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.

Índice leucocitos/eosinófilos como marcador pronóstico del choque séptico / Leukocyte/eosinophil Ratio as a Prognostic Marker of Septic Choque

Introducción: Se ha reconocido mundialmente el choque séptico como causa de una alta incidencia en la mortalidad. La incorporación de nuevos biomarcadores posibilita la obtención de un diagnóstico rápido y preciso. Objetivo: Evaluar la utilidad del índice leucocitos/eosinófilos como marcador pronóstico del choque séptico. Métodos: Se realizó una investigación en dos etapas: la primera descriptiva en la cual se detallaron las características clínicas, epidemiológicas y las variaciones de los estudios de laboratorio y la segunda explicativa de cohorte para estimar el valor predictivo del biomarcador leucocitos/eosinopenia en el choque séptico. Se realizó el recuento de eosinófilos y se obtuvo la media aritmética. Se consideró eosinopenia relativa con valores por debajo de la media de eosinófilos. Resultados: En el estudio se demostró que la leucocitosis fue de (27,4 células*mm3), la disminución del hematocrito (32,2 por ciento) y el descenso del número plaquetario (125,6 célula*mm3) prevalecen en el choque séptico. Además se refleja el descenso de los eosinófilos (18,5 células/mcl), aumento del índice leucocitos/eosinófilos (148,1) y empeoramiento del SOFA (2,8). El aumento del índice leucocitos/eosinófilos se correlaciona con el aumento de la proteína C reactiva y la procalcitonina. Conclusiones: La correlación de la leucocitosis y la eosinopenia mostró la utilidad del índice leucocitos/eosinopenia como factor de predicción del choque séptico(AU)

Introduction: Septic shock has been recognized worldwide as a cause of high incidence of mortality. The incorporation of new biomarkers makes it possible to obtain a rapid and accurate diagnosis. Objective: To evaluate the usefulness of the leukocyte/eosinophil ratio as a prognostic marker of septic shock. Methods: An investigation was carried out in two stages: in the first (the descriptive phase) the clinical and epidemiological characteristics and variations of the laboratory studies were detailed and in the second (the explanatory cohort phase), the predictive value of the leukocytes/eosinopenia biomarker in septic shock was estimated. The eosinophil count was performed and the arithmetic mean was obtained. Relative eosinopenia was considered with eosinophil values below the average. Results: The study showed that leukocytosis was 27.4 cells*mm3, hematocrit decreased in 32.2percent and decreased platelet number (125.6 cells*mm3) prevail in septic shock. In addition, a decrease in eosinophils (18.5 cells/mcl), an increase in the leukocyte/eosinophil ratio (148.1) and worsening of SOFA (2.8) are reflected. The increase in the leukocyte/eosinophil ratio is correlated with the increase in C-reactive protein and procalcitonin. Conclusions: The correlation of leukocytosis and eosinopenia showed the usefulness of the leukocyte/eosinopenia index as a predictor of septic shock(AU)

Análise longitudinal dos parâmetros ventilatórios e escore SOFA de pacientes com COVID-19 hospitalizados em uma UTI no Sul do Brasil / Longitudinal analysis of ventilatory parameters and SOFA score of patients with COVID-19 hospitalised in an ICU in southern Brazil

Introdução: embora o Coronavírus da Síndrome Respiratória Aguda Grave 2 (SARS-CoV-2) seja mais conhecido por causar patologias respiratórias substanciais, o vírus também pode resultar em várias manifestações extrapulmonares, sobretudo nas alas de cuidados intensivos. Frente a essas implicações multissistêmicas, a monitoração do suporte ventilatório e utilização do escore Sequential Organ Failure Assessment (SOFA) foram fundamentais no manejo do paciente crítico com COVID-19 nas Unidades de Terapia Intensiva (UTIs) durante a pandemia. Objetivo: esse estudo pretende analisar os parâmetros ventilatórios e escore SOFA de pacientes com COVID-19 numa UTI no sul do Brasil e as principais complicações ocasionadas. Metodologia: foi realizado um estudo de coorte retrospectivo que analisou prontuários de pacientes com diagnóstico de COVID-19 na UTI do Hospital Nossa Senhora da Conceição, no estado de Santa Catarina, entre março de 2020 a dezembro de 2021. Resultados: foram incluídos 448 pacientes, com média de idade de 58,5 (±15,1) anos, mediana de internação de 15 (9-24) dias e média de ventilação mecânica de 15 (±8,7) dias, evoluindo para óbito 63,3%. Durante a internação, 86,4% das pessoas sofreram complicações, dentre as mais prevalentes Insuficiência Renal Aguda (46,8%) seguida por Pneumonia Associada à Ventilação (41,9%) e Choque séptico (22%). Na evolução clínica, o escore SOFA e a relação da pressão parcial de oxigênio pela fração de oxigênio inspirado (PaO2/FiO2) foram fatores de desfecho desfavorável nas três semanas de internação, com SOFA ≥ 5 e relação PaO2/FiO2 < 200. Além disso, 3 dos 6 componentes do SOFA (renal, respiratório e coagulação) tiveram relação com a ocorrência de complicações. Conclusão: o escore SOFA e a relação PaO2/FiO2 tiveram relação no prognóstico de pacientes com COVID-19 durante as três semanas de internação na UTI. Além disso, o SOFA se mostrou um possível indicador de complicações intra-hospitalares durante a evolução clínica.

Introduction: although Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is best known for causing significant respiratory pathologies, the virus can also result in various extrapulmonary manifestations, particularly in intensive care wards. Faced with these multisystem implications, monitoring ventilatory support and using the Sequential Organ Failure Assessment (SOFA) score were fundamental in managing critically ill patients with COVID-19 in Intensive Care Units (ICUs) during the pandemic. Objective: this study will analyse the ventilatory parameters and SOFA score of patients with COVID-19 in an ICU in southern Brazil and the main complications caused. Methodology: a retrospective cohort study was carried out that analysed medical records of patients diagnosed with COVID-19 in the ICU of Hospital Nossa Senhora da Conceição, in the state of Santa Catarina, between March 2020 and December 2021. Results: 448 patients were included, with a mean age of 58.5 (±15.1) years, a median hospital stay of 15 (9-24) days, and mean mechanical ventilation of 15 (±8.7) days, with 63.3% dying. During hospitalisation, 86.4% of people suffered complications, among the most prevalent Acute Renal Failure (46.8%), followed by Ventilation Associated Pneumonia (41.9%) and Septic Shock (22%). In the clinical evolution, the SOFA score and the ratio of partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2) were factors of unfavourable outcome in the three weeks of hospitalisation, with SOFA ≥ 5 and PaO2/FiO2 ratio < 200. In addition, three of the six components of the SOFA (renal, respiratory and coagulation) were related to the occurrence of complications. Conclusion: the SOFA score and the PaO2/FiO2 ratio were related to the prognosis of patients with COVID-19 during the three weeks of ICU stay. Furthermore, the SOFA proved to be a possible indicator of in-hospital complications during clinical evolution.

Papel del Delta de PCO2 en la evaluación pronóstica de morbimortalidad en una cohorte de pacientes de un hospital latinoamericano / Role of PCO2 Delta in the Prognostic Evaluation of Morbidity and Mortality in a Cohort of Patients from a Latin American Hospital

Introducción. El shock séptico es la manifestación más grave de sepsis con tasas de letalidad que pueden llegar hasta el 80%. En los últimos años, ha cobrado relevancia la diferencia arteriovenosa de dióxido de carbono, por su implicación teórica en el metabolismo anaerobio y su significado respecto del normal funcionamiento celular. Por lo antes mencionado, creemos necesario realizar un estudio que nos permita establecer la utilidad de la diferencia arteriovenosa de dióxido de carbono en el paciente con shock séptico de la unidad de cuidados intensivos, como medida indirecta de la perfusión tisular y de la utilización de oxígeno por los tejidos, que nos permita establecer un diagnóstico precoz y el pronóstico de los pacientes críticamente enfermos. Métodos. Estudio observacional, descriptivo y transversal. Muestra de veintiocho pacientes adultos. Resultados. Como se ha registrado en otras series, la mayor parte de los pacientes afectados por shock séptico, en nuestro estudio, fueron hombres mayores de 65 años, con al menos una comorbilidad, siendo el principal sitio de infección el respiratorio (67,9%), asociado a una alta tasa de mortalidad (67%). Conclusiones. Los pacientes con diferencia arteriovenosa de PCO2 mayor a 6 mmHg tienen un riesgo aumentado de muerte de 3,2 veces. (AU)

Introduction. Septic shock is the most serious manifestation of sepsis with mortality rates that can reach up to 80%. In recent years, the arteriovenous carbon dioxide difference has gained relevance, due to its theoretical implication in anaerobic metabolism and its significance with respect to normal cell function. Due to the aforementioned, we believe it is necessary to carry out a study that allows us to establish the usefulness of the arteriovenous carbon dioxide difference in the patient with septic shock in the intensive care unit as an indirect measure of tissue perfusion and utilization. of oxygen through the tissues, which allows us to establish an early diagnosis and prognosis of critically ill patients. Methods. Observational, descriptive and cross-sectional study. Sample of 28 adult patients. Results. As has been reported in other series, most of the patients affected by septic shock in our study were men over 65 years of age, with at least one comorbidity, the main site of infection being respiratory (67.9%), associated with a high mortality rate (67%) Conclusions. Patients with an arteriovenous PCO2 difference greater than 6 mmHg have a 3.2-fold increased risk of death. (AU)

Asociación entre índice de masa corporal y mortalidad en pacientes críticos con choque séptico / Association between body mass index and mortality in critical ill patients with septic shock

INTRODUCCIÓN. La paradoja de la obesidad propone que, en determinadas enfermedades, los enfermos con obesidad tienen menor mortalidad. OBJETIVO. Asociar el índice de masa corporal con la mortalidad a 30 días en adultos con choque séptico. MATERIALES Y MÉTODOS. Estudio observacional, analítico, retrospectivo, multicéntrico. Se analizaron 673 pacientes con choque séptico, ingresados en terapia intensiva de dos hospitales de la ciudad de la ciudad de Quito ­ Ecuador, durante enero 2017 - diciembre 2019. Criterios de inclusión: Mayores a 18 años, choque séptico, registro de peso, talla y condición vital al día 30. Criterios de exclusión: Orden de no reanimación, embarazadas, protocolo de donación de órganos, cuidados paliativos. Las variables se recolectaron a partir de las historias clínicas digitales y físicas de los centros participantes. Las estimaciones de riesgo calculadas se presentaron como OR (Odds Ratio) en el análisis bivariado y OR Adj (OR ajustado) para el análisis multivariado. Un valor de p <0.05 se consideró estadísticamente significativo. Todos los análisis estadísticos se realizaron usando el software estadístico R® (Versión 4.1.2). RESULTADOS. La edad promedio fue de 65 años, índice de masa corporal promedio 25,9 Kg/m2 (+4,9 Kg/m2). El 54,3% tuvo índice de masa corporal > 25 Kg/m2. La mortalidad general fue 49.2%. Sujetos con sobrepeso y obesidad tuvieron menor mortalidad, OR: 0,48 (IC 95%: 0.34, 0.68; p <0.0001) y OR 0.45 (IC 95 %: 0.28, 0.70; p =0.001) respectivamente, con similar tendencia en el análisis multivariado. Los sujetos con peso bajo tuvieron la mayor mortalidad (OR: 2.12. IC 95%: 0.91 - 5.54. p: 0.097). DISCUSIÓN. Los resultados obtenidos apoyan la teoría de paradoja de obesidad, sin embargo, no se realizó evaluación según los niveles de obesidad. CONCLUSIÓN. La mortalidad en choque séptico es menor en sujetos con sobrepeso y obesidad comparada con sujetos con peso normal o bajo peso.

The obesity paradox proposes that, in certain diseases, patients with obesity have lower mortality. OBJECTIVE. To associate body mass index with 30-day mortality in adults with septic shock. MATERIALS AND METHODS. Observational, analytical, retrospective, multicenter, retrospective study. We analyzed 673 patients with septic shock, admitted to intensive care in two hospitals in the city of Quito - Ecuador, during January 2017 - December 2019. Inclusion criteria: older than 18 years, septic shock, weight, height and vital condition at day 30. Exclusion criteria: Do not resuscitate order, pregnant women, organ donation protocol, palliative care. Variables were collected from the digital and physical medical records of the participating centers. Calculated risk estimates were presented as OR (Odds Ratio) in bivariate analysis and OR Adj (adjusted OR) for multivariate analysis. A p value <0.05 was considered statistically significant. All statistical analyses were performed using R® statistical software (Version 4.1.2). RESULTS. The mean age was 65 years, mean body mass index 25.9 kg/m2 (+4.9 kg/m2). Body mass index > 25 kg/m2 was 54.3%. Overall mortality was 49.2%. Overweight and obese subjects had lower mortality, OR: 0.48 (95% CI: 0.34, 0.68; p<0.0001) and OR 0.45 (95 % CI: 0.28, 0.70; p=0.001) respectively, with similar trend in multivariate analysis. Underweight subjects had the highest mortality (OR: 2.12. 95% CI: 0.91 - 5.54. p: 0.097). DISCUSSION. The results obtained support the obesity paradox theory, however, assessment according to obesity levels was not performed. CONCLUSIONS. Mortality in septic shock is lower in overweight and obese subjects compared to normal weight or underweight subjects.

Shock séptico de foco respiratorio por Pasteurella multocida en un paciente inmunocompetente. Caso Clínico / Septic shock originating from a pulmonary focus caused by Pasteurella multocida. Report of one case

Pasteurella multocida is a gram-negative coccobacillus bacterium found as a commensal in the oropharynx of domestic animals such as cats and dogs and some farm animals. Soft tissue infections and occasionally bacteremia in immunocompromised patients with direct contact with animals are described. We report a 61 year old male with a history of scratches and close contact with domestic cats, with a septic shock originating from a pulmonary focus, requiring mechanical ventilation and vasopressors. Blood cultures disclosed the presence of Pasteurella multocida. He responded successfully to antimicrobials.

Clinical management and prognosis for descending necrotizing mediastinitis / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the clinical characteristics, treatment experiences and prognostic factors for descending necrotizing mediastinitis (DNM). Methods: A retrospective analysis was performed on the data of 22 patients with DNM diagnosed and treated in Henan Provincial People's Hospital from January 2016 to August 2022, including 16 males and 6 females, aged 29-79 years. After admission, all patients underwent CT scanning of the maxillofacial, cervical, and thoracic regions to confirm their diagnoses. Emergency incision and drainage were performed. The neck incision was treated with continuous vacuum sealing drainage. According to the prognoses, the patients were divided into cure group and death group, and the prognostic factors were analyzed. SPSS 25.0 software was used to analyze the clinical data. Rusults: The main complaints were dysphagia (45.5%, 10/22) and dyspnea (50.0%, 11/22). Odontogenic infection accounted for 45.5% (10/22) and oropharyngeal infection accounted for 54.5% (12/22). There were 16 cases in the cured group and 6 cases in the death group, with a total mortality rate of 27.3%. The mortality rates of DNM typeⅠand typeⅡwere respectively 16.7% and 40%. Compared with the cured group, the death group had higher incidences for diabetes, coronary heart disease and septic shock (all P<0.05). There were statistically significant differences between the cure group and the death group in procalcitonin level (50.43 (137.64) ng/ml vs 2.92 (6.33) ng/ml, M(IQR), Z=3.023, P<0.05) and acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score (16.10±2.40 vs 6.75±3.19, t=6.524, P<0.05). Conclution: DNM is rare, with high mortality, high incidence of septic shock, and the increased procalcitonin level and APACHE Ⅱ score combined diabetes and coronary heart disease are the poor prognostic factors for DNM. Early incision and drainage combined with continuous vacuum sealing drainage technique is a better way to treat DNM.

Clinical value of new coagulation biomarkers in pediatric sepsis / 中华儿科杂志

Objective: To evaluate the clinical value of new coagulation biomarkers including soluble thrombomodulin (sTM) and tissue plasminogen activator inhibitor complex (t-PAI·C) for the diagnosis and prognosis of sepsis in children. Methods: The prospective observational study enrolled 59 children who were diagnosed with sepsis including severe sepsis and septic shock in the Department of Pediatric Critical Care Medicine of Shanghai Children's Medical Center affiliated to the Medical College of Shanghai Jiao Tong University from June 2019 to June 2021. The sTM, t-PAI·C and conventional coagulation tests were detected on illness day one of sepsis. Twenty healthy children were selected as the control group, and the above parameters were detected on the day of inclusion. Children with sepsis were divided into survival group and non-survival group according to prognosis at discharge. Baseline comparisons between groups were performed using Mann-Whitney U test. Multivariate Logistic regression analysis was used to evaluate the risk factors for the diagnosis and prognosis of sepsis in children. Receiver operating characteristic (ROC) curve was conducted to evaluate the predictive values of above variables for the diagnosis and prognosis of sepsis in children. Results: The sepsis group included 59 patients (39 boys and 20 girls), aged 61(22, 136)months. There were 44 patients in the survival group and 15 patients in the non-survival group, respectively. The control group consisted of 20 boys, aged 107 (94,122) months. Patients in the sepsis group had higher sTM and t-PAI·C ((12 (9, 17)×103 vs. 9(8, 10)×103 TU/L, 10(6, 22) vs. 2 (1, 3) μg/L, Z=-2.15, -6.05, both P<0.05) compared with children in the control group. The t-PAI·C was superior to sTM for the diagnosis of sepsis. The areas under the curve (AUC) of t-PAI·C and sTM for the diagnosis of sepsis were 0.95 and 0.66, respectively, and the optimal cut-off value were 3 μg/L and 12×103 TU/L, respectively. Patients in the survival group had lower sTM (10 (8, 14)×103 vs. 17 (11, 36)×103 TU/L, Z=-2.73, P=0.006) than those in the non-survival group. Logistic regression analysis showed that sTM was a risk factor for death at discharge (OR=1.14, 95%CI 1.04-1.27, P=0.006). The AUC of sTM and t-PAI·C for predicting death at discharge were 0.74 and 0.62, respectively, and the optimal cut-off values were 13×103 TU/L and 6 μg/L, respectively. The AUC of sTM combined with platelet counts for predicting death at discharge was 0.89, which was superior to sTM and t-PAI·C. Conclusion: The sTM and t-PAI·C had clinical application values in diagnosing and predicting prognosis in pediatric sepsis.

Diagnosis and treatment of pediatric septic shock in pediatric intensive care units from hospitals of different levels / 中华儿科杂志

Objective: To investigate the differences in clinical characteristics, diagnosis, and treatment of pediatric septic shock in pediatric intensive care unit (PICU) among hospitals of different levels. Methods: This retrospective study enrolled 368 children with septic shock treated in the PICU of Beijing Children's Hospital, Henan Children's Hospital, and Baoding Children's Hospital from January 2018 to December 2021. Their clinical data were collected, including the general information, location of onset (community or hospital-acquired), severity, pathogen positivity, consistence of guideline (the rate of standard attainment at 6 h after resuscitation and the rate of anti-infective drug administration within 1 h after diagnosis), treatment, and in-hospital mortality. The 3 hospitals were national, provincial, and municipal, respectively. Furthermore, the patients were divided into the tumor group and the non-tumor group, and into the in-hospital referral group and the outpatient or emergency admission group. Chi-square test and Mann-Whitney U test were used to analyze the data. Results: The 368 patients aged 32 (11, 98) months, of whom 223 were males and 145 females. There were 215, 107, and 46 patients with septic shock, with males of 141, 51, and 31 cases, from the national, provincial, and municipal hospitals, respectively. The difference in pediatric risk of mortality Ⅲ (PRISM Ⅲ) scores among the national,provincial and municipal group was statistically significant (26(19, 32) vs.19(12, 26) vs. 12(6, 19), Z=60.25,P<0.001). The difference in community acquired septic shock among the national,provincial and municipal group was statistically significant (31.6%(68/215) vs. 84.1%(90/107) vs. 91.3%(42/46), χ2=108.26,P<0.001). There were no significant differences in compliance with guidelines among the 3 groups (P>0.05). The main bacteria detected in the national group were Klebsiella pneumoniae (15.4% (12/78)) and Staphylococcus aureus (15.4% (12/78)); in the provincial group were Staphylococcus aureus (19.0% (12/63)) and Pseudomonas aeruginosa (12.7% (8/63)), and in the municipal group were Streptococcus pneumoniae (40.0% (10/25)) and Enteric bacilli (16.0% (4/25)). The difference in the proportion of virus and the proportion of 3 or more initial antimicrobials used among the national,provincial and municipal group was statistically significant (27.7% (43/155) vs. 14.9% (13/87) vs. 9.1% (3/33), 22.8%(49/215) vs. 11.2%(12/107) vs. 6.5%(3/46), χ2=8.82, 10.99, both P<0.05). There was no difference in the in-hospital mortality among the 3 groups (P>0.05). Regarding the subgroups of tumor and non-tumor, the national group had higher PRISM Ⅲ (31(24, 38) vs. 22 (21, 28) vs.16 (9, 22), 24 (18, 30) vs. 17(8, 24) vs. 10 (5, 16), Z=30.34, 10.45, both P<0.001), and it was the same for the subgroups of in-hospital referral and out-patient or emergency admission (29 (21, 39) vs. 23 (17, 30) vs. 15 (10, 29), 23 (17, 29) vs. 18 (10, 24) vs. 11 (5, 16), Z=20.33, 14.25, both P<0.001) as compared to the provincial and municipal group. There was no significant difference in the in-hospital mortality among the 2 pairs of subgroups (all P>0.05). Conclusion: There are differences in the severity, location of onset, pathogen composition, and initial antibiotics of pediatric septic shock in children's hospitals of different levels, but no differences in compliance with guidelines and in-hospital survival rate.

Influence of the Pre-shock State on the Prognosis of Medical Patients with Sepsis: A Retrospective Cohort Study / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the effects of the pre-shock state on the mortality of patients with sepsis.@*METHODS@#We enrolled patients with sepsis admitted to the medical intensive care unit of a tertiary care university hospital. These patients were then classified into three groups: sepsis, pre-shock state, and septic shock. The primary outcome was the 28-day mortality rate. The secondary outcomes were the 90-day, 180-day, and 1-year mortality rates.@*RESULTS@#A total of 303 patients (groups: sepsis 135 [44.6%]), pre-shock state (93 [30.7%]), and septic shock (75 [24.8%]) completed the 1-year follow-up. The mortality rates at 28 days, 90 days, and 180 days and 1 year were significantly higher in the pre-shock state group than those of the sepsis group, but significantly lower than those in the septic shock group, especially among older patients. When compared with the pre-shock state group, the sepsis group had significantly lower mortality risks at 28 days, 90 days, and 180 days and 1 year, whereas the sepsis shock group had higher mortality risks at these time points.@*CONCLUSION@#The mortality rates of patients in the pre-shock state were notably different from those of patients with sepsis or septic shock. The introduction of a modified sepsis severity classification, which includes sepsis, pre-shock state, and septic shock, could offer valuable additional prognostic information.

Xuebijing injection, a Chinese patent medicine, against severe pneumonia: Current research progress and future perspectives / 中西医结合学报

Severe pneumonia is one of the most common infectious diseases and the leading cause of sepsis and septic shock. Preventing infection, balancing the patient's immune status, and anti-coagulation therapy are all important elements in the treatment of severe pneumonia. As multi-target agents, Xuebijing injection (XBJ) has shown unique advantages in targeting complex conditions and saving the lives of patients with severe pneumonia. This review outlines progress in the understanding of XBJ's anti-inflammatory, endotoxin antagonism, and anticoagulation effects. From the hundreds of publications released over the past few years, the key results from representative clinical studies of XBJ in the treatment of severe pneumonia were selected and summarized. XBJ was observed to effectively suppress the release of pro-inflammatory cytokines, counter the effects of endotoxin, and assert an anticoagulation effect in most clinical trials, which are consistent with experimental studies. Collectively, this evidence suggests that XBJ could play an important and expanding role in clinical medicine, especially for sepsis, septic shock and severe pneumonia. Please cite this article as: Zhang M, Zheng R, Liu WJ, Hou JL, Yang YL, Shang HC. Xuebijing injection, a Chinese patent medicine, against severe pneumonia: Current research progress and future perspectives. J Integr Med. 2023; 21(5): 413-422.

Role of coagulation dysfunction in thrombocytopenia-related death in patients with septic shock / 中华危重病急救医学

OBJECTIVE@#To explore the effect of thrombocytopenia on the prognosis of patients with septic shock and its mechanism in leading to death.@*METHODS@#A retrospective case-control study was conducted. Patients with septic shock admitted to emergency intensive care unit (EICU) and intensive care unit (ICU) in Peking University People's Hospital from April 1, 2015 to January 31, 2023 were enrolled. Patients were divided into the thrombocytopenia group and the non-thrombocytopenia group, according to whether the minimum platelet count was less than 100×109/L within 24 hours after admission to ICU. The outcome index was the mortality during ICU stay. The baseline data, hospitalization information and laboratory test results of the two groups were compared, and the risk factors of in-hospital death were analyzed by Logistic regression, and the mediation effect was performed by Bootstrap method.@*RESULTS@#A total of 301 patients with septic shock were enrolled, of which 172 (57.1%) had thrombocytopenia and 129 (42.9%) did not. There were significant differences between the two groups in age, mortality, disseminated intravascular coagulation (DIC), continuous renal replacement therapy, and level of creatinine, urea nitrogen, total bilirubin, white blood cell count, lymphocyte count, prothrombin time (PT) and activated partial thromboplastin time (APTT). Univariate Logistic regression analysis showed thrombocytopenia [odds ratio (OR) = 4.478], continuous renal replacement therapy (OR = 4.601), DIC (OR = 6.248), serum creatinine (OR = 1.005), urea nitrogen (OR = 1.126), total bilirubin (OR = 1.006) and PT (OR = 1.126) were risk factors of death during hospitalization in patients with septic shock (all P < 0.05). Multivariate Logistic regression analysis showed that thrombocytopenia [OR = 3.338, 95% confidence interval (95%CI) was 1.910-5.834, P = 0.000], continuous renal replacement therapy (OR = 3.175, 95%CI was 1.576-6.395, P = 0.001) and PT (OR = 1.077, 95%CI was 1.011-1.147, P = 0.021) were independent risk factors for in-hospital mortality in patients with septic shock. Mediation analysis showed that 51% of the deaths due to thrombocytopenia in patients with septic shock were due to coagulopathy.@*CONCLUSIONS@#Thrombocytopenia is a powerful predictor of death in septic shock patients, and half of all thrombocytopenia-related deaths may be due to abnormal coagulation function.

Time-related association between fluid balance and prognosis in sepsis patients: a cohort study based on MIMIC-IV database / 中华危重病急救医学

OBJECTIVE@#To investigate time-related association between fluid balance and prognosis in sepsis patients.@*METHODS@#A retrospective cohort study was conducted based on the data of sepsis patients in the Medical Information Database for Intensive Care-IV 2.0 (MIMIC-IV 2.0) from 2008 to 2019. Sepsis patients aged ≥ 18 years who were admitted to intensive care unit (ICU) for at least 2 days were included. The daily fluid balance and cumulative fluid balance (CFB) were calculated from days 1 to 7 after ICU admission. According to CFB,the patients were divided into negative fluid balance group (CFB% < 0%), fluid balance group (0% ≤ CFB% ≤ 10%), and fluid overload group (CFB% > 10%). In-hospital mortality was the primary outcome. Multifactorial Logistic regression was used to analyze time-related association between different CFB and the risk of in-hospital mortality in patients with sepsis during 7 days after ICU admission. In addition, subgroup analysis was performed on patients with septic shock and patients with sepsis who stayed in the ICU for 7 days or longer.@*RESULTS@#A total of 11 437 patients with sepsis were included, of which 6 595 were male and 4 842 were female. The mean age was (64.4±16.4) years. A total of 10 253 patients (89.6%) survived and 1 184 patients (10.4%) died during hospitalization. Compared with the survival group, patients in the death group were older, lighter, had higher sequential organ failure assessment (SOFA), simplified acute physiology score II (SAPS II), longer ICU stay, higher incidence of septic shock, and higher proportion of invasive mechanical ventilation, renal replacement therapy (RRT) and vasoactive drugs. In terms of comorbidities, congestive heart failure, renal disease, liver disease, and malignancy were more common in the death group. The death group had a higher daily fluid balance than the survival group during 7 days after ICU admission, the CFB in the two groups gradually increased with length of ICU stay. After adjusting variables such as age, gender, race, SOFA score, SAPS II score, comorbidities, and the use of invasive mechanical ventilation, RRT and vasoactive drugs, multivariate Logistic regression analysis showed that fluid overload on day 1 after ICU admission was a protective factor for the reduced risk of in-hospital mortality in sepsis patients [odds ratio (OR) = 0.74, 95% confidence interval (95%CI) was 0.64-0.86, P = 0.001]. However, fluid overload on day 3 was a risk factor for in-hospital mortality in sepsis patients (OR = 1.70, 95%CI was 1.47-1.97, P < 0.001) and the risk of in-hospital mortality was significantly increased from day 4 to day 7. Furthermore, the same results were obtained in patients with septic shock and sepsis patients who stayed in the ICU for 7 days or longer.@*CONCLUSIONS@#Fluid overload on day 1 was associated with reduced in-hospital mortality. However, from the third day, fluid overload increases the risk of in-hospital mortality. Thus, managing fluid balance at different times may improve prognosis.

Research progress of exosomes in the diagnosis and treatment of sepsis / 中华危重病急救医学

Sepsis is a life-threatening organ dysfunction caused by infection that lead to dysregulation of the host response. Sepsis and septic shock with a high mortality threaten human health at present, which are important medical and health problems. Early diagnosis and treatment decision-making for sepsis and septic shock still need to be improved. Exosomes are extracellular vesicles with a diameter of 30-150 nm formed by the fusion of multi-vesicle bodies and cell membranes. Exosomes can effectively transport a variety of bioactive substances such as proteins, lipids, RNA, DNA, and participate in the regulation of inflammatory response, immune response, infection and other pathophysiological processes. In recent years, exosomes have become one of the important methods for the diagnosis and treatment of systemic inflammatory diseases. This article will focus on the basic and clinical research of sepsis, and focus on the research progress of exosomes in the diagnosis and targeted therapy of sepsis.

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.

Clinical Characteristics and Risk Factors in Children with Acute Leukemia Complicated with Multiple Drug Resistant Bacterial Septicemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics and risk factors of acute leukemia complicated with multi-drug resistant bacterial septicemia in children.@*METHODS@#The clinical data of children with acute leukemia complicated with septicemia admitted to the Affiliated Hospital of Guangdong Medical University from January 2013 to May 2021 were retrospectively analyzed. Their flora composition and drug resistance were also analyzed. The children were divided into multi-drug resistant bacteria (MDRB) group and non-multi-drug resistant bacteria (non-MDRB) group according to the drug sensitivity results, and the differences in clinical data between the two group were compared.@*RESULTS@#A total of 108 children had drug sensitivity results, 47 cases in the MDRB group, including 26 strians of Gram-positive bacteria (G+), the most common multi-drug resistant G+ bacteria were coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, and the most common multi-drug resistant Gram-negative bacteria G- bacteria were Escherichia coli and Klebsiella pneumoniae subspecies pneumoniae. Compared with non-MDRB group, children in MDRB group had higher C-reactive protein (CRP) level and mortality rate (P <0.001, P =0.009), lower initial empirical anti-infection efficiency (P <0.001), and were more likely to have septic shock (P =0.003). Logistic analysis showed that the risk factors of acute leukemia complicated with MDRB septicemia in children were previous MDRB infection (OR =6.763, 95% CI: 1.141-40.092, P =0.035), duration of agranulocytosis before infection≥7 days (OR =3.071, 95% CI: 1.139-8.282, P =0.027), and previous use of antimicrobial drugs within 90 days before infection (OR =7.675, 95% CI: 1.581-37.261, P =0.011).@*CONCLUSIONS@#The clinical features of acute leukemia complicated with MDRB septicemia in children include a heavy inflammatory response, significantly elevated CRP, susceptibility to secondary septic shock, low efficiency of initial empirical anti-infective therapy, and high mortality rate. Previous MDRB infection, duration of agranulocytosis before infection≥7 days, and previous use of antimicrobial drugs within 90 days before infection are risk factors of acute leukemia complicated with MDRB septicemia in children.

The value of maximal rate of left ventricular pressure in evaluating cardiac function in patients with sepsis-induced cardiomyopathy / 中华危重病急救医学

OBJECTIVE@#To investigate the value of maximal rate of left ventricular pressure (dp/dtmax) in evaluating the changes of cardiac function before and after heart rate reduction in patients with sepsis-induced cardiomyopathy (SIC).@*METHODS@#A single-center, prospective randomized controlled study was conducted. Adult patients with sepsis/septic shock admitted to the department of intensive care unit (ICU) of Tianjin Third Central Hospital from April 1, 2020 to February 28, 2022 were enrolled. Speckle tracking echocardiography (STE) and pulse indication continuous cardiac output (PiCCO) monitoring were performed immediately after the completion of the 1 h-Bundle therapy. The patients with heart rate over 100 beats/minutes were selected and randomly divided into esmolol group and regular treatment group, 55 cases in each group. All patients underwent STE and PiCCO monitoring at 6, 24 and 48 hours after admission in ICU and calculated acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA). Primary outcome measure: change in dp/dtmax after reducing heart rate by esmolol. Secondary outcome measures: correlation between dp/dtmax and global longitudinal strain (GLS); changes of vasoactive drug dosage, oxygen delivery (DO2), oxygen consumption (VO2) and stroke volume (SV) after the administration of esmolol; proportion of heart rate reaching the target after the administration of esmolol; 28-day and 90-day mortality in two groups.@*RESULTS@#Baseline data on age, gender, body mass index, SOFA score, APACHE II score, heart rate, mean arterial pressure, lactic acid, 24-hour fluid balance, sepsis etiology and prior comorbidities were similar between esmolol group and regular treatment group, there were no significant differences between the two groups. All SIC patients achieved the target heart rate after 24 hours of esmolol treatment. Compared with regular treatment group, parameters reflecting myocardial contraction such as GLS, global ejection fraction (GEF) and dp/dtmax were significantly increased in esmolol group [GLS: (-12.55±4.61)% vs. (-10.73±4.82)%, GEF: (27.33±4.62)% vs. (24.18±5.35)%, dp/dtmax (mmHg/s): 1 312.1±312.4 vs. 1 140.9±301.0, all P < 0.05], and N-terminal pro-brain natriuretic peptide (NT-proBNP) significantly decreased [μg/L: 1 364.52 (754.18, 2 389.17) vs. 3 508.85 (1 433.21, 6 988.12), P < 0.05], DO2 and SV were significantly increased [DO2 (mL×min-1×m-2): 647.69±100.89 vs. 610.31±78.56, SV (mL): 49.97±14.71 vs. 42.79±15.77, both P < 0.05]. The system vascular resistance index (SVRI) in esmolol group was significantly higher than that in regular treatment group (kPa×s×L-1: 287.71±66.32 vs. 251.17±78.21, P < 0.05), even when the dosage of norepinephrine was similar between the two groups. Pearson correlation analysis showed that dp/dtmax was negatively correlated with GLS in SIC patients at 24 hours and 48 hours after ICU admission (r values were -0.916 and -0.935, respectively, both P < 0.05). Although there was no significant difference in 28-day mortality between esmolol group and regular treatment group [30.9% (17/55) vs. 49.1% (27/55), χ2 = 3.788, P = 0.052], the rate of esmolol use in patients who died within 28 days was lower than that in patients who survived [38.6% (17/44) vs. 57.6% (38/66), χ2 = 3.788, P = 0.040]. In addition, esmolol has no effect on the 90-day mortality of patients. Logistic regression analysis showed that after adjusting for SOFA score and DO2 factors, patients who used esmolol had a significantly lower risk of 28-day mortality compared with patients who did not use esmolol [odds ratio (OR) = 2.700, 95% confidence interval (95%CI) was 1.038-7.023, P = 0.042].@*CONCLUSIONS@#dp/dtmax in PiCCO parameter can be used as a bedside indicator to evaluate cardiac function in SIC patients due to its simplicity and ease of operation. Esmolol control of heart rate in SIC patients can improve cardiac function and reduce short-term mortality.

Diagnostic and prognostic value of neutrophil CD64, IL-6, and PCT in ICU patients with sepsis / 中华危重病急救医学

OBJECTIVE@#To explore the significance of neutrophil CD64 (nCD64), interleukin-6 (IL-6), and procalcitonin (PCT) alone and in combination in the diagnosis and prognosis evaluation of patients with sepsis.@*METHODS@#A prospective study was conducted. Adult patients admitted to the Western Intensive Care Unit (ICU) of Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University from September 2020 to October 2021 were selected as subjects. The venous blood of the selected patients was collected within 6 hours of entering the ICU to measure the levels of nCD64, IL-6 and PCT. The levels of nCD64, IL-6 and PCT of septic patients were measured again on the 3rd and 7th days after admission to ICU. According to the diagnostic criteria of Sepsis-3, the patients were divided into sepsis group and non-sepsis group to evaluate the diagnostic value of nCD64, IL-6 and PCT in sepsis. The patients with sepsis were divided into sepsis group and septic shock group according to their condition on admission to ICU, and the evaluation value of three biomarkers for sepsis was evaluated. Sepsis patients were divided into the survival group and the death group according to survival after 28 days, and the relationship between the three biomarkers and the prognosis of sepsis was evaluated.@*RESULTS@#Finally, 47 patients with sepsis, 43 patients with septic shock, and 41 patients without sepsis were enrolled. Seventy-six patients with sepsis survived and 14 died after 28 days. (1) The levels of nCD64, IL-6 and PCT on the first day of ICU admission in the sepsis group were significantly higher than those in the non-sepsis group [nCD64: 26.95 (14.05, 86.18) vs. 3.10 (2.55, 5.10), IL-6 (ng/L): 93.45 (52.73, 246.30) vs. 34.00 (9.76, 62.75), PCT (μg/L): 6.63 (0.57, 68.50) vs. 0.16 (0.08, 0.35), all P < 0.01]. The receiver operator characteristic curve (ROC curve) showed that the area under curve (AUC) of nCD64, IL-6 and PCT in the diagnosis of sepsis were 0.945, 0.792 and 0.888, respectively. The diagnostic value of nCD64 was the highest. When the cut-off value of nCD64 was 7.45, the sensitivity and specificity were 92.2% and 95.1% respectively. When nCD64, IL-6 and PCT were diagnosed in pairs or in combination, the combination of the three had the highest diagnostic performance, with AUC of 0.973, sensitivity of 92.2% and specificity of 97.6%. (2) The levels of nCD64, IL-6 and PCT in septic shock group were higher than those in sepsis group on the 1st, 3rd and 7th day after admission to ICU. ROC curve analysis showed that nCD64, IL-6 and PCT had some accuracy in evaluating the severity of sepsis on the 1st, 3rd and 7th day after entering ICU, with AUC ranging from 0.682 to 0.777. (3) The levels of nCD64, IL-6 and PCT in the death group were significantly higher than those in the survival group. Except for the nCD64 and PCT values on the first day after admission to the ICU, there were significant differences between the two groups in all indicators at other time points. ROC curve analysis showed that the AUC of nCD64, IL-6 and PCT predicting the prognosis of sepsis at each time point ranged from 0.600 to 0.981. The clearance rates of nCD64, IL-6 and PCT at 3 and 7 days after ICU admission were calculated by dividing the difference between the 1st and 3rd or 7th days after entering the ICU by the value at the 1st day. Logistic regression was used to analyze their predictive value for the prognosis of sepsis. The results showed that the clearance rates of nCD64, IL-6 and PCT on the 3rd and 7th day of ICU were protective factors for 28-day mortality in patients with sepsis, except the clearance rate of IL-6 on the 7th day.@*CONCLUSIONS@#nCD64, IL-6 and PCT have good value as biomarkers for the diagnosis of sepsis. The diagnostic value of nCD64 is higher than that of PCT and IL-6. When they are used together, the diagnostic value is the highest. nCD64, IL-6 and PCT have certain value in evaluating the severity and predicting the prognosis of patients with sepsis. The higher the clearance rate of nCD64, IL-6 and PCT, the lower the 28-day mortality risk of patients with sepsis.

Comparison between the 2020 international guidelines for the management of sepsis and septic shock and the Japanese guidelines for the management of sepsis / 中华危重病急救医学

In 2021, the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM) jointly released the Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2020 with 93 recommendations. In the same year, the Japanese Society of Intensive Care Medicine (JSICM) and the Japanese Association for Acute Medicine (JAAM) also cooperated to publish the Japanese clinical practice guidelines for management of sepsis and septic shock 2020, covering 118 clinical issues in 22 areas. In this paper, 50 items in the contents of the two guidelines are compared in accordance with the order of international guidelines, including screening, initial resuscitation, mean arterial pressure, transfer to intensive care unit (ICU), diagnosis of infection, timing of antimicrobial administration, biomarkers for initiation of antimicrobial therapy, selection of antibiotic, antifungal therapy, antiviral therapy, infusion of antibiotic, pharmacokinetics and pharmacodynamics, source of infection control, antimicrobial de-escalation strategy, course of antimicrobial administration, biomarkers for discontinuation of antibiotic, fluid management, vasoactive agents, positive inotropic agents, monitoring and intravenous access, fluid balance, oxygenation targets, high-flow nasal cannula oxygen therapy, noninvasive ventilation, protective ventilation in acute respiratory distress syndrome (ARDS), low tidal volume in respiratory failure patients with non-ARDS, lung recruitment maneuvers, prone position ventilation, muscle relaxants, extracorporeal membrane oxygenation (ECMO), glucocorticoids, blood purification, red blood cell (RBC) transfusion, immunoglobulin, stress ulcer prevention, prevention of venous thromboembolism (VTE), renal replacement therapy, glycemic management, vitamin C, sodium bicarbonate therapy, nutrition, treatment goals, palliative care, peer support groups, transition of care, screening economic and social support, education for the knowledge about sepsis to the patients and their families, common decision-making, discharge planning, cognitive therapy and follow-up after discharge. It is convenient for everyone to understand some views in the field of sepsis and septic shock, and deepen their understanding.

Infections sévères vue au service des urgences du Centre Hospitalier Universitaire Mahavoky Atsimo: Facteurs pronostics et Issue / Severe infections at the emergency department of the Mahavoky Atsimo teaching hospital: prognosis factors and outcome

: Une infection sévère constitue une situation préoccupante, car elle s'accompagne d'un taux élevé mortalité dans le monde. L'objectif de cette étude était de déterminer les facteurs pronostiques des infections sévères vues dans le service Accueil­triage­Urgence (ATU) du Centre Hospitalier Universitaire (CHU) Mahavoky Atsimo. Méthodes : Il s'agit d'une étude rétrospective et analytique réalisée dans le service ATU du CHU Mahavoky Atsimo durant 24 mois (Janvier 2020-Décembre 2021). Nous avons inclus tous les patients avec une infection sévère, âgés de 15 et plus ayant un score qSOFA≥2. Résultats : la prévalence d'infection sévère était de 9,8% dont 68,3% de sepsis et 31,7% de choc septique. Les principales étiologies étaient la pneumopathie (26,8%), le paludisme (22%), les méningites (14,6%). Le taux de létalité était de 43,9%. L'âge moyen des patients était de 48,34ans ±2,46 avec une majorité masculine (61%). Les facteurs prédictifs d'un mauvais pronostic étaient : l'HTA (p=0,009), la présence de cardiopathie (p=0,001), l'antécédent d'infection urinaire (p=0,000), le score de Glasgow (p=0,006), le score qSOFA (p=0,010), l'extrémité froide (p=0,000), la présence des signes de lutte (p = 0,005), les râle s crépitants (p = 0,005), la VS élevée (p=0,002), l'élévation de la procalcitonine (p<0,0005), le traitement par quinolone (p=0,048), l'utilisation d'amine Vasopressive (p=0,040), la durée longue de perfusion de catécholamines (p=0,039), l'oxygénothérapie (p= 0,014) et l'utilisation de canule oropharyngée (p=0,003). Conclusions: L'infection sévère est une situation difficile à maîtriser. Le pronostic reste dépendant à la fois de la rapidité du diagnostic et de l'instauration rapide d'un traitement adapté au germe en cause