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1.
Int J Med Sci ; 21(8): 1552-1558, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38903925

RESUMO

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.


Assuntos
Raquianestesia , Dexmedetomidina , Hipnóticos e Sedativos , Humanos , Dexmedetomidina/administração & dosagem , Dexmedetomidina/efeitos adversos , Raquianestesia/métodos , Masculino , Feminino , Adulto , Hipnóticos e Sedativos/administração & dosagem , Pessoa de Meia-Idade , Método Duplo-Cego , Infusões Intravenosas , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Período de Recuperação da Anestesia , Hemodinâmica/efeitos dos fármacos , Sedação Consciente/métodos
2.
Int J Med Sci ; 21(7): 1265-1273, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38818478

RESUMO

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.


Assuntos
Diferenciação Celular , Microglia , Neuralgia , Pregabalina , Animais , Pregabalina/farmacologia , Pregabalina/uso terapêutico , Microglia/efeitos dos fármacos , Microglia/patologia , Neuralgia/tratamento farmacológico , Neuralgia/patologia , Neuralgia/etiologia , Ratos , Diferenciação Celular/efeitos dos fármacos , Masculino , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Modelos Animais de Doenças , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia , Ratos Sprague-Dawley , Humanos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia
3.
Int J Mol Sci ; 25(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38473954

RESUMO

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.


Assuntos
Disfunção Cognitiva , Glicoproteínas , Isoflurano , Complicações Cognitivas Pós-Operatórias , Ratos , Animais , Isoflurano/farmacologia , Microglia , Citocinas/farmacologia , Caspase 1 , Aprendizagem em Labirinto , Inibidores da Tripsina/farmacologia
4.
Medicina (Kaunas) ; 60(6)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38929588

RESUMO

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.


Assuntos
Anafilaxia , Benzodiazepinas , Humanos , Anafilaxia/tratamento farmacológico , Anafilaxia/induzido quimicamente , Masculino , Benzodiazepinas/efeitos adversos , Benzodiazepinas/uso terapêutico , Feminino , Pessoa de Meia-Idade , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/uso terapêutico , Adulto , Idoso
5.
Int J Mol Sci ; 24(6)2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36982408

RESUMO

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.


Assuntos
Ketamina , Neuralgia , Ratos , Animais , Ketamina/farmacologia , Ketamina/uso terapêutico , Ratos Sprague-Dawley , Antagonistas de Aminoácidos Excitatórios/farmacologia , Medição da Dor , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo
6.
J Anesth ; 37(1): 32-38, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36309903

RESUMO

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.


Assuntos
Cardiopatias Congênitas , Humanos , Criança , Cardiopatias Congênitas/cirurgia , Cianose/complicações , Cianose/cirurgia , Tromboelastografia , Testes de Coagulação Sanguínea , Hipóxia/complicações
7.
Pain Pract ; 23(5): 535-542, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36840382

RESUMO

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.


Assuntos
Síndromes da Dor Regional Complexa , Ketamina , Humanos , Ketamina/uso terapêutico , Analgésicos/uso terapêutico , Índice de Perfusão , Síndromes da Dor Regional Complexa/tratamento farmacológico , Síndromes da Dor Regional Complexa/etiologia , Infusões Intravenosas
8.
Anesthesiology ; 136(3): 448-458, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35051263

RESUMO

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.


Assuntos
Anestésicos Inalatórios/farmacologia , Anestésicos Intravenosos/farmacologia , Neoplasias Colorretais/cirurgia , Propofol/farmacologia , Sevoflurano/farmacologia , Linfócitos T Reguladores/imunologia , Adulto , Anestésicos Inalatórios/imunologia , Anestésicos Intravenosos/imunologia , Neoplasias Colorretais/imunologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Propofol/imunologia , Estudos Prospectivos , Sevoflurano/imunologia , Linfócitos T Reguladores/efeitos dos fármacos
9.
Int J Med Sci ; 19(9): 1399-1407, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36035371

RESUMO

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.


Assuntos
Anestésicos Inalatórios , Exossomos , Isoflurano , Anestesia Geral , Animais , Citocinas , Ratos
10.
Eur J Anaesthesiol ; 38(Suppl 1): S58-S66, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33399376

RESUMO

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 (P < 0.001). The incidence of POD was not significantly different between groups (34 versus 17% in Mod and Deep NMB groups, respectively; P = 0.129). The amount of postoperative bleeding until postoperative day 2 was significantly greater in the Mod NMB group than in the Deep NMB group (P = 0.027). 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.


Assuntos
Artroplastia de Quadril , Delírio , Bloqueio Neuromuscular , Idoso , Artroplastia de Quadril/efeitos adversos , Citocinas , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Método Duplo-Cego , Humanos , Estudos Prospectivos , Método Simples-Cego
11.
Int J Mol Sci ; 22(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299098

RESUMO

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.


Assuntos
Apirase/antagonistas & inibidores , Neoplasias do Colo/prevenção & controle , Polímeros/farmacologia , Macrófagos Associados a Tumor/efeitos dos fármacos , Compostos de Tungstênio/farmacologia , Animais , Antígenos CD , Apoptose , Proliferação de Células , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Prognóstico , Células Tumorais Cultivadas , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Int J Med Sci ; 17(18): 2941-2946, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173414

RESUMO

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.


Assuntos
Neoplasias da Mama/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Receptores Opioides mu/genética , Adulto , Idoso , Anestesia por Inalação/estatística & dados numéricos , Anestesia Intravenosa/estatística & dados numéricos , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Mastectomia/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Polimorfismo de Nucleotídeo Único , República da Coreia/epidemiologia , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Resultado do Tratamento
13.
Int J Med Sci ; 17(4): 428-436, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32174773

RESUMO

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.


Assuntos
Anestésicos Intravenosos/farmacologia , Imunidade Adaptativa/efeitos dos fármacos , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Dexmedetomidina/administração & dosagem , Dexmedetomidina/farmacologia , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Rim/efeitos dos fármacos , Rim/imunologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Midazolam/farmacologia , Propofol/administração & dosagem , Propofol/farmacologia
14.
Eur J Anaesthesiol ; 37(3): 187-195, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31860601

RESUMO

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; 300 ml [200 to 494] vs. 415 ml [240 to 601]; difference: 117 ml (95% CI, 9 to 244; P = 0.044). The mean ±â€ŠSD surgeon's satisfaction with the intra-operative surgical conditions was greater in the deep neuromuscular blockade group than in the moderate neuromuscular blockade group; 3.5 ±â€Š1.0 vs. 2.9 ±â€Š0.9 (P = 0.004). In intergroup comparisons of respiratory variables, peak inspiratory pressure was lower in the deep neuromuscular blockade group overall (P < 0.001). 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], (P = 0.023). 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).


Assuntos
Anestésicos , Bloqueio Neuromuscular , Perda Sanguínea Cirúrgica/prevenção & controle , Humanos , Bloqueio Neuromuscular/efeitos adversos , Dor Pós-Operatória , Rocurônio
15.
Int J Med Sci ; 16(9): 1287-1294, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588195

RESUMO

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.


Assuntos
Anestesia Geral/efeitos adversos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Isoflurano/efeitos adversos , Propofol/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Anestésicos Intravenosos/efeitos adversos , Animais , Biomarcadores/metabolismo , Citocinas/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Linfócitos/efeitos dos fármacos , Masculino , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/sangue , Fator de Transcrição CHOP/sangue
17.
BMC Cancer ; 18(1): 159, 2018 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-29415668

RESUMO

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.


Assuntos
Neoplasias da Mama/cirurgia , Células Matadoras Naturais/efeitos dos fármacos , Éteres Metílicos/administração & dosagem , Propofol/administração & dosagem , Linfócitos T Citotóxicos/efeitos dos fármacos , Anestésicos Gerais/administração & dosagem , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Células Cultivadas , Técnicas de Cocultura , Citocinas/metabolismo , Feminino , Humanos , Células MCF-7 , Mastectomia/métodos , Pessoa de Meia-Idade , Sevoflurano
18.
Anesthesiology ; 129(5): 921-931, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30074934

RESUMO

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.


Assuntos
Anestésicos Inalatórios/farmacologia , Anestésicos Intravenosos/farmacologia , Neoplasias da Mama/cirurgia , Propofol/farmacologia , Sevoflurano/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Pessoa de Meia-Idade
19.
Int J Med Sci ; 15(4): 352-358, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29511370

RESUMO

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.


Assuntos
Anestésicos Inalatórios/efeitos adversos , Inflamação/tratamento farmacológico , Receptores de Quinase C Ativada/genética , Traumatismo por Reperfusão/tratamento farmacológico , Receptor 4 Toll-Like/genética , Anestésicos Inalatórios/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/patologia , Isoflurano/administração & dosagem , Isoflurano/efeitos adversos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Propofol/administração & dosagem , Propofol/efeitos adversos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia
20.
Int J Med Sci ; 14(10): 994-1001, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28924371

RESUMO

Background: Traditionally, minimum alveolar concentration (MAC) has been used as the standard measure to compare the potencies of volatile anesthetics. However, it reflects the spinal mechanism of immobility rather than the subcortical mechanism of analgesia. Recently, the surgical pleth index (SPI) derived from photoplethysmographic waveform was shown to reflect the intraoperative analgesic component. This study was designed to compare the SPI values produced by equi-MAC of two commonly used volatile anesthetics, sevoflurane and desflurane. Methods: Seventy-two patients undergoing arthroscopic shoulder surgery were randomly assigned to two groups receiving either sevoflurane (n = 36) or desflurane (n = 36). General anesthesia was maintained with the respective volatile anesthetic only. A vaporizer was adjusted to maintain end-tidal anesthetic concentration at age-corrected 1.0 MAC throughout the study period. The SPI value as an analgesic estimate and the bispectral index (BIS) value as a hypnotic estimate were recorded at predefined time points during the standardized surgical procedure. Results: During the steady state of age-corrected 1.0 MAC, mean SPI values throughout the entire study period were significantly higher in the sevoflurane group than in the desflurane group (38.1 ±â€…12.8 vs. 30.7 ±â€…8.8, respectively, P = 0.005), and mean BIS values were significantly higher in the sevoflurane group than in the desflurane group (40.7 ±â€…5.8 vs. 36.8 ±â€…6.2, respectively, P = 0.008). Conclusions: Equi-MAC of sevoflurane and desflurane did not produce similar surgical pleth index values. Therefore, sevoflurane and desflurane may have different analgesic properties at equipotent concentrations.


Assuntos
Anestesia por Inalação/métodos , Anestésicos Inalatórios/administração & dosagem , Cuidados Intraoperatórios/métodos , Isoflurano/análogos & derivados , Éteres Metílicos/administração & dosagem , Dor/prevenção & controle , Adulto , Artroscopia/efeitos adversos , Artroscopia/métodos , Bloqueio do Plexo Braquial/métodos , Desflurano , Feminino , Humanos , Isoflurano/administração & dosagem , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Procedimentos Ortopédicos/efeitos adversos , Procedimentos Ortopédicos/métodos , Dor/etiologia , Manejo da Dor/métodos , Estudos Prospectivos , Sevoflurano , Ombro/cirurgia
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