This study aimed to assess cognition in patients with severe sepsis or septic shock and whether cognitive impairment was associated with clinical and laboratory parameters. We conducted a cohort study of patients with severe sepsis and septic shock evaluated within 24 h and one year after ICU discharge. Demographic, clinical and laboratory data were analyzed, and the following neuropsychological tests were applied: Consortium to Establish Registry for Alzheimer’s Disease, Mini-Mental State Examination, and Trail Making Test forms A and B. We included 33 patients, mean age of 49, 19% were female. Patients underperformed on most measures 24 h after ICU discharge, with improvement on follow-up. IQCODE, APACHE II scores, NSE and IFN-γ levels at ICU discharge were associated with poor cognitive performance, while higher educational level was associated with good cognitive performance. The time to first antibiotic dose, accumulated dose of haloperidol during UCI stay and mean glycemia were also associated with poor cognitive outcome. In general, patients with severe sepsis or septic shock have cognitive impairment that can improve over time. This improvement was associated with factors identified during their ICU stay, such as cognitive reserve, educational level, mean glycemia during ICU stay and NSE level.
Sepsis can lead to long-term cognitive changes, including memory and learning deficits, which are known as septic encephalopathy (SE). SE also includes behavioral changes. The underlying mechanism of SE is unknown, and several mechanisms have been proposed. This study investigated late anxiety-like behavior, serum cytokine levels and brain cytokine production in C57BL/6 mice subjected to polymicrobial sepsis induced by sublethal cecum ligature and puncture (CLP). Anxiety-like behavior and locomotor activity were assessed in mice 10 days after sham operation or CLP procedure using the elevated plus maze, contextual fear conditioning, and open field test. Brain and serum concentrations of the cytokines TNF-α, IFN-γ, IL-1β, IL-6, and IL-10 were determined by ELISA. We found that mice subjected to polymicrobial sepsis presented anxiety-like behavior, which was accompanied by increased serum TNF-α and brain TNF-α, IFN-γ, IL-1β, and IL-6 levels, 10 days after the surgical procedure. These findings suggest an involvement of central nervous system inflammatory mediators in the anxiety-like symptoms found in SE.
Sepsis is a complex disease and is the cause of many deaths worldwide. Sepsis pathogenesis involves a dysregulated inflammatory response with consequent production of inflammatory mediators and reactive species. The production and excessive release of these substances into the systemic circulation trigger various cellular and metabolic alterations that are observed during the disease evolution. Thus, more studies have been carried out to investigate the therapeutic potential of plants such as Morus nigra L., popularly known as black mulberry. Studies have shown that plants belonging to the Morus genus are rich in secondary metabolites such as flavonoids which are associated with important biological activities as antioxidant and anti-inflammatory actions. Based on this context, the objective of our study was to evaluate the anti-inflammatory and antioxidant properties of Morus nigra L. in a sepsis model induced by LPS. Male C57BL/6 mice were distributed in four groups: control, sepsis, sepsis treated with leaf extract of mulberry, and sepsis treated with mulberry pulp. The animals were treated with 100 μL of their respective treatments for twenty-one days. Sepsis was induced at the 21st day with lipopolysaccharide (LPS) by intraperitoneal injection. The animals were euthanized 24 hours after receiving the LPS injection. The data obtained were analyzed in GraphPad Prism 6.0 software. Our results showed that treatment with either extract significantly decreased the number of leukocytes in the bronchoalveolar lavage fluid and serum levels of TNF in septic animals. Regarding the redox status, the treatments significantly decreased the antioxidant activity of the enzyme glutathione peroxidase. Regarding metalloproteinase type 2, it was observed that the treatment with black mulberry pulp was able to significantly reduce the activity of this enzyme concerning the sepsis group. Finally, these results together promoted an increase in the animal's survival that received the black mulberry leaf or pulp extract.
The involvement of TNF-α type 1 receptor (TNFR1) in memory deficits induced by sepsis was explored by using TNFR1 knockout (KO) mice. We reported that wild type (WT) mice presented memory deficits in the novel object recognition test 10 days after sepsis induced by cecum ligation and perforation (CLP). These deficits were not observed in TNFR1 KO mice. The involvement of serum and brain cytokines TNF-α, IL-1β, IL-6, IFN-γ and IL-10 was then investigated. TNFR1 KO mice had higher serum levels of TNF-α and IL-1β, and brain levels of TNF-α than WT mice. After CLP, the brain levels of TNF-α, IL-1β, IL-6 and IFN-γ increased in both WT and KO mice. Our next step was to determine the expression of inflammatory cytokines, BDNF and TrKb in the hippocampus. The absence of TNFR1 in mice subjected to polymicrobial sepsis resulted in higher BDNF expression in the hippocampus. In conclusion, after CLP, memory is preserved in the absence of TNFR1. This finding was associated with increased BDNF expression in the hippocampus.
Objective: Sepsis survivors present a wide range of sequelae; few studies have evaluated psychiatric disorders after sepsis. The objective of this study was to define the prevalence of and risk factors for anxiety, depression and post-traumatic stress disorder (PTSD) symptoms in sepsis survivors. Method: Anxiety, depression and post-traumatic stress symptoms in severe sepsis and septic shock survivors 24 h and 1 year after intensive care unit (ICU) discharge were assessed using the Beck Anxiety/Depression Inventories and the PTSD Checklist-Civilian Version. Differences in psychiatric symptoms over time and the influence of variables on these symptoms were calculated with marginal models. Results: A total of 33 patients were enrolled in the study. The frequencies of anxiety, depression and PTSD 24 h after ICU discharge were 67%, 49%, and 46%, respectively and, among patients reevaluated 1 year after ICU discharge, the frequencies were 38%, 50%, and 31%, respectively. Factors associated with PTSD included serum S100B level, age, and Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) score. Factors associated with depression included patient age and cumulative dose of dobutamine. IQCODE score and cumulative dose of haloperidol in the ICU were associated with anxiety after ICU discharge. Conclusion: Patients who survive sepsis have high levels of psychiatric symptoms. Sepsis and associated treatment-related exposures may have a role in increasing the risk of subsequent depression, anxiety, and PTSD.
Introdução Nas últimas décadas, como consequência dos esforços em reduzir o tempo de internação hospitalar, da preferência dos pacientes e familiares por receber atendimento em casa e, recentemente, da pandemia de COVID-19 observou-se um aumento crescente da modalidade de terapia antimicrobiana parenteral ambulatorial (OPAT). Objetivo Avaliar a densidade de incidência e consumo de antimicrobiano por OPAT após janeiro de 2020 e sua correlação com a pandemia de COVID-19. Metodologia: Estudo realizado pela Comissão de Controle de Infecção Domiciliar (CCID) do Serviço de Atenção Domiciliar (AD) de uma operadora de saúde em Belo Horizonte (BH) entre janeiro de 2020 e agosto de 2021. Foram calculados densidade de incidência de OPAT, dose diária definida (DDD) e dias de terapia (DOT) por 1000 pacientes-dia. Correlações entre número de OPAT, DDD e DOT e número de casos notificados de SG, SRAG, casos confirmados e doses de vacina distribuídas também foram realizadas. Resultado Entre janeiro de 2020 a agosto de 2021, foram realizadas 4.784 OPAT em 2.566.502 pacientes-dia em AD. A densidade de incidência média no período foi de 1,87 OPAT por 1.000 pacientes/dia. A DDD total por 1000 pacientes-dia apresentou tendência a redução a partir de maio de 2021 quando comparada com o mesmo período de 2020, o DDD total em agosto de 2021 foi de 11,09; 26,7% menor quando comparado ao mesmo período de 2020. O DOT também apresentou queda no mesmo período, após maio de 2020 houve queda média de 16,7%, com agosto de 2021 registrando DOT de 13,49 por 1.000 pacientes-dia em atenção domiciliar, 24,9% menor do que o mesmo período de 2020. Após análises de correlação entre número de OPAT, DDD total e DOT com número de notificações de SG, notificações de SRAG, casos confirmados de COVID-19 e vacinas recebidas em BH, encontramos uma correlação moderada entre a quantidade de vacinas recebidas em BH e o DDD total e DOT entre janeiro e agosto de 2021 (r de -0,68 e -0,57, respectivamente). Discussão A pandemia de COVID-19 impôs diversos desafios ao serviço de atenção domiciliar. A necessidade de racionalização da ocupação do leito de internação catalisou a reestruturação do serviço de OPAT e a criação de CCID. As taxas de OPAT sofreram influência de indicadores epidemiológicos locais e apresenta tendência a redução na medida que avança o controle da pandemia. Nosso estudo demonstrou que a vacinação contra COVID-19 impactou positivamente o consumo de antibióticos no serviço.
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