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Sample records for induced severe sepsis

  1. Ketoprofen impairs immunosuppression induced by severe sepsis and reveals an important role for prostaglandin E2.

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    Brogliato, Ariane Rennó; Antunes, Carlos A; Carvalho, Renato S; Monteiro, Ana Paula T; Tinoco, Rodrigo F; Bozza, Marcelo T; Canetti, Claudio; Peters-Golden, Marc; Kunkel, Steven L; Vianna-Jorge, Rosane; Benjamim, Claudia Farias

    2012-12-01

    The mechanism of immunosuppression induced by severe sepsis is not fully understood. The production of prostaglandin E2 (PGE2) during sepsis is well known, but its role in long-term consequences of sepsis has not been explored. The current study evaluates the role of PGE2 in the development of immunosuppression secondary to sepsis and its potential as therapeutic target. Cecal ligation and puncture was used as an experimental model for sepsis induction in Balb/c and C57BL/6 mice. Immunosuppression was evaluated by the response to secondary infection with Aspergillus fumigatus in sepsis survivors. The role of prostanoids was evaluated in vivo and in vitro by treatment with the cyclooxygenase inhibitor ketoprofen. Balb/c mice were more susceptible than C57BL/6 to severe sepsis and to secondary infection, with a greater mortality rate. Prostaglandin E2 concentrations found in bronchoalveolar lavage in sham and cecal ligation and puncture group after fungal challenge were much higher in Balb/c than in C57BL/6 mice. Ketoprofen treatment improved survival of septic Balb/c mice subjected to secondary infection, while also enhancing macrophage phagocytosis and neutrophil recruitment to the lungs. We identified a pivotal role for PGE2 acting on EP4 receptors in modulating cytokine production differentially by sham and septic macrophages. Furthermore, sepsis also altered key enzymes in PGE2 synthesis and degradation. Our results indicate the involvement of PGE2 in severe sepsis-induced immunosuppression. Inhibition of PGE2 production represents an attractive target to improve innate immune response against secondary infection in the immunocompromised host.

  2. Anthracyclines Induce DNA Damage Response-Mediated Protection against Severe Sepsis

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    Figueiredo, Nuno; Chora, Angelo; Raquel, Helena; Pejanovic, Nadja; Pereira, Pedro; Hartleben, Björn; Neves-Costa, Ana; Moita, Catarina; Pedroso, Dora; Pinto, Andreia; Marques, Sofia; Faridi, Hafeez; Costa, Paulo; Gozzelino, Raffaella; Zhao, Jimmy L.; Soares, Miguel P.; Gama-Carvalho, Margarida; Martinez, Jennifer; Zhang, Qingshuo; Döring, Gerd; Grompe, Markus; Simas, J. Pedro; Huber, Tobias B.; Baltimore, David; Gupta, Vineet; Green, Douglas R.; Ferreira, João A.; Moita, Luis F.

    2014-01-01

    Summary Severe sepsis remains a poorly understood systemic inflammatory condition with high mortality rates and limited therapeutic options in addition to organ support measures. Here we show that the clinically approved group of anthracyclines acts therapeutically at a low dose regimen to confer robust protection against severe sepsis in mice. This salutary effect is strictly dependent on the activation of DNA damage response and autophagy pathways in the lung, as demonstrated by deletion of the ataxia telangiectasia mutated (Atm) or the autophagy-related protein 7 (Atg7) specifically in this organ. The protective effect of anthracyclines occurs irrespectively of pathogen burden, conferring disease tolerance to severe sepsis. These findings demonstrate that DNA damage responses, including the ATM and Fancony Anemia pathways, are important modulators of immune responses and might be exploited to confer protection to inflammation-driven conditions, including severe sepsis. PMID:24184056

  3. Severe sepsis in older adults.

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    Umberger, Reba; Callen, Bonnie; Brown, Mary Lynn

    2015-01-01

    Severe sepsis may be underrecognized in older adults. Therefore, the purpose of this article is to review special considerations related to early detection of severe sepsis in older adults. Normal organ changes attributed to aging may delay early detection of sepsis at the time when interventions have the greatest potential to improve patient outcomes. Systems are reviewed for changes. For example, the cardiovascular system may have a limited or absent compensatory response to inflammation after an infectious insult, and the febrile response and recruitment of white blood cells may be blunted because of immunosenescence in aging. Three of the 4 hallmark responses (temperature, heart rate, and white blood cell count) to systemic inflammation may be diminished in older adults as compared with younger adults. It is important to consider that older adults may not always manifest the typical systemic inflammatory response syndrome. Atypical signs such as confusion, decreased appetite, and unsteady gait may occur before sepsis related organ failure. Systemic inflammatory response syndrome criteria and a comparison of organ failure criteria were reviewed. Mortality rates in sepsis and severe sepsis remain high and are often complicated by multiple organ failures. As the numbers of older adults increase, early identification and prompt treatment is crucial in improving patient outcomes.

  4. Intranuclear interactomic inhibition of NF-κB suppresses LPS-induced severe sepsis

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    Park, Sung-Dong [Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Cheon, So Yeong [Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Park, Tae-Yoon; Shin, Bo-Young [Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Oh, Hyunju; Ghosh, Sankar [Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Koo, Bon-Nyeo, E-mail: koobn@yuhs.ac [Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Lee, Sang-Kyou, E-mail: sjrlee@yonsei.ac.kr [Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2015-08-28

    Suppression of nuclear factor-κB (NF-κB) activation, which is best known as a major regulator of innate and adaptive immune responses, is a potent strategy for the treatment of endotoxic sepsis. To inhibit NF-κB functions, we designed the intra-nuclear transducible form of transcription modulation domain (TMD) of RelA (p65), called nt-p65-TMD, which can be delivered effectively into the nucleus without influencing the cell viability, and work as interactomic inhibitors via disruption of the endogenous p65-mediated transcription complex. nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines, including TNF-α, IL-1β, or IL-6 from BV2 microglia cells stimulated by lipopolysaccharide (LPS). nt-p65-TMD did not inhibit tyrosine phosphorylation of signaling mediators such as ZAP-70, p38, JNK, or ERK involved in T cell activation, but was capable of suppressing the transcriptional activity of NF-κB without the functional effect on that of NFAT upon T-cell receptor (TCR) stimulation. The transduced nt-p65-TMD in T cell did not affect the expression of CD69, however significantly inhibited the secretion of T cell-specific cytokines such as IL-2, IFN-γ, IL-4, IL-17A, or IL-10. Systemic administration of nt-p65-TMD showed a significant therapeutic effect on LPS-induced sepsis model by inhibiting pro-inflammatory cytokines secretion. Therefore, nt-p65-TMD can be a novel therapeutics for the treatment of various inflammatory diseases, including sepsis, where a transcription factor has a key role in pathogenesis, and further allows us to discover new functions of p65 under normal physiological condition without genetic alteration. - Highlights: • The nt-p65-TMD is intra-nuclear interactomic inhibitor of endogenous p65. • The nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines. • The excellent therapeutic potential of nt-p65-TMD was confirmed in sepsis model.

  5. Is there NO treatment for severe sepsis?

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    Cauwels A

    2008-01-01

    Full Text Available Sepsis is a systemic inflammatory response syndrome in the presence of suspected or proven infection, and it may progress to or encompass organ failure (severe sepsis and hypotension (septic shock. Clinicians possess an arsenal of supportive measures to combat severe sepsis and septic shock, and some success, albeit controversial, has been achieved by using low doses of corticosteroids or recombinant human activated protein C. However, a truly effective mediator-directed specific treatment has not been developed yet. Treatment with low doses of corticosteroids or with recombinant human activated protein C remains controversial and its success very limited. Attempts to treat shock by blocking LPS, TNF or IL-1 were unsuccessful, as were attempts to use interferon-gamma or granulocyte colony stimulating factor. Inhibiting nitric oxide synthases held promise but met with considerable difficulties. Scavenging excess nitric oxide or targeting molecules downstream of inducible nitric oxide synthase, such as soluble guanylate cyclase or potassium channels, might offer other alternatives.

  6. Sepsis-induced Cardiomyopathy

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    Romero-Bermejo, Francisco J; Ruiz-Bailen, Manuel; Gil-Cebrian, Julián; Huertos-Ranchal, María J

    2011-01-01

    Myocardial dysfunction is one of the main predictors of poor outcome in septic patients, with mortality rates next to 70%. During the sepsis-induced myocardial dysfunction, both ventricles can dilate and diminish its ejection fraction, having less response to fluid resuscitation and catecholamines, but typically is assumed to be reversible within 7-10 days. In the last 30 years, It´s being subject of substantial research; however no explanation of its etiopathogenesis or effective treatment have been proved yet. The aim of this manuscript is to review on the most relevant aspects of the sepsis-induced myocardial dysfunction, discuss its clinical presentation, pathophysiology, etiopathogenesis, diagnostic tools and therapeutic strategies proposed in recent years. PMID:22758615

  7. Severe sepsis management are we doing enough?

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    Ahrens, Tom; Vollman, Kathleen

    2003-10-01

    For the first time in medical history, a drug has been shown to reduce the mortality associated with sepsis, the leading cause of death in many ICUs. Optimal use by appropriate selection of patients and early recognition of sepsis could save thousands of lives. Nurses play a major role in recognizing severe sepsis. By using the concepts introduced here, nurses can play a direct role in saving the lives of patients with sepsis.

  8. Improving multidisciplinary severe sepsis management using the Sepsis Six .

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    Bhat, Amar; Asghar, Maryam; Raulia, Gagandeep; Mandal, Amit Keiran John

    2016-12-01

    Each year in the UK, it is estimated that more than 100,000 people are admitted to hospital with sepsis and around 37,000 people will die as a result of the condition. We present an audit, re-audit and the implications these have had on the management of severe sepsis using the Sepsis Six, ultimately through actively promoting teamwork to initiate the protocol. This led to a significant improvement in management, decreasing admissions to the intensive care unit (ITU), length of stay in hospital and the number of patient deaths.The initial audit and re-audit were done over 2-month periods. All clerking notes of patients with a medical consultant diagnosis of 'sepsis' on post-take ward round were analysed and further screened for presence of severe sepsis according to national guidelines.There was significant improvement from only 1% of patients being appropriately managed (according to the existing guidelines) to 67% of eligible subjects adhering to the protocol (psepsis with trust-wide updated protocols, resulting in a decrease in hospital morbidity and mortality. © Royal College of Physicians 2016. All rights reserved.

  9. Severe sepsis secondary to emphysematous cystitis

    African Journals Online (AJOL)

    M.M. Gargouri

    We present the case of a patient with EC who presented with severe sepsis of unknown origin. He ... Peer review under responsibility of Pan African Urological Surgeons' ... nantly on the left side, minimal dysuria and fever for the previous 7.

  10. Designing a Pediatric Severe Sepsis Screening Tool

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    Robert eSepanski

    2014-06-01

    Full Text Available We sought to create a screening tool with improved predictive value for pediatric severe sepsis and septic shock that can be incorporated into the electronic medical record and actively screen all patients arriving at a pediatric Emergency Department (ED. Gold standard severe sepsis cases were identified using a combination of coded discharge diagnosis and physician chart review from 7,402 children who visited a pediatric ED over two months. The tool’s identification of severe sepsis was initially based on International Consensus Conference on Pediatric Sepsis (ICCPS parameters that were refined by an iterative, virtual process that allowed us to propose successive changes in sepsis detection parameters in order to optimize the tool’s predictive value based on receiver operating curve (ROC characteristics. Age-specific normal and abnormal values for heart rate (HR and respiratory rate (RR were empirically derived from 143,603 children seen in a second pediatric ED over three years. Univariate analyses were performed for each measure in the tool to assess its association with severe sepsis and to characterize it as an early or late indicator of severe sepsis. A split-sample was used to validate the final, optimized tool. The final tool incorporated age-specific thresholds for abnormal HR and RR and employed a linear temperature correction for each category. The final tool’s positive predictive value was 48.7%, a significant, nearly three-fold improvement over the original ICCPS tool. False positive Systemic Inflammatory Response Syndrome (SIRS identifications were nearly six-fold lower.

  11. Thromboelastometry in patients with severe sepsis and disseminated intravascular coagulation.

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    Sivula, Mirka; Pettilä, Ville; Niemi, Tomi T; Varpula, Marjut; Kuitunen, Anne H

    2009-09-01

    Severe sepsis induces coagulopathy, which may lead to disseminated intravascular coagulation (DIC). Thromboelastometry is a point-of-care whole blood coagulation monitor, which has been validated in human endotoxemia model. We assessed thromboelastometry in severe sepsis and overt DIC and investigated its applicability in differentiating sepsis-related coagulation disturbances. Thromboelastometry (EXTEM and FIBTEM tests) and traditional coagulation assays were analyzed in 28 patients with severe sepsis, 12 of who fulfilled the criteria of overt DIC on admission. Ten healthy persons served as controls. Coagulation parameters, clotting time, clot formation time (CFT), alpha angle, maximal clot firmness (MCF) and lysis index at 60 min, were registered. In patients with overt DIC, EXTEM MCF, CFT and alpha angle differed from that in both healthy controls and patients without DIC, indicating hypocoagulation (MCF 52, 63 and 68 mm; CFT 184, 88 and 73 s; and alpha angle 58, 72 and 76 degrees , respectively, P coagulation assays showed progressively worsening coagulopathy from controls to septic patients without DIC and further to those with overt DIC. We conclude that thromboelastometry may be a valuable tool in assessing whole blood coagulation capacity in patients with severe sepsis with and without overt DIC.

  12. 4G/5G polymorphism of PAI-1 gene is associated with multiple organ dysfunction and septic shock in pneumonia induced severe sepsis: prospective, observational, genetic study.

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    Madách, Krisztina; Aladzsity, István; Szilágyi, Agnes; Fust, George; Gál, János; Pénzes, István; Prohászka, Zoltán

    2010-01-01

    Activation of inflammation and coagulation are closely related and mutually interdependent in sepsis. The acute-phase protein, plasminogen activator inhibitor-1 (PAI-1) is a key element in the inhibition of fibrinolysis. Elevated levels of PAI-1 have been related to worse outcome in pneumonia. We aimed to evaluate the effect of functionally relevant 4G/5G polymorphism of PAI-1 gene in pneumonia induced sepsis. We enrolled 208 Caucasian patients with severe sepsis due to pneumonia admitted to an intensive care unit (ICU). Patients were followed up until ICU discharge or death. Clinical data were collected prospectively and the PAI-1 4G/5G polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. Patients were stratified according to the occurrence of multiple organ dysfunction syndrome, septic shock or death. We found that carriers of the PAI-1 4G/4G and 4G/5G genotypes have a 2.74-fold higher risk for multiple organ dysfunction syndrome (odds ratio [OR] 95% confidence interval [CI] = 1.335 - 5.604; p = 0.006) and a 2.57-fold higher risk for septic shock (OR 95%CI = 1.180 - 5.615; p = 0.018) than 5G/5G carriers. The multivariate logistic regression analysis adjusted for independent predictors, such as age, nosocomial pneumonia and positive microbiological culture also supported that carriers of the 4G allele have a higher prevalence of multiple organ dysfunction syndrome (adjusted odds ratio [aOR] = 2.957; 95%CI = 1.306 -6.698; p = 0.009) and septic shock (aOR = 2.603; 95%CI = 1.137 - 5.959; p = 0.024). However, genotype and allele analyses have not shown any significant difference regarding mortality in models non-adjusted or adjusted for acute physiology and chronic health evaluation (APACHE) II. Patients bearing the 4G allele had higher disseminated intravascular coagulation (DIC) score at admission (p = 0.007) than 5G/5G carriers. Moreover, in 4G allele carriers the length of ICU stay of non-survivors was longer

  13. Sepsis-Induced Cardiomyopathy: Mechanisms and Treatments

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    Yan-Cun Liu

    2017-08-01

    Full Text Available Sepsis is a lethal syndrome with a high incidence and a weighty economy burden. The pathophysiology of sepsis includes inflammation, immune dysfunction, and dysfunction of coagulation, while sepsis-induced cardiomyopathy (SIC, defined as a global but reversible dysfunction of both sides of the heart induced by sepsis, plays a significant role in all of the aspects above in the pathogenesis of sepsis. The complex pathogenesis of SIC involves a combination of dysregulation of inflammatory mediators, mitochondrial dysfunction, oxidative stress, disorder of calcium regulation, autonomic nervous system dysregulation, and endothelial dysfunction. The treatments for SIC include the signal pathway intervention, Chinese traditional medicine, and other specific therapy. Here, we reviewed the latest literatures on the mechanisms and treatments of SIC and hope to provide further insights to researchers and create a new road for the therapy of sepsis.

  14. Continuous Renal Replacement Therapy for Severe Obstetric Sepsis

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    D. L. Shukevich

    2010-01-01

    Full Text Available Objective: to improve the results of treatment for severe obstetric sepsis by pathogenetically founded continuous renal replacement therapies as extracorporeal homeostatic correction. Subjects and methods. Forty-two women with severe abdominal sepsis were divided into 3 groups: 1 14 women with severe extragenital abdominal sepsis who received standard intensive care (a control group; 2 12 women with severe obstetric sepsis who had standard intensive care (a study group; 3 16 with severe obstetric sepsis who had the standard intensive care supplemented with continuous renal replacement therapy (an intervention group. Results. In Group 2, endogenous intoxication and multiple organ dysfunction were controlled later than in Group 1, mortality rates being 41.7 and 7.1%, respectively. Clinical laboratory differences were due to gestosis recorded in 100% of the patients with severe obstetric sepsis. When continuous renal replacement therapy was incorporated into the complex therapy of severe obstetric sepsis, there was a prompter regression of endogenous intoxication and multiple organ dysfunction, mortality was decreased by an average of 35% as compared with that during standard therapy. Conclusion. The inclusion of continuous renal replacement therapy into the complex treatment program for severe obstetric sepsis made it possible to reduce control time _ for endogenous intoxication and multiple organ dysfunction and to decrease mortality by an average of 35% as compared with that during standard intensive care. Key words: obstetric sepsis, abdominal sepsis, gestosis, endogenous intoxication, multiple organ dysfunction, renal replacement therapy.

  15. Sepsis-induced brain dysfunction.

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    Adam, Nicolas; Kandelman, Stanislas; Mantz, Jean; Chrétien, Fabrice; Sharshar, Tarek

    2013-02-01

    Systemic infection is often revealed by or associated with brain dysfunction, which is characterized by alteration of consciousness, ranging from delirium to coma, seizure or focal neurological signs. Its pathophysiology involves an ischemic process, secondary to impairment of cerebral perfusion and its determinants and a neuroinflammatory process that includes endothelial activation, alteration of the blood-brain barrier and passage of neurotoxic mediators. Microcirculatory dysfunction is common to these two processes. This brain dysfunction is associated with increased mortality, morbidity and long-term cognitive disability. Its diagnosis relies essentially on neurological examination that can lead to specific investigations, including electrophysiological testing or neuroimaging. In practice, cerebrospinal fluid analysis is indisputably required when meningitis is suspected. Hepatic, uremic or respiratory encephalopathy, metabolic disturbances, drug overdose, sedative or opioid withdrawal, alcohol withdrawal delirium or Wernicke's encephalopathy are the main differential diagnoses. Currently, treatment consists mainly of controlling sepsis. The effects of insulin therapy and steroids need to be assessed. Various drugs acting on sepsis-induced blood-brain barrier dysfunction, brain oxidative stress and inflammation have been tested in septic animals but not yet in patients.

  16. Detection of intracytoplasmic Th1/Th2 cytokine profiles in patients with sepsis and severe sepsis

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    Ahmadinejad Z

    2007-06-01

    Full Text Available Background: Sepsis is the leading cause of death in critically ill patients throughout the world. The incidence is increasing despite the major advances in the development of antimicrobial agents and other supportive treatments. Based on multiple studies, it has been shown that patient outcome depends on Th1 and Th2 cytokine response. Moreover, whenever the Th2 response is predominant, the sepsis is more severe. The aim of this study was to evaluate the correlation between cytokine levels and the severity of sepsis in patients. Methods: A cross-sectional study on the cellular levels of several pro-inflammatory cytokines was carried out in patients with sepsis and severe sepsis. The study included 37 patients (24 men and 13 women, 26 of them had sepsis and 11 had the severe form of sepsis Thirty-seven healthy volunteers served as controls. The average age of the patients was 57 years (±23.3 years, with a range of 21 to 92 years. From the whole blood of the subjects, we separated the monocytes and leukocytes, which were then cultured. Using an ELISA method, we measured levels of IFN- and IL-12 (associated with Th1, and IL-4 and IL-10 (associated with Th2 in the cultured cells with and without cell stimulation. Results: No correlation was found for IFN- production in the cells of patients with sepsis and severe sepsis, regardless of whether the patients had died or survived. However, IL-12 levels were significantly decreased in severe sepsis compared with those of sepsis patients (P=0.048. Furthermore, the cells of expired patients also had significantly decreased IL-12 levels compared with those of surviving patients (P=0.028. We also found that the levels of IFN-, IL-4, and IL-10 were decreased in patients compared with those of controls, which correlated to their production. However, there was no correlation for IL-12 production between the cells of the patients compared with those of the controls. There was also no correlation for

  17. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

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    Dellinger, R Phillip; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven A; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui

    2013-02-01

    at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO2/FIO2 ratio of ≤ 100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 hrs) for patients with early ARDS and a Pao2/Fio2 180 mg/dL, targeting an upper blood glucose ≤ 180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 hrs after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 hrs of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary

  18. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012.

    Science.gov (United States)

    Dellinger, R P; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui

    2013-02-01

    positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO (2)/FiO (2) ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a PaO (2)/FI O (2) insulin dosing when two consecutive blood glucose levels are >180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic

  19. Ensemble models of neutrophil trafficking in severe sepsis.

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    Sang Ok Song

    Full Text Available A hallmark of severe sepsis is systemic inflammation which activates leukocytes and can result in their misdirection. This leads to both impaired migration to the locus of infection and increased infiltration into healthy tissues. In order to better understand the pathophysiologic mechanisms involved, we developed a coarse-grained phenomenological model of the acute inflammatory response in CLP (cecal ligation and puncture-induced sepsis in rats. This model incorporates distinct neutrophil kinetic responses to the inflammatory stimulus and the dynamic interactions between components of a compartmentalized inflammatory response. Ensembles of model parameter sets consistent with experimental observations were statistically generated using a Markov-Chain Monte Carlo sampling. Prediction uncertainty in the model states was quantified over the resulting ensemble parameter sets. Forward simulation of the parameter ensembles successfully captured experimental features and predicted that systemically activated circulating neutrophils display impaired migration to the tissue and neutrophil sequestration in the lung, consequently contributing to tissue damage and mortality. Principal component and multiple regression analyses of the parameter ensembles estimated from survivor and non-survivor cohorts provide insight into pathologic mechanisms dictating outcome in sepsis. Furthermore, the model was extended to incorporate hypothetical mechanisms by which immune modulation using extracorporeal blood purification results in improved outcome in septic rats. Simulations identified a sub-population (about 18% of the treated population that benefited from blood purification. Survivors displayed enhanced neutrophil migration to tissue and reduced sequestration of lung neutrophils, contributing to improved outcome. The model ensemble presented herein provides a platform for generating and testing hypotheses in silico, as well as motivating further experimental

  20. Culture-Negative Severe Sepsis: Nationwide Trends and Outcomes.

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    Gupta, Shipra; Sakhuja, Ankit; Kumar, Gagan; McGrath, Eric; Nanchal, Rahul S; Kashani, Kianoush B

    2016-12-01

    Although 28% to 49% of severe sepsis hospitalizations have been described as being "culture negative," there are very limited data on the epidemiology and outcomes of those with culture-negative severe sepsis (CNSS). The objectives of this study were to investigate the proportion and trends of CNSS and its association with mortality. Using the Nationwide Inpatient Sample (NIS) database from 2000 to 2010, we identified adults hospitalized with severe sepsis. Those without any specific organism codes were identified as "with CNSS." We examined the proportion of CNSS hospitalizations and rates of mortality associated with it. We also assessed the independent effect of CNSS on mortality. Of 6,843,279 admissions of patients with severe sepsis, 3,226,406 (47.1%) had culture-negative results. The age-adjusted proportion of CNSS increased from 33.9% in 2000 to 43.5% in 2010 (P sepsis (OR, 1.75; 95% CI, 1.72-1.77). CNSS among hospitalized patients is common, and its proportion is on the rise. CNSS is associated with greater acute organ dysfunction and mortality. Having CNSS is an independent predictor of death. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  1. [Effects of phentolamine on haemodynamics of patients with severe sepsis].

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    Yang, W; Li, X B; Zhou, Y; Mo, X M

    2017-02-07

    Objective: To explore the effects of phentolamine on hemodynamic of patients with severe sepsis . Methods: From January 2015 to August 2016, using random number table, 59 patients with severe sepsis were divided into research group and the control group by conventional treatment in Department of Emergency, the Second People's Hospital of Nanning City. The patients of the research group were given phentolamine injection. The CI, ITBVI, EVLWI, SVRI of the patients were monitored by PICCO on 6, 12, 24, 48, 72 h before and after treatment. Measuring clearance of blood lactic acid, lactic acid, comparing two groups of blood lactic acid, lactic acid clearance change tendency, 28 d survival rate and time of the two groups in the ICU of patients was observed. Results: CI, SVRI, ITBVI of the research group was increased obviously, and EVLWI decreased obviously(PPhentolamine can significantly improve the early condition of hemodynamic and the survival rates of patients with severe sepsis.

  2. Severe Sepsis in Severely Malnourished Young Bangladeshi Children with Pneumonia: A Retrospective Case Control Study.

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    Mohammod Jobayer Chisti

    Full Text Available In developing countries, there is no published report on predicting factors of severe sepsis in severely acute malnourished (SAM children having pneumonia and impact of fluid resuscitation in such children. Thus, we aimed to identify predicting factors for severe sepsis and assess the outcome of fluid resuscitation of such children.In this retrospective case-control study SAM children aged 0-59 months, admitted to the Intensive Care Unit (ICU of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh from April 2011 through July 2012 with history of cough or difficult breathing and radiologic pneumonia, who were assessed for severe sepsis at admission constituted the study population. We compared the pneumonic SAM children with severe sepsis (cases = 50 with those without severe sepsis (controls = 354. Severe sepsis was defined with objective clinical criteria and managed with fluid resuscitation, in addition to antibiotic and other supportive therapy, following the standard hospital guideline, which is very similar to the WHO guideline.The case-fatality-rate was significantly higher among the cases than the controls (40% vs. 4%; p<0.001. In logistic regression analysis after adjusting for potential confounders, lack of BCG vaccination, drowsiness, abdominal distension, acute kidney injury, and metabolic acidosis at admission remained as independent predicting factors for severe sepsis in pneumonic SAM children (p<0.05 for all comparisons.We noted a much higher case fatality among under-five SAM children with pneumonia and severe sepsis who required fluid resuscitation in addition to standard antibiotic and other supportive therapy compared to those without severe sepsis. Independent risk factors and outcome of the management of severe sepsis in our study children highlight the importance for defining optimal fluid resuscitation therapy aiming at reducing the case fatality in such children.

  3. Severe postpartum sepsis with prolonged myocardial dysfunction: a case report

    Directory of Open Access Journals (Sweden)

    Chen Katherine T

    2010-10-01

    Full Text Available Abstract Introduction Severe sepsis during pregnancy or in the postpartum period is a rare clinical event. In non obstetric surviving patients, the cardiovascular changes seen in sepsis and septic shock are fully reversible five to ten days after their onset. We report a case of septic myocardial dysfunction lasting longer than ten days. To the best of our knowledge, this is the first report of prolonged septic myocardial dysfunction in a parturient. Case presentation A 24 year old Hispanic woman with no previous medical history developed pyelonephritis and severe sepsis with prolonged myocardial dysfunction after a normal spontaneous vaginal delivery. Conclusions Septic myocardial dysfunction may be prolonged in parturients requiring longer term follow up and pharmacologic treatment.

  4. Severe sepsis and septic shock due to Plasmodium vivax infection.

    Science.gov (United States)

    Chalkias, Athanasios; Aridas, Sotirios; Karageorgopoulos, Drosos E; Stratiotis, Georgios; Mystrioti, Dimitra; Mallios, Athanasios; Nakos, Ioannis; Mpellos, Nikolaos; Ganotopoulou, Asimina; Xanthos, Theodoros

    2013-04-01

    Plasmodium vivax malaria is typically characterized by a mild and benign clinical course. Organ dysfunction is rarely seen, whereas acute lung injury has been found to occur after starting antimalarial treatment. We present an unusual case of severe sepsis and septic shock due to Plasmodium vivax monoinfection.

  5. Antioxidant protection of statins in acute kidney injury induced by sepsis

    Directory of Open Access Journals (Sweden)

    Franciele do Nascimento Santos

    2014-10-01

    Full Text Available Objective Evaluating the effect of preconditioning with simvastatin in acute kidney injury induced by sepsis. Method Male adult Wistar rats were divided into the following groups: SHAM (control; SHAM+Statin (0.5 mg/kg simvastatin, orally; Sepsis (cecal puncture ligation – CPL; Sepsis+Statin. Physiological parameters, peritoneal fluid culture, renal function, oxidative metabolites, severity of acute kidney injury and animal survival were evaluated. Results The treatment with simvastatin in induced sepsis showed elevation of creatinine clearance with attenuation of generation of oxidative metabolites, lower severity of acute kidney injury and reduced mortality. Conclusion This investigation confirmed the renoprotection with antioxidant principle of the simvastatin in acute kidney injury induced by sepsis in an experimental model.

  6. Injuria renal aguda en la sepsis grave Acute kidney injury in severe sepsis

    Directory of Open Access Journals (Sweden)

    Hernán Trimarchi

    2009-06-01

    Full Text Available La sepsis afecta al 40% de los pacientes críticos, siendo su mortalidad de aproximadamente un 30% en el caso de la sepsis grave, y de 75% con injuria renal aguda, la cual sucede en el 20-51% de los casos. Se realizó un estudio prospectivo, observacional, longitudinal, en 80 pacientes sépticos graves en el lapso de 1 año para determinar el desarrollo de injuria renal aguda y su relación con la mortalidad; correlacionar antecedentes clínicos y variaciones del laboratorio con la mortalidad; determinar la tasa de mortalidad de la sepsis grave; relacionar óbito y foco séptico primario; evaluar la predictibilidad de mortalidad según niveles de creatinina de ingreso y sus variaciones finales. Se definieron dos grupos: Obito (n = 25 y No-óbito (n = 55. Analizados según la creatinina de ingreso, 39 tenían valores normales de creatinina (10 óbitos y 41 la presentaban elevada (15 óbitos; según la creatinina de egreso, 48 presentaron creatinina normal y fallecieron 7, mientras que 32 tenían daño renal agudo, de los cuales 18 fallecieron. De los 25 pacientes fallecidos, el 72% presentaron daño renal. De éstos, 7 pacientes vivos y 2 fallecidos requirieron hemodiálisis. El foco primario más frecuente fue el respiratorio (26.4%. El desarrollo de daño renal es un alto predictor de mortalidad en la sepsis, independientemente de los valores iniciales de creatinina. Edad más avanzada, hipertensión arterial, score APACHE más elevado, anemia más grave, hipoalbuminemia, hiperfosfatemia e hiperkalemia se asociaron a mayor mortalidad. La mortalidad global fue 31.3%. La imposibilidad de identificar el foco séptico primario se asoció a mayor mortalidad. El foco respiratorio se relacionó a mayor riesgo de requerir hemodiálisis.Sepsis affects 40% of critically ill patients, with a reported mortality of approximately 30% in severe sepsis, raising to 75% when acute kidney injury ensues, which occurs in about 20-51% of cases. The present study

  7. Double Volume Exchange Transfusion in Severe Neonatal Sepsis.

    Science.gov (United States)

    Aradhya, Abhishek Somasekhara; Sundaram, Venkataseshan; Kumar, Praveen; Ganapathy, Suja Mariam; Jain, Ashish; Rawat, Amit

    2016-02-01

    To study the efficacy and safety of double volume exchange transfusion (DVET) in neonates > 1000 g birth weight with severe sepsis. Eighty-three neonates weighing >1000 g with severe sepsis were randomly assigned to DVET or standard therapy (ST) group. Primary outcome was mortality by 14 d from enrollment. A 21 % reduction in mortality, albeit non-significant, by 14 d from enrollment was observed in DVET group in comparison to ST group [RR: 0.79 (95 % C.I 0.45-1.3); p 0.4]. A similar trend in mortality reduction was observed with early mortality and mortality by discharge in DVET group. No difference was observed in normalization of dysfunctional organs by 14 d. Cardiovascular and hematological system benefitted the most, followed by renal dysfunction with DVET. A significant improvement in post DVET IgG, IgA, IgM, C3 and base deficit was observed. No serious adverse effects occurred following DVET. In neonates >1000 g with severe sepsis, DVET was associated with a trend towards decrease in mortality by 14 d from enrollment. A significant improvement in immunoglobulin and complement C3 levels and acid base status were observed following DVET. DVET is a safe procedure in severely sick and septic neonates.

  8. Sepsis-induced acute kidney injury in patients with cirrhosis.

    Science.gov (United States)

    Angeli, Paolo; Tonon, Marta; Pilutti, Chiara; Morando, Filippo; Piano, Salvatore

    2016-01-01

    Acute kidney injury (AKI) is a common and life-threatening complication in patients with cirrhosis. Recently, new criteria for the diagnosis of AKI have been proposed in patients with cirrhosis by the International Club of Ascites. Almost all types of bacterial infections can induce AKI in patients with cirrhosis representing its most common precipitating event. The bacterial infection-induced AKI usually meets the diagnostic criteria of hepatorenal syndrome (HRS). Well in keeping with the "splanchnic arterial vasodilation hypothesis", it has been stated that HRS develops as a consequence of a severe reduction of effective circulating volume related to splanchnic arterial vasodilation and to an inadequate cardiac output. Nevertheless, the role of bacterial infections in precipitating organ failures, including renal failure, is enhanced when their course is characterized by the development of a systemic inflammatory response syndrome (SIRS), thus, when sepsis occurs. Sepsis has been shown to be capable to induce "per se" AKI in animals as well as in patients conditioning also the features of renal damage. This observation suggests that when precipitated by sepsis, the pathogenesis and the clinical course of AKI also in patients with cirrhosis may differentiate to a certain extent from AKI with another or no precipitating factor. The purpose of this review is to describe the features of AKI precipitated by bacterial infections and to highlight whether infection and/or the development of SIRS may influence its clinical course, and, in particular, the response to treatment.

  9. Intensive insulin therapy and pentastarch resuscitation in severe sepsis.

    Science.gov (United States)

    Brunkhorst, Frank M; Engel, Christoph; Bloos, Frank; Meier-Hellmann, Andreas; Ragaller, Max; Weiler, Norbert; Moerer, Onnen; Gruendling, Matthias; Oppert, Michael; Grond, Stefan; Olthoff, Derk; Jaschinski, Ulrich; John, Stefan; Rossaint, Rolf; Welte, Tobias; Schaefer, Martin; Kern, Peter; Kuhnt, Evelyn; Kiehntopf, Michael; Hartog, Christiane; Natanson, Charles; Loeffler, Markus; Reinhart, Konrad

    2008-01-10

    The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids. In a multicenter, two-by-two factorial trial, we randomly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10% pentastarch, a low-molecular-weight hydroxyethyl starch (HES 200/0.5), or modified Ringer's lactate for fluid resuscitation. The rate of death at 28 days and the mean score for organ failure were coprimary end points. The trial was stopped early for safety reasons. Among 537 patients who could be evaluated, the mean morning blood glucose level was lower in the intensive-therapy group (112 mg per deciliter [6.2 mmol per liter]) than in the conventional-therapy group (151 mg per deciliter [8.4 mmol per liter], Ptherapy group than in the conventional-therapy group (17.0% vs. 4.1%, Ptherapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer's lactate. The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia. As used in this study, HES was harmful, and its toxicity increased with accumulating doses. (ClinicalTrials.gov number, NCT00135473.) 2008 Massachusetts Medical Society

  10. Blister fluid and serum cytokine levels in severe sepsis in humans reflect skin dysfunction.

    Science.gov (United States)

    Koskela, M; Ala-Kokko, T I; Gäddnäs, F; Herzig, K-H; Karhu, T; Oikarinen, A; Koivukangas, V

    2017-01-01

    Knowledge of sepsis-related end-organ inflammation in vivo is limited. We investigated the cytokine response in skin and in serum in sepsis and its relation to multiorgan failure (MOF) and survival. Cytokines were analysed in serum and in suction blister fluid of intact skin of 44 patients with severe sepsis and 15 healthy controls. Blister fluid and serum samples were collected within 48 h of the first sepsis-induced organ failure. This is a substudy of a larger follow-up study on wound healing in sepsis. Cytokine levels were higher in patients with sepsis vs. controls (interleukin [IL]-10, blisters: 65.9 vs. 4.3 pg/ml, P blisters: 41.9 vs. 0.03 pg/ml, P blister fluid than patients without MOF. In blister fluid, survivors had lower levels of IL-10 (43.3 vs. 181.9 pg/ml, P = 0.024) and bFGF (15.8 vs. 31.9 pg/ml, P = 0.006) than non-survivors. In serum, survivors had higher levels of vascular endothelial growth factor (VEGF) (152.2 vs. 14.7 pg/ml, P = 0.012) and lower levels of IL-6 (38.5 vs. 91.1 pg/ml, P = 0.011) than non-survivors. The blister fluid levels of bFGF, TNF and VEGF did not correlate with the serum levels. Cytokine responses in skin blister fluid in patients with sepsis differed from those in healthy controls. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  11. Clinical Significance of Tissue Factor and CD13 Double-Positive Microparticles in Sirs Patients with Trauma and Severe Sepsis.

    Science.gov (United States)

    Matsumoto, Hisatake; Yamakawa, Kazuma; Ogura, Hiroshi; Koh, Taichin; Matsumoto, Naoya; Shimazu, Takeshi

    2017-04-01

    Activated immune cells such as monocytes are key factors in systemic inflammatory response syndrome (SIRS) following trauma and sepsis. Activated monocytes induce almost all tissue factor (TF) expression contributing to inflammation and coagulation. TF and CD13 double-positive microparticles (TF/CD13MPs) are predominantly released from these activated monocytes. This study aimed to evaluate TF/CD13MPs and assess their usefulness as a biomarker of pathogenesis in early SIRS following trauma and sepsis. This prospective study comprising 24 trauma patients, 25 severe sepsis patients, and 23 healthy controls was conducted from November 2012 to February 2015. Blood samples were collected from patients within 24 h after injury and diagnosis of severe sepsis and from healthy controls. Numbers of TF/CD13MPs were measured by flow cytometry immediately thereafter. Injury Severity Score (ISS) and Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were calculated at patient enrollment. APACHE II and SOFA scores and International Society of Thrombosis and Haemostasis (ISTH) overt disseminated intravascular coagulation (DIC) diagnostic criteria algorithm were calculated at the time of enrollment of severe sepsis patients. Numbers of TF/CD13MPs were significantly increased in both trauma and severe sepsis patients versus controls and correlated significantly with ISS and APACHE II score in trauma patients and with APACHE II and ISTH DIC scores in severe sepsis patients. Increased numbers of TF/CD13MPs correlated significantly with severities in the acute phase in trauma and severe sepsis patients, suggesting that TF/CD13MPs are important in the pathogenesis of early SIRS following trauma and sepsis.

  12. Immunohistochemical detection of CCR2 and CX3CR1 in sepsis-induced lung injury.

    Science.gov (United States)

    An, Jun-Ling; Ishida, Yuko; Kimura, Akihiko; Tsokos, Michael; Kondo, Toshikazu

    2009-11-20

    Sepsis is a systemic inflammatory disease with high mortality. In the present study, we immunohistochemically examined CCR2 and CX3CR1 expression in sepsis-induced lung injury, and discussed its availability for the postmortem diagnosis of sepsis. Lung samples were obtained from different lung lobes of nine sepsis and eight control cases with postmortem intervals between 12 and 48h. Immunohistochemically, mononuclear cells recruited into the lungs expressed CCR2 and CX3CR1 in both sepsis and non-septic groups. In double-color immunofluorescence analysis, CCR2- or CX3CR1-positive cells could be identified as CD68-positive macrophages. Moreover, most of CD68-positive macrophages expressed both CCR2 and CX3CR1. Morphometrically, the average of CCR2- and CX3CR1-positive macrophages was significantly increased in sepsis group, compared with control group (sepsis vs. control: 41.6+/-1.3% vs. 8.0+/-0.4% in CCR2; 36.2+/-1.3% vs. 9.2+/-0.4% in CX3CR1). These observations implied that CCR2- or CX3CR1-positive macrophages were recruited into the lungs under several pathological conditions. In particular, their recruitment might be more evident in sepsis. Moreover, from the forensic aspects, immunohistochemical detection of CCR2 and CX3CR1 expression in the lungs can be considered as valuable diagnostic tools for the postmortem diagnosis of sepsis.

  13. New criteria for selecting the proper antimicrobial chemotherapy for severe sepsis and septic shock.

    Science.gov (United States)

    Periti, P; Mazzei, T

    1999-07-01

    The mortality rate resulting from severe bacterial sepsis, particularly that associated with shock, still approaches 50% in spite of appropriate antimicrobial therapy and optimum supportive care. Bacterial endotoxins that are part of the cell wall are one of the cofactors in the pathogenesis of sepsis and septic shock and are often induced by antimicrobial chemotherapy even if it is administered rationally. Not all antimicrobial agents are equally capable of inducing septic shock; this is dependant on their mechanism of action rather than on the causative pathogen species. The quantity of endotoxin released depends on the drug dose and whether filaments or spheroplast formation predominates. Some antibiotics such as carbapenems, ceftriaxone, cefepime, glycopeptides, aminoglycosides and quinolones do not have the propensity to provoke septic shock because their rapid bactericidal activity induces mainly spheroplast or fragile spheroplast-like bacterial forms.

  14. Biomarkers of Delirium in a Low-Risk Community-Acquired Pneumonia-Induced Sepsis.

    Science.gov (United States)

    Tomasi, Cristiane Damiani; Vuolo, Francieli; Generoso, Jaqueline; Soares, Márcio; Barichello, Tatiana; Quevedo, João; Ritter, Cristiane; Dal-Pizzol, Felipe

    2017-01-01

    There are different theories about the pathophysiology of sepsis-associated encephalopathy (SAE), and the majority of our knowledge was derived from critically ill patients. 7In less severe sepsis, it is probable that neuroinflammation can be a major aspect of SAE development. We hypothesized that in non-severe septic patients, blood biomarkers of inflammation, endothelial activation, coagulation, and brain function would be different when compared to patients with and without brain dysfunction. A total of 30 patients presenting with community-acquired pneumonia (CAP)-induced sepsis were included of which 10 (33 %) developed SAE. Eight medical patients admitted to the general ward, except due to sepsis or infection, which developed delirium were included as delirium, non-sepsis group. From all measured biomarkers, only brain-derived neurotrophic factor (BDNF), regulated upon activation normal T cell expressed, and presumably secreted (RANTES), and interleukin (IL)-10 where significantly different when compared to SAE and sepsis groups. In addition, SAE patients presented higher levels of BDNF, vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), platelet-derived growth factor (PDGF)-AB/BB and RANTES when compared to delirium patients. In conclusion, the profile of biomarkers differs between SAE, sepsis, and delirium patients, suggesting that pathways related to SAE are different from delirium and from sepsis itself.

  15. Heart-rate variability depression in porcine peritonitis-induced sepsis without organ failure.

    Science.gov (United States)

    Jarkovska, Dagmar; Valesova, Lenka; Chvojka, Jiri; Benes, Jan; Danihel, Vojtech; Sviglerova, Jitka; Nalos, Lukas; Matejovic, Martin; Stengl, Milan

    2017-05-01

    Depression of heart-rate variability (HRV) in conditions of systemic inflammation has been shown in both patients and experimental animal models and HRV has been suggested as an early indicator of sepsis. The sensitivity of HRV-derived parameters to the severity of sepsis, however, remains unclear. In this study we modified the clinically relevant porcine model of peritonitis-induced sepsis in order to avoid the development of organ failure and to test the sensitivity of HRV to such non-severe conditions. In 11 anesthetized, mechanically ventilated and instrumented domestic pigs of both sexes, sepsis was induced by fecal peritonitis. The dose of feces was adjusted and antibiotic therapy was administered to avoid multiorgan failure. Experimental subjects were screened for 40 h from the induction of sepsis. In all septic animals, sepsis with hyperdynamic circulation and increased plasma levels of inflammatory mediators developed within 12 h from the induction of peritonitis. The sepsis did not progress to multiorgan failure and there was no spontaneous death during the experiment despite a modest requirement for vasopressor therapy in most animals (9/11). A pronounced reduction of HRV and elevation of heart rate developed quickly (within 5 h, time constant of 1.97 ± 0.80 h for HRV parameter TINN) upon the induction of sepsis and were maintained throughout the experiment. The frequency domain analysis revealed a decrease in the high-frequency component. The reduction of HRV parameters and elevation of heart rate preceded sepsis-associated hemodynamic changes by several hours (time constant of 11.28 ± 2.07 h for systemic vascular resistance decline). A pronounced and fast reduction of HRV occurred in the setting of a moderate experimental porcine sepsis without organ failure. Inhibition of parasympathetic cardiac signaling probably represents the main mechanism of HRV reduction in sepsis. The sensitivity of HRV to systemic inflammation may allow

  16. Functional polymorphisms of interferon-gamma affect pneumonia-induced sepsis.

    Directory of Open Access Journals (Sweden)

    Ding Wang

    Full Text Available OBJECTIVE: Sepsis is an inflammatory syndrome caused by infection, and both its incidence and mortality are high. Because interferon-gamma (IFN-γ plays an important role in inflammation, this work assessed IFN-γ single nucleotide polymorphism (SNPs that may be associated with sepsis. METHODS: A total of 196 patients with pneumonia-induced sepsis and 213 age- and sex-matched healthy volunteers participated in our study from July 2012 to July 2013 in Guangzhou, China. Patient clinical information was collected. Clinical pathology was assessed in subgroups defined based on clinical criteria, APACHE II (acute physiology and chronic health evaluation and SOFA (sepsis-related organ failure assessment scores and discharge rate. Four functional SNPs, -1616T/C (rs2069705, -764G/C (rs2069707, +874A/T (rs2430561 and +3234C/T (rs2069718, were genotyped by Snapshot in both sepsis patients and healthy controls. Pearson's chi-square test or Fisher's exact test were used to analyze the distribution of the SNPs, and the probability values (P values, odds ratios (OR and 95% confidence intervals (CIs were calculated. RESULTS: No mutations in the IFN-γ -764G/C SNP were detected among the participants in our study. The +874A/T and +3234C/T SNPs were in strong linkage disequilibrium (LD (r(2 = 0.894. The -1616 TC+TT, +874 AT+AA genotype and the TAC haplotype were significantly associated with sepsis susceptibility, while the CTT haplotype was associated with protection against sepsis incidence. Genotype of -1616 TT wasn't only protective against severity of sepsis, but also against higher APACHE II and SOFA scores as +874 AA and +3234 CC. The TAC haplotype was was protective against progression to severe sepsis either. CONCLUSION: Our results suggest that functional IFN-γ SNPs and their haplotypes are associated with pneumonia-induced sepsis.

  17. Sepsis

    DEFF Research Database (Denmark)

    Perner, Anders; Gordon, Anthony C; De Backer, Daniel

    2016-01-01

    Sepsis is a major growing global burden and a major challenge to intensive care clinicians, researchers, guideline committee members and policy makers, because of its high and increasing incidence and great pathophysiological, molecular, genetic and clinical complexity. In spite of recent progress......, short-term mortality remains high and there is growing evidence of long-term morbidity and increased long-term mortality in survivors of sepsis both in developed and developing countries. Further improvement in the care of patients with sepsis will impact upon global health. In this narrative review...... and subsequent outcomes are to be improved in patients with sepsis....

  18. Efficacy and effectiveness of recombinant human activated protein C in severe sepsis of adults

    Directory of Open Access Journals (Sweden)

    Greiner, Wolfgang

    2007-07-01

    risk of death, but not in patients with a low risk of death. Bleeding events and mortality are considerable higher in studies in the usual care setting compared to clinical trials. In a number of subgroup analyses, both retrospectively and prospectively performed, DAA was not significantly associated with improved survival. The role of concurrent therapy with heparin is unclear, as DAA was only effective in reducing mortality in patients without heparin. There was no significant long-term survival benefit associated with DAA beyond the initial 28 days. Also, there is a lack of studies assessing prospectively functional ability, health-related quality of life, and morbidity in the long-term. In the subgroup of patients with a high risk of death, therapy with DAA ranges at the top level of generally accepted costs per LYG or QALY, in the subgroup of patients with low risk of death, cost effectiveness ratios were higher than those accepted for resource allocation. Conclusion: Due to the lack of effectiveness of DAA in patients with severe sepsis and a low risk of death as well as with regard to the high bleeding rates in the usual care setting, indication for DAA therapy. In those subgroups with no significant survival benefit, prospective studies with adequate sample size are needed. With regard to the heterogeneity of severe sepsis, comorbidity and concurrent medication have to be taken into account in further studies. Studies with alternative study designs, for example studies comparing heparin alone or in combination with DAA to placebo, as well as studies conducted by different researchers are needed. Costs induced by bleeding events should also be taken into account in future studies, as bleeding events are the major complica-tion associated the DAA therapy.

  19. Nosography of systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, and multiple organ dysfunction syndrome in internal medicine patients

    Directory of Open Access Journals (Sweden)

    Silvia Spoto

    2015-09-01

    Full Text Available Sepsis is defined by the presence of at least two systemic inflammatory response syndrome criteria associated with an infection microbiologically or clinically evidenced. In Italy sepsis is responsible for 80,000 hospital admissions per year and, in the last decades, severe sepsis and septic shock cases are increasing, in correlation with the increased prevalence of multi-drugresistant microbial strains. The predominant etiologic agents are Gram-positive and Gram-negative bacteria, but sepsis caused by fungi is increasing. The host response with both inflammatory and anti-inflammatory processes is responsible for organic failures, which complicate the syndrome, and for the susceptibility to secondary infections. The impairment of one or more organs or systems may be the onset clinical presentation. The organ dysfunctions complicating sepsis involve mainly cardiorespiratory system, kidneys, hemostatis and central nervous system. Fever or hypothermia, tachycardia, tachypnea, leukocytosis or leukopenia, elevated blood levels of lactate and procalcitonin, hypotension are diagnostically sensitive findings for sepsis. Definitive diagnosis requires isolation of the pathogen from blood sample or from the focus of infection. Therapeutic success against sepsis depends on the appropriate use of antibiotics, on the treatment of hemodynamic and respiratory disorder and on general supportive care. In some cases the use of activated protein C is to take in consideration.

  20. Early detection and treatment of patients with severe sepsis by prehospital personnel.

    Science.gov (United States)

    Guerra, Wayne F; Mayfield, Thomas R; Meyers, Mary S; Clouatre, Anne E; Riccio, John C

    2013-06-01

    Severe sepsis is a condition with a high mortality rate, and the majority of patients are first seen by Emergency Medical Services (EMS) personnel. This research sought to determine the feasibility of EMS providers recognizing a severe sepsis patient, thereby resulting in better patient outcomes if standard EMS treatments for medical shock were initiated. We developed the Sepsis Alert Protocol that incorporates a screening tool using point-of-care venous lactate meters. If severe sepsis was identified by EMS personnel, standard medical shock therapy was initiated. A prospective cohort study was conducted for 1 year to determine if those trained EMS providers were able to identify 112 severe sepsis patients before arrival at the Emergency Department. Outcomes of the sample of severe sepsis patients were examined with a retrospective case control study. Trained EMS providers transported 67 severe sepsis patients. They identified 32 of the 67 severe sepsis patients correctly (47.8%). Overall mortality for the sample of 112 severe sepsis patients transported by EMS was 26.7%. Mortality for the sample of severe sepsis patients for whom the Sepsis Alert Protocol was initiated was 13.6% (5 of 37), crude odds ratio for survival until discharge was 3.19 (95% CI 1.14-8.88; p = 0.040). This pilot study is the first to utilize EMS providers and venous lactate meters to identify patients in severe sepsis. Further research is needed to validate the Sepsis Alert Protocol and the potential associated decrease in mortality. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Serum lipids and disease severity in children with severe meningococcal sepsis.

    NARCIS (Netherlands)

    Vermont, C.L.; Brinker, M. den; Kakeci, N.; Kleijn, E.D. de; Rijke, Y.B. de; Joosten, K.F.; Groot, R. de; Hazelzet, J.A.

    2005-01-01

    OBJECTIVE: To evaluate the role of cholesterol and lipoproteins in children with severe meningococcal sepsis. DESIGN: Retrospective observational study. SETTING: A university-affiliated pediatric intensive care unit. PATIENTS: Fifty-seven patients admitted to the pediatric intensive care unit with m

  2. Obesity Exacerbates Sepsis-Induced Oxidative Damage in Organs.

    Science.gov (United States)

    Petronilho, Fabricia; Giustina, Amanda Della; Nascimento, Diego Zapelini; Zarbato, Graciela Freitas; Vieira, Andriele Aparecida; Florentino, Drielly; Danielski, Lucinéia Gainski; Goldim, Mariana Pereira; Rezin, Gislaine Tezza; Barichello, Tatiana

    2016-12-01

    Sepsis progression is linked to the imbalance between reactive oxygen species and antioxidant enzymes. Sepsis affects multiple organs, but when associated with a chronic inflammatory disease, such as obesity, it may be exacerbated. We hypothesized that obesity could aggravate the oxidative damage to peripheral organs of rats submitted to an animal model of sepsis. Male Wistar rats aged 8 weeks received hypercaloric nutrition for 2 months to induce obesity. Sepsis was induced by cecal ligation and puncture (CLP) procedure, and sham-operated rats were considered as control group. The experimental groups were divided into sham + eutrophic, sham + obese, CLP + eutrophic, and CLP + obese. Twelve and 24 h after surgery, oxidative damage to lipids and proteins and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in the liver, lung, kidney, and heart. The data indicate that obese rats subjected to sepsis present oxidative stress mainly in the lung and liver. This alteration reflected an oxidative damage to lipids and proteins and an imbalance of SOD and CAT levels, especially 24 h after sepsis. It follows that obesity due to its pro-inflammatory phenotype can aggravate sepsis-induced damage in peripheral organs.

  3. Reduced mortality after the implementation of a protocol for the early detection of severe sepsis.

    Science.gov (United States)

    Westphal, Glauco A; Koenig, Álvaro; Caldeira Filho, Milton; Feijó, Janaína; de Oliveira, Louise Trindade; Nunes, Fernanda; Fujiwara, Kênia; Martins, Sheila Fonseca; Roman Gonçalves, Anderson R

    2011-02-01

    We evaluate the impact that implementing an in-hospital protocol for the early detection of sepsis risk has on mortality from severe sepsis/septic shock. This was a prospective cohort study conducted in 2 phases at 2 general hospitals in Brazil. In phase I, patients with severe sepsis/septic shock were identified and treated in accordance with the Surviving Sepsis Campaign guidelines. Over the subsequent 12 months (phase II), patients with severe sepsis/septic shock were identified by means of active surveillance for signs of sepsis risk (SSR). We compared the 2 cohorts in terms of demographic variables, the time required for the identification of at least 2 SSRs, compliance with sepsis bundles (6- and 24-hour), and mortality rates. We identified 217 patients with severe sepsis/septic shock (102 during phase I and 115 during phase II). There were significant differences between phases I and II in terms of the time required for the identification of at least 2 SSRs (34 ± 48 vs 11 ± 17 hours; P detection of sepsis promoted early treatment, reducing in-hospital mortality from severe sepsis/septic shock. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. The Epidemiology of Hospital Death Following Pediatric Severe Sepsis: When, Why, and How Children With Sepsis Die.

    Science.gov (United States)

    Weiss, Scott L; Balamuth, Fran; Hensley, Josey; Fitzgerald, Julie C; Bush, Jenny; Nadkarni, Vinay M; Thomas, Neal J; Hall, Mark; Muszynski, Jennifer

    2017-09-01

    The epidemiology of in-hospital death after pediatric sepsis has not been well characterized. We investigated the timing, cause, mode, and attribution of death in children with severe sepsis, hypothesizing that refractory shock leading to early death is rare in the current era. Retrospective observational study. Emergency departments and ICUs at two academic children's hospitals. Seventy-nine patients less than 18 years old treated for severe sepsis/septic shock in 2012-2013 who died prior to hospital discharge. None. Time to death from sepsis recognition, cause and mode of death, and attribution of death to sepsis were determined from medical records. Organ dysfunction was assessed via daily Pediatric Logistic Organ Dysfunction-2 scores for 7 days preceding death with an increase greater than or equal to 5 defined as worsening organ dysfunction. The median time to death was 8 days (interquartile range, 1-12 d) with 25%, 35%, and 49% of cumulative deaths within 1, 3, and 7 days of sepsis recognition, respectively. The most common cause of death was refractory shock (34%), then multiple organ dysfunction syndrome after shock recovery (27%), neurologic injury (19%), single-organ respiratory failure (9%), and nonseptic comorbidity (6%). Early deaths (≤ 3 d) were mostly due to refractory shock in young, previously healthy patients while multiple organ dysfunction syndrome predominated after 3 days. Mode of death was withdrawal in 72%, unsuccessful cardiopulmonary resuscitation in 22%, and irreversible loss of neurologic function in 6%. Ninety percent of deaths were attributable to acute or chronic manifestations of sepsis. Only 23% had a rise in Pediatric Logistic Organ Dysfunction-2 that indicated worsening organ dysfunction. Refractory shock remains a common cause of death in pediatric sepsis, especially for early deaths. Later deaths were mostly attributable to multiple organ dysfunction syndrome, neurologic, and respiratory failure after life-sustaining therapies

  5. A biomarker panel to discriminate between systemic inflammatory response syndrome SIRS and sepsis and sepsis severity

    NARCIS (Netherlands)

    Punyadeera, C.; Schneider, E. M.; Schaffer, D.; Hsu, H-Y.; Joos, T.O.; Kriebel, F; Weiss, M.; Verhaegh, W.F.J.

    2009-01-01

    In this study we report on initial efforts to discover putative biomarkers for differential diagnosis of a systemic inflammatory response syndrome (SIRS) vs. sepsis; and different stages of sepsis. In addition, we also investigated whether there are proteins that can discriminate between patients wh

  6. A biomarker panel to discriminate between systemic inflammatory response syndrome SIRS and sepsis and sepsis severity

    NARCIS (Netherlands)

    Punyadeera, C.; Schneider, E. M.; Schaffer, D.; Hsu, H-Y.; Joos, T.O.; Kriebel, F; Weiss, M.; Verhaegh, W.F.J.

    2009-01-01

    In this study we report on initial efforts to discover putative biomarkers for differential diagnosis of a systemic inflammatory response syndrome (SIRS) vs. sepsis; and different stages of sepsis. In addition, we also investigated whether there are proteins that can discriminate between patients

  7. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy

    Science.gov (United States)

    Hotchkiss, Richard S.; Monneret, Guillaume; Payen, Didier

    2014-01-01

    Sepsissevere life-threatening infection with organ dysfunction — initiates a complex interplay of host pro- and anti-inflammatory processes. In a real sense, sepsis can be considered a race to the death between the pathogens and the host immune system. It is the proper balance between the often competing pro- and anti-inflammatory pathways that determines the fate of the individual. Although the field of sepsis research has witnessed the failure of many highly-touted clinical trials, a better understanding of the pathophysiological basis of the disorder and the mechanisms responsible for the associated pro- and anti-inflammatory responses is leading to a novel approach to treat this highly lethal condition. Biomarker-guided immunotherapy administered to patients at the proper immune phase of sepsis represents a potential major advance in the treatment of sepsis and more broadly in the field of infectious disease. PMID:24232462

  8. [Endotoxin adsortion as adjuvant therapy in gram negative severe sepsis].

    Science.gov (United States)

    Candel, F J; Martínez-Sagasti, F; Borges, M; Maseda, E; Herrera-Gutiérrez, M; Garnacho-Montero, J; Maynar, F J; Zaragoza, R; Mensa, J; Azanza, J R

    2010-09-01

    The mortality rate of severe sepsis and septic shock remains still high. Within the last years a better knowledge of its physiopathology and the implementation of a group of measures addressed to a fast identification and early treatment of the septic patients have proved to reduce mortality rate. Likewise, it continues being investigated in modulating the inflammatory response and limiting the harmful action of the bacterial products on the immune system. As a result of this research some endotoxin adsorber devices have been designed to control one of the most important targets that start the inflammatory cascade when gram negative microorganisms are involved.The usefulness that these endotoxin removal devices might have as adjuvant treatment in the Septic Syndrome and its applicability are reviewed in this paper. Likewise a profile of patient that might be to the benefit of this therapy is suggested according to the current knowledge.

  9. PROTEOMIC AND EPIGENOMIC MARKERS OF SEPSIS-INDUCED DELIRIUM (SID

    Directory of Open Access Journals (Sweden)

    Adonis eSfera

    2015-10-01

    Full Text Available In elderly population sepsis is one of the leading causes of intensive care unit (ICU admissions in the United States. Sepsis-induced delirium (SID is the most frequent cause of delirium in ICU (1. Together delirium and SID represent under recognized public health problems which place an increasing financial burden on the US health care system, currently estimated at 143 to 152 billion dollars per year (2. The interest in SID was recently reignited as it was demonstrated that, contrary to prior beliefs, cognitive deficits induced by this condition may be irreversible and lead to dementia (3-4. Conversely, it is construed that diagnosing SID early or mitigating its full blown manifestations may preempt geriatric cognitive disorders. Biological markers specific for sepsis and SID would facilitate the development of potential therapies, monitor the disease process and at the same time enable elderly individuals to make better informed decisions regarding surgeries which may pose the risk of complications, including sepsis and delirium.This article proposes a battery of peripheral blood markers to be used for diagnostic and prognostic purposes in sepsis and SID. Though each individual marker may not be specific enough, we believe that together as a battery they may achieve the necessary accuracy to answer two important questions: who may be vulnerable to the development of sepsis, and who may develop SID and irreversible cognitive deficits following sepsis?

  10. The Parenteral Vitamin C Improves Sepsis and Sepsis-Induced Multiple Organ Dysfunction Syndrome via Preventing Cellular Immunosuppression

    Science.gov (United States)

    Chai, Yan-Fen

    2017-01-01

    Cellular immunosuppression appears to be involved in sepsis and sepsis-induced multiple organ dysfunction syndrome (MODS). Recent evidence showed that parenteral vitamin C (Vit C) had the ability to attenuate sepsis and sepsis-induced MODS. Herein, we investigated the impact of parenteral Vit C on cellular immunosuppression and the therapeutic value in sepsis. Using cecal ligation and puncture (CLP), sepsis was induced in WT and Gulo−/− mice followed with 200 mg/Kg parenteral Vit C administration. The immunologic functions of CD4+CD25+ regulatory T cells (Tregs) and CD4+CD25− T cells, as well as the organ functions, were determined. Administration of parenteral Vit C per se markedly improved the outcome of sepsis and sepsis-induced MODS of WT and Gulo−/− mice. The negative immunoregulation of Tregs was inhibited, mainly including inhibiting the expression of forkhead helix transcription factor- (Foxp-) 3, cytotoxic T lymphocyte associated antigen- (CTLA-) 4, membrane associated transforming growth factor-β (TGF-βm+), and the secretion of inhibitory cytokines [including TGF-β and interleukin- (IL-) 10], as well as CD4+ T cells-mediated cellular immunosuppression which was improved by parenteral Vit C in WT and Gulo−/− septic mice. These results suggested that parenteral Vit C has the ability to improve the outcome of sepsis and sepsis-induced MODS and is associated with improvement in cellular immunosuppression. PMID:28210072

  11. Serum lipopolysaccharide binding protein levels predict severity of lung injury and mortality in patients with severe sepsis.

    Directory of Open Access Journals (Sweden)

    Jesús Villar

    Full Text Available BACKGROUND: There is a need for biomarkers insuring identification of septic patients at high-risk for death. We performed a prospective, multicenter, observational study to investigate the time-course of lipopolysaccharide binding protein (LBP serum levels in patients with severe sepsis and examined whether serial serum levels of LBP could be used as a marker of outcome. METHODOLOGY/PRINCIPAL FINDINGS: LBP serum levels at study entry, at 48 hours and at day-7 were measured in 180 patients with severe sepsis. Data regarding the nature of infections, disease severity, development of acute lung injury (ALI and acute respiratory distress syndrome (ARDS, and intensive care unit (ICU outcome were recorded. LBP serum levels were similar in survivors and non-survivors at study entry (117.4+/-75.7 microg/mL vs. 129.8+/-71.3 microg/mL, P = 0.249 but there were significant differences at 48 hours (77.2+/-57.0 vs. 121.2+/-73.4 microg/mL, P<0.0001 and at day-7 (64.7+/-45.8 vs. 89.7+/-61.1 microg/ml, p = 0.017. At 48 hours, LBP levels were significantly higher in ARDS patients than in ALI patients (112.5+/-71.8 microg/ml vs. 76.6+/-55.9 microg/ml, P = 0.0001. An increase of LBP levels at 48 hours was associated with higher mortality (odds ratio 3.97; 95%CI: 1.84-8.56; P<0.001. CONCLUSIONS/SIGNIFICANCE: Serial LBP serum measurements may offer a clinically useful biomarker for identification of patients with severe sepsis having the worst outcomes and the highest probability of developing sepsis-induced ARDS.

  12. The effect of hospital volume on mortality in patients admitted with severe sepsis.

    Directory of Open Access Journals (Sweden)

    Sajid Shahul

    Full Text Available IMPORTANCE: The association between hospital volume and inpatient mortality for severe sepsis is unclear. OBJECTIVE: To assess the effect of severe sepsis case volume and inpatient mortality. DESIGN SETTING AND PARTICIPANTS: Retrospective cohort study from 646,988 patient discharges with severe sepsis from 3,487 hospitals in the Nationwide Inpatient Sample from 2002 to 2011. EXPOSURES: The exposure of interest was the mean yearly sepsis case volume per hospital divided into tertiles. MAIN OUTCOMES AND MEASURES: Inpatient mortality. RESULTS: Compared with the highest tertile of severe sepsis volume (>60 cases per year, the odds ratio for inpatient mortality among persons admitted to hospitals in the lowest tertile (≤10 severe sepsis cases per year was 1.188 (95% CI: 1.074-1.315, while the odds ratio was 1.090 (95% CI: 1.031-1.152 for patients admitted to hospitals in the middle tertile. Similarly, improved survival was seen across the tertiles with an adjusted inpatient mortality incidence of 35.81 (95% CI: 33.64-38.03 for hospitals with the lowest volume of severe sepsis cases and a drop to 32.07 (95% CI: 31.51-32.64 for hospitals with the highest volume. CONCLUSIONS AND RELEVANCE: We demonstrate an association between a higher severe sepsis case volume and decreased mortality. The need for a systems-based approach for improved outcomes may require a high volume of severely septic patients.

  13. Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis

    DEFF Research Database (Denmark)

    Perner, Anders; Haase, Nicolai; Guttormsen, Anne B

    2012-01-01

    Hydroxyethyl starch (HES) [corrected] is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis.......Hydroxyethyl starch (HES) [corrected] is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis....

  14. Development of a mortality prediction formula due to sepsis/severe sepsis in a medical intensive care unit

    Directory of Open Access Journals (Sweden)

    Anant Mohan

    2015-01-01

    Full Text Available Background: Although sepsis is one of the leading causes of mortality in hospitalized patients, information regarding early predictive factors for mortality and morbidity is limited. Materials and Methods: Patients fulfilling the Infectious Disease Society of America criteria of sepsis within the medical intensive care unit (ICU were included over two years. Apart from baseline hematological, biochemical, and metabolic parameters, Acute Physiology and Chronic Health Evaluation II (APACHE II, Simplified Acute Physiology Score II and III (SAPS II and SAPS III, and Sequential Organ Function Assessment (SOFA scores were calculated on day 1 of admission. Patients were followed till death or discharge from the ICU. Results: One hundred patients were enrolled over two years (54% males. The overall mortality was 53%, (69.5% in females, 38.8% in males (P < 0.01. Mortality was 65.7%, 55.7%, and 33.3% in patients with septic shock, severe sepsis, and sepsis, respectively. Patients who died were significantly older than the survivors (mean age, 57.37 ± 20.42 years and 44.29 ± 15.53 years respectively, P < 0.01. Nonsurvivors were significantly more anemic and had higher APACHE II, SAPS II, SAPS III, and SOFA scores. The presence of acute respiratory distress syndrome and renal dysfunction were associated with higher mortality (75% and 70.2%, respectively. There was no significant difference in the duration of mechanical ventilation or ICU stay between survivors and nonsurvivors. On multivariate analysis, significant predictors of mortality with odds ratio greater than 2 included the presence of anemia, SAPS II score greater than 35, SAPS III score greater than 47, and SOFA score greater than 6 at day 1 of admission. Conclusion: Several demographic and laboratory parameters as well as composite critical illness scoring systems are reliable early predictors of mortality in sepsis. A sepsis mortality prediction formula (AIIMS Sepsis Score based on SAPS II

  15. Sepsis-Induced Myocardial Depression and Takotsubo Syndrome

    Directory of Open Access Journals (Sweden)

    Mustafa Kemal Arslantaş

    2015-08-01

    Full Text Available Sepsis induced temporary myocardial dysfunction characterized as impairment of myocardial contraction is an important cause of mortality and morbidity in intensive care units. Takotsubo syndrome (TS is temporary ballooning and dysfunction of the apical part of left ventricle without significant stenosis of coronary arteries. Recently, it was suggested that impairment in regional catecholamine distribution caused by stress factors and excessive cardiac sympathetic activity mechanism play role in sepsis such as other causes of TS. Additionally, vasopressor agents (as noradrenaline which are widely used in sepsis treatment may be triggering factor. Serial case reports of sepsis associated TS are reported, however pathophysiology, diagnosis and treatment strategies of these two different syndromes is not obvious.

  16. The effects and mechanisms of insulin on systemic inflammatory response and immune cells in severe trauma, burn injury, and sepsis.

    Science.gov (United States)

    Deng, Hu-Ping; Chai, Jia-Ke

    2009-10-01

    Insulin resistance, hyperglycemia, inflammatory disorders and immune dysfunction cause high morbidity and mortality in patients with severe trauma, burn injuries, or sepsis. Many studies have shown that intensive insulin therapy can combat insulin resistance, decrease blood glucose levels, and induce anabolic processes, thus, decreasing morbidity and mortality. Moreover, in recent years, it has been proven that insulin can attenuate systemic inflammatory responses and modulate the proliferation, apoptosis, differentiation and immune functions of certain immune cells, especially monocytes/macrophages, neutrophils, and T cells associated with severe trauma, burn injury, or sepsis. This effect of insulin may expand our understanding of intensive insulin therapy in critically ill patients. This review attempts to summarize studies on the modulatory effects and mechanisms of insulin therapy on systemic inflammation and immune cells in severe trauma, burn injury and sepsis, and further propose some questions for future studies.

  17. Soluble ST2 plasma concentrations predict mortality in severe sepsis

    NARCIS (Netherlands)

    J.J. Hoogerwerf; M.W.T. Tanck; M.A.D. van Zoelen; X. Wittebole; P.F. Laterre; T. van der Poll

    2010-01-01

    Patients with sepsis-after surviving the initial hyperinflammatory phase-display features consistent with immunosuppression, including hyporesponsiveness of immunocompetent cells to bacterial agents. Immunosuppression is thought to be facilitated by negative regulators of toll-like receptors, includ

  18. Soluble ST2 plasma concentrations predict mortality in severe sepsis

    NARCIS (Netherlands)

    Hoogerwerf, J.J.; Tanck, M.W.T.; van Zoelen, M.A.D.; Wittebole, X.; Laterre, P.F.; van der Poll, T.

    2010-01-01

    Patients with sepsis-after surviving the initial hyperinflammatory phase-display features consistent with immunosuppression, including hyporesponsiveness of immunocompetent cells to bacterial agents. Immunosuppression is thought to be facilitated by negative regulators of toll-like receptors,

  19. Identifying patients with severe sepsis using administrative claims: patient-level validation of the angus implementation of the international consensus conference definition of severe sepsis.

    Science.gov (United States)

    Iwashyna, Theodore J; Odden, Andrew; Rohde, Jeffrey; Bonham, Catherine; Kuhn, Latoya; Malani, Preeti; Chen, Lena; Flanders, Scott

    2014-06-01

    Severe sepsis is a common and costly problem. Although consistently defined clinically by consensus conference since 1991, there have been several different implementations of the severe sepsis definition using ICD-9-CM codes for research. We conducted a single center, patient-level validation of 1 common implementation of the severe sepsis definition, the so-called "Angus" implementation. Administrative claims for all hospitalizations for patients initially admitted to general medical services from an academic medical center in 2009-2010 were reviewed. On the basis of ICD-9-CM codes, hospitalizations were sampled for review by 3 internal medicine-trained hospitalists. Chart reviews were conducted with a structured instrument, and the gold standard was the hospitalists' summary clinical judgment on whether the patient had severe sepsis. Three thousand one hundred forty-six (13.5%) hospitalizations met ICD-9-CM criteria for severe sepsis by the Angus implementation (Angus-positive) and 20,142 (86.5%) were Angus-negative. Chart reviews were performed for 92 randomly selected Angus-positive and 19 randomly-selected Angus-negative hospitalizations. Reviewers had a κ of 0.70. The Angus implementation's positive predictive value was 70.7% [95% confidence interval (CI): 51.2%, 90.5%]. The negative predictive value was 91.5% (95% CI: 79.0%, 100%). The sensitivity was 50.4% (95% CI: 14.8%, 85.7%). Specificity was 96.3% (95% CI: 92.4%, 100%). Two alternative ICD-9-CM implementations had high positive predictive values but sensitivities of Angus implementation of the international consensus conference definition of severe sepsis offers a reasonable but imperfect approach to identifying patients with severe sepsis when compared with a gold standard of structured review of the medical chart by trained hospitalists.

  20. Comparison of Cox and Gray's survival models in severe sepsis

    DEFF Research Database (Denmark)

    Kasal, Jan; Andersen, Zorana Jovanovic; Clermont, Gilles

    2004-01-01

    Although survival is traditionally modeled using Cox proportional hazards modeling, this approach may be inappropriate in sepsis, in which the proportional hazards assumption does not hold. Newer, more flexible models, such as Gray's model, may be more appropriate.......Although survival is traditionally modeled using Cox proportional hazards modeling, this approach may be inappropriate in sepsis, in which the proportional hazards assumption does not hold. Newer, more flexible models, such as Gray's model, may be more appropriate....

  1. Sepsis

    DEFF Research Database (Denmark)

    Perner, Anders; Rhodes, Andrew; Venkatesh, Bala

    2017-01-01

    Because of its high incidence and clinical complexity, sepsis is a major challenge to clinicians and researchers and a global burden to healthcare systems and society. Despite recent progress, short- and long-term morbidity, mortality and costs remain high in both developed and developing countri...

  2. Modelling severe Staphylococcus aureus sepsis in conscious pigs: are implications for animal welfare justified?

    DEFF Research Database (Denmark)

    Olsen, Helle G; Kjelgaard-Hansen, Mads; Tveden-Nyborg, Pernille;

    2016-01-01

    A porcine model of haematogenous Staphylococcus aureus sepsis has previously been established in our research group. In these studies, pigs developed severe sepsis including liver dysfunction during a 48 h study period. As pigs were awake during the study, animal welfare was challenged...

  3. Associations of Hospital and Patient Characteristics with Fluid Resuscitation Volumes in Patients with Severe Sepsis

    DEFF Research Database (Denmark)

    Hjortrup, Peter Buhl; Haase, Nicolai; Wetterslev, Jørn;

    2016-01-01

    PURPOSE: Fluid resuscitation is a key intervention in patients with sepsis and circulatory impairment. The recommendations for continued fluid therapy in sepsis are vague, which may result in differences in clinical practice. We aimed to evaluate associations between hospital and patient...... characteristics and fluid resuscitation volumes in ICU patients with severe sepsis. METHODS: We explored the 6S trial database of ICU patients with severe sepsis needing fluid resuscitation randomised to hydroxyethyl starch 130/0.42 vs. Ringer's acetate. Our primary outcome measure was fluid resuscitation volume......, lower respiratory SOFA subscore and surgery were all independently associated with increased fluid resuscitation volumes. CONCLUSIONS: Hospital characteristics adjusted for patient baseline values were associated with differences in fluid resuscitation volumes given in the first 3 days of severe sepsis...

  4. Exogenous Carbon Monoxide Decreases Sepsis-Induced Acute Kidney Injury and Inhibits NLRP3 Inflammasome Activation in Rats

    Directory of Open Access Journals (Sweden)

    Peng Wang

    2015-08-01

    Full Text Available Carbon monoxide (CO has shown various physiological effects including anti-inflammatory activity in several diseases, whereas the therapeutic efficacy of CO on sepsis-induced acute kidney injury (AKI has not been reported as of yet. The purpose of the present study was to explore the effects of exogenous CO on sepsis-induced AKI and nucleotide-binding domain-like receptor protein 3 (NLRP3 inflammasome activation in rats. Male rats were subjected to cecal ligation and puncture (CLP to induce sepsis and AKI. Exogenous CO delivered from CO-releasing molecule 2 (CORM-2 was used intraperitoneally as intervention after CLP surgery. Therapeutic effects of CORM-2 on sepsis-induced AKI were assessed by measuring serum creatinine (Scr and blood urea nitrogen (BUN, kidney histology scores, apoptotic cell scores, oxidative stress, levels of cytokines TNF-α and IL-1β, and NLRP3 inflammasome expression. CORM-2 treatment protected against the sepsis-induced AKI as evidenced by reducing serum Scr/BUN levels, apoptotic cells scores, increasing survival rates, and decreasing renal histology scores. Furthermore, treatment with CORM-2 significantly reduced TNF-α and IL-1β levels and oxidative stress. Moreover, CORM-2 treatment significantly decreased NLRP3 inflammasome protein expressions. Our study provided evidence that CORM-2 treatment protected against sepsis-induced AKI and inhibited NLRP3 inflammasome activation, and suggested that CORM-2 could be a potential therapeutic candidate for treating sepsis-induced AKI.

  5. Exogenous Carbon Monoxide Decreases Sepsis-Induced Acute Kidney Injury and Inhibits NLRP3 Inflammasome Activation in Rats.

    Science.gov (United States)

    Wang, Peng; Huang, Jian; Li, Yi; Chang, Ruiming; Wu, Haidong; Lin, Jiali; Huang, Zitong

    2015-08-31

    Carbon monoxide (CO) has shown various physiological effects including anti-inflammatory activity in several diseases, whereas the therapeutic efficacy of CO on sepsis-induced acute kidney injury (AKI) has not been reported as of yet. The purpose of the present study was to explore the effects of exogenous CO on sepsis-induced AKI and nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation in rats. Male rats were subjected to cecal ligation and puncture (CLP) to induce sepsis and AKI. Exogenous CO delivered from CO-releasing molecule 2 (CORM-2) was used intraperitoneally as intervention after CLP surgery. Therapeutic effects of CORM-2 on sepsis-induced AKI were assessed by measuring serum creatinine (Scr) and blood urea nitrogen (BUN), kidney histology scores, apoptotic cell scores, oxidative stress, levels of cytokines TNF-α and IL-1β, and NLRP3 inflammasome expression. CORM-2 treatment protected against the sepsis-induced AKI as evidenced by reducing serum Scr/BUN levels, apoptotic cells scores, increasing survival rates, and decreasing renal histology scores. Furthermore, treatment with CORM-2 significantly reduced TNF-α and IL-1β levels and oxidative stress. Moreover, CORM-2 treatment significantly decreased NLRP3 inflammasome protein expressions. Our study provided evidence that CORM-2 treatment protected against sepsis-induced AKI and inhibited NLRP3 inflammasome activation, and suggested that CORM-2 could be a potential therapeutic candidate for treating sepsis-induced AKI.

  6. Euglycemic hyperinsulinemia in severe sepsis and septic shock.

    Science.gov (United States)

    Su, Fuhong; Wang, Zhen; Bruhn, Alejandro; Verdant, Colin; Cai, Ying; Vincent, Jean-Louis

    2006-01-01

    Recent studies have suggested that strict glucose control with intensive insulin therapy in critically ill patients may result in better outcomes. Whether this is also true in septic shock has not been determined. In addition, whether it is the insulin administration per se or the glucose control that contributes to the beneficial effects is unclear. We raised the hypothesis that euglycemic hyperinsulinemia (EH) might improve the outcome from septic shock due to peritonitis. Fourteen anesthetized, mechanically ventilated, and hemodynamically monitored sheep received 1.5 g/kg body weight i.p. feces to induce sepsis. Ringer's lactate and 6% hydroxyethyl starch solutions were infused throughout the experiment to prevent hypovolemia. Two hours after feces injection, the animals were randomized to either an EH group (n = 7) receiving insulin 0.25 U/ kg/h, 20% glucose (to maintain blood glucose at 40-90 mg/dl), and potassium (to maintain the potassium level at 4.0- 5.5 mmol/l) or a control group (n = 7) with no intervention. All animals were studied until their spontaneous death or for 30 h. The EH group received a greater volume of 20% glucose, but blood glucose and potassium concentrations were similar in the two groups. No significant differences were found in hemodynamic variables. The circulating interleukin-6 levels increased in both groups after feces injection, but tended to be lower in the EH group (p shock model, EH decreased blood interleukin-6 concentrations but did not change hemodynamics or improve the outcome. Copyright 2006 S. Karger AG, Basel.

  7. Soluble RAGE as a severity marker in community acquired pneumonia associated sepsis

    OpenAIRE

    2012-01-01

    Abstract Background Community-acquired pneumonia (CAP) is considered the most important cause of death from infectious disease in developed countries. Severity assessment scores partially address the difficulties in identifying high-risk patients. A lack of specific and valid pathophysiologic severity markers affect early and effective sepsis therapy. HMGB-1, sRAGE and RAGE have been involved in sepsis and their potential as severity markers has been proposed. The aim of this study was to eva...

  8. May thrombopoietin be a useful marker of sepsis severity assessment in patients with SIRS entering the emergency department?

    Science.gov (United States)

    Segre, Elisabetta; Pigozzi, Luca; Lison, Davide; Pivetta, Emanuele; Bosco, Ornella; Vizio, Barbara; Suppo, Umberto; Turvani, Fabrizio; Morello, Fulvio; Battista, Stefania; Moiraghi, Corrado; Montrucchio, Giuseppe; Lupia, Enrico

    2014-10-01

    Thrombopoietin (TPO), a growth factor primarily involved in regulating thrombopoiesis, has been recently implicated in the pathogenesis of sepsis. TPO levels are, indeed, greatly increased in patients with sepsis compared to control subjects, and correlate with sepsis severity. The aim of this study was to evaluate TPO as predictive biomarker of sepsis and of sepsis severity in patients entering the emergency department (ED) with systemic inflammatory response syndrome (SIRS). This was a prospective observational study. Ours is a sub-study of the 'Need-speed trial', a multi-center observational study involving six Italian centers affiliated to the GREAT Italian Network. TPO was measured by ELISA. We enrolled 13 patients with SIRS (6 with acute pancreatitis, 3 with acute heart failure, 1 with pulmonary embolism, and 3 with allergic reactions), and 40 patients with sepsis, eight of whom had severe sepsis and three septic shock. TPO was significantly higher in patients with sepsis than with SIRS. In addition, TPO was higher in patients with severe sepsis than with sepsis, and in patients with septic shock than with severe sepsis, although these differences did not reach the statistical significance. Our preliminary results suggest that TPO may have the potential to be considered a promising early biomarker for both the diagnosis of sepsis and the assessment of sepsis severity in patients with SIRS entering the ED.

  9. Cardiopulmonary Arrest and Resuscitation in Severe Sepsis and Septic Shock: A Research Model.

    Science.gov (United States)

    Chalkias, Athanasios; Spyropoulos, Vaios; Koutsovasilis, Anastasios; Papalois, Apostolos; Kouskouni, Evaggelia; Xanthos, Theodoros

    2015-03-01

    Cardiopulmonary resuscitation in patients with severe sepsis and septic shock is challenging and usually unsuccessful. The aim of the present study is to describe our swine model of cardiac arrest and resuscitation in severe sepsis and septic shock. In this prospective randomized animal study, 10 healthy female Landrace-Large White pigs with an average weight of 20 ± 1 kg (aged 19 - 21 weeks) were the study subjects. Septicemia was induced by an intravenous infusion of a bolus of 20-mL bacterial suspension in 2 min, followed by a continuous infusion during the rest of the experiment. After septic shock was confirmed, the animals were left untreated until cardiac arrest occurred. All animals developed pulseless electrical activity between the fifth and sixth hours of septicemia, whereas five (50%) of 10 animals were successfully resuscitated. Coronary perfusion pressure was statistically significantly different between surviving and nonsurviving animals. We found a statistically significant correlation between mean arterial pressure and unsuccessful resuscitation (P = 0.046), whereas there was no difference in end-tidal carbon dioxide (23.05 ± 1.73 vs. 23.56 ± 1.70; P = 0.735) between animals with return of spontaneous circulation and nonsurviving animals. During the 45-min postresuscitation monitoring, we noted a significant decrease in hemodynamic parameters, although oxygenation indices and lactate clearance were constantly increased (P = 0.001). This successful basic swine model was for the first time developed and may prove extremely useful in future studies on the periarrest period in severe sepsis and septic shock.

  10. The redistribution of granulocytes following E. coli endotoxin induced sepsis

    DEFF Research Database (Denmark)

    Toft, P; Lillevang, S T; Tønnesen, Else Kirstine

    1994-01-01

    Infusion of endotoxin elicits granulocytopenia followed by increased numbers of granulocytes in peripheral blood. The purpose of this study was to investigate the redistribution and sequestration of granulocytes in the tissues following E. coli endotoxin induced sepsis. From 16 rabbits granulocytes...

  11. Acute kidney injury and inflammatory response of sepsis following cecal ligation and puncture in d-galactose-induced aging rats.

    Science.gov (United States)

    Liu, Chao; Hu, Jie; Mao, Zhi; Kang, Hongjun; Liu, Hui; Fu, Wanlei; Lv, Yangfan; Zhou, Feihu

    2017-01-01

    Recently, the d-galactose (d-gal)-induced mimetic aging rat model has been widely used in studies of age-associated diseases, which have shown that chronic d-gal exposure induces premature aging similar to natural aging in rats. With the increasing rate of sepsis in the geriatric population, an easy-access animal model for preclinical studies of elderly sepsis is urgently needed. This study investigates whether a sepsis model that is established in d-gal-induced aging rats can serve as a suitable model for preclinical studies of elderly patients with sepsis. To investigate the acute kidney injury (AKI) and inflammatory response of sepsis following cecal ligation and puncture (CLP) in d-gal-induced aging rats. Twelve-week-old male Sprague Dawley rats were divided into low-dose d-gal (L d-gal, 125 mg/kg/d), high-dose d-gal (H d-gal, 500 mg/kg/d), and control groups. After daily subcutaneous injection of d-gal for 6 weeks, the CLP method was used to establish a sepsis model. The mortality was 73.3%, 40%, and 33.3% in the H d-gal, L d-gal, and control groups, respectively. Blood urea nitrogen, creatinine, plasma neutrophil gelatinase-associated lipocalin, interleukin-6, interleukin-10, and tumor necrosis factor-α were markedly increased in the H d-gal group after establishment of the sepsis model (H d-gal vs control, Paging rats are more likely to die from sepsis than are young rats, and probably this is associated with increased severity of septic AKI and an increased inflammatory response. Therefore, use of the high-dose- d-gal-induced aging rat model of sepsis for preclinical studies can provide more useful information for the treatment of sepsis in elderly patients.

  12. Association between PAI-1 polymorphisms and plasma PAI-1 level with sepsis in severely burned patients.

    Science.gov (United States)

    Chi, Y F; Chai, J K; Yu, Y M; Luo, H M; Zhang, Q X; Feng, R

    2015-08-21

    We investigated the association between plasminogen activator inhibitor-1 (PAI-1) polymorphisms and plasma PAI-1 level with sepsis in severely burned patients. A total of 182 patients with burn areas lager than 30% of the body surface area were enrolled in this study. Peripheral blood samples were obtained from 103 patients with sepsis (sepsis group) and 79 patients without sepsis (control group). An allele-specific polymerase chain reaction assay was used to determine PAI-1 polymorphism 4G/5G distribution. Plasma PAI-1 levels were detected using an enzyme-linked immunosorbent assay. The frequency of the 4G/4G genotype and the 4G allele frequency in the sepsis group were 42.7 and 62.1% respectively, which were significantly higher than those in the control group (P PAI-1 level than the control group (P PAI-1 concentrations were significantly higher in the 4G/4G genotype (P PAI-1 gene may be related to the susceptibility to burn sepsis and that the 4G/4G genotype may be an important genetic risk factor of burn sepsis. Additionally, PAI-1 concentrations in the serum are increased in patients with burn sepsis.

  13. Plasma HSPA12B is a potential predictor for poor outcome in severe sepsis.

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    Ran Zhang

    Full Text Available INTRODUCTION: Endothelium-derived molecules may be predictive to organ injury. Heat shock protein (HSP A12B is mainly located in endothelial cells, which can be detected in the plasma of septic patients. Whether it is correlated with prognosis of sepsis remains unclear. METHODS: Extracellular HSPA12B (eHSPA12B was determined in plasma of septic mice at 6 h, 12 h, 24 h and 48 h after cecal ligation and puncture (CLP. It was also detected in plasma of patients with severe sepsis, sepsis, systemic inflammatory response syndrome and healthy volunteers. The predictive value for prognosis of severe sepsis was assessed by receiver operating curve (ROC and Cox regression analyses. RESULTS: eHSPA12B was elevated in plasma of CLP mice at 6 h and peaked at 24 h after surgery. A total of 118 subjects were included in the clinical section, including 66 patients with severe sepsis, 21 patients with sepsis, 16 patients with SIRS and 15 volunteers. Plasma eHSPA12B was significantly higher in patients with severe sepsis than in patients with sepsis, SIRS and volunteers. The level of eHSPA12B was also higher in non-survivals than survivals with severe sepsis. The area under the curve (AUC of eHSPA12B in predicting death among patients with severe sepsis was 0.782 (0.654-0.909 in ROC analysis, much higher than that of IL-6 and IL-10. Cox regression analysis showed that cardiovascular diseases, IL-6 and eHSPA12B were risk factors for mortality in patients with severe sepsis. Survival curve demonstrated a strikingly significant difference between 28-day survival rates of patients with an eHSPA12B lower or not lower than 1.466 ng/ml. CONCLUSIONS: Plasma eHSPA12B is elevated in both septic mice and patients. It may be a good predictor for poor outcome in patients with severe sepsis.

  14. Management of the open abdomen using negative pressure wound therapy with instillation in severe abdominal sepsis

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    Pablo Sibaja

    2017-01-01

    NPWT-I in patients with severe abdominal sepsis had promising results, since we obtained higher fascia closure rates, lower mortality and reduced hospital and ICU length of stay with no complications due to this therapeutic approach.

  15. Making the journey safe: recognising and responding to severe sepsis in accident and emergency

    Science.gov (United States)

    Pinnington, Sarah; Atterton, Brigid; Ingleby, Sarah

    2016-01-01

    Severe sepsis is a clinical emergency. Despite the nationwide recognition of the sepsis six treatment bundle as the first line emergency treatment for this presentation, compliance in sepsis six provision remains inadequately low. The project goals were to improve compliance with the implementation of the Sepsis Six in patients with severe sepsis and/or septic shock. In improving timely care delivery it was anticipated improvements would be made in relation to patient safety and experience, and reductions in length of stay (LoS) and mortality. The project intended to make the pathway for those presenting with sepsis safe and consistent, where sepsis is recognised and treated in a timely manner according to best practice. The aim of the project was to understand the what the barriers where to providing safe effective care for the patient presenting with severe sepsis in A&E. Using the Safer Clinical Systems (SCS) tools developed byte Health Foundation and Warwick University, the project team identified the hazards and associated risks in the septic patient pathway. The level of analysis employed enabled the project team to identify the major risks, themes, and factors of influence within this pathway. The analysis identified twenty nine possible interventions, of which six were chosen following option appraisal. Further interventions were recommended to the accident and emergency as part of a business case and further changes in process. Audits identified all severely septic patients presenting to A&E in October 2014 (n=67) and post intervention in September 2015 (n=93). Compared analysis demonstrated an increase in compliance with the implementation of the sepsis six care bundle from 7% to 41%, a reduction in LoS by 1.9 days and a decrease in 30 day mortality by 50%. Additional audit reviewed the management of 10 septic patients per week for the duration of the project to assess the real time impact of the selected interventions.

  16. NK cells promote neutrophil recruitment in the brain during sepsis-induced neuroinflammation

    Science.gov (United States)

    He, Hao; Geng, Tingting; Chen, Piyun; Wang, Meixiang; Hu, Jingxia; Kang, Li; Song, Wengang; Tang, Hua

    2016-01-01

    Sepsis could affect the central nervous system and thus induces neuroinflammation, which subsequently leads to brain damage or dysfunction. However, the mechanisms of generation of neuroinflammation during sepsis remain poorly understood. By administration of lipopolysaccharides (LPS) in mice to mimic sepsis, we found that shortly after opening the blood–brain barrier, conventional CD11b+CD27+ NK subset migrated into the brain followed by subsequent neutrophil infiltration. Interestingly, depletion of NK cells prior to LPS treatment severely impaired neutrophil recruitment in the inflamed brain. By in vivo recruitment assay, we found that brain-infiltrated NK cells displayed chemotactic activity to neutrophils, which depended on the higher expression of chemokines such as CXCL2. Moreover, microglia were also responsible for neutrophil recruitment, and their chemotactic activity was significantly impaired by ablation of NK cells. Furthermore, depletion of NK cells could significantly ameliorate depression-like behavior in LPS-treated mice. These data indicated a NK cell-regulated neutrophil recruitment in the blamed brain, which also could be seen on another sepsis model, cecal ligation and puncture. So, our findings revealed an important scenario in the generation of sepsis-induced neuroinflammation. PMID:27270556

  17. Effects of hydroxyethyl starch in subgroups of patients with severe sepsis

    DEFF Research Database (Denmark)

    Müller, Rasmus G; Haase, Nicolai; Wetterslev, Jørn;

    2013-01-01

    It has been speculated that certain subgroups of sepsis patients may benefit from treatment with hydroxyethyl starch (HES) 130/0.42, specifically in the earlier resuscitation of patients with more severely impaired circulation.......It has been speculated that certain subgroups of sepsis patients may benefit from treatment with hydroxyethyl starch (HES) 130/0.42, specifically in the earlier resuscitation of patients with more severely impaired circulation....

  18. Interleukin 10.G microsatellite in the promoter region of the interleukin-10 gene in severe sepsis

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background The highly polymorphic interleukin 10.G (IL10.G) microsatellite located in the promoter region of the interleukin-10 (IL-10) gene exerts a positive transcriptional regulatory effect on IL-10 gene expression and correlates with the in vitro IL-10 secretion. This study was conducted to investigate whether IL10.G microsatellite is associated with the incidence and /or the outcome of severe sepsis.Methods One hundred and fifteen patients with severe sepsis who had been treated at the intensive care unit of the university hospital were studied. One hundred and forty-one healthy individuals served as controls. IL10.G microsatellite genotyping was performed with the following two methods: fluorescent based polymerase chain reaction (PCR) techniques and silver staining of the amplified DNA fragment in polyacrylamide gel. Alleles were defined according to the size of the amplified DNA product.Results Ten alleles and 36 genotypes were detected both in the patients with severe sepsis and in the healthy controls. Allele IL10.G9 and allele IL10.G13 were the commonest alleles with the frequencies of 32.6% and 21.3% respectively in the patients with severe sepsis, and 34% and 27% respectively in the healthy controls. The allele frequencies of IL10.G microsatellite were neither different between the patients with severe sepsis and the healthy controls (P > 0.05), nor between survivors and non-survivors (P > 0.05). However, the frequency of one common allele IL10.G13 was slightly lower in the patients with severe sepsis than in the healthy controls (21.3% vs 27%, P > 0.05), and the frequency of allele IL10.G9 was slightly higher in the non-survivors than in the survivors (37.1% vs 28.1%, P > 0.05).Conclusion IL10.G microsatellite may neither contribute to the susceptibility to severe sepsis nor to the fatal outcome of severe sepsis.

  19. Predictors of Severe Sepsis among Patients Hospitalized for Community-Acquired Pneumonia.

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    Beatriz Montull

    Full Text Available Severe sepsis, may be present on hospital arrival in approximately one-third of patients with community-acquired pneumonia (CAP.To determine the host characteristics and micro-organisms associated with severe sepsis in patients hospitalized with CAP.We performed a prospective multicenter cohort study in 13 Spanish hospital, on 4070 hospitalized CAP patients, 1529 of whom (37.6% presented with severe sepsis. Severe sepsis CAP was independently associated with older age (>65 years, alcohol abuse (OR, 1.31; 95% CI, 1.07-1.61, chronic obstructive pulmonary disease (COPD (OR, 1.75; 95% CI, 1.50-2.04 and renal disease (OR, 1.57; 95% CI, 1.21-2.03, whereas prior antibiotic treatment was a protective factor (OR, 0.62; 95% CI, 0.52-0.73. Bacteremia (OR, 1.37; 95% CI, 1.05-1.79, S pneumoniae (OR, 1.59; 95% CI, 1.31-1.95 and mixed microbial etiology (OR, 1.65; 95% CI, 1.10-2.49 were associated with severe sepsis CAP.CAP patients with COPD, renal disease and alcohol abuse, as well as those with CAP due to S pneumonia or mixed micro-organisms are more likely to present to the hospital with severe sepsis.

  20. Probability of developing severe sepsis in patients of elderly and senile age with necrotic erysipelas

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    Shapkin Yu.G.

    2015-06-01

    Full Text Available Objective: the probable determination of severe sepsis in patients of elderly and senile age with necrotic erysipelas based on a comprehensive assessment (clinical examination using systems — scales and determination of the level markers of SIRS. Material and methods. The analysis of peculiarities of necrotic erysipelas clinical course in 59 patients. The first group consisted of 17 patients with severe sepsis, the second — 18 patients with sepsis without multiple organ failure, in the comparison group —22 patients with local infection. We determined albumin, urea, creatinine, pro-calcitonin of plasma. The scale SAPS III was used to quantify SIRS, scale SOFA —to determine the extent of damage to organs and systems. Results. The most sensitive marker of developing sepsis in patients with necrotic erysipelas was procalcitonin. The second important indicator of SIRS severity in patients with necrotic erysipelas was the blood albumin. Scale SAPS III also allows to select a group of patients with high risk of developing severe sepsis. Use of the SOFA to predict the scale has been found out to be less important. Conclusion. A comprehensive assessment of the severity of the condition by scale SAPS III in combination with determining the levels of procalcitonin and plasma albumin is advisable to apply for prediction the probability of developing severe sepsis in patients of elderly and senile age with necrotic erysipelas. For the last indicator it is important to assess of absolute values and the decrease of its concentration.

  1. Does the presence of a urinary catheter predict severe sepsis in a bacteraemic cohort?

    Science.gov (United States)

    Melzer, M; Welch, C

    2017-04-01

    Sepsis is a major cause of mortality with an estimated 37,000 deaths in the UK each year. This study aimed to determine host factors that can predict severe sepsis in a bacteraemic cohort. From December 2012 to November 2013, demographic, clinical and microbiological data were collected on consecutive patients with bacteraemia at a London teaching hospital. These data were used to categorize patients as having severe or non-severe sepsis. Multi-variate logistic regression was used to determine the association between host factors and severe sepsis. Five hundred and ninety-four bacteraemic episodes occurred in 500 patients. The majority of cases were in patients aged >50 years (382/594, 64.3%) and in males (346/594, 58.2%). The most common isolates were Escherichia coli (207/594, 34.8%) and meticillin-susceptible Staphylococcus aureus (57/594, 9.6%). In logistic regression multi-variable analysis, site of infection was significantly associated with severe sepsis. For catheter-associated urinary tract infections, the association was significant after adjustment for age, sex, Charlson comorbidity index and where infection was acquired (odds ratio 3.94, 95% confidence interval 1.70-9.11). Urinary catheters increase the risk of severe sepsis. They should only be used if clinically indicated. If inserted, a care bundle approach should be used and the anticipated removal date should be recorded unless a long-term catheter is required. In the context of sepsis, the presence of a urinary catheter should prompt immediate implementation of 'Sepsis Six' and consideration of transfer to a critical care unit. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  2. Talactoferrin in Severe Sepsis: Results From the Phase II/III Oral tAlactoferrin in Severe sepsIS Trial

    NARCIS (Netherlands)

    Vincent, J.L.; Marshall, J.C.; Dellinger, R.P.; Simonson, S.G.; Guntupalli, K.; Levy, M.M.; Singer, M.; Malik, R.; Pickkers, P.

    2015-01-01

    OBJECTIVE: Talactoferrin alfa is a recombinant form of the human glycoprotein, lactoferrin, which has been shown to have a wide range of effects on the immune system. This phase II/III clinical trial compared talactoferrin with placebo, in addition to standard of care, in patients with severe sepsis

  3. Effect of an electronic medical record alert for severe sepsis among ED patients.

    Science.gov (United States)

    Narayanan, Navaneeth; Gross, A Kendall; Pintens, Megan; Fee, Christopher; MacDougall, Conan

    2016-02-01

    Severe sepsis and septic shock are a major health concern worldwide. The objective of this study is to determine if Severe Sepsis Best Practice Alert (SS-BPA) implementation was associated with improved processes of care and clinical outcomes among patients with severe sepsis or septic shock presenting to the emergency department (ED). This is a single-center, before-and-after observational study. The intervention group (n = 103) consisted of adult patients presenting to the ED with severe sepsis or septic shock during a 7-month period after implementation of the SS-BPA. The control group (n = 111) consisted of patients meeting the same criteria over a prior 7-month period. The SS-BPA primarily acts by automated, real-time, algorithm-based detection of severe sepsis or septic shock via the electronic medical record system. The primary outcome was in-hospital mortality. Secondary outcomes included hospital length of stay (LOS), time to antibiotic administration, and proportion of patients who received antibiotics within the target 60 minutes. Time to antibiotics was significantly reduced in the SS-BPA cohort (29 vs 61.5 minutes, P sepsis or septic shock among ED patients is associated with significantly improved timeliness of antibiotic administration and reduced hospital LOS. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. [The nonlinear relationship between the resuscitation therapy and intensive insulin therapy in severe sepsis and septic shock patients].

    Science.gov (United States)

    Wang, Da-ming; Zhu, Bin; Ding, Liang-cai; Liu, Ning; Zhang, Jin-song

    2010-06-01

    To study the relationship between the resuscitation therapy and intensive insulin therapy on stress-induced hyperglycemia in severe sepsis and septic shock patients, and to evaluate the value on nonlinear viewpoint in the treatment of patients with sepsis. The data of 129 hospitalized patients with severe sepsis and septic shock were analyzed and they were divided into eight groups every 6 hours in ascending order for full recovery. The resuscitation therapy time of each group was compared with insulin dosage in each unit time with nonlinear least square method. The relationship of the exponential function fit very well between the resuscitation therapy time of each group and the insulin dosage in each unit time. The exponential curve equation was y=e0.739 3-0.015 2x2 (a=0.739 3, b=0.015 2) and the curve fit very well (R2=0.976 943 6). It conforms to the nonlinear viewpoint that the resuscitation therapy time is closely correlated with recovery of dysfunction of endocrine system during the treatment for patients with severe sepsis and septic shock. Therefore, the essence of successful treatment is to concentrate on helping the body rebuild the disorganized network and the recovery of physiological harmony rather than to support and repair the damaged organs.

  5. Monocyte and lymphocyte surface molecules in severe sepsis and non-septic critically ill Patients.

    Science.gov (United States)

    Jämsä, Joel; Syrjälä, Hannu; Huotari, Virva; Savolainen, Eeva-Riitta; Ala-Kokko, Tero

    2017-06-01

    The aim of the present study was to investigate whether expression of monocyte and lymphocyte surface molecules differs between patients with severe sepsis and non-septic patients treated in the intensive care unit (ICU). The expression of monocyte CD14, CD40, CD80 and HLA-DR, and lymphocyte CD69 were analyzed using quantitative flow cytometry on three consecutive days in 27 patients with severe sepsis and in 15 non-septic patients. Receiver operating characteristic analyses were performed and each corresponding area under the curve (AUC) was determined. The results showed that the expression levels of CD40 on monocytes and CD69 on CD4+ T cells and on natural killer (NK) cells were highest in patients with severe sepsis (p sepsis and positive blood culture compared with those with negative blood culture (p sepsis detection were 0.836 for CD40, 0.872 for CD69 on NK cells, and 0.795 for CD69 on CD4+ T cells. These findings suggest that monocyte CD40 and CD69 on NK cells and CD4+ T cells could prove useful for new approaches in the identification of severe sepsis in the ICU. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  6. The Potential Role of Hemopexin and Heme Oxygenase-1 Inducer in a Model of Sepsis

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    Passainte S. Hassaan

    2015-01-01

    Full Text Available Background and Aims. Sepsis can evoke disseminated intravascular coagulation, resulting in multiple organ failure and death. Heme oxygenase-1 (HO-1 and hemopexin (HPx can mediate cytoprotective mechanisms against these deleterious effects. This study aims to determine a role for HO-1 and HPx in coagulopathy induced by septic inflammation and define whether they can enhance the production of anti-inflammatory cytokine IL-10. Materials and Methods. 48 healthy male albino rats were divided equally into 4 groups: control group: animals subjected to laparotomy and bowel manipulation; CLP group: severe sepsis induced by cecal ligation puncture (CLP; CLP + hemin group: animals received single intraperitoneal injection of hemin (50 µmol/kg 12 h before sepsis induction; CLP + HPx group: animals received single HPx dose (150 µg/rat, i.v. 30 min before sepsis induction. Survival rates were calculated. Prothrombin time (PT, activated partial thromboplastin time (APTT, and activated protein C (APC, liver HO-1, serum, and liver IL-10 levels were measured, 48 hrs after sepsis induction. Liver and lung were excised for histopathological examination. Results. Hemin and HPx administration upregulated liver HO-1 and IL-10. They prolonged PT, PTT and increased APC. They reduced the inflammatory infiltrate and thrombosis in liver and lung parenchyma. However, hemin was superior in controlling coagulopathy and HO-1 production, while HPx was more potent stimulant of IL-10 expression. Conclusions. Hemin and HPx have a potential beneficial effect in severe sepsis regarding coagulopathy and inflammation.

  7. Severe Cystic Periventricular Leukomalacia in a Premature Infant with Capnocytophaga Sepsis

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    W. Thomas Bass

    2014-11-01

    Full Text Available Capnocytophaga is an opportunistic gram-negative anaerobic bacillus found in the oropharyngeal cavity of mammals and is associated with periodontal disease in humans. Sepsis, osteomyelitis, lung abscess, endocarditis, and meningitis have been reported in humans following animal bites. Perinatal infection with Capnocytophaga is infrequent and is generally considered to have a low risk of morbidity to the mother and fetus. We report a case of neonatal Capnocytophaga sepsis associated with the development of severe cystic periventricular leukomalacia

  8. Immunoparalysis: Clinical and immunological associations in SIRS and severe sepsis patients.

    Science.gov (United States)

    Papadopoulos, Panagiotis; Pistiki, Aikaterini; Theodorakopoulou, Maria; Christodoulopoulou, Theodora; Damoraki, Georgia; Goukos, Dimitris; Briassouli, Efrossini; Dimopoulou, Ioanna; Armaganidis, Apostolos; Nanas, Serafim; Briassoulis, George; Tsiodras, Sotirios

    2017-04-01

    This study was designed to identify changes in the monocytic membrane marker HLA-DR and heat shock proteins (HSPs) in relation to T-regulatory cells (T-regs) and other immunological marker changes in patients with systemic inflammatory response syndrome (SIRS) or sepsis/septic shock. Healthy volunteers, intensive care unit (ICU) patients with SIRS due to head injury and ICU patients with severe sepsis/septic shock were enrolled in the current study. Determination of CD14+/HLA-DR+ cells, intracellular heat-shock proteins and other immunological parameters were performed by flow cytometry and RT-PCR techniques as appropriate. Univariate and multivariate analysis examined associations of CD14/HLA-DR, HSPs, T-regs and suppressor of cytokine signalling (SOCS) proteins with SIRS, sepsis and outcome. Fifty patients (37 with severe sepsis and 13 with SIRS) were enrolled, together with 20 healthy volunteers used as a control group. Compared to healthy individuals, patients with SIRS and severe sepsis showed progressive decline of their CD14/HLA-DR expression (0% to 7.7% to 50% within each study subpopulation, pSIRS patients compared to controls and fell significantly in severe sepsis/septic shock patients (pSIRS and sepsis were found for CD14/HLA-DR expression and monocyte and polymorphonuclear cell levels of HSP70 and 90. The role of these biomarkers in assessing the prognosis of sepsis needs to be further explored and validated in prospective studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Protective effects of rosmarinic acid on sepsis-induced DNA damage in the liver of Wistar albino rats

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    Hatice Gul Goktas

    2015-06-01

    Full Text Available Sepsis is an imbalance between pro and anti-inflammatory responses. Sepsis induced multiple organ failure that is associated with mortality is characterized by liver, renal, cardiovascular and pulmonary dysfunction and reactive oxygen species (ROS are believed to be involved in the development of sepsis. Plant polyphenols may act as antioxidants by different mechanisms such as free radical scavenging, metal chelation and protein binding. Data indicates possible beneficial effects of plant derived phenolic compounds against sepsis. Rosmarinic acid (RA (α-O-caffeoyl-3,4-dihydroxyphenyllactic acid is a phenolic compound commonly found in various plants such as Rosmarinus officinalis (rosemary, Origanum vulgare (oregano, Thymus vulgaris (thyme, Mentha spicata (spearmint, Perilla frutescens (perilla, Ocimum basilicum (sweet basil and several other medicinal plants. It has been shown that RA has many biological activities including antioxidant, anti-inflammatory, antiallergic, anticancer and actimicrobial and is widely used in cosmetic and food industry. In the present study, we aimed to determine the protective effects of RA against the oxidative DNA damage induced by sepsis in Wistar albino rats. The rats were divided into four groups; sham, sepsis induced, RA-treated, RA treated and sepsis induced groups. Wistar rats were subjected to sepsis by cecal ligation puncture. The liver tissues were carefully dissected from their attachments and totally excised. The concentrations of the hepatic tissue cells were adjusted to approximately 2 x 106 cells/ml. Standard and formamidopyrimidine-DNA glycosylase (Fpg modified comet assay described by Singh et al were used. There were no statistically significant differences in terms of tail length, tail intensity and tail moment between the sham group and the RA-treated groups (p>0.05. The DNA damage was found significantly higher in the sepsis-induced group compared to the sham group (p0.05, and the DNA damage

  10. Sepsis-induced morbidity in mice: effects on body temperature, body weight, cage activity, social behavior and cytokines in brain.

    Science.gov (United States)

    Granger, Jill I; Ratti, Pietro-Luca; Datta, Subhash C; Raymond, Richard M; Opp, Mark R

    2013-07-01

    Infection negatively impacts mental health, as evidenced by the lethargy, malaise, and cognitive deficits experienced during illness. These changes in central nervous system processes, collectively termed sickness behavior, have been shown in animal models to be mediated primarily by the actions of cytokines in brain. Most studies of sickness behavior to date have used bolus injection of bacterial lipopolysaccharide (LPS) or selective administration of the proinflammatory cytokines interleukin-1β (IL-1β) or IL-6 as the immune challenge. Such models, although useful for determining mechanisms responsible for acute changes in physiology and behavior, do not adequately represent the more complex effects on central nervous system (CNS) processes of a true infection with replicating pathogens. In the present study, we used the cecal ligation and puncture (CLP) model to quantify sepsis-induced alterations in several facets of physiology and behavior of mice. We determined the impact of sepsis on cage activity, body temperature, food and water consumption and body weights of mice. Because cytokines are critical mediators of changes in behavior and temperature regulation during immune challenge, we also quantified sepsis-induced alterations in cytokine mRNA and protein in brain during the acute period of sepsis onset. We now report that cage activity and temperature regulation in mice that survive are altered for up to 23 days after sepsis induction. Food and water consumption are transiently reduced, and body weight is lost during sepsis. Furthermore, sepsis decreases social interactions for 24-48 h. Finally, mRNA and protein for IL-1β, IL-6, and tumor necrosis factor-α (TNFα) are upregulated in the hypothalamus, hippocampus, and brain stem during sepsis onset, from 6h to 72 h post sepsis induction. Collectively, these data indicate that sepsis not only acutely alters physiology, behavior and cytokine profiles in brain, but that some brain functions are impaired for

  11. Acute Kidney Injury in Pediatric Severe Sepsis: An Independent Risk Factor for Death and New Disability.

    Science.gov (United States)

    Fitzgerald, Julie C; Basu, Rajit K; Akcan-Arikan, Ayse; Izquierdo, Ledys M; Piñeres Olave, Byron E; Hassinger, Amanda B; Szczepanska, Maria; Deep, Akash; Williams, Duane; Sapru, Anil; Roy, Jason A; Nadkarni, Vinay M; Thomas, Neal J; Weiss, Scott L; Furth, Susan

    2016-12-01

    The prevalence of septic acute kidney injury and impact on functional status of PICU survivors are unknown. We used data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic acute kidney injury. Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study: acute kidney injury was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no acute kidney injury or stage 1 acute kidney injury ("no/mild acute kidney injury") were compared with those with stage 2 or 3 acute kidney injury ("severe acute kidney injury"). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher and increased by 1 from baseline. One hundred twenty-eight PICUs in 26 countries. Children with severe sepsis in the Sepsis PRevalence, OUtcomes, and Therapies study. None. One hundred two (21%) of 493 patients had severe acute kidney injury. More than twice as many patients with severe acute kidney injury died or developed new moderate disability compared with those with no/mild acute kidney injury (64% vs 30%; p sepsis and high mortality rates, septic acute kidney injury is independently associated with further increased death or new disability.

  12. IL-10 polymorphism is associated with increased incidence of severe sepsis

    Institute of Scientific and Technical Information of China (English)

    SHU Qiang(舒 强); FANG Xiangming(方向明); CHEN Qixing(陈齐兴); Frank Stuber

    2003-01-01

    Objective To investigate whether three biallelic polymorphisms at positions -592, -819 and -1082 in the promoter region of the IL-10 gene are associated with increased incidence of severe sepsis.Methods The IL-10 -592, -819 and -1082 polymorphisms were typed using polymerase chain reaction followed by digestion with the restriction enzymes RsaⅠ, MaeⅢ and MnlⅠ, respectively.Results Patients with severe sepsis were more likely to have IL-10 -1082 allele 1, compared with controls (P0.05). No significant differences in the genotype distribution and allele frequencies of the IL-10 -592 and IL-10 -819 polymorphisms were observed between patients with severe sepsis and heathy controls, nor between surviving and dead patients (P> 0.05). Conclusions The polymorphism at position -1082 in the promoter region of the IL-10 gene may be associated with susceptibility to severe sepsis. In constrast, the other two highly linked IL-10 polymorphisms are not associated with incidence or the outcome of severe sepsis.

  13. An unbiased systems genetics approach to mapping genetic loci modulating susceptibility to severe streptococcal sepsis.

    Directory of Open Access Journals (Sweden)

    Nourtan F Abdeltawab

    2008-04-01

    Full Text Available Striking individual differences in severity of group A streptococcal (GAS sepsis have been noted, even among patients infected with the same bacterial strain. We had provided evidence that HLA class II allelic variation contributes significantly to differences in systemic disease severity by modulating host responses to streptococcal superantigens. Inasmuch as the bacteria produce additional virulence factors that participate in the pathogenesis of this complex disease, we sought to identify additional gene networks modulating GAS sepsis. Accordingly, we applied a systems genetics approach using a panel of advanced recombinant inbred mice. By analyzing disease phenotypes in the context of mice genotypes we identified a highly significant quantitative trait locus (QTL on Chromosome 2 between 22 and 34 Mb that strongly predicts disease severity, accounting for 25%-30% of variance. This QTL harbors several polymorphic genes known to regulate immune responses to bacterial infections. We evaluated candidate genes within this QTL using multiple parameters that included linkage, gene ontology, variation in gene expression, cocitation networks, and biological relevance, and identified interleukin1 alpha and prostaglandin E synthases pathways as key networks involved in modulating GAS sepsis severity. The association of GAS sepsis with multiple pathways underscores the complexity of traits modulating GAS sepsis and provides a powerful approach for analyzing interactive traits affecting outcomes of other infectious diseases.

  14. Severe Maternal Sepsis in the UK, 2011–2012: A National Case-Control Study

    Science.gov (United States)

    Acosta, Colleen D.; Kurinczuk, Jennifer J.; Lucas, D. Nuala; Tuffnell, Derek J.; Sellers, Susan; Knight, Marian

    2014-01-01

    Background In light of increasing rates and severity of sepsis worldwide, this study aimed to estimate the incidence of, and describe the causative organisms, sources of infection, and risk factors for, severe maternal sepsis in the UK. Methods and Findings A prospective case-control study included 365 confirmed cases of severe maternal sepsis and 757 controls from all UK obstetrician-led maternity units from June 1, 2011, to May 31, 2012. Incidence of severe sepsis was 4.7 (95% CI 4.2–5.2) per 10,000 maternities; 71 (19.5%) women developed septic shock; and five (1.4%) women died. Genital tract infection (31.0%) and the organism Escherichia coli (21.1%) were most common. Women had significantly increased adjusted odds ratios (aORs) of severe sepsis if they were black or other ethnic minority (aOR = 1.82; 95% CI 1.82–2.51), were primiparous (aOR = 1.60; 95% CI 1.17–2.20), had a pre-existing medical problem (aOR = 1.40; 95% CI 1.01–1.94), had febrile illness or were taking antibiotics in the 2 wk prior to presentation (aOR = 12.07; 95% CI 8.11–17.97), or had an operative vaginal delivery (aOR = 2.49; 95% CI 1.32–4.70), pre-labour cesarean (aOR = 3.83; 95% CI 2.24–6.56), or cesarean after labour onset (aOR = 8.06; 95% CI 4.65–13.97). Median time between delivery and sepsis was 3 d (interquartile range = 1–7 d). Multiple pregnancy (aOR = 5.75; 95% CI 1.54–21.45) and infection with group A streptococcus (aOR = 4.84; 2.17–10.78) were associated with progression to septic shock; for 16 (50%) women with a group A streptococcal infection there was sepsis. A limitation of this study was the proportion of women with sepsis without an identified organism or infection source (16.4%). Conclusions For each maternal sepsis death, approximately 50 women have life-threatening morbidity from sepsis. Follow-up to ensure infection is eradicated is important. The rapid progression to severe sepsis highlights the importance

  15. Effectiveness and safety of procalcitonin evaluation for reducing mortality in adults with sepsis, severe sepsis or septic shock.

    Science.gov (United States)

    Andriolo, Brenda Ng; Andriolo, Regis B; Salomão, Reinaldo; Atallah, Álvaro N

    2017-01-18

    Serum procalcitonin (PCT) evaluation has been proposed for early diagnosis and accurate staging and to guide decisions regarding patients with sepsis, severe sepsis and septic shock, with possible reduction in mortality. To assess the effectiveness and safety of serum PCT evaluation for reducing mortality and duration of antimicrobial therapy in adults with sepsis, severe sepsis or septic shock. We searched the Central Register of Controlled Trials (CENTRAL; 2015, Issue 7); MEDLINE (1950 to July 2015); Embase (Ovid SP, 1980 to July 2015); Latin American Caribbean Health Sciences Literature (LILACS via BIREME, 1982 to July 2015); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; EBSCO host, 1982 to July 2015), and trial registers (ISRCTN registry, ClinicalTrials.gov and CenterWatch, to July 2015). We reran the search in October 2016. We added three studies of interest to a list of 'Studies awaiting classification' and will incorporate these into formal review findings during the review update. We included only randomized controlled trials (RCTs) testing PCT-guided decisions in at least one of the comparison arms for adults (≥ 18 years old) with sepsis, severe sepsis or septic shock, according to international definitions and irrespective of the setting. Two review authors extracted study data and assessed the methodological quality of included studies. We conducted meta-analysis with random-effects models for the following primary outcomes: mortality and time spent receiving antimicrobial therapy in hospital and in the intensive care unit (ICU), as well as time spent on mechanical ventilation and change in antimicrobial regimen from a broad to a narrower spectrum. We included 10 trials with 1215 participants. Low-quality evidence showed no significant differences in mortality at longest follow-up (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.65 to 1.01; I(2) = 10%; 10 trials; N = 1156), at 28 days (RR 0.89, 95% CI 0.61 to 1.31; I(2

  16. Acute kidney injury with hydroxyethyl starch 130/0.42 in severe sepsis

    DEFF Research Database (Denmark)

    Müller, Rasmus Gamborg; Haase, Nicolai; Lange, T

    2015-01-01

    BACKGROUND: We aimed to detail the effects of hydroxyethyl starch (HES) vs. Ringer's on kidney function including the interaction with mortality in post-hoc analyses as resuscitation with HES 130/0.42 increased mortality in the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial. METHODS...... on mortality was reduced when adjusting for AKI stage as a time-dependent covariate (P = 0.15). CONCLUSION: In patients with severe sepsis, HES appeared to increase the rate of severe AKI and use of RRT within the first 5 days. The increased mortality observed with HES may have been partly mediated through...

  17. A case report of thyroid storm induced by acute sepsis

    Institute of Scientific and Technical Information of China (English)

    Chiu-Yin Yeh; Wen-Liang Yu

    2016-01-01

    Thyroid storm is a rare but life-threatening condition, which can be induced by many critical diseases. We reported a 40-year-old woman with thyroid goiter manifesting with acute sepsis-induced hyperthyroidism. She mainly presented with abdominal bloating, diarrhea, lower limbs edema and exertional dyspnea. The lactate was 9.5 mmol/L and procalcitonin was 3.8 ng/mL, suggesting acute sepsis. The thyroid echo showed bilateral thyroid goiter. Relevant data included a thyroid-stimulating hormone level of 0.03 mIU/mL;free tetraiodothyronine, 5.67 ng/dL;thyroid-stimulating hormone receptor antibody, 76.9%(normal range, < 14%); and antimicrosomal antibody titer, 1:102 400 (normal range,<1:100), suggesting toxic goiter with thyroid storm. Piperacillin/tazobactam, methimazole and Lugol's iodine achieved a good outcome. The symptoms of early sepsis and those of thyroid storm could be similar. Therefore, a careful history taking, a thorough physical examination and a high degree of suspicion could make early diagnosis and appropriate treatment.

  18. A case report of thyroid storm induced by acute sepsis

    Directory of Open Access Journals (Sweden)

    Chiu-Yin Yeh

    2016-03-01

    Full Text Available Thyroid storm is a rare but life-threatening condition, which can be induced by many critical diseases. We reported a 40-year-old woman with thyroid goiter manifesting with acute sepsis-induced hyperthyroidism. She mainly presented with abdominal bloating, diarrhea, lower limbs edema and exertional dyspnea. The lactate was 9.5 mmol/L and procalcitonin was 3.8 ng/mL, suggesting acute sepsis. The thyroid echo showed bilateral thyroid goiter. Relevant data included a thyroid-stimulating hormone level of 0.03 μIU/mL; free tetraiodothyronine, 5.67 ng/dL; thyroid-stimulating hormone receptor antibody, 76.9% (normal range, < 14%; and antimicrosomal antibody titer, 1:102400 (normal range, < 1:100, suggesting toxic goiter with thyroid storm. Piperacillin/tazobactam, methimazole and Lugol's iodine achieved a good outcome. The symptoms of early sepsis and those of thyroid storm could be similar. Therefore, a careful history taking, a thorough physical examination and a high degree of suspicion could make early diagnosis and appropriate treatment.

  19. Renal replacement therapy in sepsis-induced acute renal failure

    Directory of Open Access Journals (Sweden)

    Rajapakse Senaka

    2009-01-01

    Full Text Available Acute renal failure (ARF is a common complication of sepsis and carries a high mortality. Renal replacement therapy (RRT during the acute stage is the mainstay of therapy. Va-rious modalities of RRT are available. Continuous RRT using convective methods are preferred in sepsis-induced ARF, especially in hemodynamically unstable patients, although clear evidence of benefit over intermittent hemodialysis is still not available. Peritoneal dialysis is clearly inferior, and is not recommended. Early initiation of RRT is probably advantageous, although the optimal timing of dialysis is yet unknown. Higher doses of RRT are more likely to be beneficial. Use of bio-compatible membranes and bicarbonate buffer in the dialysate are preferred. Anticoagulation during dialysis must be carefully adjusted and monitored.

  20. Whole gut washout for severe sepsis: review of technique and preliminary results.

    Science.gov (United States)

    Alverdy, J; Piano, G

    1997-01-01

    The purpose of this study was to determine the safety and feasibility of whole gut washout for severe sepsis in human beings. High-volume polyethylene glycol-3500 was administered to patients with severe sepsis. Body temperature, white blood cell count, and ventilatory indexes were recorded 24 hours before and 24 hours after whole gut washout. A significant decrease in febrile response was observed after gut washout with polyethylene glycol. Improvements in PaO2, positive end-expiratory pressure, and peak airway pressure were observed. The washout was well tolerated in all but one patient. High-volume whole gut washout for severe sepsis appears safe in critically ill patients and may offer some promise in reducing enterogenic inflammation after catabolic stress.

  1. Predictive value of NGAL for use of renal replacement therapy in patients with severe sepsis

    DEFF Research Database (Denmark)

    Hjortrup, P B; Haase, N; Treschow, F;

    2015-01-01

    BACKGROUND: The predictive value of plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) for use of renal replacement therapy (RRT) and acute kidney injury (AKI) is not established in patients with severe sepsis. METHODS: This was a prospective observational study in three general...... intensive care units (ICUs) in adult ICU patients with severe sepsis needing fluid resuscitation and a sub-study of the 6S trial. Plasma and urine were sampled at baseline and NGAL was measured using particle-enhanced turbidimetric immunoassay (The NGAL Test). Outcome measures were use of RRT in ICU......ROCs. CONCLUSION: In ICU patients with severe sepsis, plasma and urine NGAL had low predictive power for use of RRT, AKI and 90-day mortality. These results were supported by sensitivity and exploratory analyses....

  2. Lipid Metabolic Disturbances in Severe Sepsis: Clinical Significance and New Methods of Correction

    Directory of Open Access Journals (Sweden)

    O. G. Malkova

    2009-01-01

    Full Text Available Objective: to reveal the basic regularities in the development of lipid metabolic disturbances in severe sepsis and to evaluate the efficiency of parenteral use of new balanced lipid emulsions in this cohort of patients. Subjects and methods. A prospective study was conducted in 88 patients with severe sepsis of different etiologies in the intensive care unit (ICI, Sverdlovsk Regional Clinical Hospital One. Among the lipid metabolic parameters, serum cholesterol, triglycerides (TG, high-density lipoproteins, low-density lipoproteins, and atherogenicity index were measured. Out of the systemic inflammatory markers and the additional criteria for sepsis severity, the serum levels of C-reactive protein, nitric oxide, lactate, D-dimers, the anti-inflammatory cytokine IL-4 and the proinflammatory cytokine IL-8 were determined. Serum was taken on days 1, 3, 5, and 7 after admission to the ICI. The quantitative attributes were comparatively analyzed by the statistical program «Statistica 6.0». Results. The severity assessed by the APACHE II scale, the degree of multiple organ failures (MOF evaluated by the SOFA scale, and lung lesion according to the MURREY scale were found to be closely related to the baseline serum TG levels in patients with severe sepsis. The findings suggest that patients with high TG levels have much higher resuscitative mortality rates. The clinical evaluation of the efficiency of the new method for correction of lipid metabolic disturbances in severe sepsis has indicated that the patients receiving balanced (omega-3 fatty acids-enriched fat emulsions as 20% Lipoplus solution had lower APACHE II scores within the first 7 days of intensive therapy and significantly more positive SOFA MOF changes. Specific changes were revealed in the presence of systemic inflammatory markers, such as C-reactive protein, IL-8, and IL-4, which confirms that balanced lipid emulsions are able to affect the system of pro- and anti

  3. Procalcitonin as a predictor of sepsis and outcome in severe trauma patients: A prospective study

    Directory of Open Access Journals (Sweden)

    Nonika Rajkumari

    2013-01-01

    Full Text Available Introduction: Despite the advances in medical sciences, the morbidity and mortality due to sepsis in severe trauma patients remains high; hence the need for early and accurate diagnosis. Very few prospective studies are available in a country like India, which tried to analyze the prediction of sepsis using serum procalcitonin (PCT in such a large scale among trauma patients. This study explores the role of the biomarker PCT in early diagnosis of sepsis and prediction of outcomes in severe trauma cases. Materials and Methods: We studied the patient population prospectively in two different groups. One with acute trauma but no clinical evidence of sepsis and the second group with clinical evidence of sepsis and are followed. Bronchoalveolar lavage, tracheal aspirates, pus, urine, body fluids from sterile body sites, etc., were collected including blood for culture and serum for PCT assays. Such assays were done on samples collected on days 1 and 4 and then compared. Additionally, C-reactive protein (CRP and erythrocyte sedimentation rate (ESR levels were also tested. Antimicrobial sensitivity tests were carried out for all the isolates from the clinical samples and correlated with the clinically suspected cases of sepsis. Outcomes of the patients were noted. Results: Patients with high initial PCT levels (>2 ng/ml in severe trauma cases had poor outcomes and risk of developing complications. Its correlation with severe outcomes was better marked as compared with CRP and ESR levels. The difference in PCT levels between days 1 and 4 in group two patients was statistically significant (P = 0.006 but were not statistically significant for CRP (P = 0.646 and ESR (P = 0.935. The study also shows that PCT levels fall in response to appropriate antimicrobial treatment. Conclusion: PCT is a useful biomarker for early and accurate prediction of sepsis in severe trauma patients. If used in adjunct to clinical findings, it proves to be a good biomarker for

  4. High Levels of Methylarginines Were Associated with Increased Mortality in Patients with Severe Sepsis

    DEFF Research Database (Denmark)

    Myglegård Mortensen, Karoline; Itenov, Theis Skovsgaard; Haase, Nicolai;

    2016-01-01

    INTRODUCTION: Nitric oxide (NO) likely plays a pivotal role in the pathogenesis of sepsis. Arginine is a substrate for NO, whereas the methylated arginines - asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) - are endogenous byproducts of proteolysis that inhibit NO product......INTRODUCTION: Nitric oxide (NO) likely plays a pivotal role in the pathogenesis of sepsis. Arginine is a substrate for NO, whereas the methylated arginines - asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) - are endogenous byproducts of proteolysis that inhibit...... NO production.We investigated if high plasma levels of ADMA, SDMA and arginine/ADMA ratio were associated with 90-day mortality in patients with severe sepsis or septic shock. METHODS: We included 267 adult patients admitted to intensive care unit with severe sepsis or septic shock. The patients had previously...... been included in the randomized controlled trial "Scandinavian Starch for Severe Sepsis and Septic Shock (6S)". ADMA, SDMA and arginine/ADMA ratio were measured in plasma. The risk of death within 90 days were estimated in multivariate Cox regression analyses adjusted for gender, age ≥ 65 years, major...

  5. Developing the surveillance algorithm for detection of failure to recognize and treat severe sepsis.

    Science.gov (United States)

    Harrison, Andrew M; Thongprayoon, Charat; Kashyap, Rahul; Chute, Christopher G; Gajic, Ognjen; Pickering, Brian W; Herasevich, Vitaly

    2015-02-01

    To develop and test an automated surveillance algorithm (sepsis "sniffer") for the detection of severe sepsis and monitoring failure to recognize and treat severe sepsis in a timely manner. We conducted an observational diagnostic performance study using independent derivation and validation cohorts from an electronic medical record database of the medical intensive care unit (ICU) of a tertiary referral center. All patients aged 18 years and older who were admitted to the medical ICU from January 1 through March 31, 2013 (N=587), were included. The criterion standard for severe sepsis/septic shock was manual review by 2 trained reviewers with a third superreviewer for cases of interobserver disagreement. Critical appraisal of false-positive and false-negative alerts, along with recursive data partitioning, was performed for algorithm optimization. An algorithm based on criteria for suspicion of infection, systemic inflammatory response syndrome, organ hypoperfusion and dysfunction, and shock had a sensitivity of 80% and a specificity of 96% when applied to the validation cohort. In order, low systolic blood pressure, systemic inflammatory response syndrome positivity, and suspicion of infection were determined through recursive data partitioning to be of greatest predictive value. Lastly, 117 alert-positive patients (68% of the 171 patients with severe sepsis) had a delay in recognition and treatment, defined as no lactate and central venous pressure measurement within 2 hours of the alert. The optimized sniffer accurately identified patients with severe sepsis that bedside clinicians failed to recognize and treat in a timely manner. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  6. Lipoxin A4 protects against lipopolysaccharide-induced sepsis by promoting innate response activator B cells generation.

    Science.gov (United States)

    Cheng, Qiong; Wang, Zheng; Ma, Ruihua; Chen, Yongtao; Yan, Yan; Miao, Shuo; Jiao, Jingyu; Cheng, Xue; Kong, Lingfei; Ye, Duyun

    2016-10-01

    Sepsis is a serious disease that leads to severe inflammation, dysregulation of immune system, multi-organ failure and death. Innate response activator (IRA) B cells, which produce granulocyte-macrophage colony-stimulating factor (GM-CSF), protect against microbial sepsis. Lipid mediator lipoxin A4 (LXA4) exerts anti-inflammatory and immunoregulatory effects, and it has been reported that LXA4 receptor ALX/FPR2 is expressed on B cells. Here, we investigated the potential role of LXA4 on IRA B cells in lipopolysaccharide (LPS)-induced sepsis. We found that LXA4 significantly promoted the expansion of splenic IRA B cells and increased GM-CSF expression in splenic B cells with LPS stimulation. After splenectomy, LXA4 treatment did not change the serum or peritoneal IL-1β, IL-6 and TNF-α levels in LPS-induced sepsis. LXA4 accelerated the migration of peritoneal B cells to spleen for their differentiation into IRA B cells, whereas this effect was independent of peritoneal macrophage. Furthermore, LXA4 enhanced the phosphorylation level of signal transducer and activator of transcription 5 (STAT5) in splenic B cells. These results suggest that LXA4 protects against LPS-induced sepsis by promoting the generation and migration of splenic IRA B cells, and the underlying molecular mechanism may be related to STAT5 activation. It might provide new insights and therapeutic approaches for treating sepsis.

  7. Characterization of an animal model of severe sepsis associated with respiratory dysfunction

    Directory of Open Access Journals (Sweden)

    Luciano Cesar Pontes de Azevedo

    2007-01-01

    Full Text Available PURPOSE: Pathophysiological studies in humans regarding sepsis are difficult to perform due to ethical and methodological concerns. In this context, animal models of sepsis can be useful to better understand this condition and to test therapeutic strategies. The purpose of this study was to characterize a feasible and clinically relevant model of sepsis in pigs that could be useful for testing different therapeutic interventions. METHODS: 5 White Large pigs were anesthetized, arterial and pulmonary catheters were introduced, and sepsis was induced by fecal peritonitis. Several biochemical indicators of organ dysfunction and infectious parameters were measured. The pigs were monitored until death, when fragments of organs were removed for pathology. Three animals without peritonitis served as controls and were sacrificed 24 hours after surgery without developing significant changes in organ function. RESULTS: Septic pigs survived 17 hours on average (range, 16-18 h, and Escherichia coli was recovered from blood cultures. They developed a significant decrease in left ventricular work and a nonsignificant reduction in mixed venous oxygen saturation. Respiratory dysfunction was characterized by a decrease in the PaO2/FiO2 ratio and respiratory compliance. Pathology of the lungs revealed areas of pulmonary collapse, hemorrhage, pulmonary congestion, and discrete neutrophil infiltrate. CONCLUSIONS: Fecal peritonitis in pigs is a clinically relevant model of sepsis associated with acute lung injury without direct pulmonary insult. This model may prove to be useful for studying pathogenic aspects of secondary lung injury as well as for validating ventilatory or pharmacologic interventions.PROPOSTA: Estudos sobre sepse envolvendo sua fisiopatologia são difíceis de serem realizados devido a razões éticas e metodológicas. Neste sentido, modelos animais criam oportunidades de estudos para entender a fisiopatologia e testar estratégias terapêuticas. O

  8. Classification of sepsis, severe sepsis and septic shock: the impact of minor variations in data capture and definition of SIRS criteria.

    Science.gov (United States)

    Klein Klouwenberg, Peter M C; Ong, David S Y; Bonten, Marc J M; Cremer, Olaf L

    2012-05-01

    To quantify the effects of minor variations in the definition and measurement of systemic inflammatory response syndrome (SIRS) criteria and organ failure on the observed incidences of sepsis, severe sepsis and septic shock. We conducted a prospective, observational study in a tertiary intensive care unit in The Netherlands between January 2009 and October 2010. A total of 1,072 consecutive adults were included. We determined the upper and lower limits of the measured incidence of sepsis by evaluating the influence of the use of an automated versus a manual method of data collection, and variations in the number of SIRS criteria, concurrency of SIRS criteria, and duration of abnormal values required to make a particular diagnosis. The measured incidence of SIRS varied from 49% (most restrictive setting) to 99% (most liberal setting). Subsequently, the incidences of sepsis, severe sepsis and septic shock ranged from 22 to 31%, from 6 to 27% and from 4 to 9% for the most restrictive versus the most liberal measurement settings, respectively. In non-infected patients, 39-98% of patients had SIRS, whereas still 17-6% of patients without SIRS had an infection. The apparent incidence of sepsis heavily depends on minor variations in the definition of SIRS and mode of data recording. As a consequence, the current consensus criteria do not ensure uniform recruitment of patients into sepsis trials.

  9. Circulating Angiopopietin-1 Correlates With the Clinical Course of Multiple Organ Dysfunction Syndrome and Mortality in Patients With Severe Sepsis

    Science.gov (United States)

    Lin, Shu-Min; Chung, Fu-Tsai; Kuo, Chih-Hsi; Chou, Pai-Chien; Wang, Tsai-Yu; Chang, Po-Jui; Lo, Yu-Lun; Huang, Chien-Da; Lin, Horng-Chyuan; Wang, Chun-Hua; Kuo, Han-Pin

    2015-01-01

    Abstract To determine plasma concentrations of angiopoietin (Ang)-1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF) in patients with sepsis-induced multiple organ dysfunction syndrome (MODS) and determine their association with mortality. The study prospectively recruited 96 consecutive patients with severe sepsis in a l intensive care unit of a tertiary hospital. Plasma Ang-1, Ang-2, Tie-2, and VEGF levels and MODS were determined in patients on days 1, 3, and 7 of sepsis. Univariate and Cox proportional hazards analysis were performed to develop a prognostic model. Days 1, 3, and 7 plasma Ang-1 concentrations were persistently decreased in MODS patients than in non-MODS patients (day1: 4.0 ± 0.5 vs 8.0 ± 0.5 ng/mL, P MODS on day 7 of sepsis, Ang-1 levels were increased from day 1 (4.7 ± 0.6 ng/mL vs 9.1 ± 1.4 ng/mL, n = 43, P = 0.004). Plasma Ang-1 levels were lower in nonsurvivors than in survivors on days 1 (4.0 ± 0.5 vs 7.1 ± 0.5 ng/mL, P MODS and mortality. Ang-1 level less than the median value was the only independent predictor of mortality (hazard ratio, 2.57; 95% CI 1.12–5.90, P = 0.025). Persistently decreased Ang-1 levels are associated with MODS and subsequently, mortality in patients with sepsis. PMID:25997069

  10. The impact of nationwide education program on clinical practice in sepsis care and mortality of severe sepsis: a population-based study in Taiwan.

    Directory of Open Access Journals (Sweden)

    Yu-Chun Chen

    Full Text Available OBJECTIVES: We investigated the effect of a nationwide educational program following surviving sepsis campaign (SSC guidelines. Physicians' clinical practice in sepsis care and patient mortality rate for severe sepsis were analyzed using a nationally representative cohort. METHODS: Hospitalizations for severe sepsis with organ failure from 1997 to 2008 were extracted from Taiwan's National Health Insurance Research Database (NHIRD, and trends in sepsis incidence and mortality rates were analyzed. A before-and-after study design was used to evaluate changes in the utilization rates of SSC items and changes in severe sepsis mortality rates occurred after a national education program conducted by the Joint Taiwan Critical Care Medicine Committee since 2004. A total of 39,706 hospitalizations were analyzed, which consisted of a pre-intervention cohort of 14,848 individuals (2000-2003 and a post-intervention cohort of 24,858 individuals (2005-2008. RESULTS: The incidence rate of severe sepsis increased from 1.88 per 1,000 individuals in 1997 to 5.07 per 1,000 individuals in 2008. The cumulative mortality rate decreased slightly from 48.2% for the pre-intervention cohort to 45.9% for the post-intervention cohort. The utilization rates of almost all SSC items changed significantly between the pre-intervention and post-intervention cohorts. These changes of utilization rates were found to be associated with mild reduction in mortality rate. CONCLUSION: The nationwide education program through a national professional society has a significant impact on physicians' clinical practice and resulted in a slight but significant reduction of severe sepsis mortality rate.

  11. Prognostic value and therapeutic potential of TREM-1 in Streptococcus pyogenes- induced sepsis.

    Science.gov (United States)

    Horst, Sarah A; Linnér, Anna; Beineke, Andreas; Lehne, Sabine; Höltje, Claudia; Hecht, Alexander; Norrby-Teglund, Anna; Medina, Eva; Goldmann, Oliver

    2013-01-01

    TREM-1 (triggering receptor expressed on myeloid cells) is a surface molecule expressed on neutrophils and macrophages which has been implicated in the amplification of inflammatory responses triggered during infection. In the present study, we have investigated the clinical significance of TREM-1 in Streptococcus pyogenes-induced severe sepsis in both experimentally infected mice as well as in patients with streptococcal toxic shock. We found that S. pyogenes induced a dose-dependent upregulation of TREM-1 in in vitro cultured phagocytic cells and in the organs of S. pyogenes-infected mice. Furthermore, we reported a positive correlation between serum levels of soluble TREM-1 (sTREM-1) and disease severity in infected patients as well as in experimentally infected mice. Hence, sTREM-1 may represent a useful surrogate marker for streptococcal sepsis. We found that modulation of TREM-1 by administration of the TREM-1 decoy receptor rTREM-1/Fc substantially attenuated the synthesis of inflammatory cytokines. More importantly, treatment of S. pyogenes-infected septic mice with rTREM-1/Fc or the synthetically produced conserved extracellular domain LP17 significantly improved disease outcome. In summary, our data suggest that TREM-1 may not only represent a valuable marker for S. pyogenes infection severity but it may also be an attractive target for the treatment of streptococcal sepsis.

  12. STRUCTURAL CHANGES OF THE HEART DURING SEVERE SEPSIS OR SEPTIC SHOCK

    NARCIS (Netherlands)

    Smeding, Lonneke; Plotz, Frans B.; Groeneveld, A. B. Johan; Kneyber, Martin C. J.

    2012-01-01

    Cardiovascular dysfunction is common in severe sepsis or septic shock. Although functional alterations are often described, the elevated serum levels of cardiac proteins and autopsy findings of myocardial immune cell infiltration, edema, and damaged mitochondria suggest that structural changes to th

  13. Two cases of severe sepsis caused by Bacillus pumilus in neonatal infants

    NARCIS (Netherlands)

    Kimouli, Maria; Vrioni, Georgia; Papadopoulou, Magdalini; Koumaki, Vasiliki; Petropoulou, Dimitra; Gounaris, Antonios; Friedrich, Alexander W.; Tsakris, Athanassios

    Bacillus pumilus is an environmental contaminant that has been rarely associated with clinical infections. Here, two cases of severe sepsis caused by B. pumilus are described in two full-term neonates; one in a female infant with no factors predisposing her to infection and the other in a male

  14. Variability in targeted arterial oxygenation levels in patients with severe sepsis or septic shock

    DEFF Research Database (Denmark)

    Dahl, R M; Grønlykke, L; Haase, N

    2015-01-01

    of arterial oxygen (PaO2 ) and mortality. METHODS: We extracted data from two Scandinavian clinical trials of ICU patients with severe sepsis or septic shock. We calculated average PaO2 and fraction of inspired oxygen (FiO2 ) from trial inclusion and the following 5 days, and assessed the association between...

  15. Severe sepsis due to Chryseobacterium indologenes in an immunocompetent adventure traveler.

    Science.gov (United States)

    McKew, Genevieve

    2014-11-01

    Chryseobacterium indologenes is an environmental organism which is usually an opportunistic pathogen, most usually associated with nosocomial or device-related infections. This case, affecting a fit and well adventure traveler, demonstrates that it may be an agent of severe sepsis in otherwise healthy humans. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  16. Two cases of severe sepsis caused by Bacillus pumilus in neonatal infants

    NARCIS (Netherlands)

    Kimouli, Maria; Vrioni, Georgia; Papadopoulou, Magdalini; Koumaki, Vasiliki; Petropoulou, Dimitra; Gounaris, Antonios; Friedrich, Alexander W.; Tsakris, Athanassios

    2012-01-01

    Bacillus pumilus is an environmental contaminant that has been rarely associated with clinical infections. Here, two cases of severe sepsis caused by B. pumilus are described in two full-term neonates; one in a female infant with no factors predisposing her to infection and the other in a male infan

  17. Cardiac hyporesponsiveness in severe sepsis is associated with nitric oxide-dependent activation of G protein receptor kinase.

    Science.gov (United States)

    Dal-Secco, Daniela; DalBó, Silvia; Lautherbach, Natalia E S; Gava, Fábio N; Celes, Mara R N; Benedet, Patricia O; Souza, Adriana H; Akinaga, Juliana; Lima, Vanessa; Silva, Katiussia P; Kiguti, Luiz Ricardo A; Rossi, Marcos A; Kettelhut, Isis C; Pupo, André S; Cunha, Fernando Q; Assreuy, Jamil

    2017-07-01

    G protein-coupled receptor kinase isoform 2 (GRK2) has a critical role in physiological and pharmacological responses to endogenous and exogenous substances. Sepsis causes an important cardiovascular dysfunction in which nitric oxide (NO) has a relevant role. The present study aimed to assess the putative effect of inducible NO synthase (NOS2)-derived NO on the activity of GRK2 in the context of septic cardiac dysfunction. C57BL/6 mice were submitted to severe septic injury by cecal ligation and puncture (CLP). Heart function was assessed by isolated and perfused heart, echocardiography, and β-adrenergic receptor binding. GRK2 was determined by immunofluorescence and Western blot analysis in the heart and isolated cardiac myocytes. Sepsis increased NOS2 expression in the heart, increased plasma nitrite + nitrate levels, and reduced isoproterenol-induced isolated ventricle contraction, whole heart tension development, and β-adrenergic receptor density. Treatment with 1400W or with GRK2 inhibitor prevented CLP-induced cardiac hyporesponsiveness 12 and 24 h after CLP. Increased labeling of total and phosphorylated GRK2 was detected in hearts after CLP. With treatment of 1400W or in hearts taken from septic NOS2 knockout mice, the activation of GRK2 was reduced. 1400W or GRK2 inhibitor reduced mortality, improved echocardiographic cardiac parameters, and prevented organ damage. Therefore, during sepsis, NOS2-derived NO increases GRK2, which leads to a reduction in β-adrenergic receptor density, contributing to the heart dysfunction. Isolated cardiac myocyte data indicate that NO acts through the soluble guanylyl cyclase/cGMP/PKG pathway. GRK2 inhibition may be a potential therapeutic target in sepsis-induced cardiac dysfunction.NEW & NOTEWORTHY The main novelty presented here is to show that septic shock induces cardiac hyporesponsiveness to isoproterenol by a mechanism dependent on nitric oxide and mediated by G protein-coupled receptor kinase isoform 2. Therefore

  18. Relationship of Adrenocortical Function and TCM Syndrome Typing in Elderly Patients with Severe Sepsis

    Institute of Scientific and Technical Information of China (English)

    吴海云; 危成筠; 朱广卿; 许强; 张健; 王士雯

    2004-01-01

    Objective: To explore the relationship between TCM Syndrome typing and adrenocortical function in elderly patients with severe sepsis, and to see whether TCM Syndrome Differentiation can provide clinical clues in identifying relative adrenal insufficiency (RAI) in patients with severe sepsis. Methods: Six ty-one old patients with severe sepsis were classified into four types according to TCM Syndrome Differentiation: The severe invasion of toxic-heat type (Type SITH, n = 21 ); the Qi stagnation and blood stasis type ( Type QSBS, n = 11); the sudden depletion of Yang-Qi type ( Type SDYQ, n = 16); and the exhaustion of Qi-Yin type (Type EOQY, n = 13). The base-line level of plasma cortisol in patients of different types and their response to corticotropin stimulation were compared, which were also compared with those of 12 healthy elderly persons synchronously. Results: The base-line level of plasma cortisol was not significantly different between patients of different Syndrome types (P>0.05), but they were all sgnificantly higher than that in the healthy persons ( P<0.05). Compared with Type QSBS and Type EOQY, Type SITH and Type SDYQ showed less cortisol concentration increment after corticotropin stimulation ( P<0.05). RAI was more prevalent in patients of Type SITH and Type SDYQ than in patients of Type QSBS and Type EOQY (57% vs 25 %, P<0.01). Conclusion: In old patients with severe sepsis, different TCM Syndrome types are associated with different adrenocortical function status. TCM Syndrome differentiation can provide clinical clues in identifying old patients with severe sepsis who have also RAI.

  19. Mitochondrial DNA haplogroups are associated with severe sepsis and mortality in patients who underwent major surgery.

    Science.gov (United States)

    Jiménez-Sousa, Maria Angeles; Tamayo, Eduardo; Guzmán-Fulgencio, María; Heredia, María; Fernández-Rodríguez, Amanda; Gómez, Esther; Almansa, Raquel; Gómez-Herreras, José I; García-Álvarez, Mónica; Gutiérrez-Junco, Sandra; Bermejo-Martin, Jesús F; Resino, Salvador

    2015-01-01

    To analyse whether mitochondrial DNA (mtDNA) haplogroups are associated with severe sepsis and mortality after major surgery. We performed a case-control study on 240 cardiac or abdominal surgery patients developing severe sepsis (Case-group) and 267 cardiac or abdominal surgery patients without severe sepsis and with systemic inflammatory response syndrome (SIRS, Control-group). Furthermore, a longitudinal substudy was performed for analysing the survival in septic patients. Only European white patients within the N macro-cluster were included. Case-group underwent cardiac surgery had lower frequencies of cluster HV (p = 0.005) and haplogroup H (p = 0.005) and higher frequencies of cluster JT (p = 0.028) than Control-group; but no significant differences were found for abdominal surgery. Besides, both cluster HV and haplogroup H were associated with decreased odds of severe sepsis (adjusted odds ratio (aOR) = 0.45 (95%CI = 0.25; 0.82); p = 0.009 and aOR = 0.48 (95%CI = 0.26; 0.87); p = 0.015, respectively) among patients underwent cardiac surgery. In Case-group, 45.4% (109/240) patients died with a survival median of 39 (95%CI = 31.4; 46.62) days. When the clusters were examined, 41% (55/134) patients within cluster HV died versus 71.4% (10/14) patients within cluster IWX (p = 0.018). Additionally, patients within cluster IWX had an increased risk of death (adjusted hazard ratio (aHR) = 2.22; (95%CI = 1.14; 4.34); p = 0.019). European mitochondrial haplogroups might be related to the onset of severe sepsis in patients who underwent major cardiac surgery, but not in patients underwent major abdominal surgery. Besides, mtDNA haplogroups could have influence on mortality in septic patients. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  20. Acute and long-term dysphagia in critically ill patients with severe sepsis: results of a prospective controlled observational study.

    Science.gov (United States)

    Zielske, Joerg; Bohne, Silvia; Brunkhorst, Frank M; Axer, Hubertus; Guntinas-Lichius, Orlando

    2014-11-01

    Dysphagia is a major risk factor for morbidity and mortality in critically ill patients treated in intensive care units (ICUs). Structured otorhinolaryngological data on dysphagia in ICU survivors with severe sepsis are missing. In a prospective study, 30 ICU patients with severe sepsis and thirty without sepsis as control group were examined using bedside fiberoptic endoscopic evaluation of swallowing after 14 days in the ICU (T1) and 4 months after onset of critical illness (T2). Swallowing dysfunction was assessed using the Penetration-Aspiration Scale (PAS). The Functional Oral Intake Scale was applied to evaluate the diet needed. Primary endpoint was the burden of dysphagia defined as PAS score >5. At T1, 19 of 30 severe sepsis patients showed aspiration with a PAS score >5, compared to 7 of 30 in critically ill patients without severe sepsis (p = 0.002). Severe sepsis and tracheostomy were independent risk factors for severe dysphagia with aspiration (PAS > 5) at T1 (p = 0.042 and 0.006, respectively). 4-month mortality (T2) was 57 % in severe sepsis patients compared to 20 % in patients without severe sepsis (p = 0.006). At T2, more severe sepsis survivors were tracheostomy-dependent and needed more often tube or parenteral feeding (p = 0.014 and p = 0.040, respectively). Multivariate analysis revealed tracheostomy at T1 as independent risk factor for severe dysphagia at T2 (p = 0.030). Severe sepsis appears to be a relevant risk factor for long-term dysphagia. An otorhinolaryngological evaluation of dysphagia at ICU discharge is mandatory for survivors of severe critical illness to plan specific swallowing rehabilitation programs.

  1. Dynamic cerebral autoregulation to induced blood pressure changes in human experimental and clinical sepsis.

    Science.gov (United States)

    Berg, Ronan M G; Plovsing, Ronni R; Bailey, Damian M; Holstein-Rathlou, Niels-Henrik; Møller, Kirsten

    2016-11-01

    Previous studies have demonstrated that dynamic cerebral autoregulation to spontaneous fluctuations in blood pressure is enhanced following lipopolysaccharide (LPS) infusion, a human experimental model of early sepsis, whereas by contrast it is impaired in patients with severe sepsis or septic shock. In this study, we hypothesized that this pattern of response would be identical during induced changes in blood pressure. Dynamic cerebral autoregulation was assessed in nine healthy volunteers and six septic patients. The healthy volunteers underwent a 4-h intravenous infusion of LPS (total dose: 2 ng kg(-1) ). Mean arterial blood pressure (MAP, arterial transducer) and middle cerebral artery blood flow velocity (MCAv, transcranial Doppler ultrasound) were recorded continuously during thigh-cuff deflation-induced changes in MAP for the determination of a modified rate of regulation (RoR). This was performed before and after LPS infusion in healthy volunteers, and within 72 h following clinical diagnosis of sepsis in patients. In healthy volunteers, thigh-cuff deflation caused a MAP reduction of 16 (13-20) % at baseline and 18 (16-20) % after LPS, while the MAP reduction was 12 (11-13) % in patients (Psepsis, they remain inconclusive with regard to more advanced stages of disease, because thigh-cuff deflation failed to induce sufficient MAP reductions in patients. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  2. [Impairment of oxygenation of patients in surgical intensive care : Early symptom of severe sepsis].

    Science.gov (United States)

    Hückstädt, M; Hofmann, G O; Mendel, T; Stuttmann, R; Hilbert-Carius, P

    2016-11-01

    Sepsis and septic shock are major contributors to morbidity and mortality in intensive care patients. Early identification and adequate therapy are of utmost importance to reduce the still high mortality in patients with severe sepsis. Many of the pathophysiologic changes are nonspecific. Thus, a combination of symptoms and laboratory results are necessary to confirm the diagnosis. Impairment of the Horovitz index is identified as being a primal prognostic criterion for early diagnosis in serious progression of sepsis, after exclusion of a few differential diagnoses. Based on this fact, the prevalence of this symptom compared to other sepsis parameters is of specific interest. In a retrospective study 33 cases of serious sepsis were analysed during the patient's course of intensive care treatment focusing on oxygenation. The deterioration of oxygenation, meaning a drop in the Horovitz index below 200 mm Hg (25.7 kPa) or a decrease in paO2 by 67.5 mm Hg (9 kPa) in spontaneously breathing patients with sepsis was the mean inclusion criteria. We compared the sequence of occurrence of known sepsis markers (e. g. PCT, WBC, CRP) with the deterioration in oxygenation to answer the question whether impairment of oxygenation could be an early symptom of severe sepsis. The Mann Whitney U‑test and a discriminant analysis were performed to verify differences of the variables investigated between surviving and deceased patients. Furthermore a regression analysis was performed to confirm the results of the discriminant analysis. The mean drop in the Horovitz index was 90 ± 24 mm Hg (12 ± 3.2 kPa) within 4.5 h respectively. This was highly significant (p sepsis. In more than ¾ of all cases this symptom occurred in an earlier stage than other organ dysfunctions. In 79 % of cases, patients showed an impairment of oxygenation before PCT increased on values of >2 ng/ml. In 76 % of cases impairment of oxygenation occurred earlier than all other

  3. Meta-analysis shows that infants who have suffered neonatal sepsis face an increased risk of mortality and severe complications.

    Science.gov (United States)

    Bakhuizen, Sabine E; de Haan, Timo R; Teune, Margreet J; van Wassenaer-Leemhuis, Aleid G; van der Heyden, Jantien L; van der Ham, David P; Mol, Ben Willem J

    2014-12-01

    Infants suffering from neonatal sepsis face an increased risk of early death and long-term neurodevelopmental delay. This paper analyses and summarises the existing data on short-term and long-term outcomes of neonatal sepsis, based on 12 studies published between January 2000 and 1 April 2012 and covering 3669 neonates with sepsis. Infants who have suffered neonatal sepsis face an increased risk of mortality and severe complications such as brain damage and, or, neurodevelopmental delay. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  4. Protocol Adherence for Severe Sepsis and Septic Shock Management in the Emergency Department; a Clinical Audit

    Directory of Open Access Journals (Sweden)

    Mostafa Alavi-Moghaddam

    2017-01-01

    Full Text Available Introduction: Although significant development in the field of medicine is achieved, sepsis is still a major issue threatening humans’ lives. This study was aimed to audit the management of severe sepsis and septic shock patients in emergency department (ED according to the present standard guidelines.Method: This is a prospective audit on approaching adult septic patients who were admitted to ED. The audit checklist was created based on the protocols of Surviving Sepsis Campaign and British Royal College recommendations. The mean knowledge score and the compliance rate of studied measures regarding standard protocols were calculated using SPSS version 21.Results: 30 emergency medicine residents were audited (63.3% male. The mean knowledge score of studied residents regarding standard guidelines were 5.07 ± 1.78 (IQR = 2 in pre education and 8.17 ± 1.31 (IQR = 85 in post education phase (p < 0.001. There was excellent compliance with standard in 4 (22% studied measures, good in 2 (11%, fair in 1 (6%, weak in 2 (11%, and poor in 9 (50%. 64% of poor compliance measures correlated to therapeutic factors. After training, score of 5 measures including checking vital signs in < 20 minute, central vein pressure measurement in < 1 hour, blood culture request, administration of vasopressor agents, and high flow O2 therapy were improved clinically, but not statistically.Conclusion: The protocol adherence in management of severe sepsis and septic shock for urine output measurement, central venous pressure monitoring, administration of inotrope agents, blood transfusion, intravenous antibiotic and hydration therapy, and high flow O2 delivery were disappointingly low. It seems training workshops and implementation of Clinical audit can improve residents’ adherence to current standard guidelines regarding severe sepsis and septic shock.

  5. 重症监护病房感染相关性淤积性黄疸患者的临床分析%The clinical analysis of severe sepsis induced cholestasis jaundice patients in intensive care unit

    Institute of Scientific and Technical Information of China (English)

    徐前程; 查磊; 刘小彬; 陈尚华

    2016-01-01

    Objective To investigate the epidemiological characteristics and prognosis assessment mortality risk factors of severe sepsis induced cholestasis jaundice (SSICJ) patients admitted into intensive care unit (ICU), and to strengthen acknowledge of SSICJ and guild clinical treatment. Methods The clinical data of 60 SSICJ patients were retrospectively analyzed with statistical description. All the patients admitted to the ICU of the Wuhu second people′s hospital affiliated to Wannan medical college from January 2011 to December 2013 were assigned to two groups (survival group and non-survival group) according to the survival outcome. Logistic regression analysis was employed to identify independent risk factors of the death of SSICJ during ICU stay. Results The respiratory system was the most common site of infection [42%(25/60)], followed by abdominal infection and blood stream infection 22%(13/60),12%(7/60) respectively. Fifty-two patients were positive in bacterial isolation and 73 strains were identified , Gram-negative bacteria was the most common pathogens [48%(35/73)], followed by Gram-positive bacteria [30%(22/73)] and fungi [22%(16/73)]. Nosocomial infections accounted for [48%(29/60)] of the enrolled patients. Overall ICU mortality of SSICJ patients was[35%(21/60)], with nosocomial infections and chronic disease infections, septic shock, the ICU mortality were increased to [41%(12/29)], [64%(9/14)], [77%(17/22)] respectively. The patient with continue increaseing cholestasis jaundice in non-survival group was more than survival group[0%(0/31) vs 86%(18/21), P<0.01], the AST was similar in the two groups[(82±21) U/L vs(89±27) U/L, P=0.30]. Logistic regression analysis showed that APACHEⅡscores[odds(OR)=2.34, 95%CI 1.20-5.81, P=0.032], coexist with septic shock(OR=4.43, 95%CI 1.76-7.38, P=0.049), pre-ICU therapy time(OR=1.56,95%CI 1.05-3.78, P=0.015) were the independent risk factors of ICU mortality. Conclusion SSICJ was a common cause of ICU admission

  6. Relationship between adrenal function and prognosis in patients with severe sepsis

    Institute of Scientific and Technical Information of China (English)

    YANG Yi; LIU Ling; ZHAO Bo; LI Mao-qin; WU Bin; YAN Zheng; GU Qin; SUN Hua; QIU Hai-bo

    2007-01-01

    Background It is known that the hypothalamic-pituitary-adrenal (HPA) axis is highlighted by stimulation, such as sepsis,trauma, etc, when corticortropin increases and plasma cortisol levels enhance. Relative adrenal insufficiency is not uncommon in critically ill patients and may occur in severe sepsis patients with high plasma cortisol levels. It has been demonstrated that a short corticotropin test has a good prognostic value and is helpful in identifying patients with septic shock at high risk for death, but it has not been established for all severe sepsis patients, especially in China. The aim of this study is to explore the relationship between adrenal function and prognosis in patients with severe sepsis.Methods This prospective study was conducted between July and December 2004 in 6 teaching hospitals. Two hundred and forty patients with severe sepsis were enrolled in this study. A short corticotropin stimulation test was performed in all patients by intravenous injection of 250 μg of corticotropin. Blood samples were taken immediately before the test (T0), 30 (T30) and 60 (T60) minutes afterward, and the plasma cortisol concentration was measured by radio-immunoassay. At the onset of severe sepsis, the following parameters were recorded: age, sex, Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ, heart rate, mean arterial pressure (MAP), arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2), peripheral blood of hemoglobin, platelets and leukocyte concentration and the number of organ failure. Patients were designated into two groups (survival and non-survival groups) according to the 28-day mortality. Relative adrenal insufficiency was defined as the difference between T0 and the highest value of T30 or T60 (△Tmax) ≤9 μg/dl.Results (1) Two hundred and forty patients with severe sepsis were included in this study, with 134 patients in the survival group and 106 in the non-survival group. The 28-day mortality was 44

  7. Sepsis Induces Hematopoietic Stem Cell Exhaustion and Myelosuppression through Distinct Contributions of TRIF and MYD88

    Directory of Open Access Journals (Sweden)

    Huajia Zhang

    2016-06-01

    Full Text Available Toll-like receptor 4 (TLR4 plays a central role in host responses to bacterial infection, but the precise mechanism(s by which its downstream signaling components coordinate the bone marrow response to sepsis is poorly understood. Using mice deficient in TLR4 downstream adapters MYD88 or TRIF, we demonstrate that both cell-autonomous and non-cell-autonomous MYD88 activation are major causes of myelosuppression during sepsis, while having a modest impact on hematopoietic stem cell (HSC functions. In contrast, cell-intrinsic TRIF activation severely compromises HSC self-renewal without directly affecting myeloid cells. Lipopolysaccharide-induced activation of MYD88 or TRIF contributes to cell-cycle activation of HSC and induces rapid and permanent changes in transcriptional programs, as indicated by persistent downregulation of Spi1 and CebpA expression after transplantation. Thus, distinct mechanisms downstream of TLR4 signaling mediate myelosuppression and HSC exhaustion during sepsis through unique effects of MyD88 and TRIF.

  8. Early sepsis bundle compliance for non-hypotensive patients with intermediate versus severe hyperlactemia.

    Science.gov (United States)

    Leisman, Daniel E; Zemmel D'Amore, Jason A; Gribben, Jeanie L; Ward, Mary Frances; Masick, Kevin D; Bianculli, Andrea R; Bradburn, Kathryn H; D'Angelo, John K; Doerfler, Martin E

    2017-06-01

    To compare the association of 3-h sepsis bundle compliance with hospital mortality in non-hypotensive sepsis patients with intermediate versus severe hyperlactemia. This was a cohort study of all non-hypotensive, hyperlactemic sepsis patients captured in a prospective quality-improvement database, treated October 2014 to September 2015 at five tertiary-care centers. We defined sepsis as 1) infection, 2) ≥2 SIRS criteria, and 3) ≥1 organ dysfunction criterion. "Time-zero" was the first time a patient met all sepsis criteria. systolic blood pressure>90 mmHg, mean arterial pressure>65 mmHg, and serum lactate≥2.2 mmol/L. Primary exposures: 1) intermediate(2.2-3.9 mmol/L) versus severe(≥4.0 mmol/L) hyperlactemia and 2) full 3-h bundle compliance. Bundle elements: The primary outcome was 60-day in-hospital mortality. 2417 patients met inclusion criteria. 704(29%) had lactate≥4.0 mmol/L versus 1775 patients with lactate 2.2-3.9 mmol/L. Compliance was 75% for antibiotics and 53% for fluids. Full-compliance was comparable between lactate groups (n=200(29%) and 488(28%), respectively). We observed 424(17.5%) mortalities: intermediate/non-compliant - 182(14.9%), intermediate/compliant - 41(8.4%), severe/non-compliant - 147(29.2%), severe/compliant - 54(27.0%) [difference-of-differences=4.3%, CI=2.6-5.9%]. In multivariable regression, mortality predictors included severe hyperlactemia (OR=1.99, CI=1.51-2.63) and bundle compliance (OR=0.62, CI=0.42-0.90), and their interaction was significant: p(interaction)=0.022. We observed a significant interaction between 3-h bundle compliance and initial hyperlactemia. Bundle compliance may be associated with greater mortality benefit for non-hypotensive sepsis patients with less severe hyperlactemia. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. [Implementation of an automatic alarms system for early detection of patients with severe sepsis].

    Science.gov (United States)

    Ferreras, José María; Judez, Diego; Tirado, Gabriel; Aspiroz, Carmen; Martínez-Álvarez, Rosa; Dorado, Paloma; Ezpeleta, Ana; Marrón, Rafael; Gargallo, Begoña; Herranz, Clara

    2015-10-01

    The objective of this study was to assess the usefulness of a software tool integrated into the medical electronic history at the time of emergency triage. The aim was the early detection of patients with severe sepsis, and the potential impact of this software tool on reducing the mortality rate in patients treated. The study consisted of two comparative samples. Patient selection was performed retrospectively into two groups using ICD-9 codes from the hospital and emergency department discharge reports. The codes were 038.9, 995.9 and 995.92 for sepsis, and 785.52 for severe sepsis and septic shock. The sample called «alarms» consisted of patients studied after implementing the sepsis alarm system in the Emergency Department computer system. There were two types of alarms, a serious one and an alert one depending on the on vital signs defined. The historical sample called «no alarms» consisted of patients seen in the Emergency Department during the year before the introduction of the alarm system. The compliance rate of the sepsis treatment package was higher in the «alarms» sample, compared to the sample without alarms, with blood cultures, 96.3% versus 80.9% (Psepsis allows acting earlier, better compliance with basic measures, and a reduction in hospital stay and mortality. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  10. Endothelial dysfunction assessed by brachial artery ultrasound in severe sepsis and septic shock.

    Science.gov (United States)

    Becker, Leandro; Prado, Karen; Foppa, Murilo; Martinelli, Nidiane; Aguiar, Cynthia; Furian, Thiago; Clausell, Nadine; Rohde, Luis Eduardo

    2012-06-01

    Noninvasive evaluation of endothelial function may be accomplished by ultrasound assessment of flow-mediated vasodilation (FMD) of the brachial artery. This study aims to investigate the role of FMD analysis on intrahospital prognosis of patients with sepsis. Adult patients admitted to the intensive care unit with severe sepsis or septic shock were consecutively included. Brachial artery FMD was measured upon admission, after 24 and 72 hours. A group of apparently healthy subjects paired for sex and age was used as controls. Patients were followed up to discharge or death. We studied 42 patients (mean age, 51 ± 19 years) with sepsis predominantly of abdominal or respiratory etiology (75%). Acute Physiology And Chronic Health Evaluation II risk score was 23 ± 7, and intrahospital mortality rate was 33%. Flow-mediated vasodilation in septic patients was significantly lower than in healthy controls (1.5 ± 7% vs 6 ± 4%, P < .001). Most of the nonsurvivors (86%) showed a decline in sequential FMD analyses, whereas only 43% of survivors showed a reduction of FMD (P = .01). In nonsurvivors, FMD was significantly lower 72 hours after sepsis onset (-3.3% ± 10% vs 5.2% ± 4%; P < .05; time-group interaction P value = .03). Brachial FMD is altered in septic patients with hemodynamic instability, and its deterioration may be an early marker of unfavorable prognosis. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Changes in tissue perfusion parameters in dogs with severe sepsis/septic shock in response to goal-directed hemodynamic optimization at admission to ICU and the relation to outcome.

    Science.gov (United States)

    Conti-Patara, Andreza; de Araújo Caldeira, Juliana; de Mattos-Junior, Ewaldo; de Carvalho, Haley da Silva; Reinoldes, Adriane; Pedron, Bruno Gregnanin; Patara, Marcelo; Francisco Talib, Mariana Semião; Faustino, Marcelo; de Oliveira, Clair Motos; Cortopassi, Silvia Renata Gaido

    2012-08-01

    To evaluate the changes in tissue perfusion parameters in dogs with severe sepsis/septic shock in response to goal-directed hemodynamic optimization in the ICU and their relation to outcome. Prospective observational study. ICU of a veterinary university medical center. Thirty dogs with severe sepsis or septic shock caused by pyometra who underwent surgery and were admitted to the ICU. Severe sepsis was defined as the presence of sepsis and sepsis-induced dysfunction of one or more organs. Septic shock was defined as the presence of severe sepsis plus hypotension not reversed with fluid resuscitation. After the presumptive diagnosis of sepsis secondary to pyometra, blood samples were collected and clinical findings were recorded. Volume resuscitation with 0.9% saline solution and antimicrobial therapy were initiated. Following abdominal ultrasonography and confirmation of increased uterine volume, dogs underwent corrective surgery. After surgery, the animals were admitted to the ICU, where resuscitation was guided by the clinical parameters, central venous oxygen saturation (ScvO(2)), lactate, and base deficit. Between survivors and nonsurvivors it was observed that the ScvO(2), lactate, and base deficit on ICU admission were each related independently to death (P = 0.001, P = 0.030, and P dogs with severe sepsis and septic shock; animals with a higher ScvO(2) and lower base deficit at admission to the ICU have a lower probability of death. © Veterinary Emergency and Critical Care Society 2012.

  12. Human Myeloid-derived Suppressor Cells are Associated With Chronic Immune Suppression After Severe Sepsis/Septic Shock.

    Science.gov (United States)

    Mathias, Brittany; Delmas, Amber L; Ozrazgat-Baslanti, Tezcan; Vanzant, Erin L; Szpila, Benjamin E; Mohr, Alicia M; Moore, Frederick A; Brakenridge, Scott C; Brumback, Babette A; Moldawer, Lyle L; Efron, Philip A

    2017-04-01

    We hypothesized that after sepsis in humans, MDSCs will be persistently increased, functionally immunosuppressive, and associated with adverse clinical outcomes. Cancer and sepsis have surprisingly similar immunologic responses and equally dismal long term consequences. In cancer, increased myeloid-derived suppressor cells (MDSCs) induce detrimental immunosuppression, but little is known about the role of MDSCs after sepsis. Blood was obtained from 74 patients within 12 hours of severe sepsis/septic shock (SS/SS), and at set intervals out to 28 days, and also in 18 healthy controls. MDSCs were phenotyped for cell surface receptor expression and enriched by cell sorting. Functional and genome-wide expression analyses were performed. Multiple logistic regression analysis was conducted to determine if increased MDSC appearance was associated with in-hospital and long-term outcomes. After SS/SS, CD33CD11bHLA-DR MDSCs were dramatically increased out to 28 days (P < 0.05). When co-cultured with MDSCs from SS/SS patients, antigen-driven T-cell proliferation and TH1/TH2 cytokine production were suppressed (P < 0.05). Additionally, septic MDSCs had suppressed HLA gene expression and up-regulated ARG1 expression (P < 0.05). Finally, SS/SS patients with persistent increased percentages of blood MDSCs had increased nosocomial infections, prolonged intensive care unit stays, and poor functional status at discharge (P < 0.05). After SS/SS in humans, circulating MDSCs are persistently increased, functionally immunosuppressive, and associated with adverse outcomes. This novel observation warrants further studies. As observed in cancer immunotherapy, MDSCs could be a novel component in multimodality immunotherapy targeting detrimental inflammation and immunosuppression after SS/SS to improve currently observed dismal long-term outcomes.

  13. Edaravone, a hydroxyl radical scavenger, ameliorates the severity of pulmonary hypertension in a porcine model of neonatal sepsis.

    Science.gov (United States)

    Yamaguchi, Sachiko; Hussein, Mohamed Hamed; Daoud, Ghada AbdEl-Hamid; Goto, Tatenobu; Kato, Shin; Kakita, Hiroki; Mizuno, Haruo; Ito, Tetsuya; Fukuda, Sumio; Kato, Ineko; Suzuki, Satoshi; Hashimoto, Takashi; Togari, Hajime

    2011-01-01

    Systemic infection in the newborn (neonatal sepsis) is the most common cause of neonatal mortality. Neonatal sepsis is complicated by pulmonary hypertension. In this study, we analyzed the effect of edaravone, a free radical scavenger that is known to reduce the production of inflammatory mediators, such as tumor necrosis factor α (TNFα), on pulmonary hypertension. Experimental and sham groups were drawn from 19 three-day-old piglets; 5 underwent a modified procedure of cecal ligation and perforation (CLP) (CLP group), 8 underwent CLP followed 30 min later by edaravone intravenous administration (edaravone group), and 6 did not undergo CLP and did not receive edaravone (sham group). To evaluate the pulmonary blood pressure despite the sepsis-induced low cardiac output, mean arterial blood pressure (mABP), mean pulmonary arterial pressure (mPAP), and comparative pulmonary hypertension ratio (mPAP/mABP) were determined. Serum TNFα levels were measured before the procedure and at 1, 3, and 6 h after. The mPAP levels were higher in the CLP group at 9 h compared to the edaravone group. The mPAP/mABP ratio was lower in the edaravone and sham groups compared to the CLP group at 6 and 9 h. TNFα in the edaravone and sham groups were lower at 1 and 3 h compared to that in the CLP group. In all animals, mPAP/mABP at 6 h correlated with serum levels of TNFα at 1, 3, and 6 h. These findings suggest that edaravone ameliorates the severity of pulmonary hypertension in a neonatal sepsis model by reducing serum TNFα levels.

  14. Soluble RAGE as a severity marker in community acquired pneumonia associated sepsis

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    Narvaez-Rivera Rodrigo M

    2012-01-01

    Full Text Available Abstract Background Community-acquired pneumonia (CAP is considered the most important cause of death from infectious disease in developed countries. Severity assessment scores partially address the difficulties in identifying high-risk patients. A lack of specific and valid pathophysiologic severity markers affect early and effective sepsis therapy. HMGB-1, sRAGE and RAGE have been involved in sepsis and their potential as severity markers has been proposed. The aim of this study was to evaluate HMGB-1, RAGE and sRAGE levels in patients with CAP-associated sepsis and determine their possible association with clinical outcome. Method We evaluated 33 patients with CAP-associated sepsis admitted to the emergency room and followed in the medical wards. Severity assessment scores (CURB-65, PSI, APACHE II, SOFA and serologic markers (HMGB-1, RAGE, sRAGE were evaluated on admission. Results Thirty patients with a diagnosis of CAP-associated sepsis were enrolled in the study within 24 hours after admission. Fourteen (46.6% had pandemic (H1N1 influenza A virus, 2 (6.6% had seasonal influenza A and 14 other diagnoses. Of the patients in the study group, 16 (53.3% had a fatal outcome. ARDS was observed in 17 (56.6% and a total of 22 patients had severe sepsis on admission (73%. The SOFA score showed the greatest difference between surviving and non-surviving groups (P = .003 with similar results in ARDS patients (P = .005. sRAGE levels tended to be higher in non-surviving (P = .058 and ARDS patients (P = .058. Logistic regression modeling demonstrated that SOFA (P = .013 and sRAGE (P = .05 were the only variables that modified the probability of a fatal outcome. Conclusion The association of elevated sRAGE with a fatal outcome suggests that it may have an independent causal effect in CAP. SOFA scores were the only clinical factor with the ability to identify surviving and ARDS patients.

  15. Use of a semiquantitative procalcitonin kit for evaluating severity and predicting mortality in patients with sepsis

    Directory of Open Access Journals (Sweden)

    Kenzaka T

    2012-05-01

    Full Text Available Tsuneaki Kenzaka,1 Masanobu Okayama,2 Shigehiro Kuroki,1 Miho Fukui,3 Shinsuke Yahata,3 Hiroki Hayashi,3 Akihito Kitao,3 Eiji Kajii,2 Masayoshi Hashimoto41Division of General Medicine, 2Division of Community and Family Medicine, Center for Community Medicine, Jichi Medical University School of Medicine, Shimotsuke; 3Department of General Medicine, Toyooka Public Hospital, Toyooka; 4Department of Family and Community Medicine, Kobe University Graduate School of Medicine, Kobe, JapanBackground: The aim of this study was to evaluate the clinical usefulness of a semiquantitative procalcitonin kit for assessing severity of sepsis and early determination of mortality in affected patients.Methods: This was a prospective, observational study including 206 septic patients enrolled between June 2008 and August 2009. Disseminated intravascular coagulation (DIC, Sequential Organ Failure Assessment (SOFA, Acute Physiology and Chronic Health Evaluation (APACHE II scores were measured, along with semiquantitative procalcitonin concentrations. Patients were divided into three groups based on their semiquantitative procalcitonin concentrations (group A, <2 ng/mL; group B ≥ 2 ng/mL < 10 ng/mL; group C ≥ 10 ng/mL.Results: A significant difference in DIC, SOFA, and APACHE II scores was found between group A and group C and between group B and group C (P < 0.01. Patients with severe sepsis and septic shock had significantly higher procalcitonin concentrations than did patients with less severe disease. The rate of patients with septic shock with high procalcitonin concentrations showed an upward trend. There was a significant (P < 0.01 difference between the three groups with regard to numbers of patients and rates of severe sepsis, septic shock, DIC, and mortality.Conclusion: Semiquantitative procalcitonin concentration testing can be helpful for early assessment of disease severity in patients with sepsis. Furthermore, it may also help in predicting early

  16. Pentraxin 3 in patients with severe sepsis or shock: the ALBIOS trial.

    Science.gov (United States)

    Caironi, Pietro; Masson, Serge; Mauri, Tommaso; Bottazzi, Barbara; Leone, Roberto; Magnoli, Michela; Barlera, Simona; Mamprin, Filippo; Fedele, Andrea; Mantovani, Alberto; Tognoni, Gianni; Pesenti, Antonio; Gattinoni, Luciano; Latini, Roberto

    2017-01-01

    The long pentraxin PTX3 is a key component of the humoral arm of innate immunity related to sepsis severity and mortality. We evaluated the clinical and prognostic significance of circulating PTX3 in the largest cohort ever reported of patients with severe sepsis or septic shock. Plasma PTX3 was measured on days 1, 2 and 7 after randomization of 958 patients to albumin or crystalloids for fluid resuscitation in the multicentre Albumin Italian Outcome Sepsis (ALBIOS) trial. We tested the association of PTX3 and its changes over time with clinical severity, prevalent and incident organ dysfunctions, 90-day mortality and treatment. PTX3 was high at baseline (72 [33-186] ng/mL) and rose with the severity and number of organ dysfunctions (P < 0·001) and the incidence of subsequent new failures. The PTX3 concentration dropped from day 1 to 7, but this decrease was less pronounced in patients with septic shock (P = 0·0004). Higher concentrations of PTX3 on day 1 predicted incident organ dysfunctions. Albumin supplementation was associated with lower levels of PTX3 in patients with septic shock (P = 0·005) but not in those without shock. In a fully adjusted multivariable model, PTX3 on day 7 predicted 90-day mortality. Smaller drops in PTX3 predicted higher 90-day mortality. In severe sepsis and septic shock, early high PTX3 predict subsequent new organ failures, while a smaller drop in circulating PTX3 over time predicts an increased risk of death. Patients with septic shock show lower levels of PTX3 when assigned to albumin than to crystalloids. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

  17. The role of the open abdomen procedure in managing severe abdominal sepsis: WSES position paper.

    Science.gov (United States)

    Sartelli, Massimo; Abu-Zidan, Fikri M; Ansaloni, Luca; Bala, Miklosh; Beltrán, Marcelo A; Biffl, Walter L; Catena, Fausto; Chiara, Osvaldo; Coccolini, Federico; Coimbra, Raul; Demetrashvili, Zaza; Demetriades, Demetrios; Diaz, Jose J; Di Saverio, Salomone; Fraga, Gustavo P; Ghnnam, Wagih; Griffiths, Ewen A; Gupta, Sanjay; Hecker, Andreas; Karamarkovic, Aleksandar; Kong, Victor Y; Kafka-Ritsch, Reinhold; Kluger, Yoram; Latifi, Rifat; Leppaniemi, Ari; Lee, Jae Gil; McFarlane, Michael; Marwah, Sanjay; Moore, Frederick A; Ordonez, Carlos A; Pereira, Gerson Alves; Plaudis, Haralds; Shelat, Vishal G; Ulrych, Jan; Zachariah, Sanoop K; Zielinski, Martin D; Garcia, Maria Paula; Moore, Ernest E

    2015-01-01

    The open abdomen (OA) procedure is a significant surgical advance, as part of damage control techniques in severe abdominal trauma. Its application can be adapted to the advantage of patients with severe abdominal sepsis, however its precise role in these patients is still not clear. In severe abdominal sepsis the OA may allow early identification and draining of any residual infection, control any persistent source of infection, and remove more effectively infected or cytokine-loaded peritoneal fluid, preventing abdominal compartment syndrome and deferring definitive intervention and anastomosis until the patient is appropriately resuscitated and hemodynamically stable and thus better able to heal. However, the OA may require multiple returns to the operating room and may be associated with significant complications, including enteroatmospheric fistulas, loss of abdominal wall domain and large hernias. Surgeons should be aware of the pathophysiology of severe intra-abdominal sepsis and always keep in mind the option of using open abdomen to be able to use it in the right patient at the right time.

  18. Rapid hemodilution is associated with increased sepsis and mortality among patients with severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    MAO En-qiang; FEI Jian; PENG Yi-bing; HUANG Jie; TANG Yao-qing; ZHANG Sheng-dao

    2010-01-01

    Background Hemoconcentration may be an important factor that determines the progression of severe acute pancreatitis (SAP). In addition, it has been proposed that biomarkers may be useful in predicting subsequent necrosis in SAP. However, it is still uncertain whether hemodilution in a short term can improve outcome. We aimed to investigate the effect of rapid hemodilution on the outcome of patients with SAP.Methods One hundred and fifteen patients were admitted prospectively according to the criteria within 24 hours of SAP onset. Patients were randomly assigned to either rapid hemodilution (hematocrit (HCT) <35%, n=56) or slow hemodilution (HCT 235%, n=59) within 48 hours of onset. Balthazar CT scores were calculated on admission, day 7, and day 14, after onset of the disease. Time interval for sepsis presented, incidence of sepsis within 28 days and in-hospital survival rate were determined.Results The amount of fluid used in rapid hemodilution was significantly more than that used in slow hemodilution (P <0.05) on the admission day, the first day, and the second day. There were significant differences between the rapid and slow hemodilution group in terms of hematocrit, oxygenation index, pH values, APACHE II scores and organ dysfunction at different time during the first week. There were significant differences in the time interval to sepsis in rapid hemodilution ((7.4 1.9) days) compared with the slow hemodilution group ((10.2 2.3) days), and the incidence of sepsis (78.6%) was higher in the rapid group compared to the slow (57.6%) in the first 28 days. The survival rate of the slow hemodilution group (84.7%) was better than the rapid hemodilution (66.1%. P<0.05).Conclusions Rapid hemodilution can increase the incidence of sepsis within 28 days and in-hospital mortality. Hematocrit should be maintained between 30%-40% in the acute response stage.

  19. Effect of plasmapheresis on the immune system in endotoxin-induced sepsis

    DEFF Research Database (Denmark)

    Toft, P; Schmidt, R; Broechner, A C

    2008-01-01

    BACKGROUND: It has been proposed that plasmapheresis is most effective when applied early in Gram-negative sepsis. We therefore studied the effect of early plasmapheresis on immunity in experimental Escherichia coli endotoxin-induced sepsis. METHODS: 20 pigs received 30 microg/kg of E. coli...

  20. The redistribution of granulocytes following E. coli endotoxin induced sepsis

    DEFF Research Database (Denmark)

    Toft, P; Lillevang, S T; Tønnesen, Else Kirstine

    1994-01-01

    Infusion of endotoxin elicits granulocytopenia followed by increased numbers of granulocytes in peripheral blood. The purpose of this study was to investigate the redistribution and sequestration of granulocytes in the tissues following E. coli endotoxin induced sepsis. From 16 rabbits granulocytes...... were isolated, labelled with Indium and reinjected intravenously. Eight rabbits received an infusion of E. coli endotoxin 2 micrograms kg-1 while eight received isotonic saline. The redistribution of granulocytes was imaged with a gamma camera and calculated with a connected computer before and 2 and 6...... hours after infusion of endotoxin or saline. Serum cortisol and interleukin-1 beta were measured. In another seven rabbits, respiratory burst activity and degranulation of granulocytes were measured prior to and from 5 min to 6 hours after infusion of E. coli endotoxin 2 micrograms kg-1 BW. Following...

  1. The redistribution of granulocytes following E. coli endotoxin induced sepsis

    DEFF Research Database (Denmark)

    Toft, P; Lillevang, S T; Tønnesen, Else Kirstine

    1994-01-01

    Infusion of endotoxin elicits granulocytopenia followed by increased numbers of granulocytes in peripheral blood. The purpose of this study was to investigate the redistribution and sequestration of granulocytes in the tissues following E. coli endotoxin induced sepsis. From 16 rabbits granulocytes...... were isolated, labelled with Indium and reinjected intravenously. Eight rabbits received an infusion of E. coli endotoxin 2 micrograms kg-1 while eight received isotonic saline. The redistribution of granulocytes was imaged with a gamma camera and calculated with a connected computer before and 2 and 6...... hours after infusion of endotoxin or saline. Serum cortisol and interleukin-1 beta were measured. In another seven rabbits, respiratory burst activity and degranulation of granulocytes were measured prior to and from 5 min to 6 hours after infusion of E. coli endotoxin 2 micrograms kg-1 BW. Following...

  2. The scoring system for patients with severe sepsis after orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Shun-Wei Huang; Xiang-Dong Guan; Xiao-Shun He; Juan Chen; Bin Ouyang

    2006-01-01

    BACKGROUND:Because of the complicated pathological features after liver transplantation, severe sepsis is dififcult to treat and often leads to death. This study was undertaken to analyze the role of orthotopic liver transplantation (OLT) in patients with severe sepsis and to evaluate the effect of the scoring system. METHODS:Fifty-six patients conformed to the inclusion criteria. They were divided into two groups: non-OLT group (group A) and OLT group (group B). Besides the general data of the patients, the surveillance of blood lactate, the number of failed organs, acute physiology and chronic health evaluationⅡ(APACHEⅡ) and mutiple organ dysfunction score (MODS) were evaluated at the 1st, 3rd and 7th day after OLT. RESULTS:The mortality during hospitalization was 30%in the non-OLT group and 57.6%in the other group. The level of blood lactate at the 1st day of OLT increased more signiifcantly in the OLT group than in the non-OLT group (P CONCLUSIONS: The persistently higher level of blood lactate during 7 days may be a dependent risk factor. Immunosuppression may be another risk factor for OLT patients. The mortality of OLT in patients with severe sepsis in 28 days is almost double that in non-OLT patients. The MODS score is better than the APACHEⅡscore in the assessment of organ failure in OLT patients with severe sepsis. The standard scoring system could be improved or a new scoring system that includes the blood lactate score should be established for liver transplantation.

  3. Procalcitonin kinetics as a prognostic marker in severe sepsis/septic shock

    Directory of Open Access Journals (Sweden)

    Banani Poddar

    2015-01-01

    Full Text Available Background and Aims: To evaluate the prognostic value of change (fall in serum procalcitonin level (PCT in critically ill adults with severe sepsis/septic shock. Methods: This was a prospective observational study in a general purpose Intensive Care Unit of a teaching Institute. PCT was measured at admission (D0 and after 72-96 h (D4 by electrochemi-luminescence immunoassay (BRAHMS PCT kit in adults (>18 years admitted with severe sepsis or septic shock. Change in procalcitonin values from D0 to D4 was correlated with the primary outcome, that is, 28 days mortality. All results are reported as median (interquartile range. Results: A total of 171 (100 males of 181 patients were included. The median age was 46 years (range 19-79. 137 patients were in septic shock and 34 in severe sepsis. The sequential organ failure assessment (SOFA score in all patients was 11 (9-14.91 (53.2% patients survived at 28 days (survivors. The baseline procalcitonin was similar in two groups (3.48 [1.04-15.85] vs. 5.27 [1.81-23.57] ng/ml in survivors and nonsurvivors [NS] respectively. The procalcitonin change was 1.58 (0.20-8.52 in survivors and 0.28 (-1.38-6.17 in NS (P = 0.01. The C-statistic of percentage change in procalcitonin from D0 to D4 to predict survival was 0.73 (95% confidence interval [CI]: 0.65-0.82 when compared to 0.78 (95% CI: 0.71-0.86 for change of SOFA score. For an absolute fall in procalcitonin of >1 ng/ml, a 70% fall predicted survival with 75% sensitivity and 64% specificity. Conclusions: In critically ill-patients with severe sepsis/septic shock, change (fall in procalcitonin is associated with good outcome.

  4. IκB Kinase Inhibitor Attenuates Sepsis-Induced Cardiac Dysfunction in CKD.

    Science.gov (United States)

    Chen, Jianmin; Kieswich, Julius E; Chiazza, Fausto; Moyes, Amie J; Gobbetti, Thomas; Purvis, Gareth S D; Salvatori, Daniela C F; Patel, Nimesh S A; Perretti, Mauro; Hobbs, Adrian J; Collino, Massimo; Yaqoob, Muhammad M; Thiemermann, Christoph

    2017-01-01

    Patients with CKD requiring dialysis have a higher risk of sepsis and a 100-fold higher mortality rate than the general population with sepsis. The severity of cardiac dysfunction predicts mortality in patients with sepsis. Here, we investigated the effect of preexisting CKD on cardiac function in mice with sepsis and whether inhibition of IκB kinase (IKK) reduces the cardiac dysfunction in CKD sepsis. Male C57BL/6 mice underwent 5/6 nephrectomy, and 8 weeks later, they were subjected to LPS (2 mg/kg) or sepsis by cecal ligation and puncture (CLP). Compared with sham operation, nephrectomy resulted in significant increases in urea and creatinine levels, a small (Psepsis or endotoxemia in mice; this effect may be caused by increased cardiac NF-κB activation and iNOS expression. Copyright © 2016 by the American Society of Nephrology.

  5. Hospital staff education on severe sepsis/septic shock and hospital mortality: an original hypothesis

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    Capuzzo Maurizia

    2012-11-01

    Full Text Available Abstract Background Signs of serious clinical events overlap with those of sepsis. We hypothesised that any education on severe sepsis/septic shock may affect the outcome of all hospital patients. We designed this study to assess the trend of the mortality rate of adults admitted to hospital for at least one night in relationship with a hospital staff educational program dedicated to severe sepsis/septic shock. Methods This study was performed in six Italian hospitals in the same region. Multidisciplinary Sepsis Teams members were selected by each hospital management among senior staff. The education included the following steps: i the Teams were taught about adult learning, problem based learning, and Surviving Sepsis guidelines, and provided with educational material (literature, electronic presentations, scenarios of clinical cases for training and booklets; ii they started delivering courses and seminars each to their own hospital staff in the last quarter of 2007. To analyse mortality, we selected adult patients, admitted for at least one night to the wards or units present in all the study hospitals and responsible for 80% of hospital deaths. We fitted a Poisson model with monthly hospital mortality rates from December 2003 to August 2009 as dependent variable. The effect of the educational program on hospital mortality was measured as two dummy variables identifying a first (November 2007 to December 2008 and a second (January to August 2009 education period. The analysis was adjusted for a linear time trend, seasonality and monthly average values of age, Charlson score, length of stay in hospital and urgent/non-urgent admission. Results The hospital staff educated reached 30.6% at the end of June 2009. In comparison with the pre-education period, the Relative Risk of death of the patient population considered was 0.93 (95% confidence interval [CI] 0.87-0.99; p 0.025 for in-patients in the first, and 0.89 (95% CI 0.81-0.98; p 0.012 for

  6. Lipid Isolated from a Leishmania donovani Strain Reduces Escherichia coli Induced Sepsis in Mice through Inhibition of Inflammatory Responses

    Directory of Open Access Journals (Sweden)

    Subhadip Das

    2014-01-01

    Full Text Available Sepsis is the reflection of systemic immune response that manifests in the sequential inflammatory process in presence of infection. This may occur as a result of gram-negative bacterial sepsis including Escherichia coli infection that gives rise to excessive production of inflammatory mediators and causes severe tissue injuries. We have reported earlier that the lipid of attenuated Leishmania donovani suppresses the inflammatory responses in arthritis patients. Using heat killed E. coli stimulated macrophages, we have now investigated the effect of leishmanial total lipid (LTL isolated from Leishmania donovani (MHO/IN/1978/UR6 for amelioration of the inflammatory mediators and transcriptional factor with suppression of TLR4-CD14 expression. To evaluate the in vivo effect, E. coli induced murine sepsis model was used focusing on the changes in different parameter(s of lung injury caused by sepsis, namely, edema, vascular permeability, and pathophysiology, and the status of different cytokine-chemokine(s and adhesion molecule(s. Due to the effect of LTL, E. coli induced inflammatory cytokine-chemokine(s levels were significantly reduced in serum and bronchoalveolar lavage fluid simultaneously. LTL also improved the lung injury and suppressed the cell adhesion molecules in lung tissue. These findings indicate that LTL may prove to be a potential anti-inflammatory agent and provide protection against gram-negative bacterial sepsis with pulmonary impairment.

  7. Interleukin-1 receptor antagonist gene polymorphism and mortality in patients with severe sepsis

    Science.gov (United States)

    ARNALICH, F; LÓPEZ-MADERUELO, D; CODOCEO, R; LOPEZ, J; SOLIS-GARRIDO, L M; CAPISCOL, C; FERNANDEZ-CAPITÁN, C; MADERO, R; MONTIEL, C

    2002-01-01

    This study aims to determine the influence of the polymorphism within the intron 2 of the interleukin-1 receptor antagonist gene (IL-1RN*) on the outcome of severe sepsis, and to assess its functional significance by correlating this polymorphism with the total production of interleukin-1 receptor antagonist (IL-1Ra) protein determined in stimulated peripheral blood mononuclear cells (PBMC). A group of 78 patients with severe sepsis (51 survivors and 27 nonsurvivors) was compared with a healthy control group of 130 blood donors, and 56 patients with uncomplicated pneumonia. We found a significant association between IL-1RN* polymorphism and survival. Thus, after adjusting for age and APACHE II score, multiple logistic regression analysis showed that patients homozygotes for the allele *2 had a 6·47-fold increased risk of death (95% CI 1·01–41·47, P = 0·04). Besides, compared with patients homozygous or heterozygous for the allele *1, IL-1RN*2 homozygotes produced significantly lower levels of IL-1Ra from their PBMC. Our results suggest that insufficient production of this cytokine might contribute, among other factors, to the higher mortality rate found in severe sepsis patients with the IL-1RN*2 homozygous genotype. PMID:11876758

  8. Early bacterial genome detection in body fluids from patients with severe sepsis: a pilot study.

    Science.gov (United States)

    Dugard, Anthony; Chainier, Delphine; Barraud, Olivier; Garnier, Fabien; Ploy, Marie-Cécile; Vignon, Philippe; François, Bruno

    2012-08-01

    The purpose of this study is to evaluate the feasibility and interest of real-time polymerase chain reaction (RT-PCR) testing for bacterial genomes in body fluids other than blood in patients with acute severe sepsis. Twenty-six consecutive patients admitted for severe sepsis or septic shock were prospectively studied. Body fluids were sampled as clinically indicated and tested using standard microbiological methods and modified RT-PCR methods (universal PCR and specific PCRs). Results of standard microbiological tests were compared with those of PCR tests. Direct RT-PCR testing was successfully performed on all nonblood body fluids. Of 29 body fluids collected, 23 were positive for at least 1 microorganism with conventional tests. Of 18 microbiological tests positive for a single microorganism, 15 fully agreed with RT-PCR assays, and the remaining 3 samples were infected with bacteria not screened by PCR testing. Among the 5 polymicrobial results obtained with conventional tests, RT-PCR agreed in 4 patients. The RT-PCR tests allowed additional clinically relevant bacterial identification in 3 of 6 samples with negative microbiological culture. Our results indicate that direct PCR testing may improve the detection of bacteria in body fluids other than blood in patients with acute severe sepsis. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Stress disorders following prolonged critical illness in survivors of severe sepsis.

    Science.gov (United States)

    Wintermann, Gloria-Beatrice; Brunkhorst, Frank Martin; Petrowski, Katja; Strauss, Bernhard; Oehmichen, Frank; Pohl, Marcus; Rosendahl, Jenny

    2015-06-01

    To examine the frequency of acute stress disorder and posttraumatic stress disorder in chronically critically ill patients with a specific focus on severe sepsis, to classify different courses of stress disorders from 4 weeks to 6 months after transfer from acute care hospital to postacute rehabilitation, and to identify patients at risk by examining the relationship between clinical, demographic, and psychological variables and stress disorder symptoms. Prospective longitudinal cohort study, three assessment times within 4 weeks, 3 months, and 6 months after transfer to postacute rehabilitation. Patients were consecutively enrolled in a large rehabilitation hospital (Clinic Bavaria, Kreischa, Germany) admitted for ventilator weaning from acute care hospitals. We included 90 patients with admission diagnosis critical illness polyneuropathy or critical illness myopathy with or without severe sepsis, age between 18 and 70 years with a length of ICU stay greater than 5 days. None. Acute stress disorder and posttraumatic stress disorder were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, criteria by a trained and experienced clinical psychologist using a semistructured clinical interview for Diagnostic and Statistical Manual of Mental Disorders. We further administered the Acute Stress Disorder Scale and the Posttraumatic Symptom Scale-10 to assess symptoms of acute stress disorder and posttraumatic stress disorder. Three percent of the patients had an acute stress disorder diagnosis 4 weeks after transfer to postacute rehabilitation. Posttraumatic stress disorder was found in 7% of the patients at 3-month follow-up and in 12% after 6 months, respectively. Eighteen percent of the patients showed a delayed onset of posttraumatic stress disorder. Sepsis turned out to be a significant predictor of posttraumatic stress disorder symptoms at 3-month follow-up. A regular screening of post-ICU patients after discharge from

  10. Cytokine profile in severe Gram-positive and Gram-negative abdominal sepsis.

    Science.gov (United States)

    Surbatovic, Maja; Popovic, Nada; Vojvodic, Danilo; Milosevic, Ivan; Acimovic, Gordana; Stojicic, Milan; Veljovic, Milic; Jevdjic, Jasna; Djordjevic, Dragan; Radakovic, Sonja

    2015-06-16

    Sepsis is a principal cause of death in critical care units worldwide and consumes considerable healthcare resources. The aim of our study was to determine whether the early cytokine profile can discriminate between Gram-positive and Gram-negative bacteraemia (GPB and GNB, respectively) and to assess the prognostic value regarding outcome in critically ill patients with severe abdominal sepsis. The outcome measure was hospital mortality. Blood samples were obtained from 165 adult patients with confirmed severe abdominal sepsis. Levels of the proinflammatory mediators TNF-α, IL-8, IL-12 and IFN-γ and the anti-inflammatory mediators IL-1ra, IL-4, IL-10 and TGF-β1 were determined and correlated with the nature of the bacteria isolated from the blood culture and outcome. The cytokine profile in our study indicated that the TNF-α levels were 2-fold, IL-8 were 3.3-fold, IFN-γ were 13-fold, IL-1ra were 1.05-fold, IL-4 were 1.4-fold and IL-10 were 1.83-fold higher in the GNB group compared with the GPB group. The TNF-α levels were 4.7-fold, IL-8 were 4.6-fold, IL-1ra were 1.5-fold and IL-10 were 3.3-fold higher in the non-survivors compared with the survivors.

  11. Effects of peroxisome proliferator-activated receptor-β/δ on sepsis induced acute lung injury

    Institute of Scientific and Technical Information of China (English)

    Wang Cairui; Zhou Guopeng; Zeng Zeng

    2014-01-01

    Background Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the first steps in the development of multiple organ failure induced by sepsis.A systemic excessive inflammatory reaction is currently the accepted mechanism of the pathogenesis of sepsis.Several studies have suggested a protective role of the peroxisome proliferator activated receptor-β/δ (PPAR-β/δ) in related inflammatory diseases.But the role of PPARβ/δ in ALI remains uncertain.The aim of this study was to investigate the role and possible mechanism of PPARβ/δ in ALI induced by sepsis.Methods Cecal ligation and puncture (CLP) was used as a sepsis model.Rats were randomly divided into four groups,the control group (CON,n=6),sham-operation group (SHAM,n=12),cecal ligation and puncture group (CLP,n=30),GW501516 group (CLP+GW,n=25),which underwent CLP and were subcutaneously injected with the PPAR-β/δ agonist GW501516 (0.05 mg/100 g body weight).Survival was monitored to 24 hours after operation.Blood pressure,serum creatinine,blood urea nitrogen,aspartate aminotrasferase and alanine aminotrasferase were measured after CLP.Concentrations of tumor necrosis factor α (TNF-α) and interleukin (IL)-1β in serum were detected by enzyme linked immunosorbent assay (ELISA) kits.Lung tissue samples were stained with H&E and scored according to the degree of inflammation.Bacterial colonies were counted in the peritoneal fluid.Alveolar macrophages were cultured and incubated with GW501516 (0.15 μmol/L) and PPARβ/δ adenovirus and then treated with Lipopolysaccharide (2 μg/ml) for 2 hours.The TNF-α,IL-1β and IL-6 RNA in lung and alveolar macrophages were determined by real-time PCR.Phosphorylation of signal transducer and activator of transcription 3 (STAT3) in lung and alveolar macrophages was detected by Western blotting.Results GW501516 significantly increased the survival of septic rats,decreased histological damage of the lungs,reduced inflammatory cytokines in serum and

  12. Blood glucose control in patients with severe sepsis and septic shock

    Institute of Scientific and Technical Information of China (English)

    Hiroyuki Hirasawa; Shigeto Oda; Masataka Nakamura

    2009-01-01

    The main pathophysiological feature of sepsis is the uncontrollable activation of both pro- and anti-inflammatory responses arising from the overwhelming production of mediators such as pro- and anti-inflammatory cytokines. Such an uncontrollable inflammatory response would cause many kinds of metabolic derangements.One such metabolic derangement is hyperglycemia.Accordingly, control of hyperglycemia in sepsis is considered to be a very effective therapeutic approach. However, despite the initial enthusiasm, recent studies reported that tight glycemic control with intensive insulin therapy failed to show a beneficial effect on mortality of patients with severe sepsis and septic shock. One of the main reasons for this disappointing result is the incidence of harmful hypoglycemia during intensive insulin therapy. Therefore, avoidance of hypoglycemia during intensive insulin therapy may be a key issue in effective tight glycemic control.It is generally accepted that glycemic control aimed at a blood glucose level of 80-100 mg/dL, as initially proposed by van den Berghe, seems to be too tight and that such a level of tight glycemic control puts septic patients at increased risk of hypoglycemia. Therefore,now many researchers suggest less strict glycemic control with a target blood glucose level of 140-180 mg/dL.Also specific targeting of glycemic control in diabetic patients should be considered. Since there is a significant correlation between success rate of glycemic control and the degree of hypercytokinemia in septic patients,some countermeasures to hypercytokinemia may be an important aspect of successful glycemic control. Thus,in future, use of an artificial pancreas to avoid hypoglycemia during insulin therapy, special consideration of septic diabetic patients, and control of hypercytokinemia should be considered for more effective glycemic control in patients with severe sepsis and septic shock.

  13. Predictive Value of IL-8 for Sepsis and Severe Infections After Burn Injury: A Clinical Study.

    Science.gov (United States)

    Kraft, Robert; Herndon, David N; Finnerty, Celeste C; Cox, Robert A; Song, Juquan; Jeschke, Marc G

    2015-03-01

    The inflammatory response induced by burn injury contributes to increased incidence of infections, sepsis, organ failure, and mortality. Thus, monitoring postburn inflammation is of paramount importance but, so far, there are no reliable biomarkers available to monitor and/or predict infectious complications after burn. As interleukin 8 (IL-8) is a major mediator for inflammatory responses, the aim of our study was to determine whether IL-8 expression can be used to predict postburn sepsis, infections, and mortality. Plasma cytokines, acute-phase proteins, constitutive proteins, and hormones were analyzed during the first 60 days after injury from 468 pediatric burn patients. Demographics and clinical outcome variables (length of stay, infection, sepsis, multiorgan failure [MOF], and mortality) were recorded. A cutoff level for IL-8 was determined using receiver operating characteristic analysis. Statistical significance is set at P Patients were grouped according to their average IL-8 levels relative to this cutoff and stratified into high (H) (n = 133) and low (L) (n = 335) groups. In the L group, regression analysis revealed a significant predictive value of IL-8 to percent of total body surface area burned and incidence of MOF (P inflammatory and acute-phase responses compared with the L group (P burn patients.

  14. Matrix-metalloproteinase-2, -8 and -9 in serum and skin blister fluid in patients with severe sepsis.

    Science.gov (United States)

    Gäddnäs, Fiia P; Sutinen, Meeri M; Koskela, Marjo; Tervahartiala, Taina; Sorsa, Timo; Salo, Tuula A; Laurila, Jouko J; Koivukangas, Vesa; Ala-Kokko, Tero I; Oikarinen, Aarne

    2010-01-01

    Matrix metalloproteinases (MMPs) have various roles in inflammatory states. They seem to be able to modulate endothelial barriers and regulate the activity of chemokines and cytokines. The timely development of the levels during severe sepsis and thereafter have not been investigated. In addition it was of interest to study alterations of MMP-levels in intact skin, as the skin is the largest barrier against external pathogens and MMPs have not been studied at organ level in human sepsis. The aim of this study was to investigate the timely development of serum and skin MMP-2, -8 and -9 levels in human severe sepsis and their association with disease severity and mortality. Forty-four patients with severe sepsis and fifteen healthy controls were included in this prospective longitudinal study. The amounts of MMP-2, -8 and -9 were analyzed from serum at days 1, 4, 6, 8, and 10, and from skin suction blister fluid at days 1 and 5 from the beginning of severe sepsis. Additionally, samples from the survivors were obtained after three and six months. The levels of MMP-2 and -8 were up-regulated in severe sepsis in comparison to healthy controls in skin blister fluid and serum. Compared to the controls MMP-9 levels were lower in sepsis from the fourth day on in serum and both the first and fifth day in skin blister fluid. Active forms of MMP-2 and -9 were present only in severe sepsis. The non-survivors had higher pro- and active MMP-2 levels than the survivors in skin blister fluid samples. Furthermore, MMP-2 levels were more pronounced in blister fluid and serum samples in patients with more severe organ failures. In the survivors at 3 and 6 month follow-up the MMP levels had returned to normal. MMP-2 and -8 are elevated in serum and blister fluid in severe sepsis, implying that they may play a significant role in the pathogenesis of severe sepsis and organ dysfunctions. Active forms of MMP-2 and 9 were only present in patients with severe sepsis, and higher MMP-2 levels

  15. Guidance on patient Identification and Administration of Recombinant Human Activated protein C for the Treatment of Severe Sepsis

    Directory of Open Access Journals (Sweden)

    Gary Garber

    2002-01-01

    Full Text Available Approximately one-third of cases of severe sepsis result in death. Endogenous activated protein C (ApC plays a key role in the regulation of the inflammation, fibrinolysis and coagulation associated with severe sepsis. In a recently published phase III trial, protein C Worldwide Evaluation in Severe Sepsis (pROWESS, intravenous administration of recombinant human ApC (rhApC 24 µg/kg/h for 96 h to patients with severe sepsis resulted in a 6.1% reduction in absolute mortality and a 19.4% reduction in the relative risk of death from any cause within 28 days (number needed to treat = 16. This dose is now being applied in clinical practice.

  16. T helper type 2-polarized invariant natural killer T cells reduce disease severity in acute intra-abdominal sepsis.

    Science.gov (United States)

    Anantha, R V; Mazzuca, D M; Xu, S X; Porcelli, S A; Fraser, D D; Martin, C M; Welch, I; Mele, T; Haeryfar, S M M; McCormick, J K

    2014-11-01

    Sepsis is characterized by a severe systemic inflammatory response to infection that is associated with high morbidity and mortality despite optimal care. Invariant natural killer T (iNK T) cells are potent regulatory lymphocytes that can produce pro- and/or anti-inflammatory cytokines, thus shaping the course and nature of immune responses; however, little is known about their role in sepsis. We demonstrate here that patients with sepsis/severe sepsis have significantly elevated proportions of iNK T cells in their peripheral blood (as a percentage of their circulating T cells) compared to non-septic patients. We therefore investigated the role of iNK T cells in a mouse model of intra-abdominal sepsis (IAS). Our data show that iNK T cells are pathogenic in IAS, and that T helper type 2 (Th2) polarization of iNK T cells using the synthetic glycolipid OCH significantly reduces mortality from IAS. This reduction in mortality is associated with the systemic elevation of the anti-inflammatory cytokine interleukin (IL)-13 and reduction of several proinflammatory cytokines within the spleen, notably interleukin (IL)-17. Finally, we show that treatment of sepsis with OCH in mice is accompanied by significantly reduced apoptosis of splenic T and B lymphocytes and macrophages, but not natural killer cells. We propose that modulation of iNK T cell responses towards a Th2 phenotype may be an effective therapeutic strategy in early sepsis.

  17. Selective V1a agonism attenuates vascular dysfunction and fluid accumulation in ovine severe sepsis

    Science.gov (United States)

    Yamamoto, Yusuke; Sousse, Linda; Bartha, Eva; Jonkam, Collette; Hasselbach, Anthony K.; Traber, Lillian D.; Cox, Robert A.; Westphal, Martin; Enkhbaatar, Perenlei; Traber, Daniel L.

    2012-01-01

    Vasopressin analogs are used as a supplement to norepinephrine in septic shock. The isolated effects of vasopressin agonists on sepsis-induced vascular dysfunction, however, remain controversial. Because V2-receptor stimulation induces vasodilation and procoagulant effects, a higher V1a- versus V2-receptor selectivity might be advantageous. We therefore hypothesized that a sole, titrated infusion of the selective V1a-agonist Phe2-Orn8-Vasotocin (POV) is more effective than the mixed V1a-/V2-agonist AVP for the treatment of vascular and cardiopulmonary dysfunction in methicillin resistant staphylococcus aureus pneumonia-induced, ovine sepsis. After the onset of hemodynamic instability, awake, chronically instrumented, mechanically ventilated, and fluid resuscitated sheep were randomly assigned to receive continuous infusions of either POV, AVP, or saline solution (control; each n = 6). AVP and POV were titrated to maintain mean arterial pressure above baseline − 10 mmHg. When compared with that of control animals, AVP and POV reduced neutrophil migration (myeloperoxidase activity, alveolar neutrophils) and plasma levels of nitric oxide, resulting in higher mean arterial pressures and a reduced vascular leakage (net fluid balance, chest and abdominal fluid, pulmonary bloodless wet-to-dry-weight ratio, alveolar and septal edema). Notably, POV stabilized hemodynamics at lower doses than AVP. In addition, POV, but not AVP, reduced myocardial and pulmonary tissue concentrations of 3-nitrotyrosine, VEGF, and angiopoietin-2, thereby leading to an abolishment of cumulative fluid accumulation (POV, 9 ± 15 ml/kg vs. AVP, 110 ± 13 ml/kg vs. control, 213 ± 16 ml/kg; P < 0.001 each) and an attenuated cardiopulmonary dysfunction (left ventricular stroke work index, PaO2-to-FiO2 ratio) versus control animals. Highly selective V1a-agonism appears to be superior to unselective vasopressin analogs for the treatment of sepsis-induced vascular dysfunction. PMID:22961865

  18. Selective V(1a) agonism attenuates vascular dysfunction and fluid accumulation in ovine severe sepsis.

    Science.gov (United States)

    Rehberg, Sebastian; Yamamoto, Yusuke; Sousse, Linda; Bartha, Eva; Jonkam, Collette; Hasselbach, Anthony K; Traber, Lillian D; Cox, Robert A; Westphal, Martin; Enkhbaatar, Perenlei; Traber, Daniel L

    2012-11-15

    Vasopressin analogs are used as a supplement to norepinephrine in septic shock. The isolated effects of vasopressin agonists on sepsis-induced vascular dysfunction, however, remain controversial. Because V(2)-receptor stimulation induces vasodilation and procoagulant effects, a higher V(1a)- versus V(2)-receptor selectivity might be advantageous. We therefore hypothesized that a sole, titrated infusion of the selective V(1a)-agonist Phe(2)-Orn(8)-Vasotocin (POV) is more effective than the mixed V(1a)-/V(2)-agonist AVP for the treatment of vascular and cardiopulmonary dysfunction in methicillin resistant staphylococcus aureus pneumonia-induced, ovine sepsis. After the onset of hemodynamic instability, awake, chronically instrumented, mechanically ventilated, and fluid resuscitated sheep were randomly assigned to receive continuous infusions of either POV, AVP, or saline solution (control; each n = 6). AVP and POV were titrated to maintain mean arterial pressure above baseline - 10 mmHg. When compared with that of control animals, AVP and POV reduced neutrophil migration (myeloperoxidase activity, alveolar neutrophils) and plasma levels of nitric oxide, resulting in higher mean arterial pressures and a reduced vascular leakage (net fluid balance, chest and abdominal fluid, pulmonary bloodless wet-to-dry-weight ratio, alveolar and septal edema). Notably, POV stabilized hemodynamics at lower doses than AVP. In addition, POV, but not AVP, reduced myocardial and pulmonary tissue concentrations of 3-nitrotyrosine, VEGF, and angiopoietin-2, thereby leading to an abolishment of cumulative fluid accumulation (POV, 9 ± 15 ml/kg vs. AVP, 110 ± 13 ml/kg vs. control, 213 ± 16 ml/kg; P < 0.001 each) and an attenuated cardiopulmonary dysfunction (left ventricular stroke work index, PaO(2)-to-FiO(2) ratio) versus control animals. Highly selective V(1a)-agonism appears to be superior to unselective vasopressin analogs for the treatment of sepsis-induced vascular dysfunction.

  19. Successful treatment of severe sepsis and diarrhea after vagotomy utilizing fecal microbiota transplantation: a case report.

    Science.gov (United States)

    Li, Qiurong; Wang, Chenyang; Tang, Chun; He, Qin; Zhao, Xiaofan; Li, Ning; Li, Jieshou

    2015-02-09

    Dysbiosis of intestinal microbiota likely plays an important role in the development of gut-derived infections, making it a potential therapeutic target against sepsis. However, experience with fecal microbiota transplantation (FMT) in the treatment of sepsis and knowledge of the underlying mechanisms are extremely lacking. In this article, we describe a case of a patient who developed sepsis after a vagotomy and later received an infusion of donor feces microbiota, and we report our findings. A 44-year-old woman developed septic shock and severe watery diarrhea 4 days after undergoing a vagotomy. Antibiotics, probiotics and supportive treatment strategies were used for about 30 day after surgery, but the patient's fever, bacteremia and watery diarrhea persisted. Considering the possibility of intestinal dysbiosis, we evaluated the structure and composition of the patient's fecal microbiota using 16S rDNA-based molecular techniques. As expected, the gut microbiota was extensively disrupted; therefore, a donor fecal suspension was delivered into the patient by nasoduodenal tube. The patient's clinical outcomes and shifts of the gut microbiota following the treatment were also determined. Dramatically, the patient's septic symptoms and severe diarrhea were successfully controlled following FMT. Her stool output markedly declined after 7 days and normalized 16 days after FMT. A significant modification in her microbiota composition was consistently seen, characterized by a profound enrichment of the commensals in Firmicutes and depletion of opportunistic organisms in Proteobacteria. Furthermore, we identified a reconstituted bacterial community enriched in Firmicutes and depleted of Proteobacteria members that was associated with fecal output, plasma markers of inflammation and T helper cells. In this report, we describe our initial experience with FMT, in which we successfully used it in the treatment of a patient with sepsis and severe diarrhea after a vagotomy. Our

  20. Immunotherapy: A promising approach to reverse sepsis-induced immunosuppression.

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    Patil, Naeem K; Bohannon, Julia K; Sherwood, Edward R

    2016-09-01

    Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host responses to infection (Third International Consensus definition for Sepsis and septic shock). Despite decades of research, sepsis remains the leading cause of death in intensive care units. More than 40 clinical trials, most of which have targeted the sepsis-associated pro-inflammatory response, have failed. Thus, antibiotics and fluid resuscitation remain the mainstays of supportive care and there is intense need to discover and develop novel, targeted therapies to treat sepsis. Both pre-clinical and clinical studies over the past decade demonstrate unequivocally that sepsis not only causes hyper-inflammation, but also leads to simultaneous adaptive immune system dysfunction and impaired antimicrobial immunity. Evidences for immunosuppression include immune cell depletion (T cells most affected), compromised T cell effector functions, T cell exhaustion, impaired antigen presentation, increased susceptibility to opportunistic nosocomial infections, dysregulated cytokine secretion, and reactivation of latent viruses. Therefore, targeting immunosuppression provides a logical approach to treat protracted sepsis. Numerous pre-clinical studies using immunomodulatory agents such as interleukin-7, anti-programmed cell death 1 antibody (anti-PD-1), anti-programmed cell death 1 ligand antibody (anti-PD-L1), and others have demonstrated reversal of T cell dysfunction and improved survival. Therefore, identifying immunosuppressed patients with the help of specific biomarkers and administering specific immunomodulators holds significant potential for sepsis therapy in the future. This review focusses on T cell dysfunction during sepsis and discusses the potential immunotherapeutic agents to boost T cell function during sepsis and improve host resistance to infection.

  1. Open abdomen procedure in managing abdominal compartment syndrome in a child with severe fungal peritonitis and sepsis after gastric perforation

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    Wei Lai

    2016-04-01

    Full Text Available Abdominal compartment syndrome with increased abdominal pressure resulted in multi-organ dysfunctions can be lethal in children. The open abdomen procedure intentionally leaves the abdominal cavity open in patients with severe abdominal sepsis and abdominal compartment syndrome by temporarily relieving the abdominal pressure. We reported our experience of open abdomen procedure in successfully treating a 4-year old boy with abdominal compartment syndrome caused by severe fungal peritonitis and sepsis after gastric perforation.

  2. Presence of hypogammaglobulinemia - a risk factor of mortality in patients with severe sepsis, septic shock, and SIRS.

    Science.gov (United States)

    Průcha, M; Zazula, R; Herold, I; Dostál, M; Hyánek, T; Bellingan, G

    2013-01-01

    In this retrospective study we assessed the frequency of hypogammaglobulinemia in 708 patients with SIRS, severe sepsis and septic shock. We evaluated the relationship between hypogammaglobulinemia IgG, IgM and 28 day mortality. Total of 708 patients and 1,513 samples were analyzed. In the three subgroups we investigated, patients met the criteria of SIRS, severe sepsis and septic shock. IgG hypogammaglobulinemia was demonstrated in 114 patients with severe sepsis (25.2%), 11 septic shock patients (24.4%), and in 29 SIRS patients (13.9%). IgM hypogammaglobulinemia was documented in 55 patients with severe sepsis (12.2%), 6 septic shock patients (13.3%), and in 17 SIRS patients (8.1%). Mortality of patients with severe sepsis and normal IgG levels was significantly lower (111 patients; 32.8%) compared with those with IgG hypogammaglobulinemia (49 patients; 43.0%; p=0.001). Mortality of patients with septic shock and IgG hypogammaglobulinemia (n=5) was significantly higher compared with those with normal IgG levels (45.5% vs. 38.2%; p=0.001). Mortality of patients with severe sepsis and IgM hypogammaglobulinemia did not differ from that of patients with normal IgM levels (37.0 vs. 41.8%). Mortality of patients with septic shock and IgM hypogammaglobulinemia was significantly higher compared with those with normal IgM levels (50% vs. 38.5%; p=0.0001). This study documented relatively high incidence of hypogammaglobulinemia IgG and IgM in patients with severe sepsis, septic shock and SIRS respectively. The presence of IgG hypogammaglobulinemia in patients with severe sepsis is independent factor of mortality.

  3. Severe sepsis caused by Aeromonas hydrophila in a patient using tocilizumab: a case report

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    Makino Ichiro

    2011-10-01

    Full Text Available Abstract Introduction Aeromonas species do not commonly cause disease in humans. However, when disease is seen, it often occurs in patients with underlying immunosuppression or malignancy and has a high fatality rate. Case presentation A 72-year-old Japanese woman with rheumatoid arthritis treated with tocilizumab (which has an immunosuppressive effect presented with severe epigastric pain. She had a fever with chills, hypotension and jaundice. She was diagnosed with acute suppurative cholangitis and treated with cefoperazone-sulbactam and an endoscopic drainage was performed. Jaundice was slightly improved, but the shock state and inflammatory reactions were prolonged as typical of septic shock. On the second day after admission, an electrocardiogram showed ST segment elevation and echocardiography showed ventricular wall dysfunction. Coronary arteries were patent in coronary angiography and she was diagnosed with stress-induced cardiomyopathy. Blood cultures showed Aeromonas hydrophila. A stool culture was negative for A. hydrophila. On day six, her white blood cell count and neutrophils were normalized and cefoperazone-sulbactam treatment was halted. Left ventricular function normalized on day twelve and a laparoscopic cholecystectomy for cholelithiasis was performed on the 16th day of hospitalization. A culture from the bile showed A. hydrophila. Eighteen days after surgery, tocilizumab treatment was restarted and there were no complications. Two months after restarting tocilizumab, our patient is stable without any serious events. Conclusion We present a rare case of A. hydrophila sepsis and acute suppurative cholangitis in an elderly patient with gallstones and rheumatoid arthritis using tocilizumab. This clinical course may suggest that preemptive treatment for cholelithiasis prior to using molecular-targeting agents might be feasible in elderly patients.

  4. Flecainide Improve Sepsis Induced Acute Lung Injury by Controlling Inflammatory Response

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    Jia Song

    2016-08-01

    Full Text Available Background: Flecainide is an antiarrhythmic agent that is used primarily in the treatment of cardiac arrhythmias. Some evidences also suggest that flecainide can participate in alveolar fluid clearance and inflammatory responses. This experiment was aimed to evaluate the effects of flecainide on sepsis induced acute lung injury in a rat model. Methods: Rats were treated with subcutaneous infusion of saline or flecainide (0.1 or 0.2 mg/kg/hr by a mini-osmotic pump. Subcutaneous infusion was started 3 hours before and continued until 8 hours after intraperitoneal injection of saline or endotoxin. Animals were sacrificed for analyses of severity of acute lung injury with wet to dry (W/D ratio and lung injury score (LIS in lung and inflammatory responses with level of leukocyte, polymorphonuclear neutrophils (PMNs and inteleukin-8 (IL-8 in bronchoalveolar lavages fluid (BALF. Results: Flecainide markedly improved dose dependently sepsis induced acute lung injury as analysed by W/D ratio (from 2.24 ± 0.11 to 1.76 ± 0.09, p < 0.05 and LIS (from 3 to 1, p < 0.05, and inflammatory response as determined by leukocyte (from 443 ± 127 to 229 ± 95, p < 0.05, PMNs (from 41.43 ± 17.63 to 2.43 ± 2.61, p < 0.05 and IL-8 (from 95.00 ± 15.28 to 40.00 ± 10.21, p < 0.05 in BALF. Conclusions: Flecanide improve sepsis induced acute lung injury in rats by controlling inflammatory responses.

  5. Mortality Predictors in Renal Transplant Recipients with Severe Sepsis and Septic Shock

    Science.gov (United States)

    de Carvalho, Mônica Andrade; Freitas, Flávio Geraldo Rezende; Silva Junior, Hélio Tedesco; Bafi, Antônio Toneti; Machado, Flávia Ribeiro; Pestana, José Osmar Medina

    2014-01-01

    Introduction The growing number of renal transplant recipients in a sustained immunosuppressive state is a factor that can contribute to increased incidence of sepsis. However, relatively little is known about sepsis in this population. The aim of this single-center study was to evaluate the factors associated with hospital mortality in renal transplant patients admitted to the intensive care unit (ICU) with severe sepsis and septic shock. Methods Patient demographics and transplant-related and ICU stay data were retrospectively collected. Multiple logistic regression was conducted to identify the independent risk factors associated with hospital mortality. Results A total of 190 patients were enrolled, 64.2% of whom received kidneys from deceased donors. The mean patient age was 51±13 years (males, 115 [60.5%]), and the median APACHE II was 20 (16–23). The majority of patients developed sepsis late after the renal transplantation (2.1 [0.6–2.3] years). The lung was the most common infection site (59.5%). Upon ICU admission, 16.4% of the patients had ≤1 systemic inflammatory response syndrome criteria. Among the patients, 61.5% presented with ≥2 organ failures at admission, and 27.9% experienced septic shock within the first 24 hours of ICU admission. The overall hospital mortality rate was 38.4%. In the multivariate analysis, the independent determinants of hospital mortality were male gender (OR = 5.9; 95% CI, 1.7–19.6; p = 0.004), delta SOFA 24 h (OR = 1.7; 95% CI, 1.2–2.3; p = 0.001), mechanical ventilation (OR = 30; 95% CI, 8.8–102.2; p<0.0001), hematologic dysfunction (OR = 6.8; 95% CI, 2.0–22.6; p = 0.002), admission from the ward (OR = 3.4; 95% CI, 1.2–9.7; p = 0.02) and acute kidney injury stage 3 (OR = 5.7; 95% CI,1.9–16.6; p = 0.002). Conclusions Hospital mortality in renal transplant patients with severe sepsis and septic shock was associated with male gender, admission from the wards

  6. High-dose ascorbate with low-dose amphotericin B attenuates severity of disease in a model of the reappearance of candidemia during sepsis in the mouse.

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    Leelahavanichkul, Asada; Somparn, Poorichaya; Bootprapan, Tanabodee; Tu, Hongbin; Tangtanatakul, Pattarin; Nuengjumnong, Ratchanok; Worasilchai, Navaporn; Tiranathanagul, Khajohn; Eiam-ong, Somchai; Levine, Mark; Chinampon, Ariya; Srisawat, Nattachai

    2015-08-01

    Amphotericin B (Ampho B) isa fungicidal drug that causes cell wall injury. Pharmacological ascorbate induces the extracellular prooxidants, which might enter the Ampho B-induced cell wall porosity and act synergistically.W e tested low-dose Ampho B with a short course of pharmacological ascorbate using a mouse model of sepsis preconditioned with an injection of Candida albicans 6 h prior to cecal ligation and puncture (CLP). In this model, candidemia reappeared as early as 6 h after CLP with a predictably high mortality rate. This characteristic mimics sepsis in the phase of immunosuppression inpatients. Using the model, at 12- and 18-h post-CLP, we administered isotonic (pH neutralized) pharmacological ascorbate intravenously with low-dose Ampho B or sodium deoxycholate, vehicle-controlled, administered IP. The survival rate of low-dose Ampho B plus ascorbate was 53%, compared with ascorbate combination therapy due to less severe sepsis. Moreover, ascorbate enhanced the effectiveness of phagocytosis against C. albicans in human phagocytic cells. Taken together, the data indicate that the new mouse model simulates sepsis-induced immunosuppression and that the combination of pharmacological ascorbate with an antifungal drug is a potentially effective treatment that may reduce nephrotoxicity, and perhaps also increase fungicidal activity in patients with systemic candidiasis caused by Candida albicans.

  7. Impact of Metformin Use on Lactate Kinetics in Patients with Severe Sepsis and Septic Shock.

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    Park, Joongmin; Hwang, Sung Yeon; Jo, Ik Joon; Jeon, Kyeongman; Suh, Gee Young; Lee, Tae Rim; Yoon, Hee; Cha, Won Chul; Sim, Min Seob; Carriere, Keumhee Chough; Yeon, Seungmin; Shin, Tae Gun

    2017-05-01

    We aimed to evaluate the impact of metformin use on lactate kinetics in patients with severe sepsis and septic shock. We analyzed data from a registry that included patients who presented to the emergency department and met criteria for severe sepsis or septic shock. Patients were divided into two groups based on metformin use. We compared lactate concentrations, lactate clearance (LC), and normalization at 6 h (H6) and 24 h (H24) after the initial (H0) measurement. Propensity score matching, multiple logistic, and linear regression analysis via a generalized estimating equations method were used. Of 1,318 patients, 71 patients were in the metformin use group and all 71 were selected in a one to two propensity matching. Metformin users showed significantly higher lactate levels at H0 (5.3 vs. 4.4 mmol/L) and H6 (3.8 vs. 2.9 mmol/L) in all patients, although in the matched subset, the effect was marginal (H0, 5.3 vs. 4.9 mmol/L; H6, 3.8 vs. 3.2 mmol/L; H24, 2.7 vs. 2.4 mmol/L). Mean LC (H6, 29% vs. 34%; H24, 43% vs. 49%) and normalization rate (H6, 27% vs. 28%; H24, 49% vs. 52%) were also not significantly different. Although metformin use appeared to be associated with higher lactate levels before using the propensity score method, no significant association was found between metformin use and lactate kinetics variables in the balanced matched subset data. Lactate levels in metformin users were initially elevated in the early phase of resuscitation from severe sepsis and septic shock. However, there was no significant difference in lactate levels, LC, and normalization over the initial 24 h period based on metformin use.

  8. Mitochondrial N-formyl peptides induce cardiovascular collapse and sepsis-like syndrome.

    Science.gov (United States)

    Wenceslau, Camilla Ferreira; McCarthy, Cameron G; Szasz, Theodora; Goulopoulou, Styliani; Webb, R Clinton

    2015-04-01

    Fifty percent of trauma patients who present sepsis-like syndrome do not have bacterial infections. This condition is known as systemic inflammatory response syndrome (SIRS). A unifying factor of SIRS and sepsis is cardiovascular collapse. Trauma and severe blood loss cause the release of endogenous molecules known as damage-associated molecular patterns. Mitochondrial N-formyl peptides (F-MIT) are damage-associated molecular patterns that share similarities with bacterial N-formylated peptides and are potent immune system activators. The goal of this study was to investigate whether F-MIT trigger SIRS, including hypotension and vascular collapse via formyl peptide receptor (FPR) activation. We evaluated cardiovascular parameters in Wistar rats treated with FPR or histamine receptor antagonists and inhibitors of the nitric oxide pathway before and after F-MIT infusion. F-MIT, but not nonformylated peptides or mitochondrial DNA, induced severe hypotension via FPR activation and nitric oxide and histamine release. Moreover, F-MIT infusion induced hyperthermia, blood clotting, and increased vascular permeability. To evaluate the role of leukocytes in F-MIT-induced hypotension, neutrophil, basophil, or mast cells were depleted. Depletion of basophils, but not neutrophils or mast cells, abolished F-MIT-induced hypotension. Rats that underwent hemorrhagic shock increased plasma levels of mitochondrial formylated proteins associated with lung damage and antagonism of FPR ameliorated hemorrhagic shock-induced lung injury. Finally, F-MIT induced vasodilatation in isolated resistance arteries via FPR activation; however, F-MIT impaired endothelium-dependent relaxation in the presence of blood. These data suggest that F-MIT may be the link among trauma, SIRS, and cardiovascular collapse. Copyright © 2015 the American Physiological Society.

  9. Phenol-Soluble Modulins Contribute to Early Sepsis Dissemination Not Late Local USA300-Osteomyelitis Severity in Rabbits.

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    Benjamin Davido

    Full Text Available In bone and joint infections (BJIs, bacterial toxins are major virulence factors: Panton-Valentine leukocidin (PVL expression leads to severe local damage, including bone distortion and abscesses, while α-hemolysin (Hla production is associated with severe sepsis-related mortality. Recently, other toxins, namely phenol-soluble modulins (PSMs expressed by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA strain USA300 (LAC WT were shown to have ex vivo intracellular cytotoxic activity after S. aureus invasion of osteoblasts, but their in vivo contribution in a relatively PVL-sensitive osteomyelitis model remains poorly elucidated.We compared the outcomes of experimental rabbit osteomyelitises induced with pvl+hla+psms+ LAC WT and its isogenic Δpsm derivatives (LAC Δpsmα and LAC Δpsmαβhld using an inoculum of 3 × 108 CFUs. Mortality, hematogenous spread (blood culture, spleen and kidney, lung and bone involvements were assessed in two groups (non-survivors of severe sepsis and survivors sacrificed on day (D 14.Severe sepsis-related mortality tended to be lower for Δpsm derivatives (Kaplan-Meier curves, P = .06. Non-survivors' bone LAC-Δpsmα (6.9 log10 CFUs/g of bone, P = .04 or -Δpsmαβhld (6.86 log10 CFUs/g of bone, P = .014 densities were significantly higher than LAC WT (6.43 log10 CFUs/g of bone. Conversely, lung Δpsmαβhld CFUs were significantly lower than LAC WT (P = .04. LAC Δpsmα, Δpsmαβhld and WT induced similar bone damage in D14 survivors, with comparable bacterial densities (respectively: 5.89, 5.91, and 6.15 log10 CFUs/g of bone. Meanwhile, pulmonary histological scores of inflammation were significantly higher for LAC Δpsmα- and Δpsmαβhld-infected rabbits compared to LAC WT (P = .04 and .01, respectively but with comparable lung bacterial densities.Our experimental results showed that deactivating PSM peptides significantly limited bacterial dissemination from bone during the early

  10. Natural Killer Cell Assessment in Peripheral Circulation and Bronchoalveolar Lavage Fluid of Patients with Severe Sepsis: A Case Control Study

    Science.gov (United States)

    Souza-Fonseca-Guimaraes, Paulo; Guimaraes, Fernando; Natânia De Souza-Araujo, Caroline; Maria Boldrini Leite, Lidiane; Cristina Senegaglia, Alexandra; Nishiyama, Anita; Souza-Fonseca-Guimaraes, Fernando

    2017-01-01

    Sepsis is a complex systemic inflammatory syndrome, the most common cause of which is attributed to systemic underlying bacterial infection. The complete mechanisms of the dynamic pro- and anti-inflammatory processes underlying the pathophysiology of sepsis remain poorly understood. Natural killer (NK) cells play a crucial role in the pathophysiology of sepsis, leading to exaggerated inflammation due their rapid response and production of pro-inflammatory cytokines such as interferon gamma (IFN-γ). Several studies have already shown that NK cells undergo lymphopenia in the peripheral blood of patients with sepsis. However, our understanding of the mechanisms behind its cellular trafficking and its role in disease development is restricted to studies in animal models. In this study, we aimed to compare the human NK cell subset (CD56bright or dim) levels in the peripheral blood and bronchoalveolar lavage (BAL) fluid of sepsis patients. We conducted a case-control study with a sample size consisting of 10 control patients and 23 sepsis patients enrolled at the Hospital Cajuru (Curitiba/PR, Brazil) from 2013 to 2015. Although we were able to confirm previous observations of peripheral blood lymphopenia, no significant differences were detected in NK cell levels in the BAL fluid of these patients. Overall, these findings strengthened the evidence that peripheral blood lymphopenia is likely to be associated with cell death as a consequence of sepsis. PMID:28287491

  11. Natural Killer Cell Assessment in Peripheral Circulation and Bronchoalveolar Lavage Fluid of Patients with Severe Sepsis: A Case Control Study.

    Science.gov (United States)

    Souza-Fonseca-Guimaraes, Paulo; Guimaraes, Fernando; Natânia De Souza-Araujo, Caroline; Maria Boldrini Leite, Lidiane; Cristina Senegaglia, Alexandra; Nishiyama, Anita; Souza-Fonseca-Guimaraes, Fernando

    2017-03-12

    Sepsis is a complex systemic inflammatory syndrome, the most common cause of which is attributed to systemic underlying bacterial infection. The complete mechanisms of the dynamic pro- and anti-inflammatory processes underlying the pathophysiology of sepsis remain poorly understood. Natural killer (NK) cells play a crucial role in the pathophysiology of sepsis, leading to exaggerated inflammation due their rapid response and production of pro-inflammatory cytokines such as interferon gamma (IFN-γ). Several studies have already shown that NK cells undergo lymphopenia in the peripheral blood of patients with sepsis. However, our understanding of the mechanisms behind its cellular trafficking and its role in disease development is restricted to studies in animal models. In this study, we aimed to compare the human NK cell subset (CD56(bright or dim)) levels in the peripheral blood and bronchoalveolar lavage (BAL) fluid of sepsis patients. We conducted a case-control study with a sample size consisting of 10 control patients and 23 sepsis patients enrolled at the Hospital Cajuru (Curitiba/PR, Brazil) from 2013 to 2015. Although we were able to confirm previous observations of peripheral blood lymphopenia, no significant differences were detected in NK cell levels in the BAL fluid of these patients. Overall, these findings strengthened the evidence that peripheral blood lymphopenia is likely to be associated with cell death as a consequence of sepsis.

  12. Outcomes and Resource Use of Sepsis-associated Stays by Presence on Admission, Severity, and Hospital Type.

    Science.gov (United States)

    Jones, Stephen L; Ashton, Carol M; Kiehne, Lisa B; Nicolas, Juan C; Rose, Alexis L; Shirkey, Beverly A; Masud, Faisal; Wray, Nelda P

    2016-03-01

    To establish a baseline for the incidence of sepsis by severity and presence on admission in acute care hospital settings before implementation of a broad sepsis screening and response initiative. A retrospective cohort study using hospital discharge abstracts of 5672 patients, aged 18 years and above, with sepsis-associated stays between February 2012 and January 2013 at an academic medical center and 5 community hospitals in Texas. Sepsis was present on admission in almost 85% of cases and acquired in-hospital in the remainder. The overall inpatient death rate was 17.2%, but was higher in hospital-acquired sepsis (38.6%, medical; 29.2%, surgical) and Stages 2 (17.6%) and 3 (36.4%) compared with Stage 1 (5.9%). Patients treated at the academic medical center had a higher death rate (22.5% vs. 15.1%, Psepsis and the detection of sepsis in the prehospitalization and early hospitalization period. Hospital characteristics and case mix should be accounted for in cross-hospital comparisons of sepsis outcomes and costs.

  13. Molecular Hydrogen Therapy Ameliorates Organ Damage Induced by Sepsis

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    Yijun Zheng

    2016-01-01

    Full Text Available Since it was proposed in 2007, molecular hydrogen therapy has been widely concerned and researched. Many animal experiments were carried out in a variety of disease fields, such as cerebral infarction, ischemia reperfusion injury, Parkinson syndrome, type 2 diabetes mellitus, metabolic syndrome, chronic kidney disease, radiation injury, chronic hepatitis, rheumatoid arthritis, stress ulcer, acute sports injuries, mitochondrial and inflammatory disease, and acute erythema skin disease and other pathological processes or diseases. Molecular hydrogen therapy is pointed out as there is protective effect for sepsis patients, too. The impact of molecular hydrogen therapy against sepsis is shown from the aspects of basic vital signs, organ functions (brain, lung, liver, kidney, small intestine, etc., survival rate, and so forth. Molecular hydrogen therapy is able to significantly reduce the release of inflammatory factors and oxidative stress injury. Thereby it can reduce damage of various organ functions from sepsis and improve survival rate. Molecular hydrogen therapy is a prospective method against sepsis.

  14. Structured lipid emulsion as nutritional therapy for the elderly patients with severe sepsis

    Institute of Scientific and Technical Information of China (English)

    CHEN Jin; YAN Jing; CAI Guo-long; XU Qiang-hong; GONG Shi-jin; DAI Hai-wen; YU Yi-hua

    2013-01-01

    Background The nutritional support is one of the important therapeutic strategies for the elderly patients with severe sepsis,but there is controversial in choosing a parenteral nutrition formulation.This study was designed to compare the therapeutic effects of structured lipid emulsion,physically mixed medium,and long-chain fat emulsion in the treatment of severe sepsis in elderly patients.Methods A total number of 64 elder patients with severe sepsis were enrolled in the study.After a week of enteral nutritional support,the patients were randomly divided into research (structured lipid emulsion as parenteral alimentation) and control groups (physically mixed medium and long-chain fat emulsion as parenteral alimentation).The alterations of plasma albumin,lipid metabolism,and blood glucose level were recorded after parenteral alimentation and were compared between the two groups.Results The plasma levels of albumin,prealbumin,cholesterol,and triglyceride were decreased in all the patients after one week of enteral nutritional support treatment (t=7.78,P=0.000; t=10.21,P=0.000; t=7.99,P=0.000; and t=10.99,P=0.000).Further parenteral alimentation with different lipid emulsions had significant effects on the serum prealbumin and albumin (t=3.316,P=0.002; t=3.200,P=0.002),whilst had no effects on the blood glucose and triglyceride level (t=7.78,P=0.000; t=4.228,P=0.000).In addition,the two groups had a significantly different Apache Ⅱ score,ventilator time,and hospital stay time (t=-2.213,P=0.031;t=2.317,P=0.024; t=2.514,P=0.015).Conclusions The structured lipid emulsion was safe as parenteral nutrition for elderly patients with severe sepsis.It was demonstrated to be superior to the physically mixed medium and long-chain fat emulsion with respect to the protein synthesis and prognosis.

  15. Evaluation of recombinant activated protein C for severe sepsis at a tertiary academic medical center

    Directory of Open Access Journals (Sweden)

    Anger KE

    2013-06-01

    Full Text Available Kevin E Anger,1 Jeremy R DeGrado,1 Bonnie C Greenwood,1 Steven A Cohen,2 Paul M Szumita1 1Department of Pharmacy, Brigham and Women’s Hospital, Boston, MA, USA; 2Department of Family Medicine and Population Health, Division of Epidemiology, Virginia Commonwealth University, Richmond, VA, USA Purpose: Early clinical trials of recombinant human activated protein C (rhAPC for severe sepsis excluded patients at high risk of bleeding. Recent literature suggests bleeding rates are higher in clinical practice and may be associated with worsened outcomes. Our objective was to evaluate baseline demographics; incidence, and risk factors for major bleeding; and mortality of patients receiving rhAPC for severe sepsis at our institution. Methods: A retrospective study was performed for all patients receiving rhAPC for treatment of severe sepsis at a tertiary academic medical center from January 2002 to June 2009. Demographic information, clinical variables, intensive care unit, and hospital outcomes were recorded. Results: Of the 156 patients that received rhAPC, 54 (34.6% did not meet institutional criteria for safe use at baseline due to bleeding precaution or contraindication. Twenty-three (14.7% patients experienced a major bleeding event. Multivariate analysis demonstrated baseline International Normalized Ratio ≥2.5 (odds ratio [OR] 3.68, 95% confidence interval [CI]: 1.28–10.56; P = 0.03 and platelet count ≤100 × 103/mm3 (OR 2.86, 95% CI: 1.07–7.67; P = 0.01 as significant predictors of a major bleed. Overall hospital mortality was 57.7%. Multivariate analysis demonstrated the presence of ≥3 organ dysfunctions (OR 2.46, 95% CI: 1.19–5.09; P < 0.05 and medical intensive care unit admission (OR 1.99, 95% CI: 1.00–3.98; P = 0.05 were independent variables associated with hospital mortality. Conclusion: Patients receiving rhAPC at our institution had higher APACHE II scores, mortality, and major bleeding events than published

  16. Sepsis-Induced Takotsubo Cardiomyopathy Leading to Torsades de Pointes

    Science.gov (United States)

    Kamran, Haroon; El-Sherif, Nabil

    2016-01-01

    Background. Takotsubo cardiomyopathy (TCM) is sudden and reversible myocardial dysfunction often attributable to physical or emotional triggers. Case Report. We describe a 51-year-old man presented to emergency department with sepsis from urinary tract infection (UTI). He was placed on cefepime for UTI and non-ST-elevation myocardial infarction protocol given elevated troponins with chest pain. Subsequently, patient was pulseless with torsades de pointes (TdP) and then converted to sinus rhythm with cardioversion. An echocardiogram revealed low ejection fraction with hypokinesis of the apical wall. Over 48 hours, the patient was extubated and stable on 3 L/min nasal cannula. He underwent a cardiac catheterization to evaluate coronary artery disease (CAD) and was found to have mild nonobstructive CAD with no further findings. Conclusion. TCM is a rare disorder presenting with symptoms similar to acute coronary syndrome. Though traditionally elicited by physical and emotional triggers leading to transient left ventricular dysfunction, our case suggests that it may also be triggered by a urinary tract infection and lead to severe QT prolongation and a malignant ventricular arrhythmia in TdP. PMID:27525128

  17. Sepsis-Induced Takotsubo Cardiomyopathy Leading to Torsades de Pointes

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    Nirav Patel

    2016-01-01

    Full Text Available Background. Takotsubo cardiomyopathy (TCM is sudden and reversible myocardial dysfunction often attributable to physical or emotional triggers. Case Report. We describe a 51-year-old man presented to emergency department with sepsis from urinary tract infection (UTI. He was placed on cefepime for UTI and non-ST-elevation myocardial infarction protocol given elevated troponins with chest pain. Subsequently, patient was pulseless with torsades de pointes (TdP and then converted to sinus rhythm with cardioversion. An echocardiogram revealed low ejection fraction with hypokinesis of the apical wall. Over 48 hours, the patient was extubated and stable on 3 L/min nasal cannula. He underwent a cardiac catheterization to evaluate coronary artery disease (CAD and was found to have mild nonobstructive CAD with no further findings. Conclusion. TCM is a rare disorder presenting with symptoms similar to acute coronary syndrome. Though traditionally elicited by physical and emotional triggers leading to transient left ventricular dysfunction, our case suggests that it may also be triggered by a urinary tract infection and lead to severe QT prolongation and a malignant ventricular arrhythmia in TdP.

  18. Acute kidney injury and inflammatory response of sepsis following cecal ligation and puncture in D-galactose-induced aging rats

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    Liu C

    2017-03-01

    Full Text Available Chao Liu,1,* Jie Hu,1,* Zhi Mao,1,* Hongjun Kang,1 Hui Liu,1 Wanlei Fu,2 Yangfan Lv,2 Feihu Zhou1 1Department of Critical Care Medicine, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China; 2Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of China *These authors contributed equally to this work Background: Recently, the D-galactose (D-gal-induced mimetic aging rat model has been widely used in studies of age-associated diseases, which have shown that chronic D-gal exposure induces premature aging similar to natural aging in rats. With the increasing rate of sepsis in the geriatric population, an easy-access animal model for preclinical studies of elderly sepsis is urgently needed. This study investigates whether a sepsis model that is established in D-gal-induced aging rats can serve as a suitable model for preclinical studies of elderly patients with sepsis.Objective: To investigate the acute kidney injury (AKI and inflammatory response of sepsis following cecal ligation and puncture (CLP in D-gal-induced aging rats.Methods: Twelve-week-old male Sprague Dawley rats were divided into low-dose D-gal (L D-gal, 125 mg/kg/d, high-dose D-gal (H D-gal, 500 mg/kg/d, and control groups. After daily subcutaneous injection of D-gal for 6 weeks, the CLP method was used to establish a sepsis model.Results: The mortality was 73.3%, 40%, and 33.3% in the H D-gal, L D-gal, and control groups, respectively. Blood urea nitrogen, creatinine, plasma neutrophil gelatinase-associated lipocalin, interleukin-6, interleukin-10, and tumor necrosis factor-α were markedly increased in the H D-gal group after establishment of the sepsis model (H D-gal vs control, P<0.05 at 12 h and 24 h post-CLP. The rate of severe AKI (RIFLE-F at 24 h post-CLP was 43% for both the control and L D-gal groups and 80% for the H D-gal group.Conclusion: High-dose-D-gal-induced aging rats are

  19. CCR4 Controls the Suppressive Effects of Regulatory T Cells on Early and Late Events during Severe Sepsis.

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    Raphael Molinaro

    Full Text Available Sepsis is a deadly disease characterized by an overwhelming release of inflammatory mediators and the activation of different types of cells. This altered state of cell activation, termed leukocyte reprogramming, contributes to patient outcome. However, the understanding of the process underlying sepsis and the role of regulatory T cells (Tregs in sepsis remains to be elucidated. In this study, we investigated the role of CCR4, the CCL17/CCL22 chemokine receptor, in the innate and acquired immune responses during severe sepsis and the role of Tregs in effecting the outcome. In contrast with wild-type (WT mice subjected to cecal ligation and puncture (CLP sepsis, CCR4-deficient (CCR4-/- septic mice presented an increased survival rate, significant neutrophil migration toward the infection site, a low bacterial count in the peritoneum, and reduced lung inflammation and serum cytokine levels. Thus, a better early host response may favor an adequate long-term response. Consequently, the CCR4-/- septic mice were not susceptible to secondary fungal infection, in contrast with the WT septic mice. Furthermore, Tregs cells from the CCR4-/- septic mice showed reduced suppressive effects on neutrophil migration (both in vivo and in vitro, lymphocyte proliferation and ROS production from activated neutrophils, in contrast with what was observed for Tregs from the WT septic mice. These data show that CCR4 is involved in immunosuppression after severe sepsis and suggest that CCR4+ Tregs negatively modulate the short and long-term immune responses.

  20. CCR4 Controls the Suppressive Effects of Regulatory T Cells on Early and Late Events during Severe Sepsis.

    Science.gov (United States)

    Molinaro, Raphael; Pecli, Cyntia; Guilherme, Rafael F; Alves-Filho, José Carlos; Cunha, Fernando Q; Canetti, Claudio; Kunkel, Steven L; Bozza, Marcelo T; Benjamim, Claudia F

    2015-01-01

    Sepsis is a deadly disease characterized by an overwhelming release of inflammatory mediators and the activation of different types of cells. This altered state of cell activation, termed leukocyte reprogramming, contributes to patient outcome. However, the understanding of the process underlying sepsis and the role of regulatory T cells (Tregs) in sepsis remains to be elucidated. In this study, we investigated the role of CCR4, the CCL17/CCL22 chemokine receptor, in the innate and acquired immune responses during severe sepsis and the role of Tregs in effecting the outcome. In contrast with wild-type (WT) mice subjected to cecal ligation and puncture (CLP) sepsis, CCR4-deficient (CCR4-/-) septic mice presented an increased survival rate, significant neutrophil migration toward the infection site, a low bacterial count in the peritoneum, and reduced lung inflammation and serum cytokine levels. Thus, a better early host response may favor an adequate long-term response. Consequently, the CCR4-/- septic mice were not susceptible to secondary fungal infection, in contrast with the WT septic mice. Furthermore, Tregs cells from the CCR4-/- septic mice showed reduced suppressive effects on neutrophil migration (both in vivo and in vitro), lymphocyte proliferation and ROS production from activated neutrophils, in contrast with what was observed for Tregs from the WT septic mice. These data show that CCR4 is involved in immunosuppression after severe sepsis and suggest that CCR4+ Tregs negatively modulate the short and long-term immune responses.

  1. Predictive ability of circulating osteoprotegerin as a novel biomarker for early detection of acute kidney injury induced by sepsis.

    Science.gov (United States)

    Schaalan, Mona; Mohamed, Waleed

    2017-06-01

    Though significant progress has been made towards new diagnostic approaches for early detection of acute kidney injury (AKI) induced by different factors, there is still an urgent demand for a more specific and predictive biomarker for each type. The aim of this study is to unravel the potential diagnostic utility of circulating osteoprotegerin (OPG) in septic patients who developed AKI in the ICU, compared to cystatin C (a renal function maker) and KIM-1 (a kidney damage marker). Eighty patients (male = 43, female = 37) with ages ranging from 42 to 46 years and with sepsis, 40 of whom developed AKI, and 30 healthy controls were enrolled in this prospective study. Results revealed significant progressive elevation of OPG, along with cystatin C and KIM-1, among sepsis, severe sepsis, and sepsis-AKI patients. The progression of OPG levels paralleled the deterioration of kidney and endothelial functions from sepsis to sepsis-AKI, revealed as progressively increased levels of serum E-selectin (15.3%), endothelin-1 (ET-1) (19.6%), and decreased nitric oxide (NO) (29.7%), associated with elevations of TNF-α (25.5%) and TGF-β (18%). Their comparative prognostic validity of sepsis-AKI was assessed using ROC analysis, which revealed that OPG, KIM-1, and cystatin C showed similar AUCs (0.827-0.83) but with different sensitivities, viz., 84%, 88%, and 92%, respectively. Although cystatin showed 82% specificity, OPG showed a higher, similar specificity to KIM-1 of 85%, indicating its potential function as a marker of renal damage such as KIM-1. This study revealed a significant elevation of circulating OPG in septic patients with different levels of severity and those who progressed to AKI. Moreover, OPG showed a significant correlation to KIM-1 and cystatin, as well as conventional renal, inflammatory, and endothelial markers. Having a similar specificity to KIM-1, as evidenced by the ROC analysis, OPG has the potential to serve as a reliable biomarker of kidney damage

  2. Clinical Practice Guidelines for Severe Sepsis Treatment. Guía de práctica clínica para el tratamiento de la sepsis grave.

    OpenAIRE

    2009-01-01

    Clinical Practice Guidelines for Severe Sepsis Treatment. It is a syndrome of inflammatory systemic response caused by documented infection (clinical and/or microbiological), associated with organic dysfunction (respiratory, renal, hepatic, cardiovascular, haematological and neurological), hypotension or hypoperfusion. This document includes a review and update of the concept, risk factors, diagnosis and treatment. It includes assessment guidelines focused on the most important aspects to be ...

  3. TLR4-dependent internalization of CX3CR1 aggravates sepsis-induced immunoparalysis.

    Science.gov (United States)

    Ge, Xin-Yu; Fang, Shang-Ping; Zhou, Miao; Luo, Jing; Wei, Juan; Wen, Xue-Ping; Yan, Xiao-Di; Zou, Zui

    2016-01-01

    Sepsis, the most severe manifestation of infection, poses a major challenge to health-care systems around the world. Limited ability to clean and remove the pathogen renders difficulty in septic patients to recover from the phase of immunoparalysis. The present study found the vital role of CX3CR1 internalization on sepsis-induced immunoparalysis. A mouse model with cecal ligation and puncture (CLP) and cell model with lipopolysaccharides (LPS) were employed to explore the relationship between CX3CR1 internalization and septic immunoparalysis. Immunoparalysis model in mice was established 4 days after CLP with significantly decreased proinflammatory cytokines. Flow cytometry analysis found a decreased surface expression of CX3CR1 during immunoparalysis, which was associated with reduced mRNA level and increased internalization of CX3CR1. G-protein coupled receptor kinase 2 (GRK2) and β-arrestin2 were significantly increased during septic immunoparalysis and involved in the internalization of CX3CR1. TLR4(-/-) or TLR4 inhibitor-treated macrophages exhibited an inhibited expression of GRK2 and β-arrestin2, along with reduced internalization of CX3CR1. Moreover, the knockdown of GRK2 and β-arrestin2 inhibited the internalization of CX3CR1 and led to a higher response on the second hit, which was associated with an increased activation of NF-κB. The critical association between internalization of CX3CR1 and immunosuppression in sepsis may provide a novel reference for clinical therapeutics.

  4. Endothelium dependent vasomotion and in vitro markers of endothelial repair in patients with severe sepsis: an observational study.

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    Sabrina H van Ierssel

    Full Text Available BACKGROUND: Outcome in sepsis is mainly defined by the degree of organ failure, for which endothelial dysfunction at the macro- and microvascular level is an important determinant. In this study we evaluated endothelial function in patients with severe sepsis using cellular endothelial markers and in vivo assessment of reactive hyperaemia. MATERIALS AND METHODS: Patients with severe sepsis (n = 30 and 15 age- and gender- matched healthy volunteers were included in this study. Using flow cytometry, CD34+/KDR+ endothelial progenitor cells (EPC, CD31+ T-cells, and CD31+/CD42b- endothelial microparticles (EMP were enumerated. Migratory capacity of cultured circulating angiogenic cells (CAC was assessed in vitro. Endothelial function was determined using peripheral arterial tonometry at the fingertip. RESULTS: In patients with severe sepsis, a lower number of EPC, CD31+ T-cells and a decreased migratory capacity of CAC coincided with a blunted reactive hyperaemia response compared to healthy subjects. The number of EMP, on the other hand, did not differ. The presence of organ failure at admission (SOFA score was inversely related with the number of CD31+ T-cells. Furthermore, the number of EPC at admission was decreased in patients with progressive organ failure within the first week. CONCLUSION: In patients with severe sepsis, in vivo measured endothelial dysfunction coincides with lower numbers and reduced function of circulating cells implicated in endothelial repair. Our results suggest that cellular markers of endothelial repair might be valuable in the assessment and evolution of organ dysfunction.

  5. Coupled plasma haemofiltration filtration in severe sepsis: systematic review and meta-analysis.

    Science.gov (United States)

    Hazzard, Ian; Jones, S; Quinn, T

    2015-12-01

    Coupled plasma filtration and adsorption (CPFA) has been used in the treatment of severe sepsis with the intention of removing the proinflammatory and anti-inflammatory mediators from the systemic circulation. It is believed that this interrupts and moderates the septic cascade, but there is uncertainty about the benefits of this therapy. A systematic review and meta-analysis were performed to estimate the effects of CPFA on mortality in severe sepsis. The Cochrane CENTRAL Register of Controlled Trials, CINAHL, EMBASE, MEDLINE-EBSCO-Host, MEDLINE and ProQuest, were searched from 1997 to 2013. Randomised controlled trials, prospective cohort studies and retrospective cohort studies were included using the Centre for Reviews and Dissemination (CRD) framework. Data were abstracted using standard pro forma, and studies independently reviewed by two authors to confirm inclusion criteria. Quality of studies and risk of bias were assessed using the Grading of Recommendations, Assessment, Development and Evaluation Working Group (GRADE) and Critical Appraisal Skills (CASP) criteria, respectively. Meta-analysis was performed using Review Manager (RevMan V.5.1) software. The primary outcome was 28-day mortality. Secondary outcomes were mediator adsorption (picograms/mL), mean arterial BP (mm Hg) and oxygenation ratio. 17 studies met the inclusion criteria (n=441 patients, 242 CPFA). 14 studies reported the primary outcome of 28-day mortality. There were 88 deaths in CPFA patients versus 118 in those receiving haemofiltration: OR 0.34 (95% CI 0.24 to 0.13). Point estimates of effect on the secondary outcomes of mean arterial pressure and oxygen ratio favoured CPFA. Studies were small and heterogenous. Evidence for CPFA in severe sepsis is sparse, of poor quality and further research is required, however, this meta-analysis noted improvements in survival rates of those patients treated with CPFA. Published by the BMJ Publishing Group Limited. For permission to use (where not

  6. Comportamiento del fallo renal agudo en niños con sepsis grave Behavior of acute renal failure in children presenting with severe sepsis

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    María del Carmen Saura Hernández

    2010-03-01

    Full Text Available INTRODUCCIÓN. El objetivo de esta investigación fue determinar los factores de riesgo asociados al fallo renal agudo (FRA en un grupo de niños con sepsis grave atendidos entre enero del 2004 y diciembre del 2008. MÉTODOS. Se realizó un estudio observacional y analítico con una muestra de 171 pacientes. Se constituyeron dos grupos: el de estudio, integrado por 38 pacientes con estado de choque séptico o disfunción múltiple de órganos (DMO y FRA, y un grupo control, conformado por 133 niños en igual estadio de sepsis pero con función renal normal. Se revisaron las historias clínicas y se tuvieron en cuenta variables epidemiológicas, factores de riesgo de FRA y evolución de los casos. RESULTADOS. La incidencia de FRA fue del 22,2 %, y aunque disminuyó considerablemente en los 3 últimos años del estudio, la mortalidad fue del 42,1 %, mayoritariamente en el DMO (89,5 %. Se encontró dependencia entre la insuficiencia renal y la respuesta diurética no adecuada a la fluidoterapia (51,2 %, la inestabilidad hemodinámica por más de 24 h (46,5 %, la disfunción miocárdica (43,3 % y el uso de medicamentos nefrotóxicos (42,8 %. CONCLUSIONES. La respuesta diurética no adecuada a la fluidoterapia, la inestabilidad hemodinámica por más de 24 h, la disfunción miocárdica y el uso de medicamentos nefrotóxicos incrementan el riesgo de FRA en la sepsis grave, la cual duplica la mortalidad en relación con los pacientes que conservan la función renal. No obstante, la prevención de las formas graves de sepsis y un tratamiento adecuado de ésta disminuyen la incidencia de FRA.INTRODUCTION: The aim of present research was to determine the risk factor associated with the acute renal failure (ARF in a group of children with severe sepsis seen between January, 2004 and December, 2008. METHODS: An analytical and observational study was conducted in a sample including 171 patients. There were two groups: the study-group with 138 patients with

  7. Dog-bite induced sepsis : a report of four cases

    NARCIS (Netherlands)

    Hovenga, S; Tulleken, JE; Moller, LVM; Jackson, SA; Van der Werf, TS; Zijlstra, JG

    1997-01-01

    Occasionally, a dog-bite is complicated by a systemic overwhelming infection. We report four consecutive patients who were admitted to our intensive care unit because of sepsis syndrome following dog-bites. The history of these patients did not reveal any immunocompromising conditions. Capnocytophag

  8. Complement depletion deteriorates clinical outcomes of severe abdominal sepsis: a conspirator of infection and coagulopathy in crime?

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    Jianan Ren

    Full Text Available BACKGROUND: The complement depletion commonly occurred during sepsis, but it was often underestimated compared with severe infection or coagulation dysfunction. OBJECTIVE: This study was designed to investigate the alteration of complement system in patients with severe abdominal sepsis and evaluate the role of complement depletion in prognosis of such patients. The relationship between complement depletion and infection or coagulopathy was also explored. METHODS: Forty-five patients with severe abdominal sepsis were prospectively conducted among individuals referral to SICU. Currently recommended treatments, such as early goal-directed resuscitation, source control and antibiotics therapy, were performed. Acute physiology and chronic health evaluation II (APACHE II and sepsis related organ failure assessment (SOFA scores were employed to evaluate severity. Plasma levels of C3, C4, CRP, PCT, D-dimer and other parameters were detected within eight times of observation. The 28-day mortality, length of stay, and postoperative complications were compared between complement depletion and non-complement depletion groups. RESULTS: Within the study period, eight (17.8% patients died, five of them suffering from complement depletion. The overall incidence of complement depletion was 64.4%. At admission, mean complement C3 and C4 levels were 0.70 and 0.13 mg/mL, respectively. Using ROC analysis for mortality prediction, the area under the curve of C3 was 0.926 (95% CI, 0.845-0.998, P<0.001, with optimal cutpoint value of 0.578 mg/mL. Complement C3 depletion was shown to be no correlation to severity scores, however, strongly correlated with elevated D-dimer, PCT concentrations and increased postoperative complications. CONCLUSIONS: Complement C3 depletion was found to be connected to poor prognosis in severe abdominal sepsis. This depletion seems to be associated with coagulopathy and aggravated infection during sepsis, which should be paid close

  9. [Experience in the treatment of severe forms of sepsis by extracorporeal therapy and hyperbaric oxygenation].

    Science.gov (United States)

    Zhidkov, K P; Klechikov, V Z; Bogatyr', M N

    1997-01-01

    The results of multiple modality treatment of 81 patients with sepsis complicated by multiple organ failure are assessed. In 40 patients the traditional therapy of sepsis was supplemented with extracorporeal methods (hemoperfusion, autotransfusion of UV-exposed blood, and perfusion of xenospleen slices) and hyperbaric oxygenation (HBO) sessions. In the patients treated traditionally the mortality was 94%, whereas addition of extracorporeal treatment and HBO decreased this value to 40%. Hence, extracorporeal treatment and HBO are recommended for the treatment of sepsis.

  10. Clinical predictors for severe sepsis in patients with necrotizing fasciitis: an observational cohort study in northern Thailand

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    Khamnuan P

    2015-07-01

    Full Text Available Patcharin Khamnuan,1,2 Wilaiwan Chongruksut,3 Kijja Jearwattanakanok,4 Jayanton Patumanond,5 Apichat Tantraworasin,3 1Clinical Epidemiology Program, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 2Department of Nursing, Phayao Hospital, Phayao, Thailand; 3Department of Surgery, Faculty of Medicine, Chiang Mai University, 4Department of Surgery, Nakornping Hospital, Chiang Mai, Thailand; 5Clinical Epidemiology Unit, Clinical Research Center, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand Background: Necrotizing fasciitis (NF is a life-threatening infection of skin and fascia. Its progress is extremely fast, with extensive necrosis. Delay in treatment, with subsequent huge soft tissue loss and associated severe sepsis, remains a major cause of death in the management of NF. Objective: The aim of this study was to explore clinical characteristics that may be used to predict severe sepsis in patients with NF, in the context of routine clinical practice in northern Thailand. Methods: A retrospective observational cohort study was conducted. The patient cohort in this study consisted of all patients who were diagnosed with NF by surgical or pathological confirmation. The follow-up period started with the admission date and ended with the discharge date. The clinical variables were collected from patients registered at three provincial hospitals in northern Thailand from 2009 to 2012. The clinical predictors for severe sepsis were analyzed using multivariable risk regression. Results: A total of 1,452 patients were diagnosed with NF, either with severe sepsis (n=237 [16.3%] or without severe sepsis (n=1,215 [83.7%]. From the multivariable analysis, female sex (relative risk [RR] =1.51; 95% confidence interval [CI] =1.04–2.20, diabetes mellitus (RR =1.40; 95% CI =1.25–1.58, chronic heart disease (RR =1.31; 95% CI =1.15–1.49, hemorrhagic bleb (RR =1.47; 95% CI =1.32–1.63, skin necrosis (RR =1.45; 95% CI =1

  11. Normalization of Activated Partial Thromboplastin Time Correlates with Low Levels of Dabigatran in a Patient with Severe Sepsis

    DEFF Research Database (Denmark)

    Højland, Rikke Ebenhard; Thorup, Stine Borch; Rasmussen, Bodil Steen

    2015-01-01

    treated with dabigatran etexilate was admitted to intensive care unit with severe sepsis and acute renal failure and in need of bilateral lower limp amputation due to ischemia. The patient had severe coagulopathy and was treated with continuous venovenous hemofiltration in attempt to remove dabigatran......The oral anticoagulant dabigatran etexilate can be a challenge when patients need acute surgery. Sepsis and acute renal failure exacerbate the anticoagulant effect. There is no specific reversal agent for dabigatran etexilate, but it can be removed by hemodialysis. We present a case where a patient...

  12. Acute Kidney Injury in Severe Sepsis and Septic Shock in Patients with and without Diabetes Mellitus: A Multicenter Study.

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    Marion Venot

    Full Text Available Whether diabetes mellitus increases the risk of acute kidney injury (AKI during sepsis is controversial.We used a case-control design to compare the frequency of AKI, use of renal replacement therapy (RRT, and renal recovery in patients who had severe sepsis or septic shock with or without diabetes. The data were from the Outcomerea prospective multicenter database, in which 12 French ICUs enrolled patients admitted between January 1997 and June 2009.First, we compared 451 patients with severe sepsis or septic shock and diabetes to 3,277 controls with severe sepsis or septic shock and without diabetes. Then, we compared 318 cases (with diabetes to 746 matched controls (without diabetes. Diabetic patients did not have a higher frequency of AKI (hazard ratio [HR], 1.18; P = 0.05] or RRT (HR, 1.09; P = 0.6. However, at discharge, diabetic patients with severe sepsis or septic shock who experienced acute kidney injury during the ICU stay and were discharged alive more often required RRT (9.5% vs. 4.8%; P = 0.02, had higher serum creatinine values (134 vs. 103 µmoL/L; P<0.001 and had less often recovered a creatinine level less than 1.25 fold the basal creatinine (41.1% vs. 60.5%; P<0.001.In patients with severe sepsis or septic shock, diabetes is not associated with occurrence of AKI or need for RRT but is an independent risk factor for persistent renal dysfunction in patients who experience AKI during their ICU stay.

  13. Positive Effect of SeptimebTM on Mortality Rate in Severe Sepsis: a Novel Non Antibiotic Strategy

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    Leila Kouti

    2012-09-01

    Full Text Available Background:Septimebis a new herbal-derived remedy, recently approved for its potential immunomodulatory effects.Regarding the key role of immune system in the pathogenesis of severe sepsis and lack of any standard treatment for improving survival of these patients;weevaluated the effect of Septimeb -as an adjutant to standard treatment-on inflammatory biomarkers and mortality rates in patients with severe sepsis.Methods:In this multicenter, randomized, single-blind trial, we assigned patients with severe sepsis and Acute Physiology and Chronic Health Evaluation (APACHE II score of more than 20 toreceive standard treatment of severe sepsis (control group or standard treatment plus Septimeb. This group was treated with Septimeb for 14 days then followed up for another14 days. APACHE score, Sequential Organ Failure Assessment (SOFA and Simplified Acute Physiology Score (SAPS were calculated daily. Blood samples were analyzed for interleukin 2 tumor necrosis factor-α, total antioxidant power, platelet growth factor and matrix metalloproteinase 2.Results:A total of 29 patients underwent randomization(13 in control group and 16 in Septimeb group. There was significant difference between the Septimeb and control group in the 14 days mortality rate(18.8% vs. 53.85 respectively, P=0.048. Compared to control group,Septimebwas significantly effective in improving SAPS(P= 0.029, SOFA(P=0.003 and APACHE II(P=0.008 scores. Inflammatory biomarkers didn’t change significantly between the two groups(P>0.05.Conclusion Septimeb reduces mortality rates among patients with severe sepsis and it could be added as a safe adjutant to standard treatment of sepsis.

  14. Drotrecogin alfa (activated in severe sepsis: a systematic review and new cost-effectiveness analysis

    Directory of Open Access Journals (Sweden)

    Brophy James M

    2007-06-01

    Full Text Available Abstract Background Activated drotrecogin alfa (human activated protein C, rhAPC, is produced by recombinant DNA technology, and purports to improve clinical outcomes by counteracting the inflammatory and thrombotic consequences of severe sepsis. Controversy exists around the clinical benefits of this drug and an updated economic study that considers this variability is needed. Methods A systematic literature review was performed using Medline, Embase and the International Network of Agencies for Health Technology Assessment (INAHTA databases to determine efficacy, safety and previous economic studies. Our economic model was populated with systematic estimates of these parameters and with population life tables for longer term survival information. Monte Carlo simulations were used to estimate the incremental cost-effectiveness ratios (ICERs and variance for the decision analytic models. Results Two randomized clinical trials (RCTS of drotrecogin alfa in adults with severe sepsis and 8 previous economic studies were identified. Although associated with statistical heterogeneity, a pooled analysis of the RCTs did not show a statistically significant 28-day mortality benefit for drotrecogin alfa compared to placebo either for all patients (RR: 0.93, 95% CI: 0.69, 1.26 or those at highest risk as measured by APACHE II ≥ 25 (RR: 0.90, 95% CI: 0.54, 1.49. Our economic analysis based on the totality of the available clinical evidence suggests that the cost-effectiveness of drotrecogin alfa is uncertain ( Conclusion The evidence supporting the clinical and economic attractiveness of drotrecogin alfa is not conclusive and further research appears to be indicated.

  15. The effectiveness of synthetic glucocorticoids on the disease course, treatment, and outcome of severe sepsis and septic shock

    Directory of Open Access Journals (Sweden)

    Jelena Dumančić

    2016-03-01

    Full Text Available Due to the high morbidity and mortality rates, severe sepsis and septic shock, present a major global public health problem. The treatment and management of severe sepsis and septic shock is based on a set of international guidelines called the Surviving sepsis campaign (SSC. SSC guidelines suggest the use of hydrocortisone at a dose of 200 mg IV in adult patients with septic shock refractory to fluid resuscitation and vasopressors. During the last century, the importance of cortisol as an essential hormone at times of stress, such as septic shock, has been recognized. Therefore, the therapeutic use of synthetic glucocorticoids has been the subject of many studies during the last few decades but their results are not consistent. Two of the largest studies (CORTICUS and French study showed different effects of synthetic glucocorticoids on mortality rates, but they both showed a significantly shorter duration of septic shock. There is an ongoing large, multicenter, double-blind, randomized study (ADRENAL study and its primary goal is to assess the impact of hydrocortisone therapy on 90-day survival rate. It is expected that the results of this study might provide answers to the questions raised by previously conducted studies. This review will summarize the pathophysiology of sepsis and septic shock and the role of cortisol in its development, and will highlight the most important clinical studies pertaining to synthetic glucocorticoid administration in sepsis and septic shock.

  16. Thyroidectomy for the treatment of Graves’ thyrotoxicosis in thioamide-induced agranulocytosis and sepsis

    Science.gov (United States)

    Cooray, Shamil D; Kulkarni, Jaideep; Borschmann, Michael; Kotowicz, Mark

    2017-01-01

    A 51 year old man presented with sepsis in the setting of thioamide-induced agranulocytosis. Empiric broad-spectrum antibiotics was followed by directed narrow-spectrum antibiotics, and his neutrophil count recovered with support from granulocyte-colony stimulating factor (G-CSF) analogue transfusions. After a brief period of multi-modal therapy for nine days including potassium iodide (Lugol’s iodine), cholestyramine, propanolol and lithium to temper his persisting hyperthyroidism, a total thyroidectomy was performed while thyroid hormone levels remained at thyrotoxic levels. Postoperative recovery was uncomplicated and he was discharged home on thyroxine. There is limited available evidence to guide treatment in this unique cohort of patients who require prompt management to avert impending clinical deterioration. This case report summarises the successful emergent control of thyrotoxicosis in the setting of thioamide-induced agranulocytosis complicated by sepsis, and demonstrates the safe use of multi-modal pharmacological therapies in preparation for total thyroidectomy. Learning points: Thioamide-induced agranulocytosis is an uncommon but potentially life-threatening complication of which all prescribers and patients need to be aware. A multi-modal preoperative pharmacological approach can be successful, even when thioamides are contraindicated, when needing to prepare a thyrotoxic patient for semi-urgent total thyroidectomy. There is not enough evidence to confidently predict the safe timing when considering total thyroidectomy in this patient cohort, and therefore it should be undertaken when attempts have first been made to safely reduce thyroid hormone levels. Thyroid storm is frequently cited as a potentially severe complication of thyroid surgery undertaken in thyrotoxic patients, although the evidence does not demonstrate this as a common occurrence.

  17. Adhesion molecules involved in neutrophil recruitment during sepsis-induced acute kidney injury.

    Science.gov (United States)

    Herter, Jan M; Rossaint, Jan; Spieker, Tilmann; Zarbock, Alexander

    2014-01-01

    Acute kidney injury (AKI) is a common complication in critically ill patients and is associated with high mortality. Recruitment of neutrophils is a hallmark in the pathogenesis of AKI. Although ischemia-reperfusion injury (IRI) is a frequently used research model of AKI, the clinical relevance of IRI-induced AKI is limited. Epidemiologically, sepsis is the prevailing cause of kidney injury. However, it is still unknown whether these distinct entities of AKI share the same pathophysiological mechanisms. This study was initiated to investigate the molecular mechanisms of neutrophil recruitment into the kidney in a murine model of sepsis-induced AKI. By using a flow cytometry-based method, we show that the two β2-integrins Mac-1 and LFA-1 as well as E-selectin and P-selectin are involved in neutrophil recruitment into the kidney after induction of sepsis. The molecular mechanisms of neutrophil recruitment were further investigated using intravital microscopy, demonstrating that blocking one of these four molecules reduces the number of adherent leukocytes. This was accompanied by a renal upregulation of E-selectin, P-selectin and ICAM-1 (the counter-receptor of β2-integrins on endothelial cells) after sepsis induction. We conclude that blocking P-selectin, E-selectin, Mac-1 or LFA-1 protects mice from sepsis-induced AKI.

  18. Cytokine and acute phase protein mRNA expression in liver tissue from pigs with severe sepsis caused by intravenous inoculation of Staphylococcus aureus

    DEFF Research Database (Denmark)

    Nielsen, Ole Lerberg; Olsen, Helle Gerda; Iburg, Tine

    2010-01-01

    The aim was to substantiate previous findings of hepatic dysfunction in a porcine model of Staphylococcus aureus induced severe sepsis. Nine pigs were inoculated intravenously once or twice with 108S. aureus per kilogram body weight and killed 12, 24 and 48 h later. Three pigs served as controls....... Blood was sampled for bacteriology, haematology and clinical pathology. Tissues were collected at necropsy for bacteriology, gene expression analysis and histology. Bacterial counts in blood remained low, decreased in the lungs, liver and spleen, but increased in bone. All infected pigs developed sepsis...... of IL-6, IL-8, IL-1β, and CRP. N o increase could be detected in the IL-1α or TNFα liver-mRNA levels. IL-6, IL-8 and IL-1β expression peaked at 24 hours (2-5 fold compared to the control group). In conclusion, the increased liver cytokine mRNA levels indicate a local hepatic, non-infectious inflammatory...

  19. Prediction about severity and outcome of sepsis by pro-atrial natriuretic peptide and pro-adrenomedullin

    Institute of Scientific and Technical Information of China (English)

    WANG Rui-lan; KANG Fu-xin

    2010-01-01

    Objective:Measurement of biomarkers is a potential approach to early prediction of the risk of mortality in patients with sepsis. The aim of the present study was to evaluate the prognostic value of pro-atrial natriuretic peptide (pro-ANP) and pro-adrenomedullin (proADM) levels in a cohort of medical intensive care patients and to compare it with that of other known biomarkers and physiological scores.Methods:Blood samples of 51 consecutive critically ill patients admitted to the intensive care unit and 53 age-matched healthy control people were evaluated in this prospective study. The prognostic value of pro-ANP and pro-ADM levels was compared with that of acute physiology and chronic health evaluation (APACHE) Ⅱ scores and various biomarkers such as C-reactive protein, interleukin-6 and procalcitonin. Pro-ANP and pro-ADM were detected by a new sandwich immunoassay.Results: On admission, 25 patients had systemic inflammatory response syndrome (SIRS), 12 sepsis, 9 severe sepsis and 5 septic shock. At that time, the median levels (ng/ml) of pro-ANP and pro-ADM were 87.22 and 0.34 respectively in patients with SIRS, 1533.30 and 2.23 in those with sepsis, 1098.73 and 4.57 in those with severe sepsis, and 1933.94 and 8.21 in those with septic shock.With the increasing severity of disease, the levels of pro-ANP and pro-ADM were gradually increased. On admission,the circulating levels of pro-ANP and pro-ADM in patients with sepsis, severe sepsis,or septic shock were significantly higher in non-survivors than in survivors (P<0.05). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the areas under the curve (AUCs) for pro-ANP and pro-ADM were 0.89 and 0.87 respectively, which was similar to the AUCs for procalcitonin and APACHE Ⅱ scores.Conclusion: Pro-ANP and pro-ADM are valuable biomarkers for prediction of severity of septic patients.

  20. [Serum lactate as a biomarker of severe sepsis in children with cancer, neutropenia and fever].

    Science.gov (United States)

    Pacheco-Rosas, Daniel Octavio; Huelgas-Plaza, Ana Celia; Miranda-Novales, María Guadalupe

    2014-01-01

    INTRODUCCIÓN: la neutropenia es una complicación frecuente secundaria a la quimioterapia en los pacientes con cáncer, en quienes la prevalencia de sepsis es de 12.9 a 17.4 % y la letalidad es de 16 %. El objetivo de este estudio fue determinar la utilidad del lactato como biomarcador de sepsis grave en niños con cáncer, fiebre y neutropenia. MÉTODOS: se realizó un estudio de prueba diagnóstica fase II. Se midieron los niveles del lactato al ingreso. Los episodios de neutropenia se clasificaron en tres grupos: I, con sepsis II, sin sepsis; III, pacientes neutropénicos sin fiebre (controles). Se calculó sensibilidad, especificidad, valores predictivos positivo y negativo e índices de verosimilitud. El estándar de oro fue el diagnóstico clínico de sepsis grave.

  1. [Advances in the study of the relationship between autophagy and sepsis-induced lung injury].

    Science.gov (United States)

    Wang, Xingtong; Li, Hengyu; Xia, Zhaofan

    2014-08-01

    Sepsis is one of the most common pathogenetic causes of acute lung injury (ALI), and at present there is still a lack of effective targeted techniques and methods for its prevention and treatment. Autophagy is a homeostatic mecha- nism common to all eukaryotic cells, including adaption to environment, defense against invasion of pathogens, and maintenance of cellular homeostasis. Autophagy is also involved in a variety of lung-related diseases. In septic lung injury, autophagy not only serves to dissipate dysfunctional organelles, but also inhibits the release of inflammatory cytokines. This review aims at eliciting the role of autophagy in sepsis-induced ALI and further exploring the potential targets of autophagy in inhibiting inflammation, in an effort to provide a new perspective for clinical treatment of sepsis-induced ALI.

  2. Negative Modulation of NO for Diaphragmatic Contractile Reduction Induced by Sepsis and Restraint Position

    Institute of Scientific and Technical Information of China (English)

    XIANG Jian; GUAN Su-dong; SONG Xiang-he; WANG Hui-yun; GU Zhen-yong

    2014-01-01

    In practice of forensic medicine, potential disease can be associated with fatal asphyxia in re-straint position. Research has demonstrated that nitric oxide (NO) and nitric oxide synthase (NOS) are plentifully distributed in skeletal muscle, contributing to the regulation of contractile and relaxation. In the current study, respiratory functions, indices of diaphragmatic biomechanical functions ex vivo, as well as NO levels in serum, the expressions of diaphragmatic inducible NOS (iNOS) mRNA, and the effects of L-NNA on contractility of the diaphragm were observed in sepsis induced by cecal ligation and punc-ture (CLP) under the condition of restraint position. The results showed that in the CLP12-18 h rats, respiratory dysfunctions; indices of diaphragmatic biomechanical functions (Pt, +dT/dtmax, -dT/dtmax, CT, Po, force over the full range of the force-frequency relationship and fatigue resistance ) declined progressive-ly; the NO level in serum, and iNOS mRNA expression in the diaphragm increased progressively; force increased significantly at all stimulation frequencies after L-NNA pre-incubation. Restraint position 1 h in CLP12 h rats resulted in severe respiratory dysfunctions after relative stable respiratory functions, almost all the indices of diaphragmatic biomechanical functions declined further, whereas little change took place in NO level in serum and diaphragmatic iNOS mRNA expression; and the effects of L-NNA were lack of statistical significance compared with those of CLP12 h, but differed from CLP18 h group. These results suggest that restraint position and sepsis act together in a synergistic manner to aggravate the great reduction of diaphragmatic contractility via, at least in part, the negative modulation of NO, which may contribute to the pathogenesis of positional asphyxia.

  3. Staphylococcus aureus sepsis induces early renal mitochondrial DNA repair and mitochondrial biogenesis in mice.

    Directory of Open Access Journals (Sweden)

    Raquel R Bartz

    Full Text Available Acute kidney injury (AKI contributes to the high morbidity and mortality of multi-system organ failure in sepsis. However, recovery of renal function after sepsis-induced AKI suggests active repair of energy-producing pathways. Here, we tested the hypothesis in mice that Staphyloccocus aureus sepsis damages mitochondrial DNA (mtDNA in the kidney and activates mtDNA repair and mitochondrial biogenesis. Sepsis was induced in wild-type C57Bl/6J and Cox-8 Gfp-tagged mitochondrial-reporter mice via intraperitoneal fibrin clots embedded with S. aureus. Kidneys from surviving mice were harvested at time zero (control, 24, or 48 hours after infection and evaluated for renal inflammation, oxidative stress markers, mtDNA content, and mitochondrial biogenesis markers, and OGG1 and UDG mitochondrial DNA repair enzymes. We examined the kidneys of the mitochondrial reporter mice for changes in staining density and distribution. S. aureus sepsis induced sharp amplification of renal Tnf, Il-10, and Ngal mRNAs with decreased renal mtDNA content and increased tubular and glomerular cell death and accumulation of protein carbonyls and 8-OHdG. Subsequently, mtDNA repair and mitochondrial biogenesis was evidenced by elevated OGG1 levels and significant increases in NRF-1, NRF-2, and mtTFA expression. Overall, renal mitochondrial mass, tracked by citrate synthase mRNA and protein, increased in parallel with changes in mitochondrial GFP-fluorescence especially in proximal tubules in the renal cortex and medulla. Sub-lethal S. aureus sepsis thus induces widespread renal mitochondrial damage that triggers the induction of the renal mtDNA repair protein, OGG1, and mitochondrial biogenesis as a conspicuous resolution mechanism after systemic bacterial infection.

  4. Does C-reactive protein independently predict mortality in adult community-acquired bacteremia patients with known sepsis severity?

    DEFF Research Database (Denmark)

    Gradel, Kim O; Jensen, Thøger G; Kolmos, Hans J

    2013-01-01

    We evaluated whether sepsis severity and C-reactive protein (CRP) level on admission prognostically corroborated or annulled each other in adult patients with incident community-acquired bacteremia (Funen, Denmark, 2000-2008). We used logistic regression and area under the receiver operating...

  5. Effects of hydroxyethyl starch 130/0.42 vs. Ringer's acetate on cytokine levels in severe sepsis

    DEFF Research Database (Denmark)

    Anthon, C T; Müller, R B; Haase, N

    2017-01-01

    BACKGROUND: The Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial showed increased 90-day mortality with hydroxyethyl starch (HES) 130/0.42 vs. Ringer's acetate. To explore the underlying pathophysiology, we compared early changes in plasma cytokine concentrations between patients res...

  6. 烧伤脓毒症发病机制与防治对策%The pathogenesis and management of severe sepsis after burns

    Institute of Scientific and Technical Information of China (English)

    姚咏明; 盛志勇; 柴家科

    2008-01-01

    Sepsis and septic shock as a result of an invasire infection are challenging problems in extensively burned patients, and frequently end in multiple organ dysfunction syndrome (MODS).It is of great significance to further elucidate the pathogenetic mechanisms, and to seek novel intervention strategies to prevent and treat sepsis/MODS secondary to severe bums. A more complete understanding of the pathogenetic mechanisms of postburn sepsis would certainly elicit a number of potential therapeutic strategies for it. It is our belief that compre hensive clinical measures for management of severe sepsis should include rapid, adequate fluid resuscitation for bum shock, early feeding, effective control of infection, early escharectomy, and reinforcement of organ support. Once bum wound sepsis occurs, prompt removal of infected necrotic tissue is the key procedure to ensure a successful result. Further study is necessary to determine the precise mechanisms of these protective effects and the clinical advantages for postburn sepsis using evidence-based methodology system.

  7. Effect of empirical treatment with moxifloxacin and meropenem vs meropenem on sepsis-related organ dysfunction in patients with severe sepsis: a randomized trial.

    Science.gov (United States)

    Brunkhorst, Frank M; Oppert, Michael; Marx, Gernot; Bloos, Frank; Ludewig, Katrin; Putensen, Christian; Nierhaus, Axel; Jaschinski, Ulrich; Meier-Hellmann, Andreas; Weyland, Andreas; Gründling, Matthias; Moerer, Onnen; Riessen, Reimer; Seibel, Armin; Ragaller, Maximilian; Büchler, Markus W; John, Stefan; Bach, Friedhelm; Spies, Claudia; Reill, Lorenz; Fritz, Harald; Kiehntopf, Michael; Kuhnt, Evelyn; Bogatsch, Holger; Engel, Christoph; Loeffler, Markus; Kollef, Marin H; Reinhart, Konrad; Welte, Tobias

    2012-06-13

    Early appropriate antimicrobial therapy leads to lower mortality rates associated with severe sepsis. The role of empirical combination therapy comprising at least 2 antibiotics of different mechanisms remains controversial. To compare the effect of moxifloxacin and meropenem with the effect of meropenem alone on sepsis-related organ dysfunction. A randomized, open-label, parallel-group trial of 600 patients who fulfilled criteria for severe sepsis or septic shock (n = 298 for monotherapy and n = 302 for combination therapy). The trial was performed at 44 intensive care units in Germany from October 16, 2007, to March 23, 2010. The number of evaluable patients was 273 in the monotherapy group and 278 in the combination therapy group. Intravenous meropenem (1 g every 8 hours) and moxifloxacin (400 mg every 24 hours) or meropenem alone. The intervention was recommended for 7 days and up to a maximum of 14 days after randomization or until discharge from the intensive care unit or death, whichever occurred first. Degree of organ failure (mean of daily total Sequential Organ Failure Assessment [SOFA] scores over 14 days; score range: 0-24 points with higher scores indicating worse organ failure); secondary outcome: 28-day and 90-day all-cause mortality. Survivors were followed up for 90 days. Among 551 evaluable patients, there was no statistically significant difference in mean SOFA score between the meropenem and moxifloxacin group (8.3 points; 95% CI, 7.8-8.8 points) and the meropenem alone group (7.9 points; 95% CI, 7.5-8.4 points) (P = .36). The rates for 28-day and 90-day mortality also were not statistically significantly different. By day 28, there were 66 deaths (23.9%; 95% CI, 19.0%-29.4%) in the combination therapy group compared with 59 deaths (21.9%; 95% CI, 17.1%-27.4%) in the monotherapy group (P = .58). By day 90, there were 96 deaths (35.3%; 95% CI, 29.6%-41.3%) in the combination therapy group compared with 84 deaths (32.1%; 95% CI, 26.5%-38.1%) in

  8. Procalcitonin Clearance for Early Prediction of Survival in Critically Ill Patients with Severe Sepsis

    Directory of Open Access Journals (Sweden)

    Mohd Basri Mat Nor

    2014-01-01

    Full Text Available Introduction. Serum procalcitonin (PCT diagnosed sepsis in critically ill patients; however, its prediction for survival is not well established. We evaluated the prognostic value of dynamic changes of PCT in sepsis patients. Methods. A prospective observational study was conducted in adult ICU. Patients with systemic inflammatory response syndrome (SIRS were recruited. Daily PCT were measured for 3 days. 48 h PCT clearance (PCTc-48 was defined as percentage of baseline PCT minus 48 h PCT over baseline PCT. Results. 95 SIRS patients were enrolled (67 sepsis and 28 noninfectious SIRS. 40% patients in the sepsis group died in hospital. Day 1-PCT was associated with diagnosis of sepsis (AUC 0.65 (95% CI, 0.55 to 0.76 but was not predictive of mortality. In sepsis patients, PCTc-48 was associated with prediction of survival (AUC 0.69 (95% CI, 0.53 to 0.84. Patients with PCTc-48 > 30% were independently associated with survival (HR 2.90 (95% CI 1.22 to 6.90. Conclusions. PCTc-48 is associated with prediction of survival in critically ill patients with sepsis. This could assist clinicians in risk stratification; however, the small sample size, and a single-centre study, may limit the generalisability of the finding. This would benefit from replication in future multicentre study.

  9. Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid.

    Science.gov (United States)

    Fisher, Bernard J; Kraskauskas, Donatas; Martin, Erika J; Farkas, Daniela; Wegelin, Jacob A; Brophy, Donald; Ward, Kevin R; Voelkel, Norbert F; Fowler, Alpha A; Natarajan, Ramesh

    2012-07-01

    Bacterial infections of the lungs and abdomen are among the most common causes of sepsis. Abdominal peritonitis often results in acute lung injury (ALI). Recent reports demonstrate a potential benefit of parenteral vitamin C [ascorbic acid (AscA)] in the pathogenesis of sepsis. Therefore we examined the mechanisms of vitamin C supplementation in the setting of abdominal peritonitis-mediated ALI. We hypothesized that vitamin C supplementation would protect lungs by restoring alveolar epithelial barrier integrity and preventing sepsis-associated coagulopathy. Male C57BL/6 mice were intraperitoneally injected with a fecal stem solution to induce abdominal peritonitis (FIP) 30 min prior to receiving either AscA (200 mg/kg) or dehydroascorbic acid (200 mg/kg). Variables examined included survival, extent of ALI, pulmonary inflammatory markers (myeloperoxidase, chemokines), bronchoalveolar epithelial permeability, alveolar fluid clearance, epithelial ion channel, and pump expression (aquaporin 5, cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, and Na(+)-K(+)-ATPase), tight junction protein expression (claudins, occludins, zona occludens), cytoskeletal rearrangements (F-actin polymerization), and coagulation parameters (thromboelastography, pro- and anticoagulants, fibrinolysis mediators) of septic blood. FIP-mediated ALI was characterized by compromised lung epithelial permeability, reduced alveolar fluid clearance, pulmonary inflammation and neutrophil sequestration, coagulation abnormalities, and increased mortality. Parenteral vitamin C infusion protected mice from the deleterious consequences of sepsis by multiple mechanisms, including attenuation of the proinflammatory response, enhancement of epithelial barrier function, increasing alveolar fluid clearance, and prevention of sepsis-associated coagulation abnormalities. Parenteral vitamin C may potentially have a role in the management of sepsis and ALI associated with sepsis.

  10. Adjustment of Dysregulated Ceramide Metabolism in a Murine Model of Sepsis-Induced Cardiac Dysfunction.

    Science.gov (United States)

    Chung, Ha-Yeun; Kollmey, Anna S; Schrepper, Andrea; Kohl, Matthias; Bläss, Markus F; Stehr, Sebastian N; Lupp, Amelie; Gräler, Markus H; Claus, Ralf A

    2017-04-15

    Cardiac dysfunction, in particular of the left ventricle, is a common and early event in sepsis, and is strongly associated with an increase in patients' mortality. Acid sphingomyelinase (SMPD1)-the principal regulator for rapid and transient generation of the lipid mediator ceramide-is involved in both the regulation of host response in sepsis as well as in the pathogenesis of chronic heart failure. This study determined the degree and the potential role to which SMPD1 and its modulation affect sepsis-induced cardiomyopathy using both genetically deficient and pharmacologically-treated animals in a polymicrobial sepsis model. As surrogate parameters of sepsis-induced cardiomyopathy, cardiac function, markers of oxidative stress as well as troponin I levels were found to be improved in desipramine-treated animals, desipramine being an inhibitor of ceramide formation. Additionally, ceramide formation in cardiac tissue was dysregulated in SMPD1(+/+) as well as SMPD1(-/-) animals, whereas desipramine pretreatment resulted in stable, but increased ceramide content during host response. This was a result of elevated de novo synthesis. Strikingly, desipramine treatment led to significantly improved levels of surrogate markers. Furthermore, similar results in desipramine-pretreated SMPD1(-/-) littermates suggest an SMPD1-independent pathway. Finally, a pattern of differentially expressed transcripts important for regulation of apoptosis as well as antioxidative and cytokine response supports the concept that desipramine modulates ceramide formation, resulting in beneficial myocardial effects. We describe a novel, protective role of desipramine during sepsis-induced cardiac dysfunction that controls ceramide content. In addition, it may be possible to modulate cardiac function during host response by pre-conditioning with the Food and Drug Administration (FDA)-approved drug desipramine.

  11. PPARβ/δ regulates glucocorticoid- and sepsis-induced FOXO1 activation and muscle wasting.

    Directory of Open Access Journals (Sweden)

    Estibaliz Castillero

    Full Text Available FOXO1 is involved in glucocorticoid- and sepsis-induced muscle wasting, in part reflecting regulation of atrogin-1 and MuRF1. Mechanisms influencing FOXO1 expression in muscle wasting are poorly understood. We hypothesized that the transcription factor peroxisome proliferator-activated receptor β/δ (PPARβ/δ upregulates muscle FOXO1 expression and activity with a downstream upregulation of atrogin-1 and MuRF1 expression during sepsis and glucocorticoid treatment and that inhibition of PPARβ/δ activity can prevent muscle wasting. We found that activation of PPARβ/δ in cultured myotubes increased FOXO1 activity, atrogin-1 and MuRF1 expression, protein degradation and myotube atrophy. Treatment of myotubes with dexamethasone increased PPARβ/δ expression and activity. Dexamethasone-induced FOXO1 activation and atrogin-1 and MuRF1 expression, protein degradation, and myotube atrophy were inhibited by PPARβ/δ blocker or siRNA. Importantly, muscle wasting induced in rats by dexamethasone or sepsis was prevented by treatment with a PPARβ/δ inhibitor. The present results suggest that PPARβ/δ regulates FOXO1 activation in glucocorticoid- and sepsis-induced muscle wasting and that treatment with a PPARβ/δ inhibitor may ameliorate loss of muscle mass in these conditions.

  12. Global end-diastolic volume increases to maintain fluid responsiveness in sepsis-induced systolic dysfunction

    NARCIS (Netherlands)

    R.J. Trof (R.); I. Danad (Ibrahim); A.B.J. Groeneveld (Johan)

    2013-01-01

    textabstractBackground: Sepsis-induced cardiac dysfunction may limit fluid responsiveness and the mechanism thereof remains unclear. Since cardiac function may affect the relative value of cardiac filling pressures, such as the recommended central venous pressure (CVP), versus filling volumes in gui

  13. Effect of sepsis on behavioral changes on the ketamine-induced animal model of schizophrenia.

    Science.gov (United States)

    Comim, Clarissa M; Silva, Napoleão C; Patrício, Janini J; Palmas, Daphne; Mendonça, Bruna P; Bittencourt, Mariana O; Cassol-Jr, Omar J; Barichello, Tatiana; Zugno, Alexandra I; Quevedo, João; Dal-Pizzol, Felipe

    2015-04-15

    This study aimed to evaluate the effect of sepsis on behavioral changes on the ketamine-induced animal model of schizophrenia. Male Wistar rats underwent Cecal Ligation and Perporation (CLP) with "basic support" or were sham-operated. After 30 days, the animals were submitted to a model of schizophrenia by injection of Ketamine. The behavior tests were performed after 30 min of the injection of Ketamine or saline. Ketamine in doses of 15 and 25mg/kg increased locomotor activity, latency to first contact in the social interaction and stereotyped behavior. Some changes caused by sepsis may be associated with a predisposition to develop schizophrenia in the animal model.

  14. A severe, late reaction to radiological contrast media mimicking a sepsis syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Burton, P.R.; Jarmolowski, E.; Raineri, F.; Buist, M.D.; Wriedt, H.R. [Dandenong Hospital, Dandenong, VIC (Australia). Intensive Care Unit

    1999-08-01

    An unusual, severe delayed reaction to non-ionic intravenous contrast media was observed. A 44-year-old man underwent a computed tomography scan with non-ionic contrast media. Four hours later the patient collapsed with hypotension and cardiovascular shock. Aggressive management (including inotropic support and fluid resuscitation) was instituted in the intensive care unit. Rigorous imaging and biochemical and microbiological investigation failed to identify a source of this man`s circulatory collapse. A rapid recovery ensued and at 3 months follow-up the patient was suffering no residual effects from this event. To our knowledge, this is only the second report of a severe delayed reaction to radiological contrast media and the first that manifested as a prolonged hypotensive syndrome. Despite the introduction of non-ionic low osmolar radiological contrast media (NIM), the incidence of adverse reactions to these agents remains at between 3 and 12%. Most of these reactions are acute, self-limiting events (nausea, vomiting, urticaria, diarrhoea) and no treatment is required. The mortality rate of these adverse reactions has been quoted at 0.0020.009% of all procedures. Most of these severe reactions are acute anaphylactoid events manifested by hypotension and bronchospasm. Delayed adverse reactions to NIM have been reported to occur with a frequency of between 8.0 and 27.1%. These reactions are almost uniformly self-limiting and non-life threatening, requiring minimal intervention. We report an unusual late adverse reaction to NIM, which presented with many of the features of a severe sepsis syndrome. Non-ionic low osmolar radiological contrast media has the capacity to cause severe delayed reactions in rare instances, but the pathophysiological mechanisms of these reactions are poorly understood and, therefore, diagnosis and management of this clinical situation presented many difficulties. Copyright (1999) Blackwell Science Pty Ltd 6 refs.

  15. USA300 Methicillin-Resistant Staphylococcus aureus Bacteremia and the Risk of Severe Sepsis: Is USA300 MRSA Associated with More Severe Infections?

    Science.gov (United States)

    Kreisel, Kristen M.; Stine, O. Colin; Johnson, J. Kristie; Perencevich, Eli N.; Shardell, Michelle D.; Lesse, Alan J.; Gordin, Fred M.; Climo, Michael W.; Roghmann, Mary-Claire

    2011-01-01

    Objective USA300 methicillin-resistant Staphylococcus aureus (MRSA) is increasing as a cause of severe community-associated bacteremic infections. We assessed severe sepsis in response to infection in patients with USA300 MRSA compared to non-USA300 MRSA bacteremia. Methods A cohort study was conducted from 1997–2008 comparing sepsis in response to infection in 271 patients with MRSA bacteremia from four VA hospitals. Results Sixty-seven (25%) patients with MRSA bacteremia were USA300 MRSA; 204 (75%) were non-USA300 MRSA. The proportion of MRSA bacteremia caused by USA300 MRSA increased over time (χ2 p<0.0001). Adjusting for age and nosocomial infection, patients with USA300 MRSA bacteremia were more likely to have severe sepsis or septic shock in response to infection than patients with non-USA300 MRSA bacteremia (adjusted Relative Risk=1.82; 95% CI: 1.16–2.87; p=0.01). Conclusions This suggests that patients with USA300 MRSA are more likely to develop severe sepsis in response to their infection, which could be due to host or bacterial differences. PMID:21558047

  16. Alert cell strategy in SIRS-induced vasculitis: sepsis and endothelial cells.

    Science.gov (United States)

    Matsuda, Naoyuki

    2016-01-01

    Sepsis refers to systemic inflammatory response syndrome and organ failure resulting from infection. Inflammatory receptors (e.g., Toll-like receptors and nucleotide oligomerization domain) recognize bacterial components as inflammatory ligands. These are expressed not only in leukocytes but also in major organs and vascular endothelial cells. "Alert cell" is defined as the cell that expresses the inflammatory receptor and intracellular signaling system to produce inflammatory mediators such as inflammatory cytokines, chemokines, nitric oxide, and prostanoids in organs and the vasculature. NF-κB and AP-1, which are the transcriptional factors of these inflammatory molecules, are important regulators of multiple organ failure in sepsis and systemic inflammation. The vascular endothelial injury would induce multiple organ failure as tissue ischemia and organ death. Drug discovery targeted at alert cells holds a promise for therapy of inflammation including sepsis.

  17. Blood glucose control in patients with severe sepsis and septic shock

    OpenAIRE

    Hirasawa, Hiroyuki; Shigeto ODA; Nakamura, Masataka

    2009-01-01

    The main pathophysiological feature of sepsis is the uncontrollable activation of both pro- and anti-inflammatory responses arising from the overwhelming production of mediators such as pro- and anti-inflammatory cytokines. Such an uncontrollable inflammatory response would cause many kinds of metabolic derangements. One such metabolic derangement is hyperglycemia. Accordingly, control of hyperglycemia in sepsis is considered to be a very effective therapeutic approach. However, despite the i...

  18. Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats

    NARCIS (Netherlands)

    L. Zafrani (Lara); B. Ergin (Bulent); Kapucu, A. (Aysegul); C. Ince (Can)

    2016-01-01

    textabstractBackground: The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Methods: Twenty-seven Wistar

  19. Disseminated Intravascular Coagulation in a Novel Porcine Model of Severe Staphylococcus aureus Sepsis Fulfills Human Clinical Criteria

    DEFF Research Database (Denmark)

    Soerensen, K. E.; Olsen, H. G.; Skovgaard, Kerstin

    2013-01-01

    Summary Sepsis is a common and often fatal complication in human patients in intensive care units. Relevant and well characterized animal models of sepsis may provide valuable information on pathophysiological mechanisms and be a mean of testing new therapeutic strategies. Large animal models...... of Staphylococcus aureus sepsis are rare, even though S. aureus increasingly affects human patients. Sepsis changes the haemostatic balance and leads to endothelial cell (EC) activation, coagulopathy and, in severe cases, disseminated intravascular coagulation (DIC). The aim of this study was to characterize...

  20. Early detection of severe sepsis in the emergency room: diagnostic value of plasma C-reactive protein, procalcitonin, and interleukin-6.

    Science.gov (United States)

    Uusitalo-Seppälä, Raija; Koskinen, Pertti; Leino, Aila; Peuravuori, Heikki; Vahlberg, Tero; Rintala, Esa M

    2011-12-01

    To determine the diagnostic values of plasma C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) using an electrochemiluminescence immunoassay (ECLIA) method (Roche Diagnostics GmbH, Mannheim, Germany) to identify severe sepsis in an emergency room (ER) setting. This was a single-centre prospective follow-up study of 539 consecutive adult patients admitted to the ER with suspected infection. Blood samples were taken concurrently with blood cultures at admission. Patients were divided into 5 groups on the basis of systemic inflammatory response syndrome (SIRS) criteria, documentation of bacterial infection, and organ dysfunction. Fifty-nine patients with no SIRS or bacterial infection, 68 patients with bacterial infection but no SIRS, 54 patients with SIRS but no bacterial infection, 309 patients with sepsis (SIRS and bacterial infection), and 49 patients with severe sepsis (sepsis and organ failure) were evaluated. In a logistic regression model, the odds ratio (OR) for PCT was 1.58 (95% confidence interval (CI) 1.37-1.82, p sepsis, but the difference in AUC was not significant between PCT and IL-6. In multivariate logistic regression analysis, after adjusting for confounders, PCT and IL-6 remained significant independent predictors of severe sepsis. PCT and IL-6 proved superior to CRP in detecting patients with severe sepsis. The findings thus support the use of either PCT or IL-6 as an early tool to diagnose severe sepsis. The automatic ECLIA method allows even night-shift measurements.

  1. Prognostic value of ventricular diastolic dysfunction in patients with severe sepsis and septic shock

    Science.gov (United States)

    Rolando, Gustavo; Espinoza, Emilio Daniel Valenzuela; Avid, Emelin; Welsh, Sebastián; Pozo, Juan Del; Vazquez, Alejandro Risso; Arzani, Yanina; Masevicius, Fabio Daniel; Dubin, Arnaldo

    2015-01-01

    Objectives To evaluate the prevalence of myocardial dysfunction and its prognostic value in patients with severe sepsis and septic shock. Methods Adult septic patients admitted to an intensive care unit were prospectively studied using transthoracic echocardiography within the first 48 hours after admission and thereafter on the 7th-10th days. Echocardiographic variables of biventricular function, including the E/e' ratio, were compared between survivors and non-survivors. Results A total of 99 echocardiograms (53 at admission and 46 between days 7 - 10) were performed on 53 patients with a mean age of 74 (SD 13) years. Systolic and diastolic dysfunction was present in 14 (26%) and 42 (83%) patients, respectively, and both types of dysfunction were present in 12 (23%) patients. The E/e' ratio, an index of diastolic dysfunction, was the best predictor of hospital mortality according to the area under the ROC curve (0.71) and was an independent predictor of outcome, as determined by multivariate analysis (OR = 1.36 [1.05 - 1.76], p = 0.02). Conclusion In septic patients admitted to an intensive care unit, echocardiographic systolic dysfunction is not associated with increased mortality. In contrast, diastolic dysfunction is an independent predictor of outcome. PMID:26761470

  2. Clinical Practice Guidelines for Severe Sepsis Treatment. Guía de práctica clínica para el tratamiento de la sepsis grave.

    Directory of Open Access Journals (Sweden)

    José Noel Marrero.

    2009-03-01

    Full Text Available Clinical Practice Guidelines for Severe Sepsis Treatment. It is a syndrome of inflammatory systemic response caused by documented infection (clinical and/or microbiological, associated with organic dysfunction (respiratory, renal, hepatic, cardiovascular, haematological and neurological, hypotension or hypoperfusion. This document includes a review and update of the concept, risk factors, diagnosis and treatment. It includes assessment guidelines focused on the most important aspects to be accomplished.Guía de práctica clínica para el tratamiento de la sepsis grave. Síndrome de respuesta inflamatoria sistémica debido a infección documentada (clínica y/o microbiológicamente, asociada a disfunción de órganos (respiratorio, renal, hepático, cardiovascular, hematológico y neurológico, hipotensión o hipoperfusión. El documento revisa y actualiza el concepto, factores de riesgo, diagnóstico y tratamiento. Concluye con su guía de evaluación, enfocada en los aspectos más importantes a cumplir.

  3. Consecutive thrombelastography clot strength profiles in patients with severe sepsis and their association with 28-day mortality

    DEFF Research Database (Denmark)

    Ostrowski, Sisse R; Windeløv, Nis A; Ibsen, Michael

    2013-01-01

    sepsis admitted to the intensive care unit (ICU). Clinical scores/variables, infection, TEG, biochemistry, therapy, and overall mortality were recorded. RESULTS: Fifty patients (60% men, median age 62 years, 28-day mortality 24%) were included. At admission, 22%, 48%, and 30% had a hypocoagulable......PURPOSE: The aim of this study was to assess associations between consecutive thrombelastography (TEG) profiles and standard coagulation tests and disease severity and mortality in patients with severe sepsis. MATERIALS AND METHODS: This was a prospective observational study of adults with severe......, normocoagulable, and hypercoagulable TEG clot strength (maximum amplitude [MA]), respectively. Hypocoagulable patients had higher Sequential Organ Failure Assessment and disseminated intravascular coagulation scores compared with hypercoagulable patients and higher 28-day mortality compared with normocoagulable...

  4. Antibody to endotoxin core glycolipid reverses reticuloendothelial system depression in an animal model of severe sepsis and surgical injury

    Energy Technology Data Exchange (ETDEWEB)

    Aldridge, M.C.; Chadwick, S.J.; Cheslyn-Curtis, S.; Rapson, N.; Dudley, H.A.

    1987-10-01

    To study the effect of severe sepsis on the function of the reticuloendothelial system (RES) we have measured the clearance kinetics and organ distribution of both low-dose technetium tin colloid (TTC) and /sup 75/selenomethionine-labelled E. coli in rabbits 24 hours after either sham laparotomy or appendix devascularization. Sepsis resulted in similar delayed blood clearance and reduced liver (Kupffer cell) uptake of both TTC and E. coli. To investigate the ability of polyclonal antibody to E. coli-J-5 (core glycolipid) to improve RES function in the same model of sepsis, further animals were pretreated with either core glycolipid antibody or control serum (10 ml IV) 2 hours before induction of sepsis. TTC clearance kinetics were determined 24 hours later. Antibody pretreated animals showed: a reduced incidence of bacteremia; normalization of the rate of blood clearance and liver uptake of TTC; and a 'rebound' increase in splenic uptake of TTC. We conclude that antibody to E. coli-J-5 enhances bacterial clearance by the RES.

  5. The accuracy of pulse oximetry in emergency department patients with severe sepsis and septic shock: a retrospective cohort study

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    Lord Jason A

    2010-05-01

    Full Text Available Abstract Background Pulse oximetry is routinely used to continuously and noninvasively monitor arterial oxygen saturation (SaO2 in critically ill patients. Although pulse oximeter oxygen saturation (SpO2 has been studied in several patient populations, including the critically ill, its accuracy has never been studied in emergency department (ED patients with severe sepsis and septic shock. Sepsis results in characteristic microcirculatory derangements that could theoretically affect pulse oximeter accuracy. The purposes of the present study were twofold: 1 to determine the accuracy of pulse oximetry relative to SaO2 obtained from ABG in ED patients with severe sepsis and septic shock, and 2 to assess the impact of specific physiologic factors on this accuracy. Methods This analysis consisted of a retrospective cohort of 88 consecutive ED patients with severe sepsis who had a simultaneous arterial blood gas and an SpO2 value recorded. Adult ICU patients that were admitted from any Calgary Health Region adult ED with a pre-specified, sepsis-related admission diagnosis between October 1, 2005 and September 30, 2006, were identified. Accuracy (SpO2 - SaO2 was analyzed by the method of Bland and Altman. The effects of hypoxemia, acidosis, hyperlactatemia, anemia, and the use of vasoactive drugs on bias were determined. Results The cohort consisted of 88 subjects, with a mean age of 57 years (19 - 89. The mean difference (SpO2 - SaO2 was 2.75% and the standard deviation of the differences was 3.1%. Subgroup analysis demonstrated that hypoxemia (SaO2 2 was in the 90-93% range the SaO2 was Conclusions Pulse oximetry overestimates ABG-determined SaO2 by a mean of 2.75% in emergency department patients with severe sepsis and septic shock. This overestimation is exacerbated by the presence of hypoxemia. When SaO2 needs to be determined with a high degree of accuracy arterial blood gases are recommended.

  6. Heat Shock Protein A12B Protects Vascular Endothelial Cells Against Sepsis-Induced Acute Lung Injury in Mice.

    Science.gov (United States)

    Chen, Yi; Wang, Lei; Kang, Qiuxiang; Zhang, Xu; Yu, Guifang; Wan, Xiaojian; Wang, Jiafeng; Zhu, Keming

    2017-01-01

    Pulmonary endothelial injury is a critical process in the pathogenesis of acute lung injury (ALI) during sepsis. Heat shock protein A12B (HSPA12B) is mainly expressed in endothelial cells and protects against several harmful factors. However, the effects of HSPA12B in sepsis-induced ALI and its potential mechanisms of action remain unclear. For in vivo experiments, C57BL/6 mice were randomly divided into four groups (n=15): a sham operation group, a cecal ligation and puncture (CLP) group, a HSPA12B siRNA-CLP group and a negative control (NC) siRNA-CLP group. The mice were treated by nasal inhalation of 2-OMe-modified HSPA12B siRNA or NC siRNA. Sepsis was induced by CLP. Samples were harvested 24 and 48 hours post-CLP surgery. Pathological changes and scoring of lung tissue samples were monitored using hematoxylin and eosin staining. Levels of pro-inflammatory cytokines (e.g., interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6) and myeloperoxidase activity in bronchoalveolar lavage fluid were analyzed by ELISA. Pulmonary edema was assessed using a wet-to-dry weight ratio. Neutrophils and alveolar macrophages were counted using flow cytometry. Pulmonary endothelial cell apoptosis was detected by TUNEL staining. Expression levels of MAPK family signaling molecules and caspase-3 were measured by Western blot analysis. In addition, 7-day survival was recorded. For in vitro experiments, human umbilical vein endothelial cells were pre-transfected with HSPA12B siRNA or pIRES2-EGFP-HSPA12B-Flag plasmid and treated with lipopolysaccharide; subsequently, the expression levels of MAPK family signaling molecules and caspase-3 were measured by Western blotting. Nasal inhalation of nano-polymer-encapsulated HSPA12B siRNA specifically downregulated mRNA and protein expression levels of HSPA12B in lung tissues. The administration of HSPA12B siRNA aggravated lung pathological injury, upregulated pro-inflammatory cytokine (e.g., IL-1β, TNF-α, and IL-6) expression, and

  7. Platelets induce apoptosis during sepsis in a contact-dependent manner that is inhibited by GPIIb/IIIa blockade.

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    Matthew Sharron

    Full Text Available PURPOSE: End-organ apoptosis is well-described in progressive sepsis and Multiple Organ Dysfunction Syndrome (MODS, especially where platelets accumulate (e.g. spleen and lung. We previously reported an acute sepsis-induced cytotoxic platelet phenotype expressing serine protease granzyme B. We now aim to define the site(s of and mechanism(s by which platelet granzyme B induces end-organ apoptosis in sepsis. METHODS: End-organ apoptosis in murine sepsis (i.e. polymicrobial peritonitis was analyzed by immunohistochemistry. Platelet cytotoxicity was measured by flow cytometry following 90 minute ex vivo co-incubation with healthy murine splenocytes. Sepsis progression was measured via validated preclinical murine sepsis score. MEASUREMENTS AND MAIN RESULTS: There was evident apoptosis in spleen, lung, and kidney sections from septic wild type mice. In contrast, there was a lack of TUNEL staining in spleens and lungs from septic granzyme B null mice and these mice survived longer following induction of sepsis than wild type mice. In co-incubation experiments, physical separation of septic platelets from splenocytes by a semi-permeable membrane reduced splenocyte apoptosis to a rate indistinguishable from negative controls. Chemical separation by the platelet GPIIb/IIIa receptor inhibitor eptifibatide decreased apoptosis by 66.6±10.6% (p = 0.008. Mice treated with eptifibatide in vivo survived longer following induction of sepsis than vehicle control mice. CONCLUSIONS: In sepsis, platelet granzyme B-mediated apoptosis occurs in spleen and lung, and absence of granzyme B slows sepsis progression. This process proceeds in a contact-dependent manner that is inhibited ex vivo and in vivo by the platelet GPIIb/IIIa receptor inhibitor eptifibatide. The GPIIb/IIIa inhibitors and other classes of anti-platelet drugs may be protective in sepsis.

  8. Dietary Omega-3 Fatty Acids Increase Survival and Decrease Bacterial Load in Mice Subjected to Staphylococcus aureus-Induced Sepsis.

    Science.gov (United States)

    Svahn, Sara L; Ulleryd, Marcus A; Grahnemo, Louise; Ståhlman, Marcus; Borén, Jan; Nilsson, Staffan; Jansson, John-Olov; Johansson, Maria E

    2016-04-01

    Sepsis caused by Staphylococcus aureus is increasing in incidence. With the alarming use of antibiotics,S. aureus is prone to become methicillin resistant. Antibiotics are the only widely used pharmacological treatment for sepsis. Interestingly, mice fed high-fat diet (HFD) rich in polyunsaturated fatty acids have better survival of S. aureus-induced sepsis than mice fed HFD rich in saturated fatty acids (HFD-S). To investigate what component of polyunsaturated fatty acids, i.e., omega-3 or omega-6 fatty acids, exerts beneficial effects on the survival of S. aureus-induced sepsis, mice were fed HFD rich in omega-3 or omega-6 fatty acids for 8 weeks prior to inoculation with S. aureus Further, mice fed HFD-S were treated with omega-3 fatty acid metabolites known as resolvins. Mice fed HFD rich in omega-3 fatty acids had increased survival and decreased bacterial loads compared to those for mice fed HFD-S after S. aureus-induced sepsis. Furthermore, the bacterial load was decreased in resolvin-treated mice fed HFD-S after S. aureus-induced sepsis compared with that in mice treated with vehicle. Dietary omega-3 fatty acids increase the survival of S. aureus-induced sepsis by reversing the deleterious effect of HFD-S on mouse survival.

  9. A retrospective comparison of helicopter transport versus ground transport in patients with severe sepsis and septic shock.

    Science.gov (United States)

    Kashyap, Rahul; Anderson, Peter W; Vakil, Abhay; Russi, Christopher S; Cartin-Ceba, Rodrigo

    2016-12-01

    Helicopter emergency medical services (HEMS) extend the reach of a tertiary care center significantly. However, its role in septic patients is unclear. Our study was performed to clarify the role of HEMS in severe sepsis and septic shock. This is a single-center retrospective cohort study. This study was performed at Mayo Clinic, Rochester, MN, in years 2007-2009. This study included a total of 181 consecutive adult patients admitted to the medical intensive care unit meeting criteria for severe sepsis or septic shock within 24 h of admission and transported from an acute care facility by a helicopter or ground ambulance. The primary predictive variable was the mode of transport. Multiple demographic, clinical, and treatment variables were collected and analyzed with univariate analysis followed by multivariate analysis. The patients transported by HEMS had a significantly faster median transport time (1.3 versus 1.7 h, p ground. Distance traveled was not an independent predictor of hospital mortality on multivariate analysis. HEMS transport is associated with faster transport time, carries sicker patients, and is associated with higher hospital mortality compared with ground ambulance services for patients with severe sepsis or septic shock.

  10. The Pro12Ala Polymorphism of PPAR-γ Gene Is Associated with Sepsis Disease Severity and Outcome in Chinese Han Population.

    Science.gov (United States)

    Ma, Guoda; Wang, Haiyang; Mo, Guixi; Cui, Lili; Li, You; Shao, Yiming; Liu, Xin; Xie, Yuliu; Li, Jia; Fu, Jiawu; Tao, Hua; Zhao, Bin; Zhang, Liangqing; Li, Keshen

    2014-01-01

    Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a ligand-binding nuclear receptor, and its activation plays a prominent role in regulating the inflammatory response. Therefore, PPAR-γ has been suggested as a candidate gene for sepsis. In the present study, we investigated the association between the Pro12Ala polymorphism of PPAR-γ and sepsis in a Han Chinese population. A total of 308 patients with sepsis and 345 healthy controls were enrolled in this study. Genotyping was performed using the polymerase chain reaction-ligation detection reaction (PCR-LDR) method. No significant differences were detected in the allele and genotype distributions of the PPAR-γ Pro12Ala SNP between septic patients and controls (P = 0.622 for genotype; P = 0.629 for allele). However, stratification by subtypes (sepsis, septic shock, and severe sepsis) revealed a statistically significant difference in the frequency of the Ala allele and Ala-carrier genotype between the patients with the sepsis subtype and the healthy controls (P = 0.014 for allele and P = 0.012, for genotype). Moreover, significant differences were found in the frequency of the Ala allele and genotype between the sepsis survivors and nonsurvivors (all P = 0.002). In the survivors, the PPAR-γ Pro12Ala genotype was significantly associated with decreased disease severity and recovery time (all P < 0.001). Thus, genetic polymorphism is thought to play a role in the development and outcome of sepsis.

  11. Matrix metaHoproteinase-8 inhibitors mitigate sepsis-induced myocardial injury in rats

    Institute of Scientific and Technical Information of China (English)

    Zhou Xiaorui; Lu Jiakai; Chen Dong; Wang Wei; Cai Qing; Li Tongxun; Zhang Jinglan

    2014-01-01

    Background Sepsis-induced myocardial injury (SIMI) is caused by a variety of mechanisms.The aim of the study is to investigate the effects of metalloproteinase-8 (MMP-8) on SIMI and its mechanisms in rats.Methods Forty male Sprague Dawley rats were randomly divided into four groups:MMP-8 inhibitor (M8I),dexamethasone (DEX),sepsis,and sham groups.The sepsis model was established by cecal ligation and puncture (CLP).Rats in the M8I group immediately received an intraperitoneal injection of M8I (0.1 mg/kg) after CLP.Rats in the DEX group immediately received an intraperitoneal (IP) injection of DEX (2 mg/kg).Rats in the sepsis and sham groups received intraperitoneal injections of normal saline.Rats were sacrificed 12 hours after CLP.Paraffin sections were stained with hematoxylin and eosin to observe the myocardium.The myocardial ultrastructure was observed with transmission electron microscopy.MMP-8,tumor necrosis factor-α (TNF-α),and interleukin-1β (IL-1β) were detected by immunohistochemistry.The expression of MMP-8 was measured by Western blotting.TNF-α and IL-1β levels in serum and myocardial tissue were determined by enzyme-linked immunosorbent assay.Results Compared with the sham group,the myocardium in the sepsis group was seriously injured.MMP-8,TNF-α and IL-1β expression was higher in the sepsis group than in the sham group.Treatment with M8I or DEX,however,attenuated sepsis induced histopathological changes in the heart,and was associated with significant reductions in serum and myocardial levels of TNF-α and IL-1β (P <0.05).M8I significantly inhibited MMP-8 expression in myocardial tissue (P <0.05).In addition,treatment with DEX was not associated with a change in myocardial levels of MMP-8 (P >0.05).Conclusion MMP-8 inhibitor attenuated myocardial injury in septic rats,which might be related to reduced expression of TNF-α and IL-1β.

  12. Influence of endotoxin-induced sepsis on the requirements of propofol-fentanyl infusion rate in pigs

    DEFF Research Database (Denmark)

    Bollen, Peter; Nielsen, Bjørn J; Toft, Palle

    2007-01-01

    Endotoxin-induced sepsis in pigs is a recognized experimental model for the study of human septic shock. Generally, pigs are brought into general anaesthesia before sepsis is induced. It is our experience that drug dosages of propofol and fentanyl need to be reduced during endotoxin-induced sepsis......, in order to prevent respiratory and cardiovascular depression, but the scientific evidence for this observation is lacking. Therefore, we measured the consumption of propofol and fentanyl at equal level of anaesthesia in pigs with (n = 5) and without (n = 5) endotoxin-induced sepsis, using the cerebral...... state index (CSI) as measure of anaesthetic depth. Infusion rates of propofol (P propofol and 12 microg/kg/hr (S.D. 2) for fentanyl, whereas...

  13. StO₂ guided early resuscitation in subjects with severe sepsis or septic shock: a pilot randomised trial.

    Science.gov (United States)

    Nardi, Olivier; Polito, Andrea; Aboab, Jérôme; Colin, Gwenhael; Maxime, Virginie; Clair, Bernard; Friedman, Diane; Orlikowski, David; Sharshar, Tarek; Annane, Djillali

    2013-06-01

    The scientific community has agreed upon developing accurate monitoring of tissue perfusion and oxygenation to improve the management of subjects with sepsis. This pilot study aimed to investigate the feasibility of targeting tissue oxygen saturation (StO₂) in addition to the currently recommended resuscitation goals, central venous pressure, mean arterial pressure and central venous oxygen saturation, in patients with severe sepsis or septic shock. A pilot, single-centre, randomised, non-blinded trial recruited 30 subjects with severe sepsis upon intensive care unit admission at an academic medical centre in France. Subjects were randomly assigned to a 6 h resuscitation strategy following the Surviving Sepsis Campaign guidelines with (experimental) or without (control) StO₂. StO₂ was measured over several muscles (masseter, deltoid and pectoral or thenar muscles), and a StO₂ above 80 % over at least 2 muscles was the therapeutic goal. The primary outcome was evaluated as follows: 7-day mortality or worsening of SOFA score between day 7 and study onset, i.e., DSOFA > 0). Thirty subjects were included in the study over a period of 40 weeks. Fifteen subjects were included in each group. Monitoring of StO₂ over three areas was performed in the experimental group. However, measures over the pectoral muscle provided poor results. At study day 7, there were 5/15 (33.3 %) subjects who died or had a DSOFA > 0 in the experimental arm and 4/15 (26.6 %) who died or had a DSOFA > 0 in the control arm (p = 1.00). This pilot study was the first randomised controlled trial using an algorithm derived from the SSC recommendations, which included StO₂ as a treatment goal. However, the protocol showed no clear trend for or against targeting StO₂.

  14. An increase in mean platelet volume from baseline is associated with mortality in patients with severe sepsis or septic shock.

    Directory of Open Access Journals (Sweden)

    Chan Ho Kim

    Full Text Available Mean platelet volume (MPV is suggested as an index of inflammation, disease activity, and anti-inflammatory treatment efficacy in chronic inflammatory disorders; however, the effect of MPV on sepsis mortality remains unclear. Therefore, we investigated whether the change in MPV between hospital admission and 72 hours (ΔMPV72h-adm predicts 28-day mortality in severe sepsis and/or septic shock.We prospectively enrolled 345 patients admitted to the emergency department (ED who received standardized resuscitation (early goal-directed therapy for severe sepsis and/or septic shock between November 2007 and December 2011. Changes in platelet indices, including ΔMPV72h-adm, were compared between survivors and non-survivors by linear mixed model analysis. The prognostic value of ΔMPV72h-adm for 28-day mortality was ascertained by Cox proportional hazards model analysis.Thirty-five (10.1% patients died within 28 days after ED admission. MPV increased significantly during the first 72 hours in non-survivors (P = 0.001 and survivors (P < 0.001; however, the rate of MPV increase was significantly higher in non-survivors (P = 0.003. Nonetheless, the difference in the platelet decline rate over the first 72 hours did not differ significantly between groups (P = 0.360. In multivariate analysis, ΔMPV72h-adm was an independent predictor of 28-day mortality, after adjusting for plausible confounders (hazard ratio, 1.44; 95% confidence interval, 1.01-2.06; P = 0.044.An increase in MPV during the first 72 hours of hospitalization is an independent risk factor for adverse clinical outcomes. Therefore, continuous monitoring of MPV may be useful to stratify mortality risk in patients with severe sepsis and/or septic shock.

  15. Levels of soluble Fc gamma RIII correlate with disease severity in sepsis

    NARCIS (Netherlands)

    Kobold, ACM; Zijlstra, JG; Koene, HR; de Haas, M; Kallenberg, CGM; Tervaert, JWC

    1998-01-01

    Neutrophil activation is thought to play a crucial role in the pathogenesis of sepsis. During activation, neutrophils adhere to and migrate through the endothelium. Therefore, the amount of circulating neutrophils does not adequately reflect the total amount of neutrophils that are involved in the

  16. Levels of soluble Fc gamma RIII correlate with disease severity in sepsis

    NARCIS (Netherlands)

    Kobold, ACM; Zijlstra, JG; Koene, HR; de Haas, M; Kallenberg, CGM; Tervaert, JWC

    1998-01-01

    Neutrophil activation is thought to play a crucial role in the pathogenesis of sepsis. During activation, neutrophils adhere to and migrate through the endothelium. Therefore, the amount of circulating neutrophils does not adequately reflect the total amount of neutrophils that are involved in the p

  17. Persistent Sepsis-Induced Hypotension without Hyperlactatemia: A Distinct Clinical and Physiological Profile within the Spectrum of Septic Shock

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    Glenn Hernandez

    2012-01-01

    Full Text Available Introduction. A subgroup of septic shock patients will never develop hyperlactatemia despite being subjected to a massive circulatory stress. Maintenance of normal lactate levels during septic shock is of great clinical and physiological interest. Our aim was to describe the clinical, hemodynamic, perfusion, and microcirculatory profiles associated to the absence of hyperlactatemia during septic shock resuscitation. Methods. We conducted an observational study in septic shock patients undergoing resuscitation. Serial clinical, hemodynamic, and perfusion parameters were registered. A single sublingual microcirculatory assessment was performed in a subgroup. Patients evolving with versus without hyperlactatemia were compared. Results. 124 septic shock patients were included. Patients without hyperlactatemia exhibited lower severity scores and mortality. They also presented higher platelet counts and required less intensive treatment. Microcirculation was assessed in 45 patients. Patients without hyperlactatemia presented higher PPV and MFI values. Lactate was correlated to several microcirculatory parameters. No difference in systemic flow parameters was observed. Conclusion. Persistent sepsis-induced hypotension without hyperlactatemia is associated with less organ dysfunctions and a very low mortality risk. Patients without hyperlactatemia exhibit less coagulation and microcirculatory derangements despite comparable macrohemodynamics. Our study supports the notion that persistent sepsis-induced hypotension without hyperlactatemia exhibits a distinctive clinical and physiological profile.

  18. Individual patient data meta-analysis of hydroxyethyl starch 130/0.4-0.42 versus crystalloid for fluid resuscitation in patients with severe sepsis

    DEFF Research Database (Denmark)

    Hammond, Naomi E; Haase, Nicolai; Billot, Laurent;

    2014-01-01

    BACKGROUND: The Crystalloid versus Hydroxyethyl Starch Trial (CHEST) and the Scandinavian Starch in Severe Sepsis/ Septic Shock (6S) trial reported that 6% hydroxyethyl starch (HES) is associated with increased use of renal replacement therapy and death in critically ill patients. Data collection...... was harmonised between the two trials in order to facilitate a preplanned individual patient data meta-analysis (IPDMA) of patients with severe sepsis. OBJECTIVES AND RATIONALE: To publish a statistical analysis plan (SAP) for an IPDMA of patients with severe sepsis enrolled in the 6S trial and the CHEST....... Subgroups have been defined based on pre-randomisation variables. CONCLUSION: We developed a preanalysis SAP to combine data on patients with severe sepsis from the 6S trial and the CHEST. Prepublication of our SAP will reduce the risk of bias in the reporting of the results and improve confidence...

  19. Association between high levels of blood macrophage migration inhibitory factor, inappropriate adrenal response, and early death in patients with severe sepsis.

    NARCIS (Netherlands)

    Emonts, M.; Sweep, C.G.J.; Grebenchtchikov, N.I.; Geurts-Moespot, A.; Knaup, M.; Chanson, A.L.; Erard, V.; Renner, P.; Hermans, P.W.M.; Hazelzet, J.A.; Calandra, T.

    2007-01-01

    BACKGROUND: Identification of new therapeutic targets remains an imperative goal to improve the morbidity and mortality associated with severe sepsis and septic shock. Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine and counterregulator of glucocorticoids, has recently

  20. C5a regulates IL-12+ DC migration to induce pathogenic Th1 and Th17 cells in sepsis.

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    Ning Ma

    Full Text Available OBJECTIVE: It is well known that complement system C5a is excessively activated during the onset of sepsis. However, it is unclear whether C5a can regulate dentritic cells (DCs to stimulate adaptive immune cells such as Th1 and Th17 in sepsis. METHODS: Sepsis was induced by cecal ligation and puncture (CLP. CLP-induced sepsis was treated with anti-C5a or IL-12. IL-12(+DC, IFNγ(+Th1, and IL-17(+Th17 cells were analyzed by flow cytometry. IL-12 was measured by ELISA. RESULTS: Our studies here showed that C5a induced IL-12(+DC cell migration from the peritoneal cavity to peripheral blood and lymph nodes. Furthermore, IL-12(+DC cells induced the expansion of pathogenic IFNγ(+Th1 and IL-17(+Th17 cells in peripheral blood and lymph nodes. Moreover, IL-12, secreted by DC cells in the peritoneal cavity, is an important factor that prevents the development of sepsis. CONCLUSION: Our data suggests that C5a regulates IL-12(+DC cell migration to induce pathogenic Th1 and Th17 cells in sepsis.

  1. Use of recombinant human soluble thrombomodulin in patients with sepsis-induced disseminated intravascular coagulation after intestinal perforation

    Directory of Open Access Journals (Sweden)

    Takashi eTagami

    2015-02-01

    Full Text Available Background: Anticoagulant therapy has been evaluated with respect to its potential usefulness in reducing the high mortality rates associated with severe sepsis, including sepsis-induced disseminated intravascular coagulation (DIC after intestinal perforation. We examined the hypothesis that recombinant human soluble thrombomodulin (rhTM is effective in the treatment of patients with septic shock with sepsis-induced DIC after laparotomy for intestinal perforation. Methods: We performed propensity-score and instrumental variable analyses of the Japanese Diagnosis Procedure Combination inpatient database, a nationwide administrative database. The main outcome was 28-day in-hospital all-cause mortality.Results: We categorized eligible patients (n = 2202 from 622 hospitals into the rhTM group (n = 726 and control group (n = 1476. Propensity-score matching created 621 matched pairs of patients with and without rhTM. There was no significant difference in 28-day mortality between the two groups in the unmatched analysis (rhTM vs. control, 25.3% vs. 23.4%, respectively; difference, 1.9%; 95%CI, −1.9 to 5.7, nor in the propensity-score matched analysis (rhTM vs. control, 26.1% vs. 24.8%, respectively; difference, 1.3%; 95%CI, −3.6 to 6.1. The logistic analysis showed no significant association between the use of rhTM and the mortality in propensity-score matched patients ((OR, 1.1; 95%CI, 0.82−1.4. The instrumental variable analyses, using the hospital rhTM-prescribing proportion as the variable, found that receipt of rhTM was not associated with the reduction in the mortality (risk difference, −6.7%; 95%CI, −16.4 to 3.0.Conclusions: We found no association between administration of rhTM and 28-day mortality in mechanically ventilated patients with septic shock and concurrent DIC after intestinal perforation.

  2. Quality of Life of Severe Sepsis Survivors After Hospital Discharge Calidad de vida de sobrevivientes de sepsis grave después del alta hospitalar Qualidade de vida de sobreviventes de sepse grave após alta hospitalar

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    Ligia Marcia Contrin

    2013-06-01

    Full Text Available AIMS: to evaluate the quality of life in severe sepsis survivors, using specific QoL questionnaires: the EuroQol-5 Dimensions and the Visual Analogue Scale (EQ-VAS. METHOD: This case-control study was performed in patients discharged from a teaching hospital after being admitted to the ICU with severe sepsis. Medical records from 349 patients were retrieved from the hospital sepsis registry. Each patient with sepsis was considered as a case. Patients who were admitted immediately after the sepsis episode were considered as controls, provided that they did not have sepsis and survived the ICU admission. This specific study population included 100 patients. RESULTS: The sepsis group showed higher mortality at 1 year compared with critically ill patients. However, the control group showed no sepsis. Older patients (>60 years in the sepsis group had a significantly higher prevalence of problems. There were no differences in EQ-VAS between respondents from both groups. CONCLUSIONS: After discharge from ICU, sepsis survivors of sepsis had a higher mortality rate than critically ill patients without sepsis. Older patients with sepsis had more moderate and severe problems in all five quality of life dimensions evaluated. OBJETIVO: Evaluación de la calidad de vida de los sobrevivientes de sepsis grave con los instrumentos EuroQol-5D y la Escala Analógica Visual (EQ-VAS. MÉTODO: Estudio caso-control anidado en pacientes que recibieron alta de la unidad de cuidados intensivos (UCI de un hospital de enseñanza después de la admisión con sepsis grave. La selección fue realizada a partir del registro de sepsis conteniendo 349 pacientes y cada paciente con sepsis fue considerado como un caso y el que fue hospitalizado inmediatamente después fue seleccionado como control, desde que no tuviera sepsis y hubiera sobrevivido a la hospitalización en la UCI y la sepsis, totalizando 100 sujetos. RESULTADOS: El grupo de sepsis mostró una mayor mortalidad a 1 a

  3. [Management and orientation of severely infected patients : relevance of a « Sepsis Fast-Track »].

    Science.gov (United States)

    Juillerat, André; Vivekanantham, Hari; Burger, Raphaël; Hausser, Joëlle; Fumeaux, Thierry

    2017-09-06

    Sepsis is a syndrome defined by a life-threatening organ dysfunction caused by a dysregulated host response to an infection. The early recognition of this syndrome in the emergency department (ED) can lead to a better prognosis, when associated with a standardized management focusing on identification of the infectious source, its treatment, and appropriate organ support. Therefore, the implementation of a « Sepsis Fast Track », by analogy with similar protocols regarding stroke or ST-elevated myocardial infarct, deserves interest. The aim of this article is to review the available evidences that support an implementation of such an initiative, and to identify the key elements that permit its integration in the ED setting of a secondary-care hospital.

  4. Lung protective ventilation induces immunotolerance and nitric oxide metabolites in porcine experimental postoperative sepsis.

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    Jesper Sperber

    Full Text Available Low tidal volume ventilation is beneficial in patients with severe pulmonary dysfunction and would, in theory, reduce postoperative complications if implemented during routine surgery. The study aimed to investigate whether low tidal volume ventilation and high positive end-expiratory pressure (PEEP in a large animal model of postoperative sepsis would attenuate the systemic inflammatory response and organ dysfunction. Thirty healthy pigs were randomized to three groups: Group Prot-7h, i.e. protective ventilation for 7 h, was ventilated with a tidal volume of 6 mL x kg(-1 for 7 h; group Prot-5h, i.e. protective ventilation for 5 h, was ventilated with a tidal volume of 10 mL x kg(-1 for 2 h, after which the group was ventilated with a tidal volume of 6 mL x kg(-1; and a control group that was ventilated with a tidal volume of 10 mL x kg(-1 for 7 h. In groups Prot-7h and Prot-5h PEEP was 5 cmH2O for 2 h and 10 cmH2O for 5 h. In the control group PEEP was 5 cmH2O for the entire experiment. After surgery for 2 h, postoperative sepsis was simulated with an endotoxin infusion for 5 h. Low tidal volume ventilation combined with higher PEEP led to lower levels of interleukin 6 and 10 in plasma, higher PaO2/FiO2, better preserved functional residual capacity and lower plasma troponin I as compared with animals ventilated with a medium high tidal volume and lower PEEP. The beneficial effects of protective ventilation were seen despite greater reductions in cardiac index and oxygen delivery index. In the immediate postoperative phase low VT ventilation with higher PEEP was associated with reduced ex vivo plasma capacity to produce TNF-α upon endotoxin stimulation and higher nitrite levels in urine. These findings might represent mechanistic explanations for the attenuation of systemic inflammation and inflammatory-induced organ dysfunction.

  5. Ketamine attenuates sepsis-induced acute lung injury via regulation of HMGB1-RAGE pathways.

    Science.gov (United States)

    Li, Kehan; Yang, Jianxue; Han, Xuechang

    2016-05-01

    High mobility group box protein 1 (HMGB1) and receptor for the advanced glycation end product (RAGE) play important roles in the development of sepsis-induced acute lung injury (ALI). Ketamine is considered to confer protective effects on ALI during sepsis. In this study, we investigated the effects of ketamine on HMGB1-RAGE activation in a rat model of sepsis-induced ALI. ALI was induced in wild type (WT) and RAGE deficient (RAGE(-/-)) rats by cecal ligation and puncture (CLP) or HMGB1 to mimic sepsis-induced ALI. Rats were randomly divided to six groups: sham-operation+normal saline (NS, 10 mL/kg), sham-operation+ketamine (10 mg/kg), CLP/HMGB1+NS (10 mL/kg), CLP/HMGB1+ketamine (5 mg/kg), CLP/HMGB1+ketamine (7.5 mg/kg), and CLP/HMGB1+ketamine (10 mg/kg) groups. NS and ketamine were administered at 3 and 12 h after CLP/HMGB1 via intraperitoneal injection. Pathological changes of lung, inflammatory cell counts, expression of HMGB1 and RAGE, and concentrations of various inflammatory mediators in bronchoalveolar lavage fluids (BALF) and lung tissue were then assessed. Nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPK) signaling pathways in the lung were also evaluated. CLP/HMGB1 increased the wet to dry weight ratio and myeloperoxidase activity in lung, the number of total cells, neutrophils, and macrophages in the BALF, and inflammatory mediators in the BALF and lung tissues. Moreover, expression of HMGB1 and RAGE in lung tissues was increased after CLP. Ketamine inhibited all the above effects. It also inhibited the activation of IκB-α, NF-κB p65, and MAPK. Ketamine protects rats against HMGB1-RAGE activation in a rat model of sepsis-induced ALI. These effects may partially result from reductions in NF-κB and MAPK. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  6. Immunosuppression after sepsis: systemic inflammation and sepsis induce a loss of naive T-cells but no enduring cell-autonomous defects in T-cell function.

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    Robby Markwart

    Full Text Available Sepsis describes the life-threatening systemic inflammatory response (SIRS of an organism to an infection and is the leading cause of mortality on intensive care units (ICU worldwide. An acute episode of sepsis is characterized by the extensive release of cytokines and other mediators resulting in a dysregulated immune response leading to organ damage and/or death. This initial pro-inflammatory burst often transits into a state of immune suppression characterised by loss of immune cells and T-cell dysfunction at later disease stages in sepsis survivors. However, despite these appreciations, the precise nature of the evoked defect in T-cell immunity in post-acute phases of SIRS remains unknown. Here we present an in-depth functional analysis of T-cell function in post-acute SIRS/sepsis. We document that T-cell function is not compromised on a per cell basis in experimental rodent models of infection-free SIRS (LPS or CpG or septic peritonitis. Transgenic antigen-specific T-cells feature an unaltered cytokine response if challenged in vivo and ex vivo with cognate antigens. Isolated CD4(+/CD8(+ T-cells from post-acute septic animals do not exhibit defects in T-cell receptor-mediated activation at the the level of receptor-proximal signalling, activation marker upregulation or expansion. However, SIRS/sepsis induced transient lymphopenia and gave rise to an environment of immune attenuation at post acute disease stages. Thus, systemic inflammation has an acute impact on T-cell numbers and adaptive immunity, but does not cause major cell-autonomous enduring functional defects in T-cells.

  7. Role of cellular events in the pathophysiology of sepsis.

    Science.gov (United States)

    Bhan, Chandra; Dipankar, Pankaj; Chakraborty, Papiya; Sarangi, Pranita P

    2016-11-01

    Sepsis is a dysregulated host immune response due to an uncontrolled infection. It is a leading cause of mortality in adult intensive care units globally. When the host immune response induced against a local infection fails to contain it locally, it progresses to sepsis, severe sepsis, septic shock and death. Literature survey was performed on the roles of different innate and adaptive immune cells in the development and progression of sepsis. Additionally, the effects of septic changes on reprogramming of different immune cells were also summarized to prepare the manuscript. Scientific evidences to date suggest that the loss of balance between inflammatory and anti-inflammatory responses results in reprogramming of immune cell activities that lead to irreversible tissue damaging events and multi-organ failure during sepsis. Many surface receptors expressed on immune cells at various stages of sepsis have been suggested as biomarkers for sepsis diagnosis. Various immunomodulatory therapeutics, which could improve the functions of immune cells during sepsis, were shown to restore immunological homeostasis and improve survival in animal models of sepsis. In-depth and comprehensive knowledge on the immune cell activities and their correlation with severity of sepsis will help clinicians and scientists to design effective immunomodulatory therapeutics for treating sepsis.

  8. Magnolol attenuates sepsis-induced gastrointestinal dysmotility in rats by modulating inflammatory mediators

    Institute of Scientific and Technical Information of China (English)

    Tie-Cheng Yang; Shu-Wen Zhang; Li-Na Sun; Hong Wang; Ai-Min Ren

    2008-01-01

    AIM:To investigate the protective effects of magnolol on sepsis-induced inflammation and intestinal dysmotility.METHODS:Sepsis was induced by a single intraperitoneal injection of lipopolysaccharide (LPS).Male Wistar rats were randomly assigned to one of three treatment groups:magnolol prior to LPS injection (LPS/Mag group);vehicle prior to LPS injection (LPS/Veh group);vehicle prior to injection of saline (Control/Veh).Intestinal transit and circular muscle mechanical activity were assessed 12 h after LPS injection.Tumor necrosis factor-a (TNF-α),interleukin-10 (IL-10),monoo/te chemoattractant protein-1 (MCP-1) and inducible nitric oxide synthase (iNOS) mRNA in rat ileum were studied by RT-PCR 2 h after LPS injection.Nuclear factor-KB (NF-Kβ) activity in the intestine was also investigated at this time using electrophoretic mobility shift assay.In addition,antioxidant activity was determined by measuring malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity in the intestine 2 h after LPS injection.RESULTS:Magnolol significantly increased intestinal transit and circular muscle mechanical activity in LPS-treated animals.TNF-α,MCP-1 and iNOS mRNA expression in the small intestine were significantly reduced after magnolol treatment in LPS-induced septic animals,compared with untreated septic animals.Additionally,magnolol significantly increased IL-10 mRNA expression in septic rat ileum.Magnolol also significantly suppressed NF-kβ activity in septic rat intestine.In addition,magnolol significantly decreased MDA concentration and increased SOD activity in rat ileum.CONCLUSION:Magnolol prevents sepsis-induced suppression of intestinal motility in rats.The potential mechanism of this benefit of magnolol appears to be modulation of self-amplified inflammatory events and block of oxidative stress in the intestine.

  9. Enhanced Innate Inflammation Induced by Anti-BTLA Antibody in Dual Insult Model of Hemorrhagic Shock/Sepsis.

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    Cheng, Tingting; Bai, Jianwen; Chung, Chun-Shiang; Chen, Yaping; Biron, Bethany M; Ayala, Alfred

    2016-01-01

    Sepsis following hemorrhagic shock is a common clinical condition, in which innate immune system suffers from severe suppression. B and T lymphocyte attenuator (BTLA) is an immune-regulatory coinhibitory receptor expressed not only on adaptive, but also on innate immune cells. Our previous data showed that BTLA gene deficient mice were protected from septic mortality when compared with wild-type control C57BL/6 mice. Here, we extended our study by treating C57BL/6 mice with an anti-BTLA monoclonal antibody (clone 6A6; reported to have the ability to neutralize or agonize/potentiate BTLA signaling) in a mouse model of hemorrhagic shock (Hem) followed by sepsis induced by cecal ligation and puncture (CLP); positing initially that if BTLA engagement was neutralized, like gene deficiency, an anti-BTLA mAb would have the similar effects on the inflammatory response/morbidity in these mice after such insults. Here, we report that BTLA expression is elevated on innate immune cells after Hem/CLP. However, anti-BTLA antibody treatment increased cytokine (TNF-α, IL-12, IL-10)/chemokine (KC, MIP-2, MCP-1) levels and inflammatory cells (neutrophils, macrophages, dendritic cells) recruitment in the peritoneal cavity, which in turn aggravated organ injury and elevated these animals' mortality in Hem/CLP. When compared with the protective effects of our previous study using BTLA gene deficient mice in a model of lethal septic challenge, we further confirmed BTLA's contribution to enhanced innate cell recruitment, elevated IL-10 levels, and reduced survival, and that engagement of antibody with BTLA potentiates/exacerbates the pathophysiology in Hem/sepsis.

  10. Concurrent administration of heparin and activated protein C in a patient with pulmonary embolism and severe sepsis with positive outcome

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    Juneja Deven

    2009-01-01

    Full Text Available Results of the PROWESS trial suggested that heparin may reduce the efficacy of recombinant human activated protein C (rhAPC and the XPRESS study also showed increased bleeding complications in patients receiving heparin with rhAPC. Although it has been shown that heparin prophylaxis may be used along with rhAPC, no study has shown the interaction between continuous heparin infusion and rhAPC. Here, we report a case of severe sepsis with pulmonary embolism who was concurrently administered heparin and rhAPC infusions, with positive results and no bleeding complications.

  11. The use of sequential organ failure assessment parameters in an awake porcine model of severe Staphylococcus aureus sepsis

    DEFF Research Database (Denmark)

    Sørensen, Karen E.; Nielsen, Ole L.; Birck, Malene M.;

    2012-01-01

    and analysed for SOFA parameters. Dysfunction/failure was observed in the respiratory, haemostatic and hepatic system of all infected animals, together with initial cardiovascular dysfunction. The pulmonary system was the first to fail clinically, which corresponds with similar human findings, whereas......The human sequential organ failure assessment (SOFA) scoring system is used worldwide in intensive care units for assessing the extent of organ dysfunction/failure in patients with severe sepsis. An increasing number of septic cases are caused by Gram-positive bacteria as Staphylococcus aureus...

  12. Declining mortality due to severe sepsis and septic shock in Spanish intensive care units: A two-cohort study in 2005 and 2011.

    Science.gov (United States)

    Sánchez, B; Ferrer, R; Suarez, D; Romay, E; Piacentini, E; Gomà, G; Martínez, M L; Artigas, A

    To analyze the evolution of sepsis-related mortality in Spanish Intensive Care Units (ICUs) following introduction of the Surviving Sepsis Campaign (SSC) guidelines and the relationship with sepsis process-of-care. A prospective cohort study was carried out, with the inclusion of all consecutive patients presenting severe sepsis or septic shock admitted to 41 Spanish ICUs during two time periods: 2005 (Edusepsis study pre-intervention group) and 2011 (ABISS-Edusepsis study pre-intervention group). Patients with severe sepsis or septic shock admitted to Spanish ICUs. All ICU admissions from the emergency department or wards and all ICU patients with a diagnosis of severe sepsis or septic shock. A total of 1348 patients were included: 630 in the 2005 group and 718 in the 2011 group. None. ICU mortality, 28-day mortality and Hospital mortality, hospital length of stay, ICU length of stay and compliance with the resuscitation bundle. Compliance with the resuscitation bundle was significantly greater in the 2011 group (5.7% vs. 9.9%; p=0.005), and was associated to lower mortality (OR 0.602 [0.365-0.994]; p=0.048). The 2011 group had lower absolute in-hospital mortality (44.0% vs. 32.6%; p=0.01), 28-day mortality (36.5% vs. 23.0%; p=0.01), and adjusted mortality (OR 0.64 [0.49-0.83], p=0.001). Mortality related to severe sepsis or septic shock in Spain decreased between two patient cohorts in 2005 and 2011, and was attributable to earliness and improvement in sepsis care. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  13. Beneficial antimicrobial effect of the addition of an aminoglycoside to a β-lactam antibiotic in an E. coli porcine intensive care severe sepsis model.

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    Paul Skorup

    Full Text Available This study aimed to determine whether the addition of an aminoglycoside to a ß-lactam antibiotic increases the antimicrobial effect during the early phase of Gram-negative severe sepsis/septic shock. A porcine model was selected that considered each animal's individual blood bactericidal capacity. Escherichia coli, susceptible to both antibiotics, was given to healthy pigs intravenously during 3 h. At 2 h, the animals were randomized to a 20-min infusion with either cefuroxime alone (n = 9, a combination of cefuroxime+tobramycin (n = 9, or saline (control, n = 9. Blood samples were collected hourly for cultures and quantitative polymerase chain reaction (PCR. Bacterial growth in the organs after 6 h was chosen as the primary endpoint. A blood sample was obtained at baseline before start of bacterial infusion for ex vivo investigation of the blood bactericidal capacity. At 1 h after the administration of the antibiotics, a second blood sample was taken for ex vivo investigation of the antibiotic-induced blood killing activity. All animals developed severe sepsis/septic shock. Blood cultures and PCR rapidly became negative after completed bacterial infusion. Antibiotic-induced blood killing activity was significantly greater in the combination group than in the cefuroxime group (p<0.001. Growth of bacteria in the spleen was reduced in the two antibiotic groups compared with the controls (p<0.01; no difference was noted between the two antibiotic groups. Bacterial growth in the liver was significantly less in the combination group than in the cefuroxime group (p<0.05. High blood bactericidal capacity at baseline was associated with decreased growth in the blood and spleen (p<0.05. The addition of tobramycin to cefuroxime results in increased antibiotic-induced blood killing activity and less bacteria in the liver than cefuroxime alone. Individual blood bactericidal capacity may have a significant effect on antimicrobial outcome.

  14. SeptiFast real-time PCR for detection of bloodborne pathogens in patients with severe sepsis or septic shock.

    Science.gov (United States)

    Markota, Andrej; Seme, Katja; Golle, Andrej; Poljak, Mario; Sinkovič, Andreja

    2014-09-01

    Several studies have been performed investigating the role of a real-time multiplex polymerase chain reaction assay LightCycler SeptiFast with inconsistent results. In prospective evaluation of adult patients with severe sepsis or septic shock SeptiFast assay and blood culture results were compared regarding concordance, the impact of SeptiFast assay on antimicrobial therapy adjustment, time to results and the role of SeptiFast assay as a marker of disease severity. 63 blood sample sets were collected from 57 patients. 51 (80.9%) results were concordant negative and 7 (11.1%) concordant posi- tive. In one (1.6%) sample set blood culture was positive and SeptiFast assay negative, in three (4.8%) sample sets with negative blood cultures pathogens were detected by SeptiFast assay and in one (1.6%)patient an additional pathogen was detected by SeptiFast assay. If blood culture is considered as "gold standard", 1 (1.6%) SeptiFast false negative and 4 (6.3%) false positive results were identified (sensitivity 87.5%, specificity 92.6%, negative predictive value 97.8%). Antibiotic treatment was adjusted according to SeptiFast assay in 4 (6.3%) cases. Time to final results was significantly shorter with SeptiFast assay (32 +/- 23 h vs. 97 +/- 28 h, p sepsis and septic shock but it cannot replace the blood culture.

  15. Treatment of patients with severe sepsis using Ulinastatin and Thymosin α1: a prospective, randomized, controlled pilot study

    Institute of Scientific and Technical Information of China (English)

    CHEN Hao; HE Ming-yan; LI Yu-min

    2009-01-01

    Background Tradition treatment of sepsis and new therapies, including high dose corticosteroids and non-steroidal anti-inflammatory drugs, have proven unsuccessful in improving survival. This study aimed to evaluate the potential efficacy of immunomodulating therapy using Ulinastatin (UTI) plus Thymosin α1 (Tα1) for improving organ function and reducing mortality in patients with severe sepsis.Methods A prospective study was carried out with randomized and controlled clinical analysis of 114 patients conforming to the enrollment standard. All patients had severe sepsis and received standard supportive care and antimicrobial therapy. Fifty-nine patients were also administered UTI plus Tα1 (defined as Group A), 55 patients were given a placebo (defined as Group B). Clinical parameters were determined by evaluation with the Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ), multiple organ failure (MOF) and the Glasgow Coma Scores (GCS) on entry and after therapy on the 3rd, 8th, and 28th day. By flow cytometery and ELISA lymphocyte subsets and cytokines were analyzed. Survival analysis was determined by the Kaplan-Meier method at 28, 60, and 90 days. Results Based on comparison of the two groups, patients in Group A exhibited a better performance in organ failure scores which was noticeable soon after initiation of treatment. Patients in Group A also demonstrated a better resolution of pre-existing organ failures during the observation period. After initiation of treatment, significant improvements in the CD4+/CD8+ ratio, a quicker balance between proinflammatory mediators such as tumor necrosis factor a, interleukin 6 and anti-inflammatory cytokines including interleukin 4 and interleukin 10 were found. This was followed by cumulative survival increases of 17.3% at 28 days, 28.9% at 60 days, and 31.4% at 90 days in Group A. The reduction in mortality was accompanied by a considerably shorter stay in the ICU and a shorter length of supportive

  16. The Impact of Timing of Antibiotics on Outcomes in Severe Sepsis and Septic Shock: A Systematic Review and Meta-analysis

    Science.gov (United States)

    Sterling, Sarah A.; Miller, W. Ryan; Pryor, Jason; Puskarich, Michael A.; Jones, Alan E.

    2015-01-01

    Objectives We sought to systematically review and meta-analyze the available data on the association between timing of antibiotic administration and mortality in severe sepsis and septic shock. Data Sources and Study Selection A comprehensive search was performed using a pre-defined protocol. Inclusion criteria: adult patients with severe sepsis or septic shock, reported time to antibiotic administration in relation to ED triage and/or shock recognition, and mortality. Exclusion criteria: immunosuppressed populations, review article, editorial, or non-human studies. Data Extraction Two reviewers screened abstracts with a third reviewer arbitrating. The effect of time to antibiotic administration on mortality was based on current guideline recommendations: 1) administration within 3 hours of ED triage; 2) administration within 1 hour of severe sepsis/septic shock recognition. Odds Ratios (OR) were calculated using a random effect model. The primary outcome was mortality. Data Synthesis 1123 publications were identified and 11 were included in the analysis. Among the 11 included studies, 16,178 patients were evaluable for antibiotic administration from ED triage. Patients who received antibiotics more than 3 hours after ED triage (antibiotic administration from severe sepsis/septic shock recognition. Patients who received antibiotics more than 1 hour after severe sepsis/shock recognition (5 hours in antibiotic administration from severe sepsis/shock recognition. Conclusion Using the available pooled data we found no significant mortality benefit of administering antibiotics within 3 hours of ED triage or within 1 hour of shock recognition in severe sepsis and septic shock. These results suggest that currently recommended timing metrics as measures of quality of care are not supported by the available evidence. PMID:26121073

  17. Skeletal Muscle and Lymphocyte Mitochondrial Dysfunctions in Septic Shock Trigger ICU-Acquired Weakness and Sepsis-Induced Immunoparalysis

    Directory of Open Access Journals (Sweden)

    Quentin Maestraggi

    2017-01-01

    Full Text Available Fundamental events driving the pathological processes of septic shock-induced multiorgan failure (MOF at the cellular and subcellular levels remain debated. Emerging data implicate mitochondrial dysfunction as a critical factor in the pathogenesis of sepsis-associated MOF. If macrocirculatory and microcirculatory dysfunctions undoubtedly participate in organ dysfunction at the early stage of septic shock, an intrinsic bioenergetic failure, sometimes called “cytopathic hypoxia,” perpetuates cellular dysfunction. Short-term failure of vital organs immediately threatens patient survival but long-term recovery is also severely hindered by persistent dysfunction of organs traditionally described as nonvital, such as skeletal muscle and peripheral blood mononuclear cells (PBMCs. In this review, we will stress how and why a persistent mitochondrial dysfunction in skeletal muscles and PBMC could impair survival in patients who overcome the first acute phase of their septic episode. First, muscle wasting protracts weaning from mechanical ventilation, increases the risk of mechanical ventilator-associated pneumonia, and creates a state of ICU-acquired muscle weakness, compelling the patient to bed. Second, failure of the immune system (“immunoparalysis” translates into its inability to clear infectious foci and predisposes the patient to recurrent nosocomial infections. We will finally emphasize how mitochondrial-targeted therapies could represent a realistic strategy to promote long-term recovery after sepsis.

  18. Skeletal Muscle and Lymphocyte Mitochondrial Dysfunctions in Septic Shock Trigger ICU-Acquired Weakness and Sepsis-Induced Immunoparalysis.

    Science.gov (United States)

    Maestraggi, Quentin; Lebas, Benjamin; Clere-Jehl, Raphaël; Ludes, Pierre-Olivier; Chamaraux-Tran, Thiên-Nga; Schneider, Francis; Diemunsch, Pierre; Geny, Bernard; Pottecher, Julien

    2017-01-01

    Fundamental events driving the pathological processes of septic shock-induced multiorgan failure (MOF) at the cellular and subcellular levels remain debated. Emerging data implicate mitochondrial dysfunction as a critical factor in the pathogenesis of sepsis-associated MOF. If macrocirculatory and microcirculatory dysfunctions undoubtedly participate in organ dysfunction at the early stage of septic shock, an intrinsic bioenergetic failure, sometimes called "cytopathic hypoxia," perpetuates cellular dysfunction. Short-term failure of vital organs immediately threatens patient survival but long-term recovery is also severely hindered by persistent dysfunction of organs traditionally described as nonvital, such as skeletal muscle and peripheral blood mononuclear cells (PBMCs). In this review, we will stress how and why a persistent mitochondrial dysfunction in skeletal muscles and PBMC could impair survival in patients who overcome the first acute phase of their septic episode. First, muscle wasting protracts weaning from mechanical ventilation, increases the risk of mechanical ventilator-associated pneumonia, and creates a state of ICU-acquired muscle weakness, compelling the patient to bed. Second, failure of the immune system ("immunoparalysis") translates into its inability to clear infectious foci and predisposes the patient to recurrent nosocomial infections. We will finally emphasize how mitochondrial-targeted therapies could represent a realistic strategy to promote long-term recovery after sepsis.

  19. Urinary exosomal activating transcriptional factor 3 as the early diagnostic biomarker for sepsis-induced acute kidney injury.

    Science.gov (United States)

    Panich, Tanaporn; Chancharoenthana, Wiwat; Somparn, Poorichaya; Issara-Amphorn, Jiraphorn; Hirankarn, Nattiya; Leelahavanichkul, Asada

    2017-01-07

    An early sepsis-induced acute kidney injury (sepsis-AKI) biomarker is currently in needed. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a candidate of sepsis-AKI biomarker but with different cut-point values. Urinary exosomal activating transcriptional factor 3 (uATF3) has been mentioned as an interesting biomarker. We conducted experiments in mice and a prospective, multicenter study in patients as a proof of concept that urine exosome is an interesting biomarker. An early expression of ATF3 in kidney of CD-1 mice at 6 h after cecal ligation and puncture implied the possibility of uATF3 as an early sepsis-AKI biomarker. Increase serum creatinine (Scr) ≥0.3 mg/dL from the baseline was used as an AKI diagnosis and urine was analyzed for uATF3 and uNGAL. Patients with baseline Scr at admission ≥1.5 mg/dL were excluded. The analysis showed higher Scr, uNGAL and uATF3 in patients with sepsis-AKI in comparison with patients with sepsis-non-AKI and healthy volunteers. A fair correlation, r(2) = 0.47, between uATF3 and uNGAL was showed in sepsis-AKI group with Scr ≥2 mg/dL. To see if uATF3 could be an early sepsis-AKI biomarker, urine sample was collected daily during the first week of the admission. In sepsis-AKI and sepsis-non-AKI groups, uNGAL were 367 ± 43 ng/mL and 183 ± 23 ng/mL, respectively; and uATF3 were 19 ± 4 ng/mL and 1.4 ± 0.8 ng/mL, respectively. With the mean value of uNGAL and uATF3 in sepsis AKI as a cut-off level, AUROC of uNGAL and uATF3 were 64% (95% CI 0.54 to 0.74) and 84% (95% CI 0.77 to 0.91), respectively. Urine exosome is an interesting source of urine biomarker and uATF3 is an interesting sepsis-AKI biomarker.

  20. Modelling severe Staphylococcus aureus sepsis in conscious pigs: are implications for animal welfare justified?

    DEFF Research Database (Denmark)

    Olsen, Helle G; Kjelgaard-Hansen, Mads; Tveden-Nyborg, Pernille

    2016-01-01

    by the severity of induced disease, which in some cases necessitated humane euthanasia. A pilot study was therefore performed in order to establish the sufficient inoculum concentration and application protocol needed to produce signs of liver dysfunction within limits of our pre-defined humane endpoints. Four.......33 min (n = 1) caused alterations in parameters similar to what had been seen in our previous studies, i.e., increasing bilirubin and aspartate aminotransferase, as well as histopathological occurrence of intravascular fibrin split products in the liver. This pig was however euthanised after 30 h...

  1. Coefficient of Variation of Coarsely Sampled Heart Rate is Associated With Early Vasopressor Independence in Severe Sepsis and Septic Shock.

    Science.gov (United States)

    Brown, Samuel M; Tate, M Quinn; Jones, Jason P; Kuttler, Kathryn G; Lanspa, Michael J; Rondina, Matthew T; Grissom, Colin K; Mathews, V J

    2015-10-01

    To determine whether variability of coarsely sampled heart rate and blood pressure early in the course of severe sepsis and septic shock predicts successful resuscitation, defined as vasopressor independence at 24 hours after admission. In an observational study of patients admitted with severe sepsis or septic shock from 2009 to 2011 to either of 2 intensive care units (ICUs) at a tertiary-care hospital, in whom blood pressure was measured via an arterial catheter, we sampled heart rate and blood pressure every 30 seconds over the first 6 hours of ICU admission and calculated the coefficient of variability of those measurements. Primary outcome was vasopressor independence at 24 hours; and secondary outcome was 28-day mortality. We studied 165 patients, of which 97 (59%) achieved vasopressor independence at 24 hours. Overall, 28-day mortality was 15%. Significant predictors of vasopressor independence at 24 hours included the coefficient of variation of heart rate, age, Acute Physiology and Chronic Health Evaluation II, the number of increases in vasopressor dose, mean vasopressin dose, mean blood pressure, and time-pressure integral of mean blood pressure less than 60 mm Hg. Lower sampling frequencies (up to once every 5 minutes) did not affect the findings. Increased variability of coarsely sampled heart rate was associated with vasopressor independence at 24 hours after controlling for possible confounders. Sampling frequencies of once in 5 minutes may be similar to once in 30 seconds. © The Author(s) 2014.

  2. Admission cell free DNA levels predict 28-day mortality in patients with severe sepsis in intensive care.

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    Avital Avriel

    Full Text Available The aim of the current study is to assess the mortality prediction accuracy of circulating cell-free DNA (CFD level at admission measured by a new simplified method.CFD levels were measured by a direct fluorescence assay in severe sepsis patients on intensive care unit (ICU admission. In-hospital and/or twenty eight day all-cause mortality was the primary outcome.Out of 108 patients with median APACHE II of 20, 32.4% have died in hospital/or at 28-day. CFD levels were higher in decedents: median 3469.0 vs. 1659 ng/ml, p<0.001. In multivariable model APACHE II score and CFD (quartiles were significantly associated with the mortality: odds ratio of 1.05, p = 0.049 and 2.57, p<0.001 per quartile respectively. C-statistics for the models was 0.79 for CFD and 0.68 for APACHE II. Integrated discrimination improvement (IDI analyses showed that CFD and CFD+APACHE II score models had better discriminatory ability than APACHE II score alone.CFD level assessed by a new, simple fluorometric-assay is an accurate predictor of acute mortality among ICU patients with severe sepsis. Comparison of CFD to APACHE II score and Procalcitonin (PCT, suggests that CFD has the potential to improve clinical decision making.

  3. Early goal-directed therapy in severe sepsis and septic shock: a contemporary review of the literature.

    Science.gov (United States)

    Rivers, Emanuel P; Coba, Victor; Whitmill, Melissa

    2008-04-01

    Aggressive approaches to acute diseases such as acute myocardial infarction, trauma, and stroke have improved outcomes. Early goal-directed therapy for severe sepsis and septic shock represents a similar approach. An analysis of the literature assessing external validity and generalizability of this intervention is lacking. Eleven peer-reviewed publications (1569 patients) and 28 abstracts (4429 patients) after the original early goal-directed therapy study were identified from academic, community and international settings. These publications total 5998 patients (3042 before and 2956 after early goal-directed therapy). The mean age, sex, APACHE II scores and mortality were similar across all studies. The mean relative and absolute risk reduction was 0.46 +/- 26% and 20.3 +/- 12.7%, respectively. These findings are superior to the original early goal-directed therapy trial which showed figures of 34% and 16%, respectively. A consistent and similar decrease in healthcare resource consumption was also found. Early goal-directed therapy modulates systemic inflammation and results in significant reductions in morbidity, mortality, and healthcare resource consumption. Early goal-directed therapy has been externally validated and is generalizable across multiple healthcare settings. Because of these robust findings, further emphasis should be placed on overcoming logistical, institutional, and professional barriers to implementation which can save the life of one of every six patients presenting with severe sepsis and septic shock.

  4. The Back Alley Revisited: Sepsis after Attempted Self-Induced Abortion

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    Saultes, Teresa A

    2009-11-01

    Full Text Available While unsafe abortions have become rare in the United States, the practice persists. We present a 24-year-old female with a 21-week twin gestation who presented to the emergency department with complications of an attempted self-induced abortion. Her complicated clinical course included sepsis, chorioamnionitis, fetal demise, and a total abdominal hysterectomy with bilateral salpingo-oophorectomy for complications of endomyometritis. We discuss unsafe abortions, risk factors, and the management of septic abortion. Prompt recognition by the emergency physician and aggressive management of septic abortion is critical to decreasing maternal morbidity and mortality.[West J Emerg Med. 2009;10(4:278-280.

  5. The Pro12Ala Polymorphism of PPAR-γ Gene Is Associated with Sepsis Disease Severity and Outcome in Chinese Han Population

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    Guoda Ma

    2014-01-01

    Full Text Available Peroxisome proliferator-activated receptor-γ (PPAR-γ is a ligand-binding nuclear receptor, and its activation plays a prominent role in regulating the inflammatory response. Therefore, PPAR-γ has been suggested as a candidate gene for sepsis. In the present study, we investigated the association between the Pro12Ala polymorphism of PPAR-γ and sepsis in a Han Chinese population. A total of 308 patients with sepsis and 345 healthy controls were enrolled in this study. Genotyping was performed using the polymerase chain reaction-ligation detection reaction (PCR-LDR method. No significant differences were detected in the allele and genotype distributions of the PPAR-γ Pro12Ala SNP between septic patients and controls (P=0.622 for genotype; P=0.629 for allele. However, stratification by subtypes (sepsis, septic shock, and severe sepsis revealed a statistically significant difference in the frequency of the Ala allele and Ala-carrier genotype between the patients with the sepsis subtype and the healthy controls (P=0.014 for allele and P=0.012, for genotype. Moreover, significant differences were found in the frequency of the Ala allele and genotype between the sepsis survivors and nonsurvivors (all P=0.002. In the survivors, the PPAR-γ Pro12Ala genotype was significantly associated with decreased disease severity and recovery time (all P<0.001. Thus, genetic polymorphism is thought to play a role in the development and outcome of sepsis.

  6. Early detection and treatment of severe sepsis in the emergency department: identifying barriers to implementation of a protocol-based approach.

    Science.gov (United States)

    Burney, Mara; Underwood, Joseph; McEvoy, Shayna; Nelson, Germaine; Dzierba, Amy; Kauari, Vepuka; Chong, David

    2012-11-01

    Despite evidence to support efficacy of early goal-directed therapy for resuscitation of patients with severe sepsis and septic shock in the emergency department, implementation remains incomplete. To identify and address specific barriers at our institution and maximize benefits of a planned sepsis treatment initiative, a baseline assessment of knowledge, attitudes, and behaviors regarding detection and treatment of severe sepsis was performed. An online survey was offered to nurses and physicians in the emergency department of a major urban academic medical center. The questionnaire was designed to assess (1) baseline knowledge and self-reported confidence in identification of systemic inflammatory response syndrome and sepsis; (2) current practices in treatment; (3) difficulties encountered in managing sepsis cases; (4) perceived barriers to implementation of a clinical pathway based on early quantitative resuscitation goals; and (5) to elicit suggestions for improvement of sepsis treatment within the department. Respondents (n = 101) identified barriers to a quantitative resuscitation protocol for sepsis. These barriers included the inability to perform central venous pressure/central venous oxygen saturation monitoring, limited physical space in the emergency department, and lack of sufficient nursing staff. Among nurses, the greatest perceived contributor to delays in treatment was a delay in diagnosis by physicians; among physicians, a delay in availability of ICU beds and nursing delays were the greatest barriers. Despite these issues, respondents indicated that a written protocol would be helpful to them. Knowledge gaps and procedural hurdles identified by the survey will inform both educational and process components of an initiative to improve sepsis care in the emergency department. Copyright © 2012 Emergency Nurses Association. Published by Mosby, Inc. All rights reserved.

  7. Design of an electronic medical record (EMR-based clinical decision support system to alert clinicians to the onset of severe sepsis

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    Fountain S

    2016-04-01

    Full Text Available Background: The aim of our study was to design an electronic medical record ­based alert system to detect the onset of severe sepsis with sensitivity and positive predictive value (PPV above 50%. Methods: The PPV for each of seven potential criteria for suspected infection (white blood cell count (WBCC >12 or 0.1 K/uL or immature granulocyte % >1%, temperature >38 C. or 50%, the charts of sixty consecutive patients who met CMS criteria for severe sepsis were reviewed to calculate the sensitivity of organ dysfunction plus any one of the suspected infection criteria. Results: Four proposed criteria for suspected infection had PPV >50%: WBCC >12 x 10 9 /L (69%; 95%CI:53­84%, Temperature >38C. (84%; 95%CI:68­100%, Temperature <36C. (57% 95%CI:36­78%, and initiation of antibiotics (70% 95%CI:56­84%. These four criteria were present in 53/60 of the patients with severe sepsis by CMS criteria, yielding a sensitivity of 88.3% (95%CI: 80.2­96.4%. Alert criteria were satisfied before the onset of severe sepsis in 25/53 cases, and within 90 minutes afterwards in 28/53 cases. Conclusions: Our criteria for suspected infection plus organ dysfunction yields reasonable sensitivity and PPV for the detection of severe sepsis in real­time.

  8. Sepsis pathophysiology and anesthetic consideration.

    Science.gov (United States)

    Yuki, Koichi; Murakami, Naoka

    2015-01-01

    Sepsis remains to be a significant health care issue associated with high mortality and healthcare cost, despite the extensive effort to better understand the pathophysiology of the sepsis. Recently updated clinical guideline for severe sepsis and septic shock, "Surviving Sepsis Campaign 2012", emphasizes the importance of early goal-directed therapy, which can be implemented in intraoperative management of sepsis patients. Herein, we review the updates of current guideline and discuss its application to anesthesic management. Furthermore, we review the recent advance in knowledge of sepsis pathophysiology, focusing on immune modulation, which may lead to new clinical therapeutic approach to sepsis.

  9. Sepsis Pathophysiology and Anesthetic Consideration

    OpenAIRE

    Yuki, Koichi; Murakami, Naoka

    2015-01-01

    Sepsis remains to be a significant health care issue associated with high mortality and healthcare cost, despite the extensive effort to better understand the pathophysiology of the sepsis. Recently updated clinical guideline for severe sepsis and septic shock, “Surviving Sepsis Campaign 2012”, emphasizes the importance of early goal-directed therapy, which can be implemented in intraoperative management of sepsis patients. Herein, we review the updates of current guideline and discuss its ap...

  10. Antimicrobial peptides in human sepsis

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    Lukas eMartin

    2015-08-01

    Full Text Available Nearly 100 years ago, antimicrobial peptides (AMPs were identified as an important part of innate immunity. They exist in species from bacteria to mammals and can be isolated in body fluids and on surfaces constitutively or induced by inflammation. Defensins have anti-bacterial effects against Gram-positive and Gram-negative bacteria as well as anti-viral and anti-yeast effects. Human neutrophil peptides (HNP 1-3 and human beta-defensins (HBDs 1-3 are some of the most important defensins in humans. Recent studies have demonstrated higher levels of HNP -1-3 and HBD-2 in sepsis. The bactericidal/permeability increasing protein (BPI attenuates local inflammatory response and decreases systemic toxicity of endotoxins. Moreover, BPI might reflect the severity of organ dysfunction in sepsis. Elevated plasma lactoferrin is detected in patients with organ failure. HNP-1-3, lactoferrin, BPI and heparin-binding protein (HBP are increased in sepsis. Human lactoferrin peptide 1-11 (hLF 1-11 possesses antimicrobial activity and modulates inflammation. The recombinant form of lactoferrin (talactoferrin alpha, TLF has been shown to decrease mortality in critically ill patients. A phase II/III study with TLF in sepsis did not confirm this result. The growing number of multiresistant bacteria is an ongoing problem in sepsis therapy. Furthermore, antibiotics are known to promote the liberation of pro-inflammatory cell components and thus augment the severity of sepsis. Compared to antibiotics, AMPs kill bacteria but also neutralize pathogenic factors such as lipopolysaccharide (LPS. The obstacle to applying naturally occurring AMPs is their high nephro- and neurotoxicity. Therefore, the challenge is to develop peptides to treat septic patients effectively without causing harm. This overview focuses on natural and synthetic AMPs in human and experimental sepsis and their potential to provide significant improvements in the treatment of critically ill with severe

  11. High-Mobility Group Box-1 Protein Serum Levels Do Not Reflect Monocytic Function in Patients with Sepsis-Induced Immunosuppression

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    Nadine Unterwalder

    2010-01-01

    Full Text Available Background. High-mobility group box-1 (HMGB-1 protein is released during “late sepsis” by activated monocytes. We investigated whether systemic HMGB-1 levels are associated with indices of monocytic activation/function in patients with sepsis-induced immunosuppression. Methodology. 36 patients (31 male, 64±14 years with severe sepsis/septic shock and monocytic deactivation (reduced mHLA-DR expression and TNF-α release were assessed in a subanalysis of a placebo-controlled immunostimulatory trial using GM-CSF. HMGB-1 levels were assessed over a 9-day treatment interval. Data were compared to standardized biomarkers of monocytic immunity (mHLA-DR expression, TNF-α release. Principle findings. HMGB-1 levels were enhanced in sepsis but did not differ between treatment and placebo groups at baseline (14.6 ± 13.5 versus 12.5 ± 11.5 ng/ml, P=.62. When compared to controls, HMGB-1 level increased transiently in treated patients at day 5 (27.8±21.7 versus 11.0±14.9, P=.01. Between group differences were not noted at any other point of assessment. HMGB-1 levels were not associated with markers of monocytic function or clinical disease severity. Conclusions. GM-CSF treatment for sepsis-induced immunosuppression induces a moderate but only transient increase in systemic HMGB-1 levels. HMGB-1 levels should not be used for monitoring of monocytic function in immunostimulatory trials as they do not adequately portray contemporary changes in monocytic immunity.

  12. Comparing the effect of hydroxyethyl starch 130/0.4 with balanced crystalloid solution on mortality and kidney failure in patients with severe sepsis (6S - Scandinavian Starch for Severe Sepsis/Septic Shock trial): Study protocol, design and rationale for a double-blinded, randomised clinical trial

    DEFF Research Database (Denmark)

    Perner, Anders; Haase, Nicolai; Wetterslev, Jørn

    2011-01-01

    ABSTRACT: BACKGROUND: By tradition colloid solutions have been used to obtain fast circulatory stabilisation in shock, but high molecular weight hydroxyethyl starch (HES) may cause acute kidney failure in patients with severe sepsis. Now lower molecular weight HES 130/0.4 is the preferred colloid...... in Scandinavian intensive care units (ICUs) and 1st choice fluid for patients with severe sepsis. However, HES 130/0.4 is largely unstudied in patients with severe sepsis. METHODS/DESIGN: The 6S trial will randomise 800 patients with severe sepsis in 30 Scandinavian ICUs to masked fluid resuscitation using either...... replacement therapy or ventilator support and 28-day and 1/2- and one-year mortality. The sample size will allow the detection of a 10% absolute difference between the two groups in the composite endpoint with a power of 80%. DISCUSSION: The 6S trial will provide important safety and efficacy data on the use...

  13. Protective effects of Xuebijing on endothelium in sepsis -induced acute kidney injury

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    Wei WANG

    2017-04-01

    Full Text Available Objective  To explore the protective effect of Xuebijing on the endothelium and extracellular matrix in sepsis-induced acute kidney injury (AKI rats for providing a new clinical treatment strategy. Methods  The method of cecal ligation and puncture (CLP was used to duplicate severe sepsis model. Thirty healthy male SD rats were randomly divided into 3 groups: Sham group (n=10, NS group (normal saline 4ml/kg, n=10, Xuebijing group (Xuebijing 4ml/kg, n=10. 6h after CLP, the rats were sacrificed and their kidneys were resected and histopathological characteristic was observed by light microscopic and transmission electron microscopic techniques. The expressions of ET-1 mRNA, iNOS mRNA, MMP-9 mRNA, TIMP-1 mRNA in the renal tissues were measured semi-quantitatively by reverse transcription-polymerase chain reaction (RT-PCR. Results  The histopathological changes in renal tissue were observed by light microscope. The changes of renal glomerulus and renal tubuli in Xuebijing group were better than NS group. The ultrastructural changes in renal tissue were observed under electron microscope. Compared with NS group, ultrastructural changes of renal glomerulus and proximal convoluted tubule were smaller in Xuebijing group. The expressions of ET-1mRNA (0.631±0.169 vs 0.770±0.154, P<0.05, iNOS mRNA (0.507±0.071 vs 0.587±0.073, P<0.05, MMP-9mRNA (0.641±0.082 vs 0.742±0.116, P<0.05 and TIMP-1 mRNA (0.434±0.052 vs 0.520±0.049, P<0.01 were significantly lower in XBJ group renal tissues than in NS group. The expressions of ET-1 mRNA(0.770±0.154 vs 0.394±0.105, P<0.01, iNOS mRNA (0.587±0.073 vs 0.326±0.085, P<0.01, MMP-9 mRNA (0.742±0.116 vs 0.356±0.055, P<0.01 and TIMP-1 mRNA (0.520±0.049 vs 0.351±0.041, P<0.05 in renal tissues were more significantly increased in NS group compared with sham group. Conclusions  Xuebijing could reduce the levels of ET-1, iNOS, MMP-9 and TIMP-1 mRNA, protect the stability of endothelium and extracellular

  14. Low-pressure cardiac tamponade masquerading as severe sepsis diagnosed with a bedside ultrasound and as the initial presentation of malignancy.

    Science.gov (United States)

    Conti, Ricardo Augusto Slaibi; Oppenheim, Ian Mandeville

    2014-01-01

    We report a patient with low-pressure cardiac tamponade masquerading as sepsis and as the initial presentation of malignancy. A quick diagnosis was done by the intensivist performing a bedside ultrasound. The diagnosis of low-pressure cardiac tamponade is a challenge because the classic physical signs of cardiac tamponade can be absent. It is made even more challenging when the vital sign changes and physical examination findings mimic severe sepsis. One of the benefits of a bedside ultrasound in the assessment of a patient with an initial diagnosis of severe sepsis or septic shock is the rapid diagnosis of cardiac tamponade if it is present. A 55-year-old male presented to the emergency department with weakness, cough, and syncope. His examination was notable only for dusky mottling of his cheeks, chest, and neck. Specifically, there was no jugular venous distension or pulsus paradoxus. A chest radiograph showed a right upper lobe infiltrate, whereas his electrocardiogram showed only sinus tachycardia. His white blood cell count and lactic acid were elevated. The sepsis protocol was started and a bedside ultrasound revealed signs of cardiac tamponade. The patient immediately improved after a pericardiocentesis. Analysis of the pericardial biopsy revealed adenocarcinoma, later determined to be from a pulmonary primary source. Because low-pressure cardiac tamponade is life-threatening and difficult to diagnose, evaluation of the pericardium with a bedside ultrasound should be considered in patients with syncope, severe sepsis, or shock.

  15. Diverse and Tissue Specific Mitochondrial Respiratory Response in A Mouse Model of Sepsis-Induced Multiple Organ Failure

    DEFF Research Database (Denmark)

    Karlsson, Michael; Hara, Naomi; Morata, Saori

    2016-01-01

    Mitochondrial function is thought to play a role in sepsis-induced multiple organ failure. However, the temporal and organ specific alterations in mitochondrial function has yet to be fully elucidated. Many studies show reduced phosphorylating capacity while others have indicated that mitochondrial...... respiration is enhanced. The objective of the study was to evaluate the temporal dynamics of brain and liver mitochondrial function in a mouse model of sepsis.Sepsis was induced by cecal ligation and puncture. Controls were sham operated. Using high-resolution respirometry, brain and liver homogenates from 31......-production was detected.Liver homogenate from the septic mice displayed a significant increase of the respiratory control ratio at 6 hours. In the 24-hour group, the rate of maximal oxidative phosphorylation, as well as LEAK respiration, was significantly increased compared to controls and the resultant respiratory...

  16. HMGB1 redox during sepsis.

    Science.gov (United States)

    Abdulmahdi, Wasan; Patel, Devika; Rabadi, May M; Azar, Tala; Jules, Edson; Lipphardt, Mark; Hashemiyoon, Rameen; Ratliff, Brian B

    2017-10-01

    During sepsis, the alarmin HMGB1 is released from tissues and promotes systemic inflammation that results in multi-organ damage, with the kidney particularly susceptible to injury. The severity of inflammation and pro-damage signaling mediated by HMGB1 appears to be dependent on the alarmin's redox state. Therefore, we examined HMGB1 redox in kidney cells during sepsis. Using intravital microscopy, CellROX labeling of kidneys in live mice indicated increased ROS generation in the kidney perivascular endothelium and tubules during lipopolysaccharide (LPS)-induced sepsis. Subsequent CellROX and MitoSOX labeling of LPS-stressed endothelial and kidney proximal tubule cells demonstrated increased ROS generation in these cells as sepsis worsens. Consequently, HMGB1 oxidation increased in the cytoplasm of kidney cells during its translocation from the nucleus to the circulation, with the degree of oxidation dependent on the severity of sepsis, as measured in in vivo mouse samples using a thiol assay and mass spectrometry (LC-MS/MS). The greater the oxidation of HMGB1, the greater the ability of the alarmin to stimulate pro-inflammatory cyto-/chemokine release (measured by Luminex Multiplex) and alter mitochondrial ATP generation (Luminescent ATP Detection Assay). Administration of glutathione and thioredoxin inhibitors to cell cultures enhanced HMGB1 oxidation during sepsis in endothelial and proximal tubule cells, respectively. In conclusion, as sepsis worsens, ROS generation and HMGB1 oxidation increases in kidney cells, which enhances HMGB1's pro-inflammatory signaling. Conversely, the glutathione and thioredoxin systems work to maintain the protein in its reduced state. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Bacteremic Urinary Tract Infection Caused by Multidrug-Resistant Enterobacteriaceae Are Associated With Severe Sepsis at Admission: Implication for Empirical Therapy.

    Science.gov (United States)

    Lee, Yi-Chien; Hsiao, Chih-Yen; Hung, Miao-Chiu; Hung, Sheng-Che; Wang, Hung-Ping; Huang, Yun-Jhong; Wang, Jann-Tay

    2016-05-01

    The purpose of this study is to compare the clinical features and treatment outcomes among patients with bacteremic urinary tract infection (UTI) caused by multidrug-resistant (MDR) and non-MDR Enterobacteriaceae and to identify whether MDR pathogens were independently associated with severe sepsis or septic shock at presentation.The clinical data of adult patients visiting and being treated at Chia-Yi Christian Hospital due to bacteremic UTI caused by Enterobacteriaceae from January 2006 to August 2015 were retrospectively analyzed.A total of 585 patients were enrolled. Among them, 220 (37.6%) were caused by the MDR Enterobacteriaceae. A total of 206 patients (35.2%) developed severe sepsis or septic shock at presentation. Patients in the MDR group tend to be male and have a past history of gout, recurrent UTI, prior hospitalization, hydronephrosis, renal stone, ureteral stone, indwelling urinary catheter, newly development of renal dysfunction, severe sepsis or septic shock, intensive care unit (ICU) admission, receipt of ineffective empirical therapy, longer hospital stay, and higher in-hospital mortality (2.7% vs 1.9%, P = 0.569). Using multivariate logistic regression analysis, it is revealed that independent predictors associated with severe sepsis or septic shock at presentation were liver cirrhosis (OR 2.868; 95% CI 1.439-5.716; P = 0.003), indwelling urinary catheter (OR 1.936; 95% CI 1.238-3.027; P = 0.004), and MDR Enterobacteriaceae (OR 1.447; 95% CI 1.002-2.090; P = 0.049).Multidrug resistance was associated with the development of severe sepsis or septic shock upon presentation among patients with bacteremic UTI caused by Enterobacteriaceae. Therefore, empirical antibiotics therapy for patients with UTI presented with severe sepsis and/or septic shock should be more broad-spectrum to effectively cover MDR Enterobacteriaceae.

  18. A multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype.

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    Didier Payen

    Full Text Available BACKGROUND: To investigate the association between severity of acute kidney injury (AKI and outcome, systemic inflammatory phenotype and HLA genotype in severe sepsis. METHODOLOGY/PRINCIPAL FINDINGS: Prospective multicenter observational study done in 4 intensive care units in two university hospitals. Severe sepsis and septic shock patients with at least 2 organ failures based on the SOFA score were classified: 1 "no AKI", 2 "mild AKI" (grouping stage 1 and 2 of AKIN score and 3 "severe AKI" (stage 3 of AKIN score. Sequential measurements: The vasopressor dependency index (VDI; dose and types of drugs to evaluate the association between hemodynamic status and the development of early AKI; plasma levels of IL-10, macrophage migration inhibitory factor (MIF, IL-6 and HLA-DR monocyte expression. Genotyping of the 13 HLA-DRB1 alleles with deduction of presence of HLA-DRB3, -DRB4 and -DRB5 genes. We used multivariate analysis with competitive risk model to study associations. Overall, 176 study patients (146 with septic shock were classified from AKIN score as "no AKI" (n = 43, "mild AKI" (n = 74 or "severe AKI" (n = 59. The VDI did not differ between groups of AKI. After adjustment, "mild and severe AKI" were an independent risk factor for mortality (HR 2.42 95%CI[1.01-5.83], p = 0.048 and HR 1.99 95%CI[1.30-3.03], p = 0.001 respectively. "Severe AKI" had higher levels of plasma IL-10, MIF and IL-6 compared to "no AKI" and mild AKI (p<0.05 for each, with no difference in mHLA-DR at day 0. HLA-DRB genotyping showed a significantly lower proportion of 4 HLA-DRB alleles among patients requiring renal replacement therapy (RRT (58% than in patients with severe AKI who did not receive RRT (84% (p = 0.004. CONCLUSIONS: AKI severity is independently associated with mortality and plasma IL-10, MIF or IL-6 levels. Presence of 4 alleles of HLA-DRB in severe AKI patients seems associated with a lower need of RRT.

  19. Colloids for the Initial Management of Severe Sepsis and Septic Shock in Pediatric Patients: A Systematic Review.

    Science.gov (United States)

    Medeiros, Daniela Nasu Monteiro; Ferranti, Juliana Ferreira; Delgado, Artur Figueiredo; de Carvalho, Werther Brunow

    2015-11-01

    The goal of this study was to perform a systematic review of the literature assessing the use of colloids for the initial treatment of severe sepsis and septic shock in pediatric patients. The PICO [Patient, Intervention, Comparison, Outcome] method was used for the selection of studies, and the Cochrane Bias Tool was used to analyze the quality of the selected studies. Relevant studies were sought using the following databases: EMBASE (1980 to March 2014), PubMed (1970 to March 2014), Cochrane (1980 to March 2014), Web of Science, and Scopus. Searches used the following key words: isotonic solution, crystalloid, saline solution, colloid, resuscitation, fluid therapy, sepsis and septic shock, starch, and gelatin. The filters children and clinical trial were used when possible. Study selection was performed by 1 examiner. The selected articles were analyzed by 2 examiners who validated the articles according to the Cochrane Bias Tool. Discrepancies were resolved by consensus or by a third examiner. A total of 110 articles were selected based on the key words. Of these, 99 were excluded because they assessed postoperative follow-up, burn cases, cardiac surgery, or nutritional therapy or were review articles, guidelines, or editorials. One study was included after an analysis of previous reviews. A total of 12 articles were selected for analysis because they were reports of clinical trials conducted with prospective cohorts and they analyzed the use of crystalloids and colloids or colloids only in the initial treatment of severe sepsis or septic shock in children and adolescents. The total number of patients was 4375, and they ranged in age from 2 months to 15 years, with most patients between 5 and 15 years. Five studies assessed patients diagnosed with malaria, 5 assessed patients with dengue shock syndrome, 1 studied febrile diseases, and 1 examined the progression of patients with septic shock caused by various causes. The studies analyzed did not find evidence to

  20. Noninvasive sensors in critical care medicine: near-infrared spectroscopy for the detection of altered microvascular blood flow in severe sepsis and septic shock

    Science.gov (United States)

    Walz, J. Matthias; Soller, Babs; Soyemi, Olusola; Yang, Ye; Landry, Michelle; Heard, Stephen O.

    2006-10-01

    It is estimated that 750,000 cases of severe sepsis occur in the United States annually, at least 225,000 of which are fatal, resulting in significant utilization of healthcare resources and expenses. Significant progress in the understanding of pathophysiology and treatment of this condition has been made lately. Among the newer treatment strategies for critically ill patients are the administration of early goal directed therapy, and Recombinant Human Activated Protein C (Drotrecogrin alfa (activated) [DTAA]) for severe sepsis. However, mortality remains unacceptably high.

  1. Erythropoietin attenuates renal and pulmonary injury in polymicrobial induced-sepsis through EPO-R, VEGF and VEGF-R2 modulation.

    Science.gov (United States)

    Heitrich, Mauro; García, Daiana Maria de Los Ángeles; Stoyanoff, Tania Romina; Rodríguez, Juan Pablo; Todaro, Juan Santiago; Aguirre, María Victoria

    2016-08-01

    Sepsis remains the most important cause of acute kidney injury (AKI) and acute lung injury (ALI) in critically ill patients. The cecal ligation and puncture (CLP) model in experimental mice reproduces most of the clinical features of sepsis. Erythropoietin (EPO) is a well-known cytoprotective multifunctional hormone, which exerts anti-inflammatory, anti-oxidant, anti-apoptotic and pro-angiogenic effects in several tissues. The aim of this study was to evaluate the underlying mechanisms of EPO protection through the expression of the EPO/EPO receptor (EPO-R) and VEGF/VEF-R2 systems in kidneys and lungs of mice undergoing CLP-induced sepsis. Male inbred Balb/c mice were divided in three experimental groups: Sham, CLP, and CLP+EPO (3000IU/kg sc). Assessment of renal functional parameters, survival, histological examination, immunohistochemistry and/or Western blottings of EPO-R, VEGF and VEGF-R2 were performed at 18h post-surgery. Mice demonstrated AKI by elevation of serum creatinine and renal histologic damage. EPO treatment attenuates renal dysfunction and ameliorates kidney histopathologic changes. Additionally, EPO administration attenuates deleterious septic damage in renal cortex through the overexpression of EPO-R in tubular interstitial cells and the overexpression of the pair VEGF/VEGF-R2. Similarly CLP- induced ALI, as evidenced by parenchymal lung histopathologic alterations, was ameliorated through pulmonary EPO-R, VEGF and VEGF-R2 over expression suggesting and improvement in endothelial survival and functionality. This study demonstrates that EPO exerts protective effects in kidneys and lungs in mice with CLP-induced sepsis through the expression of EPO-R and the regulation of the VEGF/VEGF-R2 pair.

  2. Mesenchymal stem cells in alleviating sepsis-induced mice cardiac dysfunction via inhibition of mTORC1-p70S6K signal pathway.

    Science.gov (United States)

    Huang, Wei; Fan, Wensi; Wang, Yabin; Han, Dong; Li, Xiujuan; Li, Shuang; Li, Congye; Xu, Bin; Huang, Yuesheng; Fu, Xiaobin; Cao, Feng

    2017-01-01

    Sepsis-induced cardiac dysfunction remains a major cause of morbidity and mortality in patients suffered from severe trauma. Mesenchymal stem cells (MSCs) -based treatment has been verified as a promising approach to mitigate the sepsis-induced cardiac dysfunction, but the mechanism is still ambiguous. Thus, our study was designed to explore the potential role of MSCs in sepsis-induced cardiac dysfunction. In vivo bioluminescence imaging revealed 80% acute donor cell death of bone marrow-derived MSCs (BM-MSCs) within 3 days after transplantation. However, echocardiography demonstrated that systolic function in wild-type mice group were reduced after sepsis, while the cardiac function was relatively well persevered in cardiac-conditional deletion of Raptor (component of mTORC1 complex) mice group. Raptor KO group treated with BM-MSCs appeared better cardiac function than other groups (PRaptor-Knock down) and BM-MSC could attenuate the level of proinflammatory cytokines and promote the expression of anti-inflammatory cytokine accompanied by mTORC2-Akt activation (PRaptor-O.E) and BM-MSC could aggravate the inflammatory response accompanied by the activation of mTORC1-p70S6K and inhibition of mTORC2-Akt (P<0.05). The immunomodulatory property of MSC is related to the inhibition of mTORC1-p70S6K and activation of mTORC2-Akt signaling pathway. mTORC1-p70S6K and mTORC2-Akt pathways were involved in the therapeutic adjuncts of MSC. The possible mechanism due to MSC`s immunomodulatory property through activation of mTORC2-Akt and inhibition of mTORC1-p70S6K signal pathways which may lead to modulate the expression of inflammation cytokines.

  3. [New recommendations on the use of human albumin solutions in patients with severe sepsis and septic shock. A critical evaluation of the literature].

    Science.gov (United States)

    Latour-Pérez, J

    2013-01-01

    The third edition of the Surviving Sepsis Campaign guidelines opens the door to the use of albumin for fluid resuscitation in patients with severe sepsis and septic shock. This recommendation is based on a recent meta-analysis that included studies with evidence of insufficient plasma expansion in the control group and studies performed in children with malaria with clear statistical heterogeneity (P for interaction=.02). After excluding pediatric studies, the confidence interval of the effect estimate was consistent with a mortality excess in the group treated with albumin (OR=.87 [95%CI: .71 to 1.07]). Two new randomized studies reported after publication of the meta-analysis found no benefit in patients treated with albumin. Given the uncertainty about the true effect of albumin (due to the existence of indirectness and imprecision) and its cost considerations, it is suggested not to use albumin in the initial resuscitation of patients with severe sepsis and septic shock (GRADE2C).

  4. The most commonly used disease severity scores are inappropriate for risk stratification of older emergency department sepsis patients: an observational multi-centre study.

    Science.gov (United States)

    de Groot, Bas; Stolwijk, Frank; Warmerdam, Mats; Lucke, Jacinta A; Singh, Gurpreet K; Abbas, Mo; Mooijaart, Simon P; Ansems, Annemieke; Esteve Cuevas, Laura; Rijpsma, Douwe

    2017-09-11

    Sepsis recognition in older emergency department (ED) patients is difficult due to atypical symptom presentation. We therefore investigated whether the prognostic and discriminative performance of the five most commonly used disease severity scores were appropriate for risk stratification of older ED sepsis patients (≥70 years) compared to a younger control group (<70 years). This was an observational multi-centre study using an existing database in which ED patients who were hospitalized with a suspected infection were prospectively included. Patients were stratified by age < 70 and ≥70 years. We assessed the association with in-hospital mortality (primary outcome) and the area under the curve (AUC) with receiver operator characteristics of the Predisposition, Infection, Response, Organ dysfunction (PIRO), quick Sequential Organ Failure Assessment (qSOFA), Mortality in ED Sepsis (MEDS), and the Modified and National Early Warning (MEWS and NEWS) scores. In-hospital mortality was 9.5% ((95%-CI); 7.4-11.5) in the 783 included older patients, and 4.6% (3.6-5.7) in the 1497 included younger patients. In contrast to younger patients, disease severity scores in older patients associated poorly with mortality. The AUCs of all disease severity scores were poor and ranged from 0.56 to 0.64 in older patients, significantly lower than the good AUC range from 0.72 to 0.86 in younger patients. The MEDS had the best AUC (0.64 (0.57-0.71)) in older patients. In older and younger patients, the newly proposed qSOFA score (Sepsis 3.0) had a lower AUC than the PIRO score (sepsis 2.0). The prognostic and discriminative performance of the five most commonly used disease severity scores was poor and less useful for risk stratification of older ED sepsis patients.

  5. 5-氟尿嘧啶对重症感染大鼠细胞因子的双相调节作用%Effect of 5-fluorouraeil on modulation of immunity-associated cytokine during severe sepsis in rat

    Institute of Scientific and Technical Information of China (English)

    芦灵军; 胥楠; 陈晓理

    2008-01-01

    Objective To observe the effect of 5-fluorouracil(5-FU)on modulation of the disorders of proinflammatory and anti-inflammatory cytokines in the severe sepsis as a result of intra-abdominal infection in rat,and to investigate the mechanism of efficacy of 5-FU in the treatment of severe sepsis.Methods Thirty female Wistar rats were randomly divided into three groups:control group,severe sepsis group and 5-FU group.Healthy rats served as control(n=10).Severe sepsis was induced by peritoneal injection of 1.8×1012cfu/L E.coli with the volume of 10 ml/kg body weight.In the 5-FU group,50 mg/kg of 5-FU was injected intraperitonealy 40 minutes after severe sepsis was induced.All rats were sacrificed 6 hours after operation.The mortality and the ascites rate were assessed 6 hours after sepsis.At the same time the wet weight of the 1ung was measured and venous blood was collected for determination of concentrations of interleukin-6(IL-6)and IL-10.Results Compared with those of severe sepsis group,the mortality and the ascites rate at 6 hours were decreased significantly in 5-FU group(P<0.05 and P<0.01).The wet weight of lung in severe sepsis group was higher significantly than that in control group(P<0.01).The lung tissue wet weight in 5-FU group was lower than that of severe sepsis group(P<0.05),but it showed no difference when compared with that of control group.The levels of IL-6 and IL-10 in severe sepsis group were higher significantly than those in control group(both P<0.01).The level of IL-6 in 5-FU group was lower than that in severe sepsis group,but with no difference compared with that of control group.The level of IL-10 in 5-FU group was also lower than that in severe sepsis group,but higher than that in control group(both P<0.01).Conclusion 5-FU may 10wer simultaneously the level of proinflammatory IL-6 and anti-inflammatory IL-10.alleviate lung edema and inflammation.5-FU has the protective effect against severe sepsis in rat.%目的 观察5-

  6. NOS3 Protects Against Systemic Inflammation and Myocardial Dysfunction in Murine Polymicrobial Sepsis

    OpenAIRE

    Bougaki, Masahiko; Searles, Robert J.; Kida, Kotaro; Yu, JiaDe; Buys, Emmanuel; Ichinose, Fumito

    2010-01-01

    NO has been implicated in the pathogenesis of septic shock. However, the role of NO synthase 3 (NOS3) during sepsis remains incompletely understood. Here, we examined the impact of NOS3 deficiency on systemic inflammation and myocardial dysfunction during peritonitis-induced polymicrobial sepsis. Severe polymicrobial sepsis was induced by colon ascendens stent peritonitis (CASP) in wild-type (WT) and NOS3-deficient (NOS3KO) mice. NOS3KO mice exhibited shorter survival time than did WT mice af...

  7. Candidemia-induced pediatric sepsis and its association with free radicals, nitric oxide, and cytokine level in host.

    Science.gov (United States)

    Kumar, Dharmendra; Kumar, Abhai; Singh, Smita; Tilak, Ragini

    2015-04-01

    Candida species has become the seventh most frequent causal microorganisms of nosocomial sepsis. Prematurity and low birth weights are strongly associated with the development of neonatal nosocomial bloodstream infections. Candida albicans has been the species most often associated with neonatal infections, but recently, there has been a changing pattern in the isolates recovered from neonates with invasive candidiasis, which poses resistance to the existing class of azoles such as fluconazole antifungals along with cross resistance to newer triazoles, which results in a therapeutic challenge in invasive fungal infections causing high incidence of mortality. Candida species was isolated from blood of neonates and children younger than 15 years admitted to hospital and susceptible for Candida-induced sepsis. Polymerase chain reaction-based identification and confirmation of individual Candida species were done using DNA sequencing. Antibiotic susceptibility assay and resistance pattern for fluconazole, voriconazole, and amphotericin were done for all the isolates. Furthermore, the change in free radical, cytokine release, and nitric oxide synthase expression and nitric oxide release from polymorphonuclear leukocytes isolated from control and pediatric sepsis cases were also performed. The present study probably for the first time reports the change in increasing incidence of nonalbicans Candida-induced sepsis in neonates and children admitted to the intensive care unit of hospital, and current antibiotics load posing resistance for antifungal treatment strategy and provide serious threats in future treatment. The increase in free radicals in polymorphonuclear leukocytes and increase in expression of nitric oxide synthase expression and nitric oxide release in Candida-infected pediatric sepsis cases underlie the role of host factor in dissemination and invasiveness of infection from exogenous sources and pathogenesis of systemic inflammation during sepsis. Copyright

  8. Cystathionine-γ-lyase gene silencing with siRNA in monocytes/ macrophages attenuates inflammation in cecal ligation and puncture-induced sepsis in the mouse

    Indian Academy of Sciences (India)

    A Badiei; ST Chambers; RR Gaddam; M Bhatia

    2016-03-01

    Hydrogen sulphide is an endogenous inflammatory mediator produced by cystathionine-γ-lyase (CSE) in macrophages. To determine the role of H2S and macrophages in sepsis, we used small interference RNA (siRNA) to target the CSE gene and investigated its effect in a mouse model of sepsis. Cecal ligation puncture (CLP)-induced sepsis is characterized by increased levels of myeloperoxidase (MPO) activity, morphological changes in liver and pro-inflammatory cytokines and chemokines in the liver and lung. SiRNA treatment attenuated inflammation in the liver and lungs of mice following CLP-induced sepsis. Liver MPO activity increased in CLP-induced sepsis and treatment with siRNA significantly reduced this. Similarly, lung MPO activity increased following induction of sepsis with CLP while siRNA treatment significantly reduced MPO activity. Liver and lung cytokine and chemokine levels in CLP-induced sepsis reduced following treatment with siRNA. These findings show a crucial pro-inflammatory role for H2S synthesized by CSE in macrophages in sepsis and suggest CSE gene silencing with siRNA as a potential therapeutic approach for this condition.

  9. PICU婴儿脓毒症及严重脓毒症临床特征及预后危险因素分析%Sepsis and severe sepsis in PICU infant: analysis of risk factors and clinical feature

    Institute of Scientific and Technical Information of China (English)

    李璧如; 安康; 曹清; 赵醴; 钱娟; 王莹

    2013-01-01

    目的 分析PICU婴儿脓毒症、严重脓毒症的临床特征,探讨影响其预后的危险因素.方法 对2006年1月至2011年12月我院PICU收治的141例脓毒症患儿运用回顾性病例对照(存活组与死亡组)的研究策略,以患儿入院日为研究起点,死亡或出院为终点,进行临床特点分析.并选择性别、年龄、是否有基础疾病、脓毒症严重程度、脏器受累数、入PICU当天的危重病评分、血生化指标(乳酸、白蛋白、血糖)、血气指标(碱剩余、碳酸氢根、pH值)、是否休克、培养阳性等14个变量,建立Logistic回归模型,分析预后的危险因素.结果 141例患儿的年龄1~12个月,其中脓毒症72例,严重脓毒症69例,死亡29例,病死率为20.6%.29例死亡患儿中,13例有基础疾病.脓毒症和严重脓毒症患儿的感染部位均以肺部为主,分别占47.2%(34/72)、47.8%(33/69);血培养均有34例阳性,分别占47.2% (34/72)、49.3% (34/69).单因素分析显示,性别、基础疾病、年龄、脓毒症严重程度、休克、脏器受累数、危重病例评分、血乳酸、血气pH值、碱剩余、碳酸氢根与脓毒症死亡有关.经逐步引入剔除法,建立Logistic回归模型,仍然与死亡相关的因素包括脓毒症严重程度(OR=22.5,95%CI=5.089,99.475)和脏器受累数(OR=3.305,95%CI=2.152,5.075).结论 婴儿脓毒症严重程度越重和器官受累数越多,死亡风险越大.%Objective To analyze the clinical characteristics of PICU infant with sepsis,severe sepsis,and to explore the impact of prognostic factors.Methods We conducted a retrospective study of 141 cases (from January 2006 to December 2011) who were diagnosed as sepsis and severe sepsis to identify the clinical characteristics.There were 14 variables of the PICU admission day which concluded gender,age,underlying diseases,sepsis severity,organ involvement,critical score,blood biochemistry (lactate,albumin,glucose),blood gas (base excess

  10. Protective Effects of Cucurbitacin B on Acute Lung Injury Induced by Sepsis in Rats

    Science.gov (United States)

    Hua, Shu; Liu, Xing; Lv, Shuguang; Wang, Zhifang

    2017-01-01

    Background The aim of this study was to investigate the protective effects of cucurbitacin B (CuB) on sepsis-induced acute lung injury (ALI) in rats. Material/Methods An ALI model was made by cecal ligation and puncture (CLP) in SD rats. Rats were randomly divided into 5 groups (n=15 per group): animals undergoing a sham CLP (sham group); animals undergoing CLP (CLP control group); animals undergoing CLP and treated with CuB at 1 mg/kg of body weight (bw) (low-dose CuB [L-CuB] group), animals undergoing CuB at 2 mg/kg of bw (mid-dose CuB [M-CuB] group); and animals undergoing CuB at 5 mg/kg of bw (high-dose CuB [H-CuB] group). Samples of blood and lung tissue were harvested at different time points (6, 12, and 24 hour post-CLP surgery) for the detection of indicators which represented ALI. Five rats were respectively sacrificed at each time point. Pathological changes of lung tissue were observed by H&E staining. Another 50 rats were distributed into the same five groups to record the 72 hour survival rates. Results Treatment with CuB significantly increased the blood gas PaO2 levels and decreased lung wet/dry (W/D) ratio (ptumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), (pprotection effects in a dose-depended manner. Conclusions CuB can effectively improve the pulmonary gas exchange function, reduce pulmonary edema, and inhibit the inflammatory response in the lung, revealing that CuB may serve as a potential therapeutic strategy for sepsis-induced ALI. PMID:28315572

  11. Vitamin D deficiency at admission is not associated with 90-day mortality in patients with severe sepsis or septic shock: Observational FINNAKI cohort study.

    Science.gov (United States)

    Ala-Kokko, Tero I; Mutt, Shivaprakash J; Nisula, Sara; Koskenkari, Juha; Liisanantti, Janne; Ohtonen, Pasi; Poukkanen, Meri; Laurila, Jouko J; Pettilä, Ville; Herzig, Karl-Heinz

    2016-01-01

    Introduction Low levels of vitamin D have been associated with increased mortality in patients that are critically ill. This study explored whether vitamin D levels were associated with 90-day mortality in severe sepsis or septic shock. Methods Plasma vitamin D levels were measured on admission to the intensive care unit (ICU) in a prospective multicentre observational study. Results 610 patients with severe sepsis were included; of these, 178 (29%) had septic shock. Vitamin D deficiency (D deficiency (28.3% vs. 28.5%, p = 0.789). Diabetes was more common among patients deficient compared to those not deficient in vitamin D (30% vs. 18%, p D deficiency (31% vs. 16%, p D levels could not predict 90-day mortality ( 0.9; and D deficiency detected upon ICU admission was not associated with 90-day mortality in patients with severe sepsis or septic shock. Key messages In severe sepsis and septic shock, a vitamin D deficiency upon ICU admission was not associated with increased mortality. Compared to patients with sufficient vitamin D, patients with deficient vitamin D more frequently exhibited diabetes, elevated C-reactive protein levels, and hospital-acquired infections upon ICU admission, and they more frequently developed acute kidney injury.

  12. Markers of endothelial damage and coagulation impairment in patients with severe sepsis resuscitated with hydroxyethyl starch 130/0.42 vs Ringer acetate

    DEFF Research Database (Denmark)

    Müller, Rasmus; Ostrowski, Sisse Rye; Haase, Nicolai;

    2016-01-01

    PURPOSE: The Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial showed increased mortality in patients resuscitated with hydroxyethyl starch 130/0.42 (HES) vs Ringer acetate. Different effects of the fluids on the endothelium may have contributed to the observed outcome. We aimed...

  13. Long-term outcomes in patients with severe sepsis randomised to resuscitation with hydroxyethyl starch 130/0.42 or Ringer’s acetate

    DEFF Research Database (Denmark)

    Perner, Anders; Haase, Nicolai; Winkel, Per

    2014-01-01

    and centralised allocation data that included 804 patients with severe sepsis needing fluid resuscitation in 26 general intensive care units (ICUs) in Scandinavia. Patients were allocated to fluid resuscitation using either 6% HES 130/0.42 or Ringer's acetate during ICU admission. We assessed mortality rates at 6...

  14. Calibrated versus uncalibrated arterial pressure waveform analysis in monitoring cardiac output with transpulmonary thermodilution in patients with severe sepsis and septic shock: an observational study

    NARCIS (Netherlands)

    Slagt, C.; Helmi, M.; Malagon, I.; Groeneveld, A.B.

    2015-01-01

    BACKGROUND: Cardiac output (CO) measurement is often required in critically ill patients. The performances of newer, less invasive techniques require evaluation in patients with severe sepsis and septic shock. OBJECTIVES: To compare calibrated arterial pressure waveform analysis-derived CO (COap, Vo

  15. The influence of volume and intensive care unit organization on hospital mortality in patients admitted with severe sepsis: a retrospective multicentre cohort study.

    NARCIS (Netherlands)

    Peelen, L.; Keizer, N.F. de; Peek, N.; Scheffer, G.J.; Voort, P.H. van der; Jonge, E. de

    2007-01-01

    INTRODUCTION: The aim of the study was to assess the influence of annual volume and factors related to intensive care unit (ICU) organization on in-hospital mortality among patients admitted to the ICU with severe sepsis. METHODS: A retrospective cohort study was conducted using the database of the

  16. Calibrated versus uncalibrated arterial pressure waveform analysis in monitoring cardiac output with transpulmonary thermodilution in patients with severe sepsis and septic shock: an observational study

    NARCIS (Netherlands)

    Slagt, C.; Helmi, M.; Malagon, I.; Groeneveld, A.B.

    2015-01-01

    BACKGROUND: Cardiac output (CO) measurement is often required in critically ill patients. The performances of newer, less invasive techniques require evaluation in patients with severe sepsis and septic shock. OBJECTIVES: To compare calibrated arterial pressure waveform analysis-derived CO (COap,

  17. Calibrated versus uncalibrated arterial pressure waveform analysis in monitoring cardiac output with transpulmonary thermodilution in patients with severe sepsis and septic shock: an observational study

    NARCIS (Netherlands)

    Slagt, C.; Helmi, M.; Malagon, I.; Groeneveld, A.B.

    2015-01-01

    BACKGROUND: Cardiac output (CO) measurement is often required in critically ill patients. The performances of newer, less invasive techniques require evaluation in patients with severe sepsis and septic shock. OBJECTIVES: To compare calibrated arterial pressure waveform analysis-derived CO (COap, Vo

  18. Diuretics induced uremia and nonrecovery of renal function in a patient with acute renal failure caused by sepsis

    Science.gov (United States)

    Sahu, P. K.; Pal, A.; Panda, J.; Patnaik, S.

    2011-01-01

    Sepsis is a clinical syndrome related to severe infection and is characterized by systemic inflammation and injury to multiple organs and functional systems. Sepsis is one of the main causes of acute renal failure (ARF). Diuretics are frequently administered during ARF. However, there is scant evidence that diuretics provide any benefit to the patients with ARF. This case report highlights the occurrence of uremia and nonrecovery of renal function after administration of diuretics in a patient with ARF caused by sepsis. It is suggested that physicians should be cautious in prescribing diuretics to patients with ARF due to septicemia. Diuretics cause uremia and may lead to false diagnosis of chronic renal failure and nonrecovery of renal function. The patient may unnecessarily require prolonged dialysis. PMID:22022011

  19. Diuretics induced uremia and nonrecovery of renal function in a patient with acute renal failure caused by sepsis

    Directory of Open Access Journals (Sweden)

    P K Sahu

    2011-01-01

    Full Text Available Sepsis is a clinical syndrome related to severe infection and is characterized by systemic inflammation and injury to multiple organs and functional systems. Sepsis is one of the main causes of acute renal failure (ARF. Diuretics are frequently administered during ARF. However, there is scant evidence that diuretics provide any benefit to the patients with ARF. This case report highlights the occurrence of uremia and nonrecovery of renal function after administration of diuretics in a patient with ARF caused by sepsis. It is suggested that physicians should be cautious in prescribing diuretics to patients with ARF due to septicemia. Diuretics cause uremia and may lead to false diagnosis of chronic renal failure and nonrecovery of renal function. The patient may unnecessarily require prolonged dialysis.

  20. 儿童严重脓毒症呼吸支持策略%Respiratory support strategy of severe sepsis in children

    Institute of Scientific and Technical Information of China (English)

    喻文亮

    2015-01-01

    2012国际脓毒血症指南对严重脓毒症的定义作了重新界定.现结合指南与机械通气相关最新进展对严重脓毒症的呼吸支持策略进行简要概述,包括氧气疗法、机械通气适应证、机械通气对感染性休克的支持作用、机械通气时药物选择及通气策略、机械通气时血流动力学监测等.%The definition of severe sepsis has been renewed in 2012 international guidelines for management of severe sepsis and septic shock.This article summarizes briefly respiratory support strategy of severe sepsis which incorporated with new guideline and recent progress in sepsis and mechanical ventilation (MV).Oxygen therapy,indication of mechanical ventilation,the support roles of MV on septic shock,drug selection,MV strategy and hemodynamic monitoring are included in this article.

  1. Sepsis-induced cardiac mitochondrial dysfunction involves altered mitochondrial-localization of tyrosine kinase Src and tyrosine phosphatase SHP2.

    Directory of Open Access Journals (Sweden)

    Qun S Zang

    Full Text Available Our previous research demonstrated that sepsis produces mitochondrial dysfunction with increased mitochondrial oxidative stress in the heart. The present study investigated the role of mitochondria-localized signaling molecules, tyrosine kinase Src and tyrosine phosphatase SHP2, in sepsis-induced cardiac mitochondrial dysfunction using a rat pneumonia-related sepsis model. SD rats were given an intratracheal injection of Streptococcus pneumoniae, 4×10(6 CFU per rat, (or vehicle for shams; heart tissues were then harvested and subcellular fractions were prepared. By Western blot, we detected a gradual and significant decrease in Src and an increase in SHP2 in cardiac mitochondria within 24 hours post-inoculation. Furthermore, at 24 hours post-inoculation, sepsis caused a near 70% reduction in tyrosine phosphorylation of all cardiac mitochondrial proteins. Decreased tyrosine phosphorylation of certain mitochondrial structural proteins (porin, cyclophilin D and cytochrome C and functional proteins (complex II subunit 30kD and complex I subunit NDUFB8 were evident in the hearts of septic rats. In vitro, pre-treatment of mitochondrial fractions with recombinant active Src kinase elevated OXPHOS complex I and II-III activity, whereas the effect of SHP2 phosphatase was opposite. Neither Src nor SHP2 affected complex IV and V activity under the same conditions. By immunoprecipitation, we showed that Src and SHP2 consistently interacted with complex I and III in the heart, suggesting that complex I and III contain putative substrates of Src and SHP2. In addition, in vitro treatment of mitochondrial fractions with active Src suppressed sepsis-associated mtROS production and protected aconitase activity, an indirect marker of mitochondrial oxidative stress. On the contrary, active SHP2 phosphatase overproduced mtROS and deactivated aconitase under the same in vitro conditions. In conclusion, our data suggest that changes in mitochondria

  2. Effects of gamma oryzanol on factors of oxidative stress and sepsis-induced lung injury in experimental animal model

    Directory of Open Access Journals (Sweden)

    Elmira Zolali

    2015-12-01

    Full Text Available Objective (s: There is corroborating evidence to substantiate redox imbalance and oxidative stress in sepsis that finally leads to organ damage or even death. Gamma oryzanol (GO is one of the major bioactive components in rice bran has been considered to function as an antioxidant. The present study was carried out to evaluate the antioxidant activity of gamma oryzanol in vitro and its efficacy in sepsis. Materials and Methods: To induce sepsis, cecal ligation and puncture (CLP method was performed on the rats. A study group of forty male Wistar rats were divided into the following groups: sham group; CLP group; 50 mg/kg GO- treated CLP group and 100 mg/kg GO- treated CLP group. GO was administered with an oral gavage 2 hr prior to inducing sepsis. Tissue and blood samples were collected 12 hr after CLP to prepare tissue sections for histopathological study and assay the oxidative stress biomarkers including: SOD (Superoxide Dismutase, TAC (total antioxidant capacity, MDA (Malondialdehyde, MPO (Myeloperoxidase and PAI-1 (Plasminogen Activator Inhibitor-1. Data are given as mean ± SD. The ANOVA with Tukey post hoc test was used to determine the differences between groups and P Results: TAC level increased in GO- treated CLP groups (P

  3. Antimicrobial-induced endotoxaemia in patients with sepsis in the field of acute pyelonephritis.

    Directory of Open Access Journals (Sweden)

    Giamarellos-Bourboulis E

    2003-01-01

    Full Text Available BACKGROUND: In vitro results have shown that antimicrobial agents may induce the Gram-negative bacteria to release endotoxins (LPS, which in turn, could trigger the secretion of cytokines from monocytes. AIMS: To compare the effect of cefuroxime, netilmicin or ciprofloxacin on serum levels of LPS and tumour necrosis factor-alpha (TNFalpha. METHODS: Seventy-four patients with acute pyelonephritis caused by Gram-negative bacteria and signs of sepsis were randomly assigned to receive one of three intravenous regimens of cefuroxime, netilmicin or ciprofloxacin. Blood samples were collected before therapy and at specified time intervals for 96 hours after the initiation of treatment for the determination of serum levels of LPS and of TNFalpha. RESULTS: Patients treated with cefuroxime presented an early peak of LPS and of TNFalpha in serum two hours after the initiation of treatment compared to the other study groups. After that time interval, concentrations of LPS and TNFalpha were similar in all the study groups. Fever accompanied by endotoxaemia was still detected for 48 hours after the start of therapy in 36, 37.5 and 36% of patients treated with cefuroxime, netilmicin and ciprofloxacin respectively. The corresponding figures for these agents at 72 hours were 28, 12.5 and 24%, respective and 12, 4.2 and 4% at 96 hours (P value not significant. CONCLUSIONS: With the exception of an early peak in the serum levels of LPS and TNFalpha in patients treated with cefuroxime, no significant difference could be detected amongst the study groups as far as their effect on serum levels of LPS and TNFalpha were concerned. This suggests that these three antimicrobial agents may be administered safely at the early stages of sepsis.

  4. Sepsis Caused by Achromobacter Xylosoxidans in a Child with Cystic Fibrosis and Severe Lung Disease.

    Science.gov (United States)

    Stobbelaar, Kim; Van Hoorenbeeck, Kim; Lequesne, Monique; De Dooy, Jozef; Ho, Erwin; Vlieghe, Erika; Ieven, Margaretha; Verhulst, Stijn

    2016-08-08

    BACKGROUND Achromobacter xylosoxidans is an aerobic, motile, Gram-negative, opportunistic pathogen that can be responsible for various severe nosocomial and community-acquired infections. It has been found in immunocompromised patients and patients with several other underlying conditions, but the clinical role of this microorganism in cystic fibrosis is unclear. CASE REPORT We describe a case of septic shock caused by A. xylosoxidans in a 10-year-old child with cystic fibrosis and severe lung disease. CONCLUSIONS As the prevalence of A. xylosoxidans in cystic fibrosis patients is rising and patient-to-patient transmission is highly probable, further studies are warranted to determine its role and to document the appropriate treatment strategy for eradication and long-term treatment of this organism.

  5. Tenecteplase for ST-elevation myocardial infarction in a patient treated with drotrecogin alfa (activated for severe sepsis: a case report

    Directory of Open Access Journals (Sweden)

    Barra Lillian

    2009-11-01

    Full Text Available Abstract Introduction Drotrecogin alfa (activated (DrotAA, an activated protein C, promotes fibrinolysis in patients with severe sepsis. There are no reported cases or studies that address the diagnosis and treatment of myocardial infarction in septic patients treated with DrotAA. Case presentation A 59-year-old Caucasian man with septic shock secondary to community-acquired pneumonia treated with DrotAA, subsequently developed an ST-elevation myocardial infarction 12 hours after starting DrotAA. DrotAA was stopped and the patient was given tenecteplase thrombolysis resulting in complete resolution of ST-elevation and no adverse bleeding events. DrotAA was restarted to complete the 96-hour course. The sepsis resolved and the patient was discharged from hospital. Conclusion In patients with severe sepsis or septic shock complicated by myocardial infarction, it is difficult to determine if the myocardial infarction is an isolated event or caused by the sepsis process. The efficacy and safety of tenecteplase thrombolysis in septic patients treated with DrotAA need further study.

  6. Genetic variation in the TNF receptor-associated factor 6 gene is associated with susceptibility to sepsis-induced acute lung injury

    Directory of Open Access Journals (Sweden)

    Song Zhenju

    2012-08-01

    well as after LPS stimulation (P = 0.009 and P = 0.005. Moreover, the concentrations of TNF-α and IL-6 in cell culture supernatants were also significantly higher in the subjects with rs4755453GG genotype than in subjects with CG and CC genotype. None of the 14 tagSNPs showed associations with risk of death and severity among ALI cases. Conclusions Our findings indicated that common genetic variants in TRAF6 were significantly associated with susceptibility to sepsis-induced ALI in Chinese Han population. This was the first genetic evidence supporting a role for TRAF6 in ALI.

  7. Mechanical ventilation alone, and in the presence sepsis, induces peripheral skeletal muscle catabolism in neonatal pigs

    Science.gov (United States)

    Reduced rates of skeletal muscle accretion are a prominent feature of the metabolic response to sepsis in infants and children. Septic neonates often require medical support with mechanical ventilation (MV). The combined effects of MV and sepsis in muscle have not been examined in neonates, in whom ...

  8. Mechanical ventilation and sepsis induce skeletal muscle catabolism in neonatal pigs

    Science.gov (United States)

    Reduced rates of skeletal muscle accretion are a prominent feature of the metabolic response to sepsis in infants and children. Septic neonates often require medical support with mechanical ventilation (MV). The combined effects of MV and sepsis in muscle have not been examined in neonates, in whom ...

  9. Sepsis Caused by Extended-Spectrum Beta-Lactamase (ESBL)-Positive K. pneumoniae and E. coli: Comparison of Severity of Sepsis, Delay of Anti-Infective Therapy and ESBL Genotype

    Science.gov (United States)

    Steinmetz, Ivo; Kohler, Christian; Pfeifer, Yvonne; Gastmeier, Petra; Schwab, Frank; Kola, Axel; Deja, Maria; Leistner, Rasmus

    2016-01-01

    Infections with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are associated with increased mortality. Outcome differences due to various species of ESBL-E or ESBL genotypes are not well investigated. We conducted a cohort study to assess risk factors for mortality in cases of ESBL-E bacteremia (K. pneumoniae or E. coli) and the risk factors for sepsis with organ failure. All consecutive patients of our institution from 2008 to 2011 with bacteremia due to ESBL-E were included. Basic epidemiological data, underlying comorbidities, origin of bacteremia, severity of sepsis and delay of appropriate anti-infective treatment were collected. Isolates were PCR-screened for the presence of ESBL genes and plasmid-mediated AmpC β-lactamases. Cox proportional hazard regression on mortality and multivariable logistic regression on risk factors for sepsis with organ failure was conducted. 219 cases were included in the analysis: 73.1% due to E. coli, 26.9% due to K. pneumoniae. There was no significant difference in hospital mortality (ESBL-E. coli, 23.8% vs. ESBL-K. pneumoniae 27.1%, p = 0.724). However, the risk of sepsis with organ failure was associated in cases of K. pneumoniae bacteremia (OR 4.5, p<0.001) and patients with liver disease (OR 3.4, p = 0.004) or renal disease (OR 6.8, p<0.001). We found significant differences in clinical presentation of ESBL-E bacteremia due to K. pneumoniae compared to E. coli. As K. pneumoniae cases showed a more serious clinical presentation as E. coli cases and were associated with different risk factors, treatment and prevention strategies should be adjusted accordingly. PMID:27442425

  10. Sepsis Caused by Extended-Spectrum Beta-Lactamase (ESBL)-Positive K. pneumoniae and E. coli: Comparison of Severity of Sepsis, Delay of Anti-Infective Therapy and ESBL Genotype.

    Science.gov (United States)

    Sakellariou, Christian; Gürntke, Stephan; Steinmetz, Ivo; Kohler, Christian; Pfeifer, Yvonne; Gastmeier, Petra; Schwab, Frank; Kola, Axel; Deja, Maria; Leistner, Rasmus

    2016-01-01

    Infections with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are associated with increased mortality. Outcome differences due to various species of ESBL-E or ESBL genotypes are not well investigated. We conducted a cohort study to assess risk factors for mortality in cases of ESBL-E bacteremia (K. pneumoniae or E. coli) and the risk factors for sepsis with organ failure. All consecutive patients of our institution from 2008 to 2011 with bacteremia due to ESBL-E were included. Basic epidemiological data, underlying comorbidities, origin of bacteremia, severity of sepsis and delay of appropriate anti-infective treatment were collected. Isolates were PCR-screened for the presence of ESBL genes and plasmid-mediated AmpC β-lactamases. Cox proportional hazard regression on mortality and multivariable logistic regression on risk factors for sepsis with organ failure was conducted. 219 cases were included in the analysis: 73.1% due to E. coli, 26.9% due to K. pneumoniae. There was no significant difference in hospital mortality (ESBL-E. coli, 23.8% vs. ESBL-K. pneumoniae 27.1%, p = 0.724). However, the risk of sepsis with organ failure was associated in cases of K. pneumoniae bacteremia (OR 4.5, pESBL-E bacteremia due to K. pneumoniae compared to E. coli. As K. pneumoniae cases showed a more serious clinical presentation as E. coli cases and were associated with different risk factors, treatment and prevention strategies should be adjusted accordingly.

  11. Modelling severe Staphylococcus aureus sepsis in conscious pigs: are implications for animal welfare justified?

    DEFF Research Database (Denmark)

    Olsen, Helle G; Kjelgaard-Hansen, Mads; Tveden-Nyborg, Pernille;

    2016-01-01

    ), and 30 mL (n = 1), corresponding to infusion durations of 3.33, 6.66, and 10 min at dose rates of 3 × 10(7), 1.5 × 10(7), and 1 × 10(7) cfu/min/kg BW, respectively. Blood samples were drawn for complete blood count, clinical chemistry, and inflammatory markers before and every 6 h after inoculation....... Prior to euthanasia, a galactose elimination capacity test was performed to assess liver function. Pigs were euthanised 48 h post inoculation for necropsy and histopathological evaluation. While infusion times of 6.66 min, and higher, did not induce liver dysfunction (n = 3), the infusion time of 3...

  12. Association of IL-10 (-819T/C, -592A/C and -1082A/G) and IL-6 -174G/C gene polymorphism and the risk of pneumonia-induced sepsis.

    Science.gov (United States)

    Mao, Zheng-Rong; Zhang, Shao-Lei; Feng, Bo

    2017-03-01

    Association between inherited variants and the risks of sepsis is controversial. To evaluate the risk of pneumonia-induced sepsis by examining its linkage with polymorphisms of IL-6 and IL-10. Samples were obtained from 188 pneumonia-induced sepsis patients, 162 pneumonia patients and 200 healthy controls. Subjects with IL-10 -1082 AA genotypes and IL-6 -174 CC genotype had a higher risk of sepsis and increased mRNA levels. The variants of IL-10 -1082 A allele and IL-6 -174 C allele contributed to an increased risk of pneumonia-induced sepsis.

  13. Clinical Usefulness of Procalcitonin and C-Reactive Protein as Outcome Predictors in Critically Ill Patients with Severe Sepsis and Septic Shock.

    Directory of Open Access Journals (Sweden)

    Jeong-Am Ryu

    Full Text Available Sepsis is a major cause of mortality and morbidity in critically ill patients. Procalcitonin (PCT and C-reactive protein (CRP are the most frequently used biomarkers in sepsis. We investigated changes in PCT and CRP concentrations in critically ill patients with sepsis to determine which biochemical marker better predicts outcome. We retrospectively analyzed 171 episodes in 157 patients with severe sepsis and septic shock who were admitted to the Samsung Medical Center intensive care unit from March 2013 to February 2014. The primary endpoint was patient outcome within 7 days from ICU admission (treatment failure. The secondary endpoint was 28-day mortality. Severe sepsis was observed in 42 (25% episodes from 41 patients, and septic shock was observed in 129 (75% episodes from 120 patients. Fifty-five (32% episodes from 42 patients had clinically-documented infection, and 116 (68% episodes from 99 patients had microbiologically-documented infection. Initial peak PCT and CRP levels were not associated with treatment failure and 28-day mortality. However, PCT clearance (PCTc and CRP (CRPc clearance were significantly associated with treatment failure (p = 0.027 and p = 0.030, respectively and marginally significant with 28-day mortality (p = 0.064 and p = 0.062, respectively. The AUC for prediction of treatment success was 0.71 (95% CI, 0.61-0.82 for PCTc and 0.71 (95% CI, 0.61-0.81 for CRPc. The AUC for survival prediction was 0.77 (95% CI, 0.66-0.88 for PCTc and 0.77 (95% CI, 0.67-0.88 for CRPc. Changes in PCT and CRP concentrations were associated with outcomes of critically ill septic patients. CRP may not be inferior to PCT in predicting outcome in these patients.

  14. Sepsis: An update in management.

    Science.gov (United States)

    Galen, Benjamin T; Sankey, Christopher

    2015-11-01

    Hospitalists are a critical link in providing evidence-based care for patients with sepsis across the disease spectrum, from early recognition to recovery. The past decade of sepsis research has led to significant findings that will change clinical practice for hospital medicine practitioners. Although the incidence of severe sepsis in the United States has continued to rise, in-hospital mortality has declined. Management of the spectrum of sepsis disorders is no longer restricted to the intensive care unit (ICU). This review article will provide an update in the management of sepsis for hospitalists based on recently published pivotal studies. The expanding evidence base in sepsis includes early goal-directed therapy/clinical endpoints/sepsis bundles, antibiotics and source control, volume resuscitation, ICU considerations (including the use of insulin and corticosteroids), mortality/complications, and the newly recognized condition of "sepsis survivorship".

  15. 烧伤脓毒症诊断与综合防治策略%Diagnosis and comprehensive management of sepsis after burn

    Institute of Scientific and Technical Information of China (English)

    柴家科

    2013-01-01

    Sepsis induced by invasive infection is a challenging problem and the major cause of death after severe burn.With the increasing understanding of sepsis,diagnostic criteria of sepsis were proposed and revised consecutively so that they could be consistent with the clinical practice.Being different from other trauma and critical diseases,diagnostic criteria of sepsis after severe burn were also proposed,and they need further clinical verification.It is believed that comprehensive measures for the treatment of severe sepsis after burn should be advocated.These measures include rapid and effective resuscitation of burn shock,early escharectomy and closure of burn wound,metabolic support,immunoregulation and anti-inflammation,reinforcement of organ support,etc.Although a number of advances have been achieved in the past decades,the mechanism of sepsis need further elucidation,diagnostic criteria of sepsis need further revision,and novel therapeutic measures for burn sepsis should be developed.

  16. Diabetic patients with severe sepsis admitted to intensive care unit do not fare worse than non-diabetic patients: a nationwide population-based cohort study.

    Directory of Open Access Journals (Sweden)

    Cheng-Wei Chang

    Full Text Available BACKGROUND: We sought to examine whether type 2 diabetes increases the risk of acute organ dysfunction and of hospital mortality following severe sepsis that requires admission to an intensive care unit (ICU. METHODS: Nationwide population-based retrospective cohort study of 16,497 subjects with severe sepsis who had been admitted for the first time to an ICU during the period of 1998-2008. A diabetic cohort (n = 4573 and a non-diabetic cohort (n = 11924 were then created. Relative risk (RR of organ dysfunctions, length of hospital stay (LOS, 90-days hospital mortality, ICU resource utilization and hazard ratio (HR of mortality adjusted for age, gender, Charlson-Deyo comorbidity index score, surgical condition and number of acute organ dysfunction, were compared across patients with severe sepsis with or without diabetes. RESULTS: Diabetic patients with sepsis had a higher risk of developing acute kidney injury (RR, 1.54; 95% confidence interval (CI, 1.44-1.63 and were more likely to be undergoing hemodialysis (15.55% vs. 7.24% in the ICU. However, the diabetic cohort had a lower risk of developing acute respiratory dysfunction (RR = 0.96, 0.94-0.97, hematological dysfunction (RR = 0.70, 0.56-0.89, and hepatic dysfunction (RR = 0.77, 0.63-0.93. In terms of adjusted HR for 90-days hospital mortality, the diabetic patients with severe sepsis did not fare significantly worse when afflicted with cardiovascular, respiratory, hepatic, renal and/or neurologic organ dysfunction and by numbers of organ dysfunction. There was no statistically significant difference in LOS between the two cohorts (median 17 vs. 16 days, interquartile range (IQR 8-30 days, p = 0.11. Multiple logistic regression analysis to predict the occurrence of mortality shows that being diabetic was not a predictive factor with an odds ratio of 0.972, 95% CI 0.890-1.061, p = 0.5203. INTERPRETATION: This large nationwide population-based cohort study suggests

  17. [Decrease of the incidence of sepsis syndrome after early enteral nutrition of patients with severe burns].

    Science.gov (United States)

    Pereira, J L; Gómez-Cia, T; Garrido, M; Parejo, J; Jódar, E; Serrano, P; Romero, H; Fraile, J; Franco, A; García-Luna, P P

    1996-01-01

    The objective of this study was to evaluate the effect of early enteral nutrition on the incidence of the septic syndrome as well as its tolerance, in patients with severe burns. We retrospectively studied 64 patients older than 15 years of age, with a greater than 20% burned body surface area. They were divided into 2 groups as a function of the time elapsed between the beginning of Enteral Nutrition and the time of the burning: 23 patients were given Enteral Nutrition within 24 hours after the burn, and in 41 patients the enteral nutrition was started later than 24 hours after sustaining the thermal injury. Both groups were similar with respect to age, sex, percentage of 2nd and 3rd degree burns, incidence of inhalation, and deaths. All patients received the Enteral Nutrition through a nasogastric tube, with administration of a polymeric, hyperprotein and hypocaloric formula through a continuous infusion pump. In our study we saw a reduction of the incidence of the septic syndrome in the patients who received early enteral Nutrition (26%; 6 patients of a total of 23), with respect to those who did non receive early Enteral Nutrition (54%; 22 patients of a total of 41), with a statistical significance of p > 0.05. There were no differences between both groups with respect to the digestive tolerance to Enteral Nutrition. From our study we can deduce that early Enteral Nutrition reduces the incidence of septic complications, without this increasing the digestive intolerance to the same.

  18. Lipocalin 2 deficiency dysregulates iron homeostasis and exacerbates endotoxin-induced sepsis

    DEFF Research Database (Denmark)

    Srinivasan, Gayathri; Aitken, Jesse D; Zhang, Benyue

    2012-01-01

    Various states of inflammation, including sepsis, are associated with hypoferremia, which limits iron availability to pathogens and reduces iron-mediated oxidative stress. Lipocalin 2 (Lcn2; siderocalin, 24p3) plays a central role in iron transport. Accordingly, Lcn2-deficient (Lcn2KO) mice exhib...... mortality, suggesting that Lcn2 may act as an antioxidant in vivo by regulating iron homeostasis. Thus, Lcn2-mediated regulation of labile iron protects the host against sepsis. Its small size and simple structure may make Lcn2 a deployable treatment for sepsis....

  19. Overexpression of HO-1 Contributes to Sepsis-Induced Immunosuppression by Modulating the Th1/Th2 Balance and Regulatory T-Cell Function.

    Science.gov (United States)

    Yoon, Seong-Jin; Kim, So-Jin; Lee, Sun-Mee

    2017-05-15

    Countervailing anti-inflammatory response and immunosuppression can cause death in late sepsis. Depletion and dysfunction of T cells are critical for developing sepsis-induced immunosuppression. Heme oxygenase-1 (HO-1) has a regulatory effect on differentiation and function of T cells and anti-inflammatory properties. We therefore investigated the immunosuppressive role of HO-1 in sepsis with a focus on its effects on helper T-cell (Th) differentiation and regulatory T cells (Treg). Sepsis was induced by cecal ligation and puncture (CLP). Mice were intraperitoneally injected with zinc protoporphyrin (ZnPP; 25 mg/kg), an HO-1 inhibitor, or hemin (20 mg/kg), an HO-1 inducer, at 24 and 36 hours post-CLP. Splenocytes were isolated 48 hours post-CLP. Mice were intranasally infected with Pseudomonas aeruginosa 4 days post-CLP as a secondary pneumonia infection model. ZnPP improved survival and bacterial clearance, whereas hemin had the opposite effect in septic mice. CLP induced lymphocyte apoptosis and a proinflammatory Th1 to anti-inflammatory Th2 shift, which was attenuated by ZnPP. ZnPP attenuated the CLP-induced Treg population and protein expression of inhibitory costimulatory molecules. Furthermore, ZnPP improved survival in the secondary pneumonia infection model. Our findings suggest that HO-1 overexpression contributes to sepsis-induced immunosuppression during late phase sepsis by promoting Th2 polarization and Treg function.

  20. Acute lung inflammation in Klebsiella pneumoniae B5055-induced pneumonia and sepsis in BALB/c mice: a comparative study.

    Science.gov (United States)

    Kumar, Vijay; Chhibber, Sanjay

    2011-10-01

    Lungs play an important role in the body's defense against a variety of pathogens, but this network of immune system-mediated defense can be deregulated during acute pulmonary infections. The present study compares acute lung inflammation occurring during Klebsiella pneumoniae B5055-induced pneumonia and sepsis in BALB/c mice. Pneumonia was induced by intranasal instillation of bacteria (10(4) cfu), while sepsis was developed by placing the fibrin-thrombin clot containing known amount of bacteria (10(2) cfu) into the peritoneal cavity of animals. Mice with sepsis showed 100% mortality within five post-infection days, whereas all the animals with pneumonia survived. In animals suffering from K. pneumoniae B5055-induced pneumonia, all the inflammatory parameters (TNF-α, IL-1α, MPO, MDA, and NO) were found to be maximum till third post-infection day, after that, a decline was observed, whereas in septic animals, all the above-mentioned markers of inflammation kept on increasing. Histopathological study showed presence of alternatively activated alveolar macrophages (or foam cells) in lungs of mice with pneumonia after third post-infection day, which might have contributed to the induction of resolution of inflammation, but no such observation was made in lungs of septic mice. Hence, during pneumonia, controlled activation of macrophages may lead to resolution of inflammation.

  1. Pediatric Sepsis.

    Science.gov (United States)

    Prusakowski, Melanie K; Chen, Audrey P

    2017-02-01

    Pediatric sepsis is distinct from adult sepsis in its definitions, clinical presentations, and management. Recognition of pediatric sepsis is complicated by the various pediatric-specific comorbidities that contribute to its mortality and the age- and development-specific vital sign and clinical parameters that obscure its recognition. This article outlines the clinical presentation and management of sepsis in neonates, infants, and children, and highlights some key populations who require specialized care. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Quality of life and pruritus in patients with severe sepsis resuscitated with hydroxyethyl starch long-term follow-up of a randomised trial

    DEFF Research Database (Denmark)

    Wittbrodt, Piotr; Haase, Nicolai; Butowska, Dominika

    2013-01-01

    INTRODUCTION: The effects of hydroxyethyl starch (HES) on patient-centered outcome measures have not been fully described in patients with severe sepsis. We assessed health-related quality of life (HRQoL) and the occurrence of pruritus in patients with severe sepsis randomized to resuscitation...... with HES 130/0.42 or Ringer's acetate. METHODS: We did post hoc analyses of the Danish survivors (n = 295) of the 6S trial using mailed questionnaires on self-perceived HRQoL (Short Form (SF) - 36) and pruritus. RESULTS: Median 14 months (interquartile range 10 to 18) after randomization, 182 (61%) and 185...... (62%) completed questionnaires were obtained for the assessment of HRQoL and pruritus, respectively. Responders were older than nonresponders, but characteristics at randomization of the responders in the HES vs. Ringer's groups were comparable. At follow-up, the patients in the HES group had lower...

  3. Layer-specific quantification of myocardial deformation in sepsis-induced Takotsubo cardiomyopathy

    Science.gov (United States)

    Hung, Ming-Jui; Kao, Yu-Cheng; Chen, Wei-Siang; Mao, Chun-Tai; Chen, Tien-Hsing; Yang, Ning-I.; Ko, Ta; Liang, Chung-Yu

    2016-01-01

    Abstract Introduction: Little is known about the time-course changes in left ventricular myocardial deformation in patients with Takotsubo cardiomyopathy (TC) using layer-specific quantification of myocardial deformation assessed by 2-dimensional speckle tracking echocardiography (2DSTE). Case summary: In this retrospective 2DSTE follow-up study of 3 female patients with sepsis-induced TC, we examined changes in strain among the 3 myocardial layers, and examined the changes in left ventricular diastolic function and right ventricular systolic function. In all 3 patients, there was improvement of at least 15% in left ventricular ejection fractions, and improvement in left ventricular longitudinal and circumferential strains. The absolute differences in left ventricular global strains between the endocardium and epicardium, and between the first and the third 2DSTE studies reflect the following: a decrease in all 3 myocardial layers in patients with acute TC; and a slower improvement in mid-myocardial and epicardial function during recovery of TC. In addition, the right ventricular free wall strains were also impaired in the acute stage of TC with gradual improvement during recovery. Conclusions: Left ventricular strains did not fully recover even 1 month after acute TC. In addition, right ventricular free wall strains were also impaired in all 3 patients initially. In this case series, we found that layer-specific 2DSTE is a more sensitive method for myocardial function assessment than standard echocardiography. PMID:27858884

  4. Dynamic cerebral autoregulation to induced blood pressure changes in human experimental and clinical sepsis

    DEFF Research Database (Denmark)

    Berg, Ronan M G; Plovsing, Ronni R; Bailey, Damian M

    2016-01-01

    (Pvolunteers at baseline; Pvolunteers after LPS). The corresponding RoR values increased from 0·46 (0·31-0·49) s(-1) at baseline to 0·58 (0·36-0·74) s(-1) after LPS (Pvolunteers, whereas they were similar to values observed in patients [0·43 (0·36-0·52) s...... shock. In this study, we hypothesized that this pattern of response would be identical during induced changes in blood pressure. Dynamic cerebral autoregulation was assessed in nine healthy volunteers and six septic patients. The healthy volunteers underwent a 4-h intravenous infusion of LPS (total dose......R). This was performed before and after LPS infusion in healthy volunteers, and within 72 h following clinical diagnosis of sepsis in patients. In healthy volunteers, thigh-cuff deflation caused a MAP reduction of 16 (13-20) % at baseline and 18 (16-20) % after LPS, while the MAP reduction was 12 (11-13) % in patients...

  5. {sup 18}F-fluorodeoxyglucose positron emission tomography combined with whole-body computed tomographic angiography in critically ill patients with suspected severe sepsis with no definite diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Mandry, Damien [CHU Nancy, Pole d' imagerie, Nancy (France); University of Lorraine, Faculty of Medicine, Nancy (France); INSERM, UMR 947, Nancy (France); Tatopoulos, Alexis; Lemarie, Jeremie; Bollaert, Pierre-Edouard; Gibot, Sebastien [University of Lorraine, Faculty of Medicine, Nancy (France); CHU de Nancy - Hopital Central, Service de Reanimation Medicale, Nancy (France); INSERM, UMR 1116, Nancy (France); Chevalier-Mathias, Elodie [CHU Nancy, Pole d' imagerie, Nancy (France); INSERM, UMR 947, Nancy (France); Nancyclotep, Experimental Imaging Platform, Nancy (France); Roch, Veronique [CHU Nancy, Pole d' imagerie, Nancy (France); Nancyclotep, Experimental Imaging Platform, Nancy (France); Olivier, Pierre [CHU Nancy, Pole d' imagerie, Nancy (France); University of Lorraine, Faculty of Medicine, Nancy (France); Nancyclotep, Experimental Imaging Platform, Nancy (France); Marie, Pierre-Yves [CHU Nancy, Pole d' imagerie, Nancy (France); University of Lorraine, Faculty of Medicine, Nancy (France); INSERM, UMR 1116, Nancy (France); Nancyclotep, Experimental Imaging Platform, Nancy (France)

    2014-10-15

    Timely identification of septic foci is critical in patients with severe sepsis or septic shock of unknown origin. This prospective pilot study aimed to assess {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET), combined with whole-body computed tomographic angiography (CTA), in patients with suspected severe sepsis and for whom the prior diagnostic workup had been inconclusive. Patients hospitalized in an intensive care unit with a suspected severe sepsis but no definite diagnosis after 48 h of extensive investigations were prospectively included and referred for a whole body FDG-PET/CTA. Results from FDG-PET/CTA were assessed according to the final diagnosis obtained after follow-up and additional diagnostic workup. Seventeen patients were prospectively included, all on mechanical ventilation and 14 under vasopressor drugs. The FDG-PET/CTA exam 1) was responsible for only one desaturation and one hypotension, both quickly reversible under treatment; 2) led to suspect 16 infectious sites among which 13 (81 %) could be confirmed by further diagnostic procedures; and 3) triggered beneficial changes in the medical management of 12 of the 17 study patients (71 %). The FDG-PET/CTA images showed a single or predominant infectious focus in two cases where CTA was negative and in three cases where CTA exhibited multiple possible foci. Whole-body FDG-PET/CTA appears to be feasible, relatively safe, and provides reliable and useful information, when prospectively planned in patients with suspected severe sepsis and for whom prior diagnostic workup had been inconclusive. The FDG-PET images are particularly helpful when CTA exhibits no or multiple possible sites. (orig.)

  6. Effects of hydroxyethyl starch 130/0.42 vs. Ringer's acetate on cytokine levels in severe sepsis.

    Science.gov (United States)

    Anthon, C T; Müller, R B; Haase, N; Hjortrup, P B; Møller, K; Lange, T; Wetterslev, J; Perner, A

    2017-09-01

    The Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial showed increased 90-day mortality with hydroxyethyl starch (HES) 130/0.42 vs. Ringer's acetate. To explore the underlying pathophysiology, we compared early changes in plasma cytokine concentrations between patients resuscitated with HES vs. Ringer's acetate. In a subgroup of 226 patients from the 6S trial, we calculated delta plasma concentrations of tumour necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-10 from randomization to day 2. We used multiple linear and logistic regression analyses to assess differences between the groups and associations between delta cytokine concentrations and 90-day mortality, respectively. Baseline characteristics and day 2 mortality were comparable between the groups. We observed similar delta cytokine concentrations in the HES vs. Ringer's group (mean difference in delta TNF-α: -1.5 pg/ml (95% CI, -4.9 to 1.9), P = 0.39; IL-6: 36.0 pg/ml (-24.1 to 96.1), P = 0.24; IL-10: -3.9 pg/ml (-21.1 to 28.9), P = 0.76). In all included patients, we observed a linear relationship between increases in TNF-α and 90-day mortality (P = 0.005). Resuscitation with HES 130/0.42 vs. Ringer's acetate did not appear to affect plasma concentrations of TNF-α, IL-6 or IL-10 differently during the first days after randomization into the 6S trial. In the overall cohort, increases in TNF-α were associated with increased 90-day mortality. Although interpretation should be done with caution, it seems unlikely that the increased mortality observed with the use HES in the 6S trial is signalled by early changes in three biomarkers of systemic inflammation. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  7. Increased Neutrophil Gelatinase-Associated Lipocalin is Associated with Mortality and Multiple Organ Dysfunction Syndrome in Severe Sepsis and Septic Shock.

    Science.gov (United States)

    Wang, Biao; Chen, Gang; Zhang, Jun; Xue, Jiping; Cao, Yifei; Wu, Yunfu

    2015-09-01

    This study examines the clinical utility of increased neutrophil gelatinase-associated lipocalin (NGAL) as an indicator of mortality and multiple organ dysfunction syndrome (MODS) in severe sepsis and septic shock. We designed a prospective cohort study in an intensive care unit, and 123 patients with severe sepsis or septic shock were included. Data were used to determine a relationship between NGAL and the development of MODS and mortality. These associations were determined by the Mann-Whitney U test, log-rank test, Cox proportional hazards regression analyses, and plotting the receiver operating characteristic curve. Patients with high NGAL (75th percentile) had increased risk of mortality and MODS compared with patients with low NGAL (log-rank test, P MODS on day 1, and 37 patients (30%) on day 7. The area under the receiver operating characteristic curve showed that high NGAL could predict mortality (0.6385) during intensive care unit stay. After adjustment for confounding risk factors chosen by backward elimination by Cox regression analysis, high NGAL remained an independent predictor of mortality and MODS (hazard ratios, 2.128 [95% confidence interval, 1.078-4.203; P = 0.030] and 1.896 [95% confidence interval, 1.012-3.552; P = 0.046], respectively). High plasma NGAL independently predicts mortality and MODS in severe sepsis and septic shock.

  8. Modulating effects of pycnogenol® on oxidative stress and DNA damage induced by sepsis in rats.

    Science.gov (United States)

    Taner, Gökçe; Aydın, Sevtap; Bacanlı, Merve; Sarıgöl, Zehra; Sahin, Tolga; Başaran, A Ahmet; Başaran, Nurşen

    2014-11-01

    The aim of this study was to evaluate the protective effects of Pycnogenol® (Pyc), a complex plant extract from the bark of French maritime pine, on oxidative stress parameters (superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities and total glutathione (GSH) and malondialdehyde (MDA) levels), an inflammatory cytokine (tumor necrosis factor alpha (TNF-α) level) and also DNA damage in Wistar albino rats. Rats were treated with 100 mg/kg intraperitonally Pyc following the induction of sepsis by cecal ligation and puncture. The decreases in MDA levels and increases in GSH levels, and SOD and GPx activities were observed in the livers and kidneys of Pyc-treated septic rats. Plasma TNF-α level was found to be decreased in the Pyc-treated septic rats. In the lymphocytes, kidney, and liver tissue cells of the sepsis-induced rats, Pyc treatment significantly decreased the DNA damage and oxidative base damage using standard alkaline assay and formamidopyrimidine DNA glycosylase-modified comet assay, respectively. In conclusion, Pyc treatment might have a role in the prevention of sepsis-induced oxidative damage not only by decreasing DNA damage but also increasing the antioxidant status and DNA repair capacity in rats.

  9. Protective Role of Liriodendrin in Sepsis-Induced Acute Lung Injury.

    Science.gov (United States)

    Yang, Lei; Li, Dihua; Zhuo, Yuzhen; Zhang, Shukun; Wang, Ximo; Gao, Hongwei

    2016-10-01

    In current study, we investigated the role of liriodendrin, a constituent isolated from Sargentodoxa cuneata (Oliv.) Rehd. Et Wils (Sargentodoxaceae), in cecal ligation and puncture (CLP)-induced acute lung inflammatory response and injury (ALI). The inflammatory mediator levels in bronchoalveolar lavage fluid (BALF) were determined by enzyme-linked immunosorbent assay (ELISA). Pathologic changes in lung tissues were evaluated via pathological section with hematoxylin and eosin (H&E) staining. To investigate the mechanism whereby liriodendrin regulates lung inflammation, the phosphorylation of the NF-kB (p65) and expression of vascular endothelial growth factor (VEGF) were determined by western blot assay. We show that liriodendrin treatment significantly improved the survival rate of mice with CLP-induced sepsis. Pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration were markedly decreased by liriodendrin. In addition, liriodendrin decreased the production of the proinflammatory mediators including (TNF-α, IL-1β, MCP-1, and IL-6) in lung tissues. Vascular permeability and lung myeloperoxidase (MPO) accumulation in the liriodendrin-treated mice were substantially reduced. Moreover, liriodendrin treatment significantly suppressed the expression of VEGF and activation of NF-kB in the lung. We further show that liriodendrin significantly reduced the production of proinflammatory mediators and downregulated NF-kB signaling in LPS-stimulated RAW 264.7 macrophage cells. Moreover, liriodendrin prevented the generation of reactive oxygen species (ROS) by upregulating the expression of SIRT1 in RAW 264.7 cells. These findings provide a novel theoretical basis for the possible application of liriodendrin in clinic.

  10. Effect of pentoxifylline on lung inflammation and gas exchange in a sepsis-induced acute lung injury model

    Directory of Open Access Journals (Sweden)

    I.S. Oliveira-Junior

    2006-11-01

    Full Text Available Experimental models of sepsis-induced pulmonary alterations are important for the study of pathogenesis and for potential intervention therapies. The objective of the present study was to characterize lung dysfunction (low PaO2 and high PaCO2, and increased cellular infiltration, protein extravasation, and malondialdehyde (MDA production assessed in bronchoalveolar lavage in a sepsis model consisting of intraperitoneal (ip injection of Escherichia coli and the protective effects of pentoxifylline (PTX. Male Wistar rats (weighing between 270 and 350 g were injected ip with 10(7 or 10(9 CFU/100 g body weight or saline and samples were collected 2, 6, 12, and 24 h later (N = 5 each group. PaO2, PaCO2 and pH were measured in blood, and cellular influx, protein extravasation and MDA concentration were measured in bronchoalveolar lavage. In a second set of experiments either PTX or saline was administered 1 h prior to E. coli ip injection (N = 5 each group and the animals were observed for 6 h. Injection of 10(7 or 10(9 CFU/100 g body weight of E. coli induced acidosis, hypoxemia, and hypercapnia. An increased (P < 0.05 cell influx was observed in bronchoalveolar lavage, with a predominance of neutrophils. Total protein and MDA concentrations were also higher (P < 0.05 in the septic groups compared to control. A higher tumor necrosis factor-alpha (P < 0.05 concentration was also found in these animals. Changes in all parameters were more pronounced with the higher bacterial inoculum. PTX administered prior to sepsis reduced (P < 0.05 most functional alterations. These data show that an E. coli ip inoculum is a good model for the induction of lung dysfunction in sepsis, and suitable for studies of therapeutic interventions.

  11. Blocking Cyclic Adenosine Diphosphate Ribose-mediated Calcium Overload Attenuates Sepsis-induced Acute Lung Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    Qian-yi Peng; Yu Zou; Li-Na Zhang; Mei-Lin Ai; Wei Liu; Yu-Hang Ai

    2016-01-01

    Background:Acute lung injury (ALI) is a common complication of sepsis that is associated with high mortality.Intracellular Ca2+ overload plays an important role in the pathophysiology of sepsis-induced ALI,and cyclic adenosine diphosphate ribose (cADPR) is an important regulator of intracellular Ca2+ mobilization.The cluster of differentiation 38 (CD38)/cADPR pathway has been found to play roles in multiple inflammatory processes but its role in sepsis-induced ALI is still unknown.This study aimed to investigate whether the CD38/cADPR signaling pathway is activated in sepsis-induced ALI and whether blocking cADPR-mediated calcium overload attenuates ALI.Methods:Septic rat models were established by cecal ligation and puncture (CLP).Rats were divided into the sham group,the CLP group,and the CLP+ 8-bromo-cyclic adenosine diphosphate ribose (8-Br-cADPR) group.Nicotinamide adenine dinucleotide (NAD+),cADPR,CD38,and intracellular Ca2+ levels in the lung tissues were measured at 6,12,24,and 48 h after CLP surgery.Lung histologic injury,tumor necrosis factor (TNF)-α,malondialdehyde (MDA) levels,and superoxide dismutase (SOD) activities were measured.Results:NAD+,cADPR,CD38,and intracellular Ca2+ levels in the lungs of septic rats increased significantly at 24 h after CLP surgery.Treatment with 8-Br-cADPR,a specific inhibitor of cADPR,significantly reduced intracellular Ca2+ levels (P =0.007),attenuated lung histological injury (P =0.023),reduced TNF-α and MDA levels (P < 0.001 and P =0.002,respectively) and recovered SOD activity (P =0.031) in the lungs of septic rats.Conclusions:The CD38/cADPR pathway is activated in the lungs of septic rats,and blocking cADPR-mediated calcium overload with 8-Br-cADPR protects against sepsis-induced ALI.

  12. Current treatment of sepsis and endotoxaemia.

    Science.gov (United States)

    Periti, P

    2000-09-01

    This article reviews the new criteria for selecting the proper antimicrobial agent and dosage regimen for standard treatment of severe sepsis, with the intention of preventing septic shock. After introducing new concepts on the pathogenesis of sepsis and septic shock, the authors analyse the parameters of beta-lactam antibacterial activity, the antibiotic-induced release of bacterial endotoxin and the interrelationships between pharmacokinetics and pharmacodynamics of antibiotics in the search for an optimum dosage regimen of antimicrobial mono- or polytherapy for severely ill septic patients admitted to the intensive care unit. The mortality rate resulting from severe bacterial sepsis, particularly that associated with shock, still approaches 50% in spite of appropriate antimicrobial therapy and optimum supportive care. Bacterial endotoxins that are part of the cell wall are one of the cofactors in the pathogenesis of sepsis and septic shock and are often induced by antimicrobial chemotherapy, even if administered rationally. Not all antimicrobial agents are equally capable of inducing septic shock; this is dependent on their mechanism of action rather than on the causative pathogen species. The quantity of endotoxin released depends on the drug dose and whether filaments or spheroplast formation predominate. Some antibiotics, such as carbapenems, ceftriaxone, cefepime, glycopeptides, aminoglycosides and quinolones, do not have the propensity to provoke septic shock because their rapid bacterial activity induces mainly spheroplast or fragile spheroplast-like bacterial forms.

  13. 脓毒症/严重脓毒症患儿维生素D水平与预后%Relationship of vitamin D in children with sepsis/severe sepsis and outcomes in PICU

    Institute of Scientific and Technical Information of China (English)

    尹冰如; 钱素云; 成怡冰; 陆国平; 祝益民

    2016-01-01

    Objective To determine the vitamin D status in children with sepsis/severe sepsis in pediatric intensive care unit (PICU) in order to explor the association between vitamin D status and clinical outcomes,in turn to provide evidence for optimizing nutrition support.Methods It was a prospective,observational,multi-center study,carried out in patients with sepsis/severe sepsis from March 1,2013,to March 30,2014,in the PICUs of three tertiary-care children's hospitals.Total serum 25-hydroxy vitamin D [25 (OH) D] was measured by using an enzyme-linked immunosorbent assay at admission.The association of vitamin D status at admission with length of PICU length of stay,total hospital stay,in-hospital mortality,28-days mortality and costs were analyzed.Results A total of 194 patients includng 117 boys (60.3%)and 77 girls (39.7%) were enrolled.There were 96 patients with sepsis and 98 with severe sepsis.The mortality on discharge and 28 days were 6.7% and 24.2% respectively.The median vitamin D level was 9.79 ng/mL (5.32,18.46) at admission.Of them 77.8% (151/194) had vitamin D deficiency and 50.5% (98/194) had severe vitamin D deficiency.Patients with severe vitamin D deficiency,had higher mortality on discharge (P =0.011).Vitamin D status had no significant correlations with 28 days mortality,length of PICU stay,total hospital stay and costs.Conclusions More than three-quarters (77.8%) of children with sepsis/severe sepsis in PICUs had Vitamin D deficiency.Patients with severe vitamin D deficiency at admission had higher risk of mortality at discharge.%目的 了解儿童重症监护病房(pediatric intensive care unit,PICU)脓毒症/严重脓毒症患儿维生素D缺乏程度;分析患者入院时维生素D水平与预后之间的关系.方法 本研究为多中心、前瞻性、观察性研究.以2013年3月1日至2014年3月30日期间入住3家儿童医院PICU符合危重症标准的脓毒症/严重脓毒症患儿作为研究对象.入组患者入院24h

  14. Biomarkers of sepsis

    Science.gov (United States)

    2013-01-01

    Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440

  15. Omega-9 Oleic Acid Induces Fatty Acid Oxidation and Decreases Organ Dysfunction and Mortality in Experimental Sepsis

    Science.gov (United States)

    Oliveira, Flora Magno de Jesus; Burth, Patrícia; Bozza, Patrícia Torres; Castro Faria, Mauro Velho; Silva, Adriana Ribeiro; de Castro-Faria-Neto, Hugo Caire

    2016-01-01

    Sepsis is characterized by inflammatory and metabolic alterations, which lead to massive cytokine production, oxidative stress and organ dysfunction. In severe systemic inflammatory response syndrome, plasma non-esterified fatty acids (NEFA) are increased. Several NEFA are deleterious to cells, activate Toll-like receptors and inhibit Na+/K+-ATPase, causing lung injury. A Mediterranean diet rich in olive oil is beneficial. The main component of olive oil is omega-9 oleic acid (OA), a monounsaturated fatty acid (MUFA). We analyzed the effect of OA supplementation on sepsis. OA ameliorated clinical symptoms, increased the survival rate, prevented liver and kidney injury and decreased NEFA plasma levels in mice subjected to cecal ligation and puncture (CLP). OA did not alter food intake and weight gain but diminished reactive oxygen species (ROS) production and NEFA plasma levels. Carnitine palmitoyltransferase IA (CPT1A) mRNA levels were increased, while uncoupling protein 2 (UCP2) liver expression was enhanced in mice treated with OA. OA also inhibited the decrease in 5' AMP-activated protein kinase (AMPK) expression and increased the enzyme expression in the liver of OA-treated mice compared to septic animals. We showed that OA pretreatment decreased NEFA concentration and increased CPT1A and UCP2 and AMPK levels, decreasing ROS production. We suggest that OA has a beneficial role in sepsis by decreasing metabolic dysfunction, supporting the benefits of diets high in monounsaturated fatty acids (MUFA). PMID:27078880

  16. Soluble B and T Lymphocyte Attenuator Correlates to Disease Severity in Sepsis and High Levels Are Associated with an Increased Risk of Mortality

    Science.gov (United States)

    Sundén-Cullberg, Jonas; Magnuson, Anders; Hultgren, Olof

    2017-01-01

    Introduction and aims B- and T-lymphocyte Attenuator (BTLA), Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death 1 (PD-1) are co-inhibitory receptors that regulate T cell activation. In the present study of ICU-treated patients we measured plasma concentrations of their soluble isoforms, with the aim to evaluate their potential as sepsis biomarkers and utility as prognostic indicators. Methods 101 patients with sepsis, 28 patients with non-infectious critical illness (ICU controls) and 31 blood donors (healthy controls, HC) were included in the study. Plasma concentrations of soluble BTLA (sBTLA), CTLA-4 (sCTLA-4) and PD-1 (sPD-1) were measured with ELISA in serial blood samples. Comparisons were made with Mann-Whitney U test and correlations were assessed with Spearman’s Rank correlation test. Cox proportional hazard models, with sBTLA and sPD-1 as fixed and sBTLA as time-varying covariates, were used to determine association with 28-day mortality. Results sBTLA levels were significantly higher in the sepsis cohort (median 14 ng/mL, IQR 8–29) compared to ICU controls (9 ng/mL, IQR 5–26, p = 0.048) and HC (2.9 ng/mL, IQR 0.9–9.1, psepsis non-survivors than in survivors (baseline median 28 ng/mL, IQR 13–41 vs 13 ng/mL, IQR 8–23, p = 0.04). After adjustment for age and comorbidities, the relative risk of 28 day mortality was nearly 5-fold higher in sepsis patients with a baseline sBTLA > 21 ng/mL, compared to those with a level below this threshold. sBTLA was even more associated with mortality in the time-varying analysis. sPD-1 levels were lower in the sepsis cohort compared to HC but not compared to ICU controls and were not associated with mortality. sCTLA-4 was detectable in only one subject. Conclusion Plasma concentrations of soluble BTLA were increased early in sepsis/septic shock and correlated to severity of disease. A baseline concentration >21ng/mL was associated with a poor prognosis. PMID:28056053

  17. Risk Factors of Death in 120 Patients with Severe Sepsis%120例严重感染患者死亡危险因素分析

    Institute of Scientific and Technical Information of China (English)

    李元贵; 马希刚

    2011-01-01

    Objective To investigate the fatality and risk factors in critically ill patients with severe sepsis.Methods The data of 120 patients with severe sepsis were reviewed retrospectively. These patients received treatment in ICU of Ningxia Medical University Hospital from January 2005 to December 2009. Patients'general condition and clinical information were recorded. Simple logistic regression was taken to analyze all the risk factors, and statistically significant variables were selected and used in multivariate and unconditioned Logistic regression analysis. Results The overall morbidity of severe sepsis was 8.2% ( 120/1463 ), and the overall fatality of severe sepsis was 70.0% (84/120). Univariate analysis showed that aging、 hospital stays, APACHE Ⅱ score, SOFA score, chronic disease history, low albumin ( < 35g · L - 1 ), base excess ( BE ), mechanical ventilation, intravenous catheter and other invasive examination and the number of failed organ were associated with death. Multivariate analysis showed that aging、APACHE Ⅱ score and the number of failed organ were independent factors for the patients in death with severe sepsis. Conclusion The fatality of severe sepsis was high. Aging,nitial APACHE Ⅱ score ≥ 20 points, or/and the number of failed organ were related to the death with severe sepsis.%目的 调查严重感染患者的病死率和病死危险因素.方法 回顾性调查宁夏医科大学附属医院重症医学科(ICU)2005年1月-2009年12月5年期间收治的120例严重感染患者.记录患者的一般情况与临床资料等,对上述资料进行单因素分析,选择有意义的变量(P<0.05)进行多因素非条件Logistic回归分析,分析严重感染患者病死危险因素.结果 2005-2009年间,宁夏医科大学附属医院重症医学科的严重感染总发生率为8.2%(120/1463),总病死率为70.0%(84/120).单因素分析结果显示:老龄、总住院时间、APACHEⅡ评分、SOFA评分、慢

  18. Common TNF-alpha, IL-1 beta, PAI-1, uPA, CD14 and TLR4 polymorphisms are not associated with disease severity or outcome from Gram negative sepsis

    DEFF Research Database (Denmark)

    Jessen, Kristine Marie; Lindboe, Sarah Bjerre; Petersen, Anncatrine Luisa;

    2007-01-01

    Several studies have investigated single nucleotide polymorphisms (SNPs) in candidate genes associated with sepsis and septic shock with conflicting results. Only few studies have combined the analysis of multiple SNPs in the same population....

  19. [Role of autophagy in ameliorating sepsis-induced acute lung injury by allicinin in mice].

    Science.gov (United States)

    Peng, Yue; Jiang, Yu; Ou, Hao; Xing, Wei; Yang, Mingshi; Gao, Min

    2017-08-28

    To investigate roles of autophagy in ameliorating sepsis-induced acute lung injury by allicinin in mice.
 Methods: A total of 152 male Balb/c mice (8-week old) were randomly divided into a sham group, a septic model group, an allicin treatment group, and an autophagy inhibition group. Septic mouse model was established by cecal ligation and puncture (CLP). Mice in the allicin treatment group were given allicin (30 mg/kg, intra-peritoneal injection) at 6 and 12 h, while those in the autophagy inhibition group were given autophagy inhibitor 3-MA (15 mg/kg, intra-peritoneal injection) at half an hour after allicin administration. Mice in the model and sham group were administered with the same amount of saline. Twenty mice in each group were randomly chosen to observe the 7 d survival rate. The other 12 mice were killed at 24 h, and the bronchoalveolar lavage fluid (BALF) (n=6) and lung tissues (n=6) were collected. ELISA was used to detect the tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the BALF. Hematoxylin-eosin staining was preformed to show the morphological changes in the lung tissues. Malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD) in the lung tissues were examined. The expression of LC3B and Beclin-1 was determined by immunohistochemical analysis.
 Results: Compared with the sham group, the 7 d survival rate and lung SOD activity were decreased in the CLP group (P<0.05); the lung morphological damage score, the levels of TNF-α and IL-6 in the BALF, MDA content in the lung, and expression of LC3B and Beclin-1 were increased greatly in the CLP group (P<0.05). Compared with the CLP group, the 7 d survival rate, lung SOD activity and the expressions of LC3B and Beclin-1 were increased significantly in the allicin treatment group (P<0.05); the lung morphological damage scores, the levels of TNF-α and IL-6 in the BALF and MDA content in the lung were decreased obviously in the allicin treatment group (P<0

  20. Endothelial (NOS3 E298D) and inducible (NOS2 exon 22) nitric oxide synthase polymorphisms, as well as plasma NOx, influence sepsis development.

    Science.gov (United States)

    Martin, Guadalupe; Asensi, Víctor; Montes, A Hugo; Collazos, Julio; Alvarez, Victoria; Pérez-Is, Laura; Carton, José A; Taboada, Francisco; Valle-Garay, Eulalia

    2014-11-15

    Nitric oxide (NO) influences susceptibility to infection and hemodynamic failure (HF) in sepsis. NOS3 and NOS2 SNPs might modify plasma nitrite/nitrate (NOx) levels, sepsis development, hemodynamics and survival. 90 severely septic and 91 non-infected ICU patients were prospectively studied. NOS3 (E298D), NOS3 (-786 T/C), NOS3 (27 bp-VNTR), and NOS2A (exon 22) SNPs and plasma NOx levels were assessed. 21 patients (11.6%) died, 7 with sepsis. TT homozygotes and T allele carriers of NOS3 (E298D) and AG carriers of the NOS2A (exon 22) SNPs were more frequent among septic compared to non-infected ICU patients (p NOS3 (E298D) SNP (p = 0.006). Sepsis independently associated with HF, increased NOx, peripheral neutrophils, and fibrinogen levels, decreased prothrombin and the presence of the NOS3 (E298D) and NOS2A (exon 22) SNPs. A low APACHE II score was the only variable associated with sepsis survival. NOx was independently associated with sepsis, HF, decreased neutrophils and higher APACHE. NOS3 (E298D) and NOS2A (exon 22) SNPs, individually and in combination, and plasma NOx, associated with sepsis development. NOx associated with HF and fatal outcome. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Monocyte Profiles in Critically Ill Patients With Pseudomonas Aeruginosa Sepsis

    Science.gov (United States)

    2017-02-02

    Pseudomonas Infections; Pseudomonas Septicemia; Pseudomonas; Pneumonia; Pseudomonal Bacteraemia; Pseudomonas Urinary Tract Infection; Pseudomonas Gastrointestinal Tract Infection; Sepsis; Sepsis, Severe; Critically Ill

  2. Endotoxin dosage in sepsis

    Directory of Open Access Journals (Sweden)

    Vincenzo Rondinelli

    2012-03-01

    Full Text Available Introduction. Endotoxin, a component of the cell wall of Gram-negative bacteria is a major contributor to the pathogenesis of septic shock and multiple organ failure (MOF. Its entry into the bloodstream stimulates monocytes/macrophages which once activated produce and release cytokines, nitric oxide and other mediators that induce systemic inflammation, endothelial damage, organ dysfunction, hypotension (shock and MOF.The aim of this study is to evaluate the usefulness of a quantitative test for the dosage of endotoxin to determine the risk of severe Gram-negative sepsis. Materials and methods. In the period January 2009 - June 2011 we performed 897 tests for 765 patients, mostly coming from the emergency room and intensive care, of which 328 (43% women (mean age 53 and 437 (57% male (mean age 49. Fifty-nine patients, no statistically significant difference in sex, were monitored by an average of two determinations of EA.All patients had procalcitonin values significantly altered.The kit used was EAA (Endotoxin Activity Assay Estor Company, Milan, which has three ranges of endotoxin activity (EA: low risk of sepsis if <0.40 units, medium if between 0.40 and 0.59; high if 0.60. Results. 78 out of 765 patients (10% had a low risk, 447 (58% a medium risk and 240 (32% a high risk.The dosage of EA, combined with that of procalcitonin, has allowed a more targeted antibiotic therapy. Six patients in serious clinical conditions were treated by direct hemoperfusion with Toraymyxin, a device comprising a housing containing a fiber polypropylene and polystyrene with surface-bound polymyxin B, an antibiotic that removes bacterial endotoxins from the blood. Conclusions.The test is useful in risk stratification as well as Gram negative sepsis, to set and monitor targeted therapies, also based on the neutralization of endotoxin.

  3. Behavioral deficits in sepsis-surviving rats induced by cecal ligation and perforation

    Directory of Open Access Journals (Sweden)

    T. Barichello

    2007-06-01

    Full Text Available Sepsis and its complications are the leading causes of mortality in intensive care units, accounting for 10-50% of deaths. Intensive care unit survivors present long-term cognitive impairment, including alterations in memory, attention, concentration, and/or global loss of cognitive function. In the present study, we investigated behavioral alterations in sepsis-surviving rats. One hundred and ten male Wistar rats (3-4 months, 250-300 g were submitted to cecal ligation and puncture (CLP, and 44 were submitted to sham operation. Forty-four rats (40% survived after CLP, and all sham-operated animals survived and were used as control. Twenty animals of each group were used in the object recognition task (10 in short-term memory and 10 in long-term memory, 12 in the plus-maze test and 12 in the forced swimming test. Ten days after surgery, the animals were submitted individually to an object recognition task, plus-maze and forced swimming tests. A significant impairment of short- and long-term recognition memory was observed in the sepsis group (recognition index 0.75 vs 0.55 and 0.74 vs 0.51 for short- and long-term memory, respectively (P < 0.05. In the elevated plus-maze test no difference was observed between groups in any of the parameters assessed. In addition, sepsis survivors presented an increase in immobility time in the forced swimming test (180 vs 233 s, P < 0.05, suggesting the presence of depressive-like symptoms in these animals after recovery from sepsis. The present results demonstrated that rats surviving exposure to CLP, a classical sepsis model, presented recognition memory impairment and depressive-like symptoms but not anxiety-like behavior.

  4. Pharmacological management of sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Fletcher, J.R.

    1985-01-01

    Systemic sepsis continues to be the most-difficult management problem in caring for the combat casualty. The complications of sepsis pervade all areas of injury to soldiers in the field, whether it is mechanical (missiles), thermal (burns), chemical, biological, or radiation injury. With the advent of tactical nuclear weapons, the problem of sepsis will be much higher in future wars than has previously been experienced through the world. The purpose of this chapter is a) to review the data suggesting pharmacological agents that may benefit the septic patient, and b) to emphasize the adjunctive therapies that should be explored in clinical trials. The pharmacological management of sepsis remains controversial. Most of the drugs utilized clinically treat the symptoms of the disease and are not necessarily directed at fundamental mechanisms that are known to be present in sepsis. A broad data base is emerging, indicating that NSAID should be used in human clinical trials. Prostaglandins are sensitive indicators of cellular injury and may be mediators for a number of vasoactive chemicals. Opiate antagonists and calcium channel blockers require more in-depth data; however, recent studies generate excitement for their potential use in the critically ill patient. Pharmacological effects of antibiotics, in concert with other drugs, suggest an entirely new approach to pharmacological treatment in sepsis. There is no doubt that new treatment modalities or adjunctive therapies must be utilized to alter the poor prognosis of severe sepsis that we have observed in the past 4 decades.

  5. Severe Agranulocytosis following Simultaneous Administration of Chlorpromazine and Trimethoprim-Sulfamethoxazole in a Patient with Sepsis: A Possible Toxic Combination

    Directory of Open Access Journals (Sweden)

    Anil Jha

    2016-01-01

    Full Text Available Background. Chlorpromazine and trimethoprim-sulfamethoxazole (TMP/SMX are two commonly prescribed medications by physicians. Either of those medications could cause fatal drug-induced agranulocytosis, with an unclear underlying mechanism. The likelihood of simultaneous prescription of both medications is high and could hypothetically result in severe agranulocytosis that is resistant to treatment. Case Presentation. We are presenting a case of a patient with psychosis on chlorpromazine who was prescribed TMP/SMX for a urinary tract infection. Consequently, the patient developed severe agranulocytosis and septicemia. Patient was managed by granulocyte colony-stimulating factor; however, the time to neutrophil recovery was delayed when compared to the average reported time published by previous studies. Conclusions. Simultaneous use of chlorpromazine and TMP/SMX is a possible toxic combination that could induce severe agranulocytosis. Further reports are needed to confirm this observation.

  6. Salidroside ameliorates sepsis-induced acute lung injury and mortality via downregulating NF-κB and HMGB1 pathways through the upregulation of SIRT1.

    Science.gov (United States)

    Lan, Kuo-Cheng; Chao, Sung-Chuan; Wu, Hsiao-Yi; Chiang, Chia-Lien; Wang, Ching-Chia; Liu, Shing-Hwa; Weng, Te-I

    2017-09-20

    Sepsis is a life-threatening medical condition. Salidroside, a substance isolated from Rhodiola rosea, possesses antioxidant and anti-inflammatory properties. The effect and mechanism of salidroside on sepsis-induced acute lung injury still remains to be well clarified. Here, we investigated the effect and mechanism of salidroside on septic mouse models and explored the role of salidroside-upregulated SIRT1. Salidroside inhibited the inflammatory responses and HMGB1 productions in bacterial lipopolysaccharide (LPS)-treated macrophages and mice. Salidroside could also reverse the decreased SIRT1 protein expression in LPS-treated macrophages and mice. Salidroside also alleviated the sepsis-induced lung edema, lipid peroxidation, and histopathological changes and the mortality, and improved the lung PaO2/FiO2 ratio in cecal ligation and puncture (CLP)-induced septic mice. Salidroside significantly decreased the serum TNF-α, IL-6, NO, and HMGB1 productions, pulmonary inducible NO synthase (iNOS) and phosphorylated NF-κB-p65 protein expressions, and pulmonary HMGB1 nuclear translocation in CLP septic mice. Moreover, sepsis decreased the SIRT1 protein expression in the lungs of CLP septic mice. Salidroside significantly upregulated the SIRT1 expression and inhibited the inflammatory responses in CLP septic mouse lungs. These results suggest that salidroside protects against sepsis-induced acute lung injury and mortality, which might be through the SIRT1-mediated repression of NF-κB activation and HMGB1 nucleocytoplasmic translocation.

  7. Heparin-Binding Protein (HBP): A Causative Marker and Potential Target for Heparin Treatment of Human Sepsis-Induced Acute Kidney Injury.

    Science.gov (United States)

    Fisher, Jane; Russell, James A; Bentzer, Peter; Parsons, Devyn; Secchia, Stefano; Mörgelin, Matthias; Walley, Keith R; Boyd, John H; Linder, Adam

    2017-09-01

    Sepsis-induced acute kidney injury (AKI) is a common condition with high morbidity and mortality. Neutrophil-derived heparin-binding protein (HBP) induces vascular leakage and is a promising biomarker of sepsis-induced organ dysfunction. It remains unknown if HBP is prognostic of AKI in septic shock and if HBP could play a role in the pathophysiology of sepsis-induced AKI. To determine the association of plasma HBP levels with development of AKI, investigate the role of HBP in the pathophysiology of sepsis-induced AKI, and test the effect of blocking HBP using heparin derivatives. In 296 septic shock patients from the randomized multicenter Vasopressin and Septic Shock Trial (VASST) plasma HBP levels were associated with development of AKI and need for renal replacement therapy (RRT). Human renal tubular cells were exposed to recombinant HBP to evaluate inflammation and heparin derivatives were used to abrogate these effects. Finally, mice were exposed to HBP with and without heparin derivatives and the kidneys examined for signs of inflammation. Plasma HBP levels were significantly higher in patients with AKI and those requiring RRT. HBP levels identified patients with moderate AKI with an area under curve (AUC) of 0.85. HBP increased IL-6 production in renal tubular epithelial cells. Different heparin derivatives abrogated the HBP-induced increased inflammatory response in vitro and in vivo. Elevated plasma HBP is associated with development of sepsis-induced AKI and HBP is involved in its pathophysiology. Our studies suggest that heparin(s) could be tested for efficacy and safety of prevention of sepsis-induced AKI.

  8. Surviving sepsis in the critical care environment.

    Science.gov (United States)

    Benedict, Lara

    2015-01-01

    The management of sepsis and septic shock in the intensive care environment is a complex task requiring the cooperation of a multidisciplinary team. The Surviving Sepsis Campaign provides systematic guidelines for the recognition, early intervention, and supportive management of sepsis. Critical care nurses are instrumental in ensuring that these guidelines and other sources of evidence-based practice are used for patients with severe sepsis or septic shock. This article discusses the pathophysiologic processes in severe sepsis and septic shock and discusses the appropriate interventions as recommended by the Surviving Sepsis Campaign. Recommended early treatments are reviewed along with interventions related to hemodynamics, perfusion, and supportive care in the critical care environment.

  9. Patient Characteristics, Management, and Predictors of Outcome from Severe Community-Onset Staphylococcal Sepsis in Northeast Thailand: A Prospective Multicenter Study.

    Science.gov (United States)

    West, T Eoin; Wikraiphat, Chanthiwa; Tandhavanant, Sarunporn; Ariyaprasert, Pitchayanant; Suntornsut, Pornpan; Okamoto, Shawna; Mahavanakul, Weera; Srisamang, Pramot; Phiphitaporn, Sunchai; Anukunananchai, Jirasak; Chetchotisakd, Ploenchan; Peacock, Sharon J; Chantratita, Narisara

    2017-02-06

    Staphylococcus aureus infection is a persistent threat in resource-restricted settings in southeast Asia but informative data about this disease remain limited. We analyzed characteristics, management, and predictors of outcome in severely septic patients with community-onset S. aureus infection in northeast Thailand. We performed a prospective, multicenter observational cohort study of community-onset S. aureus sepsis in four referral hospitals recruiting patients at least 14 years of age admitted between March 2010 and December 2013. One hundred and nineteen patients with severe staphylococcal sepsis were enrolled. Diabetes was the most common underlying condition. Methicillin-resistant infection was rare. Twenty-eight-day mortality was 20%. Ninety-two percent of patients received appropriate antibiotic therapy and 82% were administered intravenous fluids on the first hospital day, although only 14% were managed in an intensive care unit (ICU). On univariable analysis, clinical variables at enrollment significantly associated with death at 28 days were coagulopathy or respiratory failure. Plasma interleukin (IL) -8 concentration alone accurately predicted mortality (area under the receiver operating curve = 0.82, 95% confidence interval = 0.73-0.90). In multivariable analysis, addition of IL-8 concentration to a mortality prediction model containing clinical variables further improved the predictive ability of the model. We conclude that severe staphylococcal sepsis in northeast Thailand causes significant mortality. Diabetes is a common preexisting condition and most patients are managed outside the ICU even if they receive vasoactive/inotropic agents or mechanical ventilation. While clinical factors apparent on presentation including coagulopathy and respiratory failure predict death, plasma IL-8 improves this prediction.

  10. Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock

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    Suarez Arturo

    2010-01-01

    Full Text Available Abstract Background Lactate clearance, a surrogate for the magnitude and duration of global tissue hypoxia, is used diagnostically, therapeutically and prognostically. This study examined the association of early lactate clearance with selected inflammatory, coagulation, apoptosis response biomarkers and organ dysfunction scores in severe sepsis and septic shock. Methods Measurements of serum arterial lactate, biomarkers (interleukin-1 receptor antagonist, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha, intercellular adhesion molecule-1, high mobility group box-1, D-Dimer and caspase-3, and organ dysfunction scores (Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology Score II, Multiple Organ Dysfunction Score, and Sequential Organ Failure Assessment were obtained in conjunction with a prospective, randomized study examining early goal-directed therapy in severe sepsis and septic shock patients presenting to the emergency department (ED. Lactate clearance was defined as the percent change in lactate levels after six hours from a baseline measurement in the ED. Results Two-hundred and twenty patients, age 65.0 +/- 17.1 years, were examined, with an overall lactate clearance of 35.5 +/- 43.1% and in-hospital mortality rate of 35.0%. Patients were divided into four quartiles of lactate clearance, -24.3 +/- 42.3, 30.1 +/- 7.5, 53.4 +/- 6.6, and 75.1 +/- 7.1%, respectively (p p p Conclusions Early lactate clearance as a surrogate for the resolution of global tissue hypoxia is significantly associated with decreased levels of biomarkers, improvement in organ dysfunction and outcome in severe sepsis and septic shock.

  11. Common TNF-α, IL-1β, PAI-1, uPA, CD14 and TLR4 polymorphisms are not associated with disease severity or outcome from Gram negative sepsis

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    Eugen-Olsen Jesper

    2007-09-01

    Full Text Available Abstract Background Several studies have investigated single nucleotide polymorphisms (SNPs in candidate genes associated with sepsis and septic shock with conflicting results. Only few studies have combined the analysis of multiple SNPs in the same population. Methods Clinical data and DNA from consecutive adult patients with culture proven Gram negative bacteremia admitted to a Danish hospital between 2000 and 2002. Analysis for commonly described SNPs of tumor necrosis-α, (TNF-α, interleukin-1β (IL-1β, plasminogen activator-1 (PAI-1, urokinase plasminogen activator (uPA, CD14 and toll-like receptor 4 (TLR4 was done. Results Of 319 adults, 74% had sepsis, 19% had severe sepsis and 7% were in septic shock. No correlation between severity or outcome of sepsis was observed for the analyzed SNPs of TNF-α, IL-1β, PAI-1, uPA, CD14 or TLR-4. In multivariate Cox proportional hazard regression analysis, increasing age, polymicrobial infection and haemoglobin levels were associated with in-hospital mortality. Conclusion We did not find any association between TNF-α, IL-1β, PAI-1, uPA, CD14 and TLR4 polymorphisms and outcome of Gram negative sepsis. Other host factors appear to be more important than the genotypes studied here in determining the severity and outcome of Gram negative sepsis.

  12. Role of plasma bactericidal/permeability-increasing protein, group IIA phospholipase A(2), C-reactive protein, and white blood cell count in the early detection of severe sepsis in the emergency department.

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    Uusitalo-Seppälä, Raija; Peuravuori, Heikki; Koskinen, Pertti; Vahlberg, Tero; Rintala, Esa M

    2012-09-01

    To study the diagnostic values of bactericidal/permeability-increasing protein (BPI), group IIA phospholipase A(2) (PLA(2)GIIA), white blood cell count (WBC), and C-reactive protein (CRP) in identifying severe sepsis upon admission in an emergency room. This was a single-centre prospective cohort study involving 525 adult patients admitted to the emergency room with suspected infection. Plasma samples were taken concurrently with the blood cultures. Forty-nine patients with severe sepsis and 476 other patients (58 with no systemic inflammatory response syndrome (SIRS) and no bacterial infection, 63 with bacterial infection but no SIRS, 53 with SIRS but no bacterial infection, and 302 with sepsis but no organ dysfunction) were evaluated. BPI and PLA(2)GIIA were measured by time-resolved fluoroimmunoassay, and CRP with an immunoturbidimetric assay. WBC was measured using an automatic cell counter. There was a positive correlation between the plasma levels of PLA(2)GIIA and CRP (Pearson's correlation coefficient 0.60, p sepsis from others (OR 1.37, 95% Cl 1.05-1.78, p = 0.019). After adjusting for confounders PLA(2)GIIA remained a significant independent predictor of severe sepsis. PLA(2)GIIA seemed to be superior to CRP, BPI, and WBC in differentiating patients with severe sepsis. BPI gave no additional information in this respect.

  13. Sepsis in frail patient

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    Andrea Beltrame

    2016-12-01

    Full Text Available Frailty is defined as a clinical syndrome in which three or more of the following criteria are present: unintentional weight loss, self-reported exhaustion, weakness (grip strength, slow walking speed and low physical activity. Sepsis is defined as an inflammatory response to infection, with severe sepsis and septic shock being the most severe forms. The incidence of severe sepsis increases with older age and several studies have shown that there are many risk factors that predispose the elderly to a higher incidence of sepsis. Pre-existing co-morbidities such as cancer, diabetes, obesity, human immunodeficiency virus, and renal or pulmonary disease can cause sepsis, but other factors including poor lifestyle habits (i.e., smoking, drug or alcohol abuse, malnutrition, and endocrine deficiencies, which are frequent in the elderly, may also predispose to severe infections. Other risk factors for sepsis include recurrent hospitalization, especially in the Intensive Care Unit, and nursing home residence, where interventions such as urinary catheterization or multiple drug use are quite frequent and many studies reported that people above 65 years of age are three times more likely to be admitted to hospital than those aged 16-64 years, and have a higher risk of prolonged hospital stays, institutionalization and death. Clinical evaluation of the frail patient with sepsis poses some challenges. The immune response becomes progressively less efficient with increasing age thereby causing an altered response to infection and it is important to know that the clinical evaluation of the so-called fragile patient with severe infection should take into account the sometimes unusual signs and symptoms that, if identified, can lead to early diagnosis. Laboratory diagnostics can also be of great help in this setting. The treatment of sepsis in the fragile patient can be empirical or based on microbiological culture. Moreover, frail patient population presents

  14. Cordyceps sinensis preserves intestinal mucosal barrier and may be an adjunct therapy in endotoxin-induced sepsis rat model: a pilot study

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    Gu, Guo-Sheng; Ren, Jian-An; Li, Guan-Wei; Yuan, Yu-Jie; Li, Ning; Li, Jie-Shou

    2015-01-01

    Background: Cordyceps sinensis (C. sinensis), a traditional Chinese medicine, exhibits various pharmacological activities such as reparative, antioxidant, and apoptosis inhibitory effects. Intestinal barrier dysfunction plays a vital role in the progression of sepsis. We aimed to explore the effect of C. sinensis on the gut barrier and evaluate its efficacy in sepsis. Methods: A murine model of gut barrier dysfunction was created by intraperitoneal injection of endotoxin. C. sinensis or saline was administered orally after the induction of sepsis. Alterations of intestinal barrier were evaluated and compared in terms of epithelial cell apoptosis, proliferation index (PI), intercellular tight junction (TJ) and proliferating cell nuclear antigen (PCNA). Results: C. sinensis significantly decreased the percentage of apoptotic cells and promoted mucosal cells proliferation indicated by enhanced PI and PCNA expression in the intestinal mucosa compared to control group. The TJs between epithelial cells which were disrupted in septic rats were also restored by treatment of C. sinensis. In survival studies, C. sinensis was demonstrated to confer a protection against the lethal effect of sepsis. Conclusion: These results suggest that C. sinensis has gut barrier-protection effect in endotoxin-induced sepsis by promoting the proliferation and inhibiting the apoptosis of intestinal mucosal cells, as well as restoring the TJs of intestinal mucosa. C. sinensis may have the potential to be a useful adjunct therapy for sepsis. PMID:26221273

  15. Neurologic complications of sepsis.

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    Schmutzhard, E; Pfausler, B

    2017-01-01

    Over the past decades, the incidence of sepsis and resultant neurologic sequelae has increased, both in industrialized and low- or middle-income countries, by approximately 5% per year. Up to 300 patients per 100 000 population per year are reported to suffer from sepsis, severe sepsis, and septic shock. Mortality is up to 30%, depending on the precision of diagnostic criteria. The increasing incidence of sepsis is partially explained by demographic changes in society, with aging, increasing numbers of immunocompromised patients, dissemination of multiresistant pathogens, and greater availability of supportive medical care in both industrialized and middle-income countries. This results in more septic patients being admitted to intensive care units. Septic encephalopathy is a manifestation especially of severe sepsis and septic shock where the neurologist plays a crucial role in diagnosis and management. It is well known that timely treatment of sepsis improves outcome and that septic encephalopathy may precede other signs and symptoms. Particularly in the elderly and immunocompromised patient, the brain may be the first organ to show signs of failure. The neurologist diagnosing early septic encephalopathy may therefore contribute to the optimal management of septic patients. The brain is not only an organ failing in sepsis (a "sepsis victim" - as with other organs), but it also overwhelmingly influences all inflammatory processes on a variety of pathophysiologic levels, thus contributing to the initiation and propagation of septic processes. Therefore, the best possible pathophysiologic understanding of septic encephalopathy is essential for its management, and the earliest possible therapy is crucial to prevent the evolution of septic encephalopathy, brain failure, and poor prognosis. © 2017 Elsevier B.V. All rights reserved.

  16. Hydrogen Gas Protects Against Intestinal Injury in Wild Type But Not NRF2 Knockout Mice With Severe Sepsis by Regulating HO-1 and HMGB1 Release.

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    Yu, Yang; Yang, Yongyan; Bian, Yingxue; Li, Yuan; Liu, Lingling; Zhang, Hongtao; Xie, Keliang; Wang, Guolin; Yu, Yonghao

    2017-09-01

    The intestine plays an important role in the pathogenesis of sepsis. Hydrogen gas (H2), which has anti-oxidative, anti-inflammatory, and anti-apoptotic effects, can be effectively used to treat septic mice. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive master switch that regulates the expression of antioxidant and protective enzymes. This study investigated the effects of 2% H2 on intestinal injuries and the underlying mechanisms in a mouse model of severe sepsis. Male Nrf2 knockout mice (Nrf2-KO) and wild-type (WT) mice were randomized into four groups: sham, sham+H2, cecal ligation and puncture (CLP), and CLP+H2. The survival rate was observed and recorded within 7 days, and pro-inflammatory cytokines (TNF-α, IL-6, HMGB1), anti-inflammatory cytokine (IL-10), antioxidant enzymes (superoxide dismutase, and catalase ), and oxidative products (MDA, 8-iso-PGF2α) were detected in the serum and intestine using an enzyme-linked immunosorbent assay. In addition, the protein and mRNA levels of heme oxygenase-1 (HO-1) and high mobility group box 1 (HMGB1) were measured by Western blotting and quantitative PCR, respectively. Immunofluorescence and immunohistochemistry were used to measure HMGB1 and HO-1 release into the intestine, respectively. The results showed that therapy with 2% H2 increased the survival rate, alleviated the injuries caused by oxidative stress and inflammation, reduced HMGB1 levels but increased HO-1 levels in WT septic mice, but not in Nrf2-KO mice. These data demonstrate that 2% H2 inhalation may be a promising therapeutic strategy for intestinal injuries caused by severe sepsis through the regulation of HO-1 and HMGB1 release. In addition, Nrf2 plays a key role in the protective effects of H2 against intestinal damage in this disease.

  17. 重症监护病房严重感染的诊治%Diagnosis and management of severe sepsis in ICU

    Institute of Scientific and Technical Information of China (English)

    马晓春; 丁仁或

    2011-01-01

    Severe sepsis and septic shock are the main causes of death in critically ill patients. However, the diagnosis and treatment of severe infection is still facing many challenges. In order to guide clinical practice,the authors briefly summarize strategy of diagnosis and treatments to severe sepsis,which include timely and appropriate application of antibiotics,fluid resuscitation,anticoagulation,and so on.%严重感染和感染性休克是重症患者死亡的最主要原因,然而,重症感染的诊治仍面临着诸多挑战.文章从重症感染的诊断、及时和恰当应用抗生素以及综合治疗等方面简要论述了重症感染诊治的思路和策略,以期对临床实践起到一个抛砖引玉的作用.

  18. Early goal-directed therapy reduces mortality in adult patients with severe sepsis and septic shock: Systematic review and meta-analysis

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    Legese Chelkeba

    2015-01-01

    Full Text Available Introduction: Survival sepsis campaign guidelines have promoted early goal-directed therapy (EGDT as a means for reduction of mortality. On the other hand, there were conflicting results coming out of recently published meta-analyses on mortality benefits of EGDT in patients with severe sepsis and septic shock. On top of that, the findings of three recently done randomized clinical trials (RCTs showed no survival benefit by employing EGDT compared to usual care. Therefore, we aimed to do a meta-analysis to evaluate the effect of EGDT on mortality in severe sepsis and septic shock patients. Methodology: We included RCTs that compared EGDT with usual care in our meta-analysis. We searched in Hinari, PubMed, EMBASE, and Cochrane central register of controlled trials electronic databases and other articles manually from lists of references of extracted articles. Our primary end point was overall mortality. Results: A total of nine trails comprising 4783 patients included in our analysis. We found that EGDT significantly reduced mortality in a random-effect model (RR, 0.86; 95% confidence interval [CI], 0.72–0.94; P = 0.008;   I 2 =50%. We also did subgroup analysis stratifying the studies by the socioeconomic status of the country where studies were conducted, risk of bias, the number of sites where the trials were conducted, setting of trials, publication year, and sample size. Accordingly, trials carried out in low to middle economic income countries (RR, 0.078; 95% CI, 0.67–0.91; P = 0.002; I2 = 34% significantly reduced mortality compared to those in higher income countries (RR, 0.93; 95% CI, 0.33–1.06; P = 0.28; I2 = 29%. On the other hand, patients receiving EGDT had longer length of hospital stay compared to the usual care (mean difference, 0.49; 95% CI, –0.04–1.02; P = 0.07; I2 = 0%. Conclusion: The result of our study showed that EGDT significantly reduced mortality in patients with severe sepsis and septic shock. Paradoxically

  19. Metabolomic Analyses of Brain Tissue in Sepsis Induced by Cecal Ligation Reveal Specific Redox Alterations--Protective Effects of the Oxygen Radical Scavenger Edaravone.

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    Hara, Naomi; Chijiiwa, Miyuki; Yara, Miki; Ishida, Yusuke; Ogiwara, Yukihiko; Inazu, Masato; Kuroda, Masahiko; Karlsson, Michael; Sjovall, Fredrik; Elmér, Eskil; Uchino, Hiroyuki

    2015-12-01

    The pathophysiology of sepsis-associated encephalopathy (SAE) is complex and remains incompletely elucidated. Dysregulated reactive oxygen species (ROS) production and mitochondrial-mediated necrotic-apoptotic pathway have been proposed as part of the pathogenesis. The present study aimed at analyzing the preventive effect of the free radical scavenger edaravone on sepsis-induced brain alterations. Sepsis was induced by cecal ligation and puncture (CLP) and the mice were divided into three groups-CLP vehicle (CLPV), CLP and edaravone (MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one) (CLPE), and sham-operated (Sham). Mice in CLPV and CLPE were injected with saline or edaravone intraperitoneally at a dose of 10 mg/kg twice daily. The treatments were initiated 4 days prior to the surgical procedure. Mortality, histological changes, electron microscopy (EM), and expression of Bcl-2 family genes (Bcl-2 and Bax) were analyzed in selected brain regions. CLPE showed significant improvement in survival compared with CLPV 18 h postinduction of sepsis (P free radical scavenger edavarone reduces mortality of septic mice and protects against sepsis-induced neuronal cell death.

  20. Immunosuppression after Sepsis: Systemic Inflammation and Sepsis Induce a Loss of Naïve T-Cells but No Enduring Cell-Autonomous Defects in T-Cell Function

    Science.gov (United States)

    Markwart, Robby; Condotta, Stephanie A.; Requardt, Robert P.; Borken, Farina; Schubert, Katja; Weigel, Cynthia; Bauer, Michael; Griffith, Thomas S.; Förster, Martin; Brunkhorst, Frank M.; Badovinac, Vladimir P.; Rubio, Ignacio

    2014-01-01

    Sepsis describes the life-threatening systemic inflammatory response (SIRS) of an organism to an infection and is the leading cause of mortality on intensive care units (ICU) worldwide. An acute episode of sepsis is characterized by the extensive release of cytokines and other mediators resulting in a dysregulated immune response leading to organ damage and/or death. This initial pro-inflammatory burst often transits into a state of immune suppression characterised by loss of immune cells and T-cell dysfunction at later disease stages in sepsis survivors. However, despite these appreciations, the precise nature of the evoked defect in T-cell immunity in post-acute phases of SIRS remains unknown. Here we present an in-depth functional analysis of T-cell function in post-acute SIRS/sepsis. We document that T-cell function is not compromised on a per cell basis in experimental rodent models of infection-free SIRS (LPS or CpG) or septic peritonitis. Transgenic antigen-specific T-cells feature an unaltered cytokine response if challenged in vivo and ex vivo with cognate antigens. Isolated CD4+/CD8+ T-cells from post-acute septic animals do not exhibit defects in T-cell receptor-mediated activation at the the level of receptor-proximal signalling, activation marker upregulation or expansion. However, SIRS/sepsis induced transient lymphopenia and gave rise to an environment of immune attenuation at post acute disease stages. Thus, systemic inflammation has an acute impact on T-cell numbers and adaptive immunity, but does not cause major cell-autonomous enduring functional defects in T-cells. PMID:25541945

  1. CRTH2 is a critical regulator of neutrophil migration and resistance to polymicrobial sepsis.

    Science.gov (United States)

    Ishii, Makoto; Asano, Koichiro; Namkoong, Ho; Tasaka, Sadatomo; Mizoguchi, Kosuke; Asami, Takahiro; Kamata, Hirofumi; Kimizuka, Yoshifumi; Fujiwara, Hiroshi; Funatsu, Yohei; Kagawa, Shizuko; Miyata, Jun; Ishii, Ken; Nakamura, Masataka; Hirai, Hiroyuki; Nagata, Kinya; Kunkel, Steven L; Hasegawa, Naoki; Betsuyaku, Tomoko

    2012-06-01

    Although arachidonic acid cascade has been shown to be involved in sepsis, little is known about the role of PGD(2) and its newly found receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), on the septic response. Severe sepsis is associated with the failure of neutrophil migration. To investigate whether CRTH2 influences neutrophil recruitment and the lethality during sepsis, sepsis was induced by cecal ligation and puncture (CLP) surgery in mice. CRTH2 knockout (CRTH2(-/-)) mice were highly resistant to CLP-induced sepsis, which was associated with lower bacterial load and lower production of TNF-α, IL-6, and CCL3. IL-10, an anti-inflammatory cytokine, was higher in CRTH2(-/-) mice, blunting CLP-induced lethality in CRTH2(-/-) mice. Neutrophil accumulation in the peritoneum was more pronounced after CLP in CRTH2(-/-) mice, which was associated with higher CXCR2 levels in circulating neutrophils. Furthermore, sepsis caused a decrease in the level of acetylation of histone H3, an activation mark, at the CXCR2 promoter in wild-type neutrophils, suggesting that CXCR2 expression levels are epigenetically regulated. Finally, both pharmacological depletion of neutrophils and inhibition of CXCR2 abrogated the survival benefit in CRTH2(-/-) mice. These results demonstrate that genetic ablation of CRTH2 improved impaired neutrophil migration and survival during severe sepsis, which was mechanistically associated with epigenetic-mediated CXCR2 expression. Thus, CRTH2 is a potential therapeutic target for polymicrobial sepsis.

  2. Management of the patient with sepsis in emergency department: a new alternative protocol

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    Manuel Monti

    2014-10-01

    Full Text Available Sepsis is a clinical syndrome induced from the host response to an infection. Severe sepsis is the leading cause of death in critically ill patients. The introduction of the early goaldirected therapy (EGDT has been able to reduce mortality in patients with severe sepsis/ septic shock. However, sepsis mortality rates remain high compared to other critical illnesses. Many studies have pointed out that the use of arterial line placement and the execution of central venous pressure and central venous oxygen saturation measurements are the most difficult EGDT elements to carry out in community hospitals. For these reasons, the present independent review examines recent pathogenic, diagnostic, and therapeutic development in sepsis with particular relevance to the emergency practice, following the latest guidelines published in February 2013 and several recent studies. We propose a non-invasive alternative protocol which can replace the standard treatment with non-substantial changes in the patient outcome though overcoming the obstacles of a invasive method.

  3. Effects of continuous erythropoietin receptor activator in sepsis-induced acute kidney injury and multi-organ dysfunction.

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    Camila E Rodrigues

    Full Text Available BACKGROUND: Despite advances in supportive care, sepsis-related mortality remains high, especially in patients with acute kidney injury (AKI. Erythropoietin can protect organs against ischemia and sepsis. This effect has been linked to activation of intracellular survival pathways, although the mechanism remains unclear. Continuous erythropoietin receptor activator (CERA is an erythropoietin with a unique pharmacologic profile and long half-life. We hypothesized that pretreatment with CERA would be renoprotective in the cecal ligation and puncture (CLP model of sepsis-induced AKI. METHODS: RATS WERE RANDOMIZED INTO THREE GROUPS: control; CLP; and CLP+CERA (5 µg/kg body weight, i.p. administered 24 h before CLP. At 24 hours after CLP, we measured creatinine clearance, biochemical variables, and hemodynamic parameters. In kidney tissue, we performed immunoblotting--to quantify expression of the Na-K-2Cl cotransporter (NKCC2, aquaporin 2 (AQP2, Toll-like receptor 4 (TLR4, erythropoietin receptor (EpoR, and nuclear factor kappa B (NF-κB--and immunohistochemical staining for CD68 (macrophage infiltration. Plasma interleukin (IL-2, IL-1β, IL-6, IL-10, interferon gamma, and tumor necrosis factor alpha were measured by multiplex detection. RESULTS: Pretreatment with CERA preserved creatinine clearance and tubular function, as well as the expression of NKCC2 and AQP2. In addition, CERA maintained plasma lactate at normal levels, as well as preserving plasma levels of transaminases and lactate dehydrogenase. Renal expression of TLR4 and NF-κB was lower in CLP+CERA rats than in CLP rats (p<0.05 and p<0.01, respectively, as were CD68-positive cell counts (p<0.01, whereas renal EpoR expression was higher (p<0.05. Plasma levels of all measured cytokines were lower in CLP+CERA rats than in CLP rats. CONCLUSION: CERA protects against sepsis-induced AKI. This protective effect is, in part, attributable to suppression of the inflammatory response.

  4. Experimental models of sepsis and septic shock: an overview

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    Garrido Alejandra G.

    2004-01-01

    Full Text Available Sepsis remains a major cause of morbidity and mortality in surgical patients and trauma victims, mainly due to sepsis-induced multiple organ dysfunction. In contrast to preclinical studies, most clinical trials of promising new treatment strategies for sepsis have fails to demonstrate efficacy. Although many reasons could account for this discrepancy, the misinterpretation of preclinical data obtained from experimental studies, and especially the use of animal models that do not adequately mimic human sepsis may have been contributing factors. In this review, the benefits and limitations of various animal models of sepsis are discussed to clarify the extend to which findings are relevant to human sepsis, particularly with respect to the subsequent design and execution of clinical trials. Such models include intravascular infusion of endotoxin or live bacteria, bacterial peritonitis, cecal ligation and perforation, soft tissue infection, pneumonia or meningitis models, using different animal species including rats, mice, rabbits, dogs, pigs, sheep and nonhuman primates. Despite several limitations, animal models remain essential in the development of all new therapies for sepsis and septic shock, because they provide fundamental information about the pharmacokinetics, toxicity, and mechanism of drug action that cannot be duplicated by other methods. New therapeutic agents should be studies in infection models, even after the initiation of the septic process. Furthermore, debility conditions need to be reproduced to avoid the exclusive use of healthy animals, which often do not represent the human septic patient.

  5. CIRCULATING MICROPARTICLES, BLOOD CELLS, AND ENDOTHELIUM INDUCE PROCOAGULANT ACTIVITY IN SEPSIS THROUGH PHOSPHATIDYLSERINE EXPOSURE.

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    Zhang, Yan; Meng, Huan; Ma, Ruishuang; He, Zhangxiu; Wu, Xiaoming; Cao, Muhua; Yao, Zhipeng; Zhao, Lu; Li, Tao; Deng, Ruijuan; Dong, Zengxiang; Tian, Ye; Bi, Yayan; Kou, Junjie; Thatte, Hemant S; Zhou, Jin; Shi, Jialan

    2016-03-01

    Sepsis is invariably accompanied by altered coagulation cascade; however, the precise role of phosphatidylserine (PS) in inflammation-associated coagulopathy in sepsis has not been well elucidated. We explored the possibility of exposed PS on microparticles (MPs), blood cells, as well as on endothelium, and defined its role in procoagulant activity (PCA) in sepsis. PS-positive MPs and cells were detected by flow cytometry, while PCA was assessed with clotting time, purified coagulation complex, and fibrin formation assays. Plasma levels of PS MPs derived from platelets, leukocytes (including neutrophils, monocytes, and lymphocytes), erythrocytes, and endothelial cells were elevated by 1.49-, 1.60-, 2.93-, and 1.53-fold, respectively, in septic patients. Meanwhile, PS exposure on blood cells was markedly higher in septic patients than in controls. Additionally, we found that the endothelial cells (ECs) treated with septic serum in vitro exposed more PS than with healthy serum. Isolated MPs/blood cells from septic patients and cultured ECs treated with septic serum in vitro demonstrated significantly shortened coagulation time, greatly enhanced intrinsic/extrinsic FXa generation, and increased thrombin formation. Importantly, confocal imaging of MPs or septic serum-treated ECs identified binding sites for FVa and FXa to form prothrombinase, and further supported fibrin formation in the area where PS exposure was abundant. Pretreatment with lactadherin blocked PS on MPs/blood cells/ECs, prolonged coagulation time by at least 25%, reduced FXa/thrombin generation, and inhibited fibrin formation by approximately 85%. Our findings suggest a key role for PS exposed on MPs, blood cells, and endothelium in augmenting coagulation in sepsis. Therefore, therapies targeting PS may be of particular importance.

  6. Coste-efectividad de drotrecogina alfa (activada en el tratamiento de la sepsis grave en España Cost-effectiveness of drotrecogin alpha [activated] in the treatment of severe sepsis in Spain

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    José A Sacristán

    2004-02-01

    grupo de pacientes con 2 o más fallos orgánicos. En el análisis de sensibilidad, los resultados oscilaron desde 7.322 a 16.493 euros por AVG. Los factores que más influyeron en los resultados fueron la modificación de la eficacia de drotrecogina alfa (activada, el ajuste de la supervivencia según la comorbilidad inicial y la aplicación de descuento a los AVG. Conclusiones: El tratamiento con drotrecogina alfa (activada presenta una relación coste-efectividad favorable en comparación con otras intervenciones sanitarias comúnmente utilizadas en España.Introduction: The PROWESS clinical trial has shown that treatment with drotrecogin alpha (activated in patients with severe sepsis is associated with a reduction in the absolute risk of death compared with standard treatment. The aim of the present study was to assess the cost-effectiveness of drotrecogin alpha (activated versus that of standard care in the treatment of severe sepsis in Spain. Patients and methods: A decision analysis model was drawn up to compare costs to hospital discharge and the long-term efficacy of drotrecogin alpha (activated versus those of standard care in the treatment of severe sepsis in Spain from the perspective of the health care payer. Most of the information for creating the model was obtained from the PROWESS clinical trial. A two-fold baseline analysis was performed: a for all patients included in the PROWESS clinical trial and b for the patients with two or more organ failures. The major variables for clinical assessment were the reduction in mortality and years of life gained (YLG. Cost-effectiveness was expressed as cost per YLG. A sensitivity analysis was applied using 3% and 5% discount rates for YLG and by modifying the patterns of health care, intensive care unit costs, and life expectancy by initial co-morbidity and therapeutic efficacy of drotrecogin alpha (activated. Results: Treatment with drotrecogin alfa (activated was associated with a 6.0% drop in the absolute risk

  7. Cardiomyocyte specific expression of Acyl-coA thioesterase 1 attenuates sepsis induced cardiac dysfunction and mortality

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Congying [Departments of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Dong, Ruolan [Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China); Chen, Chen [Departments of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Wang, Hong, E-mail: hong.wang1988@yahoo.com [Departments of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Wang, Dao Wen, E-mail: dwwang@tjh.tjmu.edu.cn [Departments of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China)

    2015-12-25

    Compromised cardiac fatty acid oxidation (FAO) induced energy deprivation is a critical cause of cardiac dysfunction in sepsis. Acyl-CoA thioesterase 1 (ACOT1) is involved in regulating cardiac energy production via altering substrate metabolism. This study aims to clarify whether ACOT1 has a potency to ameliorate septic myocardial dysfunction via enhancing cardiac FAO. Transgenic mice with cardiomyocyte specific expression of ACOT1 (αMHC-ACOT1) and their wild type (WT) littermates were challenged with Escherichia coli lipopolysaccharide (LPS; 5 mg/kg i.p.) and myocardial function was assessed 6 h later using echocardiography and hemodynamics. Deteriorated cardiac function evidenced by reduction of the percentage of left ventricular ejection fraction and fractional shortening after LPS administration was significantly attenuated by cardiomyocyte specific expression of ACOT1. αMHC-ACOT1 mice exhibited a markedly increase in glucose utilization and cardiac FAO compared with LPS-treated WT mice. Suppression of cardiac peroxisome proliferator activated receptor alpha (PPARa) and PPARγ-coactivator-1α (PGC1a) signaling observed in LPS-challenged WT mice was activated by the presence of ACOT1. These results suggest that ACOT1 has potential therapeutic values to protect heart from sepsis mediated dysfunction, possibly through activating PPARa/PGC1a signaling. - Highlights: • ACOT1 has potential therapeutic values to protect heart from sepsis mediated dysfunction. • ACOT1 can regulate PPARa/PGC1a signaling pathway. • We first generate the transgenic mice with cardiomyocyte specific expression of ACOT1.

  8. Interleukin-18 gene deletion protects against sepsis-induced cardiac dysfunction by inhibiting PP2A activity.

    Science.gov (United States)

    Okuhara, Yoshitaka; Yokoe, Shunichi; Iwasaku, Toshihiro; Eguchi, Akiyo; Nishimura, Koichi; Li, Wen; Oboshi, Makiko; Naito, Yoshiro; Mano, Toshiaki; Asahi, Michio; Okamura, Haruki; Masuyama, Tohru; Hirotani, Shinichi

    2017-09-15

    Interleukin-18 (IL-18) neutralization protects against lipopolysaccharide (LPS)-induced injuries, including myocardial dysfunction. However, the mechanism is yet to be fully elucidated. The aim of the present study was to determine whether IL-18 gene deletion prevents sepsis-induced cardiac dysfunction and to elucidate the potential mechanisms underlying IL-18-mediated cardiotoxicity by LPS. Ten-week-old male wild-type (WT) and IL-18 knockout (IL-18 KO) mice were intraperitoneally administered LPS. Serial echocardiography showed better systolic pump function and less left ventricular (LV) dilatation in LPS-treated IL-18 KO mice compared with those in LPS-treated WT mice. LPS treatment significantly decreased the levels of phospholamban (PLN) and Akt phosphorylation in WT mice compared with those in saline-treated WT mice, while the LPS-induced decrease in the phosphorylation levels was attenuated in IL-18 KO mice compared with that in WT mice. IL-18 gene deletion also attenuated an LPS-induced increase of type 2 protein phosphatase 2A (PP2A) activity, a molecule that dephosphorylates PLN and Akt. There was no difference in type 1 protein phosphatase (PP1) activity. To address whether IL-18 affects PLN and Akt phosphorylation via PP2A activation in cardiomyocytes, rat neonatal cardiac myocytes were cultured and stimulated using 100ng/ml of recombinant rat IL-18. Exogenous IL-18 decreased the level of PLN and Akt phosphorylation in cardiomyocytes. PP2A activity but not PP1 activity was increased by IL-18 stimulation in cardiomyocytes. IL-18 plays a pivotal role in advancing sepsis-induced cardiac dysfunction, and the mechanisms underlying IL-18-mediated cardiotoxicity potentially involve the regulation of PLN and Akt phosphorylation through PP2A activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Clinical Effects of a Longer Duration of Polymyxin B-Immobilized Fiber Column Direct Hemoperfusion Therapy for Severe Sepsis and Septic Shock.

    Science.gov (United States)

    Yamashita, Chizuru; Hara, Yoshitaka; Kuriyama, Naohide; Nakamura, Tomoyuki; Nishida, Osamu

    2015-08-01

    Polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) therapy is widely used for the treatment of severe sepsis and septic shock, and is generally performed for 2 h. Although previous studies demonstrated the efficacy of PMX-DHP therapy, it currently remains unclear whether its optimal duration is 2 h. This retrospective study analyzed 37 patients with septic shock who showed a poor clinical response to 2 h of PMX-DHP, and underwent a longer duration of this therapy. The mean duration of PMX-DHP therapy was 15.8 ± 7.9 h, and none of the patients developed adverse events, which enabled the therapy to be performed safely. The pressure catecholamine index [CAIP = catecholamine index/mean arterial pressure; catecholamine index = dopamine + dobutamine + (adrenaline + noradrenaline) × 100 μg/kg per min], as an indicator of hemodynamics, improved significantly in the survival group in the period between the start and 24 h after the end of PMX-DHP therapy (P hemodynamics and pulmonary oxygenation capacity of patients with severe sepsis/septic shock. Strict prospective studies are needed in the future.

  10. Increased extracellular heat shock protein 90α in severe sepsis and SIRS associated with multiple organ failure and related to acute inflammatory-metabolic stress response in children.

    Science.gov (United States)

    Fitrolaki, Michaela-Diana; Dimitriou, Helen; Venihaki, Maria; Katrinaki, Marianna; Ilia, Stavroula; Briassoulis, George

    2016-08-01

    Mammalian heat-shock-protein (HSP) 90α rapidly responses to environmental insults. We examined the hypothesis that not only serum HSP72 but also HSP90α is increased in the systemic inflammatory response syndrome (SIRS), severe-sepsis (SS), and/or sepsis (S) compared to healthy children (H); we assessed HSP90α relation to (a) multiple organ system failure (MOSF) and (b) inflammatory-metabolic response and severity of illness.A total of 65 children with S, SS, or SIRS and 25 H were included. ELISA was used to evaluate extracellular HSP90α and HSP72, chemiluminescence interleukins (ILs), flow-cytometry neutrophil-CD64 (nCD64)-expression.HSP90α, along with HSP72, were dramatically increased among MOSF patients. Patients in septic groups and SIRS had elevated HSP90α compared to H (P SIRS, and MOSF, HSP90α is related to the inflammatory stress, fever, outcome endpoints, and predicted mortality and inversely related to the low-LDL/low-HDL stress metabolic pattern.

  11. Early response roles for prolactin cortisol and circulating and cellular levels of heat shock proteins 72 and 90α in severe sepsis and SIRS.

    Science.gov (United States)

    Vardas, K; Apostolou, K; Briassouli, E; Goukos, D; Psarra, K; Botoula, E; Tsagarakis, S; Magira, E; Routsi, C; Nanas, S; Briassoulis, G

    2014-01-01

    To evaluate the early heat shock protein (HSP) and hormonal stress response of intensive care unit (ICU) patients with severe sepsis/septic shock (SS) or systemic inflammatory response syndrome (SIRS) compared to healthy subjects (H). Patients with early (first 48 hrs) SS (n = 29) or SIRS (n = 29) admitted to a university ICU and 16 H were enrolled in the study. Serum prolactin, cortisol, and plasma ACTH were determined using immunoassay analyzers. ELISA was used to evaluate extracellular HSPs (eHSP90α, eHSP72) and interleukins. Mean fluorescence intensity (MFI) values for intracellular HSPs (iHSP72, iHSP90α) were measured using 4-colour flow-cytometry. Prolactin, cortisol, and eHSP90α levels were significantly increased in SS patients compared to SIRS and H (P SIRS compared to H (P SIRS eHSP90α was related with eHSP72, IL-6, and IL-10. Prolactin, apart from cortisol, may have a role in the acute stress response in severe sepsis. In this early-onset inflammatory process, cortisol relates to eHSP90α, monocytes suppress iHSP72, and plasma eHSP72 increases.

  12. Kiss-induced severe anaphylactic reactions

    Directory of Open Access Journals (Sweden)

    Atanasković-Marković Marina

    2010-01-01

    Full Text Available Introduction. Ingestion is the principal route for food allergens to trigger allergic reaction in atopic persons. However, in some highly sensitive patients severe symptoms may develop upon skin contact and by inhalation. The clinical spectrum ranges from mild facial urticaria and angioedema to life-threatening anaphylactic reactions. Outline of Cases. We describe cases of severe anaphylactic reactions by skin contact, induced by kissing in five children with prior history of severe anaphylaxis caused by food ingestion. These cases were found to have the medical history of IgE mediated food allergy, a very high total and specific serum IgE level and very strong family history of allergy. Conclusion. The presence of tiny particles of food on the kisser's lips was sufficient to trigger an anaphylactic reaction in sensitized children with prior history of severe allergic reaction caused by ingestion of food. Allergic reaction provoked with food allergens by skin contact can be a risk factor for generalized reactions. Therefore, extreme care has to be taken in avoiding kissing allergic children after eating foods to which they are highly allergic. Considering that kissing can be a cause of severe danger for the food allergic patient, such persons should inform their partners about the risk factor for causing their food hypersensitivity.

  13. Anti-inflammatory effects of mangiferin on sepsis-induced lung injury in mice via up-regulation of heme oxygenase-1.

    Science.gov (United States)

    Gong, Xia; Zhang, Li; Jiang, Rong; Ye, Mengliang; Yin, Xinru; Wan, Jingyuan

    2013-06-01

    Sepsis, a serious unbalanced hyperinflammatory condition, is a tremendous burden for healthcare systems, with a high mortality and limited treatment. Increasing evidences indicated that some active components derived from natural foods have potent anti-inflammatory properties. Here we show that mangiferin (MF), a natural glucosyl xanthone found in both mango and papaya, attenuates cecal ligation and puncture-induced mortality and acute lung injury (ALI), as indicated by reduced systemic and pulmonary inflammatory responses. Moreover, pretreatment with MF inhibits sepsis-activated mitogen-activated protein kinases and nuclear factor kappa-light-chain-enhancer of activated B cells signaling, resulting in inhibiting production of proinflammatory mediators. Notably, MF dose-dependently up-regulates the expression and activity of heme oxygenase (HO)-1 in the lung of septic mice. Further, these beneficial effects of MF on the septic lung injury were eliminated by ZnPP IX, a specific HO-1 inhibitor. Our results suggest that MF attenuates sepsis by up-regulation of HO-1 that protects against sepsis-induced ALI through inhibiting inflammatory signaling and proinflammatory mediators. Thereby, MF may be effective in treating sepsis with ALI. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Functional polymorphism in exon 5 and variant haplotype of the interleukin-1 receptor-associated kinase 1 gene are associated with susceptibility to and severity of sepsis in the Chinese population

    Institute of Scientific and Technical Information of China (English)

    FANG Yu; ZHANG Lu; ZHOU Gang-qiao; WANG Zhi-fu; ZENG Zhao-shu; LUO Zhi-yi; LI Lei; LIU Bao-chi

    2011-01-01

    Background The interleukin-1 (IL-1) receptor-associated kinase 1 (IRAKI) is believed to play an important role in the pathogenesis of sepsis. Recent studies have suggested that the IRAK1 functional genetic variant could affect the severity of sepsis in Caucasians. In this report, we have investigated whether polymorphisms at the IRAK1 gene are associated with the susceptibility to and severity of sepsis among the Chinese population. Methods Haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected from the HapMap database.They were genotyped in 255 patients with sepsis and 260 control subjects by PCR/restriction fragment length polymorphism (RFLP) analysis. The association between the selected htSNPs and the susceptibility to and severity of sepsis were estimated by Logistic regression with adjustments for age, sex, smoking, drinking, chronic disease status,Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score and primary diseases. Results rs1059702 was selected to represent the six linked htSNPs for IRAK1. Genotype frequencies of the htSNPs were in Hardy-Weinberg equilibrium for females, as were allele frequencies for both sex groups. Associations were observed in females between the htSNPs C/C genotype and increased susceptibility to sepsis (odds ratio (OR), 5.46;95% confidence interval (Cl), 1.12-26.67; P=0.018), and such associations were also observed between the IRAK1variant haplotype (CC/C-allele) and increased susceptibility to sepsis (OR, 1.68; 95% Cl, 1.05-2.70; P=0.031) when compared with the T/T + T/C genotype and the wild-type haplotype (TC + TT/T-allele). In the multiple organ dysfunction syndrome (MODS) subgroup, the variant haplotype was also associated with increased severity of sepsis (OR, 2.37; 95%Cl, 1.13-4.94; P=0.02) when compared with the wild haplotype. This association was not significant in male patients. Conclusions The functional polymorphism in exon 5 and the variant haplotype of IRAK1 gene mediate

  15. Early diagnosis of sepsis using serum hemoglobin subunit Beta.

    Science.gov (United States)

    Yoo, Hayoung; Ku, Sae-Kwang; Kim, Shin-Woo; Bae, Jong-Sup

    2015-02-01

    The development of new sepsis-specific biomarkers is mandatory to improve the detection and monitoring of the disease. Hemoglobin is the main oxygen and carbon dioxide carrier in cells of the erythroid lineage and is responsible for oxygen delivery to the respiring tissues of the body. Hemoglobin subunit beta (HBβ) is a component of a larger protein called hemoglobin. The aim of this study was to evaluate blood levels of HBβ in septic patients. A prospective study of 82 patients with sepsis was conducted. Furthermore, C57BL/6 mice were subjected to cecal ligation and puncture (CLP) surgery. Alternatively, human umbilical vein endothelial cells (HUVECs) or C57BL/6 mice were exposed to lipopolysaccharide (LPS, 100 ng/ml to HUVECs or 10 mg/kg to mice). The data showed that LPS induced upregulation of the synthesis and secretion of HBβ in LPS-treated HUVECs and in LPS-injected and CLP mice. In patients admitted to the intensive care unit with sepsis, circulating levels of HBβ were significantly high (sepsis, 64.93-114.76 ng/ml, n = 30; severe sepsis, 157.37-268.69 ng/ml, n = 22; septic shock, 309.98-427.03 ng/ml, n = 30) when compared to the levels of control donors (9.76-12.28 ng/ml, n = 21). Patients with septic shock had higher HBβ levels when compared to patients with severe sepsis. Furthermore, the HBβ levels in septic patients were higher than those in healthy volunteers. These results suggest that in septic patients, HBβ blood level is related to the severity of sepsis and may represent a novel endothelial cell dysfunction marker. Moreover, HBβ can be used as a biomarker to determine the severity of sepsis.

  16. [Effect of methylene blue on changes in inducible nitric oxide synthase in lung of rats with sepsis].

    Science.gov (United States)

    Dai, Cheng; Wang, Yi; Yu, Xiangyou

    2016-02-01

    To study the time course of effect of methylene blue on inducible nitric oxide synthase (iNOS) mRNA transcription and protein expression in lung tissue of rats with sepsis, and its mechanism. 126 female Wistar rats were randomly divided into sham group, sepsis group and methylene blue group. Each group was subdivided into 0-, 6-, 12-, 18-, 24-, 30-, and 36-hour subgroups according to the time after operation, with 6 rats in each subgroup. A model of sepsis was reproduced by cecal ligation and puncture (CLP), and the rats in sham group were only opened the abdominal cavity and isolated the membrane of the appendix without CLP. Rats in methylene blue group were given injection of 15 mg/kg methylene blue at all time points after CLP, the remaining rats were given 0.9%NaCl solution in same amount. Six hours after the injection, the rats were sacrificed and the lung tissue was harvested immediately. The expression of iNOS mRNA and protein in lung tissues were determined by real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and Western Blot respectively, and the changes in histopathology were observed using hematoxylin and eosin (HE) staining. Compared with sham group, the expression of iNOS mRNA was significantly up-regulated at 6, 12, 18 and 24 hours after CLP in sepsis group (2(-ΔΔCt): 2.42±0.66 vs. 1.00±0.38 at 6 hours, P = 0.002; 2.54±0.76 vs. 1.00±0.27 at 12 hours, P = 0.000; 5.46±2.26 vs. 1.00±0.38 at 18 hours, P = 0.000; 3.03±0.62 vs. 1.00±0.33 at 24 hours, P = 0.001), and iNOS protein expression was significantly up-regulated at 12, 18 and 24 hours (gray value: 2.54±0.45 vs. 1.00±0.35 at 12 hours, P = 0.000; 2.65±0.64 vs. 1.00±0.33 at 18 hours, P = 0.000; 3.03±0.59 vs. 1.00±0.24 at 24 hours, P = 0.000). Compared with sepsis group, the expression of iNOS mRNA was significantly down-regulated at 6, 12, 18 and 24 hours in methylene blue group (2(-ΔΔCt): 1.55±0.82 vs. 2.42±0.66 at 6 hours, P = 0.034; 1.84±0.42 vs. 2

  17. Blood transfusion practices in sepsis

    Directory of Open Access Journals (Sweden)

    TVSP Murthy

    2014-01-01

    Full Text Available Sepsis is a clinical syndrome characterised by systemic inflammation due to infection. There is a spectrum with severity ranging from sepsis to severe sepsis and septic shock. Even with optimal treatment, mortality due to severe sepsis or septic shock is significant and poses a challenge to management. Antibiotics, source control, resuscitation with fluids, vasopressor and inotropic agents are the main-stay of treatment for septic shock. These may be supplemented with transfusion of red blood cells and or blood products, in the case of anaemia to sustain sufficient oxygen delivery [1] or to manage associated haematological issues. Transfusion in sepsis has always been a debatable issue, especially in relation to choice of the fluid and the role of blood or blood product transfusion.

  18. Streptococcal Sepsis

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    Maureen T. Fleming

    1997-01-01

    Full Text Available Objective: The purpose of this study was to determine the compliance rate with a maternal risk-factor-based guideline for the prevention of neonatal group B streptococcal (GBS sepsis.

  19. Procalcitonina como biomarcador de prognóstico da sepse grave e choque séptico Procalcitonin as a prognostic biomarker of severe sepsis and septic shock

    Directory of Open Access Journals (Sweden)

    José Raimundo Araujo de Azevedo

    2012-12-01

    como, redução do PCT-c 24 horas, associaram-se à elevação expressiva da mortalidade de pacientes com sepse grave e choque séptico.OBJECTIVE: To evaluate the tendency of the plasma concentration and clearance of procalcitonin (PCT-c as biomarkers of prognosis of patients with severe sepsis and septic shock, compared to another early prognosis marker, the number of SIRS criteria at sepsis diagnosis. METHODS: We conducted a prospective, observational, cohort study, with patients with severe sepsis and septic shock. The serum procalcitonin was determined at diagnosis of sepsis and after 24 and 48 hours. Demographic data, APACHE IV, SOFA score on arrival, number of SIRS criteria at diagnosis, site of infection and microbiological results were recorded. RESULTS: Twenty-eight patients were included, 19 clinical and nine surgical. In 13 (46.4% the source of sepsis was pulmonary, abdominal in seven (25.0%, urinary in five (17.9% and soft tissue in three cases (10.7%. Fifteen patients had severe sepsis and 13 septic shock. Overall mortality was 17.9% (five patients, three with septic shock. Twenty-eight PCT determinations were performed at sepsis diagnosis, 27 after 24 hours and 26 after 48 hours. The initial concentration was not significantly different between survivors and non-survivors groups, but the differences between the two groups after 24 and 48 hours were statistically significant. There was no difference in the number of SIRS criteria. The 24-hour procalcitonin clearance proved to be significantly higher in the group of survivors (-3.0 versus -300.0, p = 0.028. Although the 48-hour procalcitonin clearance has shown to be higher in the group of survivors when compared to non-survivors, the difference did not reach statistical significance. CONCLUSION: Persistently high procalcitonin concentrations in plasma, as well as reduced 24-hours PCT clearence, were associated with a significant increase in mortality in patients with severe sepsis and septic shock.

  20. Sepsis associated encephalopathy (SAE): a review.

    Science.gov (United States)

    Green, Rebecca; Scott, L Keith; Minagar, Alireza; Conrad, Steven

    2004-05-01

    Sepsis associated encephalopathy (SAE) is a poorly understood condition that is associated with severe sepsis and appears to have a negative influence on survival. The incidence of encephalopathy secondary to sepsis is unknown. Amino acid derangements, blood-brain barrier disruption, abnormal neurotransmitters, and direct CNS effect are possible causes of septic encephalopathy. Research has not defined the pathogenesis of SAE.

  1. The evolutionary logic of sepsis.

    Science.gov (United States)

    Rózsa, Lajos; Apari, Péter; Sulyok, Mihály; Tappe, Dennis; Bodó, Imre; Hardi, Richárd; Müller, Viktor

    2017-09-09

    The recently proposed Microbiome Mutiny Hypothesis posits that members of the human microbiome obtain information about the host individuals' health status and, when host survival is compromised, switch to an intensive exploitation strategy to maximize residual transmission. In animals and humans, sepsis is an acute systemic reaction to microbes invading the normally sterile body compartments. When induced by formerly mutualistic or neutral microbes, possibly in response to declining host health, sepsis appears to fit the 'microbiome mutiny' scenario except for its apparent failure to enhance transmission of the causative organisms. We propose that the ability of certain species of the microbiome to induce sepsis is not a fortuitous side effect of within-host replication, but rather it might, in some cases, be the result of their adaptive evolution. Whenever host health declines, inducing sepsis can be adaptive for those members of the healthy human microbiome that are capable of colonizing the future cadaver and spread by cadaver-borne transmission. We hypothesize that such microbes might exhibit switches along the 'mutualist - lethal pathogen - decomposer - mutualist again' scenario, implicating a previously unsuspected, surprising level of phenotypic plasticity. This hypothesis predicts that those species of the healthy microbiome that are recurring causative agents of sepsis can participate in the decomposition of cadavers, and can be transmitted as soil-borne or water-borne infections. Furthermore, in individual sepsis cases, the same microbial clones that dominate the systemic infection that precipitates sepsis, should also be present in high concentration during decomposition following death: this prediction is testable by molecular fingerprinting in experimentally induced animal models. Sepsis is a leading cause of human death worldwide. If further research confirms that some cases of sepsis indeed involve the 'mutiny' (facultative phenotypic switching) of

  2. Pediatric sepsis:early recognition and timely treatment of pediatric severe sepsis and septic shock%再论儿童脓毒症——如何早期识别和治疗严重脓毒症和脓毒性休克

    Institute of Scientific and Technical Information of China (English)

    王莹; 史柳红

    2012-01-01

    儿童严重脓毒症、脓毒性休克是PICU中患儿的主要死亡原因之一,早期识别、及时诊断、尽早治疗是改善预后、降低病死率之关键.该文再次强调了儿童脓毒症新定义,并推荐国外的儿童脓毒症筛查方案及早期目标导向治疗(EGDT)方案,旨在指导国内儿科医师的诊断和治疗,改善严重脓毒症、脓毒性休克儿童的预后,提高生存率.%Pediairic severe sepsis and septic shock is one of leading causes of death in pediatric intensive care unit. Early recognition and resuscitation of pediatrie severe sepsis and septic shock is the key strategy io improve prognosis and reduce the mortality. This review reemphasized tine new definition of periiatric sepsis and recommended pediatrie sepsis screening protocol and early goal-directed therapy ( KGDT) protocol. The purpose of this review is to provide guidance for Chinese pediatrician to improve outcome of periiatrie severe sepsis and septic shock and increase the survival rate in clinical practice.

  3. Assessment of sepsis-induced immunosuppression at ICU discharge and 6 months after ICU discharge.

    Science.gov (United States)

    Zorio, Violette; Venet, Fabienne; Delwarde, Benjamin; Floccard, Bernard; Marcotte, Guillaume; Textoris, Julien; Monneret, Guillaume; Rimmelé, Thomas

    2017-12-01

    Increase in mortality and in recurrent infections in the year following ICU discharge continues in survivors of septic shock, even after total clinical recovery from the initial septic event and its complications. This supports the hypothesis that sepsis could induce persistent long-term immune dysfunctions. To date, there is almost no data on ICU discharge and long-term evolution of sepsis-induced immunosuppression in septic shock survivors. The aim of this study was to assess the persistence of sepsis-induced immunosuppression by measuring expression of human leukocyte antigen DR on monocytes (mHLA-DR), CD4+ T cells, and regulatory T cells (Treg) at ICU discharge and 6 months after ICU discharge in patients admitted to the ICU for septic shock. In this prospective observational study, septic shock survivors with no preexisting immune suppression or treatment interfering with the immune system were included. mHLA-DR, CD4+ T cells, and Treg expression were assessed on day 1-2, 3-4, and 6-8 after ICU admission, at ICU discharge, and 6 months after ICU discharge. A total of 40 patients were enrolled during their ICU stay: 21 males (52.5%) and 19 females, median age 68 years (IQR 58-77), median SOFA score on day 1-2 was 8 (IQR 7-9), and median ICU length of stay was 11 days (IQR 7-24). Among these 40 patients, 33 were studied at ICU discharge and 15 were disposed for blood sampling 6 months after ICU discharge. On day 1-2, mHLA-DR expression was abnormally low for all patients [median 4212 (IQR 2640-6047) AB/C] and remained abnormally low at ICU discharge for 75% of them [median 10,281 (IQR 7719-13,035) AB/C]. On day 3-4, 46% of patients presented CD4+ lymphopenia [median 515 (IQR 343-724) mm(-3)] versus 34% at ICU discharge [median 642 (IQR 459-846) mm(-3)]. Among patients with a 6-month blood sample, normal values of mHLA-DR were found for all patients [median 32,616 (IQR 24,918-38,738) AB/C] except for one and only another one presented CD4+ lymphopenia. While

  4. Sepsis and mechnaical ventilation restrain translation initiation in skeletal muscle by inducing AMPK-associated TSC[2] restriction of mTOR signaling in pigs

    Science.gov (United States)

    In skeletal muscle, AMP-activated protein kinase (AMPK) acts as a cellular energy sensor of AMP: ATP and modulates translation by repressing mammalian target of rapamycin (mTOR) activation. Endotoxin (LPS)-induced sepsis reduces muscle protein synthesis by blunting translation initiation. We hypothe...

  5. Rotation thromboelastography for the detection and characterization of lipoteichoid acid-induced activation of haemostasis in an in vitro sepsis model.

    Science.gov (United States)

    Sucker, C; Paniczek, S; Scharf, R E; Litmathe, J; Hartmann, M

    2013-03-01

    In gram-positive sepsis, lipoteichoic acid (LTA) can induce alterations of haemostasis, potentially leading to disseminated intravascular coagulation. Here, we demonstrate the effects of LTA on haemostasis in an in vitro model of gram-positive sepsis based on rotation thromboelastrography (ROTEM). In this model, LTA leads to time- and dose-dependent shortening of the clotting time (CT), whereas other ROTEM parameters are unaffected. Following heat shock simulation, the LTA effect was blunted with equal CTs in the presence and in the absence of LTA. In addition, the shortening of CT by LTA was inhibited by addition of the protein synthesis inhibitor. Our work demonstrates that the ROTEM system is capable of detecting the LTA effect on haemostasis and provides a sensitive in vitro tool for research into the links between gram-positive sepsis and coagulation.

  6. Sepsis (For Parents)

    Science.gov (United States)

    ... Your Child Natural Disasters: How Families Can Help Sepsis KidsHealth > For Parents > Sepsis Print A A A ... Infections When to Call the Doctor What Is Sepsis? Sepsis is when the immune system responds to ...

  7. Calibrated versus uncalibrated arterial pressure waveform analysis in monitoring cardiac output with transpulmonary thermodilution in patients with severe sepsis and septic shock: an observational study.

    Science.gov (United States)

    Slagt, Cornelis; Helmi, Mochamat; Malagon, Ignacio; Groeneveld, A B Johan

    2015-01-01

    Cardiac output (CO) measurement is often required in critically ill patients. The performances of newer, less invasive techniques require evaluation in patients with severe sepsis and septic shock. To compare calibrated arterial pressure waveform analysis-derived CO (COap, VolumeView/EV1000) and the uncalibrated form (COfv, FloTrac/Vigileo) with transpulmonary thermodilution derived CO (COtptd). A prospective, observational, single-centre study. ICU of a general teaching hospital. Twenty consecutive patients with severe sepsis or septic shock requiring haemodynamic monitoring by VolumeView/EV1000 and receiving mechanical ventilation. Connection of FloTrac/Vigileo to radial artery catheter already in situ. Radial (COfv) and femoral (COap) arterial waveform-derived CO measurements were compared with COtptd with respect to bias, precision, limits of agreement and percentage error, and the percentage error in the course of time since the last calibration of COap by COtptd. In comparing COap with COtptd (n = 267 paired measurements), the bias was 0.02 and limits of agreement were -2.49 to 2.52 l min, with a percentage error of 31%. The percentage error between COap and COtptd remained less than 30% until 8 h after calibration. In comparing COfv with COtptd (n = 301), the bias was -0.86 l min and limits of agreement were -4.48 to 2.77 l min, with a percentage error of 48%. The biases of COap and COfv correlated with systemic vascular resistance [r = 0.13 (P = 0.029) and r = 0.42 (P arterial waveform analysis technique. Compared with the uncalibrated COfv, the recently introduced calibrated arterial pressure waveform analysis-derived COap was more accurate and less dependent on vascular tone for up to 8 hours after callibation when monitoring CO in patients with severe sepsis and septic shock. The COap and COfv methods have poor to moderate CO-tracking abilities.

  8. Relationship between age/gender-induced survival changes and the magnitude of inflammatory activation and organ dysfunction in post-traumatic sepsis.

    Directory of Open Access Journals (Sweden)

    Susanne Drechsler

    Full Text Available Age/gender may likely influence the course of septic complications after trauma. We aimed to characterize the influence of age/gender on the response of circulating cytokines, cells and organ function in post-traumatic sepsis. We additionally tested whether post-traumatic responses alone can accurately predict outcomes in subsequent post-traumatic sepsis. A mouse 2-hit model of trauma/hemorrhage (TH, 1(st hit and cecal ligation and puncture (CLP, 2(nd hit was employed. 3, 15 and 20 month (m old female (♀ and male (♂ CD-1 mice underwent sublethal TH followed by CLP 2 days later. Blood was sampled daily until day 6 post-TH and survival was followed for 16 days. To compare general response patterns among groups, we calculated two scores: the inflammatory response (including KC, MIP-1α, TNFα, MCP-1, IFNγ, IL-1β,-5,-6,-10 and the organ dysfunction score (Urea, ALT, AST and LDH. Moreover, mice were retrospectively divided into survivors (SUR and dying (DIE based on post-CLP outcome. In general, females survived better than males and their survival did not correspond to any specific estrus cycle phase. Pre-CLP phase: the post-TH inflammatory score was weakest in 3 m♂ but there were no changes among remaining groups (similar lack of differences in the organ dysfunction score. TH induced a 40% increase of IFNγ, MIP-1α and IL-5 in 15 m♂ SUR (vs. DIE but predictive accuracy for post-CLP outcomes was moderate. Post-CLP phase: while stable in males, inflammatory response score in 15 m and 20 m females decreased with age at day 1 and 2 post-CLP. SUR vs. DIE differences in inflammatory and organ dysfunction score were evident but their magnitude was comparable across age/gender. Nearly identical activation of the humoral inflammatory and organ function compartments, both across groups and according to sepsis severity, suggests that they are not directly responsible for the age/gender-dependent disparity in TH-CLP survival in the studied young

  9. Relevance of Candida and other mycoses for morbidity and mortality in severe sepsis and septic shock due to peritonitis.

    Science.gov (United States)

    Lichtenstern, Christoph; Herold, Christina; Mieth, Markus; Brenner, Thorsten; Decker, Sebastian; Busch, Cornelius J; Hofer, Stefan; Zimmermann, Stefan; Weigand, Markus A; Bernhard, Michael

    2015-07-01

    This single-centre retrospective cohort study evaluated the incidence and outcome of mycoses in critical ill patients (n = 283) with sepsis due to peritonitis. Overall mortality was 41.3%, and the 28-day mortality was 29.3%. Fungal pathogens were found in 51.9%. The common first location was the respiratory tract (66.6%), followed by the abdominal site (19.7%). Candida colonisation was found in 64.6%, and invasive Candida infection in 34.0%. Identified fungi were Candida spp. in 98.6% and Aspergillus spp. in 6.1%. Patients with fungal pathogens showed a higher rate of postoperative peritonitis, APACHE II and tracheotomy. In comparison to patients without fungal pathogens, these patients showed a longer duration on mechanical ventilation, and a higher overall mortality. Patients with Candida-positive swabs from abdominal sites had more fascia dehiscence and anastomosis leakage. Seventy-two patients (48.9%) received antifungal therapy, 26 patients were treated empirically. Antifungal therapy was not associated with a decrease in mortality. Age and renal replacement therapy were associated with mortality. In conclusion, fungi are common pathogens in critically ill patients with peritonitis, and detection of fungi is associated with an increase in overall mortality. Particularly, Candida-positive abdominal swabs are associated with an increase in morbidity. However, we were not able to demonstrate a survival benefit for antifungal therapy in peritonitis patients. © 2015 Blackwell Verlag GmbH.

  10. Empirical mono- versus combination antibiotic therapy in adult intensive care patients with severe sepsis – A systematic review with meta-analysis and trial sequential analysis

    DEFF Research Database (Denmark)

    Sjövall, Karl Fredrik Lennart; Perner, Anders; Hylander Møller, Morten

    2017-01-01

    Objectives To assess benefits and harms of empirical mono- vs. combination antibiotic therapy in adult patients with severe sepsis in the intensive care unit (ICU). Methods We performed a systematic review according to the Cochrane Collaboration methodology, including meta-analysis, risk of bias...... reviewers independently evaluated studies for inclusion, extracted data, and assessed risk of bias. Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated and the risk of random errors was assessed by TSA. Results Thirteen RCTs (n = 2633) were included; all were judged as having high risk......, indicating that a 20% relative risk difference in mortality may be excluded between the two groups. For the other outcomes, TSA indicated lack of data and high risk of random errors. Conclusions This systematic review of RCTs with meta-analysis and TSA demonstrated no differences in mortality or other...

  11. All that seems sepsis is not sepsis

    Directory of Open Access Journals (Sweden)

    Vivek S Guleria

    2013-01-01

    Full Text Available Catastrophic antiphospholipid antibody syndrome (CAPS resembles severe sepsis in its acute presentation, with features of systemic inflammatory response syndrome (SIRS leading to multiple organ dysfunction. Infections are the best known triggers of CAPS. This emphasizes the need for early diagnosis and aggressive treatment as the mortality is as high as 50%. We present a 42-year-old woman who developed SIRS postoperatively and was eventually diagnosed as CAPS.

  12. Early Response Roles for Prolactin Cortisol and Circulating and Cellular Levels of Heat Shock Proteins 72 and 90α in Severe Sepsis and SIRS

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    K. Vardas

    2014-01-01

    Full Text Available Objective. To evaluate the early heat shock protein (HSP and hormonal stress response of intensive care unit (ICU patients with severe sepsis/septic shock (SS or systemic inflammatory response syndrome (SIRS compared to healthy subjects (H. Methods. Patients with early (first 48 hrs SS (n=29 or SIRS (n=29 admitted to a university ICU and 16 H were enrolled in the study. Serum prolactin, cortisol, and plasma ACTH were determined using immunoassay analyzers. ELISA was used to evaluate extracellular HSPs (eHSP90α, eHSP72 and interleukins. Mean fluorescence intensity (MFI values for intracellular HSPs (iHSP72, iHSP90α were measured using 4-colour flow-cytometry. Results. Prolactin, cortisol, and eHSP90α levels were significantly increased in SS patients compared to SIRS and H (P<0.003. ACTH and eHSP72 were significantly higher in SS and SIRS compared to H (P<0.005. SS monocytes expressed lower iHSP72 MFI levels compared to H (P=0.03. Prolactin was related with SAPS III and APACHE II scores and cortisol with eHSP90α, IL-6, and lactate (P<0.05. In SS and SIRS eHSP90α was related with eHSP72, IL-6, and IL-10. Conclusion. Prolactin, apart from cortisol, may have a role in the acute stress response in severe sepsis. In this early-onset inflammatory process, cortisol relates to eHSP90α, monocytes suppress iHSP72, and plasma eHSP72 increases.

  13. Thrombin generation in abdominal sepsis is Rho-kinase-dependent.

    Science.gov (United States)

    Wang, Yongzhi; Braun, Oscar Ö; Zhang, Su; Norström, Eva; Thorlacius, Henrik

    2015-05-08

    Sepsis causes severe derangements of the coagulation system. However, the signaling mechanisms regulating sepsis-induced thrombin generation remain elusive. Herein, we hypothesized that Rho-kinase might be an important regulator of thrombin generation in abdominal sepsis. Abdominal sepsis was induced by cecal ligation and puncture (CLP) in C57Bl/6 mice. Thrombin generation, coagulation factors, lung histology and myeloperoxidase (MPO) activity were determined 6 h and 24 h after induction of CLP. Induction of CLP triggered a systemic inflammatory response characterized by neutrophil accumulation and tissue injury in the lung as well as thrombocytopenia and leukocytopenia. Administration of Y-27632, a Rho-kinase inhibitor, attenuated these markers of systemic inflammation in CLP animals. Moreover, peak thrombin formation was decreased by 77% and 81% in plasma from mice 6 h and 24 h after induction of CLP. Total thrombin generation was reduced by 64% and 67% 6 h and 24 h after CLP induction, respectively. Notably, administration of Y-27632 increased peak formation by 99% and total thrombin generation by 66% in plasma from septic animals. In addition, CLP markedly decreased plasma levels of prothrombin, factor V and factor X at 6 h and 24 h. Interestingly, Rho-kinase inhibition significantly enhanced levels of prothrombin, factor V and factor X in plasma from septic mice. In addition, inhibition of Rho-kinase decreased CLP-induced elevations of CXCL2 by 36% and interleukin-6 by 38%. These novel findings suggest that sepsis-induced thrombin generation is regulated by Rho-kinase. Moreover, inhibition of Rho-kinase reverses sepsis-evoked consumption of coagulation factors. Thus, our results show that targeting Rho-kinase signaling might protect against coagulation dysfunction in abdominal sepsis.

  14. [Recognizing prevention and treatment of burn sepsis with the concept of holistic integrative medicine].

    Science.gov (United States)

    Huan, J N

    2017-04-20

    Sepsis remains a major cause of death in severe burns. The effect of sepsis management is influenced by its complicated pathophysiologic changes. In order to improve the outcome of burn sepsis, the predisposing factor of sepsis after burn analyzed by advanced technology, the early prevention, antibiotics therapy, and combined treatment in severe burns with sepsis are discussed using the concept of holistic integrative medicine.

  15. Clinical and microbiological features of maternal sepsis: a retrospective study.

    Science.gov (United States)

    Abir, G; Akdagli, S; Butwick, A; Carvalho, B

    2017-02-01

    Identifying pregnant women with sepsis is challenging because diagnostic clinical and laboratory criteria overlap with normal pregnant physiologic indices. Our primary study aim was to describe clinical and laboratory characteristics of women diagnosed with sepsis, severe sepsis and septic shock. Our secondary aim was to determine positive predictive values for International Classification of Disease (ICD)-9 billing codes for sepsis, severe sepsis, and septic shock. After gaining Institutional Review Board approval, we identified women with ICD-9 codes for sepsis, severe sepsis and septic shock who were admitted to a single tertiary obstetric center from 2007-2013. Diagnoses were confirmed using criteria from the International Sepsis Definitions Conference report. Demographic, obstetric, vital signs and laboratory data were abstracted by medical chart review. We identified 190 women with sepsis-related ICD-9 codes: of these, 35 (18%) women met the criteria for a clinical diagnosis of sepsis, severe sepsis or septic shock. Twenty (57%) women had a sepsis-related diagnosis after cesarean delivery. Twenty-one (60%) women had one or more pre-existing medical conditions and 19 (54%) women had one or more obstetric-related conditions. The genital tract was the most common site of infection. We observed considerable heterogeneity in maternal vital signs and laboratory indices for women with ICD-9 codes for sepsis, severe sepsis, and septic shock. The positive predictive value for each sepsis-related ICD-9 code was low: 16% (95% CI 10 to 24%) for sepsis, 10% (95% CI 3 to 25%) for severe sepsis and 24% (95% CI 10 to 46%) for septic shock. We identified marked heterogeneity in patient characteristics, clinical features, laboratory indices and microbiological findings among cohorts of women diagnosed with maternal sepsis, severe sepsis or septic shock. Based on our findings, the incidence of maternal sepsis using ICD-9 codes may be significantly overestimated. Copyright

  16. A pig model of acute Staphylococcus aureus induced pyemia

    DEFF Research Database (Denmark)

    Nielsen, O. L.; Iburg, T.; Aalbæk, B.;

    2009-01-01

    Background: Sepsis caused by Staphylococcus aureus constitutes an important cause of morbidity and mortality in humans, and the incidence of this disease-entity is increasing. In this paper we describe the initial microbial dynamics and lesions in pigs experimentally infected with S. aureus....... aureus isolated from man and an extension of the timeframe aiming at inducing sepsis, severe sepsis and septic shock....

  17. Stat3 and C/EBPβ synergize to induce miR-21 and miR-181b expression during sepsis.

    Science.gov (United States)

    McClure, Clara; McPeak, Melissa B; Youssef, Dima; Yao, Zhi Q; McCall, Charles E; El Gazzar, Mohamed

    2017-01-01

    Myeloid-derived suppressor cells (MDSCs) increase late sepsis immunosuppression and mortality in mice. We reported that microRNA (miR) 21 and miR-181b expression in Gr1(+)CD11b(+) myeloid progenitors increase septic MDSCs in mice by arresting macrophage and dendritic cell differentiation. Here, we report how sepsis regulates miR-21 and miR-181b transcription. In vivo and in vitro binding studies have shown that C/EBPα transcription factor, which promotes normal myeloid cell differentiation, binds both miRNA promoters in Gr1(+)CD11b(+) cells from sham mice. In contrast, in sepsis Gr1(+)CD11b(+) MDSCs miR-21 and miR-181b promoters bind both transcription factors Stat3 and C/EBPβ, which co-imunoprecipitate as a single complex. Mechanistically, transcription factor Rb phosphorylation supports Stat3 and C/EBPβ accumulation at both miRNA promoters, and C/EBPβ or Stat3 depletion by siRNA in sepsis Gr1(+)CD11b(+) MDSCs inhibits miR-21 and miR-181b expression. To further support this molecular path for MDSC accumulation, we found that Stat3 and C/EBP binding at miR-21 or miR-181b promoter was induced by IL-6, using a luciferase reporter gene transfection into naive Gr1(+)CD11b(+) cells. Identifying how sepsis MDSCs are generated may inform new treatments to reverse sepsis immunosuppression.

  18. Sepse, sepse grave e choque séptico: aspectos clínicos, epidemiológicos e prognóstico em pacientes de Unidade de Terapia Intensiva de um Hospital Universitário Sepsis, severe sepsis and septic shock: clinical, epidemiological and prognostic characteristics of patients in an intensive care unit in a university hospital

    Directory of Open Access Journals (Sweden)

    Renan Henrique de Carvalho

    2010-10-01

    Full Text Available INTRODUÇÃO: Sepse é considerada doença grave com alta mortalidade. O objetivo desse estudo foi determinar a incidência e evolução da sepse em pacientes críticos. MÉTODOS: Foi realizada vigilância prospectiva de sepse na Unidade de Terapia Intensiva de Adultos, de abril-dezembro de 2007. RESULTADOS: A frequência de pacientes/dia foi 442. Setenta e cinco (18,6% pacientes tinham sepse; destes, 72% hospitalar. As taxas de sepse grave e choque séptico por paciente/dia foram 5,0 e 3,1, respectivamente. A mortalidade total foi 34,6%. Sessenta e um por cento dos casos tinham diagnóstico microbiológico. CONCLUSÕES: A sepse apresentou-se numa frequência maior, do que a usualmente descrita na literatura.INTRODUCTION: Sepsis is considered to be a severe disease with high mortality. The objective of this study was to determine the incidence and evolution of sepsis among critically ill patients. METHODS: Prospective surveillance of sepsis was performed in the adult intensive care unit, between April and December 2007. RESULTS: The patient frequency/day was 442. Seventy-five patients (18.6% had sepsis and 72% of these cases were hospital-acquired. The rates of severe sepsis and septic shock per patient/day were 5.0 and 3.1, respectively. The total mortality was 34.6% and 61% of the cases had microbiological diagnoses. CONCLUSIONS: Sepsis presented with higher frequency than is usually described in the literature.

  19. No further incidence of sepsis after splenectomy for severe trauma: a multi-institutional experience of the trauma registry of the DGU with 1,630 patients

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    Heuer M

    2010-06-01

    Full Text Available Abstract Objective Non-operative management of blunt splenic injury in adults has been applied increasingly at the end of the last century. Therefore, the lifelong risk of overwhelming post-splenectomy infection has been the major impetus for preservation of the spleen. However, the prevalence of posttraumatic infection after splenectomy in contrast to a conservative management is still unknown. Objective was to determine if splenectomy is an independent risk factor for the development of posttraumatic sepsis and multi-organ failure. Methods 13,433 patients from 113 hospitals were prospective collected from 1993 to 2005. Patients with an injury severity score > 16, no isolated head injury, primary admission to a trauma center and splenic injury were included. Data were allocated according to the operative management into 2 groups (splenectomy (I and conservative managed patients (II. Results From 1,630 patients with splenic injury 758 patients undergoing splenectomy compared with 872 non-splenectomized patients. 96 (18.3% of the patients with splenectomy and 102 (18.5% without splenectomy had apparent infection after operation. Additionally, there was no difference in mortality (24.8% versus 22.2% in both groups. After massive transfusion of red blood cells (> 10 non-splenectomy patients showed a significant increase of multi-organ failure (46% vs. 40% and sepsis (38% vs. 25%. Conclusions Non-operative management leads to lower systemic infection rates and mortality in adult patients with moderate blunt splenic injury (grade 1-3 and should therefore be advocated. Patients with grade 4 and 5 injury, patients with massive transfusion of red blood cells and unstable patients should be managed operatively.

  20. Sepsis otopathy: experimental sepsis leads to significant hearing impairment due to apoptosis and glutamate excitotoxicity in murine cochlea

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    Joachim Schmutzhard

    2013-05-01

    Hearing loss is frequent in intensive care patients and can be due to several causes. However, sepsis has not been examined as a possible cause. The aim of this study is to assess the influence of experimental sepsis on hearing thresholds and to evaluate pathological changes in the cochlea. The cecal ligation puncture technique was used to induce sepsis in 18 mice. Results were compared with those from 13 sham-operated and 13 untreated control mice. The hearing thresholds of the animals were evaluated with auditory evoked brainstem responses prior to the induction of sepsis and again at the peak of the disease. Immediately after the second measurement, the mice were sacrificed and the inner ears harvested and prepared for further evaluation. The cochleae were examined with light microscopy, electron microscopy and immunohistochemistry for Bax, cleaved caspase-3 and Bcl-2. The mice with sepsis showed a significant hearing loss but not the control groups. Induction of apoptosis could be shown in the supporting cells of the organ of Corti. Furthermore, excitotoxicity could be shown at the basal pole of the inner hair cells. In this murine model, sepsis leads to significant hearing impairment. The physiological alteration could be linked to apoptosis in the supporting cells of the organ of Corti and to a disturbance of the synapses of the inner hair cells.

  1. Impact of sepsis on CD4 T cell immunity

    Science.gov (United States)

    Cabrera-Perez, Javier; Condotta, Stephanie A.; Badovinac, Vladimir P.; Griffith, Thomas S.

    2014-01-01

    Sepsis remains the primary cause of death from infection in hospital patients, despite improvements in antibiotics and intensive-care practices. Patients who survive severe sepsis can display suppressed immune function, often manifested as an increased susceptibility to (and mortality from) nosocomial infections. Not only is there a significant reduction in the number of various immune cell populations during sepsis, but there is also decreased function in the remaining lymphocytes. Within the immune system, CD4 T cells are important players in the proper development of numerous cellular and humoral immune responses. Despite sufficient clinical evidence of CD4 T cell loss in septic patients of all ages, the impact of sepsis on CD4 T cell responses is not well understood. Recent findings suggest that CD4 T cell impairment is a multipronged problem that results from initial sepsis-induced cell loss. However, the subsequent lymphopenia-induced numerical recovery of the CD4 T cell compartment leads to intrinsic alterations in phenotype and effector function, reduced repertoire diversity, changes in the composition of naive antigen-specific CD4 T cell pools, and changes in the representation of different CD4 T cell subpopulations (e.g., increases in Treg frequency). This review focuses on sepsis-induced alterations within the CD4 T cell compartment that influence the ability of the immune system to control secondary heterologous infections. The understanding of how sepsis affects CD4 T cells through their numerical loss and recovery, as well as function, is important in the development of future treatments designed to restore CD4 T cells to their presepsis state. PMID:24791959

  2. Neonatal sepsis

    Science.gov (United States)

    ... are infected after delivery. The following increase an infant's risk of sepsis after delivery: Having a catheter in a blood vessel for ... Providing a clean place for birth Delivering the baby within 12 to 24 hours of when the membranes break (Cesarean delivery should be done in women within 4 to ...

  3. The Surviving Sepsis Campaign: past, present and future.

    Science.gov (United States)

    Schorr, Christa A; Dellinger, R Phillip

    2014-04-01

    The Surviving Sepsis Campaign (SSC) was created in 2002 and consists of severe sepsis management guidelines and a sepsis performance improvement program. The second revision of the guidelines, published in 2013, are sponsored by 30 international scientific organizations and contain changes in recommendations for fluids and vasopressor administration. The new 3- and 6-hour sepsis 'bundles' (sets of care elements) include a software program that can be downloaded free from the Surviving Sepsis Campaign website (www.survivingsepsis.org). The traditional intensive care unit and emergency department champion-driven sepsis performance improvement program continues internationally with the kick off of a new grant-funded hospital floor sepsis performance improvement initiative.

  4. Successful treatment of sepsis-induced disseminated intravascular coagulation in a patient with idiopathic thrombocytopenic purpura using recombinant human soluble thrombomodulin.

    Science.gov (United States)

    Koga, Tomohiro; Inoue, Daisuke; Okada, Akitomo; Aramaki, Toshiyuki; Yamasaki, Satoshi; Nakashima, Munetoshi; Kawakami, Atsushi; Eguchi, Katsumi

    2011-12-01

    Disseminated intravascular coagulation (DIC) may complicate a variety of disorders that contribute to mortality, particularly those related to bleeding. It is therefore very difficult to manage DIC in patients with known bleeding disorders. We treated a 62-year-old woman with idiopathic thrombocytopenic purpura (ITP) complicated with sepsis-induced DIC. She had been diagnosed with ITP 8 months prior to admission. Laboratory tests showed an elevation of d-dimer and endotoxin, while pyelonephritis was shown by abdominal computed tomography. Escherichia coli was detected by blood culture. Based on these findings, the patient was diagnosed with sepsis-induced DIC due to urinary tract infection. Thrombocytopenia was refractory despite the use of antibiotics and platelet transfusion, but it was promptly improved in response to recombinant human soluble thrombomodulin (rTM). We suggest that rTM provides a new therapeutic strategy for DIC patients with high hemorrhagic risk.

  5. Severe Hypertriglyceridemia Induced Pancreatitis in Pregnancy

    OpenAIRE

    Natasha Gupta; Seema Ahmed; Lemuel Shaffer; Paula Cavens; Josef Blankstein

    2014-01-01

    Acute pancreatitis caused by severe gestational hypertriglyceridemia is a rare complication of pregnancy. Acute pancreatitis has been well associated with gallstone disease, alcoholism, or drug abuse but rarely seen in association with severe hypertriglyceridemia. Hypertriglyceridemia may occur in pregnancy due to normal physiological changes leading to abnormalities in lipid metabolism. We report a case of severe gestational hypertriglyceridemia that caused acute pancreatitis at full term an...

  6. Early Expansion of Circulating Granulocytic Myeloid-derived Suppressor Cells Predicts Development of Nosocomial Infections in Patients with Sepsis.

    Science.gov (United States)

    Uhel, Fabrice; Azzaoui, Imane; Grégoire, Murielle; Pangault, Céline; Dulong, Joelle; Tadié, Jean-Marc; Gacouin, Arnaud; Camus, Christophe; Cynober, Luc; Fest, Thierry; Le Tulzo, Yves; Roussel, Mikael; Tarte, Karin

    2017-08-01

    Sepsis induces a sustained immune dysfunction responsible for poor outcome and nosocomial infections. Myeloid-derived suppressor cells (MDSCs) described in cancer and inflammatory processes may be involved in sepsis-induced immune suppression, but their clinical impact remains poorly defined. To clarify phenotype, suppressive activity, origin, and clinical impact of MDSCs in patients with sepsis. Peripheral blood transcriptomic analysis was performed on 29 patients with sepsis and 15 healthy donors. A second cohort of 94 consecutive patients with sepsis, 11 severity-matched intensive care patients, and 67 healthy donors was prospectively enrolled for flow cytometry and functional experiments. Genes involved in MDSC suppressive functions, including S100A12, S100A9, MMP8, and ARG1, were up-regulated in the peripheral blood of patients with sepsis. CD14(pos)HLA-DR(low/neg) monocytic (M)-MDSCs were expanded in intensive care unit patients with and without sepsis and CD14(neg)CD15(pos) low-density granulocytes/granulocytic (G)-MDSCs were more specifically expanded in patients with sepsis (P sepsis. G-MDSCs, made of immature and mature granulocytes expressing high levels of degranulation markers, were specifically responsible for arginase 1 activity. High initial levels of G-MDSCs, arginase 1, and S100A12 but not M-MDSCs were associated with subsequent occurrence of nosocomial infections. M-MDSCs and G-MDSCs strongly contribute to T-cell dysfunction in patients with sepsis. More specifically, G-MDSCs producing arginase 1 are associated with a higher incidence of nosocomial infections and seem to be major actors of sepsis-induced immune suppression.

  7. Intestine-specific Mttp deletion decreases mortality and prevents sepsis-induced intestinal injury in a murine model of Pseudomonas aeruginosa pneumonia.

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    Jessica A Dominguez

    Full Text Available BACKGROUND: The small intestine plays a crucial role in the pathophysiology of sepsis and has been referred to as the "motor" of the systemic inflammatory response. One proposed mechanism is that toxic gut-derived lipid factors, transported in mesenteric lymph, induce systemic injury and distant organ failure. However, the pathways involved are yet to be defined and the role of intestinal chylomicron assembly and secretion in transporting these lipid factors is unknown. Here we studied the outcome of sepsis in mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO, which exhibit a block in chylomicron assembly together with lipid malabsorption. METHODOLOGY/PRINCIPAL FINDINGS: Mttp-IKO mice and controls underwent intratracheal injection with either Pseudomonas aeruginosa or sterile saline. Mttp-IKO mice exhibited decreased seven-day mortality, with 0/20 (0% dying compared to 5/17 (29% control mice (p<0.05. This survival advantage in Mttp-IKO mice, however, was not associated with improvements in pulmonary bacterial clearance or neutrophil infiltration. Rather, Mttp-IKO mice exhibited protection against sepsis-associated decreases in villus length and intestinal proliferation and were also protected against increased intestinal apoptosis, both central features in control septic mice. Serum IL-6 levels, a major predictor of mortality in human and mouse models of sepsis, were elevated 8-fold in septic control mice but remained unaltered in septic Mttp-IKO mice. Serum high density lipoprotein (HDL levels were reduced in septic control mice but were increased in septic Mttp-IKO mice. The decreased levels of HDL were associated with decreased hepatic expression of apolipoprotein A1 in septic control mice. CONCLUSIONS/SIGNIFICANCE: These studies suggest that strategies directed at blocking intestinal chylomicron secretion may attenuate the progression and improve the outcome of sepsis through effects

  8. O-glycoside biomarker of apolipoprotein C3: responsiveness to obesity, bariatric surgery, and therapy with metformin, to chronic or severe liver disease and to mortality in severe sepsis and graft vs host disease.

    Science.gov (United States)

    Harvey, Stephen B; Zhang, Yan; Wilson-Grady, Joshua; Monkkonen, Teresa; Nelsestuen, Gary L; Kasthuri, Raj S; Verneris, Michael R; Lund, Troy C; Ely, E Wesley; Bernard, Gordon R; Zeisler, Harald; Homoncik, Monika; Jilma, Bernd; Swan, Therese; Kellogg, Todd A

    2009-02-01

    The glyco-isoforms of intact apolipoprotein C3 (ApoC3) were used to probe glycomic changes associated with obesity and recovery following bariatric surgery, liver diseases such as chronic hepatitis C (CHC) and alcoholic liver cirrhosis, as well as severe, multiorgan diseases such as sepsis and graft vs host disease (GVHD). ApoC3 glyco-isoform ratios responded to unique stimuli that did not correlate with serum lipids or with other blood components measured in either a control population or a group of extremely obese individuals. However, glyco-isoform ratios correlated with obesity with a 1.8-fold change among subjects eligible for bariatric surgery relative to a nonobese control population. Bariatric surgery resulted in rapid change of isoform distribution to that of nonobese individuals, after which the distribution was stable in each individual. Although multiple simultaneous factors complicated effector attribution, the isoform ratios of very obese individuals were nearly normal for diabetic individuals on metformin therapy. Glyco-isoform ratios were sensitive to liver diseases such as chronic hepatitis C and alcoholic liver cirrhosis. The correlation coefficient with fibrosis was superior to that of current assays of serum enzyme levels. Diseases of pregnancy that can result in liver damage, HELLP syndrome and pre-eclampsia, did not alter ApoC3 glyco-isoform ratios. Early after umbilical cord blood transplantation the isoform ratios changed and returned to normal in long-term survivors. Larger changes were observed in persons who died. GVHD had little effect. Persons with severe sepsis showed altered ratios. Similar cut-points for mortality (3.5-fold difference from controls) were found for UCBT and sepsis. Similar values characterized liver cirrhosis. Overall, while changes of glyco-isoform ratios occurred in many situations, individual stability of isoform distribution was evident and large changes were limited to high-level disease. If ratio changes

  9. Caracterização físico-química da acidose metabólica induzida pela expansão volêmica inicial com solução salina a 0,9% em pacientes com sepse grave e choque séptico Physicochemical characterization of metabolic acidosis induced by normal saline resuscitation of patients with severe sepsis and septic shock

    Directory of Open Access Journals (Sweden)

    Marcelo Park

    2011-06-01

    Full Text Available OBJETIVO: O objetivo deste estudo foi caracterizar e quantificar a acidose metabólica causada pela expansão volêmica inicial na reanimação de pacientes com sepse grave e choque séptico. MÉTODOS: Uma coleta de sangue para caracterização físico-química do equilíbrio ácido-básico antes e após a expansão volêmica com 30 mL/kg de solução salina a 0,9%. O diagnóstico e a quantificação da acidose metabólica foram feitas com o uso do "standard base excess" (SBE. RESULTADOS: Oito pacientes com 58 ± 13 anos e APACHE II de 20 ± 4 foram expandidos com 2000 ± 370 mL de solução salina a 0,9%. Houve queda do pH de 7,404 ± 0,080 para 7,367 ± 0,086 (P=0,018 associada a elevação da PCO2 de 30 ± 5 mmHg para 32 ± 2 mmHg (P=0,215 e queda do SBE de -4,4 ± 5,6 para -6,0 ± 5,7 mEq/L (P=0,039. Esta queda do SBE foi associada ao poder acidificante de dois fatores: elevação não significativa do "strong ion gap" (SIG de 6,1 ± 3,4 para 7,7 ± 4,0 mEq/L (P=0,134 e queda não significativa do "strong ion diference" aparente inorgânico (SIDai de 40 ± 5 para 38 ± 4 mEq/L (P=0,318. Em contraposição, houve queda da albumina sérica de 3,1 ± 1,0 para 2,6 ± 0,8 mEq/L (P=0,003, que teve um poder alcalinizante sobre o SBE. A elevação do cloro sérico de 103 ± 10 para 106 ± 7 mEq/L (POBJECTIVE: The aim of this study was to characterize and quantify metabolic acidosis that was caused by initial volume expansion during the reanimation of patients with severe sepsis and septic shock. METHODS: A blood sample was drawn for physicochemical characterization of the patient's acid-base equilibrium both before and after volume expansion using 30 mL/kg 0.9% saline solution. The diagnosis and quantification of metabolic acidosis were based on the standard base excess (SBE. RESULTS: Eight patients with a mean age of 58 ± 13 years and mean APACHE II scores of 20 ± 4 were expanded using 2,000 ± 370 mL of 0.9% saline solution. Blood pH dropped

  10. The Effect of Sepsis on the Erythrocyte.

    Science.gov (United States)

    Bateman, Ryon M; Sharpe, Michael D; Singer, Mervyn; Ellis, Christopher G

    2017-09-08

    Sepsis induces a wide range of effects on the red blood cell (RBC). Some of the effects including altered metabolism and decreased 2,3-bisphosphoglycerate are preventable with appropriate treatment, whereas others, including decreased erythrocyte deformability and redistribution of membrane phospholipids, appear to be permanent, and factors in RBC clearance. Here, we review the effects of sepsis on the erythrocyte, including changes in RBC volume, metabolism and hemoglobin's affinity for oxygen, morphology, RBC deformability (an early indicator of sepsis), antioxidant status, intracellular Ca(2+) homeostasis, membrane proteins, membrane phospholipid redistribution, clearance and RBC O₂-dependent adenosine triphosphate efflux (an RBC hypoxia signaling mechanism involved in microvascular autoregulation). We also consider the causes of these effects by host mediated oxidant stress and bacterial virulence factors. Additionally, we consider the altered erythrocyte microenvironment due to sepsis induced microvascular dysregulation and speculate on the possible effects of RBC autoxidation. In future, a better understanding of the mechanisms involved in sepsis induced erythrocyte pathophysiology and clearance may guide improved sepsis treatments. Evidence that small molecule antioxidants protect the erythrocyte from loss of deformability, and more importantly improve septic patient outcome suggest further research in this area is warranted. While not generally considered a critical factor in sepsis, erythrocytes (and especially a smaller subpopulation) appear to be highly susceptible to sepsis induced injury, provide an early warning signal of sepsis and are a factor in the microvascular dysfunction that has been associated with organ dysfunction.

  11. Endocrine dysfunction in sepsis: a beneficial or deleterious host response?

    Science.gov (United States)

    Gheorghiţă, Valeriu; Barbu, Alina Elena; Gheorghiu, Monica Livia; Căruntu, Florin Alexandru

    2015-03-01

    Sepsis is a systemic, deleterious inflammatory host response triggered by an infective agent leading to severe sepsis, septic shock and multi-organ failure. The host response to infection involves a complex, organized and coherent interaction between immune, autonomic, neuroendocrine and behavioral systems. Recent data have confirmed that disturbances of the autonomic nervous and neuroendocrine systems could contribute to sepsis-induced organ dysfunction. Through this review, we aimed to summarize the current knowledge about the endocrine dysfunction as response to sepsis, specifically addressed to vasopressin, copeptin, cortisol, insulin and leptin. We searched the following readily accessible, clinically relevant databases: PubMed, UpToDate, BioMed Central. The immune system could be regarded as a "diffuse sensory organ" that signals the presence of pathogens to the brain through different pathways, such as the vagus nerve, endothelial activation/dysfunction, cytokines and neurotoxic mediators and the circumventricular organs, especially the neurohypophysis. The hormonal profile changes substantially as a consequence of inflammatory mediators and microorganism products leading to inappropriately low levels of vasopressin, sick euthyroid syndrome, reduced adrenal responsiveness to ACTH, insulin resistance, hyperglycemia as well as hyperleptinemia. In conclusion, clinical diagnosis of this "pan-endocrine illness" is frequently challenging due to the many limiting factors. The most important benefits of endocrine markers in the management of sepsis may be reflected by their potential to be used as biomarkers in different scoring systems to estimate the severity of the disease and the risk of death.

  12. Severe photosensitivity reaction induced by topical diclofenac

    OpenAIRE

    Akat, Pramod B.

    2013-01-01

    Albeit uncommon, photosensitivity reaction induced by diclofenac can be an unfortunate adverse reaction complicating its use as a topical analgesic. We here present a case of a patient who suffered such a reaction as a result of exposure to diclofenac, employed as a topical analgesic for low backache. The lesions healed with conservative management without extensive scarring or other complications.

  13. Severe photosensitivity reaction induced by topical diclofenac

    Directory of Open Access Journals (Sweden)

    Pramod B Akat

    2013-01-01

    Full Text Available Albeit uncommon, photosensitivity reaction induced by diclofenac can be an unfortunate adverse reaction complicating its use as a topical analgesic. We here present a case of a patient who suffered such a reaction as a result of exposure to diclofenac, employed as a topical analgesic for low backache. The lesions healed with conservative management without extensive scarring or other complications.

  14. Crossing the handover chasm: Clinicians' perceptions of barriers to the early detection and timely management of severe sepsis and septic shock.

    Science.gov (United States)

    Matthaeus-Kraemer, Claudia T; Thomas-Rueddel, Daniel O; Schwarzkopf, Daniel; Rueddel, Hendrik; Poidinger, Bernhard; Reinhart, Konrad; Bloos, Frank

    2016-12-01

    The purpose was to identify barriers to the early detection and timely management of severe sepsis throughout the emergency department (ED), general ward (GW), intermediate care unit (IMC), and the intensive care unit (ICU). Five multicenter focus group discussions with 29 clinicians were conducted. Discussions were based on a moderation guide were recorded and transcribed. Qualitative analysis was performed according to the principles of the concept mapping method and the framework approach. The major causes of the delayed detection and treatment could be summarized in a framework of communication errors and handover difficulties throughout patients' course of treatment, which can be divided into 5 core areas: inadequate histories before hospital admission; poorly coordinated handovers between the ambulance service and the ED; delayed patient transfer between the ED and the GW as well as delays in patient transfers between the GW and the ICU by, for example, a lack of bed capacity and a shortage of staff. Generally, participants from all wards mentioned that the urgency with which septic patients needed to be treated was not communicated. Our study shows the need to improve intra- and interunit handover processes in hospital care, which would ensure a holistic treatment concept, thereby improving patient care. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Clinical significance of plasma level of AT-Ⅲ determination in sepsis patients

    Institute of Scientific and Technical Information of China (English)

    Wei Chen; Zhi-Hua Hu; Chen-Mian

    2015-01-01

    Objective:Through measure changes of anticoagulant enzyme (AT-Ⅲ) activity in plasma in sepsis patients, this paper discusses the clinical significance of AT-Ⅲ activity changes in predicting sepsis occurrence and prognosis.Methods: The non-sepsis 30 cases, with sepsis 76 cases, including 25 cases of severe sepsis, use method of thrombin gelatum lacuna for determining activity of AT-Ⅲ in plasma, platelet count and APACHEⅢ score simultaneously. Results:Sepsis group, severe sepsis groups contrast with the non-sepsis group respectively, activity of AT-Ⅲ reduced significantly (P<0.01), severe sepsis group lower than sepsis group (P=0.055).Conclusion:AT-Ⅲ activity reduced early in sepsis patients, with patient's condition aggravat, its value further reduced, hints measurement of AT-Ⅲ activity has certainly clinical significance in predicting sepsis occurrence and prognosis.

  16. Exogenous carbon monoxide inhibits neutrophil infiltration in LPS-induced sepsis by interfering with FPR1 via p38 MAPK but not GRK2

    Science.gov (United States)

    Wang, Xu; Qin, Weiting; Song, Mingming; Zhang, Yisen; Sun, Bingwei

    2016-01-01

    Excessive neutrophil infiltration in vital organs is life-threatening to patients who suffer from sepsis. We identified a critical role of exogenous carbon monoxide (CO) in the inhibition of neutrophil infiltration during lipopolysaccharide (LPS)-induced sepsis. CO delivered from carbon monoxide-releasing molecule 2 (CORM-2) dramatically increased the survival rate of C57BL/6 mice subjected to LPS in vivo. CORM-2 significantly suppressed neutrophil infiltration in liver and lung as well as markers of inflammatory responses. Affymetrix GeneChip array analysis revealed that the increased expression of chemoattractant receptor formyl peptide receptor 1 (FPR1) may contribute to the excessive neutrophil infiltration. The under agarose migration assay demonstrated that LPS stimulation promoted migration to the ligand of FPR1, N-Formyl-Met-Leu-Phe (fMLP) but that CORM-2 treatment inhibited this promotion. Further studies demonstrated that CORM-2 internalized FPR1 by inhibiting p38 mitogen-activated protein kinase (MAPK) but not G protein-coupled receptor kinase 2 (GRK2), which may explain the inhibitory effect of CORM-2 on LPS-stimulated neutrophils. In summary, our study demonstrates that exogenous CO inhibits sepsis-induced neutrophil infiltration by interfering with FPR1 via p38 MAPK but not GRK2. PMID:27144520

  17. A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury.

    Science.gov (United States)

    Gomez, Hernando; Ince, Can; De Backer, Daniel; Pickkers, Peter; Payen, Didier; Hotchkiss, John; Kellum, John A

    2014-01-01

    Given that the leading clinical conditions associated with acute kidney injury (AKI), namely, sepsis, major surgery, heart failure, and hypovolemia, are all associated with shock, it is tempting to attribute all AKI to ischemia on the basis of macrohemodynamic changes. However, an increasing body of evidence has suggested that in many patients, AKI can occur in the absence of overt signs of global renal hypoperfusion. Indeed, sepsis-induced AKI can occur in the setting of normal or even increased renal blood flow. Accordingly, renal injury may not be entirely explained solely on the basis of the classic paradigm of hypoperfusion, and thus other mechanisms must come into play. Herein, we put forward a "unifying theory" to explain the interplay between inflammation and oxidative stress, microvascular dysfunction, and the adaptive response of the tubular epithelial cell to the septic insult. We propose that this response is mostly adaptive in origin, that it is driven by mitochondria, and that it ultimately results in and explains the clinical phenotype of sepsis-induced AKI.

  18. Intervention of Dietary Dipeptide Gamma-l-Glutamyl-l-Valine (γ-EV) Ameliorates Inflammatory Response in a Mouse Model of LPS-Induced Sepsis.

    Science.gov (United States)

    Chee, MacKenzie E; Majumder, Kaustav; Mine, Yoshinori

    2017-07-26

    Sepsis, the systemic inflammatory response syndrome (SIRS) with infection is one of the leading causes of death in critically ill patients in the developed world due to the lack of effective antisepsis treatments. This study examined the efficacy of dietary dipeptide gamma-l-glutamyl-l-valine (γ-EV), which was characterized previously as an anti-inflammatory peptide, in an LPS-induced mouse model of sepsis. BALB/c mice were administered γ-EV via oral gavage followed by an intraperitoneal injection of LPS to induce sepsis. The γ-EV exhibited antisepsis activity by reducing the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in plasma and small intestine. γ-EV also reduced the phosphorylation of the signaling proteins JNK and IκBα. We concluded that γ-EV could possess an antisepsis effect against bacterial infection in intestine. This study proposes a signaling mechanism whereby the calcium-sensing receptor (CaSR) allosterically activated by γ-EV stimulates the interaction of β-arrestin2 with the TIR(TLR/IL-1R) signaling proteins TRAF6, TAB1, and IκBα to suppress inflammatory signaling.

  19. Cardioprotective effect of metformin in lipopolysaccharide-induced sepsis via suppression of toll-like receptor 4 (TLR4) in heart.

    Science.gov (United States)

    Vaez, Haleh; Rameshrad, Maryam; Najafi, Moslem; Barar, Jaleh; Barzegari, Abolfazl; Garjani, Alireza

    2016-02-05

    Sepsis-induced myocardial dysfunction is a serious organ complication. In the present study, we investigated the effect of metformin on myocardial dysfunction and TLR4 activity in LPS-induced sepsis. Male Wistar rats were randomly divided into 3 groups (n=6): control received normal saline (0.5ml), LPS group received lipopolysaccharide (0.5mg/kg; i.p), and metformin treated group received LPS (0.5mg/kg)+metformin (100mg/kg; i.p). 9h later the hemodynamic parameters were recorded, blood samples were collected, and the hearts were removed and weighted. The concentration of TNF-α, content of MYD88, the phosphorylation of AMPK, and the rate of TLR4 expression in the heart were assessed. In the animals treated with metformin, the preservation of left ventricular function was associated with the reduction of myeloperoxidase activity (31%, Pmetformin group while the content of TLRs adapter protein of MyD88 was reduced by 45% (Pmetformin on TLR4 expression and MYD88 protein level. These results suggest that metformin exhibits cardioprotective effects in sepsis by suppression of TLR4 activity, at least in part through pathways involving AMPK activation.

  20. RAGE deficiency attenuates the protective effect of Lidocaine against sepsis-induced acute lung injury.

    Science.gov (United States)

    Zhang, Zhuo; Zhou, Jie; Liao, Changli; Li, Xiaobing; Liu, Minghua; Song, Daqiang; Jiang, Xian

    2017-04-01

    Lidocaine (Lido) is reported to suppress inflammatory responses and exhibit a therapeutic effect in models of cecal ligation and puncture (CLP)-induced acute lung injury (ALI). The receptor for advanced glycation end product (RAGE) exerts pro-inflammatory effects by enhancing pro-inflammatory cytokine production. However, the precise mechanism by which Lido confers protection against ALI is not clear. ALI was induced in RAGE WT and RAGE knockout (KO) rats using cecal ligation and puncture (CLP) operations for 24 h. The results showed that Lido significantly inhibited CLP-induced lung inflammation and histopathological lung injury. Furthermore, Lido significantly reduced CLP-induced upregulation of HMGB1 and RAGE expression and activation of the NF-κB and MAPK signaling pathways. With the use of RAGE KO rats, we demonstrate here that RAGE deficiency attenuates the protective effect of Lido against CLP-induced lung inflammatory cell infiltration and histopathological lung injury. These results suggest that RAGE deficiency attenuates the protective effect of Lido against CLP-induced ALI by attenuating the pro-inflammatory cytokines production.

  1. Thyroid hormone disorders and sepsis.

    Science.gov (United States)

    Luo, Bin; Yu, Zhui; Li, Yinping

    2017-01-01

    Sepsis is a systemic inflammatory response syndrome with high mortality, which results from severe infection and can lead to secondary organ dysfunction. It is one of the most common cause of death in intensive care unit. Clinical reports have shown that sepsis was often accompanied by thyroid dysfunction, which is called "low triiodothyronine (T3)" syndrome and characterized by decreased blood total T3 and free T3, and by normal or decreased thyroxine (T4) and thyroid stimulating hormone (TSH). This syndrome may greatly affect the prognosis of patients with sepsis. The main purpose of this review is to illustrate the role of thyroid hormone disorder in the development and prognosis of sepsis.

  2. Diminished responsiveness to dobutamine as an inotrope in mice with cecal ligation and puncture-induced sepsis: attribution to phosphodiesterase 4 upregulation.

    Science.gov (United States)

    Sakai, Mari; Suzuki, Tokiko; Tomita, Kengo; Yamashita, Shigeyuki; Palikhe, Sailesh; Hattori, Kohshi; Yoshimura, Naoki; Matsuda, Naoyuki; Hattori, Yuichi

    2017-06-01

    Dobutamine has been used in septic shock for many years as an only inotrope, but its benefit has been questioned. We weighed the effects of dobutamine and milrinone as inotropes in mice with cecal ligation and puncture (CLP)-induced polymicrobial sepsis. CLP-induced septic mice exhibited significant cardiac inflammation, as indicated by greatly increased mRNAs of proinflammatory cytokines and robust infiltration of inflammatory cells in the ventricular myocardium. Elevations of plasma cardiac troponin-I showed cardiac injury in CLP mice. Noninvasive echocardiographic assessment of cardiac function revealed that despite preserved left ventricular function in the presence of fluid replacement, the dobutamine inotropic response was significantly impaired in CLP mice compared with sham-operated controls. By contrast, milrinone exerted inotropic effects in sham-operated and CLP mice in an equally effective manner. Surface expression levels of β1-adrenoceptors and α-subunits of three main G protein families in the myocardium were unaffected by CLP-induced sepsis. Plasma cAMP levels were significantly elevated in both sham-operated and CLP mice in response to milrinone but only in sham-operated controls in response to dobutamine. Of phosphodiesterase (PDE) isoforms, PDE4D, but not PDE3A, both of which are responsible for cardiac cAMP hydrolysis, was significantly upregulated in CLP mouse myocardium. We define a novel mechanism for the impaired responsiveness to dobutamine as an inotrope in sepsis, and understanding the role of PDE4D in modulating cardiac functional responsiveness in sepsis may open the potential of a PDE4D-targeted therapeutic option in septic patients with low cardiac output who have a need for inotropic support.NEW & NOTEWORTHY Advisability of the usefulness of dobutamine in septic shock management is limited. Here, we reveal that the effect of dobutamine as a positive inotrope is impaired in mice with cecal ligation and puncture-induced sepsis

  3. Trauma ans sepsis induced splanchnic and hepatic ischemia and reperfusion injury

    NARCIS (Netherlands)

    T. Tadros (Tamer)

    2002-01-01

    textabstractMODS is, with an iocidence of 10-25% and a mortality of 50-70%, the most severe complication after severe trauma 72_ MODS is a prototypical exemplar of the application of complexity theory to an understandiog of the pathophysiology of critical illness 56, 74_ It arises through the

  4. Advances in treatment of severe sepsis%全身严重感染治疗进展

    Institute of Scientific and Technical Information of China (English)

    缪晓辉; 姚静娟

    2008-01-01

    近年来有关全身严重感染的病理生理、病原、早期诊断和救治等的研究取得很大进展,尤其是在救治方面,既往的很多观点得到更新,甚至完全否定了个别传统救治经验。标志性的文献是刊登在2004年组人活化蛋白C(rhAPC)可以降低全身严重感染/感染性休克的患者病死率。1989-2000年期间由1690例患者参加的PROWESS(Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis)研究,结果表明,有2个以上器官功能受损的全身严重感染患者,使用rhAPC后病死率比对照组下降了13%。但是,之后的临床研究都没有支持PROWESS的研究结果。

  5. Sepsis: Multiple Abnormalities, Heterogeneous Responses, and Evolving Understanding

    Science.gov (United States)

    Iskander, Kendra N.; Osuchowski, Marcin F.; Stearns-Kurosawa, Deborah J.; Kurosawa, Shinichiro; Stepien, David; Valentine, Catherine

    2013-01-01

    Sepsis represents the host's systemic inflammatory response to a severe infection. It causes substantial human morbidity resulting in hundreds of thousands of deaths each year. Despite decades of intense research, the basic mechanisms still remain elusive. In either experimental animal models of sepsis or human patients, there are substantial physiological changes, many of which may result in subsequent organ injury. Variations in age, gender, and medical comorbidities including diabetes and renal failure create additional complexity that influence the outcomes in septic patients. Specific system-based alterations, such as the coagulopathy observed in sepsis, offer both potential insight and possible therapeutic targets. Intracellular stress induces changes in the endoplasmic reticulum yielding misfolded proteins that contribute to the underlying pathophysiological changes. With these multiple changes it is difficult to precisely classify an individual's response in sepsis as proinflammatory or immunosuppressed. This heterogeneity also may explain why most therapeutic interventions have not improved survival. Given the complexity of sepsis, biomarkers and mathematical models offer potential guidance once they have been carefully validated. This review discusses each of these important factors to provide a framework for understanding the complex and current challenges of managing the septic patient. Clinical trial failures and the therapeutic interventions that have proven successful are also discussed. PMID:23899564

  6. Development of Immunopathobiogenesis on SIRS-Sepsis

    Directory of Open Access Journals (Sweden)

    A Guntur Hermawan

    2009-04-01

    Full Text Available Over the past decade, sepsis has been diagnosed according to consensus guidelines established in 1991 as an infection in addition to the symptoms of systemic inflammatory response syndrome (SIRS. In addition to the previous criteria, the 2001 conference added several new diagnostic criteria for sepsis. Of particular interest was the inclusion of the biomarkers procalcitonin (PCT and C-reactive protein (CRP, despite the overall conclusion that it was premature to use biomarkers for sepsis diagnosis. The primary recommendation of the panel was the implementation of the Predisposition, insult Infection, Response, and Organ dysfunction (PIRO.The immune system has traditionally been devided into innate and adaptive components, each of which has a different role and function in defending the host against infectious agents. Stimulation of different TLRs induces distinct patterns of gene expression, which not only leads to the activation of innate immunity but also increasing evidence supports an additional critical role for TLRs in orchestrating the development of adaptive immune responses. The superantigens are able to induce toxic shock syndrome and can sometimes cause multiple organ failure via adaptive immune system. The superantigenic activity of the bacterial exotoxins can be attributed to their ability to cross-link major histocompatibility complex class II molecules on antigen-presenting cells outside the peptide groove with T-cell receptors to form a trimolecular complex. This trimolecular interaction leads to uncontrolled release of a number of proinflammatory cytokines. Proinflammatory cytokines especially IFN-γ and TNF-α, the key cytokines causing toxic shock syndrome. KEYWORDS: sepsis, innate immunity, adaptive.

  7. Decreased Tissue COX5B Expression and Mitochondrial Dysfunction during Sepsis-Induced Kidney Injury in Rats

    Science.gov (United States)

    Böhm, Lennert; Braunecker, Stefan; Adler, Christoph; De Robertis, Edoardo; Cirillo, Fabrizio

    2017-01-01

    Background. Sepsis is defined as a life-threatening organ dysfunction due to a dysregulated host response to infection. Sepsis is the dominant cause of acute kidney injury (AKI), accounting for nearly 50% of episodes of acute renal failure. Signaling cascades and pathways within the kidney are largely unknown and analysis of these molecular mechanisms may enhance knowledge on pathophysiology and possible therapeutic options. Material and Methods. 26 male Wistar rats were assigned to either a sham group (control, N = 6) or sepsis group (N = 20; cecal ligature and puncture model, 24 and 48 hours after CLP). Surviving rats (n = 12) were decapitated at 24 hours (early phase; n = 6) or 48 hours (late phase; n = 6) after CLP and kidneys removed for proteomic analysis. 2D-DIGE and DeCyder 2D software (t-test, P cytochrome c oxidase subunit B (COX5b), myosin-6 (MYH6), and myosin-7 (MYH7). A significant correlation with the proteins was found for mitochondrial energy production and electron transport. Conclusions. COX5B could be a promising biomarker candidate since a significant association was found during experimental sepsis in the present study. For future research, COX5B should be evaluated as a biomarker in both human urine and serum to identify sepsis. PMID:28246552

  8. The reasons of Thrombocytopenia and its management in children with severe sepsis%严重脓毒症患儿血小板减少原因剖析及处理对策分析

    Institute of Scientific and Technical Information of China (English)

    刘连凤; 李敏; 于永慧; 王玉娟; 孙印兰; 赵金芳

    2012-01-01

    目的 结合血常规、凝血功能及骨髓细胞学检查,探讨严重脓毒症患儿血小板减少的原因及临床处理措施.方法 72例严重脓毒症患儿根据预后分为死亡组及存活组,对血小板计数变化与预后关系进行分析;结合凝血功能监测与骨髓细胞学检查分析血小板减少的原因.结果 死亡组与存活组相比,入院当天及入院后第7天血小板计数差异有统计学意义(P<0.05).29例血小板减少患儿中,20例(68.97%)伴有凝血功能异常;9例(31.03%)骨髓巨核系成熟障碍;13例血小板<50×109/L中给予积极处理11例(84.62%),纠正7例(63.64%),死亡4例(36.36%);未能积极处理2例(15.38%),全部死亡.结论 血小板持续进行性下降提示预后差.血小板减少有两大原因,一是凝血功能障碍致血小板过度消耗;二是骨髓巨核系成熟障碍.二者处理措施有别,针对病因积极处理可显著改善预后.%Objective To investigate the reasons of thrombocytopenia and its therapy strategy in children with severe sepsis by monitoring peripheral blood routine test, myelogram and coagulation function evaluation. Methods 72 patients of children with severe sepsis were divided into two groups according to survival (n=58)or death (n=14). The relationship of the dynamic changes of blood platelets count and the prognosis between the two groups was analyzed. Combined with coagulation function examination and marrow morphology analysis, the reasons of thrombocytopenia in sepsis were investigated. Results There was a significant difference of blood platelets count on the day of admission and 7th day after admission between the survival group and the death group. In the 29 children with thrombocytopenia, 20 cases (68.97%) were accompanied with coagulation disorder and 9 cases (31.03%) with megakaryocytes dysmaturity of bone marrow. In the 13 children with PLT<50× 109/L, 11 cases (84.62%) were given active management, and their blood

  9. Oestrogen sulfotransferase ablation sensitizes mice to sepsis.

    Science.gov (United States)

    Chai, Xiaojuan; Guo, Yan; Jiang, Mengxi; Hu, Bingfang; Li, Zhigang; Fan, Jie; Deng, Meihong; Billiar, Timothy R; Kucera, Heidi R; Gaikwad, Nilesh W; Xu, Meishu; Lu, Peipei; Yan, Jiong; Fu, Haiyan; Liu, Youhua; Yu, Lushan; Huang, Min; Zeng, Su; Xie, Wen

    2015-08-10

    Sepsis is the host's deleterious systemic inflammatory response to microbial infections. Here we report an essential role for the oestrogen sulfotransferase (EST or SULT1E1), a conjugating enzyme that sulfonates and deactivates estrogens, in sepsis response. Both the caecal ligation and puncture (CLP) and lipopolysaccharide models of sepsis induce the expression of EST and compromise the activity of oestrogen, an anti-inflammatory hormone. Surprisingly, EST ablation sensitizes mice to sepsis-induced death. Mechanistically, EST ablation attenuates sepsis-induced inflammatory responses due to compromised oestrogen deactivation, leading to increased sepsis lethality. In contrast, transgenic overexpression of EST promotes oestrogen deactivation and sensitizes mice to CLP-induced inflammatory response. The induction of EST by sepsis is NF-κB dependent and EST is a NF-κB-target gene. The reciprocal regulation of inflammation and EST may represent a yet-to-be-explored mechanism of endocrine regulation of inflammation, which has an impact on the clinical outcome of sepsis.

  10. Neuro-oxidative-nitrosative stress in sepsis

    DEFF Research Database (Denmark)

    Berg, Ronan M G; Møller, Kirsten; Bailey, Damian M

    2011-01-01

    Neuro-oxidative-nitrosative stress may prove the molecular basis underlying brain dysfunction in sepsis. In the current review, we describe how sepsis-induced reactive oxygen and nitrogen species (ROS/RNS) trigger lipid peroxidation chain reactions throughout the cerebrovasculature and surrounding...

  11. Much Ado About the New Definitions of Sepsis

    Directory of Open Access Journals (Sweden)

    Copotoiu Sanda-Maria

    2016-04-01

    Full Text Available Following the publication of the new definition of sepsis (Sepsis-3, a plethora of articles have been published in medical journals. Recognizing the epidemiological importance of the previous definitions, first issued in 1992 (Sepsis-1, and subsequently revised in 2001 (Sepsis-2, the most recent opinion emphasizes the failure “to provide adequate groups of patients with homogenous aetiologies, presentations and outcomes”, and blamed one of the causes “for the failure of several randomized controlled trials (RCTs, that tested the efficacy of adjuvant sepsis therapies”. This review summarizes the recent advances in sepsis definition.

  12. Laboratory detection of sepsis: biomarkers and molecular approaches.

    Science.gov (United States)

    Riedel, Stefan; Carroll, Karen C

    2013-09-01

    Sepsis, severe sepsis, and septic shock cause significant morbidity and mortality worldwide. Rapid diagnosis and therapeutic interventions are desirable to improve the overall mortality in patients with sepsis. However, gold standard laboratory diagnostic methods for sepsis, pose a significant challenge to rapid diagnosis of sepsis by physicians and laboratories. This article discusses the usefulness and potential of biomarkers and molecular test methods for a more rapid clinical and laboratory diagnosis of sepsis. Because new technologies are quickly emerging, physicians and laboratories must appreciate the key factors and characteristics that affect the clinical usefulness and diagnostic accuracy of these test methodologies. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Risk factors for severe sepsis in community-onset bacteraemic urinary tract infection: impact of antimicrobial resistance in a large hospitalised cohort.

    Science.gov (United States)

    Shaw, Evelyn; Benito, Natividad; Rodríguez-Baño, Jesús; Padilla, Belén; Pintado, Vicente; Calbo, Esther; Pallarés, M Angeles; Gozalo, Mónica; Ruiz-Garbajosa, Patricia; Horcajada, Juan Pablo

    2015-03-01

    To determine risks factors associated with severe sepsis or septic shock (SS) at admission in patients with community-onset bacteraemic urinary tract infection (CO-BUTI) including the impact of multidrug-resistant (MDR) bacteria. We analysed a prospective cohort of all consecutive episodes of CO-BUTI requiring hospitalisation in 8 tertiary hospitals of Spain between October 2010 and June 2011. Of an overall of 525 CO-BUTI episodes, 175 (33%) presented with SS at admission. MDR bacteria were isolated in 29% (51/175) of episodes with SS and in 33% (117/350) of those without SS (p = 0.32). The main MDR microorganism was Escherichia coli in both groups (25% and 28% respectively). Independent risk factors associated with SS at admission were: having fatal underlying conditions, McCabe score II/III (OR 1.90; 95%CI 1.23-2.92; p = 0.004), presence of an indwelling urethral catheter (OR 3.01; 95%CI 1.50-6.03; p = 0.002) and a history of urinary tract obstruction (OR 1.56; 95%CI 1.03-2.34; p = 0.03). After considering interactions, indwelling urethral catheters were a risk factor only for patients without fatal underlying conditions. SS at hospital admission occurred in a third of CO-BUTI. Mainly host factors, and not the causative microorganisms or antimicrobial resistance patterns had an impact on the presence of SS. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  14. Syzygium jambolanum treatment improves survival in lethal sepsis induced in mice

    Directory of Open Access Journals (Sweden)

    Amaral Flávia MM

    2008-10-01

    Full Text Available Abstract Background The leaves and the fruits from Syzygium jambolanum DC.(Myrtaceae, a plant known in Brazil as sweet olive or 'jambolão', have been used by native people to treat infectious diseases, diabetes, and stomachache. Since the bactericidal activity of S. jambolanum has been confirmed in vitro, the aim of this work was to evaluate the effect of the prophylactic treatment with S. jambolanum on the in vivo polymicrobial infection induced by cecal ligation and puncture (CLP in mice. Methods C57Bl/6 mice were treated by the subcutaneous route with a hydroalcoholic extract from fresh leaves of S. jambolanum (HCE. After 6 h, a bacterial infection was induced in the peritoneum using the lethal CLP model. The mice were killed 12 h after the CLP induction to evaluate the cellular influx and local and systemic inflammatory mediators' production. Some animals were maintained alive to evaluate the survival rate. Results The prophylactic HCE treatment increased the mice survival, the neutrophil migration to infectious site, the spreading ability and the hydrogen peroxide release, but decreased the serum TNF and nitrite. Despite the increased migration and activation of peritoneal cells the HCE treatment did not decrease the number of CFU. The HCE treatment induced a significant decrease on the bone marrow cells number but did not alter the cell number of the spleen and lymph node. Conclusion We conclude that the treatment with S. jambolanum has a potent prophylactic anti-septic effect that is not associated to a direct microbicidal effect but it is associated to a recruitment of activated neutrophils to the infectious site and to a diminished systemic inflammatory response.

  15. Relationship between serum albumin level and prognosis in children with sepsis, severe sepsis and septic shock%脓毒症、严重脓毒症及脓毒性休克患儿血清白蛋白水平与预后关系的研究

    Institute of Scientific and Technical Information of China (English)

    王书华

    2015-01-01

    Objective To investigate the correlation of serum albumin level with prognosis in children with sepsis,severe sepsis and septic shock.Methods One hundred and forty-two patients were selected as the research objects,there were 50 cases of sepsis,48 cases of severe sepsis,44 cases of septic shock.Serum albumin were detected after inclusion in the study within 24 h.And the incidence of hypoalbuminemia and patient' s prognosis in each group were observed and compared.Results There were 30 cases (60.0%) of hypoalbuminemia in sepsis group,and 41 cases (85.4%) and 44 cases (100%) in severe sepsis and septic shock group.There was significant difference in the incidence of hypoalbuminemia among the three groups(P < 0.05).The fatality rate and survival rate among the three groups had significant differences (P < 0.05).Children' s PCIS score was positively correlated with the levels of albumin,and the fatality rate was negatively correlated with the levels of albumin (P < 0.05).Conclusions The incidence of hypoalbuminemia in children with severe sepsis and septic shock is significantly higher than that in the patients with sepsis.There is close correlation of the level of serum albumin in children with its prognosis.%目的 探讨脓毒症、严重脓毒症及脓毒性休克患儿血清白蛋白水平与预后的相关性.方法 选取南阳市第一人民医院收治的142例患儿作为研究对象,其中脓毒症50例,严重脓毒症48例,脓毒性休克44例,对三组患儿均在纳入研究之后24h检测血清白蛋白,观察并对比各组患儿预后及低白蛋白血症发生情况.结果 脓毒症组30例(60.0%)患儿发生低白蛋白血症,严重脓毒症组和脓毒性休克组分别为41例(85.4%)和44例(100.0%),各组患儿低白蛋白血症发生率比较差异有统计学意义(P<0.05);且各组低白蛋白血症患儿病死率、存活率比较差异有统计学意义(P<0.05),患儿PCIS评分、病死率与血清白蛋白浓度分

  16. Dynamic changes in thrombin generation in abdominal sepsis in mice.

    Science.gov (United States)

    Wang, Yongzhi; Braun, Oscar O; Zhang, Su; Luo, Lingtao; Norström, Eva; Thorlacius, Henrik

    2014-10-01

    Systemic inflammatory response syndrome and severe infections are associated with major derangements in the coagulation system. The purpose of this study was to examine the dynamic alterations in thrombin generation in abdominal sepsis. Abdominal sepsis was induced by cecal ligation and puncture (CLP) in C57/Bl6 mice. Cecal ligation and puncture caused a systemic inflammatory response, with neutrophil recruitment and tissue damage in the lung as well as thrombocytopenia and leukocytopenia. Thrombin generation, coagulation factors, lung histology, and myeloperoxidase activity was determined 1, 3, 6, and 24 h after induction of CLP. It was found that thrombin generation was increased 1 h after CLP and that thrombin generation started to decrease at 3 h and was markedly reduced 6 and 24 h after CLP induction. Platelet-poor plasma from healthy mice could completely reverse the inhibitory effect of CLP on thrombin generation, suggesting that sepsis caused a decrease in the levels of plasma factors regulating thrombin generation in septic animals. Indeed, it was found that CLP markedly decreased plasma levels of prothrombin, factor V, and factor X at 6 and 24 h. Moreover, we observed that CLP increased plasma levels of activated protein C at 6 h, which returned to baseline levels 24 h after CLP induction. Finally, pretreatment with imipenem/cilastatin attenuated the CLP-evoked decrease in thrombin generation and consumption of prothrombin 24 h after CLP induction. Our novel findings suggest that thrombin generation is initially increased and later decreased in abdominal sepsis. Sepsis-induced reduction in thrombin generation is correlated to changes in the plasma levels of coagulation factors and activated protein C. These findings help explain the dynamic changes in global hemostasis in abdominal sepsis.

  17. The effects of colloids or crystalloids on acute respiratory distress syndrome in swine (Sus scrofa models with severe sepsis: analysis on extravascular lung water, IL-8, and VCAM-1

    Directory of Open Access Journals (Sweden)

    Rismala Dewi

    2016-04-01

    Full Text Available Background: Acute respiratory distress syndrome (ARDS is a fatal complication of severe sepsis. Due to its higher molecular weight, the use of colloids in fluid resuscitation may be associated with fewer cases of ARDS compared to crystalloids. Extravascular lung water (EVLW elevation and levels of interleukin-8 (IL-8 and vascular cell adhesion molecule-1 (VCAM-1 have been studied as indicators playing a role in the pathogenesis of ARDS. The aim of the study was to determine the effects of colloid or crystalloid on the incidence of ARDS, elevation of EVLW, and levels of IL-8 and VCAM-1, in swine models with severe sepsis.Methods: This was a randomized trial conducted at the Laboratory of Experimental Surgery, School of Veterinary Medicine, IPB, using 22 healthy swine models with a body weight of 8 to 12 kg. Subjects were randomly allocated to receive either colloid or crystalloid fluid resuscitation. After administration of endotoxin, clinical signs of ARDS, EVLW, IL-8, and VCAM-1 were monitored during sepsis, severe sepsis, and one- and three hours after fluid resuscitation. Analysis of data using the Wilcoxon test , Kolmogorov-Smirnov test, Mann-Whitney test, unpaired t test.Results: Mild ARDS was more prevalent in the colloid group, while moderate ARDS was more frequent in the crystalloid group. EVLW elevation was lower in the colloid compared to the crystalloid group. There was no significant difference in IL-8 and VCAM-1 levels between the two groups.Conclusion: The use of colloids in fluid resuscitation does not decrease the probability of ARDS events compared to crystalloids. Compared to crystalloids, colloids are associated with a lower increase in EVLWI, but not with IL-8 or VCAM-1 levels.

  18. 血清降钙素原对脓毒症严重程度评估及预后研究%Research on Prognosis and Severity Evaluation of Serum Procalcitonin to Sepsis

    Institute of Scientific and Technical Information of China (English)

    谈昀; 曾宪飞; 白晓

    2014-01-01

    目的:探讨血清降钙素原(procalcitonin,PCT)在脓毒症患者中的临床应用价值,并为医院控制感染、合理使用抗生素提供科学依据。方法回顾性分析武警陕西总队医院2011年5月~2013年5月 ICU患者201例,根据感染严重程度分为4组,全身性炎症反应综合征(SIRS)63例、脓毒症(Sepsis)40例、严重脓毒症(Severe sepsis)70例、脓症性休克(Septic shock)19例,监测入住ICU 1,3,5,7,10,14和17天各组患者血中PCT,hs-CRP及WBC水平及据患者症状必要时进行血培养动态分析,以及PCT对脓毒症诊断的灵敏度、特异度、阳性预测值、阴性预测值和诊断符合率。结果 PCT水平 SIRS(1.92 ng/ml)组与脓毒症(10.8 ng/ml)组、严重脓毒症(24.0 ng/ml)和脓毒症休克(34.0 ng/ml)组相比,差异有统计学意义(q1=13.8,q2=15.6,q3=17.9,P均<0.05),四组 hs-CRP浓度、WBC计数相比,差异无统计学意义(F=5.10,P>0.05),PCT水平与脓毒症严重程度呈正相关性(r=0.781)。阴性符合率血培养26.6%,且 PCT对脓毒症诊断的灵敏度、特异度、阳性预测值(PPV)和阴性预测值(NPV)分别为87.2%,85.4%,78.9%和89.3%;对脓毒症诊断符合率85.0%,PCT水平上升(≥1.0 ng/ml)是28天生存率的独立指标。结论 PCT与 hs-CRP及 WBC相比,能更好地评价脓毒症的严重程度,且动态判断脓毒症的预后情况更为敏感,与血培养联合检测,可提高脓毒症鉴别诊断准确率,同时指导临床合理应用抗生素,PCT浓度每天的变化可协助预测 ICU病房中脓毒症患者存在的死亡风险,减少并发症发生和降低死亡率。%Objective To study the serum procalcitonin (PCT)in patients with sepsis clinical application value,for the hospi-tal,infection control,to provide a scientific basis for reasonable Shaanxi General of antibiotics

  19. Ischemic stroke induces gut permeability and enhances bacterial translocation leading to sepsis in aged mice

    Science.gov (United States)

    Verma, Rajkumar; Venna, Venugopal R.; Liu, Fudong; Chauhan, Anjali; Koellhoffer, Edward; Patel, Anita; Ricker, Austin; Maas, Kendra; Graf, Joerg; McCullough, Louise D.

    2016-01-01

    Aging is an important risk factor for post-stroke infection, which accounts for a large proportion of stroke-associated mortality. Despite this, studies evaluating post-stroke infection rates in aged animal models are limited. In addition, few studies have assessed gut microbes as a potential source of infection following stroke. Therefore we investigated the effects of age and the role of bacterial translocation from the gut in post-stroke infection in young (8-12 weeks) and aged (18-20 months) C57Bl/6 male mice following transient middle cerebral artery occlusion (MCAO) or sham surgery. Gut permeability was examined and peripheral organs were assessed for the presence of gut-derived bacteria following stroke. Furthermore, sickness parameters and components of innate and adaptive immunity were examined. We found that while stroke induced gut permeability and bacterial translocation in both young and aged mice, only young mice were able to resolve infection. Bacterial species seeding peripheral organs also differed between young (Escherichia) and aged (Enterobacter) mice. Consequently, aged mice developed a septic response marked by persistent and exacerbated hypothermia, weight loss, and immune dysfunction compared to young mice following stroke. PMID:27115295

  20. Efecto de la mezcla ozono/oxigeno combinado con levofloxacina en un modelo de sepsis peritoneal en rata (Efect of ozone/oxygen mixture combined with levofloxacin in a model of peritoneal sepsis induced in rats

    Directory of Open Access Journals (Sweden)

    DMV. Zullyt Zamora Rodríguez

    2007-09-01

    Full Text Available ResumenEl objetivo de este trabajo fue evaluar el efecto de la mezcla ozono/oxígeno combinado con antibiótico y aplicado terapéuticamente en un modelo de sepsis peritoneal en rata. El estudio fue realizado en ratas Wistar macho (200-250 g, los cuales fueron divididos aleatoriamente en cinco grupos: 1. inducción de la infección peritoneal, sin tratamiento alguno; 2. infectados y tratados con levofloxacina (25mg/kg; 3. infectados y tratados con la mezcla ozono/oxigeno por vía intraperitoneal, a la dosis de 1 mg/kg de peso; 4 y 5. infectados y tratados con Levofloxacina (25 mg/kg más la mezcla ozono/oxigeno i.p a 0,4 y 1 mg/kg, respectivamente. Se determinó el porciento de mortalidad de los animales mediante la observación diaria y también se registró el peso de los animales. Los resultados mostraron que los grupos de animales que recibieron tratamientos combinados de antibiótico y la mezcla ozono/oxígeno tuvieron un elevado porciento de sobrevivencia, siendo del 77 hasta el 100 % a las 120 h y entre el 66 y el 77 % a las 240 h. Sin embargo, en el grupo tratado con antibiótico fue de un 77% a las 120 h, pero ya a las 240 h el por ciento de sobrevivencia fue del 33 %. Este estudio demostró la efectividad de la combinación de la mezcla ozono/oxígeno con un antibiótico de última generación. Sin embargo, la aplicación sola de ozono de forma terapéutica, por vía intraperitoneal, en este modelo de sepsis no fue efectivo por lo cual se requiere evaluar otras dosis y vías de administración del ozono. AbstractThe aim of this research was to evaluate the effect of ozone / oxygen mixture (OOM combined with an antibiotic and applied therapeutically in a model of peritoneal sepsis induced by rat faecal material. The study was performed in male Wistar rats weighing 200-250 g. The animals were divided in five groups. The first one was the infected control with faecal material alone. The second was also infected and treated with

  1. OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS

    Directory of Open Access Journals (Sweden)

    REYHANEH SEPEHR

    2013-07-01

    Full Text Available Reactive oxygen species (ROS have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI in adults and bronchopulmonary dysplasia (BPD in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD, referred to as NADH redox ratio (NADH RR has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2 pups, hyperoxic (90% O2 pups, pups treated with LPS (normoxic + LPS, and pups treated with LPS and hyperoxia (hyperoxic + LPS. Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~ 31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure.

  2. OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS.

    Science.gov (United States)

    Sepehr, Reyhaneh; Audi, Said H; Maleki, Sepideh; Staniszewski, Kevin; Eis, Annie L; Konduri, Girija G; Ranji, Mahsa

    2013-07-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI) in adults and bronchopulmonary dysplasia (BPD) in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD), referred to as NADH redox ratio (NADH RR) has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS) exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2) pups, hyperoxic (90% O2) pups, pups treated with LPS (normoxic + LPS), and pups treated with LPS and hyperoxia (hyperoxic + LPS). Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure.

  3. Sepsis in intensive care patients: challenges in diagnosis and prognostication

    NARCIS (Netherlands)

    Klein Klouwenberg, P.M.C.

    2015-01-01

    Sepsis is a syndrome that arises when the body’s response to a severe infection injures its own tissues. It is a major and increasing cause of in-hospital morbidity and mortality. Despite recent advances in the management of sepsis, the morbidity and mortality caused by sepsis remain unacceptably hi

  4. Sepsis in intensive care patients: challenges in diagnosis and prognostication