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

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+macrophages 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.

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.

Long-Term Neurophysiological Outcomes in Patients Undergoing Coronary Artery Bypass Grafting

Abstract Introduction: This study aims to evaluate late postoperative neurophysiological outcomes in patients after coronary artery bypass grafting (CABG). Methods: Forty-five male patients with stable coronary artery disease aged 45-69 years underwent extended neuropsychological assessment using the software Status PF and electroencephalographical examination 3-5 days before CABG and 5-7 years after CABG. Postoperative decline in cognitive functions was determined by a 20% decrease in the cognitive indicator compared to that at baseline on 20% of the tests included in the Status PF battery. Statistical analysis was performed using the software STATISTICA 10.0. Multiple regression was used to identify demographic, clinical, and electroencephalographical variables associated with adverse cognitive outcomes. Results: Cognitive decline was observed in 54% of the patients in the long-term postoperative period. Five to seven years after CABG, all patients have shown an increase in the theta rhythm power compared to the preoperative values, which is most pronounced in the frontal and temporal areas of the right hemisphere (P=0.04), along with a decrease in the alpha rhythm in the posterior areas of the cortex (P=0.005). Multiple regression has reported that the main predictors of cognitive impairment are slower mean alpha frequency, decreased theta-2 rhythm with eyes closed in the right temporal area, and increased theta-2 rhythm with eyes open in the left temporal area (F(5.39)=8.81; P<0.00007; adjusted R-squared=0.57). Conclusion: Our findings indicate that 54% of the patients suffer from postoperative cognitive decline associated with increased theta and decreased alpha rhythms 5-7 years after CABG.

Long-Term Neurophysiological Outcomes in Patients Undergoing Coronary Artery Bypass Grafting.

INTRODUCTION: This study aims to evaluate late postoperative neurophysiological outcomes in patients after coronary artery bypass grafting (CABG). METHODS: Forty-five male patients with stable coronary artery disease aged 45-69 years underwent extended neuropsychological assessment using the software Status PF and electroencephalographical examination 3-5 days before CABG and 5-7 years after CABG. Postoperative decline in cognitive functions was determined by a 20% decrease in the cognitive indicator compared to that at baseline on 20% of the tests included in the Status PF battery. Statistical analysis was performed using the software STATISTICA 10.0. Multiple regression was used to identify demographic, clinical, and electroencephalographical variables associated with adverse cognitive outcomes. RESULTS: Cognitive decline was observed in 54% of the patients in the long-term postoperative period. Five to seven years after CABG, all patients have shown an increase in the theta rhythm power compared to the preoperative values, which is most pronounced in the frontal and temporal areas of the right hemisphere (P=0.04), along with a decrease in the alpha rhythm in the posterior areas of the cortex (P=0.005). Multiple regression has reported that the main predictors of cognitive impairment are slower mean alpha frequency, decreased theta-2 rhythm with eyes closed in the right temporal area, and increased theta-2 rhythm with eyes open in the left temporal area (F(5.39)=8.81; P<0.00007; adjusted R-squared=0.57). CONCLUSION: Our findings indicate that 54% of the patients suffer from postoperative cognitive decline associated with increased theta and decreased alpha rhythms 5-7 years after CABG.

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)

[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.

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 30minutes 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).

S100B protein and neuron-specific enolase as predictors of postoperative cognitive dysfunction in aged dogs: a case-control study.

OBJECTIVE: Postoperative cognitive dysfunction (POCD) may be related to brain injury. S100B protein and neuron-specific enolase (NSE) have been investigated as potential biochemical markers of neural cell injury in animals and humans. This study aimed to investigate the association between POCD, brain injury and serum concentrations of S100B and NSE after periodontal surgery in aged dogs. STUDY DESIGN: Prospective observational animal study. ANIMALS: A total of 24 male and female dogs undergoing periodontal surgery. METHODS: Dogs were separated into two groups based on age: control group, 10 dogs ≤ 8 years and aged group, 14 dogs > 8 years. Cognitive function was measured preoperatively and on the seventh postoperative day using the Canine Cognitive Dysfunction Rating scale and the Age-Related Cognitive and Affective Disorders scale. S100B protein and NSE serum concentrations were measured before and immediately after the surgery. RESULTS: POCD was not observed after surgery in the present study. Serum concentrations of S100B and NSE were increased postoperatively in the control group but not in the aged group (p = 0.04 and 0.03, respectively). Preoperative S100B serum concentrations were significantly higher in the aged group (p = 0.01). CONCLUSIONS: There was no association between POCD and high concentrations of S100B and NSE in dogs. However, increased postoperative serum concentrations of S100B and NSE were found in the control group after surgery, an effect that may indicate neural damage. CLINICAL RELEVANCE: The results suggest that anesthesia and oral surgery are associated with higher postoperative serum concentrations of S100B and NSE in dogs ≤ 8 years old, which may indicate neural damage. Serum concentrations of S100B were elevated in aged dogs before anesthesia, a finding that might be related to chronic preoperative brain damage.

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

Oxidative stress and mitochondrial dysfunction contributes to postoperative cognitive dysfunction in elderly rats.

Postoperative cognitive dysfunction (POCD) is defined by cognitive impairment determined by neuropsychological tests from before to after surgery. Several mechanisms have been proposed in this bidirectional communication between the immune system and the brain after surgery. We aimed at understanding the mechanisms underlying POCD elderly rats in an experimental tibial fracture model. Elderly male Wistar rats were subjected to tibial fracture (TF) model. Control (sham) and fracture (TF) groups were followed to determine nitrite/nitrate concentration; oxidative damage to lipids and proteins; the activity of antioxidant enzymes (superoxide dismutase-SOD and catalase-CAT), mitochondrial respiratory chain enzymes, and creatine kinase (CK); and BDNF levels in the hippocampus and prefrontal cortex (at 24 h and at seven days) and cognitive function through habituation to the open field task and novel object recognition task (only at seven days). TF group presented increased concentration of nitrite/nitrate, hippocampal lipid peroxidation at seven days, protein oxidative damage in the prefrontal cortex and hippocampus at 24 h, decreased antioxidant activity in both structures on the first postoperative day and compromised function of the mitochondrial respiratory chain complexes as well as the CK enzyme. In addition, the levels of BDNF were reduced and memory function was impaired in the TF group. In conclusion, elderly rats submitted to an experimental model of tibial fracture displayed memory impairment accompanied by an increase in oxidative stress, mitochondrial dysfunction and reduced neurotrophin level.

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.

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.

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.

[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 pós­operatório em pacientes idosos: estudo piloto.

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 3 rd 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.

[Impact of postoperative cognitive decline in quality of life: a prospective study]. / Impacto do declínio cognitivo pós­operatório na qualidade de vida: estudo prospectivo.

BACKGROUND: Regardless the progress in perioperative care postoperative cognitive decline (PCD) has been accepted unequivocally as a significant and frequent complication of surgery in older patients. The aim of this study was to evaluate the incidence of postoperative cognitive decline and its influence on quality of life three months after surgery. METHODS: Observational, prospective study in a Post-Anesthesia Care Unit (PACU) in patients aged above 45 years, after elective major surgery. Cognitive function was assessed with Montreal Cognitive Assessment (MOCA); Quality of life (QoL) was assessed using SF-36 Health Survey (SF-36). Assessments were performed preoperatively (T0) and 3 months after surgery (T3). RESULTS: Forty-one patients were studied. The incidence of PCD 3 months after surgery was 24%. At T3 MOCA scores were lower in patients with PCD (median 20 vs. 25, p=0.009). When comparing the median scores for each of SF-36 domains, there were no differences between patients with and without PCD. In patients with PCD, and comparing each of SF-36 domains obtained before and three months after surgery, had similar scores for every of the 8 SF-36 areas while patients without PCD had better scores for six domains. At T3 patients with PCD presented with higher levels of dependency in personal activities of daily living (ADL). CONCLUSION: Three months after surgery patients without PCD had significant improvement in MOCA scores. Patients with PCD obtained no increase in SF-36 scores but patients without PCD improved in almost all SF-36 domains. Patients with PCD presented higher rates of dependency in personal ADL after surgery.

Pathological changes of the hippocampus and cognitive dysfunction following frontal lobe surgery in a rat model.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a known complication after intracranial surgery. Impaired hippocampal neurogenesis has been associated with cognitive dysfunction in animal models. METHODS: In order to assess hippocampal changes after brain surgery, a frontal lobe corticectomy was performed in ten adult Wistar rats (group 4). Three different control groups (n = 10 each) included no treatment (G1), general anesthesia alone (G2), and craniectomy without dural opening (G3). Twenty-four hours after surgery, half of the animals were killed, and the mRNA levels for IL-6, TNF-α, and brain-derived growth factor (BDNF) in the contralateral hippocampus were assessed by qPCR. Seven days later, the remaining animals underwent anxiety and memory testing. Afterwards, the number of immature neurons in the hippocampal cortex was measured by doublecortin (DCX) staining. RESULTS: Twenty-four hours after surgery, mRNA levels of IL-6 and TNF-α increased and BDNF decreased in both surgical groups G3 and G4 (p = 0.012). Cognitive tests demonstrated an increase in anxiety levels and memory impairment in surgical groups compared with non-surgical animals. These changes correlated with an inhibition of hippocampal neurogenesis evidenced by a decreased number of new neurons (mean ± SD for G1-4: 66.4 ± 24; 57.6 ± 22.2; 21.3 ± 3.78; 5.7 ± 1.05, p < 0.001, non-parametric ANOVA). CONCLUSIONS: Intracranial surgery was demonstrated to induce an inflammatory reaction within the hippocampus that compromised neurogenesis and impaired normal cognitive processing. Corticectomy had a greater effect than craniotomy alone, indicating a central trigger for hippocampal inflammatory changes. POCD after craniotomy may originate from a central inflammatory response resulting from surgical trauma to the brain parenchyma.

The effect of sugammadex on postoperative cognitive function and recovery / O efeito de sugamadex sobre a função cognitiva e recuperação no pós-operatório

Abstract Background and objective: Sugammadex is the first selective relaxant binding agent. When compared with neostigmine, following sugammadex administration patients wake earlier and have shorter recovery times. In this study, we hypothesized that fast and clear awakening in patients undergoing general anesthesia has positive effects on cognitive functions in the early period after operation. Methods: Approved by the local ethical committee, 128 patients were enrolled in this randomized, prospective, controlled, double-blind study. Patients were allocated to either Sugammadex group (Group S) or the Neostigmine group (Group N). The primary outcome of the study was early postoperative cognitive recovery as measured by the Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE). After baseline assessment 12-24 h before the operation. After the operation, when the Modified Aldrete Recovery Score was ≥9 the MMSE and 1 h later the MoCA tests were repeated. Results: Although there was a reduction in MoCA and MMSE scores in both Group S and Group N between preoperative and postoperative scores, there was no statistically significant difference in the slopes (p > 0.05). The time to reach TOF 0.9 was 2.19 min in Group S and 6.47 min in Group N (p < 0.0001). Recovery time was 8.26 min in Group S and 16.93 min in Group N (p < 0.0001). Conclusion: We showed that the surgical procedure and/or accompanying anesthetic procedure may cause a temporary or permanent regression in cognitive function in the early postoperative period. However, better cognitive performance could not be proved in the Sugammadex compared to the Neostigmine.

Resumo Justificativa e objetivo: Sugamadex é o primeiro agente de ligação relaxante seletivo. Após a administração de sugamadex, os tempos de despertar e de recuperação dos pacientes são menores, em comparação com neostigmina. Neste estudo, a hipótese foi que um despertar mais rápido e claro dos pacientes submetidos à anestesia geral tem efeitos positivos sobre as funções cognitivas no pós-operatório imediato. Métodos: Após a aprovação do Comitê de Ética local, 128 pacientes foram incluídos neste estudo prospectivo, randômico, controlado e duplo-cego. Os pacientes foram designados para o grupo sugamadex (Grupo S) ou grupo neostigmina (Grupo N). O desfecho primário do estudo foi a recuperação cognitiva no pós-operatório imediato, de acordo com a mensuração da Avaliação de Montreal da Função Cognitiva (MoCA) e com o Mini Exame do Estado Mental (MMSE), após a avaliação inicial 12-24 h antes da operação. Após a operação, quando o escore de recuperação de Aldrete modificado era ≥ 9, o teste MMSE e, uma hora depois, o teste MoCA foram repetidos. Resultados: Embora tenha havido uma redução nos escores de MoCA e MMSE tanto no Grupo S quanto no Grupo N, entre os escores pré- e pós-operatório não houve diferença estatisticamente significativa nas reduções (p > 0,05). O tempo para atingir TOF 0,9 foi de 2,19 min no Grupo S e de 6,47 min no Grupo N (p < 0,0001). O tempo de recuperação foi de 8,26 min no Grupo S e de 16,93 min no Grupo N (p < 0,0001) Conclusão: Mostramos que o procedimento cirúrgico e/ou procedimento anestésico de acompanhamento pode causar uma regressão temporária ou permanente da função cognitiva no pós-operatório imediato. No entanto, um desempenho cognitivo melhor não pode ser provado no grupo sugamadex em comparação com o grupo neostigmina.

The effect of sugammadex on postoperative cognitive function and recovery.

BACKGROUND AND OBJECTIVE: Sugammadex is the first selective relaxant binding agent. When compared with neostigmine, following sugammadex administration patients wake earlier and have shorter recovery times. In this study, we hypothesized that fast and clear awakening in patients undergoing general anesthesia has positive effects on cognitive functions in the early period after operation. METHODS: Approved by the local ethical committee, 128 patients were enrolled in this randomized, prospective, controlled, double-blind study. Patients were allocated to either Sugammadex group (Group S) or the Neostigmine group (Group N). The primary outcome of the study was early postoperative cognitive recovery as measured by the Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE). After baseline assessment 12-24h before the operation. After the operation, when the Modified Aldrete Recovery Score was ≥9 the MMSE and 1h later the MoCA tests were repeated. RESULTS: Although there was a reduction in MoCA and MMSE scores in both Group S and Group N between preoperative and postoperative scores, there was no statistically significant difference in the slopes (p>0.05). The time to reach TOF 0.9 was 2.19min in Group S and 6.47min in Group N (p<0.0001). Recovery time was 8.26min in Group S and 16.93min in Group N (p<0.0001). CONCLUSION: We showed that the surgical procedure and/or accompanying anesthetic procedure may cause a temporary or permanent regression in cognitive function in the early postoperative period. However, better cognitive performance could not be proved in the Sugammadex compared to the Neostigmine.

[The effect of sugammadex on postoperative cognitive function and recovery]. / O efeito de sugamadex sobre a função cognitiva e recuperação no pós-operatório.

BACKGROUND AND OBJECTIVE: Sugammadex is the first selective relaxant binding agent. When compared with neostigmine, following sugammadex administration patients wake earlier and have shorter recovery times. In this study, we hypothesized that fast and clear awakening in patients undergoing general anesthesia has positive effects on cognitive functions in the early period after operation. METHODS: Approved by the local ethical committee, 128 patients were enrolled in this randomized, prospective, controlled, double-blind study. Patients were allocated to either Sugammadex group (Group S) or the Neostigmine group (Group N). The primary outcome of the study was early postoperative cognitive recovery as measured by the Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE). After baseline assessment 12-24h before the operation. After the operation, when the Modified Aldrete Recovery Score was ≥9 the MMSE and 1h later the MoCA tests were repeated. RESULTS: Although there was a reduction in MoCA and MMSE scores in both Group S and Group N between preoperative and postoperative scores, there was no statistically significant difference in the slopes (p>0.05). The time to reach TOF 0.9 was 2.19min in Group S and 6.47min in Group N (p<0.0001). Recovery time was 8.26min in Group S and 16.93min in Group N (p<0.0001). CONCLUSION: We showed that the surgical procedure and/or accompanying anesthetic procedure may cause a temporary or permanent regression in cognitive function in the early postoperative period. However, better cognitive performance could not be proved in the Sugammadex compared to the Neostigmine.