatic I/R injury was induced by clamping the portal vein for 30 min. In isoflurane group, the mice were pretreated with 1.4% isoflurane 30 min before the surgery. The protective effect of isoflurane preconditioning against hepatic I/R injury was evaluated by assessing the pathological score of HE staining of the liver tissue and serum ALT and AST levels. Serum IL-1β and IL-18 levels and the protein expression of GSDMS were detected by ELISA and Western blotting to evaluate the inhibitory effect of isoflurane preconditioning on pyroptosis. Western blotting and immunofluroescence were used to detect the protein expression of caspase-11 in the liver tissues to evaluate the inhibitory effect of isoflurane preconditioning on noncanonical pyroptosis pathway.@*RESULTS@#The Suzuki's score of the liver tissue was significantly higher in I/R group than in the sham group ( < 0.05), while the score in the isoflurane group was significantly lower than that in the I/R group ( < 0.05). Serum ALT and AST levels significantly increased in the sham group ( < 0.05), and were significantly lower in isoflurane group than in I/R group ( < 0.05). The serum levels of IL-1β and IL-18 were significantly higher in I/R group than in sham group ( < 0.05), and were significantly lower in isoflurane group than in I/R group ( < 0.05). The expression of GSDMD in the I/R group was significantly higher than that in sham group, and was significantly lower in isoflurane group than in I/R group ( < 0.05). The hepatic expression of caspase-11 was significantly higher in I/R group than in sham group ( < 0.05), and was significantly lower in isoflurane group than in I/R group ( < 0.05).@*CONCLUSIONS@#Isoflurane preconditioning has protective effect against hepatic I/R injury, which is related to the inhibition of the noncanonical pyroptosis pathway.
Subject(s)
Animals , Mice , Caspases, Initiator , Ischemic Preconditioning , Isoflurane , Liver , Mice, Inbred C57BL , Pyroptosis , Reperfusion InjuryABSTRACT
INTRODUCTION AND OBJECTIVES: Isoflurane, an inhalational general anesthetic widely used in medical practice, belonging to the group of volatile liquids together with desflurane and sevoflurane, with various properties including sedation, hypnosis and anesthesia of patients undergoing treatment. surgical acts. Volatile inhalational anesthetics (halogenated) as mechanism of action, has the property of increasing inhibitory synaptic transmission at postsynaptic level by potentiating ion channels regulated by ligand activated by alpha-aminobutyric acid (GABA). Flumazenil is a benzodiazepine antagonist belonging to the group of imidazobenzodiazepine. It is currently known that there is no specific drug capable of antagonizing the effects of halogenates that allow the rapid and complete recovery of general anesthesia, for this reason this work focuses its efforts on demonstrating whether flumazenil has the ability to reverse the actions of the patient. isoflurane and allow an early restoration of the level of consciousness. MATERIAL AND METHODS: The study to be performed is a clinical type of longitudinal, prospective, unicentric and double blind. The sample will be formed by patients who are going to be subjected to a balanced general anesthesia. The sample will be divided into 2 large groups: group C (control) and group F (Flumazenil). At the end of the surgery, the mixture will be administered according to the selected group in a random manner (Flumazenil 0.25 mg or 0.9% solution in a 20 cc syringe) and the time of extubation, recovery time of the level of consciousness, time of discharge UCPA and hemodynamic state (FC, TAM and SO2). RESULTS: The flumazenil group showed a significantly shorter time from injection to extubation than the placebo group (p = 0.007). Differences in terms of shorter times needed to achieve Aldrete of 9 points in the flumazenil group (P = 0.04) were observed as were shorter anesthetic arousal times represented by a Ramsey 2. Heart rate, mean arterial pressure and saturation they had similar values between the 2 groups. CONCLUSION: The study showed that a single dose of 0.25 mg of flumazenil administered at the end of the surgical act, just after completing all surgical stimulation was beneficial (P = 0.007) in the context of extubation times and shorter anesthetic arousal times.
INTRODUCCIÓN Y OBJETIVOS: El isoflurano un anestésico general inhalatorio usado ampliamente en la práctica médica, perteneciente al grupo de los líquidos volátiles junto con el desflurano y sevoflurano, con variadas propiedades entre las que se encuentran la sedación, hipnosis y anestesia de los pacientes sometidos a actos quirúrgicos. Los anestésicos inhalatorios volátiles (halogenados) como mecanismo de acción, tiene la propiedad de aumentar la transmisión sináptica inhibidora a nivel postsináptico potenciando los canales iónicos regulados por ligando activados por ácido alfa-aminobutírico (GABA). El flumazenil es un antagonista benzodiazepínico perteneciente al grupo de los imidazobenzodiazepina. Se conoce actualmente que no existe un fármaco específico capaz de antagonizar los efectos de los halogenados que permitan la recuperación rápida y completa de la anestesia general, por tal motivo este trabajo centra sus esfuerzos en demostrar si el flumazenil tiene la capacidad para revertir las acciones del isoflurane y permitir un restablecimiento temprano del nivel de conciencia. MATERIALES Y MÉTODOS: El estudio a realizar es de tipo clínico de corte longitudinal, prospectivo, unicéntrico y doble ciego. La muestra se conformará por pacientes que vayan a ser sometidos a anestesia general balanceada. Se procederá a dividir la muestra en 2 grandes grupos: grupo C (control) y grupo F (flumazenil). Al final de la cirugía se administrará la mezcla según grupo seleccionado de manera al azar (flumazenil 0,25 mg o solución 0,9% en una jeringa de 20 cc) y se valorará el tiempo de extubación, tiempo de recuperación del nivel de conciencia, tiempo de alta de la UCPA y estado hemodinámico (FC, TAM y SO2). RESULTADOS: El grupo de flumazenil presentó un tiempo desde la inyección hasta la extubación significativamente más bajo que el grupo placebo (p = 0,007). Se observaron diferencias en términos de tiempos más bajos necesario para alcanzar Aldrete de 9 puntos en el grupo flumazenil (P = 0,04) al igual que tiempos de despertar anestésico más cortos representados por un Ramsey 2. La frecuencia cardíaca, presión arterial media y la saturación tuvieron valores similares entre los 2 grupos. CONCLUSIÓN: El estudio demostró que una única dosis de 0,25 mg de flumazenil administrado al final del acto quirúrgico, justo después de culminar toda estimulación quirúrgica fue beneficiosa (P = 0,007) en el contexto de tiempos de extubación y tiempos de despertar anestésico más cortos.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Flumazenil/pharmacology , GABA Modulators/pharmacology , Isoflurane/antagonists & inhibitors , Double-Blind Method , Prospective Studies , Longitudinal Studies , Flumazenil/administration & dosage , GABA Modulators/administration & dosage , Airway Extubation , Anesthesia, GeneralABSTRACT
The forkhead protein (FoxO) family plays a crucial role in regulating oxidative stress, cell proliferation, and apoptosis.FoxO6, a member of the FoxO family, helps regulate oxidative stress in gastric cancer and hepatocellular carcinoma.However, it is unclear whether FoxO6 participates in the protective effect of isoflurane preconditioning in liver injurycaused by oxidative stress in ischemia. In this study, we explored the role and mechanism of FoxO6 in the protective effectof isoflurane preconditioning during hepatocyte injury caused by oxygen-glucose deprivation (OGD). Cells from the humanfetal hepatocyte (LO2) line were incubated with 0%, 1%, 2%, 2.5%, 3%, 3.5%, 4%, or 5% isoflurane for 3 h and thenexposed to OGD. Data showed that 3% isoflurane preconditioning inhibited FoxO6 expression, caspase-3 activity, andreactive oxygen species production and promoted cell viability. FoxO6 overexpression abolished the effects of 3%isoflurane preconditioning on caspase-3 activity, reactive oxygen species production, and cell viability in these cells.Moreover, FoxO6 regulated nuclear factor erythroid 2-related factor (Nrf2) expression via c-Myc after 3% isofluranepreconditioning and OGD exposure. Thus, isoflurane preconditioning prevented OGD-induced injury in LO2 cells bymodulating FoxO6, c-Myc, and Nrf2 signaling
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The aim of this study was to assess the effects of chemical restraint, general anesthesia and opioid treatment on hematological components in Cuniculus paca. Eight healthy, adult, captivity female animals , underwent three laparoscopic procedures with a 15-day interval were evaluated. After physical restraint, an association of ketamine (25mg/kg) and midazolam (0.5mg/kg) was administered intramuscularly for chemical restraint. Posteriorly, anesthesia was induced and maintained with isoflurane; and randomly administered methadone (0.5mg/kg), tramadol (5mg/kg) or saline-placebo (0,1mL/kg) intramuscularly. After pharmacological restraint and in the final laparoscopy stage, venous blood samples were obtained for complete blood count, total plasma protein (TP), creatinine, alanine aminotransferase (ALT), sodium, potassium, chloride and ionized calcium analysis. During general anesthesia, hemoglobin, TP concentration and lymphocytes decreased (P=0.029; <0.001; 0.022 respectively), whereas the potassium levels increased (P=0.034). In conclusion, chemical restraint with ketamine/midazolam association causes a slight decrease in blood cellular components. Isoflurane anesthesia for laparoscopic procedure lead to decrease in hemoglobin, lymphocytes and protein concentrations, while potassium increased, without any influence from the tramadol or methadone treatment. However, these alterations were transient, and its hematologic values can collaborate in carrying out epidemiological, pathophysiological or case studies in the Cuniculus paca.(AU)
O objetivo do presente estudo foi avaliar os efeitos de contenção química, anestesia geral e tratamento com opiáceos nos parâmetros hematológicos em Cuniculus paca. Foram avaliados oito animais saudáveis, fêmeas, adultas, de cativeiro, que foram submetidas a três procedimentos laparoscópicos, com intervalo de 15 dias. Após a contenção física, uma associação de cetamina (25mg/kg) e midazolam (0,5mg/kg) foi administrada por via intramuscular para contenção química. Posteriormente, a anestesia foi induzida e mantida com isoflurano, e administrou-se aleatoriamente metadona (0,5mg/kg), tramadol (5mg/kg) ou placebo salina por via intramuscular. Após a contenção farmacológica e em estágio final da laparoscopia, foram obtidas amostras de sangue venoso para contagem sanguínea completa, proteína de plasma total (TP), creatinina, alanina aminotransferase (ALT), cálcio, sódio, potássio e cloreto ionizado. Durante a anestesia geral, a concentração de hemoglobina, TP e linfócitos diminuiu (P= 0,029;< 0,001; 0,022, respectivamente), enquanto os níveis de potássio aumentaram (P= 0,034). Em conclusão, a contenção química com associação de cetamina/midazolam promove uma ligeira diminuição dos componentes celulares do sangue. A anestesia com isoflavano para o procedimento laparoscópico levou a uma diminuição das concentrações de hemoglobina, linfócitos e proteínas, enquanto o potássio aumentou, sem qualquer influência do tratamento com tramadol ou metadona. No entanto, essas alterações foram transitórias, e os seus valores hematológicos obtidos podem colaborar na realização de estudos epidemiológicos, fisiopatológicos ou casuísticas para Cuniculus paca.(AU)
Subject(s)
Animals , Female , Cuniculidae/surgery , Cuniculidae/blood , Anesthesia/veterinary , Anesthetics/blood , Tramadol/administration & dosage , Midazolam/administration & dosage , Isoflurane/administration & dosage , Ketamine/administration & dosage , Methadone/administration & dosageABSTRACT
Introduction: Minimal alveolar concentration (MAC) ofvolatile anaesthetics is that which prevent movement in50% of subjects in response to a noxious stimulus. MACis influenced by several drugs like fentanyl, midazolam,propofol, clonidine. Various successful studies have been doneto demonstrate the effect of IV anaesthetics and opioids onMAC of various inhaled anaesthetics in balanced anaesthesiasettings. To assess the effect of a perioperative lidocaineinfusion on the MAC of isoflurane in a balanced anaesthesiatechnique by correlating it with the depth of anaesthesia asassessed by the Bispectral Index (BIS).Material and methods: It is a prospective randomized studyconsisting of 100 patients. The patients were categorized intogroup L and group S, Group L received a bolus of 1.5mg/kg of lidocaine five minutes before the induction of generalanaesthesia followed by 1.5mg/kg/hr of lidocaine infusiontill the end of the surgical procedure or upto a maximum ofthree hours (whichever was earlier). Group S received salinesimilarly. BIS was maintained between 40 to 60 and MAC ofisoflurane was measured in both group.Result: Significant difference with regard to MAC ofisoflurane used to maintain anaesthesia was noted betweenthe two groups. It was found overall average MAC ofisoflurane in Group L was (0.761±0.011) and control groupwas (0.885±0.020).Conclusion: Our study found that lidocaine loading dosefollowed by infusion significantly reduces volatile anaestheticrequirement as measured by MAC of isoflurane.
ABSTRACT
Objective To investigate whether Wnt/β-catenin signaling pathway mediating the neuroprotection of isoflurane post-conditioning in hippocampal neurons damage induced by ischemia/reperfusion injury in rats.Methods According to the randomized principle, 60 male Sprague-Dawley rats were randomly divided into five groups (12 rats in each group):sham group (group S), model group (group M), ISO+model group (group MI), ISO+model+DKK-1 group (group MDI) and model+DKK-1 group (group MD).A rat model of middle cerebral artery occlusion (MCAO) was established with 90 min ischemia followed by 24 hreperfusion.Group S was only exposed to one side of the internal carotid artery without fishing line.Isoflurane post-conditioning groups (group MI, MDI) were immediately treated with 1.5%isoflurane for 60 min at the onset of reperfusion.DKK-1 (5μg/kg) was injected intracerebroventricularly 30 min before the model established in group MDI and group MD.After reperfusion for 24 h, Longa score method was used for neurological deficit score.HE staining and Tunel fluorescence was employed to observe the morphological changes of neurons.Immunohistochemistry and Western Blot were applied to detect the expression of target protein in CA1 region.Results Compared with group S, the neurobehavioral score, the number of apoptosis and the expression of Bax and GSK-3βprotein in group M all increased (P<0.05), while the expression ofβ-catenin and Bcl-2/Bax ratio decreased (P<0.05) ;Compared with group M, the neurobehavioral score, the number of apoptosis and the expression of Bax protein were significantly decreased (P<0.05), while the expression of Bcl-2, β-catenin protein and the Bcl-2/Bax ratio were significantly increased (P<0.05) in group MI.Compared with group MI, the neurobehavioral score, the number of apoptosis, Bax and GSK-3βprotein in group MDI were significantly increased (P<0.05), while the Bcl-2, β-catenin protein expression, and Bcl-2/Bax ratio were significantly decreased (P<0.05).Conclusion Isoflurane post-conditioning may protect the hippocampus neurons against cerebral ischemic reperfusion-induced damage via the way that the Wnt/β-catenin signaling pathway regulates the expression levels of Bcl-2 and Bax proteins in rats.
ABSTRACT
OBJECTIVE@#To investigate the effect of ulinastatin pretreatment on isoflurane-induced mitochondria-dependent neuronal apoptosis in the hippocampus of rats.@*METHODS@#Thirty-six male SD rats were randomly assigned into control group, isoflurane group and ulinastatin group. In the latter two groups, the rats were subjected to acute exposure to 0.75% isoflurane for 6 h and pretreated with 50 000 U/kg of ulinastatin before isoflurane exposure, respectively. After the treatments, apoptosis of the hippocampal neurons was detected using TUNEL assay, and the mitochondrial membrane potential (△ ψm) was measured using JC-1 mitochondrial membrane potential kit; cytochrome C release and caspase-3 activity were examined with Western blotting, and intracellular reactive oxygen species (ROS) was detected using the fluorescent probe H2DCFDA.@*RESULTS@#Compared with those in the control group, the rats with acute exposure to isoflurane showed markedly increased TUNEL-positive cells in the hippocampus ( < 0.05), which were obviously reduced by ulinastatin pretreatment ( < 0.05). The △ψm of the hippocampal neurons was significantly reduced after isoflurane exposure ( < 0.05), and was partly recovered by ulinastatin pretreatment ( < 0.05). Acute exposure to isoflurane resulted in obviously increased cellular ROS, cytochrome C release and caspase-3 activity in the hippocampal neurons ( < 0.05), and these changes were significantly inhibited by ulinastatin pretreatment ( < 0.05).@*CONCLUSIONS@#Ulinastatin pretreatment provides neuroprotection against isoflurane-induced apoptosis of the hippocampal neurons in rats possibly by inhibiting mitochondria-dependent apoptosis pathway.