Sevo Group Research Articles

Sevoflurane and isoflurane anesthesia induce redox imbalance, but only sevoflurane impairs vascular contraction.

Volatile anesthetics may cause vascular dysfunction; however, underlying effects are unclear. The aim of the present study was to investigate whether sevoflurane and isoflurane affect vascular function, nitric oxide (NO) bioavailability, and biomarkers of oxidative stress and inflammation. Wistar rats were divided into three experimental groups: Not anesthetized (control group) or submitted to anesthesia with isoflurane (Iso group) or sevoflurane (Sevo group). Hemodynamic parameters were monitored during anesthesia, and blood gas values and biochemical determinants were analyzed. Isometric contractions were recorded in aortic rings. Vasoconstriction induced by potassium chloride (KCl) and phenylephrine (Phe) were measured. No differences in hemodynamic parameters and blood gasses variables were observed. Impaired KCl and Phe-induced contractions were observed in endothelium-intact aorta of Sevo compared to Iso and Control groups. Redox imbalance was found in Sevo and Iso groups. Reduced NO bioavailability and increased activity of matrix metalloproteinase 2 (MMP-2) were observed in Sevo, but not in the Iso group. While reduced IL-10 and IL-1β were observed in Sevo, increases in IL-1β in the Iso group were found. Sevoflurane, but not isoflurane, anesthesia impairs vasocontraction, and reduced NO and cytokines and increased MMP-2 activity may be involved in vascular dysfunction after sevoflurane anesthesia.

The analgesic effect of total intravenous anaesthesia with propofol versus inhalational anaesthesia for acute postoperative pain after hepatectomy: a randomized controlled trial

BackgroundPostoperative pain control can be challenging in patients undergoing hepatectomy. A previous retrospective study on hepatobiliary/ pancreatic surgeries showed better postoperative pain control in patients who received propofol TIVA. The aim of this study was to determine the analgesic effect of propofol TIVA for hepatectomy. This clinical study has been registered at ClinicalTrials.gov (NCT03597997).MethodsA prospective randomized controlled trial was performed to compare the analgesic effect of propofol TIVA versus inhalational anaesthesia. Patients aged between 18 and 80 years old with an American Society of Anesthesiologist (ASA) physical status of I-III scheduled for elective hepatectomy were recruited. Ninety patients were randomly allocated to receive either propofol TIVA (TIVA group) or inhalational anaesthesia with sevoflurane (SEVO group). Perioperative anaesthetic/analgesic management was the same for both groups. Numerical rating scale (NRS) pain scores, postoperative morphine consumption, quality of recovery, patient satisfaction and adverse effects were evaluated during the acute postoperative period and at 3 and 6 months after surgery.ResultsNo significant differences were found for acute postoperative pain scores (both at rest and during coughing) and postoperative morphine consumption between TIVA and SEVO groups. Patients given TIVA had lower pain scores with coughing at 3 months after surgery (p = 0.014, and FDR < 0.1). TIVA group was associated with better quality of recovery on postoperative day (POD) 3 (p = 0.038, and FDR < 0.1), less nausea (p = 0.011, and FDR < 0.1 on POD 2; p = 0.013, and FDR < 0.1 on POD 3) and constipation (p = 0.013, and FDR < 0.1 on POD 3).ConclusionPropofol TIVA did not improve acute postoperative pain control compared to inhalational anaesthesia in patients who underwent hepatectomy. Our results do not support the use of propofol TIVA for reducing acute postoperative pain after hepatectomy.

Effect of Sevoflurane on the Proliferation of A549 Lung Cancer Cells

Background and Objectives: Sevoflurane has opposing effects on cancer progression, depending on its concentration and the cancer type. This study investigated the effects of sevoflurane on the proliferation of A549 lung cancer cells. Materials and Methods: In vitro, the number of A549 cells exposed to different concentrations of sevoflurane was counted. The size and weight of tumors from a xenograft mouse model exposed to air or sevoflurane were measured in vivo experiments. Additionally, hematoxylin and eosin staining and immunohistochemical detection of Ki-67 in the harvested tumor tissues were performed. Results: A total of 72 culture dishes were used and 24 dishes were assigned to each group: Air group; 2% Sevo group (air + 2% sevoflurane); and 4% Sevo group (air + 4% sevoflurane). The number of A549 cells in the 2% Sevo group was less than that in the Air and 4% Sevo groups (Air: 7.9 ± 0.5; 0.5, 2% Sevo: 6.8 ± 0.4, 4% Sevo: 8.1 ± 0.3; p = 0.000). The tumor size was not significantly different between the two groups (Air: 1.5 ± 0.7, 2% Sevo: 2.4 ± 1.9; p = 0.380). Conclusions: The in vitro data showed that sevoflurane inhibited the proliferation of A549 lung cancer cells in a concentration-specific manner. However, the in vivo data showed no correlation between sevoflurane exposure and A549 cell proliferation. Thus, further research is required to understand fully the effects of sevoflurane on cancer progression and to reconcile differences between the in vitro and in vivo experimental results.

Sevoflurane preconditioning improves neuroinflammation in cerebral ischemia/reperfusion induced rats through ROS-NLRP3 pathway

AimWe aimed to study the influence of sevoflurane on the nucleotide-binding domain and Leucine-rich repeat protein 3 (NLRP3) pathways in rats with cerebral ischemia/reperfusion (I/R) injury. MethodsSixty Sprague–Dawley rats were equally divided into five groups randomly: sham-operated, cerebral I/R, sevoflurane (Sevo), NLRP3 inhibitor-treated (MCC950), and sevoflurane and NLRP3 inducer-treated groups. Rats’ neurological functions were assessed using Longa scoring after 24 h of reperfusion, after which they were sacrificed, and cerebral infarction area was determined by triphenyl tetrazolium chloride staining. Pathological changes in damaged portions were assessed using hematoxylin-eosin and Nissl staining, and cell apoptosis was detected by terminal-deoxynucleotidyl transferase-mediated nick end labeling staining. Interleukin 1 beta (IL-1β), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18), malondialdehyde (MDA), and superoxide dismutase (SOD) levels in brain tissues were determined using enzyme-linked immunosorbent assay. Reactive oxygen species (ROS) levels were analyzed using a ROS assay kit. Protein levels of NLRP3, caspase-1, and IL-1β were determined by western blot. ResultsNeurological function scores, cerebral infarction areas, and neuronal apoptosis index were decreased in the Sevo and MCC950 groups than in the I/R group. IL-1β, TNF-α, IL-6, IL-18, NLRP3, caspase-1, and IL-1β levels decreased in the Sevo and MCC950 groups (p < 0.05). ROS and MDA levels increased, but SOD levels increased in the Sevo and MCC950 groups than in the I/R group. NLPR3-inducer nigericin eliminated the protective effects of sevoflurane on cerebral I/R injury in rats. ConclusionSevoflurane could alleviate cerebral I/R-induced brain damage by inhibiting the ROS-NLRP3 pathway.

Sevoflurane Preconditioning and Total Knee Arthroplasty Bleeding: Randomized Controlled Trial

Background: Total knee arthroplasty (TKA) is a highly complex and effective surgery even though its perioperative bleeding may increase the need for blood transfusion and its associated infection risk, cardiovascular overload, increased costs, and mortality. As the tourniquet reduces intraoperative bleeding, it may be associated with postoperative bleeding, venous thrombosis, and distal ischemia. The reperfusion may trigger a local and systemic inflammatory response. Anesthetic preconditioning (APC) with sevoflurane minimizes ischemia-reperfusion syndrome (IRS). This study evaluated the effects of APC with sevoflurane on perioperative bleeding in TKA. Methods: We allocated 30 patients into two groups: a sevo group (sevoflurane 2% for 15 minutes before the tourniquet) and a control group (propofol infusion). Laboratory tests were collected right before the tourniquet (LAB PRE, in the operating room) and after its release at four moments: LAB POST (immediately after), LAB 2 (two hours after), LAB 12 (12 hours after), and LAB 24 (24 hours after). The volume of the suction drain was measured at one, two, 12, and 24 hours after the end of the surgery. Antifibrinolytics were not administered. Results: There was no statistically significant difference in bleeding-related variables, such as drained volume and hemoglobin and hematocrit measurements. Drainage volume was higher in the first two hours after the procedure, while hematocrit decreased pre- to postoperatively and between two and 12 hours post-procedure. Conclusion: Sevoflurane as an anesthetic preconditioning did not reduce postoperative bleeding in TKA surgery.

Sevoflurane alleviates lung injury and inflammatory response compared with propofol in a rat model of VV ECMO.

Although venovenous extracorporeal membrane oxygenation (VV ECMO) is a reasonable salvage treatment for acute respiratory distress syndrome (ARDS), it requires sedating the patient. Sevoflurane and propofol have pulmonary protective and immunomodulatory properties. This study aimed to compare the effectiveness of sevoflurane and propofol on rats with induced ARDS undergoing VV ECMO. Fifteen sprague-dawley (SD) rats were randomly divided into three groups: Con group, sevoflurane (Sevo) group and propofol (Pro) group. Arterial blood gas tests were performed at time pointsT0 (baseline), T1 (the time to ARDS), and T2 (weaning from ECMO). Oxygenation index (PaO2/FiO2) was calculated, and lung edema assessed by determining the lung wet:dry ratio. The protein concentration in bronchial alveolar lavage fluid (BALF) was determined by using bicinchoninic acid assay. Haematoxylin and eosin staining was used to evaluate the lung pathological scores in each group. IL-1β and TNF-α were also measured in the BALF, serum and lung. Oxygenation index showed improvement in the Sevo group versus Pro group. The wet:dry ratio was reduced in the Sevo group compared with propofol-treated rats. Lung pathological scores were substantially lower in the Sevo group versus the Pro group. Protein concentrations in the BALF and levels of IL-1β and TNF-α in the Sevo group were substantially lower versus Pro group. This study demonstrates that compared with propofol, sevoflurane was more efficacious in improving oxygenation and decreasing inflammatory response in rat models with ARDS subject to VV ECMO treatment.

Protective Effects of Dexmedetomidine on Hippocampal Neurons in Rats Anesthetized with Sevoflurane

To explore effects of dexmedetomidine (Dex) on cognitive function and hippocampal neuronal apoptosis in rats anesthetized with sevoflurane (Sevo), and regulation of brain-derived neurotrophic factor (BDNF) and its downstream signaling. 30 Sprague-Dawley (SD) rats were randomly divided into control group inhaled 29% concentration oxygen), Sevo group (2 L/min oxygen flow +1.5% Sevo), Dex+Sevo group (after injection of 20 μg/kg Dex, treated with 2L/min oxygen flow+1.5% Sevo). Haematoxylin and eosin (HE) staining and Nissl’s staining were adopted to detect morphological and functional changes in hippocampus of rats. Apoptosis was detected by immunofluorescence, BDNF expression was detected by immunohistochemistry. Reverse transcription PCR (RT-PCR) was conducted to detect mRNA expression of key proteins in downstream signaling of BDNF. The results showed that Sevo induced apoptosis of hippocampus neurons, while Dex improved Sevo induced apoptosis. In contrast to the control, the positive expression of BDNF in hippocampus of Sevo group was notably decreased (P &lt; 0.05), and that of Dex+Sevo group was notably higher in contrast to Sevo group (P &lt; 0.05). Signaling pathways of MAPK, PI3K-Akt, and Ras were predicted by String software as the downstream pathways of BDNF. RT-PCR results showed that these 3 signaling pathways were involved in Dex improving Sevo-induced cognitive impairment and hippocampal neuron apoptosis. In conclusion, Dex could improve cognitive dysfunction and hippocampal neuron apoptosis in rats induced by Sevo, and the mechanism was related to upregulation of BDNF expression and activation of pathways of MAPK, PI3K-Akt, and Ras.

Glibenclamide Ameliorates the Expression of Neurotrophic Factors in Sevoflurane Anaesthesia-induced Oxidative Stress and Cognitive Impairment in Hippocampal Neurons of Old Rats.

IntroductionSeveral antidiabetic medications have been proposed as prospective treatments for cognitive impairments in type 2 diabetes patients, glibenclamide (GBC) among them. Our research aimed to evaluate the impact of GBC on hippocampal learning memory and inflammation due to enhanced neurotrophic signals induced by inhalation of sevoflurane.Material and MethodsRats (Sprague Dawley, both sexes) were assigned to four groups: a control (vehicle, p.o.), GBC (10 mg/kg b.w.; p.o.), low-dose sevoflurane and low-dose sevoflurane + GBC (10 mg/kg b.w.; p.o.) for 23 days. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining was performed to analyse the count of apoptotic cells and ELISA was conducted to assess the protein signals. A Western blot, a Y-maze test, and a Morris maze test were performed, and the results analysed. Blood and tissues were collected, and isolation of RNA was performed with qRT-PCR.ResultsThe Morris maze test results revealed an improvement in the length of the escape latency on days 1 (P < 0.05), 2 (P < 0.01), 3, and 4 in the low-dose Sevo group. Time spent in the quadrant and crossing axis and the percentage of spontaneous alterations showed a substantial decrease in the low-dose Sevo group which received GBC at 10 mg/kg b.w. Significant increases were shown in IL-6 and TNF-α levels in the low-dose Sevo group, whereas a decrease was evident in the GBC group.ConclusionOur results indicate that glibenclamide may be a novel drug to prevent sevoflurane inhalation-induced impaired learning and reduce brain-derived neurotrophic factor release, which may be a vital target for the development of potential therapies for cognitive deficits and neurodegeneration.

Type of anesthesia and quality of recovery in male patients undergoing lumbar surgery: a randomized trial comparing propofol-remifentanil total i.v. anesthesia with sevoflurane anesthesia

BackgroundPrevious studies have shown that women achieve a better quality of postoperative recovery from total intravenous anesthesia (TIVA) than from inhalation anesthesia, but the effect of anesthesia type on recovery in male patients is unclear. This study therefore compared patient recovery between males undergoing lumbar surgery who received TIVA and those who received sevoflurane anesthesia.MethodsEighty male patients undergoing elective one- or two-level primary transforaminal lumbar interbody fusion (TLIF) were randomly divided into two groups: the TIVA group (maintenance was achieved with propofol and remifentanil) or sevoflurane group (SEVO group: maintenance was achieved with sevoflurane and remifentanil). The quality of recovery-40 questionnaire (QoR-40) was administered before surgery and on postoperative days 1 and 2 (POD1 and POD2). Pain scores, postoperative nausea and vomiting, postoperative hospital stay, anesthesia consumption, and adverse effects were recorded.ResultsThe QoR-40 scores were similar on the three points (Preoperative, POD1 and POD2). Pain scores were significantly lower in the SEVO group than in the TIVA group on POD1 (30.6 vs 31.4; P = 0.01) and POD2 (32 vs 33; P = 0.002). There was no significant difference in the postoperative hospital stay or complications in the postanesthesia care unit between the TIVA group and the SEVO group.ConclusionsThis study demonstrates that the quality of recovery is not significantly different between male TLIF surgery patients who receive TIVA and those who receive sevoflurane anesthesia. Patients in the TIVA group had better postoperative analgesic effect on POD2.Trial registrationThis was registered at http://www.chictr.org.cn (registration number ChiCTR-IOR-16007987, registration date: 24/02/2016).

Сравнение показателей гемодинамики и вентиляции при использовании различных методик анестезиологического обеспечения лапароскопической холецистэктомии

Актуальность. Все шире используются лапароскопические оперативные вмешательства, в том числе у лиц пожилого возраста с серьезными сопутствующими заболеваниями. Ретроспективное изучение осложнений, которые имели место при проведении лапароскопических оперативных вмешательств, продемонстрировало, что абсолютное их большинство не связано с техникой операции, а обусловлено развитием сердечных и легочных нарушений. Цель: оценка эффективности и безопасности различных вариантов анестезиологического обеспечения лапароскопической холецистэктомии на основании исследования динамики основных гемодинамических и вентиляционных параметров гомеостаза у больных в периоперационном периоде. Материалы и методы. Обследовано 120 пациентов (средний возраст — 50 (38–63) лет), которым выполнялись оперативные вмешательства по поводу желчнокаменной болезни и острого холецистита методом лапароскопической холецистэктомии. Больные были разделены на 3 группы исследования. Группа TIVA (n = 40) — тотальная внутривенная анестезия (ТВА) на основе пропофола и фентанила с инфузией гипнотика через перфузор. Скорость инфузии пропофола осуществлялась по разработанной болюсно-инфузионной схеме 10–8–6; анестезиолог самостоятельно выбирал достаточную, по его мнению, скорость инфузии пропофола. Группа SEVO (n = 40) — ингаляционная анестезия на основе севофлурана методом низкого потока и фентанила. Группа ТСI (n = 40) — ТВА на основе пропофола и фентанила с инфузией гипнотика по целевой концентрации с помощью перфузора B. Braun perfusor space; анестезиолог не должен был нарушать нижнюю (3,5 мкг/мл) и верхнюю (5,5 мкг/мл) границы целевых концентраций препарата в эффекторных зонах (математическая модель Shnеider). Результаты. Показатели гемодинамики во всех группах имели закономерные колебания во время анестезиологической подготовки пациентов на этапах инсуффляции углекислого газа в брюшную полость и десуффляции. Внутрибрюшное давление у пациентов всех групп не превышало 10 мм рт.ст. Во время индукции в анестезию отмечалось снижение показателей системной и центральной гемодинамики. Так, показатели среднего артериального давления по сравнению с исходными данными уменьшались на 17,70 ± 2,33 %, особенно у пациентов группы TIVA (p &lt; 0,001). Подобные изменения связаны с тем, что препараты, которые использовались для индукции анестезии, снижали тонус симпатической нервной системы, перераспределяли объем циркулирующей крови в емкостную сосудистую сеть, что способствовало уменьшению преднагрузки, а также за счет периферической вазодилатации. На этапе интубации также отмечалось изменение показателей гемодинамики по типу гипердинамической реакции, что было обусловлено симпатоадреналовой реакцией на ларингоскопию и интубацию. Более выраженные изменения отмечались в группе TIVA. Так, показатели среднего артериального давления по сравнению с предыдущим этапом увеличивались на 22,2 ± 2,9 % (р &lt; 0,001). Сопоставление изменений показателей гемодинамики в зависимости от варианта анестезиологического обеспечения показало их статистическую сопоставимость (p &lt; 0,05) и менее выраженные колебания в группах TCI и SEVO, чем в группе с тотальной внутривенной анестезией (TIVA). Анализ показателей вентиляции легких и оксигенации (SaO2, EtCO2) в условиях пневмоперитонеума показал их стабильность и управляемость у пациентов всех групп. Случаев повышения EtCO2 более 45 мм рт.ст. не обнаружено, все анестезии проводились в условиях умеренной гипервентиляции. В то же время показатели среднего давления в дыхательных путях были достоверно выше при применении тотальной внутривенной анестезии с целевой концентрацией анестетика (группа ТСI) и при применении тотальной внутривенной анестезии (группа TIVA), чем при использовании ингаляционного анестетика. Это обусловлено бронходилатирующим эффектом севофлурана, проведением низкопоточной ингаляционной анестезии. Выводы. Сравнительные исследования между группами имеют незначительные различия при использовании севофлурана и пропофола по методу ТСІ как составляющей анестезиологического обеспечения. Лучшая стабильность и предсказуемость изменений гемодинамики в интраоперационном периоде были обнаружены в группах с применением ингаляционной низкопоточной анестезии севофлураном и инфузии пропофола по целевой концентрации (ТСI). Повышенное внутрибрюшное давление до 10 мм вод.ст. за счет карбоксиперитонеума продолжительностью до 1 часа при использовании ингаляционного агента севофлуран методом низкого потока или при внутривенной анестезии пропофолом не вызывало существенных изменений показателей вентиляции и оксигенации и легко поддавалось коррекции изменением настройки параметров вентиляции.

Different Anesthetic Drugs Mediate Changes in Neuroplasticity During Cognitive Impairment in Sleep-Deprived Rats via Different Factors.

BackgroundPerioperative neuro-cognitive disorders (PND) are preoperative and postoperative complications of multiple nervous systems, typically manifested as decreased memory and learning ability after surgery. It was used to replace the original definition of postoperative cognitive dysfunctions (POCD) from 2018. Our previous studies have shown that sevoflurane inhalation can lead to cognitive dysfunction in Sprague-Dawley rats, but the specific mechanism is still unclear.Material/MethodsThirty-six male Sprague-Dawley rats were randomly divided into 6 groups (n=6): the SD group was given 24-h acute sleep deprivation; Sevoflurane was inhaled for 2 h in the Sevo group. Two mL propofol was injected into the tail vein of rats in the Prop group. The rats in the SD+Sevo group and SD+Prop group were deprived of sleep before intervention in the same way as before.ResultsWe noted significant behavioral changes in rats treated with SIK3 inhibitors or tau phosphorylation agonists before propofol injection or sevoflurane inhalation, with associated protein levels and dendritic spine density documented. Sevoflurane anesthesia-induced cognitive impairment following acute sleep deprivation was more pronounced than sleep deprivation-induced cognitive impairment alone and resulted in increased brain SIK3 levels, increased phosphorylation of total tau and tau, and decreased acetylation modifications. After using propofol, the cognitive function returned to baseline levels with a series of reversals of cognitive dysfunction.ConclusionsThese results suggest that sevoflurane inhalation via the SIK3 pathway aggravates cognitive impairment after acute sleep deprivation and that propofol anesthesia reverses the effects of sleep deprivation by affecting modifications of tau protein.

Comparison of serum dynamic thiol/disulphide homeostasis and nitric oxide levels of total intravenous vs inhaled anaesthesia in endoscopic transsphenoidal pituitary surgery.

Transsphenoidal pituitary surgery (TPS) is traditionally performed under general anaesthesia. This study aimed to compare the effects of total intravenous anaesthesia (TIVA) or sevoflurane, an inhalation anaesthetic, on thiol-disulphide homeostasis in patients undergoing endoscopic endonasal TPS. In this study, 84 patients scheduled for TPS were randomly categorised into two groups: propofol (n=42, the TIVA group) or sevoflurane (n=42, the SEVO group). Blood samples were taken before induction of general anaesthesia and at the 30minutes of postoperation. Serum native thiol and total thiol levels were detected, and the number of dynamic disulphide bonds and related ratios were calculated from these values. Serum nitric oxide (NO) levels were measured using a chemiluminescence method. Although native thiol levels in TIVA postoperation group were markedly increased (P<.05), total thiol levels in SEVO postoperation group were significantly decreased (P<.01). Disulphide levels were declined in both groups (P<.05 for TIVA and P=.001 for SEVO groups). Disulphide/native thiol (P<.05 for both groups) and disulphide/total thiol ratios (P<.05 for TIVA and P<.01 for SEVO groups) were depressed in postoperation groups. We found a marked elevation in native thiol/total thiol ratio in both groups (P<.05 for TIVA and P<.01 for SEVO groups). There was significant augmentation in serum NO levels in the SEVO postoperation group (P<.05). These results are the first to show that both TIVA and sevoflurane showed similar antioxidant effect with reduced disulphide levels, but sevoflurane may offer more robust oxidative stress protection and augmented NO production than TIVA during TPS. However, the clinical effect is needed to further investigate.

Effects of Sevoflurane on Lewis Lung Carcinoma Cell Proliferation In Vivo and In Vitro.

Background and objectives: There are several studies that sevoflurane could enhance proliferation of cancer cells, while others suggest no effect on clinical outcome. We conducted in vivo and in vitro experiments to investigate the effects of sevoflurane, a volatile anesthetic, on proliferation and outcomes of Lewis lung carcinoma (LLC) cells. Materials and Methods: A total of 37 mice were injected with LLC cells to compare the tumor size and survival of the sevoflurane exposed group (sevo group) and control group. The sevo group was exposed to 2% sevoflurane and 4 L/min of oxygen for 1 h per day 3 times per week, and the control group was exposed only to 4 L/min of oxygen. In vitro study, 12 plates incubated with LCC cells. 6 plates were exposed to 2% sevoflurane for 1 hr/day for 3 days and 6 plates were not exposed, and cell proliferation was compared after 3 days. Results: There were no significant differences in survival or tumor size between mice exposed to sevoflurane and control mice (survival: 29.06 ± 4.45 vs. 28.76 ± 3.75, p = 0.836; tumor size: 0.75 (0.41–1.02) vs. 0.49 (0.11–0.79), p = 0.153). However, in vitro study, the proliferation of LLC cells exposed to sevoflurane increased by 9.2% compared to the control group (p = 0.018). Conclusions: Sevoflurane (2 vol%) exposure could promote proliferation of LLC cells in vitro environment, but may not affect proliferation of LLC cells in vivo environment. These results suggest that in vitro studies on the effects of anesthetics on cancer may differ from those of in vivo or clinical studies.

Metabolik Sendromlu Koroner Baypas Hastalarında Uygulanan İki Farklı Anestezi Tipinin Postoperatif Karaciğer Fonksiyonları Üzerine Etkisi

Objective: One of the factors affecting liver functions in open coronary surgery (CABG) of patients with metabolic syndrome (MS) may be the anesthetic drugs used. For this purpose, we investigated the effects of midazolam-based total intravenous anesthesia (TIVA) and sevoflurane-based inhalation anesthesia on liver functions and postoperative complications in patients with MS who wiould undergo open coronary bypass surgery. Method: A total f 76 patients were included in our study. A statistically significant difference was not found between the TIVA (n=38) and SEVO (n=38) groups in terms of gender, age, body mass index (BMI), Euroscore values, presence of preoperative comorbidity, blood product transfusion, postoperative complications, and 30-day mortality rates. (p&gt;0.05). Preoperative and postoperative laboratory parameters, ALT, AST, LDH, and glucose values were comparable between both groups. Results: 76 patients were included in our study. There was a statistically significant difference between the TIVA (n=38) and SEVO (n=38) groups in terms of gender, age, body mass index (BMI), euroscore values, presence of preoperative comorbidity, blood product transfusion, postoperative complications, and 30-day mortality rates. There was no difference (p&gt;0.05). When compared according to preoperative and postoperative laboratory parameters, ALT, AST, LDH, and glucose values were found similar in both groups. Conclusion: In our study, we found that TIVA and SEVO groups are not superior to each other in coronary bypass patients with metabolic syndrome. Studies investigating detailed parameters with more patients will be guiding for this issue

Koroner Arter Cerrahisi Geçiren Hastalarda İntravenöz Anestezi ve İnhalasyon Anestezisinin Kırmızı Hücre Dağılım Genişliği ve Ortalama Platelet Volümü Üzerine Etkileri

INTRODUCTION: The effects of midazolam-based intravenous anesthesia (TIVA) and sevoflurane-based inhalation anesthesia (SEVO) maintenance on postoperative hematological parameters were compared in patients undergoing coronary artery surgery. METHODS: The 100 patients included in the study were divided into two groups according to the anesthesia management: All patients' anesthesia inductions were performed with 10 μgkg-1 fentanyl, 0.15 mgkg-1 midazolam, and 0.8 mgkg-1 rocuronium. Anesthesia was maintained with total intravenous anesthesia in the TIVA group patients, while sevoflurane was used in the SEVO group patients. Demographic, clinical, operative data, red cell distribution width (RDW), and mean platelet volume (MPV) values were recorded. RESULTS: Except that the extubation time was shorter in the SEVO group, no difference was observed between the groups in terms of all these variables. There was a significant increase in postoperative RDW and MPV measurements in both groups. Postoperative RDW value was lower in the inhalation anesthesia group compared to the TIVA group (p=0.013). DISCUSSION AND CONCLUSION: In our study, RDW was found to be lower in the inhalation anesthesia group, indicating less inflammation. There was no difference in terms of postoperative complications and mortality.

A multimodal sevoflurane-based sedation regimen in combination with targeted temperature management in post-cardiac arrest patients reduces the incidence of delirium: An observational propensity score-matched study

BackgroundRecent studies suggest that volatile anaesthetics are safe, efficient, and reliable alternatives to the use of intravenous anaesthetics for out-of-hospital cardiac arrest (OHCA) patients admitted to the intensive care unit (ICU). We hypothesised that volatile anaesthetics may reduce the incidence of delirium rather than intravenous sedatives. This retrospective study aimed to investigate whether sevoflurane combined with higher targeted temperature management could decrease the incidence of delirium when compared with intravenous anaesthetics with lower targeted temperature management. MethodsUsing a propensity score-matched analysis, we retrospectively compared a target temperature management (32−34 °C) method along with intravenous sedation (TTM-33/IV) and a modified target temperature management (34−36 °C) method along with sevoflurane sedation (mTTM-36/sevo). We used the confusion assessment method for the ICU to measure the incidence of delirium. We calculated the time-dependent risk on delirium using the multivariate Cox regression model. ResultsThe incidence of delirium was significantly lower (p = 0.001) in OHCA patients of the mTTM-36/sevo group (9/56, 16.1%) than in those of the TTM-33/IV group (25/67, 37.3%). Mechanical ventilation and lengths of stay in the ICU (p < 0.001) and hospital stay (p = 0.04) were shorter in the mTTM-36/sevo group. Patients in the TTM-33/IV group required more midazolam, propofol, and fentanyl. We observed no significant difference in mortality. ConclusionA multimodal sevoflurane-based sedation regimen together with targeted temperature management resulted in a lower incidence of delirium and a shorter duration for mechanical ventilation and ICU length of stay than did the treatment with intravenous sedation combined with the classical cooling protocol.

AMPK-SIRT1-PGC1α Signal Pathway Influences the Cognitive Function of Aged Rats in Sevoflurane-Induced Anesthesia.

To understand the effect of AMP-activated protein kinase (AMPK)-SIRT1 (silent information regulator 1)-PPARγ coactivator-1α (PGC1α) signaling pathway on the cognitive function of sevoflurane-anesthetized aged rats. Aged rats were divided into Normal group, Sevo group (Sevoflurane anesthesia), Sevo + AICAR (the AMPK activator) group, Sevo + EX527 group (the AMPK inhibitor), and Sevo + AICAR + EX527 group. The cognitive function of rats was determined by the Morris water maze. Hippocampal neuronal apoptosis was evaluated by TUNEL and Fluoro-Jade C (FJC) staining, and the expression of cleaved caspase-3 was detected by immunohistochemistry. ROS, SOD, and MDA levels and the fluorescence intensity of GFAP in the hippocampus were assayed. The mitochondrial membrane potential (MMP), mitochondrial mass, ATP level, and the expression of AMPK-SIRT1-PGC1α were determined by the corresponding methods. Rats in the Sevo group manifested significant extension in the escape latency, with fewer platform crossings; and meanwhile, the apoptotic rate, the number of FJC-positive cells, and the fluorescence intensity of GFAP of neurons were elevated, with up-regulation of cleaved caspase-3. Moreover, the level of MDA and ROS was increased evidently, with significant down-regulation of SOD activity, ATP, mitochondrial mass and MMP levels, and AMPK, SIRT1 and PGC-1α protein expressions. However, sevoflurane-induced changes above were improved after the administration of AICAR, and EX527 could reverse AICAR-induced improvements in Sevo-anesthetized aged rats. Activating AMPK-SIRT1-PGC1α pathway can improve the cognitive function and mitigate the neuronal injury in Sevo-anesthetized aged rats by antagonizing the oxidative stress and maintaining the mitochondrial function.

Efficacy and safety of evogliptin in the treatment of type 2 diabetes mellitus in a Brazilian population: a randomized bridging study

BackgroundEvogliptin (EVO) is a potent and selective dipeptidyl peptidase-4 inhibitor (DPP4i) developed for the treatment of type 2 diabetes mellitus (T2DM). DPP4is are known to exhibit a better glucose-lowering effect in Asians compared to other ethnic groups. Once EVO’s clinical development program was conducted in Asian patients, this bridging study was designed to validate for the Brazilian population the efficacy and safety of the approved dose regimen (once-daily 5.0 mg).MethodsIn this randomized, double-blind, double-dummy, parallel trial, 146 patients with T2DM with inadequate glycemic control on diet and exercise (7.5% ≤ HbA1c ≤ 10.5%) were randomly assigned to a 12-week once-daily treatment with EVO 2.5 mg (N = 35), EVO 5 mg (N = 36), EVO 10 mg (N = 36), or sitagliptin (SITA) 100 mg (N = 39). Absolute changes (Week 12—baseline) in HbA1c, fasting plasma glucose (FPG) and body weight (BW) were obtained. One-sided one sample t test was used to determine if mean HbA1c reduction in each group was < − 0.5% (beneficial metabolic response). An analysis of covariance estimated the change in HbA1c and FPG adjusted by baseline HbA1c, FPG, body mass index (BMI) and study site. Response rates to treatment were also established. No between-group statistical comparisons were planned.ResultsHbA1c mean reductions were − 1.26% (90% CI − 1.7%, − 0.8%), − 1.12% (90% CI − 1.4%, − 0.8%), − 1.29% (90% CI − 1.6%, − 1.0%), and − 1.15% (90% CI − 1.5%, − 0.8%) in groups EVO 2.5 mg, EVO 5 mg, EVO 10 mg, and SITA 100 mg, respectively. FPG levels showed a mean increase of 10.89 mg/dL in group EVO 2.5 mg, with significant mean reductions of − 18.94 mg/dL, − 21.17 mg/dL, and − 39.90 mg/dL in those treated with EVO 5 mg, EVO 10 mg, and SITA 100 mg, respectively. BW showed significant reductions of approximately 1 kg in patients treated with EVO 5 mg, EVO 10 mg, and SITA 100 mg. Mean adjusted reductions of HbA1c and FPG levels confirmed the significant clinical benefit of all study treatments. The clinical benefit of EVO’s “target” dose (5 mg) was confirmed. No safety concerns were identified.ConclusionsThese results validate for the Brazilian population the approved dose regimen of EVO (once-daily 5 mg).Trial registration ClinicalTrials.gov Identifier: NCT02689362 (first posted on 02/23/2016).

Effects of sevoflurane on microglial polarization after traumatic brain injury in rats

Objective To evaluate the effects of sevoflurane on microglial polarization after traumatic brain injury (TBI) in rats. Methods Seventy-two healthy adult male Sprague-Dawley rats, weighing 230-250 g, were divided into 3 groups (n=24 each) using a random number table method: sham operation group (group Sham), group TBI, and TBI plus sevoflurane anesthesia group (group TBI+ Sevo). TBI models were established by using Feeney′s method in TBI and TBI+ Sevo groups, 30 min later 2.4% sevoflurane was inhaled for 1 h once a day for 3 consecutive days in TBI+ Sevo group, while pure oxygen was inhaled instead in Sham and TBI groups.At 1, 3, 7 and 14 days after establishing the model, 6 rats were selected, the neurological function was evaluated with the modified neurologic severity score (mNSS), and tail venous blood samples were taken for determination of tumor necrosis factor-a (TNF-α), interleukin-1beta (IL-1β) and IL-6 concentrations by enzyme-linked immunosorbent assay.The rats were then sacrificed, the limbic cortical tissues of brain contusion lesion were taken for determination of cell apoptosis (by TUNEL) and expression of microglial marker Iba-1, microglial M1 phenotypic marker CD86 and microglial M2 phenotypic marker CD206 (by Western blot). Results Compared with group Sham, the mNSS score, apoptosis rate of cortical cells, expression of Iba-1, CD86 and CD206, and concentrations of serum TNF-α, IL-1β and IL-6 were significantly increased in TBI and TBI+ Sevo groups (P<0.05). Compared with TBI group, the mNSS score, apoptosis rate of cortical cells, expression of Iba-1 and CD86 and concentrations of serum TNF-α, IL-1β and IL-6 were significantly decreased, and the expression of CD206 was up-regulated in TBI+ Sevo group (P<0.05). Conclusion The mechanism by which sevoflurane anesthesia reduces TBI may be related to promoting microglial polarization and inhibiting systemic inflammatory response in rats. Key words: Anesthetics, inhalation; Craniocerebral trauma; Microglia; Polarization

Effect of DHA on sevoflurane-induced activation of microglia

Objective To evaluate the effect of DHA on sevoflurane-induced activation of microglia. Methods N9 mouse microglia were seeded in culture plates (1 ml) or culture dishes (10 ml) at a density of 1×106 cells/ml and divided into 4 groups (n=18 each) using a random number table method: control group (C group), DHA group, sevoflurane group (Sevo group) and DHA plus sevoflurane group (DHA+ Sevo group). Group C received no treatment.Cells were incubated in the culture medium containing 25 μmol/L DHA in DHA and DHA+ Sevo groups.Cells were exposed to 2% sevoflurane in Sevo and DHA+ Sevo groups.At 24 h of culture, activated microglia were detected and counted by immunohistochemistry, the rate of CD11b positive cells was calculated, the expression of microglial biomarker CD11b was detected by Western blot, and the concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) were determined by enzyme-linked immunosorbent assay. Results Compared with C and DHA groups, the rate of CD11b positive cells was significantly increased, the expression of CD11b was up-regulated, and the concentrations of TNF-α and IL-1β were increased in Sevo group (P<0.05). Compared with Sevo group, the rate of CD11b positive cells was significantly decreased, the expression of CD11b was down-regulated, and the concentrations of TNF-α and IL-1β were decreased in DHA+ Sevo group (P<0.05). Conclusion DHA can decrease inflammatory responses through reducing sevoflurane-induced activation of microglia. Key words: Fatty acids, unsaturated; Anesthetics, inhalation; Microglia