Leclercia adecarboxylata infective endocarditis in a man with mitral stenosis: A case report and review of the literature.

BACKGROUND: Infective endocarditis (IE) is a rare disease with a high mortality rate. Leclercia adecarboxylata (L. adecarboxylata) is a movable Gram-negative bacillus of enterobacteriaceae, and it can rarely be a pathogen which often affects immunodeficient patients. There are about three cases of immunocompetent patients with monomicrobial L. adecarboxylata infection. There are only three reported cases of IE caused by L. adecarboxylata in the world. The mitral valve is often affected in IE, and the prognosis for IE with mitral valve lesions is often poor. CASE SUMMARY: A 51-year-old man was found to have moderate to severe mitral stenosis on echocardiography. He came to our Cardiothoracic Surgery Department for surgical management. A diastolic murmur was heard on auscultation of the heart in the mitral region. On the second day of hospitalisation, he presented with slurred speech, reduced muscle strength in the left limb, and acute cerebral infarction on cranial computed tomography. Surgical treatment was decided to postpone. On the ninth day of admission, the patient developed a sudden high fever and shock and was transferred to the Cardiac Intensive Care Unit, where echocardiogram revealed an anterior mitral valve leaflet vegetation. After empirical anti-infective treatment with vancomycin (1g q12h), an emergency valve replacement was performed. Bacterial culture identified L. adecarboxylata. Anti-infective treatment with piperacillin-tazobactam (4.5g q8h) was added for 4 wk. Follow-up echocardiography showed normal bioprosthetic valve function after mitral valve replacement. CONCLUSION: We report the first case of L. adecarboxylata IE in China, and clinicians should pay attention to this pathogen.

Early administration of hydrocortisone, vitamin C, and thiamine in adult patients with septic shock: a randomized controlled clinical trial.

BACKGROUND: The combination therapy of hydrocortisone, vitamin C, and thiamine has been proposed as a potential treatment in patients with sepsis and septic shock. However, subsequent trials have reported conflicting results in relation to survival outcomes. Hence, we performed this randomized controlled trial (RCT) to evaluate the efficacy and safety of early combination therapy among adult patients with septic shock. METHODS: This single-center, double-blind RCT enrolled adult patients with diagnosis of septic shock within 12 h from Northern Jiangsu People's Hospital between February 2019 and June 2021. Recruited patients were randomized 1:1 to receive intervention (hydrocortisone 200 mg daily, vitamin C 2 g every 6 h, and thiamine 200 mg every 12 h) or placebo (0.9% saline) for 5 days or until ICU discharge. The primary endpoint was 90-day mortality. The secondary endpoints included mortality at day 28, ICU discharge, and hospital discharge; shock reversal; 72-h Delta SOFA score; ICU-free days, vasopressor-free days, and ventilator support -free days up to day 28; ICU length of stay (LOS) and hospital LOS. RESULTS: Among 426 patients randomized, a total of 408 patients with septic shock were included in the per-protocol (PP) analysis, of which 203 were assigned to the intervention group and 205 to the placebo group. In the PP population, the primary outcome of 90-day mortality was 39.9% (81/203) and 39.0% (80/205) in the intervention and the placebo groups, respectively, and was not significantly different (P = 0.86). There was no significant difference between two groups in 28-day mortality (36.5% vs. 36.1%, P = 0.94) or the ICU mortality (31.5% vs. 28.8%, P = 0.55) and hospital mortality (34.5% vs. 33.2%, P = 0.78). No other secondary outcomes showed significant differences between two groups, including shock reversal, vasopressor-free days, and ICU LOS. Intention-to-treat analysis included all the 426 patients and confirmed these results (all P > 0.05). CONCLUSION: Among adult patients with septic shock, early use of hydrocortisone, vitamin C, and thiamine combination therapy compared with placebo did not confer survival benefits. Trial registration ClinicalTrials.gov: NCT03872011 , registration date: March 12, 2019.

Retrospective Study of Critically Ill COVID-19 Patients With and Without Extracorporeal Membrane Oxygenation Support in Wuhan, China.

Background: Extracorporeal membrane oxygenation (ECMO) might benefit critically ill COVID-19 patients. But the considerations besides indications guiding ECMO initiation under extreme pressure during the COVID-19 epidemic was not clear. We aimed to analyze the clinical characteristics and in-hospital mortality of severe critically ill COVID-19 patients supported with ECMO and without ECMO, exploring potential parameters for guiding the initiation during the COVID-19 epidemic. Methods: Observational cohort study of all the critically ill patients indicated for ECMO support from January 1 to May 1, 2020, in all 62 authorized hospitals in Wuhan, China. Results: Among the 168 patients enrolled, 74 patients actually received ECMO support and 94 not were analyzed. The in-hospital mortality of the ECMO supported patients was significantly lower than non-ECMO ones (71.6 vs. 85.1%, P = 0.033), but the role of ECMO was affected by patients' age (Logistic regression OR 0.62, P = 0.24). As for the ECMO patients, the median age was 58 (47-66) years old and 62.2% (46/74) were male. The 28-day, 60-day, and 90-day mortality of these ECMO supported patients were 32.4, 68.9, and 74.3% respectively. Patients survived to discharge were younger (49 vs. 62 years, P = 0.042), demonstrated higher lymphocyte count (886 vs. 638 cells/uL, P = 0.022), and better CO2 removal (PaCO2 immediately after ECMO initiation 39.7 vs. 46.9 mmHg, P = 0.041). Age was an independent risk factor for in-hospital mortality of the ECMO supported patients, and a cutoff age of 51 years enabled prediction of in-hospital mortality with a sensitivity of 84.3% and specificity of 55%. The surviving ECMO supported patients had longer ICU and hospital stays (26 vs. 18 days, P = 0.018; 49 vs. 29 days, P = 0.001 respectively), and ECMO procedure was widely carried out after the supplement of medical resources after February 15 (67.6%, 50/74). Conclusions: ECMO might be a benefit for severe critically ill COVID-19 patients at the early stage of epidemic, although the in-hospital mortality was still high. To initiate ECMO therapy under tremendous pressure, patients' age, lymphocyte count, and adequacy of medical resources should be fully considered.

Initial fluid resuscitation (30 mL/kg) in patients with septic shock: More or less?

OBJECTIVES: The 2018 Surviving Sepsis Campaign (SSC) recommends rapid administration of 30 mL/kg crystalloid fluids for hypotension or lactate ≥4 mmol/L in patients with septic shock; however, there is limited evidence to support this recommendation. The purpose of this study was to examine the relationship between initial fluid resuscitation doses and prognosis in patients with septic shock. METHODS: This was a multicenter prospective observational study of adult patients with septic shock who were admitted to four intensive care units (ICUs) in a total of three Jiangsu Province teaching hospitals over a 3-year span from May 8, 2018, to June 15, 2021. Each enrolled patients with septic shock was categorized into the low-volume (below 20 mL/kg fluid), medium-volume (20-30 mL/kg fluid) or high-volume (above 30 mL/kg fluid) fluid group according to the initial infusion dose given for fluid resuscitation. Various demographic attributes and other variables were collected from medical records. Logistic regression and Kaplan-Meier curve analysis were used to determine the relationship between initial fluid resuscitation doses and patient outcomes. MEASUREMENTS AND MAIN RESULTS: A total of 302 patients who presented to the ICU were diagnosed with septic shock. The 28-day mortality was highest in the high-volume group (48.3%) and lowest in the medium-volume group (26.3%, P < 0.05). Patients who completed 30 mL/kg initial fluid resuscitation in the first 1-2 h had the lowest 28-day mortality rate (22.8%, P < 0.05). Logistic regression showed that a medium initial fluid volume dose was an independent protective factor, with the odds ratio (OR) indicating significantly decreased mortality (OR, 0.507; 95% confidence interval, 0.310-0.828; P = 0.007; P < 0.05). A Kaplan-Meier curve stratified by initial fluid resuscitation dose was constructed for the probability of 28-day mortality. The medium-volume fluid group showed a significantly lower 28-day mortality rate than the high-volume group or the low-volume group (log-rank test, P = 0.0016). CONCLUSION: In septic shock patients, an initial fluid resuscitation rate of 20-30 mL/kg within the first hour may be associated with reduced 28-day mortality; however, this result needs to be confirmed by further high-quality randomized controlled clinical trials. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-OOC-17013223. Registered 2 November 2017, http://www.chictr.org.cn/showproj.aspx?proj=22674.

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.

Mesenchymal stem cells regulate the Th17/Treg cell balance partly through hepatocyte growth factor in vitro.

INTRODUCTION: Mesenchymal stem cells (MSCs) exert immunomodulatory functions by inducing the development and differentiation of naive T cells into T cells with an anti-inflammatory regulatory T cell (Treg) phenotype. Our previous study showed that hepatocyte growth factor (HGF) secreted by MSCs had immunomodulatory effects in the context of lipopolysaccharide (LPS) stimulation. We hypothesized that HGF is a key factor in the MSC-mediated regulation of the T helper 17 (Th17) cell/regulatory T (Treg) cell balance. METHODS: We investigated the effects of MSCs on the differentiation of CD4+ T cells and the functions of Th17/Treg cells in response to LPS stimulation by performing in vitro coculture experiments. MSCs were added to the upper chambers of cell culture inserts, and CD4+ T cells were plated in the lower chambers, followed by treatment with LPS or an anti-HGF antibody. Th17 (CD4+CD3+RORrt+) and Treg (CD4+CD25+Foxp3+) cell frequencies were analysed by flow cytometry, and the expression of Th17 cell- and Treg cell-related cytokines in the CD4+ T cells or culture medium was measured by quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Neutrophil functions were determined by flow cytometry after a coculture with Th17/Treg cells. RESULTS: The percentage of CD4+CD25+Foxp3+ cells was significantly increased in the CD4+ T cell population, while the percentage of CD4+CD3+RORrt+ cells was significantly decreased after MSC coculture. However, the MSC-induced effect was significantly inhibited by the anti-HGF antibody (p < 0.05). Furthermore, MSCs significantly inhibited the CD4+ T cell expression of IL-17 and IL-6 but increased the expression of IL-10 (p < 0.05 or p < 0.01); these effects were inhibited by the anti-HGF antibody (p < 0.05). In addition, CD4+ T cells cocultured with MSCs significantly inhibited neutrophil phagocytic and oxidative burst activities (p < 0.05 or p < 0.01); however, these MSC-induced effects were inhibited by the anti-HGF antibody (p < 0.05). CONCLUSION: These data suggested that MSCs induced the conversion of fully differentiated Th17 cells into functional Treg cells and thereby modulated the Th17/Treg cell balance in the CD4+ T cell population, which was partly attributed to HGF secreted by the MSCs.

Effect of Low-Dose Hydrocortisone Therapy in Adult Patients With Septic Shock: A Meta-Analysis With Trial Sequential Analysis of Randomized Controlled Trials.

BACKGROUND: The efficacy of low-dose hydrocortisone therapy in the management of septic shock remains controversial in critical care for many years. Hence, we performed this meta-analysis of randomized controlled trials (RCTs) with trial sequential analysis (TSA) to evaluate its effect on clinical outcome among adult patients with septic shock. METHODS: We identified relevant RCTs published from inception to March 7, 2018 comparing low-dose hydrocortisone with placebo or no intervention in adults admitted to the intensive care unit (ICU) for septic shock. Meta-analyses were performed for the primary and secondary outcomes. The risk of bias was assessed using the Cochrane Collaboration's instrument. Trial sequential analysis was used to pool the results from the included studies for the primary outcomes. RESULTS: Thirteen studies were retrieved by our literature search strategy. There were no significant differences in 28-day mortality (odds ratio [OR] = 0.90, 95% confidence interval [CI] = 0.81-1.00; P = .05) and hospital mortality (OR = 0.91, 95% CI = 0.82-1.02; P = .09) between the 2 groups, which were confirmed by TSA. However, there was a significant improvement in shock reversal in the hydrocortisone group (OR = 1.33, 95% CI = 1.02-1.72; P = .03). Furthermore, subgroup analyses revealed that hydrocortisone plus fludrocortisone statistically reduced the rate of 28-day mortality (OR = 0.79, 95% CI = 0.64-0.97; P = .03), ICU mortality (OR = 0.77, 95% CI = 0.63-0.95; P = .02), and hospital mortality (OR = 0.77, 95% CI = 0.63-0.95; P = .01) in comparison with the placebo, the results were also confirmed by TSA. CONCLUSION: Among adult patients with septic shock, the use of low-dose hydrocortisone compared with control did not confer overall survival benefits, albeit improving shock reversal rate. The benefit of reducing 28-day mortality, ICU mortality, and hospital mortality was observed in combination use of hydrocortisone and fludrocortisone.

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.

Predictive accuracy of Sepsis-3 definitions for mortality among adult critically ill patients with suspected infection.

BACKGROUND: Sepsis-3 definitions have been published recently; however, their diagnostic value remains controversial. This study was to assess the accuracy of Sepsis-3 definitions compared to Sepsis-1 definitions by stratifying mortality among adult critically ill patients with suspected infection. METHODS: A multicenter, prospective cohort study was conducted from November 10, 2017 to October 10, 2018, in five Intensive Care Units (ICUs) at four teaching hospitals. Thirty-day mortality was compared across categories for both Sepsis-3 definitions and Sepsis-1 definitions, which were evaluated by logistic regression analysis followed by measurement of the area under the receiver operating characteristic curve (AUROC) for predicting 30-day mortality rates. RESULTS: Of the 749 enrolled patients, 644 (85.9%) were diagnosed with sepsis according to the Sepsis-1 definitions. Among those patients, 362 were diagnosed with septic shock (362/749, 48.3%). However, according to the Sepsis-3 definitions, there were 483 patients with a diagnosis of sepsis (483/749, 64.5%), among whom 299 patients were diagnosed with septic shock (299/749, 39.9%). According to the Sepsis-3 definitions, sepsis (sepsis and septic shock) patients had higher 30-day mortality (41.8%) than sepsis patients according to the Sepsis-1 definitions (31.8%, χ = 5.552, P = 0.020). The AUROC of systemic inflammatory response syndrome (SIRS) and quick sequential organ failure assessment (qSOFA) scores with regard to 30-day mortality rates were 0.609 (0.566-0.652) and 0.694 (0.654-0.733), respectively. However, the AUROC of SOFA scores (0.828 [0.795-0.862]) were significantly higher than that of SIRS or qSOFA scores (P < 0.001). CONCLUSION: In adult critically ill patients with suspected infection, the Sepsis-3 definitions were relatively accurate in stratifying mortality and were superior to the Sepsis-1 definitions. TRIAL REGISTRATION: www.chictr.org.cn (ChiCTR-OOC-17013223).

Effects of restrictive red blood cell transfusion on the prognoses of adult patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials.

PURPOSE: Restrictive red blood cell transfusion strategies remain controversial in patients undergoing cardiac surgery. We performed a meta-analysis to assess the prognostic benefits of restrictive red blood cell transfusion strategies in patients undergoing cardiac surgery. METHODS: We identified randomized clinical trials through the 9th of December 2017 that investigated a restrictive red blood cell transfusion strategy versus a liberal transfusion strategy in patients undergoing cardiac surgery. Individual patient data from each study were collected. Meta-analyses were performed for the primary and secondary outcomes. The risk of bias was assessed using the Cochrane Risk of Bias Tool. A trial sequential analysis (TSA)-adjusted random-effects model was used to pool the results from the included studies for the primary outcomes. RESULTS: Seven trials involving a total of 8886 patients were included. The TSA evaluations suggested that this meta-analysis could draw firm negative results, and the data were sufficient. There was no evidence that the risk of 30-day mortality differed between the patients assigned to a restrictive blood cell transfusion strategy and a liberal transfusion strategy (odds ratio (OR) 0.98; 95% confidence interval (CI) 0.77 to 1.24; p = 0.87). Furthermore, the study suggested that the restrictive transfusion strategy was not associated with significant increases in pulmonary morbidity (OR 1.09; 95% CI 0.88 to 1.34; p = 0.44), postoperative infection (OR 1.11; 95% CI 0.95 to 1.3; p = 0.58), acute kidney injury (OR 1.03; 95% CI 0.92 to 1.14; p = 0.71), acute myocardial infarction (OR 1.01; 95% CI 0.80 to 1.27; p = 0.78), or cerebrovascular accidents (OR 0.97; 95% CI 0.72 to 1.30; p = 0.66). CONCLUSIONS: Our meta-analysis demonstrates that the restrictive red blood cell transfusion strategy was not inferior to the liberal strategy with respect to 30-day mortality, pulmonary morbidity, postoperative infection, cerebrovascular accidents, acute kidney injury, or acute myocardial infarction, and fewer red blood cells were transfused.

Effect of levosimendan on prognosis in adult patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: Small trials suggest that levosimendan is associated with a favorable outcome in patients undergoing cardiac surgery. However, recently published larger-scale trials did not provide evidence for a similar benefit from levosimendan. We performed a meta-analysis to assess the survival benefits of levosimendan in patients undergoing cardiac surgery and to investigate its effects in subgroups of patients with preoperative low-ejection fraction (EF). METHODS: We identified randomized clinical trials through 20 April 2017 that investigated levosimendan therapy versus control in patients undergoing cardiac surgery. Individual patient data from each study were compiled. Meta-analyses were performed for primary outcomes, secondary outcomes and serious adverse events, and subgroup analyses according to the preoperative EF of enrolled patients were also conducted. The risk of bias was assessed using the Cochrane risk-of-bias tool. RESULTS: Seventeen studies involving a total of 2756 patients were included. Levosimendan therapy was associated with a significant reduction in 30-day mortality (RR 0.67; 95% CI, 0.49 to 0.93; p = 0.02) and reduced the risk of death in single-center trials (RR 0.49; 95% CI, 0.30 to 0.79; p = 0.004) and in subgroup trials of inferior quality (RR 0.39; 95% CI, 0.17 to 0.92; p = 0.02); however, in multicenter and in high-quality subgroup-analysis trials, no significant difference in mortality was observed between patients who received levosimendan therapy and controls (p > 0.05). However, in high-quality subgroup trials, levosimendan therapy was associated with reduced mortality in patients in a preoperative low-EF subgroup (RR 0.58; 95% CI, 0.38 to 0.88; p = 0.01). Similarly, only patients in the preoperative low-EF subgroup benefited in terms of reduced risk of renal replacement therapy (RR 0.54; 95% CI, 0.34 to 0.85; p = 0.007). Furthermore, levosimendan therapy was associated with a significant reduction in intensive care unit (ICU) length of stay (MDR -17.19; 95% CI, -34.43 to -2.94; p = 0.02). CONCLUSIONS: In patients undergoing cardiac surgery, the benefit of levosimendan in terms of survival was not shown in multicenter or in high-quality trials; however, levosimendan therapy was associated with reduced mortality in patients with preoperative ventricular systolic dysfunction.

Early initiation of low-dose hydrocortisone treatment for septic shock in adults: A randomized clinical trial.

BACKGROUND: Physiologic dose hydrocortisone is part of the suggested adjuvant therapies for patients with septic shock. However, the association between the corticosteroid therapy and mortality in patients with septic shock is still not clear. Some authors considered that the mortality is related to the time frame between development of septic shock and start of low dose hydrocortisone. Thus we designed a placebo-controlled, randomized clinical trial to assess the importance of early initiation of low dose hydrocortisone for the final outcome. METHODS: A total of 118 patients with septic shock were recruited in the study. All eligible patients were randomized to receive hydrocortisone (n=58) or normal saline (n=60). The study medication (hydrocortisone and normal saline) was initiated simultaneously with vasopressors. The primary end-point was 28-day mortality. The secondary end-points were the reversal of shock, in-hospital mortality and the duration of ICU and hospital stay. RESULTS: The proportion of patients with reversal of shock was similar in the two groups (P=0.602); There were no significant differences in 28-day or hospital all-cause mortality; length of stay in the ICU or hospital between patients treated with hydrocortisone or normal saline. CONCLUSION: The early initiation of low-dose of hydrocortisone did not decrease the risk of mortality, and the length of stay in the ICU or hospital in adults with septic shock. TRIAL REGISTRATION: www.clinicaltrials.govNCT02580240.

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.

[Effect of Xuebijing injection treatment on acute respiratory distress syndrome: a multicenter prospective randomized control clinical trial].

OBJECTIVE: To assess the therapeutic effect of Xuebijing injection on adult patients with acute respiratory distress syndrome (ARDS). METHODS: A multicenter prospective randomized control study was conducted at 10 intensive care units in Jiangsu province. A total of 172 early ARDS patients were randomly divided into Xuebijing treatment and control groups. All patients received routine therapy of ARDS while additional Xuebijing injection 100 ml was administered in the treatment group intravenously for 7 days. Lung injury score, acute physiology and chronic health evaluation II (APACHE II) score, multiple organ dysfunction score (MODS) and PaO2/FiO2 of the patients was recorded before and after treatment. Mortality at 28 days and the duration of mechanical ventilation were compared between two groups. RESULTS: Ninety-one patients were assigned to receive Xuebijing injection and 81 patients as control; Mortality at Days 28 and 90, the duration of mechanical ventilation and ventilation free days showed no difference between two groups (P > 0.05). PaO2/FiO2 improved after randomization versus pre-treatment in all patients. There was no significant difference between two groups. Murray scores were not significantly different between two groups. In a subgroup analysis of patients with pulmonary infection, pulmonary contusion and extra-pulmonary cause, two groups had no difference in mortality at Day 28, mortality at Day 90, the duration of mechanical ventilation, ventilation free days and days of ICU stay (P > 0.05). CONCLUSION: The treatment of Xuebijing injection early in course of ARDS does not improve the mortality of ARDS patients. But it may improve lung function and oxygenation. Further studies are warranted.

[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.

[Effects of electrical activity of diaphragm on the titration of positive end-expiratory pressure in a model of acute respiratory distress syndrome].

OBJECTIVE: To explore the relationship of electrical activity of diaphragm (EAdi) and positive end-expiratory pressure (PEEP) in a rabbit model of acute respiratory distress syndrome (ARDS). METHODS: The rabbit model of ARDS was induced by an intratracheal infusion of hydrochloric acid. After a sufficient amount of recruitment maneuvers (RM), the level: the PEEP levels were (10.4 ± 1.0) cm H2O in EAdi group and (9.7 ± 2.1) cm H2O in rabbits were divided into 2 groups: (1) PEEP titration with EAdi (EAdi group); (2) PEEP titration with maximum oxygenation (maximum oxygenation group). The tidal volume was 6 ml/kg in 2 groups. Pulmonary mechanics, gas exchange and hemodynamic were observed in two groups at baseline, after lung injury and ventilation 1, 2, 3 h respectively. RESULTS: (1) PEEP maximum oxygenation group. There was no significant difference between two groups (P > 0.05). (2) Pulmonary mechanics:there was no significant difference in peak pressure (Ppeak) and mean pressure (Pm) between two groups at ventilation 1, 2, 3 h (P > 0.05). (3) Gas exchange: at ventilation 1, 2, 3 h, the oxygenation index (PaO2/FiO2) in EAdi group was higher than that of after lung injury (P < 0.05) and there was no significant difference in PaO2/FiO2 and partial pressure of arterial carbon dioxide (PaCO2) between two groups (P > 0.05). (4) Hemodynamic: at ventilation 1, 2, 3 h, the heart rate (HR) and mean artery pressure (MAP) in EAdi group had no significant differences with baseline, after lung injury and maximum oxygenation group (P > 0.05). CONCLUSION: EAdi may be an ideal method for PEEP titration at post-RM in an ARDS model.

[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.