Significado biológico y utilidad clínica del lactato en la sepsis / Biological significance and clinical utility of lactate in sepsis

La sepsis es un problema global de salud y la progresión hacia el shock séptico se asocia con un incremento marcado de la morbimortalidad. En este escenario, el aumento del lactato plasmático demostró ser un indicador de gravedad y un predictor de mortalidad, y suele interpretarse casi exclusivamente como marcador de baja perfusión tisular. Sin embargo, últimamente se produjo un cambio de paradigma en la exégesis del metabolismo y propiedades biológicas del lactato. En efecto, la adaptación metabólica al estrés, aun con adecuado aporte de oxígeno, puede justificar la elevación del lactato circulante. Asimismo, otras consecuencias fisiopatológicas de la sepsis, como la disfunción mitocondrial, se asocian con el desarrollo de hiperlactatemia sin que necesariamente se acompañen de baja perfusión tisular. Interpretar el origen y la función del lactato puede resultar de suma utilidad clínica en la sepsis, especialmente cuando sus niveles circulantes fundamentan las medidas de reanimación.

Sepsis is a global health problem; progression to septic shock is associated with a marked increase in morbidity and mortality. In this setting, increased plasma lactate levels demonstrated to be an indicator of severity and a predictor of mortality, and are usually interpreted almost exclusively as a marker of low tissue perfusion. However, a recent paradigm shift has occurred in the exegesis of lactate metabolism and its biological properties. Indeed, metabolic adaptation to stress, even with an adequate oxygen supply, may account for high circulating lactate levels. Likewise, other pathophysiological consequences of sepsis, such as mitochondrial dysfunction, are associated with the development of hyperlactatemia, which is not necessarily accompanied by low tissue perfusion. Interpreting the origin and function of lactate may be of great clinical utility in sepsis, especially when circulating lactate levels are the basis for resuscitative measures.

Pileflebitis en pediatría: un desafío diagnóstico / Pylephlebitis in pediatrics: A diagnostic challenge

La pileflebitis es definida como la trombosis supurativa de la vena porta como complicación de infecciones abdominales. En pediatría, la etiología más frecuente es la apendicitis, generalmente de diagnóstico tardío, que se presenta como sepsis, con una elevada mortalidad. Para el diagnóstico son necesarios métodos de diagnóstico por imágenes; los más utilizados son la ecografía Doppler y la angiotomografía. El tratamiento se basa en la intervención quirúrgica, la antibioticoterapia y la anticoagulación. Esta última tiene indicación controvertida, pero podría mejorar el pronóstico y disminuir la morbimortalidad. Se presenta un caso clínico de pileflebitis secundaria a sepsis por Escherichia coli con punto de partida en una apendicitis aguda, en un paciente pediátrico que evoluciona a la transformación cavernomatosa de la vena porta. Es de importancia conocer el manejo de esta entidad, ya que, una vez superado el cuadro inicial, requerirá un minucioso seguimiento por la posibilidad de evolucionar a la insuficiencia hepática.

Pylephlebitis is defined as suppurative thrombosis of the portal vein as a complication of abdominal infections. In pediatrics, the most frequent etiology is appendicitis, generally of late diagnosis, presenting as sepsis, with a high mortality rate. Imaging methods are necessary for diagnosis; the most common are the Doppler ultrasound and computed tomography angiography. Treatment is based on surgery, antibiotic therapy, and anticoagulation. The indication for the latter is controversial, but it may improve prognosis and decrease morbidity and mortality. Here we describe a clinical case of pylephlebitis secondary to Escherichia coli sepsis, which started as acute appendicitis in a pediatric patient who progressed to cavernomatous transformation of the portal vein. It is important to know the management of this disease because, once the initial symptoms are overcome, it will require close follow-up due to a potential progression to liver failure.

Microbiological characteristics of bloodstream infections in a reference hospital in northeastern Brazil / Características microbiológicas de infecções da corrente sanguínea em hospital de referência no nordeste do Brasil

Abstract Routine blood culture is used for the detection of bloodstream infections by aerobic and anaerobic bacteria and by common pathogenic yeasts. A retrospective study was conducted in a public hospital in Maceió-AL, by collecting data of all medical records with positive blood cultures. Out of the 2,107 blood cultures performed, 17% were positive with Staphylococcus coagulase negative (51.14%), followed by Staphylococcus aureus (11.21%) and Klebsiella pneumoniae (6.32%). Gram-positive bacteria predominated among positive blood cultures, highlighting the group of Staphylococcus coagulase-negative. While Gram-negative bacteria had a higher number of species among positive blood cultures.

Resumo A cultura sanguínea de rotina é usada para a detecção de infecções na corrente sanguínea por bactérias aeróbias e anaeróbias e por leveduras patogênicas comuns. Estudo retrospectivo realizado em hospital público de Maceió-AL, por meio da coleta de dados de todos os prontuários com culturas sanguíneas positivas. Das 2.107 culturas sanguíneas realizadas, 17% foram positivas com Staphylococcus coagulase negativo (51,14%), seguido por Staphylococcus aureus (11,21%) e Klebsiella pneumoniae (6,32%). As bactérias Gram-positiva predominaram entre as culturas de sangue positivas, destacando-se o grupo das Staphylococcus coagulase-negativo. Enquanto as bactérias Gram-negativas apresentaram um número maior de espécies entre as culturas de sangue positivas.

Clasificación de riesgo y tiempo puerta-antibiótico en pacientes con sospecha de sepsis / Risk classification and door-to-antibiotic time in patients with suspected sepsis / Classificação de risco e tempo porta-antibiótico no paciente com suspeita de sepse

Objetivo: evaluar la asociación entre la clasificación de riesgo y el tiempo puerta-antibiótico en pacientes con sospecha de sepsis. Método: estudio de cohorte retrospectivo, con una muestra de 232 pacientes con sospecha de sepsis atendidos en el departamento de emergencias. Se dividieron en 2 grupos: con y sin clasificación de riesgo. Una vez identificado el tiempo puerta-antibiótico, se realizó un análisis de varianza de un factor con la prueba post hoc de Bonferroni o la prueba t de Student independiente para variables cuantitativas continuas; pruebas de correlación de Pearson, correlación biserial puntual o correlación biserial para análisis de asociación; y procedimiento de bootstrap cuando no había distribución normal de variables. Para el análisis de los datos se utilizó el software Statistical Package for the Social Sciences. Resultados: el tiempo puerta-antibiótico no difirió entre el grupo que recibió clasificación de riesgo en comparación con el que no fue clasificado. El tiempo puerta-antibiótico fue significativamente más corto en el grupo que recibió una clasificación de riesgo de alta prioridad. Conclusión: no hubo asociación entre el tiempo puerta-antibiótico y si se realizó o no la clasificación de riesgo, ni con la hospitalización en enfermería y en unidad de cuidados intensivos, ni con la duración de la estancia hospitalaria. Se observó que cuanto mayor era la prioridad, más corto era el tiempo puerta-antibiótico.

Objective: to evaluate the association between risk classification and door-to-antibiotic time in patients with suspected sepsis. Method: retrospective cohort study, with a sample of 232 patients with suspected sepsis treated at the emergency department. They were divided into 2 groups: with and without risk classification. Once the door-to-antibiotic time was identified, one-way analysis of variance was performed with Bonferroni post hoc test or independent Student's t-test for continuous quantitative variables; Pearson correlation tests, point-biserial correlation or biserial correlation for association analyses; and bootstrap procedure when there was no normal distribution of variables. For data analysis, the Statistical Package for the Social Sciences software was used. Results: the door-to-antibiotic time did not differ between the group that received risk classification compared to the one that was not classified. Door-to-antibiotic time was significantly shorter in the group that received a high priority risk classification. Conclusion: there was no association between door-to-antibiotic time and whether or not the risk classification was performed, nor with hospitalization in infirmaries and intensive care units, or with the length of hospital stay. It was observed that the higher the priority, the shorter the door-to-antibiotic time.

Objetivo: avaliar a associação entre a realização de classificação de risco e o tempo porta-antibiótico no paciente com suspeita de sepse. Método: estudo de coorte retrospectivo, com amostra de 232 pacientes com suspeita de sepse atendidos no pronto atendimento. Foram distribuídos em 2 grupos: com e sem classificação de risco. Identificado o tempo porta-antibiótico, realizou-se análise de variância de um fator com post hoc de Bonferroni ou teste T-Student independente para variáveis quantitativas contínuas; testes de correlação de Pearson, correlação bisserial por pontos ou correlação bisserial para análises de associação; e procedimento de bootstrap quando não havia distribuição normal de variáveis. Para a análise dos dados foi utilizado o software Statistical Package for the Social Sciences. Resultados: o tempo porta-antibiótico não diferiu entre o grupo que recebeu classificação de risco comparado ao que não foi classificado. O tempo porta-antibiótico foi significativamente menor no grupo que recebeu classificação de risco de alta prioridade. Conclusão: não houve associação entre o tempo porta-antibiótico e a realização ou não da classificação de risco, tampouco com internação em enfermaria e em unidade de terapia intensiva, ou com o tempo de internação hospitalar. Observou-se que quanto maior a prioridade, menor o tempo porta-antibiótico.

Respuesta de procalcitonina ante co-infección e infección secundaria por bacterias multirresistentes en pacientes COVID -19 / Procalcitonin response in co-infection and secondary infection by multidrug resistant bacteria in COVID -19 patients

INTRODUCCIÓN. La procalcitonina, es un biomarcador que puede usarse como apoyo diagnóstico en infecciones bacterianas y la monitorización del tratamiento antibiótico, sobre todo en pacientes con sepsis. De ahí que, fue utilizado durante la pandemia COVID-19 OBJETIVO. Determinar los valores de procalcitonina en pacientes con COVID-19 y definir una p osible correlación entre su incremento y vinculación en coinfección o infección secundaria por Klebsiella pneumoniae y Pseudomonas aeruginosa con multidrogo resistencia y resistencia extendida a los antibióticos. MATERIALES Y MÉTODOS. Estudio retrospectivo observacional, descriptivo transversal, realizado del 1 de mayo al 31 de octubre del 2020 en el Hospital de Especialidades Carlos Andrade Marín sobre 7028 pacientes adultos, hospitalizados, con diagnóstico de COVID-19, y resultados de procalcitonina, cuyas muestras de secreción traqueal y/o hemocultivo presentaron desarrollo de Klebsiella pneumoniae y Pseudomonas aeruginosa. Su análisis estadístico fue desarrollado mediante la prueba Chi Cuadrado de Pearson. RESULTADOS. Se recibieron 861 muestras de hemocultivo y 391 de secreción traqueal, obteniéndose: 32% aislamientos de Klebsiella pneumoniae y Pseudomonas aeruginosa multidrogo y extremadamente resistente. Entre los pacientes COVID-19 que fallecieron, 34,4% mostraron incrementos de procalcitonina. Al contrario, entre los pacientes que sobrevivieron sólo en 8,8% se observó incrementos de procalcitonina evidenciándose un vínculo entre el incremento de procalcitonina y mortalidad. CONCLUSIONES. No existe diferencia en relación al incremento en los valores de procalcitonina en pacientes COVID-19 con co-infección o infección secundaria por Klebsiella pneumoniae y Pseudomonas aeruginosa multidrogo y extremadamente resistente y los valores de procalcitonina en pacientes con coinfección e infección secundaria con otro tipo de aislamientos bacterianos.

INTRODUCTION. Procalcitonin is a biomarker that can be used as a diagnostic support in bacterial infections and the monitoring of antibiotic treatment, especially in patients with sepsis. Hence, it was used during the COVID-19 pandemic OBJECTIVE. To determine the values of procalcitonin in patients with COVID-19 and to define a possible correlation between its increase and linkage in co-infection or secondary infection by Klebsiella pneumoniae and Pseudomonas aeruginosa with multidrug resistance and extended resistance to antibiotics. MATERIALS AND METHODS. Retrospective observational, descriptive cross-sectional study, conducted from May 1 to October 31, 2020 at the Hospital de Especialidades Carlos Andrade Marín on 7028 adult patients, hospitalized, with diagnosis of COVID-19, and procalcitonin results, whose tracheal secretion and/or blood culture samples presented development of Klebsiella pneumoniae and Pseudomonas aeruginosa. Their statistical analysis was developed using Pearson's Chi-squared test. RESULTS. We received 861 blood culture and 391 tracheal secretion samples, obtaining: 32% isolates of Klebsiella pneumoniae and multidrug-resistant and extremely resistant Pseudomonas aeruginosa. Among the COVID-19 patients who died, 34.4% showed increased procalcitonin levels. On the contrary, among patients who survived, only 8.8% showed increased procalcitonin levels, showing a link between increased procalcitonin levels and mortality. CONCLUSIONS. There is no difference in relation to the increase in procalcitonin values in COVID-19 patients with co-infection or secondary infection by Klebsiella pneumoniae and multidrug-resistant and extremely resistant Pseudomonas aeruginosa and procalcitonin values in patients with co-infection and secondary infection with other types of bacterial isolates.

Herramientas para el diagnóstico de la sepsis / Tools for Diagnosis in Sepsis

La sepsis representa en la actualidad un problema emergente en salud. Los consensos alcanzados sobre las definiciones de sepsis y sus complicaciones asociadas han permitido establecer con mayor precisión la magnitud del problema. A pesar de la instauración de protocolos uniformes de actuación, la sepsis continúa siendo la primera causa de muerte en la Unidad de Cuidados Intensivos Pediátricos (UCIP) y la cuarta causa de defunción en los hospitalizados no coronarios.1 La sepsis severa fue definida en The Third International Consensus Definitions for Sepsis an Septic Shock como el síndrome de respuesta inflamatoria sistémica asociada a infección que cursa con disfunción aguda de un órgano, hipoperfusión o hipotensión, considerada como un proceso continuo.2 Se han realizado diversos estudios donde la mortalidad anual atribuible a sepsis grave es de 135 000 casos en Europa, y es superior en Estados Unidos con 200 000 casos, superada discretamente por las muertes por infarto agudo de miocardio. Estados Unidos ocupa el lugar número 11 como causa aislada de fallecimiento, se estima que más de 500 pacientes mueren diariamente a consecuencia de esta enfermedad, hecho que se transforma en un significativo desafío para la salud pública.3 Por lo que significa lo anteriormente expuesto, en reuniones de consensos, los laboratorios se han visto retados y han facilitado el diagnóstico con herramientas útiles. Marcadores biológicos de infección El retraso en la instauración de un tratamiento adecuado de las infecciones y de la sepsis se asocia a una mayor mortalidad, por lo que es crucial establecer un diagnóstico precoz en este contexto. Los análisis microbiológicos que confirman o no la presencia de infección suelen tardar, en ese sentido se han buscado marcadores biológicos que puedan servir como indicadores fiables de la infección grave y la sepsis. Dada la complejidad creciente de la fisiopatología de la sepsis a medida que avanza en su conocimiento, es probable que el éxito llegue, no a través de un único marcador, sino a través de la combinación de varios de ellos que tengan en cuenta distintos aspectos de la respuesta del huésped. La combinación de varios marcadores puede ayudar a vencer las limitaciones en sensibilidad y especificidad de un solo biomarcador. Características de un marcador ideal Precisión Sensibilidad alta: pacientes que presentan respuesta inflamatoria mínima o ausente. Especificidad: lograr discriminar la infección de otros padecimientos que causan el síndrome de respuesta inflamatoria sistémica (SRIS). Valor predictivo positivo (VPP) y valor predictivo negativo (VPN). Diagnóstico certero con reactantes de fase aguda La proteína C reactiva (PCR) de alta sensibilidad es un marcador precoz de infección e inflamación con una vida media plasmática de 19 h. Su concentración plasmática en adulto sano es de 0,08 mg/dL. Su biocinética se hace útil como marcador de respuesta terapéutica y diagnóstica de infecciones intercurrentes. Las determinaciones seriadas de estas es un buen indicador de la actividad inflamatoria. Sus grandes elevaciones se deben a infecciones bacterianas. Las determinaciones seriadas diarias de PCR pueden ser útiles para el diagnóstico precoz en las infecciones nosocomiales es de ≥ 5 mg/dL o ≥ 25 % del valor previo. La procalcitonina es una hormona producida por células parenquimatosas, proteína de la familia CAPA precursora de la calcitonina. En condiciones normales las concentraciones en sangre son muy bajas, menor de 0,09 ng/mL. Tienen una vida media de 22-35 h. No se conocen valores umbrales, diagnósticos y pronósticos, pero los valores mayores de 2 ng/mL suelen indicar la presencia de sepsis. Los valores mayores de 10 ng/mL suelen asociarse a sepsis grave y shock séptico. Los niveles de procalcitonina (PCT) son superiores a la PCR en el diagnóstico de sepsis por lo que debería ser incluida en las guías diagnósticas de sepsis. Podemos decir además, que la interleucina 6 (IL-6), fue descrita inicialmente como interferón beta-2, como factor de crecimiento de plasmocitoma o factor estimulante de hepatocitos.4 Es generada por un único gen que codifica un producto de 212 aminoácidos y es la citoquina que más consistentemente se ha asociado con la mortalidad por sepsis, por su acción proinflamatoria es uno de los principales inductores de la síntesis de la PCR en el hígado, por lo que muestra picos séricos más precoces que esta.5 Las determinaciones secuenciales de estas en el suero plasma en pacientes internados en la unidad de cuidados intensivos han demostrado ser útiles para evaluar la severidad del síndrome de respuesta inflamatoria(AU)

Prevalencia de sepsis neonatal confirmada microbiológicamente en una maternidad de la Ciudad Autó noma de Buenos Aires / Prevalence of microbiologically confirmed neonatal sepsis at a maternity center in the City of Buenos Aires

Introducción. En neonatos internados es frecuente sospechar sepsis neonatal, pero solo en el 25 % al 30 % se confirma con cultivos positivos. La selección del esquema antibiótico basándose en la epidemiología local favorece el uso racional y minimiza sus efectos colaterales. Objetivo primario. Describir la prevalencia de sepsis precoz y tardía con rescate microbiológico y sus características clínicas. Población y método. Estudio transversal retrospectivo, realizado del 1 de enero de 2013 al 31 de diciembre de 2017, en una maternidad pública de Argentina, que incluyó todos los recién nacidos internados en la unidad con diagnóstico de sepsis precoz y tardía con rescate microbiológico, y aquellos reingresados dentro del mes de vida. Resultados. Ingresaron 3322 recién nacidos, 1296 evaluados por sospecha de sepsis precoz, cultivos positivos en 25 (1,9 %; tasa: 0,86 ‰). El 52 % eran menores de 33 semanas de edad gestacional. Microorganismos: Escherichia coli 5, Listeria monocytogenes 4, Streptococcus agalactiae (SGB) 3, Streptococcus pneumoniae 3. Sepsis tardía (tasa 8,73 ‰), el 68 % ocurridas en menores de 33 semanas. Microorganismos intrahospitalarios: Staphylococcus coagulasa negativos 115, Staphylococcus aureus 47, Escherichia coli 30, Cándida spp. 16, Enterococcus faecalis 13, Klebsiella pneumoniae 11 y Streptococcus agalactiae 10. En los reingresos: E. coli 11, S. aureus 12, SGB 3 y Haemophilus influenzae 3. Conclusiones. Se observa en el período estudiado una frecuencia de sepsis precoz similar a los reportes internacionales, con predominio de E. coli y L. monocytogenes. La tasa de sepsis tardía presentó una tendencia descendente en los años analizados, con predominio de los cocos grampositivos

Introduction. Neonatal sepsis is often suspected in hospitalized newborn infants, but only in 25­30% of cases it is confirmed via a positive culture. Selecting the antibiotics based on local epidemiology favors their rational use and minimizes their side effects. Primary objective. To describe the prevalence of early- and late-onset sepsis with microorganism isolation and their clinical characteristics. Population and method. Retrospective, cross-sectional study conducted between 01-01-2013 and 12-31-2017 in a public maternity center of Argentina in all hospitalized newborn infants with a diagnosis of early- and late-onset sepsis with microorganism isolation, and those re-admitted in their first month of life. Results. A total of 3322 newborn infants were admitted; 1296 were assessed for suspected early- onset sepsis; 25 had a positive culture (1.9%; rate: 0.86‰). Of these, 52% were born before 33 weeks of gestation. Microorganisms: Escherichia coli 5, Listeria monocytogenes 4, Streptococcus agalactiae (SGB) 3, Streptococcus pneumoniae 3. Also, 68% of late-onset sepsis cases (rate: 8.73‰) occurred in infants born before 33 weeks of gestation. Hospital-acquired microorganisms: coagulase-negative Staphylococcus 115, Staphylococcus aureus 47, Escherichia coli 30, Candida spp. 16, Enterococcus faecalis 13, Klebsiella pneumoniae 11, and Streptococcus agalactiae 10. In re-admissions: E. coli 11, S. aureus 12, SGB 3, and Haemophilus influenzae 3. Conclusions. During the study period, the frequency of early-onset sepsis was similar to international reports, with a predominance of E. coli and L. monocytogenes. The rate of late-onset sepsis showed a downward trend in the analyzed years, with a predominance of Gram-positive cocci.

Mortalidad de la sepsis en la unidad de cuidados intensivos / Mortality from sepsis in intensive care unit

INTRODUCCIÓN. La sepsis es un estado de disfunción multisistémica, que se produce por una respuesta desregulada del huésped a la infección. Diversos factores influyen en la gravedad, manifestaciones clínicas y progresión de la sepsis, tales como, heterogeneidad inmunológica y regulación dinámica de las vías de señalización celular. La evolución de los pacientes depende del tratamiento oportuno, las escalas de puntuación clínica permiten saber la mortalidad estimada. OBJETIVO. Evaluar la mortalidad en la unidad de cuidados intensivos; establecer el manejo y la utilidad de aplicar paquetes de medidas o "bundlers" para evitar la progresión a disfunción, fallo multiorgánico y muerte. METODOLOGÍA. Modalidad de investigación tipo revisión sistemática. Se realizó una búsqueda bibliográfica en bases de datos como Google académico, Mendeley, ScienceDirect, Pubmed, revistas como New England Journal Medicine, Critical Care, Journal of the American Medical Association, British Medical Journal. Se obtuvo las guías "Sobreviviendo a la sepsis" actualización 2021, 3 guías internacionales, 10 estudios observacionales, 2 estudios multicéntricos, 5 ensayos aleatorizados, 6 revisiones sistémicas, 5 metaanálisis, 1 reporte de caso clínico, 4 artículos con opiniones de expertos y actualizaciones con el tema mortalidad de la sepsis en UCI con un total de 36 artículos científicos. RESULTADOS. La mortalidad de la sepsis en la unidad de cuidados intensivos, fue menor en el hospital oncológico de Guayaquil, seguido de Australia, Alemania, Quito, Francia, Estados Unidos de Norteamérica y Vietnan, La mortalidad más alta se observa en pacientes con enfermedades del tejido conectivo. DISCUSIÓN. La aplicación de los paquetes de medidas o "bundlers" en la sepsis, se asocia con una mejor supervivencia y menores días de estancia hospitalaria. CONCLUSIÓN. Las escalas SOFA, APACHE II y SAPS II ayudan a predecir la mortalidad de forma eficiente, en la detección y el tratamiento temprano en pacientes con enfermedades agudas y de alto riesgo.

INTRODUCTION. Sepsis is a state of multisystem dysfunction, which is caused by a dysregulated host response to infection. Several factors influence the severity, clinical manifestations and progression of sepsis, such as immunological heterogeneity and dynamic regulation of cell signaling pathways. The evolution of patients depends on timely treatment, clinical scoring scales allow to know the estimated mortality. OBJECTIVE. To evaluate mortality in the intensive care unit; to establish the management and usefulness of applying bundlers to prevent progression to dysfunction, multiorgan failure and death. METHODOLOGY. Systematic review type research modality. A bibliographic search was carried out in databases such as Google Scholar, Mendeley, ScienceDirect, Pubmed, journals such as New England Journal Medicine, Critical Care, Journal of the American Medical Association, British Medical Journal. We obtained the guidelines "Surviving Sepsis" update 2021, 3 international guidelines, 10 observational studies, 2 multicenter studies, 5 randomized trials, 6 systemic reviews, 5 meta-analyses, 1 clinical case report, 4 articles with expert opinions and updates on the subject of sepsis mortality in ICU with a total of 36 scientific articles. RESULTS. The mortality of sepsis in the intensive care unit, was lower in the oncological hospital of Guayaquil, followed by Australia, Germany, Quito, France, United States of America and Vietnam, The highest mortality is observed in patients with connective tissue diseases. DISCUSSION. The application of bundlers in sepsis is associated with better survival and shorter days of hospital stay. CONCLUSIONS. The SOFA, APACHE II and SAPS II scales help to predict mortality efficiently in the early detection and treatment of patients with acute and high-risk disease.

Especificidad y sensibilidad de la procalcitonina y la interleucina-6 en pacientes oncológicos con bacteriemia y hemocultivo positivo / Specificity and sensitivity of procalcitonin and interleukin-6 in cancer patients with bacteremia and positive blood culture

Introducción: Se ha reportado la utilidad de la procalcitonina para predecir bacteriemia en pacientes oncológicos con fiebre, pero existen pocos datos sobre la utilidad de la interleucina 6. Este estudio tuvo como objetivo establecer la especificidad y sensibilidad de la procalcitonina y la interleucina en pacientes oncológicos con bacteriemia y sangre positiva. cultura. Métodos : Este estudio transversal, de fuente prospectiva, se realizó en el Hospital de SOLCA, Guayaquil. El período de estudio fue de enero a diciembre de 2015. Se incluyeron pacientes mayores de edad y menores de 65 años con diagnóstico de enfermedad oncológica con diagnóstico de SIRS, sepsis o shock séptico. Las variables fueron presencia de bacteriemia, procalcitonina (PCT), interleucina-6 (IL-6), edad, sexo y reporte de hemocultivo. La muestra fue no probabilística . Se utilizó estadística descriptiva e inferencial. Se analizaron dos grupos: la presencia y ausencia de bacteriemia, y en cada grupo se realizó una prueba diagnóstica de procalcitonina e interleucina-6. Resultados : Participaron un total de 169 pacientes, 69 con hemocultivos positivos (G1) y 100 controles sin bacteriemia (G2). La procalcitonina fue de 14,6 en G1 frente a 0,54 ng/ml en G2 ( P = 0,0001). IL-6 fue de 1479,47 ng/ml en G1 frente a 4,37 ng/ml en G2 ( P < 0,001). La sensibilidad (S) de la PCT fue del 81,2 %, la especificidad (E) del 79 % y el área bajo la curva de 0,862. P<0.0001. La S de IL-6 fue 98,6%, la E fue 95% y el área bajo la curva fue 0,996 P<0,0001. Conclusión: La interleucina-6 es una buena prueba como predictor de bacteriemia en pacientes oncológicos por su alto valor de especificidad y para establecer que si se tiene bacteriemia es por su alta especificidad.

Introduction: The utility of procalcitonin to predict bacteremia in cancer patients with fever has been reported, but few data exist on the utility of interleukin 6. This study aimed to establish the specificity and sensitivity of procalcitonin and interleukin in cancer patients with bacteremia and positive blood culture. Methods: This cross-sectional study, from a prospective source, was carried out at the Hospital de SOLCA, Guayaquil. The study period was from January to December 2015. Patients of legal age and under 65 years of age with a diagnosis of oncological disease with a diagnosis of SIRS, sepsis, or septic shock were included. The variables were the presence of bacteremia, procalcitonin (PCT), interleukin-6 (IL-6), age, sex, and blood culture report. The sample was nonprobabilistic. Descriptive and inferential statistics were used. Two groups were analyzed: the presence and absence of bacteremia, and a diagnostic test for procalcitonin and interleukin-6 was performed in each group. Results: A total of 169 patients participated, 69 with positive blood cultures (G1) and 100 controls without bacteremia (G2). Procalcitonin was 14.6 in G1 vs 0.54 ng/ml in G2 (P =0.0001). IL-6 was 1479.47 ng/ml in G1 vs 4.37 ng/ml in G2 (P < 0.001). The sensitivity (S) of PCT was 81.2%, the specificity (E) was 79%, and the area under the curve was 0.862. P<0.0001. The S of IL-6 was 98.6%, the E was 95%, and the area under the curve was 0.996 P<0.0001. Conclusion: Interleukin-6 is a good test as a predictor of bacteremia in cancer patients due to its high specificity value and to establish that if you have bacteremia, it is due to its high specificity.

Accuracy of mortality indicators due sepsis-associated deaths in the Federal District / Acurácia dos indicadores de mortalidade devido a sepse dos óbitos ocorridos no Distrito Federal / Precisión de los indicadores de mortalidad por sepsis de las defunciones ocurridas en el Distrito Federal

Background: Sepsis currently represents a challenge for health systems, this fact may be related to the spread of bacterial resistance, the increase in the population of elderly, immunosuppressed individuals, and the improvement of emergency care, favoring the survival of critically ill patients. This article aimed to evaluate the accuracy of mortality indicators due to sepsis in 2018. Method: Validation study of death certificates that occurred in the Federal District in 2018. Declarations whose basic causes of death identified were classified as garbage codes were identified, which were investigated by a multidisciplinary team, capable of reclassifying them with codes that allow for the improvement of health data. In order to assess accuracy, sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios of death certificates from sepsis were calculated, with 95% confidence intervals. Results: A total of 6.244 statements were evaluated, of which 233 (3.74%) presented sepsis as the underlying cause before being investigated and only 35 (0.56%) maintained it after the investigation. The filling of statements with sepsis as the underlying cause by physicians showed a sensitivity of 0.9% (95%CI: 0.6 to 1.3) and a specificity of 92.0% (95%CI: 90.9 to 93.1). Conclusion: The low accuracy of the declarations demonstrates the non-reliability of the underlying cause of death from sepsis, especially the completion of death certificates that occurred in the Federal District in 2018.(AU)

Justificativa: A sepse, atualmente, representa um desafio para os sistemas de saúde, tal fato pode estar relacionado com a disseminação da resistência bacteriana, o aumento da população de idosos, os indivíduos imunossuprimidos, e a melhoria do atendimento de emergência, favorecendo a sobrevivência de pacientes críticos. Este artigo teve por objetivo avaliar a acurácia dos indicadores de mortalidade devido à sepse em 2018. Método: Estudo de validação da causa básica dos óbitos ocorridos no Distrito Federal em 2018. Foram identificadas as declarações de óbito cujas causas básicas de morte apontadas foram classificadas como garbage code sepse, as quais foram investigadas por uma equipe multidisciplinar, capacitada para reclassificá-las com códigos que permitem o aprimoramento dos dados em saúde. A fim de avaliar a acurácia, foram calculados os valores de sensibilidade, especificidade, valores preditivos positivo e negativo, razões de verossimilhança positiva e negativa das declarações dos óbitos por sepse, com intervalos de confiança de 95%. Resultados: Um total de 6.244 declarações foram avaliadas, das quais 233 (3,74%) apresentavam a sepse como causa básica antes de serem investigadas e apenas 35 (0,56%) mantiveram-na após a investigação. O preenchimento das declarações com a sepse enquanto causa básica pelos médicos apresentou sensibilidade de 0,9% (IC95%: 0,6 a 1,3) e especificidade de 92,0% (IC95%: 90,9 a 93,1). Conclusão: A baixa acurácia das declarações demonstra a não fidedignidade da causa básica de óbito por sepse, sobretudo, do preenchimento das declarações dos óbitos ocorridos no Distrito Federal em 2018.(AU)

Justificación: Sepsis representa en la actualidad un desafío para los sistemas de salud, este hecho puede estar relacionado con propagación de resistencias bacterianas, aumento de la población de ancianos, inmunodeprimidos, y mejora de la atención de urgencias, favoreciendo la supervivencia de los pacientes críticos. Este artículo tuvo como objetivo evaluar la precisión de los indicadores de mortalidad por sepsis en 2018. Método: Estudio de validación de causa básica de muertes ocurridas en Distrito Federal en 2018. Se identificaron actas de defunción cuyas causas básicas de muerte fueron clasificadas como sepsis código basura y fueron investigadas por un equipo multidisciplinario capacitado para reclasificarlas con códigos que permitan la mejora de datos de salud. Para evaluar la precisión, se calcularon sensibilidad, especificidad, valores predictivos positivo y negativo y razones de verosimilitud positiva y negativa de certificados de defunción por sepsis, con intervalos de confianza del 95%. Resultados: se evaluaron 6.244 declaraciones, de las cuales 233 (3,74%) tenían como causa básica la sepsis antes de ser investigadas y solo 35 (0,56%) mantuvieron después de investigación. Realización de declaraciones con sepsis como causa subyacente por parte de los médicos mostró sensibilidad del 0,9% (95%IC: 0,6 a 1,3) y especificidad del 92,0% (95%IC: 90,9 a 93,1). Conclusión: Baja precisión de las declaraciones demuestra la poca confiabilidad de la causa subyacente de muerte por sepsis, especialmente la finalización de los certificados de defunción ocurridos en Distrito Federal en 2018.(AU)

The association of hyperglycemia with the development of infectious complications in adult Filipino patients with acute lymphoblastic leukemia

Abstract Introduction Hyperglycemia occurs in Acute Lymphoblastic Leukemia (ALL) due to chemotherapeutic agents and may be stress-induced. Given the potential impact of hyperglycemia on the clinical outcomes of ALL patients, we sought to determine the association of hyperglycemia with the development of infectious complications. Methods This is a retrospective cohort involving adult Filipino ALL patients admitted at a tertiary referral center. Patients were stratified according to blood glucose levels and infections were classified into microbiologically and clinically defined infections. Logistic regression was performed to determine whether hyperglycemia was associated with the development of infectious complications. Results Of the 174 patients admitted for ALL, only 76 patients (44%) underwent blood glucose monitoring and were thus included in this study. Hyperglycemia was observed in 64 patients (84.21%). Infectious complications were seen in 56 patients (73.68%), of whom 37 patients (48.68%) had microbiologically defined infections and 19 (25%) had clinically defined infections. The respiratory tract was the most common site of infection and gram-negative bacteria were the predominant isolates. Hyperglycemia significantly increased the likelihood of infectious complications, particularly at blood glucose levels ≥ 200 mg/dL. Conclusion Hyperglycemia is associated with an increased likelihood of infectious complications in Filipino ALL patients. With sepsis being one of the main causes of mortality in this population, our study provides compelling evidence for us to consider routine blood glucose monitoring in order to manage and potentially decrease the occurrence of infections in these patients.

Síndrome hemofagocítico asociado a varicela / Hemofagocytic syndrome associated with varicella

Presentación del caso. Lactante femenina de 14 meses de edad con desarrollo psicomotor normal, sin comórbidos. Con historia de un día de fiebre de 40 °C, intermitente, acompañada de evacuaciones diarreicas y vómitos. Fue llevada por sus padres a una clínica privada sin notar mejoría con el tratamiento médico indicado. Posteriormente, presentó deterioro clínico y fue llevada a un hospital, donde se diagnosticó un síndrome febril agudo, diarrea con deshidratación leve y faringitis. Al cuarto día de evolución inició con máculas y pápulas que progresaron a vesículas y costras. Además, presentó intolerancia a la vía oral, disnea, distensión abdominal, coma y desequilibrio hidroelectrolítico. Intervención terapéutica. Inició el tratamiento con hidratación parenteral, antivirales, esteroides endovenosos y antihistamínicos; se diagnosticó shock séptico con compromiso respiratorio, se proporcionó ventilación mecánica asistida y fue referida al hospital de tercer nivel para atención por medicina crítica. Los estudios reportaron un derrame pleural derecho del 40 % y hepatomegalia. Continuó el tratamiento con antibiótico terapia, hidratación parenteral, antivirales, diuréticos, antipiréticos y hemoderivados, presentó mejoría, continuó el manejo terapéutico. Evolución clínica. El día 18 presentó fiebre, hepatoesplenomegalia, los exámenes reportaron elevación de ferritina, triglicéridos y citopenia se diagnosticó un síndrome hemofagocítico que evolucionó con una falla multisistémica y falleció al siguiente día

Case presentation. A 14-month-old female infant with normal psychomotor development, without comorbidities. With a one-day history of fever of 40 °C, intermittent, accompanied by diarrhea and vomiting. She was taken by her parents to a private clinic without improvement with the indicated medical treatment. Subsequently, she presented clinical deterioration and was taken to a hospital, where she was diagnosed with acute febrile syndrome, diarrhea with mild dehydration, and pharyngitis. On the fourth day of evolution, she started with macules and papules that progressed to vesicles and crusts. In addition, she presented oral intolerance, dyspnea, abdominal distension, coma, and hydro electrolytic imbalance. Therapeutic intervention. She started treatment with parenteral hydration, antivirals, intravenous steroids, and antihistamines; septic shock with respiratory distress was diagnosed, assisted mechanical ventilation was provided, and she was referred to a tertiary hospital for critical care medicine. Studies reported a 40 % right pleural effusion and hepatomegaly. She continued treatment with antibiotic therapy, parenteral hydration, antivirals, diuretics, antipyretics, and hemoderivatives, presented improvement, and continued therapeutic management. Clinical evolution. On day 18 he presented fever and hepatosplenomegaly. Tests reported elevated ferritin, triglycerides, and cytopenia, and was diagnosed with hemophagocytic syndrome that evolved with multisystemic failure and died the following day

Bioinformatics analysis and key gene verification of sepsis myocardial macrophage microarray data based on GEO database / 中华心血管病杂志

Objective: Bioinformatics analysis was used to screen differentially expressed genes (DEGs) in macrophages of sepsis myocardial injury and to verify key genes. Methods: Experiment 1 (gene chip and bioinformatics analysis): The gene chip data GSE104342 of cardiac macrophages in septic mice was downloaded from Gene Expression Omnibus database. DEGs were obtained by R language analysis. DAVID online database was used to obtain gene ontology and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEGs. STRING online database was used for protein-protein interaction network analysis of DEGs, and then key genes were screened by using Cytoscape software and molecular complex detection (MCODE) plug-ins. Experiment 2 (sepsis model construction and related protein verification): Ten male C57BL/6 mice, aged 8-14 weeks. Five mice were randomly selected as control group, and 5 mice were selected as the sepsis group by building a mice sepsis model in vivo. Echocardiography was used to detect the cardiac function. Hematoxylin-eosin staining was used to assess the cardiac morphology. TUNEL staining was used to evaluate cardiomyocyte apoptosis. Immunofluorescence staining was used to detect the expression of differentiation antigen cluster 206 (CD206),inducible nitric oxide synthases (iNOS),F4/80,suppressor of cytokine signaling 3 (Socs3) ,interleukin 1 receptor antagonist (Il1rn) and chemokine C-C motif ligand 7 (Ccl7) protein. RAW264.7 macrophages were cultured in vitro and divided into 2 groups: LPS groupstimulated by lipopolysaccharide (LPS, 1 mg/L) and blank control group treated with equal-volume phosphate buffer solution. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the expression of Socs3, Il1rn and Ccl7 in vitro. Results: Experiment 1: 24 647 genes were screened in GSE104342 dataset and 177 genes (0.72%) were differential expression, including 120 up-regulated genes and 57 down-regulated genes. Gene ontology enrichment analysis showed that DEGs were mainly involved in inflammatory response, immune response, apoptosis regulation and antigen processing and presentation. KEGG signaling pathway analysis showed that DEGs in cardiac macrophages of septic mice were mainly enriched in cytokine-cytokine receptor interaction, tumor necrosis factor signaling pathway, NOD like receptor signaling pathway. Three hub genes were obtained by STRING and Cytoscape analysis, including Socs3, Il1rn and Ccl7. Experiment 2: In vivo, it was found that compared with the control group, the cardiac function of the sepsis mice decreased significantly, the myocardial cells were significantly edema, inflammatory cell infiltration, myocardial fiber rupture, some myocardial nuclei dissolved and disappeared, and the cardiomyocyte apoptosis increased, suggesting that the sepsis myocardial injury model of mice was successfully constructed. Compared with the control group, the expression of CD206 in the myocardium of septic mice was down-regulated, the expression of iNOS, F4/80, Socs3, Il1rn and Ccl7 were up-regulated. In addition, there was co-localization between Socs3, Il1rn, Ccl7 and F4/80 protein. Compared with the blank control group, the expression of Socs3, Il1rn and Ccl7 significantly upregulated after LPS intervention in vitro by RT-PCR. Conclusions: The selected key genes Socs3, Il1rn and Ccl7 were up-regulated in myocardial macrophages of septic mice. Socs3, Il1rn and Ccl7 are expected to become new targets for the diagnosis and treatment of sepsis cardiac injury.

Efficacy and safefy of Polymyxin B treatment for neutropenic patients suffering from refractory Gram-negative bacterial bloodstream infection / 中华血液学杂志

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.

A single-center study on the distribution and antibiotic resistance of pathogens causing bloodstream infection in patients with hematological malignancies / 中华血液学杂志

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.

Liensinine attenuates inflammation and oxidative stress in spleen tissue in an LPS-induced mouse sepsis model / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Sepsis is a complex syndrome caused by multiple pathogens and involves multiple organ failure, particularly spleen dysfunction. In 2017, the worldwide incidence was 48.9 million sepsis cases and 11 million sepsis-related deaths were reported (Rudd et al., 2020). Inflammation, oxidative stress, and apoptosis are the most common pathologies seen in sepsis. Liensinine (LIE) is a bisbenzylisoquinoline-type alkaloid extracted from the seed embryo of Nelumbo nucifera. Lotus seed hearts have high content of LIE which mainly has antihypertensive and antiarrhythmic pharmacological effects. It can exert anti-carcinogenic activity by regulating cell, inflammation, and apoptosis signaling pathways (Manogaran et al., 2019). However, its protective effect from sepsis-induced spleen damage is unknown. In this research, we established a mouse sepsis model induced by lipopolysaccharide (LPS) and investigated the protective effects of LIE on sepsis spleen injury in terms of inflammatory response, oxidative stress, and apoptosis.

Enhanced endoplasmic reticulum RyR1 receptor phosphorylation leads to diaphragmatic dysfunction in septic rats / 南方医科大学学报

OBJECTIVE@#To explore the role of endoplasmic reticulum ryanodine receptor 1 (RyR1) expression and phosphorylation in sepsis- induced diaphragm dysfunction.@*METHODS@#Thirty SPF male SD rats were randomized equally into 5 groups, including a sham-operated group, 3 sepsis model groups observed at 6, 12, or 24 h following cecal ligation and perforation (CLP; CLP-6h, CLP-12h, and CLP-24h groups, respectively), and a CLP-24h group with a single intraperitoneal injection of KN- 93 immediately after the operation (CLP-24h+KN-93 group). At the indicated time points, diaphragm samples were collected for measurement of compound muscle action potential (CMAP), fatigue index of the isolated diaphragm and fitted frequencycontraction curves. The protein expression levels of CaMK Ⅱ, RyR1 and P-RyR1 in the diaphragm were detected using Western blotting.@*RESULTS@#In the rat models of sepsis, the amplitude of diaphragm CMAP decreased and its duration increased with time following CLP, and the changes were the most obvious at 24 h and significantly attenuated by KN-93 treatment (P < 0.05). The diaphragm fatigue index increased progressively following CLP (P < 0.05) irrespective of KN- 93 treatment (P>0.05). The frequency-contraction curve of the diaphragm muscle decreased progressively following CLP, and was significantly lower in CLP-24 h group than in CLP-24 h+KN-93 group (P < 0.05). Compared with that in the sham-operated group, RyR1 expression level in the diaphragm was significantly lowered at 24 h (P < 0.05) but not at 6 or 12 following CLP, irrespective of KN-93 treatment; The expression level of P-RyR1 increased gradually with time after CLP, and was significantly lowered by KN-93 treatment at 24 h following CLP (P < 0.05). The expression level of CaMKⅡ increased significantly at 24 h following CLP, and was obviously lowered by KN-93 treatment (P < 0.05).@*CONCLUSION@#Sepsis causes diaphragmatic dysfunction by enhancing CaMK Ⅱ expression and RyR1 receptor phosphorylation in the endoplasmic reticulum of the diaphragm.

Completion rates of bundle treatment of among patients with sepsis shock in intensive care departments of hospitals in Jiangsu Province from 2016 to 2020 years / 中华内科杂志

Current clinical approaches for septic shock increasingly incorporate bundle treatment, a multi-component approach that uses a collection of tests and agents to assist in the identification and treatment of infection. The present study analyzed completion rates of 3 h and 6 h bundle treatment among patients with septic shock in intensive care units (ICUs) of hospitals in Jiangsu Province from 2016 to 2020, using data from the Jiangsu Provincial Intensive Care Medical Quality Control Center. Current approaches and factors affecting treatment completion were assessed.The completion rates of 3 h and 6 h bundle treatment in ICUs of all medical units in Jiangsu Province and in ICUs of hospitals of different levels were recorded. Analyses show that the completion rate of 3 h and 6 h bundle treatment for patients with septic shock in ICUs in Jiangsu Province increased year by year from 2016 to 2020.The completion rate of 3 h bundle treatment increased from 69.82% (3 604/5 162) to 82.47% (8 915/10 775) (all P<0.001). The completion rate of 6 h bundle treatment increased from 62.69% (3 236/5 162) to 72.54% (7 816/10 775) (all P<0.001). In addition, year by year, the completion rate of 3 h bundle treatment in ICUs in tertiary hospitals increased, from 69.80% (3 596/5 152) to 82.23% (7 375/8 969), while the completion rate of 6 h bundle treatment increased from 62.69% (3 230/5 152) to 72.18% (6 474/8 969) (all P<0.001). Completion rates in secondary hospitals also increased year by year, from 80.00% (8/10) to 85.27% (1 540/1 806) for 3 h treatment and from 60.00% (6/10) to 74.31% (1 342/1 806) (all P<0.001) for 6 h treatment. Completion rates for 3 h treatment in first-tier cities (83.99% (2 099/2 499)) and second-tier cities (84.68% (3 952/4 667)) was higher than in third-tier cities (79.36% (2 864/3 609)). The completion rate of 6 h bundle treatment gradually decreased in first-line (77.19% (1 929/2 499)), second-line (74.37% (3 471/4 667)), and third-line (66.94% (2 416/3 609)) cities (all P<0.001). The data collectively show that from 2016 to 2020, the completion rate of bundle treatment in septic shock patients in ICUs in Jiangsu Province improved significantly.

Dose-response association between fluid overload and hospital mortality in patients with sepsis / 中华内科杂志

Objective: To investigate dose-response associations between fluid overload (FO) and hospital mortality in patients with sepsis. Methods: The current cohort study was prospective and multicenter. Data were derived from the China Critical Care Sepsis Trial, which was conducted from January 2013 to August 2014. Patients aged≥18 years who were admitted to intensive care units (ICUs) for at least 3 days were included. Fluid input/output, fluid balance, fluid overload (FO), and maximum FO (MFO) were calculated during the first 3 days of ICU admission. The patients were divided into three groups based on MFO values: MFO<5%L/kg, MFO 5%-10%L/kg, and MFO≥10% L/kg. Kaplan-Meier analysis was used to predict time to death in hospital in the three groups. Associations between MFO and in-hospital mortality were evaluated via multivariable Cox regression models with restricted cubic splines. Results: A total of 2 070 patients were included in the study, of which 1 339 were male and 731 were female, and the mean age was (62.6±17.9) years. Of 696 (33.6%) who died in hospital, 968 (46.8%) were in the MFO<5%L/kg group, 530 (25.6%) were in the MFO 5%-10%L/kg group, and 572 (27.6%) were in the MFO≥10%L/kg group. Deceased patients had significantly higher fluid input than surviving patients during the first 3 days [7 642.0 (2 874.3, 13 639.5) ml vs. 5 738.0 (1 489.0, 7 153.5)ml], and lower fluid output [4 086.0 (1 367.0, 6 354.5) ml vs. 6 130.0 (2 046.0, 11 762.0) ml]. The cumulative survival rates in the three groups gradually decreased with length of ICU stay, and they were 74.9% (725/968) in the MFO<5% L/kg group, 67.7% (359/530) in the MFO 5%-10%L/kg group, and 51.6% (295/572) in the MFO≥10%L/kg group. Compared with the MFO<5%L/kg group, the MFO≥10%L/kg group had a 49% increased risk of inhospital mortality (HR=1.49, 95%CI 1.28-1.73). For each 1% L/kg increase in MFO, the risk of in-hospital mortality increased by 7% (HR=1.07, 95% CI 1.05-1.09). There was a"J-shaped"non-linear association between MFO and in-hospital mortality with a nadir of 4.1% L/kg. Conclusion: Higher and lower optimum fluid balance levels were associated with an increased risk of in-hospital mortality, as reflected by the observed J-shaped non-linear association between fluid overload and inhospital mortality.