A nonlinear relationship between the hemoglobin level and prognosis of elderly patients with sepsis: an analysis based on MIMIC-IV / 中华危重病急救医学

OBJECTIVE@#To investigate the correlation of hemoglobin (Hb) level with prognosis of elderly patients diagnosed as sepsis.@*METHODS@#A retrospective cohort study was conducted. Information on the cases of elderly patients with sepsis in the Medical Information Mart for Intensive Care-IV (MIMIC-IV), including basic information, blood pressure, routine blood test results [the Hb level of a patient was defined as his/her maximum Hb level from 6 hours before admission to intensive care unit (ICU) and 24 hours after admission to ICU], blood biochemical indexes, coagulation function, vital signs, severity score and outcome indicators were extracted. The curves of Hb level vs. 28-day mortality risk were developed by using the restricted cubic spline model based on the Cox regression analysis. The patients were divided into four groups (Hb < 100 g/L, 100 g/L ≤ Hb < 130 g/L, 130 g/L ≤ Hb < 150 g/L, Hb ≥ 150 g/L groups) based on these curves. The outcome indicators of patients in each group were analyzed, and the 28-day Kaplan-Meier survival curve was drawn. Logistic regression model and Cox regression model were used to analyze the relationship between Hb level and 28-day mortality risk in different groups.@*RESULTS@#A total of 7 473 elderly patients with sepsis were included. There was a "U" curve relationship between Hb levels within 24 hours after ICU admission and the risk of 28-day mortality in patients with sepsis. The patients with 100 g/L ≤ Hb < 130 g/L had a lower risk of 28-day mortality. When Hb level was less than 100 g/L, the risk of death decreased gradually with the increase of Hb level. When Hb level was ≥ 130 g/L, the risk of death gradually increased with the increase of Hb level. Multivariate Logistic regression analysis revealed that the mortality risks of patients with Hb < 100 g/L [odds ratio (OR) = 1.44, 95% confidence interval (95%CI) was 1.23-1.70, P < 0.001] and Hb ≥ 150 g/L (OR = 1.77, 95%CI was 1.26-2.49, P = 0.001) increased significantly in the model involving all confounding factors; the mortality risks of patients with 130 g/L ≤ Hb < 150 g/L increased, while the difference was not statistically significant (OR = 1.21, 95%CI was 0.99-1.48, P = 0.057). The multivariate Cox regression analysis suggested that the mortality risks of patients with Hb < 100 g/L [hazard ratio (HR) = 1.27, 95%CI was 1.12-1.44, P < 0.001] and Hb ≥ 150 g/L (HR = 1.49, 95%CI was 1.16-1.93, P = 0.002) increased significantly in the model involving all confounding factors; the mortality risks of patients with 130 g/L ≤ Hb < 150 g/L increased, while the difference was not statistically significant (HR = 1.17, 95%CI was 0.99-1.37, P = 0.053). Kaplan-Meier survival curve showed that the 28-day survival rate of elderly septic patients in 100 g/L ≤ Hb < 130 g/L group was significantly higher than that in Hb < 100 g/L, 130 g/L ≤ Hb < 150 g/L and Hb ≥ 150 g/L groups (85.26% vs. 77.33%, 79.81%, 74.33%; Log-Rank test: χ2 = 71.850, P < 0.001).@*CONCLUSIONS@#Elderly patients with sepsis exhibited low mortality risk if their 100 g/L ≤ Hb < 130 g/L within 24 hours after admission to ICU, and both higher and lower Hb levels led to increased mortality risks.

Research progress of ferroptosis in sepsis / 中华危重病急救医学

Sepsis is a systemic disease with severe health consequences, and it was redefined in 2016 as a life-threatening organ dysfunction caused by an abnormal host response to infection and is a global public health priority. In recent years, there has been increasing recognition of the role of dysregulated micronutrient iron metabolism in the pathogenesis of sepsis. The concept of ferroptosis, an iron-dependent, non-apoptotic mode of cell death characterized by the accumulation of lipid reactive oxygen species (ROS), was first proposed by Dixon et al. in 2012. As a novel mode of programmed cell death, ferroptosis differs in morphological and biochemical characteristics from various forms of cell death, such as apoptosis, autophagy, necrosis and lysis. Recent studies have shown that ferroptosis plays an important regulatory role in the development of sepsis and has become a research focus and highlight for the diagnosis and prognosis of related diseases. Therefore, this paper reviews the latest developments in ferroptosis in sepsis, in order to further understanding its pathogenesis and providing new therapeutic targets for sepsis-related organ dysfunction.

Effects of vaccination status on the disease severity of patients with coronavirus disease 2019 / 中华危重病急救医学

Objective:To evaluate the effect of 2019 novel coronavirus inactivated vaccine on the disease severity of patients with Delta variant of coronavirus disease 2019.Methods:A retrospective analysis was performed on 704 patients with coronavirus disease 2019 infected with Delta variant who were older than 18 years old and admitted in the coronavirus disease 2019 designated hospital of Yangzhou (Subei Hospital New Area Branch) from July 2021 to September 2021. They were divided into severe (severe, critical) group and non-severe (light, ordinary) group according to the clinical characteristics of patients. According to the vaccination status, they were divided into 0-dose group, 1-dose group and 2-dose group. We evaluated the effects of vaccination on the severity of the disease and the production of antibodies, and analyzed the influencing factors leading to the severe group of coronavirus disease 2019.Results:The proportion of severe group in the 2-dose vaccinated group was significantly lower than that in the 1-dose vaccinated group and 0-dose vaccinated group [3.02% (7/232) vs. 9.48% (22/232), 15.83% (38/240), P < 0.05]. The time from onset to admission (day: 1.97±1.66 vs. 2.66±2.70), age (years: 45.3±12.2 vs. 63.6±17.0), direct bilirubin [DBil (μmol/L): 3.70±1.83 vs. 5.30±5.13], lactate dehydrogenase [LDH (U/L): 240.69±74.29 vs. 256.30±85.18], creatinine [SCr (μmol/L): 63.38±19.86 vs. 70.23±25.43], interleukin-6 [IL-6 (ng/L): 7.32 (1.54, 17.40) vs. 18.38 (8.83, 33.43)], creatine kinase [CK (U/L): 66.00 (43.00, 99.75) vs. 78.00 (54.50, 144.00)] and D-dimer [mg/L: 0.30 (0.08, 0.49) vs. 0.41 (0.23, 0.69)] of patients in the 2-dose group were significantly lower than those in the 0-dose group (all P < 0.05), while platelet [PLT (×10 9/L): 176.69±60.25 vs. 149.25±59.07], white blood cell count [WBC (×10 9/L): 5.43±1.77 vs. 5.03±1.88] and lymphocyte [LYM (×10 9/L): 1.34±0.88 vs. 1.17±0.50] were significantly higher than those in the 0-dose group (all P < 0.05). The titer of immunoglobulin G (IgG) in the 2-dose group was significantly higher than those in the 1-dose group and 0-dose group on the 10th day after admission [U/L: 130.94 (92.23, 326.31), 113.18 (17.62, 136.20), 117.85 (33.52, 156.73), both P < 0.05], and higher than 0-dose group on the 16th day [U/L: 156.12 (120.32, 167.76) vs. 126.52 (61.34, 149.57), P < 0.05]. The proportion of complete 2-dose vaccination [10.45% (7/67) vs. 35.32% (225/637)], LYM (×10 9/L: 1.09±0.32 vs. 1.25±0.56) and PLT (×10 9/L: 138.55±68.03 vs. 166.93±59.70) in the severe group were significantly lower than those in the non-severe group ( P < 0.05), while the time from onset to admission (day: 3.01±2.99 vs. 2.25±2.09), the length of hospital stay (day: 28±18 vs. 16±6), male proportion [77.61% (52/67) vs. 34.54% (220/637)], age (years: 69.13±12.63 vs. 52.28±16.53), DBil [μmol/L: 4.20 (3.18, 6.65) vs. 3.60 (2.80, 4.90], LDH (U/L: 310.61±98.33 vs. 238.19±72.14), SCr (μmol/L: 85.67±38.25 vs. 65.98±18.57), C-reactive protein [CRP (μmol/L): 28.12 (11.32, 42.23) vs. 8.49 (2.61, 17.58)], IL-6 [ng/L: 38.38 (24.67, 81.50) vs. 11.40 (4.60, 22.07)], CK [U/L: 140.00 (66.00, 274.00) vs. 72.80 (53.00, 11.00)] and the D-dimer [mg/L: 0.46 (0.29, 0.67) vs. 0.35 (0.19, 0.57)] in the severe group were significantly higher than those in the non-severe group (all P < 0.05). Multivariate regression analysis showed that the odds ratio ( OR) of severe group was 0.430 ( P = 0.010) in the 1-dose group and the 2-dose group compared with the 0-dose group. However, the risk of severe group was 0.381-fold in the 2-dose group compared with the 0-dose group [ OR = 0.381, 95% confidence interval (95% CI) was 0.121-1.199] which was not statistically significant, when the age was included in the regression analysis ( P > 0.05). PLT ( OR = 0.992, 95% CI was 0.986-0.998) were protective factors, but older than 60 years old ( OR = 3.681, 95% CI was 1.637-8.278), CK ( OR = 1.001, 95% CI was 1.000-1.001), IL-6 ( OR = 1.006, 95% CI was 1.002-1.010), SCr ( OR = 1.020, 95% CI was 1.007-1.033) were risk factors for severe group (all P < 0.05). Conclusions:Compared with the 0-dose vaccinated patients, the coronavirus disease 2019 patients infected with delta variant and fully vaccinated with 2-dose 2019 novel coronavirus inactivated vaccine had lower level of IL-6, SCr, CK and D-dimer, and higher PLT, LYM and IgG titer, who were not easy to develop into the severe condition.

Study on the relationship between ventricular function parameters obtained by echocardiography and prognosis of patients with sepsis / 中华危重病急救医学

Objective:To investigate the epidemiological characteristics of septic cardiomyopathy and explore the relationship between the relevant indexes measured by echocardiography and the prognosis of patients with sepsis.Methods:A case-control study was conducted. The data of patients with sepsis admitted to the department of critical care medicine of Jiangsu Subei People's Hospital Affiliated to Yangzhou University and the department of critical care medicine of Beijing Electric Power Hospital of State Grid Corporation of China from June 2018 to June 2021 were enrolled. The general information and 28-day prognosis were recorded. At the same time, ultrasonic parameters obtained by transthoracic echocardiography within 24 hours after intensive care unit (ICU) admission were recorded. The differences in ultrasound indexes between the death group and the survival group on 28 days were compared. Parameters with significant statistical differences between the death group and the survival group were included in the Logistic regression analysis to find the independent risk factors for the prognosis of patients with sepsis, the predictive value of each index for the prognosis of patients with sepsis was evaluated by receiver operator characteristic curve (ROC curve).Results:A total of 145 patients with sepsis were enrolled, including 106 patients with septic shock. Among the 145 patients, septic cardiomyopathy was found in 73 patients, with the incidence of 50.3%. The incidence of left ventricular diastolic dysfunction cardiomyopathy was 41.4% ( n = 60), the incidence of left ventricular systolic dysfunction cardiomyopathy was 24.8% ( n = 36), and the incidence of right ventricular systolic dysfunction cardiomyopathy was 12.4% ( n = 18). At 28 days, 98 patients survived and 47 died, with the mortality of 32.4%. The peak e' velocity by tissue Doppler imaging (e') and right ventricular myocardial systolic tricuspid annulus velocity (RV-Sm) of the death group were significantly lower than those of the survival group [e' (cm/s): 7.81±1.12 vs. 8.61±1.02, RV-Sm (cm/s): 12.12±2.04 vs. 13.73±1.74, both P < 0.05], left ventricular ejection fraction (LVEF) and left ventricular systolic mitral annulus velocity (LV-Sm) in the death group were slightly higher than those in the survival group [LVEF: 0.550±0.042 vs. 0.548±0.060, LV-Sm (cm/s): 8.92±2.11 vs. 8.23±1.71], without significant differences (both P > 0.05). Parameters with significant statistical differences between the two groups were included in the Logistic regression analysis and showed that e' and RV-Sm were independent risk factors for the 28-day prognosis of patients with sepsis [e': odds ratio ( OR) = 0.623, 95% confidence interval (95% CI) was 0.410-0.947, P = 0.027; RV-Sm: OR = 0.693, 95% CI was 0.525-0.914, P = 0.010]. ROC curve analysis showed that the area under the ROC curve (AUC) of e' for predicting the 28-day prognosis of patients with sepsis was 0.657, 95% CI was 0.532-0.781, P = 0.016, the best cut-off value was 8.65 cm/s, the sensitivity was 62.1%, and the specificity was 73.4%. The AUC of RV-Sm for predicting the 28-day prognosis of patients with sepsis was 0.641, 95% CI was 0.522-0.759, P = 0.030, the best cut-off value was 14.80 cm/s, the sensitivity was 96.6%, and the specificity was 26.6%. Conclusions:The incidence of septic cardiomyopathy is high. The LVEF measured by early echocardiography has no predictive value for 28-day prognosis in septic patients, while RV-Sm and e' are important predictors for 28-day prognosis.

Effects of different crystalloid resuscitation on renal function in septic shock rabbits under the guidance of pulse indicator continuous cardiac output / 中华危重病急救医学

Objective:To study the effect of different crystalloid resuscitation on renal function in septic shock rabbits, and to provide a theoretical basis for the choice of crystalloid for clinical fluid resuscitation.Methods:Thirty-six healthy male New Zealand white rabbits were divided into six groups by random number table: control group, model group, and four crystalloid groups including normal saline (NS) group, lactate Ringer solution (LR) group, acetate Ringer solution (AR) group, and sodium potassium magnesium calcium glucose injection (SPMCG) group, with 6 rabbits in each group. Rabbits were infused with Escherichia coli lipopolysaccharide (LPS) 500 μg/kg via the marginal ear vein (infused at a constant speed within 20 minutes), and then continued to infuse in an increase of 300 μg/kg every 10 minutes, the maximum dose was 2 mg/kg, until the mean arterial pressure (MAP) dropped to 60% of the basal value, the septic shock model was considered to be successfully reproduced. The rabbits in the control group were not injected with LPS, and other operations were the same as in the model group. Different crystalloid groups were given crystal solution immediately after modeling for resuscitation (predetermined fluid volume 60 mL/kg, transfusion within 3 hours). The volume stress test was performed every hour to guide the fluid volume, and the stroke volume index increase rate (ΔSVI) < 15% was the end point of resuscitation. The control group and the model group were given NS 4 mL·kg -1·h -1 to maintain the physiological requirement. All groups were given tracheotomy and mechanical ventilation, and the hemodynamic changes were monitored by pulse-indicated continuous cardiac output (PiCCO). The dynamic changes of hemodynamic indexes, arterial blood gas analysis, electrolytes, blood glucose and renal function biomarkers were monitored before modeling, immediately after modeling and 3, 6, and 12 hours after resuscitation. Results:① Hemodynamic indicators: after modeling, the MAP in the model group and the four fluid resuscitation groups decreased significantly, the cardiac index (CI) increased, and the systemic vascular resistance index (SVRI), global end-diastolic volumn index (GEDVI) decreased. After different crystalloid resuscitation at different time points, MAP, SVRI, and GEDVI increased in the four crystalloid groups. ②Arterial blood gas analysis, electrolytes, blood glucose: blood lactic acid (Lac) in the model group and the four fluid resuscitation groups increased after model success. After fluid resuscitation, the Lac of each crystalloid group began to decrease and reached to the lowest at 12 hours. Compared with the LR, AR and SPMCG groups, the pH value decreased in the NS group at 6 hours and 12 hours of fluid resuscitation (6 hours: 7.29±0.00 vs. 7.40±0.02, 7.35±0.02, 7.37±0.02; 12 hours: 7.27±0.02 vs. 7.38±0.02, 7.39±0.02, 7.35±0.01; all P < 0.05). After fluid resuscitation, blood Cl - levels at 3, 6, and 12 hours in the NS group were significantly higher than those in the LR, AR and SPMCG groups (mmol/L: 113.4±0.6 vs. 101.4±3.6, 108.0±1.1, 106.0±0.8 at 3 hours; 115.1±2.0 vs. 101.1±2.7, 109.0±2.2, 105.3±0.6 at 6 hours; 116.9±0.1 vs. 104.2±4.4, 107.6±1.7, 108.7±0.6 at 12 hours; all P < 0.05). There was no significant difference in blood glucose at each time point among the four crystalloid groups. ③ Biomarkers of renal function: blood and urine neutrophil gelatinase associated lipocalin (NGAL) and cystatin C (Cys C) were significantly increased in the model group and four fluid resuscitation groups. After fluid resuscitation, blood, urine NGAL and Cys C decreased. There was no significant difference in blood, urine NGAL and Cys C at all the time points among the different fluid resuscitation groups. Conclusions:In the rabbit model of septic shock induced by Escherichia coli LPS, hyperchloremia and acidosis occurred after NS resucitation, but did not occur during the recovery of LR, AR and SPMCG. There was no difference in the effects of different crystalloid resuscitation on renal function in septic shock rabbits.

Physical cooling in sepsis patients with fever: a randomized controlled clinical study / 中华急诊医学杂志

Objective:Sepsis patients usually have a fever, but it is still controversial about whether sepsis patients with fever need cooling treatment. This study aimed to evaluate the effect of external physical cooling on the prognosis of sepsis patients.Methods:This study was a single-center, open-label, randomized clinical trial. Adult sepsis patients with body temperature above 38.3 °C admitted to the Critical Care Medicine of Northern Jiangsu People's Hospital from June 2020 to December 2020 were selected, and randomly assigned in a 1∶1 ratio to the cooling group and control group. Patients in the cooling group used external physical cooling methods to reduce their core body temperature to the normal range (36.5-37.5°C) within 4 h of enrollment and maintained for 48 h. Standard care was implemented in the control group at all times, and all antipyretic treatments were prohibited. The 28-day mortality, 72 h-Δ sequential organ failure assessment (SOFA) score (SOFA score at enrollment–SOFA score after 72 h), length of hospital stay and length of ICU stay were compared between the two groups.Results:A total of 53 patients (32 males and 21 females) were enrolled in the study, including 26 patients in the cooling group and 27 patients in the control group. There were no statistical differences in age, sex, source of infection, SOFA score and body temperature between the two groups (all P>0.05). There was no significant difference in the 28-day mortality between the cooling group and the control group ( RR=1.38, 95% CI: 0.62-3.07, P=0.430). The 72 h-ΔSOFA score of the cooling group was significantly higher than that of the control group, the mean difference between the two groups was 1.90 (95% CI: 0.09-3.71, P=0.040), and there was no significant difference in length of hospital stay, length of ICU stay and 28-day mortality between the two groups. Conclusions:External physical cooling management can not significantly reduce the 28-day mortality of sepsis patients. However, external physical cooling can reduce the 72-h SOFA score in sepsis patients, and improve the organ function of patients.

Xuebijing injection improve pulmonary vascular barrier function in ARDS by up-regulating claudin-5 expression through PI3K/Akt/FOXO1 signaling pathway / 中华危重病急救医学

Objective:To study the signaling pathway of the up-regulation of claudin-5 expression by Xuebijing injection.Methods:Animal and cell models of acute respiratory distress syndrome (ARDS) were induced by lipopolysaccharide (LPS). ① In vivo study, 20 male Sprague-Dawley (SD) rats were randomly divided into 4 groups: control group, LPS group (LPS injection 10 mg/kg for 12 hours), Xuebijing control group (Xuebijing injection 1 mg/kg, twice a day, for 3 days), and Xuebijing intervention group (LPS injection after pretreatment of Xuebijing injection), according to random number method with 5 rats in each group. The lung tissues were taken to detect lung dry/wet weight ratio (W/D) and the morphological changes in each group. Claudin-5, phosphorylated forkhead box transcription factor O1 (p-FOXO1), total FOXO1 (t-FOXO1), phosphorylated Akt (p-Akt) and total Akt (t-Akt) in lung tissues were detected by immunohistochemical staining (IHC) and Western blotting. ② In vitro study, human pulmonary microvascular endothelial cells (HPMECs) were divided into 6 groups (5 holes in each group): control group, Xubijing control group (incubated with 2 g/L Xubijing for 24 hours), phosphoinositide 3-kinases (PI3K) signaling pathway LY294002 control group (incubated with 10 μmol/L LY294002 for 1 hour), LPS group (incubated with 1 mg/L LPS for 12 hours), Xubijing intervention group (incubated with 2 g/L Xuebijing for 24 hours, then with 1 mg/L LPS for 12 hours) and LY294002 intervention group (incubated with 10 μmol/L LY294002 for 1 hour, then with 2 g/L and Xubijing for 24 hours, and then with 1 mg/L LPS for 12 hours). The expression levels of claudin-5, p-FOXO1, t-FOXO1, p-Akt and t-Akt of HPMECs in each group were assessed by Western blotting. Results:In vivo study: ① Compared with the control group, the lung W/D ratio increased significantly in LPS group (6.79±0.42 vs. 4.19±0.13), and decreased significantly after the intervention of Xuebijing (4.92±0.38 vs. 6.79±0.42, P < 0.01). ② Morphological changes of lung tissue: compared with the control group, the injury of lung tissue in LPS group was more serious, which was significantly improved after Xuebijing intervention. ③ Expression levels of claudin-5, p-Akt/t-Akt and p-FOXO1/t-FOXO1: the expression levels of claudin-5, p-Akt/t-Akt and p-FOXO1/t-FOXO1 in LPS group were significantly decreased as compared with the control group (claudin-5/GAPDH: 0.33±0.03 vs. 1.03±0.07, p-Akt/t-Akt: 0.18±0.02 vs. 1.01±0.13, p-FOXO1/t-FOXO1: 0.16±0.06 vs. 1.00±0.19, all P < 0.01). After the intervention of Xuebijing, the expression levels were significantly increased as compared with the LPS group (claudin-5/GAPDH: 0.53±0.05 vs. 0.33±0.03, p-Akt/t-Akt: 0.56±0.12 vs. 0.18±0.02, p-FOXO1/t-FOXO1: 0.68±0.10 vs. 0.16±0.06, all P < 0.01). In vitro study: compared with the control group, the expression level of claudin-5 in the LPS group was significantly decreased (claudin-5/β-actin: 0.45±0.03 vs. 1.01±0.15, P < 0.01), and the expression level of claudin-5 in Xuebijing intervention group was also significantly decreased (claudin-5/β-actin: 0.80±0.08 vs. 1.01±0.15, P < 0.01). After the intervention of LY294002, the expression of claudin-5 was significantly decreased as compared with the Xubijing intervention group (claudin-5/β-actin: 0.41±0.02 vs. 0.80±0.08, P < 0.01). Conclusion:Xuebijing injection improve pulmonary vascular barrier function in rats with ARDS by up-regulating claudin-5 expression through PI3K/Akt/FOXO1 signaling pathway.

Advances in the clinical value of tissue inhibitors of metalloproteinase-2 and insulin-like growth factor binding protein 7 in sepsis associated-acute kidney injury / 中华危重病急救医学

Sepsis is an important cause of acute kidney injury (AKI). About 60% of sepsis patients will develop AKI. At present, the standard of clinical diagnosis of AKI is still based on the changes in serum creatinine and urine volume. Because of its lag in time, it may lead to delay in treatment and increase the mortality. To find a new biomarker similar to "troponin" for the diagnosis of AKI, and to achieve the early diagnosis and prevention of AKI, is of great significance to reduce the mortality of AKI. In recent years, it has been found that tissue inhibitors of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) can be used for early diagnosis of sepsis associated-acute kidney injury (SA-AKI). They also have important values in risk stratification, prognosis judgment, intervention and other aspects of SA-AKI. In this paper, the research progress of the application of TIMP-2 and IGFBP7 in SA-AKI is reviewed.

Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2021, interpretation and expectation / 中华危重病急救医学

The Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2021 (2021 guideline) was recently released. The guidelines summarized the evidences from literatures through to July 2019, and composed by 6 parts as "screening and early treatment", "infection", "hemodynamic management", "ventilation", "additional therapies" and "long-term outcomes and goals of care" with a total of 93 items and 99 recommendations. Compared with the 2016 guideline (96 recommendations), although the total number of recommendations in the 2021 guideline is similar, the number of "strong recommendations (recommend)" in 2021 guideline has dropped significantly, while as the number of "weak recommendations (suggest)" has increased significantly, and the level of the quality of evidence on which the recommendations are based has been significantly lowered. Furthermore, 2021 guideline has also markedly deleted or simplified the recommendations regarding infection prevention, acute respiratory distress syndrome (ARDS) treatment, nutritional support and so on. While, the most obvious improvement appears in the segment of "long-term outcomes and goals of care", in which the patients and their families could get help in term of determining their physical rehabilitation and discharge follow-up plans and formulating exact goals of care. 2021 guideline did not adopt new and emerging therapies or treatments, such as metagenomic next-generation sequencing (mNGS), diaphragm protective ventilation, timing of initiating renal replacement therapy for acute kidney injury, early mobility, endotoxin adsorption, tranexamic acid, E-medicine and telemedicine, big data & artificial intelligence and other new therapies. Collectively, it may suggest the 2021 guideline tend to be conservative and simplified rather than fairly optimized and logicalized, which may arouse controversy in the future and affect clinician compliance.

Risk factors of early septic shock-related thrombocytopenia and its impact on prognosis / 中华危重病急救医学

Objective:To investigate the risk factors and prognosis of early septic shock-related thrombocytopenia.Methods:Retrospective analysis of clinical data of patients with septic shock admitted to the department of intensive care unit (ICU) of Northern Jiangsu People's Hospital from June 2016 to November 2020 was conducted. According to the lowest platelet count (PLT) in the early stage of septic shock (within 24 hours of using vasoactive drugs), the patients were divided into mild thrombocytopenia group [PLT (50-100)×10 9/L], severe thrombocytopenia group (PLT < 50×10 9/L) and normal platelet group (PLT > 100×10 9/L). The differences in general information, laboratory indicators, mechanical ventilation time, length of ICU stay, in-hospital stay, and 28-day mortality among the three groups were analyzed. Multivariate Logistic regression was used to analyze the influencing factors of thrombocytopenia, and the 28-day Kaplan-Meier survival curve of patients with different PLT levels was drawn. Results:A total of 486 patients with septic shock were enrolled, including 123 patients with mild thrombocytopenia, 75 patients with severe thrombocytopenia and 288 patients with normal platelets. Patients with diabetes ( χ2 = 30.460, P < 0.001), abdominal infection ( χ2 = 15.024, P = 0.001), urinary tract infection ( χ2 = 36.633, P < 0.001), bloodstream infection ( χ2 = 7.755, P = 0.022), Gram negative (G -) bacilli infection ( χ2 = 19.569, P < 0.001), hyperlactic acidemia ( H = 23.404, P < 0.001), elevated procalcitonin (PCT, H = 43.368, P < 0.001), high acute physiology and chronic health evaluation Ⅱ (APACHEⅡ, F = 11.122, P < 0.001) and high sequential organ failure assessment (SOFA, F = 84.328, P < 0.001) were more likely to have thrombocytopenia within 24 hours of septic shock. Multivariate Logistic regression analysis of early septic shock-related thrombocytopenia showed that, diabetes [odds ratio ( OR) = 0.19, 95% confidence interval (95% CI) was 0.08-0.42, P < 0.001], urinary tract infection ( OR = 0.33, 95% CI was 0.13-0.83, P = 0.018), G - bacilli infection ( OR = 0.20, 95% CI was 0.07-0.58, P = 0.003), hyperlactic acidemia ( OR = 1.25, 95% CI was 1.07-1.46, P = 0.005) and high APACHEⅡ score ( OR = 0.85, 95% CI was 0.78-0.92, P < 0.001) were independent risk factors for platelets < 50×10 9/L. Abdominal infection was an independent risk factor for PLT (50-100)×10 9/L ( OR = 0.56, 95% CI was 0.34-0.95, P = 0.03). High SOFA score was an independent risk factor for PLT ≤ 100×10 9/L [PLT < 50×10 9/L: OR = 2.03, 95% CI was 1.65-2.52, P < 0.001; PLT (50-100)×10 9/L: OR = 1.31, 95% CI was 1.16-1.48, P < 0.001]. There were no significant differences in mechanical ventilation time, length of ICU stay, and in-hospital stay among the three groups ( H values were 0.142, 2.134, and 3.990, respectively, all P > 0.05). The 28-day mortality of septic shock patients increased with the severity of thrombocytopenia ( χ2 = 40.406, P < 0.001), and the 28-day mortality of severe thrombocytopenia group and mild thrombocytopenia group was significantly higher than those of the normal platelet group [66.7% (50/75), 43.1% (53/123) vs. 27.8% (80/288), both P < 0.05]. Kaplan-Meier survival curve analysis showed that the 28-day survival rate gradually decreased with the decrease of PLT, and the 28-day survival rate was higher in the normal platelet group (Log-Rank test: χ2 = 80.667, P < 0.001). Conclusions:Diabetes, abdominal infection, urinary tract infection, G - bacilli infection, hyperlactic acidemia, high APACHEⅡ score, and high SOFA score are independent risk factors for early septic shock-related thrombocytopenia. Early thrombocytopenia in patients with septic shock indicates a high risk of 28-day death.

Effect of the completion time of initial 30 mL/kg fluid resuscitation on the prognosis of patients with septic shock / 中华危重病急救医学

Objective:To investigate the effect of the completion time of initial 30 mL/kg fluid resuscitation on the prognosis of patients with septic shock.Methods:An observational study was conducted. The inpatients with septic shock admitted to intensive care unit (ICU) of Northern Jiangsu People's Hospital, Affiliated Hospital of Yangzhou University and Jiangdu People's Hospital from October 1st, 2018 to September 30th, 2020 were enrolled. The general data including gender, age, body mass index (BMI), patient source, site of infection, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score and arterial blood lactic acid (Lac) at ICU admission, fluid resuscitation dose, completion time of initial 30 mL/kg fluid resuscitation, mechanical ventilation, incidence of acute kidney injury (AKI), continuous renal replacement therapy (CRRT), length of ICU stay and 28-day mortality. The relationship between the completion time of initial 30 mL/kg fluid resuscitation and ΔSOFA score (the difference between SOFA score 3 hours of fluid resuscitation and initial SOFA score) was analyzed. In addition, according to the completion time (T) of initial 30 mL/kg fluid resuscitation, the patients were divided into T ≤ 1 hour group, 1 hour < T≤2 hours group, 2 hours < T≤3 hours group and T > 3 hours group, and the observation parameters among the groups were compared.Results:① A total of 131 patients were enrolled, including 94 males and 37 females with an average age of (68.3±15.0) years old. The median APACHE Ⅱ score was 27 (21, 34), the median of initial SOFA score was 12 (10, 14), the median of initial Lac was 5.0 (3.4, 7.1) mmol/L, and the most common source of infection was lung, with a total of 87 patients (66.41%). The completion time of initial 30 mL/kg fluid resuscitation and ΔSOFA score fitted the Logistic curve ( Y = -1.062 6 X2+4.407 9 X+0.961 8), which suggested that the early or late completion time of initial fluid resuscitation had adverse effects on the prognosis of patients with septic shock.② There was no significant difference in infection site, initial APACHE Ⅱ score, initial Lac, and initial SOFA score among different completion time of initial 30 mL/kg fluid resuscitation groups. The respiratory support rate, the incidence of AKI and the ratio of CRRT in the T ≤1 hour group were significantly higher than those in the 1 hour < T≤2 hours group, 2 hours < T≤3 hours group and T > 3 hours group (respiratory support rate: 78.57% vs. 75.51%, 42.86%, 75.00%; incidence of AKI: 57.14% vs. 20.41%, 21.43%, 50.00%; ratio of CRRT: 35.71% vs. 0%, 7.14%, 16.67%), the differences among the groups were statistically significant (all P < 0.05). The 28-day mortality was the highest in the T ≤ 1 hour group (64.29%), and the lowest in the 1 hour < T ≤2 hours group (22.45%), 35.71% in the 2 hours < T ≤ 3 hours group, 33.33% in the T > 3 hours, and the difference among the groups was statistically significant ( P < 0.01). Conclusions:Completion of initial 30 mL/kg fluid resuscitation in 1-2 hours after septic shock may reduce the 28-day mortality and improve organ dysfunction, and initial fluid resuscitation prematurely or too late may increase 28-day mortality. But further research and verification are needed.

Diagnostic value of the Sepsis-3 standard for patients with sepsis: a multi-center prospective, observational clinical study / 中华危重病急救医学

Objective:To explore the value of Sepsis-3 standard in diagnosis of patients with sepsis.Methods:Patients who were infected or suspected of infection in intensive care unit (ICU) of six hospitals in Jiangsu Province from September 2017 to August 2018 were enrolled. They were divided into four groups: group A was in accordance with Sepsis-1 and Sepsis-3, group B only met the Sepsis-1 standard, group C only met the Sepsis-3 standard, and both Sepsis-1 and Sepsis-3 standard did not match in group D. The age, gender, underlying disease, diagnosis and source of infection, vital signs within 24 hours of ICU, systemic inflammatory response syndrome (SIRS) score, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score, quick sequential organ failure assessment (qSOFA) score, the length of ICU stay, total hospitalization time, 28-day mortality rate, etc. were recorded. The above collected data were compared and analyzed in groups, and the receiver operating characteristic (ROC) curves of each scoring standard were drawn and calculated. The area under the ROC curve (AUC), and the Youden index of each score was calculated to predict the optimal cut-off value of 28-day mortality in patients with sepsis and its corresponding sensitivity and specificity. Results:A total of 527 patients with infection or suspected infection were enrolled in the study, including 324 patients in group A, 113 patients in group B, 22 patients in group C, 68 patients in group D, and 28-day mortality were 38.9%, 17.7%, 31.8%, and 11.8%, respectively, and there was statistically significant difference among four groups ( P < 0.05). The SIRS scores of the A, B, C, D groups were 3 (1), 2 (1), 1 (0), 1 (0), APACHEⅡ scores were 17 (10), 11 (10), 15 (8), 12 (8), qSOFA score were 2 (1), 1 (1), 1 (1), 1 (2), SOFA scores were 8 (6), 1 (0), 7 (4), 1 (0), respectively, there were statistically significant differences among four group (all P < 0.05). Values of SOFA, qSOFA and SIRS scores were evaluated by ROC to predict the value of 28-day mortality. The results showed that AUC and 95% confidence interval of SOFA score was superior to qSOFA score and SIRS score [0.71 (0.66-0.76) vs. 0.59 (0.55-0.64), 0.57 (0.51-0.62), both P < 0.01]. According to the Youden index, the best cut-off values for the 28-day mortality of SOFA, qSOFA and SIRS scores for sepsis were 7, 2 and 2, respectively, and the sensitivity was 69.4%, 60.1%, 53.6%, the specificity was 61.8%, 76.2%, 51.1%, respectively. Conclusions:The Sepsis-3 standard is superior to the Sepsis-1 standard in the diagnosis and prediction of 28-day mortality in patients with sepsis. qSOFA can be used as an early tool for rapid screening of patients with high-risk sepsis in the ICU bedside.

Evaluation of microcirculatory changes after bundle therapy and prognostic value by the ratio of transcutaneous oxygen pressure and transcutaneous carbon dioxide pressure in the treatment of septic shock / 中华危重病急救医学

Objective@#To evaluate microcirculatory changes after bundle therapy and prognostic values of the ratio of transcutaneous oxygen pressure and transcutaneous carbon dioxide pressure (PtcO2/PtcCO2) in the treatment of septic shock.@*Methods@#A retrospective analysis was conducted. Patients with septic shock admitted to department of intensive care unit (ICU) of Northern Jiangsu People's Hospital from July 2017 to February 2019 were enrolled. The gender, age, infection site, acute physiology and chronic health evaluationⅡ (APACHEⅡ), the length of ICU stay and 28-day prognosis were collected; PtcCO2, PtcO2, PtcO2/PtcCO2 ratio, arterial lactate (Lac), central venous oxygen saturation (ScvO2), mean arterial pressure (MAP) were measured before treatment (at admission) and 6 hours after bundle treatment. According to the 28-day prognosis, the patients were divided into survival group and death group, and the differences of each index between the two groups were compared. The risk factors of prognosis were analyzed by binary Logistic regression analysis. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of the related indicators for the 28-day mortality of septic shock patients.@*Results@#A total of 78 patients with septic shock were enrolled, with 47 cases in survival group and 31 cases in death group. Compared with survival group, APACHEⅡ score and PtcCO2 were higher and PtcO2/PtcCO2 ratio was lower in death group [APACHEⅡ: 28.33±6.35 vs. 21.61±6.64, PtcCO2 (mmHg, 1 mmHg = 0.133 kPa): 51.80±19.05 vs. 38.17±6.79, PtcO2/PtcCO2 ratio: 1.20±0.72 vs. 1.80±0.81, all P < 0.05]. Compared with before treatment, the PtcO2/PtcCO2 ratio, Lac, MAP were substantially improved at 6 hours of bundle therapy [PtcO2/PtcCO2 ratio: 1.76±0.81 vs. 1.56±0.82, Lac (mmol/L): 3.74±2.40 vs. 4.42±2.60, MAP (mmHg): 83.34±7.58 vs. 71.00±5.36, all P < 0.05], and there was no changes in PtcCO2 and ScvO2. The PtcO2/PtcCO2 ratio at 6 hours of bundle therapy in the survival group was significantly higher than before treatment and was higher than that in death group (2.13±0.75 vs. 1.80±0.81, 1.19±0.53, both P < 0.05). There was no significant difference in PtcO2/PtcCO2 ratio of death group before and after treatment (1.19±0.53 vs. 1.20±0.72, P > 0.05). The binary Logistic regression showed that PtcO2/PtcCO2 ratio at 6 hours of bundle therapy and APACHEⅡ score were risk factors of prognosis [PtcO2/PtcCO2 ratio: odds ratio (OR) = 7.876, P = 0.026; APACHEⅡ score: OR = 0.846, P = 0.035]. ROC curve analysis showed that 6-hour of PtcO2/PtcCO2 ratio, APACHEⅡscore and 6-hour Lac level could predict 28-day mortality in septic shock patients, and the area under curve (AUC) was 0.864, 0.784, and 0.752 respectively. The cut-off value of 6-hour PtcO2/PtcCO2 ratio for predicting mortality in septic shock patients was 1.42, the sensitivity was 87.0%, and the specificity was 73.3%. In addition, the patients were divided into two groups according to whether the 6-hour PtcO2/PtcCO2 ratio was greater than 1.42. The results showed that: compared with the PtcO2/PtcCO2 < 1.42 group, the APACHEⅡ score in PtcO2/PtcCO2 ≥ 1.42 group was lower, the 6-hour Lac level was lower, 24-hour Lac reaching standard rate was higher and the 28-day mortality was lower.@*Conclusions@#Compared with the traditional metabolic parameters, the improvement of early microcirculatory perfusion in patients with septic shock can reflect the effect of bundle therapy. The PtcO2/PtcCO2 ratio at 6 hours of bundle therapy can be used as a new index to predict the prognosis of patients with septic shock which supports the monitoring and evaluation of microcirculation in the early stage of treatment in septic shock.

Elevated plasma histone is an independent risk factor for the development of septic cardiomyopathy / 中华危重病急救医学

Objective@#To investigate the epidemiology and independent risk factors of septic cardiomyopathy.@*Methods@#A prospective study was conducted. Patients with sepsis in intensive care unit (ICU) of Subei People's Hospital of Jiangsu Province, Yangzhou University, Fuxing Hospital, Capital Medical University and Beijing Electric Power Hospital from May 2016 to August 2019 were enrolled. All patients received standardized treatments according to the Surviving Sepsis Campaign (SSC) guidelines. Blood were collected within 24 hours of admission to ICU, and plasma histone H4, cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were detected by enzyme linked immunosorbent assay (ELISA). Transthoracic echocardiography was performed to record the ultrasonic parameters within 24 hours after admission. Sequential organ failure assessment (SOFA) score, usage of vasopressor drugs, and the prognosis of ICU were recorded. Patients were divided into two groups according to whether cardiomyopathy occurred or not, and the differences of each index between the two groups were compared. The correlation between plasma histone H4 and SOFA score, cTnI, NT-proBNP were investigated. Multivariate binary Logistic regression was used to determine the risk factors for septic cardiomyopathy. The predictive value of histone H4 in septic cardiomyopathy was shown by the receiver operating characteristic (ROC) curve.@*Results@#121 patients were included in this study, and there were 60 patients (49.6%) with septic cardiomyopathy. Thirty-six patients died, with an ICU mortality of 29.8%. ① Correlation analysis showed that plasma histone H4 in patients with septic cardiomyopathy was positively correlated with cTnI, SOFA score and NT-proBNP (r value was 0.512, 0.403 and 0.274, respectively, all P < 0.01). ② Compared with the non-cardiomyopathy group, the plasma histone H4, cTnI, usage of vasopressor drugs, SOFA score and ICU mortality in the cardiomyopathy group were significantly increased [histone H4 (mg/L): 0.26 (0.23, 0.30) vs. 0.22 (0.17, 0.27), cTnI (μg/L): 0.21 (0.17, 0.30) vs. 0.18 (0.14, 0.22), usage of vasopressor drugs: 83.3% (50/60) vs. 65.6% (40/61), SOFA score: 11 (9, 12) vs. 9 (8, 10), ICU mortality: 40.0% (24/60) vs. 19.7% (12/61), all P < 0.05]. Multivariate binary Logistic regression analysis showed that high histone H4 level [odds ratio (OR) = 6.502, 95% confidence interval (95%CI) was 1.203-78.231, P = 0.044] and usage of vasopressor drugs (OR = 2.622, 95%CI was 1.034-6.849, P = 0.042) were independent risk factors for septic cardiomyopathy. ④ ROC curve analysis showed the cut-off of histones H4 for predicting septic cardiomyopathy was 0.24 mg/L, the area under the curve was 0.684 (P < 0.01), with the sensitivity of 65.2%, and specificity of 68.9%.@*Conclusions@#Septic cardiomyopathy had a high incidence. Higher plasma histone H4 and the usage of vasopressor drugs were independent risk factors for septic cardiomyopathy.

Evaluation of microcirculatory changes after bundle therapy and prognostic value by the ratio of transcutaneous oxygen pressure and transcutaneous carbon dioxide pressure in the treatment of septic shock / 中华危重病急救医学

Objective To evaluate microcirculatory changes after bundle therapy and prognostic values of the ratio of transcutaneous oxygen pressure and transcutaneous carbon dioxide pressure (PtcO2/PtcCO2) in the treatment of septic shock. Methods A retrospective analysis was conducted. Patients with septic shock admitted to department of intensive care unit (ICU) of Northern Jiangsu People's Hospital from July 2017 to February 2019 were enrolled. The gender, age, infection site, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ), the length of ICU stay and 28-day prognosis were collected; PtcCO2, PtcO2, PtcO2/PtcCO2 ratio, arterial lactate (Lac), central venous oxygen saturation (ScvO2), mean arterial pressure (MAP) were measured before treatment (at admission) and 6 hours after bundle treatment. According to the 28-day prognosis, the patients were divided into survival group and death group, and the differences of each index between the two groups were compared. The risk factors of prognosis were analyzed by binaryLogistic regression analysis. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of the related indicators for the 28-day mortality of septic shock patients. Results A total of 78 patients with septic shock were enrolled, with 47 cases in survival group and 31 cases in death group. Compared with survival group, APACHEⅡ score and PtcCO2 were higher and PtcO2/PtcCO2 ratio was lower in death group [APACHEⅡ:28.33±6.35 vs. 21.61±6.64, PtcCO2 (mmHg, 1 mmHg = 0.133 kPa): 51.80±19.05 vs. 38.17±6.79, PtcO2/PtcCO2 ratio: 1.20±0.72 vs. 1.80±0.81, all P < 0.05]. Compared with before treatment, the PtcO2/PtcCO2 ratio, Lac, MAP were substantially improved at 6 hours of bundle therapy [PtcO2/PtcCO2 ratio: 1.76±0.81 vs. 1.56±0.82, Lac (mmol/L):3.74±2.40 vs. 4.42±2.60, MAP (mmHg): 83.34±7.58 vs. 71.00±5.36, all P < 0.05], and there was no changes in PtcCO2 and ScvO2. The PtcO2/PtcCO2 ratio at 6 hours of bundle therapy in the survival group was significantly higher than before treatment and was higher than that in death group (2.13±0.75 vs. 1.80±0.81, 1.19±0.53, both P < 0.05). There was no significant difference in PtcO2/PtcCO2 ratio of death group before and after treatment (1.19±0.53 vs. 1.20±0.72, P > 0.05). The binary Logistic regression showed that PtcO2/PtcCO2 ratio at 6 hours of bundle therapy and APACHEⅡ score were risk factors of prognosis [PtcO2/PtcCO2 ratio: odds ratio (OR) = 7.876, P = 0.026; APACHEⅡscore: OR = 0.846, P = 0.035]. ROC curve analysis showed that 6-hour of PtcO2/PtcCO2 ratio, APACHEⅡscore and 6-hour Lac level could predict 28-day mortality in septic shock patients, and the area under curve (AUC) was 0.864, 0.784, and 0.752 respectively. The cut-off value of 6-hour PtcO2/PtcCO2 ratio for predicting mortality in septic shock patients was 1.42, the sensitivity was 87.0％, and the specificity was 73.3％. In addition, the patients were divided into two groups according to whether the 6-hour PtcO2/PtcCO2 ratio was greater than 1.42. The results showed that: compared with the PtcO2/PtcCO2 < 1.42 group, the APACHEⅡ score in PtcO2/PtcCO2 ≥ 1.42 group was lower, the 6-hour Lac level was lower, 24-hour Lac reaching standard rate was higher and the 28-day mortality was lower. Conclusions Compared with the traditional metabolic parameters, the improvement of early microcirculatory perfusion in patients with septic shock can reflect the effect of bundle therapy. The PtcO2/PtcCO2 ratio at 6 hours of bundle therapy can be used as a new index to predict the prognosis of patients with septic shock which supports the monitoring and evaluation of microcirculation in the early stage of treatment in septic shock.

Elevated plasma histone is an independent risk factor for the development of septic cardiomyopathy / 中华危重病急救医学

Objective To investigate the epidemiology and independent risk factors of septic cardiomyopathy. Methods A prospective study was conducted. Patients with sepsis in intensive care unit (ICU) of Subei People's Hospital of Jiangsu Province, Yangzhou University, Fuxing Hospital, Capital Medical University and Beijing Electric Power Hospital from May 2016 to August 2019 were enrolled. All patients received standardized treatments according to the Surviving Sepsis Campaign (SSC) guidelines. Blood were collected within 24 hours of admission to ICU, and plasma histone H4, cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were detected by enzyme linked immunosorbent assay (ELISA). Transthoracic echocardiography was performed to record the ultrasonic parameters within 24 hours after admission. Sequential organ failure assessment (SOFA) score, usage of vasopressor drugs, and the prognosis of ICU were recorded. Patients were divided into two groups according to whether cardiomyopathy occurred or not, and the differences of each index between the two groups were compared. The correlation between plasma histone H4 and SOFA score, cTnI, NT-proBNP were investigated. Multivariate binaryLogistic regression was used to determine the risk factors for septic cardiomyopathy. The predictive value of histone H4 in septic cardiomyopathy was shown by the receiver operating characteristic (ROC) curve. Results 121 patients were included in this study, and there were 60 patients (49.6％) with septic cardiomyopathy. Thirty-six patients died, with an ICU mortality of 29.8％. ① Correlation analysis showed that plasma histone H4 in patients with septic cardiomyopathy was positively correlated with cTnI, SOFA score and NT-proBNP (r value was 0.512, 0.403 and 0.274, respectively, all P < 0.01). ② Compared with the non-cardiomyopathy group, the plasma histone H4, cTnI, usage of vasopressor drugs, SOFA score and ICU mortality in the cardiomyopathy group were significantly increased [histone H4 (mg/L):0.26 (0.23, 0.30) vs. 0.22 (0.17, 0.27), cTnI (μg/L): 0.21 (0.17, 0.30) vs. 0.18 (0.14, 0.22), usage of vasopressor drugs:83.3％ (50/60) vs. 65.6％ (40/61), SOFA score: 11 (9, 12) vs. 9 (8, 10), ICU mortality: 40.0％ (24/60) vs. 19.7％ (12/61), all P < 0.05]. Multivariate binary Logistic regression analysis showed that high histone H4 level [odds ratio (OR) = 6.502, 95％ confidence interval (95％CI) was 1.203-78.231, P = 0.044] and usage of vasopressor drugs (OR = 2.622, 95％CI was 1.034-6.849, P = 0.042) were independent risk factors for septic cardiomyopathy. ④ ROC curve analysis showed the cut-off of histones H4 for predicting septic cardiomyopathy was 0.24 mg/L, the area under the curve was 0.684 (P < 0.01), with the sensitivity of 65.2％, and specificity of 68.9％. Conclusions Septic cardiomyopathy had a high incidence. Higher plasma histone H4 and the usage of vasopressor drugs were independent risk factors for septic cardiomyopathy.

Prediction value of plasma histone in prognosis of sepsis patients / 中华危重病急救医学

Objective To explore the value of plasma histones in predicting the prognosis of sepsis patients. Methods The patients with sepsis admitted to intensive care unit (ICU) of Subei People's Hospital of Jiangsu Province Affiliated to Yangzhou University from May 2016 to June 2018 were enrolled as the research subjects, and healthy volunteers were selected as healthy control at the same period. The plasma levels of histones, cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), sequential organ failure assessment (SOFA) score, lactate (Lac), procalcitonin (PCT) on admission 24 hours, and use of vasoconstrictor agents, the length of ICU stay and ICU mortality were recorded. The patients were divided into survival group and death group according to the prognosis, and the differences of each index between the two groups were compared. Multivariate binary Logistic regression analysis was carried out to identify the independent risk factors of death. The correlation between histone and the levels of cTnI, NT-proBNP, PCT and Lac was analyzed. The value of plasma histone, cTnI, NT-proBNP, PCT and Lac in predicting the prognosis of patients was analyzed by receiver operating characteristic (ROC) curve. According to the threshold value of histone in predicting prognosis, the patients were divided into two groups, and the differences of various indicators between the two groups were compared. Results ① A total of 93 sepsis patients were included, with 29 cases of ICU death, and the mortality was 31.2%. ② Compared with the healthy control group, histones, cTnI, NT-proBNP were significant increased, besides, histones, cTnI in the death group were further increased compared with the survival group;in addition, SOFA, proportion of vasoconstrictor use were also significant higher than those in the survival group [histones (mg/L): 0.33 (0.28,0.45) vs. 0.22 (0.17,0.29), cTnI (μg/L): 0.25±0.13 vs. 0.20±0.08, SOFA: 11 (8, 12) vs. 9 (8, 11), the rate of vasopressor use: 93.1% (27/29) vs. 68.8% (44/64), all P < 0.05]. Statistically significant indicators between the two groups were included in multivariate binary Logistic regression analysis. The result showed that the independent risk factors affecting the prognosis of patients were the rate of vasopressor use [odds ratio (OR) = 5.277, P = 0.043] and the level of histone (OR = 79.244, P = 0.036). ③ The plasma histone level were positively correlated with cTnI (r = 0.577, P = 0.000), SOFA (r = 0.469, P = 0.000), NT-proBNP (r = 0.349, P = 0.001) and Lac (r = 0.357, P = 0.000), while there was no significant correlation between histone and PCT (r = 0.133, P = 0.205). ④ ROC curve analysis showed that the area under ROC curve (AUC) of histone predicting prognosis was 0.769 (P = 0.000); when the cut-off point was 0.30 mg/L, the sensitivity and specificity were 72.4% and 81.2% respectively. The AUC of SOFA score was 0.653 (P = 0.018), and the sensitivity and specificity were 58.6% and 70.3% respectively when the cut-off point was 10.50; while cTnI, NT-proBNP, Lac and PCT had little value in predicting the prognosis of patients. ⑤ Compared with the group with histone level lower than 0.3 mg/L, the group with histones level greater than 0.3 mg/L had higher SOFA score, more doses of vasopressor, higher cTnI, NT-proBNP, Lac and PCT levels, and higher ICU mortality [SOFA: 11 (10, 12) vs. 9 (8, 10), use of vasopressor: 84.8% (28/33) vs. 76.7% (46/60), cTnI (μg/L): 0.28 (0.19, 0.32) vs. 0.18 (0.12, 0.22), NT-proBNP (ng/L): 3 624.0 (2 800.0, 5 260.0) vs. 2 512.0 (1 361.8, 3 590.8), Lac (mmol/L): 2.25 (1.85, 3.50) vs. 1.60 (1.25, 2.35), PCT (μg/L): 2.10 (1.30, 4.03) vs. 1.60 (1.26, 2.33), ICU mortality: 48.5% (16/33) vs. 21.7% (13/60), all P < 0.05], while no statistical difference in the length of ICU stay was found. Conclusions The independent risk factors for ICU mortality of sepsis patients were high histone level and the use of vasopressor. Plasma histone can be regarded as an indicator in predicting the prognosis of patients with sepsis.

Clinical progress of vasopressin in the treatment of septic shock / 中华危重病急救医学

Septic shock is a serious stage of sepsis with a hospital mortality rate of more than 40%. The pathophysiology of septic shock is vasodilation and increased permeability. Fluid resuscitation, vasopressor drugs are usually used to maintain the perfusion pressure of the main organs. However, infectious patients usually have the irresponsive vessel to catecholamines and may lead to obvious side effects using high doses of norepinephrine or dopamine. Recent studies have shown that vasopressin (AVP) improves hemodynamics, increases tissue perfusion, and synergizes with norepinephrine in patients with septic shock, showing extent application prospects in the treatment of septic shock. The practice of AVP in septic shock is reviewed in this article in order to provide a reference for clinicians.

Biomarkers for the early diagnosis of sepsis / 中华危重病急救医学

Sepsis is the main cause of higher morbidity and mortality in hospitalized patients. Rapid recognition of sepsis as the cause of deterioration is desirable, so effective treatment can be initiated rapidly. More than 170 different biomarkers have been assessed for potential use in sepsis, more for prognosis than for diagnosis. None have sufficient specificity or sensitivity to be routinely employed in clinical practice. Therefore, it is essential for clinicians to seek more specific and sensitive biomarkers to early identify and diagnosis of sepsis patients, and further assess the severity and predict prognosis. Thus, combined biomarkers may be more effective than a single biomarker. This article focused on the current novel biomarkers of sepsis and their potential use at the bedside to guide clinical decision-making.

Impact of timing of antibiotic bundle therapy on outcomes in septic shock patients: a multicenter retrospective investigation / 中华全科医师杂志

The clinical data of 372 patients with septic shock admitted in departments of critical care medicine of three Grade A tertiary hospitals from January 2013 to December 2015 were retrospectively reviewed,including 211 survival cases and 161 fatal cases.According to septic shock early goal-directed therapy implementation,117 patients received bundle therapy (bundle group),including 30 cases with bundle goal-fully achieved,and 87 cases with bundle goal-partly achieved;and 255 cases received conventional treatment (non-bundle group).Muhiple logistic regression analysis showed that the multiple organ dysfunction syndrome score,length of ICU stay and first time using of antibiotics were independent risk factors for prognosis of septic shock (P ＜ 0.05).There was no significant difference in case fatality rate between bundle group and non-bundle group (46.2％ vs.42.0％,P ＞ 0.05),while the fatality in bundle goal-fully achieved group(20.0％)was significantly lower than that of goal-partly achieved group (55.2％) and non-bundle group (42.0％) (P ＜ 0.05).Survival curve analysis showed that the medial survival time in bundle goal-fully achieved group was significantly higher than that in non-bundle group (19.4 vs.10.5 days,P ＜0.05) and that in control group plus goal-partly achieved group(19.4 vs.12.9 days,P ＜0.05).Multiple Logistic regression analysis showed that central venous oxygen saturation and antibiotics using within one hour were protective factors for prognosis of septic shock (P ＜ 0.05).The results indicate that antibiotic bundle treatment of all indicators up to standards could significantly reduce the mortality of septic patients and early antibiotics is important in bundle treatment.