Objective To investigate the changes in osteoprotegerin (OPG) / receptor activator of nuclear factor-κB ligand (RANKL) ratio in sepsis-associated acute lung injury (SA-ALI) and the role of regulation of this ratio on the inflammatory response in SA-ALI. Methods Eighteen C57BL/6 male mice were randomly divided into sham operation group, cecal ligation and perforation (CLP) group and RANKL group, with 6 mice in each group. Before the experiment, the RANKL group was intraperitoneally injected with 5 μg (0.2 mL) of recombinant RANKL antibody, whereas both the sham operation group and the CLP group were intraperitoneally injected with a volume-matched normal saline. One hour later, the sham operation group underwent only abdominal exploration and repositioning, while the other groups underwent the CLP surgery to induce the SA-ALI model. After 24 h of modelling, all mice were sacrificed and samples were collected. Pathological evaluation of lung tissues was performed by haematoxylin-eosin staining; enzyme-linked immunosorbent assay was used to detect serum concentrations of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β; while the mRNA and protein expression of OPG and RANKL, along with their ratio values, were detected by real-time polymerase chain reaction for quantitative analysis and protein immunoblotting. Results The SA-ALI mouse model was successfully established. Compared with the sham operation group, mice in the CLP group showed disturbed alveolar structure, obvious alveolar and interstitial haemorrhage and inflammatory cell infiltration, elevated serum levels of IL-6, TNF-α and IL-1β (P<0.05), significantly increased mRNA and protein expression of OPG and elevated OPG/RANKL ratio in lung tissue (P<0.05), whereas RANKL mRNA and protein expression was significantly decreased (P<0.05). Compared with the CLP group, the pathological damage of lung tissue in the RANKL group was reduced, the infiltration of alveolar and interstitial inflammatory cells was significantly improved, and the alveolar structure and morphology were more regular, with lower serum levels of IL-6, TNF-α and IL-1β (P<0.05), significantly lower mRNA and protein expression of OPG and OPG/RANKL ratio in lung tissue (P<0.05), and significantly higher mRNA and protein expression of RANKL in lung tissue (P<0.05). Conclusion The alteration of OPG/RANKL ratio may be related to the pathophysiological process of SA-ALI, and the decrease in its level may reflect the attenuation of the inflammatory response in SA-ALI.
ObjectiveTo evaluate the clinical efficacy of fish oil containing lipid emulsion (FO) in sepsis. MethodsRandomized controlled trials about fish oil containing lipid emulsion in sepsis,which were published from 1980,were searched from the following electronic databases:PubMed,Embase,Foreign Medical Journal Service,Cochrane Library,CNKI,Wanfang Database,and VIP Database. The articles screening,quality assessment and data extraction were conducted by two reviewers independently. The methodological quality of trials was assessed by Jadad's scale. All data was analyzed by Review Manager 5.2 software. ResultsFifteen studies involving 794 participants met the inclusion criteria. The meta-analysis results were as follows:compared with the control group,①FO could shorten the length of ICU stay[WMD=-5.59,95%CI(-7.65,-3.53)] and the length of hospital stay[WMD=-10.48,95%CI(-14.67,-6.29)],and also decrease the 28-day mortality[RR=0.69,95%CI(0.52,0.93)]. ②FO could reduce the concentration of TNF-α[WMD=31.78,95%CI(5.63,57.92)] and improve oxygenation index[WMD=41.95,95%CI(30.80,53.11)] in septic patients. ③There was no statistical significance in the decrease of C-reactive protein (CRP) between two groups(P>0.05). ConclusionThe administration of FO in septic patients can significantly shorten the length of ICU stay and hospital stay,decrease the 28-day mortality,reduce the concentration of TNF-α and improve oxygenation index. However,it shows no significant difference in the decrease of CRP compared with the administration of traditional lipid emulsion. All of the above results show that the septic patients can benefit from the administration of fish oil containing lipid emulsion.
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, and is the leading cause of death in intensive care unit patients due to limited therapies currently. As is known to all, endotoxin is important in the pathogenesis of sepsis, whereby infection triggers a systemic inflammatory response, resulting in release of pro- and anti-inflammatory cytokines, which are thought to be responsible for the tissue damage that occurs in sepsis patients. Therefore, removing endotoxins is considered as an effective way to improve the conditions of sepsis patients. Both Toraymaxin (PMX) and adsorptive membrane such as oXiris can remove endotoxins by adsorption, and in this review we will summarize current studies, included in vitro study, animal study, and clinical research to show the benefit from endotoxin removal by oXiris, and also give some suggestions about oXiris clinical practice from experienced experts.
Objective To systematically review the efficacy of enteral nutrition with eicosapentaenoic acid ( EPA) , gamma-linolenicacid ( GLA) , and anti-oxidants for patients with sepsis. Methods We searched the PubMed, EMbase, Cochrane Library, Wanfang Database, CNKI and VIP for all randomized controlled trials about the efficacy of an enteral diet enriched with EPA, GLA, and anti-oxidants for patients with sepsis. The quality of the studies was evaluated by the method recommended by Cochrane Collaboration. Meta-analysis was conducted using the Cochrane Collaboration’s RevMan 5.0 software.Results Three RCTs involving 350 patients were included in our systematic review. The results showed a significant reduction in the length of ICU stay ( MD =6.21, 95% CI: 4.61-8.19; P lt;0.00001) and hospital stay ( P lt;0.0001) , a fewer development of neworgan dysfunctions in the patients fed with the study diet and no more adverse events were observed. However, no significant difference in 28-day mortality of all cause was revealed( RR=0.83, 95% CI: 0.60-1.16, P = 0.27) . There were controversial results about the duration of mechanical ventilation.Conclusion A diet enriched with EPA, GLA, and elevated antioxidants is safe and beneficial for the clinical outcome 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.
ObjectiveTo systematically review the efficacy of antibiotic treatment in sepsis patients under the guidance of procalcitonin. MethodsDatabases including PubMed, The Cochrane Library (Issue 9, 2016), EMbase, Web of Science, CBM, WanFang Data, VIP and CNKI were electronically searched from inception to September 2016 to collect randomized controlled trials (RCTs) about antibiotic treatment in sepsis under the guidance of procalcitonin. Two reviewers independently screened literature, extracted data and assessed the risk bias of included studies, and then meta-analysis was performed by RevMan 5.3 software. ResultsA total of 15 RCTs involving 3 328 sepsis patients were included. Among them, 1 649 were in the procalcitionin group and 1 679 patients in the control group. The results of meta-analysis showed that:the PCT group could significantly reduce the using time of antibiotics (MD=-2.37, 95%CI -2.96 to -1.78, P<0.000 01), the ICU length of stay (MD=-0.26, 95%CI -0.46 to -0.07, P=0.007), the hospital length of stay (MD=-2.78, 95%CI -4.53 to -1.04, P=0.002), as well as the 28-day mortality (MD=0.78, 95%CI 0.66 to 0.93, P=0.005). There were no significant differences between the two groups in ICU mortality, in-hospital mortality and clinical cure rate. ConclusionUsing the procalcitontin to guide the antibiotic treatment in sepsis can reduce the patients' use of antibiotics, ICU length of stay, in-hospital length of stay and 28-day mortality, but can not reduce the patients' ICU mortality, in-hospital mortality and clinical cure rate. Due to the limited quality and quantity of included studies, the current conclusions are needed more studies to validate.
Sepsis is not only a common critical disease , but also a common complication and cause of death of patients in intensive care unit. It has the characteristics of dangerous condition, rapid development and high mortality. How to treat sepsis to improve the prognosis and quality of life of patients is very important. Timely and reasonable anti-infection is a vatal part in the treatment of sepsis. This article will review the progress of anti-infective therapy in adult patients with sepsis, starting from empirical anti-infection, procalcitonin-guided anti-infection, bacterial culture combined drug sensitivity test-guided anti-infection and anti-infection with antimicrobial peptides, aiming to provide a certain basis and reference for the anti-infective treatment of adult sepsis.
ObjectiveTo investigate the effect of polymyxin B hemoperfusion on the prognosis of patients with sepsis and septic shock by meta-analysis.MethodsSupplemented by manual search and document traceability, the US National Library of Medicine Pubmed, the Dutch Medical Abstracts Embase database, and the Cochrane clinical trial database were searched. Randomized controlled trials (RCTs) were collected from January 1998 to October 2018 for the treatment of sepsis and septic shock with polymyxin B hemoperfusion, only limited to English publications. The collected RCTs were evaluated and the prognosis of patients with sepsis and septic shock was analyzed by the Cochrane Collaboration.ResultsFinally six RCTs were included, and a total of 926 patients were analyzed, with 471 patients in the polymyxin B hemoperfusion group and 455 patients in the control group. The mortality rate was 36.3% (171/471) in the polymyxin B hemoperfusion group and 39.1% (178/455) in the control group. Hemoperfusion with polymyxin B could not reduce the patient mortality (RR=0.80, 95% CI 0.56 to 1.15, P=0.233). A subgroup analysis was taken on the patients with moderate to severe septic shock. Four RCTs were included in total and 418 patients were analyzed, with 207 patients in the polymyxin B hemoperfusion group and 211 in the control group. The mortality rate was 38.65% (80/207) in the polymyxin B hemoperfusion group and 50.71% (107/211) in the control group were. The hemoperfusion of polymyxin B could significantly reduce the mortality of patients with moderate to severe septic shock (RR=0.70, 95% CI 0.52 to 0.96, P=0.025).ConclusionsOlymyxin B hemoperfusion can not improve the prognosis of patients with sepsis and septic shock. However, compared with conventional treatment, polymyxin B hemoperfusion can improve the 28-day mortality rate of patients of severe septic shock. Due to the limit number of randomized controlled trials, more high-quality trials are needed to a further confirmation.
ObjectiveTo investigate the changes of platelet-leukocyte aggregates (PLA) level in patients with sepsis and its diagnostic value in sepsis complicated with acute respiratory distress syndrome (ARDS).MethodsA prospective study was carried in adult sepsis patients admitted to our hospital from January 2015 to November 2016. According to the 2012 " Berlin definition” diagnostic criteria, 58 cases of sepsis with ARDS were allocated to an experimental group and 139 cases of sepsis non-ARDS patients were allocated to a control group. Immediately after the diagnosis of sepsis, elbow vein blood samples were collected for flow cytometry assay of PLA. The acute physiology and chronic health assessment II (APACHE II score) of each group was performed and the receiver operating characteristic (ROC) curve was drawn.ResultsPlatelet-neutrophil aggregates (PNA) and platelet-lymphocyte aggregates (PLyA) in the experimental group were higher than those in the control group, but there were no significant differences (both P>0.05). The platelet-monocyte aggregates (PMA) of the experimental group was significantly higher than that of the control group (P<0.05). Peripheral blood PMA was positively correlated with APACHE II score (r=0.671, P<0.001). When PMA was used as the test variable, the area under the curve (AUC) was 0.945 with significant diagnostic value (P<0.001), and optimal cutoff value of PMA was 8.25%, with diagnostic sensitivity of 0.806 and diagnostic specificity of 0.951. When APACHE II was used as the test variable, AUC was 0.930, with significant diagnostic value (P<0.001), and optimal threshold of APACHE II was 16.500 with diagnostic sensitivity of 0.871 and diagnostic specificity of 0.852.ConclusionPMA is of great value in the diagnosis of sepsis with ARDS.
ObjectiveTo explore the effect of continuous renal replacement therapy (CRRT) to treat sepsis associated acute kidney injury (AKI) in patients aged over 80.MethodsForty-one patients diagnosed with sepsis and AKI were enrolled in geriatric RICU department of Huadong Hospital from January 2013 to July 2018, 38 patients were male and 3 were female. All patients were treated with anti-infection and fluid resuscitation therapy. After comprehensive judgment of the indication of renal replacement, they were divided into two groups by the choices of using CRRT. There were 20 patients in CRRT group and 21 in control group. Clinical data such as age, body mass index, previous diseases, 28-day mortality rate, blood cells, APACHEⅡ as well as SOFA scores were compared between two groups. Blood renal function and inflammatory markers at the first day were also compared to those after 3-day treatment of initial time.ResultsNo statistical difference was observed in sex ratio, age, body mass index and previous diseases between two groups (all P>0.05). There was also no difference in APACHEⅡ score, SOFA score, blood cells, hemoglobin and survival time. The 28-day mortality rate in CRRT group was lower than that in control group (P<0.05). The levels of serum UA and C reactive protein (CRP) in CRRT group decreased after 3-day treatment compared with those at the onset, and the differences were statistically significant (all P<0.05). The level of serum blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA) and cystain C in control group increased after 3 days compared with those at the onset, and the difference were statistically significant (all P<0.05). There was no significant difference in serum BUN, Cr, UA, cystain C, CRP and procalcitonin (PCT) between two groups at the onset (all P>0.05). After 3 days of CRRT, the levels of serum PCT, BUN, Cr and UA in CRRT group were lower than those in the control group (all P<0.05).ConclusionCRRT can improve hyperuricemia, control deterioration of renal function, reduce early systemic inflammatory response and 28-day mortality rate in aged patients with sepsis and AKI.