ObjectiveTo investigate the potential role and mechanism of hydrogen sulfide (H2S) in regulating arterial baroreflex (ABR) in septic rats. MethodsThe rat model of cecal ligation and puncture (CLP) induced sepsis was established. Fortyseven male SpargueDawley rats were randomly divided into 9 groups: ① Sham operation (SO)+0.9% NaCl (NS) intravenous injection (i.v.) group; ② SO+NaHS i.v. group; ③ CLP+NaHS i.v. group; ④ SO+artificial cerebrospinal fluid (aCSF) bilater nucleus tractus solitarii (NTS) microinjection group; ⑤ SO+NaHS bilater NTS microinjection group; ⑥ SO+vehicle (DMSO)+NaHS group; ⑦ SO+Gli+NaHS group; ⑧ CLP+vehicle (DMSO) group; ⑨ CLP+Gli group. The ABR function was measured before administration and 5 min and 30 min after administration. Results① The ABR value of rats at different time in the same group: Compared with the ABR value before administration in the SO+NaHS i.v. group, CLP+NaHS i.v. group, SO+NaHS bilater NTS microinjection group, and SO+vehicle+NaHS group, the ABR values of rats significantly decreased at 5 min and 30 min after administration (Plt;0.05, Plt;0.01), which significantly increased in the CLP+Gli group at 5 min and 30 min after administration (Plt;0.05). ② The ABR value of rats at the same time in the different groups: Before administration, the ABR value of rat in the CLP+NaHS i.v. group was significantly lower than that in the SO+NS i.v. group or SO+NaHS i.v.group (Plt;0.05). At 5 min and 30 min after adminis tration, the ABR value of rat in the CLP+NaHS i.v. group was significantly lower than that in the SO+NS i.v. group or SO+NaHS i.v. group (Plt;0.05), which in the SO+NaHS i.v. group or SO+NaHS bilater NTS microinjection group was significantly lower than that in the SO+NS i.v. group or SO+aCSF bilater NTS microinjection group, respectively (Plt;0.05, Plt;0.01), in the SO+Gli+NaHS group or CLP+Gli group was significantly higher than that in the SO+vehicle+NaHS group or CLP+vehicle group, respectively (Plt;0.05). ConclusionsH2S plays an adverse role in septic ABR function, and opening KATP channel located at the pathway of ABR, may be the mechanism involved in the downregulation of ABR function in septic rat. Notably, the NTS may be also responsible for reduction of ABR value.
Objective To explore the application of regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT) for patients with sepsis and hyperlactacidemia, and to provide a basis for the clinical application of RCA in such patients. Methods Sepsis patients who underwent RCA-CRRT at West China Hospital of Sichuan University between May 2021 and May 2023 were retrospectively included. Patients were divided into a normal lactate group (≤2.0 mmol/L) and a hyperlactacidemia group (>2.0 mmol/L) based on their initial lactate levels before CRRT, and subgroup analysis was performed on patients with moderate hyperlactacidemia (2 mmol/L<lactate level<4 mmol/L) and severe hyperlactacidemia (≥4.0 mmol/L). Propensity score matching (PSM) was used, and baseline characteristics and outcome measures of different groups of patients were compared. Results A total of 441 patients were included, with 228 in the normal lactate group and 213 in the hyperlactacidemia group. Before PSM, there were statistically significant differences in the proportion of liver failure, proportion of chronic kidney disease, mean arterial pressure, bicarbonate, total bilirubin, creatinine, activated partial thromboplastin time, international standardized ratio, procalcitonin, and interleukin-6 between the normal lactate group and the hyperlactacidemia group (P<0.05). After PSM, there were 162 patients in both the normal lactate group and the hyperlactacidemia group. There was no statistically significant difference in baseline characteristics between the two groups of patients (P>0.05). The incidence of citric acid accumulation in the normal lactate group and the hyperlactacidemia group was 13.0% and 25.9%, respectively (P<0.05). There was no statistically significant difference in the incidence of metabolic acidosis, metabolic alkalosis, hypernatremia, filter coagulation events, or in-hospital mortality between the two groups (P>0.05). Kaplan-Meier survival analysis showed that there was no statistically significant difference in the first extracorporeal circulation lifespan between the normal lactate group and the hyperlactacidemia group (P>0.05). Among 213 patients with hyperlactacidemia, 186 had moderate hyperlactacidemia and 27 had severe hyperlactacidemia. Before PSM, there were statistically significant differences in the proportion of male, proportion of diabetes, albumin level, international standardized ratio, and interleukin-6 between moderate and severe hyperlactacidemia groups (P<0.05). After PSM, there were 22 patients in both the moderate and severe hyperlactacidemia groups. There was no statistically significant difference in baseline characteristics between the two groups of patients (P>0.05). The incidence of citric acid accumulation was 18.2% and 50.0% in the moderate and severe hyperlactacidemia groups, respectively (P<0.05). There was no statistically significant difference in the incidence of metabolic acidosis, metabolic alkalosis, hypernatremia, filter coagulation events, or in-hospital mortality between the two groups (P>0.05). Kaplan-Meier survival analysis showed that there was no statistically significant difference in the first extracorporeal circulation lifespan between the moderate and severe hyperlactacidemia groups (P>0.05). Conclusion When RCA is used for CRRT anticoagulation in patients with sepsis and hyperlactacidemia, the incidence of citric acid accumulation is high (especially in patients with severe hyperlactacidemia), and should be closely monitored.
ObjectiveTo detecte the expressions of phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene and protein in peripheral blood mononuclear cells (PBMC) of patients with sepsis and to explore its role in the pathogenesis of acute obstructive suppurative cholangitis (AOSC).
MethodsThe PBMC and serum were separated from AOSC patients (n=25) before treatment and in 1 week after recure, and healthy volunteers (normal control group, n=15). The serum levels of lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α) and interleukin 10 (IL-10) were detected by enzyme linked immunosorbent assay (ELISA) methods. The mRNA and protein expression levels of PTEN, nuclear fator κB P65 (NF-κB), and inhibitor of NF-κB (IκB) were detected by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, respectively.
ResultsThe levels of LPS, TNF-α, and IL-10 before treatment were significantly higher than those of normal control group (P < 0.05), the indicators were significantly decreased and close to normal levels in 1 week after recure. The mRNA and protein expression levels of PTEN and IκB before treatment were lower than those of normal control group (P < 0.05), NF-κB P65 was higher than those of normal control group (P < 0.05), while the phosphorylation levels of PTEN and IκB were higher than those normal control group (P < 0.05), and in 1 week after recure, the above indicators returned to normal levels.
ConclusionsSepsis shift may be associated with the occurrence of intestinal LPS, and caused the imbalance between proinflammatory and anti-inflammatory cytokines in the body. PTEN for phosphorylation activation of IκB or directly activation of NF-κB participate the originating process of sepsis, hinting a therapeutic potentialities in the early stage of sepsis.
Objective To retrospectively analyze the clinical characteristics of different lactate trajectories in sepsis patients receiving mechanical ventilation (MV) and to investigate their associations with acute kidney injury (AKI) and in-hospital death risk, aiming to provide references for early renal protection in critically ill sepsis patients. Methods Data from sepsis patients receiving MV were extracted from the Medical Information Mart for Intensive Care Ⅳ (MIMIC-Ⅳ) database. The daily mean lactate values over the first 10 days were calculated. The latent class trajectory model (LCTM) was used to identify lactate trajectories over time and group the patients accordingly. AKI was the primary outcome measure, while in-hospital death was the secondary outcome measure. Logistic regression and Cox regression analyses were used to explore the associations between different lactate trajectories and these outcomes. Kaplan-Meier curves were drawn to compare in-hospital death risks among different lactate trajectory groups. Results A total of 2 062 MV-treated sepsis patients were included. After LCTM analysis, 1 396 patients were classified into the low lactate trajectory group, 451 into the moderate lactate trajectory group, and 215 into the high lactate trajectory group. After adjusting for confounding factors, the high lactate trajectory group was associated with an increased risk of AKI and in-hospital death (P<0.05). Conclusions In sepsis patients receiving MV, those with high lactate trajectories have a higher risk of AKI. Lactate trajectory changes can serve as an early assessment indicator for AKI and mortality risk in critically ill sepsis patients.
ObjectiveTo explore the clinical effects of exogenous glutamine on patients suffering from sepsis with hypoalbuminemia in emergency department.
MethodsEighty-six patients with sepsis and hypoalbuminemia enrolled from January to November 2013 in the Emergency Department of our hospital were randomly divided into treatment group and control group. Forty-three patients in the control group were given conventional treatments, while the other 43 in the treatment group were treated with glutamine therapy based on the conventional treatments. The clinical efficacy of the two groups including inflammatory markers, albumin level, APACHEⅡ score and SAPSⅡ score, mortality, length of hospital stay were analyzed on day 7, 14, and 28 after being enrolled. A comprehensive analysis of the clinical effects in these two groups was performed.
ResultsEighty-six cases were enrolled in this study. The mortality on day 14 and 28 in the treatment group was significantly lower than that in the control group (P<0.05). Inflammatory markers (WBC count, CRP concentration, and PCT concentration) in patients of the treatment group were gradually decreased, whereas serum albumin levels were gradually increased compared with the control group (P<0.05). The cure rate of patients in the treatment group was significantly higher than that in the control group, while the average length of stay was shorter than the control group (P<0.05) on day 28.
ConclusionExogenous glutamine supplementation can improve patient cure rates and reduce hospital stays which has good clinical effects on patients with sepsis and hypoalbuminemia in emergency department.
Objective
To explore the relationship between central venous-to-arterial carbon dioxide difference/arterial-to-venous oxygen difference ration [P(cv-a)CO2/C(a-cv)O2] and arterial lactate in patients with sepsis.
Methods
A retrospective analysis was carried on 36 septic patients who were admitted to the Intensive Care Unit of Nanjng Drum-tower Hospital affiliated to Medical School of Nanjing University from May 2013 to November 2013. Cardiac index was measured by transpulmonary thermodilution. At the same time, femoral artery and central venous blood were collected to measure the value of arterial lactate and central venous oxygen saturation (ScvO2) by blood gas analysis and calculate central venous-to-arterial carbon dioxide difference [P(cv-a)CO2], arterial-to-venous oxygen difference [C(a-cv)O2], and their ration [P(cv-a)CO2/C(a-cv)O2], oxygen delivery (DO2) and oxygen consumption (VO2). The subjects were divided intoahyperlactatemia group (≥2 mmol/L) andanormal lactate group (< 2 mmol/L) according to arterial lactate value. P(cv-a)CO2/C(a-cv)O2 and other oxygen metabolism parameters were compared between two groups.
Receiver
operating characteristic (ROC) curve was used to evaluate the accuracy of P(cv-a)CO2/C(a-cv)O2 and other parameters for diagnosis of hyperlactatemia. Results A total of 36 patients with 119 data were collected. Compared with the normal lactate group, P(cv-a)CO2/C(a-cv)O2 was significantly higher [(1.38±0.76)mm Hg/mL vs. (2.31±1.01) mm Hg/mL, P < 0.01], ScvO2, DO2 and VO2 were significantly lower in the hyperlactatemia group [ScvO2: (74.26±9.13)% vs. (70.29±9.72)%; DO2: (505.52±208.39) mL/(min·m2) vs. (429.98±173.63) mL/(min·m2)]; VO2: (129.01±54.94) mL/(min·m2) vs. (109.99±38.79) mL/(min·m2), P < 0.05]. P(cv-a)CO2 had no significant difference between two groups [(5.76±3.70) mm Hg vs. (6.59±3.70) mm Hg, P > 0.05]. P(cv-a)CO2/C(a-cv)O2 was positively correlated with lactate (r=0.646, P < 0.01). ScvO2 was negatively correlated with lactate (r=-0.277, P < 0.01). DO2 and VO2 had no significant correlation with lactate (P > 0.05). The area under ROC curve (AUC) of P(cv-a)CO2 /C(a-cv)O2 for diagnosis of hyperlactatemia was 0.820, with 95% confidence interval (95%CI) of 0.715 - 0.925(P < 0.001); The AUC of ScvO2 was 0.622, with 95%CI of 0.520 - 0.724(P=0.025).
Conclusion
Compared with the traditional oxygen metabolism parameters, P(cv-a)CO2/C(a-cv)O2 can accurately diagnose hyperlactatemia, and isareliable parameter to reflect oxygen metabolism in patients with sepsis.
Sepsis, a serious clinical syndrome known as organs dysfunction caused by an unbalanced host inflammatory response to infection, is of great concern in emergency medicine. Over the past two decades, the definition of sepsis has changed from systemic inflammatory response syndrome lead by infection to organs damage caused by infection. Under the new diagnostic criterion, septic patients are too serious to be treated in Emergency Department, and need intensive treatment of Intensive Care Unit. In this paper, by analyzing the development process from infection to sepsis and expounding the role of cytokines in the development of sepsis, we think that measures should be taken at the early stage of infection in order to prevent and block the occurrence of sepsis.
【Abstract】 Objective To study the effects of glutamine (Gln) combined with growth hormone （GH） on the levels of cytokine (TNF-α, IL-1, IL-6), coritsol and amino acid metabolism in septic rats. Methods Ten out of 79 SD rats were randomly collected as the control group. Thirty of 69 septic SD rats, which were made by cecal ligation and perforation (CLP) method and were given parenteral nutrition (PN) lived to day 6. They were also randomly divided into three groups as follows: septic group (n=10), parenteral supplemented glutamine group (Gln group, n=10), and Gln combined with GH (Gln+GH group, n=10). On the 6th day, blood drew from portal veins of the dead rats was used to detect the levels of TNF-α， IL-1， IL-6 and cortisol by ELISA. The plasma concentrations of free amino acids were determined by amino acid auto-analyzer. The muscle tissue of extensor digitorum longus was used to determine 3-methyl-histidine (3-MH) by high performance liquid chromatographic (HPLC). Results Except for the control group, most rats developed celiac abscess, hepatic abscess and pulmonary infection. The serum levels of TNF-α, IL-1, IL-6 and cortisol were significantly higher in the septic group than those of the other three groups, and they were significantly lower in the Gln+GH group than those of the Gln group, P＜0.05. Compared with the other three groups, the concentration of total amino acid in the septic group increased more, among which the glutamine and the branched chain amino acids were prominent. Most of concentrations of the amino acids decreased in the Gln group and the Gln+GH group, and the decreased amplitude of the Gln+GH group was larger, P＜0.05, albeit its level of Gln markedly increased. The concentration of 3-MH in muscle tissue was the highest in septic group, and it was significantly higher in the Gln group than that of the Gln+GH group, P＜0.01. ConclusionIt may be necessary to supplement GH combined with Gln as the content of PN to decrease cytokine levels and im-prove amino acid metabolism for septic case.
【Abstract】Objective To explore the effect and indication of splenectomy in liver transplantation. Methods From January 2001 to April 2006, 260 patients underwent piggyback orthotopic liver transplantation (PBOLT), and 28 patients had undergone combined PBOLT and splenectomy (splenectomy group). These patients were compared to 56 randomly selected non-splenectomy patients from the same transplant period, meaningly two controls were selected for every non-splenectomy case. Two groups were analyzed with respect to rate of infection and survival rate, as well as biopsy-proven acute allograft rejection within 30 days after transplantation. Results Rate of infection in the splenectomy group was higher than that in the non-splenectomy patients (85.7% vs 55.4%, P＜0.05). Acute rejection and survival rates in the splenectomy group were lower than those in the non-splenectomy patients (3.6% vs 14.3%, P＜0.05; 46.4% vs 82.1%, P＜0.05). Conclusion Concomitant splenectomy with PBOLT has a significantly higher patient mortality rate; it is mainly due to its septic complications. At present, unless there is a certain indication for splenectomy, this procedure is not recommended.
ObjectivesTo systematically review the prognostic value of plasma soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) level in predicting 28-day mortality in sepsis.MethodsPubMed, The Cochrane Library, EMbase, Web of Science, CBM, CNKI, VIP and WanFang Data databases were electronically searched to collect studies about the prognostic value of plasma sTREM-1 in early 28-day mortality in sepsis from inception to April 16th, 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using Stata 14.0 software.ResultsA total of 13 studies involving 1 115 patients were included. The results of meta-analysis showed that the sensitivity and specificity were 79% and 77%, respectively. The positive likelihood ratio and the negative likelihood ratio were 3.4 and 0.28, respectively. The diagnostic ratio was 12. The overall area under the summary receiver operator characteristic (SROC) curve was 0.80.ConclusionsCurrent evidence shows that plasma sTREM-1, as a single index, may play a prognostic role in the early 28-day mortality of sepsis in patients. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
