Types of Septic Cardiomyopathy: Prognosis and Influencing Factors - A Clinical Study.

Objective: To explore the prognostic outcomes associated with different types of septic cardiomyopathy and analyze the factors that exert an influence on these outcomes. Methods: The data collected within 24 hours of ICU admission included cardiac troponin I (cTnI), N-terminal pro-Brain Natriuretic Peptide (NT-proBNP); SOFA (sequential organ failure assessment) scores, and the proportion of vasopressor use. Based on echocardiographic outcomes, septic cardiomyopathy was categorized into left ventricular (LV) systolic dysfunction, LV diastolic dysfunction, and right ventricular (RV) systolic dysfunction. Differences between the mortality and survival groups, as well as between each cardiomyopathy subgroup and the non-cardiomyopathy group were compared, to explore the influencing factors of cardiomyopathy. Results: A cohort of 184 patients were included in this study, with LV diastolic dysfunction having the highest incidence rate (43.5%). The mortality group had significantly higher SOFA scores, vasopressor use, and cTnI levels compared to the survival group; the survival group had better LV diastolic function than the mortality group (p < 0.05 for all). In contrast to the non-cardiomyopathy group, each subgroup within the cardiomyopathy category exhibited elevated levels of cTnI. The subgroup with left ventricular diastolic dysfunction demonstrated a higher prevalence of advanced age, hypertension, diabetes mellitus, coronary artery disease, and an increased mortality rate; the RV systolic dysfunction subgroup had higher SOFA scores and NT-proBNP levels, and a higher mortality rate (P < 0.05 for all); the LV systolic dysfunction subgroup had a similar mortality rate (P > 0.05). Conclusion: Patients with advanced age, hypertension, diabetes mellitus, or coronary artery disease are more prone to develop LV diastolic dysfunction type of cardiomyopathy; cardiomyopathy subgroups had higher levels of cTnI. The RV systolic dysfunction cardiomyopathy subgroup had higher SOFA scores and NT-proBNP levels. The occurrence of RV systolic dysfunction in patients with sepsis significantly increased the mortality rate.

Identification and validation of the diagnostic signature associated with immune microenvironment of acute kidney injury based on ferroptosis-related genes through integrated bioinformatics analysis and machine learning.

Background: Acute kidney injury (AKI) is a common and severe disease, which poses a global health burden with high morbidity and mortality. In recent years, ferroptosis has been recognized as being deeply related to Acute kidney injury. Our aim is to develop a diagnostic signature for Acute kidney injury based on ferroptosis-related genes (FRGs) through integrated bioinformatics analysis and machine learning. Methods: Our previously uploaded mouse Acute kidney injury dataset GSE192883 and another dataset, GSE153625, were downloaded to identify commonly expressed differentially expressed genes (coDEGs) through bioinformatic analysis. The FRGs were then overlapped with the coDEGs to identify differentially expressed FRGs (deFRGs). Immune cell infiltration was used to investigate immune cell dysregulation in Acute kidney injury. Functional enrichment analysis and protein-protein interaction network analysis were applied to identify candidate hub genes for Acute kidney injury. Then, receiver operator characteristic curve analysis and machine learning analysis (Lasso) were used to screen for diagnostic markers in two human datasets. Finally, these potential biomarkers were validated by quantitative real-time PCR in an Acute kidney injury model and across multiple datasets. Results: A total of 885 coDEGs and 33 deFRGs were commonly identified as differentially expressed in both GSE192883 and GSE153625 datasets. In cluster 1 of the coDEGs PPI network, we found a group of 20 genes clustered together with deFRGs, resulting in a total of 48 upregulated hub genes being identified. After ROC analysis, we discovered that 25 hub genes had an area under the curve (AUC) greater than 0.7; Lcn2, Plin2, and Atf3 all had AUCs over than this threshold in both human datasets GSE217427 and GSE139061. Through Lasso analysis, four hub genes (Lcn2, Atf3, Pir, and Mcm3) were screened for building a nomogram and evaluating diagnostic value. Finally, the expression of these four genes was validated in Acute kidney injury datasets and laboratory investigations, revealing that they may serve as ideal ferroptosis markers for Acute kidney injury. Conclusion: Four hub genes (Lcn2, Atf3, Pir, and Mcm3) were identified. After verification, the signature's versatility was confirmed and a nomogram model based on these four genes effectively distinguished Acute kidney injury samples. Our findings provide critical insight into the progression of Acute kidney injury and can guide individualized diagnosis and treatment.

Early Diastolic Peak Velocity of Mitral Valve Annulus and Right Ventricular Systolic Tricuspid Annular Velocity as Predictors in Assessing Prognosis of Patients with Sepsis.

Objective: To analyze the epidemiological data of patients with septic cardiomyopathy and investigate the relationship between ultrasonic parameters and prognosis of patients with sepsis. Methods: In this study, we enrolled patients with sepsis who were treated at the Department of Critical Care Medicine in the Beijing Electric Power Hospital (No.1 Taipingqiao Xili, Fengtai District, Beijing) from January 2020 to June 2022. All patients received standardized treatment. Their general medical status and 28-day prognosis were recorded. Transthoracic echocardiography was performed within 24 hours after admission. We compared the ultrasound indexes between the mortality group and the survival group at the end of 28 days. We included parameters with significant difference in the logistic regression model to identify the independent risk factors for prognosis and evaluated their predictive value using receiver operating characteristic (ROC) curve. Results: We included 100 patients with sepsis in this study; the mortality rate was 33% and the prevalence rate of septic cardiomyopathy was 49%. The peak e' velocity and right ventricular systolic tricuspid annulus velocity (RV-Sm) of the survival group were significantly higher than those of the mortality group (P < 0.05). Results of logistic regression analysis showed that the peak e' velocity and RV-Sm were independent risk factors for prognosis. The area under curve of the peak e' velocity and the RV-Sm was 0.657 and 0.668, respectively (P < 0.05). Conclusion: The prevalence rate of septic cardiomyopathy in septic patients is high. In this study, we found that the peak e' velocity and right ventricular systolic tricuspid annulus velocity were important predictors of short-term prognosis.

[Study on the relationship between ventricular function parameters obtained by echocardiography and prognosis of patients with sepsis].

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.

Elevated plasma histone H4 level predicts increased risk of mortality in patients with sepsis.

BACKGROUND: Histones play a vital role in the pathogenesis of sepsis. However, studies on histones and the prognosis of sepsis patients are scarce. This study aims to investigate the relationship between histones and other biomarkers of sepsis. Furthermore, we aim to determine the role histones play in the prognosis of sepsis patients to explore the possibility of using them as a potential biomarker of sepsis. METHODS: We performed a prospective observational study on 136 patients. One hundred twenty-six of them had sepsis, and 10 were enrolled as healthy controls. Baseline blood samples were collected for plasma histone H4, cardiac troponin I (TnI), N-terminal pro-b-type natriuretic peptide (NT-proBNP), procalcitonin (PCT), and lactate. The site of infection, the use of vasopressor, and assessment scores of sequential organ failure were documented within 24 hours of admission. The duration of ICU stay and mortality was also recorded. RESULTS: The mean plasma histone levels of the patients were significantly higher than the healthy controls (P<0.001). Compared with the 89 survivors, the 37 patients who died had a higher rate of sequential organ failure assessment (SOFA) scores (P=0.002), more frequent use of vasopressors (P=0.033), and higher levels of histone H4 (P<0.001). Binary logistic regression analysis showed that high plasma histone H4 levels were independent risk factors for predicting mortality. The area under the receiver operating characteristic curve (0.731) verified that high plasma histone H4 level significantly predicted mortality. Plasma histone H4 levels positively correlated with the SOFA score, and plasma cardiac TnI. CONCLUSIONS: For patients with sepsis in the ICU, an elevated level of plasma histone H4 could be a risk factor associated with an increased mortality rate. Therefore, plasma histone H4 may be a useful biomarker for determining the prognosis of these patients.

Elevated Plasma Histone H4 Levels Are an Important Risk Factor in the Development of Septic Cardiomyopathy

Background: Myocardial impairment is a major complication and an important prognostic predictor of sepsis. Therefore, early and accurate diagnosis as well as timely management of septic cardiomyopathy is critical to achieve favorable outcomes. Aims: To investigate the risk factors of septic cardiomyopathy. Study Design: Cross-sectional study. Methods: This study performed between May 2016 and June 2018 recruited 93 septic patients from the intensive care unit. All patients received standardized treatments. Septic patients were divided into two groups: non cardiomyopathy (n=45) and septic cardiomyopathy group (n=48). Blood samples were collected and transthoracic echocardiography was performed within 24 hours of intensive care unit admission. Septic patients with one ultrasound abnormality but no history of heart disease were diagnosed as having septic cardiomyopathy. Plasma histones, cardiac troponin I, and N-terminal pro-brain natriuretic peptide were measured using ELISA. Sequential Organ Failure Assessment scores, vasopressor use, and the outcomes of intensive care unit stay were analyzed. Spearman rank analysis was used to determine the correlation between plasma histone H4 and other parameters. Binary logistic regression and receiver operating characteristic curve analysis were used to determine the risk factors for septic cardiomyopathy. Results: Compared with the non-cardiomyopathy group, the septic cardiomyopathy group had significantly higher plasma H4 and cardiac troponin I levels, a higher Sequential Organ Failure Assessment score, more frequent vasopressor use, and a higher mortality rate (p<0.05). Plasma histone H4 levels positively correlated with cardiac troponin I (r=0.577, p<0.001), N-terminal pro-brain natriuretic peptide (r=0.349, p=0.001), and Sequential Organ Failure Assessment scores (r=0.469, p<0.001). Binary logistic regression and receiver operating characteristic curve analyses revealed that elevated plasma histone H4 levels and vasopressor use were important risk factors for septic cardiomyopathy (p<0.05). Conclusion: Elevated plasma histone H4 levels could be used to predict septic cardiomyopathy in patients with sepsis.

[Prediction value of plasma histone in prognosis of sepsis patients].

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.

Effects of intensive blood pressure lowering on mortality and cardiovascular and renal outcomes in type 2 diabetic patients: A meta-analysis.

BACKGROUND: Previous studies have demonstrated that intensive blood pressure (BP) lowering treatment reduces the risk of all-cause mortality and provides greater vascular protection for patients with hypertension. Whether intensive BP lowering treatment is associated with such benefits in patients with type 2 diabetes mellitus remain unknown. We aimed to clarify these benefits by method of meta-analysis. METHODS: The PubMed, EMBASE, Science Citation Index and Cochrane Library databases were searched to identify randomized controlled trials (RCT) that fulfilled study inclusion criteria. Two investigators independently extracted and summarized the relevant data of the included trials. Random-effects model was applied to calculate the estimates of all effect measures. RESULTS: We included 16 RCTs and our meta-analysis showed that intensive BP lowering treatment vs less intensive BP lowering treatment resulted in significant reductions in the all-cause mortality risk [relative risk (RR), 0.82; 95% CI, 0.70-0.96], major CV events (RR, 0.82; 95% CI, 0.73-0.92, MI (RR, 0.86; 95% CI, 0.77-0.96), stroke (RR, 0.72; 95% CI, 0.60-0.88, CV death (RR, 0.73; 95% CI, 0.58-0.92) and albuminuria progression (RR, 0.91 95% CI, 0.84-0.98). However, intensive BP lowering treatment had no clear effect on non-CV death (RR, 0.97; 95% CI, 0.79-1.20), heart failure (HF) (RR, 0.88; 95% CI, 0.71-1.08) or end-stage kidney disease (ESKD) (RR, 1.00; 95% CI, 0.75-1.33). Subgroup analysis showed that the reduction in all cause-mortality was consistent across most patient groups, and intensive BP lowering treatment had a clear benefit even in patients with systolic blood pressure lower than 140 mm Hg. However, the benefit differed in patients with different CV risk (≥10%: RR, 0.77, 95%CI, 0.64-0.91; <10%: RR, 1.04, 95%CI, 0.84-1.29; Phetero = 0.028). CONCLUSIONS: Our data indicate that intensive BP lowering treatment provides greater benefits than less intensive treatment among patients with type 2 diabetes mellitus. Further studies are required to more clearly evaluate the benefits and harms of BP targets below those currently recommended with intensive BP lowering treatment.

[Elevated plasma histone is an independent risk factor for the development of septic cardiomyopathy].

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.

[Variability of peripheral arterial peak velocity predicts fluid responsiveness in patients with septic shock].

OBJECTIVE: To explore the accuracy of fluid responsiveness assessment by variability of peripheral arterial peak velocity and variability of inferior vena cava diameter (ΔIVC) in patients with septic shock. METHODS: A prospective study was conducted. The patients with septic shock undergoing mechanical ventilation (MV) admitted to intensive care unit (ICU) of Beijing Electric Power Hospital from January 2016 to December 2017 were enrolled. According to sepsis bundles of septic shock, volume expansion (VE) was conducted. The increase in cardiac index (ΔCI) after VE ≥ 10% was defined as liquid reaction positive (responsive group), ΔCI < 10% was defined as the liquid reaction negative (non-responsive group). The hemodynamic parameters [central venous pressure (CVP), intrathoracic blood volume index (ITBVI), stroke volume variation (SVV), ΔIVC, variability of carotid Doppler peak velocity (ΔCDPV), and variability of brachial artery peak velocity (ΔVpeak-BA)] before and after VE were monitored. The correlations between the hemodynamic parameters and ΔCI were explored by Pearson correlation analysis. Receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of all hemodynamic parameters on fluid responsiveness. RESULTS: During the study, 74 patients with septic shock were included, of whom 9 were excluded because of peripheral artery stenosis, recurrent arrhythmia or abdominal distension influencing the ultrasound examination, and 65 patients were finally enrolled in the analysis. There were 31 patients in the responsive group and 34 in the non-responsive group. SVV, ΔIVC, ΔCDPV and ΔVpeak-BA before VE in responsive group were significantly higher than those of the non-responsive group [SVV: (12.3±2.4)% vs. (9.2±2.1)%, ΔIVC: (22.3±5.3)% vs. (15.5±3.7)%, ΔCDPV: (15.3±3.3)% vs. (10.3±2.4)%, ΔVpeak-BA: (14.5±3.3)% vs. (9.6±2.3)%, all P < 0.05]. There was no significant difference in CVP [mmHg (1 mmHg = 0.133 kPa): 7.5±2.5 vs. 8.2±2.6] or ITBVI (mL/m2: 875.2±173.2 vs. 853.2±192.0) between the responsive group and non-responsive group (both P > 0.05). There was no significant difference in hemodynamic parameter after VE between the two groups. Correlation analysis showed that SVV, ΔIVC, ΔCDPV, and ΔVpeak-BA before VE showed significant linearity correlation with ΔCI (r value was 0.832, 0.813, 0.854, and 0.814, respectively, all P < 0.05), but no correlation was found between CVP and ΔCI (r = -0.342, P > 0.05) as well as ITBVI and ΔCI (r = -0.338, P > 0.05). ROC curve analysis showed that the area under ROC curve (AUC) of SVV, ΔIVC, ΔCDPV, and ΔVpeak-BA before VE for predicting fluid responsiveness was 0.857, 0.826, 0.906, and 0.866, respectively, which was significantly higher than that of CVP (AUC = 0.611) and ITBVI (AUC = 0.679). When the optimal cut-off value of SVV for predicting fluid responsiveness was 11.5%, the sensitivity was 70.4%, and the specificity was 94.7%. When the optimal cut-off value of ΔIVC was 20.5%, the sensitivity was 60.3%, and the specificity was 89.7%. When the optimal cut-off value of ΔCDPV was 13.0%, the sensitivity was 75.2%, and the specificity was 94.9%. When the optimal cut-off value of ΔVpeak-BA was 12.7%, the sensitivity was 64.8%, and the specificity was 89.7%. CONCLUSIONS: Ultrasound assessment of ΔIVC, ΔCDPV, and ΔVpeak-BA could predict fluid responsiveness in patients with septic shock receiving mechanical ventilation. ΔCDPV had the highest predictive value among these parameters.

Exploring the best predictors of fluid responsiveness in patients with septic shock.

OBJECTIVE: To evaluate respiratory variations in carotid and brachial peak velocity and other hemodynamic parameters to predict responsiveness to fluid challenge. METHODS: A prospective observational study was performed on mechanically ventilated patients with septic shock. Outcomes included the measurements of central venous pressure, intrathoracic blood volume index, stroke volume variation (SVV), pleth variability index(PVI), and ultrasound assessments of respiratory variations in inferior vena cava diameter (ΔIVC), carotid Doppler peak velocity (ΔCDPV), and brachial artery peak velocity (ΔVpeak brach). RESULTS: All patients received 200 mL normal saline challenge. There were 27 responders and 22 non-responders. Responders had higher SVV, PVI, ΔIVC, ΔCDPV, and ΔVpeak brach measurements. In addition, all these measurements had statistically significant linear correlations with changes in cardiac index (CI).When responders were defined by ΔCI≥10%, receiver operating characteristics (ROC) curve analysis showed that fluid responsiveness could be predicted:11.5% optimal cut-off 1evels of SVV with sensitivity of 75% and specificity of 85%, 15.5% optimal cut-off 1evels of PVI with sensitivity of 65% and specificity of 80%, 20.5% optimal cut-off 1evels of ΔIVC with sensitivity of 67% and specificity of 77%, 13% optimal cut-off 1evels of ΔCDPV with sensitivity of 78%% and specificity of 90%, 11.7% optimal cut-off 1evels of ΔVpeak brach with sensitivity of 70% and specificity of 80%. CONCLUSION: Ultrasound assessment of ΔIVC and ΔVpeak brach, especially ΔCDPV, could predict fluid responsiveness and might be recommended as a continuous and noninvasive method to monitor functional hemodynamic parameter in mechanically ventilated patients with septic shock.

Improved sepsis bundles in the treatment of septic shock: a prospective clinical study.

BACKGROUND: Sepsis bundles can decrease mortality in patients with severe sepsis or septic shock. However, current methods of measuring pressure, such as central venous pressure, are inadequate. This study investigated the effect of improved sepsis bundles informed by pulse-indicated continuous cardiac output. METHODS: We compared the outcome of treatment with sepsis bundles informed by either conventional pressure measurements or pulse-indicated continuous cardiac output. Patients in 2 groups received fluid resuscitation, standard antibiotics, and oxygen therapy. RESULTS: A total of 105 patients with septic shock were randomly divided into 2 groups: the conventional sepsis bundle group (n = 52) or the improved sepsis bundle group (ISBG, n =53). The ISBG significantly reduced the mean Acute Physiology and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment scores. Significantly fewer ISBG-treated patients received vasoactive drugs compared to conventional sepsis bundle group-treated patients. In addition, patients in the ISBG exhibited a significantly increased arterial blood lactate clearance rate and required less total fluid resuscitation and a shorter duration of mechanical ventilation and stay in the intensive care unit. CONCLUSIONS: Pulse-indicated continuous cardiac output-directed sepsis bundles can reduce the severity of septic shock, provide more accurate fluid resuscitation, and reduce the duration of mechanical ventilation and stay in the intensive care unit.

[A prospective clinical study of pleth variability index in prediction of volume responsiveness in patients with septic shock].

OBJECTIVE: To evaluate the role of pleth variability index ( PVI ) by passive leg raising ( PLR ) test in volume responsiveness and volume status prediction in patients with septic shock. METHODS: A prospective randomized controlled trial ( RCT ) was conducted. Eighty-seven patients suffering from septic shock undergoing mechanical ventilation in Department of Critical Care Medicine of Subei People's Hospital from June 2012 to September 2014 were enrolled. The hemodynamic changes before and after PLR were monitored by pulse indicated continuous cardiac output ( PiCCO ) and PVI monitoring. Responsive group: positive fluid response was defined as an increase in cardiac index ( CI )≥10% after PLR. Unresponsive group: negative fluid response was defined as an increase in CI<10% after PLR. The hemodynamic parameters, including heart rate ( HR ), mean arterial pressure ( MAP ), central venous pressure ( CVP ), stroke volume variation ( SVV ), CI and PVI, and the changes in cardiac parameters (ΔHR, ΔMAP, ΔCVP, ΔSVV, ΔCI, and ΔPVI ) before and after PLR were determined. The relations between hemodynamic parameters and their changes with ΔCI were analyzed by the Pearson analysis. The role of the parameters for volume responsiveness prediction was evaluated by receiver operating characteristic ( ROC ) curves. RESULTS: 145 PLRs in 87 patients with septic shock were conducted, with 67 in responsive group and 78 in unresponsive group. There were no statistically significant differences in HR, MAP, CVP and CI before PLR between the responsive and unresponsive groups. SVV and PVI in responsive group were significantly higher than those in the unresponsive group [ SVV: ( 16.9±3.1 )% vs. ( 8.4±2.2 ) %, t = 9.078, P = 0.031; PVI: ( 20.6±4.3 )% vs. ( 11.1±3.2 )%, t = 19.189, P = 0.022 ]. There were no statistically significant differences in HR, MAP, CVP, SVV, and PVI after PLR between the responsive group and unresponsive group. CI in the responsive group was significantly higher than that in the unresponsive group ( mL×s(-1)×m(-2): 78.3±6.7 vs. 60.0±8.3, t = 2.902, P = 0.025 ). There were no statistically significant differences in ΔHR, ΔMAP, ΔCVP between responsive group and unresponsive group. ΔSVV, ΔCI and ΔPVI in responsive group were significantly higher than those in the unresponsive group [ ΔSVV: ( 4.6±1.5 )% vs. ( 1.8±0.9 )%, t = 11.187, P = 0.022; ΔCI ( mL×s(-1)×m(-2) ): 18.3±1.7 vs. 1.7±0.5, t = 3.696, P = 0.014; ΔPVI: ( 6.4±1.1 )% vs. ( 1.3±0.2 )%, t = 19.563, P = 0.013 ]. No significant correlation between HR, MAP or CVP before PLR and ΔCI was found. SVV ( r = 0.850, P = 0.015 ) and PVI ( r = 0.867, P = 0.001 ) before PLR were correlated with ΔCI. It was shown by ROC curve that the area under ROC curve ( AUC ) for SVV fluid responsiveness prediction was 0.948, and cut-off of SVV was 12.4%, the sensitivity was 85.4%, and specificity was 86.6%. The AUC for PVI fluid responsiveness prediction was 0.957, and cut-off was 14.8%, the sensitivity was 87.5%, and specificity was 84.8%. It was higher than other hemodynamic parameters ( HR, MAP, CVP ). CONCLUSIONS: PVI and SVV can better predict fluid responsiveness in mechanically ventilating patients with septic shock after PLR. PVI as a new continuous, noninvasive and functional hemodynamic parameter has the same accuracy as SVV.

[Clinical studies of surviving sepsis bundles according to PiCCO on septic shock patients].

OBJECTIVE: To explore the effect of early goal-directed therapy (EGDT) according to pulse indicated continuous cardiac output (PiCCO) on septic shock patients. METHODS: Eighty-two septic shock patients in Subei People's Hospital of Jiangsu Province from January 2009 to December 2012 were enrolled and randomly divided into two groups using a random number table, standard surviving sepsis bundle group (n=40) and modified surviving sepsis bundles group (n=42). The patients received the standard EGDT bundles in standard surviving sepsis bundle group. PiCCO catheter was placed in modified surviving sepsis bundles group. Fluid resuscitation was guided by intrathoracic blood volume index (ITBVI) with the aim of 850-1 000 mL/m(2). Dobutamine was used to improve the heart function according to left ventricular contractile index (dPmax) and stroke volume index (SVI). The mean arterial blood pressure (MAP) was maintained 65 mmHg (1 mmHg=0.133 kPa) or above with norepinephrine. Extra-vascular lung water was monitored for the titration of liquid and diuretics. The acute physiology and chronic health evaluation II (APACHEII) score, sequential organ failure assessment (SOFA) score, the number of patients needed vasopressor, serum procalcitonin (PCT), lactic acid and lactate extraction ratio, the amount of fluid resuscitation, duration of mechanical ventilation, duration of intensive care unit (ICU) stay, hospital mortality were recorded in both groups. RESULTS: After treatment, the APACHEII score, SOFA score and the number of patients needed vasopressor were gradually reduced in both groups, and those in modified surviving sepsis bundle group were significantly lower than those of standard sepsis bundle group at 72 hours (APACHEII score: 13.1±6.5 vs. 20.9±7.5, SOFA score: 8.8±4.3 vs. 14.6±4.9, the number of patients needed vasopressor: 8 vs. 17, all P<0.05). Arterial blood lactate clearance rate was gradually increased after treatment in both groups. Lactate clearance rate in modified surviving sepsis bundle group was significantly higher than that of standard surviving sepsis bundle group [6 hours: (18.2±8.3)% vs. (10.8±7.5)%, t=-6.036, P=0.001; 12 hours: (22.6±7.3)% vs. (12.4±8.1)%, t=-4.536, P=0.001; 24 hours: (27.8±5.6)% vs. (16.4±9.5)%, t=-5.882, P=0.000]. The amount of fluid resuscitation within 6 hours in modified surviving sepsis bundle group increased significantly compared with standard surviving sepsis bundle group (3 608±715 mL vs. 2 809±795 mL, t=-3.865, P=0.033). The amount of fluid resuscitation within 24, 48 and 72 hours in modified surviving sepsis bundle group was significantly less than that of standard modified surviving sepsis bundle group with the nadir at 72 hours (918±351 mL vs. 1 805±420 mL, t=5.907, P=0.037). Duration of mechanical ventilation (98.4±20.3 hours vs. 143.3±29.6 hours, t=9.766, P=0.001) and ICU stay (7.1±3.1 days vs. 9.5±2.5 days, t=2.993, P=0.004) were significantly reduced in modified surviving sepsis bundle group compared with standard surviving sepsis bundle group. The hospital mortality in modified surviving sepsis bundle group was slightly lower than that in standard surviving sepsis bundle group [16.7% (7/42) vs. 17.5%(7/40), χ (2)=0.010, P=0.920]. CONCLUSIONS: Modified surviving sepsis bundle treatment according PiCCO can reduce the severity of disease in patients with septic shock, can make more accurately guide fluid resuscitation, and can reduce lung water and duration of mechanical ventilation and ICU stay. It has great clinical significance.

[The impact of different fluid management on mortality in patients with septic shock].

OBJECTIVE: To find out the influential effect of different fluid management on mortality of patients with septic shock in different phases. METHODS: From March 2007 to December 2009, a retro spective controlled study was conducted on the clinical data of 107 adult patients with septic shock in the intensive care unit (ICU) of Subei Hospital of Jiangsu Province. The patients were divided into survival group ( n =68) and non survival group ( n =39) according to the final outcome. A number of demographic and variables were collected from the medical record. The acute physiology and chronic health evaluationII (APACHEII) score, sequential organ failure assessment (SOFA), liquid intake and output volume and its balance daily within 1 week, 24 hour early goal directed therapy (EGDT) and conservative late fluid management (CLFM) were compared between two groups. The Logistic regression statistics was used to determine the relationship between APACHEII, SOFA, EGDT, CLFM and survival. RESULTS: The single variable analysis showed that there was significant difference in the parameters of oxygenation index in 7 days ,arterial blood lactate clearance within 24 hours, acute lung injury, length of mechanical ventilation, length of ICU stay and in hospital, the goal of fluid management including 24 hour EGDT, 24 hour CLFM, fluid balance in 24 hours, total fluid input within 7 days, negative fluid balance and times during 7 days between two groups. Logistic regression showed that failure to achieve 24 hour EGDT and late CLFM,a negative balance of <2 000 ml, total fluid input of >20 000 ml within 1 week were independent risk factors of death, and odds ratio ( OR ) was 4.159, 4.431, 23.788 and 4.353, respectively, the P value was 0.035, 0.019, 0.000, 0.025, respectively. The 28 day mortality in 24 hour EGDT and CLFM group (12.5%) was significantly lower than that of 24 hour EGDT with liberal late fluid management (LLFM) group (46.2%) and that in the group of patients in whom with failure to have 24 hour EGDT with CLFM or LLFM (30.0%, 76.2%, P<0.05 or P <0.01). CONCLUSION: Both early achievement of 24 hour EGDT and late CLFM for the patients with septic shock can lower mortality.

[Changes of plasma fibrinogen level among acute ischemic stroke subtypes according to TOAST criteria and effects of Songling Xuemaikang].

OBJECTIVE: To investigate the changes of plasma fibrinogen level among acute ischemic stroke (ACI) subtypes according to Trial of Org10172 in Acute Stroke Treatment (TOAST) criteria and effects of Songling Xuemaikang. METHOD: The 160 patients with acute ischemic stroke were divided into two groups randomly: treatment group 85 cases (Songling Xuemaikang + Shuxuetong + Aspirin enterie coated tablets), control group 75 cases (Shuxuetong + Aspirin enterie ccoated tablets). The plasma fibrinogen was detected before and after treatment. RESULT: Compared with OC subtype, Fbg was higher in LAA, CE and SAO subtypes (P < 0.05). Compared with UE subtype, Fbg was higher in LAA, CE and SAO subtypes (P < 0.05). There was a significantly difference between LAA and SAO (P < 0.05). In LAA, SAO, CE of treatment group,the Fbg level were lowered significantly at the 15th day compared with pretherapy (P < 0.05). There was a significantly difference of Fbg between treatment group and control group In LAA, SAO and CE subtypes at the 15th day (P < 0.05). CONCLUSION: Fbg produces a marked effect at the pathomechanism of LAA, SAO and CE subtypes. Songling Xuemaikang can depress the plasma fibrinogen level of ACI, and be an effective adjunctive therapy on ACI.

[Study of erythromycin and metoclopramide in treatment of feeding intolerance of critically ill patients in intensive care unit].

OBJECTIVE: To compare the effect of erythromycin and metoclopramide on feeding intolerance of critically ill patients in intensive care unit (ICU). METHODS: One hundred and fifty-two critically ill patients in ICU who needed early enteral nutrition exceeding 7 days between January 2007 and January 2009 were included in the study. The patients were randomly divided into three groups: erythromycin group (200 mg intravenous drip, once every 12 hours), metoclopramide group (10 mg intravenous injection, once every 8 hours), and combination therapy group. The whole experiment was carried out for 7 days. Residual gastric volume was aspirated and measured every day at 03:00, 09:00, 15:00 and 21:00. The daily mean gastric residual volume was compared. At the same time, the daily effectiveness of erythromycin and metoclopramide on the success of feeding was also compared. The factors associated with a poor response to prokinetic therapy were looked for. RESULTS: The daily gastric residual volume in the combination therapy group was smallest, the maximum was (40+/-8) ml; the maximum of gastric residual volume in erythromycin group was (42+/-7) ml; the maximum of gastric residual volume in metoclopramide group was (59+/-8) ml (P<0.05 or P<0.01). The successful rate of feeding was highest in the combination therapy group, and it was as high as 97.4%, the erythromycin group ranked the second (90.0%), and that of the metoclopramide group was lowest (89.5%, P<0.05 or P<0.01). Factors that were associated with a poor response to prokinetic therapy was high pretreatment 24-hour gastric residual volume (r=-0.584, P=0.000), high blood sugar level (r=-0.345, P=0.029), a high acute physiology and chronic health evaluation II (APACHEII) score (r=-0.437, P=0.005), and requirement for inotropic drug support (r=-0.389, P=0.041). CONCLUSION: Low dose of erythromycin could improve the successful rate of feeding in critically ill patients in ICU. The combined administration of erythromycin and metoclopramide was more effective. Its side effect was minimal.

[A prospective randomized control clinical study of the effect of Xuebijing injection on prognosis of acute respiratory distress syndrome patients].

OBJECTIVE: To study the effect of Xuebijing injection on prognosis, immune function, adrenal function and inflammatory reaction during the treatment of acute respiratory distress syndrome (ARDS). METHODS: From January 2008 through December 2008, a clinical study was conducted on consecutive adult patients with ARDS in intensive care unit (ICU). The patients were divided into Xuebijing group (31 patients) and control group (30 patients). Both groups were treated with the routine therapy of ARDS, and in addition, Xuebijing injection was used in a dose of 100 ml twice a day for 7 days in Xuebijing group. Duration of mechanical ventilation (MV) and ICU length of stay, 28-day mortality, acute physiology and chronic health evaluation II (APACHE II), Murray and Marshall scores were recorded in both groups. Every patient was given one injection of corticotrophin 250 microg intravenously before and after treatment, and plasma cortisol level was detected by radio-immunoassay before the injection (T0) and 30 minutes (T30) and 60 minutes (T60) after the injection. The ratio of adrenal insufficiency was evaluated according to diagnostic criteria of relative adrenal insufficiency, which was defined as the difference between T0 and the highest value of T30 or T60 (Delta Tmax)< or =248.4 nmol/L. Human leukocyte antigen-DR (HLA-DR), subpopulations of T lymphocyte (CD4(+)/CD8(+)), interleukin-6 (IL-6), IL-10 in peripheral blood was also determined. RESULTS: Murray (1.5+/-1.5) and Marshall score (2.9+/-2.7) and the level of IL-6 [(3.4+/-1.9) micromol/L], IL-10 [(1.5+/-0.8) micromol/L] in the Xuebijing group were decreased significantly after the use of Xuebijing compared with control group [4.3+/-3.1, 6.3+/-4.1, (8.9+/-10.2) micromol/L, (4.2+/-4.8) micromol/L, respectively, all P<0.01], while the values of HLA-DR (41.1+/-10.1), CD4(+) (58.0+/-10.7), CD4(+)/CD8(+) (1.9+/-0.3) were increased compared with control group [30.6+/-15.0, 50.5+/-16.2, 1.4+/-0.7, respectively, P<0.05 or P<0.01]. The ratio of adrenal insufficiency in Xuebijing group (45.2%) was lower than that of control group (83.3%), while that of Delta Tmax [(328.4+/-278.3) micromol/L] was higher than that of control group [(172.8+/-110.8) micromol/L, both P<0.01]. MV duration [(4.0+/-3.3) days] and ICU length of stay [(8.4+/-4.2) days] were less than those of control group [(5.9+/-3.8) days, (12.0+/-7.6) days, both P<0.05], and 28-day mortality in Xuebijing group was 35.5%, which was 11.2% less than that of control group (46.7%), but there was no statistically significant difference between two groups (P>0.05). CONCLUSION: Xuebijing injection improves organ function, decreases MV duration and ICU length of stay in ARDS patients. The underlying mechanism may involve modulation of the immune function, decrease in the degree of adrenal insufficiency, and modulation of regulating inflammatory reaction.

[The impact of sepsis bundles on mortality in patients with sepsis shock: a prospective clinical study].

OBJECTIVE: To survey the impact of sepsis bundle on prognosis of septic shock. METHODS: From January 2007 to June 2008, a prospective clinical study was conducted on consecutive adult patients with sepsis shock in intensive care unit (ICU). The study of sepsis bundle on septic shock was divided into before training (from January to September 2007) and trained phases (from October 2007 to June 2008), and the patients were divided into control group and death group. The relationship between sepsis bundle index and prognosis at 6 hours and 24 hours was analyzed with logistic regression analysis. The independent factors of death due to septic shock were looked for. The compliance of sepsis bundles, duration of mechanical ventilation (MV), ICU stay, and 28-day mortality were noted. RESULTS: One hundred patients, including 51 patients before training and 49 patients after training were enrolled for study. Thirty-six patients survived and 64 patients died. All the patients met the criteria for the diagnosis of sepsis shock. Through analysis of the parameters with logistic regression, it could be found that 6-hour early goal-directed therapy (EGDT) and 24-hour EGDT were the two independent protective factors of death, and standardized regression coefficient was 0.046 and 0.120 respectively (both P < 0.01). Compliance with sepsis bundles was low in training phase, the compliance increased apparently after training. Among them, 6-hour EGDT and 24-hour EGDT compliance increased to 55.1%, 65.3% from 19.6%, 35.3% (both P < 0.01). Compared with the group before training, the duration of MV [(166.6+/-156.4) hours vs. (113.6+/-73.6) hours], that of ICU stay [(9.4+/-7.6) days vs. (6.0+/-3.9) days] and 28-day mortality (72.5% vs. 55.1%, P < 0.05 or P < 0.01) was significantly lower after training. CONCLUSION: Sepsis bundle is able to improve survival rate in patients in septic shock. Compliance with sepsis bundles is low before training, and training can improve the compliance and decrease mortality rate of septic shock.