Progress on the researches of acupuncture preconditioning before surgery / 中国针灸

This paper reviews the researches on acupuncture preconditioning before surgery in recent years and explores its application value from three aspects, i.e. relieving preoperative anxiety, preventing from postoperative cognitive dysfunction, and preventing from postoperative gastrointestinal dysfunction. As a relatively safe non-drug treatment, acupuncture has the underlying advantages in participating into multidisciplinary coordination in the enhanced recovery after surgery (ERAS). By building up higher-quality medical evidences and revealing the effect mechanism of acupuncture from multi-dimenisonal aspects, it is expected that acupuncture technology can be coordinated with ERAS to optimize the clinical path in the perioperative period, and boost the development of the perioperative medicine ultimately.

The postoperative cognitive dysfunction induced by central inflammation with possible involvement of the gut-brain axis

Abstract Background: Postoperative cognitive dysfunction is widely recognized as severe postoperative central nervous dysfunction and has a significant impact on the 'patient's physical and mental health. Methods: Postoperative models of tibial fracture in aged rats were established, including the control group, model group, CCL11 protein injection group, and saline injection group. Morris water maze test was used to detect the behavioral characteristics of rats. Enzyme-Linked Immunosorbent Assay was used or determine the content of CCL11 and CXCL10. Immunofluorescence staining was used to detect the distribution of CD14+CD163+macro-phages in colon tissues and CD11b+CCR3+microglia cells in hippocampal tissues. Western blot analyzed NOX1 and STAT3 expression in hippocampus tissues. Results: Water maze test results confirmed severe cognitive impairment in CCL11 rats. The content of CCL11 and CXCL10 in the CCL11 group was much higher than that of the model group. The distribution of macrophage and microglia cells in the CCL11 model group was greater than that in the model group and the saline group. The expression of NOX1 and STAT3 in the CCL11 group was higher compared with the model group. Conclusion: Abnormal macrophage function and excessive CCL11 secretion were observed in the rats with lower limb fractures after surgery. Postoperative central inflammation in rats with lower limb fracture induced postoperative cognitive dysfunction through the gut-brain axis molecular mechanism.

Prevention of dexmedetomidine on postoperative delirium and early postoperative cognitive dysfunction in elderly patients undergoing hepatic lobectomy / 中南大学学报(医学版)

OBJECTIVES@#Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common operative neurocognitive disorders, which places a heavy burden on patients, families and society. Therefore, it is very important to search for preventive drugs. Previous studies have demonstrated that perioperative use of dexmedetomidine resulted in a decrease the incidence of POD and POCD. But the specific effect of dexmedetomidine on elderly patients undergoing hepatic lobectomy and its potential mechanism are not clear. This study aims to evaluate the efficacy of intraoperative use of dexmedetomidine on preventing POD and POCD in elderly patients undergoing hepatic lobectomy and the influence on the balance between proinflammation and anti-inflammation.@*METHODS@#This trial was designed as a single-center, prospective, randomized, controlled study. One hundred and twenty hospitalized patients from January 2019 to December 2020, aged 60-80 years old with American Society of Anesthesiologists (ASA) II-III and scheduled for hepatic lobectomy, were randomly allocated into 3 groups (n=40) using a random number table: A C group, a Dex1 group, and a Dex2 group. After anesthesia induction, saline in the C group, dexmedetomidine [0.3 μg/(kg·h)] in the Dex1 group, and dexmedetomidine [0.6 μg/(kg·h)] in the Dex2 group were infused until the end of operation. The incidences of hypotension and bradycardia were compared among the 3 groups. Confusion Assessment Method (CAM) for assessing POD and Mini Mental State Examination (MMSE) for evaluating POCD were recorded and venous blood samples were obtained for the determination of neuron specific enolase (NSE), TNF-α, IL-1β, and IL-10 at the different time below: the time before anesthesia (T0), and the first day (T1), the third day (T2), the fifth day (T3), and the seventh day (T4) after operation.@*RESULTS@#Compared with the C group, the incidences of bradycardia in the Dex1 group or the Dex2 group increased (both P<0.05) and there was no difference in hypotension in the Dex1 group or the Dex2 group (both P>0.05). The incidences of POD in the C group, the Dex1 group, and the Dex2 group were 22.5%, 5.0%, and 7.5%, respectively. The incidences of POD in the Dex1 group or the Dex2 group declined significantly as compared to the C group (both P<0.05). However, there is no difference in the incidence of POD between the Dex1 group and the Dex2 group (P>0.05). The incidences of POCD in the C group, the Dex1 group, and the Dex2 group were 30.0%, 12.5%, and 10.0%, respectively. The incidences of POCD in the Dex1 group and the Dex2 group declined significantly as compared to the C group (both P<0.05). And no obvious difference was seen in the incidence of POCD in the Dex1 group and the Dex2 group (P>0.05). Compared with the C group, the level of TNF-α and IL-1β decreased and the level of IL-10 increased at each time points (from T1 to T4) in the Dex1 group and the Dex2 group (all P<0.05). Compared with the Dex1 group, the level of IL-1β at T2 and IL-10 from T1 to T3 elevated in the Dex2 group (all P<0.05). Compared with the T0, the concentrations of NSE in C group at each time points (from T1 to T4) and in the Dex1 group and the Dex2 group from T1 to T3 increased (all P<0.05). Compared with the C group, the level of NSE decreased from T1 to T4 in the Dex1 group and the Dex2 group (all P<0.05).@*CONCLUSIONS@#Intraoperative dexmedetomidine infusion can reduce the incidence of POCD and POD in elderly patients undergoing hepatic lobectomy, and the protective mechanism appears to involve the down-regulation of TNF-α and IL-1β and upregulation of IL-10 expression, which lead to rebalance between proinflammation and anti-inflammation.

Effect of electroacupuncture pretreatment on hippocampal oxidative stress in aged mice with postoperative cognitive dysfunction / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) pretreatment on hippocampal oxidative stress in aged mice with postoperative cognitive dysfunction (POCD) and explore the relevant mechanism of EA pretreatment on the improvement of learning and memory in POCD aged mice.@*METHODS@#A total of 72 healthy male aged mice were randomized into a blank group, a model group, a medication group and an EA group, 18 mice in each one. In each group, 1-day, 3-day and 7-day subgroups were divided separately, 6 mice in each subgroup. In the EA group, "Baihui" (GV 20) and "Dazhui" (GV 14) were selected and stimulated with EA, using continuous wave (15 Hz, 1 mA), continuously for 30 min, once a day, for 5 days consecutively. In the medication group, 10% minocycline was injected intraperitoneally, 40 mg/kg, once a day, consecutively for 5 days. In the blank and the control group, intraperitoneal injection of 0.9% sodium chloride solution was given with equal dosage. Except the blank group, at the end of intervention, partial hepatectomy was conducted to establish POCD model in the rest groups. Morris water maze test was adopted to evaluate the learning and memory ability of the aged mice. ELISA was used to determine the contents of reactive oxygen species (ROS) and malondialdehyde (MDA) in the hippocampal tissue. Western blot method was applied to detect the protein expressions of superoxide dismutase 1 (SOD 1) and superoxide dismutase 2 (SOD 2) in the hippocampal tissue.@*RESULTS@#Compared with the blank group, the percentage of platform quadrant residence time was obviously reduced in the mice in the model group (@*CONCLUSION@#Electroacupuncture pretreatment at "Baihui" (GV 20) and "Dazhui" (GV 14) may increase the learning and memory ability of POCD aged mice, which is probably related to the decrease of oxidative stress and the strengthening of hippocampal antioxidant capacity.

S100B level and cognitive dysfunction after robotic-assisted laparoscopic radical prostatectomy procedures: a prospective observational study / Nível de S100B e disfunção cognitiva após prostatectomia radical laparoscópica assistida por robô: estudo observacional prospectivo

Abstract Background: The present study investigated the association between Postoperative Cognitive Dysfunction (POCD) and increased serum S100B level after Robotic-Assisted Laparoscopic Radical Prostatectomy (RALRP). Methods: The study included 82 consecutive patients who underwent RALRP. Serum S100B levels were determined preoperatively, after anesthesia induction, and at 30 minutes and 24 hours postoperatively. Cognitive function was assessed using neuropsychological testing preoperatively, and at 7 days and 3 months postoperatively. Results: Twenty four patients (29%) exhibited POCD 7 days after surgery, and 9 (11%) at 3 months after surgery. Serum S100B levels were significantly increased at postoperative 30 minutes and 24 hours in patients displaying POCD at postoperative 7 days (p = 0.0001 for both) and 3 months (p = 0.001 for both) compared to patients without POCD. Duration of anesthesia was also significantly longer in patients with POCD at 7 days and 3 months after surgery compared with patients without POCD (p = 0.012, p = 0.001, respectively), as was duration of Trendelenburg (p = 0.025, p = 0.002, respectively). Composite Z score in tests performed on day 7 were significantly correlated with duration of Trendelenburg and duration of anesthesia (p = 0.0001 for both). Conclusions: S100B increases after RALRP and this increase is associated with POCD development. Duration of Trendelenburg position and anesthesia contribute to the development of POCD. Trial Registry Number: Clinicaltrials.gov (N° NCT03018522).

Resumo Introdução: O presente estudo investigou a associação entre Disfunção Cognitiva Pós-Operatória (DCPO) e aumento do nível sérico de S100B após Prostatectomia Radical Laparoscópica Assistida por Robô (PRLAR). Métodos: O estudo incluiu 82 pacientes consecutivos submetidos à PRLAR. Os níveis séricos de S100B foram determinados: no pré-operatório, após indução anestésica, e aos 30 minutos e 24 horas do pós-operatório. A função cognitiva foi avaliada com testes neuropsicológicos no pré-operatório, no 7° dia pós-operatório (7 DPO) e aos 3 meses após a cirurgia (3 MPO). Resultados: Observamos 24 pacientes (29%) com DCPO no 7 DPO e 9 pacientes com DCPO (11%) após 3 meses da cirurgia. Quando comparados com os pacientes sem DCPO, os níveis séricos de S100B estavam significantemente aumentados aos 30 minutos e às 24 horas do pós-operatório nos pacientes que apresentaram DCPO no 7 DPO (p= 0,0001 para os dois momentos) e 3 meses após a cirurgia (p= 0,001 para os dois momentos) A duração anestésica também foi significantemente maior em pacientes com DCPO no 7 DPO e 3 MPO em comparação com pacientes sem DCPO (p= 0,012, p= 0,001, respectivamente), assim como a duração da posição de Trendelenburg (p= 0,025, p= 0,002, respectivamente). O escore Z composto nos testes realizados no 7 DPO foi significantemente correlacionado com a duração da posição de Trendelenburg e a duração da anestesia (p= 0,0001 para ambos). Conclusão: S100B aumenta após PRLAR e o aumento está associado ao desenvolvimento de DCPO. A duração anestésica e o tempo decorrido em posição de Trendelenburg contribuem para o desenvolvimento de DCPO. Número de registro do estudo: Clinicaltrials.gov (n° NCT03018522)

Incidencia del déficit cognitivo postoperatorio en anestesia regional y general en una institución de cuarto nivel en Bucaramanga (Santander, Colombia) en el año 2017 / Postoperative cognitive dysfunction incidence for regional and general anesthesia in a level four institution in Bucaramanga (Santander, Colombia) during 2017 / Incidência do déficit cognitivo pós-operatório em anestesia regional e geral em uma instituição de quarto nível em Bucaramanga (Santander, Colômbia) em 2017

Introducción. En el proceso de envejecimiento, la mayoría de los sistemas orgánicos mantienen su funcionamiento basal, pero existe una reducción de la reserva funcional y de la capacidad para compensar el estrés fisiológico, lo que hace que los pacientes de mayor edad sean más propensos a complicaciones postoperatorias. Se realizó un estudio en instituciones de Bucaramanga para determinar la incidencia de déficit cognitivo postoperatorio y los factores de riesgo asociados. Metodología. Estudio observacional analítico de cohorte prospectivo realizado en instituciones de salud de Bucaramanga durante 2017 con pacientes mayores de 55 años intervenidos bajo anestesia regional, general balanceada o anestesia total intravenosa. Resultados. Se estudiaron 173 pacientes, 112 mujeres (64.74%) y 61 hombres (35.26%) operados. Las técnicas anestésicas más empleadas fueron: Regional (46.24%) y General balanceada (44.51%). La incidencia de Déficit Cognitivo Postoperatorio a corto plazo fue 6.36% en pacientes previamente sanos, con valor P significativo (0.001) ajustado. Se detectó deterioro cognitivo del 51.41% con alteraciones en los dominios de lenguaje, atención y memoria; con aumento en la evaluación a largo plazo. Durante el seguimiento de pacientes a largo plazo resultó en un 11.55%, determinando la incidencia de Déficit Cognitivo Postoperatorio tardío en un 17.91%. La técnica anestésica con mayor proporción de déficit a largo plazo fue la anestesia mixta, comparada con anestesia regional. Discusión. En la actualidad no existe una definición estandarizada de Déficit Cognitivo Postoperatorio, se ha observado mayor frecuencia y mayor prolongación en pacientes de edad avanzada. El estudio demostró una incidencia temprana significativamente menor, comparándolo con artículos internacionales, pero una incidencia mayor en déficit postoperatorio tardío, resultado de mayores complicaciones intraoperatorias, comparado con otros estudios. Conclusiones. El Déficit Cognitivo Postoperatorio involucra múltiples factores de riesgo; en el estudio se encontró mayor asociación con la edad, la escolaridad, la hipotensión y la anestesia general. No hubo asociación entre comorbilidades y el Déficit Cognitivo Postoperatorio. Se determinó la presencia de hipotensión para desarrollo de este déficit. Cómo citar: Contreras-Forero FJ, Ochoa ME, Perez M, Pinillos M, Celis L, Valencia-Guampe JS, et al. Incidencia del déficit cognitivo postoperatorio en anestesia regional y general en una institución de cuarto nivel en bucaramanga (santander, colombia) en el año 2017. MedUNAB. 2020;23(3): 450-463. Doi: https://doi.org/10.29375/01237047.3711

Introduction. Within the aging process, most organic systems maintain their basal functions. However, there is a reduction in functional reserve and the capacity to compensate physiological stress, which makes older patients more prone to postoperative complications. A study was performed in institutions in Bucaramanga to determine the incidence of postoperative cognitive dysfunction and the associated risk factors. Methodology. This was a analytical observational prospective cohort study performed in healthcare institutions in Bucaramanga in 2017 with patients older than 55 years of age under regional, balanced general or total intravenous anesthesia. Results. One hundred and seventy-three operated patients were studied, among which 112 (64.74%) were women and 61 (35.26%) were men. The most commonly used anesthetic techniques were: regional (46.24%) and balanced general (44.51%). Short-term Postoperative Cognitive Dysfunction incidence was 6.36% in previously healthy patients, with an adjusted significant P value (0.001). Cognitive deterioration was detected in 51.41% of patients, with alterations in their mastery of language, attention and memory. This increased for the long-term evaluation. During long-term patient follow-up, it resulted in 11.55%, determining the incidence of delayed Postoperative Cognitive Dysfunction at 17.91%. The anesthetic technique with the highest proportion of long- term dysfunction was mixed anesthesia, compared to regional anesthesia. Discussion. There is currently no standardized definition for Postoperative Cognitive Dysfunction. It has been observed more frequently and for longer extensions in older patients. The study demonstrated a significantly lower early incidence when compared to international articles, but a greater incidence of delayed postoperative dysfunction as a result of more intraoperative complications compared to other studies. Conclusions. Postoperative Cognitive Dysfunction involves multiple risk factors. The study observed a greater association with age, level of education, hypotension and general anesthesia. There was no association between comorbidities and Postoperative Cognitive Dysfunction. The presence of hypotension was determined for developing this dysfunction. Cómo citar: Contreras-Forero FJ, Ochoa ME, Perez M, Pinillos M, Celis L, Valencia-Guampe JS, et al. Incidencia del déficit cognitivo postoperatorio en anestesia regional y general en una institución de cuarto nivel en bucaramanga (santander, colombia) en el año 2017. MedUNAB. 2020;23(3): 450-463. Doi: https://doi.org/10.29375/01237047.3711

Introdução. No processo de envelhecimento, a maioria dos sistemas orgânicos mantém seu funcionamento basal, mas há uma diminuição da reserva funcional e da capacidade de compensar o estresse fisiológico que torna os pacientes idosos mais sujeitos a complicações pós-operatórias. Foi realizado um estudo em instituições da cidade de Bucaramanga para determinar a incidência de déficit cognitivo pós-operatório e os fatores de risco associados. Métodos. Estudo observacional analítico de coorte prospectivo realizado em instituições de saúde em Bucaramanga durante o ano de 2017 em pacientes com idade superior a 65 anos operados sob anestesia regional, geral balanceada ou anestesia geral intravenosa. Resultados. Foram estudados 173 pacientes, 112 mulheres (64.74%) e 61 homens (35.26%) operados. As técnicas anestésicas mais utilizadas foram: regional (46.24%) e geral balanceada (44.51%). A incidência de déficit cognitivo pós-operatório de curto prazo foi de 6.36% em pacientes previamente saudáveis, com um valor P significativo (0.001) ajustado. Detectou- se deterioração cognitiva de 51.41% com alterações nos domínios da linguagem, atenção e memória; com aumento na avaliação de longo prazo. No seguimento a longo prazo dos pacientes resultou em 11.55%, determinando a incidência de déficit cognitivo pós-operatório tardio em 17.91%. A técnica anestésica com maior proporção de déficit no longo prazo foi a anestesia mista, em comparação com a anestesia regional. Discussão. Atualmente não existe uma definição padronizada de Déficit Cognitivo Pós-operatório, a qual observa-se com maior frequência e por mais tempo em pacientes idosos. O estudo demonstrou incidência precoce significativamente menor, em comparação com resultados de artigos internacionais, mas maior incidência de déficit pós-operatório tardio, resultado de maiores complicações intraoperatórias, em comparação com outros estudos. Conclusões. O Déficit Cognitivo Pós-operatório envolve múltiplos fatores de risco; o estudo encontrou maior associação com idade, escolaridade, hipotensão e anestesia geral. Não houve associação entre comorbidades e Déficit Cognitivo Pós-operatório. Determinou-se a presença de hipotensão para o desenvolvimento desse déficit. Cómo citar: Contreras-Forero FJ, Ochoa ME, Perez M, Pinillos M, Celis L, Valencia-Guampe JS, et al. Incidencia del déficit cognitivo postoperatorio en anestesia regional y general en una institución de cuarto nivel en bucaramanga (santander, colombia) en el año 2017. MedUNAB. 2020;23(3): 450-463. Doi: https://doi.org/10.29375/01237047.3711

Progress on the roles of glia in postoperative cognitive dysfunction / 生物医学工程学杂志

Postoperative cognitive dysfunction (POCD) is one of the most common complications after surgery under general anesthesia and usually manifests as newly presented cognitive impairment. However, the mechanism of POCD is still unclear. In addition to neurons, glial cells including microglia, astrocytes and oligodendrocytes, represent a large cell population in the nervous system. The bi-directional communication between neurons and glia provides basis for neural circuit function. Recent studies suggest that glial dysfunctions may contribute to the occurrence and progress of POCD. In this paper, we review the relevant work on POCD, which may provide new insights into the mechanism and therapeutic strategy for POCD.

Effects of sevoflurane on the cognitive function and the quantity of alpha 7 nicotinicacetycholine receptors in the hippocampus of elderly model rats / 医学研究生学报

ObjectiveSome studies reported that α7nAChR is closely related to the cognitive function. However, the elderly patients have become a high-risk group of postoperative cognitive dysfunction. The aim of this study was to explore the effect of sevoflurane inhalation on the cognitive function and the quantity of alpha 7nicotinic acetycholine receptors in the hippocampus of elderly model rats.MethodsAdult male Sprague-Dawley rats (N=72) were given subcutaneous injection of D-galactose on the neck for 6 weeks to establish elderly models. The model rats were divided into 4 groups randomly: control group (group Con, n=18) with 6h exposure carrier gas (2L/min Air+2L/min O2); Sevoflurane group (group Sev, n=18) with 6 h exposure to 3.2% sevoflurane through carrier gas. Sev+α7nAChR antagonist group (group Sev+M) injected with methyllycaconitine, after 24 h inhaled of 3.2% sevoflurane and carrier gas for 6 h. Sev+α7nAChR agonist group (group Sev+P, n=18) injected with PNU-282987, after 24 h inhaled of 3.2% sevoflurane and carrier gas for 6 h. Morris water maze experiments were conducted on 6 rats in each group 2 h, 1 week and 4 weeks after treatments, respectively. Every cycle after the behavioral test, the hippocampi were taken out. RT-qPCR method was used to detect α7nAChR mRNA expression. Western blotting was used to detect α7nAChR proteins expression.ResultsBehavioral test: compared with Con group at 2 h after awakening, indicators of working memory and spatial probe test in Sev group and Sev+M group decreased significantly (P0.05). RT-qPCR: compared with Con group at 2 h and 1 w after awakening, the expression of alpha 7nAChR mRNA in the other groups was down-regulated, while at 4 w it was up-regulated (P<0.05).Western blot: protein expression of alpha 7nAChR was down-regulated in the 2 h, 1 w Sev group and the Sev+M group after awakening, and up-regulated in the 4 w group after awakening (P<0.05).ConclusionInhalation of 3.2% sevoflurane for 6 h can cause 7nAChR metabolic disturbance in hippocampus of aging model rats and lead to a short-term (1 w) decline in learning and memory ability of the rats, but this effect is reversible. The PNU-282987 agonist can alleviate the temporary decrease of learning and memory caused by sevoflurane.

Characterization of quantitative EEG in patients with postoperative cognitive dysfunction / 医学研究生学报

Objective Very few studies have been reported on the application of quantitative electroencephalogram (qEEG) in patients with postoperative cognitive dysfunction (POCD). This study was to investigate the qEEG features of POCD and provide some help for the early detection and diagnosis of the condition. Methods We enrolled 31 postoperative patients treated in our Department of Critical Care Medicine from January 2018 to October 2018. Based on the pre- and post-operative scores on the Mini-Mental State Examination (MMSE), we divided the patients into a POCD (MMSE score >2, n = 11) and a non-POCD control group (MMSE score ≤2, n = 20). Using the brain function instrument, the electrode set according to the standard international 10-20 system and with bipolar longitudinal F3-P3 and F4-P4 four channels, we conducted bedside monitoring for all the patients and calculated the average value of the consecutive clips of 10-min qEEG. Then, we analyzed the amplitude-integrated EEG (aEEG), relative frequency band energy, relative α variability and spectrum entropy, and the correlation of relative frequency band energy and relative α variability with the MMSE scores. Results Compared with the non-POCD controls, the POCD patients showed significant decreases in the total MMSE scores (28.35 ± 1.27 vs 18.91 ± 2.34, P < 0.05), orientation score (9.75 ± 0.44 vs 6.82 ± 1.47, P < 0.05) and memory score (2.90 ± 0.31 vs 2.09 ± 1.04, P < 0.05) as well as in the concentration, calculation, recalling and language scores (all P < 0.05); and the POCD patients also exhibited marked reduction in the left α variability ([22.59 ± 10.98]% vs [14.39 ± 8.25]%, P < 0.05), right α variability ([24.07 ± 9.73]% vs [15.70 ± 9.59]%, P < 0.05), left α frequency band energy ([7.17 ± 4.73] vs [3.83 ± 2.62] μV2, P < 0.05) and right α frequency band energy ([6.94 ± 4.53] vs [3.82 ± 2.51] μV2, P < 0.05). The MMSE scores were found to be negatively correlated with left α variability (r = -0.793, P = 0.004), right α variability (r = -0.835, P = 0.001), left α frequency band energy (r = -0.633, P = 0.037) and right α frequency band energy (r = -0.682, P = 0.021). Conclusion Quantitative EEG of POCD patients is characterized by significantly decreased α variability and α frequency band energy, which may contribute to the early detection and diagnosis of POCD.

Research progress of the role of postoperative pain in the development of postoperative cognitive dysfunction in geriatric patients / 南方医科大学学报

Previous studies have shown that postoperative cognitive dysfunction (POCD) is related to multiple factors including age, postoperative trauma, inflammation, postoperative pain, and anesthesia, among which postoperative pain is thought to play an important role in the development of POCD. This review summarizes the recent findings in the study of the role of postoperative pain in the pathogenesis of POCD in light of nerve injuries, neural remodeling and stress, and the progress in the prevention and treatment of POCD in elderly patients. It is of vital important to assess the postoperative pain and formulate adequate analgesic regimens for effective prevention and management of POCD to protect the brain functions of elderly patients.

Varenicline modulates autophagy through PKR/STAT3 pathway to improve postoperative cognitive dysfunction / 中国药理学通报

Aim To evaluate whether varenicline could regulate autophagy through PKR/STAT3 pathway to improve postoperative cognitive dysfunction. Methods Forty healthy male C57BL/6J mice, aged 18 months and weighing (27. 5 ± 2. 5) g, were randomly divided into four groups (n = 10) j control group (CON group), laparotomy group (LAP group), laparotomy with varenicline administration group (Var + LAP group) and varenicline group (Var group). The mice in Var + LAP group and Var group were treated with varenicline (1 mg kg"1 d"1) one day before operation and lasted until 13th day after operation. The other two groups were treated with equal amount of normal saline instead of varenicline. The model of postoperative cognitive dysfunction was established by laparotomy under sevofiurane anesthesia. The novel object recognition task was performed on 10th ~ 12th day after laparotomy, and the Y-maze test was performed on 14th day after laparotomy to detect the cognitive function of the mice. The expression levels of AT8 and LC3B in hippocampus were detected by Western blot and immunofluorescence staining. The expression levels of p-PKR and p-STAT3 were detected by Western blot, and the interaction between STAT3 and PKR was detected by double labeled immunofluorescence staining. Results Compared with CON group, the error numbers and the latency in LAP group increased, the discrimination index decreased, accompanied with the increased expression levels of AT8 and p-PKR, the decreased expression levels of LC3 B and p-STAT3, and the increased interaction of STAT3 and PKR. Compared with LAP group, the error numbers and the latency in Var + LAP group decreased, and the discrimination index increased, associated with the decreased expression of AT8 and p-PKR, the increased expression of LC3B and p-STAT3, and the decreased interaction of STAT3 and PKR. Conclusions Vareni-cline regulates autophagy and eliminates hyperphospho-rylated tau through PKR/STAT3 pathway to improve postoperative cognitive dysfunction.

Una complicación quirúrgica escasamente sospechada: la disfunción cognitiva postoperatoria / A poorly suspected surgical complication: postoperative cognitive dysfunction

Numerosas enfermedades requieren como tratamiento una cirugía, ya sea de emergencia o electiva. Las cirugías pueden tener diversas complicaciones; sin embargo no se consideran las posibles alteraciones cognitivas postoperatorias: delirio del despertar anestésico, delirio postoperatorio y disfunción cognitiva postoperatoria (DCPO). La DCPO es un síndrome clínico caracterizado por alteraciones en la memoria, concentración, atención, comprensión del lenguaje e integración social posterior al uso de anestesia y cirugía que persiste después de tres meses; aunque algunos reportes consideran que no sería una entidad clínica individual. Su incidencia varía del 5,1 al 52,5% dependiendo de la población estudiada, tipo de cirugía, tiempo de la evaluación desde la cirugía y batería neuropsicológica empleada. Los factores de riesgo para DCPO son: edad avanzada, deterioro cognitivo previo, gravedad de enfermedades coexistentes, severidad de la cirugía, duración y tipo de la anestesia, ocurrencia de complicaciones y nivel educativo; siendo imprescindible la realización de una evaluación neuropsicológica antes y después de la cirugía para su diagnóstico. Los mecanismos etiopatogénicos propuestos son: la edad, cambios en la perfusión cerebral, disturbios del sueño, inflamación, efectos de los agentes anestésicos, y fundamentalmente la neuroinflamación. La DCPO es una entidad frecuente y escasamente sospechada, aunque su diagnóstico es controversial. Se sugiere que los pacientes que serán sometidos a cirugías electivas mayores, en especial las cardiacas y cerebrales, sean sometidos a evaluación neuropsicológica previa y a los 3 meses, así como a monitoreo electroencefalográfico intraoperatorio para disminuir la incidencia de DCPO.

Many diseases require surgery as a treatment, either emergency or elective. Surgeries can have various complications; However, the possible postoperative cognitive alterations are not considered: delirium of anesthetic awakening, postoperative delirium and postoperative cognitive dysfunction (PCDP). DCPO is a clinical syndrome characterized by alterations in memory, concentration, attention, understanding of language and social integration after the use of anesthesia and surgery that persists after three months; although some reports consider that it would not be an individual clinical entity. Its incidence varies from 5.1 to 52.5% depending on the population studied, type of surgery, time of evaluation from surgery and neuropsychological battery used. The risk factors for DCPO are: advanced age, previous cognitive impairment, severity of coexisting diseases, severity of the surgery, duration and type of anesthesia, occurrence of complications and educational level; It is essential to carry out a neuropsychological evaluation before and after the surgery for its diagnosis. The proposed etiopathogenic mechanisms are: age, changes in cerebral perfusion, sleep disturbances, inflammation, effects of anesthetic agents, and fundamentally neuroinflammation. The DCPO is a frequent and rarely suspected entity, although its diagnosis is controversial. It is suggested that patients who will undergo major elective surgeries, especially cardiac and cerebral surgeries, undergo previous neuropsychological evaluation at 3 months, and intraoperative electroencephalographic monitoring to reduce the incidence of DCPO.

Anesthesia and Alzheimer disease - Current perceptions / Anestesia e doença de Alzheimer - Percepções atuais

Abstract Background and objectives: It has been speculated that the use of anesthetic agents may be a risk factor for the development of Alzheimer disease. The objective of this review is to describe and discuss pre-clinical and clinical data related to anesthesia and this disease. Content: Alzheimer disease affects about 5% of the population over 65 years old, with age being the main risk factor and being associated with a high morbidity. Current evidence questions a possible association between anesthesia, surgery, and long-term cognitive effects, including Alzheimer disease. Although data from some animal studies suggest an association between anesthesia and neurotoxicity, this link remains inconclusive in humans. We performed a review of the literature in which we selected scientific articles in the PubMed database, published between 2005 and 2016 (one article from 1998 due to its historical relevance), in English, which address the possible relationship between anesthesia and Alzheimer disease. 49 articles were selected. Conclusion: The possible relationship between anesthetic agents, cognitive dysfunction, and Alzheimer disease remains to be clarified. Prospective cohort studies or randomized clinical trials for a better understanding of this association will be required.

Resumo Justificativa e objetivos: Tem sido especulado que o uso de agentes anestésicos possa ser um fator de risco para o desenvolvimento de doença de Alzheimer. O objetivo desta revisão é descrever e discutir dados pré-clínicos e clínicos relacionados com a anestesia e essa doença. Conteúdo: A doença de Alzheimer afeta cerca de 5% da população com mais de 65 anos, a idade é o principal fator de risco e está associada a uma elevada morbidade. A evidência atual questiona uma possível associação entre anestesia, cirurgia e efeitos cognitivos em longo prazo, o que inclui a doença de Alzheimer. Embora os dados obtidos em alguns dos estudos animais sugiram uma associação entre anestesia e neurotoxicidade, esse elo permanece inconclusivo em humanos. Fizemos uma revisão da literatura em que foram selecionados artigos científicos na base de dados Pubmed, publicados entre 2005 e 2016 (um de 1998 pela relevância histórica), em inglês, que abordam a eventual relação entre anestesia e doença de Alzheimer. Foram eleitos 49 artigos. Conclusão: A possível relação entre agentes anestésicos, disfunção cognitiva e doença de Alzheimer permanece por esclarecer. Serão necessários estudos de coorte prospetivos ou ensaios clínicos randomizados para melhor compreensão dessa associação.

Effects of cerebral oxygen changes during coronary bypass surgery on postoperative cognitive dysfunction in elderly patients: a pilot study / Efeitos das alterações no oxigênio cerebral durante cirurgia de revascularização do miocárdio sobre a disfunção cognitiva no pós-operatório em pacientes idosos: estudo piloto

Abstract Background and objectives: Postoperative cognitive dysfunction is common after cardiac surgery. Adequate cerebral perfusion is essential and near infrared spectroscopy (NIRS) can measure cerebral oxygenation. Aim of this study is to compare incidence of early and late postoperative cognitive dysfunction in elderly patients treated with conventional or near infrared spectroscopy monitoring. Methods: Patients undergoing coronary surgery above 60 years, were included and randomized to 2 groups; control and NIRS groups. Peroperative management was NIRS guided in GN; and with conventional approach in control group. Test battery was performed before surgery, at first week and 3rd month postoperatively. The battery comprised clock drawing, memory, word list generation, digit spam and visuospatial skills subtests. Postoperative cognitive dysfunction was defined as drop of 1 SD (standard deviation) from baseline on two or more tests. Mann-Whitney U test was used for comparison of quantitative measurements; Chi-square exact test to compare quantitative data. Results: Twenty-one patients in control group and 19 in NIRS group completed study. Demographic and operative data were similar. At first week postoperative cognitive dysfunction were present in 9 (45%) and 7 (41%) of patients in control group and NIRS group respectively. At third month 10 patients (50%) were assessed as postoperative cognitive dysfunction; incidence was 4 (24%) in NIRS group (p:0.055). Early and late postoperative cognitive dysfunction group had significantly longer ICU stay (1.74 + 0.56 vs. 2.94 + 0.95; p < 0.001; 1.91 + 0.7 vs. 2.79 + 1.05; p < 0.01) and longer hospital stay (9.19 + 2.8 vs. 11.88 + 1.7; p < 0.01; 9.48 + 2.6 vs. 11.36 + 2.4; p < 0.05). Conclusion: In this pilot study conventional monitoring and near infrared spectroscopy resulted in similar rates of early postoperative cognitive dysfunction. Late cognitive dysfunction tended to ameliorate with near infrared spectroscopy. Early and late cognitive declines were associated with prolonged ICU and hospital stays.

Resumo Justificativa e objetivos: A disfunção cognitiva no pós-operatório é comum após cirurgia cardíaca. A perfusão cerebral adequada é essencial e a espectroscopia no infravermelho próximo (NIRS) pode medir a oxigenação cerebral. O objetivo deste estudo foi comparar a incidência de disfunção cognitiva no pós-operatório, precoce e tardio, em pacientes idosos tratados com monitoração convencional ou espectroscopia no infravermelho próximo. Métodos: Os pacientes submetidos à cirurgia coronariana, acima de 60 anos, foram incluídos e randomicamente alocados em dois grupos: grupo controle e grupo NIRS. O manejo dos pacientes no período perioperatório foi feito com NIRS no grupo NH e com abordagem convencional no grupo controle A bateria de testes foi feita antes da cirurgia, na primeira semana e no terceiro mês de pós-operatório. A bateria incluiu o desenho do relógio, a memória, a geração de uma lista de palavras, a sequência de dígitos e subtestes que exigem habilidades visuoespaciais.Disfunção cognitiva no pós-operatório foi definida como queda de um DP (desvio-padrão) da fase basal em dois ou mais testes. O teste U de Mann Whitney foi usado para comparação de medidas quantitativa e o teste exato do qui-quadrado para comparar dados quantitativos. Resultados: Vinte e um pacientes do grupo controle e 19 do grupo NIRS concluíram o estudo. Os dados demográficos e operacionais foram semelhantes. Na primeira semana, nove pacientes (45%) do GC e sete pacientes (41%) do grupo NIRS apresentaram disfunção cognitiva no pós-operatório. No terceiro mês, 10 pacientes (50%) foram avaliados como disfunção cognitiva no pós-operatório; a incidência foi de quatro (24%) no grupo NIRS (p = 0,055). O grupo que apresentou disfunção cognitiva no pós-operatório precoce e tardio teve uma permanência significativamente maior na UTI (1,74 + 0,56 vs. 2,94 + 0,95; p < 0,001; 1,91 + 0,7 vs. 2,79 + 1,05; p < 0,01) e permanência hospitalar mais longa (9,19 + 2,8 vs. 11,88 + 1,7; p < 0,01; 9,48 + 2,6 vs. 11,36 + 2,4; p < 0,05). Conclusão: Neste estudo piloto, a monitoração convencional e a espectroscopia no infravermelho próximo resultaram em taxas semelhantes de disfunção cognitiva no pós-operatório precoce. A disfunção cognitiva tardia tende a melhorar com espectroscopia no infravermelho próximo. Os declínios cognitivos precoces e tardios foram associados a internações prolongadas tanto em UTI quanto hospitalares.

Effects of different anesthesia levels on perioperative cerebral oxygen metabolism and postoperative cogni-tive function in elderly patients / 实用医学杂志

Objective To investigate the effects of different levels of anesthesia on perioperative cerebral oxygen metabolism and postoperative cognitive function in the elderly patients. Methods One hundred elderly pa-tients receiving gastric cancer surgery were divided into two groups:group D(BIS value 30-39) and group L(BIS value 50-59). Blood samples were collected at T0,T1,T2,T3 and T4. Da-jvO2 and CERO2 were calculated at the same time.MMSE score was recorded at the time point of 1,3 and 7 d after operation.Results Compared with the T0,Da-jvO2 and CERO2 were both decreased in the two groups at T2-T4(P<0.05).Compared with the group L, the group D were decreased more obviously(P < 0.05). Compared with preoperative score,MMSE score was de-creased at the time point of 1,3d in the group L as well as 1d in the group D(P<0.05).Compared with the group L,group D was significantly increased at the time point of 1 and 3 d(P < 0.05). Conclusion BIS value was maintained at 30-39 can decrease perioperative cerebral oxygen metabolism and improve postoperative cognitive function in the elderly patients.

The role of blood brain barrier in postoperative cognitive dysfunction of elderly mice / 复旦学报（医学版）

Objective To observe the changes of learning and memory ability in aged mice after appendectomy or isoflurane exposure and the permeability of blood brain barrier (BBB) in hippocampus in order to find the reasons for the destruction of BBB damgge.Methods Thirty C57BL mice (18-month) were randomly divided into 3 groups:control group (group C),surgery group (group S) and inhalation group (group Ⅰ).The permeability of BBB in hippocampus was detected with Evans-blue (EB) quantification.The alterations of tight junction protein were measured by occludin and claudin-5 using Western blot on the same day.The changes of two matrix metalloproteinases MMP-2 and MMP-9 were detected.Results Compared with the control group and inhalation group,surgery group had longer escape latencies and less platform crossings,and EB leaked into the hippocampus.The expression of occludin decreased,while the expressions of MMP-2 and MMP-9 increased.Conclusions MMP-2 and MMP-9 may cause the decrease of the expression of tight junction occludin protein,and lead to the destruction of BBB,which resultes in postoperative cognitive dysfunction.

Effects of postoperative analgesia with oxycodone on postoperative cognitive dysfunction in aged patients undergoing laparascopic cholecystectomy / 临床麻醉学杂志

Objective To investigate effects of postoperative analgesia with oxycodone on post-operative cognitive dysfunction in aged patients undergoing laparascopic cholecystectomy. Methods One hundred and twenty patients scheduled for laparascopic cholecystectomy with general anesthesia,57 males and 63 females,aged 70-80 years,ASA physical status Ⅰ or Ⅱ,were enrolled in the present study.The patients were divided randomly into fentanyl group,sufentanil group and oxycodone group (n=40)according to postoperative analgesia.Visual analog scale (VAS)scores, nausea or vomiting,itching and analgesics consumption of all patients were recorded in the postopera-tive 48 h.Neuropsychological testing was performed with mini-mental state examination (MMSE)on the 7th postoperative day.Results There was no statistical significance between the three groups in VAS scores at different time points in the postoperative 48 h.The incidence of itching,nausea or vomiting in oxycodone group was lower than that in fentanyl group and sufentanil group (P<0.05). Analgesics consumption in fentanyl group and sufentanil group exhibited a negative correlation with MMSE scores on the 7th postoperative day (P<0.01).There was no correlation between analgesics consumption and MMSE scores in oxycodone group.The incidence of POCD was 15 (37.5%)in fent-anyl group,13 (32.5%)in sufentanil group and 7 (17.5%)in oxycodone group.The incidence of POCD in oxycodone group was lower than those in fentanyl group and sufentanil group (P<0.05). Conclusion Oxycodone,replacing fentanyl or sufentanil,can be used for postoperative analgesia and reduce the incidence of POCD with less nausea,vomiting and itching in aged patients.

Relationship of impaired brain function after sevoflurane-nitrous oxide anesthesia and CREB signal pathway / 局解手术学杂志

Objective To explore the relationship of impaired brain function after emergency inhalation anesthesia of sevoflurane com -bined with nitrous oxide and cyclic AMP response element binding protein(CREB)signal pathway.Methods A total of 442 patients who were admitted into our hospital from January 2014 to April 2017 were selected as the object of this study.And these patients were divided into 3 groups according to different anesthesia ways,namely the inhalation anesthesia group(118 cases),the local anesthesia group(206 cases), and the control group(118 cases).The blood cyclic adenosine monophosphate(cAMP)concentration were examined by the mini mental state examination(MMSE)score scale.At the same time,the 60 rats were randomly divided into the anesthesia group(n=30)and the con-trol group(n=30).The learning and memory function of the two groups were evaluated by Morris water maze test,and the expressions of cAMP and CREB were measured.Results The blood cAMP concentration and MMSE score in the inhalation anesthesia group were signifi -cantly decreased after inhalation anesthesia(P<0.05).In the place navigation test,rats of the anesthesia group cost much more time to find the platform compared with rats in the control group, and rats of the anesthesia group encountered less times of crossing the platform com-pared with rats in the control group,and the difference was significant(P<0.05).Western blot showed that patients of the anesthesia group had lower cAMP and expression of p-CREB protein,with significant difference(P<0.05).Conclusion Brain function decline after sevoflu-rane inhalation anesthesia combined with nitrous oxide may induced by increasing the nucleus of the second messenger CAMP /Ca2+pathway and decreasing the expression of CREB.

The clinical effects of Dexmedetomidine on analgesia and postoperative cognitive function in elderly patients with lumbar spine surgery / 中华老年医学杂志

Objective To investigate the clinical effects of Dexmedetomidine on analgesia and postoperative cognitive function in elderly patients with lumbar spine surgery.Methods The patients were randomly divided into the control group (n=88) and the study group (n=100).The patients in the study group were treated with Dexmedetomidine at a loading dose of 1.0 μg/kg for 15 min,and 0.3 μg · kg-1 · h 1 was continuously pumped.The anesthetic mode and drugs in the control group were similar to those in study group,except that Dexmedetomidine in the study group was replaced with physiological saline in the control group.Intraoperatively used dose of analgesic drugs,and pain and cognitive function changes were compared between the two groups.Results The intraoperatively used doses of Remifentanil,Fentanyl and propofol were significantly lower in the study group than in the control group (P＜0.05).The VAS scores were markedly lower in the study group than in the control group (2.6±0.5 vs.4.5± 1.2,t=4.9398,P=0.0000).The MMSE scores were higher in the study group than in the control group (28.0 ± 1.3 vs.26.0 ± 2.5,t =-6.6484,P=0.0000).Conclusions Intraoperative use of Dexmedetomidine for treatment of the elderly patients with lumbar surgery will not only reduce the perioperatively used dose of analgesic and sedative drug,but also reduce postoperative pain and improve postoperative cognitive function.

Effect of lidocaine on the postoperative inflammatory factors and cognitive dysfunction for elderly patients undergoing spinal operation / 药物评价研究

Objective To explore the effect of lidocaine with intravenous infusion on the postoperative inflammatory factors and cognitive dysfumction for elderly patients undergoing spinal operation.Method 80 elderly patients undergoing spinal operation in Central hospital of Baoji were enrolled from Janua-y 2015 to January 2016,of which patients divided into two groups randomly,control group (n =40) accepted routine general anesthesia,and study group (n =40) adopted intravenous lidocaine based on the patiems in control group,comparing the MMSE score and the incidence of postoperative cognitive dysfunction (POCD) with before operation,detecting and analyzing the difference of inflammatory and immunity factors.Results The MMSE score of the study group after three days of operation was significantly lower than that of the control group,the difference was statistically significant (P ＜ 0.05).The incidence of POCD in the study group was significantly lower than that in the control group,the difference was statistically significant (P ＜ 0.05).The serum levels of IgA,IgM and IgG in the study group after seven days of operation were significantly higher than those in the control group,the difference was statistically significant (P ＜ 0.05).After three days and seven days postoperatively,the serum levels of interleukin-6 (IL-6) in the study group were significantly lower than those in the control group,the difference was statistically significant (P ＜ 0.05).And there was no significance of TNF-α between two groups at any time point.Conclusions Intravenous lidocaine for patients undergoing spinal operation could inhibit the inflammatory response,improve the function of immunity,and decrease the incidence of POCD,which deserved popularization in clinic.