RESUMEN
Background: Continuous intravenous infusion of remimazolam may be suitable for sedation in patients undergoing regional anaesthesia. However, there have been no studies comparing remimazolam and dexmedetomidine for this purpose. This study compared emergence from sedation between dexmedetomidine and remimazolam following continuous intravenous infusion in patients undergoing spinal anaesthesia. Methods: This double-blinded, randomised controlled trial assessed the sedative effects of dexmedetomidine and remimazolam. Following spinal anaesthesia, patients were sedated using continuous intravenous infusion of either dexmedetomidine (D group) or remimazolam (R group).The D group received dexmedetomidine administered at 6 mL/kg/h (6 µg/kg/h) for 10 minutes, followed by 1 mL/kg/h (1 µg/kg/h). The R group received remimazolam administered at 6 mL/kg/h (6 mg/kg/h) for 10 minutes, followed by 1 mL/kg/h (1 mg/kg/h). Sedation levels were evaluated using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. The time to reach MOAA/S ≤ 3 from the start of drug infusion and the time to reach MOAA/S = 5 from the end of infusion were recorded. Hemodynamic parameters and respiratory rate were also monitored. Results: The R group reached MOAA/S ≤ 3 significantly faster than the D group during induction of sedation (4 ± 1 minutes and 11 ± 3 minutes, respectively, p < 0.001). The R group also reached MOAA/S = 5 significantly faster than the D group during emergence from sedation (11 ± 3 minutes and 16 ± 5 minutes, respectively, p < 0.001). Both groups maintained stable hemodynamic parameters and respiratory rate without any significant differences, although the mean heart rate was significantly lower in the D group than in the R group after the start of infusion. Conclusion: Remimazolam demonstrated significantly faster induction of and emergence from sedation compared to dexmedetomidine, with no significant differences in haemodynamics or respiratory depression.
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Anestesia Raquidea , Dexmedetomidina , Hipnóticos y Sedantes , Humanos , Dexmedetomidina/administración & dosificación , Dexmedetomidina/efectos adversos , Anestesia Raquidea/métodos , Masculino , Femenino , Adulto , Hipnóticos y Sedantes/administración & dosificación , Persona de Mediana Edad , Método Doble Ciego , Infusiones Intravenosas , Benzodiazepinas/administración & dosificación , Benzodiazepinas/efectos adversos , Periodo de Recuperación de la Anestesia , Hemodinámica/efectos de los fármacos , Sedación Consciente/métodosRESUMEN
This study investigated the effects of pregabalin on microglial differentiation in rats with neuropathic pain (NP) induced by sciatic nerve ligation and transection. After confirming NP, the rats were randomly allocated to either a pregabalin or control group. The pregabalin group received intraperitoneal injections of 10 mg/kg pregabalin, while the control group received an equivalent volume of normal saline following surgery. On postoperative day 28, neuronal damage, microglial activity, and microglial differentiation were assessed. The pregabalin group exhibited significantly less neuronal damage compared to the control group, along with a significant decrease in activated microglial expression in both the brain and spinal cord. Pregabalin treatment also significantly altered the microglial phenotype expression, with a decrease in the M1 phenotype percentage and an increase in the M2 phenotype percentage in both the brain (M1 phenotype: 43.52 ± 12.16% and 18.00 ± 8.57% in the control and pregabalin groups, respectively; difference: 27.26 [15.18-42.10], p = 0.002; M2 phenotype: 16.88 ± 6.47% and 39.63 ± 5.82% in the control and pregabalin groups, respectively; difference 22.04 [17.17-32.70], p < 0.001) and the spinal cord ipsilateral to nerve injury (M1 phenotype: 44.35 ± 12.12% and 13.78 ± 5.39% in the control and pregabalin groups, respectively; difference 30.46 [21.73-44.45], p < 0.001; M2 phenotype: 7.64 ± 3.91% and 33.66 ± 7.95% in the control and pregabalin groups, respectively; difference 27.41 [21.21-36.30], p < 0.001). Overall, pregabalin treatment significantly decreased the microglial M1 phenotype while increasing the microglial M2 phenotype in NP rats.
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Diferenciación Celular , Microglía , Neuralgia , Pregabalina , Animales , Pregabalina/farmacología , Pregabalina/uso terapéutico , Microglía/efectos de los fármacos , Microglía/patología , Neuralgia/tratamiento farmacológico , Neuralgia/patología , Neuralgia/etiología , Ratas , Diferenciación Celular/efectos de los fármacos , Masculino , Médula Espinal/efectos de los fármacos , Médula Espinal/patología , Modelos Animales de Enfermedad , Analgésicos/farmacología , Analgésicos/uso terapéutico , Nervio Ciático/efectos de los fármacos , Nervio Ciático/patología , Ratas Sprague-Dawley , Humanos , Encéfalo/efectos de los fármacos , Encéfalo/patologíaRESUMEN
This experimental study was designed to evaluate the effect of ulinastatin, a urinary trypsin inhibitor, on postoperative cognitive dysfunction (POCD) in rats under general anesthesia with isoflurane, on the aspect of behavior, as evaluated using a Y-maze test and focusing on microglial activity. Ulinastatin (50,000 U/mL) and normal saline (1 mL) were randomly (1:1) administered intraperitoneally to the ulinastatin and control groups, respectively, before general anesthesia. Anesthesia with isoflurane 1.5 volume% was maintained for 2 h. The Y-maze test was used to evaluate cognitive function. Neuronal damage using caspase-1 expression, the degree of inflammation through cytokine detection, and microglial activation with differentiation of the phenotypic expression were evaluated. Twelve rats were enrolled in the study and evenly allocated into the two groups, with no dropouts from the study. The Y-maze test showed similar results in the two groups before general anesthesia (63 ± 12% in the control group vs. 64 ± 12% in the ulinastatin group, p = 0.81). However, a significant difference was observed between the two groups after general anesthesia (17 ± 24% in the control group vs. 60 ± 12% in the ulinastatin group, p = 0.006). The ulinastatin group showed significantly lower expression of caspase-1. Pro-inflammatory cytokine levels were significantly lower in the ulinastatin group than in the control group. The ulinastatin group had a significantly lower microglial activation (41.74 ± 10.56% in the control group vs. 4.77 ± 0.56% in the ulinastatin, p < 0.001), with a significantly lower activation of M1 phenotypes (52.19 ± 7.83% in the control group vs. 5.58 ± 0.76% in the ulinastatin group, p < 0.001). Administering ulinastatin before general anesthesia prevented neuronal damage and cognitive decline after general anesthesia, in terms of the aspect of behavior, as evaluated by the Y-maze test. The protective effect of ulinastatin was associated with the inhibition of microglial activation, especially the M1 phenotype.
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Disfunción Cognitiva , Glicoproteínas , Isoflurano , Complicaciones Cognitivas Postoperatorias , Ratas , Animales , Isoflurano/farmacología , Microglía , Citocinas/farmacología , Caspasa 1 , Aprendizaje por Laberinto , Inhibidores de Tripsina/farmacologíaRESUMEN
Background and Objectives: Remimazolam, a novel benzodiazepine, is used for procedural sedation and general anesthesia due to its rapid onset and short duration of action. However, remimazolam-induced anaphylaxis (RIA) is a rare but severe complication. This study aimed to analyze RIA characteristics, focusing on cardiovascular collapse, and provide guidelines for safe remimazolam use. Methods: This study conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Research articles retrieved from PubMed on 26 May 2023, using the keywords 'remimazolam AND anaphylaxis' were evaluated based on the inclusion criteria of being written in English and aligning with the World Allergy Organization criteria for anaphylaxis, while studies not meeting these criteria were excluded. All published articles up to the search date were included without any date restrictions. The review analyzed factors such as age, sex, type of anesthesia, remimazolam dose (bolus/continuous), allergic symptoms and sign, epinephrine use, serum tryptase levels, and skin prick tests. Results: Among eleven cases, the mean age was 55.6 ± 19.6 years, with 81.8% male. Hypotension (81.8%) was the most common symptom, followed by bradycardia (54.5%) and desaturation (36.4%). Two patients experienced cardiac arrest. Serum tryptase levels confirmed anaphylaxis in ten cases. Epinephrine was the primary treatment, with intravenous doses ranging from 0.1 mg to 0.3 mg. Conclusions: Vigilance is crucial when administering remimazolam, adhering to recommended dosages, and promptly treating RIA with epinephrine. Further research is needed to understand the risk factors and refine the management strategies. Guidelines for safe remimazolam use are proposed.
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Anafilaxia , Benzodiazepinas , Humanos , Anafilaxia/tratamiento farmacológico , Anafilaxia/inducido químicamente , Masculino , Benzodiazepinas/efectos adversos , Benzodiazepinas/uso terapéutico , Femenino , Persona de Mediana Edad , Hipnóticos y Sedantes/efectos adversos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/uso terapéutico , Adulto , AncianoRESUMEN
This study aimed to investigate the effects of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, on endoplasmic reticulum (ER) stress in rats with neuropathic pain (NP). NP was induced in rats through ligation and transection of the sciatic nerve. After confirmation of NP, the animals were randomly divided into ketamine and control groups. The ketamine group was administered 50 mg/kg of ketamine at 15, 18, and 21 days after surgery. The expression of NMDA receptor subtype 2B (NR2B) and ER stress markers in the spinal cord (L5) was evaluated. The ipsilateral side of the surgery in the ketamine group was less sensitive to mechanical and cold stimulations. The expression of NR2B on the ipsilateral side was significantly lower in the ketamine group than in the control group (18.93 ± 1.40% vs. 31.08 ± 0.74%, p < 0.05). All markers for ER stress on the ipsilateral side of the surgery in both groups had higher expression than those on the contralateral side. The expression of activating transcription factor-6 (ATF-6) on the ipsilateral side was significantly lower in the ketamine group than in the control group (p < 0.05). Systemic administration of ketamine inhibited the expression of NMDA receptors and improved NP symptoms. Among the markers of ER stress, the therapeutic effect of ketamine is associated with the inhibition of ATF-6 expression.
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Ketamina , Neuralgia , Ratas , Animales , Ketamina/farmacología , Ketamina/uso terapéutico , Ratas Sprague-Dawley , Antagonistas de Aminoácidos Excitadores/farmacología , Dimensión del Dolor , Neuralgia/tratamiento farmacológico , Neuralgia/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismoRESUMEN
PURPOSE: Congenital heart disease (CHD) is divided into two groups according to cyanosis status. Cyanotic CHD has a low level of systemic oxygenation and is accompanied by increased erythropoiesis. We hypothesized that pediatric patients with CHD would exhibit different thromboelastographic profiles according to their cyanosis status. METHODS: The study recruited 70 pediatric patients younger than 12 months who were undergoing surgery for CHD. Patients were allocated to the acyanotic group or cyanotic group after preoperative evaluations of their diagnosis and peripheral oxygen saturation in the operating room on room air. After inducing anesthesia, blood samples were collected. Hematologic and thromboelastographic profiles were evaluated. RESULTS: Demographic data were similar between groups. The thromboelastographic profiles did not differ significantly between the groups. Hematologic profiles generally did not significantly differ between groups, except hematocrit (Hct) was higher in the cyanotic group (41.7 ± 6.8% vs. 35.3 ± 5.3%, p < 0.001). In patients under 3 months of age, prothrombin time (PT) (cyanotic group 15.4 ± 1.1 s vs. acyanotic group 14.2 ± 2.4 s, p = 0.02) and international normalized ratio (INR) (cyanotic group 1.24 ± 0.12 vs. acyanotic group 1.12 ± 0.27, p = 0.01) were significantly greater in the cyanotic group. CONCLUSION: There were no differences in thromboelastographic profiles between the patients with or without cyanosis, regardless of age. The Hct was higher in the cyanotic group in patients under 12 months, while the PT was prolonged and the INR was increased in the cyanotic group in patients under 3 months.
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Cardiopatías Congénitas , Humanos , Niño , Cardiopatías Congénitas/cirugía , Cianosis/complicaciones , Cianosis/cirugía , Tromboelastografía , Pruebas de Coagulación Sanguínea , Hipoxia/complicacionesRESUMEN
BACKGROUND: This study was performed to compare the perfusion index (PI) between affected and unaffected limbs in patients with complex regional pain syndrome (CRPS); it also evaluated the usefulness of the PI for monitoring the response to intravenous ketamine infusion therapy in such patients. METHODS: In total, 46 patients with CRPS in one arm or leg were enrolled in this study. The PIs of the unaffected (PIControl ) and affected (PICRPS ) limbs were simultaneously evaluated before and after treatment. RESULTS: PICRPS was significantly lower than PIControl at all time points. The change in PI from immediately before to 30 min after intravenous ketamine infusion therapy (TBefore and T30 min , respectively) in the affected limb was significantly correlated with the change in visual analog pain scale (VAS) between the two time points (r = 0.646, p < 0.001). The area under the curve for the changes in VAS and PICRPS between TBefore and T30 min was 0.928. The optimal threshold value for the change in PICRPS between TBefore and T30 min , to distinguish responders with a ≥ 50-point reduction in VAS score from nonresponders, was 22.60% with a sensitivity of 0.811 (95% CI: 0.774-0.848) and a specificity of 0.889 (95% CI: 0.848-0.930). Thirty-one patients showed a ≥ 50-point reduction in VAS score [67% (95% CI: 54%-80%)] and 15 patients showed a < 50-point reduction in VAS score [33% (95% CI: 20%-46%)]. Thirty patients showed an increased PI ≥ 22.60% [65% (95% CI: 50%-78%)] and 16 patients showed an increased PI < 22.60% [35% (95% CI: 22%-50%)]. Twenty-seven patients had a ≥ 50-point reduction in VAS score and an increased PI ≥ 22.60% [59% (95% CI: 44%-74%)]. Eleven patients had shown a < 50-point pain reduction in VAS score and increased PI < 22.60% [24% (95% CI: 13%-37%)]. CONCLUSION: The PI significantly differed between affected and unaffected limbs in patients with CRPS. The PI may be useful for monitoring the response to intravenous ketamine therapy in patients with CRPS.
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Síndromes de Dolor Regional Complejo , Ketamina , Humanos , Ketamina/uso terapéutico , Analgésicos/uso terapéutico , Índice de Perfusión , Síndromes de Dolor Regional Complejo/tratamiento farmacológico , Síndromes de Dolor Regional Complejo/etiología , Infusiones IntravenosasRESUMEN
BACKGROUND: The antitumor effects of natural killer cells, helper T cells, and cytotoxic T cells after cancer surgery were reported previously. This study hypothesized that propofol-based anesthesia would have fewer harmful effects on immune cells than volatile anesthetics-based anesthesia during colorectal cancer surgery. METHODS: In total, 153 patients undergoing colorectal cancer surgery were randomized and included in the analysis. The primary outcome was the fraction of circulating natural killer cells over time in the propofol and sevoflurane groups. The fractions of circulating natural killer, type 1, type 17 helper T cells, and cytotoxic T cells were investigated. The fractions of CD39 and CD73 expressions on circulating regulatory T cells were investigated, along with the proportions of circulating neutrophils, lymphocytes, and monocytes. RESULTS: The fraction of circulating natural killer cells was not significantly different between the propofol and sevoflurane groups until 24 h postoperatively (20.4 ± 13.4% vs. 20.8 ± 11.3%, 17.9 ± 12.7% vs. 20.7 ± 11.9%, and 18.6 ± 11.6% vs. 21.3 ± 10.8% before anesthesia and after 1 and 24 h after anesthesia, respectively; difference [95% CI], -0.3 [-4.3 to 3.6], -2.8 [-6.8 to 1.1], and -2.6 [-6.2 to 1.0]; P = 0.863, P = 0.136, and P = 0.151 before anesthesia and after 1 and 24 h, respectively). The fractions of circulating type 1 and type 17 helper T cells, cytotoxic T cells, and CD39+ and CD73+ circulating regulatory T cells were not significantly different between the two groups. The neutrophil to lymphocyte ratio in both groups remained within the normal range and was not different between the groups. CONCLUSIONS: Propofol-based anesthesia was not superior to sevoflurane-based anesthesia in terms of alleviating suppression of immune cells including natural killer cells and T lymphocytes during colorectal cancer surgery.
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Anestésicos por Inhalación/farmacología , Anestésicos Intravenosos/farmacología , Neoplasias Colorrectales/cirugía , Propofol/farmacología , Sevoflurano/farmacología , Linfocitos T Reguladores/inmunología , Adulto , Anestésicos por Inhalación/inmunología , Anestésicos Intravenosos/inmunología , Neoplasias Colorrectales/inmunología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Propofol/inmunología , Estudios Prospectivos , Sevoflurano/inmunología , Linfocitos T Reguladores/efectos de los fármacosRESUMEN
Background: We hypothesized that the expression of exosomes under general anaesthesia with an inhalational anaesthetic agent would be changed. The study was designed to confirm the effect of general anesthesia with an inhalational anaesthetic agent on the expression of exosomes in rats. Methods: After intraperitoneal administration for the mixture of ketamine and xylazine, tracheal intubation was performed. Just before the connection to ventilator, Control group and Anaesthesia group, according to anaesthesia with isoflurane, were allocated. The expressions of exosomes were checked in bronchoalveolar lavage (BAL), the blood and the tissues from the lung and the brain. Cytokines in the blood were also assessed. Results: The expressions of cluster of differentiation (CD)63 and CD81 as markers for the exosomes in the blood was increased after anaesthesia with isoflurane (CD63, 0.078 ± 0.057 % in Control group vs. 0.180 ± 0.036 % in Anaesthesia group, p = 0.02; CD81, 0.028 ± 0.034 % in Control group vs. 0.245 ± 0.054 % in Anaesthesia group, p < 0.01). However, the increased expression of them were not checked in BAL, and the tissues from the lung and the brain. The cytokines in the blood did not show any significant difference before and after anaesthesia with isoflurane. Conclusion: General anaesthesia with an inhalational anaesthetic agent increased the expression of exosomes in the blood. However, the change was limited in the blood, not the alveoli and the brain.
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Anestésicos por Inhalación , Exosomas , Isoflurano , Anestesia General , Animales , Citocinas , RatasRESUMEN
BACKGROUND: Deep neuromuscular blockade (NMB) may reduce muscle injury and related inflammation. The inflammation is one of the pathophysiological processes of peri-operative complications. OBJECTIVE: To compare the degree of inflammation and related postoperative complications including postoperative delirium (POD) and peri-operative bleeding according to the degree of NMB during general anaesthesia for total hip replacement. DESIGN: A prospective, single-blind, randomised controlled trial. SETTING: Tertiary, university hospital, single centre. PATIENTS: Eighty-two patients undergoing total hip replacement surgery were included in the final analysis. INTERVENTIONS: Moderate (Mod) and deep (Deep) NMB groups. MAIN OUTCOME MEASURES: The changes in inflammatory cytokines were measured. The incidence of POD was evaluated by using confusion assessment method (CAM). The differences of postoperative bleeding and peri-operative oxygenation in both groups were also measured. RESULTS: The NMB reversal duration was significantly longer in the Mod NMB group than in the Deep NMB group. Changes in interleukin-6 were significantly smaller in the Deep NMB group than in the Mod NMB group (Pâ<â0.001). The incidence of POD was not significantly different between groups (34 versus 17% in Mod and Deep NMB groups, respectively; Pâ=â0.129). The amount of postoperative bleeding until postoperative day 2 was significantly greater in the Mod NMB group than in the Deep NMB group (Pâ=â0.027). CONCLUSION: Our findings suggest that inflammation related to peri-operative complications could be associated with the depth of NMB during total hip replacement. However, the incidence of POD might not be associated to the depth of NMB. TRIAL REGISTRATION: National Library of Medicine (NLM) at the National Institutes of Health (NIH) of United States. (Identifier: NCT02507609). Online address: http://clinicaltrials.gov.
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Artroplastia de Reemplazo de Cadera , Delirio , Bloqueo Neuromuscular , Anciano , Artroplastia de Reemplazo de Cadera/efectos adversos , Citocinas , Delirio/diagnóstico , Delirio/epidemiología , Delirio/etiología , Método Doble Ciego , Humanos , Estudios Prospectivos , Método Simple CiegoRESUMEN
BACKGROUND: This study was designed to investigate the effect of cluster differentiation (CD)39 and CD73 inhibitors on the expresion of tumour-associated macrophages (TAMs), M1- versus M2-tumour phenotypes in mice with colon cancer. METHODS: An in vivo study of co-culture with colon cancer cells and immune cells from the bone marrow (BM) of mice was performed. After the confirmation of the effect of polyoxotungstate (POM-1) as an inhibitor of CD39 on TAMs, the mice were randomly divided into a control group without POM-1 and a study group with POM-1, respectively, after subcutaneous injection of CT26 cells. On day 14 after the injection, the mice were sacrificed, and TAMs were evaluated using fluorescence-activated cell sorting. RESULTS: In the in vivo study, the co-culture with POM-1 significantly increased the apoptosis of CT26 cells. The cell population from the co-culture with POM-1 showed significant increases in the expression of CD11b+ for myeloid cells, lymphocyte antigen 6 complex, locus C (Ly6C+) for monocytes, M1-tumour phenotypes from TAMs, and F4/80+ for macrophages. In the in vivo study, tumour growth in the study group with POM-1 was significantly limited, compared with the control group without POM-1. The expressions of Ly6C+ and major histocompatibility complex class II+ for M1-tumour phenotypes from TAMs on F4/80+ from the tumour tissue in the study group had significantly higher values compared with the control group. CONCLUSION: The inhibition of CD39 with POM-1 prevented the growth of colon cancer in mice, and it was associated with the increased expression of M1-tumour phenotypes from TAMs in the cancer tissue.
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Apirasa/antagonistas & inhibidores , Neoplasias del Colon/prevención & control , Polímeros/farmacología , Macrófagos Asociados a Tumores/efectos de los fármacos , Compuestos de Tungsteno/farmacología , Animales , Antígenos CD , Apoptosis , Proliferación Celular , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Humanos , Ratones , Ratones Endogámicos BALB C , Pronóstico , Células Tumorales Cultivadas , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Background: Genetic variations of mu-opioid receptors are well known to contribute to growth and progression of tumors. The most common single-nucleotide polymorphism (SNP) in the mu-opioid receptor 1 gene (OPRM1) is the A118G mutation. We examined the association between the recurrent breast cancer and genotypes of OPRM1 A118G SNP (AA vs. AG vs. GG) in Korean women population. Methods: We analysed medical records and genetic data of 200 patients aged more than 20 who underwent primary breast cancer surgery from June 2012 to June 2014 and diagnosed recurrent breast cancer from June 2012 to September 2019. Results: The incidence of recurrent breast cancer was 6.1%, 8.2%, and 4.8% in genotype AA, AG and GG, respectively (p=0.780). The incidence of recurrent breast cancer in volatile anaesthesia group was 7.0% and 7.1% in total intravenous anaesthesia (TIVA) group (RR = 0.984, 95% CI = 0.328 - 2.951; p = 0.978). Conclusion: OPRM1 A118G SNP had no influence on breast cancer recurrence in Korean women. Anaesthesia technique did not show significant effect on the incidence of recurrent breast cancer.
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Neoplasias de la Mama/cirugía , Recurrencia Local de Neoplasia/epidemiología , Receptores Opioides mu/genética , Adulto , Anciano , Anestesia por Inhalación/estadística & datos numéricos , Anestesia Intravenosa/estadística & datos numéricos , Mama/patología , Mama/cirugía , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Mastectomía/efectos adversos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Polimorfismo de Nucleótido Simple , República de Corea/epidemiología , Estudios Retrospectivos , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Resultado del TratamientoRESUMEN
Introduction: This study was designed to assess the effect of repetitive exposure to intravenous anesthetic agents on the immunity in mice. Materials and Methods: The mice were divided into six groups: three intravenous anesthetic agents groups (dexmedetomidine, midazolam and propofol groups), and three corresponding control groups (CD, CM, and CP groups). The intravenous injections were administered once per day for 5 days. The immunity of mice was checked after the last intravenous injection. Histopathology and immunochemistry of liver and kidneys were evaluated. Cytokine levels in the blood was also checked. vs. evaluated with cytokine levels in the blood. Results: Cluster of differentiation (CD)4+ T cells were significantly less expressed in dexmedetomidine and propofol groups, compared with the corresponding control groups [34.08 ± 5.63% in the dexmedetomidine group vs. 59.74 ± 8.64% in the CD group, p < 0.05; 25.28 ± 7.28% in the propofol group vs. 61.12 ± 2.70% in the Cp group, p < 0.05]. Apoptosis of CD4+ T cells was increased significantly in dexmedetomidine and propofol groups, compared with the corresponding control groups. Histopathological findings of liver and kidneys did not show any specific differences of any of three intravenous anesthetic agents groups with their corresponding control groups, although immunohistochemical examination indicated significantly lower expression of Toll-like receptor-4 from liver and kidneys in dexmedetomidine and propofol groups. The cytokine levels were not different between the groups. Conclusion: Repetitive exposure to dexmedetomidine and propofol reduced the expression of CD4+ T cells but did not induce any significant liver or kidney injuries.
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Anestésicos Intravenosos/farmacología , Inmunidad Adaptativa/efectos de los fármacos , Animales , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Dexmedetomidina/administración & dosificación , Dexmedetomidina/farmacología , Ensayo de Inmunoadsorción Enzimática , Inmunohistoquímica , Riñón/efectos de los fármacos , Riñón/inmunología , Hígado/efectos de los fármacos , Hígado/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Midazolam/farmacología , Propofol/administración & dosificación , Propofol/farmacologíaRESUMEN
BACKGROUND: Spinal surgery is usually performed in the prone position using a posterior approach. However, the prone position may cause venous engorgement in the back and thus increase surgical bleeding with interruption of surgery. The prone position also affects cardiac output since large vessels are compressed decreasing venous return to the heart. OBJECTIVE: We hypothesised that deep neuromuscular blockade would be associated with less surgical bleeding during spinal surgery in the prone position. DESIGN: Randomised, single blinded trial. SETTING: University teaching hospital. PARTICIPANTS: Eighty-eight patients in two groups. INTERVENTIONS: Patients were randomly assigned to moderate neuromuscular blockade or deep neuromuscular blockade. In the moderate neuromuscular blockade group, administration of rocuronium was adjusted such that the train-of-four count was one to two. In the deep neuromuscular blockade group, rocuronium administration was adjusted such that the train-of-four count was zero with a posttetanic count 2 or less. MAIN OUTCOME MEASURES: The primary outcome was the volume of intra-operative surgical bleeding. The surgeon's satisfaction with operating conditions, haemodynamic and respiratory status, and postoperative pain scores were evaluated. RESULTS: The median [IQR] volume of intra-operative surgical bleeding was significantly less in the deep neuromuscular blockade group than in the moderate neuromuscular blockade group; 300âml [200 to 494] vs. 415âml [240 to 601]; difference: 117âml (95% CI, 9 to 244; Pâ=â0.044). The meanâ±âSD surgeon's satisfaction with the intra-operative surgical conditions was greater in the deep neuromuscular blockade group than in the moderate neuromuscular blockade group; 3.5â±â1.0 vs. 2.9â±â0.9 (Pâ=â0.004). In intergroup comparisons of respiratory variables, peak inspiratory pressure was lower in the deep neuromuscular blockade group overall (Pâ<â0.001). The median [IQR] postoperative pain score was lower in the deep neuromuscular blockade group than the moderate neuromuscular blockade group; 50 [36 to 60] vs. 60 [50 to 70], (Pâ=â0.023). CONCLUSION: Deep neuromuscular blockade reduced intra-operative surgical bleeding in patients undergoing spinal surgery. This may be related to greater relaxation in the back muscles and lower intra-operative peak inspiratory pressure when compared with moderate neuromuscular blockade. TRIAL REGISTRATION: KCT0001264 (http://cris.nih.go.kr).
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Anestésicos , Bloqueo Neuromuscular , Pérdida de Sangre Quirúrgica/prevención & control , Humanos , Bloqueo Neuromuscular/efectos adversos , Dolor Postoperatorio , RocuronioRESUMEN
Background: This study investigated the effects of propofol and isoflurane on endoplasmic reticulum (ER) stress in an animal model under general anaesthesia. Methods: Rats were randomly divided into Propofol and Isoflurane groups. Anaesthesia was maintained with propofol for Propofol group or isoflurane for Isoflurane group during 3 h. ER stress from lymphocytes in blood and tissues was evaluated between two groups after euthanasia. Reactive oxygen species (ROS) from lymphocytes in blood and tissues, and cytokines in blood were also checked. An immunohistochemical assay for ER stress marker from tissues was performed. Results: After anaesthesia, the levels of CCAAT-enhancer-binding protein homologous proteins (CHOP) in blood and liver were significantly higher in Isoflurane group, compared to Propofol group [blood, 31,499 ± 4,934 (30,733, 26,441-38,807) mean fluorescence intensity (MFI) in Isoflurane group vs. 20,595 ± 1,838 (20,780, 18,866-22,232) MFI in Propofol group, p = 0.002; liver, 28,342 ± 5,535 (29,421, 23,388-32,756) MFI in Isoflurane group vs. 20,004 ± 2,155 (19,244, 18,197-22,191) MFI in Propofol group, p = 0.020]. ROS in blood was significantly higher in Isoflurane group, compared to Propofol group. However, cytokines in blood and immunohistochemical assays in tissues were similar between groups. Conclusion: Significant higher of ER stress from blood and liver were observed in rats under anaesthesia with isoflurane, compared to those that received propofol. ROS from blood also showed significant higher under anaesthesia with isoflurane. However, these findings were not associated with any changes in cytokines in blood or immunohistochemical assay in tissues.
Asunto(s)
Anestesia General/efectos adversos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Isoflurano/efectos adversos , Propofol/efectos adversos , Anestésicos por Inhalación/efectos adversos , Anestésicos Intravenosos/efectos adversos , Animales , Biomarcadores/metabolismo , Citocinas/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Linfocitos/efectos de los fármacos , Masculino , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/sangre , Factor de Transcripción CHOP/sangreRESUMEN
[This corrects the article DOI: 10.1155/2014/724753.].
RESUMEN
BACKGROUND: To clarify the effect of anaesthetic agents on cancer immunity, we evaluated the effects of propofol and sevoflurane on natural killer (NK) cell, cytotoxic T lymphocyte (CTL) counts and apoptosis rate in breast cancer and immune cells co-cultures from patients who underwent breast cancer surgery. METHODS: Venous blood samples were collected after inducing anaesthesia and at 1 and 24 h postoperatively in patients who had undergone breast cancer surgery. The patients were allocated randomly to the propofol- or sevoflurane-based anaesthesia groups. We counted and detected apoptosis in cancer cell, NK cell and CTL of patients with breast cancer by co-culture with a breast cancer cell line in both groups. We also evaluated changes in the cytokines tumour necrosis factor-alpha, interleukin (IL)-6 and IL-10 during the perioperative period. RESULTS: Forty-four patients were included in the final analysis. No difference in NK cell count, CTL count or apoptosis rate was detected between the groups. Furthermore, the number of breast cancer cells undergoing apoptosis in the breast cancer cell co-cultures was not different between the groups. No changes in cytokines were detected between the groups. CONCLUSION: Although basic science studies have suggested the potential benefits of propofol over a volatile agent during cancer surgery, propofol was not superior to sevoflurane, on the aspects of NK and CTL cells counts with apoptosis rate including breast cancer cell, during anaesthesia for breast cancer surgery in a clinical environment. TRIAL REGISTRATION: NCT02758249 on February 26, 2016.
Asunto(s)
Neoplasias de la Mama/cirugía , Células Asesinas Naturales/efectos de los fármacos , Éteres Metílicos/administración & dosificación , Propofol/administración & dosificación , Linfocitos T Citotóxicos/efectos de los fármacos , Anestésicos Generales/administración & dosificación , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Células Cultivadas , Técnicas de Cocultivo , Citocinas/metabolismo , Femenino , Humanos , Células MCF-7 , Mastectomía/métodos , Persona de Mediana Edad , SevofluranoRESUMEN
WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Clusters of differentiation 39 and 73, enzymes expressed on the surface of regulatory T cells, promote cancer recurrence and metastasis by suppressing immune cells. The authors hypothesized that propofol is less immunosuppressive than volatile anesthetics. The objective of this randomized trial was to compare the changes in cluster of differentiation 39 and 73 expression on regulatory T cells between propofol- and sevoflurane-based anesthesia during breast cancer surgery. METHODS: A total of 201 patients having breast cancer surgery were randomly assigned and analyzed (n = 99 for propofol, n = 102 for sevoflurane). Blood samples were obtained immediately before anesthesia induction and 1 and 24 h postoperatively. The frequency of cluster of differentiation 39 and 73 expression on circulating regulatory T cells (primary outcome) and the frequency of circulating type 1 and type 17 helper T cells, natural killer cells, and cytotoxic T cells were investigated. Serum cytokines and the neutrophil-to-lymphocyte ratio were also evaluated. RESULTS: Changes in cluster of differentiation 39 and 73 expression on regulatory T cells over time did not differ with propofol and sevoflurane groups (difference [95% confidence interval]: 0.01 [-2.04 to 2.06], P = 0.995 for cluster of differentiation 39; -0.93 [-3.12 to 1.26], P = 0.403 for cluster of differentiation 73). There were no intergroup differences in type 1, type 17 helper T cells, natural killer cells, cytotoxic T cells, cytokines, or the neutrophil-to-lymphocyte ratio. CONCLUSIONS: Changes in immune cells were similar with propofol and sevoflurane during breast cancer surgery. The effect of anesthetics on the perioperative immune activity may be minimal during cancer surgery.
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Anestésicos por Inhalación/farmacología , Anestésicos Intravenosos/farmacología , Neoplasias de la Mama/cirugía , Propofol/farmacología , Sevoflurano/farmacología , Linfocitos T Reguladores/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Humanos , Persona de Mediana EdadRESUMEN
Background: The study examined the difference in the expression of the receptor for activated C kinase 1 (RACK1) between anaesthesia with propofol and isoflurane in rats with myocardial ischemia-reperfusion injury (IRI). Methods: Male Sprague-Dawley rats were studied. Anaesthesia was induced with xylazine 20 µg/g by intraperitoneal injection and maintained with propofol or isoflurane. Myocardial IRI was induced by ligating the left anterior descending artery for 1 hour. Reactive oxygen species (ROS), cardiomyocyte apoptosis, the expression of RACK1 and toll-like receptor 4 (TLR4), and the heart injury score were compared between the two groups. Results: Cardiomyocyte apoptosis with ROS was significantly lower in the propofol group than in the isoflurane group. The propofol group had significantly higher RACK1 expression and lower TLR4 expression, compared with the isoflurane group (RACK1, 1970.50 ± 120.50 vs. 1350.20 ± 250.30, p<0.05; TLR4, 980.50 ± 110.75 vs. 1275.50 ± 75.35, p<0.05). However, the heart injury scores in the two groups did not differ significantly (3.56 ± 0.29 vs. 4.33 ± 0.23 in the propofol and isoflurane groups, respectively, p=0.33). Conclusion: There were significant differences in inflammation and apoptosis, including the expression of RACK1 and TLR4, after myocardial IRI between the propofol and isoflurane groups. However, both groups had similar heart injury scores.
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Anestésicos por Inhalación/efectos adversos , Inflamación/tratamiento farmacológico , Receptores de Cinasa C Activada/genética , Daño por Reperfusión/tratamiento farmacológico , Receptor Toll-Like 4/genética , Anestésicos por Inhalación/administración & dosificación , Animales , Apoptosis/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/patología , Isoflurano/administración & dosificación , Isoflurano/efectos adversos , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/genética , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Propofol/administración & dosificación , Propofol/efectos adversos , Ratas , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/genética , Daño por Reperfusión/patologíaRESUMEN
Background: Ischaemic reperfusion injury (IRI) after tourniquet release during total knee arthroplasty (TKR) is related to postoperative cerebral complications. Remote ischaemic preconditioning (RIPC) is known to minimise IRI in previous studies. Thus, we evaluated the effect of RIPC on regional cerebral oxygenation after tourniquet release during TKR. Methods: Patients undergoing TKR were randomly allocated to not receive RIPC (control group) and to receive RIPC (RIPC group). Regional cerebral oxygenation and pulmonary oxygenation were assessed up to 24 h postoperatively. The changes in serum cytokine and lactate dehydrogenase (LDH) levels were assessed and arterial blood gas analysis was performed. Total transfusion amounts and postoperative bleeding were also examined. Results: In total, 72 patients were included in the final analysis. Regional cerebral oxygenation (P < 0.001 in the left side, P = 0.003 in the right side) with pulmonary oxygenation (P = 0.001) was significantly higher in the RIPC group. The serum LDH was significantly lower in the RIPC group at 1 h and 24 h postoperatively (P < 0.001). The 24 h postoperative transfusion (P = 0.002) and bleeding amount (P < 0.001) were significantly lower in the RIPC group. Conclusions: RIPC increased cerebral oxygenation after tourniquet release during TKR by improving pulmonary oxygenation. Additionally, RIPC decreased the transfusion and bleeding amount with the serum LDH level.