RESUMEN
BACKGROUND: Hip fractures are prevalent in the elderly; however, Postoperative Cognitive Dysfunction (POCD) is a possible complication of hip fracture surgery in elderly patients. This study examines the influence and the underlying mechanism of dexmedetomidine on POCD in elderly patients following hip fracture surgery. METHODS: The retrospective study involved elderly patients with hip fracture who were treated at the Fifth Affiliated Hospital of Xinjiang Medical University from October 2021 to August 2022. During the surgery procedures, dexmedetomidine was administrated and the peripheral blood samples were collected from the patients. Inflammatory factors were measured using Enzyme-linked immunosorbent assay (ELISA), while pyroptosis-related proteins were detected through quantitative reverse transcription PCR (RT-qPCR) and western blot. Additionally, the levels of CD4+T and CD8+T cells were assessed using flow cytometry. An aged rats hip fracture model was established to further investigate the impact of dexmedetomidine on postoperative mobility, cognition function, pyroptosis and immune cells in rats. RESULTS: Postoperative cognitive function in patients did not show significant alteration when compared with pre-operation levels (p > 0.05). There were notable reduction in the levels of interleukin-18 (IL-18), Caspase-3, Gasdermin-D (GSDMD) and NLR Family Pyrin Domain Containing 3 (NLRP3) (p < 0.001), accompanied by an increase in the proportion of CD4+T cells and an decrease in CD8+T cells after operation (p < 0.01). In aged rats, postoperative exploratory activities increased compared to their preoperative state. Compared with preoperative levels, the levels of interleukin-1ß (IL-1ß), IL-18, Caspase-3, GSDMD, and NLRP3 were significantly decreased (p < 0.001), the proportion of CD4+T cells was increased, and the proportion of CD8+T cells was decreased postoperatively (p < 0.01). CONCLUSIONS: Although there was no significant alteration in postoperative cognitive function in patients, dexmedetomidine may still play a role in mitigating POCD potentially due to its effects on reducing immune inflammation and pyroptosis markers. Further research is needed to fully understand the underlying mechanisms and its clinical implications.
Asunto(s)
Dexmedetomidina , Fracturas de Cadera , Complicaciones Cognitivas Postoperatorias , Dexmedetomidina/farmacología , Fracturas de Cadera/cirugía , Humanos , Masculino , Complicaciones Cognitivas Postoperatorias/prevención & control , Complicaciones Cognitivas Postoperatorias/etiología , Femenino , Anciano , Estudios Retrospectivos , Ratas , Animales , Piroptosis/efectos de los fármacos , Anciano de 80 o más Años , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Ratas Sprague-DawleyRESUMEN
The aim of this study was to investigate the mechanism by which propofol reduces postoperative cognitive dysfunction after splenectomy in aged rats. The rats in the model group and propofol group were subjected to splenectomy, and anesthetized with isoflurane and propofol, respectively. Utilizing the western blotting to assess the expression of sirtuin-1 (SIRT1) in the hippocampus. Molecular docking technology was used to predict the binding ability of propofol and SIRT1. Behavioral tests were performed using the Morris water maze, and the hippocampus was isolated for mechanistic investigations. Molecular docking showed that propofol and SIRT1 had a strong binding affinity. The expression of SIRT1 and its related proteins Nrf2, HO-1, NQO1, and GPX4 in the model rats was decreased compared with the sham group. Moreover, the model group exhibited cognitive decline, such as extended escape latency and decreased number of platform crossings. Pathological analysis showed that the number of apoptotic neurons, the levels of oxidative stress and neuroinflammation, the iron deposition, and the expressions of ACSL4 and TFR1 were increased, while the expressions of SLC7A11 and FTH1 were decreased in the hippocampal CA1 region within the model group. These pathological changes in the propofol group were, however, less than those in the model group. Nevertheless, the SIRT1 inhibitor increased these pathological changes compared with the propofol group. Compared with isoflurane, propofol inhibits ferroptosis in the hippocampus of splenectomized rats by causing less downregulation of the SIRT1/Nrf2/GPX4 pathway, thereby reducing the negative impact on cognitive function.
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Disfunción Cognitiva , Ferroptosis , Factor 2 Relacionado con NF-E2 , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Propofol , Ratas Sprague-Dawley , Sirtuina 1 , Esplenectomía , Animales , Propofol/farmacología , Sirtuina 1/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Ratas , Masculino , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Ferroptosis/efectos de los fármacos , Ferroptosis/fisiología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Complicaciones Cognitivas Postoperatorias/metabolismo , Complicaciones Cognitivas Postoperatorias/prevención & control , Transducción de Señal/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismoRESUMEN
Postoperative cognitive dysfunction (POCD) is a common complication in elderly surgical patients, significantly affecting their quality of life. Dexmedetomidine (Dex), an anesthetic, has shown promise in alleviating POCD, but its underlying mechanism remains unclear. This study aims to explore how Dex improves POCD in aged rats by targeting the PINK1-mediated mitochondrial autophagy pathway, reducing caspase-1/11-GSDMD-induced hippocampal neuronal pyroptosis. Transcriptome sequencing identified 300 differentially expressed genes enriched in the mitochondrial autophagy pathway in Dex-treated POCD rat hippocampal tissue, with Pink1 as a key candidate. In a POCD rat model, Dex treatment upregulated hippocampal PINK1 expression. In vitro experiments using H19-7 rat hippocampal neurons revealed that Dex enhanced mitochondrial autophagy and suppressed neuronal pyroptosis by upregulating PINK1. Further mechanistic validation demonstrated that Dex activated PINK1-mediated mitochondrial autophagy, inhibiting caspase-1/11-GSDMD-induced neuronal pyroptosis. In vivo experiments confirmed Dex's ability to reduce caspase-1/11-GSDMD-dependent hippocampal neuronal pyroptosis and improve postoperative cognitive function in aged rats. Dexmedetomidine improves postoperative cognitive dysfunction in elderly rats by enhancing mitochondrial autophagy via PINK1 upregulation, mitigating caspase-1/11-GSDMD-induced neuronal pyroptosis.
Asunto(s)
Dexmedetomidina , Hipocampo , Mitofagia , Neuronas , Complicaciones Cognitivas Postoperatorias , Proteínas Quinasas , Piroptosis , Ratas Sprague-Dawley , Animales , Dexmedetomidina/farmacología , Dexmedetomidina/uso terapéutico , Ratas , Complicaciones Cognitivas Postoperatorias/tratamiento farmacológico , Complicaciones Cognitivas Postoperatorias/metabolismo , Complicaciones Cognitivas Postoperatorias/prevención & control , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Piroptosis/efectos de los fármacos , Mitofagia/efectos de los fármacos , Proteínas Quinasas/metabolismo , Proteínas Quinasas/genética , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Masculino , Envejecimiento/efectos de los fármacosRESUMEN
Neuroinflammation is a major driver of postoperative cognitive dysfunction (POCD). The cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) signaling is a prominent alarming device for aberrant double-stranded DNA (dsDNA) that has emerged as a key mediator of neuroinflammation in cognitive-related diseases. However, the role of the cGAS-STING pathway in the pathogenesis of POCD remains unclear. A POCD model was developed in male C57BL/6J mice by laparotomy under isoflurane (Iso) anesthesia. The cGAS inhibitor RU.521 and caspase-3 agonist Raptinal were delivered by intraperitoneal administration. BV2 cells were exposed to Iso and lipopolysaccharide (LPS) in the absence or presence of RU.521, and then cocultured with HT22 cells in the absence or presence of Raptinal. Cognitive function was assessed using the Morris water maze test and novel object recognition test. Immunofluorescence assays were used to observe the colocalization of dsDNA and cGAS. The downstream proteins and pro-inflammatory cytokines were detected using the Western blot and enzyme-linked immunosorbent assay (ELISA). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to assess the degree of cell death in the hippocampus following anesthesia/surgery treatment. Isoflurane/laparotomy and Iso + LPS significantly augmented the levels of cGAS in the hippocampus and BV2 cells, accompanied by mislocalized dsDNA accumulation in the cytoplasm. RU.521 alleviated cognitive impairment, diminished the levels of 2'3'-cGAMP, cGAS, STING, phosphorylated NF-κB p65 and NF-κB-pertinent pro-inflammatory cytokines (TNFα and IL-6), and repressed pyroptosis-associated elements containing cleaved caspase-3, N-GSDME, IL-1ß and IL-18. These phenotypes could be rescued by Raptinal in vivo and in vitro. These findings suggest that pharmacological inhibition of cGAS mitigates neuroinflammatory burden of POCD by dampening caspase-3/GSDME-dependent pyroptosis, providing a potential therapeutic strategy for POCD.
Asunto(s)
Caspasa 3 , Ratones Endogámicos C57BL , Nucleotidiltransferasas , Complicaciones Cognitivas Postoperatorias , Piroptosis , Animales , Masculino , Ratones , Piroptosis/efectos de los fármacos , Piroptosis/fisiología , Complicaciones Cognitivas Postoperatorias/metabolismo , Complicaciones Cognitivas Postoperatorias/prevención & control , Complicaciones Cognitivas Postoperatorias/tratamiento farmacológico , Nucleotidiltransferasas/metabolismo , Nucleotidiltransferasas/antagonistas & inhibidores , Caspasa 3/metabolismoRESUMEN
Clinical surgery can lead to severe neuroinflammation and cognitive dysfunctions. It has been reported that astrocytes mediate memory formation and postoperative cognitive dysfunction (POCD), however, the thalamic mechanism of astrocytes in mediating POCD remains unknown. Here, we report that reactive astrocytes in zona incerta (ZI) mediate surgery-induced recognition memory impairment in male mice. Immunostaining results showed that astrocytes are activated with GABA transporter-3 (GAT-3) being down-expressed, and neurons were suppressed in the ZI. Besides, our work revealed that reactive astrocytes caused increased tonic current in ZI neurons. Up-regulating the expression of GAT-3 in astrocytes ameliorates surgery-induced recognition memory impairment. Together, our work demonstrates that the reactive astrocytes in the ZI play a crucial role in surgery-induced memory impairment, which provides a new target for the treatment of surgery-induced neural dysfunctions.
Asunto(s)
Astrocitos , Proteínas Transportadoras de GABA en la Membrana Plasmática , Trastornos de la Memoria , Regulación hacia Arriba , Zona Incerta , Animales , Masculino , Proteínas Transportadoras de GABA en la Membrana Plasmática/metabolismo , Trastornos de la Memoria/metabolismo , Ratones , Regulación hacia Arriba/efectos de los fármacos , Astrocitos/metabolismo , Zona Incerta/metabolismo , Ratones Endogámicos C57BL , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Complicaciones Cognitivas Postoperatorias/metabolismo , Complicaciones Cognitivas Postoperatorias/prevención & control , Reconocimiento en Psicología/efectos de los fármacos , Reconocimiento en Psicología/fisiologíaRESUMEN
OBJECTIVE: Postoperative cognitive dysfunction (POCD) is a serious surgical complication. We assessed the different POCD incidences between anesthesia using sevoflurane and sevoflurane combined with dexmedetomidine, with propofol-based sedation in elderly patients who underwent a thoracic surgical procedure. METHODS: A total of 90 patients aged 65 to 80 years old who underwent a thoracic surgical procedure at our hospital and 15 nonsurgical participants as controls, were enrolled in this study. Patients were divided in a randomized 1:1:1 ratio into 3 groups. All participants were randomized into a trial with three anesthesia groups (P, PS, PSD) or a control group (C) of healthy matches. All trial groups received distinct anesthetic combinations during surgery, while controls mirrored patient criteria.Group P (propofol and remifentanil were maintained during the surgery), Group PS (propofol, remifentanil, and sevoflurane were maintained during the surgery), and Group PSD (propofol, remifentanil, sevoflurane, and dexmedetomidine were maintained during the surgery).All participants were rated using a series of cognitive assessment scales before and three days after surgery. All participants were interviewed over the telephone, 7 days, 30 days, and 90 days postoperatively. RESULTS: POCD incidences in the PSD (combined anesthetization with propofol, sevoflurane, and dexmedetomidine) group was significantly lower than that in the PS (combined anesthetization with propofol and sevoflurane) group, 1 day post-surgery (10.0% vs. 40.0%, P = 0.008), and the results were consistent at 3 days post-surgery. When the patients were assessed 7 days, 30 days, and 90 days postoperatively, there was no significant difference in POCD incidence among the three groups. Multivariate logistic regression analysis of POCD one day after surgery showed that education level was negatively correlated with incidence of POCD (P = 0.018) and single lung ventilation time was positively correlated with incidence of POCD (P = 0.001). CONCLUSION: For elderly patients who underwent a thoracic surgical procedure, dexmedetomidine sedation shows an obvious advantage on improving short-term POCD incidence, which is caused by sevoflurane.
Asunto(s)
Dexmedetomidina , Complicaciones Cognitivas Postoperatorias , Propofol , Sevoflurano , Procedimientos Quirúrgicos Torácicos , Humanos , Anciano , Masculino , Femenino , Procedimientos Quirúrgicos Torácicos/efectos adversos , Procedimientos Quirúrgicos Torácicos/métodos , Complicaciones Cognitivas Postoperatorias/prevención & control , Complicaciones Cognitivas Postoperatorias/epidemiología , Complicaciones Cognitivas Postoperatorias/etiología , Método Doble Ciego , Sevoflurano/administración & dosificación , Sevoflurano/efectos adversos , Anciano de 80 o más Años , Dexmedetomidina/uso terapéutico , Dexmedetomidina/administración & dosificación , Propofol/efectos adversos , Anestésicos por Inhalación/efectos adversos , Anestésicos por Inhalación/administración & dosificación , Cognición/efectos de los fármacos , Incidencia , Remifentanilo/administración & dosificación , Anestésicos Intravenosos/efectos adversosRESUMEN
OBJECTIVE: Perioperative Neurocognitive Disorders (PND) is a common neurological complication after radical colorectal cancer surgery, which increases adverse outcomes. So, our objective is to explore the influence of dexmedetomidine added to ropivacaine for transversus abdominis plane block (TAPB) on perioperative neurocognitive disorders, and to provide a new way to reduce the incidence of PND. METHODS: One hundred and eighty patients submitted to radical laparoscopic colorectal cancer surgery were randomly divided into Control group and Dex group. Ultrasound guided TAPB was performed after anesthesia induction: 0.5% ropivacaine 20 ml was injected into each transversus abdominis plane in Control group, 0.5% ropivacaine + 1 µg/kg dexmedetomidine (amounting to 20 ml) in Dex group. We observed the incidence of PND within 30 days after surgery. RESULTS: One hundred and sixty-nine cases were finally analyzed, including 84 cases in Control group and 85 cases in Dex group. Compared with Control group, there was no significant difference in terms of the incidence of PND on the 3rd day and the 7th day (P > 0.05), but the incidence significantly decreased at the 6th hour, at the 24th hour and on the 30th day after surgery (P < 0.05) in Dex group. CONCLUSION: Dexmedetomidine added to ropivacaine for TAPB can reduce the incidence of PND in the first 24 h after surgery and on the 30th postoperative day, which may be related to reduce the consumption of general anesthetics and provide satisfactory postoperative analgesia. TRIAL REGISTRATION: 29 /05/ 2021, ChiCTR2100046876.
Asunto(s)
Músculos Abdominales , Anestésicos Locales , Neoplasias Colorrectales , Dexmedetomidina , Bloqueo Nervioso , Ropivacaína , Humanos , Dexmedetomidina/administración & dosificación , Ropivacaína/administración & dosificación , Método Doble Ciego , Masculino , Femenino , Bloqueo Nervioso/métodos , Persona de Mediana Edad , Neoplasias Colorrectales/cirugía , Anestésicos Locales/administración & dosificación , Anciano , Complicaciones Cognitivas Postoperatorias/prevención & control , Complicaciones Cognitivas Postoperatorias/epidemiología , Complicaciones Cognitivas Postoperatorias/etiología , Quimioterapia Combinada , Laparoscopía/métodosRESUMEN
Postoperative cognitive impairment (POCD) is a complication of cardiopulmonary bypass (CPB). Remimazolam is an ultra-short acting benzodiazepine that can be used for anesthesia or sedation during surgery. This study investigated the role of remimazolam in inflammasome activation and microglia polarization using CPB rat model and lipopolysaccharide (LPS)-induced microglia model. The cognitive function of rats was evaluated by Morris water maze. TUNEL assay was performed to detect apoptosis. Inflammatory cytokines concentration were analyzed by enzyme-linked immunosorbent assay. Reverse transcription-polymerase chain reaction was used to assess the expression of inflammasome and M1/M2-related microglia markers. Flow cytometry was performed to evaluate the expression of CD16/32 and CD206 in microglia. The results showed that remimazolam improved the memory and learning abilities in CPB rats. CPB rats and LPS-treated microglia showed increased apoptosis, pro-inflammatory cytokines level, and inflammasome expression as well as decreased microglia activation, while the results were reversed after remimazolam treatment. Besides, remimazolam treatment promoted the expression of M2-related markers in LPS-treated microglia. Nigericin treatment reversed the increased M2-related mRNA levels and the decreased apoptosis and inflammatory responses induced by remimazolam treatment. In conclusion, remimazolam attenuated POCD after CPB through regulating neuroinflammation and microglia M2 polarization, suggesting a new insight into the clinical treatment of POCD after CPB.
Asunto(s)
Benzodiazepinas , Puente Cardiopulmonar , Microglía , Enfermedades Neuroinflamatorias , Complicaciones Cognitivas Postoperatorias , Ratas Sprague-Dawley , Animales , Microglía/metabolismo , Microglía/efectos de los fármacos , Puente Cardiopulmonar/efectos adversos , Ratas , Masculino , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Complicaciones Cognitivas Postoperatorias/metabolismo , Complicaciones Cognitivas Postoperatorias/prevención & control , Complicaciones Cognitivas Postoperatorias/etiología , Benzodiazepinas/farmacología , Citocinas/metabolismo , Apoptosis/efectos de los fármacos , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/prevención & control , Lipopolisacáridos/farmacologíaRESUMEN
Postoperative cognitive dysfunction (POCD) is a kind of serious postoperative complication in surgery with general anesthesia and it may affect patients' normal lives. Activated microglia are thought to be one of the key factors in the regulation of POCD process. Once activated, resident microglia change their phenotype and secrete kinds of cytokines to regulate inflammatory response in tissues. Among these secretory factors, brain-derived neurotrophic factor (BDNF) is considered to be able to inhibit inflammation response and protect nervous system. Therefore, the enhancement of BDNF expression derived from resident microglia is suggested to be potential treatment for POCD. In our study, we focused on the role of C8-ceramide (a kind of interventional drug) and assessed its regulatory effect on improving the expression of BDNF secreted from microglia to treat POCD. According to the results of our study, we observed that C8-ceramide stimulated primary microglia to up-regulate the expression of BDNF mRNA after being treated with lipopolysaccharide (LPS) in vitro. We proved that C8-ceramide had ability to effectively improve POCD of mice after being accepted carotid artery exposure and their abnormal behavior recovered better than that of mice from the surgery group. Furthermore, we also demonstrated that C8-ceramide enhanced the cognitive function of mice via the PKCδ/NF-κB signaling pathway. In general, our study has confirmed a potential molecular mechanism that led to the occurrence of POCD caused by surgery and provided a new clinical strategy to treat POCD.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Ceramidas , Microglía , FN-kappa B , Complicaciones Cognitivas Postoperatorias , Proteína Quinasa C-delta , Transducción de Señal , Animales , Microglía/efectos de los fármacos , Microglía/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Ratones , FN-kappa B/metabolismo , Complicaciones Cognitivas Postoperatorias/metabolismo , Complicaciones Cognitivas Postoperatorias/prevención & control , Ceramidas/metabolismo , Proteína Quinasa C-delta/metabolismo , Masculino , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Preventive anesthetic impact on the high rates of postoperative neurocognitive disorders in elderly patients is debated. The Prevention of postOperative Cognitive dysfunction by Ketamine (POCK) study aimed to assess the effect of ketamine on this condition. METHODS: This is a multicenter, randomized, double-blind, interventional study. Patients ≥60 years undergoing major orthopedic surgery were randomly assigned in a 1:1 ratio to receive preoperative ketamine 0.5 mg/kg as an intravenous bolus (n = 152) or placebo (n = 149) in random blocks stratified according to the study site, preoperative cognitive status and age. The primary outcome was the proportion of objective delayed neurocognitive recovery (dNR) defined as a decline of one or more neuropsychological assessment standard deviations on postoperative day 7. Secondary outcomes included a three-month incidence of objective postoperative neurocognitive disorder (POND), as well as delirium, anxiety, and symptoms of depression seven days and three months after surgery. RESULTS: Among 301 patients included, 292 (97%) completed the trial. Objective dNR occurred in 50 (38.8%) patients in the ketamine group and 54 (40.9%) patients in the placebo group (OR [95% CI] 0.92 [0.56; 1.51], p = 0.73) on postoperative day 7. Incidence of objective POND three months after surgery did not differ significantly between the two groups nor did incidence of delirium, anxiety, apathy, and fatigue. Symptoms of depression were less frequent in the ketamine group three months after surgery (OR [95% CI] 0.34 [0.13-0.86]). CONCLUSIONS: A single preoperative bolus of intravenous ketamine does not prevent the occurrence of dNR or POND in elderly patients scheduled for major orthopedic surgery. (Clinicaltrials.gov NCT02892916).
Asunto(s)
Ketamina , Procedimientos Ortopédicos , Complicaciones Cognitivas Postoperatorias , Cuidados Preoperatorios , Humanos , Ketamina/administración & dosificación , Ketamina/uso terapéutico , Método Doble Ciego , Anciano , Masculino , Femenino , Procedimientos Ortopédicos/efectos adversos , Complicaciones Cognitivas Postoperatorias/prevención & control , Cuidados Preoperatorios/métodos , Persona de Mediana Edad , Anciano de 80 o más Años , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Trastornos Neurocognitivos/prevención & control , Pruebas Neuropsicológicas , Delirio/prevención & controlRESUMEN
BACKGROUND: Dexmedetomidine plays a pivotal role in mitigating postoperative delirium and cognitive dysfunction while enhancing the overall quality of life among surgical patients. Nevertheless, the influence of dexmedetomidine on such complications in various anaesthesia techniques remains inadequately explored. As such, in the present study, a meta-analysis was conducted to comprehensively evaluate its effects on postoperative delirium and cognitive dysfunction. METHODS: A number of databases were searched for randomised controlled trials comparing intravenous dexmedetomidine to other interventions in preventing postoperative delirium and cognitive dysfunction in non-cardiac and non-neurosurgical patients. These databases included PubMed, Embase, and Cochrane Library. Statistical analysis and graphing were performed using Review Manager, STATA, the second version of the Cochrane risk-of-bias tool for randomised controlled trials, and GRADE profiler. MAIN RESULTS: This meta-analysis comprised a total of 24 randomised controlled trials, including 20 trials assessing postoperative delirium and 6 trials assessing postoperative cognitive dysfunction. Across these 24 studies, a statistically significant positive association was observed between intravenous administration of dexmedetomidine and a reduced incidence of postoperative delirium (RR: 0.55; 95% CI 0.47 to 0.64, p < 0.00001, I2 = 2%) and postoperative cognitive dysfunction (RR: 0.60; 95% CI 0.38 to 0.96, p = 0.03, I2 = 60%). Subgroup analysis did not reveal a significant difference in the incidence of postoperative delirium between the general anaesthesia and non-general anaesthesia groups, but a significant difference was observed in the incidence of postoperative cognitive dysfunction. Nonetheless, when the data were pooled, it was evident that the utilisation of dexmedetomidine was associated with an increased incidence of hypotension (RR: 1.42; 95% CI 1.08 to 1.86, p = 0.01, I2 = 0%) and bradycardia (RR: 1.66; 95% CI 1.23 to 2.26, p = 0.001, I2 = 0%) compared with other interventions. However, there was no significantly higher occurrence of hypertension in the DEX groups (RR = 1.35, 95% CI 0.81-2.24, p = 0.25, I2 = 0%). CONCLUSION: Compared with other interventions, intravenous dexmedetomidine infusion during non-cardiac and non-neurosurgical procedures may significantly reduce the risk of postoperative delirium and cognitive dysfunction. The results of subgroup analysis reveal a consistent preventive effect on postoperative delirium in both general and non-general anaesthesia groups. Meanwhile, continuous infusion during general anaesthesia was more effective in reducing the risk of cognitive dysfunction. Despite such findings, hypotension and bradycardia were more frequent in patients who received dexmedetomidine during surgery.
Asunto(s)
Dexmedetomidina , Delirio del Despertar , Hipotensión , Complicaciones Cognitivas Postoperatorias , Humanos , Bradicardia/epidemiología , Dexmedetomidina/uso terapéutico , Delirio del Despertar/epidemiología , Delirio del Despertar/prevención & control , Hipotensión/epidemiología , Infusiones Intravenosas , Complicaciones Cognitivas Postoperatorias/prevención & control , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
PURPOSE: Assess the efficiency of a cognitive training program using an artificial intelligence application to optimize cognitive reserve and reduce memory disturbance in patients aged 55 to 75 after Class II-III elective noncardiac surgery. DESIGN: Experimental with random assignment. METHODS: The study was conducted on 80 patients undergoing surgery at the Teknon Medical Center Hospital in Barcelona, from April 2018 to June 2021. Both groups were evaluated with cognitive tests before surgery and 7 and 30 days after surgery. The experimental group was subjected to cognitive training for 10 days before surgery to improve their cognitive reserve. FINDINGS: Significant differences were found between the study groups 30 days after surgery in the three screening tests (Mini-Cog, T@M, and MFE). The intervention group presented with fewer cognitive and memory alterations. Age and pre-existing comorbidities were not correlated with an impact on memory impairment or cognitive function. CONCLUSIONS: A cognitive training program based on artificial intelligence, prescribed and monitored by anesthesia nurses has a positive impact on increasing cognitive reserve and reducing memory disturbance in patients aged 55 to 75 undergoing Class II to III elective, noncardiac surgery. This intervention may serve as a prehabilitation strategy in patients with a risk of cognitive dysfunction evaluated by anesthesia nurses for the purpose of preserving their cognitive function and optimizing their recovery.
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Procedimientos Quirúrgicos Electivos , Trastornos de la Memoria , Complicaciones Cognitivas Postoperatorias , Humanos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Procedimientos Quirúrgicos Electivos/métodos , Procedimientos Quirúrgicos Electivos/efectos adversos , Complicaciones Cognitivas Postoperatorias/prevención & control , Trastornos de la Memoria/prevención & control , Disfunción Cognitiva , España , Inteligencia Artificial , Entrenamiento CognitivoRESUMEN
Despite their general good health, an increasing proportion of elderly individuals require surgery due to an increase in average lifespan. However, because of their increased vulnerability, these patients need to be handled carefully to make sure that surgery does not cause more harm than good. Age-related postoperative cognitive disorders (POCD) and postoperative delirium (POD), two serious consequences that are marked by adverse neuropsychologic alterations after surgery, are particularly dangerous for the elderly. In the context of gynecologic procedures, POCD and POD are examined in this narrative review. The main question is how to limit the rates of POCD and POD in older women undergoing gynecologic procedures by maximizing the risk-benefit balance. Three crucial endpoints are considered: (1) surgical procedures to lower the rates of POCD and POD, (2) anesthetic techniques to lessen the occurrence and (3) the identification of individuals at high risk for post-surgery cognitive impairments. Risks associated with laparoscopic gynecologic procedures include the Trendelenburg posture and CO2 exposure during pneumoperitoneum, despite statistical similarities in POD and POCD frequency between laparoscopic and laparotomy techniques. Numerous risk factors are associated with surgical interventions, such as blood loss, length of operation, and position holding, all of which reduce the chance of complications when they are minimized. In order to emphasize the essential role that anesthesia and surgery play in patient care, anesthesiologists are vital in making sure that anesthesia is given as sparingly and quickly as feasible. In addition, people who are genetically predisposed to POCD may be more susceptible to the disorder. The significance of a thorough strategy combining surgical and anesthetic concerns is highlighted in this article, in order to maximize results for senior patients having gynecologic surgery.
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Delirio , Procedimientos Quirúrgicos Ginecológicos , Complicaciones Cognitivas Postoperatorias , Humanos , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Procedimientos Quirúrgicos Ginecológicos/métodos , Femenino , Complicaciones Cognitivas Postoperatorias/prevención & control , Complicaciones Cognitivas Postoperatorias/etiología , Complicaciones Cognitivas Postoperatorias/epidemiología , Delirio/prevención & control , Delirio/etiología , Delirio/epidemiología , Factores de Riesgo , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Anestesia/efectos adversos , Anestesia/métodos , Anciano , Laparoscopía/efectos adversos , Laparoscopía/métodosRESUMEN
Post-operative cognitive dysfunction (POCD) is a multi-etiological symptom mainly occurred in elderly people after surgery. The activation of retinoic acid receptor α (RARα), a transcriptional factor, was previously predicated to be negatively associated with the occurrence of POCD. However, the mechanisms underlying anti-POCD effects of RARα were still unclear. In this study, AM580, a selective agonist of RARα, and all-trans-retinoic acid (ATRA), a pan agonist of RAR, significantly alleviated cognitive dysfunction and increased the expression of RARα in elderly mice after surgery, which was decreased by RO41-5253, an antagonist of RARα. A bioinformatic study further predicted that the activation of RARα might produce anti-POCD effects via the restoration of synaptic proteins. Both agonists inhibited the expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88) and the phosphorylation of nuclear factorkappa-B (NF-κB), leading to the prevention of microglial over-activation and pro-inflammatory cytokines secretion in the hippocampal regions of elderly mice after surgery. Moreover, AM580 and ATRA increased the expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95), and the phosphorylation of extracellular signal-regulated kinase (ERK) and cAMP-response element binding protein (CREB). All these results suggested that the activation of RARα prevented surgery-induced cognitive impairments via the inhibition of neuroinflammation by the reduction of the TLR4/Myd88/NF-κB pathway and the restoration of synaptic proteins by the activation of the BDNF/ERK/CREB pathway, providing a further support that RARα could be developed as a therapeutic target for POCD.
Asunto(s)
Benzoatos , FN-kappa B , Complicaciones Cognitivas Postoperatorias , Receptor alfa de Ácido Retinoico , Tetrahidronaftalenos , Animales , Ratones , Benzoatos/farmacología , Benzoatos/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Ratones Endogámicos ICR , Factor 88 de Diferenciación Mieloide/metabolismo , Enfermedades Neuroinflamatorias/prevención & control , FN-kappa B/metabolismo , Complicaciones Cognitivas Postoperatorias/prevención & control , Receptor alfa de Ácido Retinoico/agonistas , Transducción de Señal , Tetrahidronaftalenos/farmacología , Tetrahidronaftalenos/uso terapéutico , Receptor Toll-Like 4/metabolismo , Tretinoina/farmacologíaRESUMEN
BACKGROUND: The effect of two lung ventilation (TLV) with carbon dioxide artificial pneumothorax on cerebral desaturation and postoperative neurocognitive changes in elderly patients undergoing elective minimally invasive esophagectomy (MIE) is unclear. OBJECTIVES: The first aim of this study was to compare the effect of TLV and one lung ventilation (OLV) on cerebral desaturation. The second aim was to assess changes in early postoperative cognitive outcomes of two ventilation methods. METHODS: This prospective, randomized, controlled trial enrolled patients 65 and older scheduled for MIE. Patients were randomly assigned (1:1) to TLV group or OLV group. The primary outcome was the incidence of cerebral desaturation events (CDE). Secondary outcomes were the cumulative area under the curve of desaturation for decreases in regional cerebral oxygen saturation (rSO2) values below 20% relative to the baseline value (AUC.20) and the incidence of delayed neurocognitive recovery. RESULTS: Fifty-six patients were recruited between November 2019 and August 2020. TLV group had a lower incidence of CDE than OLV group [3 (10.71%) vs. 13 (48.14%), P = 0.002]. TLV group had a lower AUC.20 [0 (0-35.86) % min vs. 0 (0-0) % min, P = 0.007], and the incidence of delayed neurocognitive recovery [2 (7.4%) vs. 11 (40.7%), P = 0.009] than OLV group. Predictors of delayed neurocognitive recovery on postoperative day 7 were age (OR 1.676, 95% CI 1.122 to 2.505, P = 0.006) and AUC.20 (OR 1.059, 95% CI 1.025 to 1.094, P < 0.001). CONCLUSION: Compared to OLV, TLV had a lower incidence of CDE and delayed neurocognitive recovery in elderly patients undergoing MIE. The method of TLV combined with carbon dioxide artificial pneumothorax may be an option for these elderly patients. Chinese Clinical Trial Registry (identifier: ChiCTR1900027454).
Asunto(s)
Esofagectomía , Neumotórax Artificial , Humanos , Femenino , Masculino , Anciano , Esofagectomía/efectos adversos , Esofagectomía/métodos , Estudios Prospectivos , Neumotórax Artificial/métodos , Ventilación Unipulmonar/métodos , Complicaciones Cognitivas Postoperatorias/etiología , Complicaciones Cognitivas Postoperatorias/epidemiología , Complicaciones Cognitivas Postoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Respiración Artificial/métodos , Saturación de Oxígeno , IncidenciaRESUMEN
STUDY OBJECTIVE: To investigate whether a single dosage of esketamine injection in the anesthesia period could improve postoperative negative emotions and early cognitive function in patients undergoing non-cardiac thoracic surgery. DESIGN: A prospective single center double blinded randomized placebo-controlled trial. SETTING: Perioperative period; operating room, post anesthesia care unit and hospital ward. PATIENTS: 129 adult patients that underwent elective non-cardiac thoracic surgery under general anesthesia. INTERVENTIONS: During the operation, pharmacologic prevention of postoperative negative emotion and early cognitive disorder with 0.2 mg/kg (Low esketamine group) and 0.5 mg/kg esketamine (High esketamine group) vs. placebo. MEASUREMENTS: Emotion and early cognitive performance were assessed on the day before surgery (POD-1), postoperative day 1 (POD1) and day 3 (POD3) using HADS-A, HADS-D, Pain Visual Analogue Scale (VAS), Confusion Assessment Method (CAM), Mini-Mental State Examination (MMSE), and serum biomarkers (S100ß, BDNF, IL-6, acetylcholine, and norepinephrine). MAIN RESULTS: The high esketamine group showed significantly lower HADS-A and HADS-D scores than control group on POD1 and POD3. No significant differences were observed between the low esketamine group and the control group. The esketamine-treated groups showed lower pain VAS scores than the control group at 2 h and on the first day after operation. There were no significant differences among the three groups in CAM and MMSE scores. However, the high esketamine group had lower S100ß and IL-6 levels, and higher BDNF levels postoperatively, while serum acetylcholine and norepinephrine were not significantly different. CONCLUSIONS: A single intraoperative injection of 0.5 mg/kg esketamine can alleviate postoperative anxiety, depression, and pain to some extent. Although cognitive function behavioral evaluation did not show obvious benefits, it can also reduce the production of pro-inflammatory and brain injury-related factors while promoting the generation of brain-derived neurotrophic factor. Registration Trial registry: http://www.chictr.org.cn/; Identifier: ChiCTR2100047067.
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Anestesia General , Ketamina , Procedimientos Quirúrgicos Torácicos , Humanos , Ketamina/administración & dosificación , Ketamina/efectos adversos , Masculino , Femenino , Método Doble Ciego , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Procedimientos Quirúrgicos Torácicos/efectos adversos , Anestesia General/efectos adversos , Complicaciones Cognitivas Postoperatorias/prevención & control , Complicaciones Cognitivas Postoperatorias/etiología , Cognición/efectos de los fármacos , Emociones/efectos de los fármacos , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Dimensión del Dolor , Adulto , Factor Neurotrófico Derivado del Encéfalo/sangreRESUMEN
BACKGROUND: Remote ischemic preconditioning (RIPC) is proven to have neuroprotective protective effects. Nevertheless, the impact of RIPC on postoperative cognitive dysfunction (POCD) in patients undergoing general anesthesia is controversial. This meta-analysis of randomized controlled trials (RCTs) aimed to assess the effect of RIPC on POCD in adults after general anesthesia. METHODS: Relevant literature was obtained by searching Embase, PubMed, Web of Science, Cochrane Library, Wanfang, and China National Knowledge Infrastructure (CNKI) databases in July 2022. RCTs were included to assess the influences of RIPC on POCD in adults following general anesthesia. Two investigators independently performed literature screening, data extraction, and quality assessment based on the inclusion and exclusion criteria. The incidence of POCD, operation time, and hospital stay were analyzed by Review manager5.4 software. RESULTS: Thirteen RCTs with 1122 participants were selected for this meta-analysis. Compared to the control group, RIPC decreased the incidence of POCD (OR = 0.50, 95% CI 0.31-0.82), as well as reduced the duration of hospitalization (MD = - 0.98, 95% CI - 1.69 to - 0.27), but did not prolong operative time (MD = - 2.65, 95% CI - 7.68 to 2.37). CONCLUSION: RIPC reduced the incidence of POCD in adult patients after general anesthesia and accelerated their discharge.
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Anestesia General , Precondicionamiento Isquémico , Complicaciones Cognitivas Postoperatorias , Adulto , Humanos , Anestesia General/efectos adversos , China , Complicaciones Cognitivas Postoperatorias/prevención & control , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
STUDY OBJECTIVE: This meta-analysis aimed to assess whether continuous intravenous administration of DEX during surgery can be part of the measures to prevent the onset of postoperative delirium and postoperative cognitive dysfunction in elderly individuals following regional anesthesia. METHODS: We searched the databases of PubMed, Embase, the Cochrane Library and China National Knowledge Infrastructure (by June 1, 2023) for all available randomized controlled trials assessing whether intravenous application of dexmedetomidine can help with postoperative delirium and postoperative cognitive dysfunction in the elderly with regional anesthesia. Subsequently, we carried out statistical analysis and graphing using Review Manager software (RevMan version 5.4.1) and STATA software (Version 12.0). MAIN RESULTS: Within the scope of this meta-analysis, a total of 18 randomized controlled trials were included. Among them, 10 trials aimed to assess the incidence of postoperative delirium as the primary outcome, while the primary focus of the other 8 trials was on the incidence of postoperative cognitive dysfunction. The collective evidence from these 10 studies consistently supports a positive relationship between the intravenous administration of dexmedetomidine and a decreased risk of postoperative delirium (RR: 0.48; 95%CI: 0.37 to 0.63, p < 0.00001, I2 = 0%). The 8 literature articles and experiments evaluating postoperative cognitive dysfunction showed that continuous intravenous infusion of dexmedetomidine during the entire surgical procedure exhibited a positive preventive effect on cognitive dysfunction among the elderly population with no obvious heterogeneity (RR: 0.35; 95%CI: 0.25 to 0.49,p < 0.00001, I2 = 0%). CONCLUSION: Administering dexmedetomidine intravenously during surgery can potentially play a significant role in preventing postoperative delirium and postoperative cognitive dysfunction in patients older than 60 years with regional anesthesia according to this meta-analysis.
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Anestesia de Conducción , Dexmedetomidina , Complicaciones Cognitivas Postoperatorias , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Dexmedetomidina/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Anestesia de Conducción/métodos , Anciano , Infusiones Intravenosas , Complicaciones Cognitivas Postoperatorias/prevención & control , Complicaciones Cognitivas Postoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Delirio/prevención & control , Delirio/epidemiología , Hipnóticos y Sedantes/administración & dosificación , Disfunción Cognitiva/prevención & control , Delirio del Despertar/prevención & control , Delirio del Despertar/epidemiologíaRESUMEN
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients. Liraglutide (LRG) has high homology (97%) with natural glucagon like peptide-1, and it has been proved to be effective in some nervous system diseases. Whether LRG could regulate POCD has not been reported. METHODS: Sevoflurane (Sev) was used to simulate postoperative cognitive dysfunction (POCD) model. Morris water maze test was performed to evaluate the memory ability and neurological function of rats. Escape latency, swim distance, crossing platform times, average velocity, and targeting quadrant time were analyzed. The cell apoptosis, mRNA and protein expression were measured through flow cytometry, PCR, and western blotting, respectively. RESULTS: LRG significantly improved the memory ability and neurological function of Sev-treated rats, but 3-MA reversed the effects of LRG. LRG remarkably inhibited apoptosis but up-regulated autophagy related proteins both in vivo and in vitro levels. However, knocking down AMPK could markedly reverse the influence of LRG on apoptosis, autophagy, and cell apoptosis. CONCLUSIONS: LRG induced autophagy activation can maintain cell homeostasis and promote cell survival by blocking the apoptotic pathway. LRG could improve Sev-induced POCD via activating autophagy, inhibiting apoptosis, and regulating AMPK/mTOR signaling pathway. This study provides a novel therapeutic strategy for the prevention and treatment of POCD.